Current Issues in Molecular Biology最新文献

{"title":"Overexpression of the CAM-Derived NAC Transcription Factor KfNAC83 Enhances Photosynthesis, Water-Deficit Tolerance, and Yield in <i>Arabidopsis</i>.","authors":"Kumudu N Rathnayake, Beate Wone, Madhavi A Ariyarathne, Won C Yim, Bernard W M Wone","doi":"10.3390/cimb47090736","DOIUrl":"10.3390/cimb47090736","url":null,"abstract":"<p><p>Drought stress is a major constraint on plant photosynthesis, growth, and yield, particularly in the context of increasingly frequent and severe extreme weather events driven by global climate change. Enhancing photosynthetic efficiency and abiotic stress tolerance is therefore essential for sustaining crop productivity. In this study, we functionally characterized <i>Kalanchoë fedtschenkoi</i> NAC83 (<i>KfNAC83</i>), a transcription factor derived from a heat-tolerant obligate crassulacean acid metabolism (CAM) species, by constitutively overexpressing it in the C₃ model plant <i>Arabidopsis thaliana</i>. Transgenic <i>Arabidopsis</i> lines overexpressing <i>KfNAC83</i> exhibited significantly enhanced tolerance to water-deficit and NaCl stress, along with improved photosynthetic performance, biomass accumulation, and overall productivity. Transcriptomic analysis revealed that <i>KfNAC83</i> overexpression increased key components of the jasmonate (JA) signaling pathway in both roots and shoots, suggesting a mechanistic link between <i>KfNAC83</i> activity and enhanced abiotic stress responses. Additionally, the transgenic lines displayed increased nighttime decarboxylation activity, indicative of partial CAM-like metabolic traits. These findings demonstrate that <i>KfNAC83</i> functions as a positive regulator of abiotic stress tolerance and growth, likely through modulation of jasmonate-mediated signaling and photosynthetic metabolism. This work highlights the potential of CAM-derived transcription factors for bioengineering abiotic stress-resilient crops in the face of climate change.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184837","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 Influence of Short Peptides on Cell Senescence and Neuronal Differentiation.","authors":"Elena Sakhenberg, Natalia Linkova, Nina Kraskovskaya, Daria Krieger, Victoria Polyakova, Dmitrii Medvedev, Alexander Krasichkov, Mikhail Khotin, Galina Ryzhak","doi":"10.3390/cimb47090739","DOIUrl":"10.3390/cimb47090739","url":null,"abstract":"<p><p>It has been previously shown that some short peptides are involved in various cellular processes, such as transcription modulation and regulation of differentiation mechanisms. In particular, the effect of peptides on the neuronal differentiation of human periodontal ligament stem cells has been demonstrated. The goal of this study was to assess the effect of KED, EDR, and AEDG short peptides in stimulating the transdifferentiation of fetal MSCs into induced neuronal cells and prevention of their senescence. We applied a novel in vitro technique for neuronal cell generation, which combines the use of microRNAs, transcription factors, and small molecules to transdifferentiate fetal mesenchymal stem cells into induced cortical neurons. It was shown that the application of AEDG and KED short peptides at the end of the transdifferentiation process decreases the expression of the cell cycle marker p21 by 15% and beta-galactosidase activity by 1.51-2.4 times. However, short peptides did not affect the expression levels of TUj-1 and LaminB1, whose expression also changes during neuronal differentiation. The experiments indicate the potential of AEDG and KED short peptides as modulators of neurogenesis and geroprotectors and suggest that they can be used as stimulators of neuronal differentiation.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184954","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":"Photoinduced Inhibition of Neutrophil Extracellular Traps Formation by Dichromatic Light Irradiation.","authors":"Kahramon Mamatkulov, Yersultan Arynbek, Huy Duc Le, Nina Vorobjeva, Grigory Arzumanyan","doi":"10.3390/cimb47090729","DOIUrl":"10.3390/cimb47090729","url":null,"abstract":"<p><p>Neutrophils are the first line of defense of the human immune system against pathogens. Photobiomodulation, mediated by mitochondrial photoacceptors such as cytochrome <i>c</i> oxidase, has emerged as a method to modulate neutrophil function through targeted light exposure. Despite the extensive characterization of neutrophil extracellular traps (NETs) formation (NETosis), the wavelength-specific modulation of neutrophil photoactivation and the involvement of redox pathways remain poorly defined. In this study, the effects of monochromatic (365 nm, 415 nm, 437 nm, and 625 nm) and dichromatic LED-light irradiation on NETs formation were systematically examined. The highest netotic responses were elicited by UV-A (365 nm) and violet-blue light (415 nm), whereas 437 nm showed the lowest induction and 625 nm stimulated a moderate netotic response. The pharmacological inhibition of NETosis induced by 365 nm and 415 nm irradiation with specific NADPH oxidase inhibitor, apocynin, and mitochondrial reactive oxygen species (mtROS) scavenger, MitoTEMPO, attenuated NETs formation by engaging both enzymatic and mitochondrial oxidative sources. Notably, mtROS played a dominant role under 415 nm stimulation in contrast to 365 nm-induced NETosis as demonstrated by higher sensitivity to MitoTEMPO. Importantly, combined simultaneous irradiation with 415 nm and 625 nm LEDs resulted in a significant suppression of NETs formation by more than 50%, highlighting a potent inhibitory synergy observed for the first time and suggesting a new approach of wavelength pairing to modulate neutrophil activation. These results were further supported by measurements of ROS production using a luminol-amplified chemiluminescence assay. Collectively, these findings delineate a wavelength- and ROS-dependent framework for light-induced neutrophil activation, with mitochondrial pathways exerting central control particularly under short-wavelength irradiation.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184864","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>Astragalus membranaceus</i> Extract Attenuates Inflammatory Cytokines and Matrix-Degrading Enzymes in Human Chondrocytes: A Novel Nutraceutical Strategy for Joint Health.","authors":"Alessia Mariano, Rosario Russo, Anna Scotto d'Abusco, Fabiana Superti","doi":"10.3390/cimb47090731","DOIUrl":"10.3390/cimb47090731","url":null,"abstract":"<p><p>The dried root extract of <i>Astragalus membranaceus</i>, also known as <i>Astragali radix</i>, is widely used in traditional Chinese medicine for its multiple health benefits and well-established safety profile. <i>Astragalus</i> root extract exhibits several bioactive properties, including anti-inflammatory, antioxidant, antiviral and hepatoprotective effects. Due to its unique features, it is being investigated in a novel application as a complementary remedy in the management of joint disorders. In this study, we evaluated the effect of <i>Astragalus membranaceus</i> hydroalcoholic root extract (0.01 and 0.1 mg/mL) in vitro on the HTB-94 cell line, a well-known model for studying inflammatory pathways in human chondrocytes. The mRNA modulation levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein secretion levels were assessed using an Enzyme-Linked Immunosorbent Assay (ELISA). Results obtained demonstrated that this extract is able to decrease the tumor necrosis factor-α (TNF-α)-induced inflammatory response by downregulating both the mRNA expression and release of the pro-inflammatory mediators Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Interelukin-8 (IL-8), as well as matrix metalloproteases, including Matrix Metalloprotease-3 (MMP-3), Matrix Metalloprotease-13 (MMP-13) and A disintegrin, and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). Moreover, the interleukin and matrix metalloprotease production was also assessed in non-TNF-α-stimulated cells, revealing that the extract did not alter the basal levels of these mediators. Finally, our findings highlight the potential benefits of <i>Astragalus membranaceus</i> extract, both in terms of its favorable safety profile and its efficacy mitigating joint inflammatory responses. These results support the potential of this extract as a nutraceutical agent for joint health support.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184722","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":"Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition.","authors":"Sayaka Yonezawa, Keishi Kanno, Minami Shiozaki, Masanori Sugiyama, Masanori Ito","doi":"10.3390/cimb47090733","DOIUrl":"10.3390/cimb47090733","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with limited therapeutic options and frequent resistance to treatment. The integrator complex subunit 6 (INTS6), a regulator of RNA polymerase II transcription, has emerged as a potential tumor suppressor that modulates Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). This study aimed to clarify the role of INTS6 in EMT regulation in HCC and to explore the therapeutic potential of small activating RNA (saRNA)-mediated INTS6 induction. The Cancer Genome Atlas (TCGA) dataset was analyzed to assess the clinical relevance of INTS6 in HCC. Functional studies were conducted using a hepatoma cell line to determine the effects of INTS6 modulation on tumor behavior. Data analysis demonstrated that low INTS6 expression was associated with shorter disease-free survival and poorer prognosis in patients receiving conservative treatment. Experimental suppression of INTS6 increased mesenchymal marker expression, whereas saRNA-mediated induction suppressed these markers. Restoring INTS6 expression reduced cell migration, invasion, and proliferation through G1 cell-cycle arrest and enhanced sensitivity to sorafenib. These findings identify INTS6 as a promising therapeutic target in HCC. saRNA-mediated induction of INTS6 may provide a novel strategy, alone or in combination therapy, to overcome drug resistance and improve clinical outcomes.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184730","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":"Roxadustat as a Hypoxia-Mimetic Agent: Erythropoietic Mechanisms, Bioanalytical Detection, and Regulatory Considerations in Sports Medicine.","authors":"Elena-Christen Creangă, Cristina Ott, Alina-Crenguţa Nicolae, Cristina Manuela Drăgoi, Raluca Stan","doi":"10.3390/cimb47090734","DOIUrl":"10.3390/cimb47090734","url":null,"abstract":"<p><p>Roxadustat (ROX) is an orally active inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHI) that exerts erythropoietic, cardioprotective, and metabolic regulatory effects. Approved for the treatment of anemia associated with chronic kidney disease, ROX promotes endogenous erythropoietin production and improves iron homeostasis, providing a non-injectable alternative to conventional erythropoiesis-stimulating agents (ESAs). Its ability to enhance oxygen transport and facilitate muscle recovery has, however, led to its misuse in sports, where it is classified as a banned substance by the World Anti-Doping Agency. This review provides a comprehensive overview of the pharmacological properties of ROX, its approved and investigational clinical applications, and its chemical synthesis strategies. Particular emphasis is placed on the analytical methodologies employed for ROX detection in anti-doping settings. Techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and high-performance thin-layer chromatography (HPTLC) are critically assessed for their efficacy in detecting ROX and its metabolites in biological matrices. Given the increasing incidence of ROX misuse among athletes, ongoing optimization of detection protocols and longitudinal monitoring approaches, are essential to uphold both sports integrity and public health.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184792","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":"Macrophage Inhibitory Factor in Myocardial Oxidative Stress and Inflammation During Thioacetamide-Induced Liver Fibrosis: Modulation by Betaine.","authors":"Jasmina Djuretić, Jelena Filipovic, Milica Brankovic, Sanja Stankovic, Janko Samardzic, Danijela Vucevic, Tatjana Radosavljevic","doi":"10.3390/cimb47090728","DOIUrl":"10.3390/cimb47090728","url":null,"abstract":"<p><p>Chronic liver disease is closely associated with impaired cardiovascular function. Cardiac dysfunction is caused in part by oxidative stress and increased levels of proinflammatory and profibrogenic mediators in myocardial tissue. The present study aims to investigate the role of betaine in the modulation of MIF-mediated oxidative stress, inflammation, and fibrogenesis in heart during TAA-induced liver fibrosis in mice. The experiment is performed on wild-type and knockout <i>MIF^-/-</i> C57BL/6 mice (MIF^-/- group). They are randomly divided into groups: Control; Bet-group, received betaine (2% <i>wt</i>/<i>v</i> dissolved in drinking water); MIF^-/- mice group; MIF^-/-+Bet; TAA-group, treated with TAA (200 mg/kg b.w.), intraperitoneally, 3×/week/8 weeks); TAA+Bet; MIF^-/-+TAA, and MIF^-/-+TAA+Bet group. After eight weeks of treatment, animals are sacrificed and heart samples are taken to determine oxidative stress parameters, proinflammatory cytokines, profibrogenic factors, and histopathology of myocardial tissue. Our results suggest that MIF contributes significantly to lipid peroxidation of cardiomyocytes, as well as oxidative and nitrosative stress in myocardial tissue in mice with TAA-induced liver fibrosis compared to the control group. In addition, MIF was important for myocardial expression of the proinflammatory cytokines IL-6 and TNF as well as the profibrogenic mediators TGF-β1 and PDGF-BB in TAA-treated mice. Notably, betaine attenuated MIF effects in myocardial tissue reducing levels of MDA, AOPP, TNF, TGF-β1, PDGF-BB and increasing SOD and catalase activity in the coexistence of liver fibrosis. These results emphasize the potential of betaine as a therapeutic agent in mitigating MIF effects and demonstrate the need for further research into its optimal dosage and efficacy in preventing or slowing down cardiac dysfunction in patients with liver cirrhosis.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184839","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":"Sodium Butyrate Ameliorated Bile Acid Metabolism in Diabetes Mellitus by PI3K/AKT Signaling Pathway via the Gut-Liver Axis.","authors":"Tingting Zhao, Xi Zhang, Qian Xiang, Yadi Liu, Xuling Li, Junling Gu, Wenqian Zhang, Zhe Wang, Yiran Li, Xiaoshan Lai, Yonghua Zhao, Youhua Xu","doi":"10.3390/cimb47090732","DOIUrl":"10.3390/cimb47090732","url":null,"abstract":"<p><p>The liver and gut play a central role in modulating bile acid metabolism. Our recent study found that supplementation with sodium butyrate (NaB) from microbiota might slow diabetes progression and ameliorate liver function in diabetic mice. The role of NaB in the homeostasis of mitochondrial energy metabolism and bile acid metabolism needs to be investigated further, so this study was conducted by us. We used an ELISA kit to detect biochemical indicators related to mice; HE and PAS were used to stain and analyze tissues; CCK8 was used to detect cell viability; and WB was used to detect related indicators. We found here that NaB administration enormously reduced liver hypertrophy and steatosis in diabetic mice, improved liver and gut function and the release of inflammatory factors in diabetic mice, and ameliorated mitochondrial function both in vitro and in vivo. NaB incubation significantly increased bile acid metabolism-related receptors under diabetic conditions; the intracellular content of enzymes related to liver function was elevated within liver cells. Glucose transport proteins GLUT2 and NaB receptor GPR43 were upregulated by NaB on the cell membrane. The actuation of the intracellular signaling proteins PI3K, AKT, and GSK3 was inhibited by NaB under diabetic conditions. The present study proved that the microbiota metabolite NaB has positive effects on bile acid metabolic homeostasis by promoting mitochondrial energy metabolism in enterocytes and the liver, and the GPR43-PI3K-AKT-GSK3 signaling pathway should contribute to this effect.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184917","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":"Decoding the Tumor Microenvironment: Insights and New Targets from Single-Cell Sequencing and Spatial Transcriptomics.","authors":"Shriya Pattabiram, Prakash Gangadaran, Sanjana Dhayalan, Gargii Chatterjee, Danyal Reyaz, Kruthika Prakash, Raksa Arun, Ramya Lakshmi Rajendran, Byeong-Cheol Ahn, Kandasamy Nagarajan Aruljothi","doi":"10.3390/cimb47090730","DOIUrl":"10.3390/cimb47090730","url":null,"abstract":"<p><p>The field of oncology has been extensively studied to design more effective and efficient treatments. This review explores the advanced techniques that are transforming our comprehension of cancer and its constituents. Specifically, it highlights the signaling pathways that drive tumor progression, angiogenesis, and resistance to therapy, as well as the modern approaches used to identify and characterize these pathways within the tumor microenvironment (TME). Key pathways discussed in this review include vascular endothelial growth factor (VEGF), programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and various extracellular matrix (ECM) pathways. Conventional methods of diagnosis have yielded sufficient knowledge but have failed to reveal the heterogeneity that exists within the TME, resulting in gaps in our understanding of the cellular interaction and spatial dynamics. Single-cell sequencing (SCS) and spatial transcriptomics (ST) are effective tools that can enable the dissection of the TME with the resolution capacity of a single cell. SCS allows the capture of the unique genetic and transcriptomic profiles of individual cells along with rare cell types and new therapeutic targets. ST complements this by providing a spatial map of gene expression, showing the gene expression profiles within the tumor tissue at specific sites with good accuracy. By mapping gene expression patterns at a single cell level and correlating them with the spatial locations, researchers can uncover the intricate networks and microenvironmental influences that contribute to tumor heterogeneity.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184756","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":"Transcriptomic Analysis Reveals the Molecular Relationship Between Common Respiratory Infections and Parkinson's Disease.","authors":"Abdulaziz Albeshri, Ahmed Bahieldin, Hani Mohammed Ali","doi":"10.3390/cimb47090727","DOIUrl":"10.3390/cimb47090727","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most rapidly growing neurological disorders globally. The molecular relationship between common respiratory infections (RIs) and idiopathic Parkinson's disease (iPD) remains a controversial issue. Multiple studies have linked acute respiratory infections to PD, but the molecular mechanism behind this connection is not significantly defined. Therefore, the aim of our study was to investigate potential molecular interactions between RIs and PD. We retrieved eight publicly available RNA-seq datasets from the NCBI Gene Expression Omnibus (NCBI GEO) and performed extensive bioinformatics analysis, including differential gene expression (DGE) analysis, the identification of overlapped differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), pathway and functional enrichment analysis, the construction of protein-protein networks, and the identification of hub genes. Additionally, we applied a machine learning method, a Random Forest model (RF), to external RIs datasets to identify the most important genes. We found that ribosomal subunits, mitochondrial complex proteins, proteasome subunits, and proteins encoding ubiquitin are simultaneously downregulated and co-expressed in RIs and PD. Dysregulation of these proteins may disturb multiple pathways, such as those responsible for ribosome biogenesis, protein synthesis, autophagy, and apoptosis; the ubiquitin-proteasome system (UPS); and the mitochondrial respiratory chain. These processes have been implicated in PD's pathology, namely in the aggregation of α-synuclein, mitochondrial dysfunction, and the death of dopaminergic neuron cells. Our findings suggest that there are significant similarities in transcriptional responses and dysfunctional molecular mechanisms between RIs, PD, and aging. RIs may modulate PD-relevant pathways in an age- or immune-dependent manner; longitudinal studies are needed to examine the RIs risk factor. Therefore, future studies should experimentally investigate the influence of age, vaccination status, infection type, and severity to clarify the role of RIs in PD's pathogenesis.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184940","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}