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Journal of Cellular Physiology Jul 2022Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of...
Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of extracellular matrix resulting in liver dysfunction and cirrhosis. Melatonin (N-acetyl-5-methoxytryptamine), the main product secreted by the pineal gland, is a multitasking indolamine with important physiological functions such as anti-inflammatory and antioxidant actions, modulation of circadian rhythms, and immune system enhancement. Among the numerous biological activities of melatonin, its antifibrotic effects have received increasingly more attention. In this study, we performed a systematic review of publications of the last 10 years evaluating the mechanisms of action of melatonin against liver fibrosis. The study protocol was registered at PROSPERO (CRD42022304744). Literature research was performed employing PubMed, Scopus, and Web of Science (WOS) databases, and after screening, 29 articles were included. Results from the selected studies provided denoted the useful actions of melatonin on the development, progression, and evolution of liver fibrosis. Melatonin antifibrotic effects in the liver involved the reduction of profibrogenic markers and modulation of several cellular processes and molecular pathways, mainly acting as an antioxidant and anti-inflammatory agent. In addition, the indolamine influenced different molecular processes, such as hepatocyte apoptosis, modulation of autophagy and mitophagy, restoration of circadian rhythms, and modulation of microRNAs, among others. Although some limitations have been found regarding variability in the study design, the findings here summarized display the potential role of melatonin in ameliorating the development of liver fibrosis and its possible progression to liver cirrhosis and hepatocarcinoma.
Topics: Anti-Inflammatory Agents; Antioxidants; Humans; Liver Cirrhosis; Melatonin
PubMed: 35404472
DOI: 10.1002/jcp.30735 -
Cells Mar 2022microRNAs (miRNA, miRs) play crucial roles in cardiovascular disease regulating numerous processes, including inflammation, cell proliferation, angiogenesis, and cell... (Review)
Review
microRNAs (miRNA, miRs) play crucial roles in cardiovascular disease regulating numerous processes, including inflammation, cell proliferation, angiogenesis, and cell death. Herein, we present an updated and comprehensive overview of the functional involvement of miRs in the regulation of cardiomyocyte death, a central event in acute myocardial infarction, ischemia/reperfusion, and heart failure. Specifically, in this systematic review we are focusing on necrosis, apoptosis, and autophagy.
Topics: Apoptosis; Autophagy; Humans; MicroRNAs; Myocardial Infarction; Myocytes, Cardiac
PubMed: 35326433
DOI: 10.3390/cells11060983 -
Molecular Metabolism Jun 2022With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is... (Review)
Review
BACKGROUND
With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications.
SCOPE OF REVIEW
we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects.
MAJOR CONCLUSIONS
In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.
Topics: Apoptosis; Autophagy; Diabetes Complications; Diabetes Mellitus; Ferritins; Ferroptosis; Humans
PubMed: 35304332
DOI: 10.1016/j.molmet.2022.101470 -
Biomedicine & Pharmacotherapy =... Apr 2022Juglone (5 - hydroxy - 1, 4 - naphthalene diketone) is a kind of natural naphthoquinone, present in the roots, leaves, nut-hulls, bark and wood of walnut trees. Recent...
Juglone (5 - hydroxy - 1, 4 - naphthalene diketone) is a kind of natural naphthoquinone, present in the roots, leaves, nut-hulls, bark and wood of walnut trees. Recent studies have found that Juglone has special significance in the treatment of cancer, which plays a significant role in the resistance of cancer cell proliferation, induction of cancer cell apoptosis, induction of autophagy, anti-angiogenesis and inhibition of cancer cell migration and invasion, etc. Additionally, its derivatives also play a tumor suppressive effect. In conclusion, Juglone and its derivatives have been identified as effective anticancer drugs. This paper reviews action mechanisms of Juglone and its derivatives in cancer treatment.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Cell Movement; Cell Proliferation; DNA-Directed DNA Polymerase; Humans; NIMA-Interacting Peptidylprolyl Isomerase; Naphthoquinones; Neoplasms; Neovascularization, Pathologic; Reactive Oxygen Species
PubMed: 35272138
DOI: 10.1016/j.biopha.2022.112785 -
Frontiers in Neuroscience 2022There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and...
Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment.
BACKGROUND
There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VaD). Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood.
OBJECTIVE
To conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms.
METHODS
"Tooth Loss," "Edentulous," "Tooth Extraction and Memory Loss," "Cognition Impairment," and "Dementia" were used as keywords to search PubMed, Embase, SCI, ScienceDirect, and OpenGrey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE'S risk of bias tool.
RESULTS
The putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: (1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; (2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and (3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system.
CONCLUSION
The loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.
PubMed: 35221901
DOI: 10.3389/fnins.2022.811335 -
Frontiers in Plant Science 2022The endoplasmic reticulum (ER) stress response is triggered by any condition that disrupts protein folding and promotes the accumulation of unfolded proteins in the...
The endoplasmic reticulum (ER) stress response is triggered by any condition that disrupts protein folding and promotes the accumulation of unfolded proteins in the lumen of the organelle. In eukaryotic cells, the evolutionarily conserved unfolded protein response is activated to clear unfolded proteins and restore ER homeostasis. The recovery from ER stress is accomplished by decreasing protein translation and loading into the organelle, increasing the ER protein processing capacity and ER-associated protein degradation activity. However, if the ER stress persists and cannot be reversed, the chronically prolonged stress leads to cellular dysfunction that activates cell death signaling as an ultimate attempt to survive. Accumulating evidence implicates ER stress-induced cell death signaling pathways as significant contributors for stress adaptation in plants, making modulators of ER stress pathways potentially attractive targets for stress tolerance engineering. Here, we summarize recent advances in understanding plant-specific molecular mechanisms that elicit cell death signaling from ER stress. We also highlight the conserved features of ER stress-induced cell death signaling in plants shared by eukaryotic cells.
PubMed: 35185996
DOI: 10.3389/fpls.2022.835738 -
Journal of Integrative Neuroscience Jan 2022According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However,... (Meta-Analysis)
Meta-Analysis
According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However, the pros and cons of autophagic response strongly depend on the activation time of autophagy after injury. In this systematic review, we aimed to explore the impacts of pharmacological modulation of autophagy on infarct size in experimental ischemic stroke models. Based on our preliminary search, 3551 publications were identified. Of twenty-nine publications that met the inclusion criteria, twenty studies reported infarct volume reduction by percentage (%) with no evidence of any publication bias while nine studies reported by mm3, which had publication bias (39.25 units, standardized mean differences (SMD) = 41.92, 95% confidence interval (CI): 30.33 to 53.51). Based on a meta-analysis, the point estimate (pooled mean difference) for improvement of infarct volume during autophagy modulation according to the mm3 and percentage were 35.64 (mean differences (MD) = 35.64, 95% CI: 26.43 to 44.85, z-value = 7.58, -value < 0.001) and 14.38 (MD = 14.38, 95% CI = 10.50 to 18.26, z-value = 7.26, < 0.001) units, respectively. Despite the undeniable role of autophagy in ischemic stroke, the dichotomous effects of autophagy regarding infarct volume reduction should be taken into account. Based on our findings, the studies included in this meta-analysis mostly reported a negative relation between autophagy induction and stroke volume development due to over-activity of autophagy upon the severe ischemic stroke; therefore, further pre-clinical studies are also recommended to establish adjusted autophagy with considering a time-dependent effect as a promising therapeutic target.
Topics: Animals; Autophagy; Cerebral Infarction; Disease Models, Animal; Humans; Ischemic Stroke
PubMed: 35164447
DOI: 10.31083/j.jin2101011 -
Frontiers in Immunology 2022Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that...
Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.
Topics: Endoplasmic Reticulum Stress; Epithelial Cells; Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Nephrolithiasis; Reactive Oxygen Species
PubMed: 35154136
DOI: 10.3389/fimmu.2022.818625 -
Frontiers in Physiology 2021Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal...
Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury. This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models. The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = -30.00 [-42.09 to -17.91], < 0.00001), and serum creatinine (SCr) (20 studies, WMD = -0.91 [-1.17 to -0.66], < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease. From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.
PubMed: 35095558
DOI: 10.3389/fphys.2021.791036 -
Plants (Basel, Switzerland) Dec 2021The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities... (Review)
Review
The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.
PubMed: 35009024
DOI: 10.3390/plants11010019