Cedrol in ginger (Zingiber officinale) as a promising hair growth drug: The effects of oral and external administration on hair regeneration and its mechanism.

Ginger is an important cooking spice and herb worldwide, and scientific research has gradually confirmed the effect of ginger on preventing hair loss. Cedrol (CE) is a small sesquiterpene molecule in ginger and its external administration (EA) has shown hope in promoting hair growth, and alternative administration mode has become a potential treatment scheme to improve the efficacy of CE. The purpose of this study is to evaluate the effects of oral administration (OA) and EA of CE on hair regeneration of C57BL/6 alopecia areata (AA) mice induced by cyclophosphamide (CP) and to clarify the potential hair growth mechanism of CE in AA model in vitro and in vivo. The results showed that CE-OA has a shorter hair-turning black time and faster hair growth rate, and can lessen hair follicle damage induced by CP and promote hair follicle cell proliferation. Its effect is superior to CE-EA. At the same time, CE can increase the cytokines IFN-γ, IL-2, and IL-7 in the serum of mice, and decrease the expression of adhesion factors ICAM-1 and ELAM-1, thus alleviating the immunosuppression induced by CP. Mechanism research shows that CE regulates the JAK3/STAT3 signaling pathway, activates the Wnt3α/ß-catenin germinal center, and ameliorates oxidative stress induced by CP, thus promoting the proliferation of hair follicle cells and reversing AA. These results provide a theoretical basis for understanding the anti-AA mechanism of CE-OA, indicating that CE can be used as raw material for developing oral hair growth drugs.

The correlation of hearing prognosis and caloric test results in Meniere's disease: a follow up study.

BACKGROUND: Hearing loss is important in the diagnosis and treatment of Meniere's disease (MD). However, little is known about the factors associated with hearing changes in MD. AIMS/OBJECTIVES: This study aimed to investigate the correlation between hearing prognosis and caloric test (CT) results in MD. MATERIAL AND METHODS: Ninety consecutive patients diagnosed with unilateral definite MD underwent pure tone audiometry (PTA) and CT at initial visits, and were re-tested PTA at the 6-month follow-up. RESULTS: Fifty-three of ninety MD patients (58.89%) had abnormal CT results. The change of PTA (cPTA = initial PTA-last PTA) was negatively correlated with canal paresis (CP) values (overall association p = 0.032 and non-linear association p = 0.413). Multivariate linear model showed that as the CP value changed from 0 to 1, the cPTA decreased by -13.31 dB (95% CI: -24.03, -2.6) (p = 0.016). Stratified analysis found that the association was present in MD patients of Stage 1 and 2 (p < 0.05) but not in patients of Stage 3 and 4 (p > 0.05). CONCLUSIONS AND SIGNIFICANCE: Elevated CP values may be linked to worse hearing outcomes in MD, especially in Stage 1 and 2 patients. Conducting a caloric test at the initial consultation may aid in assessing hearing regression in MD.

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration.

JOURNAL/nrgr/04.03/01300535-202408000-00035/figure1/v/2023-12-16T180322Z/r/image-tiff Exosomes exhibit complex biological functions and mediate a variety of biological processes, such as promoting axonal regeneration and functional recovery after injury. Long non-coding RNAs (lncRNAs) have been reported to play a crucial role in axonal regeneration. However, the role of the lncRNA-microRNA-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network in exosome-mediated axonal regeneration remains unclear. In this study, we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts (FC-EXOs) and Schwann cells (SC-EXOs). Differential gene expression analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interaction network analysis were used to explore the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs. We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs, which suggests that it may promote axonal regeneration. In addition, using the miRWalk and Starbase prediction databases, we constructed a regulatory network of ceRNAs targeting Rps5, including 27 microRNAs and five lncRNAs. The ceRNA regulatory network, which included Ftx and Miat, revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury. Our findings suggest that exosomes derived from fibroblast and Schwann cells could be used to treat injuries of peripheral nervous system.

Metabolic profiling of a new synthetic cannabinoid receptor agonist, ADMB-FUBIATA, with human liver microsomes, human primary hepatocytes and human recombinant CYP450 enzymes using LC-quadrupole-orbitrap MS.

A novel synthetic cannabinoid receptor agonist (SCRA), ADMB-FUBIATA, featuring an acetamide-linked structure, has emerged on the illicit drug market. To provide dependable verification of its consumption and identify reliable biomarkers, we investigated an in vitro metabolism study of ADMB-FUBIATA incubated with human primary hepatocytes (HPHs) for the first time and correlated our findings with those from human liver microsomes (HLMs). In this work, ADMB-FUBIATA (10 µM) was incubated with HLM and HPH for 1 and 5 h, respectively, and then subjected to LC-quadrupole-orbitrap MS. A total of 25 metabolites across 8 metabolic pathways were identified after incubation with HLM and HPH, respectively. Monohydroxylation and N-dealkylation were the major metabolic pathways, and formation to ketone was first identified. In addition, the metabolism of ADMB-FUBIATA were found to be mediated by multiple CYP450 enzymes, predominantly CYP2C19, 2D6, and 3A4. This research also initially characterized the fragmentation patterns of the metabolites of ADMB-FUBIATA, elaborating on their structural relationship with ADMB-FUBIATA analogs. To effectively monitor ADMB-FUBIATA abuse, metabolites M4 and M1 were proposed as reliable biomarkers by cross-validating the HLM and HPH incubation results.

Chitosan/PLGA-based tissue engineered nerve grafts with SKP-SC-EVs enhance sciatic nerve regeneration in dogs through miR-30b-5p-mediated regulation of axon growth.

Extracellular vesicles from skin-derived precursor Schwann cells (SKP-SC-EVs) promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats. This study aimed at expanding the application of SKP-SC-EVs in nerve grafting by creating a chitosan/PLGA-based, SKP-SC-EVs-containing tissue engineered nerve graft (TENG) to bridge a 40-mm long sciatic nerve defect in dogs. SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions, supported the outgrowth and myelination of regenerated axons, and alleviated the denervation-induced atrophy of target muscles in dogs. To clarify the underlying molecular mechanism, we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons, and miR-30b-5p was the most important among others. We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK, STAT3 or CREB. Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.