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Ling Wang

Publications and source records attributed to Ling Wang.

6 recordsLinked to original sources
PubMed2026

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.

End-stage renal disease (ESRD) remains a major clinical challenge with high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during progression to ESRD, have not been studied. Here we conduct a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases. We identify 52 ESRD-associated differentially methylated CpG positions (ESRD DMPs) showing consistent association between the two cohorts and across diverse kidney diseases, implicating 144 candidate genes enriched in inflammatory and immune pathways. Five of the 52 DMPs are associated with ESRD complications, and seven with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD and its complications. Our findings highlight inflammation, immune dysregulation, and renal fibrosis as shared epigenetic drivers of ESRD progression, and identify biomarkers with potential utility for risk stratification and therapeutic intervention.

Humans↗
PubMed2026

Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happ&#xe9; animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group &#xd7; time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans↗
PubMed2026

Probiotic potential of Parabacteroides johnsonii in mitigating age-related ovarian functional decline.

The gut microbiota is increasingly recognized as a regulator of reproductive health, yet its role in ovarian aging remains unclear. Here, we combine Mendelian randomization (MR) analysis with experimental validation to investigate the causal relationship between gut microbiota and ovarian aging. MR analysis identifies four microbial taxa significantly associated with age at natural menopause. In mouse models, germ-free mice exhibit accelerated ovarian functional decline, including reduced ovarian reserve and impaired folliculogenesis. Fecal microbiota transplantation (FMT) from young donors alleviates ovarian aging phenotypes, whereas FMT from aged donors exacerbates functional decline. Metagenomic analysis reveals species-level differences between young and ovarian-aging mice, with Parabacteroides johnsonii (P. johnsonii) enriched in young mice. Administration of P. johnsonii to middle-aged mice improves ovarian reserve, reduces follicular atresia, enhances granulosa cell proliferation, and decreases systemic inflammation. These findings highlight a causal role of the gut microbiota in ovarian aging and support microbiota-targeted interventions as a potential strategy to preserve ovarian function.

Female↗
PubMed2026

BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.

Extrachromosomal circular DNA (ecDNA) is frequently generated within the nucleus, contributing to genome dynamics and heterogeneity, thereby promoting cancer cell evolution and adaptation. However, the mechanisms underlying ecDNA biogenesis remain poorly understood. Here, using genome-wide CRISPR screening in human cells, we identified the BRCA1-A and the LIG4 complexes as key drivers of ecDNA production. Following DNA segmentation, the upstream BRCA1-A complex protects DNA ends from excessive resection, promoting end-joining for circularization. Conversely, the MRN complex, which mediates end resection and thus antagonizes the BRCA1-A complex, suppresses ecDNA formation. Downstream, LIG4 conservatively mediates ecDNA production by joining the free ends of the DNA fragments. Furthermore, ecDNA from patient tumors harbors junction sites with a LIG4 signature. Notably, disruption of either LIG4 or the BRCA1-A complex in cancer cells impairs ecDNA-mediated adaptation, hindering the development of resistance to both chemotherapy and targeted therapies. Together, our study reveals the roles of the LIG4 and BRCA1-A complexes in ecDNA biogenesis, and uncovers therapeutic targets to block ecDNA-mediated adaptation for cancer treatment.

Humans↗
PubMed2026

Patient-derived organoids predict responses to chemotherapy and PARP inhibitors in advanced ovarian cancer.

BACKGROUND: While tumor organoids hold promise for personalized medicine, clinical validation of epithelial ovarian cancer (EOC) organoids as predictors of therapeutic efficacy-particularly for PARP inhibitors (PARPi)-remains unestablished. METHODS: Patient-derived organoids (PDOs) were established from treatment-naive EOC specimens and characterized by H&E staining, immunohistochemistry, and whole-exome sequencing. Drug sensitivity testing (DST) was performed using carboplatin, paclitaxel, and PARPi (olaparib and niraparib). Clinical homologous recombination deficiency (HRD) status was assessed by tumor sequencing. Organoid responses were prospectively compared to patient outcomes after first-line chemotherapy (carboplatin/paclitaxel) and PARPi maintenance. RESULTS: PDOs were successfully established from 21 of 30 patients (70%) across multiple EOC subtypes and preserved the histopathological features and genomic landscapes of their corresponding primary tumors. Organoid-based DST accurately predicted responses to first-line carboplatin/paclitaxel, with a sensitivity of 100% (95% CI 62.88-100%), specificity of 66.67% (95% CI 12.53-98.23%), accuracy of 91.67% (95% CI 61.52-99.79%), AUC of 0.95 (95% CI 0.85-1.00), and Cohen's kappa of 0.75 (95% CI 0.30-1.00). In evaluating PARPi response, organoids revealed discrepancies between genomic HRD status and actual drug responses. One HRD-positive PDO was PARPi-resistant, consistent with patient non-response, while two HRR-proficient PDOs showed PARPi sensitivity and corresponding clinical benefit. CONCLUSIONS: EOC-derived PDOs provide a robust platform for predicting chemotherapy response and offer added value in assessing PARPi efficacy beyond genomic profiling. Combination of organoid-based testing with genomic analysis may improve precision treatment strategies in EOC.

Humans↗
PubMed2025

&#x3b3;-tubulin mediates DNA double-strand break repair.

Double-strand breaks (DSBs) in DNA pose a critical threat to genomic integrity, potentially leading to the onset and progression of various diseases, including cancer. Cellular responses to such lesions entail sophisticated repair mechanisms primarily mediated by non-homologous end joining (NHEJ) and homologous recombination (HR). Interestingly, the efficient recruitment of repair proteins and completion of DSB repair likely involve complex, inter-organelle communication and coordination of cellular components. In this study, we report a role of &#x3b3;-tubulin in DSB repair. &#x3b3;-tubulin is a major microtubule nucleation factor governing microtubule dynamics. We show that &#x3b3;-tubulin is recruited to the site of DNA damage and is required for efficient DSB repair via both NHEJ and HR. Suppression of &#x3b3;-tubulin impedes DNA repair and exacerbates DNA damage accumulation. Furthermore, &#x3b3;-tubulin mediates the mobilization and formation of DNA damage foci, which serve as repair centers, thereby facilitating the recruitment of HR and NHEJ repair proteins on damaged chromatin. Finally, pharmacological inhibition of &#x3b3;-tubulin enhances the cytotoxic effect of DNA-damaging agents, consistent with the DNA repair function of &#x3b3;-tubulin, and underscoring the potential of its therapeutic intervention in cancer therapy.

DNA Breaks, Double-Stranded↗