BCL6 Alleviates Hepatic Ischemia/Reperfusion Injury Via Recruiting SIRT1 to Repress the NF-κB/NLRP3 Pathway.

Background: Hepatic ischemia/reperfusion (I/R) injury (HIRI) is an intrinsic phenomenon observed in the process of various liver surgeries. Unfortunately, there are currently few options available to prevent HIRI. Accordingly, we aim to explore the role and key downstream effects of B-cell lymphoma 6 (BCL6) in hepatic I/R (HIR).

Recombinant dsAAV9-mediated Endogenous Overexpression of Macrophage Migration Inhibitory Factor Alleviates Myocardial Ischemia-Reperfusion Injury via Activating AMPK and ERK1/2 Signaling Pathways.

Purpose: To investigate the protective effect and mechanism of enhanced expression of endogenous macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury.

Methods: A recombinant double-stranded adeno-associated virus serotype 9 with MIF or green fluorescent protein (GFP) genes (dsAAV9-MIF/GFP) was transduced into mice and neonatal rat ventricular myocytes (NRVMs). The models of cardiac 60 min ischemia and 24 h reperfusion and 12 h hypoxia/12 h reoxygenation (H/R) were established in mice and NRVMs, respectively.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

Quercetin inhibits cardiomyocyte apoptosis via Sirt3/SOD2/mitochondrial reactive oxygen species during myocardial ischemia-reperfusion injury.

Background: Myocardial ischemia/reperfusion injury (MI/RI) can lead to impaired cardiac function. Quercetin (Que) has a positive effect and improves MI/RI. Sirtuin-3 (Sirt3) is a deacetylase that ameliorates oxidative stress and is associated with MI/RI.

Edge-doped substituents as an emerging atomic-level strategy for enhancing M-N-C single-atom catalysts in electrocatalysis of the ORR, OER, and HER.

M-N-C single-atom catalysts (MN) have gained attention for their efficient use at the atomic level and adjustable properties in electrocatalytic reactions like the ORR, OER, and HER. Yet, understanding MN's activity origin and enhancing its performance remains challenging. Edge-doped substituents profoundly affect MN's activity, explored in this study by investigating their interaction with MN metal centers in ORR/OER/HER catalysis (Sub@MN, Sub = B, N, O, S, CH, NO, NH, OCH, SO; M = Fe, Co, Ni, Cu).

CITED2 Attenuates Ischemia Reperfusion-Induced Pyroptosis and Injury in Cardiomyocyte.

To examine the role of CITED2 in myocardial ischemia/reperfusion injury (MIRI) in a cell model and uncover the mechanism, hypoxia/reoxygenation (H/R) -stimulated H9C2 cell model was utilized as a MIRI cell model. Quantitative polymerase chain reaction (qPCR) as well as immunoblot assays were carried out to determine the expression of CITED2 in the MIRI cell model. MTT as well as lactate dehydrogenase assays were employed to detect the survival of H/R-stimulated H9C2 cells.

Porcine Anti-Lymphocyte Globulin, Cyclosporine A Plus Thrombopoietin Receptor Agonists Achieved Similar Efficacy and Survival Compared to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Aplastic Anemia.

Background: Immunosuppressive therapy (IST) with horse or rabbit anti-human thymocyte immunoglobulin (h-/r-ATG) and hematopoietic stem cell transplantation (HSCT) are two baseline treatments for severe aplastic anemia (SAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients. Addition of thrombopoietin receptor agonists (TPO-RAs) to standard IST therapy (h-/r-ATG) has greatly improved the survival of SAA, whereas porcine anti-lymphocyte globulin (p-ALG) combined with TPO-RAs still had a matter of debate.

Methods: We retrospectively compared the data of 48 AA patients in our center between 2020 and 2022, 23 AA patients received with p-ALG ± TPO-RAs, 25 AA patients underwent matched sibling donor (MSD-) or haploidentical (haplo-) HSCT.

AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis.

Objective: Renal ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which is associated with high incidence and mortality. AST-120 is an oral carbonaceous adsorbent that can alleviate kidney damage. This study aimed to explore the effects of AST-120 on renal IRI and the molecular mechanism.

Preliminary Evaluation of the Safety and Immunogenicity of a Novel Protein-Based Pneumococcal Vaccine in Healthy Adults Aged 18-49: A Phase Ia Randomized, Double Blind, Placebo-Controlled Clinical Study.

: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). : This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18-49 years.

Fibronectin type III domain containing 4 alleviates myocardial ischemia/reperfusion injury via the Nrf2-dependent antioxidant pathway.

Fibronectin type III domain containing 4 (FNDC4) is highly homologous with FNDC5, which possesses various cardiometabolic protective functions. Emerging evidence suggests a noteworthy involvement of FNDC4 in fat metabolism and inflammatory processes. This study aimed to characterize the role of FNDC4 in myocardial ischemia/reperfusion (MI/R) injury and decrypt its underlying mechanisms.

KLF4-induced upregulation of SOCS1 ameliorates myocardial ischemia/reperfusion injury by attenuating AC16 cardiomyocyte damage and enhancing M2 macrophage polarization.

Reperfusion strategies, the standard therapy for acute myocardial infarction (AMI), may result in ischemia/reperfusion (I/R) damage. Suppressor of cytokine signaling1 (SOCS1) exerts a cardioprotective function in myocardial I/R damage. Here, we investigated epigenetic modulators that deregulate SOCS1 in cardiomyocytes under hypoxia/reoxygenation (H/R) conditions.

Short-chain fatty acids regulate erastin-induced cardiomyocyte ferroptosis and ferroptosis-related genes.

Background: Ferroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown.

Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial.

Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment.

Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022).

Hepatic-derived BMP9 is involved in hepatic fibrosis-induced kidney injury through inhibition of renal VEGFA.

Clinical observations suggest that acute kidney injury (AKI) occurs in approximately 20-50% of hospitalized cirrhotic patients, suggesting a link between the liver and kidney. Bone morphogenetic protein 9 (BMP9) is a protein produced primarily by the liver and can act on other tissues at circulating systemic levels. Previous studies have demonstrated that controlling abnormally elevated BMP9 in acute liver injury attenuates liver injury; however, reports on whether BMP9 plays a role in liver injury-induced AKI are lacking.

Design and synthesis of matrine derivatives for anti myocardial ischemia-reperfusion injury by promoting angiogenesis.

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments.

[Identification of cardioprotective substances in Panax ginseng/P. notoginseng based on mitochondrial morphological characteristics and UPLC-Triple-TOF-MS].

Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P.

Sevoflurane postconditioning attenuates cardiomyocytes hypoxia/reoxygenation injury via PI3K/AKT pathway mediated HIF-1α to regulate the mitochondrial dynamic balance.

Background: Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.

Decoding 2.3 million ECGs: interpretable deep learning for advancing cardiovascular diagnosis and mortality risk stratification.

Aims: Electrocardiogram (ECG) is widely considered the primary test for evaluating cardiovascular diseases. However, the use of artificial intelligence (AI) to advance these medical practices and learn new clinical insights from ECGs remains largely unexplored. We hypothesize that AI models with a specific design can provide fine-grained interpretation of ECGs to advance cardiovascular diagnosis, stratify mortality risks, and identify new clinically useful information.

HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury.

S100 calcium-binding protein 16 (S100A16) is implicated in both chronic kidney disease (CKD) and acute kidney injury (AKI). Previous research has shown that S100A16 contributes to AKI by facilitating the ubiquitylation and degradation of glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) through the activation of HMG-CoA reductase degradation protein 1 (HRD1). However, the mechanisms governing S100A16-induced HRD1 activation and the upregulation of S100A16 expression in renal injury are not fully understood.

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.

Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable.