Association between red cell distribution width—albumin ratio and all-cause mortality in intensive care unit patients with heart failure

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 20, 2025

Aim The association between red cell distribution width—albumin ratio (RAR) and the risk of all-cause mortality in intensive care unit (ICU) patients with heart failure remains uncertain. This study aimed to investigate this association. Methods Clinical data from MIMIC-Ⅳ (version 2.2) database was utilized for analysis ICU failure. Patients were categorized into quartiles (Q1–Q4) based on RAR levels. Kaplan-Meier survival multivariate adjusted Cox regression models employed assess levels outcomes within 1 year. Subgroup used evaluate prognostic impact across diverse populations. Restricted cubic spline curves threshold effect quantify dose-response relationship mortality. time-concordance index curve carried out explore additional value over existing scoring systems, Serial Organ Failure Assessment (SOFA) Acute Physiology Chronic Health Evaluation Ⅱ (APACHE Ⅱ). Results encompassed a cohort 4,506 patients, indicating that individuals higher exhibited an elevated ( p < 0.001). Multivariate subgroup demonstrated Q2 [hazard (HR) 1.15, 95%CI 0.98–1.34], Q3 (HR 1.65, 1.39–1.96) Q4 2.16, 1.74–2.68) had increased compared Q1 trend 0.001), consistently observed most subgroups, except different ages. Subsequent revealed inclusion significantly improved basis SOFA APACHE Ⅱ, concordance 0.636 0.658 SOFA, 0.682 0.695 0.001 both). Conclusion found high level independently associated 1-year failure, stronger young middle-aged effect, which could potentially serve as early warning indicator high-risk

Language: Английский

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Podocyte Death in Diabetic Kidney Disease: Potential Molecular Mechanisms and Therapeutic Targets

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9035 - 9035

Published: Aug. 20, 2024

Cell deaths maintain the normal function of tissues and organs. In pathological conditions, abnormal activation or disruption cell death often leads to pathophysiological effects. Diabetic kidney disease (DKD), a significant microvascular complication diabetes, is linked high mortality morbidity rates, imposing substantial burden on global healthcare systems economies. Loss detachment podocytes are key changes in progression DKD. This review explores potential mechanisms apoptosis, necrosis, autophagy, pyroptosis, ferroptosis, cuproptosis, podoptosis podocytes, focusing how different modes contribute It recognizes limitations current research presents latest basic clinical studies targeting podocyte pathways Lastly, it focuses future treat DKD, with intention inspiring further development therapeutic strategies.

Language: Английский

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Regulatory-Associated Protein of mTOR-Mediated Signaling: A Nexus Between Tumorigenesis and Disease

Targets, Journal Year: 2024, Volume and Issue: 2(4), P. 341 - 371

Published: Nov. 7, 2024

RAPTOR (regulatory-associated protein of mTOR) is a pivotal component the mammalian target rapamycin complex 1 (mTORC1), playing central role in regulating cell growth, metabolism and stress responses. As scaffold protein, recruits key substrates such as eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) ribosomal S6 kinase (S6K), facilitating their phosphorylation by mTORC1, which turn drives synthesis, lipid cellular proliferation. Its regulatory function becomes especially crucial under conditions nutrient deprivation or stress, where it enhances stability mTORC1 complex, allowing cells to adapt fluctuating environmental cues. The hyperactivation largely mediated RAPTOR, frequently observed various cancers, contributing uncontrolled proliferation tumorigenesis. Moreover, RAPTOR’s modulation immune responses metabolic pathways extends its influence beyond oncogenesis, impacting inflammatory diseases disorders. This review meticulously elucidates structure, post-translational modifications well indispensable within emphasizing functions adaptation, response disease pathology including oncogenesis. Furthermore, explores emergent therapeutic avenues targeting RAPTOR-mediated signaling, underscoring potential revolutionize cancer treatment management related pathophysiological conditions.

Language: Английский

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ACSS2 and metabolic diseases: from lipid metabolism to therapeutic target

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 25, 2025

Elevated incidence of metabolic disorders has been reported worldwide in the recent decade, highlighting need for developing efficient therapies. These diseases result from a complex interplay various factors that contribute to disease progression, complications, and resistance current treatment options. Acetyl-CoA Synthetase Short Chain Family Member 2 (ACSS2) is nucleo-cytosolic enzyme with both lipogenic regulatory roles. Studies on ACSS2 have shown it involved pathways commonly dysregulated disorders, leading fat deposition disrupted cellular signaling. Although multiple studies suggested role rewiring during tumorigenesis, few examined its involvement pathophysiology diseases. Recent evidence indicates may pathogenesis making examination great interest potentially aiding development new therapeutic strategies. The objective this review summarize understanding ACSS2's potential as target.

Language: Английский

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Targeting lipid metabolic reprogramming to alleviate diabetic kidney disease: molecular insights and therapeutic strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Diabetic kidney disease (DKD) is one of the major complications diabetes, and its pathological progression closely associated with lipid metabolic reprogramming. Under diabetic conditions, renal cells undergo significant abnormalities, including increased uptake, impaired fatty acid oxidation, disrupted cholesterol efflux, enhanced catabolism, as adaptive responses to stress. These changes result in accumulation lipids such free acids, diacylglycerol, ceramides, leading lipotoxicity that triggers inflammation fibrosis. Hypoxia DKD microenvironment suppresses oxidation promotes synthesis through HIF-1α pathway, while chronic exacerbates disturbances via inflammatory cytokines, inflammasomes, macrophage polarization. Targeting metabolism represents a promising therapeutic strategy for alleviating DKD; however, further clinical translational studies are warranted validate efficacy safety these approaches.

Language: Английский

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A novel L-shaped ortho-quinone analog targeting adenosine A2b receptor to inhibit epithelial-mesenchymal transition in colorectal cancer cells

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(6)

Published: May 5, 2025

Language: Английский

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Molecular mechanisms of diabetic nephropathy: A narrative review

Cell Biology International, Journal Year: 2024, Volume and Issue: 48(9), P. 1240 - 1253

Published: June 30, 2024

Abstract Diabetic nephropathy (DN) is the predominant secondary resulting in global end‐stage renal disease. It attracting significant attention both domestic and international research due to its widespread occurrence, fast advancement, limited choices for prevention treatment. The pathophysiology of this condition intricate involves multiple molecular cellular pathways at various levels. This article provides a concise overview processes involved development DN. discusses factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, damage, autophagy, epigenetics. aim offer clinicians valuable reference DN's diagnosis, treatment, intervention.

Language: Английский

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Proteome characterization of liver–kidney comorbidity after microbial sepsis

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(7)

Published: April 6, 2024

Abstract Sepsis is a life‐threatening condition that occurs when the body responds to an infection but subsequently triggers widespread inflammation and impaired blood flow. These pathologic responses can rapidly cause multiple organ dysfunction or failure either one by simultaneously. The fundamental common mechanisms involved in sepsis‐induced remain unclear. Here, employing quantitative global phosphoproteomics, we examine liver's temporal proteome phosphoproteome changes after moderate sepsis induced cecum ligation puncture. In total, 4593 proteins 1186 phosphoproteins according 3275 phosphosites were identified. To characterize liver–kidney comorbidity sepsis, developed mathematical model performed cross‐analyses of liver kidney data obtained from same set mice. Beyond immune response, showed commonly disturbed pathways key regulators are linked energy metabolism consumption. Our provide open resources understand communication between as they work fight maintain homeostasis.

Language: Английский

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Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 8(1), P. 36 - 46

Published: Dec. 18, 2024

Acetyl coenzyme A (acetyl-CoA), a pivotal regulatory metabolite, is product of numerous catabolic reactions and substrate for various anabolic responses. Its role extends to crucial physiological processes, such as glucose homeostasis free fatty acid utilization. Moreover, acetyl-CoA plays significant part in reshaping the metabolic microenvironment influencing progression several diseases conditions, including cancer, insulin resistance, diabetes, heart failure, fear, neuropathic pain. This Review delves into both pathological shedding light on key players its formation within cytosol. We specifically focus impact malonyl-CoA decarboxylase (MCD), synthetase2 (ACSS2), ATP-citrate lyase (ACLY) metabolism, homeostasis, utilization, post-translational modification cellular processes. Additionally, we present implications MCD, ACSS2, ACLY clinical manifestations. also explores potential limitations targeting using small molecules different settings.

Language: Английский

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