Frailty and risk of systemic atherosclerosis: A bidirectional Mendelian randomization study.

BACKGROUND: Numerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids. METHODS: We obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis. RESULTS: Genetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12-1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05-3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08-1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78-0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI. CONCLUSION: Our study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations.

Injectable hydrogels as promising in situ therapeutic platform for cartilage tissue engineering.

Injectable hydrogels are gaining prominence as a biocompatible, minimally invasive, and adaptable platform for cartilage tissue engineering. Commencing with their synthesis, this review accentuates the tailored matrix formulations and cross-linking techniques essential for fostering three-dimensional cell culture and melding with complex tissue structures. Subsequently, it spotlights the hydrogels' enhanced properties, highlighting their augmented functionalities and broadened scope in cartilage tissue repair applications. Furthermore, future perspectives are advocated, urging continuous innovation and exploration to surmount existing challenges and harness the full clinical potential of hydrogels in regenerative medicine. Such advancements are crucial for validating the long-term efficacy and safety of hydrogels, positioning them as a promising direction in regenerative medicine to address cartilage-related ailments.

Regulatory Basis of Adipokines Leptin and Adiponectin in Epilepsy: from Signaling Pathways to Glucose Metabolism.

Epilepsy is a common and severe neurological disorder in which impaired glucose metabolism leads to changes in neuronal excitability that slow or promote the development of epilepsy. Leptin and adiponectin are important mediators regulating glucose metabolism in the peripheral and central nervous systems. Many studies have reported a strong association between epilepsy and these two adipokines involved in multiple signaling cascades and glucose metabolism. Due to the complex regulatory mechanisms between them and various signal activation networks, their role in epilepsy involves many aspects, including the release of inflammatory mediators, oxidative damage, and neuronal apoptosis. This paper aims to summarize the signaling pathways involved in leptin and adiponectin and the regulation of glucose metabolism from the perspective of the pathogenesis of epilepsy. In particular, we discuss the dual effects of leptin in epilepsy and the relationship between antiepileptic drugs and changes in the levels of these two adipokines. Clinical practitioners may need to consider these factors in evaluating clinical drugs. Through this review, we can better understand the specific involvement of leptin and adiponectin in the pathogenesis of epilepsy, provide ideas for further exploration, and bring about practical significance for the treatment of epilepsy, especially for the development of personalized treatment according to individual metabolic characteristics.

A prognostic model of patients with ovarian mucinous adenocarcinoma: a population-based analysis.

BACKGROUND: Ovarian mucinous carcinoma is a disease that requires unique treatment. But for a long time, guidelines for ovarian serous carcinoma have been used for the treatment of ovarian mucinous carcinoma. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with ovarian mucinous adenocarcinoma. METHODS: In this study, patients initially diagnosed with ovarian mucinous adenocarcinoma from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into the training group and the validation group at a ratio of 7:3. Independent risk factors for OS and CSS were determined by multivariate Cox regression analysis, and nomograms were constructed and validated. RESULTS: In this study, 1309 patients with ovarian mucinous adenocarcinoma were finally screened and randomly divided into 917 cases in the training group and 392 cases in the validation group according to a 7:3 ratio. Multivariate Cox regression analysis showed that the independent risk factors of OS were age, race, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. Independent risk factors of CSS were age, race, marital, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. According to the above results, the nomograms of OS and CSS in ovarian mucinous adenocarcinoma were constructed. In the training group, the C-index of the OS nomogram was 0.845 (95% CI: 0.821-0.869) and the C-index of the CSS nomogram was 0.862 (95%CI: 0.838-0.886). In the validation group, the C-index of the OS nomogram was 0.843 (95% CI: 0.810-0.876) and the C-index of the CSS nomogram was 0.841 (95%CI: 0.806-0.876). The calibration curve showed the consistency between the predicted results and the actual results, indicating the high accuracy of the nomogram. CONCLUSION: The nomogram provides 3-year and 5-year OS and CSS predictions for patients with ovarian mucinous adenocarcinoma, which helps clinicians predict the prognosis of patients and formulate appropriate treatment plans.

Pannexin-1 Channel Regulates ATP Release in Epilepsy.

With the deepening of research on epilepsy in recent decades, great progress has been made in the diagnosis and treatment of the disease. However, the clinical outcome remains unsatisfactory due to the confounding symptoms and complications, as well as complex intrinsic pathogenesis. A better understanding of the pathogenesis of epilepsy should be able to hinder the progress of the disease and improve the therapeutic effectiveness. Since the discovery of pannexin (Panx), unremitting efforts on the study of this gap junction protein family member have revealed its role in participating in the expression of various physiopathological processes. Among them, the activation or inhibition of Panx channel has been shown to regulate the release of adenosine triphosphate (ATP) and other signals, which is very important for the onset and control of nervous system diseases including epilepsy. In this article, we summarize the factors influencing the regulation of Panx channel opening, hoping to find a way to interfere with the activation or inhibition of Panx channel that regulates the signal transduction of ATP and other factors so as to control the progression of epilepsy and improve the quality of life of epileptic patients who fail to respond to the existing medical therapies and those at risk of surgical treatment.

Increased expression of Triad1 is associated with neuronal apoptosis after intracerebral hemorrhage in adult rats.

Objective: It has been demonstrated that Triad1 (2 RING fingers and double RING finger linked 1) negatively regulates myeloid cell growth and induces cell apoptosis. However, its functions in intracerebral hemorrhage (ICH) disease have not been conducted. In this study, the role of Triad1 in rat model of ICH was explored.Methods: We observe an increasing expression of Triad1 in areas adjacent to hematoma after ICH. Immunofluorescence shows that Triad1 is colocalized with neurons, while not microglia or astrocyte, indicates its correlation with neuronal activities following ICH.Results: As neuronal apoptosis is the most crucial event in ICH disease, the expression of active caspase-3 and p53 is also enhanced around the hematoma, which is consistent with Triad1 in expression tendency. In turn, Triad1 depletion in primary cortical neurons decreased the apoptosis of neurons after using Triad1 shRNA.Conclusion: We conclude that inhibition of Triad1 expression might protect the brain from secondary damage following ICH.