Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Language: Английский

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Consequences of Disturbing Manganese Homeostasis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14959 - 14959

Published: Oct. 6, 2023

Manganese (Mn) is an essential trace element with unique functions in the body; it acts as a cofactor for many enzymes involved energy metabolism, endogenous antioxidant enzyme systems, neurotransmitter production, and regulation of reproductive hormones. However, overexposure to Mn toxic, particularly central nervous system (CNS) due causing progressive destruction nerve cells. Exposure manganese widespread occurs by inhalation, ingestion, or dermal contact. Associations have been observed between accumulation neurodegenerative diseases such manganism, Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis. People genetic associated mutation gene impaired excretion, kidney iron deficiency, vegetarian diet are at particular risk excessive exposure Mn. This review has collected data on current knowledge source exposure, experimental supporting dispersive brain, controversies surrounding reference values biomarkers related status different matrices, competitiveness other metals, (Fe), magnesium (Mg), zinc (Zn), copper (Cu), lead (Pb), calcium (Ca). The disturbed homeostasis body connected susceptibility diseases, fertility, infectious diseases. evidence involvement metabolic type 2 diabetes mellitus/insulin resistance, osteoporosis, obesity, atherosclerosis, non-alcoholic fatty liver was discussed.

Language: Английский

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Environmental Toxicant Exposure and Depressive Symptoms

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2420259 - e2420259

Published: July 3, 2024

Importance Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research the initiation of disease prevention efforts. Objectives To comprehensively screen assess potential depressive symptoms whether systemic inflammation serves a mediator. Design, Setting, Participants A total 3427 participants from 2013-2014 2015-2016 waves National Health Nutrition Examination Survey who had information on blood or urine concentrations scores assessed by 9-item Patient Questionnaire (PHQ-9) were included. Statistical analysis was performed July 1, 2023, January 31, 2024. Exposures Sixty-two in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; perchlorate, nitrate, thiocyanate. Main Outcomes Measures An exposome-wide association study deletion-substitution-addition algorithm used with (PHQ-9 ≥5) adjusted other important covariates. mediation framework evaluate mediating role peripheral white cell count. Results Among adults included, 1735 (50.6%) women, 2683 (78.3%) younger than 65 years, 744 (21.7%) years older, 839 (24.5%) having symptoms. In terms race ethnicity, 570 (16.6%) Mexican American, 679 (19.8%) non-Hispanic Black, 1314 (38.3%) White. We identified 27 chemical compounds metals 6 prevalence symptoms, including VOC metabolites N -acetyl- S -(2-hydroxy-3-butenyl)- l -cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) equivalent-2 (OR, 1.42 1.26-1.59]). Men individuals appear more vulnerable women older individuals. Peripheral count mediated 5% 19% associations. Conclusions Relevance this representative cross-sectional toxicant exposures, associated inflammation. This provides insight into selecting targets mechanistic causes facilitating efforts reduce exposures.

Language: Английский

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Neuroinflammation and neurodegeneration in Huntington’s disease: genetic hallmarks, role of metals and organophosphates

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 17, 2025

Language: Английский

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Role of cuproptosis in understanding diseases

Human Cell, Journal Year: 2023, Volume and Issue: 36(4), P. 1244 - 1252

Published: May 8, 2023

Language: Английский

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The Role of Complexes of Biogenic Metals in Living Organisms

Inorganics, Journal Year: 2023, Volume and Issue: 11(2), P. 56 - 56

Published: Jan. 25, 2023

Biogenic metals and their various inorganic, organometallic, coordination compounds are comprehensively studied extensively used in medical practice. Since the biogenic have chemical properties corresponding to position periodic table, biological functions different. Almost all of discussed elements an ability form complexes. Furthermore, different accessible oxidation states occupied by most these enables body catalyze oxy-reduction interactions, depending on conditions. As they nature, deficiency or excess leads numerous pathological obstructions. The application metal-based as medications is connected with capability complexes, which involved many bioreactions. usefulness therapeutic diagnostic agents also pointed out.

Language: Английский

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Inhibition of Slc39a14/Slc39a8 reduce vascular calcification via alleviating iron overload induced ferroptosis in vascular smooth muscle cells

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 29, 2024

Abstract Background Vascular calcification (VC) is an independent risk factor for cardiovascular diseases. Recently, ferroptosis has been recognised as a novel therapeutic target Although association between and vascular reported, the role mechanism of iron overload in are still poorly understood. Specifically, further in-depth research required on whether metalloproteins SLC39a14 SLC39a8 involved induced by overload. Methods R language was employed differential analysis dataset, revealing correlation calcification. The experimental approaches encompassed both vitro vivo studies, incorporating use chelators models Additionally, gain- loss-of-function experiments were conducted to investigate iron’s effects comprehensively. Electron microscopy, immunofluorescence, western blotting, real-time polymerase chain reaction used elucidate how Slc39a14 Slc39a8 mediate promote Results Ferroptosis observed conjunction with (VC); consistently confirmed studies. Our results showed positive VSMCs Iron effective reversing VC exacerbates this process. expression levels metal transport proteins significantly upregulated during calcification; inhibition their alleviated VC. Conversely, overexpression promotes intracellular accumulation VSMCs. Conclusions demonstrates that occurs VC, relieves intercepting overload-induced VSMCs, providing new insights into treatment. Graphical

Language: Английский

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Copper in Human Health and Disease: A Comprehensive Review

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(11)

Published: Nov. 1, 2024

ABSTRACT This comprehensive review discusses the crucial role of copper in human health and disease as an essential trace mineral. It emphasizes significance while addressing potential risks from imbalances levels, be it excessive or inadequate. The outlines various challenges research, including toxicity concerns, data limitations, metabolic complexities, genetic influences, nutrient interactions, resource constraints. Despite these challenges, identifies specific research areas needing exploration, such homeostasis regulation, transport mechanisms, gut microbiome immune function, neurodegenerative diseases, cardiovascular health, cancer, fertility, reproductive health. purpose this is to explore important disease, which highlights delicate balance required avoid deficiency toxicity. For researchers scientists, provides gaps so aims provide insights that could advance diagnostic therapeutic strategies across medical disciplines.

Language: Английский

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Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10271 - 10287

Published: May 7, 2024

Language: Английский

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Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review

Critical Reviews in Toxicology, Journal Year: 2024, Volume and Issue: 54(1), P. 35 - 54

Published: Jan. 2, 2024

Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As used widely in Brazil, it is necessary gather evidence support actions aimed at safely using these chemicals. We investigated through a systematic review use and consequences exposure related nervous system diseases or disorders humans. The protocol was registered PROSPERO followed guidelines PRISMA-Statement. far as known, there no apparent literature this topic. search comprised following databases: PubMed; Web Science; Scopus EMBASE, groups Mesh terms strategies specific each database. Thirteen articles were selected for review. Regarding substances analyzed studies, some reported general, without separating them by type, while others summarized categories all pesticides their function (insecticides, herbicides, fungicides, etc.) chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most referred contain metal manganese (Mn) composition. disorders, addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive depression, neural tube defects, motor neurone disease, amyotrophic lateral sclerosis. Most investigations pointed mainly maneb mancozeb, leading development least one which suggests need further multicentric clinical trials prospective greater clarity research problem.

Language: Английский

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