Biomedicines最新文献

{"title":"CytoSorb^® Hemoadsorption in Post-Cardiac Arrest Syndrome After Out-of-Hospital Cardiac Arrest: A Propensity Score-Matched Cohort Study.","authors":"Julian Kreutz, Klevis Mihali, Vivien Sievertsen, Lukas Harbaum, Georgios Chatzis, Styliani Syntila, Bernhard Schieffer, Birgit Markus","doi":"10.3390/biomedicines14040930","DOIUrl":"10.3390/biomedicines14040930","url":null,"abstract":"<p><p><b>Background</b>: Post-cardiac arrest syndrome (PCAS) following out-of-hospital cardiac arrest (OHCA) is driven by global ischemia-reperfusion injury, endothelial dysfunction, and a dysregulated inflammatory response. This cascade frequently culminates in profound vasoplegia and multiorgan failure, even when guideline-directed post-resuscitation management is applied. Hemoadsorption using the CytoSorb device may attenuate hyperinflammation and vasoplegia by removing circulating inflammatory and injury-related mediators. <b>Methods</b>: This single-centre, retrospective cohort study compared adults with PCAS following OHCA who received hemoadsorption with propensity score-matched controls (1:1 matching; <i>n</i> = 50 per group). For patients treated with hemoadsorption, data were analyzed within predefined intervals covering the 24 h preceding therapy initiation (T1) and the 24 h following the completion of the hemoadsorption treatment period (T2). Controls were evaluated at time points aligned to those of their matched hemoadsorption counterparts. Hemodynamic, metabolic, respiratory, and organ injury markers were assessed. <b>Results</b>: Formal between-group comparisons of temporal change between T1 and T2 showed no statistically significant differences between hemoadsorption-treated patients and matched controls across key parameters, including VIS (Δ -18.7 vs. -7.7; <i>p</i> = 0.183) and lactate (Δ -1.8 vs. -1.25 mmol/L; <i>p</i> = 0.780), as well as markers of organ injury, pH, and oxygenation. In exploratory ANCOVA models, only base excess was associated with treatment group (<i>p</i> = 0.035). Survival to hospital discharge was comparable (48% vs. 40%; <i>p</i> = 0.423), with similar neurological outcomes. Within the hemoadsorption group, pre-post comparisons around hemoadsorption initiation (T1-T2) demonstrated marked improvements, including reduced vasoactive support (VIS 70.0 to 12.1; <i>p</i> = 0.039), substantial lactate clearance (4.1 to 1.1 mmol/L; <i>p</i> < 0.001), and declines in organ injury markers (AST, ALT, LDH, myoglobin), alongside more pronounced platelet reduction compared with controls (129 to 57 × 10³/µL vs. 189 to 123 × 10³/µL). However, adjusted analyses indicated that these changes were primarily driven by baseline shock severity rather than a treatment-specific effect. <b>Conclusions</b>: In this propensity score-matched cohort of PCAS patients after OHCA, hemoadsorption was associated with within-group physiological changes but showed no detectable advantage over matched controls, with similar survival. These findings are hypothesis-generating and warrant prospective studies with standardized timing and phenotype-guided patient selection.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Laboratory Markers in Primary Biliary Cholangitis: A Clinical Review and a Case Report.","authors":"Raffaele Radice, Giulia Pollaroli, Michela Salvatici, Chiara Corrado, Francesca Rispoli, Stefania Pacchetti, Lorenzo Drago","doi":"10.3390/biomedicines14040925","DOIUrl":"10.3390/biomedicines14040925","url":null,"abstract":"<p><strong>Background: </strong>Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by marked clinical and serological heterogeneity. Although diagnosis is mainly based on antimitochondrial antibodies (AMAs) and alkaline phosphatase (ALP), non-classical presentations remain a relevant cause of diagnostic delay. In this context, laboratory medicine plays a pivotal role in both diagnosis and long-term disease management.</p><p><strong>Methods: </strong>This manuscript represents a structured clinical review of laboratory biomarkers relevant to the diagnosis, monitoring, and prognostic stratification of PBC, integrated with a representative atypical case with long-term follow-up to illustrate the practical application of laboratory-driven diagnostic.</p><p><strong>Results: </strong>The analysis confirms the central role of immunological and biochemical markers in treatment monitoring and prognostic assessment, while highlighting their limitations in selected clinical scenarios. The reported case, characterized by persistent AMA negativity and consistently normal ALP levels, illustrates how expanded laboratory testing can support the identification of non-standard disease phenotypes. In this setting, parallel testing for AMA- and PBC-specific autoantibodies was essential to achieve a correct diagnosis. Moreover, alternative biomarkers, including gamma-glutamyl transferase (GGT) and selected immunological markers, provided clinically meaningful information when conventional markers were not informative.</p><p><strong>Conclusions: </strong>By integrating current evidence with a long-term clinical case, this work moves beyond a descriptive overview and proposes a practical, laboratory-driven diagnostic and follow-up framework for PBC. It highlights laboratory opportunities to facilitate timely diagnosis, appropriate prognostic stratification, and disease monitoring, including the assessment of associated comorbidities.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DSS Colitis Model: Traps, Tricks, and Reporting Recommendations.","authors":"Martina Perše","doi":"10.3390/biomedicines14040928","DOIUrl":"10.3390/biomedicines14040928","url":null,"abstract":"<p><p>The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model's multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut-brain axis, gut-liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a \"traps and tricks\" subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Effects of Multi-Kinase Inhibition on <i>LRRK2</i>-G2019S and Alpha-Synuclein Pathologies in Models of Parkinson's Disease.","authors":"Xiaoguang Liu, Sean Baxely, Michaeline L Hebron, Charbel Moussa","doi":"10.3390/biomedicines14040927","DOIUrl":"10.3390/biomedicines14040927","url":null,"abstract":"<p><p><b>Introduction</b>: Pathogenic mutations in leucine-rich repeat protein kinase-2 (<i>LRRK2</i>), particularly G2019S, constitute the most common cause of autosomal dominant PD. <b>Methods</b>: Mouse models encoding human mutant alpha-synuclein (<i>SNCA A53T</i>) and <i>LRRK2</i> G2019S were treated with a brain-penetrant kinase inhibitor (BK40196). Behavior, nigrostriatal and mesolimbic dopamine (DA) pathways were examined. <b>Results</b>: Mice harboring <i>LRRK2 G2019S</i> do not show age-dependent motor symptoms, but mice encoding <i>SNCA</i> A53T display motor deficits, while both strains exhibit anxiety-like behavior and BK40196 improves motor and behavioral defects. BK40196, a multi-kinase inhibitor of Abelson (Abl), Discoidin domain receptor (DDR)-1, c-KIT and FYN, alters microglial morphology and alpha-synuclein levels in <i>SNCA</i> A53T mice and improves DA neurotransmission, primarily via the nigrostriatal system. BK40196 inhibits brain LRRK2 G2019S (IC₅₀ of 89nM) and does not affect phosphorylated or total peripheral LRRK2 levels (lungs, kidneys, liver, etc.). <i>LRRK2</i> G2019S mice treated with BK40196 exhibit distinct increases in DA in mesolimbic neurons such as the nucleus accumbens (NAcc), suggesting differential mechanisms of DA neurotransmission in mutant alpha-synuclein and <i>LRRK2</i> models of PD. <b>Conclusions</b>: <i>LRRK2</i> G2019S may primarily involve mesolimbic pathways leading to nonmotor symptoms independent of the motor and behavioral manifestations associated with alpha-synuclein via the nigrostriatal system. BK40196 may provide a comprehensive and synergistic therapeutic approach that addresses multiple mechanisms to reduce the pathologies related to <i>LRRK2</i> G2019S and/or <i>SNCA</i> in PD. The multiple pathologies of PD necessitate a holistic approach that simultaneously targets inflammation and autophagy and LRRK2 inhibition.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Wound Healing: A Mystery Still to Be Solved-What Is the Future?","authors":"Montserrat Fernández-Guarino, María Luisa Hernández Bule, Stefano Bacci","doi":"10.3390/biomedicines14040926","DOIUrl":"10.3390/biomedicines14040926","url":null,"abstract":"<p><p>This perspective contains the current understanding of the cellular and molecular mechanisms involved in wound healing (the articles taken into consideration relate to the three-year period 2023-2025). Nevertheless, these biological pathways remain inadequately characterized; this is seen by the modifications leading to pathological conditions, such as keloids, chronic wounds, or hypertrophic scars and diabetic wounds. Focus is also directed to novel therapy suggested for these types of conditions. Understanding these scientific issues is crucial for professionals across many fields who see such presentations often.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracrine Induction of Cardiomyogenic Differentiation in Patient-Specific MSCs Using Conditioned Medium from iPSC-CMs.","authors":"Veronika Litvinenko, Rose Alkhateeb, Serafima Romanova, Sandaara Kovalenko, Vitalii Dzhabrailov, Mikhail A Popov, Mikhail Slotvitsky, Evgeniy G Agafonov, Vladislav V Dontsov, Sheida Frolova, Dmitriy I Zybin, Dmitriy V Shumakov, Alexander Romanov, Konstantin Agladze, Valeriya A Tsvelaya","doi":"10.3390/biomedicines14040919","DOIUrl":"10.3390/biomedicines14040919","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). <b>Materials and Methods</b>: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. <b>Results</b>: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. <b>Conclusions</b>: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This \"parallel differentiation\" platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarrier-Based Therapeutic Strategies in Myocardial Ischemia-Reperfusion Injury: A Systematic Review of Preclinical Evidence.","authors":"Michał Porada, Bartosz Pawełczak, Karolina Barańska-Pawełczak, Krzysztof Marciniec","doi":"10.3390/biomedicines14040921","DOIUrl":"10.3390/biomedicines14040921","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Myocardial ischemia-reperfusion injury (MIRI) remains an ever-growing threat in the field of cardiology, as it has become a major risk factor for unfavorable outcomes following reperfusion therapies. Oxidative stress and inflammation remain the key pathophysiological mechanisms underlying MIRI, and the presently available treatments fail to prevent this process effectively. This systematic review aimed to summarize and critically assess the latest preclinical research (2020-2026) on nanocarrier-based interventions targeting oxidative stress in MIRI, highlighting the potential of the new nanostructures in cardioprotection. <b>Methods</b>: A total of 24 studies meeting the PRISMA criteria have been found through a literature search of PubMed, Embase, and Web of Science databases published between 2020 and 2026. The studies eligible for inclusion had focused on the efficacy of nanocarrier-based interventions in preclinical studies of MIRI. <b>Results</b>: Of the 24 included studies, all investigated nanocarrier-based interventions in preclinical models of MIRI. In vitro, ex vivo, and in vivo models were diverse, with most studies being a combination of both in vitro and in vivo models. Commonly studied were lipid-based nanocarriers, polymeric nanoparticles, and biomimetic nanocarriers. Across studies assessed for this review, treatments with nanocarriers were seen to suppress inflammatory and oxidative stress pathways, with a few studies showing a suppression of cardiomyocyte apoptosis. Cardiac function was restored as determined by echocardiography analyses or ex vivo models of the myocardium, thus validating that the nanocarrier-mediated therapies are effective against MIRI. <b>Conclusions</b>: The analyzed preclinical studies indicate that the described therapies could provide a promising basis for future clinical trials in the treatment of MIRI, provided their safety and efficacy are confirmed in clinical trials.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sucralose and the Gut-Immune Axis: Emerging Evidence Linking Dysbiosis, Barrier Alterations, and Implications for Colitis and Colorectal Cancer Immunotherapy.","authors":"Aranza Mejía-Muñoz, Jessica Cedillo Monter, Héctor Iván Saldívar-Cerón, Galileo Escobedo, Sonia Leon-Cabrera","doi":"10.3390/biomedicines14040917","DOIUrl":"10.3390/biomedicines14040917","url":null,"abstract":"<p><p>Sucralose is one of the most widely used non-nutritive sweeteners and has long been considered metabolically inert and safe within established acceptable daily intake levels. However, emerging evidence suggests that chronic exposure to sucralose may alter gut microbial composition, epithelial barrier function, mucosal inflammation, and immune responses. This review examines current experimental and clinical evidence on the effects of sucralose on the gut-immune axis, with particular attention to its potential implications for colitis and colorectal cancer (CRC). Preclinical studies indicate that sucralose may reduce beneficial short-chain fatty acid-producing taxa, alter microbial metabolic pathways, disrupt epithelial barrier-related molecules, and promote inflammatory and immune changes associated with colitis severity and inflammation-driven tumorigenesis. Experimental evidence also suggests that sucralose may impair CD8⁺ T-cell fitness and reduce responsiveness to immune checkpoint inhibitors through microbiome-dependent mechanisms involving altered arginine and citrulline metabolism. Human studies further indicate that sucralose can modify gut and oral microbiome composition and influence metabolic responses, although these effects appear heterogeneous and context-dependent. Overall, the current literature suggests that sucralose may act as a modifier of microbiome-immune interactions in susceptible settings, but most mechanistic evidence remains preclinical, and human data are still insufficient to establish causality. These findings highlight the need for prospective studies to determine whether sucralose-associated microbial and immune alterations translate into clinically meaningful effects in colitis, CRC, and immunotherapy response.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Serum MOTS-c Levels and Myocardial Ischemia-Reperfusion Injury in Patients with Acute Myocardial Infarction: A Cross-Sectional Study.","authors":"Li Peng, Yanqiu Li, Xinglian Duan, Jun Long, Qin Ran, Xiaojuan Zeng, Bin Liu, Duan Wang, Jian Yang","doi":"10.3390/biomedicines14040918","DOIUrl":"10.3390/biomedicines14040918","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Percutaneous coronary intervention (PCI) effectively restores coronary flow in acute myocardial infarction (AMI), but myocardial ischemia-reperfusion injury (MIRI) remains a major prognostic determinant. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown cardiovascular protective effects, yet its association with MIRI is unclear. This study aimed to investigate the relationship between serum MOTS-c levels and MIRI in AMI patients. <b>Methods</b>: Seventy-two AMI patients undergoing PCI were enrolled and divided into MIRI (<i>n</i> = 34) and non-MIRI (<i>n</i> = 38) groups. Clinical data and MOTS-c levels in peripheral serum and intracoronary blood were compared. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed to identify MIRI predictors. <b>Results</b>: The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all <i>p</i> < 0.05). Postoperative peripheral serum MOTS-c levels were significantly lower in the MIRI group than in the non-MIRI group (<i>p</i> < 0.05), while preoperative peripheral and intracoronary MOTS-c levels showed no significant differences between groups. Multivariate logistic regression identified postoperative peripheral MOTS-c levels (OR = 0.986, 95%CI: 0.976-0.996) and preoperative TIMI grade ≥ 1 (OR = 0.036, 95%CI: 0.004-0.309) as independent protective factors for MIRI, whereas serum creatinine was identified as an independent risk factor. ROC analysis demonstrated that postoperative peripheral MOTS-c levels predicted MIRI with an area under the curve of 0.648. <b>Conclusions</b>: Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies. This finding may offer a potential novel biomarker and therapeutic direction for MIRI.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TNF-α</i> Polymorphisms in Major Depressive Disorder in Patients with and Without Cardiovascular Disease: A Systematic Review.","authors":"Antonio Avelino Ferreira Soares, Yago Rodrigues Gontijo, Dante Mafra Tourino Teixeira, Bruna Rodrigues Gontijo, Alexandre Sampaio Rodrigues Pereira, Larissa Sousa Silva Bonasser, Caroline Ferreira Fratelli, Calliandra Maria de Souza Silva, Izabel Cristina Rodrigues da Silva","doi":"10.3390/biomedicines14040922","DOIUrl":"10.3390/biomedicines14040922","url":null,"abstract":"<p><p><b>Introduction:</b> Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. <b>Methods:</b> This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between <i>TNFA</i> polymorphisms-specifically rs1800629 (-308 G/A), rs1799724 (-857 C/T), and rs1799964 (-1031 T/C)-and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. <b>Results:</b> Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. <b>Conclusions:</b> Current evidence does not support a robust etiological role for <i>TNFA</i> promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}