Background Acute myocardial infarction(AMI)is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress.Aldo-Keto Reductase 1C3(AKR1C3)is a stress-regulating gene.Nevertheless...Background Acute myocardial infarction(AMI)is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress.Aldo-Keto Reductase 1C3(AKR1C3)is a stress-regulating gene.Nevertheless,its specific role and mechanisms regarding AMI remain unclear.Methods We assessed cardiac function through echocardiography;tissue damage was evaluated using Hematoxylin and Eosin(HE)and Masson trichrome staining.AKR1C3 expression levels were measured through Reverse transcription-quantitative polymerase chain reaction and western blot.Assessed cell viability using Cell Counting Kit-8 and lactate dehydrogenase(LDH)assays.The extent of ferroptosis was determined by measuring the levels of Fe2+,boron-dipyrromethane(BODIPY)and malondialdehyde(MDA),the glutathione/glutathione disulfide(GSH/GSSG)ratio,and the expression of Glutathione Peroxidase 4(GPX4)and Solute carrier 7A11(SLC7A11).Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2-Antioxidant response element(Keap1-Nrf2-ARE)pathway activation was analyzed through western blotting.Nrf2 was inhibited with ML385and activated with(R)-Sulforaphane to investigate the Keap1-Nrf2-ARE pathway.Results The rats in the AMI group displayed reduced heart function,more tissue damage,and lower AKR1C3 expression compared to the Sham group.Similarly,hypoxia-treated H9C2 cells showed reduced viability,and decreased AKR1C3 expression.Overexpressing AKR1C3 in H9C2 cells enhanced viability.Knocking down AKR1C3 exhibited the opposite effect.Of the inhibitors tested,Ferrostatin-1 most effectively restored cell viability in hypoxia-treated H9C2 cells.Moreover,H9C2 cells subjected to hypoxia suggested Keap1-Nrf2-ARE pathway inhibition.Overexpressing AKR1C3 reduced ferroptosis and activated the Keap1-Nrf2-ARE pathway in hypoxia-treated cells,knocking down AKR1C3 exhibited the opposite effect.Further experiments using ML385 in hypoxia-treated H9C2 cells with overexpressed AKR1C3 showed decreased viability and increased ferroptosis compared to the control.Using(R)-Sulforaphane in hypoxia-treated H9C2 cells with knocked-down AKR1C3 exhibited the opposite effect.Conclusion This study's findings indicate that AKR1C3 plays a role in regulating ferroptosis in myocardial cells,with the Keap1-Nrf2-ARE pathway likely being a key mechanism behind it.展开更多
BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of pe...BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.展开更多
BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a pat...BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.展开更多
BACKGROUND Patients with different stages of colorectal cancer(CRC)exhibit different abdominal computed tomography(CT)signs.Therefore,the influence of CT signs on CRC prognosis must be determined.AIM To observe abdomi...BACKGROUND Patients with different stages of colorectal cancer(CRC)exhibit different abdominal computed tomography(CT)signs.Therefore,the influence of CT signs on CRC prognosis must be determined.AIM To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis.METHODS The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed.Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC.The three-year survival rate was analyzed using the Kaplan-Meier curve,and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis.RESULTS For patients with CRC,the three-year survival rate was 73.86%.The death group exhibited more severe characteristics than the survival group.A multivariate Cox regression model analysis showed that body mass index(BMI),degree of periintestinal infiltration,tumor size,and lymph node CT value were independent factors influencing postoperative death(P<0.05 for all).Patients with characteristics typical to the death group had a low three-year survival rate(log-rankχ2=66.487,11.346,12.500,and 27.672,respectively,P<0.05 for all).The survival time of CRC patients was negatively correlated with BMI,degree of periintestinal infiltration,tumor size,lymph node CT value,mean tumor long-axis diameter,and mean tumor short-axis diameter(r=-0.559,0.679,-0.430,-0.585,-0.425,and-0.385,respectively,P<0.05 for all).BMI was positively correlated with the degree of periintestinal invasion,lymph node CT value,and mean tumor short-axis diameter(r=0.303,0.431,and 0.437,respectively,P<0.05 for all).CONCLUSION The degree of periintestinal infiltration,tumor size,and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.展开更多
Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including color...Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.展开更多
Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive t...Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.展开更多
Objective In this study,the role and potential mechanism of transformer 2β(Tra2β)in cervical cancer were explored.Methods The transcriptional data of Tra2βin patients with cervical cancer from Gene Expression Profi...Objective In this study,the role and potential mechanism of transformer 2β(Tra2β)in cervical cancer were explored.Methods The transcriptional data of Tra2βin patients with cervical cancer from Gene Expression Profiling Interactive Analysis(GEPIA)and cBioPortal databases were investigated.The functions of Tra2βwere evaluated by using Western blot,MTT,colony formation,Transwell assays,and nude mouse tumor formation experiments.Target genes regulated by Tra2βwere studied by RNA-seq.Subsequently,representative genes were selected for RT-qPCR,confocal immunofluorescence,Western blot,and rescue experiments to verify their regulatory relationship.Results The dysregulation of Tra2βin cervical cancer samples was observed.Tra2βoverexpression in Siha and Hela cells enhanced cell viability and proliferation,whereas Tra2βknockdown showed the opposite effect.Alteration of Tra2βexpression did not affect cell migration and invasion.Furthermore,tumor xenograft models verified that Tra2βpromoted cervical cancer growth.Mechanically,Tra2βpositively regulated the mRNA and protein level of SP1,which was critical for the proliferative capability of Tra2β.Conclusion This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo,which provides a comprehensive understanding of the pathogenesis of cervical cancer.展开更多
Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis o...Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis of T2D and is recognized as a potential risk factor for T2D.In recent years,increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D。展开更多
BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patie...BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.展开更多
Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patien...Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patients.Currently,the search for new effective substances from natural drugs is a major research direction.Two Chinese medicinal materials,Saposhnikoviae Radix(Fangfeng)and Chuanxiong Rhizoma(Chuanxiong),are commonly used in the treatment of PD in China.However,the mechanism of their combination is not clear,and further research is needed.Methods:Data were collected from publicly available databases:TCMSP,UnitProt,GeneCards OMIM,PharmGKB,Therapeutic Target Database and DrugBank.Network pharmacology and molecular docking methods was used to analyze the data to discover the possible pharmacological effects of the two drugs in the treatment of PD.Results:Beta-sitosterol,Mandenol and Wallichilide were the active components of Saposhnikoviae Radix and Chuanxiong Rhizoma(FC),and they stably bonded with PD targets,including PTGS2,CASP3,AKT1 and JUN.The target genes of FC were significantly enriched in PD-associated pathways,including calcium signaling and apoptosis pathways.Moreover,the study revealed that the active components of FC may affect cellular structures,such as membrane rafts,membrane microdomains,membrane regions,and postsynaptic membranes,which,in turn,affect a variety of molecular functions and biological processes.Conclusion:The results of this study indicate the direction for clarifying the pharmacodynamic substances of FC,the extraction method of pharmacodynamic substances,as well as the mechanism and efficacy of pharmacodynamic substances.Importantly,this study provides a strategy for developing new therapeutic drugs for PD.展开更多
5-Methylcytosine(m5C)methylation contributes to the development and progression of various malignant tumors.This study aimed to explore the potential role of m5C methylation regulators(m5CMRs)in head and neck squamous...5-Methylcytosine(m5C)methylation contributes to the development and progression of various malignant tumors.This study aimed to explore the potential role of m5C methylation regulators(m5CMRs)in head and neck squamous cell carcinoma(HNSCC).Methods:The transcription data of HNSCC samples were obtained from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)databases.Subsequently,the m5C patterns in HNSCC were evaluated based on 14 m5CMRs.Then,the m5Cscore was developed to quantify m5C patterns by using principal component analysis(PCA)algorithms.Two single-cell RNA sequencing datasets and various methods were employed to assess the prognostic value and sensitivity to immunotherapy.Finally,key prognostic m5CMRs were identified using univariate COX regression analysis,and their clinical significance was validated based on the Human Protein Atlas(HPA)database and by using immunohistochemistry.Results:Two distinct m5C clusters were identified.m5C cluster A is characterized by an immune-activated microenvironment and is associated with a favorable prognosis.Notable differences were observed in prognosis,immune infiltration,and immunotherapy response between the high-and low-m5Cscore groups.Patients in the high-m5Cscore group exhibited high TMB,which is correlated with poor prognosis.The m5Cscore of epithelial cells in HNSCC was higher than that in other cells.Key prognostic m5CMRs,including NSUN2,DNMT3B,ALKBH1,and Y-Box Binding Protein 1(YBX1),were associated with poor prognosis.Conclusion:Our research indicates that in head and neck squamous cell carcinoma,the m5C modification profoundly affects the TME’s diversity and complexity,influencing prognosis and the success of immunotherapy.Targeting m5C regulatory elements may be a new method for enhancing the efficacy of immunotherapy in HNSCC.展开更多
Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to in...Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.展开更多
Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated m...Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated molecular mechanisms.Methods We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, Rho A and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.Results The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial–mesenchymal transition(EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of Rho A rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.展开更多
This study aimed to investigate the neurotoxicity induced by trichloroacetic acid(TCA)and the possible protective mechanisms of boron(B).Mouse BV2 cells were treated with TCA(0,0.39,0.78,1.56,3.12,6.25,or 12.5 mmol/L)...This study aimed to investigate the neurotoxicity induced by trichloroacetic acid(TCA)and the possible protective mechanisms of boron(B).Mouse BV2 cells were treated with TCA(0,0.39,0.78,1.56,3.12,6.25,or 12.5 mmol/L)and B(0,7.8,15.6,31.25,62.5,125,500,or 1,000 mmol/L)for 3 h and 24 h,respectively.Then,reactive oxygen species,and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure.Beyond the dose-dependent decrease in the cellular viability,it clearly increased after B supplementation(P<0.05).Moreover,B decreased oxidative damage,and significantly down-regulated IL-6 levels and up-regulated TNF-βproduction(P<0.05).B also decreased apoptosis via the p53 pathway.The present findings indicated that TCA may induce oxidative damage,whereas B mitigates these adverse effects by decreasing cell apoptosis.展开更多
The sonic hedgehog protein not only plays a key role in early embryonic development, but also has essential effects on the adult nervous system, including neural stem cell proliferation, differentiation migration and ...The sonic hedgehog protein not only plays a key role in early embryonic development, but also has essential effects on the adult nervous system, including neural stem cell proliferation, differentiation migration and neuronal axon guidance. The N-terminal fragment of sonic hedgehog is the key functional element in this process. Therefore, this study aimed to clone and analyze the N-terminal fragment of the sonic hedgehog gene. Total RNA was extracted from the notochord of a Sprague-Dawley rat at embryonic day 9 and the N-terminal fragment of sonic hedgehog was amplified by nested reverse transcription-PCR. The N-terminal fragment of the sonic hedgehog gene was successfully cloned. The secondary and tertiary structures of the N-terminal fragment of the sonic hedgehog protein were predicted using Jpred and Phyre online.展开更多
Objective:Systematic review of the efficacy and safety of neoactivin re-acute myocardial infarction with heart failure.Methods:The computer retrieved CNKI,Wan Fang,Weipu Chinese Science and Technology Periodicals Data...Objective:Systematic review of the efficacy and safety of neoactivin re-acute myocardial infarction with heart failure.Methods:The computer retrieved CNKI,Wan Fang,Weipu Chinese Science and Technology Periodicals Database(VIP),China Biomedical Literature Database(CBM),Medline,Cochrane Library,and Clinical Trail.Gov collected clinical randomized controlled trials(RCTs)of neoactivin in the treatment of acute myocardial infarction with heart failure from the establishment of the database to December 2019.Data were extracted according to the Jadad scale,disease inclusion and exclusion criteria,and RevMan 5.3 software was used for Meta analysis.Results:A total of 23 RCTs were included,with a total of 2024 patients,including 1012 patients in the control group(conventional treatment with western medicine)and 1012 patients in the test group(on the basis of the control group+neoactivin treatment).Meta analysis results show that:in the total effective rate,the test group was better than the control group,and the difference was statistically significant(OR=4.30,95%CI[3.26,5.67],P<0.00001);In terms of left ventricular ejection fraction,the test group was better than the control group,and the difference was statistically significant(OR=1.58,95%CI[1.27,1.90],P<0.00001).In terms of the left ventricular end-diastolic diameter,the test group was better than the control group,with a statistical difference Significance(OR=-0.91,95%CI[-1.50,-0.33],P=0.002);In terms of stroke volume,the test group was better than the control group,and the difference was statistically significant(OR=1.24,95%CI[0.55,1.94],P=0.0005);In terms of brain natriuretic peptide precursors,the experimental group was better than the control group,the difference was statistically significant(OR=-4.37,95%CI[-6.21,-3.25],P<0.00001);In terms of heart rate,the test group was better than the control group,and the difference was statistically significant(OR=-13.70,95%CI[-14.95,-12.46],P<0.00001);In terms of systolic blood pressure,the test group was better than the control Group,the difference was statistically significant(OR=-12.38,95%CI[-17.98,-6.79],P<0.00001);In diastolic blood pressure,the test group was better than the control group Group,the difference was statistically significant(OR=-7.42,95%CI[-8.53,-6.30],P<0.00001);In terms of adverse reactions,the difference was not statistically significant(OR=0.95,95%CI[0.29,3.16],P=0.94).Conclusions:In patients with acute myocardial infarction and heart failure,the timely application of neoactivin treatment can improve clinical efficacy,improve cardiac function,inhibit ventricular remodeling,improve blood pressure and heart rate,which has good clinical efficacy and safety.展开更多
The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting ...The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.展开更多
The gut microbiota acts as a symbiotic microecosystem that plays an indispensable role in the regulation of a number of metabolic processes in the host by secreting secondary metabolites and impacting the physiology a...The gut microbiota acts as a symbiotic microecosystem that plays an indispensable role in the regulation of a number of metabolic processes in the host by secreting secondary metabolites and impacting the physiology and pathophysiology of numerous organs and tissues through the circulatory system. This relationship, referred to as the “gut-X axis”, is associated with the development and progression of disorders, including obesity, fatty liver and Parkinson's disease. Given its importance, the gut flora is a vital research area for the understanding and development of the novel therapeutic approaches for multiple disorders. Iron is a common but necessary element required by both mammals and bacteria. As a result, iron metabolism is closely intertwined with the gut microbiota. The host's iron homeostasis affects the composition of the gut microbiota and the interaction between host and gut microbiota through various mechanisms such as nutrient homeostasis, intestinal peaceability,gut immunity, and oxidative stress. Therefore, understanding the relationship between gut microbes and host iron metabolism is not only of enormous significance to host health but also may offer preventative and therapeutic approaches for a number of disorders that impact both parties. In this review, we delve into the connection between the dysregulation of iron metabolism and dysbiosis of gut microbiota, and how it contributes to the onset and progression of metabolic and chronic diseases.展开更多
Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options.Muscle atrophy can have various causes,including myogenic,neurogenic,and other...Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options.Muscle atrophy can have various causes,including myogenic,neurogenic,and other factors.Recent investigation has underscored a compelling link between the gut microbiota and skeletal muscle.Discerning the potential differences in the gut microbiota associated with muscle atrophy-related diseases,understanding their influence on disease development,and recognizing their potential as intervention targets are of paramount importance.This review aims to provide a comprehensive overview of the role of the gut microbiota in muscle atrophy-related diseases.We summarize clinical and pre-clinical studies that investigate the potential for gut microbiota modulation to enhance muscle performance and promote disease recovery.Furthermore,we delve into the intricate interplay between the gut microbiota and muscle atrophy-related diseases,drawing from an array of studies.Emerging evidence suggests significant differences in gut microbiota composition in individuals with muscle atrophy-related diseases compared with healthy individuals.It is conceivable that these alterations in the microbiota contribute to the pathogenesis of these disorders through bacterium-related metabolites or inflammatory signals.展开更多
Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recogn...Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.展开更多
基金supported by the Traditional Chinese Medicine Bureau of Guangdong Province,Guangzhou(grant No.20231321)the Clinical research initiation program project from Shunde Hospital,Southern Medical University,Foshan(grant No.CRSP2022004)。
文摘Background Acute myocardial infarction(AMI)is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress.Aldo-Keto Reductase 1C3(AKR1C3)is a stress-regulating gene.Nevertheless,its specific role and mechanisms regarding AMI remain unclear.Methods We assessed cardiac function through echocardiography;tissue damage was evaluated using Hematoxylin and Eosin(HE)and Masson trichrome staining.AKR1C3 expression levels were measured through Reverse transcription-quantitative polymerase chain reaction and western blot.Assessed cell viability using Cell Counting Kit-8 and lactate dehydrogenase(LDH)assays.The extent of ferroptosis was determined by measuring the levels of Fe2+,boron-dipyrromethane(BODIPY)and malondialdehyde(MDA),the glutathione/glutathione disulfide(GSH/GSSG)ratio,and the expression of Glutathione Peroxidase 4(GPX4)and Solute carrier 7A11(SLC7A11).Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2-Antioxidant response element(Keap1-Nrf2-ARE)pathway activation was analyzed through western blotting.Nrf2 was inhibited with ML385and activated with(R)-Sulforaphane to investigate the Keap1-Nrf2-ARE pathway.Results The rats in the AMI group displayed reduced heart function,more tissue damage,and lower AKR1C3 expression compared to the Sham group.Similarly,hypoxia-treated H9C2 cells showed reduced viability,and decreased AKR1C3 expression.Overexpressing AKR1C3 in H9C2 cells enhanced viability.Knocking down AKR1C3 exhibited the opposite effect.Of the inhibitors tested,Ferrostatin-1 most effectively restored cell viability in hypoxia-treated H9C2 cells.Moreover,H9C2 cells subjected to hypoxia suggested Keap1-Nrf2-ARE pathway inhibition.Overexpressing AKR1C3 reduced ferroptosis and activated the Keap1-Nrf2-ARE pathway in hypoxia-treated cells,knocking down AKR1C3 exhibited the opposite effect.Further experiments using ML385 in hypoxia-treated H9C2 cells with overexpressed AKR1C3 showed decreased viability and increased ferroptosis compared to the control.Using(R)-Sulforaphane in hypoxia-treated H9C2 cells with knocked-down AKR1C3 exhibited the opposite effect.Conclusion This study's findings indicate that AKR1C3 plays a role in regulating ferroptosis in myocardial cells,with the Keap1-Nrf2-ARE pathway likely being a key mechanism behind it.
文摘BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.
文摘BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.
文摘BACKGROUND Patients with different stages of colorectal cancer(CRC)exhibit different abdominal computed tomography(CT)signs.Therefore,the influence of CT signs on CRC prognosis must be determined.AIM To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis.METHODS The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed.Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC.The three-year survival rate was analyzed using the Kaplan-Meier curve,and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis.RESULTS For patients with CRC,the three-year survival rate was 73.86%.The death group exhibited more severe characteristics than the survival group.A multivariate Cox regression model analysis showed that body mass index(BMI),degree of periintestinal infiltration,tumor size,and lymph node CT value were independent factors influencing postoperative death(P<0.05 for all).Patients with characteristics typical to the death group had a low three-year survival rate(log-rankχ2=66.487,11.346,12.500,and 27.672,respectively,P<0.05 for all).The survival time of CRC patients was negatively correlated with BMI,degree of periintestinal infiltration,tumor size,lymph node CT value,mean tumor long-axis diameter,and mean tumor short-axis diameter(r=-0.559,0.679,-0.430,-0.585,-0.425,and-0.385,respectively,P<0.05 for all).BMI was positively correlated with the degree of periintestinal invasion,lymph node CT value,and mean tumor short-axis diameter(r=0.303,0.431,and 0.437,respectively,P<0.05 for all).CONCLUSION The degree of periintestinal infiltration,tumor size,and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.
基金the Sichuan Provincial Central Leading Local Science and Technology Development Special Project(Grant No.2023ZYD0072)the National Natural Science Foundation of China(Grant No.82301785)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515111078).
文摘Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.
基金the Guangdong Medical Science and Technology Research Foundation(No.A2021345).
文摘Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.
基金supported by grants from Foshan Science and Technology Innovation Project(Medical Science and Technology Innovation Platform Construction Project)Guangdong,China[grant number FS0AA-KJ218-1301-0037]Medical Science and Technology Research Fund project of Guangdong Province,Guangdong,China[grant number A2021111].
文摘Objective In this study,the role and potential mechanism of transformer 2β(Tra2β)in cervical cancer were explored.Methods The transcriptional data of Tra2βin patients with cervical cancer from Gene Expression Profiling Interactive Analysis(GEPIA)and cBioPortal databases were investigated.The functions of Tra2βwere evaluated by using Western blot,MTT,colony formation,Transwell assays,and nude mouse tumor formation experiments.Target genes regulated by Tra2βwere studied by RNA-seq.Subsequently,representative genes were selected for RT-qPCR,confocal immunofluorescence,Western blot,and rescue experiments to verify their regulatory relationship.Results The dysregulation of Tra2βin cervical cancer samples was observed.Tra2βoverexpression in Siha and Hela cells enhanced cell viability and proliferation,whereas Tra2βknockdown showed the opposite effect.Alteration of Tra2βexpression did not affect cell migration and invasion.Furthermore,tumor xenograft models verified that Tra2βpromoted cervical cancer growth.Mechanically,Tra2βpositively regulated the mRNA and protein level of SP1,which was critical for the proliferative capability of Tra2β.Conclusion This study demonstrated the important role of the Tra2β/SP1 axis in the progression of cervical cancer in vitro and in vivo,which provides a comprehensive understanding of the pathogenesis of cervical cancer.
基金supported by the China Postdoctoral Science Foundation(No.2021M691484)。
文摘Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response.Epidemiologically,periodontitis is closely related to the occurrence,development,and poor prognosis of T2D and is recognized as a potential risk factor for T2D.In recent years,increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D。
文摘BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.
文摘Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patients.Currently,the search for new effective substances from natural drugs is a major research direction.Two Chinese medicinal materials,Saposhnikoviae Radix(Fangfeng)and Chuanxiong Rhizoma(Chuanxiong),are commonly used in the treatment of PD in China.However,the mechanism of their combination is not clear,and further research is needed.Methods:Data were collected from publicly available databases:TCMSP,UnitProt,GeneCards OMIM,PharmGKB,Therapeutic Target Database and DrugBank.Network pharmacology and molecular docking methods was used to analyze the data to discover the possible pharmacological effects of the two drugs in the treatment of PD.Results:Beta-sitosterol,Mandenol and Wallichilide were the active components of Saposhnikoviae Radix and Chuanxiong Rhizoma(FC),and they stably bonded with PD targets,including PTGS2,CASP3,AKT1 and JUN.The target genes of FC were significantly enriched in PD-associated pathways,including calcium signaling and apoptosis pathways.Moreover,the study revealed that the active components of FC may affect cellular structures,such as membrane rafts,membrane microdomains,membrane regions,and postsynaptic membranes,which,in turn,affect a variety of molecular functions and biological processes.Conclusion:The results of this study indicate the direction for clarifying the pharmacodynamic substances of FC,the extraction method of pharmacodynamic substances,as well as the mechanism and efficacy of pharmacodynamic substances.Importantly,this study provides a strategy for developing new therapeutic drugs for PD.
基金supported by grants from the Guangdong Science and Technology Development Fund(Grant No.2019A1515110662).
文摘5-Methylcytosine(m5C)methylation contributes to the development and progression of various malignant tumors.This study aimed to explore the potential role of m5C methylation regulators(m5CMRs)in head and neck squamous cell carcinoma(HNSCC).Methods:The transcription data of HNSCC samples were obtained from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)databases.Subsequently,the m5C patterns in HNSCC were evaluated based on 14 m5CMRs.Then,the m5Cscore was developed to quantify m5C patterns by using principal component analysis(PCA)algorithms.Two single-cell RNA sequencing datasets and various methods were employed to assess the prognostic value and sensitivity to immunotherapy.Finally,key prognostic m5CMRs were identified using univariate COX regression analysis,and their clinical significance was validated based on the Human Protein Atlas(HPA)database and by using immunohistochemistry.Results:Two distinct m5C clusters were identified.m5C cluster A is characterized by an immune-activated microenvironment and is associated with a favorable prognosis.Notable differences were observed in prognosis,immune infiltration,and immunotherapy response between the high-and low-m5Cscore groups.Patients in the high-m5Cscore group exhibited high TMB,which is correlated with poor prognosis.The m5Cscore of epithelial cells in HNSCC was higher than that in other cells.Key prognostic m5CMRs,including NSUN2,DNMT3B,ALKBH1,and Y-Box Binding Protein 1(YBX1),were associated with poor prognosis.Conclusion:Our research indicates that in head and neck squamous cell carcinoma,the m5C modification profoundly affects the TME’s diversity and complexity,influencing prognosis and the success of immunotherapy.Targeting m5C regulatory elements may be a new method for enhancing the efficacy of immunotherapy in HNSCC.
文摘Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022.Methods:We investigated the overall status of HVPG technology in China-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China.Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4%)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy catheters.Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.
基金supported by Science and Technology Innovation of Foshan [Grant No. 1920001001153]。
文摘Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated molecular mechanisms.Methods We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, Rho A and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.Results The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial–mesenchymal transition(EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of Rho A rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.
基金supported by the National Natural Science Foundation of China [No.21806157]the Young Scholar Scientific Research Foundation [grant No. 2018A201]
文摘This study aimed to investigate the neurotoxicity induced by trichloroacetic acid(TCA)and the possible protective mechanisms of boron(B).Mouse BV2 cells were treated with TCA(0,0.39,0.78,1.56,3.12,6.25,or 12.5 mmol/L)and B(0,7.8,15.6,31.25,62.5,125,500,or 1,000 mmol/L)for 3 h and 24 h,respectively.Then,reactive oxygen species,and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure.Beyond the dose-dependent decrease in the cellular viability,it clearly increased after B supplementation(P<0.05).Moreover,B decreased oxidative damage,and significantly down-regulated IL-6 levels and up-regulated TNF-βproduction(P<0.05).B also decreased apoptosis via the p53 pathway.The present findings indicated that TCA may induce oxidative damage,whereas B mitigates these adverse effects by decreasing cell apoptosis.
基金sponsored by the Guangdong Provincial Natural Science Foundation,No.S2012010009592the Science and Technology Talent Foundation of Guangdong Provincial Natural Science Foundation,No.30900725+2 种基金the Joint Research Program by Southern Medical University-Shunde Guizhou Hospital,No.09000608the Science Foshan Municipal Key Project in Medical Sciences,No.201008063and the Shunde Medical Research Program,No.2011050
文摘The sonic hedgehog protein not only plays a key role in early embryonic development, but also has essential effects on the adult nervous system, including neural stem cell proliferation, differentiation migration and neuronal axon guidance. The N-terminal fragment of sonic hedgehog is the key functional element in this process. Therefore, this study aimed to clone and analyze the N-terminal fragment of the sonic hedgehog gene. Total RNA was extracted from the notochord of a Sprague-Dawley rat at embryonic day 9 and the N-terminal fragment of sonic hedgehog was amplified by nested reverse transcription-PCR. The N-terminal fragment of the sonic hedgehog gene was successfully cloned. The secondary and tertiary structures of the N-terminal fragment of the sonic hedgehog protein were predicted using Jpred and Phyre online.
基金Scientific research project of guangdong administration of traditional Chinese medicine(No.20184015).
文摘Objective:Systematic review of the efficacy and safety of neoactivin re-acute myocardial infarction with heart failure.Methods:The computer retrieved CNKI,Wan Fang,Weipu Chinese Science and Technology Periodicals Database(VIP),China Biomedical Literature Database(CBM),Medline,Cochrane Library,and Clinical Trail.Gov collected clinical randomized controlled trials(RCTs)of neoactivin in the treatment of acute myocardial infarction with heart failure from the establishment of the database to December 2019.Data were extracted according to the Jadad scale,disease inclusion and exclusion criteria,and RevMan 5.3 software was used for Meta analysis.Results:A total of 23 RCTs were included,with a total of 2024 patients,including 1012 patients in the control group(conventional treatment with western medicine)and 1012 patients in the test group(on the basis of the control group+neoactivin treatment).Meta analysis results show that:in the total effective rate,the test group was better than the control group,and the difference was statistically significant(OR=4.30,95%CI[3.26,5.67],P<0.00001);In terms of left ventricular ejection fraction,the test group was better than the control group,and the difference was statistically significant(OR=1.58,95%CI[1.27,1.90],P<0.00001).In terms of the left ventricular end-diastolic diameter,the test group was better than the control group,with a statistical difference Significance(OR=-0.91,95%CI[-1.50,-0.33],P=0.002);In terms of stroke volume,the test group was better than the control group,and the difference was statistically significant(OR=1.24,95%CI[0.55,1.94],P=0.0005);In terms of brain natriuretic peptide precursors,the experimental group was better than the control group,the difference was statistically significant(OR=-4.37,95%CI[-6.21,-3.25],P<0.00001);In terms of heart rate,the test group was better than the control group,and the difference was statistically significant(OR=-13.70,95%CI[-14.95,-12.46],P<0.00001);In terms of systolic blood pressure,the test group was better than the control Group,the difference was statistically significant(OR=-12.38,95%CI[-17.98,-6.79],P<0.00001);In diastolic blood pressure,the test group was better than the control group Group,the difference was statistically significant(OR=-7.42,95%CI[-8.53,-6.30],P<0.00001);In terms of adverse reactions,the difference was not statistically significant(OR=0.95,95%CI[0.29,3.16],P=0.94).Conclusions:In patients with acute myocardial infarction and heart failure,the timely application of neoactivin treatment can improve clinical efficacy,improve cardiac function,inhibit ventricular remodeling,improve blood pressure and heart rate,which has good clinical efficacy and safety.
基金the Natural Science Foundation of Guangdong Province,China(No.2022A1515012552)Shenzhen Science and Technology Innovation Committee of China(SZSTI+3 种基金No.JCYJ20220818102611025)Research Initiation Project of Shunde Hospital,Southern Medical University(No.CRSP2022002)Research Initiation Project of the First Affiliated Hospital of Gannan Medical University(No.QD202316)Beijing Sisco Clinical Oncology Research Foundation of China(No.Y-2022METAZMS-0118).
文摘The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.
基金supported by Guangdong Basic and Applied Basic Research Foundation (2020B1515020046)“GDAS” Project of Science and Technology Development (2021GDASYL-20210102003)+1 种基金the National Natural Science Foundation of China (81900797, 82072436)State Key Laboratory of Applied Microbiology Southern China(SKLAM002-2020)。
文摘The gut microbiota acts as a symbiotic microecosystem that plays an indispensable role in the regulation of a number of metabolic processes in the host by secreting secondary metabolites and impacting the physiology and pathophysiology of numerous organs and tissues through the circulatory system. This relationship, referred to as the “gut-X axis”, is associated with the development and progression of disorders, including obesity, fatty liver and Parkinson's disease. Given its importance, the gut flora is a vital research area for the understanding and development of the novel therapeutic approaches for multiple disorders. Iron is a common but necessary element required by both mammals and bacteria. As a result, iron metabolism is closely intertwined with the gut microbiota. The host's iron homeostasis affects the composition of the gut microbiota and the interaction between host and gut microbiota through various mechanisms such as nutrient homeostasis, intestinal peaceability,gut immunity, and oxidative stress. Therefore, understanding the relationship between gut microbes and host iron metabolism is not only of enormous significance to host health but also may offer preventative and therapeutic approaches for a number of disorders that impact both parties. In this review, we delve into the connection between the dysregulation of iron metabolism and dysbiosis of gut microbiota, and how it contributes to the onset and progression of metabolic and chronic diseases.
基金Guangdong Basic and Applied Basic Research Foundation(2020B1515020046)“GDAS”Project of Science and Technology Development(2021GDASYL-20210102003)+4 种基金Natural Science Foundation of China(82072436 and 32130099)Outstanding Youth Fund of the Hunan Natural Science Foundation(2021JJ20045)Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022370)Science and Technology Program of Hunan Province(2020NK2013)Key R&D Program of Guangxi Province(2021AB20063)。
文摘Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options.Muscle atrophy can have various causes,including myogenic,neurogenic,and other factors.Recent investigation has underscored a compelling link between the gut microbiota and skeletal muscle.Discerning the potential differences in the gut microbiota associated with muscle atrophy-related diseases,understanding their influence on disease development,and recognizing their potential as intervention targets are of paramount importance.This review aims to provide a comprehensive overview of the role of the gut microbiota in muscle atrophy-related diseases.We summarize clinical and pre-clinical studies that investigate the potential for gut microbiota modulation to enhance muscle performance and promote disease recovery.Furthermore,we delve into the intricate interplay between the gut microbiota and muscle atrophy-related diseases,drawing from an array of studies.Emerging evidence suggests significant differences in gut microbiota composition in individuals with muscle atrophy-related diseases compared with healthy individuals.It is conceivable that these alterations in the microbiota contribute to the pathogenesis of these disorders through bacterium-related metabolites or inflammatory signals.
基金supported by the National Natural Science Foundation of China(No.82103140,81773290)China Postdoctoral Science Foundation(No.2020M682803)President Foundation of Nanfang Hospital,Southern Medical University,Guangdong,China(No.2020C009).
文摘Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.
