Therapeutic effects of statins on osteoarthritis: A review.

Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the ß-hydroxy ß-methylglutaryl-CoA (HMG-CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG-CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin-1ß-stimulation. Atorvastatin stimulates the STAT1-caspase-3 signaling pathway that was shown to be responsible for its anti-inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

Activation of toll-like receptor signaling in endothelial progenitor cells dictates angiogenic potential: from hypothesis to actual state.

Human endothelial progenitor cells (EPCs) were isolated from cord blood samples and enriched by magnetic activated cell sorting method based on the CD133 marker. Cells were incubated with different doses of bacterial lipopolysaccharide, ranging from 2, 5, 10, 50, 100, 200, 250, 500, to 1000 µg/ml, for 48 h. The cell survival rate was determined by using MTT assay. To confirm activation of the toll-like receptor signaling pathway, PCR array analysis was performed. Protein levels of ERK1/2, p-ERK1/2, NF-ƙB and TRIF proteins were measured using western blotting. The content of TNF-α and lipoprotein lipase activity were analyzed by immunofluorescence imaging. Flow cytometric analysis of CD31 was performed to assess the maturation rate. Cell migration was studied by the Transwell migration assay. The expression of genes related to exosome biogenesis was measured using real-time PCR analysis. In vivo gel plug angiogenesis assay was done in nude mice. Lipopolysaccharide changed endothelial progenitor cells' survival in a dose-dependent manner with maximum viable cells in groups treated with 2 µg/ml. PCR array analysis showed the activation of toll-like signaling pathways after exposure to LPS (p<0.05). Western blotting analysis indicated an induction of p-ERK1/2 and Erk1/2, NF-kB and TRIF in LPS-treated EPCs compared with the control (p<0.05). Immunofluorescence staining showed an elevation of TNF-α and lipoprotein lipase activity after lipopolysaccharide treatment (p<0.05). Lipopolysaccharide increased EPC migration and expression of exosome biogenesis-related genes (p<0.05). In vivo gel plug analysis revealed enhanced angiogenesis in cells exposed to bacterial lipopolysaccharide. Data highlighted the close relationship between the toll-like receptor signaling pathway and functional activity in EPCs.

Different types of cell death in vascular diseases.

In a mature organism, tissue homeostasis is regulated by cell division and cell demise as the two major physiological procedures. There is increasing evidence that deregulation of these processes is important in the pathogenicity of main diseases, including myocardial infarction, stroke, atherosclerosis, and inflammatory diseases. Therefore, there are ongoing efforts to discover modulating factors of the cell cycle and cell demise planners aiming at shaping innovative therapeutically modalities to the therapy of such diseases. Although the life of a cell is terminated by several modes of action, a few cell deaths exist-some of which resemble apoptosis and/or necrosis, and most of them are different from one another-that contribute to a wide range of functions to either support or disrupt the homoeostasis. Even in normal physiological conditions, cell life is severe within the cardiovascular system. Cells are persistently undergoing stretch, contraction, injurious metabolic byproducts, and hemodynamic forces, and a few of cells sustain decade-long lifetimes. The duration of vascular disease causes further exposure of vascular cells to a novel range of offences, most of which induce cell death. There is growing evidence on consequences of direct damage to a cell, as well as on responses of adjacent and infiltrating cells, which also have an effect on the pathology. In this study, by focusing on different pathways of cell death in different vascular diseases, an attempt is made to open a new perspective on the therapeutic goals associated with cell death in these diseases.

Chronic asthmatic condition modulated the onset of aging in bone marrow mesenchymal stem cells.

The emergence of an inflammatory condition such as asthma could affect the therapeutic potential of stem cells. Synopsis of previous documents yielded controversial outcomes, leading to a limitation of stem cell-based therapy in the clinical setting. This study aimed to assess the impact of asthmatic serum on the MSCs aging and dynamic growth in vitro. Rats were divided into control and asthmatic groups randomly. The asthmatic change was induced using OVA sensitization. The asthmatic structural changes are monitored by conventional Haematoxylin-Eosin staining. Thereafter, blood samples were taken and sera provided from each group. In this study, primary bone marrow mesenchymal stem cells were cultured in culture medium supplemented with normal and asthmatic serum for 7 days. The MSCs viability was examined using the MTT assay. The expression of the aging-related gene (ß-galactosidase), and stemness-related markers such as Sox2, Kfl-4 and p16INK4a were analysed by real-time PCR assay. Histological examination revealed chronic inflammatory remodelling which is identical to asthmatic changes. MTT assay showed a reduction of mesenchymal stem cell viability compared to the control group (P < .05). Real-time PCR analysis revealed a down-regulation of stemness-related markers Sox2, Kfl-4 and p16INK4a coincided with aging changes (ß-galactosidase) compared to the control group (P < .05). These data show the detrimental effect of asthmatic condition on bone marrow regenerative potential by accelerating early-stage aging in different stem cells and further progenitor cell depletion. SIGNIFICANCE OF THE STUDY: In such inflammatory conditions as asthma, the therapeutic potential of stem cells may be altered. We demonstrate that serum from asthmatic rats had the potential to reduce the viability of mesenchymal stem cells in vitro. Furthermore, we observed that the expression of the aging-related gene known ß-galactosidase was statistically increased in cells co-cultured with asthmatic serum. At the same time, expression of stemness-related markers Sox2, Kfl-4 and p16INK4a down-regulated. These results support the damaging effect of asthmatic condition on bone marrow regenerative ability by inducing early-stage aging in stem cells and additional progenitor cell reduction.

Care and prevention during the COVID-19 pandemic quarantine: sedentary lifestyle and increased risk of kidney stones.

Currently, the issue of lifestyle combined with lack of physical activity in quarantine conditions during the COVID-19 pandemic has become a major health problem in many countries around the world. Increased inactivity is associated with increased obesity as well as decreased physical activity and general health. Kidney stones are the third most common urinary tract disease. Prevention of non-communicable diseases depends on controlling risk factors such as low levels of physical activity. Kidney stones are also among the noncommunicable diseases that can be prevented by changing behavioral habits. Physical activity is a behavior that has many proven health benefits and is one of the most effective ways to prevent chronic diseases. The aim of this study was to investigate sedentary lifestyle and its relationship with oxidative stress and kidney stone formation, and finally to provide medical solutions and recommendations.

Toll-like receptor bioactivity in endothelial progenitor cells.

Cardiovascular disease is the main cause of death globally that can be mitigated by the modulation of angiogenesis. To achieve this goal, the application of endothelial progenitor cells and other stem cell types is useful. Following the onset of cardiovascular disease and pro-inflammatory conditions as seen during bacterial sepsis, endothelial progenitor cells enter systemic circulation in response to multiple cytokines and activation of various intracellular mechanisms. The critical role of Toll-like receptors has been previously identified in the dynamics of various cell types, in particular, immune cells. To our knowledge, there are a few experiments related to the role of Toll-like receptors in endothelial progenitor cell activity. Emerging data point of endothelial progenitor cells and other stem cells having the potential to express Toll-like receptors to control different activities such as multipotentiality and dynamics of growth. In this review article, we aim to collect data related to the role of Toll-like receptors in endothelial progenitor cells bioactivity and angiogenic potential.

Modulatory effect of photobiomodulation on stem cell epigenetic memory: a highlight on differentiation capacity.

Differentiation potential of stem cells into various lineages makes these cells as promising sources to treat multiple diseases. In this regard, the use of different strategies and protocols to increase differentiation capacity is highly demanded. Low-level laser therapy, a relatively noninvasive technique, has the capacity to accelerate the healing of numerous injuries and a portion of restorative capacity could be correlated with the stem cell activation and differentiation. Several mechanisms have been diagnosed to participate in orientation of stem cells to functional mature cells. Among them, the status of DNA methylation orchestrates the maintenance of tissue-specific gene expression during the differentiation procedure. DNA methylation is a momentous event in embryogenesis and functional maturation. This review article highlighted the potency of laser irradiation (low-level intensities) in the differentiation of stem cells by modulation of methylation. The analysis of these modalities could help us to understand the underlying mechanisms participating in the therapeutic effects of photobiomodulation.

Chronic non-communicable diseases in the epidemic (COVID-19): Investigation of risk factors, control and care.

INTRODUCTION: Chronic non-communicable diseases (NCDs), global health problem and it is a threat to health and the development of countries. Currently, the number of people with COVID-19 as well as the resulting death toll is rising sharply worldwide. People with underlying diseases may be at greater risk. AIM: The purpose of the present study was to investigate the chronic non-communicable diseases in the epidemic (COVID-19): Investigation of risk factors, control and care. METERIALS AND METHODS: To access the articles, including international databases Scopus, PubMed, Web of Science, Embase were searched using the keywords of chronic non-communicable diseases (NCDs), chronic, risk factors, prevention and control, self-efficacy and self-care and their various combinations using AND/OR operators. No language restrictions were applied to the search process. RESULTS: Based on the evidence, NCDs, exacerbate the negative consequences of COVID-19. according to the results of this study, Among the patients admitted with COVID-19, The most common underlying diseases, were in these people, include, cardiovascular disease, hypertension, chronic obstructive pulmonary disease (COPD), smoking, malignancy, chronic kidney disease, and diabetes mellitus. Obesity may be considered as a potential COVID-19 risk factor. CONCLUSIONS: Although lifestyle, nutrition, and medical interventions are important for the early prevention of NCDs, having the tools and resources to use information more effectively is more important One of the determining and effective factors in maintaining health and preventing the aggravation of signs and symptoms of the disease COVID-19, especially in chronic diseases, is to perform self-care behaviors.

CRISPR/Cas9 Tool for MicroRNAs Editing in Cardiac Development, Function, and Disease.

CRISPR/Cas9 is a powerful gene-editing technology. Extensive scientific data exist that the CRISPR/Cas9 system can target small, non-coding, active RNA molecules, including microRNAs (miRNAs). miRNAs have been recognized as key regulators of different cell biological processes, such as the modulation of fibrosis and cardiac hypertrophy, as well as the regulation of cardiomyocytes. Also, it has been demonstrated that miRNAs strongly affect organ evolution, and that the concentration of miRNAs can involve the differentiation, development, and function of different organs. In addition, the current findings clearly indicate that miRNAs can select and control their targets based on their concentrations. CRISPR/Cas9 genome-editing technology is a stronger system for stopping miRNAs than previous methods, including antisense inhibitors. CRISPR/Cas9 tools can be used to eliminate small areas of DNA and determine miRNA in cases where similar groups of miRNAs are in the same strand. Herein, besides other emerging strategies, we critically summarize the recent investigations linking miRNA-targeted therapeutics and CRISPR/Cas9 system to clarify and combine different delivery platforms and cell-fate engineering of miRNAs function and miRNA-based therapeutic intervention in cardiac development, function, and disease. Based on our findings from the literature, it appears that the use of the CRISPR/Cas technology provides new perspectives for understanding the molecular mechanism of cardiovascular disease and can be effective in treating and controlling cardiac development, function, and disease in the future.

Are Herbal-peptides Effective as Adjunctive Therapy in Coronavirus Disease COVID-19?

BACKGROUND: Plant antiviral peptides (AVP) are macromolecules that can inhibit the pathogenesis of viruses by affecting their pathogenic mechanism, but most of these peptides can bind to cell membranes, inhibit viral receptors, and prevent viruses. Recently, due to the coronavirus pandemic, the availability of appropriate drugs with low side effects is needed. In this article, the importance of plant peptides in viral inhibition, especially viral inhibition of the coronavirus family, will be discussed. METHODS: By searching the databases of PubMed, Scopus, Web of Science, the latest articles on plant peptides effective on the COVID-19 virus were collected and reviewed. RESULTS: Some proteins can act against the COVID-19 virus by blocking sensitive receptors in COVID-19, such as angiotensin-converting enzyme 2 (ACE2). The 23bp sequence of the ACE2 alpha receptor chain can be considered as a target for therapeutic peptides. Protease and RNAP inhibitors and other important receptors that are active against COVID-19 should also be considered. CONCLUSION: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.

Relation Between Tissue Iron Content and Polarization of Macrophages in Diabetic Ulcer and the Transitional Zone of Diabetic Ulcers with Major Amputation.

Most diabetic lower-limb amputations probably result from combinations of contributing causes rather than from unitary causes. Iron-induced damage might modulate the development of chronic diabetes complications. In this study, the relationship between tissue iron levels and polarization of macrophages in induction of angiogenesis was investigated in diabetic ulcer samples and the transitional zone of diabetic ulcers. Patients with diabetic ulcers who underwent amputation were included. The transitional zone of diabetic ulcers, from the same diabetic patients, was used as a control group. After tissue preparation, Perls Prussian blue staining and immunohistochemistry for CD11c, CD163, and CD68 markers were done. Vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), Tie2, and protein kinase B (also known as AKT) transcription of genes were measured by real-time polymerase chain reaction. For statistical analysis, we used independent samples t-test or its nonparametric equivalents, Mann-Whitney U test was used for quantitative variables, and chi-square (or Fisher's exact test) for qualitative variables. According to the results, the ratio of M2 to M1 macrophages was decreased in ulcers tissue compared to the transitional zone of diabetic ulcers. The expression of angiogenesis-related genes was increased due to hypoxia induction such as HIF and VEGF in ulcer tissue (P < .0001), but the expression of vascular stability-related genes such as Tie2 was decreased (P < .0001).In amputated diabetic ulcers, the polarization of macrophages is toward the classic type, but no connection was found in terms of tissue iron and help in the polarization of macrophages.

Comparison of tissue biomarkers in arterial and vein (arteriovenous fistula) aneurysms.

INTRODUCTION AND OBJECTIVES: Aneurysms are distinguished by inflammation, matrix degradation, and apoptosis of smooth muscle cells. In this study, specialized aneurysms tissue markers including venous and arterial aneurysms were studied. MATERIAL AND METHODS: The present cross-sectional study was conducted throughout January-September 2021. Tissue samples were collected during surgery. Hematoxylin and eosin (H&E) stains, have been utilized to identify different aneurysm types and the morphologic alterations that serve as the foundation for aneurysm diagnosis. Measurement of collagen type III, IV, CCR2, metalloproteinase (2 and 13), and granzyme K was done by ELISA method. Results were presented as the mean ± standard deviation and analyzed by t tests (Graph Pad Prism 8.4.3.686). RESULTS: During the period from January to September 2021, 14 patients with peripheral venous and arterial aneurysms were referred to Alavi Vascular Surgery Hospital and underwent surgery. Of these, 10 patients were matched and remained available for study. The level of type 3 collagen was significantly reduced in arterial aneurysm compared to venous aneurysm (p < 0.05). Granzyme K in arterial aneurysm showed increase compared to venous aneurysm (p < 0.05). Metalloproteinase 2 in arterial aneurysms higher than venous aneurysm (p < 0.001). Metalloproteinase 13 in arterial aneurysm also showed increase compared to venous aneurysm (p < 0.05). CONCLUSION: Results of this study shows differences in the level of tissue biomarkers in arterial and vein (arteriovenous fistula) aneurysms.

Assessment of Neutrophil Extracellular Traps (NETs) and Macrophage Ratio in the Inner and Outer Area of Carotid Artery Stenosis.

Background & Objective: It is noteworthy that majority of the data links neutrophil extracellular traps (NETs) to human arterial thrombosis. In the current study, extracellular neutrophil networks and macrophage polarization were assessed in the area outside and inside the Carotid artery stenosis. Methods: The sample of Carotid plaque of the patient was divided into two halves with a transverse incision; the terms inner part and outer part were used for the plaque's inner part and the adjacent area. Samples were sorted in 10% formalin for CD163, CD11c, MPO, and histone H3 immunohistochemical assessment, while part of the sample was stored at -80°C for western blotting assay for PDA4 marker. Results: Results of this study showed that the extracellular neutrophil in the inner part of the Carotid plaque was significantly increased (P<0.0001), while the number of M1 and M2 macrophages was higher in the inner part compared with the outer part of the Carotid plaque (P<0.0001). Conclusion: The distribution of NETs and the ratio of macrophages may be different in the inner and outer aspects of arterial plaque.

Exendin-4 as a Versatile Therapeutic Agent for the Amelioration of Diabetic Changes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic abnormality leading to microvascular and macrovascular complications. Non-insulin Incretin mimic synthetic peptide exendin-4 was introduced as an anti-diabetic drug which helped diabetic patients with triggering insulin secretion; further researches have revealed an effective role of exendin-4 in treatment of T2DM related diseases. Exendin-4 is approximately similar to Glucagon-like peptide, thus it can bind to the glucagon-like peptide-1 receptor (GLP-1R) and activated different signaling pathways that are involved in various bioactivities such as apoptosis, insulin secretion and inactivation of microglial. In this review, we investigated the interesting role of exendin-4 in various kinds of T2DM related disorders through the activation of different signaling pathways.

Withdrawn: A Review of Current Evidence from Cardiovascular Manifestations and Outcomes in Patients with COVID-19

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Design.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication. ©

Signaling pathways associated with structural changes in varicose veins: a case-control study.

INTRODUCTION AND OBJECTIVES: In varicose veins, blood pressure increases in the veins of the lower extremities due to mechanical stimulation and function remodeling. The aim of this study is assessment of Signaling pathways associated with structural changes in varicose veins. MATERIALS AND METHODS: This pilot study was performed on patients with varicose veins, which had undergone surgery. The healthy tissues from trauma patients or vascular bypass without underlying diseases were used for control samples. Hematoxylin-eosin, trichrome, and elastin staining were used for histopathological examination. The levels of MDA (malondialdehyde), total thiol, SOD (Superoxide dismutase) and NO (nitric oxide) level were measured using Elisa kits to evaluate the oxidative stress level. Gene expression levels of MMP2, MMP9, FOXO3a, APOE and p53 genes were determined using Real-time PCR. RESULTS: This study showed, the vascular Vein wall changes are visible in vascular collagen staining. Although these changes are observed in the structure of vascular wall collagen fibers, the accumulation of collagen and elastin was increased in the walls of varicose veins compared to the control group. The amount of nitric oxide and thiol were increased in the varicose group (P < 0.0001). The expression of metalloproteinase2 gene associated with extracellular matrix change was increased in varicose veins. However, the amount of metalloproteinase 9 was decreased in this group compared to control group. FOXO3a, APOE Genes were down-regulated in the varicose veins compared to control group, while p53 gene expression was significantly increased in the varicose group (P < 0.0001). CONCLUSION: This study demonstrated changes in oxidative stress, morphological structure, and aging pathways in varicose when compared to non-varicose veins. The changes in oxidative stress may be associated with the variations in morphological structure and aging pathways which contribute to the pathogenesis of varicose veins.

Type 2 Diabetes Mellitus Provokes Rat Immune Cells Recruitment into the Pulmonary Niche by Up-regulation of Endothelial Adhesion Molecules.

Purpose: Diabetes mellitus, especially type 2, is conceived as a devastating chronic metabolic disease globally. Due to the existence of an extensive vascular network in the pulmonary tissue, it is suggested that lungs are sensitive to the diabetic condition like other tissues. This study was designed to address the possible effect of type 2 diabetes mellitus on the promotion of pathological changes via vascular injury. Methods: Sixteen male Wistar rats were randomly allocated to the two of control and T2D groups. To induce type 2 diabetes (T2D), rats were received high-fat and a single dose of streptozotocin (STZ). On week 12, rats were euthanized and lungs samples were taken. Using hematoxylin and eosin (H&E) staining, the pathological changes were monitored. The expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and interleukin 10 (IL-10) was monitored using real-time PCR assay. The level of tumor necrosis factor-α (TNF-α) was detected using ELISA assay. Nitrosative stress was monitored using the Griess assay. Results: Pathological examination in bronchoalveolar discharge revealed the existence of mild to moderate interstitial bronchopneumonia and increased neutrophilic leukocytosis compared to the control. Enhanced ICAM-1 and VCAM-1 expression and suppression of IL-10 was found using real-time PCR analysis (P < 0.05). The levels of TNF-α and NO were increased with diabetic changes compared to the control rats (P < 0.05). Conclusion: T2D could promote pulmonary tissue injury via the production of TNF-α and up-regulation of vascular ICAM-1 and VCAM-1. The inflammatory status and vascular ICAM-1 and VCAM-1 increase immune cell recruitment into the pulmonary niche.

Diabetes mellitus can cause cardiomyopathy disorders by inducing the aging pathway.

OBJECTIVES: In this study, cardiovascular disorders were examined with a focus on the aging pathway and autophagy involvement in cardiac samples isolated from male rats with type 2 diabetes mellitus. MATERIALS AND METHODS: In the present study, male Wistar rats became diabetic with the help of a high-fat diet. Gene and protein expression levels (to evaluate Tumor Necrosis Factor-α, TNF-α) were measured by the ELISA method. Nrf2, p38, and GSK-3ß proteins in cardiac tissue samples were measured by the western blotting method. Autophagy examination was performed with immunofluorescence staining. Finally, quantitative results were calculated using statistical analysis. RESULTS: The expression of beta-galactosidase genes had a significant increase in the diabetic group (P=0.0001). However, there was no significant difference in the expression of the SERCA2a gene between the diabetic and control groups. In terms of protein expression, the amount of TNF-α protein in the diabetic group was significantly different from that of the control group (P=0.0102). The expression levels of p38, Nrf2, and GSK-3ß proteins increased compared with the control group. The use of the LC3 immunofluorescence staining technique revealed that autophagy increased in the diabetic group. CONCLUSION: Type 2 diabetes mellitus in rats will increase aging in cardiac cells. Examination of the signaling pathway indicates that this effect is related to the increase of ROS and the activity of the signaling pathway. In response, the cardiac cells try to maintain their homeostasis by increasing autophagy and decreasing inflammatory cytokines.