The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing ...The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.展开更多
The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.Howev...The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
BACKGROUND Parkinson's disease(PD)-a progressive neurodegenerative disorder-is characterized by motor and gastrointestinal dysfunction.The exploration of novel therapeutic strategies for PD is vital.AIM To investi...BACKGROUND Parkinson's disease(PD)-a progressive neurodegenerative disorder-is characterized by motor and gastrointestinal dysfunction.The exploration of novel therapeutic strategies for PD is vital.AIM To investigate the potential mechanism of action of rhapontin-a natural compound with known antioxidant and anti-inflammatory properties-in the context of PD.METHODS Network pharmacology was used to predict the targets and mechanisms of action of rhapontin in PD.Behavioral tests and tyrosine hydroxylase immunofluorescence analysis were used to assess the effect of rhapontin on symptoms and pathology in MPTP-induced mice.Interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,and IL-10 levels in tissues were measured using an enzyme-linked immunosorbent assay(ELISA).Additionally,nuclear factor erythroid 2-related factor 2(NRF2)activation was confirmed using western blotting.RESULTS NRF2 was predicted to be the key transcription factor underlying the therapeutic effects of rhapontin in PD,and its anti-PD action may be associated with its antiinflammatory and antioxidant properties.Rhapontin ameliorated the loss of dopaminergic neurons and gastrointestinal dysfunction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mice by activating NRF2.Additio-nally,rhapontin treatment significantly decreased pro-inflammatory cytokines(IL-6,TNF-α,IL-1β)in the substantia nigra,striatum,and colon,whereas it increased anti-inflammatory cytokine(IL-10)levels only in the colon,indicating the involvement of gut–brain axis in its neuroprotective potential.Finally,NRF2 was identified as a key transcription factor activated by rhapontin,particularly in the colon.CONCLUSION We elucidated the effects of rhapontin in MPTP-induced PD mouse models using a combination of network pharmacology analysis,behavioral assessments,immunofluorescence,ELISA,and Western blotting.Our findings revealed the multifaceted role of rhapontin in ameliorating PD through its anti-inflammatory and antioxidant properties,particularly by activating NRF2,paving the way for future research into targeted therapies for PD.展开更多
BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin a...BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.METHODS High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice.Mice were divided into different groups including control,model,and treatment with various doses of erianin(10,20,and 40 mg/kg)as well as ML-385+erianin group.RESULTS Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-acti-vated protein kinase(AMPK)-nuclear factor erythroid 2-related factor 2(Nrf2)-heme oxygenase-1(HO-1)pathway.Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls.Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function(left ventricular ejection fraction,left ventricular fractional shortening)and mitigated ventricular remodeling(left ventricular internal diameter at end-diastole,left ventricular internal diameter at end-systole;P<0.05 vs model group).No significant differences were observed between the ML-385+erianin and placebo-treated groups.Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation,structural disorganization,inflammatory cell infiltration,and cytolytic damage.Furthermore,it significantly reduced the serum levels of cardiac troponin I,creatine kinase,and its MB isoenzyme.However,the ML-385+erianin co-treatment failed to alleviate myocardial injury.Metabolic profiling revealed erianin-mediated improvements in glycemic regulation(glycated hemoglobin:P<0.001),plasma insulin homeostasis,and lipid metabolism(total cholesterol,triglycerides,low-density lipo-protein cholesterol reduction,and high-density lipoprotein cholesterol restoration;P<0.05 vs model group).Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin(IL)-1β,and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group,whereas no significant differences were detected between the model and ML-385+erianin groups.Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups,with the most pronounced effects in the erianin-H group(P<0.05).Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups.These protective effects were abolished in the ML-385+erianin co-treatment group,which showed no statistical differences from the model group.CONCLUSION Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.展开更多
BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound...BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-associated protein 1(Keap1)signaling pathway,which is crucial for the body’s defense against oxidative stress.The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process.There are still limited data on the roles of Nrf2,its downstream signaling molecules,and angiogenesis markers in patients undergoing NPWT.AIM To study the mechanism of NPWT in DFUs.METHODS This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital,who were divided into Control group(n=21)and NPWT group(n=19).The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment.The wound condition,erythrocyte sedimentation rate(ESR),procalcitonin(PCT),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(b-FGF),cluster of differentiation 31(CD31),and levels of oxidative stress[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(T-AOC)]were analyzed before and 7 days after treatment by the Mann-Whitney U test.RESULTS The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment.The levels of ESR,PCT,IL-6,and TNF-αwere significantly reduced in the NPWT group compared to the control group(P<0.05),while the levels of CD31,VEGF,and b-FGF showed significant increases(P<0.05).The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets(SOD,CAT,and T-AOC),accompanied by decreases in the levels of Keap1 and MDA(P<0.05).CONCLUSION NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress.Its effects could possibly be enhanced through the action of Nrf2.展开更多
A broad spectrum of liver disorders and their associated complications most notably hepatic encephalopathy impact millions of individuals worldwide,including conditions such as non-alcoholic fatty liver disease,alcoho...A broad spectrum of liver disorders and their associated complications most notably hepatic encephalopathy impact millions of individuals worldwide,including conditions such as non-alcoholic fatty liver disease,alcoholic liver injury,viral hepatitis,hepatic fibrosis,cirrhosis,and hepatocellular carcinoma.The underlying pathogenic mechanisms are multifactorial,encompassing oxidative stress,inflammatory cascades,mitochondrial impairment,and disturbances in immune homeostasis.Hepatic encephalopathy patients experience cognitive impairment,mood disturbances,and psychomotor dysfunction,significantly reducing quality of life through mechanisms including oxidative stress,neuroinflammation,and neurotransmitter imbalances.The nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway serves as a critical antioxidative defense mechanism in these conditions.Nrf2 regulates the expression of protective enzymes,while HO-1 exerts anti-inflammatory,anti-apoptotic,and antifibrotic effects through heme degradation products.Natural herbal monomers as Nrf2 activators offer advantages of low toxicity,multi-target actions,and extensive traditional use.Various herbal monomers demonstrate specific effects against different liver diseases:In fatty liver,baicalin alleviates lipid accumulation and inflammation;In alcoholic liver disease,curcumin enhances Nrf2 activity reducing oxidative damage;In drug-induced liver injury,dihydromyricetin mitigates oxidative stress;In viral hepatitis,andrographolide inhibits hepatitis C virus replication;In liver fibrosis,multiple compounds inhibit stellate cell activation.These natural compounds simultaneously alleviate hepatic dysfunction and neuropsychiatric symptoms by modulating the Nrf2/HO-1 pathway,though clinical application still faces challenges such as low bioavailability,requiring further research.展开更多
Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance ...Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance quality,storage,and transportation of the fruits.Here,we isolated a novel few spines mutant(fs2)from the wild-type(WT)inbred line WD1,a North China-type cucumber with high density fruit spines,by an ethyl methanesulfonate(EMS)mutagenesis treatment.Genetic analysis revealed that the phenotype of fs2 is controlled by a single recessive nuclear gene.We fine-mapped the fs2 locus using F_(2) and BC_(1) populations(1,802 and 420 individuals,respectively),which showed that the candidate gene of FS2(Csa4G652850)encodes an ARID-HMG transcription factor containing an AT-rich interaction domain(ARID)and a high mobility group box domain(HMG).One SNP(C to T)and one InDel(a 40-bp deletion)in the coding region of FS2 result in amino acid variation and premature translation termination in the fs2 mutant,respectively.FS2 was found to be highly expressed in the apical buds and young ovaries.In addition,experiments suggest that FS2 participates in the regulation of fruit spine initiation by activating the expression of the Tril gene in cucumber.This work provides not only an important reference for understanding the molecular mechanisms of fruit spine development but also an important resource for fruit appearance quality breeding in cucumber.展开更多
BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate...BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.展开更多
Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The d...Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.展开更多
The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and ...The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a prevalent metabolic disorder increasingly linked with hypertension,posing significant health risks.The need for a predictive model tailored for T2DM patients is evident,as...BACKGROUND Type 2 diabetes mellitus(T2DM)is a prevalent metabolic disorder increasingly linked with hypertension,posing significant health risks.The need for a predictive model tailored for T2DM patients is evident,as current tools may not fully capture the unique risks in this population.This study hypothesizes that a nomogram incorporating specific risk factors will improve hypertension risk prediction in T2DM patients.AIM To develop and validate a nomogram prediction model for hypertension in T2DM patients.METHODS A retrospective observational study was conducted using data from 26850 T2DM patients from the Anhui Provincial Primary Medical and Health Information Management System(2022 to 2024).The study included patients aged 18 and above with available data on key variables.Exclusion criteria were type 1 diabetes,gestational diabetes,insufficient data,secondary hypertension,and abnormal liver and kidney function.The Least Absolute Shrinkage and Selection Operator regression and multivariate logistic regression were used to construct the nomogram,which was validated on separate datasets.RESULTS The developed nomogram for T2DM patients incorporated age,low-density lipoprotein,body mass index,diabetes duration,and urine protein levels as key predictive factors.In the training dataset,the model demonstrated a high discriminative power with an area under the receiver operating characteristic curve(AUC)of 0.823,indicating strong predictive accuracy.The validation dataset confirmed these findings with an AUC of 0.812.The calibration curve analysis showed excellent agreement between predicted and observed outcomes,with absolute errors of 0.017 for the training set and 0.031 for the validation set.The Hosmer-Lemeshow test yielded non-significant results for both sets(χ^(2)=7.066,P=0.562 for training;χ^(2)=6.122,P=0.709 for validation),suggesting good model fit.CONCLUSION The nomogram effectively predicts hypertension risk in T2DM patients,offering a valuable tool for personalized risk assessment and guiding targeted interventions.This model provides a significant advancement in the management of T2DM and hypertension comorbidity.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus rem...Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus remain largely unknown.Here,we found that all six paralogs of C2H2 zinc finger transcription factor WIP DOMAIN PROTEIN 2(BnaWIP2)showed increased expression during the initial 12 hours of germination,and expression was further enhanced by salinity stress.Under NaCl treatment,knocking out all six BnaWIP2 paralogs in B.napus led to significantly reduced germination,while overexpression of BnaC06.WIP2 promoted germination.Transcriptomic analysis revealed that BnaC06.WIP2 downregulated a series of genes related to abscisic acid(ABA)biosynthesis and signaling,among which BnaA05.NCED3,BnaC04.ABI5-2,BnaA03.EM6,and BnaA05.EM6 were directly repressed by BnaC06.WIP2.Further analysis showed that in germinating seeds,BnaC06.WIP2 was induced by ABA and in turn restrained ABA production,indicating that BnaC06.WIP2 forms a negative feedback loop with ABA to promote seed germination under salinity stress in B.napus.Collectively,these results enhance our understanding of the novel function of BnaWIP2 and provide valuable genetic resources for breeding salinity-tolerant rapeseed varieties.展开更多
BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height....BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height.Diabetes,especially type 2 diabetes mellitus(T2DM),has been reported to impair implant healing,drastically reducing implant success rates.AIM To analyze the high-risk factors for inflammatory response and prognosis after dental implantation in patients with T2DM,and provide strong evidence for reducing the incidence of postimplant peri-implantitis(PI).METHODS We performed a retrospective review of 146 patients with T2DM who had dental implants placed at Tianjin Fifth Central Hospital,between September 2021 and September 2023,which was regarded as the observation group.Moreover,60 ageand gender-matched individuals with normal blood glucose levels served as the control group.The general information,postoperative periodontal indices,and levels of inflammatory factors were comprehensively analyzed and compared.Furthermore,the incidence of postimplant PI was counted,and multivariate logistic regression was used to identify the determinants of postimplant PI.RESULTS In terms of the periodontal indices,the probing depth,modified sulcus bleeding index,and marginal bone loss in the observation cohorts began to increase significantly at 6 months and 3 months,respectively,after the completion of dental implant restoration.The T2DM cases demonstrated significantly elevated counts of leukocytes,lymphocytes,and neutrophils compared to the controls at 24 hours postoperatively.Moreover,the TNF-α,IL-1β,and IL-6 concentrations started to increase significantly in the gingival crevicular fluid 3 months after the completion of dental implant restoration in both cohorts,with the observation group exhibiting higher levels than the controls at each time point.63 out of the 146 cases developed PI.Multivariate logistic regression analysis indicated that high glycosylated hemoglobin levels,smoking,daily tooth-brushing frequency of less than once,and the anterior tooth as the implant site independently contributed to postimplant PI in T2DM cases,while a tooth-brushing duration of≥3 minutes was a protective factor.CONCLUSION Patients with T2DM are at risk of developing PI following dental implantation.Clinically,it is necessary to enhance the identification of risk factors for postimplant PI,improve risk prediction,prevention,and control,and formulate targeted intervention countermeasures to reduce the occurrence of postimplant PI.展开更多
A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mel...A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mellitus(T2DM)based on data from randomized controlled trials(RCTs).We searched electronic databases including PubMed,Cochrane Library,Embase,and Web of Science to identify clinical trials published up to 31 March 2023.Data was pooled using a random-effects model if significant heterogeneity(I2>50%),otherwise use a fixed-effects model.Fifty-six trials that included 3317 patients were enrolled for analysis.Meta-analysis reported that probiotic/prebiotic/synbiotic supplementation significantly reduced systolic blood pressure(SBP)(weighted mean difference(WMD):-3.57 mmHg,95% confidence interval(CI):-5.36,-1.78;P=0.000),diastolic blood pressure(DBP)(WMD:-2.05 mmHg,95%CI:-3.07,-1.04;P=0.000),triglycerides(TG)(WMD:-16.10 mg/dL,95%CI:-20.16,-12.05;P=0.000),total cholesterol(TC)(WMD:-14.00 mg/dL,95%CI:-20.46,-7.55;P=0.000),low-density lipoprotein cholesterol(LDL-C)(WMD:-7.03 mg/dL,95%CI:-9.25,-4.81;P=0.000),fasting plasma glucose(FPG)(WMD:-16.57 mg/dL,95%CI:-20.39,-12.74;P=0.000),hemoglobin A1c(HbA1c)(WMD:-0.44%,95%CI:-0.68,-0.20;P=0.000),insulin(standardized mean difference(SMD):-0.37,95%CI:-0.53,-0.21;P=0.000),homeostatic model assessment of insulin resistance(HOMA-IR)(WMD:-1.05,95%CI:-1.56,-0.54;P=0.000),C-reactive protein(CRP)(SMD:-0.35,95%CI:-0.57,-0.13;P=0.002),tumor necrosis factor-α(TNF-α)(SMD:-1.07,95%CI:-1.57,-0.56;P=0.000),interleukin-6(IL-6)(SMD:-0.37,95%CI:-0.61,-0.13;P=0.003)levels,they also increased the high-density lipoprotein cholesterol(HDL-C)(WMD:3.70 mg/dL,95%CI:1.80,5.60;P=0.000)levels in T2DM patients,as compared to the placebo groups.This meta-analysis supports the use of probiotic/prebiotic/synbiotic supplementation as an adjunctive therapy to improve blood pressure,glycemic control parameters,lipid profile and inflammatory markers in patients with T2DM,which are well-known cardiovascular risk factors.展开更多
Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has bee...Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.展开更多
BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is over...BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.展开更多
BACKGROUND Coronary heart disease(CHD)is a prevalent type 2 diabetes mellitus(T2DM)complication.Further,the risk stratification before angiography may help diagnose T2DM with CHD early.However,few studies have investi...BACKGROUND Coronary heart disease(CHD)is a prevalent type 2 diabetes mellitus(T2DM)complication.Further,the risk stratification before angiography may help diagnose T2DM with CHD early.However,few studies have investigated the coronary imaging characteristics and risk factors of patients with T2DM complicated with CHD.AIM To compare the differences in coronary imaging between patients with T2DM with and without CHD,determine the risk factors of T2DM complicated with CHD,and establish a predictive tool for diagnosing CHD in T2DM.METHODS This study retrospectively analyzed 103 patients with T2DM from January 2022 to May 2024.They are categorized based on CHD occurrence into:(1)The control group,consisting of patients with T2DM without CHD;and(2)The observation group,which includes patients with T2MD with CHD.Age,sex,smoking and drinking history,CHD family history,metformin(MET)treatment pre-admission,body mass index,fasting blood glucose(FBG),triglyceride(TG),total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol(LDL-C),serum creatinine,blood urea nitrogen(BUN),alanine aminotransferase,aspartate aminotransferase,glycosylated hemoglobin(HbA1c),and coronary imaging data of both groups were collected from the medical record system.Logistic risk analysis was conducted to screen risk factors.The prediction model’s prediction efficiency was evaluated with receiver operating characteristic curves.RESULTS The control and observation groups consisted of 48 and 55 cases,respectively.The two groups were statistically different in terms of age(t=2.006,P=0.048),FBG(t=6.038,P=0.000),TG(t=2.015,P=0.047),LDL-C(t=2.017,P=0.046),and BUN(t=2.035,P=0.044).The observation group demonstrated lower proportions of patients receiving MET(χ^(2)=5.073,P=0.024)and higher proportions of patients with HbA1c of>7.0%(χ^(2)=6.980,P=0.008)than the control group.The observation group consisted of 15,17,and 23 cases of moderate stenosis,severe stenosis,and occlusion,respectively,with a greater number of coronary artery occlusion cases than the control group(χ^(2)=6.399,P=0.041).The observation group consisted significantly higher number of diffuse lesion cases at 35 compared with the control group(χ^(2)=15.420,P=0.000).The observation group demonstrated a higher right coronary artery(RCA)stenosis index(t=6.730,P=0.000),circumflex coronary artery(LCX)stenosis index(t=5.738,P=0.000),and total stenosis index(t=7.049,P=0.000)than the control group.FBG[odds ratio(OR)=1.472;95%confidence interval(CI):1.234-1.755;P=0.000]and HbA1c(OR=3.197;95%CI:1.149-8.896;P=0.026)were independent risk factors for T2DM complicated with CHD,whereas MET(OR=0.350;95%CI:0.129-0.952;P=0.040)was considered a protective factor for CHD in T2DM.CONCLUSION Coronary artery occlusion is a prevalent complication in patients with T2DM.Patients with T2MD with CHD demonstrated a higher degree of RCA and LCX stenosis than those with T2DM without CHD.FBG,HbA1c,and MET treatment history are risk factors for T2DM complicated with CHD.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-li...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-like macrophages,is associated with the most aggressive behavior.Therefore,these macrophages provide the primary growth and migratory factors to the tumor cells,including those of HCC.Current therapies are not well optimized for eliminating trans-formed cells or neutralizing the tumor immune microenvironment leukocytes,such as TAMs.Growth differentiation factor 11(GDF11)may represent a promi-sing dual therapeutic target due to its reported anti-tumorigenic and immuno-modulatory properties.AIM To characterize the effects of GDF11 in M2-like macrophages and the HCC cell interaction using a functional in vitro model.METHODS This research used THP-1 and Huh7 cell lines.We applied recombinant GDF11(50 ng/mL)every 24 hours on THP-1 differentiated macrophages with M2-like polarization using interleukin-4 and interleukin-13.Firstly,the GDF11 effects on signaling,viability,proliferation,metabolism,and redox state in macrophages were charac-terized.Subsequently,we extracted conditioned media(CM)from macrophages and performed indirect co-cultures with Huh7 cells.The functional parameters were proliferation and migration assays.Finally,we charac-terized secretion in the CM using the cytokine array membrane assay.RESULTS The present study demonstrated that GDF11 activates the canonical pathway Smad2/3 without cytotoxic or prolif-erative effects.We provide evidence that GDF11 also diminishes the pro-tumoral properties of M2-like macrophages.GDF11 promoted the reduction of the M2-like macrophage marker,cluster of differentiation 206,indicating a loss of pro-tumoral properties in these leukocytes.Furthermore,this molecule induced changes in metabolism and an increase in reactive oxygen species.Using CM derived from GDF11-treated M2-like macrophages,we observed a reduction in the proliferation and migratory capacity of liver cancer cells.Moreover,the cytokine profile was affected by GDF11 stimulus,demonstrating that this molecule alters the pro-tumoral properties of TAMs,which in turn impact the behavior of HCC-derived cells.CONCLUSION This in vitro study suggests that mitigating tumor-promoting or M2-like macrophages with GDF11 may be an effective strategy for controlling the aggressiveness of HCC.展开更多
基金supported by the Science&Technology Department of Sichuan Province(No.2019YFS0040)the Improvement Plan of“Xinglin Scholar”Scientific Research Talent,Chengdu University of Traditional Chinese Medicine(No.XKTD2022002)。
文摘The activation of the sirtuin1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species(ROS)levels.Clinical trials have demonstrated that Zhongfeng Xingnao Liquid(ZFXN)ameliorates post-stroke cognitive impairment(PSCI).However,the underlying mechanism,particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway,remains unclear.This study employed an oxygen-glucose deprivation(OGD)cell model using SHSY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation(2VO).The effects of ZFXN on learning and memory,neuroprotective activity,mitochondrial function,oxidative stress,and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro.Results indicated that ZFXN significantly increased the B-cell lymphoma 2(Bcl2)/Bcl2-associated X(Bax)ratio,reduced terminal deoxynucleotidyl transferase-mediated d UTP nickend-labeling(TUNEL)+cells,and markedly improved cognition,synaptic plasticity,and neuronal function in the hippocampus and cortex.Furthermore,ZFXN exhibited potent antioxidant activity,evidenced by decreased ROS and malondialdehyde(MDA)content and increased superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)levels.ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential(MMP),Tom 20 fluorescence intensity,adenosine triphosphate(ATP)and energy charge(EC)levels,and mitochondrial complexⅠandⅢactivity,thereby inhibiting mitochondrial damage.Additionally,ZFXN significantly increased SIRT1 activity and elevated SIRT1,nuclear Nrf2,and HO-1 levels.Notably,these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro.In conclusion,ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
基金funded by the National Natural Science Foundation of China(Grant Nos.32202502,U21A20230,32070331,32102380 and 32072580)National Key Research and Development Program(Grant No.2018YFD1000800)+3 种基金the Key-Area Research and Development Program of Guangdong Province(Grant No.2022B0202080001)the Special Fund for Seed Industry of Guangdong Province Rural Revitalization Strategy(Grant No.2022-NPY00-024)Tibet Autonomous Region of Lhasa City Science and Technology Project(Grant No.LSKJ202310)the Science and Technology Project of Bijie City(Grant No.BKK2022-3)。
文摘The transcriptional cascade and regulatory loop play crucial roles in regulating plant-specialized metabolite biosynthesis.Capsaicinoids are unique to the genus Capsicum and confer a pungent flavor to its fruits.However,the transcriptional regulation of capsaicinoid biosynthesis remains largely unknown.In this study,two AP2/ERF transcription factors(TFs),CaERF102 and CaERF111,were characterized for their role in the capsaicinoid biosynthesis process.Expression analysis of two ERFs and capsaicinoid biosynthetic genes(CBGs)suggested that they were associated with capsaicinoid biosynthesis.Both ERFs encode nuclear-localized proteins and function as transcriptional activators through their C-terminal activation motifs.The two ERF TFs participated in capsaicinoid biosynthesis by directly activating the promoters of key CBGs,and this activation was significantly enhanced when CaMYC2 was co-expressed.Moreover,CaERF102 and CaERF111 were found to interact with CaMYC2.This study helps elucidate the AP2/ERF TF regulatory network that governs capsaicinoid biosynthesis in Capsicum species.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
基金Supported by the Hainan Provincial Natural Science Foundation of China,No.823MS133 and No.821QN0979。
文摘BACKGROUND Parkinson's disease(PD)-a progressive neurodegenerative disorder-is characterized by motor and gastrointestinal dysfunction.The exploration of novel therapeutic strategies for PD is vital.AIM To investigate the potential mechanism of action of rhapontin-a natural compound with known antioxidant and anti-inflammatory properties-in the context of PD.METHODS Network pharmacology was used to predict the targets and mechanisms of action of rhapontin in PD.Behavioral tests and tyrosine hydroxylase immunofluorescence analysis were used to assess the effect of rhapontin on symptoms and pathology in MPTP-induced mice.Interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,and IL-10 levels in tissues were measured using an enzyme-linked immunosorbent assay(ELISA).Additionally,nuclear factor erythroid 2-related factor 2(NRF2)activation was confirmed using western blotting.RESULTS NRF2 was predicted to be the key transcription factor underlying the therapeutic effects of rhapontin in PD,and its anti-PD action may be associated with its antiinflammatory and antioxidant properties.Rhapontin ameliorated the loss of dopaminergic neurons and gastrointestinal dysfunction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mice by activating NRF2.Additio-nally,rhapontin treatment significantly decreased pro-inflammatory cytokines(IL-6,TNF-α,IL-1β)in the substantia nigra,striatum,and colon,whereas it increased anti-inflammatory cytokine(IL-10)levels only in the colon,indicating the involvement of gut–brain axis in its neuroprotective potential.Finally,NRF2 was identified as a key transcription factor activated by rhapontin,particularly in the colon.CONCLUSION We elucidated the effects of rhapontin in MPTP-induced PD mouse models using a combination of network pharmacology analysis,behavioral assessments,immunofluorescence,ELISA,and Western blotting.Our findings revealed the multifaceted role of rhapontin in ameliorating PD through its anti-inflammatory and antioxidant properties,particularly by activating NRF2,paving the way for future research into targeted therapies for PD.
文摘BACKGROUND Erianin is a natural bibenzyl compound extracted from Dendrobium chrysotoxum and is known for its anti-inflammatory and antioxidant properties.AIM To explore the possible therapeutic mechanisms of erianin and determine if it can reduce cardiac damage in mice with type 2 diabetes.METHODS High-fat diet and intraperitoneal injections of streptozotocin were used to induce type 2 diabetes mellitus in C57BL/6 mice.Mice were divided into different groups including control,model,and treatment with various doses of erianin(10,20,and 40 mg/kg)as well as ML-385+erianin group.RESULTS Erianin reduced oxidative stress and inflammation and alleviated diabetic cardiomyopathy through the activation of the adenosine monophosphate-acti-vated protein kinase(AMPK)-nuclear factor erythroid 2-related factor 2(Nrf2)-heme oxygenase-1(HO-1)pathway.Treatments with erianin-M and erianin-H promoted weight stabilization and normalized fasting glucose levels relative to diabetic controls.Echocardiographic assessment demonstrated that erianin dose-dependently enhanced left ventricular systolic function(left ventricular ejection fraction,left ventricular fractional shortening)and mitigated ventricular remodeling(left ventricular internal diameter at end-diastole,left ventricular internal diameter at end-systole;P<0.05 vs model group).No significant differences were observed between the ML-385+erianin and placebo-treated groups.Histopathological examination through hematoxylin-eosin staining indicated that erianin ameliorated myocardial fiber fragmentation,structural disorganization,inflammatory cell infiltration,and cytolytic damage.Furthermore,it significantly reduced the serum levels of cardiac troponin I,creatine kinase,and its MB isoenzyme.However,the ML-385+erianin co-treatment failed to alleviate myocardial injury.Metabolic profiling revealed erianin-mediated improvements in glycemic regulation(glycated hemoglobin:P<0.001),plasma insulin homeostasis,and lipid metabolism(total cholesterol,triglycerides,low-density lipo-protein cholesterol reduction,and high-density lipoprotein cholesterol restoration;P<0.05 vs model group).Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin(IL)-1β,and IL-6 were markedly suppressed in the erianin-M and erianin-H groups compared with the model group,whereas no significant differences were detected between the model and ML-385+erianin groups.Oxidative stress parameters showed decreased malondialdehyde levels accompanied by elevated superoxide dismutase and catalase activities in erianin-treated groups,with the most pronounced effects in the erianin-H group(P<0.05).Western blot analysis confirmed the significant upregulation of proteins associated with the AMPK/Nrf2/HO-1 pathway in erianin-M and erianin-H groups.These protective effects were abolished in the ML-385+erianin co-treatment group,which showed no statistical differences from the model group.CONCLUSION Erianin can effectively alleviate myocardial injury in type 2 diabetic mice by activating the AMPK-Nrf2-HO-1 pathway.
文摘BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-associated protein 1(Keap1)signaling pathway,which is crucial for the body’s defense against oxidative stress.The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process.There are still limited data on the roles of Nrf2,its downstream signaling molecules,and angiogenesis markers in patients undergoing NPWT.AIM To study the mechanism of NPWT in DFUs.METHODS This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital,who were divided into Control group(n=21)and NPWT group(n=19).The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment.The wound condition,erythrocyte sedimentation rate(ESR),procalcitonin(PCT),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(b-FGF),cluster of differentiation 31(CD31),and levels of oxidative stress[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(T-AOC)]were analyzed before and 7 days after treatment by the Mann-Whitney U test.RESULTS The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment.The levels of ESR,PCT,IL-6,and TNF-αwere significantly reduced in the NPWT group compared to the control group(P<0.05),while the levels of CD31,VEGF,and b-FGF showed significant increases(P<0.05).The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets(SOD,CAT,and T-AOC),accompanied by decreases in the levels of Keap1 and MDA(P<0.05).CONCLUSION NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress.Its effects could possibly be enhanced through the action of Nrf2.
基金supported by the National Natural Science Foundation of China(31972425)the Shanghai Agriculture Applied Technology Development Program,China(2020-02-08-00-08-F0148)。
文摘Fruit spine density is an important commercial trait for cucumber(Cucumis sativus L.).Most North China-type cucumbers that are grown over large areas have a dense-spine phenotype,which directly affects the appearance quality,storage,and transportation of the fruits.Here,we isolated a novel few spines mutant(fs2)from the wild-type(WT)inbred line WD1,a North China-type cucumber with high density fruit spines,by an ethyl methanesulfonate(EMS)mutagenesis treatment.Genetic analysis revealed that the phenotype of fs2 is controlled by a single recessive nuclear gene.We fine-mapped the fs2 locus using F_(2) and BC_(1) populations(1,802 and 420 individuals,respectively),which showed that the candidate gene of FS2(Csa4G652850)encodes an ARID-HMG transcription factor containing an AT-rich interaction domain(ARID)and a high mobility group box domain(HMG).One SNP(C to T)and one InDel(a 40-bp deletion)in the coding region of FS2 result in amino acid variation and premature translation termination in the fs2 mutant,respectively.FS2 was found to be highly expressed in the apical buds and young ovaries.In addition,experiments suggest that FS2 participates in the regulation of fruit spine initiation by activating the expression of the Tril gene in cucumber.This work provides not only an important reference for understanding the molecular mechanisms of fruit spine development but also an important resource for fruit appearance quality breeding in cucumber.
基金Supported by Hebei Province Medical Science Research Project Plan,No.20230755.
文摘BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.
基金financially supported by the Natural Science Foundation of China(No.82003766)Taishan Scholars Program(NO.tsqn202211219)+1 种基金the Key Research and Development Project of Shandong Province(No.2021ZDSYS27)Shandong Province nature fund surface project(Grant No.ZR2024MH088)。
文摘Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.
基金National Natural Science Foundation of China,No.T2341018Science and Technology Innovation Project of Chinese Academy of Traditional Chinese Medicine,No.CI2023C049YLL.
文摘The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a prevalent metabolic disorder increasingly linked with hypertension,posing significant health risks.The need for a predictive model tailored for T2DM patients is evident,as current tools may not fully capture the unique risks in this population.This study hypothesizes that a nomogram incorporating specific risk factors will improve hypertension risk prediction in T2DM patients.AIM To develop and validate a nomogram prediction model for hypertension in T2DM patients.METHODS A retrospective observational study was conducted using data from 26850 T2DM patients from the Anhui Provincial Primary Medical and Health Information Management System(2022 to 2024).The study included patients aged 18 and above with available data on key variables.Exclusion criteria were type 1 diabetes,gestational diabetes,insufficient data,secondary hypertension,and abnormal liver and kidney function.The Least Absolute Shrinkage and Selection Operator regression and multivariate logistic regression were used to construct the nomogram,which was validated on separate datasets.RESULTS The developed nomogram for T2DM patients incorporated age,low-density lipoprotein,body mass index,diabetes duration,and urine protein levels as key predictive factors.In the training dataset,the model demonstrated a high discriminative power with an area under the receiver operating characteristic curve(AUC)of 0.823,indicating strong predictive accuracy.The validation dataset confirmed these findings with an AUC of 0.812.The calibration curve analysis showed excellent agreement between predicted and observed outcomes,with absolute errors of 0.017 for the training set and 0.031 for the validation set.The Hosmer-Lemeshow test yielded non-significant results for both sets(χ^(2)=7.066,P=0.562 for training;χ^(2)=6.122,P=0.709 for validation),suggesting good model fit.CONCLUSION The nomogram effectively predicts hypertension risk in T2DM patients,offering a valuable tool for personalized risk assessment and guiding targeted interventions.This model provides a significant advancement in the management of T2DM and hypertension comorbidity.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
基金supported by the Biological Breeding-National Science and Technology Major Project(2022ZD04010)Scientific and Technological Innovation Team of Shaanxi Province(2024RS-CXTD-69)+1 种基金Key Research and Development Program of Shaanxi Province(2021LLRH-07)a grant from the Yang Ling Seed Industry Innovation Center(K3031122024).
文摘Rapeseed(Brassica napus L.)is a global oil crop.Salinity stress impedes the growth of rapeseed,especially during seed germination.The key genes mediating salinity stress response during seed germination in B.napus remain largely unknown.Here,we found that all six paralogs of C2H2 zinc finger transcription factor WIP DOMAIN PROTEIN 2(BnaWIP2)showed increased expression during the initial 12 hours of germination,and expression was further enhanced by salinity stress.Under NaCl treatment,knocking out all six BnaWIP2 paralogs in B.napus led to significantly reduced germination,while overexpression of BnaC06.WIP2 promoted germination.Transcriptomic analysis revealed that BnaC06.WIP2 downregulated a series of genes related to abscisic acid(ABA)biosynthesis and signaling,among which BnaA05.NCED3,BnaC04.ABI5-2,BnaA03.EM6,and BnaA05.EM6 were directly repressed by BnaC06.WIP2.Further analysis showed that in germinating seeds,BnaC06.WIP2 was induced by ABA and in turn restrained ABA production,indicating that BnaC06.WIP2 forms a negative feedback loop with ABA to promote seed germination under salinity stress in B.napus.Collectively,these results enhance our understanding of the novel function of BnaWIP2 and provide valuable genetic resources for breeding salinity-tolerant rapeseed varieties.
基金Supported by Tianjin Municipality Health Science and Technology Project,No.TJWJ2023MS052.
文摘BACKGROUND Dental implants are widely used to replace missing teeth.Currently,clinicians assess osseointegration success by measuring the implant’s stability within the bone and monitoring the marginal tissue height.Diabetes,especially type 2 diabetes mellitus(T2DM),has been reported to impair implant healing,drastically reducing implant success rates.AIM To analyze the high-risk factors for inflammatory response and prognosis after dental implantation in patients with T2DM,and provide strong evidence for reducing the incidence of postimplant peri-implantitis(PI).METHODS We performed a retrospective review of 146 patients with T2DM who had dental implants placed at Tianjin Fifth Central Hospital,between September 2021 and September 2023,which was regarded as the observation group.Moreover,60 ageand gender-matched individuals with normal blood glucose levels served as the control group.The general information,postoperative periodontal indices,and levels of inflammatory factors were comprehensively analyzed and compared.Furthermore,the incidence of postimplant PI was counted,and multivariate logistic regression was used to identify the determinants of postimplant PI.RESULTS In terms of the periodontal indices,the probing depth,modified sulcus bleeding index,and marginal bone loss in the observation cohorts began to increase significantly at 6 months and 3 months,respectively,after the completion of dental implant restoration.The T2DM cases demonstrated significantly elevated counts of leukocytes,lymphocytes,and neutrophils compared to the controls at 24 hours postoperatively.Moreover,the TNF-α,IL-1β,and IL-6 concentrations started to increase significantly in the gingival crevicular fluid 3 months after the completion of dental implant restoration in both cohorts,with the observation group exhibiting higher levels than the controls at each time point.63 out of the 146 cases developed PI.Multivariate logistic regression analysis indicated that high glycosylated hemoglobin levels,smoking,daily tooth-brushing frequency of less than once,and the anterior tooth as the implant site independently contributed to postimplant PI in T2DM cases,while a tooth-brushing duration of≥3 minutes was a protective factor.CONCLUSION Patients with T2DM are at risk of developing PI following dental implantation.Clinically,it is necessary to enhance the identification of risk factors for postimplant PI,improve risk prediction,prevention,and control,and formulate targeted intervention countermeasures to reduce the occurrence of postimplant PI.
基金Jiangsu College of Nursing 2023 Special Fund for Research and Development of Medical-Educational Integration。
文摘A systematic review and meta-analysis study was conducted to assess the effectiveness of probiotic/prebiotic/synbiotic supplementation on the effects of cardiovascular risk factors in patients with type 2 diabetes mellitus(T2DM)based on data from randomized controlled trials(RCTs).We searched electronic databases including PubMed,Cochrane Library,Embase,and Web of Science to identify clinical trials published up to 31 March 2023.Data was pooled using a random-effects model if significant heterogeneity(I2>50%),otherwise use a fixed-effects model.Fifty-six trials that included 3317 patients were enrolled for analysis.Meta-analysis reported that probiotic/prebiotic/synbiotic supplementation significantly reduced systolic blood pressure(SBP)(weighted mean difference(WMD):-3.57 mmHg,95% confidence interval(CI):-5.36,-1.78;P=0.000),diastolic blood pressure(DBP)(WMD:-2.05 mmHg,95%CI:-3.07,-1.04;P=0.000),triglycerides(TG)(WMD:-16.10 mg/dL,95%CI:-20.16,-12.05;P=0.000),total cholesterol(TC)(WMD:-14.00 mg/dL,95%CI:-20.46,-7.55;P=0.000),low-density lipoprotein cholesterol(LDL-C)(WMD:-7.03 mg/dL,95%CI:-9.25,-4.81;P=0.000),fasting plasma glucose(FPG)(WMD:-16.57 mg/dL,95%CI:-20.39,-12.74;P=0.000),hemoglobin A1c(HbA1c)(WMD:-0.44%,95%CI:-0.68,-0.20;P=0.000),insulin(standardized mean difference(SMD):-0.37,95%CI:-0.53,-0.21;P=0.000),homeostatic model assessment of insulin resistance(HOMA-IR)(WMD:-1.05,95%CI:-1.56,-0.54;P=0.000),C-reactive protein(CRP)(SMD:-0.35,95%CI:-0.57,-0.13;P=0.002),tumor necrosis factor-α(TNF-α)(SMD:-1.07,95%CI:-1.57,-0.56;P=0.000),interleukin-6(IL-6)(SMD:-0.37,95%CI:-0.61,-0.13;P=0.003)levels,they also increased the high-density lipoprotein cholesterol(HDL-C)(WMD:3.70 mg/dL,95%CI:1.80,5.60;P=0.000)levels in T2DM patients,as compared to the placebo groups.This meta-analysis supports the use of probiotic/prebiotic/synbiotic supplementation as an adjunctive therapy to improve blood pressure,glycemic control parameters,lipid profile and inflammatory markers in patients with T2DM,which are well-known cardiovascular risk factors.
基金supported by the National Natural Science Foundation of China[grant numbers 32271914 and 32301660]the Quality Engineering Project of Anhui Provincial Department of Education[grant number 2023zygzts007].
文摘Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.
基金Supported by the Jiangsu Provincial Health and Family Planning Commission Personnel Talent Project,No.R2017005.
文摘BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.
基金Supported by the Science and Technology Major Project of Changzhou Science and Technology Bureau,No.CE20205047Natural Science Foundation of Xinjiang Uygur Autonomous Region,No.2022D01F52Changzhou A Major Scientific Research Project of the Municipal Health Commission,No.ZD202220.
文摘BACKGROUND Coronary heart disease(CHD)is a prevalent type 2 diabetes mellitus(T2DM)complication.Further,the risk stratification before angiography may help diagnose T2DM with CHD early.However,few studies have investigated the coronary imaging characteristics and risk factors of patients with T2DM complicated with CHD.AIM To compare the differences in coronary imaging between patients with T2DM with and without CHD,determine the risk factors of T2DM complicated with CHD,and establish a predictive tool for diagnosing CHD in T2DM.METHODS This study retrospectively analyzed 103 patients with T2DM from January 2022 to May 2024.They are categorized based on CHD occurrence into:(1)The control group,consisting of patients with T2DM without CHD;and(2)The observation group,which includes patients with T2MD with CHD.Age,sex,smoking and drinking history,CHD family history,metformin(MET)treatment pre-admission,body mass index,fasting blood glucose(FBG),triglyceride(TG),total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol(LDL-C),serum creatinine,blood urea nitrogen(BUN),alanine aminotransferase,aspartate aminotransferase,glycosylated hemoglobin(HbA1c),and coronary imaging data of both groups were collected from the medical record system.Logistic risk analysis was conducted to screen risk factors.The prediction model’s prediction efficiency was evaluated with receiver operating characteristic curves.RESULTS The control and observation groups consisted of 48 and 55 cases,respectively.The two groups were statistically different in terms of age(t=2.006,P=0.048),FBG(t=6.038,P=0.000),TG(t=2.015,P=0.047),LDL-C(t=2.017,P=0.046),and BUN(t=2.035,P=0.044).The observation group demonstrated lower proportions of patients receiving MET(χ^(2)=5.073,P=0.024)and higher proportions of patients with HbA1c of>7.0%(χ^(2)=6.980,P=0.008)than the control group.The observation group consisted of 15,17,and 23 cases of moderate stenosis,severe stenosis,and occlusion,respectively,with a greater number of coronary artery occlusion cases than the control group(χ^(2)=6.399,P=0.041).The observation group consisted significantly higher number of diffuse lesion cases at 35 compared with the control group(χ^(2)=15.420,P=0.000).The observation group demonstrated a higher right coronary artery(RCA)stenosis index(t=6.730,P=0.000),circumflex coronary artery(LCX)stenosis index(t=5.738,P=0.000),and total stenosis index(t=7.049,P=0.000)than the control group.FBG[odds ratio(OR)=1.472;95%confidence interval(CI):1.234-1.755;P=0.000]and HbA1c(OR=3.197;95%CI:1.149-8.896;P=0.026)were independent risk factors for T2DM complicated with CHD,whereas MET(OR=0.350;95%CI:0.129-0.952;P=0.040)was considered a protective factor for CHD in T2DM.CONCLUSION Coronary artery occlusion is a prevalent complication in patients with T2DM.Patients with T2MD with CHD demonstrated a higher degree of RCA and LCX stenosis than those with T2DM without CHD.FBG,HbA1c,and MET treatment history are risk factors for T2DM complicated with CHD.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-like macrophages,is associated with the most aggressive behavior.Therefore,these macrophages provide the primary growth and migratory factors to the tumor cells,including those of HCC.Current therapies are not well optimized for eliminating trans-formed cells or neutralizing the tumor immune microenvironment leukocytes,such as TAMs.Growth differentiation factor 11(GDF11)may represent a promi-sing dual therapeutic target due to its reported anti-tumorigenic and immuno-modulatory properties.AIM To characterize the effects of GDF11 in M2-like macrophages and the HCC cell interaction using a functional in vitro model.METHODS This research used THP-1 and Huh7 cell lines.We applied recombinant GDF11(50 ng/mL)every 24 hours on THP-1 differentiated macrophages with M2-like polarization using interleukin-4 and interleukin-13.Firstly,the GDF11 effects on signaling,viability,proliferation,metabolism,and redox state in macrophages were charac-terized.Subsequently,we extracted conditioned media(CM)from macrophages and performed indirect co-cultures with Huh7 cells.The functional parameters were proliferation and migration assays.Finally,we charac-terized secretion in the CM using the cytokine array membrane assay.RESULTS The present study demonstrated that GDF11 activates the canonical pathway Smad2/3 without cytotoxic or prolif-erative effects.We provide evidence that GDF11 also diminishes the pro-tumoral properties of M2-like macrophages.GDF11 promoted the reduction of the M2-like macrophage marker,cluster of differentiation 206,indicating a loss of pro-tumoral properties in these leukocytes.Furthermore,this molecule induced changes in metabolism and an increase in reactive oxygen species.Using CM derived from GDF11-treated M2-like macrophages,we observed a reduction in the proliferation and migratory capacity of liver cancer cells.Moreover,the cytokine profile was affected by GDF11 stimulus,demonstrating that this molecule alters the pro-tumoral properties of TAMs,which in turn impact the behavior of HCC-derived cells.CONCLUSION This in vitro study suggests that mitigating tumor-promoting or M2-like macrophages with GDF11 may be an effective strategy for controlling the aggressiveness of HCC.
