The molecular fingerprint of neuroinflammation in COVID-19: A comprehensive discussion on molecular mechanisms of neuroinflammation due to SARS-COV2 antigens.

BACKGROUND AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 attacks the neural system directly and indirectly via various systems, such as the nasal cavity, olfactory system, and facial nerves. Considering the high energy requirement, lack of antioxidant defenses, and high amounts of metal ions in the brain, oxidative damage is very harmful to the brain. Various neuropathic pain conditions, neurological disorders, and neuropsychiatric complications were reported in Coronavirus disease 2019, prolonged Coronavirus disease 2019, and after Coronavirus disease 2019 immunization. This manuscript offers a distinctive outlook on the interconnectedness between neurology and neuropsychiatry through its meticulous analysis of complications. DISCUSSION: After recovering from Coronavirus disease 2019, approximately half of the patients reported developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Long Coronavirus disease 2019 imaging reports illustrated the hypometabolism in various parts of the brain, such as olfactory bulbs, limbic/paralimbic domains, the brainstem, and the cerebellum. Ninety imaging and neuropathological studies of Coronavirus disease 2019 have shown evidence of white matter, brainstem, frontotemporal, and oculofrontal lesions. Emotional functions, such as pleasant, long/short-term memory, movement, cognition and cognition in decision-making are controlled by these regions. The neuroinflammation and the mechanisms of defense are well presented in the discussion. The role of microglia activation, Inducible NO synthase, Cyclooxygenases ½, Reactive oxygen species, neurotoxic toxins and pro-inflammatory cytokines, such as Interleukin-1 beta, Interleukin-6 and Tumor Necrosis Factor-alpha are highlighted in neuronal dysfunction and death. Nuclear factor kappa-light-chain-enhancer of activated B cells, Mitogen-activated protein kinase, Activator Protein 1, and Interferon regulatory factors are the main pathways involved in microglia activation in Coronavirus disease 2019 neuroinflammation. CONCLUSION: The neurological aspect of Coronavirus disease 2019 should be highlighted. Neurological, psychological, and behavioral aspects of Coronavirus disease 2019, prolonged Coronavirus disease 2019, and Coronavirus disease 2019 vaccines can be the upcoming issues. We need a global awareness where this aspect of the disease should be more considered in health research.

Regulatory factors involved in Th17/Treg cell balance of immune thrombocytopenia.

Immune thrombocytopenia is a common heterogeneous autoimmune disease that is characterized by decreasing peripheral blood platelet counts and increasing risk of bleeding. Studies have shown that an imbalance between T helper 17 (Th17) and Regulatory T (Treg) cells differentiated from CD4+T-cells is a key factor influencing the development and pathogenesis of immune thrombocytopenia. Th17 cells promote the development of chronic inflammatory disorders and induce autoimmune diseases, whereas Treg cells regulate immune homeostasis and prevent autoimmune diseases. Several regulators affecting the production and maintenance of these cells are also essential for proper regulation of Th17/Treg balance; these regulatory factors include cell surface proteins, miRNAs, and cytokine signaling. In this review, we focus on the function and role of balance between Th17 and Treg cells in immune thrombocytopenia, the regulatory factors, and therapeutic goals of this balance in immune thrombocytopenia.

COVID-19: imbalance of multiple systems during infection and importance of therapeutic choice and dosing of cardiac and anti-coagulant therapies.

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.

Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways.

Atherosclerosis is one type of cardiovascular disease (CVD) in which activation of the NLRP3 inflammasome and toll-like receptor (TLR) pathways is implicated. One of the most effective treatments for atherosclerosis is the use of statin medications. Recent studies have indicated that statins, in addition to their lipid-lowering effects, exert inhibitory and/or stimulatory effects on the NLRP3 inflammasome and TLRs. Some of the statins lead to activation of the inflammasome and subsequently cause secretion of IL-1ß and IL-18. Thus, these actions may further aggravate the disease. On the other hand, some statins cause inhibition of the inflammasome or TLRs and along with lipid-lowering, help to improve the disease by reducing inflammation. In this article, we discuss these contradictory studies and the mechanisms of action of statins on the NLRP3 inflammasome and TLR pathways. The dose-dependent effects of statins on the NLRP3 complex are related to their chemistry, pharmacokinetic properties, and danger signals. Lipophilic statins have more pleiotropic effects on the NLRP3 complex in comparison to hydrophilic statins. Statins can suppress TLR4/MyD88/NF-ĸB signaling and cause an immune response shift to an anti-inflammatory response. Furthermore, statins inhibit the NF-ĸB pathway by decreasing the expression of TLRs 2 and 4. Statins are cost-effective drugs, which should have a continued future in the treatment of atherosclerosis due to both their immune-modulating and lipid-lowering effects.

Evaluating the Relationship Between Serum Level of Interleukin-6 and Rheumatoid Arthritis Severity and Disease Activity.

AIM: The aim of this study was to evaluate the relationship between Interleukin-6 (IL-6) serum level and the severity and activity of Rheumatoid Arthritis (RA). METHODS: In this cross-sectional study, 120 RA patients referred to the rheumatology clinic, the patients were diagnosed by rheumatologists according to ACR / EULAR 2010 criteria. Based on DAS28 score the patients were divided into 4 groups: Remission, Mild, Moderate and Severe. Each group contained 30 patients. Serum levels of Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF) and serum levels of IL-6, were measured. The relationship between these factors was measured and compared to the relationship between IL-6 and these factors, and the activity of the disease was evaluated based on DAS-28. RESULTS: This study showed that the serum level of IL-6 has a significant relationship with RA activity according to DAS-28 (P value <0.001). There is also a significant relationship between the ESR level, the number of painful joints, and the number of swollen joints, and the severity of the disease based on VAS. CONCLUSION: Generally the findings of this study indicate that serum level of IL-6 plays an important role in the severity and activity of RA disease and can be considered as a determining factor in evaluating the severity of RA in RA patients and it is a good guide for a step up or down of treatment.

The effect of lupus disease on the pregnant women and embryos: a retrospective study from 2010 to 2014.

BACKGROUND AND AIMS: Pregnancy in women with systemic lupus erythematosus (SLE) is one of the challenges of recent studies. Women should prevent the onset of relapses with medications before and after pregnancy, and on the other hand, the effect of these medicines considers the health and development of the fetus. In this retrospective study, the effects of anti-phospholipid syndrome and the use of common drugs such as methotrexate, cyclosporine, and azathioprine and their side effects on maternal health and ultimately the development of the fetus have been investigated. MATERIAL AND METHODS: This study is a descriptive and retrospective epidemiologic study that was conducted in 2016 to investigate maternal and fetal complications in SLE patients. We prepared forms of data recording, including age, occupation, and other important information and then analyzed them in SPSS version 22. RESULT: The results showed that the presence of anti-phospholipid syndrome in pregnant women can lead to abnormalities such as preterm, IUGR, abortion, and fetal death (P value 0.0001). It also leads to complications such as nephritis, arthritis, and preeclampsia in the mother (P value 0.003). This study suggests that methotrexate and cyclosporine medications could cause fetal developmental disorders. The P value of cyclosporine was 0.0001 and the P value of methotrexate was 0.001. CONCLUSION: Anti-phospholipid syndrome in women with SLE who intend to become pregnant can disrupt the development of the embryo. The consumption of methotrexate and cyclosporine medications before and during the pregnancy can have irreparable effects on fetal growth. Key Points • Anti-phospholipid syndrome can disrupt the development of the embryo in women with SLE who intend to become pregnant. • Methotrexate and cyclosporine consumption before and during pregnancy can affect fetal growth. • 7 to 33% of patients whose disease had been suppressed and controlled 6 months before pregnancy seams to relapse during the pregnancy. • Taking medications to control the disease during pregnancy plays an important role in the progression of pregnancy and fetus health.

An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology.

In its classical view, the renin angiotensin system (RAS) was defined as an endocrinesystem involved in blood pressure regulation and body electrolyte balance. However, the emergingconcept of tissue RAS, along with the discovery of new RAS components, increased thephysiological and clinical relevance of the system. Indeed, RAS has been shown to be expressed invarious tissues where alterations in its expression were shown to be involved in multiple diseasesincluding atherosclerosis, cardiac hypertrophy, type 2 diabetes (T2D) and renal fibrosis. In thischapter, we describe the new components of RAS, their tissue-specific expression, and theiralterations under pathological conditions, which will help achieve more tissue- and conditionspecifictreatments.

Potential Mechanism and Pathways in Cerebral Ischemia- Reperfusion Injury: Therapeutic GLANCE.

Abtract Cerebral ischemia-reperfusion injury is a progressive disease that results in the lack of oxygen and nutrients needed for cellular metabolism in neurons due to blood flow disorders. The pathogenesis of this disease is different; however, it has been shown that the onset of inflammation interacts with I/R through the production of active oxygen species and increases the apoptosis of the neural cells. Therefore, different signaling pathways interfere with the induction of inflammation and the production of active oxygen species. Therefore, the common point of these pathways leads to the appearance of apotosisinducing molecules and inhibit the expression of anti-apoptosis molecules such as BCL-2. In the other hand, due to the dual role of some of these pathways in apoptosis and angiogenesis, it can be said that further studies can be useful in finding suitable therapeutic strategies based on the pathogenesis of Cerebral ischemia-reperfusion injury inducing angiogenesis in order to repair damaged veins and prevent disease progression. Keywords: Reperfusion; Nitric Oxide; Reactive Oxygen Species; Therapeutics.

Pentraxin Level is the Key to Determine Primary Percutaneous Coronary Intervention (PCI) or Fibrinolysis.

AIMS: To examine if pentraxin can help identify patients benefitting most from primary Percutaneous Coronary Intervention (PCI) vs. fibrinolysis. METHODS: Patients with acute ST-Elevation Myocardial Infarction (STEMI) were consecutively recruited from a community center without PCI and a tertiary center with PCI facilities. Left ventricular ejection fraction (LVEF) was determined echocardiographically at baseline and 5 days after the index admission; the difference between two measurements was considered as the magnitude of improvement. We used regression models to test the hypothesis that the magnitude of the advantage of PCI over fibrinolysis in preserving LVEF 5 days after STEMI is modified by pentraxin 3 (PTX3). RESULTS: The functional advantage (LVEF) of the PCI over fibrinolysis has been determined by PTX3. LVEF was attenuated and even reversed as PTX3 level increased. The primary PCI of the participants with less than 7 ng.ml-1 PTX3 level, achieved a clinically significant increase in the LVEF as compared to fibrinolysis. At lower levels of PTX3, PCI shows a conspicuous advantage over fibrinolysis in terms of the probability of developing an LVEF <40%. CONCLUSION: We demonstrated not only the functional advantage of PCI over fibrinolysis performed within the recommended time frames but also the relative advantage of its relevance to the baseline PTX3 levels. PTX3 can play a role in determining the choice of best therapy. More than 75% of patients with STEMI who have PTX3 levels ≤7 ng.ml-1 imply the need of PCI.

What Genetics Tells us about Cardiovascular Disease in Diabetic Patients?

BACKGROUND: Long-term diabetes causes other disease development such as cardiovascular diseases (CVD). OBJECTIVE: Genetics can help us to predict cardiovascular diseases in diabetic patients. Method and Search Strategy: We searched PubMed and Google scholar for the terms: Cardiovascular disease, Diabetes, Polymorphism, Genetics from 2000 to 2017, and then included the relevant studies in our study. DISCUSSION: Essential role of inheritance in multifactorial disease is obviously clear, however, varies by disease and by other factors such as age of disease onset and subtype of disease. CVD is a multifactorial disease which can develop in diabetes patients as a result of increase in oxidative stress. It may also increase expression of pro-inflammatory factors and induce apoptosis in cardiomyocytes. CONCLUSION: Predictive polymorphisms are risk estimators for CVD incidence in diabetes patients. SNPs such as 894G>T in NOS3 gene, V16 in MnSOD gene, Rs3918188 in NOS3 gene and Rs11614913 in MiR-196a2 increase the risk of CVD in diabetic patients are precious polymorphisms for CVD prediction in diabetic population. CDKN2B, MTHFR and ACE genes have polymorphisms which increase the risk of diabetes and other polymorphisms on these genes increase the risk of CVD, we suggest these genes are valuable to study and find out if there are any polymorphisms that predict CVD susceptibility in diabetic patients.