High Glucose Treatment Induces Nuclei Aggregation of Microvascular Endothelial Cells via the - Pathway.

Background: Hyperglycemia is a major contributor to endothelial dysfunction and blood vessel damage, leading to severe diabetic microvascular complications. Despite the growing body of research on the underlying mechanisms of endothelial cell (EC) dysfunction, the available drugs based on current knowledge fall short of effectively alleviating these complications. Therefore, our endeavor to explore novel insights into the cellular and molecular mechanisms of endothelial dysfunction is crucial for the field.

Correlation of intracranial and extracranial carotid atherosclerotic plaque characteristics with ischemic stroke recurrence: a high-resolution vessel wall imaging study.

Objectives: To evaluate the ability of the plaque characteristics of extracranial carotid and intracranial arteries to predict large atherosclerotic ischemic stroke recurrence via head and neck combined high-resolution vessel wall imaging (HR-VWI).

Methods: This prospective cohort study included 169 patients with large atherosclerotic ischemic stroke who underwent head and neck combined HR-VWI from April 2022 to May 2023. The baseline clinical data and atherosclerotic plaque characteristics of the intracranial and extracranial carotid arteries were collected, and the patients were followed up for 1 year, with the endpoint event defined as recurrent ischemic stroke.

Controlins I-X, Resin Glycosides from the Seeds of and Their Biological Activities.

Ten new resin glycosides, controlins I-X (-), were isolated from the seeds of . Their structures were established by spectroscopic analysis as well as by chemical means. Compounds were identified as glycosidic acid methyl esters, considered as artifacts generated via transesterification with MeOH from natural resin glycosides.

Diagnostic performance of microRNAs for predicting response to transarterial chemoembolization in hepatocellular carcinoma: a meta-analysis.

Purpose: To provide a detailed pooled analysis of the diagnostic accuracy of microRNAs (miRNAs) in predicting the response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC).

Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science to identify studies assessing the diagnostic performance of miRNAs in predicting TACE response in HCC. Two independent reviewers performed quality assessment and data extraction using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.

Cystine-Modified Lignin-Copper Coordination Nanocarriers Improve the Therapeutic Efficacy of Tyrosine Kinase Inhibition via Cuproptosis.

The clinical application of tyrosine kinase inhibitors (TKIs) is rapidly growing and has emerged as a cornerstone in the treatment of both solid tumors and hematologic malignancies. However, resistance to TKI targets and disease progression remain inevitable. Nanocarrier-mediated delivery has emerged as a promising strategy to overcome the limitations of the TKI application.

Advances in the Development and Application of Human Organoids: Techniques, Applications, and Future Perspectives.

Organoids are three-dimensional (3D) cell cultures derived from human pluripotent stem cells or adult stem cells that recapitulate the cellular heterogeneity, structure, and function of human organs. These microstructures are invaluable for biomedical research due to their ability to closely mimic the complexity of native tissues while retaining human genetic material. This fidelity to native organ systems positions organoids as a powerful tool for advancing our understanding of human biology and for enhancing preclinical drug testing.

Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from .

The bacterium is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells.

Research on detection methods of related substances and degradation products of the antitumor drug selpercatinib.

Background: Selpercatinib, a selective RET kinase inhibitor, is approved for treating various cancers with RET gene mutations such as RET-rearranged thyroid cancer and non-small cell lung cancer. The presence of process-related and degradation impurities in its active pharmaceutical ingredient (API) can significantly affect its safety and effectiveness. However, research on detecting these impurities is limited.

The Regulation of Messenger RNAs and Biological Pathways by Long Non-Coding RNAs and Circular RNAs in Ischemic Stroke.

Our aim was to evaluate the regulation of messenger RNAs (mRNAs) and biological pathways by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in ischemic stroke. We employed weighted gene co-expression network analysis (WGCNA) to construct two co-expression networks for mRNAs with circRNAs and lncRNAs, respectively, to investigate their association with ischemic stroke. We compared the overlap of mRNAs and biological pathways in the stroke-associated modules of the two networks.

Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation.

Chemodynamic therapy (CDT) is an emerging antitumor strategy utilizing iron-initiated Fenton reaction to destroy tumor cells by converting endogenous HO into highly toxic hydroxyl radical (OH). However, the intratumoral overexpressed glutathione (GSH) and deficient acid greatly reduce CDT efficacy because of OH scavenging and decreased OH production efficiency. Even worse, the various physiological barriers, especially in glioma, further put the brakes on the targeted delivery of Fenton agents.

Enhanced antitumor efficacy of STING agonist MSA-2 by lipid nanoparticles delivering circular IL-23 mRNA and platinum-modified MSA-2 combination.

A next-generation STING agonist MSA-2 is a promising tumor immunotherapy strategy. However, the methods for improving the anti-tumor efficacy of MSA-2 are a lot of effort. We have demonstrated antitumor effect of platinum-modified MSA-2 (MSA-2-Pt) was better than MSA-2.

Successful Mechanical Thrombectomy for Bilateral Anterior Cerebral Artery Occlusions in a Rare Anatomical Variant: A Case Report.

Background: Acute ischemic stroke (AIS) is usually caused by acute occlusion of the cerebral artery. Bilateral anterior cerebral arteries (ACAs) originating from the anterior communicating branch of the same internal carotid artery are a rare anatomical variation in clinical practice. Mechanical thrombectomy (MT) of simultaneous acute occlusion of the bilateral ACAs with this variation has rarely been reported.

Enhanced co-expression of TIGIT and PD-1 on γδ T cells correlates with clinical features and laboratory parameters in patients with primary Sjögren's syndrome.

Objectives: The research aimed to assess the proportions of Gamma delta (γδ) T cells and the expression levels of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, Tim-3, and PD-1 on γδ T cells in the peripheral blood of patients diagnosed with primary Sjögren's syndrome (pSS), and to evaluate the clinical significance of these findings.

Methods: Utilizing flow cytometry, we investigated the proportion of γδ T cells and the expression of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, PD-1, and Tim-3 on γδ T cells in 37 patients diagnosed with pSS and 28 healthy controls (HC). Moreover, we explored the potential associations between the proportion of γδ T cells, TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells with clinical symptoms and laboratory parameters.

Atherogenic index of plasma and cardiovascular outcomes in female patients undergoing percutaneous coronary intervention: insights from a retrospective cohort study.

In this research, we explored the relationship between the AIP and clinical outcomes in patients undergoing PCI. A total of 2533 consecutive patients who underwent PCI were included in this retrospective cohort study, and the data from 2098 patients were used. AIP is calculated based on the log (triglycerides/high-density lipoprotein-cholesterol).

Stromal Cell Derived Factor-1 Promotes Hepatic Insulin Resistance via Inhibiting Hepatocyte Lipophagy.

Saturated fatty acid (SFA) accumulation in liver decreases hepatocyte lipophagy, a type of selective autophagy that degrades intracellular lipid droplets, leading to hepatic insulin resistance (IR), which contributes to simultaneous increases in liver glucose production and fat synthesis, resulting in hyperglycemia and dyslipidemia traits of type 2 diabetes mellitus (T2DM). Stromal cell derived factor-1 (SDF-1), a cytokine produced by hepatocytes, inhibits autophagy. In this study, we evaluated the hypothesis that SDF-1 promoted hepatic IR via inhibiting hepatocyte lipophagy during T2DM.

METTL14-mediated depression of NEIL1 aggravates oxidative damage and mitochondrial dysfunction of lens epithelial cells through regulating KEAP1/NRF2 pathways.

Abnormal base excision repair (BER) pathway and N6-methyladenosine (m6A) of RNA have been proved to be significantly related to age-related cataract (ARC) pathogenesis. However, the relationship between the Nei Endonuclease VIII-Like1 (NEIL1) gene (a representative DNA glycosylase of BER pathway) and its m6A modification remains unclear. Here, we showed that the expression of NEIL1 was decreased in the ARC anterior lens capsules and HO-stimulated SRA01/04 cells.

A Multi-Scale Computational Model of the Hepatic Circulation Applied to Predict the Portal Pressure After Transjugular Intrahepatic Portosystemic Shunt (TIPS).

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertension. In clinical practice, the diameter of the stent forming a shunt is usually selected empirically, which will influence the postoperative portal pressure. Clinical studies found that inappropriate portal pressure after TIPS is responsible for poor prognosis; however, there is no scheme to predict postoperative portal pressure.

ACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury.

Acute myocardial infarction (AMI) is associated with well-established metabolic risk factors, especially hyperlipidemia and obesity. Myocardial ischemia-reperfusion injury (mIRI) significantly offsets the therapeutic efficacy of revascularization. Previous studies indicated that disrupted lipid homeostasis can lead to lipid peroxidation damage and inflammation, yet the underlying mechanisms remain unclear.

Methyl Canthin-6-one-2-carboxylate Inhibits the Activation of the NLRP3 Inflammasome in Synovial Macrophages by Upregulating Nrf2 Expression.

Rheumatoid arthritis (RA) is an autoimmune disorder that leads to severe cartilage deterioration and synovial impairment in the joints. Previous studies have indicated that the aberrant activation of the NLRP3 inflammasome in synovial macrophages plays a significant role in the pathogenesis of RA and has been regarded as a therapeutic target for the disease. In this study, we synthesized a novel canthin-6-one alkaloid, namely methyl canthin-6-one-2-carboxylate (Cant), and assessed its effects on NLRP3 inflammasome activation in macrophages.

Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway.

Rheumatoid arthritis (RA), a form of autoimmune inflammation, is marked by enduring synovial inflammation and the subsequent impairment of joint function. Despite the availability of conventional treatments, they are often marred by significant side effects and the associated high costs. Plant-derived extracellular vesicles (PEVs) offer a compelling alternative, owing to their abundant availability, affordability, low immunogenicity, high biocompatibility, and feasibility for large-scale production.

Ursonic Acid Ameliorates HO-Induced Oxidative Damage in PC12 Cells and Prolonged the Lifespan in C. elegans by Activating MAPKs/Nrf2/HO-1 Signaling Pathway.

Growing evidence suggests that plant compounds are emerging as a tremendous source for slowing the onset and progression of Alzheimer's disease (AD). Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid with some hypoglycemic, anticancer, and antiinflammatory activities. However, the pharmacological effects of UNA on AD are still unknown.

Baseline and early changes in CT body composition can predict recurrence-free survival after radical gastrectomy: A sex-specific study.

Objective: This study aimed to explore the predictive value of baseline CT body composition and its early changes on recurrence-free survival (RFS) following radical gastrectomy, while also assessing potential sex-related differences.

Methods: We conducted a retrospective analysis of gastric cancer (GC) patients with confirmed pathology from October 2019 to May 2023. All patients underwent preoperative and postoperative CT scans to assess visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle density (SMD), along with calculating their respective rates of change.