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Fulltext Human β-defensin-1 activates autophagy in human colon cancer cells via regulation of long non-coding RNA TCONS_00014506

Eid N, Davamani F

World J Gastrointest Oncol, 2024 Jul 15;16(7):2894-2901.
PMID: 39072156 DOI: 10.4251/wjgo.v16.i7.2894

Macroautophagy (hereafter referred to as autophagy) is a prosurvival mechanism for the clearance of damaged cellular components, specifically related to exposure to various stressors such as starvation, excessive ethanol intake, and chemotherapy. This editorial reviews and comments on an article by Zhao et al, to be published in World J Gastrointestinal Oncology in 2024. Based on various molecular biology methodologies, they found that human β-defensin-1 reduced the proliferation of colon cancer cells, which was associated with the inhibition of the mammalian target of rapamycin, resulting in autophagy activation. The activation of autophagy is evidenced by increased levels of Beclin1 and LC3II/I proteins and mediated by the upregulation of long non-coding RNA TCONS_00014506. Our study discusses the impact of autophagy activation and mechanisms of autophagy, including autophagic flux, on cancer cells. Additionally, we emphasize the importance of describing the detailed methods for isolating long noncoding RNAs TCONS_00014506. Our review will benefit the scientific community and improve the overall clarity of the paper.
Fulltext Mechanistic insights into fasting-induced autophagy in the aging heart

Parvaresh H, Paczek K, Al-Bari MAA, Eid N

World J Cardiol, 2024 Mar 26;16(3):109-117.
PMID: 38576517 DOI: 10.4330/wjc.v16.i3.109

Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins, damaged organelles, and excessive lipids within mammalian cells. A growing body of data indicates that autophagy is reduced in aging cells. This reduction leads to various diseases, such as myocardial hypertrophy, infarction, and atherosclerosis. Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity. This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy (such as mitophagy). In this editorial, we summarize the mechanisms of autophagy in normal and aging hearts. In addition, the protective effect of fasting-induced autophagy in cardiac aging has been highlighted.
Dawn-to-dusk intermittent fasting is associated with overexpression of autophagy genes: A prospective study on overweight and obese cohort

Bou Malhab LJ, Madkour MI, Abdelrahim DN, Eldohaji L, Saber-Ayad M, Eid N, et al.

Clin Nutr ESPEN, 2024 Nov 12.
PMID: 39542136 DOI: 10.1016/j.clnesp.2024.11.002

AIM AND BACKGROUND: A growing body of evidence supports the impact of intermittent fasting (IF) on longevity and healthy aging via the modulation of autophagy genes. The activation of the catabolic autophagic machinery (LAMP2, LC3B, ATG5, and ATG4D) has protective effects against degenerative aging and chronic diseases. This research examined the changes in the expression of the aforementioned genes upon the observance of dawn-to-dusk IF among metabolically healthy participants with overweight and obesity.
METHODS: Fifty-one (51) participants (36 males and 15 females, 38.84 ± 11.73 years) with overweight and obesity (BMI = 29.75 ± 5.04 kg/m2) were recruited and monitored before and at the end of the commencement of the four-week IF. Six healthy subjects with normal BMI (21.4±2.20 kg/m2) were recruited only to standardize the reference for normal levels of gene expressions. At the two time points, anthropometric, biochemical, and dietary assessments were performed, and LAMP2, LC3B, ATG5, and ATG4D gene expressions were assessed using qRT-PCR on RNA extracted from whole blood samples.
RESULTS: At the end of IF, and compared to the pre-fasting levels, the relative gene expressions among participants with overweight/obesity were significantly increased for the three autophagy genes LAMP2, LC3B, and ATG5, with increments of about 4.2 folds, 1.9-fold, and 1.4-fold, respectively. In contrast, the increase in the ATG4D gene was not significant. Concomitantly, significant decreases were found in body weight, BMI, fat mass, body fat percent, hip and waist circumferences, LDL, IL-6, and TNF-a (P <0.05), While HDL, IL-10, and CD163 significantly increased (P <0.05). Binary logistic regression analysis for genetic expressions showed no significant association between high-energy intake, waist circumference, or obesity and the four gene expressions.
CONCLUSIONS: Four consecutive weeks of dawn-to-dusk IF of Ramadan is associated with the upregulation of autophagy gene expressions in participants with overweight/obesity, and this may explain, at least in part, its favorable short-term temporal metabolic and health-improving effects on early aging-related markers. Hence, IF presumably may entail a protective impact against early markers of aging and metabolic diseases in participants with overweight/obesity.
Fulltext Emerging mechanistic insights of selective autophagy in hepatic diseases

Alim Al-Bari A, Ito Y, Thomes PG, Menon MB, García-Macia M, Fadel R, et al.

Front Pharmacol, 2023;14:1149809.
PMID: 37007026 DOI: 10.3389/fphar.2023.1149809

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria (via mitophagy), and lipid droplets (LDs; via lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses (via virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases. For example, lipophagy has emerged as a defensive mechanism against chronic liver diseases. There is a prominent role for mitophagy and lipophagy in hepatic pathologies including non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and drug-induced liver injury. Moreover, these selective autophagy pathways including virophagy are being investigated in the context of viral hepatitis and, more recently, the coronavirus disease 2019 (COVID-19)-associated hepatic pathologies. The interplay between diverse types of selective autophagy and its impact on liver diseases is briefly addressed. Thus, modulating selective autophagy (e.g., mitophagy) would seem to be effective in improving liver diseases. Considering the prominence of selective autophagy in liver physiology, this review summarizes the current understanding of the molecular mechanisms and functions of selective autophagy (mainly mitophagy and lipophagy) in liver physiology and pathophysiology. This may help in finding therapeutic interventions targeting hepatic diseases via manipulation of selective autophagy.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.