Genome-wide identification of target genes of a mating-type α-domain transcription factor reveals functions beyond sexual development.

Penicillium chrysogenum is the main industrial producer of the ß-lactam antibiotic penicillin, the most commonly used drug in the treatment of bacterial infections. Recently, a functional MAT1-1 locus encoding the α-box transcription factor MAT1-1-1 was discovered to control sexual development in P. chrysogenum. As only little was known from any organism about the regulatory functions mediated by MAT1-1-1, we applied chromatin immunoprecipitation combined with next-generation sequencing (ChIP-seq) to gain new insights into the factors that influence MAT1-1-1 functions on a molecular level and its role in genome-wide transcriptional regulatory networks. Most importantly, our data provide evidence for mating-type transcription factor functions that reach far beyond their previously understood role in sexual development. These new roles include regulation of hyphal morphology, asexual development, as well as amino acid, iron, and secondary metabolism. Furthermore, in vitro DNA-protein binding studies and downstream analysis in yeast and P. chrysogenum enabled the identification of a MAT1-1-1 DNA-binding motif, which is highly conserved among euascomycetes. Our studies pave the way to a more general understanding of these master switches for development and metabolism in all fungi, and open up new options for optimization of fungal high production strains.

A clinical trial to investigate the effect of Cynatine HNS on hair and nail parameters.

OBJECTIVE: A new, novel product, Cynatine HNS, was evaluated for its effects as a supplement for improving various aspects of hair and nails in a randomized, double-blind, placebo-controlled clinical trial. METHODS: A total of 50 females were included and randomized into two groups. The active group (n = 25) received 2 capsules containing Cynatine HNS, comprised of Cynatine brand keratin (500 mg) plus vitamins and minerals, per day, and the placebo group (n = 25) received 2 identical capsules of maltodextrin per day for 90 days. End points for hair loss, hair growth, hair strength, amino acid composition, and hair luster were measured. End points were also measured for nail strength and the appearance of nails. RESULTS: The results show that subjects taking Cynatine HNS showed statistically significant improvements in their hair and nails when compared to placebo. CONCLUSION: Cynatine HNS is an effective supplement for improving hair and nails in 90 days or less. EudraCT number is 2014-002645-22.

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT).

There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.

A randomized, double-blind, placebo-controlled clinical trial to investigate the effect of Cynatine® FLX on symptoms of osteoarthritis.

OBJECTIVE: A novel product Cynatine® FLX was evaluated on symptoms associated with knee osteoarthritis in a randomized, double-blind, placebo-controlled clinical trial. METHODS: A total of 50 males and females were included and randomized into two groups. The active group (n = 25) received two capsules totaling 500 mg of Cynatine® FLX per day and the placebo group (n = 25) received an identical two capsules of maltodextrin per day for 60 days. The WOMAC® Osteoarthritis Index, SF-36, and Lequesne Index of Severity were used to evaluate the symptoms. RESULTS: The results show that Cynatine® FLX was twice as effective in reducing pain scores as compared to placebo. Cynatine® FLX showed the same effectiveness in reducing stiffness. CONCLUSION: This new product may be effective in relieving symptoms of knee osteoarthritis.