Tβ4 was down-regulated in H2O2-exposed PDLCs in dose- and time-dependent manners. Tβ4 activation with a Tβ4 peptide attenuated the H2O2-induced production of NO and PGE2 and up-regulated iNOS, COX-2, and osteoclastogenic cytokines (TNF-α, IL-1β, IL-6, IL-8, and IL-17) as well as reversed the effect on RANKL and OPG in PDLCs. Tβ4 peptide inhibited the effects of H2O2 on the activation of ERK and JNK MAPK, and NF-κB in PDLCs. Furthermore, Tβ4 peptide inhibited osteoclast differentiation, osteoclast-specific gene expression, and p38, ERK, and JNK phosphorylation and NF-κB activation in RANKL-stimulated BMMs. In addition, H2O2 up-regulated Wnt5a and its cell surface receptors, Frizzled and Ror2 in PDLCs. Wnt5a inhibition by Wnt5a siRNA enhanced the effects of Tβ4 on H2O2-mediated induction of pro-inflammatory cytokines and osteoclastogenic cytokines as well as helping osteoclastic differentiation whereas Wnt5a activation by Wnt5a peptide reversed it.

Treated cells were washed with PBS and cytosolic protein extracts were prepared using 1X cell lysis buffer (Santa Cruz Biotechnology, CA) supplemented with protease inhibitor cocktail. Protein concentrations were determined using the Bradford assay (Bio-Rad, CA, USA) as per the manufacturer's protocol. Aliquots of protein lysates were separated on sodium dodecyl sulfate–10% polyacrylamide gels and Western blotting was performed. The proteins were transferred onto a polyvinylidene difluoride membrane (Bio-Rad, CA, USA) in transfer buffer (20 mm Tris, 150 mm glycine, 20% methanol, pH 8.0; TBS-T) at 4°C and 100 V for 1 hour. The membrane was blocked with 5% dry milk in TBS-T for 1 hour at room temperature and incubated with primary antibodies (1:1000) and horseradish peroxidase (HRP)-conjugated secondary antibodies. Protein bands were detected using an enhanced chemiluminescence (ECL) system (Amersham Biosciences, Backinghamshire, UK).
Thank you for this important segment. i have read books that mention oxytocin along with other brain chemicals, if levels are low in the brain it will cause problems, of course, makes sense. low brain neurotransmitters can be restored by using amino acids (supplements) eg: tryptophan will increase serotonin and cure depression without the use toxic pharmaceutical drugs that don.t work.
In the experiments, an epithelial wound was made in the corneas of sedated rats. A Tb4 solution was applied at several concentrations to the injured eyes in one group of rats while another group was treated with a solution without Tb4. Following 12, 24 and 36 hours, the eyes were tested by microscopic observation for epithelial growth over the injured site. Investigators found the Tb4 accelerated corneal wound repair at doses of Tb4 similar to those found to repair skin wounds. When tested 24 hours after treatment, the rate of accelerated repair was proportional to the concentration of Tb4, with the highest dose (25 microgram) showing a threefold acceleration of epithelial cell migration, compared to untreated. Treatment with Tb4 showed anti-inflammatory effects, helping resolve the injury. An application to human cells in a model of human corneal cells in culture showed that Tb4 enhanced epithelial cell migration in vitro.
I am not a doctor and this is not to be taken, interpreted or construed as medical advice. Please talk with a licensed medical professional about this. These are just my own personal thoughts and not a prescription or a diagnosis or any form of health care whatsoever. In terms of doctors, here are a few directories that may help you find a good functional medicine or naturopathic practitioner in your area:
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.
Jump up ^ Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H (March 2010). "Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 153B (2): 629–39. doi:10.1002/ajmg.b.31032. PMID 19777562.
Mouse BMMs were cultured with M-CSF (30 ng/mL) and RANKL (100 ng/mL) or CM collected from PDLCs for 5 days (A) and 60 minutes (B). The mRNAs expression was determined by PCR analysis (A). The phosphorylation of MAPKs (p38, JNK, and ERK), and activation of NF-κB were determined by Western blot analysis (B). Data were representative of three independent experiments. 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.
Increasing trust and reducing fear. 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 that they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting risk-aversion.11 Nasally administered oxytocin has also been reported to reduce fear, possibly by inhibiting the amygdala (which is thought to be responsible for fear responses).12 There is no conclusive evidence for access of oxytocin to the brain through intranasal administration, however.
5-HTP (5-Hydroxytryptophan) is a chemical by-product of the protein building block L-tryptophan. It is also produced commercially from the seeds of an African plant known as Griffonia simplicifolia 5-HTP is used for sleep disorders such as insomnia, depression, anxiety, migraine and tension-type headaches, fibromyalgia, obesity, premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), attention deficit-hyperactivity disorder (ADHD), seizure disorder, and Parkinson's disease..
It should be noted that supplemental 5-HTP can cause an increase in urinary 5-HIAA, which is the major metabolite of serotonin that is excreted in the urine. Increased urinary 5-HIAA is also sometimes a diagonistic marker for carcinoid tumors due to increased conversion of tryptophan to serotonin in these tumors,[62][63] and in this case serum chromogranin A should be measured (as supplemental 5-HTP does not appear to increase chromogranin A).[63]
Formulated Supplementary Sports Foods: The edible products sold on this site are not suitable for children under 15 years of age or pregnant women: Should only be used under medical or dietetic supervision. Contact your health-care provider immediately if you suspect that you have a medical problem. The food is not a sole source of nutrition and should be consumed in conjunction with a nutritious diet; and the food should be used in conjunction with an appropriate physical training or exercise program.
Myocardial infarction and heart failure are severe causes for death in humans. Extracellular nucleotides (ATP and ADP) released at the site of myocardial damage induce thrombosis, apoptosis and necrosis. ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1, CD39) rapidly hydrolyzes ATP and ADP to AMP. An in vivo myocardial ischemia/reperfusion injury test in transgenic mice expressing human CD39 resulted in a decrease of the infarct size. The same transgene including the human CD39 cDNA driven by the murine MHC class I gene H-2Kb promoter was used for the generation of transgenic pigs via SCNT. Expression of human CD39 was detected on circulating blood cells and in myocardial tissue of the transgenic animals. After in vivo induction of myocardial ischemia/reperfusion injury, a reduction of the myocardial injury analogous to the results in the transgenic mice was found (Wheeler et al., 2012).

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.


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 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.

Last month, in the article “How To Use BPC-157: A Complete Dummies Guide To Healing The Body Like Wolverine“, I introduced the little-known concept of using BPC-157 peptide self-injections and oral BPC-157 peptide consumption (currently completely legal and not banned by sporting organizations) for everything from rapidly healing leaky gut to fixing tendon, ligament and muscle injuries.
If you’re looking for hard proof that taking 5-HTP to lose weight works, we’ve got it: In a University of Rome study, obese women who took 5-HTP began eating between 1,000 to 2,000 fewer calories per day. And even as their caloric intake plummeted to a level that would leave many dieters irritable, serotonin was soothing these ladies — and not one reported hunger or diet crankiness. Further boosting spirits: The supplements quadrupled their weight loss, compared to folks given a placebo pill. “They ate a lot less than they normally would because it was easy for them,” Dr. Bhatia notes. Hearing about such an easy way to lose weight might be enough to inspire you to try the supplement for yourself. So, we went ahead and rounded up everything you need to know to get started.
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]

But like most peptides on the market, TB-500 has limited long term studies involving human use. Although I haven’t personally used TB-500 (I can’t, since I compete in WADA sanctioned sports like triathlon and obstacle course racing), from what I’ve seen and heard from bodybuilders and athletes using the peptide, the primary side effect is a temporary sense of lethargy. Also, some people report getting a head rush when injecting TB-500, but report this head rush goes away a few minutes after injecting.
This is exactly the type of question myself, my team of coaches and the community in my Inner Circle can help to answer for you. The Inner Circle is a collective of people who are pursuing the same goals you are – trying to live a healthy, happy, adventurous, fulfilling and limitless life in a modern world. In the Inner Circle, we all help each other with questions, ideas, motivation, suggestions and much more!
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.
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]
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]
“Ultimately you’re body is going to down-regulate the enzymes needed to convert the tyrosine/l-phenylalanine into dopamine and norepinephrine; this also counts for 5 -htp being converted into serotonin. As far as I’m aware when simply supplementing amino acids to improve neurotransmitter prevalence in the brain, tolerance will build very rapidly within a one week to two week period (from personal experience). Not saying it’s not viable to help out with mood when used sparingly, just saying there’s most likely better ways for continued treatment.”
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.
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).
To evaluate the indirect effect of Tβ4 peptide on RANKL-induced osteoclastogenesis, mouse BMMs were incubated with RANKL and CM, prepared from HPDLCs treated with H2O2 and different concentrations of Tβ4, and allowed to differentiate into osteoclasts. As shown in Fig 6, Tβ4 peptide dose-dependently decreased the number of osteoclasts and TRAP activity. To determine whether the reduction in osteoclast generation by Tβ4 could be due to effects of Tβ4 peptide on viability of the BMMs, a cytotoxicity assay was performed. The viability of BMMs was not significantly affected by Tβ4 peptide (data not shown).
Uterine contraction 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.[4]
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.
Mental health is so under-funded in the UK that pills can be used as the quick-fix option. In 2014/15, 57.8million prescriptions for antidepressants or SSRIs are filled out in England alone. You can wait months on a waiting list for cognitive behavioural therapy or to see a psychiatrist, and as you wait, medication is a lifeline. In addition to this mess, pharma giants have stopped looking for the 'next Prozac', cutting funding into new treatments by 70 percent in the last decade. The bottom line is clear: SSRIs, with all their pros and cons, are here to stay.

As reactive oxygen species (ROS) have been implicated in the pathogenesis of periodontitis [24], we examined whether H2O2 could down-regulate or up-regulate Tβ4 expression in PDLCs. As shown in Fig 1A and 1B, Tβ4 mRNA and protein expressions were down-regulated by H2O2 in a time- and concentration-dependent manner. Because maximal Tβ4 mRNA and protein expressions were achieved with 200 μM H2O2 within 48 hours in PDLCs, this concentration was used in subsequent experiments.
This is exactly the type of question myself, my team of coaches and the community in my Inner Circle can help to answer for you. The Inner Circle is a collective of people who are pursuing the same goals you are – trying to live a healthy, happy, adventurous, fulfilling and limitless life in a modern world. In the Inner Circle, we all help each other with questions, ideas, motivation, suggestions and much more!
However, the Food and Drug Administration and its equivalents in other countries have issued repeated advisory notices about Melanotan II, urging consumers to stop using and purchasing this unapproved product. David Carter of the United Kingdom's Medicines and Healthcare Products Regulatory Agency was unequivocal in his denunciation, warning would-be buyers against being "fooled into thinking that Melanotan offers a shortcut to a more even tan." Liverpool John Moores University researcher Michael Evans-Brown cautioned that the peptide may be linked to dyspepsia and various cardiovascular problems, such as increases in blood pressure, while others have noted it appears to stimulate the growth of moles on the body.
Consult a health care practitioner if symptoms persist or worsen. Consult a health care practitioner prior to use: if you are pregnant or breastfeeding; if you are taking carbidopa or drugs/supplements with serotonergic activity including, but not limited to, L-tryptophan, S-adenosylmethionine (SAMe), St. John's Wort, antidepressants, pain killers, over-the-counter cough and cold medication containing dextromethorphan, anti-nausea medication and anti-migraine medication. Discontinue use and consult a health care practitioner if you show signs of weakness, oral ulcers, or abdominal pain accompanied by severe muscle pain. Do not use if you have scleroderma. Exercise caution if operating heavy machinery, driving a motor vehicle or involved in activities requiring mental alertness. Some people may experience diarrhea, nausea, vomiting, abdominal pain and drowsiness.
I’ve tried researching this on my own but haven’t been able to find much. I have Hashimoto’s Thyroiditis & my endocrinologist says I barely have any thyroid left. Would TB-500 help regenerate new thyroid growth & if so where would I inject it?? I plan on taking this along with the BPC-157 (orally) for gut inflammation to see if it can repair leaky gut & digestive issues. Thoughts?

Addiction vulnerability: Concentrations of endogenous oxytocin can impact the effects of various drugs and one's susceptibility to substance use disorders. Additionally, bilateral interactions with numerous systems, including the dopamine system, Hypothalamic–pituitary–adrenal axis and immune system, can impact development of dependence. The status of the endogenous oxytocin system might enhance or reduce susceptibility to addiction through its interaction with these systems. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect addiction vulnerability.[72] Oxytocin may be related to the place conditioning behaviors observed in habitual drug abusers.
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

Oxytocin is known to be metabolized by the oxytocinase, leucyl/cystinyl aminopeptidase.[25][26] Other oxytocinases are also known to exist.[25][27] Amastatin, bestatin (ubenimex), leupeptin, and puromycin have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as vasopressin, met-enkephalin, and dynorphin A.[27][28][29][30]
Nolen, W. A., van de Putte, J. J., Dijken, W. A., Kamp, J. S., Blansjaar, B. A., Kramer, H. J., and Haffmans, J. Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine. Acta Psychiatr.Scand 1988;78(6):676-683. View abstract.
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