Liver fibrosis, a major characteristic of chronic liver disease, is inappropriate tissue remodeling caused by prolonged parenchymal cell injury and inflammation. During liver injury, hepatic stellate cells (HSCs) undergo transdifferentiation from quiescent HSCs into activated HSCs, which promote the deposition of extracellular matrix proteins, leading to liver fibrosis. Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is the most abundant member of the highly conserved β-thymosin family and controls cell morphogenesis and motility by regulating the dynamics of the actin cytoskeleton. Tβ4 is known to be involved in various cellular responses, including antiinflammation, wound healing, angiogenesis, and cancer progression. Emerging evidence suggests that Tβ4 is expressed in the liver; however, its biological roles are poorly understood. Herein, we introduce liver fibrogenesis and recent findings regarding the function of Tβ4 in various tissues and discuss the potential role of Tβ4 in liver fibrosis with a special focus on the effects of exogenous and endogenous Tβ4. Recent studies have revealed that activated HSCs express Tβ4 in vivo and in vitro. Treatment with the exogenous Tβ4 peptide inhibits the proliferation and migration of activated HSCs and reduces liver fibrosis, indicating it has an antifibrotic action. Meanwhile, the endogenously expressed Tβ4 in activated HSCs is shown to promote HSCs activation. Although the role of Tβ4 has not been elucidated, it is apparent that Tβ4 is associated with HSC activation. Therefore, understanding the potential roles and regulatory mechanisms of Tβ4 in liver fibrosis may provide a novel treatment for patients.
Friedman, J., Roze, E., Abdenur, J. E., Chang, R., Gasperini, S., Saletti, V., Wali, G. M., Eiroa, H., Neville, B., Felice, A., Parascandalo, R., Zafeiriou, D. I., Arrabal-Fernandez, L., Dill, P., Eichler, F. S., Echenne, B., Gutierrez-Solana, L. G., Hoffmann, G. F., Hyland, K., Kusmierska, K., Tijssen, M. A., Lutz, T., Mazzuca, M., Penzien, J., Poll-The BT, Sykut-Cegielska, J., Szymanska, K., Thony, B., and Blau, N. Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Ann Neurol. 2012;71:520-530. View abstract.

Melanotan 2 works by stimulating the release of the pigment melanin from the skin. Less UV exposure is necessary with Melanotan 2 compared to “normal tanning”, and the tan that occurs with tanning injections is deeper and longer lasting than an individual’s “normal tan”. Melanotan works best (has the most noticeable effects) on people with fair skin tones.


Some differences in cardiac anatomy exist between mammals and teleosts. The zebrafish ventricle has a thin wall of compact muscle surrounding a much larger compartment of myofibers organized into elaborate trabeculae. It is intriguing that this structure is very similar to that of the embryonic mammalian ventricle prior to its septation and fusion of trabeculer myofibers into a thick, vascularized wall (Sedmera et al., 2000). That the mammalian heart has a more differentiated, contractile anatomy is apparent not only in gross cardiac structure, but also in cellular features. Teleost cardiomyocytes are 2–10 times smaller, mononucleated, have a greatly-reduced sarcoplasmic reticulum and lack the T-tubule system found in skeletal muscle and mammalian cardiac muscle (Farrell, 1992). One might speculate that the teleost heart is better designed for growth and regeneration, while the mammalian heart is better designed for sheer contractile force. Nevertheless, none of the mentioned differences between lower and higher vertebrate hearts preclude the idea that the mammalian heart could be stimulated to regenerate, especially if that regeneration is due to mobilization of a progenitor cell population.
It is highly important to understand that MT2 itself does not protect skin from burning, tan protects your skin. Until some base tan is developed users should still take care not to over-expose skin to uv rays. Starting only with the amount of exposure that the user's skin can handle without burning. It should not take long before the user can handle longer exposures to strong sunlight without adverse effects.
The structure of oxytocin is very similar to that of vasopressin. Both are nonapeptides with a single disulfide bridge, differing only by two substitutions in the amino acid sequence (differences from oxytocin bolded for clarity): Cys – Tyr – Phe – Gln – Asn – Cys – Pro – Arg – Gly – NH2.[116] A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin article. Oxytocin and vasopressin were isolated and their total synthesis reported in 1954,[122] work for which Vincent du Vigneaud was awarded the 1955 Nobel Prize in Chemistry with the citation: "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone."[123]
How does MT-1 compare to MT-2? In terms of darkening the pigmentation of skin to enhance and individuals tan, both types have been proven to work in a number of clinical trials. However, the side effects using MT-2 are more common, but offsetting this is the fact that the darkening effect using MT-2 can be seen faster. It's important to note that the dosages for Melanotan-1and Melanotan-2 are different. For example, a sometimes recommended beginning dose of MT1 is 1mg, while a beginning dose of MT2 is often only 0.25mg.

Serotonin appears to be associated with panic attacks. Although studies that have used tryptophan depletion techniques in humans do not necessarily induce a panic attack[34][35][36] it appears it may sensitize the body by an increase in neurovegetative panic symptoms and increased anxiety[37] which suggests that serotonin is protective against panic attacks, at least acutely.[38][39] A study in 24 unmedicated panic disorder patients and normal participants given 200mg 5-HTP prior to a 35% CO2 test (used to induce a panic attack-like response) noted that the test was able to induce panic attack in both panic disorder patients and normal persons and that 200mg 5-HTP was protective in both conditions but to a greater degree in persons suffering from panic disorders.[40] This has been replicated with cholecystokinin-4 induced panic attack with 200mg 5-HTP in otherwise healthy persons.[41]
The N-terminal half of β-thymosins bears a strong similarity in amino acid sequence to a very widely distributed sequence module, the WH2 module. (Wasp Homology Domain 2 - the name is derived from Wiskott-Aldrich syndrome protein).[11][12] Evidence from X-ray crystallography shows that this part of β-thymosins binds to actin in a near-identical manner to that of WH2 modules, both adopting as they bind, a conformation which has been referred to as the β-thymosin/WH2 fold. β-thymosins may therefore have evolved by addition of novel C-terminal sequence to an ancestral WH2 module.[13] However, sequence similarity searches designed to identify present-day WH2 domains[14] fail to recognise β-thymosins, (and vice versa) and the sequence and functional similarities may result from convergent evolution.[15]
I’ve used powdered 5-HTP a couple times now, it doesn’t taste great and it’s resulted in an unpleasant stomach upset that lasted 45–60 minutes. For that reason I’ll likely not continue to use it. I did not find it’s effect on mood remarkable enough that I would want to put up with the stomach upset. My go to Nootropics for mood are Rhodiola and Phenibut and my go to Biohacks for mood are meditation and no fap, I don’t feel the need to use a whole lot more mood promoting strategies.
Wow I wonder if it will help those of us with Ehlers Danlos Syndrome – a collagen disorder that causes ligament laxity and makes those with it prone to easy subluxations and early onset arthritis. I have so many injuries from my daily life due to this disorder. I know this won’t fix my faulty collagen since that is encoded in my genes but perhaps it would help with the symptoms – a bunch of torn ligaments and worn out joints. Thanks for sharing!
Letdown reflex. In lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be ‘let down’ into a collecting chamber, from where it can be extracted by compressing the areola and sucking at the nipple. Sucking by the infant at the nipple is relayed by spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland.
It is highly important to understand that MT2 itself does not protect skin from burning, tan protects your skin. Until some base tan is developed users should still take care not to over-expose skin to uv rays. Starting only with the amount of exposure that the user's skin can handle without burning. It should not take long before the user can handle longer exposures to strong sunlight without adverse effects.
It bears understanding that this type of peptide is not a treatment or cure for anything, nor should it be considered a preventative measure to skin cancer. While this tanning peptide is known to protect the skin through the natural tanning process, it is not in and of itself a foolproof UV shield, however it is an excellent way for those who don't tan otherwise to get rich golden tans without as much exposure to the sun.
A Risk Quiz; Let’s say you are one of the volunteers to whom researchers gave $100, and this option: you can either keep the money, or give it to an anonymous trustee who will either invest it and double it to $200 and return half of the extra hundred bucks to you–$50–or keep all the money for herself. So you can either increase your money by 50%, or lose it all. What would you do? Would you trust that anonymous trustee? (Remember Loss Aversion from Chapter Two, where in a similar experiment most people decided to avoid the gamble and take the sure cash.)
In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells of the supraoptic and paraventricular nuclei, and is stored in Herring bodies at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe (neurohypophysis) of the pituitary gland. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate neurons in the nucleus accumbens, a brain structure where oxytocin receptors are expressed.[31] The endocrine effects of hormonal oxytocin and the cognitive or behavioral effects of oxytocin neuropeptides are thought to be coordinated through its common release through these collaterals.[31] Oxytocin is also produced by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.[32] Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the amygdala and bed nucleus of the stria terminalis.
In another study, published in PNAS in 2010, men were given a dose of oxytocin and asked to write about their mothers. Those with secure relationships described their moms as more caring after the hormone dose. Those with troubled relationships actually saw their mothers as less caring. The hormone may help with the formation of social memories, according to the study researchers, so a whiff strengthens previous associations, whether good or bad.
The full-length Tβ4 polypeptide has been shown to be effective in reducing inflammation [44]. It is also reported that only the 4-AA, amino-terminal peptide of Tβ4, known as Ac-SDKP, can block inflammation [45]. In this study, we used a synthetically human peptide produced copy of a naturally occurring, highly conserved 43-amino acid (MW = 4964 Da) water soluble acidic peptide, originally isolated from bovine thymus tissue [46]. This peptide is produced by Fmoc solid-phase peptide synthesis in accordance with the current Good Manufacturing Practice (cGMP) regulations (21 CFR 210 and 211) of the FDA [47]. An effective healer, Tβ4 can be administered topically on the surface of cells and systemically, through injection [9–11]. In this study, Tβ4 activation by Tβ4 peptide inhibited H2O2-induced production of NO and PGE2, expression of COX-2 and iNOS, and mRNA expression of TNF- α, IL-1β, -6, -8, and -17 in cultured PDLCs. These findings suggested that Tβ4 activation possessed anti-inflammatory activity in PDLCs. These results were consistent with previous in vivo and in vitro studies [9–15]. MAPK is a proline-directed serine/threonine kinase consisting of three-enzyme modules; its targets, inducing ERK, JNK and p38 kinases, are important in cellular signal transduction pathways and exert an anti-inflammatory response [48, 49]. NF-κB is a major transcription factor involved in the release of proteins that mediate the inflammatory response, and the degradation and phosphorylation of Iκ-Bα are necessary to release NF-κB from the cytoplasmic NF-κB/Iκ-Bα complex and allow its subsequent translocation to the nucleus of the cell [50]. In this study, Tβ4 peptide down-regulated the H2O2-triggered activation of the ERK and JNK MAPKs and the NF-κB in PDLCs. These results suggested that the ERK and JNK MAPKs and the NF-κB pathway may be involved in the anti-inflammatory effects of Tβ4 activation in PDLCs. Consistent with our findings, Tβ4 treatment decreased TNF-α-induced NF-κB activation in human corneal epithelial cells [51].
Although research has shown that good communication predicts relationship success, successful communication in couples therapy won’t ensure that partners stay together. The goal is to help the two people understand each other’s point of view and come to a mutual decision, even if it’s to break up. “If people are not connected at all, then oxytocin is not going to force that connection,” Guastella says.
Chae, H. S., Kang, O. H., Choi, J. G., Oh, Y. C., Lee, Y. S., Jang, H. J., Kim, J. H., Park, H., Jung, K. Y., Sohn, D. H., and Kwon, D. Y. 5-hydroxytryptophan acts on the mitogen-activated protein kinase extracellular-signal regulated protein kinase pathway to modulate cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 cells. Biol Pharm Bull 2009;32(4):553-557. View abstract.
Few forms of trust are more basic than that between a newborn and its mother. Scientists have discovered that this relationship is strengthened by the hormone oxytocin, released when the baby stares up at mom while breast feeding. Staring lovingly at your boyfriend or girlfriend can trigger their release of oxytocin too, as can warm physical contact like touching and hugging. (Levels increase during sex and peak at orgasm, which may help explain the age-old question “But will you love me in the morning, when your oxytocin levels have dropped?”) Oxytocin reduces stress in arguing couples, helps us recognize faces, even helps us look at a face (in fact, just a pair of eyes) and identify the mood that person is in. The stuff is magic.
Uterine contractions. These are important for cervical dilation before birth and causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful uterine contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition is normal.16
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Melanotans include melanotan I (afamelanotide) and melanotan II. Both melanotan I and II are widely abused to obtain a cosmetic tan. The melanotans are potent, non-selective melanocortin receptor agonists affecting MC1, MC3, MC4 and MC5 receptors. These receptors are responsible for many physiological systems including: pigmentation, energy, sexual function, immune system, inflammation and the cardiovascular system.
A study using an oral cavity spray of 5-HTP (via the plant source of Griffonia Simplicifolia) has noted that 7.68mg of 5-HTP via 30.72mg of Griffonia Simplicifolia extract taken five times daily (total daily dose of around 40mg) has confirmed an increase in urinary 5-HIAA (from 3.71+/-1.27mg/24 hours to 8.80+/-4.02mg/24 hours; a 137% increase) relative to baseline, confirming that 5-HTP can be absorbed sublingually.[3] Similar results have been noted elsewhere with this spray, although it should be noted that it is confounded with other herbs (detailed in the appetite subsection).[2]
Some work has pointed to a potential dark side to oxytocin. Carter's group found that a single low dose of the hormone given to baby prairie voles improved their pair bonding as adults, but that higher doses interfered with that behaviour — possibly because oxytocin started to activate other receptors16. And human studies have suggested that in certain contexts, a puff of oxytocin can cause people to be more aggressive in defending themselves against outsiders or competitors17. In patients with a psychiatric condition known as borderline personality disorder, a single dose of oxytocin has been found to hinder trust and cooperation18.
In 1999 researchers in Glasgow University found that an oxidised derivative of thymosin β4 (the sulfoxide, in which an oxygen atom is added to the methionine near the N-terminus) exerted several potentially anti-inflammatory effects on neutrophil leucocytes. It promoted their dispersion from a focus, inhibited their response to a small peptide (F-Met-Leu-Phe) which attracts them to sites of bacterial infection and lowered their adhesion to endothelial cells. (Adhesion to endothelial cells of blood vessel walls is pre-requisite for these cells to leave the bloodstream and invade infected tissue). A possible anti-inflammatory role for the β4 sulfoxide was supported by the group's finding that it counteracted artificially-induced inflammation in mice.
For those deficient in tryptophan, supplemental tryptophan and 5-HTP could be somewhat effective,[17] although a meta-analysis found barely statistically significant results (Odds Ratio of 1.3-13.2) from a statistically subpar collection of studies, and based on the inclusion criteria it set it had to expand its analysis to both 5-HTP and Tryptophan to get two studies to assess.[23]
Autism: Oxytocin has been implicated in the etiology of autism, with one report suggesting autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene (OXTR). Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of OXTR with autism.[55][56] Autism may also be associated with an aberrant methylation of OXTR.[55]
FGF-2 and VEGF enhance angiogenesis in chronic wounds (Greenalgh, 1996; Kirchner et al., 2003). Thymosin β-4 increases angiogenesis, consistent with its ability to induce epicardial cells to differentiate into endothelial and smooth muscle cells of coronary vessels (Chapter 7). L-arginine enhances angiogenesis in chronic wounds by enhancing the production of endothelial nitric oxide and improving blood flow (Shi et al., 2003). L-arginine also plays a role in the formation of proline, which is essential for the structure of collagen molecules. ChrysalinTM, a synthetic peptide representing the portion of human thrombin that binds to the surface of endothelial cells, doubled the incidence of complete healing of diabetic foot ulcers in human patients (Fife et al., 2007). Another molecule used to treat peripheral artery disease, pentoxifylline, was reported to improve blood flow in chronic wounds by reducing blood viscosity (Falanga et al., 1999).
Milk ejection reflex/Letdown reflex: in lactating (breastfeeding) mothers, oxytocin acts at the mammary glands, causing milk to be 'let down' into subareolar sinuses, from where it can be excreted via the nipple.[47] Suckling by the infant at the nipple is relayed by spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland.

This is a great product, I have been having digestive problems after 13 major surgeries and suffering from Crohn's Disease my whole life. Currently I can only tolerate a liquid diet. Was very depressed, found this and started taking it and it has made a HUGE difference to my life. Only have very mild depression symptoms now, and sleep better at night. Bought the powder to get the dose right, looks like 100mg suits my 50 kg frame. Only bad thing is the packaging. The 10 grams of powder is lost in the large packet, very hard to get it out and measure the same dose every night. I purchased miniature measuring spoons from ebay and they make life much easier. Sort out the correct spoon for your dosage with the scales then off you go. Can be tricky getting it in and out of the bag, often get powder everywhere, but usually just lick it off. A pill container would work much better for this power.
For example, when a mother is nursing her baby, that stimulation from the breast is going into the brain and causing those oxytocin neurons to fire and release oxytocin directly into the brain. That's much more powerful than what happens with a nasal spray. So I think that, you know, in the future, we may have these drugs that can, in a very potent way, tap into this oxytocin system to treat many different kinds of disorders.
If you were to go on the internet, read the hype, you'd probably think it'll be something like having an ecstasy tablet or having an orgasm or something like that, but the reality is you probably wouldn't be able to distinguish it from placebo. So the effects are extremely subtle. Now, that subtlety isn't necessarily because of oxytocin itself being a subtle hormone, it's just this issue of it penetrating the brain. So when you take it intranasally, we're still trying to work out how much gets into the brain, but probably only a vanishingly small amount.
These studies demonstrate that in the animal model of TBI, early (6 hours post injury) treatment with Tβ4 i.p. at doses of 6 and 30 mg/kg reduces cortical lesion volume and hippocampal cell loss and improves functional recovery, suggesting its potential as a neuroprotective therapy for TBI. More importantly, delayed (24 hours post injury) treatment with Tβ4 administered i.p. at a dose of 6 mg/kg does not reduce lesion volume but significantly improves functional outcome in rats.34 Tβ4-induced angiogenesis, neurogenesis and oligodendrogenesis may contribute to functional recovery.34 Therefore, our data suggest that promoting endogenous neurorestorative processes using Tβ4 provides a novel therapeutic option for TBI. It should be noted that systemic administration of Tβ4 is safe and well-tolerated by animals and humans.26 Further investigation of the molecular mechanisms underlying Tβ4-mediated neuroprotection and neurorestoration is warranted.
However, as I’ve said elsewhere, depression is kind of like a check engine light on car, it’s a quiet ambiguous sign that something is not working somewhere in your neurobiology. There is literally dozens (perhaps hundreds) of different ways to attempt to treat depression. Amongst the vast number of options for treating depression, there is a couple of low hanging fruits; things you would want to start with before moving onto more radical options, like…
The enzyme dopamine decarboxylase (aromatic L-amino acid decarboxylase) mediates the conversion of 5-HTP into serotonin, and this enzyme is expressed in stomach tissue.[53] Inhibition of this enzyme in the stomach during 5-HTP ingestion is thought to promote the concentration of 5-HTP that reaches neural tissue, which is supported by a study using 100-200mg Carbidopa (pharmaceutical inhibitor) alongside 5-HTP to increase radioactivity of 5-HTP (indicative of neural accumulation) in humans.[54]
5-HTP can affect a brain chemical called serotonin. Dextromethorphan (Robitussin DM, others) can also affect serotonin. Taking 5-HTP along with dextromethorphan (Robitussin DM, others) might cause too much serotonin in the brain and can result in serious side effects including heart problems, shivering, and anxiety. Do not take 5-HTP if you are taking dextromethorphan (Robitussin DM, and others).
A: 5-HTP (5-hydroxy-tryptophan) 5-htp-5-hydroxytryptophan is converted to serotonin in the body. Because 5-HTP is related to serotonin, it should not be taken with drugs, which may affect serotonin level. These drugs are SSRI (selective serotonin reuptake inhibitors) such as Paxil (paroxetine), Zoloft (sertraline), Prozac (fluoxetine), Celexa (citalopram) and others. The list of drugs: Plavix (clopidogrel), Lipitor (atorvastatin), Uroxatral (alfuzosin), bisoprolol, aspirin and lisinopril do not affect serotonin in the body. Tramadol, however, has a weak inhibition of serotonin reuptake and can increase serotonin levels. It is therefore recommended that tramadol and 5-HTP be used with caution. The patient needs to be monitored for serotonin syndrome, which may include changes in mental status, tremor, hyperthermia, rigidity, seizure, increase sweating and shaky movement. The interaction may also cause a cerebral vasoconstrictive disorder such as Call-Fleming syndrome. It is important to discuss the use of tramadol and 5-HTP with your healthcare provider before taking 5-HTP. Lori Mendoza, RPh
The pamphlet, titled "Melanotan-2: Safe enhanced tanning" says although the drug is not approved by the Therapeutic Goods Administration (Australia's drug watchdog) and that studies into its effects are under way, it "is safe" and and its use "well documented". It says people can be referred to a "suitable doctor who is trained to prescribe MT2" so the pharmacy can dispense it to them.
There are several layers in the skin; the outer epidermis and beneath it the dermis and the subcutaneous layer. Cells in the epidermis include keratinocytes, its major cell type, that move continuously from the lower basal layer where they are formed by cell division. Other cells in the epidermis are the melanocytes that synthesize pigment and transfer it to the keratinocytes, giving our skin its color, and a wide variety of immune cells that maintain immune surveillance and secrete substances called cytokines, like interleukin 1 and 2, which are active in inflammation. The dermis contains connective tissue, mainly collagen, blood vessels, various types of immune white cells and fibroblasts.

5-HTP appears to reduce food intake secondary to increasing satiety, although most studies are currently conducted in women (in regards to 5-HTP being related to serotonin, this may be relevant; see our creatine page and the Depression section for more information). At least one study that was mixed gender supports the notion it benefits both genders, however
Friedman, J., Roze, E., Abdenur, J. E., Chang, R., Gasperini, S., Saletti, V., Wali, G. M., Eiroa, H., Neville, B., Felice, A., Parascandalo, R., Zafeiriou, D. I., Arrabal-Fernandez, L., Dill, P., Eichler, F. S., Echenne, B., Gutierrez-Solana, L. G., Hoffmann, G. F., Hyland, K., Kusmierska, K., Tijssen, M. A., Lutz, T., Mazzuca, M., Penzien, J., Poll-The BT, Sykut-Cegielska, J., Szymanska, K., Thony, B., and Blau, N. Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Ann Neurol. 2012;71(4):520-530. View abstract.
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