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.
An interesting concept that has emerged from initial findings is that regeneration and fibrosis are competing events in the vertebrate heart. That is, if there is a capacity for injury-stimulated cardiomyocyte hyperplasia beyond a certain threshold, regenerative mechanisms will overcome scarring. Results consistent with this idea came from experiments with zebrafish possessing a ts mutation in the cell-cycle checkpoint kinase Mps1 (Poss et al., 2002b). As mentioned earlier, mps1 mutants were initially identified based on their defects in caudal fin regeneration. Serendipitously, mps1 mutants also showed defects in cardiac regeneration at a temperature restrictive for the mutation (Poss et al., 2002b). Instead of regenerating muscle in response to ventricular resection injury, mps1 mutants repaired wounds by forming large, collagen-rich scars. Inhibition of Fgf signaling also stunts cardiac regeneration and causes scarring (Lepilina et al., 2006). These results indicate that even vertebrates with high cardiac regenerative capacity have a default scarring mechanism; normally, regeneration somehow restricts this pathway (Fig. 8). The implication is exciting; perhaps by stimulating regeneration in a poorly-regenerative system like the mammalian heart, scarring events characteristic of myocardial infarction would be restricted by new muscle formation. Similarly, deterring cardiac scarring mechanisms would perhaps favor regeneration in mammals.
That view has led some clinicians to try oxytocin as a treatment for psychiatric conditions such as autism spectrum disorder. But the early trials have had mixed results, and scientists are now seeking a deeper understanding of oxytocin and how it works in the brain. Researchers such as Froemke are showing that the hormone boosts neuronal signals in a way that could accentuate socially relevant input such as distress calls or possibly facial expressions. And clinical researchers are starting a wave of more ambitious trials to test whether oxytocin can help some types of autism.

The hormone does not act alone. In 2013, neuroscientist Robert Malenka at Stanford University in California and his colleagues showed that oxytocin works together with the neurotransmitter serotonin to reduce the excitability of neurons in the nucleus accumbens9, a brain region involved in reward. This process seems to support the preference of mice to return to environments where they had rewarding social interactions with other animals. “Oxytocin is part of a system,” Carter says, “and it's not the only molecule that matters, but it's one that in some way is regulatory over a large number of other systems.”
Like I said, it’s amazing stuff. And it shouldn’t come as a surprise that it affects that amazing part of your brain so intimately involved in keeping you safe…the amygdala. Remember, trust has a lot to do with survival among social animals who depend on each other for safety and protection. Show someone an untrustworthy face, and the amygdala is one of two areas that become more active than anywhere else in the brain.7 It is apparently programmed for reading trust just as it is for snakes or spiders.
The structure of oxytocin is very similar to that of vasopressin. Both are nonapeptides with a single disulfide bridge, differing only by two substitutions in the amino acid sequence (differences from oxytocin bolded for clarity): Cys – Tyr – Phe – Gln – Asn – Cys – Pro – Arg – Gly – NH2.[116] A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin article. Oxytocin and vasopressin were isolated and their total synthesis reported in 1954,[122] work for which Vincent du Vigneaud was awarded the 1955 Nobel Prize in Chemistry with the citation: "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone."[123]
Although research has shown that good communication predicts relationship success, successful communication in couples therapy won’t ensure that partners stay together. The goal is to help the two people understand each other’s point of view and come to a mutual decision, even if it’s to break up. “If people are not connected at all, then oxytocin is not going to force that connection,” Guastella says.
The diverse activities related to tissue repair may depend on interactions with receptors quite distinct from actin and possessing extracellular ligand-binding domains. Such multi-tasking by, or "partner promiscuity" of, proteins has been referred to as protein moonlighting.[14] Proteins such as thymosins which lack stable folded structure in aqueous solution, are known as intrinsically unstructured proteins (IUPs). Because IUPs acquire specific folded structures only on binding to their partner proteins, they offer special possibilities for interaction with multiple partners.[15] A candidate extracellular receptor of high affinity for thymosin β4 is the β subunit of cell surface-located ATP synthase, which would allow extracellular thymosin to signal via a purinergic receptor.[16]
Our nutrition team created these easy mix-and-match menus using the same guidelines that helped 5-HTP dieters lose weight at top speed during the University of Rome study. The idea here is simple: You’ll eat balanced meals that keep you feeling energized and awesome, but you’ll also watch portions so you’re not overeating out of habit. While using these menus, be sure to drink plenty of water and add any other zero-cal beverages you like. You’re also encouraged to season meals to your liking with unlimited herbs, spices, vinegar, mustard, and citrus juice. As always, get a doctor’s OK before trying any new plan.
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.
Horvath, G. A., Stockler-Ipsiroglu, S. G., Salvarinova-Zivkovic, R., Lillquist, Y. P., Connolly, M., Hyland, K., Blau, N., Rupar, T., and Waters, P. J. Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. Mol.Genet.Metab 2008;94:127-131. View abstract.
Its unique potential as a healing substance lies in that it interacts with cellular actin and regulates its activity. Tb4 prevents actin from assembling (polymerizing) to form filaments but supplies a pool of actin monomers (unpolymerized actin) when a cell needs filaments for its activity. A cell cannot divide if actin is polymerized. Tb4 therefore serves in vivo to maintain a reservoir of unpolymerized actin that will be put to use when cells divide, move and differentiate.
5-HTP works in the brain and central nervous system by increasing the production of the chemical serotonin. Serotonin can affect sleep, appetite, temperature, sexual behavior, and pain sensation. Since 5-HTP increases the synthesis of serotonin, it is used for several diseases where serotonin is believed to play an important role including depression, insomnia, obesity, and many other conditions.