Biomedical subjects

Miao Xu

Publications and source records attributed to Miao Xu.

4 recordsLinked to original sources

PubMed2026

Establishment of induced pluripotent stem cell line TRNDi045-A-38 carrying homozygous DOK7-related Congenital Myasthenia patient-mutation knock-in variant from parental KOLF2.1J.

DOK7-related Congenital Myasthenic Syndrome (CMS) is a rare genetic neuromuscular junction disorder. This is one of the most common of the recessive forms of CMS, often presenting with more static proximal weakness (hence also referred to as limb girdle CMS). Whole-genome sequencing of affected patients implicates frameshift duplication mutations in DOK7 as drivers of impaired neuromuscular-junction signaling. In this study, we generated a human induced pluripotent stem cell (hiPSC) line TRNDi045-A-38 from the KOLF2.1J reference line, engineered to carry homozygous DOK7 c.1124_1127dupTGCC mutation knock-in using CRISPR/Cas9. This iPSC line could be used for in vitro disease modeling to study disease pathophysiology and for therapeutic development.

Humans↗

PubMed2026

Enhanced Prediction of Peripheral Artery Disease Using Plasma Proteomics Among Individuals Without Diabetes.

BACKGROUND: Although peripheral artery disease (PAD) is an important diabetes complication, a substantial proportion of cases occur among individuals without diabetes. This study aimed to assess the predictive value of plasma proteomics in the long-term risk of PAD among individuals initially free of diabetes. METHODS: Included were 46 508 participants (6046 with prediabetes) without diabetes or major cardiovascular disease at recruitment of the UK Biobank. Using multivariable Cox regression models, a total of 2923 unique plasma proteins were assessed for the associations with incident PAD. Significant proteins were subsequently processed by a trained light gradient boosting machine classifier to determine important proteins. Using receiver operating characteristic analyses, the performance of these important proteins in predicting incident PAD were evaluated, in the whole sample and by glycemic status (normoglycemia and prediabetes). RESULTS: During a median follow-up of 12.7 years, 461 participants developed PAD. There were 107 proteins associated with incident PAD, with 103 positive associations. The LGBM approach identified 9 proteins (eg, WFDC2 [WAP 4-disulfide core domain protein 2], MMP12 [macrophage metalloelastase], and GDF15 [growth differentiation factor 15]) as the top-ranked proteins based on their importance ordering. Whereas glycated hemoglobin showed very modest predictive accuracy, a panel incorporating these top proteins showed good performance in the prediction of PAD risk (area under the curve 0.820), and it significantly enhanced the prediction beyond traditional risk factors (raising area under the curve from 0.803 to 0.837, DeLong test P=5.21×10-3). These observations were consistent for participants with normoglycemia or prediabetes. CONCLUSIONS: Plasma protein biomarkers enhance the prediction of long-term risk for PAD among individuals without diabetes, regardless of glycemic status.

Humans↗

PubMed2025

Epstein-Barr Virus Sequence Variations Among the Understudied Nasopharyngeal Carcinoma Patients of Diverse Ancestries in Southeast Asia.

Epstein-Barr virus (EBV) is associated with cancers, including lymphomas and nasopharyngeal carcinoma (NPC). To date, risk variants for NPC were mainly identified from Chinese populations, which dominated the world's total number of cases. Although Southeast Asia (SEA) countries have among the world's top yet intriguingly diverse NPC age-standardized incidence rates across subpopulations, data on EBV from SEA remains scarce. In this study, we examined 83 NPC patients of different ancestries for the presence of risk haplotypes associated with the Southern Chinese NPC and generated and analyzed 67 EBV sequences (from tissue, patient-derived xenografts and lymphoblastoid cell lines of 60 NPC patients) together with 838 published EBV genomes. Our study revealed that NPC patients of non-Chinese ancestry had fewer risk variants and haplotypes that are associated with Southern Chinese NPC and clustered distinctly from lymphomas, Southern Chinese NPC, and non-cancer controls. The distribution of non-synonymous variants was similar among NPC patients of Chinese ancestry, irrespective of geographical location. Meanwhile, non-synonymous variants in genes related to packaging, latency, and structural proteins such as BPLF1, LF3, and LMP1 varied across different ancestries. Our findings suggest possibilities of EBV adaptation to host genetics for NPC pathogenesis and warrant further research for the understudied NPC subpopulations.

Adult↗

PubMed2024

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.

Bone cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

Animals↗