Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpb/art_1124
Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). Integrated 15 transcriptomic datasets of HCC clinical samples, the first version of HCC database (HCCDB v1.0) was released in 2018. Through the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets, it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and robustness. With four years having passed, the database now needs integration of recently published datasets. Furthermore, the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial architecture. Here, we present HCCDB v2.0, an updated version that combines bulk, single-cell, and spatial transcriptomic data of HCC clinical samples. It dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples, thereby enhancing the reliability of transcriptomic meta-analysis. A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections, respectively. A novel single-cell level and 2-dimension (sc-2D) metric is proposed as well to summarize cell type-specific and dysregulated gene expression patterns. Results are all graphically visualized in our online portal, allowing users to easily retrieve data through a user-friendly interface and navigate between different views. With extensive clinical phenotypes and transcriptomic data in the database, we show two applications for identifying prognosis-associated cells and tumor microenvironment. HCCDB v2.0 is available at http://lifeome.net/database/hccdb2.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04921-w
Background Lung ischemia–reperfusion injury (IRI) is a major contributor to primary graft dysfunction (PGD) after lung transplantation. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising therapeutic agents in inflammatory diseases by ameliorating tissue damage and promoting repair. However, the anti-inflammatory efficacy of these approaches and the underlying mechanisms in lung ischemia–reperfusion injury remain incompletely understood. Methods The protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) against lung ischemia–reperfusion injury were evaluated using two delivery approaches, inhalation and intravenous injection. Both in vivo and in vitro models were employed to assess the biological activity of MSC-EVs and to elucidate the underlying molecular mechanisms. In addition, a rat orthotopic lung transplantation (OLT) model was established to further examine the translational relevance of MSC-EVs. Results MSC–EVs treatment significantly ameliorated lung IRI, with inhalation showing superior efficacy over intravenous delivery. Mechanistically, miR-22-3p within MSC-EVs targeted macrophage NLRP3, suppressing activation of the NLRP3/Caspase-1/IL-1β pathway and promoting M2 polarization. The protective efficacy was confirmed in a clinically relevant rat OLT model, underscoring their translational potential
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025060
Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder characterized by insulin secretion dysfunction and/or insulin resistance. Osteocalcin (OC), or bone γ-carboxyglutamic acid protein (BGP), is a bone matrix protein predominantly produced by osteoblasts. Vitamin K-dependent carboxylation converts OC into gamma-carboxyglutamic acid (Gla)-rich carboxylated osteocalcin (cOC), which binds to hydroxyapatite and can be decarboxylated to undercarboxylated osteocalcin (ucOC) under acidic conditions. While cOC influences bone formation and mineralization, ucOC regulates energy metabolism. This study aimed to explore the associations between T2DM, serum OC levels (including cOC and ucOC), and OC gene polymorphisms in the Chinese Han population. T2DM patients and a healthy cohort, all of Han ethnicity, were categorized into a T2DM group (n = 456) and a control group (n = 224). Serum levels of cOC and ucOC were determined via ELISA. Insulin sensitivity was assessed via HOMA-IR, and pancreatic β-cell function via HOMA-β. Nine SNPs in the OC gene were genotyped via SNaPshot. Compared with controls, T2DM patients presented significantly lower levels of ucOC, cOC, and ucOC/cOC ratio. Additionally, T2DM subjects had elevated BMI, HbA1c, HOMA-IR, ALP, TG, HDL, and LDL levels, with decreased HOMA-β, ALT, AST, hsCRP, and FFA levels. In terms of bone metabolism, T2DM patients presented increased blood phosphorus, ICTP, P1NP, and 25(OH)D levels and decreased blood calcium, N-MID, PTH, and β-CTX levels. Associations between serum cOC and ucOC and various factors were analyzed. In the T2DM group, cOC was inversely correlated with HbA1c and P1NP, and positively correlated with ALP, LDL, and N-MID. ucOC was positively associated with N-MID. In controls, cOC was positively correlated with HDL, N-MID, and PINP, while ucOC correlated with PINP. The study also examined SNPs in the OC gene and their relationships with serum cOC and ucOC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023259
The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04921-w
Lung ischemia-reperfusion injury (IRI) remains the principal driver of primary graft dysfunction (PGD) following transplantation, with no approved pharmacological prophylaxis. This study evaluated mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) delivered by inhalation versus intravenous injection in murine hilar clamp and rat orthotopic lung transplantation (OLT) models. Inhalation achieved superior attenuation of pulmonary injury relative to systemic administration. Mechanistically, MSC-EV-encapsulated miR-22-3p was delivered to alveolar macrophages, where it targeted NLRP3 and suppressed the ASC/Caspase-1/IL-1β axis, reducing pyroptosis and promoting M2 polarization. These effects lowered cytokine-driven damage and enhanced tissue repair. Efficacy was confirmed in a clinically relevant rat OLT model, supporting translational potential for PGD prevention. The findings establish a pathway-specific, cell-free therapeutic strategy with a favorable route-dependent efficacy profile.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025060
Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder characterized by insulin secretion dysfunction and/or insulin resistance. Osteocalcin (OC), or bone γ-carboxyglutamic acid protein (BGP), is a bone matrix protein predominantly produced by osteoblasts. Vitamin K-dependent carboxylation converts OC into gamma-carboxyglutamic acid (Gla)-rich carboxylated osteocalcin (cOC), which binds to hydroxyapatite and can be decarboxylated to undercarboxylated osteocalcin (ucOC) under acidic conditions. While cOC influences bone formation and mineralization, ucOC regulates energy metabolism. OC enhances adiponectin production and insulin sensitivity; however, its relationship with diabetes incidence and glucose levels remains controversial. This study aimed to explore the associations between T2DM, serum OC levels (including cOC and ucOC), and OC gene polymorphisms in the Chinese Han population. T2DM patients and a healthy cohort, all of Han ethnicity, were categorized into a T2DM group (n = 456) and a control group (n = 224). Serum levels of cOC and ucOC were determined via enzyme-linked immunosorbent assay. Insulin sensitivity was assessed via homeostatic model assessment of insulin resistance (HOMA-IR). Pancreatic β-cell function was evaluated with HOMA-β. Nine SNPs in the OC gene were selected from the International HapMap Project database: rs12563631, rs2241106, rs2277872, rs2758605, rs1543294, rs1800247, rs2842880, rs759330, and rs933489. Genotyping was conducted via the SNaPshot technique. Pearson correlation and multiple linear regression analyses were performed. Compared with controls, T2DM patients presented significantly lower levels of ucOC (0.82 ng/mL), cOC (12.19 ng/mL), and ucOC/cOC ratio (0.07) (1.17 ng/mL, 14.47 ng/mL, and 0.09, respectively). Additionally, T2DM subjects had elevated BMI (25.06 kg/m2), HbA1c (8.95%), HOMA-IR (0.61), ALP (79.00 U/L), and TG (1.50 mM). Notably, cOC levels exhibit a significant inverse correlation with HbA1c, whereas no such correlation was observed for ucOC. The CC genotype at rs933489 is associated with lower ucOC levels in Chinese Han T2DM patients. These findings provide novel perspectives on the role of OC in T2DM pathophysiology.