Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease.

Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and, thereafter, management, particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations, including inaccurate predictive values. Therefore, we suggest adding a novel non-classical risk factor, including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease, to the SCORE2 and SCORE2-OP algorithms. Adding these nonclassical risk factors can be used together with the classical risk factors (gender, smoking, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, arterial hypertension, ethnicity, etc.) to develop a new algorithm and further program to be used widely.

Volatilome is Inflammasome- and Lipidome-Dependent in Ischemic Heart Disease.

Ischemic heart disease (IHD) is a pathology of global interest because it is widespread and has high morbidity and mortality. IHD pathophysiology involves local and systemic changes, including lipidomic, proteomic, and inflammasome changes in serum plasma. The modulation in these metabolites is viable in the pre-IHD, during the IHD period, and after management of IHD in all forms, including lifestyle changes and pharmacological and surgical interventions. Therefore, these biochemical markers (metabolite changes; lipidome, inflammasome, proteome) can be used for early prevention, treatment strategy, assessment of the patient's response to the treatment, diagnosis, and determination of prognosis. Lipidomic changes are associated with the severity of inflammation and disorder in the lipidome component, and correlation is related to disturbance of inflammasome components. Main inflammasome biomarkers that are associated with coronary artery disease progression include IL-1ß, Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and caspase-1. Meanwhile, the main lipidome biomarkers related to coronary artery disease development involve plasmalogen lipids, lysophosphatidylethanolamine (LPE), and phosphatidylethanolamine (PE). The hypothesis of this paper is that the changes in the volatile organic compounds associated with inflammasome and lipidome changes in patients with coronary artery disease are various and depend on the severity and risk factor for death from cardiovascular disease in the time span of 10 years. In this paper, we explore the potential origin and pathway in which the lipidome and or inflammasome molecules could be excreted in the exhaled air in the form of volatile organic compounds (VOCs).

Transcription Factors in Brain Regeneration: A Potential Novel Therapeutic Target.

Transcription factors play a crucial role in providing identity to each cell population. To maintain cell identity, it is essential to balance the expression of activator and inhibitor transcription factors. Cell plasticity and reprogramming offer great potential for future therapeutic applications, as they can regenerate damaged tissue. Specific niche factors can modify gene expression and differentiate or transdifferentiate the target cell to the required fate. Ongoing research is being carried out on the possibilities of transcription factors in regenerating neurons, with neural stem cells (NSCs) being considered the preferred cells for generating new neurons due to their epigenomic and transcriptome memory. NEUROD1/ASCL1, BRN2, MYTL1, and other transcription factors can induce direct reprogramming of somatic cells, such as fibroblasts, into neurons. However, the molecular biology of transcription factors in reprogramming and differentiation still needs to be fully understood.

Manifestations of coronavirus infection disease-19 in anterior eye segment: An up-to-date review.

Coronavirus infection disease-19 (COVID-19) is a worldwide catastrophic emergency that first appeared in late 2019, in Wuhan, China. COVID-19 is a multitropism disease that first affects lung tissue. However, extrapulmonary manifestations have been suspected from the first COVID-19 cases. The ocular signs and symptoms were from the early changes that occur during the course of the disease. Changes in the anterior eye segment have a relatively higher incidence than the posterior eye segment. Of which, conjunctivitis, COVID-19 pharyngioceratoconjuctivitis, iridocyclitis, corneal punctate epitheliopathy, and pathomorphological changes in the physio-anatomy of the anterior eye segment. The potential pathogenesis includes direct penetration of the virus into the eye (conjunctiva, lumbus, and cornea) or due to a systemic pathway through viremia, as well as due to autoimmune antibodies against the ocular structure (immune privilege). The presence of ocular manifestations of the external anterior fibrous layer suggests a mild course of the disease.

Breathomics Detect the Cardiovascular Disease: Delusion or Dilution of the Metabolomic Signature.

Volatile organic compounds (VOCs) can be subdivided into exogenous and endogenous categories based on their origin. Analyzing the endogenous VOCs can provide insights into maintaining the internal organs' homeostasis. Despite the ongoing development and the current understanding, studies have suggested a link between cardiovascular metabolic alterations in patients with ischemic heart disease and elevated levels of ethane and isoprene detectable through exhaled breath analysis. Conversely, patients with chronic heart failure exhibit elevated acetone and pentane in their exhaled air. These substances originate from disturbances in the heart tissue, including cellular and subcellular modulations. Hypothetically, ethane levels in the exhaled breath analysis can demonstrate the severity of ischemic heart disease and, consequently, the risk of death in the next 10 years due to cardiovascular disease (CVD). Real-time direct mass spectrometry is the preferred method for assessing VOCs in exhaled breath analysis. The accuracy of this analysis depends on several factors, including the selection of the relevant breath fraction, the type of breath collection container (if used), and the pre-concentration technique.

Cytokines and Regulating Epithelial Cell Division.

Physiologically, cytokines play an extremely important role in maintaining cellular and subcellular homeostasis, as they interact almost with every cell in the organism. Therefore, cytokines play a significantly critical role in the field of pathogenic pharmacological therapy of different types of pathologies. Cytokine is a large family containing many subfamilies and can be evaluated into groups according to their action on epithelial cell proliferation; stimulatory include transforming growth factor-α (TGF-α), Interlukine-22 (IL-22), IL-13, IL-6, IL-1RA and IL-17 and inhibitory include IL-1α, interferon type I (IFN type I), and TGF-ß. The balance between stimulatory and inhibitory cytokines is essential for maintaining normal epithelial cell turnover and tissue homeostasis. Dysregulation of cytokine production can contribute to various pathological conditions, including inflammatory disorders, tissue damage, and cancer. Several cytokines have shown the ability to affect programmed cell death (apoptosis) and the capability to suppress non-purpose cell proliferation. Clinically, understanding the role of cytokines' role in epithelial tissue is crucial for evaluating a novel therapeutic target that can be of use as a new tactic in the management of carcinomas and tissue healing capacity. The review provides a comprehensive and up-to-date synthesis of current knowledge regarding the multifaceted effects of cytokines on epithelial cell proliferation, with a particular emphasis on the intestinal epithelium. Also, the paper will highlight the diverse signaling pathways activated by cytokines and their downstream consequences on epithelial cell division. It will also explore the potential therapeutic implications of targeting cytokine- epithelial cell interactions in the context of various diseases.

Endothelial Cell Aging and Autophagy Dysregulation.

Entropy is a natural process that affects all living cells, including senescence, an irreversible physiological process that impairs cell homeostasis. Age is a significant factor in disease development, and the pathogenesis of endothelial cell aging is multifactorial. Autophagy dysfunction accelerates endothelial cell aging and cell death, while autophagy preserves endothelial cell youthfulness through intracellular homeostasis and gene expression regulation. Sirt, mTORC1, and AMPK are youthfulness genes that induce autophagy by inhibiting mTOR and upregulating FIP200/Atg13/ULK1. Aged endothelial cells have decreased levels of Lamin B1, γH2AX, Ki67, BrdU, PCNA, and SA ß-Gal. Maintaining healthy young endothelial cells can prevent most cardiovascular diseases. Autophagy targeting is a potential future therapeutic strategy to modify endothelial cell age and potentially slow or reverse the aging process. This article provides state-of-the-art research on the role of autophagy in endothelial cell aging. Hypothesizing that autophagy dysregulation is associated with early endothelial cell dysfunction and further clinical sequelae, including atherosclerosis formation, leading to various cardiovascular diseases.

Incidence Rate of Post Coronary Artery Shunt Complications; Age Dependent!

BACKGROUND: Numerous complications, such as postoperative arrhythmia and stroke, have been observed following coronary artery bypass graft (CABG) surgery. AIMS: This study sought to examine the impact of aging on the incidence of post-coronary artery shunt complications. OBJECTIVES: Aging is a physiological process experienced by every living cell, beginning early in development. Age plays a crucial role in determining postoperative complications, including those related to CABG. MATERIALS AND METHODS: A retrospective analysis was conducted on 290 patients who underwent CABG at the Mordovian Republic Hospital between 2017 and 2021. The sample was divided into two age-based groups: the first group comprised 126 patients (mean age range: 55.21-60.00), and the second group included 163 patients (mean age range: 66.11-80.00). Statistical analyses employed in this study encompassed descriptive statistics, Chi-square test, T-test, one-way ANOVA test, ROC analysis, and Pearson correlation using Statistica 12 software. RESULTS: Elderly patients in the second group demonstrated a higher incidence of post-CABG arrhythmia (p<0.012528). Moreover, the second group experienced markedly longer ICU and total hospitalization days following CABG, with p-values of less than 0.000000 and 0.000072, respectively. Notably, elderly individuals in the second group faced an increased risk of developing psychosis after CABG surgery (p<0.007379). Furthermore, psychosis was found to be significantly associated with longer ICU hospitalization (p<0.000140). Postoperative stroke occurred more frequently among the elderly (second group) with a p-value of less than 0.037736. Consequently, postoperative stroke was associated with extended ICU hospitalization (p<0.000747). The usage of internal thoracic arteries (ITAs) was lower among the elderly (second group), with a p-value of less than 0.016145. Regarding correlations, a direct association was observed between age and ICU days, total hospitalization days, and the number of complications, with correlation coefficients (r) of 0.189046, 0.141415, and 0.138565, respectively. CONCLUSION: Elderly individuals in the second group who undergo CABG face a greater risk of developing psychosis, arrhythmia, prolonged total and ICU hospitalization, and stroke. The presence of arrhythmia, which is commonly observed in patients aged 63 years and older, significantly affects total hospitalization days. The number of complications is influenced by age, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, ICU hospitalization, and total hospitalization duration.

Early Prognostic Instrumental and Laboratory Biomarkers in Post-MI.

BACKGROUND: Post-myocardial infarction (MI) changes have been frequently reported in the literature and are associated with determining the prognosis. AIMS: The aim of this study is to find a prognosis marker for the favorability of determination of the medium-term outcomes in patients with acute MI. OBJECTIVES: MI patients' prognosis is poorly understood and requires further elaboration. MATERIALS AND METHODS: A single center, cross-sectional cohort study involved 211 patients' medical history with acute MI, for the period 2014-2019, had been evaluated retrospectively for 76 parameters. The data was collected from the Republic Rehabilitation Mordovian Hospital. The described measurement units were used in the local laboratories to describe the values. The descriptive values were expressed in the mean average and standard deviation. For statistical analysis, descriptive statistics, t-test independent by groups and dependent by numerical variables for repeated analysis for the same patients, multinomial logistic regression, Pearson's correlation coefficient, ROC analysis, and for clarification purposes, diagrams and bar figures were used. For performing the statistical analysis, the SPSS program, version 28 was used. RESULTS: Descriptive statistics showed a proportion of men to females 7:3. The mean age of the MI patients was 61.50 years (Std. Dev. ± 10.68), and the mean height of the sample was 171.00 cm (Std. Dev. ± 7.20). The mean body weight of the sample is 83.62 kg (Std. Dev. ± 12.35), and the body mass index (BMI) is 29.02 kg/m2 (Std. Dev. ± 5.07). The total hospitalization days are 14.79 (Std. Dev. ± 3.41). The mean heart rate (HR) beat per minute (bpm) was 79.03 (Std. Dev. ± 15.63), and the mean blood pressure was 138.53/84.09 mmHg (Std. Dev. ± 28.66/12.79). On the complete blood count (CBC), the mean level of the hemoglobin (Hb) 136.33 g/l (Std. Dev. ± 15.29), the mean level of the leukocytes (WBC) 8.76 /µl (Std. Dev. ± 2.77), the mean level of the red blood cells (RBC) 4.55 /µl (Std. Dev. ± 0.52), the mean level of the relative value of the lymphocytes 24.46 % (Std. Dev. ± 9.015), and the mean level of the thrombocytes 207.87 /µl (Std. Dev. ± 64.035). The mean erythrocytes segmentation rate (ESR) is 18.99 mm/hr (Std. Dev. ± 12.16). The regression analysis demonstrated that the dependent variable, complication, in particular, pericarditis, and the independent factor, concomitant disease, in particular, chronic heart failure, has a significant regression coefficient of 29.101 at p <0.05. Furthermore, the dependent variable, complication, in particular, pneumonitis, and the independent factor, concomitant disease, particularly, arrhythmia, have a significant regression coefficient of 21.937 at p <0.05. CONCLUSION: An elevated level of CPK-MB/LDH/Troponin I is linked to the development of arrhythmia. Patients with other medical conditions experience high diastolic blood pressure and an enlargement of the right ventricle. The early complication observed after MI is the formation of a left ventricular aneurysm. Complications arise due to low levels of potassium and calcium. Chronic Kidney Disease (CKD) contributes to the End-Diastolic Size (EDS) of the Left Ventricle (LV), Troponin I, and creatine phosphokinase-MB (CPK-MB). Advanced CKD patients have a hypertrophic left ventricle and persistently elevated post-myocardial Infarction (MI) cardiac biomarkers (CPKMB/ LDH/Troponin I) due to impaired kidney detoxification. Therefore, prolonged elevation of MI biomarkers can be an indicative of severe MI or kidney function impairment due to the chronic mild elevation in the MI biomarkers. Pericarditis development is related to the pre-existence of chronic heart failure. Moreover, pneumonitis development is related to the pre-existence of arrhythmia. Others: Hypertensive patients do not exhibit a significant increase in calcium levels, indicating that it is not a reliable biomarker in this patient population. Additionally, gender plays a crucial role in the development of ischemic heart disease, including myocardial infarction.

Autophagy as an Anti-senescent in Aging Neurocytes.

Neuron homeostasis is crucial for the organism, and its maintenance is multifactorial, including autophagy. The turnover of aberrant intracellular components is a fundamental pathogenetic mechanism for cell aging. Autophagy is involved in the acceleration of the neurocyte aging process and the modification of cell longevity. Neurocyte aging is a process of loss of cell identity through cellular and subcellular changes that include molecular loss of epigenetics, transcriptomic, proteomic, and autophagy dysfunction. Autophagy dysfunction is the hallmark of neurocyte aging. Cell aging is the credential feature of neurodegenerative diseases. Pathophysiologically, aged neurocytes are characterized by dysregulated autophagy and subsequently neurocyte metabolic stress, resulting in accelerated neurocyte aging. In particular, chaperone- mediated autophagy perturbation results in upregulated expression of aging and apoptosis genes. Aged neurocytes are also characterized by the down-regulation of autophagy-related genes, such as ATG5-ATG12, LC3-II / LC3-I ratio, Beclin-1, and p62. Slowing aging through autophagy targeting is sufficient to improve prognosis in neurodegenerative diseases. Three primary anti-senescent molecules are involved in the aging process: mTOR, AMPK, and Sirtuins. Autophagy therapeutic effects can be applied to reverse and slow aging. This article discusses current advances in the role of autophagy in neurocyte homeostasis, aging, and potential therapeutic strategies to reduce aging and increase cell longevity.

Nicotinamide Mononucleotide in the Context of Myocardiocyte Longevity.

Cellular and subcellular metabolic activities are crucial processes involved in the regulation of intracellular homeostasis, including cellular and subcellular signaling pathways. Dysregulation of intracellular regulation mechanisms is catastrophic and cumulates into cell death. To overcome the issue of dysregulation of intracellular regulation mechanisms, the preservation of subcellular and extracellular components is essential to maintain healthy cells with increased longevity. Several physiopathological changes occur during cell ageing, one of which is the dysregulation of intracellular physiology of the oxidative phosphorylation process. Nicotinamide mononucleotide (NMN) remains in the debut of anti-aging therapeutic effect. Aged myocardiocyte characterized by disrupted NMN and or its precursors or signaling pathways. Simultaneously, several other pathophysiological occur that collectively impair intracellular homeostasis. The NMN role in the antiaging effect remains unclear and several hypotheses have been introduced into describing the mechanism and the potential outcomes from NMN exogenous supply. Correction of the impaired intracellular homeostasis includes correction to the NMN metabolism. Additionally, autophagy correction, which is the key element in the regulation of intracellular intoxication, including oxidative stress, unfolding protein response, and other degradation of intracellular metabolites. Several signaling pathways are involved in the regulation mechanism of NMN effects on myocardiocyte health and further longevity. NMN protects myocardiocytes from ischemic injury by reducing anabolism and, increasing catabolism and further passing the myocardiocytes into dormant status. NMN applications include ischemic heart, disease, and failed heart, as well as dilated cardiomyopathies. Cytosolic and mitochondrial NADPH are independently functioning and regulating. Each of these plays a role in the determination of the longevity of the myocardiocytes. NMN has a cornerstone in the functionality of Sirtuins, which are an essential anti-senescent intrinsic molecule. The study aims to assess the role of NMN in the longevity and antisenescent of myocardiocytes.

Endothelial Dysfunction Under the Scope of Arterial Hypertension, Coronary Heart Disease, and Diabetes Mellitus Using the Angioscan.

BACKGROUND: Cardiovascular disease and diabetes mellitus are among the leading causes of mortality. OBJECTIVES: Our study evaluated endothelial function in patients with arterial hypertension, coronary heart disease, and diabetes mellitus. AIMS: This study aimed to assess the degree of endothelial dysfunction in individuals with cardiovascular risk factors older than 55 years of age. MATERIALS AND METHODS: A total of 112 patients were subdivided into three groups according to the existing disease; the first group consisted of 50 patients diagnosed with arterial hypertension (AH), the second group consisted of 30 patients with ischemic heart disease (IHD), and the third group included 20 patients with type 2 diabetes mellitus (DM). The control group included 12 practically healthy volunteers, comparable in age and sex. Exclusion criteria were age under 55 years, severe concomitant diseases in the acute phase or acute infectious diseases, and oncopathology. Considered factors of cardiovascular risk include dyslipidemia, elevated fasting blood glucose, hypertension, obesity, cigarette smoking, and heredity for CVD. Moreover, tests were conducted with the help of the device 'AngioScan-01' (LLC "AngioScan Electronics"). Endothelium-dependent vasodilation (EDV), the index of stiffness of the vascular wall (SI), and the atherogenic index (log (TG/HDL - C)) were evaluated. The analysis of the data obtained was carried out using the IBM SPSS Statistic programhttps://www.googleadservices.com/pag ead/aclk?sa=L&ai=DChcSEwjy-KDX7-LzAhWRqLIKHYwAC_sYABAAGgJscg&ae=2&ohost =www.google.com&cid=CAESQOD2TLneCc945_KJ3YjAEg9t9VieqY5K9UMNr2yVYMwA4K ZR_5riEqOA50vLm8hM1lBzuIWgp2D6k9wH5JPQRjQ&sig=AOD64_2ySwi8rB9R4-PM96h-N QMkfDkEPw&q&adurl&ved=2ahUKEwiKi5nX7-LzAhViwosKHRDwArMQ0Qx6BAg CEAE. RESULTS: In the control group, the atherogenic index was in the range of 3.34 (the normal is up to 3.5). The highest atherogenic index, 4.01, was observed in the DM group (differences with the control group are statistically significant). In the AH and IHD groups, the atherogenic index was 3.57 and 3.65, respectively. In the control group, the level of glycemia was 4.45 mmol/l. The highest level of fasting glucose was reported in the DM group, i.e., 6.7 mmol/l (differences with the control group were statistically significant). In the first and second groups, the fasting glucose level was 5.07 mmol/l and 5.08 mmol/l, respectively. In the control group, the mean EDV score was 2,056 ± 0.757 mm, and the lowest EDV in the DM group was 1.365 ± 0.413, but in the AH and IHD groups, it was also significantly reduced by 1.404 ± 0.440 and 1.377 ± 0.390, respectively. The stiffness index in the control group was 6.725 ± 0.776 m/s. In the DM group, this parameter was 8.258 ± 0.656 m/s; in the AH and IHD groups, it was 7.398 ± 1.330 m/s and 7.486 ± 0.816 m/s, respectively. CONCLUSION: In conclusion, the study of endothelial function using non-invasive angioscan reflects the influence of risk factors on the vascular wall. The most severe endothelial dysfunction is expressed in patients with diabetes. The results of endothelium-dependent vasodilation and the vascular wall stiffness index (SI) correspond to the scale of evaluation of the 10-year CVD mortality risk (SCORE). These results indicate a deterioration in the vascular ability to vasodilate in patients in response to mechanical deformation of the endothelium and the effect of NO on smooth muscle vascular cells.

Autophagy Behavior in Endothelial Cell Regeneration

Autophagy plays a crucial role in maintaining endothelial cell homeostasis through the turnover of intracellular components during stress conditions in a lysosomal-dependent manner. The regeneration strategy involves several aspects, including autophagy. Autophagy is a catabolic degenerative lysosomal-dependent degradation of intracellular components. Autophagy modifies cellular and subcellular endothelial cell functions, including mitochondria stress, lysosomal stress, and endoplasmic reticulum unfolded protein response. Activation of common signaling pathways of autophagy and regeneration and enhancement of intracellular endothelial cell metabolism serve as the bases for the induction of endothelial regeneration. Endothelial progenitor cells include induced pluripotent stem cells (iPSC), embryonic stem cells, and somatic cells, such as fibroblasts. Future strategies of endothelial cell regeneration involve the induction of autophagy to minimize the metabolic degeneration of the endothelial cells and optimize the regeneration outcomes.

Autophagy Behavior in Post-myocardial Infarction Injury.

Myocardial infarction and its sequalae remain the leading cause of death worldwide. Myocardial infarction (MI) survivors continue to live a poor quality of life due to extinguished heart failure. The post-MI period involves several changes at the cellular and subcellular levels, of which autophagy dysfunction. Autophagy is involved in the regulation of post-MI changes. Physiologically, autophagy preserves intracellular homeostasis by regulating energy expenditure and sources. Furthermore, dysregulated autophagy is considered the hallmark of the post-MI pathophysiological changes, which leads to the known short and long post-MI reperfusion injury sequalae. Autophagy induction strengthens self-defense mechanisms of protection against energy deprivation through economic energy sources and uses alternative sources of energy through the degradation of intracellular components of the cardiomyocyte. The protective mechanism against post-MI injury includes the enhancement of autophagy combined with hypothermia, which induces autophagy. However, several factors regulate autophagy, including starvation, nicotinamide adenine dinucleotide (NAD+), Sirtuins, other natural foods and pharmacological agents. Autophagy dysregulation involves genetics, epigenetics, transcription factors, small noncoding RNAs, small molecules, and special microenvironment. Autophagy therapeutic effects are signaling pathway-dependent and MI stage dependent. The paper covers recent advances in the molecular physiopathology of autophagy in post-MI injury and its potential target as a future therapeutic strategy.

Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!

Undeniably, endothelial cells (EC) contribute to the maintenance of the homeostasis of the organism through modulating cellular physiology, including signaling pathways, through the release of highly active molecules as well as the response to a myriad of extrinsic and intrinsic signaling factors. Review the data from the current literature on the EC role in norm and disease. Endothelium maintains a precise balance between the released molecules, where EC dysfunction arises when the endothelium actions shift toward vasoconstriction, the proinflammatory, prothrombic properties after the alteration of nitric oxide (NO) production and oxidative stress. The functions of the EC are regulated by the negative/positive feedback from the organism, through EC surface receptors, and the crosstalk between NO, adrenergic receptors, and oxidative stress. More than a hundred substances can interact with EC. The EC dysfunction is a hallmark in the emergence and progression of vascular-related pathologies. The paper concisely reviews recent advances in EC (patho) physiology. Grasping EC physiology is crucial to gauge their potential clinical utility and optimize the current therapies as well as to establish novel nanotherapeutic molecular targets include; endothelial receptors, cell adhesion molecules, integrins, signaling pathways, enzymes; peptidases.

The Metabolic Syndrome Puzzles; Possible Pathogenesis and Management.

BACKGROUND AND AIMS: Metabolic syndrome is a multifactorial pathophysiological process with complicated homeostatic disorders that arise from various systematic metabolic defects. Various theories underlie the development of metabolic syndrome but are fully not understood. METHODS: Revising PubMed and Scopus literature data on metabolic syndrome pathogenesis and management. RESULTS: The most accepted hypothesis is that a cluster of risk factors combined to obtain a truly metabolic syndrome. The pathophysiology of the metabolic syndrome depends on the underlying development path due to insulin resistance or chronic inflammation and is usually combined with neurohormonal disturbance. Meanwhile, these defects can be inherited via loss of function of certain genes that lead to severe obesity, early diabetes, or severe insulin resistance (with or without lipodystrophy). Chronic inflammation is also a driver of metabolic syndrome. Lifestyle is still the therapy of choice in managing metabolic syndrome, but unfortunately, during the lockdown, most people could not reserve a healthy regime; therefore, it can also be referred to as a pandemic with COVID-19. CONCLUSIONS: This powerful illustration shows how defects in specific encoded proteins located predominantly in the brain, pancreatic beta-cell, muscle, or fat give rise to these distinct components of the metabolic syndrome. Primarily, obesity and its sequela are the initiators of metabolic syndrome. The presence of metabolic syndrome increases the risk and severity of other pathologies' emergence, even in non-related metabolic syndrome diseases such as COVID-19. The article provides new insights into the pathogeneses and management of the metabolic syndrome.

Transcription Factors - the Essence of Heart Regeneration: A Potential Novel Therapeutic Strategy.

Myocardial cell injury and following sequelae are the primary reasons for death globally. Unfortunately, myocardiocytes in adults have limited regeneration capacity. Therefore, the generation of neo myocardiocytes from non-myocardial cells is a surrogate strategy. Transcription factors (TFs) can be recruited to achieve this tremendous goal. Transcriptomic analyses have suggested that GATA, Mef2c, and Tbx5 (GMT cocktail) are master TFs to transdifferentiate/reprogram cell linage of fibroblasts, somatic cells, mesodermal cells into myocardiocytes. However, adding MESP1, MYOCD, ESRRG, and ZFPM2 TFs induces the generation of more efficient and physiomorphological features for induced myocardiocytes. Moreover, the same cocktail of transcription factors can induce the proliferation and differentiation of induced/pluripotent stem cells into myocardial cells. Amelioration of impaired myocardial cells involves the activation of healing transcription factors, which are induced by inflammation mediators; IL6, tumor growth factor ß, and IL22. Transcription factors regulate the cellular and subcellular physiology of myocardiocytes to include mitotic cell cycling regulation, karyokinesis and cytokinesis, hypertrophic growth, adult sarcomeric contractile protein gene expression, fatty acid metabolism, and mitochondrial biogenesis and maturation. Cell therapy by transcription factors can be applied to cardiogenesis and ameliorating impaired cardiocytes. Transcription factors are the cornerstone in cell differentiation.

Endothelial cell autophagy in the context of disease development.

Endothelial cells (EC) are the anatomical boundaries between the intravascular and extravascular space. Damage to ECs is catastrophic and induces endothelial cell dysfunction. The pathogenesis is multifactorial and involves dysregulation in the signaling pathways, membrane lipids ratio disturbance, cell-cell adhesion disturbance, unfolded protein response, lysosomal and mitochondrial stress, autophagy dysregulation, and oxidative stress. Autophagy is a lysosomal-dependent turnover of intracellular components. Autophagy was recognized early in the pathogenesis of endothelial dysfunction. Autophagy is a remarkable patho (physiological) process in the cell homeostasis regulation including EC. Regulation of autophagy rate is disease-dependent and impaired with aging. Up-regulation of autophagy induces endothelial cell regeneration/differentiation and improves the function of impaired ones. The paper scrutinizes the molecular mechanisms and triggers of EC dysregulation and current perspectives for future therapeutic strategies by autophagy targeting.

Autophagy in Cancer Cell Transformation: A Potential Novel Therapeutic Strategy.

Basal autophagy plays a crucial role in maintaining intracellular homeostasis and prevents the cell from escaping the cell cycle regulation mechanisms and being cancerous. Mitophagy and nucleophagy are essential for cell health. Autophagy plays a pivotal role in cancer cell transformation, where upregulated precancerous autophagy induces apoptosis. Impaired autophagy has been shown to upregulate cancer cell transformation. However, tumor cells upregulate autophagy to escape elimination and survive the unfavorable conditions and resistance to chemotherapy. Cancer cells promote autophagy through modulation of autophagy regulation mechanisms and increase expression of the autophagyrelated genes. Whereas, autophagy regulation mechanisms involved microRNAs, transcription factors, and the internalized signaling pathways such as AMPK, mTOR, III PI3K, and ULK-1. Disrupted regulatory mechanisms are various as the cancer cell polymorphism. Targeting a higher level of autophagy regulation is more effective, such as gene expression, transcription factors, or epigenetic modification that are responsible for the up-regulation of autophagy in cancer cells. Currently, the CRISPR-CAS9 technique is available and can be applied to demonstrate the potential effects of autophagy in cancerous cells.

Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target.

Current advances in molecular pathobiology of endotheliocytes dysfunctions are promising in finding the pathogenetic links to the emergence of insulin resistance syndrome. Physiologically, human organism homeostasis is strictly controlled to maintain metabolic processes at the acquainted level. Many factors are involved in maintaining these physiological processes in the organism and any deviation is undoubtedly accompanied by specific pathologies related to the affected process. Fortunately, the body's defense system can solve and compensate for the impaired function through its multi-level defense mechanisms. The endothelium is essential in maintaining this homeostasis through its ability to modulate the metabolic processes of the organism. Pathological activity or impairment of physiological endothelium function seems directly correlated to the emergence of metabolic syndrome. The most accepted hypothesis is that endothelium distribution is due to endoplasmic reticulum stress and unfolded protein response development, which includes inhibition of long non-coding RNAs expression, cytokines disbalance, Apelin dysregulation, glycocalyx degradation, and specific microparticles. Clinically, the enhancement or restoration of normal endothelial cells can be a target for novel therapeutic strategies since the distribution of its physiological activity impairs homeostasis and results in the progression of metabolic syndrome, and induction of its physiological activity can ameliorate insulin resistance syndrome. Novel insights on the molecular mechanisms of endothelial cell dysfunction are concisely represented in this paper to enhance the present therapeutic tactics and advance the research forward to find new therapeutic targets.