The expression of Tβ4 mRNA is cell cycle dependent and is highest at the G0/G1 transition and during S-phase (), and changes in the expression of Tβ4 appear to be related to cell differentiation. It has been reported that hepatocyte growth factor, nerve growth factor or fibroblast growth factor (FGF) can increase the level of Tβ4 mRNA () and, in addition, interferon treatment augments the transcription of the Tβ4 gene (). It has also been shown that increased Tβ4 expression in cancer cells promotes metastasis, possibly by increasing cell mobility.
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.
In all groups, [intravenous tryptophan] impaired memory and psychomotor performance significantly. In conclusion, cognitive deficits in [bipolar patients] following [intravenous tryptophan] may reflect a central 5-HT vulnerability in frontal brain areas. Independent of [intravenous tryptophan], cognitive deficits in [bipolar patients] provide evidence for a trait marker for [bipolar disorders].
While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was recently reported in marmosets, tamarins, and other new world primates. Genomic sequencing of the gene for oxytocin revealed a single in-frame mutation (thymine for cytosine) which results in a single amino acid substitution at the 8-position (proline for leucine). Since this original Lee et al. paper, two other laboratories have confirmed Pro8-OT and documented additional oxytocin structural variants in this primate taxon. Vargas-Pinilla et al. sequenced the coding regions of the OXT gene in other genera in new world primates and identified the following variants in addition to Leu8- and Pro8-OT: Ala8-OT, Thr8-OT, and Val3/Pro8-OT. Ren et al. identified a variant further, Phe2-OT in howler monkeys.
Sexual activity has been found to stimulate the release of oxytocin, and it appears to have a role in erection and orgasm. The reason for this is not fully understood, but, in women, it may be that the increased uterine motility may help sperm to reach their destination. Some have proposed a correlation between the concentration of oxytocin and the intensity of orgasm.
The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene. This precursor protein also includes the oxytocin carrier protein neurophysin I. The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM).
The idea that oxytocin is central to social cognition made it an attractive candidate for treating psychiatric disorders, especially autism spectrum disorder. People with this condition, who often have problems with social interaction and communication, may not process social stimuli appropriately — and scientists theorized that oxytocin might reverse some of the symptoms. Beginning in 2010, results emerged that seemed to support this theory: researchers found that single puffs of oxytocin could temporarily improve measures of empathy and social cooperation in people with autism spectrum disorder.
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.
Recent preclinical studies by us and others have revealed that endogenous neurorestoration is present after TBI, including neurogenesis, axonal sprouting, synaptogenesis, and angiogenesis, which may contribute to the spontaneous functional recovery.13-18 In addition, treatments that promote these neurorestorative processes have been demonstrated to improve functional recovery after brain injury.19,20 However, clinical trials in TBI have primarily targeted neuroprotection, and trials directed specifically at neurorestoration have not been conducted. The essential difference between neuroprotective and neurorestorative treatments is that the former target the lesion that is still not irreversibly injured and the latter treat the intact tissue.19 Thus, neurorestorative treatments can be made available for a larger number of TBI patients.
RegeneRx is continuing with pre-clinical research, in collaborative arrangements with the National Institutes of Health, accumulating data on the effects of Tb4 and aiming for an IND application (Investigational New drug App-lication) to proceed with clinical studies. Phase I clinical trials will determine the ability of Tb4 to repair ulcers in diabetic patients and to reduce inflammation and accelerate recovery from burns and abrasions to the cornea.
As shown in Figure 1, thymic hormones also modulate the production of hypothalamus pituitary hormones and neuropeptides. Initial experiments revealed that neonatal thymectomy promotes a decrease in the number of secretory granules in acidophic cells of the adenopituitary . In the same vein, athymic nude mice display low levels of various pituitary hormones, such as PRL, GH, LH and FSH . With regard to thymic peptides, thymosin beta-4, when perfused intraventricularly, stimulates LH and LHRH secretion . Similar results were obtained with another thymic peptide, thymulin, in perfused or fragmented pituitary preparations . The administration of thymopoietin (another chemically-defined thymic hormone) in children with Hodgkin’s disease increased GH and cortisol serum levels . Moreover, thymopentin (the synthetic biologically active peptide of thymopoietin) enhances in vitro the production of ACTH and beta-endorphin . In addition, thymulin exhibits an in vitro stimulatory effect on perfused rat pituitaries, enhancing PRL, GH, TSH and LH release . Using short-term cultures of pituitary fragments, an increase in ACTH secretion occurs after in vitro thymulin addition, with no changes in GH levels and significant reductions in PRL release . A further thymosin peptide was recently isolated with the task in stimulating IL-6 release from rat glioma cells . By contrast, thymosin alpha-1 is apparently able to down regulate TSH, ACTH and PRL secretion in vivo with no modifications on GH levels . These inhibitory effects seem to occur through hypothalamic pathways. Indeed, the production of the corresponding releasing hormones by hypothalamic neurones decreased after in vitro addition of thymosin alpha-1 in medial basal hypothalamic fragments .
CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.
5-HTP is necessary for the proper functioning of your body. It is decarboxylated in the brain and liver to produce serotonin, a neurotransmitter. Serotonin is involved in the communication between nearly all of our 40 million brain cells, and is also found in large quantities in the cells of the gut, and in blood platelets. Because of its widespread distribution through the cells of the body, Serotonin is believed to have a large number of psychological and physiological effects. It has been used to treat conditions as diverse as obesity, depression, fibromyalgia, insomnia, and headaches, with varying success.
The need to balance hunting pride and social obligations, and the necessity to reconnect with a family that depends on their provisioning were likely experienced by men throughout much of human evolutionary history. Oxytocin is found in all mammals and originated in the mother-infant bond, where it helps with childbirth, nursing and bonding. In some species, this existing hormonal mechanism could then be harnessed for novel contexts – for instance, men investing in pair-bonding and family provisioning, which is rare among mammals.
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).
During clinic trials for its use as a tanning agent, melanotan II was found to be a potent stimulator of male erections. A new drug based on melanotan II, bremelanotide, was developed to take advantage of this property. It has been noted across several studies to increase rigidity and duration of male erection, as well as male sexual desire. It has also been shown to increase female sexual desire in patients with sexual arousal disorder.
The promise of repairing sun parched aging skin is alluring, especially if damage control may be attained by applying a substance that is abundant in our body. Thymosin beta 4 (Tb4), a molecule that accelerates wound healing in animals and cultured cells, "may be valuable in repairing skin damage caused by sun or even by the wear and tear of aging?" This hopeful message of Tb4's potential to restore damaged human skin was voiced at the 5th International Symposium on Aging Skin, in California (May 2001), by Dr. Allan Goldstein, Chairman of the Biochemistry Department at George Washington University and founder of RegeneRX Biopharmaceuticals. RegeneRX is carrying out preclinical research on Tb4 as a wound healer, in collaboration with scientists at the National Institutes of Health.
This anti-social effect of a social hormone brings some nuance to the story of oxytocin. In one study, researchers found that Dutch students given a snort of the hormone became more positive about fictional Dutch characters, but were more negative about characters with Arab or German names. The finding suggests that oxytocin's social bonding effects are targeted at whomever a person perceives as part of their in-group, the researchers reported in January 2011 in the journal PNAS.
I’m curious to know where you got your reconstitution calculation from; you recommend putting approx 3 cc’s in a 5 mg TB-500 which ‘almost fills’ the vial. I have been doing a ton of research on TB-500 and finding contradictory recommendations on how to reconstitute. Because the dosing for TB-500 is higher than what I’m used to with GHRH & GHRP – I felt a lower reconstitution mixture would reduce the amount I needed to take (but now I’m wondering if I’ve been over dosing based on your formula). Would really appreciate knowing how you arrived at filling an insulin syringe ‘three times’ equal to 3 cc’s – just want to make sure i’m dosing correctly
I had tennis elbow on both arms for over 3 years now. Had one surgery on the R, countless PRPs, and a stem cell treatment on both but still to no avail. Pain on the L never eased up and I just had my 3rd PRP booster injections yesterday after having my stem cells 2 months ago. So can you tell me if BPC 157 or TB 500 better suits my situation. Many thanks!
Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. No effective pharmacological treatments are available for TBI because all Phase II/III TBI clinical trials have failed. This highlights a compelling need to develop effective treatments for TBI. Endogenous neurorestoration occurs in the brain after TBI, including angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis and axonal remodeling, which may be associated with spontaneous functional recovery after TBI. However, the endogenous neurorestoration following TBI is limited. Treatments amplifying these neurorestorative processes may promote functional recovery after TBI. Thymosin beta4 (Tβ4) is the major G-actin-sequestering molecule in eukaryotic cells. In addition, Tβ4 has other properties including anti-apoptosis and anti-inflammation, promotion of angiogenesis, wound healing, stem/progenitor cell differentiation, and cell migration and survival, which provide the scientific foundation for the corneal, dermal, and cardiac wound repair multicenter clinical trials. Here, we describe Tβ4 as a neuroprotective and neurorestorative candidate for treatment of TBI.
Evidence accumulated over the past decades has overturned the traditional dogma that the adult mammalian brain cannot generate new neurons. Adult neurogenesis has been identified in all vertebrate species examined thus far including humans.44-49 Newly generated neuronal cells originate from neural stem cells in the adult brain. Neural stem cells are the self-renewing, multipotent cells that generate the neuronal and glial cells of the nervous system.50 The major function of neurogenesis in adult brain seems to replace the neurons that die regularly in certain brain areas. Granule neurons in the DG continuously die and the progenitors in the subgranular zone of the DG may proliferate at the same rate as mature neuronal death to maintain a constant DG cell number.51 Similarly, the newly proliferated cells from the subventricular zone migrate and replenish the dead olfactory bulb neurons.52 Here, we focus on DG neurogenesis which is important for spatial learning and memory. In normal adult rats, newborn neural cells migrate from the subgranular zone of the DG of the hippocampus into the granule cell layer and eventually become mature granule neurons.53 These new granule neurons extend axonal processes to their postsynaptic targets54-57 and receive synaptic input.58 TBI stimulates widespread cellular proliferation in rats and results in focal neurogenesis in the DG of the hippocampus.59,60 Some of the newly generated granule neurons integrate into the hippocampus. The integration of the injury-induced neurogenic population into the existing hippocampal circuitry coincides with the time point when cognitive recovery is observed in injured animals.44
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.
Therefore, this study was designed to investigate whether Tβ4 was up-regulated in patients with periodontitis, and this study was also designed to investigate whether Tβ4 inhibition or activation suppressed the osteoclastic differentiation in mouse bone marrow-derived macrophages (BMMs) and inflammatory response in periodontal ligament cells (PDLCs) as well as on their signaling pathways.
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)”.
In addition to its intracellular role as the major actin-sequestering molecule in cells of many multicellular animals, thymosin β4 shows a remarkably diverse range of effects when present in the fluid surrounding animal tissue cells. Taken together, these effects suggest that thymosin has a general role in tissue regeneration. This has suggested a variety of possible therapeutic applications, and several have now been extended to animal models and human clinical trials.
Why have zebrafish retained the ability to regenerate? It is thought that the capacity for organ regeneration is an ancestral condition that has occasionally been diminished in the course of vertebrate evolution (Scadding, 1977; Goss, 1992; Wagner and Misof, 1992). Thus, most biologists suspect that the molecular machinery to optimize regeneration is present but poorly-utilized in mammals. By this line of reasoning, zebrafish heart regeneration may represent an optimal utilization of universal cardiac machinery.
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.
Tβ4 is not a thymus-specific peptide but also present in most tissue and all cells except red blood cells . High amounts of Tβ4 were detected in human white blood cells, especially in neutrophils and in macrophages , expressed in developing mandible (embryonic day 12)  and hair follicles (HF) of mice . In addition, the peptide is also detected outside cells, in blood plasma and in wound and blister fluids . Although the mechanism(s) of action of exogenous Tβ4 on anti-inflammatory effects remains unclear, the high levels of Tβ4 present in human wound fluid (13 μg/mL) suggest its importance in wound healing or anti-inflammation . However, the level of Tβ4 is variable (unchanged, decreased, and increased) in GCF or biopsied gingival tissue of periodontal patients [20, 21]. Based on the observations that Tβ4 has anti-inflammatory effects [11–14], the hypothesis is that Tβ4 regulates inflammatory mediators and osteoclastogenesis in osteolytic bone disease, such as periodontitis.
RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.
At least one study using an extract of Griffonia simplicifolia (10.24mg giving 2.56mg 5-HTP; confounded with Centella asiatica and Taraxacum officinale at 11.7mg and 4.55mg Paulina cupana and 9.75mg Artichoke extract) taken in three hits, five times a day (40mg 5-HTP total), by 20 overweight or obese females (non-depressive and without eating disorders) for 4 weeks has noted an increase in satiety and reduced binge eating tendencies; the increase in satiety was said to account for the improved weight loss results seen in the experimental group when both were given weight loss advice and diets. This spray has been noted elsewhere to increase satiety (and vicariously through that, body weight) over 2 months in a similar demographic of women.