-
Frontiers in Cardiovascular Medicine 2021Atherosclerosis (AS) is a chronic vascular inflammatory disease, in which the lipid accumulation in the intima of the arteries shows yellow atheromatous appearance,...
Atherosclerosis (AS) is a chronic vascular inflammatory disease, in which the lipid accumulation in the intima of the arteries shows yellow atheromatous appearance, which is the pathological basis of many diseases, such as coronary artery disease, peripheral artery disease and cerebrovascular disease. In recent years, it has become the main cause of death in the global aging society, which seriously endangers human health. As a result, research on AS is increasing. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Recent studies have shown that chronic stress plays an important role in the occurrence and development of AS. From the etiology of disease, social, environmental and genetic factors jointly determine the occurrence of disease. Atherosclerotic cardio-cerebrovascular disease (ASCVD) is often caused by chronic stress (CS). If it cannot be effectively prevented, there will be biological changes in the body environment successively, and then the morphological changes of the corresponding organs. If the patient has a genetic predisposition and a combination of environmental factors triggers the pathogenesis, then chronic stress can eventually lead to AS. Therefore, this paper discusses the influence of chronic stress on AS in the aspects of inflammation, lipid metabolism, endothelial dysfunction, hemodynamics and blood pressure, plaque stability, autophagy, ferroptosis, and cholesterol efflux.
PubMed: 34988123
DOI: 10.3389/fcvm.2021.738654 -
BioMed Research International 2021Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and...
Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and their positive and protective effects on various cells and tissues have been reported. The mechanisms by which probiotics exert their beneficial effects in different cells and tissues were investigated, and autophagy is one of the main mechanisms to induce their positive effects. Autophagy is a conserved process that occurs in all eukaryotic cells and plays an essential role in homeostasis and cell survival by degrading damaged and dysfunctional intracellular organelles. On the other hand, the role of autophagy is diverse in different tissues and situations, and cell death derived from autophagy has been observed in some cells. This search was done in PubMed, WOS, and Scopus using the keywords probiotic, microbiota, and autophagy. The search strategy was focused on the in vitro and animal model studies, and the included filters were English language publications and full-text articles (by June 2020). Studies that investigated other underlying mechanisms except autophagy were excluded. Among more than 105 papers, 24 studies were considered eligible for more evaluation. The obtained results indicated that most studies were performed on intestinal cell lines or tissue compared with other types of cell lines and tissue. This review article discusses our current understanding of the probiotic effects through autophagy in different cell lines and tissues that would be a useful guide to daily and clinical usage of these living microorganisms, but despite promising results of this systematic review, further studies need to assess this issue. This systematic review has demonstrated that autophagy is an effective mechanism in inducing beneficial effects of probiotics in different tissues.
Topics: Animals; Autophagy; Homeostasis; Humans; Microbiota; Probiotics
PubMed: 34901266
DOI: 10.1155/2021/2931580 -
Frontiers in Cardiovascular Medicine 2021Ischemic heart disease (IHD) is a considerable health burden worldwide with high mortality and morbidity. Treatments for IHD are mainly focused on decreasing oxygen...
Ischemic heart disease (IHD) is a considerable health burden worldwide with high mortality and morbidity. Treatments for IHD are mainly focused on decreasing oxygen demand or increasing myocardial oxygen supply, including pharmacological, interventional, and surgical treatment, but there are also some limitations. Therefore, it is important to find a simple, effective, and economical treatment. As non-invasive and safe physiotherapy, electrical stimulation (ES) has a promising application in the treatment of IHD. Current studies suggest that ES can affect the occurrence and development of IHD by promoting angiogenesis, regulating autophagy and apoptosis, inhibiting the inflammatory response and oxidative stress. In this review, we focus predominantly on the mechanism of ES and the current progress of ES therapy in IHD, furthermore, give a brief introduction to the forms of ES in clinical application.
PubMed: 34805318
DOI: 10.3389/fcvm.2021.761877 -
Biomedicine & Pharmacotherapy =... Jan 2022Oleanolic acid (OA, 3 β - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi...
Oleanolic acid (OA, 3 β - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Cell Proliferation; Humans; Neoplasms; Oleanolic Acid; Signal Transduction
PubMed: 34798468
DOI: 10.1016/j.biopha.2021.112397 -
EMBO Molecular Medicine Dec 2021The cardinal stages of macroautophagy are driven by core autophagy-related (ATG) proteins, whose ablation largely abolishes intracellular turnover. Disrupting ATG genes... (Review)
Review
The cardinal stages of macroautophagy are driven by core autophagy-related (ATG) proteins, whose ablation largely abolishes intracellular turnover. Disrupting ATG genes is paradigmatic of studying autophagy deficiency, yet emerging data suggest that ATG proteins have extensive biological importance beyond autophagic elimination. An important example is ATG7, an essential autophagy effector enzyme that in concert with other ATG proteins, also regulates immunity, cell death and protein secretion, and independently regulates the cell cycle and apoptosis. Recently, a direct association between ATG7 dysfunction and disease was established in patients with biallelic ATG7 variants and childhood-onset neuropathology. Moreover, a prodigious body of evidence supports a role for ATG7 in protecting against complex disease states in model organisms, although how dysfunctional ATG7 contributes to manifestation of these diseases, including cancer, neurodegeneration and infection, in humans remains unclear. Here, we systematically review the biological functions of ATG7, discussing the impact of its impairment on signalling pathways and human pathology. Future studies illuminating the molecular relationship between ATG7 dysfunction and disease will expedite therapies for disorders involving ATG7 deficiency and/or impaired autophagy.
Topics: Apoptosis; Autophagy; Autophagy-Related Protein 7; Child; Humans; Signal Transduction
PubMed: 34725936
DOI: 10.15252/emmm.202114824 -
International Journal of Molecular... Sep 2021The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells,...
The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.
Topics: Cell Degranulation; Cornea; Extracellular Traps; Eye Diseases; Humans; Neutrophil Infiltration; Neutrophils
PubMed: 34638724
DOI: 10.3390/ijms221910386 -
European Review For Medical and... Sep 2021Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is...
OBJECTIVE
Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD), (Crohn's Disease (CD) and Ulcerative Colitis (UC)), are often associated with extraintestinal manifestations. Of these, NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs.
MATERIALS AND METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only.
RESULTS
We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included, detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics). However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes.
CONCLUSIONS
In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.
Topics: Acyltransferases; Autophagy-Related Proteins; Dyslipidemias; Female; GTP-Binding Proteins; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Hypertension; Inflammatory Bowel Diseases; Insulin Resistance; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Phospholipases A2, Calcium-Independent
PubMed: 34604973
DOI: 10.26355/eurrev_202109_26800 -
Frontiers in Neurology 2021Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported...
Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH. The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD). Our literature identified 160 possible articles, and most of them were excluded due to duplication ( = 69) and failure to meet the inclusion criteria ( = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures ( = 16), no relevant interventions ( = 3), review articles ( = 1), duplicated publications ( = 1), and studies on humans or cells ( = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models. Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.
PubMed: 34539547
DOI: 10.3389/fneur.2021.685731 -
Biomedicine & Pharmacotherapy =... Oct 2020Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the...
Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the quest for more efficient and less toxic medication strategies is still at the forefront of current research. Hedyotis diffusa Willd (HDW), a Chinese herb medicine, has received great attention in the past two decades and has been well documented in clinics for antitumor activity in a variety of human cancers. This review discussed a total of 58 different kinds of active antitumor components isolated from HDW, including iridoids, flavonoids, flavonol glycosides, anthraquinones, phenolic acids, and their derivatives, sterols, and volatile oils. Their antitumor activities include inhibition of tumor cell proliferation, induction of tumor cell apoptosis and tumor angiogenesis, regulation of the host immune response, anti-inflammatory and antioxidant, and protective autophagy. Besides, we provide up-to-date and systematic evidence for HDW antitumor activities and the possible underlying molecular mechanisms and reference for further development of novel drugs and dosage formulation in control of human cancers.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Hedyotis; Humans; Plant Extracts
PubMed: 34321173
DOI: 10.1016/j.biopha.2020.110735 -
Clinical and Translational Science Nov 2021Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of... (Meta-Analysis)
Meta-Analysis
Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of the current study were to identify the differences in mitochondrial function and iron metabolism between frail and nonfrail populations, and to investigate the contribution of different methodological approaches to the results. Searches were performed, using five online databases up to November 2019. Studies reporting measurements of mitochondrial function or iron metabolism in frail and nonfrail subjects or subjects with and without sarcopenia, were included. Pooled effect estimates were expressed as Standardized Mean Differences. Heterogeneity, expressed as I , was explored using regression analyses. In total, 107 studies, reporting 75 measures of mitochondrial function or iron metabolism, using six different experimental approaches, in three species were identified. Significant decreases in measures of oxygen consumption were observed for frail humans but not in animal models. Conversely, no differences between frail and nonfrail humans were observed for apoptosis and autophagy, in contrast to animal models. The most significant effect of the type of frailty assessment was observed for respiratory chain complexes where only subjects categorized as frail by the Fried Frailty Index showed a significant decrease in activity. We identified iron metabolism in frailty as an important knowledge gap, highlighted the need of consistent frailty diagnostic tools, and pointed out the limited translational potential of animal models. Inconsistency between studies evaluating the molecular mechanisms underlying frailty may present a barrier to the development of effective therapies.
Topics: Frailty; Humans; Iron; Mitochondria
PubMed: 34240568
DOI: 10.1111/cts.13101