Cells were incubated with 200 μM H2O2 for indicated times (A). Cells were pretreated with indicated concentrations of Tβ4 peptide (0.1–5 μg/mL) for 2 hours and then incubated with 200 μM H2O2 for 60 minutes (B). Data were representative of three independent experiments. The bar graph shows the fold increase in protein expression compared with control cells * Statistically significant differences compared with the control, p<0.05. # Statistically significant difference compared with the H2O2—treated group.
5-HTP is very reliable in increasing serotonin levels. 5-HTP is actually used as a clinical test to judge the potency of drugs that affect serotonin levels (by pairing an experimental drug with 5-HTP to induce 'serotonin syndrome', or serotonin toxicity, one can see how much that drug exacerbates serotonin biosynthesis or bioavailability by seeing how much of a 5-HTP dose is required to induce the syndrome; the lower dose indicative of higher drug potency). This test is known as the 5-HTP induced syndrome test.[8]
A: 5-HTP or 5-hydroxytryptophan is sold as a dietary supplement for "anxiety, depression, insomnia, headaches and other conditions." Because dietary supplements (e.g., 5-HTP) have not been thoroughly studied in the clinical setting, possible side effects and interactions with other drugs are not well known. However, 5-HTP does interact with prescription antidepressants, taking them together can lead to serotonin syndrome which is a rare but potentially fatal condition. Also, because herbs and supplements are not strictly regulated by the U.S. Food and Drug Administration, these products are not required to be tested for effectiveness, purity, or safety. 5-HTP has not been proven safe or effective for the treatment of depression or bipolar disorder. There are many prescription medications that have been proven safe and effective for these conditions. In general, dietary supplements should only be taken under the supervision of your health care provider. Laura Cable, Pharm.D., BCPS
A warning: unlike BPC-157, TB-500 is absolutely, 100% banned by WADA and most other global sporting organization both in-competition and out-of-competition. You should NOT use this if you are competing in any such sanctioned sport as it definitely falls under the banned category of “Peptide Hormones, Growth Factors, Related Substances and Mimetics (S2)”.

TBI patients frequently suffer from long-term deficits in cognitive and motor performance. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI.11 Some features of cognitive and motor function in humans have been successfully demonstrated in experimental brain trauma models.28-30 The controlled cortical impact (CCI) model is one of the most widely used TBI models. The CCI-TBI model has many clinically relevant features in that CCI causes not only cortical damage but also selective neuronal death in the hippocampus in rodents, leading to sensorimotor dysfunction and spatial learning and memory deficits, respectively.18,31-33

The mRNA and protein expressions were determined by PCR analysis (A) and Western blot analysis (B), respectively. The bar graph shows the fold increase in protein or mRNA expression compared with control cells * Statistically significant differences compared with the control, p<0.05. The data presented were representative of three independent experiments.

Melanotan II non-selectively mimics the action of melanocortin peptides. These are natural hormones involved with pigmentation, energy homeostasis, sexual functioning, the immune system, inflammation, and the cardiovascular system. Much like melanotan I (afamelanotide), melanotan II stimulates the production of eumelanin, causing the skin to go darker (tanning).
Silencing of the Tβ4 or Wnt5a gene was achieved by transfecting cells with small interfering RNA (siRNA). Cells were transfected with Tβ4 or Wnt5a siRNAs (30 nM) for 24 hours using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. Cells were transfected with Silencer negative control siRNA using the same protocol.

In humans, 5-HTP is the nutrient precursor to the neurotransmitter serotonin – widely known as the 'happy neurotransmitter' – meaning 5-HTP converts directly into serotonin in the brain. As well as being in our bodies, it's found naturally in the seeds of a woody shrub native to West Africa. By taking it as a supplement, in theory, you will end up with more serotonin in your brain. Serotonin deficiency is linked to depression, anxiety and a whole host of physical and mental ailments. Raising its levels seems to help brain cells send and receive chemical messages, which in turn boosts mood.
Surgery: 5-HTP can affect a brain chemical called serotonin. Some drugs administered during surgery can also affect serotonin. Taking 5-HTP before surgery might cause too much serotonin in the brain and can result in serious side effects including heart problems, shivering, and anxiety. Tell patients to stop taking 5-HTP at least 2 weeks before surgery.
Although obtaining Melanotan II and Bremelanotide is relatively easy to do, both substances come in powder form and then must be reconstituted using sterile water prior to subcutaneous injection—a method of administration that can cause lead to skin bruising, cross-contamination, or infection, if the person performing the injection is inexperienced and the syringe isn't clean.
Despite this, Tβ4’s place on the banned-substances list is warranted. It reflects the possibility that the effects of the supplement may manifest as a tangible improvement in athletes. However, any time a journalist flippantly declares it “heals damaged tissue and speeds recovery”, it should be noted that such claims are a harmful distortion of the facts.
Once the baby is born, oxytocin promotes lactation by moving the milk into the breast. When the baby sucks at the mother's breast, oxytocin secretion causes the milk to release so the baby can feed. At the same time, oxytocin is released into the brain to stimulate further oxytocin production. Once the baby stops feeding, the production of the hormone stops until the next feeding.

In 1989, a nationwide outbreak sickened over 1500 people and caused at least 30 deaths in the US. The outbreak was characterized by severe muscle pain and high white blood cell count. The culprit was later determined to be tryptophan supplements made by a specific manufacturer that were thought to be contaminated. Shortly thereafter, the FDA recalled and banned all forms of tryptophan supplements. In the meantime, an alternative supplement called 5-hydroxytryptophan (5-HTP), which is a chemical byproduct of tryptophan, was introduced as an alternative and has since become popular.
Noteworthy:  Many online sources sell an ineffective product.  Also, peptides are fragile by nature and are not effective when they are taken orally (pills, shakes, etc) because they will be broken down by the digestive process. Instead, peptides are mixed with bacteriostatic water and then injected under the skin with an insulin needle. Peptide injections in this manner are nearly painless and have clinically proven effectiveness.
At first, the mice showed an irregular smattering of neural impulses when they heard the baby's cries. Then, as the oxytocin kicked in, the signal evolved into a more orderly pattern typical of a maternal brain. The study showed in unusual detail how the hormone changed the behaviour of neurons1. “Oxytocin is helping to transform the brain, to make it respond to those pup calls,” Froemke says.

TB-500 is a synthetic version of the naturally occurring peptide present in virtually all human and animal cells, Thymosin Beta-4. This potent peptide is a member of a ubiquitous family of 16 related molecules with a high conservation of sequence and localization in most tissues and circulating cells in the body. TB-500 not only binds to actin, but also blocks actin polymerization and is the actin-sequestering molecule in eukaryotic cells.
To determine the effects of Tβ4 peptide and H2O2 on cytotoxicity, its cell viability was evaluated. A 48-h exposure to 0.1–5 μg/mL Tβ4 peptide did not affect H2O2-mediated cell viabilities (Fig 2A). In order to examine whether Tβ4 peptide suppressed ROS-induced inflammatory mediators, the ability of Tβ4 peptide on production of NO and PGE2, and expressions of COX-2 and iNOS were measured by RT-PCR, Western blot, and ELISA. Pretreatment with Tβ4 peptide dose-dependently inhibited H2O2-induced mRNA and protein expressions of COX-2 and iNOS, and NO and PGE2 production (Fig 2B–2E).
Can a supplement proven to fight blue moods also help stimulate weight loss? “Yes it can!” say experts who are now prescribing a natural compound called 5-HTP. According to top integrative health expert Tasneem Bhatia, MD, author of What Doctors Eat ($15.99, Amazon), “5-HTP is converted directly to serotonin, and serotonin makes you feel good, feel happy, feel full — and when you feel that way, you’re going to eat less.” In fact, Dr. Bhatia adds that while most appetite suppressants only target physical hunger, this one also “works to reduce ‘emotional hunger’ and stress-related urges to eat.” Dr. Oz said he left impressed after consulting with a panel of 5-HTP experts, including American Board of Obesity Medicine alum Denise E. Bruner, MD. He said the supplements may even be “a secret weapon for hunger!”

Reconstituting tanning peptide is a part of the process required for use of the product and will require full attention to get proper results. 1 or 2ml sterile water is usually used, diluting with more water will improve dosing accuracy. Lovemelanotan peptide calculator is ideal tool for anyone just starting out and not sure how to reconstitute or dose the product properly.

Studies on diabetic rats indicated significant increases in the amount of collagen and in tensile strength of light-treated wounds over controls (Stadler et al., 2001; Reddy et al., 2001). In combination with hyperbaric oxygen, light-treated skin wounds in rats closed faster (Yu et al., 1997), an effect that was associated with a more uniform rise and fall in VEGF and FGF-2 instead of the sharp peaks at day four and subsequent rapid drop-off observed in control wounds (Whelan et al., 2001). In vitro, proliferation of mouse fibroblasts was increased by over 150% and that of human epithelial cells by 155–171% (Whelan et al., 2001). Whelan et al. (2001) also reported that wound-healing time was decreased by 50% aboard a submarine, where the atmosphere is lower in oxygen and higher in carbon dioxide, and that children suffering from oral mucositis as a result of chemotherapy experienced a 47% reduction in pain. Recently, however, a randomized trial using a 980 nm diode laser to treat venous leg ulcers of 18 patients indicated no difference in reduction of ulcer size compared to the 16 control patients (Leclere et al., 2010).

Work with cell cultures and experiments with animals have shown that administration of thymosin β4 can promote migration of cells, formation of blood vessels, maturation of stem cells, survival of various cell types and lowering of the production of pro-inflammatory cytokines. These multiple properties have provided the impetus for a worldwide series of on-going clinical trials of potential effectiveness of thymosin β4 in promoting repair of wounds in skin, cornea and heart.[17]

In December 2010, the delegate made a delegate only decision to include afamelanotide (also known as melanotan I) with a cross-reference to melanocyte stimulating hormone (MSH) for inclusion into the current Poisons Standard. It was noted that afamelanotide should not be confused with a similar substance commonly known as Melanotan-II, which is a cyclic lactam synthetic analogue of α-MSH. It was noted that melanotan-II was under investigation for treating sexual dysfunction, although this has been abandoned due to side effects associated with the immune and cardiovascular systems. Its metabolite, bremelanotide, is under investigation for treating haemorrhagic shock.
Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including in females in the corpus luteum[34][35] and the placenta;[36] in males in the testicles' interstitial cells of Leydig;[37] and in both sexes in the retina,[38] the adrenal medulla,[39] the thymus[40] and the pancreas.[41] The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these different tissues.
Thymosins were discovered in the mid 1960’s, when Allan Goldstein from the Laboratory of Abraham White at the Albert Einstein College of Medicine in New York studied the role of the thymus in development of the vertebrate immune system. Since then, Dr. Goldstein founded a company that creates thymosin alpha 1 for the purpose of increasing immune cell activity, and thymosin beta 4 (TB-500) to promote wound repair and healing.
It turns out the love hormone oxytocin is two-faced. Oxytocin has long been known as the warm, fuzzy hormone that promotes feelings of love, social bonding and well-being. It's even being tested as an anti-anxiety drug. But new Northwestern Medicine® research shows oxytocin also can cause emotional pain, an entirely new, darker identity for the hormone.
It was under development as drug candidate for female sexual dysfunction and erectile dysfunction but clinical development ceased by 2003, and as of 2018, no product containing melanotan II was marketed and all commercial development had ceased.[1] Unlicensed, untested, or fraudulent products sold as "melanotan II" are found on the Internet, and purported to be effective as "tanning drugs", though side effects such as uneven pigmentation, new nevi (moles), and darkening or enlargement of existing moles are common and have led to medical authorities discouraging use.[2][3]

I have taken BPC-157 in conjunction with TB-500 after reading about someone’s experience. I used the BPC-157 at an injury/inflammation site in my shoulder. I have a pain that came out of nowhere and has prevented me from doing bench presses mainly, and shoulder presses. I also got pain when I did external rotation of my shoulder. The BPC-157 gave me good results at 250 mcg twice daily intramuscularly. The pain is not completely gone but it has definitely lessened in severity. I don’t get any pain with a reverse grip press so I have been doing those with light weight and I can now do shoulder presses. BPC-157 really blew me away on how quickly it improved my gut status. For me it only took 4 days of orally dosing with 250 mcg. So I did both the oral and intramuscular daily for a month. Two weeks into the BPC-157 I ordered TB-500 and did 1mg per week subq in my thigh because I didn’t know about injecting intramuscularly at the injury site.
Recent reports have stated that inhibitors of Wnt signaling have emerged as promising strategies for bone disease and inflammatory diseases [26, 55]. Wnt5a, one of the most common Wnt molecules that activate the non-canoical pathway, binds to Fzd and its co-receptor, Ror2 [56]. In synoviocytes from rheumatoid arthritis patients, the expressions of Wnt5a and Frizzled5 (Fzd5) were significantly enhanced [25] and their blockades inhibited synoviocyte activation [55]. Recently, Wnt5a was highly expressed in synovial tissues in a mouse model of rheumatoid arthritis where inhibition of Wnt5a-Ror2 signaling suppressed bone loss [57]. Our data demonstrated that ROS up-regulated Wnt5a and its cell surface receptors, Frizzled and Ror2, as well as mRNA and protein expressions in time- and dose-dependent manners in PDLCs.
In 20 persons undergoing alcohol withdrawal taking 5-HTP (5mg) alongside Glutamine (150mg) and D-Phenylalanine (300mg) and some minerals such as Calcium and Magnesium, it was noted that after 40 days of nutritional therapy (in a hospital setting) that all withdrawal symptoms assessed via SCL-90-R except for anxiety noted a greater reduction with nutritional support relative to placebo.[1]
Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.

Stimulation of milk ejection (milk letdown): Milk is initially secreted into small sacs within the mammary gland called alveoli, from which it must be ejected for consumption or harvesting. Mammary alveoli are surrounded by smooth muscle (myoepithelial) cells which are a prominant target cell for oxytocin. Oxytocin stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and cisterns.

Studies of oxytocin also have found that it is an important chemical messenger that controls some human behaviors and social interaction. It is oxytocin that triggers the bond between a mother and an infant, and it may also play a role in recognition, sexual arousal, trust, and anxiety. Some research shows that the hormone may affect addiction and stress as well.
Supplements haven't been tested for safety and due to the fact that dietary supplements are largely unregulated, the content of some products may differ from what is specified on the product label. Also keep in mind that the safety of supplements in pregnant women, nursing mothers, children, and those with medical conditions or who are taking medications has not been established. You can get tips on using supplements, but if you're considering the use of 5-HTP supplements, talk with your primary care provider first. Self-treating a condition and avoiding or delaying standard care may have serious consequences.
At least one study has actively differentiated between 'an increase in satiety' (sensation of fullness from food) and a 'decrease in appetite' (less desire to eat) and noted that 5-HTP causes an increase in satiety without a concomitant decrease in appetite.[9] Additionally, most studies are in exclusively females which may have more significance with interventions pertaining to serotonin metabolism; only one study mentioned above was conducted in men as well[10] but appears to suggest that it benefits both genders.
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.
About ten years ago, psychology studies started to show that single doses of oxytocin, delivered through an intranasal spray, could promote various aspects of social behaviour in healthy adults. People who inhaled oxytocin before playing an investment game were more willing to entrust their money to a stranger than were placebo-treated players10. A dose of the hormone also increased the amount of time that people spent gazing at the eye region of faces11, and improved their ability to infer the emotional state of others from subtle expressions12.
"There was no substance labelled unfit for human use so anyone that tries to bandy that comment around apart from the fact the comment is totally false, we are now starting to accrue our legal case against people that have suggested as such. Under no circumstances was anything ever injected or given to a player which was unfit for human consumption," Dank told ABC News Radio on Sunday.
A critical step in wound healing is angiogenesis. New vessels are needed to supply nutrients and oxygen to the cells involved in repair, to remove toxic materials and debris of dead cells and generate optimal conditions for new tissue formation. Another important step is the directional migration of cells into the injured area, joining up to repair the wound. This requires an attractant that will direct the cells to the wound and propel them to the site. These critical steps in wound healing are regulated by beta 4, as seen in the following experiments.
Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation.[50][51] However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.[49]

Froemke's and Tsien's work fits into a broader theory: that one way oxytocin helps social interaction and recognition is by enhancing the brain's response to socially relevant sights, sounds or other stimuli. Young has shown that the hormone helps mice to recognize and pay attention to the smells of other mice7; others found that it promotes people's ability to recognize faces8.

PDGF-BB (Mustoe et al., 1994), FGF-2 (Inadomi et al., 2004), IGF I and II (Zhao et al., 1995), TGF-β (Greenalgh, 1996), and L-arginine (Shi et al., 2003) enhance fibroblast proliferation and deposition of collagen in chronic wounds. Thymosin β4 accelerates wound repair in both young and old diabetic mice by significantly increasing wound contraction and collagen deposition. A synthetic peptide that duplicated the actin-binding domain of thymosin β4 promoted wound repair in aged mice to a degree comparable to that of the whole molecule (Philp et al., 2003). In rats with wound healing impaired by mitomycin C, the formation of granulation tissue (angiogenesis and fibroblast proliferation) was significantly advanced by hydrogel sheets composed of alginate, chitin/chitosan, and fucoidin (Murakami et al., 2010).
Melanotan II was originally developed as a treatment for sexual dysfunction. However, this was abandoned when the metabolite bremelanotide was developed instead for treatment of haemorrhagic shock. Melanotan II is usually injected subcutaneously for the purposes of sunless tanning, appetite suppression, inducing sexual desire and penile erection and other conditions such as rosacea and fibromyalgia. There are also dose forms available for nasal administration. The therapeutic dose is considered to be 0.01 mg/kg.
Half the group of burned volunteers got a whiff of Eau de Oxytocin, half got a sniff of Eau de Placebo. Those who sniffed the oxytocin were more trusting and ready to invest with an anonymous trustee a second time than were the placebo-exposed subjects. And when they were asked “Do you want to try this again?” the oxytocin-treated volunteers responded more quickly than the volunteers who hadn’t gotten the nose full of Trust Spray.6
Establishment of maternal behavior: Successful reproduction in mammals demands that mothers become attached to and nourish their offspring immediately after birth. It is also important that non-lactating females do not manifest such nurturing behavior. The same events that affect the uterus and mammary gland at the time of birth also affect the brain. During parturition, there is an increase in concentration of oxytocin in cerebrospinal fluid, and oxytocin acting within the brain plays a major role in establishing maternal behavior.
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.
The biologically active form of oxytocin, commonly measured by RIA and/or HPLC techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced straight-chain (non-cyclic) dithiol nonapeptide called oxytoceine.[120] It has been theorized that oxytoceine may act as a free radical scavenger, as donating an electron to a free radical allows oxytoceine to be re-oxidized to oxytocin via the dehydroascorbate / ascorbate redox couple.[121]
About ten years ago, psychology studies started to show that single doses of oxytocin, delivered through an intranasal spray, could promote various aspects of social behaviour in healthy adults. People who inhaled oxytocin before playing an investment game were more willing to entrust their money to a stranger than were placebo-treated players10. A dose of the hormone also increased the amount of time that people spent gazing at the eye region of faces11, and improved their ability to infer the emotional state of others from subtle expressions12.
Both the production of oxytocin and response to oxytocin are modulated by circulating levels of sex steroids. The burst of oxytocin released at birth seems to be triggered in part by cervical and vaginal stimulation by the fetus, but also because of abruptly declining concentrations of progesterone. Another well-studied effect of steroid hormones is the marked increase in synthesis of uterine (myometrial) oxytocin receptors late in gestation, resulting from increasing concentrations of circulating estrogen.

Affecting generosity by increasing empathy during perspective taking. In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80% but has no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experimental explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.13

Serotonin syndrome (Serotonin toxicity) is caused by an excess of serotonin in the brain. It is most often caused by taking more than one Serotonin-enhancing substance at the same time, such as 5-HTP and an antidepressant medication. Symptoms range in severity according to the level of intoxication and may include increased heart rate, tremor, sweating, mental agitation, seizures, shock, organ failure and death (9).
There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the baby is delivered or when the baby stops feeding.
Affecting generosity by increasing empathy during perspective taking: In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80%, but had no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed.[89] Serious methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity.[90] Empathy in healthy males has been shown to be increased after intranasal oxytocin[88][91] This is most likely due to the effect of oxytocin in enhancing eye gaze.[92] There is some discussion about which aspect of empathy oxytocin might alter – for example, cognitive vs. emotional empathy.[93] While studying wild chimpanzees, it was noted that after a chimpanzee shared food with a non-kin related chimpanzee, the subjects' levels of oxytocin increased, as measured through their urine. In comparison to other cooperative activities between chimpanzees that were monitored including grooming, food sharing generated higher levels of oxytocin. This comparatively higher level of oxytocin after food sharing parallels the increased level of oxytocin in nursing mothers, sharing nutrients with their kin.[94]

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.
But returning hunters also need to share meat with their families and friends; this is where oxytocin comes into play. It can help overcome the potentially negative social effects of testosterone. Men who were absent for longer seem to need more oxytocin to reconnect with their families; it seems that absence does indeed make the heart grow fonder, via an oxytocin blast.
Thymosin beta-4 (Tβ4) is a water-soluble, 43-amino acid, and 4.9 kDa protein that was originally isolated from bovine thymus [6]. Since Tβ4 is the major actin-sequestering molecule in eukaryotic cells and is found in all cells [7], Tβ4 has multiple diverse cellular functions, including tissue development, migration, angiogenesis, and wound healing [7]. We previously reported that Tβ4-overexpressing transgenic mice, using a construct on the skin-specific keratin-5 promoter, have abnormal tooth development and enhanced stimulation of hair growth [8]. Moreover, exogenous Tβ4 has anti-inflammatory effects in the bleomycin-induced mouse model of lung fibrosis [9], tooth extraction sockets in rats [10], rat model of myocardial ischemia [11], corneal wound healing [12], wound healing of rat palatal mucosa [13], in vitro model of cultured human gingival fibroblasts [14], and cardiac fibroblasts [15]. However, the effects of Tβ4 over expression or inhibition on differentiation are controversial. Exogenous β4 peptide inhibited osteogenic differentiation but facilitated adipogenic differentiation in human bone marrow-derived-mesenchymal stem cells (MSCs) [16]. In contrast, Tβ4 inhibition by Tβ4 siRNA attenuated odontoblastic differentiation in the odontoblast-like cells, MDPC-23 [17]. Moreover, we recently demonstrated that odontoblastic differentiation was enhanced by activation of Tβ4 by Tβ4 peptide but was decreased by Tβ4 siRNA in human dental pulp cells (HDPCs) [18]. However, the effects of Tβ4 on osteoclastic differentiation have not been reported.

Combined treatments of 5-HTP and SSRI seem to have strong synergistic effects on serotonin levels in rats and humans so that some clinicians recommend the use of slow-released 5-HTP in combination with SSRIs (R, R2, R3). However, additional clinical trials are required to demonstrate the safety and effectiveness of this approach, and combinations of 5-HTP and medications should only be used under medical supervision.