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1.
Protein phosphorylation and kinases: Potential therapeutic targets in necroptosis.
Shi, Y, Wu, C, Shi, J, Gao, T, Ma, H, Li, L, Zhao, Y
European journal of pharmacology. 2024;:176508
Abstract
Necroptosis is a pivotal contributor to the pathogenesis of various human diseases, including those affecting the nervous system, cardiovascular system, pulmonary system, and kidneys. Extensive investigations have elucidated the mechanisms and physiological ramifications of necroptosis. Among these, protein phosphorylation emerges as a paramount regulatory process, facilitating the activation or inhibition of specific proteins through the addition of phosphate groups to their corresponding amino acid residues. Currently, the targeting of kinases has gained recognition as a firmly established and efficacious therapeutic approach for diverse diseases, notably cancer. In this comprehensive review, we elucidate the intricate role of phosphorylation in governing key molecular players in the necroptotic pathway. Moreover, we provide an in-depth analysis of recent advancements in the development of kinase inhibitors aimed at modulating necroptosis. Lastly, we deliberate on the prospects and challenges associated with the utilization of kinase inhibitors to modulate necroptotic processes.
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Melatonin, a phytohormone for enhancing the accumulation of high-value metabolites and stress tolerance in microalgae: Applications, mechanisms, and challenges.
Zhao, Y, Wang, Q, Gu, D, Huang, F, Liu, J, Yu, L, Yu, X
Bioresource technology. 2024;:130093
Abstract
High-value metabolites, such as carotenoids, lipids, and proteins, are synthesized by microalgae and find applications in various fields, including food, health supplements, and cosmetics. However, the potential of the microalgal industry to serve these sectors is constrained by low productivity and high energy consumption. Environmental stressors can not only stimulate the accumulation of secondary metabolites in microalgae but also induce oxidative stress, suppressing cell growth and activity, thereby resulting in a decrease in overall productivity. Using melatonin (MT) under stressful conditions is an effective approach to enhance the productivity of microalgal metabolites. This review underscores the role of MT in promoting the accumulation of high-value metabolites and enhancing stress resistance in microalgae under stressful and wastewater conditions. It discusses the underlying mechanisms whereby MT enhances metabolite synthesis and improves stress resistance. The review also offers new perspectives on utilizing MT to improve microalgal productivity and stress resistance in challenging environments.
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3.
Non-coding RNAs and leaf senescence: Small molecules with important roles.
Li, S, Zhao, Y, Tan, S, Li, Z
Plant physiology and biochemistry : PPB. 2024;:108399
Abstract
Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.
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Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study.
Wang, W, Huang, N, Zhuang, Z, Song, Z, Li, Y, Dong, X, Xiao, W, Zhao, Y, Jia, J, Liu, Z, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2024;(1)
Abstract
BACKGROUND Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies. METHODS We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings. RESULTS Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes. CONCLUSIONS This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.
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Clinical metabolomics characteristics of diabetic kidney disease: A meta-analysis of 1875 cases with diabetic kidney disease and 4503 controls.
Yuan, Y, Huang, L, Yu, L, Yan, X, Chen, S, Bi, C, He, J, Zhao, Y, Yang, L, Ning, L, et al
Diabetes/metabolism research and reviews. 2024;(3):e3789
Abstract
AIMS: Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD. MATERIALS AND METHODS We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis. RESULTS The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p < 0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered. CONCLUSIONS We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.
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6.
Molecular Dynamics Simulation and Experimental Study of Mechanical Properties of Graphene-Cement Composites.
Li, H, Lan, F, Wang, Y, Lin, X, Zhao, Y, Zhen, Q, Chen, D
Materials (Basel, Switzerland). 2024;(2)
Abstract
To investigate the mechanical properties of graphene (G) and calcium silicate hydrate (C-S-H) composites in different directions, molecular dynamics (MD) simulations and experiments were used, and the effects of temperature, loading rate, and graphene defects were also investigated. The experimental results show that the addition of graphene can improve the flexural, compressive, and tensile strength of the composite. The results of molecular dynamics simulation show that the addition of graphene in x and z directions can enhance the tensile strength of G/C-S-H in three directions, while the addition of graphene in y direction can reduce the tensile strength of G/C-S-H. At the same time, the tensile strength of G/C-S-H decreases with the increase in temperature and increases with the increase in loading rate. Meanwhile, the mechanical properties of G/C-S-H can be improved using a certain concentration of monatomic vacancy defects, diatomic vacancy defects, and S-W defects.
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7.
Adherence to direct or vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a long-term observational study.
Salmasi, S, Safari, A, De Vera, MA, Högg, T, Lynd, LD, Koehoorn, M, Barry, AR, Andrade, JG, Deyell, MW, Rush, KL, et al
Journal of thrombosis and thrombolysis. 2024;(3):437-444
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Abstract
Our objectives were to measure long-term adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and to identify patient factors associated with adherence. Using linked, population-based administrative data from British Columbia, Canada, an incident cohort of adults prescribed OACs for AF was identified. We calculated the proportion of days covered (PDC) as a time-dependent covariate for each 90-day window from OAC initiation until the end of follow-up. Associations between patient attributes and adherence were assessed using generalized mixed effect linear regression models. 30,264 patients were included. Mean PDC was 0.69 (SD 0.28) over a median follow-up of 6.7 years. 54% of patients were non-adherent (PDC < 0.8). After controlling for confounders, factors positively associated with adherence were number of drug class switches, history of stroke or transient ischemic attack, history of vascular disease, time since initiation, and age. Age > 75 years at initiation, polypharmacy (among VKA users only), and receiving DOAC (vs. VKA) were negatively associated with adherence. PDC decreased over time for VKA users and increased for DOAC users. Over half of AF patients studied were, on average, nonadherent to OAC therapy and missed 32% of their doses. Several patient factors were associated with higher or lower adherence, and adherence to VKA declined during therapy while DOAC adherence increased slightly over time. To min im ize the risk stroke, adherence-supporting interventions are needed for all patients with AF, particularly those aged > 75 years, those with prior stroke or vascular disease, VKA users with polypharmacy, and DOAC recipients.
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Antibiotic-induced ROS-mediated Fur allosterism contributes to Helicobacter pylori resistance by inhibiting arsR activation of mutS and mutY.
Xue, J, Li, W, Zhao, Y, Wang, L, Cheng, P, Zhang, L, Zheng, Y, Zhang, W, Bi, Y, Chen, Z, et al
Antimicrobial agents and chemotherapy. 2024;(4):e0167923
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Abstract
The increasing antibiotic resistance of Helicobacter pylori primarily driven by genetic mutations poses a significant clinical challenge. Although previous research has suggested that antibiotics could induce genetic mutations in H. pylori, the molecular mechanisms regulating the antibiotic induction remain unclear. In this study, we applied various techniques (e.g., fluorescence microscopy, flow cytometry, and multifunctional microplate reader) to discover that three different types of antibiotics could induce the intracellular generation of reactive oxygen species (ROS) in H. pylori. It is well known that ROS, a critical factor contributing to bacterial drug resistance, not only induces damage to bacterial genomic DNA but also inhibits the expression of genes associated with DNA damage repair, thereby increasing the mutation rate of bacterial genes and leading to drug resistance. However, further research is needed to explore the molecular mechanisms underlying the ROS inhibition of the expression of DNA damage repair-related genes in H. pylori. In this work, we validated that ROS could trigger an allosteric change in the iron uptake regulatory protein Fur, causing its transition from apo-Fur to holo-Fur, repressing the expression of the regulatory protein ArsR, ultimately causing the down-regulation of key DNA damage repair genes (e.g., mutS and mutY); this cascade increased the genomic DNA mutation rate in H. pylori. This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori, providing crucial insights for the prevention and control of antibiotic resistance in H. pylori.
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The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Lv, X, Wang, H, Chen, C, Zhao, Y, Li, K, Wang, Y, Wang, L, Fu, S, Liu, J
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:701-714
Abstract
AIM: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). METHODS Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. RESULTS Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.
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Advances in the Interaction between Food-Derived Nanoparticles and the Intestinal Barrier.
Jiang, B, Zhao, Y, Cao, Y, Sun, C, Lu, W, Fang, Y
Journal of agricultural and food chemistry. 2024;(7):3291-3301
Abstract
The maintenance of the intestinal barrier is crucial for the overall balance of the gut and the organism. Dysfunction of the intestinal barrier is closely associated with intestinal diseases. In recent years, due to the increased presence of nanoparticles (NPs) in the human diet, there has been a growing concern regarding the safety and potential impact of these NPs on gastrointestinal health. The interactions between food-derived NPs and the intestinal barrier are numerous. This review provides an introduction to the structure and function of the intestinal barrier along with a comprehensive summary of the interactions between food NPs and the intestinal barrier. Additionally, we highlight the potential connection between the food NPs-induced dysfunction of the intestinal barrier and inflammatory bowel disease. Finally, we discuss the enhancement of food NPs on the repair of the intestinal barrier damage and the nutrients absorption. This review holds significant importance in furthering our understanding of the regulatory mechanisms of food-derived NPs on the intestinal barrier.