UNASSIGNED: Although percutaneous coronary intervention (PCI) is recommended by guidelines, data from the real world suggest that elderly non-ST-segment elevation myocardial infarction (NSTEMI) patients have a low rate of PCI and a high death rate. Lymphocyte to C-reactive protein ratio (LCR), a novel inflammatory marker, has been shown to be associated with prognosis in a variety of diseases. However, the relationship between LCR and in-hospital cardiac death in elderly NSTEMI patients is unclear. The aim of this study was to investigate the effect of LCR on in-hospital cardiac death in elderly NSTEMI patients without PCI therapy.
UNASSIGNED: This was a single-center retrospective observational study, consecutively enrolled elderly (≥75 years) patients diagnosed with NSTEMI and without PCI from February 2019 to February 2024. LCR was defined as lymphocyte count to C-reactive protein ratio. The endpoint of observation was in-hospital cardiac death. The predictive efficacy of the old and new models was evaluated by the net reclassification index (NRI) and the integrated discriminant improvement index (IDI).
UNASSIGNED: A total of 506 patients were enrolled in this study, and in-hospital cardiac death occurred in 54 patients (10.7%). Univariate logistic regression analysis showed that left ventricular ejection fraction, LCR, Killip ≥2, and N-terminal B-type natriuretic peptide proteins (NT-proBNP) were associated with the occurrence of in-hospital cardiac death. After adjusting for potential confounders, the results showed that NT-proBNP (OR = 1.695, 95% CI: 1.238-2.322) and LCR (OR = 0.262, 95% CI: 0.072-0.959) were independent risk factors for in-hospital cardiac death. After the addition of LCR to NT-proBNP, the predictive ability of the new model for in-hospital cardiac death was significantly improved (NRI = 0.278, P = 0.030; IDI = 0.017, P < 0.001).
UNASSIGNED: Lower LCR is an independent risk factor for in-hospital cardiac death in elderly NSTEMI patients without PCI, and integrating LCR improves the prediction of in-hospital cardiac death occurrence.

Isoproterenol (ISO) administration is a well-established model for inducing myocardial injury, replicating key features of human myocardial infarction (MI). The ensuing inflammatory response plays a pivotal role in the progression of adverse cardiac remodeling, characterized by myocardial dysfunction, fibrosis, and hypertrophy. The Mst1/Hippo signaling pathway, a critical regulator of cellular processes, has emerged as a potential therapeutic target in cardiovascular diseases. This study investigates the role of Mst1 in ISO-induced myocardial injury and explores its underlying mechanisms. Our findings demonstrate that Mst1 ablation in cardiomyocytes attenuates ISO-induced cardiac dysfunction, preserving cardiomyocyte viability and function. Mechanistically, Mst1 deletion inhibits cardiomyocyte apoptosis, oxidative stress, and calcium overload, key contributors to myocardial injury. Furthermore, Mst1 ablation mitigates endoplasmic reticulum (ER) stress and mitochondrial fission, both of which are implicated in ISO-mediated cardiac damage. Additionally, Mst1 plays a crucial role in modulating the inflammatory response following ISO treatment, as its deletion suppresses pro-inflammatory cytokine expression and neutrophil infiltration. To further investigate the molecular mechanisms underlying ISO-induced myocardial injury, we conducted a bioinformatics analysis using the GSE207581 dataset. GO and KEGG pathway enrichment analyses revealed significant enrichment of genes associated with DNA damage response, DNA repair, protein ubiquitination, chromatin organization, autophagy, cell cycle, mTOR signaling, FoxO signaling, ubiquitin-mediated proteolysis, and nucleocytoplasmic transport. These findings underscore the significance of Mst1 in ISO-induced myocardial injury and highlight its potential as a therapeutic target for mitigating adverse cardiac remodeling. Further investigation into the intricate mechanisms of Mst1 signaling may pave the way for novel therapeutic interventions for myocardial infarction and heart failure.

Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.

This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from databases like PubMed, EBSCO (EDS), and Google Scholar, culminating in the inclusion of 41 studies. The quality of these studies was rigorously assessed to ensure the clarity of objectives, coherence in arguments, comprehensive literature coverage, and depth of critical analysis. Findings revealed that moderate exercise enhances antioxidant defenses through hormesis, while excessive exercise may exacerbate oxidative stress. The review also highlights that while natural dietary antioxidants are beneficial, high-dose supplements could impede the positive adaptations to exercise. In conclusion, the review calls for more focused research on tailored exercise and nutrition plans to further understand these complex interactions and optimize the health outcomes for athletes and the general population.

UNASSIGNED: Stomolophus meleagris envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive because of the complicated venom components. The biological activity and molecular regulation mechanism of Troxerutin (TRX) was firstly examined as a potential treatment for jellyfish dermatitis.
UNASSIGNED: We examined the inhibit effects of the TRX on tentacle extract (TE) obtained from S. meleagris in vivo and in vitro using the mice paw swelling models and corresponding assays for Enzyme-Linked Immunosorbent Assay (ELISA) Analysis, cell counting kit-8 assay, flow cytometry, respectively. The mechanism of TRX on HaCaT cells probed the altered activity of relevant signaling pathways by RNA sequencing and verified by RT-qPCR, Western blot to further confirm protective effects of TRX against the inflammation and oxidative damage caused by TE.
UNASSIGNED: TE significantly induced the mice paw skin toxicity and accumulation of inflammatory cytokines and reactive oxygen species in vivo and vitro. Moreover, a robust increase in the phosphorylation of mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways was observed. While, the acute cutaneous inflammation and oxidative stress induced by TE were significantly ameliorated by TRX treatment. Notablly, TRX suppressed the phosphorylation of MAPK and NF-κB by initiating the nuclear factor erythroid 2-related factor 2 signaling pathway, which result in decreasing inflammatory cytokine release.
UNASSIGNED: TRX inhibits the major signaling pathway responsible for inducing inflammatory and oxidative damage of jellyfish dermatitis, offering a novel therapy in clinical applications.

BACKGROUND: Circular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown.
RESULTS: By using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P < 0.05 cutoff criteria. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of upregulated mRNAs showed enrichments in immune system process and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Infiltration of inflammatory cells and increased inflammatory cytokines were observed in diabetic PGs. Seven differently expressed circRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks analysis. PPAR signaling pathway was primarily enriched through analysis of circRNA-mRNA networks. Moreover, the circRNA-miRNA-mRNA networks highlighted an enrichment in the regulation of actin cytoskeleton.
CONCLUSIONS: The inflammatory response is elevated in diabetic PGs. The selected seven distinct circRNAs may attribute to the injury of diabetic PG by modulating inflammatory response through PPAR signaling pathway and actin cytoskeleton in diabetic PGs.

West Nile virus (WNV) is an important neurotropic virus that accounts for the emergence of human arboviral encephalitis and meningitis. The interaction of WNV with signaling pathways plays a key role in controlling WNV infection. We have investigated the roles of the AKT and ERK pathways in supporting WNV propagation and modulating the inflammatory response following WNV infection. WNV established a productive infection in neuronal cell lines originated from human and mouse. Expression of IL-11 and TNF-α was markedly up-regulated in the infected human neuronal cells, indicating elicitation of inflammation response upon WNV infection. WNV incubation rapidly activated signaling cascades of AKT (AKT-S6-4E-BP1) and ERK (MEK-ERK-p90RSK) pathways. Treatment with AKT inhibitor MK-2206 or MEK inhibitor U0126 abrogated WNV-induced AKT or ERK activation. Strong activation of AKT and ERK signaling pathways could be detectable at 24 h after WNV infection, while such activation was abolished at 48 h post infection. U0126 treatment or knockdown of ERK expression significantly increased WNV RNA levels and viral titers and efficiently decreased IL-11 production induced by WNV, suggesting the involvement of ERK pathway in WNV propagation and IL-11 induction. MK-2206 treatment enhanced WNV RNA replication accompanied with a moderate decrease in IL-11 production. These results demonstrate that engagement of AKT and ERK signaling pathways facilitates viral infection and may be implicated in WNV pathogenesis.

BMP and activin membrane-bound inhibitor (BAMBI) is a transmembrane glycoprotein, known as a pseudo-receptor for TGFβ, as, while its extracellular domain is similar to that of type I TGFβ receptors, its intracellular structure is shorter and lacks a serine/threonine phosphokinase signaling motif. BAMBI can regulate numerous biological phenomena, including glucose and lipid metabolism, inflammatory responses, and cell proliferation and differentiation. Furthermore, abnormal expression of BAMBI at the mRNA and protein levels contributes to various human pathologies, including obesity and cancer. In the present review, the structure of BAMBI is briefly introduced and its associated signaling pathways and physiological functions are described. Understanding of BAMBI structure and function may contribute to knowledge regarding the occurrence of diseases, including obesity and diabetes, among others. The present review provides a theoretical foundation for the development of BAMBI as a potential biomarker or therapeutic target.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder, with a global prevalence of 25%. Currently, there remains no approved therapy. Ramulus mori (Sangzhi) alkaloids (SZ-As), a novel natural medicine, have achieved comprehensive benefits in the treatment of type 2 diabetes; however, few studies have focused on its role in ameliorating hepatic lipid metabolic disturbance. Herein, the therapeutic effect and mechanism of SZ-As on a high-fat diet (HFD) combined with streptozotocin (STZ)-induced NAFLD mice were investigated via incorporating transcriptomics and lipidomics. SZ-As reduced body weight and hepatic lipid levels, restored pathological alternation and converted the blood biochemistry perturbations. SZ-A treatment also remarkedly inhibited lipogenesis and enhanced lipolysis, fatty acid oxidation and thermogenesis. Transcriptomics analysis confirmed that SZ-As mainly altered fatty acid oxidative metabolism and the TNF signaling pathway. SZ-As were further demonstrated to downregulate inflammatory factors and effectively ameliorate hepatic inflammation. Lipidomics analysis also suggested that SZ-As affected differential lipids including triglyceride (TG) and phosphatidylcholine (PC) expression, and the main metabolic pathways included glycerophospholipid, sphingomyelins and choline metabolism. Collectively, combined with transcriptomics and metabolomics data, it is suggested that SZ-As exert their therapeutic effect on NAFLD possibly through regulating lipid metabolism pathways (glycerophospholipid metabolism and choline metabolism) and increasing levels of PC and lysophosphatidylcholine (LPC) metabolites. This study provides the basis for more widespread clinical applications of SZ-As.

Background: Lactate, as an essential clinical evaluation index of septic shock, is crucial in the incidence and progression of septic shock. This study aims to investigate the differential expression, regulatory relationship, clinical diagnostic efficacy, and immune infiltration of lactate metabolism-related genes (LMGs) in septic shock. Methods: Two sepsis shock datasets (GSE26440 and GSE131761) were screened from the GEO database, and the common differentially expressed genes (DEGs) of the two datasets were screened out. LMGs were selected from the GeneCards database, and lactate metabolism-related DEGs (LMDEGs) were determined by integrating DEGs and LMGs. Protein-protein interaction networks, mRNA-miRNA, mRNA-RBP, and mRNA-TF interaction networks were constructed using STRING, miRDB, ENCORI, and CHIPBase databases, respectively. Receiver operating characteristic (ROC) curves were constructed for each of the LMDEGs to evaluate the diagnostic efficacy of the expression changes in relation to septic shock. Finally, immune infiltration analysis was performed using ssGSEA and CIBERSORT. Results: This study identified 10 LMDEGs, including LDHB, STAT3, LDHA, GSR, FOXM1, PDP1, GCDH, GCKR, ABCC1, and CDKN3. Enrichment analysis revealed that DEGs were significantly enriched in pathways such as pyruvate metabolism, hypoxia pathway, and immune-inflammatory pathways. PPI networks based on LMDEGs, as well as 148 pairs of mRNA-miRNA interactions, 243 pairs of mRNA-RBP interactions, and 119 pairs of mRNA-TF interactions were established. ROC curves of eight LMDEGs (LDHA, GSR, STAT3, CDKN3, FOXM1, GCKR, PDP1, and LDHB) with consistent expression patterns in two datasets had an area under the curve (AUC) ranging from 0.662 to 0.889. The results of ssGSEA and CIBERSORT both showed significant differences in the infiltration of various immune cells, including CD8 T cells, T regulatory cells, and natural killer cells, and LMDEGs such as STAT3, LDHB, LDHA, PDP1, GSR, FOXM1, and CDKN3 were significantly associated with various immune cells. Conclusion: The LMDEGs are significantly associated with the immune-inflammatory response in septic shock and have a certain diagnostic accuracy for septic shock.