Multi-target mechanism of misoprostol in pregnancy termination based on network pharmacology and molecular docking.

Misoprostol is a prostaglandin analogue that contracts the uterus, prompting the expulsion of the embryo. No systematic evaluation of the mechanisms of misoprostol has previously been performed. In this study, known targets of misoprostol were obtained from the DrugBank database; potential targets of misoprostol were predicted using data from the SwissTargetPrediction and PharmMapper databases; and the main targets of pregnancy termination were obtained from the GeneCards database. The protein-protein interaction (PPI) network of the shared genes between misoprostol and pregnancy termination was constructed using data from the STRING database, and the "misoprostol-pregnancy termination-pathway" network was constructed and potential targets was verified through molecular docking. We analyzed 37 shared target genes and obtained a network diagram of 134 potential targets, which the core therapeutic targets were HSP90AA1, EGFR, and MAPK1. GO functional and KEGG pathway enrichment analyses showed that misoprostol can modulate the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway in pregnancy termination and mainly interferes with protein phosphorylation, cell localization, and protein hydrolysis regulation processes. This research illustrates the mechanism underlying the pharmacological effect of misoprostol, namely pregnancy termination. However, further experimental verification is warranted for optimal use of misoprostol during clinical practice.

Le misoprostol est un analogue des prostaglandines qui contracte l'utérus, provoquant l'expulsion de l'embryon. Aucune évaluation systématique des mécanismes du misoprostol n'a été réalisée auparavant. Dans cette étude, les cibles connues du misoprostol ont été obtenues à partir de la base de données DrugBank ; Les cibles potentielles du misoprostol ont été prédites à l'aide des données des bases de données SwissTargetPrediction et PharmMapper ; et les principales cibles de l'interruption de grossesse ont été obtenues à partir de la base de données GeneCards. Le réseau d'interaction protéine-protéine (IPP) des gènes partagés entre le misoprostol et l'interruption de grossesse a été construit à l'aide des données de la base de données STRING, et le réseau « voie d'interruption de grossesse-misoprostol ¼ a été construit et les cibles potentielles ont été vérifiées par amarrage moléculaire. Nous avons analysé 37 gènes cibles partagés et obtenu un diagramme de réseau de 134 cibles potentielles, dont les principales cibles thérapeutiques étaient HSP90AA1, EGFR et MAPK1. Les analyses d'enrichissement des voies fonctionnelles GO et KEGG ont montré que le misoprostol peut moduler la voie de signalisation VEGF, la voie de signalisation du calcium et la voie de signalisation NF-κB lors de l'interruption de grossesse et interfère principalement avec les processus de phosphorylation des protéines, de localisation cellulaire et de régulation de l'hydrolyse des protéines. Cette recherche illustre le mécanisme sous-jacent à l'effet pharmacologique du misoprostol, à savoir l'interruption de grossesse. Cependant, une vérification expérimentale plus approfondie est justifiée pour une utilisation optimale du misoprostol au cours de la pratique clinique.

Developmental potential of non- and mono-pronuclear zygotes and associated clinical outcomes in IVF cycles.

Purpose: This study aims to evaluate the developmental potential of 0PN, 1PN, and 2PN zygotes in IVF cycles and compare their clinical outcomes. Methods: We conducted a retrospective cohort study involving IVF patients. Blastocyst formation rates were assessed with 0PN, 1PN, and 2PN zygotes. Subsequently, we collected clinical outcome data following the transfer of these zygotes. Results: The overall blastulation rate was similar between 0PN (29.6%) and 2PN (32.1%) zygotes, but 1PN zygotes exhibited a significantly lower blastulation rate (17.0%) compared to both 0PN and 2PN zygotes. Similarly, the overall rate of good-quality blastulation was comparable between 0PN (15.3%) and 2PN (17.5%) zygotes, while 1PN zygotes showed a significantly lower rate (7.0%) compared to both 0PN and 2PN. Clinical pregnancy, ectopic pregnancy, implantation, and live birth rates were similar among single blastocyst frozen embryo transfers (FET) of 0PN, 1PN, and 2PN. Additionally, no significant differences were observed between single- and double-blastocyst FET of 0PN and 2PN. Conclusions: Our findings suggest that 0PN and 2PN zygotes have comparable developmental potential, while 1PN embryos exhibit lower developmental potential. Blastocyst FET outcomes appear similar among 0PN, 1PN, and 2PN zygotes.

Structural elucidation and anti-psoriasis activity of a novel polysaccharide from Saussurea Costus.

PSCP, a novel water-soluble polysaccharide, was extracted from the root of Saussurea costus and subsequently purified using DEAE-52 cellulose and Sephadax G-50 columns. The elucidation of its structure involved various techniques including HPGPC, FT-IR, HPLC-ELSD, GC-MS, NMR, AFM, and SEM. The results show that PSCP was a homogeneous heteropoly saccharide having molecular weight of 4131 Da and mainly composed of 1-α-D-Glcp-(-2-ß-D-Fruf-1-)23-2-ß-D-Fruf. The anti-psoriasis activity of PSCP was evaluated in imiquimod-induced psoriasis in Balb/C mice. This study revealed that treatment with PSCP resulted in a significant improvement in the pathological morphology of the skin and a reduction in the PASI score. Analysis of liver RNA-Seq data indicated that the MAPK signaling pathway may play a crucial role in the ability of PSCP to ameliorate psoriasis. PSCP was found to effectively inhibit the phosphorylation of JNK, ERK, and p38, as well as down-regulate the expression of the transcription factor AP-1 (c-fos and c-jun) in the nucleus, thereby reducing the expression of inflammatory factors. These findings suggest that PSCP holds promise as a novel therapeutic approach for the treatment of psoriasis.

Novel insights into adaptive evolution based on the unusual AT-skew in Acheilognathus gracilis mitogenome and phylogenetic relationships of bitterling.

Acheilognathus gracilis, a bitterling species, distribute in lower reaches of Yangtze River. They are identified as the top-priority bitterling species for conservation as having high evolutionary distinctiveness and are at risk of extinction. In present study, we first sequenced the complete mitogenome of A. gracilis and analyzed its phylogenetic position using 13 PCGs. The A. gracilis mitogenome is 16,774 bp in length, including 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, a control region and the origin of the light strand replication. The overall base composition of A. gracilis in descending order is T 27.9 %, A 27.7 %, C 26.1 % and G 18.3 %, shows a unusual AT-skew with slightly negative. Further investigation revealed A. gracilis uses excess T over A in NADH dehydrogenase 5 (nd5), whereas the most of other bitterlings are biased toward to use A not T, implying there is likely to be unique strategy of adaptive evolution in A. gracilis. We also compared 13 PCGs of 30 bitterling mitogenomes and the results exhibit highly conservative. Phylogenetic trees constructed by 13 PCGs strongly support the monophyly of Acheilognathus and the paraphyly of Rhodeus and Tanakia. Current results will provide valuable information for follow-up research on conservation of species facing with serious population decline and can provide novel insights into the phylogenetic analysis and evolutionary biology research.

Associations between metabolic score for visceral fat and the risk of cardiovascular disease and all-cause mortality among populations with different glucose tolerance statuses.

AIMS: To investigate the associations between metabolic score for visceral fat (METS-VF) and clinical outcomes among populations with different glucose tolerance statuses. METHODS: We analysed 6827 participants aged ≥ 40 years with different glucose tolerance statuses from a cohort study. The associations between METS-VF and cardiovascular disease (CVD) events and all-cause mortality were assessed using Cox regression, restricted cubic spline and receiver operating characteristic curves. RESULTS: During a follow-up of 5.00 years, there were 338 CVD events and 307 subjects experienced all-cause death. The METS-VF quartile (Quartile 4 versus 1) was significantly related to CVD events [adjusted HRs and 95% CIs: 5.75 (2.67-12.42), 2.80 (1.76-4.48), and 3.31 (1.28-8.54) for subjects with normal glucose tolerance, prediabetes and diabetes, respectively] and all-cause mortality [adjusted HRs and 95% CIs: 2.80 (1.43-5.49), 4.15 (2.45-7.01), and 4.03 (1.72-9.42), respectively]. Restricted cubic spline suggested a dose-response association of METS-VF with the risk of CVD events and all-cause mortality. The area under curve for CVD events and all-cause mortality was higher for METS-VF than for the other obesity and IR indexes in subjects with different glucose tolerance statuses. CONCLUSIONS: The METS-VF was associated with an increased risk of CVD events and all-cause mortality and could be used as a predictive index of the risk of CVD events and all-cause mortality among populations with different glucose tolerance statuses.

Transcriptome analyses of betta fish (Betta splendens) provide novel insights into fin regeneration and color-related genes.

The betta fish (Betta splendens), an important ornamental fish, haswell-developed and colorful fins.After fin amputation, betta fish can easily regenerate finssimilar to the originalsin terms of structureand color. The powerful fin regeneration ability and a variety of colors in the betta fish are fascinating. However, the underlying molecular mechanisms are still not fully understood. In this study, tail fin amputation and regeneration experiments were performed on two kinds of betta fish: red and white color betta fish. Then, transcriptome analyseswere conducted to screen out fin regeneration and color-relatedgenes in betta fish. Through enrichment analyses of differentially expressed genes (DEGs), we founda series of enrichment pathways and genes related to finregeneration, including cell cycle (i.e. plcg2), TGF-beta signaling pathway (i.e. bmp6), PI3K-Akt signaling pathway (i.e. loxl2aand loxl2b), Wnt signaling pathway(i.e. lef1), gap junctions (i.e. cx43), angiogenesis (i.e. foxp1), and interferon regulatory factor (i.e. irf8). Meanwhile, some fin color-related pathways and genes were identified in betta fish, especially melanogenesis (i.e. tyr, tyrp1a, tyrp1b, and mc1r) and carotenoid color genes (i.e. pax3, pax7, sox10, and ednrba). In conclusion, this studycan not only enrich the research onfish tissue regeneration, but also has a potential significance for the aquaculture and breeding of the betta fish.

[Knock-down of long intergenic noncoding RNA cyclooxygenase 2 (lincRNA-COX2) inhibits apoptosis and polarization into M1 in Listeria monocytogenes-infected macrophages].

Objective To investigate the effect of long intergenic non-coding RNA COX2 (lincRNA-COX2) on apoptosis and polarization of Listeria monocytogenes (Lm)-infected RAW264.7 cells. Methods RAW264.7 cells were cultured and divided into control group (uninfected cells), Lm infection group, negative control of small interfering RNA (si-NC) group, si-NC and Lm infection group, small interfering RNA of lincRNA-COX2 (si-lincRNA-COX2) group, si-lincRNA-COX2 and Lm infection group. RAW264.7 cells were infected with MOI=10 Lm for 6 hours, and then the inhibition efficiency of siRNA transfection was detected by fluorescence microscope and quantitative real-time PCR (qRT-PCR). The expression levels of cleaved-caspase-3(c-caspase-3), caspase-3, B-cell lymphoma-2 (Bcl2), Bcl2 associated X protein (BAX), arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) were detected by Western blot analysis. Results c-caspase-3/caspase-3, BAX/Bcl2 and iNOS were significantly up-regulated, while the level of Arg1 was down-regulated in Lm-infected RAW264.7 cells compared with control group. LincRNA-COX2 knockdown inhibited the increase of protein levels for BAX/Bcl2, c-caspase-3/caspase-3 and iNOS in Lm-infected RAW264.7 cells, while the level of Arg1 in Lm-infected RAW264.7 cells was up-regulated. Conclusion Knockdown of lincRNA-COX2 can inhibit cell apoptosis and suppress the macrophage polarization into M1 type in Lm-infected RAW264.7 cells.

RGS7 silence protects palmitic acid-induced pancreatic ß-cell injury by inactivating the chemokine signaling pathway.

Impaired insulin secretion due to pancreatic ß-cell injury is an important cause of type 2 diabetes (T2D). Regulators of guanine nucleotide binding protein (G protein) signaling proteins played a key role in regulating insulin sensitivity in vivo. To explore the role of RGS7 on palmitic acid-induced pancreatic ß-cell injury, pancreatic ß-cells Beta-TC-6 and Min6 were treated with palmitic acid (PA) to similar type 2 diabetes (T2D) injury in vitro. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze cell viability, proliferation, and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the changes of inflammation-related cytokines. The expression of gene and protein was measured by quantitative real-time PCR (qRT-PCR) and western blot. PA modeling induced apoptosis, increased levels of inflammation-related cytokines, and suppressed cell viability and proliferation of pancreatic ß-cells. RGS7 silence markedly alleviated the cell injury induced by PA. RGS7 overexpression further aggravated apoptosis and inflammatory response in PA-induced pancreatic ß-cells and inhibited cell viability and proliferation. It is worth noting that RGS7 activated the chemokine signaling pathway. Silence of the key gene of the chemokine signaling pathway could eliminate the negative effect of RGS7 on PA-induced pancreatic ß-cells. RGS7 silence protects pancreatic ß-cells from PA-induced injury by inactivating the chemokine signaling pathway.

Environmental regulation and tourism industry development: evidence from China.

Tourism is a large, environment-dependent global industry. As an important policy tool for environmental protection, environmental regulation plays a significant role in development of the tourism industry. Using the panel data of 284 prefecture-level cities in China from 2004 to 2018, this paper innovatively analyzes the impact mechanism of environmental regulation on China's tourism development from the perspective of the integration of institutional and environmental economics. At the same time, this paper uses the instrumental variable two-stage least squares method (IV-2SLS) to solve the endogeneity problem of environmental regulation and China's tourism development, which makes the research conclusions more robust. The main results were as follows: (1) environmental regulation significantly promoted the development of the tourism industry. Specifically, tourist arrival (TA) and tourism revenue (TR) increased 8.79% and 8.64%, respectively, when the intensity of environmental regulation increased by 1%. This effect was still robust after applying a series of tests; (2) the impact of environmental regulation on the development of the tourism industry was heterogeneous for three aspects: the domestic and inbound tourism market, urban type, and urban location; (3) environmental regulation contributed to China's tourism industry development through industrial structure upgrading, technological innovation, and urban image promotion. Our findings offer valuable insight for the concerned authority and tourism sector to understand the positive role of environmental regulation in promoting high-quality development of the tourism industry by corresponding policy-making, industrial structure upgrading, technological innovation, and urban reputation building.

Thermal-tolerant potential of ordinary Chlorella pyrenoidosa and the promotion of cell harvesting by heterotrophic cultivation at high temperature.

During the heterotrophic cultivation of microalgae, a cooled process against temperature rise caused by the metabolism of exogenous organic carbon sources greatly increases cultivation cost. Furthermore, microalgae harvesting is also a cost-consuming process. Cell harvesting efficiency is closely related to the characteristics of the algal cells. It may be possible to change cell characteristics through controlling culture conditions to make harvesting easier. In this study, the mesophilic Chlorella pyrenoidosa was found to be a thermal-tolerant species in the heterotrophic mode. The cells could maintain their maximal specific growth rate at 40°C and reached 1.45 day-1, which is equivalent to that of cultures at 35°C but significantly higher than those cultured at lower temperatures. Interestingly, the cells cultured at 40°C were much easier to be harvested than those at lower temperatures. The harvesting efficiency of the cells cultured at 40°C reached 96.83% after sedimentation for 240 min, while the cells cultured at lower temperatures were reluctant to settle. Likely, the same circumstance occurred when cells were harvested by centrifugation or flocculation. The promotion of cell harvesting for cells cultured at high temperatures was mainly attributed to increased cell size and decreased cell surface charge. To the best of our knowledge, this is the first report that cells cultured at high temperatures can promote microalgae harvesting. This study explores a new approach to simplify the cultivation and harvesting of microalgae, which effectively reduces the microalgae production cost.

One-step co-cultivation and flocculation of microalgae with filamentous fungi to valorize starch wastewater into high-value biomass.

A novel method of one-step co-cultivation and harvesting of microalgae and fungi, for efficient starch wastewater treatment and high-value biomass production was developed. By combination of Aspergillus oryzae and Chlorella pyrenoidosa, nutrients in wastewater could be converted to useful microbial biomass, while the wastewater was purified. Moreover, the microalgae C. pyrenoidosa could gradually be encapsulated in fungal pellets which promoted the biomass harvesting. The free algal cells could be completely harvested by fungal pellets within 72 h. The synergistic effects between them greatly improved the removal efficiencies of main pollutants as the removal efficiency of COD, TN, and TP reached 92.08, 83.56, and 96.58 %, respectively. In addition, the final biomass concentration was higher than that of individual cultures. The protein and lipid concentration was also significantly improved and reached 1.92 and 0.99 g/L, respectively. This study provides a simple and efficient strategy for simultaneous wastewater treatment and high-value biomass production.

De novo gonad transcriptome analysis of elongate loach (Leptobotia elongata) provides novel insights into sex-related genes.

Elongate loach (Leptobotia elongata) is endemic in middle and upper reaches of the Yangtze River in China. Because of many anthropogenic factors such as overfishing and dam construction, the loach has become a highly endangered species. So far, the genomic resources which benefit for species conservation and utilization are still lacking in elongate loach. Therefore, the first gonad transcriptome analysis of the loach was conducted in this study, providing novel insights into sex-related genes. A total of 286,800,660 clean reads with a total length of 42.02 Gb were obtained. 18,975 differentially expressed genes (DEGs) were identified, where 12,976 DEGs, especially Sox9a, Sox9b, Igf2 and Fgfr2, were upregulated in the testis, and 5999 DEGs, especially Zp3, Eg2, Plk1, Ccnb1, Cdc20 and Mos, were upregulated in the ovary. Meanwhile, some testis-specific genes (i.e. Cald1, Atp1a, Muc2 and Ca2) and ovary-specific genes (i.e. Ca4, Tuba, Acp5, Ccna, Larp6 and Nop4) were identified and verified. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs, we found a series of enrichment pathways related to reproduction in elongate loach, such as the MAPK signaling pathway, oxytocin signaling pathway and oocyte meiosis pathway. Twelve DEGs were randomly selected to verify RNA-seq results by qPCR. In conclusion, this study provides a data source to study the molecular characteristics and regulatory mechanisms of sex-related genes in elongate loach, which has a potential to improve the resource protection and aquaculture production of the loach.

Abundance, fate, and effects of pharmaceuticals and personal care products in aquatic environments.

Pharmaceuticals and personal care products (PPCPs) are found in wastewater, and thus, the environment. In this study, current knowledge about the occurrence and fate of PPCPs in aquatic systems-including wastewater treatment plants (WWTPs) and natural waters around the world-is critically reviewed to inform the state of the science and highlight existing knowledge gaps. Excretion by humans is the primary route of PPCPs entry into municipal wastewater systems, but significant contributions also occur through emissions from hospitals, PPCPs manufacturers, and agriculture. Abundance of PPCPs in raw wastewater is influenced by several factors, including the population density and demography served by WWTPs, presence of hospitals and drugs manufacturers in the sewershed, disease burden of the population served, local regulations, and climatic conditions. Based on the data obtained from WWTPs, analgesics, antibiotics, and stimulants (e.g., caffeine) are the most abundant PPCPs in raw wastewater. In conventional WWTPs, most removal of PPCPs occurs during secondary treatment, and overall removal exceeds 90% for treatable PPCPs. Regardless, the total PPCP mass discharged with effluent by an average WWTP into receiving waters (7.35-20,160 g/day) is still considerable, because potential adverse effects of some PPCPs (such as ibuprofen) on aquatic organisms occur within measured concentrations found in surface waters.

Clinicopathological and prognostic significance of LINC00673 in human malignancy: a review and meta-analysis.

BACKGROUND: We conducted this research to investigate the relationship between long intergenic non-protein coding RNA 673 (linc00673) expression and prognosis and clinicopathological parameters in human malignancies. METHODS: The PubMed, Embase, WOS, and CNKI databases were used to collect eligible research data before 4 January 2021. Meta-analysis was performed using Stata 12.0 software. Pooled odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence interval (CIs) were calculated to evaluate the association of linc00673 expression with survival outcomes and clinical parameters. RESULTS: We finally included 17 articles and a total of 1539 cases for the meta-analysis. The results indicated that linc00673 was significantly correlated with T stage (P=0.006), tumor stage (P<0.001), lymph node metastasis (P<0.001), and distant metastasis (P<0.001). In addition, the results suggested that elevated linc00673 expression predicted a poor overall survival (OS) time (P=0.013) and acted as an independent prognostic factor (P<0.001) for OS in patients with malignancy. Although potential evidence of publication bias was found in the studies on OS in relation to tumor stage in the multivariate analysis, the trim-and-fill analysis confirmed that the results remained stable. CONCLUSIONS: Overexpression of linc00673 was significantly correlated with shorter OS time in patients with malignant tumors. Moreover, the increased expression level of linc00673 was significantly correlated with T stage, tumor stage, lymph node metastasis, and distant metastasis. The results presented in this article revealed that linc00673 might be involved in the progression and invasion of malignancy and serve as a novel prognostic biomarker and potential therapeutic target for malignancy.

NF-κB/ROS and ERK pathways regulate NLRP3 inflammasome activation in Listeria monocytogenes infected BV2 microglia cells.

Listeria monocytogenes is a food-borne pathogen responsible for neurolisteriosis, which is potentially lethal in immunocompromised individuals. Microglia are the main target cells for L. monocytogenes in central nervous system (CNS). However, the precise mechanisms by which they trigger neuroinflammatory processes remain unknown. The BV2 microglial cell line and a murine model of L. monocytogenes infection were used for experiments in this study. Listeria monocytogenes induced pyroptosis and nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome activation in BV2. Pharmacological inhibition of the NLRP3 inflammasome attenuated L. monocytogenes-induced pyroptosis. Moreover, inhibition of nuclear factor kappa-B (NF-κB) and extracellular regulated protein kinases (ERK) pathways induced a decrease in caspase1 activation and mature IL-1ß-17 secretion. Our collective findings support critical involvement of the NLRP3 inflammasome in L. monocytogenes-induced neuroinflammation and, to an extent, ROS production. In addition, ERK and NF-κB signaling play an important role in activation of the NLRP3 inflammasome, both in vitro and in vivo.

LincRNA-Cox2 regulates IL6/JAK3/STAT3 and NF-κB P65 pathway activation in Listeria monocytogenes-infected RAW264.7 cells.

Listeria monocytogenes (Lm) can lead to high mortality rates relative to other foodborne pathogens. Lm-induced inflammation is partly characterized by macrophage activation. Long non-coding RNAs (lncRNAs) have important roles in various biological processes. However, it is unknown how lncRNAs regulate the host response to Lm infection. To identify the role of lncRNA in Lm infection, we used in vitro and in vivo models. We found that lincRNA-Cox2 was highly expressed in Lm-infected RAW264.7 cells. LincRNA-Cox2 knockdown resulted in reduced proinflammatory cytokines, apoptosis, migration ability and enhanced phagocytosis of Lm. LincRNA-Cox2 knockdown also reduced the phosphorylation of Janus kinase 3 (JAK3) and signal transducer and activator of transcription (STAT3) and the nuclear translocation of nuclear factor (NF)-κB P65, which are known to be involved in inflammatory responses. Experimentally inhibiting the protein and phosphorylation levels of STAT3 resulted in reduced proinflammatory cytokines and enhanced phagocytosis of Lm by the RAW264.7 cells. Our research suggests that lincRNA-Cox2 plays important roles in inflammation, the phagocytic function and cell migration ability of RAW264.7 cells by activating interleukin (IL)-6/JAK3/STAT3 signaling, and lincRNA-Cox2 also regulates NF-κB P65 nuclear translocation. Our research provides new insights into the regulatory role of lincRNA-Cox2 in Lm infection.

Diosmetin Ameliorates Nonalcoholic Steatohepatitis through Modulating Lipogenesis and Inflammatory Response in a STAT1/CXCL10-Dependent Manner.

Nonalcoholic steatohepatitis (NASH) is an inflammatory lipotoxic disorder characterized by lipid accumulation and inflammation. Diosmetin (Dios), a flavonoid, has an active effect against nonalcoholic fatty liver disease, whereas its effect on NASH remains elusive. To investigate the effects of Dios on lipogenesis and inflammatory response and explore the molecular mechanisms of Dios on NASH, mice induced by high-fat diet (HFD), HepG2 cells stimulated by palmitic acid (PA), transcriptome sequencing, and molecular biological experiments were used. We show, by pathological analysis (HE, Oli Red O, and Masson staining) and biochemical parameters (TC, TG, LDL-C, ALT, and AST), Dios alleviated liver lipid accumulation and inflammatory injury. According to liver RNA-Seq analysis, CXCL10 and STAT1 were assumed to be the key target genes of Dios on NASH. Significantly, Dios regulated STAT1/CXCL10 signal pathway and further attenuated NASH via regulating the expression of LXRα/ß, SREBP-1c, CHREBP, and NF-κB. In conclusion, Dios is proposed to alleviate NASH through suppression of lipogenesis and inflammatory response via a STAT1/CXCL10-dependent pathway.

Prevalence and genotype distribution of human papillomavirus infection in Huzhou City, eastern China, 2018-2019.

BACKGROUND: Human papillomavirus (HPV) infection is involved in cervical cancer development, and hence understanding its prevalence and genotype distribution is important. However, there are few reports on the prevalence and genotype distribution of HPV in the city of Huzhou in China. METHODS: In this retrospective cross-sectional study, 11,506 women who visited Huzhou Maternity & Child Health Care Hospital between January 2018 and October 2019 were enrolled. The results of HPV genotyping and cytology tests were analyzed. RESULTS: The overall prevalence of HPV infection was 15.5%. The rate of high-risk (HR) HPV infection (13.5%) was higher than that of single low-risk (LR) HPV infection (2.0%) (p<0.05). The five most common HPV genotypes were HPV52 (3.3%), 16 (1.9%), 58 (1.7%), 53 (1.5%), and 81 (1.2%). The infection rate of HPV peaked in women aged 16-24 and women aged ≥55. The infection rate of HPV58 or HPV81 appeared as a single peak in women aged ≥55. The rates of HR-HPV and LR-HPV infection were higher in subjects with abnormal cytology (p<0.05). CONCLUSIONS: HPV infection is high in Huzhou, and HPV53 and HPV81 are the prevalent genotypes. HPV infection rate is associated with age and cytology. Regional HPV surveillance is essential to optimize current HPV prevention and vaccine development.

Antifungal activity and potential mechanism of magnoflorine against Trichophyton rubrum.

Coptis alkaloids show potent antifungal activity against Trichophyton rubrum (T. rubrum), which was a Tinea pedis fungus, but little of the literature was reported to investigate the antifungal activity of magnoflorine against it. Meanwhile, the potential mechanism of magnoflorine against T. rubrum is unknown. In the present study, we found that Coptis alkaloids, especially magnoflorine had significant antifungal activities against T. rubrum and Trichophyton mentagrophyte (T. mentagrophyte). The MIC values of magnoflorine against T. rubrum and T. mentagrophyte were both 62.5 µg ml-1, but magnoflorine exerted a better fungicidal efficiency against T. rubrum than T. mentagrophyte. Magnoflorine inhibited the conidia germination and hyphal growth, and changed the mycelial morphology such as deformation growth, surface peeling, and cytoplasmic contraction in T. rubrum. Magnoflorine had no significant effect on cell wall integrity. However, magnoflorine destroyed the fungal cell membrane of T. rubrum through increasing the nucleic acid leakage, reducing the activities of squalene epoxidase and CYP51 enzyme, and decreasing the content of ergosterol in hyphae. Our study supported the potential use of magnoflorine as an antifungal agent against T. rubrum and made contributions to the clinical application of magnoflorine against fungi.

Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1 signaling pathway.

Paeonol, quercetin, ß-sitosterol, and gallic acid extracted from Moutan Cortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumor activities. This work aimed to illustrate the potential anti-oxidative mechanism of monomers in human liver hepatocellular carcinoma (HepG2) cells-induced by hydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect of monomers was independence or synergy in mice stimulated by carbon tetrachloride (CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponse manner by inhibiting the generation of reactive oxygen species, increasing total antioxidant capacity, catalase and superoxide dismutase (SOD) activities, and activating the antioxidative pathway of nuclear factor E2-related factor 2/Kelchlike ECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that the in vitro antioxidant capacities of paeonol and quercetin were better than those of ß-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levels of alanine transaminase and aspartate aminotransferase, augmented the contents of glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1 proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, ß-sitosterol, and gallic acid play a defensive role against H2O2-induced oxidative stress through activating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidative properties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotective effects, which is independent rather than synergy.