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Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity.

INTRODUCTION: Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in the US and Europe. Massive hepatocyte necrosis is the predominant feature of APAP-induced acute liver injury (ALI). Liver regeneration is a vital process for survival after a toxic insult, it occurs at a relative late time point after the injurious phase. Currently, N-acetylcysteine (NAC), a glutathione precursor, is the antidote for acetaminophen overdose. However, NAC is effective only for patients who present within hours of an acute overdose, and is less effective for late-presenting patients. It

Targeting ferroptosis in cancer: molecular mechanisms and emerging therapeutic strategies.

Ferroptosis, an iron-dependent form of regulated cell death characterized by the lethal accumulation of lipid peroxides, has emerged as a pivotal pathway in cancer biology and a promising therapeutic target. This review synthesizes the core molecular machinery governing ferroptosis, detailing the critical roles of iron metabolism through systems like transferrin/transferrin receptor 1 and ferritinophagy, the cystine/glutamate antiporter system (Xc-)/glutathione/GPX4 axis, and the recently discovered FSP1/CoQ10 pathway. We further explore the intricate interplay between lipid peroxidation, amin…

A review of advances in research on mechanisms inhibiting kidney stone formation from a network pharmacology perspective.

Nephrolithiasis is a prevalent, highly recurrent urological disorder affecting 1%-15% of the global population, with 5-year recurrence rates … pathophysiology across major stone types (calcium oxalate, calcium phosphate, uric acid, struvite, cystine) and the comprehensive cellular cascade encompassing crystal nucleation, Randall's plaque/plug formation, CD44-mediated adhesion, mitochondrial reactive oxygen species burst, endoplasmic reticulum stress, NLRP3 inflammasome activation, macrophage M1 …

Association between donor animal category and amino acid profiles in bovine oocytes and embryos produced in vitro.

In vitro embryo production (IVP) is widely used in cattle breeding, however, pregnancy outcomes remain suboptimal, primarily due to variabil … ogether with greater depletion of essential amino acids such as valine, isoleucine, methionine, and cystine. In contrast, oocytes and embryos from pubertal heifers and adult cows exhibited more similar amino acid profiles. These metabolic differences were associated with oocyte quality, and embryo developmental outcomes, with the highest proportion of goo …

Ranitidine protects Müller cells against ferroptosis in diabetic retinopathy by regulating the AKT1/GSK3β pathway.

PURPOSE: This study was designed to investigate the primary targets and possible mechanisms of ranitidine (Ra) against diabetic retinopathy … tting was used to identify ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), serine/threonine-protein kinase AKT1, and glycogen synthase kinase-3β (GSK3β). RESULTS: The predicted results suggested that the potential mechanism of RMCs damage in diabetic mice is associated with ferroptosis. The cc …

Identification of the disulfidptosis-related gene G6PD as a potential biomarker and therapeutic target in pancreatic ductal adenocarcinoma by integrative bioinformatics analysis and experimental validation.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly lethal digestive system tumor with a low five-year survival rate and limited treatm … disulfidptosis-like features in the PAAD cell line SW1990 by reducing NADPH generation, suppressing cystine uptake, and promoting F-actin contraction and aggregation. CONCLUSIONS: Our study reveals the critical role of G6PD in PAAD. High G6PD expression is closely associated with unfavorable clinicopathological features and poor prognosis in PAAD patients …

Genetically Engineered Membrane-Mimetic Liposome-Wrapped Violet Phosphorus Nanoplatform for Targeted Synergistic Ferroptosis/Photothermal/Immunotherapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a highly prevalent malignancy, is mostly diagnosed at intermediate and advanced stages. Current monotherapie … ronment. RSL3 inhibits glutathione peroxidase 4 (GPX4) activity, and SSZ blocks System xc--mediated cystine uptake; their combination synergistically depletes intracellular glutathione (GSH) and potently induces ferroptosis in HCC cells. The nanoplatform-mediated PTT not only directly ablates tumor cells but also releases damage-associated molecular patte …

Inter- and Intraspecific Venom Variation in the Reclusive Rear-Fanged Black-Striped Snakes (Coniophanes).

Our current understanding of snake venom is highly biased towards species known to be medically significant in human envenomations. This vas … anscriptomes and that 18 toxin families are represented in this genus, with prominent expression of cystine-rich secretory proteins (CRiSPs) in three species and snake venom metalloproteinases (SVMPs) in all four species. In addition, we used diffusible iodine-based contrast-enhanced computed tomography (diceCT) to better understand the venom delivery sys …

Effects of MC-100093, GLT-1 enhancer, in mesolimbic brain regions of C57BL/6 mouse exposed to hydrocodone high-dose challenge using comprehensive laboratory monitoring system.

Chronic exposure and overdose of opioid cause neurotoxicity through alterations of several neurotransmitters, including glutamate. Upregulating glutamate transporter 1 (GLT-1) has been shown to attenuate the behavioral and neurochemical effects of chronic exposure to drugs of abuse. This study investigated the effects of GLT-1 enhancers-MC-100093 and ceftriaxone-on locomotor activity, respiratory exchange, and glutamate transporters (GLT-1, cystine/glutamate transporter, xCT), brain derived neurotrophic factor (BDNF), and neuroinflammatory biomarkers (TNF-α and HMGB1) in nucleus accumbens (NAc…

Циклотиды растений в иммуномодулировании и их терапевтический потенциал.

В последние годы число нарушений, связанных с иммунной деятельностью, резко возросло среди населения мира. Лечение и лечение этих заболеваний, особенно аутоиммунных расстройств, являются сложными и сложными. Имеющиеся синтетические наркотики не являются полностью эффективными и также создают серьезные побочные эффекты для пациентов. Циклотиды представляют собой класс киклокислот (28-37 аминокислот) растительного происхождения с тремя сохраненными дисульфидными соединениями, создающими циклический кистиновый узел (CCK), который делает их очень стабильными биомолекулы. Их неотъемлемая стабильнос

Совпадение в аннотации оригинала
The incidences of immune-related disorders have drastically increased in recent years across the world population. Treatment and management … d cyclic peptides (28-37 amino acids) with three conserved disulfide linkages establishing a cyclic cystine knot (CCK) motif that makes them very stable biomolecules. Their inherent stability, bioavailability and membrane-penetrating capabilities render them attractive potential pharmacological agents. Studies have demonstrated that cyclotides can either …

CBT-Cys click ligation coupled with pregnancy test strips for nucleic acid assay.

BACKGROUND: Rolling circle amplification (RCA) is a powerful nucleic acid detection method widely used in molecular diagnosis. The circular … icky ends of DNA molecules in RCA. This approach leverages a 2-cyano-6-aminobenzothiazole (CBT) and cystine (Cys-Cys) modification at the nucleic acid termini (CBT-nucleic acid-Cys-Cys). When the HAV is present, a tightly packed circular DNA is formed. After the addition of glutathione, the disulfide bond is reduced, facilitating chemical linkage between …

Implications for soluble iron accumulation, oxidative stress, and glial glutamate release in motor neuron death associated with sporadic amyotrophic lateral sclerosis.

Oxidative stress in sporadic amyotrophic lateral sclerosis (ALS) has been evidenced by accumulation of oxidatively modified products of nucl … TNF-α-converting enzyme (TACE), and glutaminase-C (GAC) were expressed mainly in microglia and that cystine/glutamate antiporter (xCT) was expressed mainly in astrocytes. We next performed cell culture experiments. Cultured microglia treated with soluble iron over-released glutamate and TNF-α via aconitase 1 and TACE, respectively. Cultured microglia trea …

HY-021068 improves neuronal ferroptosis by activating Nrf2 signaling in APP/PS1 Mice and Aβ1-42-induced HT22 cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unclear pathogenesis and no effective treatment methods. HY-021 … ession, and Tau hyperphosphorylation. Furthermore, HY increased glutathione peroxidase 4 (Gpx4) and Cystine/glutamate transporter (xCT) levels, while reduced DMT1 and transferrin receptor expression, eventually inhibiting neuronal ferroptosis. Mechanistically, HY decreased reactive oxygen species (ROS) accumulation and activated the nuclear factor erythro …

High-temperature stored soybean meal alters intestinal chyme composition and disrupts intestinal redox balance by increasing jejunal MAPK14 protein expression in broilers.

This study aimed to investigate the effects of feeding broilers basal diets with high-temperature (35°C) stored soybean meal (SBM). A total … re stored SBM altered intestinal chyme composition, increased 42-d jejunal methionine sulfoxide and cystine levels, and decreased L-leucine and lysine levels. These changes have caused 114 DEPs in the jejunum of broilers, there were 53 up-regulated and 61 down-regulated. Furthermore, the upregulated MAPK14 significantly affected the downstream transcripti …

Comparison and identification of serum metabolomic profiles in Stage B and Stage C ejection fraction preserved heart failure.

BACKGROUND: Disturbed metabolism correlates with the progression of heart failure with preserved ejection fraction (HFpEF). However, the dis … ulatory peritoneal dialysis and chronic renal failure). Three non-heart-specific metabolites, i.e., cystine (AUC = 0.919), stearic acid [FA (18:0), AUC = 0.913], and N-palmitoyl sphingomyelin (SM C 16:0, AUC = 0.898), displayed higher accuracy than N-terminal pro-B-type brain natriuretic peptide (AUC = 0.838) in differentiating Stage B and Stage C patient …

Treatment response variations to a single large bolus of enteral cholecalciferol in vitamin D deficient critically Ill children: Metabolomic insights for precision nutrition.

Vitamin D deficiency (VDD) is prevalent globally and in pediatric intensive care units, where it represents a modifiable risk factor that ma … ufficiency (serum 25-OH-D >75 nmol/L) coincided with lower circulating levels of 3-methylhistidine, cystine, S-methylcysteine, uric acid, and two lysophosphatidylcholines 7 days after treatment. Rapid correction of VDD was associated with indicators of lower oxidative stress, inflammation, and muscle protein turn-over that may contribute clinical benefits …

Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.

Glioblastoma remains the most aggressive and treatment-resistant brain malignancy, driven by genetic heterogeneity, metabolic plasticity, an … (IREB2 and ferritinophagy), lipid peroxidation enzymes (ACSL4 and ALOXs), and protective pathways (cystine transporters and glutathione peroxidase 4), limit its therapeutic potential. Extracellular vesicle-mediated iron transfer further contributes to ferroptosis resistance, fostering chemoresistance and radio-resistance. Beyond direct tumor killing, fer …

Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.

OBJECTIVE: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous au … g2FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log2FC=1.17, p=0.02) and cystine (log2FC=1.04, p=0.03) compared with control sera. CONCLUSIONS: Metabolites associated with the NAD+ pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics th …