Macrophages play a crucial role in cardiac remodeling and prognosis after myocardial infarction (MI). Our previous studies have built a scalable method for preparing scaled stem cell nanovesicles (NVs) and demonstrated their remarkable reparative effects on ischemic heart disease. To further enhance the targeted reparative capabilities of the NVs toward injured myocardium, we employed a dual modification strategy involving platelet membrane coating and miR-181a-5p loading, creating a nanovesicle termed P-181-NV. This study aimed to investigate the efficacy of P-181-NV in targeted reparative interventions for damaged myocardium and to reveal the underlying mechanisms involved. After successful construction and characteristic analysis of P-181-NV, the in vivo tracking techniques demonstrated a significant enhancement in the targeting capacity of P-181-NV toward the injured myocardium. Moreover, P-181-NV showed marked improvements in cardiac function and remodeling as observed through ultrasound echocardiography and Masson's trichrome staining. Furthermore, P-181-NV significantly augmented myocardial cell viability, angiogenic potential, and the polarization ratio of the anti-inflammatory macrophages. The findings of this study underscore the pivotal role of platelet-membrane-coated and miR-181a-5p modified stem cell nanovesicles in facilitating postmyocardial infarction cardiac repair. By modulating macrophage polarization, P-181-NV offers a promising approach for enhancing the efficacy of targeted reparative interventions for damaged myocardium. These results contribute to our understanding of the potential of nanovesicles as therapeutic agents for cardiac repair and regeneration, presenting avenues for future research and clinical applications.

Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes. The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011–2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations. In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04–1.16) and the FMI (OR = 1.08, 95% CI = 1.04–1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02–1.16) and the FMI (OR 1.07, 95% CI 1.02–1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear. Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear.

Background: G1, a specific agonist targeting the G protein–coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high‐fat feeding scenarios unexplored.Material and Methods: To address this gap, our study employed an ovariectomized high‐fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction.Results: The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high‐fat diet. Moreover, the combined impact of G1 treatment and a high‐fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance.Conclusions: These findings indicate that G1 treatment is influenced by a high‐fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy.

Based on the transforming growth factor β-activated kinase 1 (TAK1)-p38 mitogen-activated protein kinase (p38MAPK)-nucleotide-binding oligo-like receptor protein 3 (NLRP3) signalling pathway, the protective effect and mechanism of isoproterennaline (ISO)-induced cinnamaldehyde on inflammatory injury in ventricular rats were investigated. Fifty male SPF SD rats were randomly assigned to the normal group, model group, propranolol group, cinnamaldehyde low-dose group or cinnamaldehyde high-dose group. The ventricular arrhythmia model was constructed using the "6 + 1" ISO injection method. The rats in the propranolol group were given propranolol 15 mg·(kg d)⁻¹, those in the low and high-dose groups were given cinnamaldehyde 20 mg·(kg d)⁻¹ and 50 mg·(kg d)⁻¹, respectively, and those in the control and model groups received an equal volume of 0.9% NaCl solution. Changes in the serum troponin (cTnI), creatine kinase isoenzyme (CK-MB), and interleukin-1β (IL-1β) levels in SD rats were determined by ELISA. HE staining was used to observe the tissue morphology of heart disease. The mRNA expression of IL-1β and NLRP3 was determined by RT‒PCR. Mitochondrial damage was observed by transmission electron microscopy. The expression of reactive oxygen species (ROS) was detected by immunofluorescence. Western blot or immunohistochemical detection of the protein expression of IL-1β, NLRP3, TAK1, phospho-TAK1 (p-TAK1), p38MAPK, phospho-p38MAPK (p-p38MAPK), nuclear factor-κB (NF-κB),and phospho-NF-κB (p-NF-κB) was also performed. Data analysis was performed using SPSS 25.0 software. In the control SD rats, there were no obvious ventricular arrhythmias on ECG, the cardiac tissue and mitochondria were basically normal, the serum IL-1β level was low, and the expression of myocardial IL-1β, NLRP3, ROS, p-TAK1, p-p38MAPK and p-NF-κB was weak. Compared with the control group, the model group of SD rats had significant increases in ventricular arrhythmia and arrhythmia scores according to ECG (P < 0.01). Myocardial histopathological injury, cardiac weight index (HWI) and increases in serum cTnI and CK-MB levels were detected (P < 0.01). Additionally, mitochondrial damage in myocardial tissue, increased ROS fluorescence intensity, and elevated expression of myocardial p-TAK1, p-p38MAPK and p-NF-κB were detected(P < 0.01). The protein and mRNA expression of inflammation-related factors NLRP3 and IL-1β were increased (P < 0.01 or P < 0.05). Compared with those in the model group, the arrhythmia scores were decreased in the three treatment groups (P < 0.01 or P < 0.05). Cardiac histopathological morphology was significantly improved, and HWI and myocardial injury-related indicators were decreased(P < 0.01 or P < 0.05). Damaged mitochondria were significantly improved, and the expression of ROS, p-TAK1, p-p38MAPK, and p-NF-κB were decreased. The expression of inflammation-related factors in serum and myocardial tissue was decreased (P < 0.01 or P < 0.05). TAK1-p38MAPK-NLRP3 signalling is enhanced in SD rats with ventricular arrhythmia. Cinnamaldehyde can regulate TAK1-p38MAPK-NLRP3 signalling, reduce cardiomyocyte pyroptosis, antagonize myocardial inflammatory injury and protect cardiomyocytes by inhibiting oxidative stress.