Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis.

Introduction: Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis. Method: From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora. Results: The microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans. Conclusion: In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.

Polysaccharides from Callerya speciosa alleviate metabolic disorders and gut microbiota dysbiosis in diet-induced obese C57BL/6 mice.

Callerya speciosa ("Niu Dali" in Chinese) is a well-known edible plant in Southeast China. C. speciosa roots contain a high level of polysaccharides, which have been reported to show multiple health-promoting effects. In the current study, the anti-obesity effects of a crude extract of C. speciosa polysaccharides (NP) and its underlying mechanisms of action are investigated. C57BL/6 mice were divided into three groups and fed either a standard diet or a high-fat diet (HFD). The HFD + NP group mice received oral administration of NP (100 mg per kg per day) every other day for 10 weeks. NP supplementation alleviated HFD-induced diabetic biomarkers including body weight gain, hyperlipidemia, liver steatosis, and adipocyte hypertrophy. Western blot and RT-PCR analyses revealed that NP inhibited hepatic de novo lipogenesis and adipogenesis (i.e. decreased expression of Srebp1c, Fas, Cebpα, and Pparγ), stimulated adipocyte lipolysis (enhanced mRNA expression of Hsl and Mgl), and attenuated HFD-induced hepatic inflammation (decreased expression of TNF-α and NF-κB p65). Furthermore, 16S rDNA and GC-MS analyses showed that NP supplementation restored the Firmicutes/Bacteroidetes proportion, elevated colon-derived SCFAs, especially acetic acid content, and increased the relative abundance of genera associated with SCFA production in HFD-fed mice. Findings from this study suggest that NP alleviated HFD-induced obesity in a mouse model, which was possibly due to its ameliorative effects on diet-induced gut dysbiosis. Polysaccharides from C. speciosa are promising prebiotics and they may be further developed as functional foods for the management of obesity.

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions.

Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high-fat diet-induced T2DM mice and insulin-resistant (IR) HepG2 cells. In high-fat diet-induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK-TORC2-FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM.

Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by activating PINK1/Parkin-mediated mitophagy.

BACKGROUND: Tongue squamous cell carcinoma (tongue cancer) is one of the most common malignancies in the oral maxillofacial region. The tumor easily relapses after surgery, and the prognosis remains poor. Recently, zinc oxide nanoparticles (ZnO NPs) were shown to target multiple cancer cell types. In this study, we aimed to elucidate the anticancer effect of ZnO NPs on CAL 27 human tongue cancer cells and identify the role of PINK1/Parkin-mediated mitophagy in this effect. MATERIALS AND METHODS: We analyzed the dose-dependent cytotoxic effects of ZnO NPs on CAL 27 cells. Cells were cultured in media containing 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 µg/mL ZnO NPs for 24 h. We further examined the intracellular reactive oxygen species levels, monodansylcadaverine intensity and mitochondrial membrane potential following the administration of 25 µg/mL ZnO NPs for 4, 8, 12, or 24 h and investigated the role of PINK1/Parkin-mediated mitophagy in ZnO NP-induced toxicity in CAL 27 cells. RESULTS: The viability of CAL 27 cells decreased after treatment with increasing ZnO NP concentrations. The inhibitory concentration 50% of the ZnO NPs was calculated as 25 µg/mL. The ZnO NPs increased the intracellular reactive oxygen species levels and decreased the mitochondrial membrane potential in a time-dependent manner as well as activated the PINK1/Parkin-mediated mitophagy process in CAL 27 cells. CONCLUSION: Based on our findings, ZnO NPs may possess potential anticancer activity toward tongue cancer cells.

Identification and characterization of a novel ß-glucosidase via metagenomic analysis of Bursaphelenchus xylophilus and its microbial flora.

ß-glucosidases catalyze the final step of cellulose hydrolysis and are essential in cellulose degradation. A ß-glucosidase gene, cen502, was identified and isolated from a metagenomic library from Bursaphelenchus xylophilus via functional screening. Analyses indicated that cen502 encodes a 465 amino acid polypeptide that contains a catalytic domain belonging to the glycoside hydrolase family 1 (GH1). Cen502 was heterologously expressed, purified, and biochemically characterized. Recombinant Cen502 displayed optimum enzymatic activity at pH 8.0 and 38 °C. The enzyme had highest specific activity to p-nitrophenyl-ß-D-glucopyranoside (pNPG; 180.3 U/mg) and had K m and V max values of 2.334 mol/ml and 9.017 µmol/min/mg, respectively. The addition of Fe2+ and Mn2+ significantly increased Cen502 ß-glucosidase activity by 60% and 50%, respectively, while 10% and 25% loss of ß-glucosidase activity was induced by addition of Pb2+ and K+, respectively. Cen502 exhibited activity against a broad array of substrates, including cellobiose, lactose, salicin, lichenan, laminarin, and sophorose. However, Cen502 displayed a preference for the hydrolysis of ß-1,4 glycosidic bonds rather than ß-1,3, ß-1,6, or ß-1,2 bonds. Our results indicate that Cen502 is a novel ß-glucosidase derived from bacteria associated with B. xylophilus and may represent a promising target to enhance the efficiency of cellulose bio-degradation in industrial applications.