International Journal of Medical Sciences最新文献

{"title":"Associations of Hemoglobin Glycation Index with Glucose Variability and Time in Ranges in Patients with Type 2 Diabetes Undergoing Continuous Glucose Monitoring.","authors":"Xiu-Yu Wei, Jun-Sing Wang","doi":"10.7150/ijms.129813","DOIUrl":"10.7150/ijms.129813","url":null,"abstract":"<p><strong>Background: </strong>Discordance between glycated hemoglobin (HbA1c) levels and blood glucose is commonly observed in clinical practice. The hemoglobin glycation index (HGI) has been proposed as a measure to quantify individual variations in glycation. Our study aimed to investigate the association between HGI and glucose variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes (T2D) treated with metformin monotherapy.</p><p><strong>Methods: </strong>Adults with T2D treated with metformin monotherapy (daily dose ≥ 1500 mg) who had HbA1c levels ≥ 7.0% (n = 100; mean age 54.0 ± 8.2 years; 52.0% female) undergoing CGM were analyzed. Predicted HbA1c was derived from linear regression of HbA1c on fasting plasma glucose, and the HGI was calculated as observed HbA1c minus predicted HbA1c. CGM metrics-including standard deviation, coefficient of variation, mean amplitude of glycemic excursions (MAGE), and time in ranges-were analyzed to evaluate their associations with HGI.</p><p><strong>Results: </strong>HGI was significantly associated with mean sensor glucose (β = 13.60, 95% CI 5.16-22.04, p = 0.002) and CGM-derived glucose variability metrics, including standard deviation (β = 7.53, 95% CI 4.49-10.58, p < 0.001), coefficient of variation (β = 2.22, 95% CI 0.29-4.15, p = 0.025), and MAGE (β = 22.14, 95% CI 14.59-29.69, p < 0.001). These associations remained significant after multivariable adjustment. HGI was also negatively associated with time in range (β = -7.29, 95% CI -12.79 to -1.79, p = 0.010) and positively associated with time above range (β = 7.35, 95% CI 1.69-13.01, p = 0.011).</p><p><strong>Conclusion: </strong>These findings highlight a significant association between HGI and glucose variability from CGM, suggesting that HGI may serve as a complementary marker in diabetes management.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2993-2999"},"PeriodicalIF":3.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin Remodeling Subunit ARID1A Negatively Regulates the Malignant Progression of Gastrointestinal Stromal Tumors by Targeting the MEMO1 Promoter.","authors":"Yuhao Wang, Yi Shi, Shu Wang, Guanghui Xu, Ahui Fan, Liu Yutong, Haoyuan Wang, Yan Zhao, Chaosheng Peng, Yuxuan Ma, Yongzhan Nie, Jianjun Yang","doi":"10.7150/ijms.136256","DOIUrl":"10.7150/ijms.136256","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GISTs) are the most common sarcomas of the alimentary tract and are primarily characterized by malignant progression, a major cause of mortality. AT-rich interaction domain 1A (ARID1A), a core component of the chromatin-remodeling SWI/SNF complex, has been found to correlate with GIST tumor grade, although the underlying mechanism remains unclear. Its frequent inactivation across diverse cancer types reveals pleiotropic roles that intersect multiple hallmarks of cancer. In this study, we aimed to investigate the potential relationship between ARID1A and malignant progression in GISTs, as well as the underlying mechanism. Western blotting, real-time polymerase chain reaction, and immunohistochemistry were used to assess ARID1A expression in GIST tissues. Cell Counting Kit-8 (CCK-8) assays were performed to evaluate cell proliferation. Wound-healing and Transwell assays were conducted to assess cell migration and invasion. Flow cytometry was used to analyze apoptosis and cell cycle distribution. Label-free quantitative proteomics and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to identify top candidate downstream targets of ARID1A. ARID1A expression was decreased in high-risk GIST tissues. Furthermore, ARID1A knockdown in GIST cells promoted proliferation and metastasis both <i>in vitro</i> and <i>in vivo</i>, and led to reduced apoptosis and impaired cell cycle arrest. We further demonstrated that ARID1A suppresses GIST proliferation and metastasis by inhibiting MEMO1 expression and inactivating the ERK1/2 signaling pathway. Notably, this regulatory axis was observed in KIT-null GIST cells, indicating that the ARID1A-MEMO1 pathway may function independently of canonical KIT signaling. Thus, ARID1A inhibits malignant progression in GISTs, providing new insights into its role in the prevention and treatment of human GISTs and suggesting its potential as a biomarker of malignant progression in GISTs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"3027-3043"},"PeriodicalIF":3.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.","authors":"Xuanhao Wu, Xiaodan Mao","doi":"10.7150/ijms.124859","DOIUrl":"10.7150/ijms.124859","url":null,"abstract":"<p><p>Metabolic reprogramming is a hallmark of tumor initiation and progression. Previous studies have focused mainly on glucose and lipid metabolism, with emphasis on the Warburg effect and <i>de novo</i> lipogenesis. Based on the shift in research paradigms, this review focuses on amino acid metabolism, which has long been overlooked, and systematically elaborates how tumors hijack amino acid pathways to construct an immunosuppressive and protumor microenvironment. We confirm that amino acid metabolism acts as a core driver of tumor proliferation, immune evasion and therapeutic resistance. This paper further discusses the intricate regulatory crosstalk between amino acid metabolism and convent ional antitumor therapies, clarifying the potential of metabolic-targeted strategies in overcoming drug resistance and improving clinical efficacy. Deviating from the traditional perception that amino acids merely serve as auxiliary substances for glucose and lipid metabolism, we summarize their vital roles in remodeling the immunosuppressive tumor microenvironment and provide theoretical support for the clinical integration of precise metabolic targeted therapy and existing antitumor regimens combined with cutting-edge technologies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2974-2992"},"PeriodicalIF":3.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential associations of febuxostat and allopurinol with incident and worsening frailty risk in nephrology patients.","authors":"Szu-Ying Lee, Jui Wang, Kyung Don Yoo, Chia-Ter Chao, Kuo-Liong Chien, Kuan-Yu Hung","doi":"10.7150/ijms.128982","DOIUrl":"10.7150/ijms.128982","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia and gout are linked to adverse outcomes and may influence frailty risk, but evidence on the impact of uric acid (UA)-lowering therapy on frailty among nephrology patients is limited. We evaluated the association of febuxostat and allopurinol use with incident and worsening frailty in a large nephrology patient cohort.</p><p><strong>Methods: </strong>This retrospective cohort study included 19,389 adults attending nephrology clinics at a tertiary medical center in Taiwan between 2013 and 2021 with available UA and estimated glomerular filtration rate (eGFR) data. Exposure was the use of febuxostat, allopurinol, or both agents versus no UA-lowering therapy. We examined incident frailty and worsening frailty defined by the FRAIL scale after follow-up. Kaplan-Meier and Cox proportional hazards models were applied, adjusting for demographics, comorbidities, medications, baseline frailty, and laboratory data.</p><p><strong>Results: </strong>Over a median follow-up of 3.0 years, 892 (4.6%) participants developed incident frailty and 5,253 (27.1%) had worsening frailty. After adjustment, febuxostat use was associated with higher probability of incident frailty (hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.01-1.48), while allopurinol use was associated with lower probability (HR 0.65, 95% CI 0.46-0.93) compared to non-users. Both users had no alterations in incident frailty probability. Neither therapy was significantly associated with worsening frailty. Subgroup analyses showed modification effects from age and eGFR levels.</p><p><strong>Conclusions: </strong>Among nephrology patients, UA-lowering therapy showed divergent associations with frailty probability: febuxostat use correlated with higher whereas allopurinol use correlated with lower incident frailty probability, with no effect on frailty progression. Choice of UA-lowering therapy may have implications for functional outcomes in this high-risk population.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2963-2973"},"PeriodicalIF":3.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age at Menarche, Cardiometabolic Disease Prevalence, and Disease Control in Korean Women: Analysis of the Korea National Health and Nutrition Examination Survey.","authors":"Yuki Gen, Gyu-Na Lee, Kyung-Do Han, Yun Sung Jo","doi":"10.7150/ijms.137086","DOIUrl":"10.7150/ijms.137086","url":null,"abstract":"<p><strong>Background: </strong>Early menarche is linked to adverse cardiometabolic outcomes, but its relationship with disease management remains unclear. We examined associations between menarcheal age and the prevalence and control of cardiometabolic diseases in Korean women.</p><p><strong>Methods: </strong>In 25,227 women aged ≥19 years from the Korea National Health and Nutrition Examination Survey (KNHANES), 2014-2023, menarcheal age was categorized as early (<12 years), intermediate (12-15 years; reference), and late (≥16 years). Multivariable logistic regression assessed the prevalence and control of type 2 diabetes mellitus (T2DM), hypercholesterolemia, and hyper-low-density lipoprotein (LDL) cholesterolemia, stratified by menopausal status.</p><p><strong>Results: </strong>Among premenopausal women, unadjusted comparisons favored the early-menarche group, reflecting age confounding; no significant association persisted after full adjustment for body mass index, lifestyle, and socioeconomic factors. Among postmenopausal women, late menarche was independently associated with lower odds of having hypercholesterolemia (OR = 0.809, 95% CI: 0.736-0.889; <i>p</i> < 0.001) and hyper-LDL cholesterolemia (OR = 0.815, 95% CI: 0.741-0.897; <i>p</i> < 0.001); no association with T2DM was observed. In contrast, among postmenopausal women who already had hyper-LDL cholesterolemia, those with late menarche were less likely to reach adequate LDL control than those with menarche at 12 to 15 years (OR = 0.814, 95% CI 0.693-0.956; <i>p</i> = 0.019). Although both odds ratios are below 1, they carry opposite clinical meaning, reflecting a lower prevalence of disease but poorer control once disease has developed.</p><p><strong>Conclusions: </strong>The cardiometabolic effects of menarcheal age appear life-stage dependent, extending beyond prevalence to disease management. In postmenopausal women, late menarche was associated with lower odds of dyslipidemia yet, paradoxically, with poorer LDL control once disease had developed, indicating that a lower observed risk should not justify less vigilant management. These findings support integrating menarcheal age into cardiometabolic risk assessment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2911-2920"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Dexmedetomidine on Postoperative Analgesia After Video-assisted Thoracoscopic Lobectomy Surgery.","authors":"Dowon Lee, Eun Ji Park, Jae-Young Kwon, Hyae Jin Kim, Siyun Moon, Boo-Young Hwang","doi":"10.7150/ijms.136546","DOIUrl":"10.7150/ijms.136546","url":null,"abstract":"<p><strong>Background: </strong>Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that provides sedative and analgesic effects and may reduce opioid requirements without significant respiratory depression. However, evidence supporting its use in patients undergoing video-assisted thoracoscopic (VATS) lobectomy remains limited. This study aimed to evaluate the effects of perioperative dexmedetomidine on postoperative analgesic requirements and recovery outcomes in patients receiving combined epidural and general anesthesia.</p><p><strong>Materials and methods: </strong>This prospective, randomized, double-blind study enrolled 68 patients undergoing elective VATS lobectomy. Patients were randomly assigned to the dexmedetomidine group (Group D) or the saline control group (Group S). All patients received standardized general anesthesia combined with thoracic epidural blockade. Group D received an intravenous loading dose of dexmedetomidine (1.0 μg/kg over 10 minutes), followed by a continuous infusion at 0.5 μg/kg/h until 1 hour after surgery, whereas Group S received a volume-matched saline infusion. The primary outcome was total patient-controlled epidural analgesia (PCEA) consumption. Secondary outcomes included visual analog scale (VAS) scores, Ramsay sedation scores, adverse events, and patient satisfaction assessed over 48 hours postoperatively.</p><p><strong>Results: </strong>Sixty-one patients were included in the final analysis (Group D, n = 31; Group S, n = 30). Baseline demographic and intraoperative characteristics were comparable between groups. Intraoperative rocuronium requirements, cumulative patient-controlled epidural analgesia (PCEA) consumption from the intraoperative period to 48 hours postoperatively, and the number of rescue analgesic boluses administered in the post-anesthesia care unit were significantly lower in Group D than in Group S (p = 0.002, 0.001, and 0.013, respectively). Although overall postoperative pain scores were comparable between groups, VAS scores at 1 hour postoperatively were significantly lower in Group D (p = 0.038). Patient satisfaction scores were significantly higher in Group D (p = 0.005). Bradycardia 1 hour after surgery and hypotension 1 hour after one-lung ventilation occurred more frequently in Group D (p = 0.044 and 0.024, respectively), whereas the incidence of other adverse events was similar between groups.</p><p><strong>Conclusions: </strong>Perioperative dexmedetomidine infusion reduced postoperative epidural analgesic requirements and improved early postoperative pain control and patient satisfaction in patients undergoing VATS lobectomy with combined epidural and general anesthesia. Despite an increased incidence of transient bradycardia and hypotension, dexmedetomidine was well tolerated and may be considered an effective opioid-sparing adjunct in this surgical population.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2874-2883"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Renal Function, Uremic Toxins, and Cognitive Performance in Patients with Chronic Kidney Disease: A Pilot Study.","authors":"Te-Wei Cheng, Kevin Li-Chun Hsieh, Chih-Chin Kao, Hsun-Hua Lee, Yen-Chung Lin, Chien-Hung Lai","doi":"10.7150/ijms.133922","DOIUrl":"10.7150/ijms.133922","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic kidney disease (CKD) often experience cognitive decline. However, the associations between renal dysfunction, uremic toxins, and cerebrovascular changes remain unclear.</p><p><strong>Aim: </strong>This study investigated the associations between renal function, uremic toxins, cerebrovascular imaging markers, and cognitive performance in patients with CKD plus early cognitive decline through integrated biochemical, neuropsychological, and neuroimaging assessments.</p><p><strong>Design: </strong>An observational pilot study.</p><p><strong>Setting: </strong>Outpatient clinic of the physical medicine and rehabilitation department at a tertiary hospital.</p><p><strong>Population: </strong>Adult patients with stage 3-5 CKD who exhibited early cognitive decline and could complete CANTAB-based cognitive assessments.</p><p><strong>Methods: </strong>This study included 12 patients with stage 3-5 CKD who were not undergoing hemodialysis and had early cognitive decline (Clinical Dementia Rating score: 0.5 or 1.0). Cognitive performance was assessed using the CANTAB. Serum levels of total indoxyl sulfate (IS) and total p-cresyl sulfate (pCS) were measured. Brain magnetic resonance imaging was performed to evaluate qualitative imaging markers potentially associated with cognitive impairment, such as arterial stenosis of the circle of Willis. Pearson correlations between the aforementioned biomarkers were explored.</p><p><strong>Results: </strong>Both IS and pCS levels were negatively correlated with estimated glomerular filtration rate (IS: r = -0.301, p = 0.469; pCS: r = -0.461, p = 0.250). A higher estimated glomerular filtration rate was correlated with better spatial working memory strategy performance (r = 0.695, p = 0.012). However, no clear correlation was observed between cognitive performance and arterial stenosis severity.</p><p><strong>Conclusion: </strong>This pilot study suggests that renal function is associated with selected cognitive domains in patients with CKD. The overall burden of qualitative MRI lesions was low in this cohort, although structural brain abnormalities were still observed. Integration of biochemical, neuropsychological, and brain imaging biomarkers may provide a comprehensive evaluation of cognitive function in these patients.</p><p><strong>Clinical rehabilitation impact: </strong>Integrating multidomain cognitive assessments with uremic toxin profiling and noninvasive brain imaging may facilitate early identification of cognitive deficits in patients with CKD, thereby supporting individualized cognitive evaluation in rehabilitation practice.Trial Registration: NCT07272733.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2899-2910"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sjögren's Disease-Associated Renal Tubular Acidosis: An Integrated Immuno-Tubular Model of Tubular Dysfunction.","authors":"Chien-Lin Lu, Chia-Chao Wu, Te-Chao Fang, Kuo-Cheng Lu","doi":"10.7150/ijms.136917","DOIUrl":"10.7150/ijms.136917","url":null,"abstract":"<p><p>Sjögren's disease (SjD) is traditionally viewed as an autoimmune exocrinopathy; however, renal involvement-particularly renal tubular acidosis (RTA)-is an underrecognized extraglandular manifestation that often precedes classical sicca symptoms and contributes to diagnostic delay. Distal RTA (dRTA) represents the dominant phenotype and arises from immune-mediated injury to α-intercalated cells, leading to disruption of key acidification components, including vacuolar H⁺-ATPase (V-ATPase), carbonic anhydrase II (CAII), and anion exchanger 1 (AE1). Beyond impaired distal proton secretion, systemic acidosis is proposed to induce adaptive responses in the proximal tubule, based largely on general renal physiology rather than SjD-specific data. Intracellular acidification may enhance sodium-dependent dicarboxylate cotransporter 1 (NaDC-1)-mediated citrate reabsorption and mitochondrial citrate metabolism. These processes may reduce urinary citrate excretion (hypocitraturia) and promote a lithogenic milieu characterized by calcium phosphate supersaturation. This integrated distal-proximal axis provides a plausible mechanistic link between tubular dysfunction and clinical manifestations such as nephrolithiasis, nephrocalcinosis, and hypokalemic paralysis. Incomplete dRTA further expands the disease spectrum and is frequently overlooked despite its clinical relevance. Current management is centered on alkali and potassium replacement, which correct metabolic abnormalities but do not address underlying immune-mediated injury. Treatment response is stage-dependent and often limited once fibrosis is established. This review proposes an integrated immuno-tubular framework that links clinical phenotype, pathogenesis, and therapeutic strategy, and highlights the need for early detection, biomarker-driven risk stratification-particularly using hypocitraturia-and incorporation of renal-specific endpoints to enable mechanism-based and precision-guided care.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2921-2938"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Regulation of Alzheimer's Disease and Intestinal Microbiota Metabolism Mediated by the Gut-Brain Axis: A Comprehensive Analysis from a Multidisciplinary Perspective.","authors":"Peng Lu, Maolin Liu, Lei Zhang, Jing-Jing Fan, Yan Sun","doi":"10.7150/ijms.135274","DOIUrl":"10.7150/ijms.135274","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Alzheimer's disease (AD), as a neurodegenerative disease with the interaction of multiple factors, has a close association between its pathological process and the metabolic imbalance of the gut microbiota mediated by the gut-brain axis. This review systematically summarizes the molecular mechanisms by which the gut microbiota regulates the functions of the central nervous system bidirectionally through molecular pathways such as metabolites (e.g., short-chain fatty acids, tryptophan-kynurenine metabolites), immunomodulatory mediators (e.g., cytokines, chemokines), and bioactive substances (e.g., γ-aminobutyric acid, 5-hydroxytryptophan) via the gut-brain axis. It synthesizes current evidence suggesting the imbalance of microbiota homeostasis may be closely associated with the core pathologies of AD (including β-amyloid deposition and tau protein hyperphosphorylation) through mechanisms such as the activation of the C/EBPβ-AEP signaling pathway, induction of chronic neuroinflammation, oxidative stress cascade reactions, and metabolic network remodeling. These findings, primarily derived from preclinical models and correlational human studies, indicate potential mechanisms but require further causal validation and rigorous clinical translation, including the downregulation of butyrate synthesis pathways and their associated epigenetic and immunomodulatory consequences (as mechanistically dissected in Section 5.2). Multi-omics integration (metagenomics, metabolomics, spatial transcriptomics) has delineated characteristic microbial and metabolic alterations in AD, while computational approaches are beginning to elucidate the complex networks underlying these associations (see Sections 6 and 7 for details).Intervention strategies based on microbiota regulation (such as microbiota-targeted dietary interventions and postbiotics) are emerging as promising approaches, although their clinical applications remain in early stages. Preliminary evidence suggests that fecal microbiota transplantation may improve cognitive outcomes in AD patients with comorbid conditions; however, rigorous randomized controlled trials are essential to validate its efficacy and safety. Critically, translating these mechanistic insights into clinical practice requires overcoming three translational bottlenecks: inferring causality from correlational multi-omics data, resolving species/strain-level functional heterogeneity masked by genus-level taxonomy, and establishing standardized safety protocols for live biotherapeutic products. Addressing these challenges defines the near-term roadmap for precision medicine in AD. However, current research still faces challenges such as the heterogeneity of cross-omics data, the lack of technical standardization, and insufficient interdisciplinary cooperation mechanisms. In the future, it is necessary to promote the early molecular diagnosis and personalized targeted treatment of AD through longitudinal multi-omics dynamic monitoring, ","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2939-2962"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-Driven <i>Fndc5</i> Knockout Reveals Augmented Mitochondrial Structural and Dynamic Alterations in Diabetic Nephropathy.","authors":"Chien-Wei Huang, Hsin-Hung Chen, Tzu-Ming Jao, Chia-Jung Li, Junne-Ming Sung, Yau-Sheng Tsai, Jin-Shuen Chen","doi":"10.7150/ijms.131007","DOIUrl":"10.7150/ijms.131007","url":null,"abstract":"<p><p>FNDC5 has been implicated in glucose homeostasis and is associated with mitochondrial function. Its role in diabetes and diabetic nephropathy (DN) remains unclear. This study hypothesizes that FNDC5 deficiency predisposes the kidney to accelerated mitochondrial dysfunction in diabetes and DN. Systemic <i>Fndc5</i> knockout (KO) C57BL/6 mice were generated using CRISPR/Cas9. DN were induced in six-week-old <i>Fndc5</i> wild-type (WT) and KO mice using high-fat diet combined with streptozotocin injection. Weekly blood and urine analyses assessed glucose, cholesterol, triglycerides, blood urea nitrogen, creatinine, and proteinuria. At 15 weeks, kidneys and metabolic tissues including pancreas, muscle and adipose were collected for histological and molecular analyses. Results showed that while both <i>Fndc5</i> WT and KO mice were successfully induced with hyperglycemia, the <i>Fndc5</i> KO DN group exhibited a slightly lower cumulative glycemic burden compared with the WT DN group. Despite this milder metabolic stress, proteinuria remained comparable between the two groups. Furthermore, histological analysis revealed that <i>Fndc5</i> KO DN mice displayed more severe mesangial expansion, glomerular basement membrane thickening, and podocyte effacement compared with WT DN mice. The elevated lipid peroxidation, reduced PGC-1α expression, and increased DNA fragmentation were also evident in <i>Fndc5</i> KO DN. More swollen mitochondria with a significantly higher percentage of disrupted cristae were observed in <i>Fndc5</i> KO DN mice compared with WT DN mice. This was accompanied by the upregulation of mitochondrial fission-related genes (<i>Dnm1l</i> and <i>Fis1</i>), downregulation of the fusion-related gene (<i>Mfn1</i>), and reduced expression of ATP synthase subunits (ATP5A1 and ATP5B). Systemic analysis of other metabolic tissues, including the pancreas and muscle and adipose tissues, revealed increased lipid peroxidation and decreased PGC-1α expression. These findings underscore FNDC5's role in maintaining mitochondrial integrity and cellular health under diabetic conditions, positioning FNDC5 as a potential therapeutic target.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2884-2898"},"PeriodicalIF":3.7,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}