Risk factor analysis and nomogram for predicting poor symptom control in smoking asthmatics.

BACKGROUND: Smoking induces and modifies the airway immune response, accelerating the decline of asthmatics' lung function and severely affecting asthma symptoms' control level. To assess the prognosis of asthmatics who smoke and to provide reasonable recommendations for treatment, we constructed a nomogram prediction model. METHODS: General and clinical data were collected from April to September 2021 from smoking asthmatics aged ≥14 years attending the People's Hospital of Zhengzhou University. Patients were followed up regularly by telephone or outpatient visits, and their medication and follow-up visits were recorded during the 6-months follow-up visit, as well as their asthma control levels after 6 months (asthma control questionnaire-5, ACQ-5). The study employed R4.2.2 software to conduct univariate and multivariate logistic regression analyses to identify independent risk factors for 'poorly controlled asthma' (ACQ>0.75) as the outcome variable. Subsequently, a nomogram prediction model was constructed. Internal validation was used to test the reproducibility of the model. The model efficacy was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve. RESULTS: Invitations were sent to 231 asthmatics who smoked. A total of 202 participants responded, resulting in a final total of 190 participants included in the model development. The nomogram established five independent risk factors (P<0.05): FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and good or poor medication adherence. The area under curve (AUC) of the modeling set was 0.824(95%CI 0.765-0.884), suggesting that the nomogram has a high ability to distinguish poor asthma control in smoking asthmatics after 6 months. The calibration curve showed a C-index of 0.824 for the modeling set and a C-index of 0.792 for the self-validation set formed by 1000 bootstrap sampling, which means that the prediction probability of the model was consistent with reality. Decision curve analysis (DCA) of the nomogram revealed that the net benefit was higher when the risk threshold probability for poor asthma control was 4.5 - 93.9%. CONCLUSIONS: FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and medication adherence were identified as independent risk factors for poor asthma control after 6 months in smoking asthmatics. The nomogram established based on these findings can effectively predict relevant risk and provide clinicians with a reference to identify the poorly controlled population with smoking asthma as early as possible, and to select a better therapeutic regimen. Meanwhile, it can effectively improve the medication adherence and the degree of attention to complications in smoking asthma patients.

Laccase immobilization and its degradation of emerging pollutants: A comprehensive review.

The chronic lack of effective disposal of pollutants has resulted in the detection of a wide variety of EPs in the environment, with concentrations high enough to affect ecological health. Laccase, as a versatile oxidase capable of catalyzing a wide range of substrates and without producing toxic by-products, is a potential candidate for the biodegradation of pollutants. Immobilization can provide favorable protection for free laccase, improve the stability of laccase in complex environments, and greatly enhance the reusability of laccase, which is significant in reducing the cost of industrial applications. This study introduces the properties of laccase and subsequently elaborate on the different support materials for laccase immobilization. The research advances in the degradation of EDs, PPCPs, and PAHs by immobilized laccase are then reviewed. This review provides a comprehensive understanding of laccase immobilization, as well as the advantages of various support materials, facilitating the development of more economical and efficient immobilization systems that can be put into practice to achieve the green degradation of EPs.

Berberine and health outcomes: An umbrella review.

Berberine is a plant extract widely used in clinical practice. This review aimed to summarize and to grade the available evidence on the association between berberine consumption and health-related outcomes. The PubMed, Cochrane Library, and Embase databases were searched for meta-analyses of randomized controlled trials (RCTs) assessing the efficacy and safety of berberine from inception to June 30, 2022. The AMSTAR-2 and GRADE system were used to assess the methodological quality and evidence level of the included meta-analyses. A total of 11 eligible meta-analyses were identified from 235 publications, which were published in peer-reviewed journals between 2013 and 2022. The results revealed that berberine significantly affects blood glucose levels, insulin resistance, blood lipids, body parameters and composition, inflammatory markers, colorectal adenomas, and Helicobacter pylori infections as compared to controls. Common side effects of berberine consumption include gastrointestinal symptoms, such as constipation and diarrhea. Berberine is a safe medicinal plant ingredient that improves various clinical outcomes; however, there is a need for improvement of methodological quality in published meta-analyses. Additionally, the clinical effects of berberine need to be confirmed in high-quality RCTs.

Photoelectrochemical Enzyme Biosensor Based on TiO2 Nanorod/TiO2 Quantum Dot/Polydopamine/Glucose Oxidase Composites with Strong Visible-Light Response.

Although photoelectrochemical (PEC) enzyme biosensors based on visible-light detection would have a high practical value, their development has been limited by the weak visible-light response of available photoactive substrates. Here, to enhance the visible-light response of a photoelectric substrate, a TiO2 nanorods (NRs)/TiO2 quantum dots (QDs)/polydopamine (PDA)/glucose oxidase nanocomposite was prepared via hydrothermal synthesis, followed by photopolymerization. TiO2 QDs with strong light absorption and excellent photocatalytic activity were introduced between the TiO2 NRs and the PDA. An efficient electron transport interface that formed as a result of the combination of the TiO2 NRs, TiO2 QDs, and the PDA could not only transfer electrons quickly and orderly, but also substantially improve the response of the TiO2 NRs under visible light. Through a series glucose detection, a sensor based on the nanocomposite was found to exhibit superior sensing performance under visible light with a sensitivity of 4.63 µA mM-1 cm-2, a linear response over the concentration 0.1-4 mM, and a detection limit of 8.16 µM. This work proposes a biosensor that can detect under visible light, thereby expanding the application range of PEC enzyme biosensors.

The Association between Helicobacter pylori Seropositivity and Bone Mineral Density in Adults.

Objectives: Current evidence on the associations between Helicobacter pylori (H. pylori) infection and bone mineral density (BMD) is conflicting. Therefore, a nationally representative sample of adults was analyzed to investigate the associations of H. pylori seropositivity and BMD in this study. Methods: A retrospective cross-sectional study was conducted with 2555 subjects aged 40-85 years in the US National Health and Nutrition Examination Survey (NHANES) 1999-2001. Multivariable logistic regression models were performed to evaluate the associations between H. pylori seropositivity and BMD. Subgroup analyses stratified by sex, age, race, and body mass index (BMI) were performed. Results: No association was found between H. pylori seropositivity and BMD (ß = 0.006, 95% CI: -0.003 to 0.015, P = 0.177). In the subgroup analyses stratified by age, a positive association was observed between the H. pylori seropositivity and total BMD among subjects aged 40-55 years (ß = 0.018, 95% CI: 0.004 to 0.033, P = 0.012); in the subgroup analyses stratified by sex, a positive association was observed between the H. pylori seropositive and total BMD in male (ß = 0.019, 95% CI: 0.007 to 0.032, P = 0.003); in the subgroup analyses stratified by age and sex, the total BMD was higher in men aged 40-55 years with H. pylori seropositive than those with H. pylori seronegative (ß = 0.034, 95% CI: 0.013 to 0.056, P = 0.002). Conclusions: In conclusion, no association between H. pylori seropositive and total BMD was demonstrated among most middle-aged and elderly adults. H. pylori infection may not be one key factor in the loss of BMD.

Determination of Cr(VI) based on the peroxidase mimetic catalytic activity of citrate-capped gold nanoparticles.

Highly negatively charged gold nanoparticles (AuNPs) are shown to have strong simulated oxidase activity and effectively boosted the oxidation of enzyme substrate 3,3',5,5'-tetramethylbenzidine (TMB) by hexavalent chromium ion Cr(VI), resulting in the formation of oxidation product with blue color. Based on this, a facile colorimetric assay was developed to detect Cr(VI) at a range 0.008~0.156 mg/L with r = 0.996. The detection limit was estimated to be 0.52 µg/L. In addition, the colorimetric assay showed high selectivity against 28 other interfering ions. It was performed at room temperature and required about half an hour including the preparation of AuNPs. The assay was successfully applied to the determination of Cr(VI) in spiked water samples, and recoveries in the range 95.00-105.40% were obtained. This work paves a way for design of high performance sensor based on highly active nanozymes and also provides an extremely practical analytical tool for the monitoring of Cr(VI) in the environment.

Practical aptamer-based assay of heavy metal mercury ion in contaminated environmental samples: convenience and sensitivity.

Due to heavy metals' magnified pollution from their accumulation in the ecosystem, practical detection of ultra-low concentration of heavy metals in environmental sample is of great significance for environmental supervision and maintenance of people's health. Herein, a practical and sensitive assay of heavy metal mercury was developed by visually observing (or spectrum detecting) the change of cationic gold nanoparticles (AuNPs), which is directly caused by mercury ion induced hybridization between non-canonical base pairs. In this assay, signal probe's response was direct rather than the indirect salt induction, thus avoiding the defect of salt-induced indirect response. It makes the analysis more sensitive. The results showed that the response of 8.2 × 10-8 M Hg2+ could be observed with naked eye and the detection limit of Hg2+ in spectrometric determination was 4.9 × 10-11 M, which is more than one order of magnitude lower than that from indirect response pattern of signal probe. In addition, high specificity of the affinity chemistry for T-Hg-T renders the assay to be highly selective. Compared with the results of cold vapor atom adsorption spectroscopy (CVAAS), this analysis has good reliability for the detection of mercury. The results fully indicate that the developed assay is an ideal alternative for online detection of heavy metal mercury in environmental pollution samples.

Dimethyl Sulfoxide: An Ideal Electrochemical Probe for Hydroxyl Radical Detection.

In situ and real-time determination of hydroxyl radicals (•OH) in physiological and pathological processes is a great challenge due to their ultrashort lifetime. Herein, an electrochemical method was developed by using dimethyl sulfoxide (DMSO) as a trapping probe for rapid determination of •OH in aqueous solution. When DMSO reacted with •OH, an intermediate product methane sulfinic acid (MSIA) was formed, which can be electrochemically oxidized to methanesulfonic acid (MSA) on the glassy carbon electrode (GCE), resulting in a distinct voltammetric signal that is directly proportional to the concentration of •OH. Other commonly encountered reactive oxygen species (ROS), including hypochlorite anions (ClO-), superoxide anions (O2•-), sulfate radicals (SO4•-), and singlet oxygen (1O2), have showed no interference for •OH determination. Thus, an electrochemical method was developed for the determination of •OH, which exhibits a wide linear range (0.4-5120 µM) and a low limit detection of 0.13 µM (S/N = 3) and was successfully applied for the quantification of •OH in aqueous extracts of cigarette tar (ACT). Alternatively, the same reaction mechanism is also applicable for the determination of DMSO, in which a linear range of 40-320 µM and a detection limit 13.3 µM (S/N = 3) was achieved. The method was used for the evaluation of DMSO content in cell cryopreservation medium. This work demonstrated that DMSO can serve as an electrochemical probe and has valuable application potential in radical study, biological research, and environmental monitoring.

Rhein against Staphylococcus xylosus by interfering with respiratory metabolism and inducing oxidative stress.

Currently, dairy mastitis caused by Staphylococcus xylosus poses a serious challenge for dairy farming. In this study, we explored the role and mechanism of rhein against S. xylosus with the hope of providing new research ideas to solve mastitis in dairy cows and ensure the source safety of dairy products. Through in vitro antimicrobial studies, we found that the minimum inhibitory concentration (MIC) of rhein was 64 µg/mL, and it significantly interfered with the formation of S. xylosus biofilm at sub-MIC. In experiments on mastitis in mice, rhein alleviated inflammation in mammary tissue, reduced the levels of TNF-α and IL-6, and decreased the number of S. xylosus. To explore the anti-S. xylosus mechanism of rhein, we identified the relevant proteins involved in carbon metabolism (Glycolysis/gluconeogenesis, TCA cycle, Fatty acid degradation) through proteomics. Additionally, proteins associated with the respiratory chain, oxidative stress (proteins of antioxidant and DNA repair), and nitrate respiration were also found to be upregulated. Thus, rhein may act as an antibacterial agent by interfering with the respiratory metabolism of S. xylosus and inducing the production of ROS, high levels of which alter the permeability of bacterial cell membranes and cause damage to them. We measured the concentrations of extracellular ß-galactosidase and nucleic acids. Additionally, SEM observation of S. xylosus morphology showed elevated membrane permeability and damage to the cell membrane. Finally, RT-PCR experiments showed that mRNAs of key proteins of the TCA cycle (odhA, mqo) and nitrate respiration (nreB, nreC, narG) were significantly up-regulated, consistent with proteomic results. In conclusion, rhein has good anti-S. xylosus effects in vitro and in vivo, by interfering with bacterial energy metabolism, inducing ROS production, and causing cell membrane and DNA damage, which may be one of the important mechanisms of its antimicrobial activity.

Bioinformatics and Integrative Experimental Method to Identifying and Validating Co-Expressed Ferroptosis-Related Genes in OA Articular Cartilage and Synovium.

Purpose: Osteoarthritis (OA) is the most common joint disease worldwide and is the primary cause of disability and chronic pain in older adults.Ferroptosis is a type of programmed cell death characterized by aberrant iron metabolism and reactive oxygen species accumulation; however, its role in OA is not known. Methods: To identify ferroptosis markers co-expressed in articular cartilage and synovium samples from patients with OA, in silico analysis was performed.Signature genes were analyzed and the results were evaluated using a ROC curve prediction model.The biological function, correlation between Signature genes, immune cell infiltration, and ceRNA network analyses were performed. Signature genes and ferroptosis phenotypes were verified through in vivo animal experiments and clinical samples. The expression levels of non-coding RNAs in samples from patients with OA were determined using qRT-PCR. ceRNA network analysis results were confirmed using dual-luciferase assays. Results: JUN, ATF3, and CDKN1A were identified as OA- and ferroptosis-associated signature genes. GSEA analysis demonstrated an enrichment of these genes in immune and inflammatory responses, and amino acid metabolism. The CIBERSORT algorithm showed a negative correlation between T cells and these signature genes in the cartilage, and a positive correlation in the synovium. Moreover, RP5-894D12.5 and FAM95B1 regulated the expression of JUN, ATF3, and CDKN1A by competitively binding to miR-1972, miR-665, and miR-181a-2-3p. In vivo, GPX4 was downregulated in both OA cartilage and synovium; however, GPX4 and GSH were downregulated, while ferrous ions were upregulated in patient OA cartilage and synovium samples, indicating that ferroptosis was involved in the pathogenesis of OA. Furthermore, JUN, ATF3, and CDKN1A expression was downregulated in both mouse and human OA synovial and cartilage tissues. qRT-PCR demonstrated that miR-1972, RP5-894D12.5, and FAM95B1 were differentially expressed in OA tissues. Targeted interactions between miR-1972 and JUN, and a ceRNA regulatory mechanism between RP5-894D12.5, miR-1972, and JUN were confirmed by dual-luciferase assays. Conclusion: This study identified JUN, ATF3, and CDKN1A as possible diagnostic biomarkers and therapeutic targets for joint synovitis and OA. Furthermore, our finding indicated that RP5-894D12.5/miR-1972/JUN was a potential ceRNA regulatory axis in OA, providing an insight into the connection between ferroptosis and OA.

Physiological Mechanisms Underlying Tassel Symptom Formation in Maize Infected with Sporisorium reilianum.

Head smut is a soil-borne fungal disease caused by Sporisorium reilianum that infects maize tassels and ears. This disease poses a tremendous threat to global maize production. A previous study found markedly different and stably heritable tassel symptoms in some maize inbred lines with Sipingtou blood after infection with S. reilianum. In the present study, 55 maize inbred lines with Sipingtou blood were inoculated with S. reilianum and classified into three tassel symptom types (A, B, and C). Three maize inbred lines representing these classes (Huangzao4, Jing7, and Chang7-2, respectively) were used as test materials to investigate the physiological mechanisms of tassel formation in infected plants. Changes in enzyme activity, hormone content, and protein expression were analyzed in all three lines after infection and in control plants. The activities of peroxidase (POD), superoxide dismutase (SOD), and phenylalanine-ammonia-lyase (PAL) were increased in the three typical inbred lines after inoculation. POD and SOD activities showed similar trends between lines, with the increase percentage peaking at the V12 stage (POD: 57.06%, 63.19%, and 70.28% increases in Huangzao4, Jing7, and Chang7-2, respectively; SOD: 27.01%, 29.62%, and 47.07% in Huangzao4, Jing7, and Chang7-2, respectively. These were all higher than in the disease-resistant inbred line Mo17 at the same growth stage); this stage was found to be key in tassel symptom formation. Levels of gibberellic acid (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) were also altered in the three typical maize inbred lines after inoculation, with changes in GA3 and IAA contents tightly correlated with tassel symptoms after S. reilianum infection. The differentially expressed proteins A5H8G4, P09233, and Q8VXG7 were associated with changes in enzyme activity, whereas P49353, P13689, and P10979 were associated with changes in hormone contents. Fungal infection caused reactive oxygen species (ROS) and nitric oxide (NO) bursts in the three typical inbred lines. This ROS accumulation caused biofilm disruption and altered host signaling pathways, whereas NO signaling triggered strong secondary metabolic responses in the host and altered the activities of defense-related enzymes. These factors together resulted in the formation of varying tassel symptoms. Thus, interactions between S. reilianum and susceptible maize materials were influenced by a variety of signals, enzymes, hormones, and metabolic cycles, encompassing a very complex regulatory network. This study preliminarily identified the physiological mechanisms leading to differences in tassel symptoms, deepening our understanding of S. reilianum-maize interactions.

Auxin promotes hypocotyl elongation by enhancing BZR1 nuclear accumulation in Arabidopsis.

Auxin and brassinosteroids (BRs) are two major growth-promoting phytohormones that shape hypocotyl elongation; however, the cross-talk between auxin and BR in this process is not fully understood. In this study, we found that auxin-induced hypocotyl elongation is dependent on brassinazole-resistant 1 (BZR1), a core BR signaling component. Auxin promotes BZR1 nuclear accumulation in hypocotyl cells, a process dependent on mitogen-activated protein kinase 3 (MPK3) and MPK6, which are both activated by auxin and whose encoding genes are highly expressed in hypocotyls. We determined that MPK3/MPK6 phosphorylate and reduce the protein stability of general regulatory factor 4 (GRF4), a member of the 14-3-3 family of proteins that retain BZR1 in the cytoplasm. In summary, this study reveals the molecular mechanism by which auxin promotes hypocotyl elongation by enhancing BZR1 nuclear accumulation via MPK3/MPK6-regulated GRF4 protein stability.

Identifying Bioactive Ingredients and Antioxidant Activities of Wild Sanghuangporus Species of Medicinal Fungi.

Sanghuangporus refers to a group of rare medicinal fungi with remarkable therapeutic properties. However, current knowledge on the bioactive ingredients and antioxidant activities of different species of this genus is limited. In this study, a total of 15 wild strains from 8 species of Sanghuangporus were selected as the experimental materials for identification of the bioactive components (polysaccharide, polyphenol, flavonoid, triterpenoid, and ascorbic acid) and antioxidant activities (scavenging activities against hydroxyl, superoxide, DPPH, and ABTS radicals; superoxide dismutase activity; and ferric reducing ability of plasma). Notably, individual strains contained different levels of various indicators, among which Sanghuangporus baumii Cui 3573, S. sanghuang Cui 14419 and Cui 14441, S. vaninii Dai 9061, and S. zonatus Dai 10841 displayed the strongest activities. The correlation analysis of bioactive ingredients and antioxidant activities revealed that the antioxidant capacity of Sanghuangporus is mainly associated with the contents of flavonoid and ascorbic acid, followed by polyphenol and triterpenoid, and finally, polysaccharide. Together, the results obtained from the comprehensive and systematic comparative analyses contribute further potential resources and critical guidance for the separation, purification, and further development and utilization of bioactive agents from wild Sanghuangporus species, as well as the optimization of their artificial cultivation conditions.

The disturbance of thyroid-associated hormone and its receptors in brain and blood circulation existed in the early stage of mouse model of Alzheimer's disease.

BACKGROUND: Studies showed that thyroid function plays an important role in the pathology of Alzheimer's disease (AD). However, changes in brain thyroid hormone and related receptors in the early stage of AD were rarely reported. The aim of this study was to explore the relationship between the early stage of AD and local thyroid hormone and its receptors in the brain. METHODS: The animal model was established by stereotactic injection of okadaic acid (OA) into hippocampal region for the experiment, and 0.9% NS for the control. Blood sample from each mouse was collected and then the mice were sacrificed and the brain tissue was collected for detecting free triiodothyronine (FT3), free thyroid hormone (FT4), and thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH) and phosphorylated tau, amyloid-ß (Aß) and thyroid hormone receptors (THRs) in the hippocampus of the mice were detected as well. RESULTS: Enzyme-linked immunosorbent assay showed that compared with the control, FT3, FT4, TSH and TRH in brain were significantly increased in the experimental group; in the serum, FT4, TSH and TRH were increased, while FT3 had no change; western blot analysis indicated that the expression of THR α and ß in the hippocampus of the experimental group was significantly higher than that of the control. CONCLUSION: Based on the results of this study, a mouse AD model can be established successfully by injecting a small dose of OA into the hippocampus. We speculate that early AD brain and circulating thyroid dysfunction may be an early local and systemic stress repair response.

Ginseng and health outcomes: an umbrella review.

Background: Ginseng consumption has been associated with various health outcomes. However, there are no review articles summarizing these reports. Methods: PubMed, Embase, the Cochrane Library of Systematic Reviews, Scopus, CNKI and Wanfang databases were searched from inception to 31 July 2022. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence in each meta-analysis, and the results were summarized in a narrative form. Results: Nineteen meta-analyses that met the eligibility criteria were identified from among 1,233 papers. The overall methodological quality was relatively poor, with only five studies being low-quality, and 14 critically low-quality. When compared with control treatments (mainly placebo), ginseng was beneficial for improving fatigue and physical function, sexual function, menopausal symptoms, metabolic indicators, inflammatory markers, unstable angina and respiratory diseases. Adverse events included gastrointestinal symptoms and potential bleeding; however, no serious adverse events were reported. Conclusion: This umbrella review suggests that ginseng intake has beneficial therapeutic effects for diverse diseases. However, the methodological quality of studies needs to be improved considerably. In addition, it is imperative to establish the clinical efficacy of ginseng through high-quality randomized controlled trials.

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells.

BACKGROUND: Current therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PURPOSE: We aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. METHODS: The protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. RESULTS: MGQD alleviated DSS­induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. CONCLUSION: The mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

MiR-182/Sestrin2 affects the function of asthmatic airway smooth muscle cells by the AMPK/mTOR pathway.

Background and Objectives: Asthma is a chronic inflammatory airway disease and brings heavy economic and spiritual burdens to patients' families and the society. Airway smooth muscle cells (ASMCs) afect the development of asthma by secreting cytokines, growth factors, and prostates. The stress-inducing protein, Sestrin2, plays a vital role in antioxidant defense. The aim of this study is to investigate the role of Sestrin2 in asthma and its corresponding molecular mechanism. Materials and Methods: Airway remodeling was induced by construction of asthma rat model. Primary ASMCs were isolated through combining tissue block adherence and enzymatic digestion and identified by immunofluorescence staining. Gene expression was measured by quantitative real-time PCR (qPCR) and western blot (WB) experiments. Cell viability, proliferation, migration, and calcium flow of ASMCs were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-deoxyuridine (EdU), Transwell, and Fluo-3AM, respectively. The binding of miR-182 and Sestrin2 3'-untranslated region (3'-UTR) was measured by luciferase reporter system and RNA-binding protein immunoprecipitation (RIP) analysis. Results: Sestrin2 expression was upregulated in asthma rat model and cell model. Overexpression of Sestrin2 enhanced the growth, migration, and calcium flow, and inversely, repression of Sestrin2 was reduced in ASMCs from the asthma group. MiR-182, one of the microRNAs (miRNAs) that possesses the potential to regulate Sestrin2, was downregulated in ASMCs from the asthma group. Further experiments revealed that Sestrin2 was inhibited by miR-182 and that overexpression of Sestrin2 reversed the miR-182-induced inhibition of the cellular progression of ASMCs from the asthma group. This study further investigated the downstream signaling pathway of Sestrin2 and found that increased expression of Sestrin2 activated 5'-adenosine monophosphate-activated protein kinase (AMPK), leading to the inactivation of mammalian target of rapamycin (mTOR) and thus promoting the growth, migration, and calcium flow of ASMCs from the asthma group. Conclusion: This study investigated the role of Sestrin2 for the first time and further dissected the regulatory factor of Sestrin2, ultimately elucidating the downstream signaling pathway of Sestrin2 in asthma, providing a novel pathway, and improving the understanding of the development and progression of asthma.

Nigella sativa and health outcomes: An overview of systematic reviews and meta-analyses.

Background: Nigella sativa (N. sativa) consumption has been associated with various health outcomes; however, the results are not completely consistent. Objectives: This overview of systematic reviews and meta-analyses aimed to evaluate the reporting and methodological quality, and to grade the available evidence of associations between N. sativa and health outcomes. Methods: PubMed, Cochrane Library, Embase, and Scopus databases were searched from their inception to September 30, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement, Assessment of Multiple Systematic Reviews (AMSTAR) 2 checklist, and Grades of Recommendations, Assessment, Development and Evaluations (GRADE) systems were used to assess the reporting, methodological, and evidence quality for each meta-analysis, respectively. The results were synthesized in a narrative form. Results: This overview included 20 eligible meta-analyses published in peer-reviewed journals between 2013 and 2021. The overall methodological quality was relatively poor, with only one moderate quality, four low quality, and 15 critically low quality studies. For reporting quality, items two, five, eight, nine, 15, and 24 need to improve. Among the 110 outcome indicators of the quality of evidence, five were graded as moderate, 17 as low, and 88 as very low. Risk of bias, inconsistency, and imprecision were the main downgrading factors. Conclusion: This overview suggests that N. sativa is beneficial for various clinical outcomes. However, there are certain limitations to reporting and methodological quality. The clinical efficacy of N. sativa requires confirmation in high-quality, large-sample, randomized controlled trials.

Modified Gegen Qinlian decoction ameliorated ulcerative colitis by attenuating inflammation and oxidative stress and enhancing intestinal barrier function in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Gegen Qinlian decoction (MGQD), which was first documented in Treatise on Febrile Disease, is recognized as a classic prescription to treat ulcerative colitis (UC). However, its protective mechanism against UC remains to be fully elucidated. AIM OF THE STUDY: To explore the impact and the potential molecular mechanism of MGQD on dextran sodium sulfate (DSS)-induced UC mice and tumor necrosis factor alpha (TNF-α)-induced Caco-2 cell monolayer model of intestinal barrier. MATERIALS AND METHODS: The chemical components of MGQD and MGQD drug containing serum (MGQD-DS) were characterized by LC-MS/MS. The therapeutic effect of MGQD on DSS-induced UC was evaluated based on body weight, disease activity index (DAI), colon length, colonic histopathological injury, inflammatory cytokines, oxidative stress response and intestinal barrier function. Cell Counting Kit (CCK)-8 assay was applied to detect the effect of MGQD-DS on the viability of Caco-2 cells. Additionally, TNF-α-induced Caco-2 cell monolayer model of intestinal barrier was established in vitro. The Caco-2 cell monolayers were administered blank serum or MGQD-DS to observe the effects of MGQD-DS on transepithelial electrical resistance (TEER), permeability of fluorescein isothiocyanate (FITC)-dextran, inflammatory cytokines, oxidative stress indicators and intestinal epithelial barrier (IEB). RESULTS: MGQD significantly improved symptoms and pathological damage in UC mice by downregulating the expression of interleukin (IL)-1ß and malondialdehyde (MDA), attenuating the loss of goblet cells and the destruction of intestinal epithelial ultrastructure, and upregulating the expression of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), zonula occludens-1 (ZO-1), Occludin, Claudin-1 and E-cadherin. In vitro, MGQD-DS significantly reduced the flux of FITC-dextran, increased the TEER, inhibited the expression of IL-21, IL-17A and MDA, and promoted the expression of IL-4, IL-10, transforming growth factor-ß (TGF-ß), SOD, CAT, GSH, Occludin and E-cadherin in TNF-α-induced Caco-2 cell monolayer model of intestinal barrier. CONCLUSION: MGQD can ameliorate DSS-induced UC mice and TNF-α-induced Caco-2 cell monolayer model of intestinal barrier, and the protective effect is related to its inhibition of inflammation, alleviation of oxidative stress, and repair of intestinal barrier damage.

Whole genome sequencing and annotation of Daedaleopsis sinensis, a wood-decaying fungus significantly degrading lignocellulose.

Daedaleopsis sinensis is a fungus that grows on wood and secretes a series of enzymes to degrade cellulose, hemicellulose, and lignin and cause wood rot decay. Wood-decaying fungi have ecological, economic, edible, and medicinal functions. Furthermore, the use of microorganisms to biodegrade lignocellulose has high application value. Genome sequencing has allowed microorganisms to be analyzed from the aspects of genome characteristics, genome function annotation, metabolic pathways, and comparative genomics. Subsequently, the relevant information regarding lignocellulosic degradation has been mined by bioinformatics. Here, we sequenced and analyzed the genome of D. sinensis for the first time. A 51.67-Mb genome sequence was assembled to 24 contigs, which led to the prediction of 12,153 protein-coding genes. Kyoto Encyclopedia of Genes and Genomes database analysis of the D. sinensis data revealed that 3,831 genes are involved in almost 120 metabolic pathways. According to the Carbohydrate-Active Enzyme database, 481 enzymes are found in D. sinensis, of which glycoside hydrolases are the most abundant. The genome sequence of D. sinensis provides insights into its lignocellulosic degradation and subsequent applications.