Current molecular medicine最新文献

{"title":"Sulforaphane Attenuates Ulcerative Colitis by Activating Nrf2 and Suppressing the NLRP3/IL-1β Inflammasome Axis.","authors":"Hao Dong, Ling Wang, Xiaorui Ding","doi":"10.2174/0115665240512388261009111344","DOIUrl":"https://doi.org/10.2174/0115665240512388261009111344","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative Colitis (UC) is driven by disrupted epithelial barrier function and chronic inflammation, yet the interaction between oxidative stress and inflammasome signaling remains unclear. This study investigated whether Nrf2 expression correlates with NLRP3 inflammasome activity in intestinal epithelial cells under inflammatory conditions and whether the natural Nrf2 activator, Sulforaphane (SFN), modulates this axis.</p><p><strong>Methods: </strong>A UC-like inflammatory state was established in Caco-2 cells using a cytokine cocktail (TNF-α, LPS, IFN-γ, IL-1β). Nrf2 was silenced using siRNA, and SFN was administered for activate Nrf2. Gene and protein expression were assessed by qPCR, ELISA, and Western blot. Public bulk and single-cell RNA-seq datasets from UC patients were analyzed to validate clinical relevance.</p><p><strong>Results: </strong>Cytokine stimulation significantly reduced Nrf2 expression while upregulating NLRP3, IL-1β, and IL-18 (p < 0.001). Nrf2 knockdown was associated with enhanced inflammasome activation, as evidenced by increased levels of NLRP3, caspase-1, and pro-inflammatory cytokines. Conversely, SFN pretreatment restored Nrf2 expression and markedly suppressed NLRP3 and IL-18 expression (p < 0.01 to p < 0.001). Multiomic analyses of UC patient samples confirmed an inverse expression pattern between Nrf2 and NLRP3 signaling pathways.</p><p><strong>Discussion: </strong>These findings indicate that reduced Nrf2 expression is strongly associated with enhanced NLRP3 inflammasome activation in inflamed intestinal epithelial cells. Pharmacologic activation of Nrf2 by SFN correlates with restored redox balance and attenuated inflammation, supporting the Nrf2-NLRP3 axis as a potential therapeutic target warranting further investigation. Limitations include use of a single cell line and lack of in vivo validation.</p><p><strong>Conclusion: </strong>This study provides correlative evidence for a redox-inflammasome axis in UC pathogenesis and suggests that further investigation of SFN as a candidate therapeutic approach is warranted.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD9 Enhances Activation of Pregnane X Receptor Pathway and the Resistance of Hepatocellular Carcinoma Cells to Molecular Targeted Agents.","authors":"Tongya Yu, Nianrong Zhang, Jun Zhang, Junli Pang, Xinshan Deng, Huiwei Sun, Yantao Chai, Xiaojuan Li, Yue Wang, Fan Feng","doi":"10.2174/0115665240502717261007150324","DOIUrl":"https://doi.org/10.2174/0115665240502717261007150324","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Bromodomain-containing protein 9 (BRD9) is a newly identified oncogenic regulatory factor in multiple human malignancies, yet its precise roles in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to investigate the function and mechanism of BRD9 in HCC, particularly its involvement in molecular targeted drug resistance.</p><p><strong>Methods: </strong>BRD9 expression was either overexpressed or knocked down in HCC cells. PXR transcription factor activity was assessed using luciferase reporter assays, quantitative polymerase chain reaction (qPCR), and chromatin immunoprecipitation (ChIP). HCC cells were treated with serial concentrations of molecularly targeted drugs. Antitumor activity was evaluated by MTT assays, colony formation assays, flow cytometry for apoptosis analysis, and subcutaneous tumor models. Drug metabolic rates were quantified using high-performance liquid chromatography (HPLC).</p><p><strong>Results: </strong>Overexpression of BRD9 significantly enhanced the transcriptional activity of PXR and promoted the expression of PXR-dependent multidrug resistance-related genes, including CYP3A4 and ABCB1. Mechanistically, BRD9 overexpression facilitated the recruitment of PXR to the promoter and enhancer regions of CYP3A4, thereby accelerating the metabolic clearance of sorafenib in HCC cells. Functionally, enforced expression of BRD9 rendered HCC cells more resistant to molecularly targeted agents, whereas knockdown of BRD9 sensitized them to these drugs. Furthermore, combination therapy experiments demonstrated that the BRD9 smallmolecule inhibitor I-BRD9 exerted synergistic antitumor activity with sorafenib against HCC cells.</p><p><strong>Discussion: </strong>These findings reveal that BRD9 mediates molecular targeted drug resistance in HCC through enhancing the transcription factor activation of PXR. This mechanism provides a potential therapeutic target for overcoming drug resistance in HCC, and the synergistic effect of IBRD9 with sorafenib suggests a promising combination strategy.</p><p><strong>Conclusion: </strong>BRD9 promotes resistance to molecular targeted drugs in HCC via PXR-dependent transcriptional activation. Targeting BRD9 may represent a novel approach to sensitize HCC cells to existing therapies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Brain Organoids for Studying General Anesthetic Mechanisms: Developmental Vulnerability, Cellular Stress, and Translational Perspectives.","authors":"Yue Xu, Yaling Dai, Mengquan Tan, Siyuan Song","doi":"10.2174/0115665240521640261009075041","DOIUrl":"https://doi.org/10.2174/0115665240521640261009075041","url":null,"abstract":"<p><p>General anesthetics are indispensable for surgical procedures, procedural sedation, and intensive care, but their mechanisms of action in the human brain are not fully understood. Classical biochemical approaches have delineated key targets of general anesthetics, such as GABAA and NMDA receptors, ion channels, mitochondria, neurotransmission, and inflammatory pathways. However, animal models and two-dimensional cultures do not represent human-specific neurodevelopment, regional cellular diversity, or three-dimensional brain architecture. Human brain organoids offer a complementary system to investigate anesthetic effects during human development. Recent reports on cerebral, forebrain, and midbrain organoids indicate that propofol and sevoflurane may affect neural progenitor cell proliferation, neuronal differentiation, apoptosis, autophagy, mitochondrial metabolism, long non-coding RNA networks, synaptic gene programs, and regionspecific maturation. These results do not preclude clinically required anesthesia, particularly as large-scale human studies have failed to demonstrate deficits in general intelligence following single short-term exposures. Rather, organoid models help establish which types of neural cells, developmental stages, and molecular mechanisms might be vulnerable to anesthesia. This review highlights recent advances in organoid-based research on the mechanisms of general anesthesia, particularly for propofol and volatile anesthetics. It also explores how region-specific organoids, assembloids, vascularized systems, microglia-enriched models, and multi-omics techniques may help resolve developmental vulnerability and aid more targeted translational studies of anesthesia.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HDAC3 Reveals Therapeutic Vulnerability in PTENDeficient Endometrial Cancer.","authors":"Krystina Dunston, Keun Cheon Kim, Shamsun Nahar, Jung-Yoon Yoo, Amanda Hull, Mark I Hunter, Jae-Wook Jeong, Tae Hoon Kim","doi":"10.2174/0115665240502568261007060256","DOIUrl":"https://doi.org/10.2174/0115665240502568261007060256","url":null,"abstract":"<p><strong>Introduction: </strong>Endometrial Cancer (EC) is the most prevalent gynecologic malignancy, and its incidence continues to rise globally. PTEN mutations occur frequently in EC and lead to aberrant activation of the PI3K/AKT pathway, driving uncontrolled cellular proliferation and survival. In murine models, uterine-specific deletion of Pten results in rapid EC development. Emerging evidence implicates Histone Deacetylases (HDACs) as key epigenetic regulators of tumor progression, yet the specific role of HDAC3 in EC remains poorly defined.</p><p><strong>Methods: </strong>We generated uterine-specific Pten and Hdac3 double-knockout mice (Pgrcre/+Hdac3f/fPtenf/f; Hdac3d/dPtend/d) to investigate the functional and therapeutic relevance of HDAC3. Histopathologic analysis was performed to examine the effect of Hdac3 ablation on EC with Pten deficiency compared with Pten single-knockout mice (Pgrcre/+Ptenf/f; Ptend/d) at 1 and 2 months of age. To evaluate the effect of the HDAC3 inhibitor (RGFP966), 6-week-old Ptend/d (Stage Ⅰ EC) mice were treated with vehicle or RGFP966 (10 mg/kg) twice per week for 5 weeks via intraperitoneal injection.</p><p><strong>Results: </strong>Histopathological analysis revealed marked regression of EC in Hdac3d/dPtend/d mice compared to Ptend/d controls to investigate the functional and therapeutic relevance of HDAC3. Pharmacologic inhibition of HDAC3 using the selective inhibitor RGFP966 in Ptend/d mice significantly reduced tumor burden and metastatic dissemination compared to vehicle treatment. Mechanistically, HDAC3 inhibition suppressed tumor cell proliferation and enhanced apoptosis, concomitant with reduced phosphorylation of ERK1/2 and AKT levels.</p><p><strong>Discussion: </strong>While our findings demonstrate significant antitumor effects of HDAC3 inhibition in PTEN-deficient endometrial cancer, further studies are needed to define the downstream molecular pathways responsible for these effects.</p><p><strong>Conclusion: </strong>Collectively, these findings establish HDAC3 as a critical epigenetic driver of endometrial tumorigenesis and support selective HDAC3 inhibition as a promising therapeutic strategy for PTEN-deficient EC.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Molecular Targets in MASH/NASH: Linking Pathogenic Mechanisms to Therapeutic Strategies for Improved Pharmacological Management.","authors":"Sk Ashif Jan, Abhijit Debnath, Kaif Khan Ashpak Pathan, Anu Chandran, Siddhant, Rajesh Kumar Singh","doi":"10.2174/0115665240441676260621153314","DOIUrl":"https://doi.org/10.2174/0115665240441676260621153314","url":null,"abstract":"<p><p>Metabolically Dysfunctional-Associated Steatohepatitis (MASH), affecting approximately 5.27% of the global population, represents a critical unmet medical need with limited therapeutic options. The complex pathophysiology involving multiple interconnected pathways necessitates innovative therapeutic approaches beyond traditional targets. This review comprehensively examines emerging pharmacological targets for MASH treatment, focusing on novel mechanisms that address key pathogenic processes, including lipogenesis, inflammation, endoplasmic reticulum stress, and immune cell recruitment. We conducted a systematic analysis of preclinical and clinical evidence for six promising therapeutic targets: cyclophilins, ATP citrate lyase (ACLY), NLRP3 inflammasome, X-box binding protein 1 (XBP1), farnesoid X receptor (FXR), and chemokine receptors (CCR). Cyclophilin inhibitors (CRV431, NV556) demonstrate anti-fibrotic efficacy in Phase 2A trials by targeting mitochondrial dysfunction and collagen synthesis. ACLY inhibition offers advantages over acetyl-CoA carboxylase targeting by upstream modulation of de novo lipogenesis, with bempedoic acid showing clinical promise. NLRP3 inflammasome inhibitors (MCC950, JT001, GDC-2394) effectively reduce hepatic inflammation through caspase-1/IL-1β pathway modulation. XBP1 targeting addresses ER stress-mediated lipogenesis and inflammation crosstalk. FXR agonists (obeticholic acid, cilofexor, tropifexor) demonstrate robust clinical efficacy in improving steatosis, inflammation, and fibrosis. Chemokine receptor antagonists (cenicriviroc, AZD5069) show potential in reducing inflammatory cell recruitment, though mixed clinical results highlight the complexity of immune modulation. These novel targets represent a paradigm shift in MASH therapeutics, offering mechanistically distinct approaches that could enable personalized treatment strategies. The advanced clinical development of several candidates, particularly FXR agonists and cyclophilin inhibitors, suggests near-term therapeutic breakthroughs. Future combination therapies targeting multiple pathways simultaneously may optimize treatment efficacy for this multifaceted disease.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA PVT1-Mediated Regulation of Cardiovascular Diseases: A New Paradigm.","authors":"Habib Haybar, Maryam Khombi Shooshtari, Farhoodeh Ghaedrahmati, Ali Khavanin, Mina Mohammadzadeh, Melika Haybar, Shirin Azizidoost, Maryam Farzaneh","doi":"10.2174/0115665240445392260906174605","DOIUrl":"https://doi.org/10.2174/0115665240445392260906174605","url":null,"abstract":"<p><p>A notable mortality rate is related to cardiovascular disorders despite progress in therapy. Long non-coding RNAs (lncRNAs) play pivotal roles in diverse biological processes, and the abnormal regulation of their downstream signals is linked to a broad range of disorders. A lncRNA, Plasmacytoma Variant Translocation 1 (PVT1), has been found to be associated with the pathogenesis of human diseases. According to recent studies, lncRNA PVT1 participates in a variety of cellular processes, including proliferation, migration, and inflammation, via molecular axes with microRNAs and their downstream targets in neoplastic and non-neoplastic disorders. Given the involvement of these cellular processes in the pathogenesis of cardiovascular disease, we aim to clarify the function of the lncRNA PVT1 in this process. In addition, we aim to determine whether it is a prognostic factor or a potential therapeutic target in cardiovascular disorders.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursolic Acid in Cancer Therapy: Mechanistic Insights into Apoptosis, Angiogenesis, Cell Cycle Arrest, and Metastasis.","authors":"Issa S Al-Amri, Samira Farhadi, Mazen M Jamil Al-Obaidi, Abdulaziz Y AlKindi, Waleed Al Rajhi, Saad Sabbar Dahham","doi":"10.2174/0115665240506877261001062833","DOIUrl":"https://doi.org/10.2174/0115665240506877261001062833","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Ursolic acid, a naturally occurring pentacyclic triterpenoid, has been extensively investigated in preclinical studies for its anticancer effects. Although numerous studies have described its interaction with individual molecular targets, how these pathways function together in a coordinated manner is still not fully understood. This review examines available mechanistic studies to better understand how UA interacts with multiple cancer-related pathways.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Studies were selected based on their relevance to underlying mechanisms and overall study quality.</p><p><strong>Results: </strong>UA has been reported to affect several cancer-related processes, including apoptosis, angiogenesis, and cell cycle regulation. It can activate both intrinsic and extrinsic apoptotic pathways, inhibit angiogenesis through modulation of VEGF and HIF-1α, and interfere with Epithelial-Mesenchymal Transition (EMT) by regulating MMP-2 and MMP-9. In addition, UA influences key signaling pathways such as PI3K/ Akt/mTOR, MAPK/ERK, STAT3, and NF-κB.</p><p><strong>Discussion: </strong>These findings suggest that UA may act through multiple mechanisms, although their clinical relevance remains unclear.</p><p><strong>Conclusion: </strong>UA modulates multiple interconnected oncogenic pathways involved in apoptosis, angiogenesis, cell-cycle regulation, and metastasis. However, current evidence remains predominantly preclinical, and further pharmacokinetic optimization together with well-designed clinical studies is required before its therapeutic potential can be translated into clinical practice.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Gene Polymorphisms and Expression Patterns of Brown Adipose Tissue in Individuals with Obesity.","authors":"Hamid Khan, Adeel Ahmad, Mubin Mustafa Kiyani, Iqra Iftikhar, Bakhtawar Khan, Syed Shahab Ud Din Shah, Khalid Al-Regaiey, Muhammad Iqbal, Hong-Tao Li, Shahid Bashir","doi":"10.2174/0115665240449649260928095142","DOIUrl":"https://doi.org/10.2174/0115665240449649260928095142","url":null,"abstract":"<p><p>Adipose tissue plays a central role in energy homeostasis, influencing metabolism, thermoregulation, and overall health. White adipose tissue (WAT) primarily stores energy, while brown adipose tissue (BAT) dissipates energy through heat production. This thermogenic capacity of BAT is mediated by uncoupling protein 1 (UCP1), an important therapeutic target for obesity and related metabolic disorders. The activity and function of BAT are strongly influenced by genetic factors, including genes involved in temperature regulation, mitochondrial function, and energy metabolism. Key regulators such as uncoupling protein 1 (UCP1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), PR Domain Containing 16 (PRDM16), and Cell Death-Inducing DFFA-Like Effector A (CIDEA) modulate BAT activation and energy expenditure, providing potential avenues for therapeutic intervention in obesity. Moreover, genetic variants in the Fat Mass and Obesity-Associated gene (FTO), ADRB3, and LEP highlight the links between BAT activity, lipid metabolism, and obesity susceptibility. Ethnic differences in adiposity traits, including body mass index (BMI) and waist-to-hip ratio, further emphasize the need for population-specific approaches in genetic studies. This review synthesizes current knowledge on the genetic regulation of BAT and explores their practical implications for obesity management. Importantly, we highlight gaps in understanding, such as obstacles to implementing BAT-targeted therapies, and recommend future studies that integrate genetic diversity, functional analyses, and translational research to enhance strategies for improving energy balance and metabolic health.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Accuracy of Pleural Fluid Biomarkers and Nucleic Acid Amplification Tests in Tuberculous Pleural Effusion: An Umbrella Review.","authors":"Nurhayati, Achmad Shidiq, Sundari Wirasmi, Mieska Despitasari, Rahmi Anggraeni, Pesigrihastamadya Normakristagaluh, Nova Hadi Lestriandoko, Gembong Satrio Wibowanto, Muhammad Nurkhoiri Hindratno, Juli Purnomo, Zakiah Novianti, Wahid Syamsul Hadi, Hesty Lusinta, Risty Manety, Asykar Jayanti, Edy Widihartono, Harimat Hendarwan","doi":"10.2174/0115665240483646260915075032","DOIUrl":"https://doi.org/10.2174/0115665240483646260915075032","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Tuberculous Pleural Effusion (TPE) is a common but diagnostically challenging form of extrapulmonary tuberculosis. Many overlapping systematic reviews have evaluated pleural-fluid biomarkers and Nucleic Acid Amplification Tests (NAATs). This umbrella review aimed to synthesise and compare the diagnostic accuracy of pleural-fluid tests for TPE within a single appraised framework.</p><p><strong>Methods: </strong>We conducted an umbrella review (JBI methodology; PRISMA 2020 reporting) of 20 systematic reviews with meta-analysis, appraised them using AMSTAR 2, quantified primary-study overlap with the Corrected Covered Area (CCA), and summarised the certainty of evidence reported by the source reviews (GRADE).</p><p><strong>Results: </strong>Cytokine markers showed the highest accuracy (IFN-γ sensitivity 0.93, specificity 0.96; IL-27 0.94/0.97). ADA was a robust rule-out test (0.92/0.90). NAATs were highly specific but insensitive (Xpert MTB/RIF 0.52/0.99; Xpert Ultra 0.68/0.97).</p><p><strong>Discussion: </strong>The overlap among reviews was high to very high, and the apparent hierarchy was found to be influenced by reference-standard heterogeneity, indicating that the observed ranking should not be interpreted as free of methodological bias.</p><p><strong>Conclusion: </strong>No single test is optimal; pleural-fluid biomarkers and NAATs play complementary roles that depend on pre-test probability.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of NOX2 Prevents Impairment of Cardiovascular Response and Inflammatory Tissue Injury Mediated by Nitrosative/ Oxidative Stress in the Lipopolysaccharide-Induced Septic Shock Model in Rats.","authors":"Lutfiye Kara, Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Elif İkiz, Parinaz Amini Didani, Tuba Kara, Bahar Tunctan","doi":"10.2174/0115665240507626260925053620","DOIUrl":"https://doi.org/10.2174/0115665240507626260925053620","url":null,"abstract":"<p><strong>Introduction: </strong>It is unknown whether inhibition of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2 has protective effects against the impaired cardiovascular response and inflammatory tissue injury mediated by nitrosative/ oxidative stress in bacterial septic shock. Therefore, using the NOX2 inhibitor NOX2ds-stat, the effects of NOX2 inhibition on cardiovascular response were explored in a rat septic shock model induced by lipopolysaccharide (LPS), in relation to cardiovascular/renal inflammatory tissue injury.</p><p><strong>Methods: </strong>Mean arterial pressure and heart rate were obtained non-invasively using a tail cuff device in rats before and at 1, 2, 3, and 4 hours after injection of saline or LPS. The rats were treated with NOX2ds-stat (0.1, 0.3, or 1 mg/kg) 1 hour following saline or LPS injection. The diazotization method was used to measure nitrite levels in the sera and cardiovascular/renal tissues. The changes in tissue expression of proteins and/or their phosphorylation status related to nuclear factor (NF)-κB/inducible nitric oxide synthase (iNOS)- and NOX2-mediated nitrosative/oxidative stress, as well as peroxisome proliferator-activated receptor (PPAR) α/β/γ, were assessed by the immunoblotting method. Using hematoxylin and eosin staining, histopathological changes in the tissues were evaluated.</p><p><strong>Results: </strong>A decrease in blood pressure by 48 mmHg and an increase in heart rate by 112 bpm were observed 4 hours after LPS injection. While the expression/ phosphorylation of gp91phox, p47phox, 3-nitrotyrosine, NF-κB p65, iNOS, Vasodilator- Stimulated Phosphoprotein (VASP), and interleukin (IL)-1β proteins was enhanced in the thoracic aorta, renal artery, heart, and kidney tissues, in addition to the levels of nitrite in the sera and tissues of LPS-injected animals, the expression/phosphorylation of endothelial nitric oxide synthase (eNOS), PPARα, PPARβ, and PPARγ was decreased. The LPS-induced changes were ameliorated by NOX2ds-stat (1 mg/kg). NOX2ds-stat also attenuated the LPS-induced increase in scores reflecting inflammatory tissue injury.</p><p><strong>Discussion: </strong>These findings indicate that selective inhibition of NOX2 prevents both impairment of cardiovascular response and cardiovascular/renal tissue injury, presumably through suppression of NF-κB/iNOS- and NOX2-mediated nitrosative/ oxidative stress associated with increased expression of anti-inflammatory PPARα/β/γ in the rat septic shock model induced by bacterial LPS. Further studies are required to determine whether NOX2 inhibition benefits patients with septic shock.</p><p><strong>Conclusion: </strong>This study provides novel insights into the pathophysiological mechanisms of septic shock and highlights the potential therapeutic value of targeting NOX2 to improve cardiovascular response and inflammatory tissue injury.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}