Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

Sex-related differences in safety profiles, pharmacokinetics and tissue distribution of sinomenine hydrochloride in rats.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.

An Eco-Friendly Wood Adhesive Consisting of Soybean Protein and Cardanol-Based Epoxy for Wood Based Composites.

Formaldehyde-derived wood adhesives have dominated in woody composites production up to now, while facing a significant challenge in non-renewable raw materials and the formaldehyde emission. To solve these problems, an eco-friendly soybean protein-based wood adhesive was explored via the addition of renewable cardanol based epoxy (CBE) as cross-linking agent. The curing mechanism and viscosity of the adhesives were investigated and the bonding performance was evaluated with three-ply plywood. Fourier transformed infrared spectroscopy (FTIR) analysis confirmed the formation of new ether linkages and the consumption of epoxy groups in the cured adhesives, thereby improving the thermal stabilities and cohesion. Plywood bonded with the CBE-modified soybean protein-based adhesive reached the maximum wet shear strength of 1.11 MPa (4 wt.% CBE addition), a 48% increase compared to the control, whereas the viscosity of adhesive decreased by 68.2%. The wet shear strength of the plywood met the requirements of the Chinese National Standard GB/T 9846-2015 for interior plywood application. The formaldehyde-free adhesive with excellent water resistance adhesiveness performance shows great potential in woody composites as an alternative to formaldehyde derived wood adhesives.

Graphene Oxide Functionalized Cottonseed-Lignin Resin with Enhanced Wet Adhesion for Woody Composites Application.

With rising interior air pollution, health, and food shortage concerns, wood adhesives derived from non-food sustainable materials have therefore attracted considerable attention. Here we developed an eco-friendly cottonseed-lignin adhesive consisting of non-food defatted cottonseed flour (DCF), alkali lignin (AL), and graphene oxide (GO). The cation-π interaction, and hydrogen and covalent bonds between AL@GO and DCF collectively enhanced the cross-linking structure of the cured cottonseed-lignin adhesive, based on the Fourier-transform infrared spectroscopy, thermogravimetric analyses, scanning electron microscopy, and sol-gel tests. The high performance of the developed cottonseed-lignin adhesive was evidenced by its increased wet/dry shear strength and decreased rheological properties before curing and improved thermal stability and decreased soluble substances after curing. Particularly, the highest wet shear strength of poplar plywood bonded with cottonseed-lignin adhesive was 1.08 MPa, which increased by 74.2 and 54.3% as compared to the control and requirement of the Chinese standard GB/T 9846-2015 for interior plywood (≥0.7 MPa), respectively. The technology and resultant adhesives showed great potential in the preparation of green woody composites for many applications.

Improved wet shear strength in eco-friendly starch-cellulosic adhesives for woody composites.

Development of eco-friendly adhesives from renewable biomass has attracted considerable attention in recent years. Here, we present a novel approach via combination of waste newspaper (WNP) powder, oxidized glutinous rice starch, and polyamidoamine-epichlorohydrin (PAE) to prepare a formaldehyde-free starch-cellulosic adhesive (SCA) for woody composites. The oxidation treatment made the carboxyl/carbonyl groups more available in starch. Plywood bonded by the optimum SCA with 50 wt% of the WNP powder showed a wet shear strength of 0.83 MPa exceeding that of the oxidized starch adhesive by 130.5 %. During the curing process of SCA, the oxidized starch and WNP fiber participated into the crosslinking reaction with PAE via ester and ether bonds, as evidenced by FTIR analysis. The resulting cured adhesive had enhanced crystalline structures, thermal properties, hydrophobicity, wet-cohesion, rheological properties, and adhesiveness to wood. The SCA showed great potential in wood composites as an alternative to formaldehyde-derived adhesives.