Chemotherapy-Induced Molecular Changes in Skeletal Muscle

Biomedicines, Год журнала: 2023, Номер 11(3), С. 905 - 905

Опубликована: Март 15, 2023

Paraneoplastic conditions such as cancer cachexia are often exacerbated by chemotherapy, which affects the patient’s quality of life well response to therapy. The aim this narrative review was overview body-composition-related changes and molecular effects different chemotherapy agents used in treatment on skeletal-muscle remodeling. A literature search performed using Web Science, Scopus, Science Direct databases a total 77 papers retrieved. In general, survey showed that induced skeletal muscle have been studied mainly animal models mostly non-tumor-bearing rodents, whereas clinical studies essentially assessed body composition computerized tomography. Data from preclinical modulates several pathways muscle, including ubiquitin–proteasome pathway, autophagy, IGF-1/PI3K/Akt/mTOR, IL-6/JAK/STAT, NF-κB pathway; however, newest underexplored. conclusion, exacerbates wasting patients; incomplete characterization chemotherapy-related makes development new preventive anti-wasting strategies difficult. Therefore, further investigation mechanisms necessary.

Язык: Английский

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Targeting autophagy drug discovery: Targets, indications and development trends

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 267, С. 116117 - 116117

Опубликована: Янв. 23, 2024

Язык: Английский

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Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration

Antioxidants, Год журнала: 2024, Номер 13(5), С. 568 - 568

Опубликована: Май 4, 2024

Age-related macular degeneration (AMD) severely affects central vision due to progressive and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging considered an important contributor AMD pathogenesis despite multifaceted risk factors including genetic predisposition environmental agents. Wet can be managed routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for successful management dry form. The toxic carbonyls photo-oxidative degradation accumulated bisretinoids within lysosomes initiate a series events protein adduct formation, impaired autophagy flux, complement activation, chronic inflammation, which implicated AMD. Therapy based on antioxidants extensively studied promising effect reducing impact stress. This paper reviews pathogenesis, delineates effectiveness dietary nutrition supplements clinical studies, explores pre-clinical studies antioxidant molecules, extracts, formulations their mechanistic insights.

Язык: Английский

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Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation

Autophagy, Год журнала: 2024, Номер 20(9), С. 2017 - 2040

Опубликована: Май 15, 2024

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote survival during energetic stress, in part by inhibiting MTORC1, an kinase requiring sufficient levels of amino acids. We found that cells lacking displayed increased apoptotic death nutrient stress caused prolonged acid deprivation. presumed impaired macroautophagy/autophagy explained this phenotype, as a prevailing view posits initiates autophagy (often pro-survival response) through phosphorylation ULK1. Unexpectedly, however, remained unimpaired AMPK, monitored several autophagic readouts lines. More surprisingly, the absence ULK1 signaling MAP1LC3B/LC3B lipidation deprivation while AMPK-mediated S555 (a site proposed initiate autophagy) decreased upon withdrawal or pharmacological MTORC1 inhibition. In addition, activation with compound 991, glucose deprivation, AICAR blunted induced withdrawal. These results demonstrate suppress autophagy. As controlled unexpected direction, we examined how controls signaling. Paradoxically, observed reactivation Together these oppose established views inhibits universally. Moreover, they reveal roles for suppression support context findings prompt reevaluation its control affect health disease.

Язык: Английский

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Importance of Energy, Dietary Protein Sources, and Amino Acid Composition in the Regulation of Metabolism: An Indissoluble Dynamic Combination for Life

Nutrients, Год журнала: 2024, Номер 16(15), С. 2417 - 2417

Опубликована: Июль 25, 2024

This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy protein synthesis are fundamental biological processes, crucial sustenance of life growth organisms.

Язык: Английский

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Autophagy in Its (Proper) Context: Molecular Basis, Biological Relevance, Pharmacological Modulation, and Lifestyle Medicine

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(7), С. 2532 - 2554

Опубликована: Янв. 1, 2024

Autophagy plays a critical role in maintaining cellular homeostasis and responding to various stress conditions by the degradation of intracellular components.In this narrative review, we provide comprehensive overview autophagy's molecular basis, biological significance, pharmacological modulation, its relevance lifestyle medicine.We delve into intricate mechanisms that govern autophagy, including macroautophagy, microautophagy chaperone-mediated autophagy.Moreover, highlight significance autophagy aging, immunity, metabolism, apoptosis, tissue differentiation systemic diseases, such as neurodegenerative or cardiovascular diseases cancer.We also discuss latest advancements modulation their potential implications clinical settings.Finally, explore intimate connection between factors emphasizing how nutrition, exercise, sleep patterns environmental can significantly impact autophagic process.The integration medicine research opens new avenues for promoting health longevity through personalized interventions.

Язык: Английский

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Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 3, 2023

Diabetic kidney disease (DKD) is the main cause of end-stage renal worldwide, and there a lack effective treatment strategies. Autophagy highly conserved lysosomal degradation process that maintains homeostasis energy balance by removing protein aggregates damaged organelles. Increasing evidence suggests dysregulated autophagy may contribute to glomerular tubulointerstitial lesions in under diabetic conditions. Emerging studies have shown Chinese herbal medicine its active compounds ameliorate injury regulating autophagy. In this review, we summarize dysregulation or insufficiency cells, including podocytes, mesangial proximal tubular epithelial key mechanism for development DKD, focus on protective effects compounds. Moreover, systematically reviewed DKD regulated herb compound preparations, single compounds, so as provide new drug candidates clinical DKD. Finally, also candidate targets Therefore, further research with regulation their great significance realization targeted therapies

Язык: Английский

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Inhibition of autophagy; an opportunity for the treatment of cancer resistance

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Июнь 9, 2023

The process of macroautophagy plays a pivotal role in the degradation long-lived, superfluous, and damaged proteins organelles, which are later recycled for cellular use. Normal cells rely on autophagy to combat various stressors insults ensure survival. However, is often upregulated cancer cells, promoting more aggressive phenotype that allows mutated evade death after exposure therapeutic treatments. As result, has emerged as significant factor resistance across many types, with underlying mechanisms such DNA damage, cell cycle arrest, immune evasion. This review provides comprehensive summary limitations available autophagic inhibitors treatment. It also highlights urgent need explore new can synergize existing therapies achieve better patient treatment outcomes. Advancing research this field crucial developing effective treatments help improve lives patients.

Язык: Английский

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Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction

Molecules and Cells, Год журнала: 2023, Номер 46(11), С. 655 - 663

Опубликована: Окт. 23, 2023

Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, chronic infections. Additionally, the decline in autophagic activity contributes to tissue organ aging-related diseases. Several factors, such as down-regulation of autophagy components activators, oxidative damage, microinflammation, impaired flux, are linked decline. An flux impairment (AFI) has been implicated neurological disorders certain other pathological conditions. Here, enhance our understanding AFI, we conducted a comprehensive literature review findings derived from two well-studied cellular stress models: glucose deprivation replicative senescence. Glucose condition which cells heavily rely on phosphorylation for ATP generation. activated, but its hindered at autolysis step, primarily due an lysosomal acidity. Cells undergoing senescence also experience known be caused by acidity failure. Both elevate levels reactive oxygen species (ROS), affecting acidification. Mitochondrial alterations play crucial role elevating ROS generation reducing acidity, highlighting their association disease This paper delves into underlying molecular pathways AFI glucose-deprived cells, providing insights potential strategies managing that driven Furthermore, investigation roles mitochondrial sheds light effectiveness modulating function overcome offering new possibilities therapeutic interventions.

Язык: Английский

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The role of autophagy in insulin resistance and glucolipid metabolism and potential use of autophagy modulating natural products in the treatment of type 2 diabetes mellitus

Diabetes/Metabolism Research and Reviews, Год журнала: 2024, Номер 40(1)

Опубликована: Янв. 1, 2024

Type 2 diabetes mellitus (T2DM) is a severe, long-term condition characterised by disruptions in glucolipid and energy metabolism. Autophagy, fundamental cellular process, serves as guardian of health recycling renewing components. To gain comprehensive understanding the vital role that autophagy plays T2DM, we conducted an extensive search for high-quality publications across databases such Web Science, PubMed, Google Scholar, SciFinder used keywords like 'autophagy', 'insulin resistance', 'type mellitus', both individually combinations. A large body evidence underscores significance activating alleviating T2DM symptoms. An enhanced autophagic activity, either adenosine monophosphate-activated protein kinase sirtuin-1 signalling pathways or inhibiting mechanistic target rapamycin complex 1 pathway, can effectively improve insulin resistance balance metabolism key tissues hypothalamus, skeletal muscle, liver, adipose tissue. Furthermore, increase β-cell mass functionality pancreas. This review provides narrative summary regulation with emphasis on intricate connection between It also discusses therapeutic potentials natural products activation properties treatment conditions. Our findings suggest represents innovative approach treating T2DM.

Язык: Английский

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