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.2024010
The recently discovered gene TRMT13 encodes a type of RNA methylase and is a member of the CCDC family (also called CCDC76). Here, we delineate its role in papillary thyroid cancer (PTC). Bioinformatics analysis shows significant TRMT13 and ANAPC4 downregulation in PTC and reveals that the expression levels of both genes are linearly correlated. Subsequent analyses confirm that both TRMT13 and ANAPC4 expressions are downregulated in PTC tissues and that this change in expression has a significant impact on cancer diagnosis. We conduct assays on PTC cells subjected to TRMT13 and ANAPC4 silencing or overexpression to assess the biological effects of these genes. We also perform rescue experiments to validate the regulatory effects of TRMT13 on ANAPC4. A nude mouse tumor model is used to evaluate the effects of TRMT13 and ANAPC4 on PTC tumorigenesis. TRMT13 expression is decreased in PTC tissues and cell lines and is positively correlated with that of ANAPC4. Cell assays reveal that TRMT13/ANAPC4 attenuates the malignancy of PTC cells by restraining cell proliferation, migration and invasion, while rescue experiments corroborate that ANAPC4 is a downstream target of TRMT13. In the nude mouse xenograft model, both TRMT13 and ANAPC4 inhibit tumor growth, and TRMT13 and ANAPC4 expression levels are significantly associated with survival. Taken together, these findings lead to the conclusion that TRMT13 inhibits PTC growth via ANAPC4, indicating a new role of TRMT13 and providing insights into the tRNA methyltransferase and coiled-coil domain-containing protein families.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025007
Frailty is a common geriatric disease characterized by accelerated aging and the loss of biological reserves across multiple organs. Approximately 10% of people aged 65 years and older and 25%–50% of people older than 85 years are in a frail state. The increasing institutionalization, hospitalization, and mortality caused by frailty incur massive medical costs and impose a heavy health service burden. For elderly individuals with chronic and/or infectious diseases, such as COVID-19, concomitant frailty can lead to extremely high mortality rates. Moreover, except exercise and nutritional intervention, no effective medicine for treating frailty is available. However, frailty can be prevented, and prefrailty can be reversed. Therefore, effectively screening frailty in elderly individuals is a public health priority. Two main methods for assessing frailty exist: the Fried phenotype and the Rockwood frailty index. The Fried phenotype uses five items, namely, fatigue, weakness, slowness, low physical activity, and weight loss, whereas the Rockwood frailty index is based on the accumulation of age-related deficits. However, these two diagnostic tools are subjective, challenging to use and time-consuming, and are therefore unsuitable for simple, rapid, and extensive screening of frailty in clinical practice. Here, we propose a new strategy to address the above issue. We first harnessed common professional databases to perform inflammatory niche analysis for plasma proteomics from normal aging and frailty patients. We subsequently performed frailty screening and blood sample collection. A total of 852 elderly people were included in the study from January 2018 to August 2018. The assessments included demographic information collection, frailty evaluation, and physical and body composition tests. Blood samples for the determination of inflammatory cytokines were taken from 67 participants. We utilized ELISA to detect the expressions of inflammatory cytokines and chemokines. All blood samples were collected and centrifuged at 4°C and 2000 g for 20 min. The serum was aliquoted and stored properly for ELISA. Inflammatory cytokines in human sera were quantified using corresponding human ELISA kits according to the manufacturer’s protocols. The following markers were measured: IL1A, IL2, IL6, IL8, IL10, IL17, TNFα, IFNγ, GCSF, MCP2, CXCL1, CX3CL1, MMP7, and SOD1. All the statistical analyses were performed with Prism v.6.0. P < 0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was used to evaluate the performance of all the screening tools. Our inflammatory niche analysis revealed intriguing results when five datasets containing a large number of proteins related to normal aging and inflammation were utilized. The Venn diagrams in Figure 1 show 77 human senescence-associated secretory phenotype genes. Among these genes, 26 are positively correlated with normal aging, whereas 8 are negatively correlated with normal aging. However, neither are positively correlated with frailty, and only two genes are negatively correlated with frailty. Therefore, frailty is obviously distinct from normal aging. Given that most of these differential proteins are inflammatory factors, frailty and normal aging may involve different inflammatory niches. These results suggest that inflammatory factors may be candidates for frailty screening. Our ELISA detection of 15 frailty-related inflammatory factors in the serum of frailty patients screened from 852 volunteers also provided valuable results. The prevalence of frailty was 7.16% (61/852), and that of prefrailty was 41.90% (357/852). The volunteers were 65.22% female and 34.78% male, with a mean age of 70.18 ± 0.73 years. As shown in Table 1, the frail and prefrail groups were significantly older than the robust group (P < 0.001). We observed statistically significant differences in RASM, gait speed, CCI, SARC-F, ADL and MNA scores (P < 0.05), whereas no significant differences were detected with respect to sex, WHR, grip strength or drug count among the three groups. A total of 67 serum samples (nonfrail, n = 20; prefrail, n = 28; and frail, n = 19) were subjected to inflammatory factor screening. No significant difference in the expression of most inflammatory factors was detected.
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.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025143
Vascular calcification (VC) is an independent risk factor for cardiovascular morbidity and mortality, characterized by hydroxyapatite deposition in arterial walls, leading to increased stiffness, decreased compliance, and plaque rupture. No clinically acknowledged therapy reverses VC. Dihydrocapsaicin (DHC), the primary pungent capsaicinoid in chili peppers, exhibits analgesic, anticancer, anti-inflammatory, antioxidant, and anti-obesity properties. Using the Comparative Toxicogenomics Database, we identified 20 experimental target genes of DHC, including ATF4, CASP3, CASP4, CASP7, CAT, CDKN1A, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, DDIT3, EIF2S1, ERN1, HSPA5, IGF1, MAP1LC3A, MAPK1, MAPK3, and TP53. Chemical-phenotype analysis revealed associations with apoptotic processes and autophagy. In a human vascular smooth muscle cell (hVSMC) calcification model induced by 1.2 μL of 100 mM CaCl2 in α-MEM basal medium, co-treatment with DHC (0.5, 2, or 8 μL of 4 mM solution) for 3–6 h significantly inhibited calcium deposition, as quantified by Alizarin Red staining and ImageJ analysis. These findings suggest that DHC modulates VC through mechanisms involving cell death, endoplasmic reticulum stress, and calcium signaling, highlighting its potential as a therapeutic agent for VC.