The efficacy of hypothermia combined with thrombolysis or mechanical thrombectomy on acute ischemic stroke: a systematic review and meta-analysis.

Background: Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. In recent years, the safety and efficacy of hypothermia combining thrombolysis or mechanical thrombectomy have attracted widespread attention. The primary objective of the study was to evaluate the effectiveness and safety of hypothermia by combining reperfusion therapy in acute ischemic stroke patients.

Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients.

Recently, oncolytic virus (OV) therapy has shown great promise in treating malignancies. However, intravenous safety and inherent lack of immunity are two significant limitations in clinical practice. Herein, we successfully developed a recombinant Newcastle disease virus with porcine α1,3GT gene (NDV-GT) triggering hyperacute rejection.

Selenium-Doped Copper Formate Nanozymes with Antisenescence and Oxidative Stress Reduction for Atherosclerosis Treatment.

Atherosclerosis, resulting from chronic inflammation of the arterial wall, serves as the underlying cause of multiple major cardiovascular diseases. Current anti-inflammatory therapies often exhibit limited and unsatisfactory efficacy. To address this, we have designed a selenium-doped copper formate (Cuf-Se) nanozyme for the treatment of atherosclerosis, which possesses superoxide dismutase (SOD) and glutathione peroxidase (GPx)-like activities.

Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin.

Exosomes derived from microRNA-540-3p overexpressing mesenchymal stem cells promote immune tolerance the CD74/nuclear factor-kappaB pathway in cardiac allograft.

Background: Heart transplantation is a crucial intervention for severe heart failure, yet the challenge of organ rejection is significant. Bone marrow mesenchymal stem cells (BMSCs) and their exosomes have demonstrated potential in modulating T cells, dendtitic cells (DCs), and cytokines to achieve immunomodulatory effects. DCs, as key antigen-presenting cells, play a critical role in shaping immune responses by influencing T-cell activation and cytokine production.

Pyruvate Kinase M2-Responsive Release of Paclitaxel and Indoleamine 2,3-Dioxygenase Inhibitor for Immuno-Chemotherapy of Nonsmall Cell Lung Cancer.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC) but it can induce indoleamine 2,3-dioxygenase (IDO) activation, which severely lowers down its immuno-chemotherapeutic effect. To address this issue, a smart peptide hydrogelator Nap-Phe-Phe-Phe-Lys-Ser-Thr-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-T), which co-assembles with PTX and an IDO inhibitor GDC0919 to form a hydrogel GP@Gel Nap-T, is rationally designed. Upon specific phosphorylation by pyruvate kinase M2 (PKM2), an overexpressed biomarker of NSCLC, Nap-T is gradually converted to Nap-Phe-Phe-Phe-Lys-Ser-Thr(HPO)-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-Tp), leading to dehydrogelation and sustained release of PTX and GDC0919 within NSCLC tissues.

METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.

Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues.

FXR-regulated COX6A2 triggers mitochondrial apoptosis of pancreatic β-cell in type 2 diabetes.

Pancreatic β-cell apoptosis plays a crucial role in the development of type 2 diabetes. Cytochrome c oxidase subunit 6A2 (COX6A2) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells, however, whether they are involved in β-cell apoptosis is unclear. Here, we sought to investigate the role of FXR-regulated COX6A2 in diabetic β-cell apoptosis.

Coupling Probiotics with CaO Nanoparticle-Loaded CoFeCe-LDH Nanosheets to Remodel the Tumor Microenvironment for Precise Chemodynamic Therapy.

Chemodynamic therapy (CDT) has become an emerging cancer treatment strategy with advantages of tumor-specificity, high selectivity, and low systemic toxicity. However, it usually suffers from low therapeutic efficacy. This is caused by low hydroxyl radical (·OH) yield arising because of the relatively high pH, overexpressed glutathione, and low HO concentration in the tumor microenvironment (TME).

Lactobacillus murinus alleviates insulin resistance via promoting L-citrulline synthesis.

Aims: The role of Lactobacillus murinus as a potential probiotic is being explored. Our objectives were to explore the effects of Lactobacillus murinus on insulin resistance and the underlying mechanism.

Methods: Insulin resistance animal models were applied to study the effect of L.

Increased COX6A2 Promotes Pancreatic β-Cell Apoptosis and Is Suppressed in Diabetic GK Rats After Roux-en-Y Gastric Bypass.

Cytochrome c oxidase subunit 6A2 (COX6A2) expression is increased in diabetic islets. Increased COX6A2 promotes β-cell apoptosis via modulation of cyclophilin D-mediated cytochrome c release from mitochondria to the cytoplasm. Carbohydrate-responsive element-binding protein epigenetically regulates COX6A2 expression in β-cells.

Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis.

Retinal neovascularization is a leading cause of blindness. While current anti-VEGF drugs effectively inhibit pathological angiogenesis, some patients develop resistance or reduced responsiveness to treatments over time, leading to diminished effectiveness. In this study, we identified high activation of the cGAS-STING signaling pathway, which exacerbated pathological neovascularization and vessel leakage.

Drug-associated glaucoma: A real-world study based on the Food and Drug Administration adverse event reporting system database.

Background: This study aims to assess the risk of drug-associated glaucoma and track its epidemiological characteristics using real-world data.

Methods: Adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2023 were analysed. Disproportionality analysis and the Bayesian Confidence Propagation Neural Network algorithm were used.

[Advances in in vitro assessment models and screening methods for blood glucose-lowering medications].

Diabetes, a common metabolic condition, is recognized by the worldwide public health community as a serious chronic illness. International new drug discovery has long been dominated by the study and creation of blood glucose-lowering medications. Important phases in the development process of these medications include the in vitro assessment model and screening methods, which can dramatically lower the costs and risks of subsequent clinical trials and increase the effectiveness and efficiency of drug development.

CellKine clinical trial: first report from a phase 1 trial of allogeneic bone marrow-derived mesenchymal stem cells in subjects with painful lumbar facet joint arthropathy.

Background: Lumbar facet joint arthropathy (LFJA) is a major cause of low back pain (LBP), with current treatments offering limited long-term benefits. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show promise due to their immunomodulatory and trophic effects, potentially addressing underlying degenerative processes in LFJA.

Objectives: This initial report describes the outcomes of the first treated patient in an ongoing mutidisciplinary phase 1 clinical trial evaluating the safety and feasibility of intra-articular allogeneic BM-MSCs for painful LFJA.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis.

Methods: This study analyzed data from the U.S.

Multifaceted mitochondrial as a novel therapeutic target in dry eye: insights and interventions.

Dry eye, recognized as the most prevalent ocular surface disorder, has risen to prominence as a significant public health issue, adversely impacting the quality of life for individuals across the globe. Despite decades of extensive research into the chronic inflammation that characterizes dry eye, the intricate mechanisms fueling this persistent inflammatory state remain incompletely understood. Among the various cellular components under investigation, mitochondria-essential for cellular energy production and homeostasis-have attracted increasing attention for their role in dry eye pathogenesis.

Lumican Is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting Vascular Smooth Cells Senescence Through Interacting With Integrin α2β1.

Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2β1 are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear.

Association between α-klotho levels and adults with COPD in the United States.

Purpose: Chronic obstructive pulmonary disease (COPD) is accompanied by increased inflammation, persistent lung function decline, and extensive lung injury. Klotho, a well-known antiaging protein, has anti-inflammatory and antioxidative effects. However, the effects of klotho on COPD have yet to be thoroughly elucidated.

Unleashing Novel Therapeutic Strategies for Dry Eye: Targeting ROS and the cGAS-STING Signaling Pathway with Tetrahedral Framework Nucleic Acids.

Dry eye affects majority of the global population, causing significant discomfort or even visual impairment, of which inflammation plays a crucial role in the deterioration process. This highlights the need for effective and safe anti-inflammatory treatments to achieve satisfactory therapeutic outcomes. This study focuses on the potential of tetrahedral framework nucleic acids (tFNA), a self-assembled nucleic acid material, as a simple and rapid treatment for oxidative stress and inflammation-induced disorders associated with dry eye.

Gut microbiota and metabolic changes in children with idiopathic short stature.

Background: Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown.

The role of amino acid metabolism alterations in acute ischemic stroke: From mechanism to application.

Acute ischemic stroke (AIS) is the most prevalent type of stroke, and due to its high incidence, disability rate, and mortality rate, it imposes a significant burden on the health care system. Amino acids constitute one of the most crucial metabolic products within the human body, and alterations in their metabolic pathways have been identified in the microenvironment of AIS, thereby influencing the pathogenesis, severity, and prognosis of AIS. The amino acid metabolism characteristics in AIS are complex.