Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbl...Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).展开更多
As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to pr...As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,wi...Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological...Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.展开更多
The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additio...The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.展开更多
Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricl...Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricle(RV)is also affected by diabetes and may be independently responsible for adverse outcomes in diabetic patients with or without LV failure.Yu et al conducted a 30-week longitudinal evaluation of biventricular function and pathology in OVE26 diabetic mice and revealed early diastolic dysfunction preceding systolic decline,suggesting that early LV diastolic impairment precedes the later onset of systolic dysfunction.With age,the animals developed fibrosis,hypertrophy,and pulmonary arterial hypertension in the RV.The purpose of this editorial is to contextualize these findings within the existing literature by highlighting the interplay between cardiac chambers and the vasculature.We also seek to reiterate that DCM is a condition extending beyond left ventricular dysfunction.As the authors note,the right side of the heart may remain"the forgotten ventricle"in diabetic patients.We hope that the mechanisms discussed in this paper will help researchers to understand the pathogenesis of cardiovascular disease in this context and encourage clinicians to be more attentive to the associated clinical symptoms.展开更多
This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between fo...A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between foreskin length and sexual dysfunction was evaluated.A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China(Hefei,China).Clinical characteristics,including foreskin length,were collected,and sexual function was assessed by the International Index of Erectile Function-5(IIEF-5)and Premature Ejaculation Diagnostic Tool(PEDT)questionnaires.Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction.Among the 2721 erectile dysfunction(ED)patients and 1064 premature ejaculation(PE)patients,301(11.1%)ED patients and 135(12.7%)PE patients had redundant foreskin,respectively.Men in the PE group were more likely to have redundant foreskin than men in the non-PE group(P=0.004).Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED(adjusted odds ratio[aOR]=1.31,adjusted P=0.04),moderate PE(aOR=1.38,adjusted P=0.02),and probable PE(aOR=1.37,adjusted P=0.03)after adjusting for confounding variables.Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction,especially in PE patients.Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.展开更多
Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in re...Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in reduced ATP synthesis,elevated reactive oxygen species(ROS)formation,and mitochondrial malfunction,which instigates oxidative stress and cellular damage,critical elements in neurodegenerative disorders like Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and Alzheimer’s disease(AD).In addition to causing direct neuronal injury,rotenone significantly contributes to the activation of glial cells,specifically microglia and astrocytes.Activated microglia assumes a proinflammatory(M1)phenotype,distinguished by the secretion of inflammatory cytokines including tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),with the generation of nitric oxide and ROS,which exacerbate the neuronal injury.Astrocytes can intensify neuroinflammation by secreting proinflammatory molecules and impairing their neuroprotective roles.Our hypothesis is that rotenone is posited to elicit a neuroinflammatory response via mitochondrial malfunction,ROS generation,and the activation of proinflammatory pathways in microglia and astrocytes.This mechanism leads to accelerated neuronal impair-ment,promoting neurodegeneration.Comprehending the inflammatory pathways activated by rotenone is crucial for pinpointing therapeutic targets to regulate glial responses and mitigate the advancement of neurodegenerative disorders linked to mitochondrial malfunction and chronic inflammation.This review examines the function of glial cells and critical inflammatory pathways,namely Nuclear factor kappaβ(NF-κB),Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin(PI3K/AKT/mTOR),and Wnt/β-catenin signaling pathway in Parkinson’s disease,Alzheimer’s disease,and ALS,emphasizing illness-specific responses and the translational constraints of rotenone-based models.The objective is to consolidate existing understanding regarding the role of rotenone-induced mitochondrial failure in promoting glial activation and neuroinflammation,highlighting the necessity for additional research into these pathways.Despite the prevalent application of rotenone in experimental models,its specific effects on glial-mediated inflammation are inadequately comprehended,necessitating further investigation to guide the formulation of targeted therapeutic strategies.展开更多
AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 p...AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 patients with DME treated with IVC with 3+PRN regimen.Based on the estimated glomerular filtration rate(eGFR),the patients were divided into normal renal function group(n=37),impaired renal function group(n=27),and renal insufficiency group(n=36).The main outcome measures were best-corrected visual acuity(BCVA)and central subfield macular thickness(CST).Clinical parameters included blood urea nitrogen,serum creatinine,serum uric acid,glycosylated hemoglobin(HbA1c),and hemoglobin.RESULTS:The mean follow-up time was 3.9mo.The mean number of IVCs was 2.07±1.22 in the three groups.Mean BCVA improved significantly from 0.81±0.49 logMAR at baseline to 0.72±0.52 logMAR in the three groups at the final visit(P<0.001).Mean CST decreased significantly from 427.85±148.99μm at baseline to 275.31±108.31μm at final visit(P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).The three groups had no differences in baseline HbA1c levels(P>0.05).Good baseline BCVA(logMAR,P=0.001)and thicker baseline CST(P=0.041)were associated with visual acuity improvement.Higher eGFR(P<0.001),hemoglobin(P=0.032)and thicker baseline CST(P=0.017)were associated with macular edema retrogression in the conbercept-treated diabetic patients,which showed better anatomical response to IVC.CONCLUSION:Our results indicate that the renal dysfunction is the risk factor associated with the efficacy of IVC for DME.展开更多
Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis medi...Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis media,whereas the precise contribution of SIRT3 in this mechanism remains uncertain.This study aims to reveal the involvement of SIRT3 in murine ETD induced by LPS.Results:Histological analysis showed no baseline differences in ET structure between WT and SIRT3 knockout(SIRT3-KO)mice.However,LPS exposure led to increased goblet cell proliferation and MUC5 AC mucus secretion in both genotypes,with SIRT3-KO exacerbating these effects.The SIRT3-KO group displayed reduced cilia length.Functionally,SIRT3-KO mice showed a significantly higher initial POP and decreased MCC compared to the WT group after LPS exposure.Additionally,the active clearance of negative pressure(ACNP)was significantly reduced in SIRT3-KO mice,indicating compromised ET function.Conclusions:SIRT3-KO increased resistance to ET opening in mice exposed to LPS,and this effect may be related to the upregulated MUC5 AC expression,the increased surface tension of the luminal fluid and the impaired MCC function in mice exposed to LPS.展开更多
ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted usin...ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted using PubMed and Cochrane databases for relevant articles published in English between 2008 and 2023. Keywords used included “ketamine” and “upper urinary tract”.ResultsA total of 22 papers were included. Relatively few studies have focused on ketamine-associated UUT dysfunction. Exclusion criteria included lack of hydronephrosis, or pathological findings. After careful screening and exclusion, we finally adopted 11 of these papers and analyzed them. Ketamine-associated UUT dysfunction may be a concern in this field.ConclusionKetamine abuse can lead to UUT impairment and dysfunction, with symptoms such as bladder dysfunction and contracted bladder with vesicoureteral reflux, direct damage and barrier dysfunction, inflammation, apoptosis, fibrosis and stricture, and papillary necrosis. Oxidative stress, autophagy, and microvascular injury are also potential pathogenic mechanisms. The detection of these symptoms largely depends on laboratory and imaging examinations. The treatment principles of ketamine-associated UUT dysfunction are protecting the UUT, improving bladder dysfunction, and resuming normal social life. More investigations are needed to clarify the mechanisms and shed light on the treatment of ketamine-associated UUT damage.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is ...BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.展开更多
In this article,we comment on the recent network analysis by Li et al,which explores depression,anxiety,and their associated factors in individuals with noncommunicable chronic diseases(NCDs).We highlight three often-...In this article,we comment on the recent network analysis by Li et al,which explores depression,anxiety,and their associated factors in individuals with noncommunicable chronic diseases(NCDs).We highlight three often-overlooked domains in this population:Mental vulnerability(depression,anxiety,fatigue,nervousness),dysfunction in family functioning(family health,intimate partner violence),and digital exposure(media exposure,problematic internet use),and examine their dynamic interrelations within a psychosocial network framework.The findings reveal a complex system in which emotional dysregulation,family relational adversity,and digital behaviors mutually reinforce one another to heigh-ten psychiatric risk.Notably,traditional demographic factors such as gender,ethnicity,and residence had minimal impact on overall network strength.We argue that these interconnected domains represent modifiable yet underrecognized targets for mental health intervention among medically vulnerable populations.Strategies that promote emotional resilience,strengthen family systems,and enhance digital literacy may play a pivotal role in disrupting maladaptive network pathways and improving quality of life for individuals with NCDs.Future research should prioritize longitudinal and multimodal designs to clarify causal mechanisms and support tailored,systems-level psychosocial interventions.展开更多
With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis...With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.展开更多
Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore der...Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.展开更多
基金supported by China Scholarship Council(No.202106380078 to HL)the Netherlands Cardiovascular Research Initiative:The Dutch Heart Foundation(CVON 2018-28 and 2012-06 Heart Brain Connection to AMT)。
文摘Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82430018 to Q.C.,82270361 and 82570402 to H.Z.)the Nanjing Medical University Undergraduate Innovation and Entrepreneurship Training Program Fund(Grant No.202410312138Y to C.Z.)the Basic Sciences of Jiangsu Higher Education Institutions(Grant No.22KJA310002 to H.Z.)。
文摘As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
基金funded by Shanghai Yangpu District Science and Technology Commission(Grant No.YPQ202303(Xuejing Lin))Shanghai Yangpu Hospital Foundation(Grant No.Se1202420(Wenchao Wang)and Ye1202423(Juan Huang)).
文摘Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related mortality worldwide.This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms,with a particular focus on mitochondrial function and apoptosis.Methods:Differential expression analyses were performed across three datasets—The Cancer Genome Atlas(TCGA)-Liver Hepatocellular Carcinoma(LIHC),GSE36076,and GSE95698—to identify overlapping differentially expressed genes(DEGs).A prognostic risk model was then constructed.Cysteine/serine-rich nuclear protein 1(CSRNP1)expression levels in HCC cell lines were assessed via western blot(WB)and quantitative reverse transcription polymerase chain reaction(qRT-PCR).The effects of CSRNP1 knockdown or overexpression on cell proliferation,migration,and apoptosis were evaluated using cell counting-8(CCK-8)assays,Transwell assays,and flow cytometry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and intracellular and mitochondrial reactive oxygen species(mROS)levels were measured using specific fluorescent probes.WB was used to assess activation of the c-Jun N-terminal kinase(JNK)/p38 mitogen-activated protein kinase(MAPK)pathway,and pathway dependence was examined using the ROS scavenger N-Acetylcysteine(NAC)and the JNK inhibitor SP600125.Results:A six-gene prognostic model was established,comprising downregulated genes(NR4A1 and CSRNP1)and upregulated genes(CENPQ,YAE1,FANCF,and POC5)in HCC.Functional experiments revealed that CSRNP1 knockdown promoted the proliferation of HCC cells and suppressed their apoptosis.Conversely,CSRNP1 overexpression impaired mitochondrial integrity,increased both mitochondrial and cytoplasmic ROS levels,and activated the JNK/p38 MAPK pathway.Notably,treatment with NAC or SP600125 attenuated CSRNP1-induced MAPK activation and apoptosis.Conclusion:CSRNP1 is a novel prognostic biomarker and tumor suppressor in HCC.It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner.These findings suggest that CSRNP1 may serve as a potential therapeutic target in the management of HCC.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
基金Supported by Russian Science Foundation,No.23-45-10030.
文摘Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.
文摘The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.
文摘Diabetic cardiomyopathy(DCM)has long been considered as a left ventricular(LV)disease with diastolic dysfunction preceding systolic dysfunction in diabetes.However,it is increasingly recognized that the right ventricle(RV)is also affected by diabetes and may be independently responsible for adverse outcomes in diabetic patients with or without LV failure.Yu et al conducted a 30-week longitudinal evaluation of biventricular function and pathology in OVE26 diabetic mice and revealed early diastolic dysfunction preceding systolic decline,suggesting that early LV diastolic impairment precedes the later onset of systolic dysfunction.With age,the animals developed fibrosis,hypertrophy,and pulmonary arterial hypertension in the RV.The purpose of this editorial is to contextualize these findings within the existing literature by highlighting the interplay between cardiac chambers and the vasculature.We also seek to reiterate that DCM is a condition extending beyond left ventricular dysfunction.As the authors note,the right side of the heart may remain"the forgotten ventricle"in diabetic patients.We hope that the mechanisms discussed in this paper will help researchers to understand the pathogenesis of cardiovascular disease in this context and encourage clinicians to be more attentive to the associated clinical symptoms.
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
基金supported by the National Natural Science Foundation of China(No.81901543 and No.81971333)the Key Research and Development Project of Anhui Province(2022e07020014)the Joint Fund for Medical Artificial Intelligence(MAI2022Q010).
文摘A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis,which can lead to poor quality of sexual life.Here,the association between foreskin length and sexual dysfunction was evaluated.A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China(Hefei,China).Clinical characteristics,including foreskin length,were collected,and sexual function was assessed by the International Index of Erectile Function-5(IIEF-5)and Premature Ejaculation Diagnostic Tool(PEDT)questionnaires.Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction.Among the 2721 erectile dysfunction(ED)patients and 1064 premature ejaculation(PE)patients,301(11.1%)ED patients and 135(12.7%)PE patients had redundant foreskin,respectively.Men in the PE group were more likely to have redundant foreskin than men in the non-PE group(P=0.004).Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED(adjusted odds ratio[aOR]=1.31,adjusted P=0.04),moderate PE(aOR=1.38,adjusted P=0.02),and probable PE(aOR=1.37,adjusted P=0.03)after adjusting for confounding variables.Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction,especially in PE patients.Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.
文摘Rotenone is a lipophilic herbicide extensively utilized in experimental neurodegenerative models because of its capacity to disrupt complex I of the mitochondrial electron transport chain.This inhibition results in reduced ATP synthesis,elevated reactive oxygen species(ROS)formation,and mitochondrial malfunction,which instigates oxidative stress and cellular damage,critical elements in neurodegenerative disorders like Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and Alzheimer’s disease(AD).In addition to causing direct neuronal injury,rotenone significantly contributes to the activation of glial cells,specifically microglia and astrocytes.Activated microglia assumes a proinflammatory(M1)phenotype,distinguished by the secretion of inflammatory cytokines including tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),with the generation of nitric oxide and ROS,which exacerbate the neuronal injury.Astrocytes can intensify neuroinflammation by secreting proinflammatory molecules and impairing their neuroprotective roles.Our hypothesis is that rotenone is posited to elicit a neuroinflammatory response via mitochondrial malfunction,ROS generation,and the activation of proinflammatory pathways in microglia and astrocytes.This mechanism leads to accelerated neuronal impair-ment,promoting neurodegeneration.Comprehending the inflammatory pathways activated by rotenone is crucial for pinpointing therapeutic targets to regulate glial responses and mitigate the advancement of neurodegenerative disorders linked to mitochondrial malfunction and chronic inflammation.This review examines the function of glial cells and critical inflammatory pathways,namely Nuclear factor kappaβ(NF-κB),Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin(PI3K/AKT/mTOR),and Wnt/β-catenin signaling pathway in Parkinson’s disease,Alzheimer’s disease,and ALS,emphasizing illness-specific responses and the translational constraints of rotenone-based models.The objective is to consolidate existing understanding regarding the role of rotenone-induced mitochondrial failure in promoting glial activation and neuroinflammation,highlighting the necessity for additional research into these pathways.Despite the prevalent application of rotenone in experimental models,its specific effects on glial-mediated inflammation are inadequately comprehended,necessitating further investigation to guide the formulation of targeted therapeutic strategies.
基金Supported by Basic and Applied Basic Research Project of Guangzhou Science and Technology Plan(No.202201020008,No.2023A03J0584).
文摘AIM:To investigate the impact of renal dysfunction on clinical response to intravitreal conbercept injection(IVC)for diabetic macular edema(DME).METHODS:This retrospective study included a total of 100 eyes from 100 patients with DME treated with IVC with 3+PRN regimen.Based on the estimated glomerular filtration rate(eGFR),the patients were divided into normal renal function group(n=37),impaired renal function group(n=27),and renal insufficiency group(n=36).The main outcome measures were best-corrected visual acuity(BCVA)and central subfield macular thickness(CST).Clinical parameters included blood urea nitrogen,serum creatinine,serum uric acid,glycosylated hemoglobin(HbA1c),and hemoglobin.RESULTS:The mean follow-up time was 3.9mo.The mean number of IVCs was 2.07±1.22 in the three groups.Mean BCVA improved significantly from 0.81±0.49 logMAR at baseline to 0.72±0.52 logMAR in the three groups at the final visit(P<0.001).Mean CST decreased significantly from 427.85±148.99μm at baseline to 275.31±108.31μm at final visit(P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).Patients in the normal renal function group had higher baseline hemoglobin levels and thinner baseline CST than those in the impaired renal function and insufficiency renal function group(all P<0.001).The three groups had no differences in baseline HbA1c levels(P>0.05).Good baseline BCVA(logMAR,P=0.001)and thicker baseline CST(P=0.041)were associated with visual acuity improvement.Higher eGFR(P<0.001),hemoglobin(P=0.032)and thicker baseline CST(P=0.017)were associated with macular edema retrogression in the conbercept-treated diabetic patients,which showed better anatomical response to IVC.CONCLUSION:Our results indicate that the renal dysfunction is the risk factor associated with the efficacy of IVC for DME.
基金supported by the National Natural Science Foundation of China(Grant NO.82071057,82101229)National Key Research and Development Program of China(Grant NO.2023YFC2508001)。
文摘Purpose:Acute otitis media caused by gram-negative bacteria is a common otological condition among pediatric patients.Eustachian tube dysfunction(ETD)plays a pivotal role in the delayed resolution of acute otitis media,whereas the precise contribution of SIRT3 in this mechanism remains uncertain.This study aims to reveal the involvement of SIRT3 in murine ETD induced by LPS.Results:Histological analysis showed no baseline differences in ET structure between WT and SIRT3 knockout(SIRT3-KO)mice.However,LPS exposure led to increased goblet cell proliferation and MUC5 AC mucus secretion in both genotypes,with SIRT3-KO exacerbating these effects.The SIRT3-KO group displayed reduced cilia length.Functionally,SIRT3-KO mice showed a significantly higher initial POP and decreased MCC compared to the WT group after LPS exposure.Additionally,the active clearance of negative pressure(ACNP)was significantly reduced in SIRT3-KO mice,indicating compromised ET function.Conclusions:SIRT3-KO increased resistance to ET opening in mice exposed to LPS,and this effect may be related to the upregulated MUC5 AC expression,the increased surface tension of the luminal fluid and the impaired MCC function in mice exposed to LPS.
文摘ObjectiveTo review the current literature on ketamine-associated upper urinary tract (UUT) dysfunction and provide an overview of its pathogenesis and treatment principles.MethodsA literature search was conducted using PubMed and Cochrane databases for relevant articles published in English between 2008 and 2023. Keywords used included “ketamine” and “upper urinary tract”.ResultsA total of 22 papers were included. Relatively few studies have focused on ketamine-associated UUT dysfunction. Exclusion criteria included lack of hydronephrosis, or pathological findings. After careful screening and exclusion, we finally adopted 11 of these papers and analyzed them. Ketamine-associated UUT dysfunction may be a concern in this field.ConclusionKetamine abuse can lead to UUT impairment and dysfunction, with symptoms such as bladder dysfunction and contracted bladder with vesicoureteral reflux, direct damage and barrier dysfunction, inflammation, apoptosis, fibrosis and stricture, and papillary necrosis. Oxidative stress, autophagy, and microvascular injury are also potential pathogenic mechanisms. The detection of these symptoms largely depends on laboratory and imaging examinations. The treatment principles of ketamine-associated UUT dysfunction are protecting the UUT, improving bladder dysfunction, and resuming normal social life. More investigations are needed to clarify the mechanisms and shed light on the treatment of ketamine-associated UUT damage.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by the National High Level Hospital Clinical Research Funding (2022-NHLHCRF-YS-03)the National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:Post-cardiac arrest syndrome(PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation(CPR) in cardiac arrest(CA) patients.Effective cardiocerebral protection is essential for improving post-resuscitation survival.This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation.METHODS:The male Sprague-Dawley rats(10–12 weeks old,400–500 g) were divided into two groups:the control group(n=6),which received sham surgery,and the CA/CPR group(n=10),which received ventricular fibrillation(VF) followed by CPR.After 24 h,brain and heart tissues were collected for analysis.The sequencing was used to identify differentially expressed genes(DEGs) between control and CA/CPR rats.RESULTS:At 24 h after resuscitation,CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle(LV) compared to the control group.In the hippocampus,the most notable biological process was the positive regulation of tumor necrosis factor production,with key pathways related to inflammation and the immune response.In the LV,the Gene Ontology(GO)enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance,a pathway that was also relevant in the brain.Eleven common targets were identified in the DEGs of both heart and brain tissues.The reverse transcription-polymerase chain reaction(RTPCR) validation revealed significant differences in the mRNA expression of Timp1,Apln,Ccl7,and Lgals3 in both LV and hippocampus.CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS.The differential genes Timp1,Apln,Ccl7,and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.
文摘In this article,we comment on the recent network analysis by Li et al,which explores depression,anxiety,and their associated factors in individuals with noncommunicable chronic diseases(NCDs).We highlight three often-overlooked domains in this population:Mental vulnerability(depression,anxiety,fatigue,nervousness),dysfunction in family functioning(family health,intimate partner violence),and digital exposure(media exposure,problematic internet use),and examine their dynamic interrelations within a psychosocial network framework.The findings reveal a complex system in which emotional dysregulation,family relational adversity,and digital behaviors mutually reinforce one another to heigh-ten psychiatric risk.Notably,traditional demographic factors such as gender,ethnicity,and residence had minimal impact on overall network strength.We argue that these interconnected domains represent modifiable yet underrecognized targets for mental health intervention among medically vulnerable populations.Strategies that promote emotional resilience,strengthen family systems,and enhance digital literacy may play a pivotal role in disrupting maladaptive network pathways and improving quality of life for individuals with NCDs.Future research should prioritize longitudinal and multimodal designs to clarify causal mechanisms and support tailored,systems-level psychosocial interventions.
基金supported by grants from the Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)Medical Key Discipline Program of Wuxi Health Commission(Grant Nos.ZDXK2021007 and CXTD2021005)+1 种基金Top Talent Support Program for Young and MiddleAged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘With the prevalence of obesity,metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide and can cause a series of serious complications.The pathogenesis of MASLD is complex,characterized by oxidative stress,impaired mitochondrial function and lipid metabolism,and cellular inflammation.Mitochondrial biology and function are central to the physiology of the liver.It has been suggested that mitochondrial oxidative stress plays a crucial role in MASLD progression.Excessive oxidative stress response is an important trigger for the occurrence and development of MASLD.In this review,we aim to focus on the recent advances in understanding mitochondrial oxidative stress-related mechanisms in the progression of MASLD.The in-depth elaboration of its related mechanisms is hoped to help find effective methods for treating MASLD.
文摘Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.
