Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Platelets circulate in an inactive form in the body until they contact with defective areas of endothelial cells or encounter a clotting cascade [1]. Activated platelets release and express bioactive substances and acquire the ability to bind plasma fibrinogen. Abnormal activation of platelets is involved in atherosclerosis and thrombosis [2,3]. When platelets are stimulated and activated, phospholipase A2 is activated at the same time, which then cleaves membrane phospholipids and frees arachidonic acid (AA) [4]. The latter catalyzes thromboxane A2 (TXA2) via thromboxane synthetase [5], which is induced by the cyclooxygenase COX-1 to produce prostaglandins G2 and H2 [6]. TXA2 is highly unstable, with a half-life of only 30 s, and it is rapidly hydrolyzed to relatively stable thromboxane B2 (TXB2), which is then converted in the liver to 11-dehydrothromboxane B2 (11dH-TXB2), which has a longer half-life and is excreted in the urine [7]. Dehydrothromboxane B2 is the final stable metabolite of thromboxane A2, which is derived only from arachidonic acid metabolism and can represent thromboxane A2 level in the body [8]. Specifically, by inhibiting the action of COX-1, the most important enzyme in the process of arachidonic acid metabolism, aspirin inhibits the production of thromboxane A2, that is, the concentration of TXA2 affects the effect of aspirin on platelet aggregation. However, the half-life of TXA2 (including the metabolic intermediate TXB2) is too short to be accurately measured, so the detection of its metabolic end product 11dH-TXB2 can very accurately reflect the sensitivity of the body to aspirin [7]. The concentration of 11dH-TXB2 in the serum correlates well with the concentration of 11dH-TXB2 in the urine, so the determination of 11dH-TXB2 in the urine can more effectively reflect the production of TXA2 in vivo [8]. The 11dH-TXB2 concentration needs to be corrected with the urinary creatinine concentration to rule out the effects of the urine concentration and renal function, so random urine samples can be used for testing [6]. Aspirin can acetylate serine at the key site of cyclooxygenase and thus irreversibly inhibits the activity of COX-1, reduces the synthesis of TXA2, and blocks the production of TXA2 and its induced platelet aggregation. Low-dose aspirin (30–75 mg/day) can effectively inhibit 95% of COX-1 activity [7]. Since the production of TXA2 in serum is largely dependent on platelet COX-1 (a therapeutic target of aspirin), 11dH-TXB2 can be used as a monitor for aspirin-induced platelet inhibition [3]. Creatinine is a metabolic byproduct of muscle metabolism that is primarily excreted via glomerular filtration, and its level is indicative of renal function [9]. The 24-h creatinine clearance can also be used to determine the integrity of the sample or to correct the urine sample concentration with the creatinine ratio [10]. Currently, creatinine detection methods include the Jaffe method, enzymolysis spectrophotometry, HPLC, capillary electrophoresis, capillary zone electrophoresis, gas chromatography tandem mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) [11]. At present, there is no method for the simultaneous detection of 11dH-TXB2 and creatinine. When both analytes are needed, separate tests must be performed, increasing the workload and sample volume requirements. Thus, developing a method that enables the concurrent quantification of 11dH-TXB2 and creatinine in a single assay remains a critical challenge. The aim of this study was to provide a method for the simultaneous detection of 11dH-TXB2 and creatinine and to alleviate the problem that 11dH-TXB2 and creatinine cannot be simultaneously detected. By developing a standardized quantitative approach for measuring 11dHTXB2 and creatinine in human urine, this study aims to provide reliable concentration data, thereby facilitating further clinical research and methodology optimization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025025
The circadian rhythm is a phenomenon in which physiological, behavioral, and biochemical processes within an organism naturally fluctuate over a period of approximately 24 hours. This phenomenon is ubiquitous in living organisms. Disruption of circadian rhythms in mammals leads to different diseases, such as cancer, and neurodegenerative and metabolic disorders. In specific tissues, numerous genes have been found to have circadian oscillations, suggesting a broad role for rhythm genes in the regulation of gene expression. This review systematically summarizes the role of cryptochromes (CRYs) in the initiation and progression of different types of cancer and discusses the relationships between clock genes and the tumor microenvironment (TME), as well as clock-based therapeutic strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025052
Platinum drugs are widely used in lung cancer chemotherapy, but the immune characteristics of different individuals have different effects on the sensitivity and side effects of platinum drugs. In this study, we use 731 kinds of immune cell traits of 3757 healthy individuals and 429 patients with non-small cell lung cancer (NSCLC) in Xiangya Hospital of Central South University to conduct a Mendel randomized analysis in order to find out the causal relationship between some immune cell traits and the efficacy and adverse reactions of platinum drugs. We find that CD19 on CD24+CD27+ B cell (OR = 0.598, P = 0.004) is the most significant immune cell trait as the protective factor of efficacy. HLA-DR+CD8+ T cell % lymphocyte (OR = 0.427, P = 7.55 × 10–4) and HLA-DR+CD8+ T cell % T cell (OR = 0.471, P = 0.003) are the protective factors of liver injury. CD39 on CD39+ secreting CD4+ regulatory T cell (OR = 28.729, P = 0.009) and CD3 on CD39+ resting CD4 regulatory T cell (OR = 3.024, P = 0.009) are the risk factors of renal injury. Meanwhile, B cell-related traits mainly affect gastrointestinal upset and cutaneous toxicity, while T cell-related traits mainly affect other outcome variables. These findings may promote our understanding of the relationship between the efficacy and adverse reactions of platinum drugs and the immune system, and promote future development of biomarkers for predicting the efficacy and adverse reactions of platinum drugs.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21444
BACKGROUND: Icariin has the dual activity of promoting bone formation and inhibiting bone resorption, but its clinical application is plagued by low bioavailability, difficulty in controlling dosage, and a high risk of adverse reactions. OBJECTIVE: To prepare a three-dimensional scaffold containing icariin sustained-release microspheres and characterize their osteogenic activity in vitro. METHODS: A silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold (SF/CS/nHA scaffold), icariin sustained-release microspheres, and a silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold loaded with icariin sustained-release microspheres (SF/CS/nHA-ICA scaffold) were prepared. The drug loading efficiency, encapsulation efficiency, and in vitro drug release of the icariin sustained-release microspheres were characterized. The pore size, porosity, water absorption expansion rate, and hot water dissolution rate of the two scaffolds were measured. Rabbit bone marrow mesenchymal stem cells (or human rheumatoid arthritis fibroblast-like synoviocytes) were seeded on SF/CS/nHA and SF/CS/nHA-ICA scaffolds, with cells cultured alone as controls. Cell adhesion was observed by scanning electron microscopy. Cell proliferation and viability were assessed by CCK-8 assay, live/dead staining, and F-actin staining. The mRNA and protein expression of Runx-2, osteocalcin, and type I collagen in bone marrow mesenchymal stem cells were detected by RT-qPCR and western blot. RESULTS AND CONCLUSION: (1) The drug loading efficiency and encapsulation efficiency of icariin sustained-release microspheres were (29.38±0.04)% and (52.01±0.09)%, respectively, and the microspheres could sustainably release icariin for more than 90 days in vitro. (2) Scanning electron microscopy showed a honeycomb-like porous structure with interconnected pores in both scaffolds. There were no significant differences in pore size, porosity, water absorption expansion rate, or total hot water dissolution rate between the two groups (P > 0.05). (3) Scanning electron microscopy showed that both cell types adhered tightly to the scaffold surface and pores, with more extended pseudopodia on the SF/CS/nHA-ICA scaffold. CCK-8 assay, live/dead staining, and F-actin staining showed that compared with the control and SF/CS/nHA groups, the SF/CS/nHA-ICA scaffold promoted the proliferation and viability of rabbit bone marrow mesenchymal stem cells, while inhibiting the proliferation and viability of human rheumatoid arthritis fibroblast-like synoviocytes. (4) RT-qPCR and western blot showed that compared with the control and SF/CS/nHA groups, the mRNA and protein expression of Runx-2, osteocalcin, and type I collagen were increased in the SF/CS/nHA-ICA group (P < 0.05). (5) These results indicate that the icariin sustained-release microsphere three-dimensional scaffold has good cytocompatibility, and in vitro osteogenic and anti-inflammatory effects.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025055
Thromboxane A2 (TXA2) is a labile eicosanoid with a half-life of 30 s, limiting direct quantification. Its stable urinary metabolite, 11-dehydrothromboxane B2 (11dH-TXB2), reflects in vivo TXA2 biosynthesis and aspirin-mediated COX-1 inhibition. Creatinine normalization is required to correct for urine concentration and renal function. This study establishes a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of 11dH-TXB2 and creatinine in human urine. Sample pretreatment involves organic phase extraction, eliminating solid-phase extraction. The method was validated for linearity, accuracy, precision, and recovery. The linear range for 11dH-TXB2 was 0.1–50 ng/mL (r² = 0.99656) and for creatinine 10–5000 ng/mL (r² = 0.99950). Quality control accuracies ranged from 85.83% to 113.21%, with RSDs below 9.71%. Standard recoveries were 85–110%. The assay meets regulatory requirements for simultaneous quantification. This approach provides a reliable tool for monitoring aspirin response and investigating thromboxane-related pathologies.