Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP...Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.展开更多
The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or...The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or a Ph.D.program is simply not scalable.To address this problem,the Department of Computing at the University of Illinois has introduced a multidisciplinary approach to computing,which is a scalable and collaborative approach to capitalize on the tremendous demand for computer science education.The key component of the approach is the blended major,also referred to as“CS+X”,where CS denotes computer science and X denotes a non-computing field.These CS+X blended degrees enable win-win partnerships among multiple subject areas,distributing the educational responsibilities while growing the entire university.To meet the demand from non-CS majors,another pathway that is offered is a graduate certificate program in addition to the traditional minor program.To accommodate the large number of students,scalable teaching tools,such as automatic graders,have also been developed.展开更多
Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and...Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.展开更多
Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communicat...Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulatio...Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.展开更多
Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality ...Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality and flavour of meat and indirectly affects consumer preference.However,the molecular mechanisms influencing the deposition of linoleic acid in organisms are not clear.As the molecular mechanisms of linoleic acid deposition are not well understood,to investigate the main effector genes affecting the linoleic acid content,this study aimed to screen for hub genes in slow-type yellow-feathered chickens by transcriptome sequencing(RNA-Seq)and weighted gene coexpression network analysis(WGCNA).We screened for candidate genes associated with the linoleic acid content in slow-type yellow-feathered broilers.A total of 399 Tiannong partridge chickens were slaughtered at 126 days of age,fatty acid levels were measured in pectoral muscle,and pectoral muscle tissue was collected for transcriptome sequencing.Transcriptome sequencing results were combined with phenotypes for WGCNA to screen for candidate genes.KEGG enrichment analysis was also performed on the genes that were significantly enriched in the modules with the highest correlation.A total of 13310 genes were identified after quality control of transcriptomic data from 399 pectoral muscle tissues.WGCNA was performed,and a total of 26 modules were obtained,eight of which were highly correlated with the linoleic acid content.Four key genes,namely,MDH2,ATP5B,RPL7A and PDGFRA,were screened according to the criteria|GS|>0.2 and|MM|>0.8.The functional enrichment results showed that the genes within the target modules were mainly enriched in metabolic pathways.In this study,a large-sample-size transcriptome analysis revealed that metabolic pathways play an important role in the regulation of the linoleic acid content in Tiannong partridge chickens,and MDH2,ATP5B,RPL7A and PDGFRA were screened as important candidate genes affecting the linoleic acid content.The results of this study provide a theoretical basis for selecting molecular markers and comprehensively understanding the molecular mechanism affecting the linoleic acid content in muscle,providing an important reference for the breeding of slow-type yellowfeathered broiler chickens.展开更多
BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in...BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.展开更多
By establishing a mathematical model and a basic analytical framework for the impact of resource endowments on carbon intensity,a traditional panel model without spatial panel effects was firstly constructed,a Durbin-...By establishing a mathematical model and a basic analytical framework for the impact of resource endowments on carbon intensity,a traditional panel model without spatial panel effects was firstly constructed,a Durbin-Wu-Hausman test was conducted,and the model was set as a fixed-effects model based on the statistical values;secondly,the traditional panel model without spatial effects was estimated,and LM tests and robustness tests were conducted on the regression residuals.The LM test was then used to remove the fixed effect terms by the de-meaning method,and the Matlab 7.0 software was used to estimate the model.The stepwise introduction of variables was used to observe the effect of each variable on economic growth and to analyze the relationship between the magnitude and significance of the regression parameters of each variable.Finally,the path of conduction effect of resource endowment through mediating variable sinfluencing economic growth and carbon emissions,and thus carbon intensity,was constructed.The conclusion is that carbon intensity is inversely proportional to economic growth for a given level of carbon emissions.Therefore,if resource endowment promotes economic growth through mediating variables,it will lead to a decrease in carbon intensity,which is conducive to the achievement of emission reduction targets;conversely,if resource endowment hinders economic growth through mediating variables,it will lead to an increase in carbon intensity,which is not conducive to the achievement of emission reduction targets.展开更多
Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cel...Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.展开更多
Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor ...Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor education for college and university students is an urgent need of the high-quality development of the society and the internal requirement of promoting the all-round development of individuals.This study analyzes the importance of strengthening labor education for college and university students in the new era and proposes four practical pathways which draw on labor courses and campus activities,social practices,scientific research projects,and internships.After implementing these pathways,a survey of 967 students showed that students’understanding and awareness of labor was deepened,their hands-on skills and interests in science and labor practices were improved,and they became more cordially respectful to the working class.Taken together,the exploration and practice of these pathways helps college and university students to recognize their abilities,strengths,and interests,and guides them to form good labor habits that permeate all aspects of their studies and lives.展开更多
Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim ...Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.展开更多
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio...BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.展开更多
Circular RNAs(circRNAs)form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells.These RNAs mediate post-transcriptional control of gene expression and have multiple func...Circular RNAs(circRNAs)form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells.These RNAs mediate post-transcriptional control of gene expression and have multiple functions in biological processes,such as transcriptional regulation and splicing.They serve predominantly as microRNA sponges,RNA-binding proteins,and templates for translation.More importantly,circRNAs are involved in cancer progression,and may serve as promising biomarkers for tumor diagnosis and therapy.Although traditional experimental methods are usually time-consuming and laborious,substantial progress has been made in exploring potential circRNA-disease associations by using computational models,summarized signaling pathway data,and other databases.Here,we review the biological characteristics and functions of circRNAs,including their roles in cancer.Specifically,we focus on the signaling pathways associated with carcinogenesis,and the status of circRNA-associated bioinformatics databases.Finally,we explore the potential roles of circRNAs as prognostic biomarkers in cancer.展开更多
Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice f...Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice false smut balls(RBWE) remains to be investigated.Studies have shown that RBWE may be toxic to animals,but toxicological evidence is still lacking.In this study,we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/m L,respectively,with positive correlations with dose toxicity and time toxicity.After treatment with RBWE,the number of BNL CL.2 cells decreased significantly,and the morphology of BNL CL.2 cells showed atrophy and wall detachment.RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells,increased the proportion of apoptotic cells and inhibited cell proliferation.RBWE up-regulated reactive oxygen species(ROS) levels and lowered mitochondrial membrane potentials.Additionally,Western blot and q RT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo.The contents of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE.At the same time,RBWE can lead to increases in ROS and malondialdehyde contents,decreases in contents of oxidized glutathione,glutathione and reduced glutathione,as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues,demonstrating that oxidative stress occurred in mice.Moreover,liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE.In general,RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway,which provides a reference for hepatotoxicity and its mechanism of action.展开更多
Hypoxia has become an unfavorable factor affecting the sustainable development of the large yellow croaker Larimichthys crocea,an economically important mariculture fish in China.Apoptosis is a consequence of hypoxia ...Hypoxia has become an unfavorable factor affecting the sustainable development of the large yellow croaker Larimichthys crocea,an economically important mariculture fish in China.Apoptosis is a consequence of hypoxia on fish.However,the effects of hypoxia stress on apoptosis in L.crocea remain largely unknown.We investigated the effect of environmental hypoxia on apoptosis in L.crocea.Results show that hypoxia induced apoptosis in L.crocea both in vivo and in vitro.The mitochondrial membrane potential was significantly reduced in large yellow croaker fry(LYCF)cells.The expression levels of Bcell lymphoma/leukemia-2(Bcl-2)m RNA and protein were also significantly decreased in the liver and LYCF cells during 96 h and 48 h of hypoxia stress,respectively,whereas the expression level of Bcl-2 associated X(Bax)mRNA,Casp3 mRNA,and activity of caspase-3/7/9 were significantly increased,indicating that hypoxia induced caspase-dependent intrinsic apoptosis in L.crocea.The expression level of the apoptosis-inducing factor(AIF)protein was significantly increased in the liver and LYCF cells.The level of AIF protein was significantly decreased in the cytoplasm but increased in the nuclei of L.crocea,demonstrating that hypoxia induced the AIF-mediated caspase-independent intrinsic apoptosis.In addition,the activity of caspase-8 was significantly increased,indicating that hypoxia stress induced extrinsic apoptosis in L.crocea.Therefore,hypoxia induced apoptosis in L.crocea through both the intrinsic and extrinsic pathways.The present study accumulated basic biological information to help elucidate the mechanism of hypoxia response in marine fish.展开更多
Green alga Enteromorpha clathrata(E.clathrata)contains a variety of bioactive compounds,including polysaccharides,polyphenols and fat-soluble pigments etc.,among which polyphenols exhibit a wide range of medicinal pro...Green alga Enteromorpha clathrata(E.clathrata)contains a variety of bioactive compounds,including polysaccharides,polyphenols and fat-soluble pigments etc.,among which polyphenols exhibit a wide range of medicinal properties.E.clathrata polyphenols(ECPs)have shown various biological activities such as antioxidant,anti-inflammatory and antidiabetic effects;however,the potential of ECPs as an anti-cancer reagent remains unclear.The aim of this study was to investigate the anti-tumor activity and underlying mechanisms of ECPs on hepatocellular carcinoma.The cytotoxicity of Hepa1-6 cells was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and lactate dehydrogenase(LDH)assay.Flow cytometry and fluorescence microscope analysis of cell apoptosis after annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining.2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)assay was used for intracellular reactive oxygen species(ROS)detection.caspase-9 activity was determined using cspase-9 colorimetric assay.Mitochondrial transmembrane potential(Δψm)was measured using JC-1.Western blot and quantitative real-time PCR(qPCR)were used to assess the expressions of the apoptosis regulators Bax,Bcl-2,cytochrome c and caspase-3.It was found that ECPs showed a dose-dependent cytotoxicity against Hepa1-6 cells by inducing apoptosis.The apoptosis in ECPs-treated Hepa1-6 cells was accompanied by the loss of mitochondrial membrane potential,elevated ROS generation,increased release of mitochondrial cytochrome c,and up-regulation of caspase-9 and caspase-3.The expressions of Bax(pro-apoptotic molecule)and Bcl-2(apoptosis suppressor)were up-regulated and down-regulated,respectively,at both mRNA and protein levels.These molecular alterations revealed that ECPs caused apoptosis of cells through the mitochondrial pathway,suggesting that ECPs are potential candidates to be developed for liver cancer treatment.展开更多
Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichm...Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis,protein-protein interaction(PPI)network,and survival analysis based on the Gene Expression Omnibus(GEO)database.Methods By screening with highly expressed genes,we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites.Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis,PPI network,and survival analysis.Several software and platforms including Prism 8,R language,Cytoscape,DAVID,STRING,and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma(ESCC)tissue.Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer.Four genes including ALDH3A1,C2,SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer.Keratinization may greatly impact the pathogenesis of esophageal cancer.Genes ALDH3A1,C2,SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.展开更多
BACKGROUND Left-sided accessory pathways(APs)can be accessed with either a transaortic(TA)or transseptal approach(TS).For children with Marfan syndrome(MFS)who have aortic disease,the use of TA can aggravate the disea...BACKGROUND Left-sided accessory pathways(APs)can be accessed with either a transaortic(TA)or transseptal approach(TS).For children with Marfan syndrome(MFS)who have aortic disease,the use of TA can aggravate the disease,making TS the best choice for these patients.CASE SUMMARY A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness.She was diagnosed with MFS,supraventricular tachycardia,Wolff-Parkinson-White syndrome,and left-sided AP was detected by cardiac electrophysiological.Catheter ablation was successfully performed via TS under the guidance of the Ensite system.During the follow-up,no recurrence or complications occurred.CONCLUSION The TS for catheter ablation of left-sided APs can be considered in children with MFS.Adequate evaluation and selection of the appropriate puncture site are particularly important.展开更多
文摘Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.
文摘The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or a Ph.D.program is simply not scalable.To address this problem,the Department of Computing at the University of Illinois has introduced a multidisciplinary approach to computing,which is a scalable and collaborative approach to capitalize on the tremendous demand for computer science education.The key component of the approach is the blended major,also referred to as“CS+X”,where CS denotes computer science and X denotes a non-computing field.These CS+X blended degrees enable win-win partnerships among multiple subject areas,distributing the educational responsibilities while growing the entire university.To meet the demand from non-CS majors,another pathway that is offered is a graduate certificate program in addition to the traditional minor program.To accommodate the large number of students,scalable teaching tools,such as automatic graders,have also been developed.
基金supported by Postdoctoral Innovation Talents’ Support Programthe National Natural Science Foundation of China (32130099)+1 种基金the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-CXRC-038)Laboratory of Lingnan Modern Agriculture Project (NT2021005)。
文摘Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.
基金financially supported by National Natural Science Foundation of China(31901782)。
文摘Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
文摘Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.
基金This study was supported by the China Agriculture Research System of MOF and MARA(CARS-41)the Key-Area Research and Development Program of Guangdong Province,China(2020B020222002)+3 种基金the Foshan University High-level Talent Program,China(CGZ07243)the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding,China(2019B030301010)the Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes,China(2019KSYS011)the Foshan Institute of Science and Technology Postgraduate Free Exploration Fund,China(2021ZYTS36).
文摘Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality and flavour of meat and indirectly affects consumer preference.However,the molecular mechanisms influencing the deposition of linoleic acid in organisms are not clear.As the molecular mechanisms of linoleic acid deposition are not well understood,to investigate the main effector genes affecting the linoleic acid content,this study aimed to screen for hub genes in slow-type yellow-feathered chickens by transcriptome sequencing(RNA-Seq)and weighted gene coexpression network analysis(WGCNA).We screened for candidate genes associated with the linoleic acid content in slow-type yellow-feathered broilers.A total of 399 Tiannong partridge chickens were slaughtered at 126 days of age,fatty acid levels were measured in pectoral muscle,and pectoral muscle tissue was collected for transcriptome sequencing.Transcriptome sequencing results were combined with phenotypes for WGCNA to screen for candidate genes.KEGG enrichment analysis was also performed on the genes that were significantly enriched in the modules with the highest correlation.A total of 13310 genes were identified after quality control of transcriptomic data from 399 pectoral muscle tissues.WGCNA was performed,and a total of 26 modules were obtained,eight of which were highly correlated with the linoleic acid content.Four key genes,namely,MDH2,ATP5B,RPL7A and PDGFRA,were screened according to the criteria|GS|>0.2 and|MM|>0.8.The functional enrichment results showed that the genes within the target modules were mainly enriched in metabolic pathways.In this study,a large-sample-size transcriptome analysis revealed that metabolic pathways play an important role in the regulation of the linoleic acid content in Tiannong partridge chickens,and MDH2,ATP5B,RPL7A and PDGFRA were screened as important candidate genes affecting the linoleic acid content.The results of this study provide a theoretical basis for selecting molecular markers and comprehensively understanding the molecular mechanism affecting the linoleic acid content in muscle,providing an important reference for the breeding of slow-type yellowfeathered broiler chickens.
基金Supported by the Huzhou Science and Technology Plan,No.2022GY27.
文摘BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.
文摘By establishing a mathematical model and a basic analytical framework for the impact of resource endowments on carbon intensity,a traditional panel model without spatial panel effects was firstly constructed,a Durbin-Wu-Hausman test was conducted,and the model was set as a fixed-effects model based on the statistical values;secondly,the traditional panel model without spatial effects was estimated,and LM tests and robustness tests were conducted on the regression residuals.The LM test was then used to remove the fixed effect terms by the de-meaning method,and the Matlab 7.0 software was used to estimate the model.The stepwise introduction of variables was used to observe the effect of each variable on economic growth and to analyze the relationship between the magnitude and significance of the regression parameters of each variable.Finally,the path of conduction effect of resource endowment through mediating variable sinfluencing economic growth and carbon emissions,and thus carbon intensity,was constructed.The conclusion is that carbon intensity is inversely proportional to economic growth for a given level of carbon emissions.Therefore,if resource endowment promotes economic growth through mediating variables,it will lead to a decrease in carbon intensity,which is conducive to the achievement of emission reduction targets;conversely,if resource endowment hinders economic growth through mediating variables,it will lead to an increase in carbon intensity,which is not conducive to the achievement of emission reduction targets.
文摘Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.
基金supported by Research Project of Henan Provincial Social Science Circles Federation(SKL-2023-1059)Higher Education Research Project of Henan Association of Higher Education(2021SXHLX175)Research Projects from Xinxiang Municipal Social Science Circles Federation(SKL-2023-126 and SKL-2023-136).
文摘Labor education is an essential component of college and university education that can help students to develop a strong work ethic,acquire practical skills,and better understand the value of work.Strengthening labor education for college and university students is an urgent need of the high-quality development of the society and the internal requirement of promoting the all-round development of individuals.This study analyzes the importance of strengthening labor education for college and university students in the new era and proposes four practical pathways which draw on labor courses and campus activities,social practices,scientific research projects,and internships.After implementing these pathways,a survey of 967 students showed that students’understanding and awareness of labor was deepened,their hands-on skills and interests in science and labor practices were improved,and they became more cordially respectful to the working class.Taken together,the exploration and practice of these pathways helps college and university students to recognize their abilities,strengths,and interests,and guides them to form good labor habits that permeate all aspects of their studies and lives.
基金supported by the Inner Mongolia Autonomous Region Science and Technology Revitalization Foundation (2021CG0029)the National Natural Science Foundation of China (22178070)
文摘Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.
基金the National Key Research and Development Program of China,No.2017YFC0908104National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.
文摘BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.
基金supported partly by the National Natural Science Foundation of China(Grant Nos.82172946,82173290,82273029,81871969,and 81772592)the Project of the Department of Education of Guangdong Province(Grant No.2021KTSCX102)+2 种基金the Natural Science Foundation of Guangdong Province(Grant No.2022A1515010706)the Shenzhen Basic Research Fund(Grant No.JCYJ20190808163801777)the SZU Top Ranking Project(Grant No.860-00000210)。
文摘Circular RNAs(circRNAs)form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells.These RNAs mediate post-transcriptional control of gene expression and have multiple functions in biological processes,such as transcriptional regulation and splicing.They serve predominantly as microRNA sponges,RNA-binding proteins,and templates for translation.More importantly,circRNAs are involved in cancer progression,and may serve as promising biomarkers for tumor diagnosis and therapy.Although traditional experimental methods are usually time-consuming and laborious,substantial progress has been made in exploring potential circRNA-disease associations by using computational models,summarized signaling pathway data,and other databases.Here,we review the biological characteristics and functions of circRNAs,including their roles in cancer.Specifically,we focus on the signaling pathways associated with carcinogenesis,and the status of circRNA-associated bioinformatics databases.Finally,we explore the potential roles of circRNAs as prognostic biomarkers in cancer.
基金funded by the Education Department of Zhejiang Province Foundation of China(Grant No.Y202249221)。
文摘Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens.The toxicity of the water extract of rice false smut balls(RBWE) remains to be investigated.Studies have shown that RBWE may be toxic to animals,but toxicological evidence is still lacking.In this study,we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/m L,respectively,with positive correlations with dose toxicity and time toxicity.After treatment with RBWE,the number of BNL CL.2 cells decreased significantly,and the morphology of BNL CL.2 cells showed atrophy and wall detachment.RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells,increased the proportion of apoptotic cells and inhibited cell proliferation.RBWE up-regulated reactive oxygen species(ROS) levels and lowered mitochondrial membrane potentials.Additionally,Western blot and q RT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo.The contents of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE.At the same time,RBWE can lead to increases in ROS and malondialdehyde contents,decreases in contents of oxidized glutathione,glutathione and reduced glutathione,as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues,demonstrating that oxidative stress occurred in mice.Moreover,liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE.In general,RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway,which provides a reference for hepatotoxicity and its mechanism of action.
基金Supported by the NSFC-Zhejiang Joint Fund for the Integration of Industrialization and Informatization(No.U1809212)the Scientific and Technical Project of Zhejiang Province(No.2021C02069-1-2)+2 种基金the Science and Technology Innovation 2025 Major Special Project of Ningbo City(No.2021Z002)the Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculturethe K.C.Wong Magna Fund in Ningbo University。
文摘Hypoxia has become an unfavorable factor affecting the sustainable development of the large yellow croaker Larimichthys crocea,an economically important mariculture fish in China.Apoptosis is a consequence of hypoxia on fish.However,the effects of hypoxia stress on apoptosis in L.crocea remain largely unknown.We investigated the effect of environmental hypoxia on apoptosis in L.crocea.Results show that hypoxia induced apoptosis in L.crocea both in vivo and in vitro.The mitochondrial membrane potential was significantly reduced in large yellow croaker fry(LYCF)cells.The expression levels of Bcell lymphoma/leukemia-2(Bcl-2)m RNA and protein were also significantly decreased in the liver and LYCF cells during 96 h and 48 h of hypoxia stress,respectively,whereas the expression level of Bcl-2 associated X(Bax)mRNA,Casp3 mRNA,and activity of caspase-3/7/9 were significantly increased,indicating that hypoxia induced caspase-dependent intrinsic apoptosis in L.crocea.The expression level of the apoptosis-inducing factor(AIF)protein was significantly increased in the liver and LYCF cells.The level of AIF protein was significantly decreased in the cytoplasm but increased in the nuclei of L.crocea,demonstrating that hypoxia induced the AIF-mediated caspase-independent intrinsic apoptosis.In addition,the activity of caspase-8 was significantly increased,indicating that hypoxia stress induced extrinsic apoptosis in L.crocea.Therefore,hypoxia induced apoptosis in L.crocea through both the intrinsic and extrinsic pathways.The present study accumulated basic biological information to help elucidate the mechanism of hypoxia response in marine fish.
基金the National Key R&D Program of China(No.2018YFD0901105)the Ningbo Natural Science Foundation(No.202003N4128)the Scientific Research Foundation of Graduate School of Ningbo University(No.IF2021085)。
文摘Green alga Enteromorpha clathrata(E.clathrata)contains a variety of bioactive compounds,including polysaccharides,polyphenols and fat-soluble pigments etc.,among which polyphenols exhibit a wide range of medicinal properties.E.clathrata polyphenols(ECPs)have shown various biological activities such as antioxidant,anti-inflammatory and antidiabetic effects;however,the potential of ECPs as an anti-cancer reagent remains unclear.The aim of this study was to investigate the anti-tumor activity and underlying mechanisms of ECPs on hepatocellular carcinoma.The cytotoxicity of Hepa1-6 cells was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and lactate dehydrogenase(LDH)assay.Flow cytometry and fluorescence microscope analysis of cell apoptosis after annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)staining.2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)assay was used for intracellular reactive oxygen species(ROS)detection.caspase-9 activity was determined using cspase-9 colorimetric assay.Mitochondrial transmembrane potential(Δψm)was measured using JC-1.Western blot and quantitative real-time PCR(qPCR)were used to assess the expressions of the apoptosis regulators Bax,Bcl-2,cytochrome c and caspase-3.It was found that ECPs showed a dose-dependent cytotoxicity against Hepa1-6 cells by inducing apoptosis.The apoptosis in ECPs-treated Hepa1-6 cells was accompanied by the loss of mitochondrial membrane potential,elevated ROS generation,increased release of mitochondrial cytochrome c,and up-regulation of caspase-9 and caspase-3.The expressions of Bax(pro-apoptotic molecule)and Bcl-2(apoptosis suppressor)were up-regulated and down-regulated,respectively,at both mRNA and protein levels.These molecular alterations revealed that ECPs caused apoptosis of cells through the mitochondrial pathway,suggesting that ECPs are potential candidates to be developed for liver cancer treatment.
文摘Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis,protein-protein interaction(PPI)network,and survival analysis based on the Gene Expression Omnibus(GEO)database.Methods By screening with highly expressed genes,we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites.Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis,PPI network,and survival analysis.Several software and platforms including Prism 8,R language,Cytoscape,DAVID,STRING,and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma(ESCC)tissue.Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer.Four genes including ALDH3A1,C2,SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer.Keratinization may greatly impact the pathogenesis of esophageal cancer.Genes ALDH3A1,C2,SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.
文摘BACKGROUND Left-sided accessory pathways(APs)can be accessed with either a transaortic(TA)or transseptal approach(TS).For children with Marfan syndrome(MFS)who have aortic disease,the use of TA can aggravate the disease,making TS the best choice for these patients.CASE SUMMARY A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness.She was diagnosed with MFS,supraventricular tachycardia,Wolff-Parkinson-White syndrome,and left-sided AP was detected by cardiac electrophysiological.Catheter ablation was successfully performed via TS under the guidance of the Ensite system.During the follow-up,no recurrence or complications occurred.CONCLUSION The TS for catheter ablation of left-sided APs can be considered in children with MFS.Adequate evaluation and selection of the appropriate puncture site are particularly important.
