Опубликована: Янв. 1, 2024
Язык: Английский
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Окт. 30, 2024
Язык: Английский
Процитировано
16
European Journal of Heart Failure, Год журнала: 2024, Номер 26(4), С. 925 - 935
Опубликована: Март 11, 2024
Abstract Aims Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms decreased quality of life. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism action remains poorly understood. We aimed, therefore, determine whether SGLT2i influence pathology patients HFrEF. Methods results Muscle biopsies from 28 male (New York Heart association class I–III) treated (>12 months) or without were compared. Comprehensive analyses structure (immunohistochemistry), transcriptome (RNA sequencing), metabolome (liquid chromatography‐mass spectrometry) performed, serum inflammatory profiling (ELISA). Experiments mice ( n = 16) also performed. Myofiber atrophy was ~20% less taking p 0.07). Transcriptomics follow‐up measures identified a unique signature related beneficial effects on atrophy, metabolism, inflammation. Metabolomics influenced tryptophan metabolism SGLT2i: kynurenic acid 24% higher kynurenine 32% lower < 0.001). Serum that treatment associated 0.05) pro‐inflammatory cytokines by 26–64% alongside downstream interleukin (IL)‐6‐JAK/STAT3 signalling 008 0.09). IL‐6 correlated R 0.65; 0.05). indicative conserved mammalian response treatment. Conclusions Treatment anti‐atrophic, anti‐inflammatory, pro‐metabolic effects. These changes may be regulated via IL‐6–kynurenine signalling. Together, improvements following partly explained positive pathology.
Язык: Английский
Процитировано
12
Aging Cell, Год журнала: 2024, Номер 23(4)
Опубликована: Фев. 21, 2024
Evaluation of the influence primary and secondary aging on manifestation molecular cellular hallmarks is a challenging currently unresolved issue. Our study represents first demonstration distinct role chronic inflammation/physical inactivity - most important drivers aging, in regulation transcriptomic proteomic profiles human skeletal muscle. To achieve this purpose, young healthy people (n = 15), 8) older 37) patients with knee/hip osteoarthritis, model to effect long-term inflammation vastus lateralis muscle, were included study. It was revealed that widespread substantial age-related changes gene expression relative (~4000 genes regulating mitochondrial function, proteostasis, cell membrane, secretory immune response) related physical rather than aging. Primary contributed mainly (~200) encoding nuclear proteins (regulators DNA repair, RNA processing, transcription), (genes respiratory enzymes, complex assembly factors, regulators cristae formation reactive oxygen species production), as well proteostasis. found associated regulated at post-transcriptional level. The set putative their potential transcriptional can be used resource for further targeted studies investigating individual transcription factors emergence senescent phenotype.
Язык: Английский
Процитировано
11
Frontiers in Immunology, Год журнала: 2023, Номер 14
Опубликована: Окт. 23, 2023
There is an increasing interest in the pathophysiological role of kynurenine pathway tryptophan metabolism regulation immune function and inflammation. We sought to address link between this presence rheumatic diseases (RD) by conducting a systematic review meta-analysis studies reporting plasma or serum concentrations tryptophan, kynurenine, other relevant metabolites RD patients healthy controls. searched electronic databases for articles published inception 30th June 2023. Risk bias certainty evidence were assessed using Joanna Briggs Institute Critical Appraisal Checklist Grades Recommendation, Assessment, Development Evaluation Working Group system. In 24 selected analysis, compared controls, had significantly lower (standard mean difference, SMD= -0.71, 95% CI -1.03 -0.39, p<0.001; I2 = 93.6%, low evidence), higher (SMD=0.69, 0.35 1.02, 93.2%, certainty), ratios (SMD=0.88, 0.55 1.21, 92.9%, moderate 3-hydroxykynurenine (SMD=0.74, 0.30 1.18, p=0.001; 87.7%, extremely quinolinic acid (SMD=0.71, 0.31 1.11, 88.1%, certainty). By contrast, there non-significant between-group differences kynurenic acid, 3-hydroxyanthranilic ratio, ratio. meta-regression, SMD ratio not associated with age, publication year, sample size, duration, C-reactive protein, use anti-rheumatic drugs corticosteroids. subgroup was significant across different types RD, barring rheumatoid arthritis. Therefore, we have observed alterations 3-hydroxykynurenine, patients. Further research warranted determine whether these biomarkers can be useful diagnosis management patient group. (PROSPERO registration number: CRD CRD42023443718).https://www.crd.york.ac.uk/prospero, identifier CRD42023443718.
Язык: Английский
Процитировано
15
Frontiers in Molecular Neuroscience, Год журнала: 2024, Номер 16
Опубликована: Янв. 5, 2024
The initiation and progression of neurodegenerative diseases (NDs), distinguished by compromised nervous system integrity, profoundly disrupt the quality life patients, concurrently exerting a considerable strain on both economy social healthcare infrastructure. Exercise has demonstrated its potential as an effective preventive intervention rehabilitation approach among emerging therapeutics targeting NDs. As largest secretory organ, skeletal muscle possesses capacity to secrete myokines, these myokines can partially improve prognosis NDs mediating muscle-brain axis. Besides well-studied exerkines, which are secreted during exercise that pivotally exert their beneficial function, physiological function novel e.g., apelin, kynurenic acid (KYNA), lactate have been underappreciated previously. Herein, this review discusses roles exerkines mechanisms in regulating improvement NDs, especially significance functions improving NDs’ prognoses through exercise. Furthermore, several with implications ameliorating ND proposed future direction for investigation. Elucidation regulation advances understanding pathogenesis facilitates development intervene processes cure
Язык: Английский
Процитировано
6
Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0
Опубликована: Янв. 1, 2024
The proportion of the elderly population is gradually increasing as a result medical care advances, leading to subsequent surge in geriatric diseases that significantly impact quality life and pose substantial healthcare burden. Sarcopenia, characterized by age-related decline skeletal muscle mass quality, affects considerable portion older adults, particularly elderly, can adverse outcomes such frailty, fractures, bedridden, hospitalization, even mortality. Skeletal aging accompanied underlying metabolic changes. Therefore, elucidating these profiles specific mechanisms holds promise for informing prevention treatment strategies sarcopenia. This review provides comprehensive overview key metabolites identified current clinical studies on sarcopenia their potential pathophysiological alterations activity. Besides, we examine therapeutic from perspective focused regulation.
Язык: Английский
Процитировано
5
Biomolecules, Год журнала: 2025, Номер 15(1), С. 74 - 74
Опубликована: Янв. 6, 2025
In this article, we focus on kynurenic acid metabolism in neuropsychiatric disorders and the biochemical processes involved memory cognitive impairment, followed by different approaches fight against dementia. Kynurenic acid-a part of L-tryptophan catabolism-is synthesized from L-kynurenine kynurenine aminotransferases. Experimental pharmacological studies have shown that elevated levels brain are associated with impaired learning lowering can improve these symptoms. The discovery new compounds ability to block aminotransferases opens therapeutic avenues for treatment impairment newly developed Helix pomatia snail model be used assessment novel approaches. Dietary supplementation natural molecular/herbal extracts, exercise, physical activity significant impacts endogenous pharmacology reducing synthesis, factors likely significantly modulate steady-state biological conditions delay negative consequences aging, including onset pathological processes.
Язык: Английский
Процитировано
0
PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0317201 - e0317201
Опубликована: Янв. 15, 2025
Background The causes of reduced aerobic exercise capacity (ExCap) in chronic kidney disease (CKD) are multifactorial, possibly involving the accumulation tryptophan (TRP) metabolites such as kynurenine (KYN) and kynurenic acid (KYNA), known kynurenines. Their relationship to ExCap has yet be studied CKD. We hypothesised that would negatively associated with plasma levels TRP, KYN KYNA Methods included 102 patients non-dialysis CKD stages 2–5 (CKD 2–3, n = 54; 4–5, 48) 54 healthy controls, age- sex-matched 2–3 group. was assessed peak workload during a maximal cycle ergometer test. Plasma KYN, TRP were determined by high-performance liquid chromatography. Kidney function evaluated glomerular filtration rate (GFR) estimated GFR. group controls repeated tests after five years. association between using generalised linear model. Results At baseline, there significant differences all groups ExCap, KYNA, KYN/TRP. increased follow-up period. In 2–5, KYN/TRP KYNA/KYN significantly at whereas not. Kynurenines correlated GFR (p < 0.001 for all). Including statistical model, no kynurenines independently baseline. follow-up, increase related decrease 2–3. After adjusting GFR, remained an independent predictor decline Conclusion Aerobic inversely baseline follow-up.
Язык: Английский
Процитировано
0
Journal of Aging and Physical Activity, Год журнала: 2025, Номер unknown, С. 1 - 7
Опубликована: Янв. 1, 2025
Background/Objectives : Studies that have investigated the relationship between pain intensity and interference cognitive function failed to fully consider role physical may play in this relationship. Therefore, purpose of study was examine mediating self-reported middle-to-older aged adults with knee pain. Methods Middle-to-older participants ( n = 202) completed Graded Chronic Pain Scale assess interference, Short Performance Physical Battery lower-extremity function, Montreal Cognitive Assessment global function. Linear regression-based mediation analyses were used associations as mediator. Results The direct significant (β −0.269, p < .001) remained when included a mediator (c’=−0.0854, .003). also −0.149, .023) but attenuated (c’=−0.0100, .09). Conclusion partially mediated Significance/Implications Higher levels lead worse is impaired. Improving improve those
Язык: Английский
Процитировано
0
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Фев. 14, 2025
The hypermetabolic response associated with burns is characterized by skeletal muscle atrophy and an increased incidence of disability death. Significant remodeling the gut microbiota occurs after severe burn trauma. However, specific mechanisms which contribute to burn-induced remain unexplored. results showed that disruption exacerbated atrophy. Fecal metabolite analysis revealed perturbations, primarily within tryptophan (Trp) metabolic pathway. Animal models further demonstrated disorder enhanced expression indoleamine 2,3-dioxygenase 1 (IDO-1) in colon, ultimately resulting Trp depletion kynurenine (Kyn) levels serum muscle. Excessive colonic Kyn released into circulation, transported cells, binds aryl hydrocarbon receptor (AHR), consequently triggering AHR nuclear translocation initiating transcription atrophy-related genes. Notably, samples from patients exhibited depletion, supplementation alleviated rats burns. This study, for first time, demonstrates dysbiosis upregulates IDO-1, promotes Trp-Kyn metabolism, exacerbates atrophy, suggesting may be a potential therapeutic strategy.
Язык: Английский
Процитировано
0