Journal of Biomedical Research最新文献

The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills (CDDP) in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction (AAMI). Between February 2021 and February 2023, 247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned (1∶1) to receive CDDP ( n = 126) or placebo ( n = 121), with a follow-up of 48 weeks. Compared with the placebo group, the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment (least squares mean: 3.31; 95% confidence interval [CI]: 1.72-4.90; P < 0.001) and at the 48-week follow-up (least squares mean: 4.35; 95% CI: 2.76-5.94; P < 0.001). Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24- and 48-week visits with no significant difference between the two groups ( P > 0.1 for all). The incidence of major adverse cardiovascular and cerebrovascular events was 6.35% in the CDDP group and 5.79% in the placebo group ( P = 0.822). Notably, no serious adverse events were attributed to CDDP. These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.

Cholestatic liver disease, caused by the accumulation of hazardous bile acids in the liver, may result in cirrhosis, fibrosis, or liver failure. Activation of sirtuin 6 (SIRT6) prevents cholestasis-associated pathological events, such as oxidative stress and mitochondrial biogenesis dysfunction, and inhibits bile acid synthesis to alleviate cholestatic liver injury. However, it remains uncertain which pathway mediates the therapeutic effect of SIRT6 in reducing cholestasis. Therefore, we treated liver-specific Sirt6 knockout mice with N-acetylcysteine, KEAP1-NRF2-IN-1, or acadesine to alleviate oxidative stress and/or promote mitochondrial biogenesis after modeling cholestatic liver disease, but these measures did not significantly improve cholestatic symptoms. However, MDL801, a SIRT6 agonist that downregulates cholesterol 7α-hydroxylase (CYP7A1, the key enzyme in bile acid synthesis) levels, exhibited favorable therapeutic effects. Additionally, the hepatic knockdown of Cyp7a1 further demonstrated that inhibiting hepatic bile acid synthesis might be the main pathway through which SIRT6 alleviates cholestatic liver disease. These findings provide a solid basis for the potential application of SIRT6 agonists in treating cholestatic liver disease.

The current study aims to identify potential metabolic biomarkers that predict the progression to prediabetes in women with a history of gestational diabetes mellitus (GDM). We constructed a prediabetes group ( n = 42) and a control group ( n = 40) based on a 2-h 75 g oral glucose tolerance test for women with a history of GDM from six weeks to six months postpartum, and collected their clinical data and biochemical test results. We performed the plasma metabolomics analysis of the subjects at the fasting and 2-h post-load time points using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). We found that the prediabetes group was older and had higher 2-h post-load glucose levels during pregnancy than the control group. The metabolomic analysis identified 164 differential metabolites between the groups. Compared with the control group, 15 metabolites in the prediabetes group exhibited consistent change trends at both time points, including three increased and 12 decreased metabolites. By building a prediction model of the progression from GDM to prediabetes, we found that a combination of three clinical markers yielded an area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.60-0.82). We also assessed the discriminative power of the panel of 15 metabolites for distinguishing between postpartum prediabetes and normal glucose tolerance of the subjects at the fasting (AUC, 0.98; 95% CI, 0.94-1.00) and 2-h post-load (AUC, 0.99; 95% CI, 0.97-1.00) time points. The metabolic pathway analysis indicated that energy metabolism and branched-chain amino acids played a role in prediabetes development in women with a history of GDM during the early postpartum period. In conclusion, this study identified potential metabolic biomarkers and pathways associated with the progression from GDM to prediabetes in the early postpartum period. A panel of 15 metabolites showed promising discriminative power for distinguishing between postpartum prediabetes and normal glucose tolerance. These findings provide insights into the underlying pathophysiology of this transition and suggest the feasibility of developing a metabolic profiling test for the early identification of women at high risk of prediabetes following GDM.

Adiponectin receptor 1 ( Adipor1) deficiency has been shown to inhibit Th17 cell differentiation and reduce joint inflammation and bone erosion in antigen-induced arthritis mice. Additional emerging evidence indicates that Th17 cells may differentiate into pathogenic (pTh17) and non-pathogenic (npTh17) cells, with the pTh17 cells playing a crucial role in numerous autoimmune and inflammatory conditions. In the current study, we found that Adipor1 deficiency inhibited pTh17 differentiation in vitro and induced mitochondrial dysfunction in pTh17 cells. RNA sequencing demonstrated a significant increase in the expression levels of Fundc1, a gene related to mitochondrial function, in Adipor1-deficient CD4 ⁺ T cells. Fundc1 knockdown in Adipor1-deficient CD4 ⁺ T cells partially reversed the effects of Adipor1 deficiency on mitochondrial function and pTh17 differentiation. In conclusion, the current study demonstrated a novel role of Adipor1 in regulating mitochondrial function via Fundc1 to promote pTh17 cell differentiation, providing some insight into potential therapeutic targets for autoimmune and inflammatory diseases.

The skeletal muscle is the largest organ present in the body and is responsible for mechanical activities like maintaining posture, movement, respiratory function, and support for the health and functioning of other systems of the body. Skeletal muscle atrophy is a condition characterized by a reduction in muscle size, strength, and activity, which leads to an increased dependency on others for movement, an increased risk of falls, and a reduced quality of life. Various conditions like osteoarthritis, osteoporosis, and fractures are directly associated with increased muscle atrophy. Additionally, numerous risk factors, like aging, malnutrition, physical inactivity, and certain disease conditions, through distinct pathways, negatively affect skeletal muscle health and lead to muscle atrophy. Among various determinants of overall muscle health, the rate of muscle protein synthesis and degradation is an important parameter that eventually alters the fate of overall muscle health. In conditions of excessive skeletal muscle atrophy, including sarcopenia, the rate of muscle protein degradation usually exceeds the rate of protein synthesis. The availability of amino acids in the systemic circulation is a crucial step in muscle protein synthesis. The current review aims to consolidate the existing evidence on amino acids, highlight their mechanisms of action, and assess their roles and effectiveness in enhancing skeletal muscle health.

The global nutritional transition has led to the increased frequency and severity of chronic degenerative diseases worldwide, primarily driven by chronic inflammatory stress. At mealtimes, various pharmaceutical products aim to prevent such inflammatory stress, but they usually cause various systemic side effects. Therefore, the supplementation of natural and safe ingredients is a promising strategy to reduce the risk and severity of inflammatory stress-related diseases. Palmitoylethanolamide (PEA), an endocannabinoid-like mediator, has been extensively studied for its diverse actions, including anti-inflammatory, antimicrobial, immunostimulatory, neuroprotective, and pain-reducing effects, with high tolerability and safety in both animals and humans. Because of its multiple molecular targets and mechanisms of action, PEA has demonstrated therapeutic benefits in various diseases, including neurological, psychiatric, ophthalmic, metabolic, oncological, renal, hepatic, immunological, rheumatological, and gastrointestinal conditions. The current review highlights the roles and functions of PEA in various physiological and pathological conditions, further supporting its use as an important dietary agent.