- Research Article
- 10.1016/j.freeradbiomed.2026.02.031
8-Oxoguanine modifications in seed regions of miRNAs regulating P16 promote aging by reshaping gene regulatory networks.
- May 01, 2026
- Free radical biology & medicine
- Jia-Qi Guo + 9 more +9
Publications from 2021 to 2026
Showing 10 of 200 papers
8-Oxoguanine modifications in seed regions of miRNAs regulating P16 promote aging by reshaping gene regulatory networks.
Divergent Evolution of Tuberculosis Lesions During Treatment: A Longitudinal CT-Based Analysis of Progression and Regression Patterns.
Objectives: Lesion-level dynamics may reveal pulmonary tuberculosis (PTB) heterogeneity and help identify factors associated with treatment outcomes. Methods: A total of 288 serial Computed Tomography (CT) scans from 125 PTB patients were obtained from the National Institute of Allergy and Infectious Diseases (NIAID) TB Portals database (2008-2023). Lesions were segmented and annotated to obtain volume and imaging features, and a conservative longitudinal volume quantification method was used to characterize dynamic volume patterns. The proportion of lesions with different patterns was analyzed at the patient level to assess trajectory diversity. Firth's penalized logistic regression was used to identify factors associated with treatment outcomes. Results: Among 435 lesions in 125 patients, five patterns emerged: Stable, Decrease, Increase, Mix-I-D (increase then decrease), and Mix-D-I (decrease then increase). Multiple patterns coexisted in 66.7% of treatment success patients and all treatment failure patients. Mix-D-I lesions were identified more frequently in treatment failure patients (25.0% vs. 1.4%, p = 0.027), and in multivariable analysis, the presence of Mix-D-I lesions was statistically associated with treatment failure (p = 0.024). Conclusions: PTB lesions showed high trajectory heterogeneity. The presence of Mix-D-I lesions may point to an unfavorable treatment course, suggesting lesion dynamics could serve as a potential indicator for poor outcomes. By quantifying lesion-level trajectories on serial CT scans, we extend PET/CT-based evidence and support the value of routine monitoring in clinical management of tuberculosis.
Read moreTwo decades of global research on tetanus vaccines and tetanus immunoglobulins: a comprehensive bibliometric analysis and integrative review (2000–2025)
BackgroundTetanus is a severe but vaccine-preventable disease controlled by tetanus toxoid (TT) immunization and tetanus immunoglobulin (TIG) therapy. Although maternal–neonatal tetanus has been eliminated in many regions, coverage gaps and sporadic cases persist in low-resource settings. As a longstanding component of global immunization and a key conjugate carrier platform, tetanus research remains essential despite advances in novel vaccine technologies. However, the global research landscape on tetanus vaccines and immunoglobulins remains unmapped.ObjectiveThis study aimed to conduct a comprehensive bibliometric analysis of publications on TT and TIG from 2000 to 2025, to characterize research dynamics, leading contributors, and thematic evolution.MethodsWe retrieved publications from the Web of Science Core Collection (SCI-Expanded) for 2000–2025 using relevant keywords (“tetanus vaccine*” OR “tetanus toxoid*” OR “tetanus immunoglobulin*” OR “tetanus immune globulin*” OR “tetanus antitoxin*”). Following screening, 2,949 English-language articles and reviews were included. Bibliometric analyses (publication trends, funding agencies, co-authorship, co-citation, and keyword co-occurrence) were performed using VOSviewer, CiteSpace, and the bibliometrix R package.ResultsA total of 2,949 publications were analyzed. Annual output remained stable (mean ≈ 113.4), with citations peaking in 2021 (n=7,291). The USA led in volume (1,130 papers), while Switzerland achieved the highest impact (88.41 citations/article). The Centers for Disease Control and Prevention (CDC) and University of Oxford emerged as central hubs, with GlaxoSmithKline (GSK) illustrating the role of industry-academic partnerships. A strategic funding shift occurred around 2010: while the National Institutes of Health (NIH) drives foundational research, the Bill & Melinda Gates Foundation (BMGF) has become the engine for translational equity. Evolutionary trends show a shift from early cellular mechanisms toward maternal immunization coverage, implementation determinants in low- and middle-income countries (LMICs), and the expanding utility of tetanus toxoid (TT) as a conjugate vaccine carrier.ConclusionTetanus research has evolved into a dynamic model for modern vaccinology, bridging classical immunization and next-generation technology. Beyond maternal protection, the field is expanding toward conjugate platforms and recombinant biologics. Achieving global elimination requires aligning these biotechnological innovations with equitable implementation strategies in low-resource settings.
Read moreThe effect of receptive music therapy plus usual nursing care on cognitive performance and quality of life in elderly patients with type 2 diabetes mellitus and cognitive impairment
ObjectivesTo evaluate the effects of receptive music therapy (RMT) combined with usual nursing care on cognitive performance, quality of life (QoL), mood, and metabolic stability among elderly patients with type 2 diabetes mellitus (T2DM) and cognitive impairment.MethodsA randomized controlled trial enrolled 80 participants (aged 65–80 years) with T2DM and mild cognitive impairment. They were randomly assigned (1:1) to an intervention group (RMT + usual nursing care, n = 40) or control group (usual nursing care only, n = 40) for 8 weeks. Primary outcomes were changes in Montreal Cognitive Assessment (MoCA), World Health Organization Quality of Life–BREF (WHOQOL-BREF), and Geriatric Depression Scale-15 (GDS-15) scores. Secondary outcomes included glycated hemoglobin (HbA1c) and fasting glucose. Paired and independent t-tests with ANCOVA adjustment for baseline values were used.ResultsSeventy-five participants completed the study (retention = 93.7%). Compared with the control group, the intervention group showed a significant improvement in MoCA scores (Cohen’s d = 0.78; 22.5 ± 2.0 → 26.1 ± 1.8, F = 9.84, p = 0.003). Total WHOQOL-BREF scores increased from 52.5 ± 5.6 to 61.4 ± 5.1 (F = 8.73, p = 0.005), with notable gains in the psychological (+16.5%) and social (+14.2%) domains. GDS-15 scores declined markedly from 6.9 ± 1.5 to 4.1 ± 1.3 (F = 10.46, p = 0.002), indicating a ≈ 40% reduction in depressive symptoms and a positive correlation with cognitive improvement (r = 0.42, p < 0.05). Glycemic parameters remained stable (HbA1c 7.8 ± 0.9 → 7.5 ± 0.8%; p = 0.11; fasting glucose 8.4 ± 1.2 → 8.1 ± 1.0 mmol/L; p = 0.14), with no adverse events. Adherence exceeded 95%, and satisfaction was > 90%.ConclusionRMT integrated with standard nursing care significantly improved cognition, mood, and QoL in elderly patients with T2DM and cognitive impairment without affecting metabolic stability. These results support RMT as a safe, inexpensive, and feasible adjunct to conventional geriatric diabetes management, offering a holistic nursing approach to enhance mental and emotional well-being.
Read moreRare case of autoimmune pulmonary alveolar proteinosis with ANCA positivity
Pulmonary alveolar proteinosis (PAP) with concurrent anti-neutrophil cytoplasmic antibody (ANCA) positivity represents an exceptionally rare clinical phenomenon, the pathogenesis and management implications of which remain poorly understood. A 49-year-old woman was referred to our institution for evaluation of progressive respiratory symptoms. Two months prior to admission, she developed an intermittent cough productive of whitish sputum, followed by exertional dyspnea limiting ambulation to 400–500 m on level ground. Initial investigations revealed hypoxemic respiratory failure (PaO₂/FiO₂ 277 mmHg) and the characteristic “crazy-paving” pattern on chest computed tomography. Bronchoalveolar lavage yielded milky-white fluid with periodic acid-Schiff (PAS)-positive material, confirming the diagnosis of PAP. Notably, immunological evaluation demonstrated positive myeloperoxidase (MPO)-ANCA (20.03 RU/mL) (reference < 5 RU/mL), with perinuclear ANCA (p-ANCA) positive at a titer of 1:10 by indirect immunofluorescence, and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies, establishing a rare coexistence of autoimmune PAP with ANCA positivity. A comprehensive vasculitis workup—including serial urinalysis with microscopy, and otorhinolaryngological evaluation—revealed no evidence of subclinical vasculitis. The patient underwent successful bilateral whole lung lavage without the need for immunosuppressive therapy. At 3-month follow-up, p-ANCA remained positive (1:10) with MPO-ANCA at 14.15 RU/mL (reference < 5 RU/mL), while urinalysis and renal function remained within normal limits. At 12-month follow-up, the patient reported no dyspnea during daily activities and maintained oxygen saturation above 95% without supplemental oxygen. This case illustrates the rare association between autoimmune PAP and ANCA positivity, underscoring the importance of comprehensive immunological evaluation and individualized therapeutic approaches. Long-term surveillance is imperative, as vasculitic manifestations may emerge years after the initial PAP diagnosis.
Read morePredictors and clinical correlates of stent fracture after rapamycin-eluting vertebral artery stenting.
To identify predictors of stent fracture following rapamycin-eluting stent implantation for symptomatic extracranial vertebral artery stenosis and to evaluate its clinical impact. A single-center retrospective study was conducted on 140 patients (147 stents) treated between January 2021 and January 2025. Cox regression analysis was used to identify independent predictors of stent fracture, while Kaplan-Meier analysis evaluated associations between stent fracture, in-stent restenosis, and target vessel stroke. During a median follow-up of 14 months (IQR 10-17.5), fracture occurred in 23 stents (15.6%). Longer stent length (HR 1.172, 95% CI 1.078 to 1.274, P<0.001) and vessel tortuosity (HR 3.415, 95% CI 1.285 to 9.076, P=0.014) were independent predictors of stent fracture. Stent fracture was not significantly associated with in-stent restenosis or target vessel stroke. Stent fracture after rapamycin-eluting vertebral artery stenting is associated with longer stent length and tortuous anatomy. In this cohort, no significant association was observed between stent fracture and mid-term in-stent restenosis or target vessel stroke.
Read moreMiR-499-5P/PACS2/TRPV1 Axis Maintains Mitochondrial Homeostasis and Left Ventricular Function after Extreme Cold Stress.
Exposure to cold environments is physiologically challenging, with extreme cold stress (ECS) impairing the function of the left ventricle (LV) of the heart. We aimed to determine the role and mechanism of action of the miR-499-5p/phosphofurin acidic cluster sorting protein 2 (PACS2)/transient receptor potential cation channel subfamily V member 1 (TRPV1) axis in ECS-induced cardiomyocyte injury and LV dysfunction. Mice were placed in a -20 °C chamber to simulate an extremely cold environment. MiR-499-5p overexpression in the mice decreased PACS2 levels, and mitochondrial function was inhibited in vivo following ECS. Inhibiting miR-499-5p enhanced PACS2 expression, thereby reversing the structural and functional LV deficits caused by ECS. Cardiac-specific Pacs2 knock-in restored the decreases in mitophagy and mitochondrial energy metabolism caused by ECS via enhancing endoplasmic reticulum-mitochondrial calcium flux through TRPV1, a nonselective calcium channel. The findings indicate targets for preventing cardiac disease during exposure to extremely cold environments.
Read moreNaloxone plus enteral nutrition for gastrointestinal dysfunction in elderly cerebral infarction and peptic ulcer patients
BACKGROUNDCerebral infarction (CI) is a major subtype of ischemic stroke, with high incidence, recurrence rate, disability rate, and mortality rate in the elderly. Elderly CI patients are prone to peptic ulcer due to long-term use of antiplatelet drugs and stress factors, which further leads to gastrointestinal dysfunction, seriously affecting nutritional intake and rehabilitation. Naloxone, an opioid receptor antagonist, has neuroprotective potential, and enteral nutrition (EN) can improve gastrointestinal function. This study aims to explore the intervention effect of their combination.AIMTo investigate the efficacy of naloxone combined with EN on gastrointestinal dysfunction in elderly patients with CI and peptic ulcer.METHODSIn this randomized controlled trial, 110 elderly patients with CI and peptic ulcer were equally assigned to a control group (receiving standard therapy combined with EN) or a combination group (receiving standard therapy, EN, and naloxone). The National Institute of Health Stroke Scale (NIHSS) scores, Barthel Index (BI), Chinese version of the MOS 36-Item Short Form Health Survey (SF-36) scores, gastrointestinal function scores, and serum levels of motilin (MTL), gastrin (GAS), and somatostatin (SS) were compared. Adverse reactions were also recorded.RESULTSCompared with the control group, the combination group had lower NIHSS scores (5.88 ± 1.07 vs 8.73 ± 1.14, P < 0.001) and gastrointestinal dysfunction scores (5.14 ± 1.27 vs 8.62 ± 1.31, P < 0.001), higher BI (87.36 ± 4.42 vs 72.29 ± 3.23, P < 0.001) and SF-36 scores (76.26 ± 3.85 vs 70.21 ± 3.66, P < 0.001), increased serum MTL (201.31 ± 12.35 ng/L vs 186.81 ± 11.18 ng/L, P < 0.001) and GAS levels (94.46 ± 9.64 pg/mL vs 103.15 ± 10.52 pg/mL, P < 0.001), and decreased SS levels (5.69 ± 1.25 pg/mL vs 8.31 ± 1.19 pg/mL, P < 0.001). No significant difference in the incidence of adverse reactions was found between the two groups.CONCLUSIONThe combination of naloxone and EN is a safe and efficacious therapeutic approach for ameliorating gastrointestinal dysfunction and promoting overall recovery in elderly individuals with CI and peptic ulcer.
Read moreUnveiling dry eye with autoimmune features (DEAF): insights from a prospective longitudinal study.
Dry eye is a prevalent condition that commonly occurs with autoimmune diseases such as Sjögren's disease (SjD). However, some individuals with dry eye were observed to display unique features suggesting an underlying autoimmune process while failing to meet the criteria for a definitive diagnosis of any connective tissue diseases (CTDs). This study aims to describe and propose a novel concept "dry eye with autoimmune features (DEAF)" to define these patients, whose status might suggest a pre-stage of SjD or another unidentified autoimmune condition. We conducted a prospective longitudinal study in the ophthalmology clinic by continuously collecting patients with dry eye. The patients' medical history was reviewed, and the ocular examinations and extensive serology tests were conducted. In the discovery cohort, patients were randomized and clustered automatically into three groups through heatmap, PCA, and PLS-DA analysis. We defined the groups as healthy controls with dry eye symptoms (dry eye) group, dry eye patients with autoimmune features (DEAF) group, and Sjögren's disease (SjD) group according to their different characteristics. Based on the summarized characteristics, a validation cohort was subsequently extended. We analyzed clinical and serological parameters and followed up DEAF patients for 3years to monitor the development of any new onset of CTD. In the discovery cohort of 33 dry eye patients, the heatmap, PCA, and PLS-DA clustering revealed distinct features among the three groups. In the validation cohort of 59 patients, 12 were classified into the dry eye group, 28 were in the DEAF group, and 19 were in the SjD group. DEAF patients showed higher DEQ-5 and SPEED scores but lower IgG levels compared to SjD. Total OSS score was observed with no difference among the three groups, while nasal OSS level was higher than temporal conjunctive in the DEAF and SjD groups. DEAF patients showed a trend toward lower total lymphocyte and CD4+ T cell counts compared to dry eye patients. The level ofanti-α-fodrin antibody in DEAF was higher than thatin the other two groups. After a 3-year follow-up, 39.3% of DEAF patients have developed CTDs, with SjD being predominant. This study unveiled DEAF patients with significant distinctions in clinical features and serological markers. DEAF may constitute a distinct phase or entity within the autoimmune spectrum, underscoring the intricate nature of autoimmune pathogenesis. Besides, this revelation may bridge the gap between idiopathic dry eye and CTDs. However, these findings are limited to oneChinese cohort, which necessitate multiethnic validation. Keypoints •Patients with dry eye with autoimmune features (DEAF) have significant distinctions in clinical features and serological markers, compared to simple dry eye and Sjögren's disease patients. •DEAF patients may have a higher likelihood of developing connective tissue diseases (CTDs) in the future. •The proposition of DEAF could benefit dry eye patients who have underlying autoimmune disorders in terms of early diagnosis and treatment.
Read morePhysiologically Relevant Simulation of Carbohydrate Digestion: From Glycemic Index Estimation to Intestinal Cellular Responses.
Simulating carbohydrate digestion in physiologically relevant ways remains a challenge for in vitro models. In this study, the Dynamic In vitro Human Stomach (DIVHS) system was applied to investigate cereal digestion and subsequent intestinal cellular responses. Rice, millet, and corn were digested under dynamic and static conditions. Compared with the static model, the dynamic system generated smaller grain fragments, a larger chyme-enzyme contact area (451.2 ± 4.4 cm2 vs. 160.4 ± 6.0 cm2), and higher average intragastric pressure (25.0 ± 1.2 kPa vs. 7.2 ± 0.7 kPa). Salivary amylase activity also declined more gradually in the dynamic system. An empirical approach for predicting the glycemic index (eGI) was proposed, which showed improved agreement with reported human GI values compared with earlier in vitro methods. Exposure of Caco-2 cells to digested products significantly altered transcriptional profiles, including protein binding, ATP binding, and glucose transporter activity. Notably, products from the dynamic model induced stronger transcriptional responses than those from the static model, including 421 genes up-regulated and 138 down-regulated. Functional enrichment highlighted pathways related to glucose transport, energy metabolism, and cellular regulation. Overall, this study demonstrates the advantages of dynamic digestion models in replicating gastrointestinal conditions, improving GI prediction, and providing mechanistic insights into intestinal cellular responses to digested carbohydrates.
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