Targeting Methylglyoxal Metabolism to Enhance Ferroptosis Sensitivity in Tumor Therapy.

Ferroptosis, characterized by iron-dependent lipid peroxidation, is a form of oxidative cell death increasingly recognized for its role in cancer therapy. The susceptibility of cancer cells to ferroptosis varies, highlighting the need to elucidate its underlying metabolic mechanisms. This study identifies a novel pathway in which the E3 ubiquitin ligase, praja ring finger ubiquitin ligase 1 (PJA1), mediates the proteasomal degradation of glyoxalase I (GLO1) exclusively in ferroptosis-sensitive cancer cells.

Ciprofloxacin Enhances RSL3-Induced Ferroptosis by Promoting Mitochondrial Zn Accumulation via the STING1-CAV2 Pathway.

Ciprofloxacin (CFX) is a broad-spectrum antibiotic belonging to the fluoroquinolone class, widely used to treat bacterial infections by inhibiting bacterial DNA replication. Ferroptosis, a form of regulated cell death, is characterized by lipid peroxidation on cellular and organelle membranes. Our previous studies demonstrated that ciprofloxacin inhibits erastin-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) protein stability.

Evaluating in-vivo spontaneous firing rate in the brain based on neuronal noise modeling.

Even without external stimuli, neurons produce spontaneous bursts of activities. Theoretical and practical clinical considerations, suggest the importance of determining the in-vivo statistical profile of those spontaneous spikes bursts, however this task has not been accomplished yet. Currently, it is only accepted that the in-vivo value of the mean firing rate (λ) of those spontaneous bursts is below 0.

High internal phase emulsion system for curcumin delivery co-constructed by wheat gluten amyloid fibrils and Lycium barbarum polysaccharide.

Although various curcumin (Cur) delivery systems have been developed, developing efficient and stable high internal phase emulsions (HIPEs) for Cur delivery systems remains a huge challenge. Here, wheat gluten amyloid fibrils (AF) and Lycium barbarum polysaccharide (LBP) were prepared into the AF-LBP complex. The HIPEs containing AF-LBP complex (AL-HIPEs) was successfully constructed.

DAMP signaling networks: from receptors to diverse pathophysiological functions.

Background: Damage-associated molecular patterns (DAMPs) are endogenous molecules released or exposed during cellular stress, injury, or death. Initially characterized as danger signals that alert the immune system, DAMPs are now recognized as pivotal regulators of innate and adaptive immunity through receptor-mediated signaling mechanisms.

Aim Of Review: This review aims to elucidate the diverse receptors and intracellular signaling pathways activated by DAMPs and to explore their multifaceted roles in immune modulation, tissue repair, and disease pathogenesis.

Crosstalk between stromal, immune, and ovarian cancer cells in lipid-rich tumor microenvironment exhibits proliferative features.

Lipid metabolism reprogramming has long been noticed as the hallmark of ovarian cancer, in order to maintain proliferative features including rapid cell division, metastasis capability, and chemotherapy resistance, as well as to survive under environmental stress, alteration of lipid metabolic pathways takes place, especially over-expression of rate-limiting enzymes, enhances lipid uptake, fatty acid synthesis, β-oxidation, lipid storage, and cellular membrane construction. In lipid-rich ascites and omental tumor microenvironments, the biological functions of stromal and immune cells change, forming a premetastatic niche and immunosuppressive tumor microenvironment via modifying extracellular matrix components and secreting cytokines. The crosstalk between stromal, immune, and ovarian cancer cells results in tumor proliferation, metastasis, and escape of immune surveillance.

Dopamine as an endogenous regulator of innate immunity in sepsis.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, presents a major clinical challenge. While the complex interplay of inflammatory mediators and immune cells during sepsis is increasingly understood, the role of neurotransmitters, particularly dopamine, in modulating the innate immune response is emerging as a crucial area of investigation. Dopamine, traditionally recognized for its role in the central nervous system, acts as an endogenous regulator of innate immunity, significantly influencing the course and outcome of sepsis.

Metabolic reprogramming promotes apoptosis resistance in acute lymphoblastic leukemia through CASP3 lactylation.

Unlabelled: Acute lymphoblastic leukemia (ALL) is characterized by metabolic adaptations that support rapid cell proliferation and resistance to apoptosis. Our study identifies elevated sphingomyelin (SM) as a key metabolic alteration in ALL, contributing to apoptosis resistance via CASP3 (caspase 3) lactylation. Using comprehensive lipidomic analyses of plasma samples from pediatric ALL patients, we observed significantly increased SM concentrations in patients with manifest ALL compared to patients after remission.

Control model-based reliability modeling and analysis of the human baroreflex regulation function.

The steady state of the baroreflex regulation function (BRF) plays a critical role in the human body by maintaining stable blood pressure homeostasis. However, current research predominantly focuses on physiological indices without considering BRF steady-state performance. To address this gap and comprehensively examine BRF performance maintained in a steady state, this study analyzes BRF from the perspective of reliability and uses a belief reliability methodology to model BRF reliability systematically.

CYP51A1 in health and disease: from sterol metabolism to regulated cell death.

How do cells precisely coordinate sterol metabolism with survival and death signals in diverse physiological and pathological contexts? This fundamental question has gained increasing attention as accumulating evidence reveals that enzymes traditionally associated with lipid biosynthesis may have unexpected regulatory functions beyond metabolism. Cytochrome P450 family 51 subfamily A member 1 (CYP51A1), a conserved sterol 14α-demethylase essential for cholesterol synthesis, exemplifies this emerging concept. Although well-characterized as an antifungal drug target in microorganisms, the roles of human CYP51A1 in development, cell death regulation, and disease pathogenesis remain underexplored.

Pattern recognition receptors: function, regulation and therapeutic potential.

Pattern recognition receptors (PRRs) are sensors in the immune system, detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They serve as essential links between the innate and adaptive immune responses, initiating defense mechanisms against pathogens and maintaining immune homeostasis. This review examines the classification, structure, and signaling cascades of key PRR families, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), AIM2-like receptors (ALRs), and others.

Transcriptional regulation of cuproptosis resistance in cancer therapy.

Cuproptosis is a newly identified form of copper-dependent cell death. Recent studies show that solid tumors evade this process through transcriptional reprogramming, including hypoxia inducible factor 1 subunit alpha (HIF1A) and NFE2 like BZIP transcription factor 2 (NFE2L2) activation and BTB domain and CNC homolog 1 (BACH1) suppression. Targeting these pathways may restore cuproptosis sensitivity, offering a promising strategy to overcome therapy resistance in cancer.

BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.

Trained immunity, an innate immune memory, has emerged as a promising strategy to enhance host defense against sepsis, a leading cause of mortality in critical care. While Bacillus Calmette-Guérin (BCG) is the most widely used vaccine for tuberculosis prevention, its broader use as an inducer of trained immunity is limited by adverse reactions. Here, it is reported that BCG-derived outer membrane vesicles (B-OMVs) effectively trigger trained immunity to protect against experimental polymicrobial sepsis.

T Cells Expressing Ras Homolog Family Member a Display Enhanced Cytotoxicity but are Reduced in Lupus Peripheral Blood.

Objective: This study aimed to explore the expression and clinical relevance of Ras homolog family member A (RhoA) in T cell subsets from patients with systemic lupus erythematosus (SLE).

Methods: Peripheral blood samples were obtained from newly diagnosed SLE patients and age- and sex-matched healthy controls. T cell subpopulations were analyzed by flow cytometry to quantify RhoA levels and associated cytotoxic markers, including granzyme B (GrB) and perforin (PFFN).

RNA-DNA hybrid binding domain broadens the editing window of base editors.

Adenine base editors (ABEs) and cytosine base editors (CBEs) are prominent tools for precise genome editing but are hindered by limited editing activity at positions proximal to the protospacer adjacent motif (PAM). This study investigates the potential of enhancing base editors editing activity by fusing them with RNA-DNA hybrid binding domains (RHBDs). Specifically, fusing ABE8e with the RHBD of Homo sapiens RNaseH1 (RHBD1) significantly increased A-to-G editing efficiency in the PAM-proximal region (A9-A15) by up to 3.

Luspatercept for the treatment of lower-risk myelodysplastic syndrome with SF3B1 mutation: a real-world single-center research in China.

Background: Luspatercept, approved by the FDA and EMA for patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) unresponsive to erythropoiesis-stimulating agents (ESAs), lacks extensive real-world data, particularly in China.

Methods: We retrospectively analyzed 14 LR-MDS-SF3B1 patients treated with luspatercept for ≥12 weeks.

Results: Median age was 60 years (range 47-72); 42.

Attenuated notch signaling decreases T-cell factor-1+ Treg subsets in lung adenocarcinoma, assisting early patient screening.

Objective: This study aimed to investigate the role of T-cell factor-1 (TCF1) in early-stage lung adenocarcinoma (LUAD) patients and explore its clinical significance for diagnosing early LUAD.

Methods: Blood samples were collected from 34 stage IA LUAD patients and 31 healthy controls. Flow cytometry was used to analyze the levels of TCF1 in circulating T cell subpopulations.