Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1422 - 1422

Published: Jan. 11, 2023

Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well other diseases, such diabetes non-alcoholic fatty liver disease, in which inflammation the actions of various adipokines play role pathological mechanisms involved these disorders. Leptin mainly produced by adipose tissue proportion to fat stores, but it also synthesized organs, where leptin receptors are expressed. This hormone performs numerous brain, related control energy homeostasis. It neurogenesis neuroprotection, central resistance some neurological disorders, e.g., Parkinson’s Alzheimer’s diseases. In peripheral tissues, implicated regulation metabolism, bone density muscle mass. All can be affected changes levels this hormone. review will present recent advances molecular action their underlying roles situations, may interest for revealing new approaches treatment diseases adipokine might compromised.

Language: Английский

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The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(1), P. 1 - 23

Published: Feb. 27, 2024

Worldwide stroke is the second leading cause of death and third disability combined. The estimated global economic burden by over US$891 billion per year. Within three decades (1990-2019), incidence increased 70%, deaths 43%, prevalence 102%, DALYs 143%. Of 100 million people affected stroke, about 76% are ischemic (IS) patients recorded worldwide. Contextually, moves into particular focus multi-professional groups including researchers, healthcare industry, economists, policy-makers. Risk factors demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) secondary (clinically manifested collateral disorders contributing to risks) care. These risks interrelated. For example, sedentary lifestyle toxic environment both mitochondrial stress, systemic low-grade inflammation accelerated ageing; inflammageing a associated with ageing poor outcomes. Stress overload, decreased bioenergetics hypomagnesaemia vasospasm lesions heart brain all age teenagers. Imbalanced dietary patterns folate but rich red processed meat, refined grains, sugary beverages hyperhomocysteinaemia, inflammation, small vessel disease, IS risks. Ongoing 3PM research towards vulnerable population promoted European Association Predictive, Preventive Personalised Medicine (EPMA) demonstrates promising results holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as vital biosensor AI-based data interpretation reported here EPMA expert group. Collected that IS-relevant corresponding molecular pathways examples, there an evident overlap between involved diabetic retinopathy early indicator patients. Just exemplify some them such 5-aminolevulinic acid/pathway, which also characteristic altered mitophagy patterns, insomnia, stress regulation modulation microbiota-gut-brain crosstalk. Further, ceramides considered mediators oxidative cardiometabolic negatively affecting respiratory chain function fission/fusion activity, sleep-wake behaviour, vascular stiffness remodelling. Xanthine/pathway homeostasis stress-driven anxiety-like behaviour well mechanisms arterial stiffness. In order assess individual risks, application machine learning (AI tool) essential accurate performed multiparametric analysis. Aspects presented paper include needs young populations elderly, personalised assessment care, cost-efficacy, innovative technologies screening programmes, advanced education measures professionals general population-all pillars paradigm change from reactive medical services overall management EPMA.

Language: Английский

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Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

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FoxO1 as a tissue-specific therapeutic target for type 2 diabetes

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 23, 2023

Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such type 2 diabetes mellitus (T2D). The role FoxO1 in metabolism has well studied, but recently FoxO1’s potential prevention therapy debated. For example, studies shown increased activity certain tissue types contributes to T2D pathology, symptoms, comorbidities, yet other elevated reported alleviate symptoms associated with diabetes. Furthermore, opposite effects active the same type. liver, by increasing hepatic glucose production. However, either increase or decrease lipogenesis adipogenesis white adipose tissue. In skeletal muscle, reduces uptake oxidation, promotes lipid increases muscle atrophy. While show lowers pancreatic insulin production secretion, others opposite, especially response oxidative stress inflammation. Elevated hypothalamus risk developing T2D. may mitigate Alzheimer’s disease, a neurodegenerative disease strongly Conversely, accumulating evidence implicates Parkinson’s pathogenesis. Here we review actions conditions tissues abundantly express highlight some current targeting treatment.

Language: Английский

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Insulin resistance as the molecular link between diabetes and Alzheimer's disease

World Journal of Diabetes, Journal Year: 2024, Volume and Issue: 15(7), P. 1430 - 1447

Published: July 8, 2024

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.

Language: Английский

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Molecular insights of diabetic nephropathy and chemical constituents-based treatment approach

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

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Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities — preliminary data for PPPM validation

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 43 - 51

Published: Feb. 22, 2023

Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM means at least 1 out 15 persons. This number projected grow 51% year 2045. One most common complications T2DM diabetic retinopathy (DR) with an overall prevalence 30%. The total DR-related visual impairments on rise, due growing population. Proliferative (PDR) progressing DR and leading cause preventable blindness in working-age adults. Moreover, PDR characteristic systemic attributes including mitochondrial impairment, increased cell death chronic inflammation, independent predictor cascading DM-complications such ischemic stroke. Therefore, early a reliable appearing upstream this "domino effect". Global screening, timely identification DM-related complications, insufficiently implemented currently applied reactive medicine. A personalised predictive approach cost-effective targeted prevention shortly - predictive, preventive medicine (PPPM / 3PM) could make good use accumulated knowledge, preventing other severe complications. In order reach goal, stage- disease-specific biomarker panels needed characterised easy way sample collection, high sensitivity specificity analyses. current study, we tested hypothesis non-invasively collected tear fluid robust source for analysis ocular (DM-related complications) patterns suitable differential diagnosis stable versus PDR. Here, report first results comprehensive ongoing which correlate individualised patient profiles (healthy controls patients D well without co-morbidities) their metabolic fluid. Comparative mass spectrometric performed has identified following clusters differentially expressed groups comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases phosphatidyl-cholines, triglycerides, cholesterol esters, fatty acids. Our preliminary data strongly support potential clinical utility indicating unique signature stages progression. pilot study creates platform validating stratify T2DM-patients predisposed since T2DM-related stroke, our international project aims create analytical prototype "diagnostic tree" (yes/no) applicable healthrisk assessment care.

Language: Английский

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Gene expression analysis reveals diabetes-related gene signatures

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Feb. 8, 2024

Abstract Background Diabetes is a spectrum of metabolic diseases affecting millions people worldwide. The loss pancreatic β-cell mass by either autoimmune destruction or apoptosis, in type 1-diabetes (T1D) and 2-diabetes (T2D), respectively, represents pathophysiological process leading to insulin deficiency. Therefore, therapeutic strategies focusing on restoring secretory capacity may impact disease management. This study took advantage powerful integrative bioinformatic tools scrutinize publicly available diabetes-associated gene expression data unveil novel potential molecular targets associated with dysfunction. Methods A comprehensive literature search for human studies alterations the pancreas T1D T2D was performed. total 6 were selected extraction analysis. Pathway enrichment analyses differentially expressed genes (DEGs) conducted, together protein–protein interaction networks identification transcription factors (TFs). For noncoding RNAs, microRNAs (miRNAs) long RNAs (lncRNAs), which exert regulatory activities diabetes, identifying target pathways regulated these fundamental establishing robust network. Results Comparisons DEGs among showed 59 common 4 more studies. Besides mRNA, it possible identify miRNA lncRNA. Among top (TFs), HIPK2, KLF5, STAT1 STAT3 emerged as regulators altered expression. Integrated analysis protein-coding genes, miRNAs, lncRNAs pointed out several involved metabolism, cell signaling, immune system, adhesion, interactions. Interestingly, GABAergic synapse pathway only all datasets. Conclusions demonstrated power bioinformatics scrutinizing data, thereby revealing like pathway, holds promise modulating α-cells transdifferentiation into β-cells.

Language: Английский

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Unraveling the complexities of colorectal cancer and its promising therapies – An updated review

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113325 - 113325

Published: Oct. 14, 2024

Language: Английский

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Glycoproteome-Wide Discovery of Cortical Glycoproteins That May Provide Cognitive Resilience in Older Adults

Neurology, Journal Year: 2024, Volume and Issue: 102(7)

Published: March 19, 2024

Molecular omics studies have identified proteins related to cognitive resilience but unrelated Alzheimer disease and disease-related dementia (AD/ADRD) pathologies. Posttranslational modifications of with glycans can modify protein function. In this study, we glycopeptiforms associated resilience.

Language: Английский

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