Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities

Nature Metabolism, Год журнала: 2024, Номер 6(4), С. 617 - 638

Опубликована: Март 26, 2024

Язык: Английский

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Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease

American Journal Of Pathology, Год журнала: 2024, Номер 194(4), С. 510 - 524

Опубликована: Янв. 1, 2024

Язык: Английский

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Cycling back to folate metabolism in cancer

Nature Cancer, Год журнала: 2024, Номер 5(5), С. 701 - 715

Опубликована: Май 2, 2024

Язык: Английский

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Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Metabolic disorders have been identified as one of the causes drug‐induced liver injury; however, direct regulatory mechanism regarding this disorder has not yet clarified. In study, a single small molecule kinase inhibitors, with crizotinib representative drug is elucidated. First, it discovered that induced aberrant lipid metabolism and apoptosis in liver. A mechanistic study revealed treatment promoted accumulation squalene epoxidase (SQLE) by inhibiting autophagosome‐lysosome fusion which blocked autophagic degradation SQLE. maladaptive increase SQLE led to disturbances cholesterol sphingolipid via an enzymatic activity‐dependent manner. Abnormal results both steatosis inflammatory infiltration, promote cell inducing lysosomal membrane permeabilization. The restoration level or activity ameliorated hepatocyte injury. autophagy activator known metformin inhibitor terbinafine potential clinical use for alleviating hepatotoxicity.

Язык: Английский

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Multifaceted interplays between the essential players and lipid peroxidation in ferroptosis

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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MAPK13 phosphorylates PHGDH and promotes its degradation via chaperone-mediated autophagy during liver injury

Cell Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 18, 2025

Abstract Drug-induced liver injury (DILI) is the leading cause of acute failure and poses a significant clinical challenge in both diagnosis treatment. Serine synthesis pathway (SSP) links glycolysis to one-carbon cycle plays an important role cell homeostasis by regulating substance synthesis, redox gene expression. However, regulatory mechanism SSP DILI remains unclear. Phosphoglycerate dehydrogenase (PHGDH) rate-limiting enzyme SSP. Here we show that during DILI, mitogen-activated protein kinase 13 (MAPK13) activated then phosphorylates PHGDH at serine 371 upon oxidative stress, which triggers degradation via chaperone-mediated autophagy (CMA) pathway. suppresses glutathione production, thereby exacerbating cholestatic injury. Importantly, MAPK13 inhibition dietary supplementation ameliorates these injuries. Our finding demonstrates unique SSP, promotes its CMA degradation, establishes critical injury, highlights therapeutic potential inhibitor or treat

Язык: Английский

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Inhibition of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis

Nature Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Язык: Английский

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Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation

Antioxidants, Год журнала: 2024, Номер 14(1), С. 38 - 38

Опубликована: Дек. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Язык: Английский

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Metabolic dysfunction associated steatotic liver and kidney stones: what is going on?

Current Opinion in Nephrology & Hypertension, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Metabolic dysfunction associated steatotic liver disease (MASLD) is increasing throughout the world, affecting nearly one in three individuals. Kidney stone disease, which also increasing, with MASLD. Common risk factors for both, including obesity, diabetes, dyslipidemia, hypertension, and metabolic syndrome, are likely drivers of this association. We present here a review associations possible interconnections between these two common processes. Epidemiological studies discordant regarding impact sex on association MASLD incident risk. The nature kidney stones rarely taken into account.A favorable milieu uric acid formation may be created by lower urine pH resulting from defective ammonium production insulin resistance, MASLD.Endogenous oxalate synthesis, major factor calcium stones, increased via decline activity enzymes involved detoxification glyoxylate, immediate precursor oxalate. driving remain to elucidated. Potential mechanisms identified underlying include an increase both stones.

Язык: Английский

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Targeting SHMT2‐mediated membrane phospholipid remodeling for enhanced anti‐GCSCs treatment

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Cancer stem cells exhibit flexible metabolic profiles. However, the underlying mechanisms for differential pathways affecting stemness maintenance in gastric cancer are poorly understood. Here, we reveal role of serine hydroxymethyltransferase‐2 (SHMT2)/serine‐mediated crosstalk between one‐carbon metabolism and lipid cancer. Clinically, SHMT2 was significantly highly expressed Gastric (GCs) cells, associated with clinical malignant features poor prognosis patients. Mechanistically, inhibition expression resulted diminished levels metabolism, which subsequently modified composition fluidity membrane phospholipids, leading to a reduction rafts within cellular membranes. The remodeling phospholipids hindered localization γ‐secretase rafts, thereby inhibiting cleavage CD44 subsequent production CD44‐ICD. Consequently, transcriptional regulation c‐Myc KLF4 by CD44‐ICD reduced, ultimately disrupting cells. Together, these results provide compelling evidence adaptability SHMT2/serine/lipid signaling axis holds promise as potential biomarker diagnosis Furthermore, synthesized HA‐Exo‐si investigate targeted therapy GC, offering novel approach treatment

Язык: Английский

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