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Animal milk has long been claimed as the go-to source of calcium by the dairy industry, but as it turns out, milk is bad for you. Calcium from animal milk is not absorbed as well as that from plant-based sources, and it can be accompanied by a number of dangerous health problems.
1. Broken bones
In a Swedish medical study, women who consumed large quantities of dairy milk daily were more likely to sustain fractures than those who drank little to no milk.
2. Prostate cancer
3. Lactose intolerance
Cow’s milk contains a sugar called lactose that can be difficult for people to digest, resulting in symptoms such as nausea, cramps, gas, bloating, and diarrhea. It can also develop later in life and result in months of worsening symptoms.
4. Acne
In multiple studies, the consumption of all types of cow’s milk was linked to an increased prevalence and severity of acne in both boys and girls.
5. Cholesterol
A single serving of milk can contain as much as 24 mg of cholesterol, whereas vegan food has no cholesterol.
6. Ovarian cancer
A Swedish study showed that women who consumed four or more servings of dairy products each day were twice as likely to develop serous ovarian cancer as those who consumed two or fewer servings of dairy products each day.
7. Milk allergies
Unlike lactose intolerance, milk allergies, usually in young children, are characterized by potentially strong and dangerous reactions, such as vomiting or anaphylaxis.
8. Antibiotics
Many cows are pumped full of antibiotics. This practice is leading to antibiotic-resistant bacteria, which may decrease the effectiveness of antibiotics used on humans.
8. Antibiotics
Many cows are pumped full of antibiotics. This practice is leading to antibiotic-resistant bacteria, which may decrease the effectiveness of antibiotics used on humans.
10. Weight gain
Despite industry claims, a study of more than 12,000 children showed that the more milk they drank, the more weight they gained, and skim and 1 percent milk appeared, counter-intuitively, to lead to more weight gain than drinking 2 percent or whole milk. The study also found that replacing soda with milk did not lead to weight loss.
11. Bone loss
Instead of promoting bone health, animal protein in dairy products can have a calcium-leaching effect.
www.peta.org/living/food/reasons-stop-drinking-milk/
Some evidence suggests that the consumption of milk and other dairy products leads to an increased risk of prostate cancer. Conversely, dairy-free diets have been followed to slow the progress of prostate cancer.
Did you know that in Medieval England parents would tie rabbits’ feet around their babies’ necks to ward off illness? Doctors would also spit on wounds because saliva was believed to have healing properties.Indeed, history is replete with unfounded health beliefs, and to everyone’s detriment, the milk myth is among the most tenacious.Milk is much more than just a drink; it’s a cultural phenomenon that can be traced back thousands of years. And still today, the milk myth resonates loud and clear: in 2001, the average American child consumed 104 quarts of cow’s milk.Milk depletes the calcium from your bones .The milk myth has spread around the world based on the flawed belief that this protein and calcium-rich drink is essential to support good overall health and bone health in particular at any age. It is easy to understand that the confusion about milk’s imaginary benefits stems from the fact that it contains calcium – around 300 mg per cup. But many scientific studies have shown an assortment of detrimental health effects directly linked to milk consumption. And the most surprising link is that not only do we barely absorb the calcium in cow’s milk (especially if pasteurized), but to make matters worse, it actually increases calcium loss from the bones. What an irony this is! Here’s how it happens. Like all animal protein, milk acidifies the body pH which in turn triggers a biological correction. You see, calcium is an excellent acid neutralizer and the biggest storage of calcium in the body is – you guessed it… in the bones. So the very same calcium that our bones need to stay strong is utilized to neutralize the acidifying effect of milk. Once calcium is pulled out of the bones, it leaves the body via the urine, so that the surprising net result after this is an actual calcium deficit.Knowing this, you’ll understand why statistics show that countries with the lowest consumption of dairy products also have the lowest fracture incidence in their population (there’s more on this later).But the sad truth is that most mainstream health practitioners ignore these proven facts. I know it firsthand because when I was diagnosed with osteoporosis, my doctor recommended that I drink lots of milk in addition to taking Fosamax.
Fortunately, I did neither, because I knew that…Cow’s milk is custom-designed for calves
Thanks to our creative ingenuity and perhaps related to our ancient survival needs, we adopted the dubious habit of drinking another species’ milk. Nobody can dispute that cow’s milk is an excellent food source for calves. Weighing around 100 pounds at birth, a calf typically gains approximately eight times its weight by the time it is weaned. But unlike humans, once calves are weaned, they never drink milk again. And the same applies to every mammalian species on this planet.Also, each mammalian species has its own “designer” milk, and cow’s milk is no exception. For example, cow’s milk contains on average three times the amount of protein than human milk which creates metabolic disturbances in humans that have detrimental bone health consequences.
It’s important to bear in mind that mother’s milk is excellent nourishment for human babies, but its composition is very different from cow’s milk.
Scientific studies show that milk increases fracture risk
Many scientific studies contradict the conventional wisdom that milk and dairy consumption help reduce osteoporotic fractures. Surprisingly, studies demonstrating that milk and dairy products actually fail to protect bones from fractures outnumber studies that prove otherwise. Even drinking milk from a young age does not protect against future fracture risk but actually increases it. Shattering the “savings account” calcium theory, Cumming and Klineberg report their study findings as follows:
“Consumption of dairy products, particularly at age 20 years, was associated with an increased risk of hip fracture in old age. (“Case-Control Study of Risk Factors for Hip Fractures in the Elderly”. American Journal of Epidemiology. Vol. 139, No. 5, 1994).
And the 12 year long Harvard Nurses’ Health Study found that those who consumed the most calcium from dairy foods broke more bones than those who rarely drank milk. This is a broad study based on 77,761 women aged 34 through 59 years of age.
In the authors’ own words:
“These data do not support the hypothesis that higher consumption of milk or other food sources of calcium by adult women protects against hip or forearm fractures.” (Source: Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. American Journal of Public Health. 1997).
Shocking statistics ignored by mainstream medicine
In the Save Our Bones Program one of the topics I discuss is the complete disregard of scientific evidence that discredits milk and dairy products as the best source of calcium.
One exception is Amy Lanou Ph.D., nutrition director for the Physicians Committee for Responsible Medicine in Washington, D.C., who states that:
“The countries with the highest rates of osteoporosis are the ones where people drink the most milk and have the most calcium in their diets. The connection between calcium consumption and bone health is actually very weak, and the connection between dairy consumption and bone health is almost nonexistent.”
Surprised? You shouldn’t be, because as I mentioned earlier in this article…
Milk is an acidifying animal protein
Like any other animal derived protein-rich food, milk has a positive potential renal acid load (PRAL) which triggers a protective biological reaction to neutralize all the damaging acidic protein before it reaches the kidneys.
The body is designed for survival, so it sacrifices bone density to protect the kidneys and urinary tract because the latter are essential to survival. And the most readily available source of acid neutralizer is in the bones. So even though milk contains calcium, it ends up sapping your bones of that crucial mineral. But that’s not all because…
Today’s milk is a processed food
Until the end of the 19th century in Europe and the beginning of the 20th century in the US, milk was consumed unpasteurized or raw. Later on, homogenization became the industry’s standard. These processes further alter milk’s chemistry and actually increase its detrimental acidifying effects.
Raw milk advocates claim that if cow’s milk is left “as is” it is a healthy and wholesome drink. It is true that raw milk is less acidifying than processed milk and that pasteurization and homogenization may cause a long list of digestive and other health problems, but I still don’t recommend drinking any kind of cow’s milk.
Nowadays, milking cows are given antibiotics and most are also injected with a genetically engineered form of bovine growth hormone (rBGH). A man-made or synthetic hormone used to artificially increase milk production, rBGH also increases blood levels of the insulin-growth factor 1 (IGF-1) in those who drink it. And higher levels of IGF-1 are linked to several cancers.
This should not be ignored, especially in view of recent information by Samuel Epstein, MD, Professor of Environmental Medicine at the University of Illinois School of Public Health, and Chairman of the Cancer Prevention Coalition. In an article titled “Monsanto’s Hormonal Milk Poses Serious Risks of Breast Cancer, Besides Other Cancers” (www.preventcancer.com/press/releases/july8_98.htm, June 21, 1998) Dr. Epstein concludes that:
“Drinking rBGH milk would thus be expected to significantly increase IGF-1 blood levels and consequently to increase risks of developing breast cancer and promoting its invasiveness.”
Even though organic milk is from cows that are not given antibiotics or rBHG, if you truly care about your bone health and your overall health, you should…
Avoid drinking cow’s milk
As I explain in the Save Our Bones Program and contrary to mainstream recommendations, drinking milk and eating lots of dairy products are not the answer to reversing osteoporosis. And while in the Save Our Bones Program no food is completely off limits, I strongly recommend that you explore the different milk substitute options that I will list for you here.
But first, I’d like to clarify that unsweetened fermented or cultured dairy products such as yogurt, kefir, and sour cream are acid neutral. Yogurt in particular is chock-full of beneficial qualities. As is the case with milk, organic yogurt does not have rBGH, but even several of the most well-known yogurt brands have stopped using the bovine growth hormone (rBGH). You should call your favorite yogurt company to confirm. One more clarification: when I say unsweetened I mean without sugar or any artificial sweetener. However, you can add honey or stevia, a zero calorie plant-derived sweetener that is delicious and alkalizing as well. I like to carry around stevia packets in my purse so that I’m always able to sweeten food or drinks when I’m on the go.
The best milk substitutes
My favorite milk substitute is unsweetened almond milk, not only because it is alkalizing (as almonds are), but also because it’s delicious and tastes very similar to milk. I even cook with it!
If almond milk is hard to get, you can also try rice or soy milk. I strongly suggest consuming only organic soy milk to insure it’s not made with genetically modified soy. There is also some controversy about unfermented soy products, so try to use it in moderation.
What Else Haven’t They Told You? What else have you been told about bone health by your doctor or other “experts” that is flat out wrong? What other “facts” (like drinking milk does a body good) are keeping you from optimal health? Myths like these are a big reason I created the Save Our Bones Program. To give you the straight scoop on how to deal with osteoporosis the natural way.
And remember, if you ever hear someone ask “Got milk?” smile and think to yourself “No, because I know better!”
saveourbones.com/osteoporosis-milk-myth/
WHY MILK IS BAD FOR YOU
Today we need to talk about WHY milk is bad for you and your bones. Not just any milk, but specifically any milk coming from another animal. Those who know me know that I am usually a VERY positive person, and the word “bad” isn’t usually in my vocabulary. However, my goal in this video is to make you aware of what you are putting in your body so that you can see HOW important it is to eat pure foods and to see which foods are optimal for your body. There is a LOT that society has taught us that isn’t healthy, and I want to expose some of those myths. Today, I will be sharing my take on why milk is really not good for you, and I will give you alternatives that you can enjoy that are much healthier. Ok, are you ready? Here are my top reasons why MILK is BAD for you:
MILK ISN’T WHAT IT USED TO BE
Today’s milk is a processed food. Until the end of the 19th century in Europe and the beginning of the 20th century in the US, milk was consumed unpasteurized or raw. Later on, homogenization became the industry’s standard. These processes further alter milk’s chemistry and actually increase its detrimental acidifying effects.
UNWANTED INGREDIENTS
Under current industrial methods, cow’s milk is often a toxic bovine brew of man-made ingredients like bio-engineered hormones, antibiotics (55% of U.S. antibiotics are fed to livestock), and pesticides—all of which are bad for us and the environment. For example, unintentional pesticide poisonings kill an estimated 355,000 people globally each year. In addition the drugs pumped into livestock often re-visit us in our water supply.
COWS MILK BELONGS TO COWS
We are the only animals on the planet who take another animals milk and drink it for consumption. We are biologically designed to drink our own mother’s milk. Would you go and put your mouth to a cow’s nipple and start drinking it? It’s not a naturally occurring desire in my mind.
The biochemical make-up of cow’s milk is perfectly suited to turn a 65-pound newborn calf into a 400-pound cow in one year. It contains, for example, three times more protein and seven times more mineral content while human milk has 10 times as much essential fatty acids, three times as much selenium, and half the calcium. Some may like cow’s milk but drinking it is both unnecessary and potentially harmful.
IT DEPLETES BONE CALCIUM
Despite popular opinion, recent studies and exposes have shown that dairy can actually CREATE osteoporosis in your bones. According to the SAVE OUR BONES CAMPAIGN and the Physicians Committee for Responsible Medicine, not only do we barely absorb the calcium in cow’s milk (especially if pasteurized), but to make matters worse, it actually increases calcium loss from the bones. This increases your risk for fractures and more.
FREQUENT MILK CONSUMPTION = INCREASED RISK OF OSTEOPOROSIS
According to the Physicians Committee for Responsible Medicine, “The countries with the highest rates of osteoporosis are the ones where people drink the most milk and have the most calcium in their diets. The connection between calcium consumption and bone health is actually very weak, and the connection between dairy consumption and bone health is almost nonexistent.”
Do you remember the GOT MILK ads that you used to see everywhere? Did you know that they had a ____ million dollar lawsuit against that ad due to the fact that this wasn’t true?
They had to stop saying that milk creates strong bones. Many of those ads disappeared after that lawsuit.
UNNCESSARY WEIGHT GAIN
As beverages go, milk is relatively high in calories. One cup of 2% milk has 138 calories, for instance. Drinking three cups a day adds 366 calories to the diet — a lot for anyone watching their weight.
EXACERBATES ACNE & CREATES GAS
Journal of the American Academy of Dermatology found an association between dairy consumption and acne. They suggest that removing milk or dairy can help to clear your skin.
IT’S AN ACIDIFYING ANIMAL PROTEIN
Like any other animal derived protein-rich food, milk has a positive potential renal acid load (PRAL) which triggers a protective biological reaction to neutralize all the damaging acidic protein before it reaches the kidneys.
What does this mean exactly? Any body that is in an acidic state is at higher risk for cancer, disease, soreness, short recovery time, and more.
DRINKING CREATES EXCESS MUCUS
There’s not much more I need to say here. Give it a try and see for yourself.
IT PROMOTES ANIMAL CRUELTY
Many of the animals today are factory farmed and abused.
Those are just a FEW of the reasons why milk isn’t the most optimal of foods for our bodies. But remember that it doesn’t stop there. Milk is found in cheeses, yogurt, non-vegan ice creams, whey protein, whipped creams, and ANY type of dairy product. I’ve put together more links and information in the description below..So I know what you are thinking..WHAT AM I SUPPOSED TO EAT?! Don’t worry because I have a great substite for you! I highly recommend that you check out my Blueberry Milkshake, Fullyraw Coffee, Banana Nice Cream, Fullyraw Frappuccino, and more. And please take a look at my video below! Feel free to leave your thoughts and comments!
The Insulin-like Growth Factor 1 (IGF-1) Receptor is found on the surface of human cells and is activated by two different hormones, IGF-1 and IGF-2. IGF1R is frequently overexpressed in tumors, including melanomas, cancers of the colon, pancreas, prostate and kidney. In cancer cells, IGFR-1 contributes to the promotion of tumor growth by inhibition of the apoptosis, transformation and induction of angiogenesis. Feel free to use this image, just link to www.enzymlogic.com. Work done with the molecular visualization VMD program developed at the University of Illinois: www.ks.uiuc.edu/Research/vmd/
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A very thorough approach to diabetes treatment from the point of view of prevention and reversal of diabetes symptoms. Frank Shallenberger is a medical doctor combining his own testing methods called Bio-energy testing with a multi-pronged holistic treatment that includes diet, supplements and exercise. The Bio-energy test , which involves testing your body on a treadmill, evaluates how well you are producing energy and metabolizing fat, as well as your optimum caloric intake and carbohydrate intake. Also adrenal gland function, heart and lung function. Unfortunately I would have to go to his office in Nevada to get this evaluation. It used to be more available, but the economic collapse may have had an impact and the fact that his treatment plan requires patients who are motivated. www.burstingwithenergy.net/bio-energy-testing.php
The book describes his theory that diabetes is an energy production problem on a cellular level and not simply a question of the pancreas not producing enough insulin. He fully admits that his theory has not been proven but his treatment plan still works per his observations of his patients.
He distinguishes two types of Type 2 diabetes. I call them Stage 1 and Stage 2. Stage 1 involves high insulin and insulin resistance. When the pancreas creates so much insulin (produced in the islet cells), the end product is excessive free radicals. Free radicals are produced as a byproduct of all cellular energy production so it is normal until the cell is overtaxed. Then the cell becomes inefficient and produces even more free radicals as a result. In the case of the pancreas this is because of too much carbohydrates demanding high insulin production. And if you are genetically prone to diabetes this is more likely, but you don't have to be this genotype to have it happen to you. So basically everybody is headed for this route due to our high carb food culture.
Stage 2 is when the pancreas does not create enough insulin which is what happens next. This means the islet cells are destroying themselves with free radicals. So you want to catch Type 2 diabetes before it gets to this point in order to reverse it. Otherwise you have to go the insulin injecting route. For this he highly recommends Dr. Bernstein's book.
The problem with conventional medicine, he says, is the use of drugs to make the failing islet cells produce more insulin. This just makes those islet cells burn out faster. Conventional medicine does not go to the root of the problem and ask what causes insulin resistance in the first place and how it can be corrected. And how to protect the pancreas from free-radical damage. This is what his approach is about. It can also be applied to overall health and energy boosting.
His eight pronged approach addresses.
DIET: low carb, above ground vegetables, saturated fats, high protein and a balance of omega 3 and omega 6 fats. He is very high-fat friendly and also believes that the low-fat premise is erroneous.
SUPPLEMENTS: to aid oxygen metabolism, increase fat metabolism and increase insulin sensitivity, increase liver function, increase insulin output, increase adrenal function and improve and increase sleep.
EXERCISE, but not of a prolonged type that keeps your heart rate high. Counsels interval training, anaerobic burst and resistance training. 30-40 minutes a day, six days a week. Interval training of three of the days and resistance training on the other three.
SUPPORTING THE LIVER WITH ANTIOXIDENT NUTRIENTS. These are vitamins C and E, lipoic acid, glutathione (converted from N-acetyl-cysteine , selenium, manganese, copper and zinc.
To check optimum liver functioning look at albumin levels. Albumin, which is a protein in the blood is entirely made by the liver so levels of albumin are indicative of good liver function. Optimal is 4.5 g/dl to 5. Normal range is 3.5 to 5 so a doctor won't care if it's in that range even though less than 4.5 means low energy production.
Glycogen also important to the detoxifying function of the liver. Results from adequate amount of protein. Fiber from vegetables and seeds, not grains, is good for absorbing bile salts which is how the liver gets rid of toxins.
ADEQUATE SLEEP supplemented with 5-HTP and tiny bit of melatonin, not sleep medications which interfere with development of deeper levels of sleep.
STRESS REDUCTION through relaxation exercises and meditation
CORRECTING HORMONE IMBALANCES, not just insulin but thyroid, cortisol, DHEA testosterone and growth hormone imbalances.
Low levels of thyroid results in a decreased production of insulin. Mercury is toxic to the thyroid gland. And possibly fluoride and x-rays. Elevated cholesterol levels, especially LDL are indicative of thyroid hormone deficiency. Thyroid makes 7% of T3 hormone and 93% of T4 hormones. The liver converts T4 to T3. T3 vital for energy production.
Cortisol can best be measured with a saliva test.
DHEA affects insulin resistance.
Growth hormone stimulates muscle and bone cells. A deficiency contributes to loss of muscle mass which in turn aggravates insulin resistance. Growth hormone replenishment is helped by exercise, sleep and fasting. Tested with a blood test for IGF-1
OXIDATIVE MEDICINE for those too impaired to exercise.
Had to get this book through inter-library loan, but it is cheap to buy used. I just wanted to make sure it was worth having.
Structural and phylogenic analysis of four zebrafish IGFs.
(A) Sequence alignment of mature zebrafish (zf) IGF-1a, IGF-1b, IGF-2a, IGF-2b and mature human (h) IGF-1 and IGF-2. The B–C–A–D domains are labeled. Star indicates conserved cysteine. (B) Phylogenetic analysis of the vertebrate insulin/IGF family members. Amino acid sequences in the B and A domains were analyzed by the neighbor-joining method using the MEGA3 program [64]. Gaps were removed from the alignment. Bootstrap values derived from 1,000 runs are shown. Relaxins are used as an outgroup. Accession numbers for the sequences used are: human (IGF-1, NM_000618; IGF-2, NM_000612; insulin, NM_000207; relaxin, NM_080864), mouse (IGF-1, NM_010512; IGF-2, NM_010514, insulin 1, NM_008386; insulin 2, NM_008387; relaxin, NM_173184), Xenopus (IGF-1, M29857; IGF-2, BC070545), zebrafish (insulin a, NM_131056; insulin b, NM_001039064), common carp (IGF-1, EF536889; IGF-2, AF402958; insulin, X00989), trout (IGF-1, EF432852; IGF-2, EF432854; insulin, M21170), tilapia (IGF-1, AF033796; IGF-2, AF033801; IGF-3, EU272147; insulin, AF038123 ), shark (IGF-1, Z50081; IGF-2, Z50082), hagfish (IGF, M57735; insulin, V00649 ), sea lamprey (IGF, AB081462), Amphioxus insulin-like peptide mRNA (ILP, M55302). Sequence for Tetraodon, fugu and stickleback IGF-1, IGF2 and insulin were obtained by searching the Tetraodon genome (www.genoscope.cns.fr/externe/English/Projets/Projet_C/C.html), fugu genome (fugu.hgmp.mrc.ac.uk/), and stickleback genome (www.ensembl.org/Gasterosteus_aculeatus/). Sequence of sea lamprey insulin was obtained by searching sea lamprey genome (pre.ensembl.org/Petromyzon_marinus/). (C) Conserved synteny between human (Hs) and zebrafish (Zf) IGF loci. Vertical gray lines indicate a group of genes on the same chromosome, with order ignored to facilitate the comparison of orthologs and paralogs. Horizontal gray lines connect presumed orthologs within chromosome groups as well as paralogs between chromosome groups.
Autora: Iara Waitzberg Lewinski
Fonte: nutritotal.com.br/perguntas/?acao=bu&id=560&categ...
Como as proteínas do soro do leite são utilizadas?
O soro do leite é um subproduto, resultante da fabricação de queijos. Possui alto valor nutricional, conferido pela presença de proteínas com elevado teor de aminoácidos essenciais.
A proteína do leite bovino contém aproximadamente 80% de caseína e 20% de proteínas do soro. No leite humano, o percentual das proteínas do soro é modificado ao longo da lactação. O leite produzido no início da lactação, chamado colostro, contém cerca de 80% dessas proteínas. O percentual da proteína do soro no leite produzido após esse período diminui para 50%.
O concentrado protéico do soro do leite possui, em 100 g, em média 414 Kcal, 80 g de proteína, 7 g de gordura e 8 g de carboidratos. Com relação aos aminoácidos, contém alanina, arginina, asparagina, ácido aspártico, cisteína, glutamina, ácido glutâmico, glicina, histidina, isoleucina, leucina, lisina, metionina, fenilalanina, prolina, serina, treonina, triptofano, tirosina e valina. Os aminoácidos de cadeia ramificada (BCAA) perfazem 21,2% e todos os aminoácidos essenciais constituem 42,7% da composição nutricional das proteínas do soro do leite (PSL). Além disso, o soro do leite ainda é fonte de ferro (1,2 mg / 100 g), cálcio (600 mg / 100 g) e sódio (170 mg / 100 g).
As PSL são bastante utilizadas em dietas enterais e formulações infantis em virtude de seu elevado valor nutritivo. Utilizadas na forma de hidrolisados, as proteínas do leite normalmente são hipoalergênicas. Indivíduos com intolerância à lactose podem se beneficiar do consumo das PSL como importante fonte de cálcio.
Por apresentarem grande versatilidade de suas propriedades funcionais, as PSL são utilizadas como ingredientes em diversos produtos alimentícios, principalmente por sua elevada solubilidade e capacidade de gelificação.
Ao atingir o intestino delgado, as PSL são rapidamente digeridas e seus aminoácidos absorvidos, estimulando a síntese de proteínas nos tecidos. Esta propriedade contribui com o ganho de peso em pacientes pós-cirúrgicos, geriátricos, imobilizados e praticantes de atividade física. A suplementação com PSL (conhecida como Whey Protein) é bastante utilizada por indivíduos que desejam aumentar a massa muscular. Como o perfil de aminoácidos das PSL é muito similar ao das proteínas do músculo esquelético, muitos estudos classificam as PSL como um efetivo suplemento anabólico.
As PSL também podem ser utilizadas como estratégia para redução de gordura corporal. O cálcio presente nas PSL atua na supressão dos hormônios calcitrópicos, diminuindo a deposição de gordura nos tecidos adiposos. Além disso, o alto teor de BCAA das PSL afeta os processos metabólicos da regulação energética, favorecendo o controle e a redução da gordura corporal.
As PSL também agem sobre os hormônios colecistoquinina e sobre o peptídeo similar ao glucagon, promovendo aumento da saciedade. Pesquisadores observaram que quando os indivíduos ingeriram uma solução contendo 48 g de PSL 90 minutos antes da refeição, apresentaram uma redução significativa do apetite e da ingestão energética.
Estudos com animais observaram outros efeitos biológicos das PSL, como aumentar a resposta imune por meio de maior produção de glutationa celular, estimular a síntese de IGF-1 (Insulin Growth Factor I), reforçar o sistema imunológico, aumentar a longevidade, além das ações hipocolesterôlemica e antitumoral.
Bibliografia (s)
Pacheco MTB, Dias NFG, Baldini VLS Tanikawa C, Sgarbieri VC. Propriedades funcionais de hidrolisados obtidos a partir de concentrados protéicos de soro de leite. Ciênc Tecnol Aliment. 2005;25(2):333-8. Disponível em: www.scielo.br/scielo.php?pid=S010120612005000200026&s.... Acessado em: 01/03/2010.
Capitani CD, Pacheco MTB, Gumerato HF, Vitali A, Schmidt FL. Recuperação de proteínas do soro de leite por meio de conservação com polissacarídeo. Pesq Agropec Bras. 2005;40(11):1123-8. Disponível em: www.scielo.br/scielo.php?script=sci_arttext&pid=S0100.... Acessado em: 03/03/2010.
Haraguchi FK, Abreu WC, Paula H. Proteínas do soro do leite: composição, propriedades nutricionais, aplicações no esporte e benefícios para a saúde humana. Rev Nutr. 2006;19(4):479-88. Disponível em: www.scielo.br/scielo.php?pid=S141552732006000400007&s.... Acessado em: 03/03/2010.
DECA Mass IGF 1® é um suplemento compensador, desenvolvido para gerar um aumento da força e volume corporal formulado com teores ideais de macronutrientes. Contém 5 tipos de carboidratos, simples e complexos, que fornecem energia ao longo do dia para indivíduos fisicamente ativos e reposição do glicogênio muscular após o treino, 5 tipos de proteínas de alto valor biológico, Whey Protein, Proteína Hidrolisada do Trigo, Albumina, Proteina Concentrada da Soja e TRI-FX®, uma proteína rica em imunoglobulinas, lactoferrina, fatores de crescimento e fosfolipídios. TRIF-FX possui uma combinação única de elementos bioativos que ajudam a melhorar o desenvolvi-mento muscular, maximizar a resitência do corpo e acelerar a recuperação muscular. Além de vitaminas, minerais que atuam como antioxidantes e ácidos graxos que exercem funções essenciais para o organismo.
DECA Mass IGF 1® é indicado para atletas, praticantes de atividade física e indivíduos fisicamente ativos que necessitam um aporte energético maior e também para aqueles que desejam aumentar de forma saudável o volume corporal.
• Mix de carboidratos simples e complexos (maltodextrina, dextrose, frutose, frutooligossacarídeo e ribose);
• Proteínas de alto valor biológico;
• TRI-FX – lactoalbuminas, imunoglobulinas, lactoferrina, fatores de crescimento e fosfolipídeos;
• Rico em vitaminas e minerais;
• Melhora o sistema imunológico;
• Ótima relação custo benefício;
• Fonte de ácidos graxos essenciais.
Ingredientes:
Maltodextrina, Proteína Concentrada de Soja, Dextrose, Frutose, Leite em Pó Desnatado, Proteína Concentrada do Soro de Leite, Cacau em Pó, Albumina Desidratada, Proteína do Soro de Leite TRI-FX, Frutooligossacarídeo, Proteína Hidrolisada do Trigo, Mix de Minerais (Cálcio, Magnésio, Zinco, Ferro, Manganês, Flúor, Cobre, Cromo, Molibdênio, Iodo, Selênio e Fósforo), Óleo de Canola, Óleo de Coco, Óleo de Girassol, Óleo de Cártamo, Mix de Vitaminas (A, D, E, C, B1, B2, B3, B5, B6, B12, Biotina e Ácido Fólico), Ribose, Aroma Idêntico ao Natural de Chocolate e Corante INS 124.
Diabéticos: Contém Glicose e Frutose.
Colorido Artificialmente.
Contém Aromatizante Sintético Idêntico ao Natural.
Contém Glúten.
Sugestão de Uso:
Diluir 8 colheres de sopa (120g), de DECA Mass IGF 1® em 1 copo (250ml) de leite desnatado, água, suco ou vitaminas de frutas de sua preferência; e bater em liquidificador ou mixer até a diluição total do produto.Consumir 2 porções ao dia, sendo uma, preferencialmente, após o treino ou conforme orientação profissional.
Recomendação:
Crianças, gestantes e idosos, consumir preferencialmente sob orientação de nutricionista e/ou médico.
Conservar este produto ao abrigo da luz, calor e umidade. Depois de aberto, consumir preferencialmente em 30 dias.
Contra Indicação:DECA Mass IGF 1® está contra-indicado para pessoas com restrição à ingestão de carboidratos, proteína ou indivíduos alérgicos a qualquer componente do produto. Pessoas sob estas condições devem consultar um médico e/ou nutricionista antes de consumir o produto.
At the Cluny Museum, medieval culture showcases its ancestral knowledge. It took five centuries to discover that the thymus and the genitals are connected, as seen in this statue of the first man to experience desire, through a dream about a mythical serpent.....
Within the thymus, regulation of the cellular crosstalk directing T cell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding human postnatal T cell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both T cell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population of extracellular matrix (ECM)− fibroblasts, and characterize the medullary niches surrounding Hassall’s corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.
The thymus is the primary organ responsible for the generation and selection of mature, functional, and self-tolerant T cells.1 Effective T cell development is a critical component of our immune system’s ability to accurately and exclusively identify and kill foreign entities such as pathogens. During early postnatal T cell development—the period in life when T cell development is most active2—thymic seeding progenitors migrate to the thymus and mature into thymocytes. Thymic architecture is highly organized to provide spatially defined, stage-specific signaling cues to migrating thymocytes that guide development toward functional mature T cells.3,4,5,6
Recent single-cell sequencing resources demonstrating the diversity of human thymus tissue are incongruous with our current framework of thymus structure and organization,7,8,9,10,11,12,13,14,15,16,17,18,19 which describe a general migratory path thymocytes take through the cortex and medulla during conventional αβT cell development. Spatial transcriptomic sequencing of human thymus has demonstrated a deeper granularity of thymic niches and their evolution during fetal development to support different waves of non-conventional T cells.19,20 However, our understanding of how human postnatal thymus niches support conventional and non-conventional T cell development, T-lineage branching, and alternative lineage development remains limited.3,4,6 T cells generated at this stage of postnatal human development will become the foundation of our immune system, patrolling the body for decades.21 Thus, insights into early postnatal thymus niche biology are crucial to understand how our adaptive immune system is built and how perturbations in postnatal T cell development may emerge as immune dysfunction later in life.
To create a spatially defined map of tissue niches guiding human postnatal T and alternative lineage cell development, we employed multi-dimensional spatial proteomic imaging using co-detection by indexing (CODEX),22,23 single-cell transcriptomic-proteomic profiling using cellular indexing of transcriptomes and epitopes sequencing (CITE-seq),24 and single-cell assay for transposase accessible chromatin sequencing (ATAC-seq).25 Given the emerging recognition of sex differences in thymus gene expression and function,26,27,28,29,30,31 we collected and analyzed samples from male and female donors. Our analysis identifies significant sex differences during early postnatal development that affect T cell and thymus biology through common and cell type-specific mechanisms. Additionally, we highlight key cell types contributing to thymic involution that exhibit sex-based differences in thymic growth and early transition toward adipogenesis. These data suggest that kinetic differences in thymic involution are present between sexes and, importantly, that mechanisms driving thymic involution begin early in life. Altogether, these data represent a powerful age-matched spatial multiomic resource to investigate how sex-based differences in thymus biology and T cell development arise, and how they contribute to sex differences in diseases caused by immune dysfunction.
Results
Spatial multiomic profiling of human postnatal thymus identifies sex-based differences in T cells and thymus biology
We performed single-cell CITE-seq, ATAC-seq, and CODEX imaging on 4–33 months human postnatal thymuses, including 6 (3 female and 3 male) 4- to 5-month-old age-matched samples (Table S1). Each donor sample was processed simultaneously for CODEX imaging and sequencing (Figure 1A). We included a comprehensive 137 antibody panel (Data S1), allowing us to compare epigenomic, transcriptomic, and proteomic expression kinetics across developing thymocytes and enabling direct comparison of cells identified via phenotypic expression in CODEX with cells captured via CITE-seq. Prior to sequencing, we enriched CD45− non-hematopoietic cells and CD25+CD8− regulatory T (Treg) cells to ensure coverage of low-abundance cell types. After quality control and computational merging of individually sequenced patient datasets, we obtained a total of 74,334 cells with CITE-seq, including 19,434 non-T-lineage cells, and captured 25,717 nuclei with ATAC-seq. Importantly, cell proximity in CODEX tissue niches was used to screen predicted receptor-ligand interactions.
Figure 1 Spatial multiomic analysis identifies sex-biased characteristics of thymic niches
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CITE-seq cells were clustered based on transcriptional expression and annotated based on marker gene and surface protein expression (Figure S1A; Table S2).7,8 ATAC-seq clusters were computationally labeled using CITE-seq reference cluster labels, which identified 34 ATAC-seq cluster transfer labels for dataset integration (Figures 1B and S1B). We captured 54,900 thymocytes spanning development from early thymic progenitors (ETPs) to mature single positive (SP) T cells, immature innate cells, innate-like cells, and Tregs. We identified three Treg populations expressing canonical lineage markers, namely Treg progenitors (Pro-Tregs), thymic Tregs (tTregs), and recirculating/resident Tregs (rrTregs).32 We also identified antigen-presenting cells, including B cells, mast cells, monocytes, and six populations of dendritic cells (DCs).33 In addition to the activated DCs (aDCs), plasmacytoid DCs (pDCs), DC1, and DC2/3 populations described by Park et al.,7 we found proliferating populations of pDCs and DC1. We also captured 7,093 epithelial cells, including cortical epithelial cells (cTECs), medullary epithelial cells (mTECs), activated mTECs, and mimetic TECs.
Importantly, we captured 7,721 mesenchymal cells, which contribute to negative selection and thymic involution.9,19,34,35,36 Subclustering identifies important mesenchymal cell types, including two populations of endothelial cells (ECs) defined by differential expression of Notch ligands (ECs, ECs (Notch)). Additionally, we identified lymphatic ECs (LECs), pericytes, vascular smooth muscle cells (VSMCs), and five distinct fibroblast cell types, including DPP4+ capsular fibroblasts (DPP4+ capFibs), capsule fibroblasts (capFibs), medullary fibroblasts (mFibs), KRT+ fibroblasts (KRT+ Fibs), and proliferating fibroblasts (Fibs (P)).
We imaged each tissue sample with a custom 48 antibody CODEX panel to study the architecture and function of niches guiding thymocyte development, aiming to define the niche characteristics guiding T-lineage branch points. Stage-specific thymocyte phenotyping markers (CD62L, CCR7, CD1A, CD5, CD7, CD4, CD8, CD3, CD45RO, CD45RA, FOXP3, and SATB1) identified CD3+ double positive cells (DPs) undergoing T-lineage commitment toward CD4 or CD8 T cells. Phenotyping markers for non-T-lineage hematopoietic cells (CD19, CD11c, CD11b, and CD68), epithelial cells (EPCAM and KRT5/8), mural cells (MCAM and SMA), ECs (CD31), and fibroblasts (PDGFRA) identified the remaining major cell types defining thymic niche architecture. Finally, we included functional markers to define patterns of antigen presentation (CD86), human leukocyte antigen (HLA) class I and II expression (HLA-ABC and HLA-DR,DP,DQ), adhesion ligands (ICAM and VCAM), Notch ligands (DLL1, DLL4, JAG1, and JAG2), T cell activation (PD-1), self-tolerance (PD-L1), proliferation (Ki67), and enzymatic regulation (15-PDGH). In sum, our CODEX panel enabled investigation of spatially regulated mechanisms directing human T cell development.
Using neural-network-driven cell segmentation and Leiden-based clustering,23 we identified individual cells within thymic tissue for each sample (Figure S1C). We annotated cell types based on tissue location and phenotypic expression compared with CITE-seq clusters (Figure 1C), performed proximity-based neighborhood clustering to identify niches,23 and annotated niches based on location and cell type composition (Figure 1D; Figure S1D). This analysis quantified proximity-based cell-cell interactions (Figure S1E) and served as a platform to interrogate spatially defined thymic niche biology via integrated sequencing-imaging analysis.
Because of known sex differences in thymus and T cell gene expression,31 we compared our age-matched male and female samples separately. In line with prior reports of sex-biased gene expression on autosomes,37,38,39,40 only 2% of male differentially expressed genes (DEGs) were found on the Y chromosome and 0.3% of female DEGs were found on the X chromosome (Tables S3 and S4). Gene set enrichment analysis (GSEA) on male vs. female cells for each cell type identified pathways commonly upregulated in either sex (Figure 1E; Data S1). Pathways differentially regulated across hematopoietic, epithelial, and stromal cells represent cell-intrinsic sex-based differences. Female cells have higher gene expression of transcription, energy regulation, and antigen presentation. Male cells, by contrast, have increased gene expression of proinflammatory signaling, amino acid metabolism, and G protein-coupled receptors (GPCR) signaling. The top differentially expressed energy regulation and metabolism pathways were similarly sex-biased in human kidney,41 suggesting multiple organs show consistent sex-biased enrichment of pathways linked to metabolism and energy production. Our data align with sex-biased trends identified in human induced pluripotent stem cell (iPSC) lines42 and other human organs,43 indicating these pathways often differ between male and female cells across various cell types.
By contrast, some pathways showed cell type-specific sex-biased enrichment. Female T and hematopoietic cells showed enrichment of interferon signaling, and female fibroblast and perivascular cells were enriched in extracellular matrix (ECM)-centric pathways (Figure 1E). Our dataset also identified differential sex-specific pathway enrichment between cell types. Gene expression indicated higher cytokine signaling in T cells and hematopoietic cells in females and in epithelial and mesenchymal cells in males (Figure 1E). These data show significant gene expression differences in male and female thymic cells. To demonstrate sex differences at the proteomic level, we identified genes with a log fold change greater than 1 that contributed to increased chemokine signaling in male T cells. CXCR4, an important chemokine receptor in thymocyte migration and development, had increased expression in male progenitor T (pro-T) cells, which we confirmed via flow cytometry (3 male, 3 female; p = 0.03; Figure S1F). As higher levels of cytokine and interferon signaling have been previously shown to influence thymus and T cell biology,44,45 our data suggest male and female T cells develop in different signaling environments and may respond differently to cytokine stimuli.
Next, we quantified cell type abundance within male and female tissues, demonstrating differences in cortical and medullary cell distributions between sexes. When normalized to the total number of cells per lobe, female thymus lobes contained significantly more DPs (p = 0.011) and cTECs (p = 0.0023). In males, we found significantly more SPs (p = 4.2 × 10−4), CD3+ DPs (p = 9.9 × 10−4), activated mTECs (p = 0.0014), and VSMCs (p = 2.4 × 10−6) (Figure 1F). Given that thymus lobules with more DPs and cTECs would have a greater proportion of cells undergoing positive selection and lobules with more medullary cells would have more cells undergoing negative selection, these data suggest that sex differences in cell type abundance may influence the resources directed toward specific stages of thymocyte selection. Alternatively, these results may suggest that male and female thymuses are developmentally asynchronous, with males exhibiting faster growth and involution kinetics, resulting in decreased cortical-to-medullary ratios even in early neonatal stages. We focused further analyses on sequential developmental niches, including analysis of sex differences in cell types and niches at each stage.
JAG1 skews ETP development toward thymic DCs
We first analyzed the cortico-medullary junction (CMJ) where cells home to the thymus (Figure 2A). This region recruits and supports ETPs10 and is composed of ECs, VSMCs, and pericytes expressing the Notch ligand JAG1 (Figures 2B and 2C). CITE-seq demonstrated that the cell adhesion molecule used by ETPs to enter the thymus, CD62L, is quickly downregulated upon CMJ entrance through the vasculature (Figure S2A). However, recently immigrated CD62L+ double negative cells are frequently located in the subcapsular zone (Figure S2B), suggesting that ETPs enter the thymus and rapidly migrate to a subcapsular niche where DLL4, a more potent Notch ligand, is highly expressed on fibroblasts and subcapsular epithelial cells (Figures 2D and S2C). However, the concentrated presence of JAG1 at the entry point indicates that ETPs are first exposed to this Notch ligand.
Figure 2 Thymic progenitors entering via the corticomedullary junction are exposed to a gradient of Notch ligands, which influence lineage specification
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CellChat46 pathway analysis showed that JAG1-NOTCH1 interactions between endothelial and perivascular cells are enriched with ETPs (Figure 2E), while JAG1-NOTCH2 and JAG1-NOTCH3 interactions are enriched with DC1, DC1 (P), DC2/3, and aDCs (Figures 2E–2G). These data suggest that JAG1 could induce commitment toward other hematopoietic lineages, such as pDCs, conventional DCs (cDCs), or macrophages, which are known to develop within the thymus.10 As JAG ligands induce weaker Notch induction,47,48,49,50 we hypothesized that early contact with ETPs could maintain T-lineage potential while cells migrate toward DLL4 in the subcapsular niche.
We first analyzed the ability of the four thymic Notch ligands to induce T-lineage commitment or alternative lineage development from cord-blood-derived CD34+ hematopoietic stem and progenitor cells (HSPCs) in a defined, feeder-free culture system44 (Figure 2H). We included titrated concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by mast cells at the CMJ, to support DC development.51 We found that only DLL1 and DLL4 ligands induce T-lineage commitment, whereas JAG ligands or no ligand controls supported myeloid cell development and did not induce T-lineage commitment (Figure S2D). Specifically, JAG ligands with GM-CSF skewed CD68+ DC development toward CD14− DC1 cells, while no ligand controls skewed CD68+ DC development toward CD14+ DC2/3 cells (Figures 2I and S2E).
Next, to test our hypothesis that Notch signals via JAG1 ligands could act as a bridge toward later DLL4 interactions, we analyzed cells grown on JAG1 for 3, 5, or 7 days prior to DLL4 transfer (Figure 2J). We found that cells cultured on JAG ligands or no ligands for 3 days maintained reduced T-lineage commitment compared with DLL1 or DLL4 cells (pJAG1 = 0.033; pJAG2 = 0.017), whereas cells cultured on JAG ligands for longer than 3 days lost T-lineage potential (Figure 2K), indicating that JAG ligands could not support T-lineage potential.
We next analyzed the contribution of different Notch ligands to the development of male and female ETPs (Figures S2F and S2G). Our data suggest that JAG ligand interactions are more abundant and diverse in females, with JAG1-NOTCH1 interactions enriched in female ETPs and DLL4 interactions enriched in male ETPs.
Together, these data suggest that timely migration from the CMJ to DLL4 ligands at the subcapsular zone is critical for T-lineage commitment, and exposure to JAG ligands at the CMJ can guide alternative lineage development toward thymic-derived DCs. Our data further demonstrate previously unrecognized sex-biased regulation by Notch ligands.
Analysis of the subcapsular zone identifies sex-based differences in fibroblast regulation of DP development and thymus growth
From the CMJ, ETPs migrate to the subcapsular zone via a CCL25-CCR9 chemokine gradient established by cTECs and directed to pro-T, DP (P), and DP2 (Q), but not DP1 (Q) cells (Figure 3A; Figure S3A). The subcapsular niche consists of JAG1+ VCAM1+ DCs, cTECs, capsular fibroblasts, DPP4+ capsular fibroblasts, and proliferating fibroblasts, which secrete and maintain spatially regulated ECM ligands to support sequential thymocyte development (Figures 3B and 3C; Figure S3B and S3C).
Figure 3 Fibroblasts in the subcapsular zone contribute to regulation of thymus biology and T cell progenitor development
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GSEA showed that DPP4+ capsule fibroblasts were enriched in HSP90 chaperone cycle for steroid hormone receptors (padjusted = 0.0065; 18/52 pathway genes significantly upregulated) (Data S1), suggesting an enhanced response to steroid hormones and supporting their role in sex hormone-based thymic involution.9 By contrast, capFibs were enriched for genes related to cytokine (interleukin [IL]-33, padjusted = 1.50 × 10−6; IL-34, padjusted = 3.56 × 10−7) and chemokine signaling (CCL2, padjusted = 5.10 × 10−40; CXCL3, padjusted = 0.020; CXCL12, padjusted = 1.78 × 10−8; CXCL14, padjusted = 3.63 × 10−15), functions previously attributed to TECs. Furthermore, CellChat identified cortical fibroblasts as major contributors to insulin growth factor (IGF) signaling through predicted signaling to cTECs, which are found in close proximity in the cortex (Figure S3D), via IGF2-IGF1R and IGF1-IGF1R axes, and to ETPs and β-selection cells, which were found under the capsule (Figure S2B), via an IGF2-IGF2R axis (Figures 3D–3F).
We next explored the role of proliferating fibroblasts. GSEA comparisons between capFibs and Fibs (P) showed marked differences in signal transduction pathways. CapFibs resembled traditional fibroblasts, which upregulate tyrosine kinase, angiogenesis, and ECM regulation and deposition pathways, whereas Fib (P) upregulates WNT signaling and cell sensing pathways, including genes involved in transient receptor potential (TRP) channels in the stimuli sensing channels pathway and taste receptors (TASRs) (Figure 3G; Data S1). Interestingly, CODEX images identified ECM− PDGFRa+ fibroblasts lacking extra domain A fibronectin (EDA-FN) expression, indicating that Fibs (P) are not involved in fibrotic matrix deposition unlike capFibs (Figure 3H; Figure S3B). Fibs (P) form a network of PDGFRa+ cells throughout the cortex that does not overlap with the cTEC network, yet maintain cell-cell contact in specific niches and often localize near cortical capillaries (Figure S3D).
We found sex-specific differences in vascular endothelial growth factor A (VEGFA) signaling within ECM− fibroblasts (Fib (P)) and other mesenchymal cells. Although all thymic fibroblasts produce the angiogenesis growth factor VEGFA, male fibroblasts express more than female cells (Fibs (P): padjusted = 0.0306; DPP4+ capFibs: padjusted = 0.0318; mFibs: padjusted = 1.85 × 10−6) (Figure 3I). Given that postnatal male thymuses are larger than female thymuses in humans and primates26 (Figure S3E), male fibroblasts may provide increased VEGFA to support angiogenesis and rapid thymic growth observed during postnatal development.52 Additionally, male mFibs have higher expression of FGF7 (padjusted = 0.0154), which regulates thymus size.53 CellChat predicts that male Fibs (P) are enriched in FGF10 compared with females, which supports cTEC proliferation and vascular growth,53,54 and only male VSMCs express FGF18 (Figures S3F–S3H). These sex biases in fibroblast growth factor (FGF) gene expression may contribute to the larger size of early postnatal male thymuses by stimulating epithelial and EC growth and proliferation.
Comparison of DEGs between male and female mesenchymal cells found increased expression of adipogenesis, cytokine, and GPCR signaling pathways in DPP4+ capFibs (Figure 3J). We also found increased expression of APOD, a gene associated with androgen, estrogen, progesterone, and glucocorticoid signaling,55,56 across male fibroblast populations (Fibs (P): padjusted = 2.18 × 10−26, mFibs: padjusted = 8.45 × 10−32) (Figure S3I). Given the association of hormone signaling with thymic involution,29,52,57 these findings suggest early initiation of thymic involution in postnatal males.
In sum, we identified three roles for fibroblasts within the subcapsular niche: maintaining tissue structure and organization via ECM and chemokine signaling, directly regulating cTEC maintenance and expansion, and potentially coordinating T cell development directly through growth factors and cell-cell interactions.
Human postnatal thymocytes may self-select in the cortex to support positive selection of conventional αβT cells
Upon exiting the subcapsular zone, DPs migrate into the inner cortex toward the medulla, where they receive positive selection signals that guide T-lineage branching toward CD4 or CD8 SP cells (Figure 4A). For DPs to transition toward the CD4 lineage, cells must receive T cell receptor (TCR) stimulation through HLA class II interactions, yet previous mouse studies have shown transcriptional downregulation of HLA class I and II in DPs.58,59 Low transcriptional expression is hypothesized to prevent thymocyte-thymocyte self-selection during positive selection, necessitating DP interactions with cTECs to receive positive selection signals.
Figure 4 HLA class I and II interactions may support thymocyte positive selection in the inner cortical zone
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Analogous to mouse literature, quiescent human DPs do not express HLA class II transcripts and have closed CIITA promoters (Figures 4B and 4C). Despite the lack of class II mRNA, thymocytes express low levels of HLA class II protein throughout development (Figure 4B). Additionally, in contrast to mouse data, we observe constitutive class I mRNA expression, which increased as cells transitioned toward SPs (Figure 4D). This is consistent with ATAC-seq data demonstrating that the B2M promoter is open throughout thymocyte development (Figure 4E). We confirmed HLA expression via flow cytometry and found that approximately 25% of DPs express both class I and II, and over 65% of DPs are class I+ (Figure S4A). Thus, thymocyte self-selection within the cortex could support positive selection. In support of this notion, CODEX enabled us to identify locations within the cortex devoid of epithelial, fibroblast, endothelial, or DCs but packed with DPs expressing class II+ molecules concentrated at cell junctions (Figure 4F). We confirmed the absence of spindle-like cTEC projections in this niche via confocal imaging (Figure 4G). Additionally, we quantified cell-cell interactions and identified a niche (positive selection niche 1) consisting of class II+ DPs and CD3+ DPs and a niche (self-selection niche) containing mainly class II+ DPs (Figure 1D). Finally, we sorted thymocytes to isolate immature DPs (CD4+CD8+CD3−TCR−) and mature DPs (CD4+CD8+CD3+TCR+) from three donors and cultured them for 7 days in a feeder-free assay. In the absence of epithelial cells, both immature and mature DPs upregulate HLA class II proteins (Figure 4H), and immature DPs continue to mature along their developmental pathway, as indicated by increased percentage of CD27+ DPs in culture after 7 days (Figure 4I).
Next, we identified a niche that directs T-lineage commitment toward CD4 or CD8SPs. We performed differential gene expression analysis on clusters representing this lineage branch point to identify markers for our CODEX panel (Figure S4B). We found SATB1 expression increased as DPs transitioned toward SPs (Figure S4C), and compared with CD8SP transition cells, CD4SP transition cells had higher expression of this master transcription factor60 (Figures S4D and S4E). Imaging analysis confirmed increased SATB1 expression coincides with CD3 upregulation, consistent with a role in late DP development and lineage branching (Figure 4J).7 Neighborhood analysis identified a niche enriched for mature CD3+ DPs in the inner cortex, suggesting that there either exists a niche specifically for late DP development and CD4 lineage transition or that cells are pre-disposed to CD4 lineage development through their TCR and migrate as clonal populations after proliferation at the outer cortex.
We compared cortical niche organization between sexes and found differences in niche organization supporting conventional T cell development, self-selection, and cross presentation. Females showed increased neighborhood interactions between the cortical DC niche containing JAG1+ VCAM+ DCs and the mature DP niche containing CD3+ DPs, the positive selection niche 1 containing class II+ DP cells and CD3+ DP cells, and the positive selection niche 3 containing DCs and DPs (Figure S4F) as well as increased cell-cell interactions between cTECs and class II+ DPs (Figures S4G and S4H). Conversely, males had increased cell-cell interactions between cTECs and CD3+ DPs (Figures S4G and S4H). These data suggest that the proportionally larger female cortex could increase cross presentation from DCs and cTECs to class II+ DPs, possibly facilitating greater use of self-selection as an alternative mechanism for positive selection.
Taken together, spatial multiomic analysis of the inner cortex identified cortical niches supporting specific stages of DP development, including three positive selection niches, a specialized niche for self-selection, and a mature DP niche thymocytes migrate through prior to entering the medulla.
Spatial multiomics identifies key mechanisms regulating negative selection niches in the medulla
Mature DPs enter the medulla, an environment specialized for negative selection, and transition toward CD4 or CD8 lineages (Figure 5A). Within the medulla, cells specialized for negative selection localize around keratinized structures called Hassall’s corpuscles (HCs).61 HCs appear during late prenatal development and are abundant in human postnatal thymuses but rare in mice.62 Here, we demonstrate that HCs can be divided into three major components: an external epithelial border of highly keratinized cells, an inner border of cells expressing prostaglandin-degrading enzyme 15-PGDH (HPGD), and a central PDGFRa+ mass (Figure 5B). HCs produce thymic stromal lymphopoietin (TSLP),61 an analog of IL-7, which activates DCs to increase expression of class II and co-stimulatory molecules CD80 and CD86. Importantly, subclustering stromal populations identified a population of KRT+ fibroblasts resembling cells undergoing epithelial-to-mesenchymal transition (EMT)63 (Figures S5A and S5B). CITE-seq identified TSLP and 15-PGDH mRNA expression in KRT+ Fibs, mFibs, mTECs, activated mTECs, and aDCs (Figure 5C), implicating these cell types as potential contributors to the function of HCs. Finally, given the inner layer of 15-PGDH+ cells, we explored the role of prostaglandin signaling regulation within the medulla. We found that DC1 cells express high levels of PGE2, whereas DC2/3 cells and monocytes express the PTGER2 and PTGER4 receptors, and aDCs express the PTGER3 receptor (Figure 5C), suggesting prostaglandin signaling is a major regulator of DC activity near HCs.
Figure 5 HCs represent scalable organizing centers for negative selection in the neonatal thymic medulla
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CODEX imaging suggests HCs act as sub-medullary organizational centers to segregate the inner medulla into specialized niches for negative selection. CD86+ APCs, a subset of which express the co-stimulatory ligand CD40, localize near HCs and in direct contact with CD45RA+ mature SPs (Figure 5D; Figure S5C). In addition, approximately 30% of medullary area is composed of CD19+ B cells,64 which cluster into niches surrounding HCs (Figure S5D). These B cells are found in close contact with—and are often enveloped within—mTECs, potentially facilitating cross presentation with epithelial cells (Figure 5E). These results suggest thymic B cells may comprise an important source of antigen presentation for negative selection.64,65 We quantified medullary neighborhoods and identified six niches, including an mTEC maturation niche, a cross-presentation niche, and four niches specialized for negative selection, which vary in relative location to HCs or the CMJ, as well as their composition of APCs, epithelial, and T cells (Figure 1D; Figure S1D).
Negative selection niches surrounding HCs play a key role in conventional T cell and tTreg development.61 We enriched CD25+ cells for sequencing and found a population of CD25hi pro-Tregs expressing canonical Treg markers CTLA-4, TNFRSF1B (TNFR2), and TNFRSF4 (OX40); positive/negative selection markers (ITM2A, RANBP1, NCL, NME1, MIF, and ATP5G1); Treg developmental long non-coding RNA (MIR155HG)66,67,68,69; and other markers described in mice (Figure S5E). Whereas pro-Tregs expressed high levels of pro-apoptotic gene BCL2L11, mature tTreg subsets expressed the anti-apoptotic gene BCL2. Gene network reconstruction via SCENIC70 identified transcription factor networks activated during pro-Treg to tTreg transition (Figure 5F).
The thymus also contains mature, highly activated Tregs, labeled as rrTregs, believed to have recirculated from the periphery.71,72 rrTregs lack expression of CCR7 or thymic egress markers (KLF2 and S1PR1) but express IL1R2 (Figure S5F), which sequesters the inflammatory cytokine IL-1β to reduce local concentrations.73 CODEX imaging identified tTregs and rrTregs dispersed throughout the medulla, with rrTregs primarily adjacent to CD68+ DCs (Figure 5G). CellChat supported the potential of rrTregs to sequester inflammatory cytokines through interactions with DC2/3 via an IL-1β-IL-1R2 axis (Figure S5G). rrTregs also exhibited a tissue resident Treg phenotype (BATFhigh CCR8+) associated with wound healing and tissue regeneration function,74 and expressed remodeling and tissue repair-related genes such as matrix metalloproteinase enzymes (MMP25 and ADAM19) (Figure S5H). Overall, these findings illustrate Treg diversity in the thymus with their developmental trajectories and functions yet to be elucidated.
Comparisons of male and female rrTregs showed that male rrTregs had higher expression of IL-4 and IL-13, heat shock factor protein 1 (HSF1), and IL-1 signaling pathways (Figure 5H), suggesting rrTreg-mediated regulation of IL-1R2-mediated anti-inflammatory feedback checkpoints is a more prominent mechanism in male tTreg development in early postnatal thymus. Notably, male-activated mTECs have higher expression of CD40 and tumor necrosis factor (TNF) inflammatory pathways than females, possibly resulting in higher rrTreg activity (Figure S5I).
Finally, as Tregs have been shown in mouse to contribute to thymic involution through JAG1,75 we explored sex-based differences in tTreg gene expression. GSEA showed male rrTregs and tTregs have higher expression of adipogenesis pathways (Figures 5H and 5I). Given the presence of cells undergoing EMT, our data underlie the aggressive timeline of thymic involution and suggest that sex-based differences in thymus functional decline begin early in life.
Our detailed examination of the medulla identifies several niches specialized for negative selection, cross presentation, and mTEC maturation around HCs and demonstrates sex biases in inflammatory pathways and thymic involution kinetics within these niches.
Discussion
We performed spatial multiomics to construct a tissue atlas of niches guiding T cell development in early human postnatal thymus. These datasets characterize how key developmental niches drive lineage branch decisions, identify a possible mechanism for conventional αβT cell development through self-selection, and suggest additional functions for mesenchymal cell types governing thymus biology. Furthermore, we discovered several sex-specific differences in thymus cell and niche biology. As T cell development is a dynamic migratory process, knowledge of cell position in combination with proteomic, transcriptomic, and epigenomic sequencing data provides an invaluable resource to predict niche-specific signaling cues directing T cell development, and mechanisms responsible for maintaining tissue structure and directing thymic involution.
We describe an approach to sequencing analysis using multidimensional imaging to establish benchmarks for the location, ligand expression, and composition of key niches in T cell development. This enables us to analyze cell-cell interactions guided by niche composition, identifying physiologically relevant ligand-receptor interactions based on cell proximity within the tissue. Ultimately, this approach maps epigenomic, transcriptomic, and proteomic data to distinct tissue niches at single-cell resolution. Furthermore, we included equal numbers of male and female age-matched thymus samples, enabling comparison between sexes across platform modalities. Our analysis of sex-matched human early postnatal thymus demonstrates the highly plastic nature of thymus lobule organization and resource dedication. Each niche responds to sex-biased developmental kinetics, supporting robust T cell development to ultimately produce functional immune systems in different manners (Figure 6). The findings herein describe only a subset of the data, and we encourage the community to capitalize on this resource to provide further insight into sex differences and targeted niche-specific inquiries.
Figure 6 The human early postnatal thymus lobule is spatially organized into sex-biased niches to support stage-specific T cell development
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In our analysis of Notch ligands, we complemented our in silico approach with in vitro analysis. Our analysis suggests that JAG1 at the CMJ cannot support T-lineage commitment as cells migrate toward the subcapsular zone but instead skew alternative lineage development toward a CD14− DC1 subset (Figure 6). CD14 expression on DCs is linked with increased inflammatory cytokine production,76 suggesting that JAG ligands promote non-inflammatory DC phenotypes. These results highlight the importance of precise Notch signaling strength and timing in the thymus and emphasize the need for strict spatial control of different Notch ligands within thymic niches. Our observation of high JAG1 expression in the medulla and decreased DLL4 expression on cTECs outside the subcapsular zone aligns with previous studies on human postnatal thymus.77
In the subcapsular zone, we characterize the important roles of specialized fibroblasts. DPP4+ capFibs, described in mouse as cells with progenitor and anti-fibrotic potential,78,79,80,81,82 are observed as a fibroblast subset responsive to changes in systemic hormone levels. Since thymic function and involution are regulated by sex hormone levels,57,83,84,85 DPP4+ capFibs likely control these processes and are potential targets for addressing age-related thymic involution.86 Previously, only medullary fibroblasts were linked to thymocyte development and selection in the medulla.82 We demonstrate that capFibs may directly support thymocyte development in the cortex by producing growth factors like IGF2 (Figure 6). Blocking IGF2 signaling arrests thymocytes at the double negative stage,87 and our data identify capFibs as the IGF2 source, suggesting capFibs as an additional cell source of cytokines and growth factors for in vitro developmental systems. Finally, we demonstrate that ECM profiles of thymic fibroblasts are tightly regulated based on spatial localization. Future work should characterize how tissue stiffness changes as thymocytes migrate through developmental thymic niches to improve biomaterial strategies for in vitro T cell development.88
Furthermore, we identify a population of ECM− cortical fibroblasts that are enriched in cell sensing pathways, such as TASRs and TRP channels. Interestingly, TASRs regulate cell responses to local soluble substances, such as glucose, modulating release of hormones and other signaling molecules.89 Similarly, TRP channels play roles in cell sensing, such as pheromone signaling, nociception, temperature sensation, and osmoregulation.90 Given the proximity of these cells to vasculature in the cortex, Fibs (P) may play a critical role as regulatory cells by sensing environmental changes and modulating thymus size (Figure 6). Their lack of ECM production and network-like structure resemble fibroblast reticular cells (FRCs) in the lymph node, which rapidly proliferate and remodel the cortex during infection.91 Our data are generated from early postnatal thymus samples, an age with active T cell development, suggesting these fibroblasts expand the thymic cortex similarly to FRCs during infection, signaling through FGF and IGF to stromal and epithelial cells to orchestrate remodeling.
While the dogma in thymocyte positive selection suggests that DPs downregulate class II RNA to prevent self-selection and force interactions with cTECs,58,59 several studies suggest that T-lineage cells can select off each other to support CD4 T cell development.20,92,93,94 Here, we describe an inner cortical niche where class II+ DPs reside that may support positive selection via DP-DP self-selection (Figure 6). We show that immature DPs cultured without epithelial cells upregulate HLA class II and continue to mature and receive positive selection signals. Additionally, upregulated SATB1 expression identifies mature DPs in an inner cortical niche and the CD4 branch of their progeny, suggesting it may determine early lineage specificity. Future work should investigate critical features of this niche and SATB1’s role in thymocyte development.
Within the medulla, we identified a niche adjacent to HCs specialized for negative selection and highlighted the role of rrTregs in modulating the medullary inflammatory environment (Figure 6). The abundance of HCs in human but not mouse, and their proximity to negative selection niches, suggests these structures evolved to provide niche-level organization within the larger human medulla or to regulate negative selection more stringently in longer-lived species.
Comparing male and female tissue showed sex differences in both T cell and thymus biology. Studies on post-pubertal males and females show that sex hormones differentially regulate thymic involution between sexes,26,27,28,29,30,52,57,84,86 and that androgen blockers increase FOXN1 expression, thymic involution, and increased rejuvenation.29,30,52,84,86 Additionally, older males produce fewer recent thymic emigrants and have smaller thymuses compared with females.26,28 Some studies describe decreased numbers of AIRE+ mTECs with age and in females,95 potentially predisposing females who maintain greater thymic function later in life to autoimmune disease.29 These studies also observe less interlobular fat in young female thymus,26 suggesting differences in thymic involution kinetics begin pre-puberty. However, current literature has not addressed transcript-level sex differences underlying functional differences in thymic and immune function. Our analysis uncovers that female thymic cells upregulate energy regulation, transcription, and antigen-presentation pathways, whereas male cells increase proinflammatory signaling, amino acid metabolism, and GPCR signaling. These cell metabolic differences align with transcript-level sex differences in other organs41,42,43 and highlight the need for sex-based cell culture optimization in in vitro T cell culture systems.
In addition to changes common to other organs,40,41 we identify thymus-specific differences affecting key processes in thymocyte development and training. Females have a larger proportion of cortical cells per lobule, aligning with lower thymic involution rates and a larger cortex/medulla ratio.26,27,52 ETPs have enriched interactions with JAG1 as they migrate away from the CMJ, suggesting increased JAG1 interactions could skew ETP lineage commitment toward less inflammatory DC phenotypes (Figure 6). In the female cortex, we observe increased cTEC and class II+ DP interactions and increased interactions between cortical DC and positive selection niches, suggesting thymocyte self-selection may play a larger role during positive selection (Figure 6). Conversely, the female medulla shows decreased inflammatory pathway activation and fewer medullary cells. These data suggest females prioritize generating a larger repertoire of DPs over deleting autoreactive cells through negative selection, potentially contributing to sex differences in autoimmune disease prevalence in females.96
In males, we observe enriched DLL4 interactions with ETPs, which aligns with previous data demonstrating that androgen levels positively correlate with DLL4 on cTECs.29 The male cortex shows increased interactions with mature CD3+ DPs and cTECs, suggesting male thymocytes may have lower proliferation rates post β-selection, allowing sufficient space for positive selection. In the medulla, male-activated mTECs exhibit increased inflammatory pathway markers, and male Tregs exhibit higher inflammatory modulation and activate thymic involution pathways.75 Upregulation of inflammatory modulation by male rrTregs may regulate the higher proinflammatory signaling in male cells (Figure 6). Interestingly, post-pubertal males have more Tregs and fewer CD4 T cells than females, possibly due to a more inflammatory medullary environment skewing CD4 development toward the Treg lineage.31
We further explore sex differences in thymus size control mechanisms. Among fibroblast populations, we find significant differences in expression of growth and angiogenesis factors, such as VEGFA and FGFs, potentially contributing to the size difference in male and female thymuses at this age (Figure 6). These data align with and extend known sex differences in growth factor expression, including sex-biased expression of growth hormone and IGF-1 in regulating size of different tissues.97,98 Importantly, these results indicate sex-specific differences in early thymus structure maintenance and growth, which could skew T cell development. We also establish an early transition toward an adipogenic environment in males. These observations align with findings in model organisms, where young male rats exhibit higher rates of thymic involution52 and early postnatal male primates have a larger interlobular fat area.26 Together, these factors define two possible mechanisms contributing to a male-female difference in thymus size and involution kinetics.
Future studies should test how sex differences at the transcript, niche, and organ level impact differential T cell production and quality as well as explore how sex differences in other organs contribute to known differences in immune responses. Defined in vitro and organoid culture systems replicating the thymic microenvironment present powerful platforms to test if the cell type-specific and sex-specific differences identified here lead to increased autoimmune disease incidence among females and increased infection susceptibility in males. Furthermore, given the surprising sex-based differences at this early postnatal stage, future work should examine aged thymus to investigate how cellular level differences in thymic involution kinetics may translate to larger impacts on our immune system later in life.
Limitations of the study
Our analysis of intra-sex variation is limited by access to patient samples as well as the inability to conduct mechanistic experiments in the context of a whole organism. There is an opportunity for future work to further validate and expand on predicted ligand-receptor interactions.
The thymic epithelium is responsible for the secretion of thymic peptides, which intervene in some steps of intra- and extrathymic T cell differentiation. Recent data suggest that thymic hormone secretion is modulated by the neuroendocrine network, comprising thyroid, adrenals, and gonads. However, the role of the pituitary gland in this regulation is still poorly understood. In the present paper we studied the in vivo and in vitro influences of PRL on the secretion of thymulin, one of the chemically defined thymic hormones, by thymic epithelial cells (TEC). When injected daily (20-100 micrograms/20 g) in young or old C57BL/6 mice, PRL induced a specific increase in thymulin synthesis and secretion, respectively, measured by the number of thymulin-producing cells in the thymus and the peripheral levels of the hormone. This stimulation was dose dependent and reversible after the end of treatment. Similar findings have been made in animals with pituitary dwarfism, known to have low levels of circulating thymulin. This stimulatory effect was also observed in primary cultures of human and mouse TEC when PRL (10(-7) to 10(-8) M) was applied to culture supernatants, thus suggesting that PRL could act directly on TEC. In addition, we induced in vivo experimental hypoprolactinemia, treating mice with bromocriptine, a dopamine receptor agonist that inhibits pituitary PRL secretion. Bromocriptine treatment (100-200 micrograms/20 g) yielded a significant decrease in thymulin secretion that could be reversed by coincident treatment with PRL. In the light of previous observations that bovine GH can also increase thymulin production in aged dogs, we performed a series of experiments in vitro to evaluate whether GH has a direct effect on TEC. We observed that only human GH preparations that are known to have a PRL-like effect were efficient in stimulating thymulin biosynthesis and release into the culture supernatants. The effects of PRL on TEC were not restricted to thymic hormone production. We observed that TEC proliferation, as well as the numbers of a TEC subset defined by the expression of cytokeratins 3 and 10, could also be increased by PRL treatment. All these findings show that the pituitary gland directly affects TEC in terms of cytoskeletal and secretory protein expression as well as cell cycle.. This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity..
pubmed.ncbi.nlm.nih.gov/2737149/
www.cell.com/developmental-cell/fulltext/S1534-5807(24)00539-2
Công nghệ giảm béo từng phần kết hợp Dermaheal và phương pháp Mesotherapy( tiêm dưới da) đã và đang được ứng dụng trị liệu tình trạng thừa, ứ đọng cellulite rất hiệu quả tại Âu châu, Nam Mỹ từ nhiều năm qua, và gần đây rất phổ biến tại Mỹ, được đánh giá là phương pháp hiệu quả nhất để giải quyết tình trạng cellulite, giúp cải thiện lưu dẫn tĩnh mạch, bạch huyết, giảm mỡ tích tụ cục bộ để làm bề mặt da láng mịn. Trong một số trường hợp, công nghệ này được sử dụng thay thế và cho kết quả tốt hơn hút mỡ với hiệu quả toàn diện:
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Ngoài cellulite (mỡ bề mặt – Surface Cellulite hoặc Hard Fat), công nghệ này cũng được ứng dụng làm tan mỡ tích tụ (Deep Fat hoặc Soft Fat), với một số thay đổi liều lượng và thời gian điều trị.
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#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
The PowerPlate’s Pro5 advanced vibration technology is the most innovative health, training and fitness tool in the industry today. Backed by over 40 years of research, vibration training gives NeuroXcel’s clients the ability to achieve a higher level of function, independence and the chance for recovery of lost abilities. The power plate produces a vibration that is transferred to the body. This mechanical stimulus produces a stretch reflex creating involuntary muscle contractions in parts of the body our clients might not be able to do on their own. By using the PowerPlate Pro5 as part of the C.A.S.T program, NeuroXcel clients will be able to workout individual body parts or an entire body workout depending upon each individual injury and/or disorder.
Vibration training on the Power Plate is used to substantially:
* Improve muscle strength and performance
* Increase flexibility and range of motion
* Enhance critical blood flow throughout the body (oxygenation and lymph drainage)
* Increase secretion of hormones that are important in regeneration and repair processes, such as HGH (Human Growth Hormone), IGF-1, and testosterone.
* Increase bone density
* Increase of serotonin and neurotrophine, a substance that supports our thinking process.
* Decrease cortisol levels
* Enhance explosive strength
* Enhance conventional training results
* Speed training recovery
* Accelerate weight loss
* Reduce lower back pain
* Enhance pain reduction
* Improve collagen production
* Reduce appearance of cellulite
* Eliminate the effects of stress
With age, your body’s capacity to produce mortal HyperGH 14x Growth Hormone( HGH) decreases, and it'll go through a tough time burning fat and gainingmuscle.However, you need redundant support and nutrition to negotiate your pretensions, If you're a spa freak and love to work out with those heavy dumbbells and weights to gain muscle and get that paper-thin skin.
Click Then to Get HyperGH 14x From Its Review website
Indeed if you aren't a spa nut and exercise at home, also, too, your body needs commodity redundant to achieve whatever body type you ask . This helping hand should be in the form of a supplement that boosts your HGH situations and provides you with violent energy so that you enjoy your exercises and at the same time, your body gives you further than what you anticipate it to do. Helping yourself with those steroids and injectables will only give you significant side goods and spoil your internal hormone balance after a while. To give you with professional results without any side- goods, the ideal product in the request is HyperGH 14x. It boosts your muscle- structure process naturally by enhancing the needed product of HGH in your body.
About Hypergh 14x Reviews
The supplement is fully natural and organic and is, by far, the most sophisticated growth hormone- releasing system for athletes and bodybuilders without any synthetic HGH injections or anabolics. The product is available without any croaker’s tradition and does n’t intrude with the process of being drug or injections, if you're consuming any. Each natural component used in the formula for HyperGH 14x is itself a precursor to natural HGH product in your body. It's the ideal supplement to help reveal that ripped body with violent energy throughout the process and indeed latterly and get relieve of those loose muscles. You no longer need to worry about the side goods of painful and precious steroids because the results then will be way more effective and natural, which means they wo n’t fade down. rather, your body will learn to retain them.
Ingredients
L-Arginine – It will increase your immunity, improves muscle healing, complements your sexual overall performance, or even has competencies to combat cancer. It additionally will increase the manufacturing of HGH with the aid of using nearly 3 times, even at an vintage age.
L-Tyrosine – It has houses to lessen fatigue and melancholy at some stage in exercises and may complement your metabolism and muscle increase.
L-Glutamine – This factor is an amino acid that facilitates take away all of the strain and keeps muscle increase thru wholesome mobileular division. It has different blessings like boosting your immunity, reducing your blood pressure, curing diabetes, coronary heart diseases, etc.
L-Glycine – This factor is a stimulator that will increase the garage of increase hormones for your pituitary gland. Additionally, it calms down your mind and guarantees the splendid fitness of your prostate.
L-Lysine – This factor is taken in mixture with arginine due to the fact whilst mixed, they enhance HGH increase and improves immunity and genital features with the aid of using ten times.
Tribulus Terrestris Extract – This plant is used for lots of years to enhance male virility and sexual drive. It complements your overall performance in mattress so you experience like an alpha male.
Astragalus Root Extract – This factor has splendid antioxidant traits and facilitates you together along with your strain and ache stages in order that your exercises enhance. It additionally blessings your immune system.
Deer Antler Velvet – Many scientists say that deer antler velvet guarantees premier athletic overall performance and improves the coronary heart’s pumping mechanism.
GABA – Gamma Aminobutyric-Acid (GABA) stimulates HGH manufacturing. The amino acid works as a neurotransmitter that facilitates the nerve impulses to move the gaps for higher communication. Overall, it improves the frightened system.
Colostrum – Its blessings consist of muscle healing, immunity-boosting, growing bone, and lean muscle mass, and reducing strain. It consists of IGF-1, that's used to degree HGH manufacturing for your frame and has anti-getting older traits so you don’t end up sluggish, and your muscle nice doesn’t deteriorate.
L-Valine – It is a branched-chain amino acid which could best be received from nutritional dietary supplements for the reason that frame doesn’t produce it. It is basically had to enhance muscle metabolism, increase, and restore of tissues, and create nitrogen stability withinside the frame.
Pituitary Powder – It facilitates the pituitary gland to supply greater HGH and will increase your muscle electricity with the aid of using shaping and firming it.
Phosphatidylcholine – This factor is an splendid emulsifier that improves the absorption of the vitamins found in HyperGH 14x. It is useful in fats breakdown and guarantees you don’t be afflicted by melancholy, liver problems, coronary heart diseases, neurological disorders, and reminiscence loss.
L-Ornithine – When mixed with the elements cited above, this factor will increase the increase of HGH for your pituitary gland thrice.
GTF Chromium – This factor facilitates decorate Glucose hobby for your frame. It controls insulin resistance, anxiety, reduced power stages, and boosts up the general increase so you get the exceptional out of the complement.
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Bodybuilding is about discipline. With the right mindset and can-do attitude you can gain muscle fast. But you may have to throw out some of the ideas you have heard over the years. Although some things may work better for some people that will not mean that they will work for every person. Some people are genetically predisposed to be big muscle- bound men. Some men are smaller and leaner. The muscle size you will gain will be as much about the work and discipline you put into is as it is about your DNA.
The good news is that your DNA won’t prevent you from gaining as much muscle as YOU can gain. Whether that means huge and bulky or long and lean you can still gain muscle for all your efforts. Here come some tips on how to gain muscle fast for your knowledge.
How to gain Muscle Fast with 7 Step ?
1. Have a clear mindset
You need to have clear goals for what you want to accomplish and how you intend to achieve them. When do you want to see noticeable results? When do you expect to have the body of your dreams? How do you intend to do it?
Gym
Home workouts
Workout videos
Equipment you plan to use
How often do you intend to work out and how long will your sessions be? What is your meal plan? How will you improve your general health?
Diet
Supplements
Proper rest
Mental health
A clearly defined plan including the what, when, where and how will help you have a clear mindset. Research the methods you want to use and write down your plan in a journal and use the journal to note your progress.
2. Prepare for possible let injuries
The key factor for gaining muscle size is the amount of weight you lift in your workouts. You should lift the heaviest weight you can safely do to total failure. That means you cannot lift again no matter how hard you try. Unfortunately, sometimes this can cause an injury that can be viewed as set back. Try some of the methods to avoid that:
Gradually build up your routine
In the beginning, only lift about 5 to 10 pounds heavier than you normally can.
Start with 1 set of 8 to 12 reps, and increase to 3 sets before adding more weight, then start again with 1 set of 8 to 12 reps.
Talk to your doctor or trainer before getting back to normal routine.
Your body is your main hardware. Take care of it the same way you care for your weights and other equipment.
3. Your diet is king
You must maintain a healthy intake of food to gain the size and muscle you desire. Contrary to diets that reduce calories to lose weight, you need to increase your calories to give your muscles the calories they need.
Eat whole foots in their natural state rather than packaged food
You need more lean protein to build muscle.
You will need to eat more frequently during the day; up to 6 to 8 times a day.
4. Supplements are actually a good idea
We often see that supplements for losing weight may be rip offs or dangerous. It is good to know then that certain supplements are safe for bodybuilding and even avidly recommended by trainers:
Creatine will help you achieve bulk fast. Not only will you gain size, but you may notice that your lifting capacity increases too. WIN! The powder form is the best choice because you can mix it with fruit juices for the additional natural sugars that help increase creatine uptake in muscles.
Products contain IGF-1 offer a critical ingredient of factor for building muscles and increasing size.
5. Mix up your training routine to prevent plateaus and boredom.
If you aren’t interested in what you do at the gym you will not train as often as you need to in order to gain muscle fast, so change things up from time to time. Alternate gym workouts:
Train at home with no equipment at all. Instead do burpees, push-ups and chin ups. The idea is to use multiple muscle factored into the exercise.
Workout with DVDs that you trust and know well. Some routines are for weight loss more than muscle gain so choose carefully.
Perform cardio on alternate days that still work the muscles: jogging, pole walking, hiking.
6. Reduce stress in your life
Stress can cause hormonal imbalances that will cause results that are counter to your goals. If you feel that you are becoming stressed out, take a breather and find a way to relax. Contrary to popular ideas that workouts relieve stress it can actually cause you to work out less carefully and cause injury.
7. Water is all powerful
If you do not drink at least 8-8 oz. glasses of water a day your muscles will not gain size. Water is essential to good muscle health ( 1 ). So, remembering to drink water regularly during the day is also a must, not only for your muscle building but also for your good health.
By now, you should have taken note on some powerful tips and tricks for how to gain muscle fast and you may have a plan in mind to implement these ideas. One of the tips above is about diet and that one tip is very powerful to help you gain muscle naturally and more healthy. Should you need to learn more about this topic, Anabolic Cooking is a program that will show you everything about nutrition for muscle building.
Read more with us: http://ift.tt/2qcPxTB
The post 7 Tips On How To Gain Muscle Fast appeared first on Covington Country.
#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
Info pemesanan dan konsultasi, silahkan hubungi :
CS Nia
WA 0857 2656 3429
Pin BB : 5D6A2D9C
Line : cantikputihalami
Instagram : cantikputihalami16
Isi kemasan MRS body kuning10%: 5ml x 10 vial/pack
Komposisi MRS body kuning 10%:
Plateled Derived Growth Factor(PDGF) 1 mg/L
Insulin-like Growth Factor(IGF-1) 1 mg/L
Phosphatidylcholine 50 g/L
L-Carnitine(Vit.B ) 10 g/L
Triamcinolone 0,5 g/L
Sodium Hyaluronate 0,5 g/L
Multi Vitamin 0,5 g/L
Manfaat MRS body kuning 10%:
Menghilangkan lemak berlebih di titik yang disuntikkan
Meningkatkan elastisitas kulit di titik suntik dengan meningkatkan kolagen dan elastin
Dosis dan cara pemakaian: Tambahkan 1 ampul procaine caffeine dan suntikkan MRS body secara microsubcutan, 1x seminggu
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ReCharge prolonga o efeito “pump” muscular, mantendo a vascularização mais ativa por um tempo muito maior. Isto faz com que os níveis de oxigênio e nutrientes no organismo permaneçam no máximo para sua absorção pelas fibras musculares.
Com ReCharge você perceberá a diferença no seu corpo, com relação a força, tamanho e recuperação pós treino, logo nos primeiros dias de uso.
Creatina Quelada: Suplemento natural utilizado no mundo todo por pessoas que precisam ganhar força e massa, é um construtor muscular e excelente fonte de energia, além de regenerador ATP muscular, resultado em expressivo ganho de força e desempenho físico geral.
Arginina Quelada: Aminoácido necessário para síntese da creatina, sendo importantíssimo também nos processos de cicatrização, na eliminação da amônia pelo organismo e na vasodilatação, melhorando a circulação sanguínea e a nutrição celular.
Humanofort: Peptídeos de matriz embrionária do ovo, auxilia o corpo na produção de testosterona e dos fatores de crescimento IGF-1 e IGF-2, reduzindo o catabolismo e controlando os níveis de insulina e de cortisol.
Auxilia no ganho de força, massa muscular e energia
Vaso dilatação, síntese da creatina e maior nutrição celular
Aumenta a produção natural dos fatores de crescimento
Peça pela Tele-Entrega 55 3026 0912 - 9188 3132
NutriStore Sta Maria | E-mail/msn: contato@nutrirs.com
Market Reports on Saudi Arabia Provides the Trending Market Research Report on “2022-2026 Saudi Arabia Immunodiagnostics Market Database-Supplier Shares, Volume and Sales Segment Forecasts for 100 Abused Drugs, Cancer, Clinical Chemistry, Endocrine, Immunoprotein and TDM Tests”under Life Sciences Market Research Reports category. The Immunodiagnostics Market Database in Saudi Arabia is projected to exhibit highest growth rate over report offers a collection of superior market research, market analysis, and competitive intelligence and industry reports.
Saudi Arabia Immunodiagnostics Market Database provides the 2020 supplier shares, the 2020-2025 volume and sales forecasts for 100 clinical chemistry, TDM, endocrine, cancer, immunoprotein and abused drug assays, as well as comprehensive lists of companies developing or marketing new technologies and products by test, including:
Clinical Chemistry
Albumin, Alkaline Phosphatase, ALT/SGPT, Ammonia, Amylase, Apolipoprotein A-1, Apolipoprotein B, AST/SGOT, Beta-Hydroxybutyrate, Bilirubin (Direct), Bilirubin (Total), BNP, BUN (Blood Urea Nitrogen), Calcitonin, Calcium, Carbon Dioxide/Bicarbonate, Cardio hs CRP, Chloride, Cholesterol, Cholinesterase, Creatine Kinase (CK), CK-MB, Creatinine, CRP, Cystatin C, Ferritin, Fructosamine, GGT, Glucose, HDL Cholesterol, Homocysteine, hs-CRP, Insulin, Iron, Iron (Total Binding Capacity), Iron (Unsaturated Binding Capacity), LDH, LDL Cholesterol, LDL Cholesterol Direct, Lipase, Lipoprotein a, Magnesium, Microalbumin, Myoglobin, NT-proBNP, Phosphorus, Potassium, Sodium, ST2, Total Protein, Transferrin, Triglycerides, Troponin, Uric Acid
Therapeutic Drug Monitoring (TDM)
Amikacin, Apixaban, Argatroban, Betrixaban, Carbamazepine, Cyclosporin, Dabigatran, Digoxin, Edoxaban, Everolimus, Fluindione, Gentamicin, Levetiracetam, Lithium, Methotrexate, NAPA/Procainamide, Phenobarbital, Phenytoin, Quinidine, Rivaroxaban, Sirolimus, Tacrolimus, Theophylline, Tobramycin, Topirimate, Valproic Acid, Vancomycin, Warfarin
Endocrine Function
Cortisol, Estradiol, FSH, HCG, Gastrin, Growth Hormone/IGF-1, LH, Progesterone, PTH/IO PTH, Prolactin, T3, T3 Free, T3 Uptake, T4, T4 Free, TBG, Testosterone, Thyroglobulin Ab, TPO Ab, TSH
Tumor Markers and Special Chemistry
AFP, CA 15-3/27-29, CA 19-9, CEA, Ferritin, Follate (Folic Acid), Glycosylated Hemoglobin, HCG, 25-Hydroxy Vitamin D2 and D3, Occult Blood, PAP, PSA, Thyroglobulin, Vitamin B-12
Immunoproteins
C3, C4, Free Light Chains, Haptoglobin, IgA, IgE Specific, IgE Total, IgG, IgM, Immunofixation, Prealbumin, Protein Electrophoresis
Drugs of Abuse
Amphetamines, Barbiturates, Benzodiazepines, Cannabinoids/Marijuana, Cocaine, LSD, Methadone, Methaqualone, Opiates, Phencyclidine (PCP), Propoxyphene, Tricyclic Antidepressants
Browse our full report with Table of Contents:
marketreportsonsaudiarabia.com/report/762089/-saudi-arabi...
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Market Reports on Saudi Arabia provides you with an in-depth industry reports focusing on various economic, political and operational risk environment, complemented by detailed sector analysis. We have an exhaustive coverage on variety of industries – ranging from energy and chemicals to transportation, communications, constructions and mining to Food and Beverage and education. Our collection includes over 3000 up-to-date reports all researched, analysed and published by top-notch international research firms.
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#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
The benefits of using the massager are
1) Improves muscles strength and performance.
2) Increase flexibility and range of motion.
3) Enhance critical blood flow throughout the body.
4) Increase secretion of hormones that are important in regeneration and repair process, such as HGH (Human Growth Hormone) IGF-1 and testosterone.
5) Increase bone density.
6) Increase happiness hormone serotonin & neurotrophine, as substance that supports our thinking process.
7) Decrease cortisol level.
8) Rehabilitation injuries and ailments.
9) Enhance explosive strengths.
At Nutronics Labs, our health supplements are safe and effective for anyone to use! Whether you have a casual workout routine or you’re a serious athlete dedicated to a life of fitness, Nutronics Labs has the right health #deerantlervelvetsupplement that can help you take things to the next level. Despite the widespread use of supplements containing #Igf-1, we remain the only manufacturer of #deerantlervelvetspray to date that has had clinical trials done on their own products. Call at (866) 688-9490 for more information about #deerantlervelvetstudies or visit our website.
Nutronics Labs
2600 South 25th Avenue Suite T, Broadview, IL 60155, USA
(866) 688-9490
Official Website:- www.nutronicslabs.com/
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Animal M Stack is a powerful and new natural anabolic training pak whose time has come. Thanks to Universal Nutrition's research and development efforts and recent discoveries, Animal Methoxy Stak was born. Animal M Stak mimics the effects of anabolic pharmaceuticals by dramatically enhancing protein synthesis, nitrogen retention (positive nitrogen balance), and nutrition-partitioning, while simultaneously reducing muscle wasting? How?
Animal M Stak can help potentiate your body's production of all five anabolic hormones:
1. Testosterone
2. Human Growth Hormone (HGH)
3. Insulin-Like Growth Factor 1 (IGF-1)
4. Luteinizing Hormone (LH)
5. Insulin. Best of all, Animal M Stak can do this without the androgenic side-effects associated with prohormone use or even over-stressing the liver. But Animal M Stak is more than just an anabolic primer. It can help your body block the conversion of testosterone to estrogen and dihydrotestosterone (DHT)
Other Supplement Benefits
• Support your liver.
• Increase energy for unreal performance.
• Provide key vitamin and mineral support for your growing muscles. If you want to be an Animal, you've got to train like one. Now, you can without all the prohormones or ephedra.
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Name: Disha Prabhu
Degree: PhD
Academic Program: Pharmaceutical Sciences (Pharmacology)
Dissertation Title: IGF-1 regulation of Astrocytic Structure, Function and Cognition.
Testo Drive 365 is a champion among the most used portions in working out for its suitability in extending muscle mass. It is a hormone that braces cell advancement and multiplication, it moreover enlivens the IGF-1 improvement factor and has anabolic effects, it is in like manner used as a foe of developing hormone. As it is convincing, it furthermore has its weaknesses, fundamental threatening effects that I share in this article so you perceive what you enter your body before endeavoring it.
It can require a long investment of honing and eating right, if not years to get your ideal body without the guide of upgrades. These would super have the capacity to charge your activities and give you the tore body you need! After the age of 30 various men encounter trouble shedding the fat and building fit mass. This is a result of a nonappearance of testosterone, which is the thing that Testo Drive 365 will help! Crane your testosterone levels regularly and see staggering change in the activity focus. Demand your peril free primer package today through this confined time offer!
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Info pemesanan dan konsultasi, silahkan hubungi :
CS Nia
WA 0857 2656 3429
Pin BB : 5D6A2D9C
Line : cantikputihalami
Instagram : cantikputihalami16
merupakan koktail perawatan lengkap untuk mengatasi masalah lemak berlebih di tubuh. MRS body baik digunakan untuk fungsi lipolisis (penghancuran lemak di titik disuntikkan) yang umumnya dipakai untuk menghilangkan lapisan lemak berlebih pada perut, paha, dan lengan.
Kandungan tiap vial MRS body 5%:
Plateled Derived Growth Factor(PDGF) 1 mg/L
Insulin-like Growth Factor(IGF-1) 1 mg/L
Phosphatidylcholine 50 g/L
L-Carnitine(Vit.B ) 10 g/L
Triamcinolone 0,5 g/L
Sodium Hyaluronate 0,5 g/L
Multi Vitamin 0,5 g/L
Manfaat MRS body 5%:
1. Menghilangkan lemak berlebih di titik yang disuntikkan
2. Meningkatkan elastisitas kulit di titik suntik dengan meningkatkan kolagen dan elastin
3. Dosis dan cara pemakaian: Tambahkan 1 ampul procaine caffeine dan suntikkan MRS body 5% secara microsubcutan, 1x seminggu
Isi kemasan MRS body 5%: 5ml x 10 vial/pack
Informasi Tambahan :
Metode Pemakaian Micro Sub Cutan
Frekuensi Seminggu 1x
MRS body Mesologica Slimming Injection yang asli bisa di dapatkan di online shop kami dengan harga resmi dari suplayer. di jamin 100% orginal, jaminan uang kembali jika terbukti produk kami palsu.
USN Ultimate Sports Nutrition.
Pure Protein de USN es una mezcla exacta de proteína de suero de leche aislada, proteína de suero de leche aislada, caseinato de calcio, albúmina de huevo y proteínas de soja aislada.
Las proteínas estructurales son el núcleo del cuerpo humano y tienen una función específica en cada una de las células. La proteína realiza muchas funciones esenciales en el cuerpo. Se requiere para el crecimiento y la reparación de los tejidos y ayuda en el transporte de nutrientes, oxígeno y nitrógeno.
Info pemesanan dan konsultasi, silahkan hubungi :
CS Nia
Pin BB : 5D6A2D9C
WA 0857 2656 3429
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Nexgen Prowhite ( Citrex -900)
with CoQ10 & EFG
From : korea
Isi : 15amp + 15vial
Komposisi :
* 15 amp @ 5ml
Vitamin C 500mg
Collagen Extract 1000mg
L-Aspartis Acid. 60mg
Co Enzyme Q10 900mg
Pure Hydrolysed Collagen Extract
450mg
* 15 vials
Setrida L-Glutatione 18000mg
Alpha lipoic acid 600mg
L-ornithine Monohydrochloride
180mg
Cystein. 0.6mg
Copper peptide 150mg
Resilen-200 (hyalironic acid).
600mg
Alpha-Tocopherol (vit E). 360mg
L-arginie. 360mg
Myosin 2.70mg
Kinesin. 300mcg
Kandungan lain :
EGF, IGF-1, TRX, Acety Hexapeptide, BFGF, TG-F & Nucleic Acid Elements
Kegunaan :
1. mengatasi pigmentasi wajah, dekomposisi melanin hitam atau kuning, presisi wara kuliyt dengan pemulihan whitening efek yang jelas bedanya.
2. memperbaiki kulit kusam atau sifat parsial kusam kulit yang membandel.
3. menghilangkan bekas luka, bekas jerawat, bekas gatal serta bekas gigitan nyamuk.
4. antioksidant bagi tubuh dan kulit.
5. menyehatkan kerja hati, ginjal dan otak dalam darah.
6. memutihkan kulit wajah dan tubuh serta memberikan efek bercahaya bagi kulit.
7. Melembabkan kulit dan mencegah timbulnya kerutan
Dosis :
Inject 1-2x seminggu (1vial +1amp)
Nutronics Labs was the very first company to turn deer antler extract into a liposome spray over 25 years ago. Since then, many competitors have entered the marketplace touting various claims that are misleading and completely untrue. Don’t be fooled by these other brands selling inferior products. Despite the widespread use of supplements containing IGF-1, we remain the only manufacturer of best deer antler spray to date that has had clinical trials done on their own products.
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Nutronics Labs
2600 South 25th Avenue Suite T, Broadview, IL 60155, USA
(866) 688-9490
Official Website:- www.nutronicslabs.com/
Other Service We Provide:-
Best Supplements For Muscle Growth
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Antler Deer Spray
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O hGH tem atraído a atenção de muitos atletas amadores e profissionais, bem como de fisiculturistas pelo aumento da performance e crescimento muscular. Seus efeitos anabólicos/anti-catabólicos incluem o aumento da retenção de nitrogênio, aumento da síntese de proteína, e redução do catabolismo da proteína. O hGH pode promover a perda de gordura através da lipólise e pela troca da produção de energia por utilização de gordura.
Atletas e fisiculturistas vem utilizando suplementos precursores do hGH (Human Growth Hormone), especialmente aqueles que atingiram um nível de estagnação em ganhos e resultados nos treinos. Essa fase é conhecida como "plateau" e ocorre quando os ganhos deixam de ser proporcionais à quantidade de tempo e dedicação dispensados aos treinamentos.
Estudos sugerem que um aporte otimizado de aminoácidos obtidos por meio de fontes protéicas aumenta o nível plasmático de GH de forma natural no organismo. Pesquisadores concluíram que alguns deles intensificam a liberação de hGH nos exercícios (1).
Estudos indicam que os exercícios, especialmente o treinamento de força, também aumenta a concentração sérica de GH. A atividade física estimula a secreção do hormônio de crescimento (GH) que tem efeito anabólico direto ou indireto, via fator de crescimento semelhante à insulina 1 (IGF-1) (2).
GH Tropin:
GH Tropin é uma fórmula precursora natural e estimuladora do "growth factor". GH Tropin contém uma combinação poderosa e única de ingredientes ativos que atuam em sinergia, promovendo resultados rápidos, sólidos e duradouros. A fórmula avançada de GH Tropin foi cientificamente elaborada para trazer um novo nível de eficácia. GH Tropin não contém substâncias controladas ou de uso restrito, podendo ser usado por fisiculturistas e atletas de qualquer modalidade. Os benefícios podem ser maximizados através de treinamentos intensos com sobrecarga, boa nutrição e descanso apropriado.
Bodygenics - Maximum Results:
GH Tropin é fabricado de acordo com os mais rígidos controles de qualidade internacionais, para que você possa obter o máximo em resultados. GH Tropin possui ingredientes selecionados, assegurando um alto grau de pureza e eficácia.
Referências Bibliográficas:
1. Isley WL, Underwood LE, Clemmon DR. Dietary components that regulate serum somatomedin-C concentrations in human. J Clin Invest 1983;71:175-82.
2. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 2002;18:657-61.
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ZMA é a abreviação para Aspartato de Monometionina de Zinco. Estudos recentes revelaram que a suplementação de quantidades específicas de Zinco e Magnésio pode elevar os níveis de testosterona em até 30%. É uma fórmula toda mineral para o aumento da força e resistência muscular.
É usado também para incrementar a libido em mulheres e homens.
Aumento do Fator de Crescimento Insulínico (IGF-1) Concentração Máxima de Anabólicos Naturais Recuperação e desenvolvimento dos tecidos musculares Anabolismo e força muscular Ganho de massa muscular magra
Fórmula ZMA patenteada
Aumenta os níveis de Testosterona
Incrementa a libido em homens e mulheres
Aumento do Fator de Crescimento Insulínico (IGF-1)
Máxima concentração anabólica
Anabolismo e força muscular
Com Vitamina B6
Venha conhecer todo MiX X-Pharma na NutriStore Sta Maria!!
NutriStore Sta Maria | 55 3026-0912 | e-mail/msn: contato@nutrirs.com
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Silberhorn Sportsvel Velvet antler capsules are superior quality natural velvet antler supplement made from whole stick New Zealand Velvet antler which is used by 100,000's of men and women all over the world to support joint health and mobility, for today's active life styles please visit us at www.silberhorn.co.nz and keep in touch so remember to restore and maintain with Silberhorn Sportsvel.
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#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan
#JINTROPIN #KIGTROPIN #IGTROPIN #HYGETROPIN #TAITROPIN #GETROPIN #IGF-1 #IGF-1LR3 #HGH #IGTROOIN #Ansomone #Riptropin #HCG #EPO #Botox #PEG MGF #HGH Frag 176-191 #Ghrp-6 #Ghrp-2 #CJC-1295 (Without DAC)#MT-2 #TB-500 #PT-141(Bremelanotide)#DSIP(Delta Sleep Inducing Peptide)#Follistatin #Ipamorelin #Anadrol #Stanozolol #Dianabol #Provirom #T3 #Clenbuterol #Viagra#Depot Cyp 250 #Prop 100 #Tren 100 #Bold 200 #Winstrol #Deca-durabolin #Sustanon 250 #TE 250 #Masteron #Primobolan