Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 3, 2024

Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.

Язык: Английский

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A metabolic perspective of the neutrophil life cycle: new avenues in immunometabolism

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 8, 2024

Neutrophils are the most abundant innate immune cells. Multiple mechanisms allow them to engage a wide range of metabolic pathways for biosynthesis and bioenergetics mediating biological processes such as development in bone marrow antimicrobial activity ROS production NET formation, inflammation tissue repair. We first discuss recent work on neutrophil functions regulate granulopoiesis, migration trafficking well effector functions. then syndromes with impaired that influenced by genetic environmental factors nutrient availability usage. Here, we particularly focus role specific macronutrients, glucose, fatty acids, protein, micronutrients vitamin B3, regulating biology how this regulation impacts host health. A special section review primarily discusses ways deficiencies could impact increase infection susceptibility. emphasize biochemical approaches explore metabolism relation Lastly, opportunities challenges neutrophil-centered therapeutic immune-driven diseases highlight unanswered questions guide future discoveries.

Язык: Английский

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Cancer immunometabolism: advent, challenges, and perspective

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Апрель 5, 2024

Abstract For decades, great strides have been made in the field of immunometabolism. A plethora evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism center stage innate and adaptive immunomodulation. Given this, we focus changes immunometabolism, a converging series biochemical events that alters immune cell function, propose roles played by diversified metabolic derivatives enzymes, emphasize key metabolism-related checkpoints distinct types, discuss ongoing upcoming realities treatment. It is expected future research will reduce current limitations immunotherapy provide positive hand responses exert broader therapeutic role.

Язык: Английский

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Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 22, 2023

Introduction The study aimed to explore the association of serum 25(OH)D 3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients determine whether effect vitamin D (VD) is mediated by activation peroxisome proliferator-activated receptor α (PPARα) pathway. Methods contained a case-control study, vivo vitro experiments. A was conducted compare parameters between NAFLD controls evaluate NAFLD. In male Wistar rats were randomly divided into control model groups, fed standard chow diet high-fat (HFD), respectively, for 7 weeks generate an model. Then, treated with VD PPARα antagonist (MK886) weeks. Tissue collected assessed biochemical assays, morphological analysis, histological western blot analysis. , HepG2 cells incubated oleic acid (OA) induce steatosis, which evaluated staining. pretreated MK886 followed calcitriol treatment, differences lipid metabolism-related proteins detected blot. Results characterized impaired function, dyslipidemia, insulin resistance. Serum negatively associated alanine aminotransferase (ALT) deficiency risk factor no advanced fibrosis. Adequate status (25(OH)D >20 ng/mL) had protective after adjustment confounding variables. showed hyperlipidemia severe systematic inflammation, lower . treatment ameliorated both OA-induced cells. Further, inhibited anti-steatosis VD. Conclusion revealed that adequate level may act as alleviate via signaling

Язык: Английский

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Thiamine deficiency aggravates experimental colitis in mice by promoting glycolytic reprogramming in macrophages

British Journal of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Inflammatory bowel disease (IBD) is closely associated with immune dysfunction, where nutrient-mediated metabolic flux dictates cell fate and function. Thiamine a central water-soluble vitamin involved in cellular energy metabolism, its deficiency has been reported IBD patients. However, whether thiamine cause or consequence of pathogenesis remains unclear. The current study aimed to reveal the immunometabolic regulation macrophages underlying mechanism colitis development. was induced C57BL/6 mice bone marrow-derived (BMDMs), by administering thiamine-deficient diet/medium together pyrithiamine hydrobromide. frequency macrophage phenotypes their intracellular metabolism were detected using flow cytometry non-targeted metabolomics, respectively. aggravated ulcerative promoted infiltration proinflammatory M1 colonic lamina propria. Our mechanistic revealed that impaired pyruvate dehydrogenase (PDH) activity, thereby reprogramming glucose enhance glycolysis lactic acid accumulation macrophages. Using well-established PDH inhibitor (CPI-613) (galloflavin), we further demonstrated inhibition mimics, while lactate partially rescues, deficiency-induced experimental mice. provides evidence linking activation aggravation, suggesting monitoring status adjusting intake necessary protect against colitis.

Язык: Английский

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Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 30, 2024

Abstract Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with poor prognosis and limited treatment options. Recent work identifying high concentrations the cytokine interleukin-6 (IL-6) its soluble receptor (sIL-6-Rα) in peritoneal cavity patients PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides comprehensive overview current understanding role IL-6 development progression PC. We discuss mechansims by which may contribute to tumor dissemination, mesothelial adhesion invasion, stromal invasion proliferation, immune response modulation. Finally, we prospects for targeting PC, focusing on common sites origin, including ovarian, gastric, pancreatic, colorectal appendiceal cancer, mesothelioma.

Язык: Английский

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Metabolic abnormalities in the bone marrow cells of young offspring born to mothers with obesity

International Journal of Obesity, Год журнала: 2024, Номер 48(11), С. 1542 - 1551

Опубликована: Июнь 27, 2024

Язык: Английский

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Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis

Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity, Год журнала: 2025, Номер 30(1)

Опубликована: Март 29, 2025

Previous observational studies have indicated that circulating micronutrients may influence obesity risk. This study aimed to explore the causal relationship between micronutrient levels and through multivariable Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) significantly associated with 15 (selenium, zinc, copper, calcium, beta-carotene, folate, iron, magnesium, potassium, vitamins A, B6, B12, C, D, E) from published genome-wide association (GWAS) were used as instrumental variables (IVs). Three obesity-related datasets obtained GWAS. Inverse variance weighted (IVW) is main method for MR Leave-one-out analysis, MR-Pleiotropy Residual Sum Outlier (MR-PRESSO), median, MR-Egger assess pleiotropy heterogeneity. Genetically predicted of selenium calcium are causally related risk (calcium odds ratio [OR]: 1.478, 95% confidence interval [CI] 1.128–1.935, p = 0.005; OR: CI 0.005). Multivariate analysis suggested a 1.625, 1.260–2.097; 1.080, 1.003–1.163, 0.041). The p-value in Cochrane Q test, intercept MR-PRESSO > 0.05, suggesting no significant evidence or Our revealed, first time, positive correlation elevated an increased These findings provide valuable insights into obesity's underlying mechanisms. Nevertheless, further large-scale clinical required confirm our results. Level evidence: III, randomization.

Язык: Английский

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Peristomal Skin Complications: Detailed Analysis of a Web-Based Survey and Predictive Risk Factors

Healthcare, Год журнала: 2023, Номер 11(13), С. 1823 - 1823

Опубликована: Июнь 21, 2023

Patients with a stoma are at risk of developing peristomal skin complications (PSCs) that can negatively impact their quality life. This study aims to identify potential factors for dermatitis, pruritis/xerosis, infections, and ulcerations among patients evaluate preventive measures. cross-sectional involved data regarding 232 Italian stoma. A questionnaire was used collect patient characteristics, comorbidities, management data. The most frequent PSCs observed were dermatitis pruritis/xerosis in approximately 60% patients. Psoriasis strongly correlated while being overweight or obese increased the pruritis/xerosis. Class 2 obesity atopic associated an infections. Being underweight, completely nonautonomous, having inflammatory bowel disease higher ulcerations, radiotherapy strong factor ulceration. Preventive measures such as using hydrocolloid barriers, TNT gauze cleansing, low pH detergent effective preventing dermatitis. Appropriate care maintenance, including use protective film careful monitoring weight crucial minimizing

Язык: Английский

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European Society for the Study of Obesity (EASO) Position Statement on medical nutrition therapy for the management of individuals with overweight or obesity and cancer

Obesity Facts, Год журнала: 2024, Номер unknown, С. 1 - 20

Опубликована: Окт. 21, 2024

Obesity, a prevalent and multifactorial disease, is linked to range of metabolic abnormalities, including insulin resistance, dyslipidemia, chronic inflammation. These imbalances not only contribute cardiometabolic diseases but also play significant role in cancer pathogenesis. The rising prevalence obesity underscores the need investigate dietary strategies for effective weight management individuals with overweight or cancer. This European Society Study Obesity (EASO) position statement aimed summarize current evidence on provide insights major nutritional interventions, Mediterranean diet (MedDiet), ketogenic (KD), intermittent fasting (IF), that should be adopted manage MedDiet, characterized by high consumption plant-based foods moderate intake olive oil, fish, nuts, has been associated reduced risk. KD IF are emerging interventions potential benefits loss health. KD, inducing ketosis, IF, through periodic cycles, may offer anticancer effects modifying tumor metabolism improving sensitivity. Despite promising results, these approaches limited inconsistent, challenges variability adherence personalized plans.

Язык: Английский

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