Current Issues in Molecular Biology最新文献

{"title":"Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.","authors":"Yan Xi, Xinchen Yan, Jiahao Liu, Siqi Li, Xinyang Zhang, Yiwen Hou, Minjie Chu, Minfeng Yang","doi":"10.3390/cimb48040339","DOIUrl":"https://doi.org/10.3390/cimb48040339","url":null,"abstract":"<p><p>All living organisms possess a DNA damage response (DDR) that is important for genetic evolution. Cells have developed comprehensive mechanisms for addressing DNA damage, collectively called the DNA damage response and repair. External environmental stress continuously disrupts genomic integrity and triggers various pathological changes. The failure of the DDR network often drives cell carcinogenesis, and its core components not only serve as biological markers for disease monitoring but also represent highly promising molecular targets for targeted therapy. Therefore, there is a high level of interest in exploring DDR-related biomarkers as cutting-edge therapeutic regimens and developing highly sensitive tools for DDR diagnosis. These methods should assess the rate of damage occurrence and distinguish when repair pathways are activated. These kinds of advances are key to preserving genetic stability and detecting and preventing diseases early. Here, we provide a broad summary of recent advances in DDR detection technologies, with a particular focus on the complementarity between different techniques. We have also summarized current technological bottlenecks, future research paradigms, and clinical translation pathways. The insights presented in this review will contribute to the development of multidisciplinary integrated DDR detection technologies, promote the establishment of DDR biomarker detection systems, and provide crucial methodological references for targeted drug development, efficacy evaluation, and resistance mechanism research targeting the DDR pathway.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Biofilm Activity of Combinations of Cinnamic Acid and Its Derivatives with Cloxacillin Against Methicillin-Resistant <i>Staphylococcus epidermidis</i>.","authors":"Tomasz Zawiła, Denis Swolana, Marta Zawiła, Zuzanna Rzepka, Robert D Wojtyczka","doi":"10.3390/cimb48030336","DOIUrl":"10.3390/cimb48030336","url":null,"abstract":"<p><p><i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>) poses a significant clinical challenge, particularly in the context of biofilm-associated infections, with increasing antibiotic resistance further complicating infection eradication. In the present study, the effects of cinnamic acid and its derivatives (ferulic acid, <i>p</i>-coumaric acid, and sinapic acid), alone and in combination with the β-lactam antibiotic cloxacillin, on biofilm formation by a single methicillin-resistant <i>S. epidermidis</i> (MRSE) clinical strain were explored. The expression of the biofilm-associated <i>icaADBC</i> operon genes and the <i>icaR</i> repressor gene was assessed using Real-Time PCR as an exploratory analysis under sub-minimal inhibitory concentrations (sub-MICs) of the tested compounds. Furthermore, confocal microscopy was used to qualitatively assess selected structural changes in the biofilm. Their occurrence was demonstrated depending on the fractional inhibitory concentration (FIC) levels used. The results revealed variable and nonlinear patterns of gene expression in response to the tested concentrations. Additionally, compound-dependent differences in anti-biofilm-related responses were observed. Overall, the findings provide insight into the potential influence of cinnamic acid derivatives combined with cloxacillin on biofilm-associated processes in <i>S. epidermidis</i>.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tea Polysaccharides Ameliorates Non-Alcoholic Fatty Liver Disease in Mice via Regulating Macrophages Polarization by Gut Microbial Metabolites.","authors":"Daixin Liu, Ang Li, Ping Li","doi":"10.3390/cimb48030338","DOIUrl":"10.3390/cimb48030338","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and a global public health concern, for which there is currently no effective method to inhibit its progression. The pathogenesis of NAFLD is related to hepatic lipid metabolism disorders and liver inflammation. Previous studies have shown that tea polysaccharides (TPS) have the ability to regulate lipid metabolism and control inflammation. This study aimed to observe the effect of TPS on ameliorating NAFLD in a mouse model and to reveal its underlying mechanisms. In the current study, male C57BL/6J mice were fed a high-fat diet and administered 100 mg/kg TPS daily by gavage for 14 weeks. Then, liver injury indicators and macrophage polarization markers were detected. The results revealed that TPS could significantly ameliorate the progression of NAFLD and decrease liver injury indicators. Moreover, we found that treatment of NAFLD model mice with TPS could skew liver macrophages polarization from M1 to M2 type, which inhibited pro-inflammatory cytokines production and liver inflammation. Mechanistically, TPS cannot directly regulate the polarization of liver macrophages, but instead promotes the production of butyric acid by gut microbiota, which in turn regulates macrophage polarization. These findings suggest that TPS ameliorates NAFLD-associated inflammation by modulating the gut-liver axis and promoting M2 macrophage polarization, laying the foundation for the potential of TPS in the development of health foods for NAFLD.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotransformation of Maclekarpine E in Rats: CYP2C19-Mediated Metabolism, Fecal Enrichment, and Network Pharmacology-Based Anti-Ulcerative Colitis Prediction.","authors":"Yingxue Yang, Lin Wang, Jiaojiao Xue, Zhen Dong, Pi Cheng","doi":"10.3390/cimb48030335","DOIUrl":"10.3390/cimb48030335","url":null,"abstract":"<p><p>Maclekarpine E is a minor alkaloid from <i>Macleaya</i> species with reported in vitro anti-inflammatory activity, but its in vivo metabolism remains unexplored. This study investigated the metabolic fate of maclekarpine E in rats and evaluated the potential pharmacological relevance of its metabolites. Maclekarpine E was orally administered to male Sprague-Dawley rats (250 mg/kg). Plasma, urine and feces were collected and analyzed by UPLC-Q-TOF-MS/MS. CYP phenotyping was performed using recombinant human enzymes. Molecular docking against ABCG2 and ABCC2 was conducted to assess potential interactions of all fecal compounds with these efflux transporters. Network pharmacology was employed to predict potential anti-ulcerative colitis-related targets of the metabolites, generating hypotheses for future experimental validation. Nineteen phase I metabolites were identified. Biotransformations included ring-opening, demethylation and oxidation. All 19 metabolites were detected in feces, nine in plasma and two in urine. No phase II conjugates were observed. CYP2C19 was the only significantly active isoform under the tested conditions, mediating approximately 16.5% substrate depletion (<i>p</i> < 0.05). All 20 fecal compounds bound ABCG2 (ΔG < -5.0 kcal/mol); 19 bound ABCC2. Network pharmacology yielded 57 overlapping targets with ulcerative colitis, enriched in PI3K-Akt and MAPK pathways. This study provides the first comprehensive metabolic profile of maclekarpine E in rats. The compound undergoes CYP2C19-mediated oxidation and is predominantly excreted into feces. Its fecal metabolites are potential ABCG2/ABCC2 substrates and may target UC-associated pathways based on network pharmacology predictions, warranting further experimental validation.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanism of Action of Stigmasterol in Bone Formation in Osteoporosis.","authors":"Cailian Lu, Hong Li, Zhengbo Liu, Sirui Lü, Junxing Liu","doi":"10.3390/cimb48030337","DOIUrl":"10.3390/cimb48030337","url":null,"abstract":"<p><p>Osteoporosis (OP) is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture, significantly impacting patients' quality of life. Stigmasterol (STG), a natural plant sterol, has been reported to possess multiple biological activities. However, its effects on OP bone formation and underlying molecular mechanisms remain unclear. The effects of STG on OP bone formation and potential mechanisms were investigated through in vivo and in vitro experiments combined with network pharmacology analysis. An OP model was established in ovariectomized (OVX) rats, and the bone-protective effects of STG were evaluated via micro-CT analysis and histological staining. In vitro experiments, MC3T3-E1 pre-osteoblasts were used to assess STG's influence on osteogenic differentiation through Western blot analysis and ALP/ARS staining. Network pharmacology methods were used to predict potential targets and signaling pathways for STG in OP treatment, followed by mechanism validation. STG significantly improved bone microarchitecture in OVX rats, increased key osteogenic marker expression, and promoted MC3T3-E1 osteogenic differentiation in a dose-dependent manner. Network pharmacology analysis predicted 278 potential targets for STG in treating OP, with pathway enrichment analysis indicating significant involvement of the JAK/STAT pathway. Mechanistic studies revealed that STG promotes osteogenic differentiation by activating the JAK2/STAT3 signaling cascade. As an osteogenic promoter, STG effectively alleviates bone loss and enhances osteoblast differentiation by activating the JAK2/STAT3 signaling pathway.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotransmitter Systems in Alzheimer's Disease.","authors":"María Jesús Ramírez-Expósito, Cristina Cueto-Ureña, José Manuel Martínez-Martos","doi":"10.3390/cimb48030334","DOIUrl":"10.3390/cimb48030334","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the leading cause of global dementia, is a multifactorial process that goes beyond the accumulation of β-amyloid (Aβ) plaques and tau protein tangles, including glia cell-mediated neuroinflammation, vascular dysfunction, metabolic alterations, and synaptic loss. Its complex etiology also involves oxidative stress and mitochondrial dysfunction. Multiple neurotransmitter systems involved in the pathogenesis and the various cognitive and non-cognitive symptoms of AD are thus altered. The cholinergic system, historically the first to be associated with AD, suffers early degeneration and loss of neurons/receptors, correlating with cognitive impairment. The glutamatergic system, the main excitatory system, exhibits excitotoxicity due to increased extracellular glutamate and alterations in NMDA/AMPA receptor distribution, exacerbating neuronal damage. The GABAergic system, the main inhibitor, shows alterations in parvalbumin-positive interneurons, leading to hyperexcitability and dysfunction of neuronal networks. Monoaminergic systems (serotonergic, dopaminergic and noradrenergic) undergo early degeneration in key nuclei such as the raphe and locus coeruleus, contributing to the apathy, depression and sleep disturbances characteristic of AD. Other less explored systems, such as histaminergic and purinergic, are also crucial in cognitive modulation and neuroinflammation. The endocannabinoid system acts as a master modulator with neuroprotective and anti-inflammatory effects. These systems do not operate in isolation; their complex interactions generate pathological circuits that amplify neuronal dysfunction. The limited efficacy of current therapies, which are primarily symptomatic, highlights the need for multimodal approaches that may transform AD treatment toward personalized and more effective interventions.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.","authors":"Rebecca Jung, Emily Kao, Victor H Guaiquil, Ali R Djalilian, Mark I Rosenblatt","doi":"10.3390/cimb48030332","DOIUrl":"10.3390/cimb48030332","url":null,"abstract":"<p><p>Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Eupatorium lindleyanum</i> DC. Suppresses Cytokine Storm by Inhibiting NF-κB and PI3K-Akt Signaling in Sepsis-Associated and Virus-Related Acute Lung Injury.","authors":"Chen Luo, Peilin He, Yan Yang, Lian Xia, Wenjie Xu, Daike Zou, Yiduo Feng, Lian Duan, Junjie Deng, Yong Jing, Xianqin Luo","doi":"10.3390/cimb48030333","DOIUrl":"10.3390/cimb48030333","url":null,"abstract":"<p><p>Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. <i>Eupatorium lindleyanum</i> DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related activities; however, its protective mechanisms in SALI and virus-associated inflammatory lung injury remain incompletely understood. In this study, an integrated strategy combining computational prediction and experimental validation was employed to investigate the therapeutic potential and underlying mechanisms of EL. The chemical constituents of EL were characterized by UPLC-Q-TOF/MS, followed by network pharmacology, molecular docking, and molecular dynamics analyses to predict key targets and signaling pathways. A cecal ligation and puncture (CLP)-induced SALI rat model was used to evaluate lung histopathology, pulmonary edema, cytokine production, and inflammatory signaling activation. In parallel, LPS-stimulated RAW264.7 macrophages were used to assess cytokine secretion and pathway regulation in vitro. In addition, a SARS-CoV-2 pseudovirus-induced mouse model was employed to further evaluate the in vivo relevance of the representative bioactive compound hyperoside in pseudovirus-associated lung injury. A total of 32 active compounds and 697 putative targets were identified, among which 116 were associated with sepsis and COVID-19. In vivo, EL markedly alleviated lung injury, reduced the lung coefficient and wet/dry ratio, and suppressed excessive production of proinflammatory cytokines and activation of key signaling proteins. In vitro, EL dose-dependently inhibited TNF-α and IL-6 secretion and regulated the PI3K-Akt and NF-κB signaling pathways. Notably, hyperoside showed favorable predicted interactions with PI3K-Akt pathway-related targets (EGFR, PI3K, and Akt), while molecular dynamics simulations supported stable interactions with several COVID-19-related targets, including ACE2, Mpro, and RdRp. Furthermore, hyperoside significantly alleviated SARS-CoV-2 pseudovirus-associated lung injury, reduced ACE2 protein expression, and downregulated EGFR, PI3K, and Akt mRNA levels in vivo. Collectively, these findings indicate that EL exerts protective effects through multi-component, multi-target, and multi-pathway mechanisms, and support its potential value for further investigation in SALI and virus-associated inflammatory lung injury.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>MeNADP-ME3</i> Confers Salt and Drought Tolerance in <i>Arabidopsis</i> and Drives Functional Diversification of the <i>NADP-ME</i> Family in Cassava.","authors":"Shuwen Wu, Zhanming Xia, Jiazheng Zhao, Changyi Wang, Yi Min, Dayong Wang","doi":"10.3390/cimb48030331","DOIUrl":"10.3390/cimb48030331","url":null,"abstract":"<p><p>As a typical C3-C4 intermediate plant, cassava (<i>Manihot esculenta</i> Crantz) exhibits high photosynthetic efficiency and low photorespiration. NADP-malic enzyme (NADP-ME) is a key enzyme in the C4 photosynthetic pathway that provides elevated CO2 concentrations for Rubisco. However, research on NADP-ME in C3-C4 intermediate species remains limited. In this study, we identified four <i>NADP-ME</i> genes in the cassava genome, with segmental duplication serving as the primary driving force for gene evolution. Cis-acting element analysis indicated potential roles of <i>MeNADP-ME</i> genes in environmental adaptation, stress responses, and growth regulation. Expression profiling using bulk RNA sequencing and single-cell RNA sequencing revealed distinct expression patterns in different tissues and cell subsets. Comparative analysis with <i>Arabidopsis</i> (<i>Arabidopsis thaliana</i>) and maize (<i>Zea mays</i>) NADP-ME families demonstrated that <i>MeNADP-ME3</i> exhibits bundle sheath cell-specific expression analogous to <i>ZmchlC4NADP-ME</i> in maize. Notably, photosynthetic genes and plasmodesmata (PD)-related genes exhibited high co-expression within mesophyll subcluster 13 and bundle sheath cells, providing molecular evidence for a limited C4 photosynthetic pathway in cassava. Protein-protein interaction predictions implicated MeNADP-ME3 in photosynthetic carbon metabolism and photorespiration regulation. Furthermore, qRT-PCR revealed significant responsiveness of <i>MeNADP-ME3</i> to various abiotic stresses, and confocal imaging confirmed its chloroplast localization. Functional validation demonstrated that <i>Arabidopsis</i> overexpressing <i>MeNADP-ME3</i> exhibited 30-120% enhanced antioxidant enzyme activities (SOD, POD, CAT) and 20-32% reduced oxidative damage markers (MDA, H2O2) under drought and salt stresses. These findings reveal the evolutionary trajectory of <i>NADP-ME</i> genes in C3-C4 intermediate species and provide genetic resources for developing stress-tolerant cassava cultivars.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Immunotherapy in Osteoarthritis: A Clinical Trial of Autologous Dendritic Cell Immunotherapy in Knee Osteo-Arthritis.","authors":"Kurniawan Silalahi, Bhimo Aji Hernowo, Jonny Jonny, Lintang Sagoro, Chrismis Novalinda Ginting, Terawan Agus Putranto","doi":"10.3390/cimb48030330","DOIUrl":"10.3390/cimb48030330","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Osteoarthritis (OA) is a chronic inflammatory disease with limited disease-modifying therapies. This study explored a novel immunomodulatory approach using autologous, antigen-pulsed semi-mature dendritic cells (DCs) to modulate the inflammatory milieu in knee OA patients. <b>Methods</b>: In this open-label, quasi-experimental study, 29 subjects received a single subcutaneous injection of autologous DCs. Outcomes assessed at baseline and 4 weeks included the WOMAC index for symptoms and serum levels of IL-6 and TNF-α. Responses were analyzed in the overall cohort and by BMI subgroups. <b>Results</b>: The overall cohort showed a non-significant trend in WOMAC improvement (<i>p</i> = 0.080) and no change in IL-6 (<i>p</i> = 0.785) or TNF-α (<i>p</i> = 0.330). Subgroup analysis revealed differential patterns of response: WOMAC scores improved significantly only in normal-weight patients (<i>p</i> = 0.030), while serum TNF-α decreased significantly only in overweight patients (<i>p</i> = 0.025). IL-6 levels were unchanged across all groups. <b>Conclusions</b>: Autologous antigen-pulsed DC administration was associated with differential responses across BMI subgroups. Symptomatic benefit was observed in normal-weight individuals, while a reduction in systemic TNF-α occurred in overweight patients. These findings suggest that the host metabolic state may modulate the response to DC-based immunotherapy, and therefore warrant validation in a randomized, placebo-controlled trial.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}