RNA BiologyPub Date : 2026-12-31Epub Date: 2026-03-25DOI: 10.1080/15476286.2026.2643366
Magdalena Winklhofer, Göran Erik Nilsson, Sjannie Lefevre
{"title":"Long non-coding RNA transcripts in crucian carp brain - annotation and expression patterns in anoxia and reoxygenation.","authors":"Magdalena Winklhofer, Göran Erik Nilsson, Sjannie Lefevre","doi":"10.1080/15476286.2026.2643366","DOIUrl":"10.1080/15476286.2026.2643366","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, yet their role in anoxia-induced transcriptomic changes in crucian carp (<i>Carassius carassius</i>) - a species that endures months without oxygen at low temperatures - remains unclear. Because existing genome annotations focus on protein-coding genes, we aimed to annotate lncRNAs in crucian carp, assess their potential for involvement in mRNA regulation during anoxia and reoxygenation, and characterize differentially regulated lncRNAs and nearby putative interaction partners (IPs). Using next-generation RNA sequencing of the brain across normoxia, anoxia, and reoxygenation (<i>n</i> = 10 per group), we assembled 145,264 transcripts with a reference-guided approach. With CPC2, CNCI, CPAT, and FEELnc, we identified 6072 lncRNAs. Anoxia elicited a robust transcriptomic response: 56,440 transcripts were differentially expressed (adjusted <i>p</i>-value < 0.05; |log2(fold change)| > 0.38), including 1321 lncRNAs. FEELnc classification highlighted proximal RNA transcripts suggestive of cis-acting lncRNA functions. Most (60%) DElncRNA - IP interaction sites were intergenic, predominantly on the same strand within intergenic subtypes, with many features nested within genic contexts. Notably, log2-fold changes in RNA abundance of predicted DE IPs positively correlated with those of their corresponding DElncRNAs. These results provide a comprehensive lncRNA annotation for crucian carp and reveal extensive lncRNA co-expression with nearby genes during anoxia and reoxygenation, supporting a potential cis-regulatory role in the adaptive transcriptomic response to oxygen deprivation.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-21"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13023002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390871","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":"Isotopic tracing in <i>Mycobacterium tuberculosis</i>-infected alveolar epithelial cells indicates metabolic specificity to their virulence and drug-resistance status.","authors":"Subia Akram, Shyam Kumar Masakapalli, Ranjan Kumar Nanda","doi":"10.1080/21505594.2026.2723630","DOIUrl":"10.1080/21505594.2026.2723630","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a global health threat aggravated by the emergence of drug-resistant strains. <i>Mycobacterium tuberculosis</i> promotes metabolic remodeling within host cells to support its survival. Type II alveolar epithelial cells have been established as a primary niche for bacterial infection, adherence, and invasion. However, compared to macrophages, metabolic interactions within these cells, particularly the strain-specific exploitation of host metabolism, remain inadequately explored. To address this, we integrated intracellular bacterial growth and host cell viability assays with C-based proteinogenic amino acid kinetics to gain insights into metabolic changes in A549 alveolar epithelial cells infected with laboratory strains (virulent H37Rv, avirulent H37Ra) and clinical isolates (drug-resistant S6 and S11; drug-sensitive S4 and S5). Virulent strain H37Rv showed higher intracellular growth (6-fold increase) but significantly reduced host cell viability relative to avirulent H37Ra. Interestingly, the multidrug-resistant isolate S6 showed the highest intracellular growth (18-fold increase) while maintaining host cell viability. Mass isotopomer distribution analysis revealed that virulent strains showed increased reliance on central carbon metabolism, including glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. H37Rv showed greater <sup>13</sup>C enrichment in host amino acids, such as alanine (1.6-fold), compared to H37Ra. Drug-resistant isolates displayed distinct <sup>13</sup>C enrichment in TCA-derived threonine (0.21-0.25%), methionine (0.18-0.28%), and lysine (0.12-0.27%). We observed <sup>13</sup>C enrichment in essential amino acids (lysine, methionine, threonine, valine) across all infected conditions, confirming the pathogen's dependence on host-derived metabolic intermediates. These findings highlight the need to explore host-to-pathogen amino acid transport as a precise host-directed therapeutic target.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"17 1","pages":"2723630"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PSMA1, PSMA5, and PSMB2 serve as prognostic biomarkers and are correlated with tumor-infiltrating leukocytes in HCC.","authors":"Baitul Islam, Weiye Xu, Zaid Ur Rehman, Ru Zeng, Thekra Khushafa, Haiyang Yu, Jufang Huang","doi":"10.1080/15592294.2026.2726624","DOIUrl":"10.1080/15592294.2026.2726624","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related death. Proteasome (PSM) is the main intracellular proteolytic system in higher eukaryotic cells. It has been reported to be involved in the tumor's onset, metabolism, and survival, and it has been recognized as a therapeutic target for many human cancers. The 20S proteasome subunits, specifically proteasome 20S subunit alpha 1 (PSMA1), proteasome 20S subunit alpha 5 (PSMA5), and proteasome 20S subunit beta 2 (PSMB2), are overexpressed in various malignancies, including HCC. Nevertheless, the exact role of these genes in HCC prognosis remains only partially understood. Moreover, a reliable predictive biomarker for HCC is essential for supporting the implementation of personalized therapies. Therefore, this study employed a comprehensive bioinformatics approach, integrating data from cBioPortal, Human Protein Atlas (HPA), Oncomine, STRING Viruses, Kaplan-Meier plotter, and other established high-throughput databases and tools. The current study thoroughly examined the expression levels, methylation, and genomic alterations of PSM and their correlation with tumor-infiltrating leukocytes. PSMA1, PSMA5, and PSMB2 are overexpressed in various cancers, including HCC, and their expression levels are associated with tumor grade and stage. The abundance of these genes is linked to diminished DNA methylation levels and genome alterations. Moreover, there was a significant association between the expression levels of these genes and poor prognosis and immune cell infiltration. In conclusion, this study proposes PSMA1, PSMA5, and PSMB2 as biomarkers for HCC.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2726624"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967365","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":"HyLnc: a hybrid deep learning and feature-based approach for long non-coding RNA prediction.","authors":"Amrit Venkatesan, Prashasti Sinha, Jolly Basak, Ranjit Prasad Bahadur","doi":"10.1080/15476286.2026.2731913","DOIUrl":"10.1080/15476286.2026.2731913","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play important roles in gene regulation, development and disease, yet accurate identification of lncRNAs from transcriptomic data remains a major computational challenge. Existing methods often rely either on handcrafted sequence features or deep learning approaches, each with their inherent limitations in capturing the full complexity of RNA sequences. In this study, we proposed HyLnc, a computational framework that integrates transformer-based contextual embeddings with biologically meaningful sequence features for improved lncRNA prediction. A custom BERT-based model was first pre-trained on a large corpus of metazoan RNA sequences using a masked language modelling strategy to learn contextual nucleotide dependencies. The model was subsequently fine-tuned on curated datasets of lncRNAs and protein-coding transcripts and 256-dimensional deep sequence embeddings were extracted. Parallelly, 348 handcrafted features, including ORF characteristics, untranslated region (UTR) properties, nucleotide composition and Fickett scores, were computed. A multi-stage feature selection strategy was applied to identify the most informative features, resulting in optimized hybrid feature sets. Multiple machine learning classifiers were evaluated, with the RF model achieving the best performance. The proposed framework attained an accuracy of 91.30%, F1-score of 91.23% and MCC of 82.60 on an independent validation dataset, outperforming several existing lncRNA prediction tools. Thus, HyLnc demonstrates that integrating deep contextual representations with biologically interpretable features enhances lncRNA prediction. This approach provides a robust and scalable solution for large-scale transcriptome annotation and can be extended to other sequence-based prediction.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-18"},"PeriodicalIF":4.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920921","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":"Optimal pest management in Moringa (<i>Moringa oleifera</i>): a mathematical model incorporating integrated pesticide use.","authors":"Raymond Charles, Filimon Abel Mgandu","doi":"10.1080/17513758.2026.2694214","DOIUrl":"https://doi.org/10.1080/17513758.2026.2694214","url":null,"abstract":"<p><p>A mathematical model for Moringa was developed and analyzed in this study to manage the plantation's natural pests through integrated pest management (IPM). Bio-pesticides are expensive, difficult to apply and need a lengthy process. However, this method will be more efficient and less costly if chemical pesticides are added to the farming system in addition to biopesticides. Here, we examine the use of integrated pest management (IPM) combined with chemical and biological pesticides. We determine which parameter can lead to stability switches. By utilizing optimal control theory, the ideal concentration profile for both pesticides has been established to reduce side effects and maximize process economy. Numerical simulations justify the primary results.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2694214"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruidi Ding, Cunjuan Dong, Long Zhang, Zhidong Teng
{"title":"Modelling the role of macrophage polarization during pulmonary infection of Mycobacterium tuberculosis with cellular immunity.","authors":"Ruidi Ding, Cunjuan Dong, Long Zhang, Zhidong Teng","doi":"10.1080/17513758.2026.2715881","DOIUrl":"https://doi.org/10.1080/17513758.2026.2715881","url":null,"abstract":"<p><p>This paper proposes a within-host Mycobacterium tuberculosis (Mtb) infection model integrating M1/M2 macrophage conversion to explore macrophage polarization regulation in pulmonary infection with cellular immunity. The basic reproduction number <math><msub><mi>R</mi><mn>0</mn></msub></math> is calculated, and criteria on the locally and globally asymptotic stability of infection-free equilibrium <math><msub><mi>E</mi><mn>0</mn></msub></math> are established if <math><msub><mi>R</mi><mn>0</mn></msub><mo><</mo><mn>1</mn></math>. Criteria on the existence and locally asymptotic stability of immune-free infection equilibrium <math><mover><mi>E</mi><mo>¯</mo></mover></math> and immune-activated infection equilibrium <math><msup><mi>E</mi><mo>∗</mo></msup></math> are further obtained if <math><msub><mi>R</mi><mn>0</mn></msub><mo>></mo><mn>1</mn></math>. Moreover, the model exhibits forward, backward and saddle-node bifurcations at <math><mover><mi>E</mi><mo>¯</mo></mover></math>, as well as Hopf bifurcation and chaotic dynamics at <math><msup><mi>E</mi><mo>∗</mo></msup></math>, indicating that Mtb infection is highly sensitive to the dynamic shifts during macrophage polarization. Numerical simulations verify theoretical results, revealing that the effective conversion rates <math><msub><mi>γ</mi><mn>1</mn></msub></math> and <math><msub><mi>γ</mi><mn>2</mn></msub></math> between M1 and M2 macrophages are key regulators of Mtb infection progression, which may provide theoretical insights into tuberculosis latency and relapse, and offer testable predictions for immunotherapeutic strategies.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2715881"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abnormal expression of galectins and their correlation with fibrogenesis in adenomyosis.","authors":"Yuan Zhou, Mengdong Cao, Zhenzhen Wang, Yaonan Yu, Han Yu, Xue Shen","doi":"10.1080/19336918.2026.2658283","DOIUrl":"10.1080/19336918.2026.2658283","url":null,"abstract":"<p><p>This cross-sectional study investigated galectin-1, -3, and -9 in adenomyosis. Analysis of hysterectomy tissues from premenopausal women via western blot, qPCR, immunohistochemistry, and Masson's staining revealed significantly elevated galectin levels compared to controls. Galectin expression positively correlated with fibrosis severity (<i>r</i> = 0.476, 0.925, 0.563, all <i>p</i> < .05), which in turn moderately correlated with dysmenorrhea (VAS score) and uterine enlargement. Findings indicate that galectins are implicated in adenomyosis-related fibrosis and pain, suggesting their potential as therapeutic targets.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"20 1","pages":"2658283"},"PeriodicalIF":4.3,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970688","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}
PrionPub Date : 2026-12-31Epub Date: 2026-03-02DOI: 10.1080/19336896.2026.2635296
Jameson Mori, Sara Villazan Perez-Girones, Tooba Latif, Nelda Rivera, Dan Skinner, Peter Schlichting, Jan Novakofski, Nohra Mateus-Pinilla
{"title":"Maternal chronic wasting disease infection restricts fetal head size in white-tailed deer (<i>Odocoileus virginianus</i>).","authors":"Jameson Mori, Sara Villazan Perez-Girones, Tooba Latif, Nelda Rivera, Dan Skinner, Peter Schlichting, Jan Novakofski, Nohra Mateus-Pinilla","doi":"10.1080/19336896.2026.2635296","DOIUrl":"10.1080/19336896.2026.2635296","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a fatal neurodegenerative prion disease of cervids that can be transmitted through direct physical contact, indirect contact with a contaminated environment, or vertical transmission. CWD is characterized by a long incubation period followed by symptoms like loss of appetite resulting from the destruction of brain tissue. While the consequences for infected animals are clear, a previous study from our laboratory showing lower body weights in the foetuses of CWD-positive female deer suggests those consequences may be intergenerational. In this study, we addressed the impact of maternal CWD infection on foetal head development (as a proxy for brain growth) in wild white-tailed deer using data from CWD management efforts in northern Illinois, U.S.A. Multivariate, multilevel, Bayesian Gamma regression found that maternal CWD infection reduced foetal head nose-occipital length and crown-jaw circumference by 6.76% and frontal-occipital length by 11.31%. These findings suggest impeded brain development in the offspring of CWD-infected female deer, which could reduce fawns' survival and success after birth and lead to a decline in population fitness over time. This study is the first to demonstrate the detrimental effects of a prion disease on foetal brain development in any animal species regardless of whether vertical transmission has occurred.</p>","PeriodicalId":54585,"journal":{"name":"Prion","volume":"20 1","pages":"18-30"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345608","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}
Redox ReportPub Date : 2026-12-31Epub Date: 2026-06-02DOI: 10.1080/13510002.2026.2682043
Yu Ishima, Hiroshi Watanabe, Mayumi Ikeda-Imafuku, Hitoshi Maeda, Toru Maruyama, Masaki Otagiri, Victor T G Chuang
{"title":"Albumin as a dynamic extracellular redox regulator: from Cys34 oxidation biomarkers to polysulfide-mediated homeostatic mechanisms and clinical applications.","authors":"Yu Ishima, Hiroshi Watanabe, Mayumi Ikeda-Imafuku, Hitoshi Maeda, Toru Maruyama, Masaki Otagiri, Victor T G Chuang","doi":"10.1080/13510002.2026.2682043","DOIUrl":"10.1080/13510002.2026.2682043","url":null,"abstract":"<p><p>Human serum albumin (HSA) is the most abundant circulating protein and a central mediator of extracellular redox homeostasis. Its antioxidant function has been attributed primarily to the free thiol at cysteine residue 34 (Cys34), whose progressive oxidation-yielding nonmercaptoalbumin isoforms HNA1 and HNA2-serves as a sensitive biomarker of systemic oxidative stress. Advances in electrospray ionisation time-of-flight mass spectrometry have enabled precise quantification of Cys34 modifications, establishing cysteinylated albumin as a clinically applicable marker in chronic kidney disease, chronic liver disease, diabetes, and ageing-related functional decline. Beyond its role as a biomarker, oxidized albumin is now recognized as an active pathogenic mediator in preclinical models, with emerging evidence implicating ferroptosis as a potential mechanism of renal tubular cell injury, and contributing to cardiovascular risk and sarcopenia. A previously unrecognized dimension of albumin redox biology has also emerged: the presence of endogenous oxidized polysulfide bonds (Ox-PSS; RSS<sub>n</sub>-R', <i>n</i> > 1) across multiple intramolecular cysteine bridges. Quantified using the newly developed Elimination Method for Sulfide from Polysulfide, albumin polysulfides are dynamically regulated by oxidative stress and are significantly depleted in chronic kidney disease and early hepatitis, even when conventional Cys34-based markers remain unchanged. Polysulfide depletion impairs both Site II drug-binding capacity and reactive oxygen species scavenging activity, with direct implications for pharmacokinetics and therapeutic efficacy. These findings collectively reframe HSA as a dynamic polysulfide reservoir and extracellular redox regulator, highlighting albumin polysulfide modulation as a compelling emerging therapeutic strategy.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2682043"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2026-12-31Epub Date: 2026-06-26DOI: 10.1080/13510002.2026.2679333
Nirmal Kumar, Braelyn Liang, Jonathan D Geiger
{"title":"HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.","authors":"Nirmal Kumar, Braelyn Liang, Jonathan D Geiger","doi":"10.1080/13510002.2026.2679333","DOIUrl":"10.1080/13510002.2026.2679333","url":null,"abstract":"<p><strong>Background: </strong>Increased lysosomal stress responses (LSR) are commonly implicated in the pathogenesis of neurodegenerative disorders including HIV-1-associated neurocognitive disorders (HAND). The HIV-1 envelope glycoprotein gp120 causes LSR, increases levels of ferrous iron (Fe<sup>2+</sup>) in the cytosol and in mitochondria, disrupts the reactive species interactome (RSI), and increases neural cell death.</p><p><strong>Methods: </strong>Using SH-SY5Y human neuroblastoma and U87MG human astrocytoma cells treated with gp120 and pharmacological modulators, we evaluated redox signaling and LSR by redox-sensitive fluorescent probes, spinning-disk confocal microscopy, flow cytometry, Western blotting, and immunostaining.</p><p><strong>Results: </strong>Here, we report that TRPML1, an endolysosome redox-sensitive cation channel, is mechanistically involved in gp120-induced neurotoxicity. TRPML1 was activated by gp120-induced increases in cytosolic reactive oxygen species (ROS) and resulted in release of Fe<sup>2+</sup> from endolysosomes in levels sufficient to increase cytosolic levels of Fe<sup>2+</sup> and ROS as well as decrease levels of hydrogen sulfide (H<sub>2</sub>S). Reduced glutathione normally buffers intracellular Fe<sup>2+</sup>, but gp120 decreased endolysosome glutathione levels and disrupted this regulatory control mechanism thereby promoting TRPML1-mediated Fe<sup>2+</sup> efflux from endolysosomes. TRPML1 redox activation led to changes to the RSI in endolysosomes including increased ROS, lipid peroxidation, nitric oxide, and sulfane sulfur as well as decreased H<sub>2</sub>S. These changes were accompanied by increased cysteine oxidation of luminal proteins and endolysosome deacidification. Pharmacological inhibition of TRPML1 or knocking down expression levels of TRPML prevented these effects.</p><p><strong>Conclusion: </strong>Our findings suggest that TRPML1 redox activation controls gp120-induced endolysosome dysfunction and iron/redox imbalance, and further implicates TRPML1 in the pathogenesis of HAND.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2679333"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}