Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024053
SLC45A1 encodes a glucose transporter protein highly expressed in the brain. Mutations in SLC45A1 may lead to neurological diseases and developmental disorders, but its exact role is poorly understood. DNA G-quadruplexes (DNA G4s) are stable structures formed by four guanine bases and play a role in gene regulation and genomic stability. Changes in DNA G4s may affect brain development and function. The mechanism linking alterations in DNA G-quadruplex structures to SLC45A1 pathogenicity remains unknown. In this study, we identify a functional DNA G-quadruplex and its key binding site on SLC45A1 (NM_001080397.3: exon 2: c.449 G>A: p.R150K). This variant results in the upregulation of mRNA and protein expression, which may lead to intellectual developmental disorder with neuropsychiatric features. Mechanistically, the mutation is found to disrupt DNA G-quadruplex structures on SLC45A1, leading to transcriptional enhancement and a gain-of-function mutation, which further causes increased expression and function of the SLC45A1 protein. The identification of the functional DNA G-quadruplex and its effects on DNA G4s may provide new insights into the genetic basis of SLC45A1 pathogenicity and highlight the importance of DNA G4s of SLC45A1 in regulating gene expression and brain development.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261612
Critical-sized bone defects (CSBD) remain a clinical bottleneck due to insufficient osteogenic drive and uncontrolled degradation of current grafts. This study evaluates a photocrosslinked hydrogel composed of cuttlebone (CB) and bovine serum albumin (BSA) for repairing 5 mm rat calvarial CSBD. SD rats were randomized into control, positive control (Bio-Oss® Collagen), BSA, 0.5% CB/BSA, 1.5% CB/BSA, and 3.0% CB/BSA groups (n=6). After 8 weeks, micro-CT revealed no new bone in controls, whereas all CB/BSA groups exhibited significant increases in bone volume fraction, bone mineral density, and trabecular thickness (P<0.05), with reduced bone surface-to-volume ratio (P<0.05). Histology confirmed new bone formation in hydrogel groups versus loose fibrous tissue in controls. Immunohistochemistry and immunofluorescence showed elevated COL1A1, PECAM-1, and OCN expression (P<0.05). qRT-PCR and Western blotting demonstrated upregulation of WNT3A, β-catenin, VEGFA, COL1A1, PECAM-1, and OCN (P<0.05). The 3.0% CB/BSA group exhibited the most pronounced osteogenic effect. Blood routine and serum liver/kidney function tests showed no abnormalities, and major organs displayed no inflammation, necrosis, or fibrosis. These findings indicate that CB/BSA photocrosslinked hydrogel promotes bone repair with favorable in vivo safety, likely through activation of the Wnt/β-catenin signaling pathway.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025250
Long non-coding RNAs (lncRNAs) regulate diverse biological processes, yet the contribution of sperm-derived lncRNAs from infertile men to impaired embryo development during in vitro fertilization (IVF) remains unresolved. This study profiled lncRNA expression in sperm from asthenozoospermic patients exhibiting poor embryo development. Microarray analysis identified 993 differentially expressed lncRNAs, comprising 626 downregulated and 367 upregulated probes. Among these, the antisense transcript lnc-CLCN7 was validated as the most significantly dysregulated lncRNA in an expanded cohort. In situ hybridization localized lnc-CLCN7 to spermatogenic cells of primate testes and to the nuclei of HTR-8 cells. Gene Ontology and KEGG analyses associated lnc-CLCN7 with ion transport regulation, ion homeostasis, and related signaling pathways. Functional experiments demonstrated that lnc-CLCN7 directly binds histone modification marks H3K9me2/3 in HTR-8 cells, and its expression in sperm is modulated by H2O2-induced oxidative stress in a dose-dependent manner, with an early increase followed by gradual decrease; antioxidant treatment markedly increased lnc-CLCN7 expression. Dysregulation of glycolysis/gluconeogenesis and pyrimidine metabolism pathways in sperm was found to contribute to poor embryo development. These findings identify lnc-CLCN7 as an H3K9me2/3-binding, oxidative stress–responsive lncRNA that may serve as a potential biomarker for predicting poor embryo development in IVF, providing new insights into molecular mechanisms linking sperm RNA regulation to embryo quality. Limitations include a relatively small sample size and technical constraints in visualizing lnc-CLCN7 via FISH due to compacted sperm chromatin.