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Regulation on mitophagy in adenomyosis by Guizhi Fuling Wan.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling Wan (GZFLW), a canonical herbal formulation originating from Synopsis of the Golden Chamber, has been widely utilized in managing pain-associated disorders. While its therapeutic efficacy in adenomyosis (AM) characterized by severe dysmenorrhea is well-documented, the underlying pharmacological mechanisms remain elusive. Emerging evidence suggests that hypoxic mitochondrial damage in endometrial tissue constitutes a pathological hallmark of AM, wherein mitophagy regulation through the PINK1/Parkin signaling pathway plays a pivotal role in mitochond

[Effect of electroacupuncture at front-mu and back-shu points of large intestine on autophagy of Cajal interstitial cells in the colon of rats with slow transit constipation].

OBJECTIVE: To explore the effect of electroacupuncture (EA) at front-mu and back-shu points of large intestine on autophagy of Cajal interst … p, the model group showed the impaired colonic mucosal structure and reduced goblet cell count; and autophagosomes and mitochondrial swelling were markedly observed in the cytoplasm of ICCs. The average fluorescence intensity of C-kit, the mRNA expression of C-kit, and the protein expression of C-kit and P62 all decreased, while the protein expression of LC3 and …

Galactin-8 DNA methylation mediates macrophage autophagy through the MAPK/mTOR pathway to alleviate atherosclerosis.

DNA methylation modifications are an important mechanism affecting the process of atherosclerosis (AS). Previous studies have shown that Gal … intensity of GAL8, LC3, Monocyte chemoattractant protein-1(MCP-1), and other proteins. Detection of autophagosomes in macrophages by transmission electron microscopy was also performed. The foam cell model was induced with human monocytes (THP-1) and co-cultured with foam cells using siRNAs targeting GAL8, DO05, and UO126. The level of DNMT1 was detected by West …

[Autophagy reduces bacterial translocation by regulating intestinal mucosal oxidative stress].

OBJECTIVE: To investigate the mechanism of autophagy in regulating bacterial translocation in intestinal infection caused by hypervirulent K … 0.38±0.04 vs. 0.70±0.09, Beclin-1/β-actin: 0.62±0.05 vs. 0.86±0.05, both P < 0.01), and there were autophagosomes in the intestinal mucosa. These results indicated that intestinal mucosal autophagy was activated after hvKp continuous gavage. Compared with CO group, the mRNA expressions of ZO-1 and Claudin-2 in the BT- and BT+ groups were significantly decreased …

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases.

OBJECTIVES: This review examines the pharmacokinetics, modes of action and therapeutic properties of the anti-malarial drugs, hydroxychloroq … y, these drugs have multiple actions related, in part, their ability to accumulate in lysosomes and autophagosomes of phagocytic cells as well as affecting MHC Class II expression and antigen presentation; actions of the production of pro-inflammatory cytokines [e.g. interleukin-1 (IL-1) tumour necrosis factor-α (TNFα)]; control of toll-like receptor-9 activatio …

Curcumin combined with arsenic trioxide enhances autophagy and immune surveillance to inhibit immune escape in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (acute myeloid leukemia, AML) is a type of malignant hematological tumor characterized by high incidence, … nregulation of the anti-apoptotic protein Bcl-2, which was accompanied by a significant increase in autophagosomes in KG-1a cells. In both the co-culture and in vivo models, CUR combined with ATO enhanced the immunotoxic effects of NK cells on KG-1a cells by improving the immunosuppressive microenvironment. The in vivo and in vitro mechanistic studies revealed t …

["Shugan Tiaoshen" needling improves depression after ischemic stroke by regulating AMPK-dependent autophagy].

OBJECTIVES: To observe the effect of "Shugan Tiaoshen"(soothing the liver and regulating the mental activities) needling on the expressions of AMP-activated protein kinase (AMPK) and autophagy-related proteins in the prefrontal cortex of rats with depression after ischemic stroke (post-stroke depression), in order to explore its mechanisms underlying improvement of post-stroke depression behaviors. METHODS: A total of 60 male SD rats were randomly divided into sham operation (control), stroke, post-stroke depression, inhibitor, acupuncture, and acupuncture + inhibitor groups. The post-stroke

Resistance to apoptosis and autophagy leads to enhanced survival in Sertoli cells.

STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of prosurvi … cells were deprived of nutrients using Hank's balanced salt solution for 1, 2 and 3 h. Formation of autophagosomes was analyzed by using immunoblotting, immunofluorescence labeling and ultrastructural analyses. Relative mRNA levels of genes involved in the regulation of apoptosis and autophagy were evaluated. Extracellular high mobility group box protein one was …

[Influence of nicotinic acid adenine dinucleotide phosphate on autophagy in hypoxic cardiomyocytes of rats and its mechanism].

Objective: To investigate influence of nicotinic acid adenine dinucleotide phosphate (NAADP) on autophagy in hypoxic cardiomyocytes of rats … cidifying internal environment of lysosome of cardiomyocyte after hypoxia, promoting degradation of autophagosomes, reducing autophagic lysosomal accumulation, and repairing damaged autophagic flow.

Phosphorylation of EIF2S1 (eukaryotic translation initiation factor 2 subunit alpha) is indispensable for nuclear translocation of TFEB and TFE3 during ER stress.

There are diverse links between macroautophagy/autophagy pathways and unfolded protein response (UPR) pathways under endoplasmic reticulum (ER) stress conditions to restore ER homeostasis. Phosphorylation of EIF2S1/eIF2α is an important mechanism that can regulate all three UPR pathways through transcriptional and translational reprogramming to maintain cellular homeostasis and overcome cellular stresses. In this study, to investigate the roles of EIF2S1 phosphorylation in regulation of autophagy during ER stress, we used EIF2S1 phosphorylation-deficient (A/A) cells in which residue 51 was mut

BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes.

Retinal ganglion cell axons are heavily myelinated (98%) and myelin damage in the optic nerve (ON) severely affects vision. Understanding the molecular mechanism of oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes will be essential for developing new therapeutic approaches for ON demyelinating diseases. To this end, we developed a new method for isolation and culture of ON-derived oligodendrocyte lineage cells and used it to study OPC differentiation. A critical aspect of cellular differentiation is macroautophagy/autophagy, a catabolic process that allows for

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… Transport of Autophagosomes Autophagosomes (double membrane vesicles) are randomly formed throughout the cytosol, concentrating and continuously moving during the maturation process. … Liensinine suppresses autophagic degradation by blocking autophagosome–lysosome fusion and the subsequent accumulation of autophagosomes in breast cancer cells. …

The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise.

Autophagy has been described as harboring a dual role in cancer development and therapy. Depending on the context, it can exert either pro-survival or pro-death functions. Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL. We first present our main findings on the role and regulation of autophagy in these cells. Then, we provide literature-driven hypotheses that could explain mechanistically the pro-survival properties of autophagy in crizotinib-treated bulk and stem-like ALK+ ALCL cells. Finally, we discuss how the potentiation of autophagy, which occurs with combi

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… Such unwanted materials are sealed in double-membrane autophagosomes, then submitted to degradation by lytic enzymes. These catabolic reactions occur in autophagolysosomes, which are organelles resulting from the fusion between autophagosomes and lysosomes. … It is thus important in this context to investigate whether NPM-ALK could be detected in autophagosomes. …

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… Other studies suggested’ that autophagosomes form at the ER–mitochondria contact site in mammalian cells ( Hamasaki et al., 2013 ), or that the plasma membrane serves as a reservoir and participates openly in the development of positive autophagosome precursors during periods of increased autophagosome … Recycling of ATG8/LC3 occurs after closure of the autophagosome with the help of ATG4, while lysosomal enzymes in the autophagosome lumen cleave the proteins attached to the internal membrane ( Lippai and Szatmari, 2017 ). …

[Regulation of PINK1/Parkin-mediated hippocampal neuronal mitophagy with Shugan Tiaoshen acupuncture for alleviating chronic inflammatory pain and depression comorbidity].

OBJECTIVE: To observe the effects of Shugan Tiaoshen acupuncture (acupuncture for smoothing liver qi and regulating the mind) on hippocampal … the mitochondrial morphology was relatively normal, and the bilayer membrane structure intact, and autophagosomes visible; the content of ROS and MDA reduced (P<0.05) and SOD elevated (P<0.05); the protein and mRNA expression of hippocampal p62 was declined (P<0.05), and the protein and mRNA expression of PINK1, Parkin and Beclin 1 was elevated (P<0.05), and th …

[LncRNA-UCA1-microRNA-143-Notch1 regulates autophagy in myocardial ischemia reperfusion injury induced by cardiopulmonary bypass].

OBJECTIVE: To observe the degree of myocardial cell injury and the changes in autophagy level in rats with myocardial ischemia/reperfusion ( … , the myocardial cells of rats in the model group were enlarged, the intercellular space increased, autophagosomes increased, the arrangement of myocardial fibers was disordered, mitochondrial proliferated and deformed. The expression levels of lncRNA-UCA1 and Notch1 mRNA, as well as the protein expression levels of LC3-II/I and Notch1 were significantly increas …

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

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… This structure, called the autophagosome, contains the autophagic cargo. Finally, in the degradation stage, the autophagosome fuses with the lysosomal membrane and the autophagic cargo is sequestered by lysosomal hydrolases (Refs 15 , 16 , 17 ). … SIRT1-mediated activation of FoXO1 induces expression of autophagosomes, and Rab7 (GTPase) which is highly important in autophagosome formation (Ref. 51 ). …

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

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… (A) Macroautophagy involves the formation of autophagosome as a double-membrane vesicle that engulfs cytoplasmic material. The autophagosome then fuses with a lysosome in order to degrade and recycle the sequesteredcontents. … Moreover, blocking autophagy by impairing autophagosome turnover increases antigen cross-presentation, indicating that autophagosomes serve as effective transporters of antigens from APCs to T cells. …

Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells.

Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expressio

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… The autophagosomes subsequently fused with a lysosome, and the internal material was degraded. Undegraded debris within the autolysosomes was also observed. Notably, more autophagosomes were present in A549 cells than in A549/DDP cells. … During the maturation of the autophagosome, LC3 on the outer membrane is cleaved and recycled, whereas LC3 is bound to the inner membrane and remains in situ as the autophagosome fuses with the lysosome [ 26 ]. …

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome.

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-lim