Integrated Management of Cardiovascular–Renal–Hepatic–Metabolic Syndrome: Expanding Roles of SGLT2is, GLP-1RAs, and GIP/GLP-1-RAs

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 135 - 135

Published: Jan. 8, 2025

Cardiovascular-Kidney-Metabolic syndrome, introduced by the American Heart Association in 2023, represents a complex and interconnected spectrum of diseases driven shared pathophysiological mechanisms. However, this framework notably excludes liver-an organ fundamental to metabolic regulation. Building on concept, Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome incorporates liver's pivotal role disease spectrum, particularly through its involvement via dysfunction-associated steatotic liver (MASLD). Despite increasing prevalence CRHM unified management strategies remain insufficiently explored. This review addresses following critical question: How can novel anti-diabetic agents, including sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual gastric inhibitory polypeptide (GIP)/GLP-1RA, offer an integrated approach managing beyond boundaries traditional specialties? By synthesizing evidence from landmark clinical trials, we highlight paradigm-shifting potential these therapies. SGLT2is, such as dapagliflozin empagliflozin, have emerged cornerstone guideline-directed treatments for heart failure (HF) chronic kidney (CKD), providing benefits that extend glycemic control are independent diabetes status. GLP-1RAs, e.g., semaglutide, transformed obesity enabling weight reductions exceeding 15% improving outcomes atherosclerotic cardiovascular (ASCVD), diabetic CKD, HF, MASLD. Additionally, tirzepatide, GIP/GLP-1RA, enables unprecedented loss (>20%), reduces risk over 90%, improves HF with preserved ejection fraction (HFpEF), MASLD, obstructive sleep apnea. moving organ-specific approach, propose integrates agents into holistic syndrome. paradigm shift moves away fragmented, organ-centric toward more fostering collaboration across specialties marking progress precision cardiometabolic medicine.

Language: Английский

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Molecular mechanism on autophagy associated cardiovascular dysfunction in Drosophila melanogaster

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 3, 2025

As a highly conserved cellular process, autophagy has been the focus of extensive research due to its critical role in maintaining homeostasis and implications cardiovascular pathogenesis. The decline muscular function, along with neuronal system, increased sensitivity stress have recognized multiple animal models. Autophagic defects architecture dysfunction linked both physiological pathological conditions heart mammals Drosophila . In this review, we systematically analyze autophagy-associated pathways hearts fruit flies aim provide comprehensive understanding for developing potential treatments patients effective strategies agricultural applications. This analysis elucidates molecular mechanisms function under , offering significant insights into development diseases. loss key proteins, including transmembrane protein Atg9 partners Atg2 or Atg18, DmSestrin, leads cardiac hypertrophy structural abnormalities resembling age-dependent deterioration function. Members autophagy-related (Atg) gene family, nuclear skeletal lamins, mechanistic mammalian target rapamycin (mTOR) signaling are critically influential activation shown suppress laminopathy. mTORC1/C2 complexes, axis Atg2-AMPK/Sirt1/PGC-1α pathway, essential flies, governing development, growth, maturation, maintenance homeostasis. beneficial effects several interventions that enhance exercise cold stress, can influence autophagy-dependent TOR activity serine/threonine kinase Exercise increase when it is deficient inhibit excessive, highlighting dual health. review evaluates functional significance heart, particularly context relation mTORC-associated pathways. It contrasts underlying mammals. evolutionary conservation underscores value as model broader across species. study not only deepens our autophagy’s but also provides theoretical foundation application pest control.

Language: Английский

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Empagliflozin-activated AMPK elicits neuroprotective properties in reserpine-induced depression via regulating dynamics of hippocampal autophagy/inflammation and PKCζ-mediated neurogenesis

Psychopharmacology, Journal Year: 2024, Volume and Issue: 241(12), P. 2565 - 2584

Published: Aug. 19, 2024

Abstract Rationale Major depression has been an area of extensive research during the last decades, for it represents a leading cause disability and suicide. The stark rise rates influenced by life stressors, economic threats, pandemic era, resistance to classical treatments, made disorder rather challenging. Adult hippocampal neurogenesis plasticity are particularly sensitive dynamic interplay between autophagy inflammation. In fact, intricate balance two processes contributes neuronal homeostasis survival. Objectives Having demonstrated promising potentials in AMPK activation, major metabolic sensor regulator, empagliflozin (Empa) was investigated possible antidepressant properties reserpine rat model depression. Results While protocol elicited behavioral, biochemical, histopathological changes relevant depression, Empa outstandingly hindered these pathological perturbations. Importantly, autophagic response markedly declined with which disrupted AMPK/mTOR/Beclin1/LC3B machinery and, conversely, neuro-inflammation prevailed under influence NLRP3 inflammasome together oxidative/nitrative stress. Consequently, AMPK-mediated neurotrophins secretion obviously deteriorated through PKCζ/NF-κB/BDNF/CREB signal restriction. restored monoamines autophagy/inflammation balance, driven activation. By promoting atypical PKCζ phosphorylation (Thr403) subsequently phosphorylates NF-κB at Ser311, successfully reinforced BDNF/CREB neuroplasticity. latter finding supported CA3 toluidine blue staining reveal intact neurons. Conclusion current study highlights interesting role as regulator inflammatory responses pathology also pinpoints unusual contribution via AMPK/PKCζ/NF-κB/BDNF/CREB transduction. Accordingly, can have special benefits diabetic patients depressive symptoms. Limitations p -NF-κB (Ser311) on assembly activation not investigated, represent point further research. Graphical abstract

Language: Английский

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A Study of the Impact of Magnesium Supplements on Asthma Control

International Journal of Innovative Science and Research Technology (IJISRT), Journal Year: 2024, Volume and Issue: unknown, P. 3136 - 3144

Published: Aug. 21, 2024

Background: In the recent studies, relationship between magnesium and asthma has been more considered; hence, present research aimed to study this issue.  Methodology: The is a Randomized double blind placebo control trial, which conducted on asthmatic patients who have divided into two groups: group one consisting of those taken including supplement. beginning during weeks 4, 8 12, FVC, FEV1, FEV1/FVC ACT score measured. Results: 40 studied in equal groups. improvement rate gradually increased group2 was significantly higher than group1 week 12. It also 4 but not significantly. Moreover, according FVC ratio, cure higher; however, it 8th week. comparison before study. Conclusion: seems that supplement helpful improving clinical spirometric measurements patients.

Language: Английский

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AMPK activation; a potential strategy to mitigate TKI-induced cardiovascular toxicity

Archives of Physiology and Biochemistry, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Nov. 11, 2024

The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionised cancer treatment, yet concerns regarding cardiovascular toxicity have surfaced. This piece delves into the interplay between AMP-activated protein kinase (AMPK) signalling and TKI-induced toxicity. study unravels intricate relationship AMPK activation toxicity, aiming to ascertain whether can play a strategic role in mitigating adverse effects. Beyond unravelling mechanistic insights, research sets stage for future therapeutic approaches, envisioning as pivotal connection balancing effective treatment with well-being. As advances, potential not only addresses challenges but also shapes landscape personalised anticancer therapies. article explores mechanisms AMPK's impact on health, implications alleviating TKI-associated toxicities.

Language: Английский

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