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Phenothiazines enhance antibacterial activity of macrophage by inducing ROS and autophagy.

Bacterial infections pose a major global public health threat. While antibiotics have historically served as the primary treatment, the rapi … treated with phenothiazines, we observed a significant increase in lysosomal activity, induction of autophagy, and accumulation of reactive oxygen species (ROS). Importantly, co-treatment with autophagy inhibitors or ROS scavengers markedly diminished the antibacterial effects of phenothiazines. Furthermore, perphenazine (PHZ) effectively reduced organ lesi …

Патогенетическое участие аутоматики и митофагии в первичном прогрессивном мультиклерозе.

Первичный прогрессивный множественный склероз (ППМС) влияет на поднабор пациентов, страдающих НР, и характеризуется непрерывным развитием с самого начала. Молекулярные механизмы, лежащие в основе РРМС, плохо понимаются, а возможности лечения ограничены, при этом отсутствуют конкретные маркеры для раннего обнаружения и мониторинга. В ходе этого исследования изучалась роль автофагии и митофагии в РРМС. Мы обнаружили, что автофагичные маркеры (ATG5 и ATG7) и митофагиевые маркеры (Parkin and Optineurin) были значительно сокращены в сыворотке пациентов, получающих ПУПМ, по сравнению с лицами, осуще

Совпадение в аннотации оригинала
Primary progressive multiple sclerosis (PPMS) affects a subset of MS patients and is characterised by continuous progression from the onset. The molecular mechanisms underlying PPMS are poorly understood, and therapeutic options are limited, with no specific markers for early detection and monitoring. This study investigated the roles of autophagy and mitoph…

Autophagy genes and signaling pathways in endometrial decidualization and pregnancy complications.

Autophagy is a process that occurs in almost all eukaryotic cells and this process is controlled by several molecular processes. Its biological roles include the provision of energy, the maintenance of cell homeostasis, and the promotion of aberrant cell death. The importance of autophagy in pregnancy is gradually becoming recognized. In literature, it has been indicated that autophagy has three different effects on the onset and maintenance of pregnancy: embryo (embryonic development), feto-maternal immune crosstalk, and maternal (decidualization). In humans, proper decidualization is a major…

Autophagy in cholangiocarcinoma: a comprehensive review about roles and regulatory mechanisms.

The role of autophagy in cholangiocarcinogenesis and its development is intricate. Autophagy has a dual role in cholangiocarcinoma, and understanding the function and mechanism of autophagy in cholangiocarcinoma is pivotal in guiding therapeutic approaches to its treatment in clinical settings. Recent studies have revealed that autophagy is involved in the complex biological behavior of cholangiocarcinoma. In this review, we have summarized the genes and drugs that would promote or inhibit autophagy, leading to change in cellular behaviors of cholangiocarcinoma, including apoptosis, proliferat…

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy.

Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated guanine exchange factor Plekhg5 drives the UPS of Sod1. Mechanistically, Sod1 is sequestered into autophagosomal carriers, which subsequently fuse with secretory lysosomal-related organelles (LROs). Exocytosis of LROs to release Sod1 into the extracellular milieu requires the activat…

GPCR Function in Autophagy Control: A Systematic Approach of Chemical Intervention.

Autophagy facilitates the degradation of cellular content via the lysosome and is involved in cellular homeostasis and stress response pathways. As such, malfunction of autophagy is linked to a variety of diseases ranging from organ-specific illnesses like cardiomyopathy to systemic illnesses such as cancer or metabolic syndromes. Given the variety of autophagic functions within a cell and tissue, regulation of autophagy is complex and contains numerous positive and negative feedback loops. While our knowledge of mechanisms for cargo selectivity has significantly improved over the last decade,…

Unveiling the Intricacies of Autophagy in Asthma: Unraveling Novel Therapeutic Avenues.

Understanding the pathogenesis of different phenotypes of asthma, including glucocorticoid-dependent and glucocorticoid-resistant asthma, is crucial for the development of effective treatments. Autophagy, a fundamental cellular process involved in cell homeostasis, has been implicated in asthma, although the exact mechanisms remain unclear. Recent studies have identified autophagy activation in eosinophilic, neutrophilic, and paucigranulocytic asthma, providing novel insights into the disease. This comprehensive review examines the role of autophagy in the pathogenesis and treatment of asthma,…

Autophagy: A potential target for natural products in the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the mucosa of the colon and rectum. UC is characterized by recurrent episodes, often necessitating lifelong medication use, imposing a significant burden on patients. Current conventional and advanced treatments for UC have the disadvantages of insufficient efficiency, susceptibility to drug resistance, and notable adverse effects. Therefore, developing effective and safe drugs has become an urgent need. Autophagy is an intracellular degradation process that plays an important role in intestinal homeostasis. Em…

Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia.

Autophagy is activated in response to a variety of stress conditions including anti-cancer therapies, and tumors cells often depend on autophagy for survival. In this study, we have evaluated inhibition of autophagy as therapeutic strategy in acute lymphoblastic leukemia (ALL) in children, both as a single treatment and in combination with glucocorticoid (GC) Dexamethasone (Dexa). Analysis of proteomics and RNA-seq of ALL cell lines and primary samples identified an upregulation of Vps34 and ATG14 proteins and autophagy and lysosomal pathway enrichment in a genetic subgroup with a recurrent t(…

Autophagy induced by hypoxia in pulpitis is mediated by HIF-1α/BNIP3.

OBJECTIVE: Hypoxia-inducible factor-1α (HIF-1α) and its downstream factor, 19 kDa BCL-2 interacting protein 3 (BNIP3), promote cellular autophagy under hypoxic conditions. However, their roles in pulpitis are unclear. Therefore, the changes in inflammatory response and autophagy levels caused by hypoxia during pulpitis were evaluated. Additionally, the regulatory mechanism of HIF-1α/BNIP3 in cellular autophagy in pulpitis was explored. DESIGN: Pulp from dental pulp tissues of healthy individuals and patients with pulpitis (n = 10) were exposed and combined with a low oxygen simulation chamber…

Friends and Foes: The Ambivalent Role of Autophagy in HIV-1 Infection.

Autophagy has emerged as an integral part of the antiviral innate immune defenses, targeting viruses or their components for lysosomal degradation. Thus, successful viruses, like pandemic human immunodeficiency virus 1 (HIV-1), evolved strategies to counteract or even exploit autophagy for efficient replication. Here, we provide an overview of the intricate interplay between autophagy and HIV-1. We discuss the impact of autophagy on HIV-1 replication and report in detail how HIV-1 manipulates autophagy in infected cells and beyond. We also highlight tissue and cell-type specifics in the interp…

The mechanism of mitochondrial autophagy regulating Clathrin-mediated endocytosis in epilepsy.

OBJECTIVE: The objective of this study is to determine whether inhibition of mitophagy affects seizures through Clathrin-mediated endocytosi … The methylated derivative of adenine, known as 3-MA, has been extensively utilized in the field of autophagy research. The transferrin protein is internalized from the extracellular environment into the intracellular space via the CME pathway. Tf-A488 uses a fluorescent marker to track CME. Western blot showed that the expression of Parkin was significantl …

A Pyridinium fluorophore for the detection of zinc ions under autophagy conditions.

Molecular probes for sensing and imaging of various analytes and biological specimens are of great importance in clinical diagnostics, thera … essfully applied for real time monitoring of the fluctuation of intracellular free zinc ions during autophagy conditions, demonstrating its potential for cellular imaging of Zn2+ at higher intracellular concentrations.

Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia.

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expre…

Mapping the landscape: A bibliometric perspective on autophagy in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a severe condition that often leads to persistent damage of nerve cells and motor dysfunction. Autophagy is an intracellular system that regulates the recycling and degradation of proteins and lipids, primarily through lysosomal-dependent organelle degradation. Numerous publications have highlighted the involvement of autophagy in the secondary injury of SCI. Therefore, gaining a comprehensive understanding of autophagy research is crucial for designing effective therapies for SCI. METHODS: Dates were obtained from Web of Science, including articles and…

Review on the role of autophagy in the toxicity of nanoparticles and the signaling pathways involved.

As the development of nanotechnology, the application of nanoproducts and the advancement of nanomedicine, the contact of nanoparticles (NPs … d complex properties of NPs further complicate the understanding of their toxicological mechanisms. Autophagy, a fundamental cellular process, exhibits dual functions-both pro-survival and pro-death. This review offers an updated perspective on the dual roles of autophagy in nanotoxicity and examines the factors influencing autophagic responses. However, no …

Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutation of the NF1 gene that is associated with various symptoms, including … argeted using existing drugs. Among these, chloroquine (CQ) and bafilomycin A1, known to target the autophagy pathway, showed the greatest potential for selectively killing NF1-deficient Drosophila cells. When further investigating autophagy-related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction with NF1. These 14 genes ar …

The interaction of ER stress and autophagy in trophoblasts: navigating pregnancy outcome†.

The endoplasmic reticulum is a complex and dynamic organelle that initiates unfolded protein response and endoplasmic reticulum stress in response to the accumulation of unfolded or misfolded proteins within its lumen. Autophagy is a paramount intracellular degradation system that facilitates the transportation of proteins, cytoplasmic components, and organelles to lysosomes for degradation and recycling. Preeclampsia and intrauterine growth retardation are two common complications of pregnancy associated with abnormal trophoblast differentiation and placental dysfunctions and have a major imp…

Last but not least: emerging roles of the autophagy-related protein ATG4D.

The evolutionarily conserved ATG4 cysteine proteases regulate macroautophagy/autophagy through the priming and deconjugation of the Atg8-family proteins. In mammals there are four ATG4 family members (ATG4A, ATG4B, ATG4C, ATG4D) but ATG4D has been relatively understudied. Heightened interest in ATG4D has been stimulated by recent links to human disease. Notably, genetic variations in human ATG4D were implicated in a heritable neurodevelopmental disorder. Genetic analyses in dogs, along with loss-of-function zebrafish and mouse models, further support a neuroprotective role for ATG4D. Here we d…

Role of autophagy and proteostasis in neurodegenerative diseases: Exploring the therapeutic interventions.

Neurodegenerative disorders are devastating disorders characterized by gradual loss of neurons and cognition or mobility impairment. The common pathological features of these diseases are associated with the accumulation of misfolded or aggregation of proteins. The pivotal roles of autophagy and proteostasis in maintaining cellular health and preventing the accumulation of misfolded proteins, which are associated with neurodegenerative diseases like Huntington's disease (HD), Alzheimer's disease (AD), and Parkinson's disease (PD). This article presents an in-depth examination of the interplay …