Thymosin beta-4 is a naturally occurring peptide, and is found ubiquitously in our cells. A range of studies on animal models have indicated several key biological activities for Tβ4, such as “promot[ing] wound repair, tissue protection, and regeneration in the skin, eye, heart and central nervous system”. Only a handful of clinical trials in humans have attempted to explore these roles practically.
Animal studies have found high levels of both stress and oxytocin in voles that were separated from other voles. However, when the voles were given doses of oxytocin, their levels of anxiety, cardiac stress, and depression fell, suggesting that stress increases internal production of the hormone, while externally supplied doses can help reduce stress.
Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury. These effects stem in part from decreased infarct size, but additional benefits are likely due to specific antifibrotic and proangiogenic activities. Injected or transgenic Tβ4 increase blood vessel growth in large and small animal models, consistent with Tβ4 converting hibernating myocardium to an actively contractile state following ischemia. Tβ4 and its degradation products have antifibrotic effects in in vitro assays and in animal models of fibrosis not related to cardiac injury. This large number of pleiotropic effects results from Tβ4’s many interactions with cellular signaling pathways, particularly indirect regulation of cellular motility and movement via the SRF–MRTF–G-actin transcriptional pathway. Variation in effects and effect sizes in animal models may potentially be due to variable distribution of Tβ4. Preclinical studies of PK/PD relationships and a reliable pharmacodynamic biomarker would facilitate clinical development of Tβ4.

Neurovascular units within the central nervous system consist of endothelial cells, pericytes, neurons and glial cells, as well as growth factors and extracellular matrix proteins that are close to the endothelium.72,73 Neurovascular units provide niches for neural stem/progenitor cells in the adult brain and, within these units, newly-generated immature neurons are closely associated with the remodeling vasculature. The generation of new vasculature facilitates several coupled neurorestorative processes including neurogenesis and synaptogenesis, which improve functional recovery.74-76 The vascular production of stromal-derived factor 1 and angiopoietin 1 is involved in neurogenesis and promotes behavioral recovery after stroke.77 The disruption of this neurovascular coordination has been observed in a variety of brain conditions including infection, stroke and trauma.78 The injured brain promotes angiogenesis and neurogenesis,13,32,69,79-84 that may contribute to spontaneous functional recovery from injuries such as stroke and TBI. Neurorestorative agents that increase angiogenesis and neurogenesis have been shown to improve functional outcome following brain injury.19,33 Vascular endothelial cells within the neurovascular niche affect neurogenesis directly via contact with neural progenitor cells, while soluble factors from the vascular system that are released into the CNS enhance neurogenesis via paracrine signaling.85 Here, we demonstrate that Tβ4 treatment promotes both angiogenesis and neurogenesis in rats after TBI, suggesting that the neurovascular remodeling at least partially contributes to Tβ4-mediated improvement in functional recovery. A better understanding of molecular mechanisms in the neurovascular niches will be important for developing novel angiogenic and neurogenic therapies for brain injuries.
Unlike previous studies, the trial will include people with a wide range of symptoms — and one of its major aims is to uncover the set of factors that influence whether and how strongly people respond to oxytocin. Sikich will analyse many measures of cognition and social functioning, and collect blood samples to look for biomarkers — such as levels of oxytocin and the receptor it binds to — that are associated with a response. “Lin has really been trying to create conditions under which you could study the potential beneficial effects of oxytocin and really do this right,” says Carter.
The scientists discovered that oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule -- ERK (extracellular signal regulated kinases) -- that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain's fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.

People are using 5-HTP for absolutely everything from sleep disorders to OCD symptoms. After asking people in mental health Facebook groups whether they used it and why, I was inundated with responses. Sach Tennant, from London, takes it for her PMDD (premenstrual dysphoric disorder). "I only take it when I feel low and it only takes one hour to feel calm," she told me. "This month I only needed one to feel better. I don't get the zombie antidepressant feeling – you still have your emotions. Sleep is good on it. I used to have an inner voice that was male and used to bully me during PMT time. Noises seemed too loud, even like somebody eating a bag of crisps. Topping up with 5-HTP has stopped all this."
It was also shown recently that delivery of Fgfs by release from peptide nanofibers, a gradual local delivery system, can increase neovascularization and reduce in-farct size in the ischemic rodent heart (Engel et al., 2006). Related to this, zebrafish have a natural ability to synthesize Fgfs after myocardial injury, a signal that appears to recruit Fgf receptor-expressing epicardial-derived cells toward regenerating muscle (Lepilina et al., 2006). Thus, what has been and what will be discovered about zebrafish heart regeneration is quite likely to illuminate possible strategies for enhancing regeneration in the mammalian heart (see Chapter 14.4).
In a landmark 1979 study3, Cort Pedersen and Arthur Prange at the University of North Carolina in Chapel Hill showed that giving oxytocin to virgin rats could trigger maternal behaviours: the animals would build nests, lick or crouch over unfamiliar pups and even return lost pups to the nest. Researchers went on to show that oxytocin signalling in the brains of prairie voles (Microtus ochrogaster) helps the animals to form lifelong pair bonds4 — a rarity among mammals. In 2012, researchers even found a version of oxytocin in the tiny roundworm Caenorhabditis elegans, where it helps the animals find and recognize mates5.
Studies demonstrate that TB-500 is a potent, naturally occurring wound repair factor with anti-inflammatory properties. Tß4 is different from other repair factors, such as growth factors, in that it promotes endothelial and keratinocyte migration. It also does not bind to the extracellular matrix and has a very low molecular weight meaning it can travel relatively long distances through tissues. One of TB-500 key mechanisms of action is its ability to regulate the cell-building protein, Actin, a vital component of cell structure and movement. Of the thousands of proteins present in cells, actin represents up to 10% of the total proteins which therefore plays a major role in the genetic makeup of the cell.
A study published last year in Biological Psychiatry was the first to assess whether people with variations in their oxytocin-receptor gene have a harder time maintaining romantic relationships than those who don’t. Hasse Walum, a graduate student at Karolinska Institute in Stockholm, and his colleagues took advantage of Swedish twin studies that included thousands of participants, their genetic information and their answers to questions about how affectionate they were with their romantic partners. They found that women with a specific variation weren’t as close to their partners as women without it: they kissed their partners less and didn’t desire physical proximity as often. These women were also more likely to report having had a marital crisis. Although researchers don’t know exactly how this variation affects the oxytocin system, it may result in a lower number of oxytocin receptors in the brain. People with fewer receptors would be less sensitive to the hormone’s effects.
Oxytocin is a powerful hormone that acts as a neurotransmitter in the brain. It regulates social interaction and sexual reproduction, playing a role in behaviors from maternal-infant bonding and milk release to empathy, generosity, and orgasm. When we hug or kiss a loved one, oxytocin levels increase; hence, oxytocin is often called "the love hormone." In fact, the hormone plays a huge role in all pair bonding. The hormone is greatly stimulated during sex, birth, and breastfeeding. Oxytocin is the hormone that underlies trust. It is also an antidote to depressive feelings.
^ Jump up to: a b Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K (November 2005). "Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice". Proceedings of the National Academy of Sciences of the United States of America. 102 (44): 16096–101. Bibcode:2005PNAS..10216096T. doi:10.1073/pnas.0505312102. PMC 1276060. PMID 16249339.
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]
Trust is increased by oxytocin.[95][96][97] Disclosure of emotional events is a sign of trust in humans. When recounting a negative event, humans who receive intranasal oxytocin share more emotional details and stories with more emotional significance.[96] Humans also find faces more trustworthy after receiving intranasal oxytocin. In a study, participants who received intranasal oxytocin viewed photographs of human faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin.[95] This may be because oxytocin reduces the fear of social betrayal in humans.[98] Even after experiencing social alienation by being excluded from a conversation, humans who received oxytocin scored higher in trust on the Revised NEO Personality Inventory.[97] Moreover, in a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting risk aversion.[99] When there is a reason to be distrustful, such as experiencing betrayal, differing reactions are associated with oxytocin receptor gene (OXTR) differences. Those with the CT haplotype experience a stronger reaction, in the form of anger, to betrayal.[100]
The scientists discovered that oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule -- ERK (extracellular signal regulated kinases) -- that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain's fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.

There is one glaring problem, however: the supplements come with a disclaimer that recommends not taking them for more than three months. Most of the information out there on 5-HTP is anecdotal, and most of them are stories of it helping people, rather than hard facts about its scientific properties. I approached neurologists, psychologists and experimental doctors about 5-HTP, and many responses were strange. Not many people were willing to speak about it, saying they weren't qualified or hadn't read the relevant material, but there isn't much material to speak of. The main source of legitimate scientific evidence came from the University of Maryland Medical Center website, who stated that 5-HTP may work as well as certain antidepressant drugs to treat people with mild-to-moderate depression. But all the studies that support that statement were done in the 1980s and 1990s. I wanted to know if 5-HTP was a realistic alternative to SSRIs. Could I stay on 5-HTP forever, basking in its natural glory?


The reality is that people are always going to self-medicate. Boots, Amazon and H&B all sell 5-HTP, and in theory you could keep buying it and taking it for as long as you like. But it's important to know the facts. It shouldn't be used in conjunction with an SSRI, for example. In that situation, if the body is preventing serotonin breakdown while also getting extra serotonin, which leads to seriously unhealthy levels of serotonin activity.
Evidence for this role of oxytocin come from two types of experiments. First, infusion of oxytocin into the ventricles of the brain of virgin rats or non-pregnant sheep rapidly induces maternal behavior. Second, administration into the brain of antibodies that neutralize oxytocin or of oxytocin antagonists will prevent mother rats from accepting their pups. Other studies support the contention that this behavioral effect of oxytocin is broadly applicable among mammals.

Monomeric β-thymosins, i.e. those of molecular weight similar to the peptides originally isolated from thymus by Goldstein, are found almost exclusively in cells of multicellular animals.[4] Known exceptions are monomeric thymosins found in a few single-celled organisms, significantly those currently regarded as the closest relatives of multicellular animals:[5] choanoflagellates [6] and filastereans.[7] Although found in very early-diverged animals such as sponges, monomeric thymosins are absent from arthropods and nematodes, which do nevertheless possess "β-thymosin repeat proteins" which are constructed from several end-to-end repeats of β-thymosin sequences.[8] Genomics has shown that tetrapods (land vertebrates) each express three monomeric β-thymosins, which are the animal species' equivalents (orthologues) of human β4, β10 and β15 thymosins, respectively. The human thymosins are encoded by the genes TMSB4X, TMSB10 and TMSB15A and TMSB15B. (In humans, the proteins encoded by the two TMSB15 genes are identical.) Bony fish in general express orthologues of these same three, plus an additional copy of the β4 orthologue.[9]
Advice & Tips: 5-HTP is a serotonin precursor. Serotonin is well-known as a hormone that affects one's mood in a positive way, but it is probably less-well known that it increases intestinal motility. It has worked magic for my symptoms. I am completely regular now, and the majority of my days are good days, whereas before I began taking it the majority of my days were bad days that began with symptoms of constipation and intestinal pain or discomfort. For me, at least, this is not a prescription. I began taking 5-HTP after my fiancee'--who had already been taking it to help her mood and, primarily, her difficulty sleeping through the night--learned it can be helpful when taken for gastrointestinal motility, and I began taking it myself shortly after that (and felt its effects almost immediately). Although not entirely unexpected, my slightly enhanced good moods are a nice side benefit of taking the supplement. I do get some very mild undesirable side effects, especially during mid-day when I take twice my morning and evening dose of 100 mg. Sometimes my face feels hot and flushes fairly noticeably--and this may be intensified with eating--but those symptoms subside within probably 30 minutes or less.
To explore whether Tβ4 peptide-induced anti-inflammatory and anti-osteoclastogenesis were dependent on the up-regulation of Wnt5a, the effects of recombinant human (rh) Wnt5a (500 ng/mL) and Wnt5a-specific siRNA were assessed. Pretreatment of Wnt5a siRNA reversed the inhibitory effects of Tβ4 peptide on H2O2-induced iNOS and COX-2 expressions, NO and PGE2 productions, osteoclastogenic cytokines, and RANKL expression (Fig 10A–10E). In contrast, pretreatment with rhWnt5a enhanced the anti-inflammatory effects of Tβ4 peptide whereas control siRNA showed no effect on PDLCs. In accordance with anti-inflammatory results, Tβ4 peptide-suppressed osteoclast number and TRAP activity in BMM cells were reversed by exogenous treatment with Wnt5a siRNA but enhanced by rh-Wnt5a (Fig 11A–11C).
Both sexes secrete oxytocin - what about its role in males? Males synthesize oxytocin in the same regions of the hypothalamus as in females, and also within the testes and perhaps other reproductive tissues. Pulses of oxytocin can be detected during ejaculation. Current evidence suggests that oxytocin is involved in facilitating sperm transport within the male reproductive system and perhaps also in the female, due to its presence in seminal fluid. It may also have effects on some aspects of male sexual behavior.

Conclusions:  Melanotan not a treatment or cure for anything.  Nor should it be considered a preventative treatment for skin cancer.  Despite this tanning peptide being known to protect the skin through the natural tanning process, it is not in and itself a guaranteed full proof UV shield.  However, it is a great way for those who don't tan easily to get sun-kissed all year long with minimal exposure to the sun.
Despite these many roles, oxytocin is often reduced to a misleading label. While “hormone of love” may be great for catchy headlines and compelling marketing slogans, they are ultimately misleading. Jennifer Bartz from the Mount Sinai School of Medicine has found that oxytocin can have completely opposite effects on the way people behave, depending on how they view their relationships to other people.

Tβ4 is a multifunctional regenerative small peptide containing 43-amino acids, and it is the major G-actin-sequestering molecule in eukaryotic cells.21 Tβ4 has pro-survival and pro-angiogenic properties, protects tissue against damage, and promotes tissue regeneration.22,23 It also plays a key role in corneal, epidermal and cardiac wound healing.21 Tβ4 participates in axonal path-finding, neurite formation, cell proliferation, and neuronal survival.24-26 Our previous studies show that Tβ4 reduces inflammation and stimulates remyelination and improves functional recovery in animal models of experimental autoimmune encephalomyelitis (EAE) and stroke.25,27 In summary, these pleiotropic properties make Tβ4 an ideal candidate for treatment of TBI.
“The study is kind of a high-water mark for the field, putting different levels all together: a robust behaviour, a brain region, and a cellular basis for it,” says Richard Tsien, a neuroscientist also at Langone. Tsien has been studying the action of oxytocin on neuronal circuits in detail, by examining slices of the hippocampus, a region involved in learning and memory. In a 2013 study6 of rats, Tsien's team found that oxytocin selectively acts on a type of cell called an inhibitory interneuron in a way that quiets background chatter within the neuronal circuit. “Oxytocin improved signal transmission, almost doubling the ability of information to flow through the system,” Tsien says. In effect, it is producing more signal and less noise.

20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight.”


Fortunately for the players, despite the appending doom touted by the media, the current research suggests Tβ4 is safe. 23 non-clinical toxicology studies have been performed “that demonstrate the safety of Tβ4 for its current and planned uses in man”. Significantly, a human clinical trial in healthy volunteers found “intravenous administration of Tβ4 appears to be safe and well-tolerated by all subjects with no dose limiting toxicity or serious adverse events reported”. Admittedly, this trial is limited in that it only followed subjects for a period of 28 days, and thus there is a need for further research if Tβ4 is ever to be developed as a medication.

This article is authored by a PhD Candidate and her supervisory team at University of Queensland, and reflects the interests of the student’s doctoral project in undertaking the nation’s first qualitative study into experiences of Melanotan use among the general population. Dubbed ‘Project Melanotan’, the investigation aims to directly engage with ‘melanotanners’ in a non-judgemental environment, in an effort to both critically evaluate as well as understand lived experiences of melanotaning as they relate to conceptually relevant notions of risk, technology and the body.
Jump up ^ Rondanelli M, Opizzi A, Faliva M, Bucci M, Perna S (March 2012). "Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration". Eating and Weight Disorders. 17 (1): e22–8. doi:10.3275/8165. PMID 22142813.
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