Biomedical subjects

Wenbin Ma

Publications and source records attributed to Wenbin Ma.

4 recordsLinked to original sources

PubMed2026

MYDGF as a telomerase activator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) involves progressive cartilage breakdown. This is driven by impaired chondrocyte function and an imbalance in the extracellular matrix homeostasis. However, the key upstream regulators that maintain healthy chondrocytes are still not fully known. Here, we report that myeloid-derived growth factor (MYDGF) is a novel regulator of telomerase activity and is critical for cartilage health. Using a genome-wide CRISPR-Cas9 screen with a TERT reporter system, MYDGF was identified as a strong positive regulator of telomerase. Functional studies confirmed that MYDGF positively regulates TERT expression and telomerase activity in both HeLa and ATDC5 cells. In a mouse surgical destabilization of the medial meniscus (DMM) OA model, MYDGF knockout (KO) mice exhibited more severe cartilage damage. Conversely, delivering MYDGF into the knee joint using AAV virus partially alleviated cartilage injury. Transcriptome profiling revealed that MYDGF-deficient chondrocytes exhibit downregulated key pathways involved in matrix building and upregulated inflammatory signals, indicating a shift in cell state. In summary, our work establishes MYDGF as a key upstream factor for both telomerase and cartilage matrix homeostasis remodeling. It connects telomerase function to chondrocyte health. These findings also highlight MYDGF as a promising new target for treating osteoarthritis.

Cartilage degeneration↗

PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

PubMed2025

RNA-DNA hybrid binding domain broadens the editing window of base editors.

Adenine base editors (ABEs) and cytosine base editors (CBEs) are prominent tools for precise genome editing but are hindered by limited editing activity at positions proximal to the protospacer adjacent motif (PAM). This study investigates the potential of enhancing base editors editing activity by fusing them with RNA-DNA hybrid binding domains (RHBDs). Specifically, fusing ABE8e with the RHBD of Homo sapiens RNaseH1 (RHBD1) significantly increased A-to-G editing efficiency in the PAM-proximal region (A9-A15) by up to 3.5-fold, while reducing off-target cytosine editing. Additionally, RHBD1 is compatible with ABEmax, BE4max, and dual base editor (eA&C-BEmax), enhancing their editing activity at the PAM-proximal bases. Notably, RHBD1-fused BE4max led to a 3.1-fold improvement in C-to-T editing efficiency at PAM-proximal region (C9-C12). Furthermore, we demonstrated that RHBD1-fused ABE8e could effectively edit disease-related single nucleotide variations (SNVs) in human cells and validated its efficacy in adult mouse liver. These findings highlight the significance of the RHBD in expanding editing window and the applicability of base editors for gene therapy and disease modeling.

Gene Editing↗

PubMed2024

Genetic association between epilepsy and gliomas: Insights from Mendelian randomization and single-cell transcriptomic analyses.

BACKGROUND: Seizures are prevalent in glioma patients, especially in those with low-grade gliomas. The interaction between gliomas and epilepsy involves complex biological mechanisms that are not fully understood. METHODS: We collected Genome-Wide Association Study data for epilepsy and gliomas, performed differential expression analysis, and conducted Gene Ontology (GO) enrichment analysis on the identified genes. Single-cell RNA sequencing data (scRNA-seq) from GSE221534 dataset in Gene Expression Omnibus (GEO) were used to analyze cell-cell interactions within glioma samples from patients with and without epilepsy. RESULTS: Mendelian Randomization (MR) analysis revealed significant associations between genetic variants related to epilepsy and glioma risk, suggesting a potential causal relationship, especially in astrocytomas. Differential expression analysis identified epilepsy-related genes that were significantly upregulated in astrocytoma tissues compared to normal brain tissues. GO enrichment analysis indicated that these genes are involved in critical biological processes such as neurogenesis and cellular signaling. The scRNA-seq analysis showed, compared to non-epileptic samples, glioma stem cells, microglia, and NK cells are increased in the core regions of astrocytomas in epileptic patients. Additionally, intercellular communication between tumor cells and other non-tumor cells is markedly enhanced in astrocytoma samples from epileptic patients. CONCLUSION: This study provides evidence of a genetic association between epilepsy and gliomas and elucidates the biological mechanisms through which epilepsy may influence glioma progression.

Humans↗