Structural analysis of a soluble polysaccharide GSPA-0.3 from the root of Panax ginseng C. A. Meyer and its adjuvant activity with mechanism investigation.

A novel polysaccharide (GSPA-0.3) was isolated and purified from the root of cultivated Panax ginseng C. A. Meyer, and its structure, adjuvant activities, and mechanisms for inducing the maturation of mouse dendritic 2.4 cells (DC2.4) were extensively studied. Fraction GSPA-0.3, mainly composed by the galacturonic acid, galactose, arabinose, glucose, rhamnose, mannose, and xylose, had a molecular weight of 62,722 Da. The main chain of GSPA-0.3 was composed of →3)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →3, 4)-α-D-GalpA-(1→. Branched chains comprised α-L-Araf-(1→3, 5)-α-L-Araf-(1→5)-α-L-Araf-(1→, α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Galp-(1→4)-ß-D-Galp-(1→4)-ß-D-Galp-(1→, and α-D-GalpA-(1→ units connected to the C3 position of →3, 4)-α-D-GalpA-(1→. In vivo, GSPA-0.3 was found to stimulate the production of IgG, IgG1, and IgG2a; increase the splenocyte proliferation index; and promote the expression of GATA-3, T-bet, IFN-γ, and IL-4 in H1N1 vaccine-immunized mice. Moreover, GSPA-0.3 significantly increased the levels of neutralizing antibodies in the mice, and its adjuvant activity was found to be superior to aluminum adjuvant (Alum adjuvant). Mechanistic investigations showed that GSPA-0.3 activated the TLR4-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and NF-κB proteins and gens. The results presented herein suggested that GSPA-0.3 could significantly promote the efficacy of the H1N1 vaccine by modulating Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway.

Mitophagy in metabolic syndrome.

Metabolic syndrome (MS), a chronic and non-communicable pathological condition, is characterized by a constellation of clinical manifestations including insulin resistance, abdominal adiposity, elevated blood pressure, and perturbations in lipid metabolism. The prevalence of MS has increased dramatically in both developed and developing countries and has now become a truly global problem. Excessive energy intake and concomitant obesity are the main drivers of this syndrome. Mitophagy, in which cells degrade damaged mitochondria through a selective form of autophagy, assumes a crucial position in the regulation of mitochondrial integrity and maintenance. Abnormal mitochondrial quality could result in a spectrum of pathological conditions related to metabolic dysfunction, including metabolic syndrome, cardiovascular ailments, and neoplasms. Recently, there has been a proliferation of research pertaining to the process of mitophagy in the context of MS, and there are various regulatory pathways in MS, including pathways like the ubiquitin-dependent mechanism and receptor-mediated mechanisms, among others. Furthermore, studies have uncovered that the process of mitophagy serves a defensive function in the advancement of Metabolic Syndrome, and inhibition of mitophagy exacerbates the advancement of MS. As a result, the regulation of mitophagy holds great promise as a therapeutic approach in the management of Metabolic Syndrome. In this comprehensive analysis, the authors present a synthesis of the diverse regulatory pathways involved in mitophagy in the context of Metabolic Syndrome, as well as its modes of action in metabolic disorders implicated in the development of MS, Including obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM), offering novel avenues for the prophylaxis and therapeutic management of MS.

Hesperidin alleviates insulin resistance by improving HG-induced oxidative stress and mitochondrial dysfunction by restoring miR-149.

BACKGROUND: Hesperidin, a natural flavanone, has been proven to have multiple protective effects in diabetic rats, such as antioxidant, anti-inflammatory and anti-apoptotic effects. However, the molecular mechanisms underlying the effects of hesperidin are not well elucidated. METHODS: LO2 cells were stimulated with high glucose (HG, 33 mM) for 24 h to establish a model of oxidative stress. Then, cell viability was determined using the MTT assay. The antioxidant activities, including the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, mitochondrial membrane potential (MMP) and adenosine-triphosphate (ATP) production, were measured with the corresponding kits. The levels of gene expression, protein expression and methylation were detected using qRT-PCR, western blotting and methylation-specific PCR (MSP) assays, respectively. RESULTS: Compared to the NG treatment, hesperidin treatment increased the viability and improved the oxidative stress, mitochondrial dysfunction and insulin resistance of HG-treated LO2 cells, and these effects were correlated with heightened SOD and GPx activities, increased MMP level and ATP generation, reduced MDA, ROS and glucose levels, and activated GSK3ß/AKT and inactivated IRS1 signals. Mechanistically, hesperidin treatment enhanced the miR-149 expression level by reducing its promoter methylation by inhibiting DNMT1. Importantly, knockdown of miR-149 obviously abolished the biological roles of hesperidin. CONCLUSIONS: Our findings demonstrated that hesperidin treatment ameliorated HG-induced insulin resistance by reducing oxidative stress and mitochondrial dysfunction partly by suppressing DNMT1-mediated miR-149 silencing.

Efficacy and safety of Chinese medicine for obstructive sleep apnea: A protocol for systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is significant public concern. Clinical practice indicates that Chinese medicine has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of Chinese medicine for OSA. METHODS: Data in PubMed, Embase, Web of Science, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSA children were identified, in which the effects of Chinese medicine on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of Chinese medicine for OSA were evaluated in terms of apnea hypopnea index (AHI, the average and lowest blood oxygen, the Epworth Sleep Scale [ESS], and adverse effects). CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of Chinese medicine for OSA. PROSPERO REGISTRATION NUMBER: CRD42020154864.

Efficacy and safety of montelukast for pediatric obstructive sleep apnea syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Pediatric obstructive sleep apnea syndrome (OSAS) is significant public concern. Clinical practice indicates that montelukast has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of montelukast for pediatric OSAS. METHODS: Data in Pubmed, EMBASE, CENTRAL, CBM, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSAS children were identified, in which the effects of montelukast on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of montelukast in the treatment of pediatric OSAS were evaluated in terms of apnea hypopnea index (AHI), the Pittsburgh Sleep Quality Index, the Epworth Sleep Scale (ESS), neck circumference, important index in Polysomnography: sleep efficiency, desaturation index, total sleep time. CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of montelukast in the treatment of pediatric OSAS. PROSPERO REGISTRATION NUMBER: CRD42020146940.

Berberine ameliorates obesity-induced chronic inflammation through suppression of ER stress and promotion of macrophage M2 polarization at least partly via downregulating lncRNA Gomafu.

BACKGROUND: Berberine has been established as a potential drug for inflammation and metabolic disorder. Here, we aimed to explore the effects and the underlying mechanisms of berberine on obesity-induced chronic inflammation. METHODS: Mice were fed with high-fat diet to induce obesity. Inflammation in adipocytes were induced with treatment of free fatty acids. The expression of IL-4, CD206, ARG1 and other markers were used to identify M1 and M2 polarization. The expression of GPR78 and CHOP were used to evaluate endoplasmic reticulum stress. H&E staining was used to reveal the adipose tissue macrophage and adipocytes enlargement. RESULTS: Berberine treatment attenuated endoplasmic reticulum stress and inflammation in obese mice and free fatty acids-treated adipocytes. Overexpression of lncRNA Gomafu partially blocked the protective effects of berberine in free fatty acids-treated adipocytes by increasing endoplasmic reticulum stress. Moreover, Gomafu overexpression partly reversed berberine-induced enhancement of M2 polarization in macrophages. Finally, Gomafu overexpression induced ER stress and inflammation in mice, which were improved by berberine administration. CONCLUSIONS: Berberine improves obesity-induced chronic inflammation by alleviating endoplasmic reticulum stress and consequently promoting macrophage M2 polarization. And these protective effects were mediated at least partly by the suppression of lncRNA Gomafu.

Research advances on microbial genetics in China in 2015.

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

[The role of the carboxy-terminal domain of the RNA polymerase II on coupling mRNA transcription with processing].

The carboxy-terminal domain of the largest subunit of the RNA polymerase II (CTD) is comprised of multiple repeats of a conserved heptapeptide with the consensus sequence-Tyr-Ser-Pro-Thr-Ser-Pro-Ser-. In the past decade,much attention has been payed to this specific structure. Many experiments showed that the CTD played a pivotal role in the coupling mechanism that links mRNA transcription with processing by associating with the transcriptional and processing factors. The recent advance of the structure and functions is summarized in this paper.