Cell Biochemistry and Function最新文献

Osteoking (OK) exerts bone formation-promoting effects on menopausal osteoporosis and osteoporotic fractures. However, it remains to be determined whether OK ameliorates type 2 diabetic osteoporosis (T2DOP) via PI3K/AKT/GSK-3β pathway activation. Thus, the T2DOP animal model was established in db/db mice in this study. Microcomputed tomography (micro-CT) analysis revealed that OK significantly increased bone strength, improved bone metabolism, and promoted bone formation. GS and p-GSK-3β expression levels were increased in OK group as compared with db/db group by western blot analysis. IL-6, IL-17A, IFN-γ, TNF-α, and IL-1β were lower levels in the OK group compared to the db/db group, nevertheless, the IL-10 level was significantly higher. Furthermore, an in vitro cells model was constructed by stimulating with high glucose (HG, 30 mM). ALP protein was significantly elevated in the OK treatment group. Administration of OK at 0.288 mg/mL significantly increased p-AKT/AKT expression, while, combined with LY294002, an inhibitor of PI3K, OK significantly reduced the expression levels of p-PI3K/PI3K, p-AKT/AKT, and p-GSK-3β/GSK-3β. In conclusion, this study reveals OK exhibits efficacy against T2DOP in db/db mice by promoting osteogenesis of preosteoblast MC3T3-E1 cells through PI3K/AKT/GSK-3β pathway regulation.

Individuals with type 1 diabetes mellitus (T1DM) experience an increased risk of cardiovascular disease (CVD). To improve early detection and prevention strategies, a better understanding of early vascular changes is needed. Although coronary artery (CA) damage is a known T1DM complication, its underlying proteomic basis remains unclear. This study used a proteomic approach to identify differentially expressed proteins in the CAs of T1DM rat models, with the goal of identifying novel proteins and pathways associated with early diagnosis and prevention of CA complications. We established a streptozotocin-induced T1DM model in male Sprague–Dawley rats and conducted tandem mass tag-based quantitative proteomics and bioinformatics analyses to investigate protein expression profiles in CAs. The analyses identified 443 differentially expressed proteins, with 229 upregulated and 214 downregulated proteins. Functional annotation and pathway enrichment analyses revealed that these proteins primarily participate in lipid metabolism, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, peroxisome function, and butanoate metabolism. Validation experiments using Western blotting analysis and quantitative real-time PCR confirmed significant upregulation of 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), fatty acid-binding protein 4 (FABP4), and platelet glycoprotein 4 (CD36) at the protein and mRNA levels in diabetic rat CAs, consistent with the proteomic results. Our findings indicate that HMGCS2, FABP4, and CD36 may serve as important molecular markers for the early diagnosis or therapeutic targeting of CA damage in T1DM. The observed molecular changes appear to be linked to the PPAR signaling pathway.

Clinical trial registration. Not applicable.

Platelets, crucial components of blood, play a vital role in hemostasis and clinical treatments. However, current platelet storage methods at 22 ± 2°C face significant limitations, including a short shelf life (5–7 days), high risk of bacterial contamination, and progressive accumulation of metabolites such as lactic acid during prolonged storage. These issues impair transfusion efficacy and severely restrict the clinical utility of platelets. In contrast, cold storage at 4°C offers potential advantages: it extends platelet shelf life, reduces bacterial contamination risks, minimizes metabolite accumulation, and better preserves platelet hemostatic function. Mitochondria, as essential organelles in platelets, are central to energy metabolism, activation, adenosine triphosphate production, and regulation of cellular processes. They are of great significance for maintaining platelet physiological function and biological activity. This review examines the role of mitochondria in refrigerated platelet storage, focusing on their impact on energy metabolism, apoptosis, and post-transfusion clearance. Additionally, we discuss mitochondrial-targeted intervention strategies and future research directions to optimize platelet storage methods and enhance clinical transfusion outcomes.

Apoptosis represents a critical noninflammatory mechanism for cell clearance in both physiological and pathological contexts, precisely regulated through the balance between proapoptotic and antiapoptotic signaling. Three well-characterized apoptotic pathways have been identified: (1) the intrinsic (mitochondria-mediated) pathway, (2) the extrinsic (death receptor-mediated) pathway, and (3) the endoplasmic reticulum (ER)-stress pathway. These processes are coordinated through the mitochondria-associated ER membrane (MAMs), which serves as a vital coupling platform between mitochondria and the ER. MAMs play pivotal roles in maintaining Ca²⁺ homeostasis and regulating apoptosis through dynamic alterations in architecture (e.g., gap width, contact number) that influence Ca²⁺ trafficking and tethering protein expression. Key protein complexes localized at MAMs (including the IP3Rs-Grp75-VDAC1 complex, Mfn1/Mfn2 complex, and PTPIP51-containing complex) regulate apoptosis through three primary mechanisms: Ca²⁺ homeostasis maintenance, lipid synthesis and transport, and mitochondrial morphology and dynamics. Furthermore, MAMs-mediated mitochondrial dynamics, particularly mitochondrial fission and cristae remodeling, contribute to apoptosis by facilitating Bax/Drp1 dimerization. This review systematically examines: how MAMs' structural dynamics influence Ca²⁺ signaling and tethering protein expression, the roles of MAMs-tethered proteins and their regulators in Ca²⁺ homeostasis, lipid metabolism, and mitochondrial dynamics, and the impact of mitochondrial dynamics on Bax/Drp1 dimerization during apoptosis.

Fibrosarcoma cells exhibit low sensitivity to chemotherapy and significant drug resistance, emphasizing the urgent need for effective, low-toxicity therapeutic agents with reliable production methods and novel treatment strategies. Cordycepin (3′-deoxyadenosine) has shown promising therapeutic potential in cancer treatment. In this study, cordycepin was produced using a genetically engineered Pichia pastoris strain cultured in an inorganic salt medium and purified to over 98% purity via macroporous resin chromatography, providing a cost-effective production alternative. The effects of cordycepin on the human fibrosarcoma cell line HT1080 were assessed using microscopic examination, scratch assays, CCK-8 assays, and flow cytometry (Annexin V-FITC/PI staining). The results demonstrated that cordycepin significantly inhibited cell activity at an effective concentration of 100 μmol/L. Key observations included changes in cell morphology, reduced migration, inhibited proliferation, cell cycle arrest at the G0/G1 and G2/M phases, and induction of apoptosis. Network pharmacology analysis identified 31 potential targets of cordycepin in fibrosarcoma, with its effects on Akt1 (protein kinase B) and disruption of protein phosphorylation pathways emerging as key mechanisms underlying its therapeutic efficacy. Western blot analysis further confirmed that cordycepin simultaneously downregulated both the expression and phosphorylation levels of Akt in a dose-dependent manner.

Primary cilia, microtubule-based sensory organelles that protrude from the cell surface, are integral to sensing the cellular microenvironment and mediating intercellular signal transduction. They play a crucial role in maintaining homeostasis of major human organs. While primary cilia have been extensively characterized in other organs and linked to tumorigenesis, their specific roles within the digestive system—particularly their pathological loss in digestive cancers—remain poorly defined. Emerging evidence now reveals that cell type-specific ciliary loss (e.g., in cholangiocytes, pancreatic ductal epithelial cells, and gastrointestinal stromal cells and fibroblasts) disrupts critical signaling homeostasis, driving malignant transformation in disorders such as cholangiocarcinoma, chronic pancreatitis, pancreatic ductal adenocarcinoma, and colon cancer. This review synthesizes how ciliary dysfunction in digestive cell subtypes alters key oncogenic pathways (e.g., Hedgehog, Wnt/β-catenin, and PDGFRα signaling) to accelerate tumor initiation and progression. We further explore the therapeutic potential of pharmacologically restoring ciliary integrity to reverse pathway dysregulation, proposing cilia-targeted strategies for early diagnosis and intervention in inflammation-associated digestive malignancies.

Nonalcoholic steatohepatitis (NASH), a highly prevalent metabolic-related fatty liver disease, has become a major global health issue with limited therapeutic options. Recent studies indicated that ostreolysin (Oly), a protein derived from oyster mushrooms, could be a potential therapeutic agent for NASH. In this study, recombinant Oly (rOly) was expressed in E. coli BL21 (DE3) and purified using Q Sepharose and TOYOPEARL chromatography, with its identity confirmed by SDS-PAGE and mass spectrometry. Indb/db mice, subcutaneous injection of rOly at 0.5 and 1 mg/kg every 2 days for 30 days significantly reduced body weight by 14.1% in the high-dose group (p < 0.01), improved insulin resistance (insulin resistance index decreased by 35%, p < 0.05), and alleviated hepatic steatosis as shown by HE and Oil Red O staining.In vitro, rOly induced browning of 3T3-L1 preadipocytes, evidenced by 1.8-fold upregulation of UCP1 (p < 0.05) and 2.3-fold upregulation of ATGL (p < 0.01). Mechanistic studies revealed that rOly inhibited Hedgehog signaling pathway genes Gli1 and Ptch1 by 70% and 65% (p < 0.0001), respectively, promoting beige adipocyte differentiation. These findings demonstrate that rOly enhances energy metabolism by promoting preadipocyte browning via Hedgehog pathway inhibition, providing a promising basis for treating obesity and metabolic diseases.

Smilax glabra Roxb. is a natural herb, exhibits significant uric acid lowering effect in clinical. However, the specific mechanism remains to be clarified. To study this problem, intraperitoneal injection of Potassium oxazinate (PO) and Hypoxanthine (HX) induced hyperuricemia in mice model, and mice were divided into control, model, and model plus ethanol extract (TFL), ethyl acetate extract (TFL_Y), n-butanol extract (TFL_Z), and residual aqueous extract (TFL_S) of Smilax glabra Roxb., And then a follow-up test. Furthermore, possible pharmacological components were detected by UPLC-Q-TOF-MS. The results showed that serum creatinine, blood urea nitrogen, d-lactate, lipopolysaccharide levels and xanthine oxidase. They could upregulate renal OAT1 and ABCG2, downregulate renal URAT1, reduce renal tubular dilation and interstitial inflammatory cell infiltration. Moreover, they could upregulate intestinal tight junction proteins, increase the number of intestinal goblet cells, and repair damage to the intestinal barrier. Moreover, 16S rRNA sequencing analysis showed that restored intestinal microbiota by increasing probiotic bacteria (Candidatus Saccharimonas, Lachnospiraceae NK4A136_group) and reducing pathogenic bacteria (Helicobacter). Furthermore, it was found that all control taint flavonoids such as Neoastalbin, Astibin, Neoiosastilbin, Isoastalbin, Engeletin, and Isoengeletin.