Genome-wide map of N6-methyladenosine circular RNAs identified in mice model of severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options.N6-methyladenosine(m6A)modification of circRNAs plays important roles in physiological and pathological processes.However,the roles of m6A circRNA in the pathological process of SAP remains unknown.AIM To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP.METHODS The SAP in C57BL/6 mice was induced using 4%sodium taurocholate salt.The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing.The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis.The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNAmicroRNA networks.The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP.RESULTS Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing,of which 32 were upregulated and 25 downregulated.Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP,such as regulation of autophagy and protein digestion.In m6A circRNA–miRNA networks,several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs,such as miR-24-3p,miR-26a,miR-92b,miR-216b,miR-324-5p and miR-762.Notably,the total m6A level of circRNAs was reduced,while the demethylase alkylation repair homolog 5 was upregulated in SAP.CONCLUSION m6A modification of circRNAs may be involved in the pathogenesis of SAP.Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.

Activities of autonomic neurotransmitters in meibomian gland tissues are associated with menopausal dry eye

The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.

Protective effect and mechanism of ginsenoside Rg1 on H2O2 induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro

OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1(Rg1) on H_2O_2-induced hippocampal neurons aging in vitro.METHODS The primary culture hippo.campal neurons(7 d) were randomly placed into six groups:normal control group,H_2O_2(200 μM) treat.ment group,and H_2O_2+Rg1(1,5 and 10μM) groups.The neurons were with Rg1(1,5 and 10 μmol·L^(-1))for 6 h.H_2O_2(200 μmol · L-1) was added to the medium and incubate for 18 h.The Dihydroethidium(DHE) staining was performed for ROS production assessment.The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis.The immunoblot was used to deter.mine the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L^(-1)) significantly reduced the ROS production,attenuated H_2O_2-induced neuronal damage and apoptosis(P<0.05,P<0.01).The immunoblot results showed that Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally,Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased IL-1β and IL-18 release in the supernatant.CONCLUSION The protective effect of Rg1 in H_2O_2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation.

Buyang Huanwu Decoction fraction protects against cerebral ischemia/reperfusion injury by attenuating the inflammatory response and cellular apoptosis

Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effect and mechanism of Buyang Huanwu Decoction fraction on ischemic injury both in vivo and in vitro. In vivo experiments showed that 50-200 mg/kg Buyang Huanwu Decoction fraction reduced infarct volume and pathological injury in ischemia/reperfusion rats, markedly inhibited expression of nuclear factor-KB and tumor necrosis factor-a and promoted nestin protein expression in brain tissue. Buyang Huanwu Decoction fraction （200 mg/kg） exhibited significant effects, which were similar to those of 100 mg/kg Ginkgo biloba extract. In vitro experimental results demonstrated that 10-100 mg/L Buyang Huanwu Decoction fraction significantly improved cell viability, decreased the release of lactate dehydrogenase and malondialdehyde levels, and inhibited the rate of apoptosis in HT22 cells following oxygen-glucose deprivation. Buyang Huanwu Decoction fraction （100 mg/L） exhibited significant effects, which were similar to those of 100 mg/L Ginkgo biloba extract. These findings suggest that Buyang Huanwu Decoction fraction may represent a novel, protective strategy against cerebral ischemia/reperfusion injury in rats and oxygen-glucose deprivation-induced damage in HT22 cells in vitro by attenuating the inflammatory response and cellular apoptosis.

Heavy Metal Assessment among Chinese Nonferrous Metal-exposed Workers from the Jinchang Cohort Study

Environmental exposure to heavy metals has been linked to a wide range of human health hazards. We detected the levels of 15 metals in urine samples from 500 representative sub-samples in an ongoing occupational cohort study （Jinchang Cohort） to directly evaluate metal exposure levels. Fifteen metals, namely As, Ba, Be, Cd, Cs, Cr, Co, Cu, Pb, Mn, Ni, Se, TI, U, and Zn, were detected by inductively coupled plasma quadruple mass spectrometry. The results showed that median creatinine adjustment and geometric mean urinary metal levels were higher in the heavy metal-exposed group, except Se and Zn, than other reported general or occupational populations. Further studies should address the effects of heavy metals on human health.

Prognostic Factors in COVID-19 Pneumonia with Severe Acute Respiratory Distress Syndrome: An Observational Study

Purpose: To identify prognostic factors in patients with coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS). Methods: In this study, we included 45 patients with COVID-19-associated ARDS hospitalized at The First Affiliated Hospital of Yangtze University in Jingzhou, Hubei, China, between January 22, 2020, and March 6, 2020. Clinical data and outcomes were reviewed and analyzed according to the Berlin definition. Findings: Men were more likely to develop severe ARDS than women (11 [91.7%] vs. 1 [8.3%]). Factors associated with severe ARDS included sex (male) (hazard ratio [HR], 13.75;95% confidence interval [CI], 1.45 - 130.24), neutrophil count (HR, 55.00;95% CI, 5.02 - 602.15), lymphocyte count (HR, 40.00;95% CI, 4.83 - 331.00), prothrombin time (HR, 12.14;95% CI, 1.19 - 123.62), D-dimer (HR, 11.00;95% CI, 1.16 - 103.94), total bilirubin levels (HR, 5.00;95% CI, 0.93 - 26.79), albumin (HR, 17.5;95% CI, 2.67 - 114.85), blood urea nitrogen levels (HR, 28.60;95% CI, 2.89 - 283.06), lactate dehydrogenase levels (HR, 6.00;95% CI, 1.17 - 30.73), and C-reactive protein levels (HR, 15.87;95% CI, 2.40 - 111.11). Conclusion: Laboratory indicators, such as neutrophil count and lymphocyte count, could play an important role in the diagnosis of severe ARDS and guide clinical decision-making for patients with ARDS.

Mammographic density and risk of breast cancer recurrence and mortality

To the Editor:Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females.Due to the advantages of low pain,high resolution,and good reproducibility,mammography is widely used in early breast cancer clinical screening.Mammography density(MD)is the proportion of dense breast tissue in mammograms and is one of the strongest risk factors for breast cancer.Studies have shown that high MD increases breast cancer risk by 4 to 6 times.A previous meta-analysis of 13 case-control studies showed a positive correlation(odds ratio[OR]:1.52,95%confidence interval[CI]:1.39-1.66)between percentage dense area and breast cancer risk,[1]but it did not assess the relationship between MD and breast cancer prognosis.

Biomimetic Ti-6Al-4V alloy/gelatin methacrylate hybrid scaffold with enhanced osteogenic and angiogenic capabilities for large bone defect restoration

Titanium-based scaffolds are widely used implant materials for bone defect treatment.However,the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone integration.To tackle these challenges,it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone defects.Herein,inspired by the microstructure and mechanical properties of natural bone tissue,we developed a Ti-6Al-4V alloy(TC4)/gelatin methacrylate(GelMA)hybrid scaffold with dual bionic features(GMPT)for bone defect repair.GMPT is composed of a hard 3D-printed porous TC4 metal scaffold(PT)backbone,which mimics the microstructure and mechanical properties of natural cancellous bone,and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular matrix.Ascribed to the unique dual bionic design,the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT,as confirmed by the in vitro and rabbit radius bone defect experimental results.Moreover,controlling the concentration of GelMA(10%)in GMPT can further improve the osteogenesis and angiogenesis of GMPT.The fundamental mechanisms were revealed by RNA-Seq analysis,which showed that the concentration of GelMA significantly influenced the expression of osteogenesis-and angiogenesis-related genes via the Pi3K/Akt/mTOR pathway.The results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects.