This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Objective:To investigate the effect of hypoxemia(HYP)on the expression of myeloid cell trigger receptor-1(TREM-1)in macrophage exosomes(Exo)and the effect of TREM-1 on the biological behavior of ovarian cancer cells.Methods:The expression of TREM-1 in 27 cases of epithelial ovarian cancer tissues and 30 cases of benign ovarian cysts were detected by immuno-histochemical staining.The human mononuclear cell line THP-1 was induced into macrophages by chemical induction method,and the siRNA silencing TREM-1 was transfected into the differentiated macrophages under HYP conditions.The macrophages Exo derived from normoxia(NOR)and HYP were isolated and co-cultured with the ovarian cancer cell line SKOV3.The cells were divided into the NOR-Exo group,HYP-Exo-siRNA group,HYP-Exo-siTREM-1 group and Control group.Transwell assay,scratch assay and Western blot were used to detect the invasion,migration,epithelial-mesenchymal transition(EMT)ability of ovarian cancer cells in each group,the expression of TREM-1 protein in cells,and the protein phosphorylation levels of P65,ERK1/2 and AKT in the NF-κB,ERK1/2 and AKT signaling pathways,respectively.Results:Compared with benign ovarian cyst,the expression of TREM-1 in ovarian cancer macrophage was significantly increased(P<0.05).Compared with NOR,HYP could significantly promote the expression of TREM-1 in macrophage and its Exo(P<0.05).Compared with Control group,the invasion,migration and EMT ability and the protein phosphorylation levels of P65,ERK1/2 and AKT in HYP-Exo-siRNA group and HYP-Exo-siTREM-1 group were significantly in-creased(P<0.05),there was no significant change in the NOR-Exo group(P>0.05).Compared with HYP-Exo-siRNA group,the above detection indexes in NOR-Exo group and HYP-Exo-siTREM-1 group were significantly decreased(P<0.05).Conclusion:HYP can up-regulate the EMT,invasion and migration ability of ovarian cancer cells by promoting the high expression of TREM-1 in Exo de-rived from macrophages,which may be related to the activation of NF-κB,ERK1/2 and AKT signaling pathways.

Objective:To investigate the effect of hypoxemia(HYP)on the expression of myeloid cell trigger receptor-1(TREM-1)in macrophage exosomes(Exo)and the effect of TREM-1 on the biological behavior of ovarian cancer cells.Methods:The expression of TREM-1 in 27 cases of epithelial ovarian cancer tissues and 30 cases of benign ovarian cysts were detected by immuno-histochemical staining.The human mononuclear cell line THP-1 was induced into macrophages by chemical induction method,and the siRNA silencing TREM-1 was transfected into the differentiated macrophages under HYP conditions.The macrophages Exo derived from normoxia(NOR)and HYP were isolated and co-cultured with the ovarian cancer cell line SKOV3.The cells were divided into the NOR-Exo group,HYP-Exo-siRNA group,HYP-Exo-siTREM-1 group and Control group.Transwell assay,scratch assay and Western blot were used to detect the invasion,migration,epithelial-mesenchymal transition(EMT)ability of ovarian cancer cells in each group,the expression of TREM-1 protein in cells,and the protein phosphorylation levels of P65,ERK1/2 and AKT in the NF-κB,ERK1/2 and AKT signaling pathways,respectively.Results:Compared with benign ovarian cyst,the expression of TREM-1 in ovarian cancer macrophage was significantly increased(P<0.05).Compared with NOR,HYP could significantly promote the expression of TREM-1 in macrophage and its Exo(P<0.05).Compared with Control group,the invasion,migration and EMT ability and the protein phosphorylation levels of P65,ERK1/2 and AKT in HYP-Exo-siRNA group and HYP-Exo-siTREM-1 group were significantly in-creased(P<0.05),there was no significant change in the NOR-Exo group(P>0.05).Compared with HYP-Exo-siRNA group,the above detection indexes in NOR-Exo group and HYP-Exo-siTREM-1 group were significantly decreased(P<0.05).Conclusion:HYP can up-regulate the EMT,invasion and migration ability of ovarian cancer cells by promoting the high expression of TREM-1 in Exo de-rived from macrophages,which may be related to the activation of NF-κB,ERK1/2 and AKT signaling pathways.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

OBJECTIVES: The global burden of non-alcoholic fatty liver disease (NAFLD) is rising. An alternative term, metabolic dysfunction-associated fatty liver disease (MAFLD), instead highlights the associated metabolic risks. This cohort study examined patient classifications under NAFLD and MAFLD criteria and their associations with all-cause mortality. METHODS: Participants who attended a paid health check-up (2012-2015) were included. Hepatic steatosis (HS) was diagnosed ultrasonographically. NAFLD was defined as HS without secondary causes, while MAFLD involved HS with overweight/obesity, type 2 diabetes mellitus, or ≥2 metabolic dysfunctions. Mortality was tracked via the Taiwan Death Registry until November 30, 2022. RESULTS: Of 118,915 participants, 36.9% had NAFLD, 40.2% had MAFLD, and 32.9% met both definitions. Participants with NAFLD alone had lower mortality, and those with MAFLD alone had higher mortality, than individuals with both conditions. After adjustment for potential confounders, the hazard ratios (HRs) for all-cause mortality were 1.08 (95% confidence interval [CI], 0.78 to 1.48) for NAFLD alone and 1.26 (95% CI, 1.09 to 1.47) for MAFLD alone, relative to both conditions. Advanced fibrosis conferred greater mortality risk, with HRs of 1.93 (95% CI, 1.44 to 2.58) and 2.08 (95% CI, 1.61 to 2.70) for advanced fibrotic NAFLD and MAFLD, respectively. Key mortality risk factors for NAFLD and MAFLD included older age, unmarried status, higher body mass index, smoking, diabetes mellitus, chronic kidney disease, and advanced fibrosis. CONCLUSIONS All-cause mortality in NAFLD and/or MAFLD was linked to cardiometabolic covariates, with risk attenuated after multivariable adjustment. A high fibrosis-4 index score, indicating fibrosis, could identify fatty liver disease cases involving elevated mortality risk.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.