The Metabolic Syndrome Puzzles; Possible Pathogenesis and Management.

BACKGROUND AND AIMS: Metabolic syndrome is a multifactorial pathophysiological process with complicated homeostatic disorders that arises due to a combination of 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 metabolic syndrome depends on the underlying path of development, due to insulin resistance or chronic inflammation, and is usually combined with neurohormonal disturbance. While these defects can be inherited via loss of function of certain genes that lead to either 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 the management of 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 metabolic syndrome.

Coagulopathy and Brain Injury Pathogenesis in Post-Covid-19 Syndrome.

The post-COVID neurological syndrome has been coined, which describes the functional and structural sequelae of coronavirus infection disease-19 (COVID-19) in the brain. Mild/severe manifestations of the post-COVID neurological syndrome have been identified in approximately 33.00% of COVID-19 survivors. The presence of neurological complications after COVID allowed neuropathologists to investigate in-depth the role of viral infection in neurons. The pathophysiology of the post-COVID neurological syndrome involved the development of a systematic response, including coagulopathy characterized by the formation of microthrombi. Coagulopathy, an old term for a new disease, describes the discrepancy between pro-coagulant and anticoagulant systems due to overexpression of pro-coagulant substances and or their receptors in addition to suppression of the anticoagulant molecules and or their receptors. Vascular endothelial cells and hepatocytes play a central role in the regulation of hemostasis that is disrupted during the acute phase response (APR) of coronavirus-19 (COVID-19). Currently, coagulopathy and inflammation are termed together since both form a complementary system, indicated by the elevation of inflammatory biomarkers (APR) and fibrinolysis biomarkers (D-dimer/fibrin). The later events of the post-COVID neurological syndrome are primarily induced by coagulopathy and direct viral tropism. Therefore, the paper introduces the hypothesis of coagulopathy induced post-COVID neurological syndrome.

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.