Arginine reprograms metabolism in liver cancer via RBM39

Cell, Journal Year: 2023, Volume and Issue: 186(23), P. 5068 - 5083.e23

Published: Oct. 6, 2023

Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels elevated murine patient hepatocellular carcinoma (HCC), despite reduced expression synthesis genes. Tumor cells accumulate high due to increased uptake arginine-to-polyamine conversion. Importantly, the promote tumor formation via further reprogramming, including changes glucose, amino acid, nucleotide, fatty acid metabolism. Mechanistically, binds RNA-binding motif protein 39 (RBM39) control RBM39-mediated upregulation asparagine leads enhanced uptake, creating positive feedback loop sustain oncogenic Thus, second messenger-like molecule reprograms growth.

Language: Английский

---

Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint

EBioMedicine, Journal Year: 2022, Volume and Issue: 83, P. 104216 - 104216

Published: Aug. 17, 2022

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions impede T-cell anti-tumour responses have been identified. Immunotherapies block checkpoints revolutionized the treatment paradigm for many patients advanced-stage tumours. However, metabolic constraints soluble factors exist within TME exacerbate functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial mechanisms - elevated immunosuppressive metabolites enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts extracellular ATP adenosine, dysregulated bioenergetic purinergic signalling, ionic imbalance operate in collectively suppress We discuss how scientific advances could help overcome complex obstacles T-lymphocytes, aiming stimulate further research developing new therapeutic strategies by harnessing full potential system combating cancer.

Language: Английский

---

IL-4 and IL-13: Regulators and Effectors of Wound Repair

Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 41(1), P. 229 - 254

Published: Feb. 4, 2023

Type 2 immunity mediates protective responses to helminths and pathological allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. cytokines are known promote fibrosis, an overzealous repair response, their contribution healthy is less well understood. This review discusses evidence that canonical type cytokines, IL-4 IL-13, integral process through two main pathways. First, essential for progression effective repair, IL-13 suppress initial inflammatory response injury. Second, these regulate how extracellular matrix modified, broken down, rebuilt and/or amplifies multiple aspects many pathways highly redundant can be induced by other signals. Therefore, exact IL-4Rα signaling remains difficult unravel.

Language: Английский

---

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 31, 2023

Abstract Background Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and leading cause pain disability in aged population. However, underlying biological mechanism has not been fully understood. This study aims to reveal causal effect circulation metabolites on OA susceptibility. Methods A two-sample Mendelian Randomization (MR) analysis was performed estimate causality GDMs OA. genome-wide association (GWAS) 486 used as exposure, whereas 8 different phenotypes, including any-site (All OA), knee and/or hip (knee/hip OA, spine finger thumb (hand were set outcomes. Inverse-variance weighted (IVW) for calculating estimates. weight mode, median, MR-egger, MR-PRESSO sensitive analysis. Furthermore, metabolic pathway via web-based Metaconflict 4.0. All statistical analyses R software. Results In this MR analysis, a total 235 causative associations between phenotypes observed. After false discovery rate (FDR) correction 9 robust 7 (e.g., arginine, kynurenine, isovalerylcarnitine) 5 finally identified. Additionally, eleven significant pathways 4 identified by Conclusion The finding our suggested that can be considered useful circulating biomarkers screening prevention clinical practice, also serve candidate molecules future exploration drug target selection.

Language: Английский

---

L-arginine metabolism as pivotal interface of mutual host–microbe interactions in the gut

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 26, 2023

L-arginine (L-arg) is a versatile amino acid and central intestinal metabolite in mammalian microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways the regulation cell division growth. It also serves source carbon, nitrogen, energy or substrate for protein synthesis. Consequently, can simultaneously modify immune functions, intraluminal metabolism, microbiota, pathogenesis. While dietary intake, turnover de novo synthesis usually supply sufficient amounts, expression several key enzymes metabolism change rapidly dramatically following inflammation, sepsis, injury. availability be restricted due to increased catabolism, transforming into an essential acid. Here, we review enzymatic cells their role function, colonization resistance, pathogenesis gut.

Language: Английский

---

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial

Nutrients, Journal Year: 2022, Volume and Issue: 14(23), P. 4984 - 4984

Published: Nov. 23, 2022

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve muscle function stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 60 years persistent fatigue attending post-acute outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either combination 1.66 g plus 500 mg liposomal vitamin C or placebo for 28 days. The primary outcome the distance walked on 6 min walk test. Secondary outcomes handgrip strength, flow-mediated dilation, persistence. Fifty participants placebo. Forty-six (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received intervention which they allocated completed study. At days, increased (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) induced greater improvement strength (+3.4 (7.5) kg) compared (+1 (6.6) kg, 0.03). dilation active group than (14.3% (7.3) vs. 9.4% (5.8), reported two (8.7%) 21 (80.1%; < 0.0001). supplementation improved walking performance, function, long COVID. This supplement may, therefore, be considered restore relieve symptoms this patient population.

Language: Английский

---

The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8725 - 8725

Published: May 13, 2023

Tobacco smoking is a major cause of chronic obstructive pulmonary disease (COPD) and atherosclerotic cardiovascular (ASCVD). These diseases share common pathogenesis significantly influence each other's clinical presentation prognosis. There increasing evidence that the mechanisms underlying comorbidity COPD ASCVD are complex multifactorial. Smoking-induced systemic inflammation, impaired endothelial function oxidative stress may contribute to development progression both diseases. The components present in tobacco smoke can have adverse effects on various cellular functions, including macrophages cells. Smoking also affect innate immune system, impair apoptosis, promote respiratory vascular systems. purpose this review discuss importance comorbid course ASCVD.

Language: Английский

---

In Situ Hybridization of Polymeric Curcumin to Arginine-Derived Carbon Quantum Dots for Synergistic Treatment of Bacterial Infections

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(22), P. 26457 - 26471

Published: May 29, 2023

Effective infectious keratitis treatment must eliminate the pathogen, reduce inflammatory response, and prevent persistent damage to cornea. Infectious is generally treated with broad-spectrum antibiotics; however, they have risk of causing corneal epithelial cell drug resistance. In this study, we prepared a nanocomposite (Arg-CQDs/pCur) from arginine (Arg)-derived carbon quantum dots (Arg-CQDs) polymeric curcumin (pCur). Partial carbonization hydrochloride in solid state by mild pyrolysis resulted formation CQDs, which exhibited enhanced antibacterial activity. pCur was formed polymerization curcumin, further crosslinking reduced its cytotoxicity improved antioxidative, anti-inflammatory, pro-proliferative activities. The situ conjugated Arg-CQDs form Arg-CQDs/pCur nanocomposite, showed minimum inhibitory concentration ca. 10 μg mL-1, >100-fold >15-fold lower than that precursor respectively, against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa. combined antibacterial, properties, long-term retention on cornea enabled synergistic bacterial keratitis. rat model, it can effectively treat P. aeruginosa-induced at 4000-fold commercially used drug, Sulmezole eye drops. nanocomposites great potential for application anti-inflammatory nanoformulations clinical use diseases.

Language: Английский

---

The effects of arginine and branched-chain amino acid supplementation to reduced-protein diet on intestinal health, cecal short-chain fatty acid profiles, and immune response in broiler chickens challenged with Eimeria spp.

Poultry Science, Journal Year: 2023, Volume and Issue: 102(7), P. 102773 - 102773

Published: May 9, 2023

We investigated the effects of supplementing arginine (Arg) and branched-chain amino acids (BCAA) in broilers fed reduced-protein diets challenged with Eimeria spp. All birds were same starter diet meeting Cobb 500 nutrient specifications from d 1 to 9. Four grower diets: positive control (PC) 20.0% crude protein (CP); negative (NC) 17.5% CP; or NC supplemented Arg BCAA at 50% above recommendations (ARG BCAA) 9 28. Birds allocated a 2 × 4 factorial arrangement (4 diets, each without challenge), 8 replicates per treatment. On 14, challenge groups orally gavaged mixed Intestinal permeability was higher (P < 0.05) than PC, whereas ARG did not differ significantly PC. 28, significant interaction 0.01) observed CD8+: CD4+ ratios cecal tonsils (CT), increased all except for group. 21, found CD4+CD25+ percentages CT that only PC groups. 21 interactions macrophage nitric oxide (NO) production. In nonchallenged birds, NO group other groups, but both bile anticoccidial IgA concentrations The results suggest exacerbates impact on intestinal integrity, this could be mitigated by supplementations. Arginine supplementations beneficial against infection enhancing immune responses. supplementation tended more pronounced compared supplementation.

Language: Английский

---

Bench-to-Bedside Studies of Arginine Deprivation in Cancer

Molecules, Journal Year: 2023, Volume and Issue: 28(5), P. 2150 - 2150

Published: Feb. 24, 2023

Arginine is a semi-essential amino acid which becomes wholly essential in many cancers commonly due to the functional loss of Argininosuccinate Synthetase 1 (ASS1). As arginine vital for plethora cellular processes, its deprivation provides rationale strategy combatting arginine-dependent cancers. Here we have focused on pegylated deiminase (ADI-PEG20, pegargiminase)–mediated therapy from preclinical through clinical investigation, monotherapy combinations with other anticancer therapeutics. The translation ADI-PEG20 first vitro studies positive phase 3 trial depletion cancer highlighted. Finally, this review discusses how identification biomarkers that may denote enhanced sensitivity beyond ASS1 be realized future practice, thus personalising patients cancer.

Language: Английский

---