Abstract: Cholesterol is an important lipid for maintaining cell membrane fluidity and generation of various hormones and bile acids. Thus, it is critical to maintain cholesterol homeostasis including absorption, trafficking, biosynthesis, and efflux; dysregulation of cholesterol homeostasis may lead to human disorders such as atherosclerosis. As a cholesterol sensor, nuclear receptor liver X receptor (LXR) is an important factor regulating cholesterol homeostasis. Extensive research has been carried out to examine the roles of LXR in atherosclerosis. In this review, we summarize our current understanding of the mechanisms how LXR regulates cholesterol synthesis, efflux, absorption, and conversion of cholesterol esters to cholesterol in the context of atherosclerosis. In addition, we also discuss the possibility of targeting LXR and cholesterol homeostasis as a potential interventional strategy for treating atherosclerosis.

Abstract: Background Cardiovascular Disease (CVD) is the leading cause of mortality and morbidity worldwide. Four out of five CVD deaths are due to myocardial infarction or stroke. Despite many initiatives that have been established for CVD prevention and risk management, and new therapies to treat existing CVD, patients continue to die from cardiac events. Clearly, we need to identify new therapeutic targets and strategies. Metabolomics offers a novel solution to this problem, as metabolomics-based biomarkers do not only indicate the presence or absence of a disease, but are also capable of assessing risks of developing the disease and detecting the disease prior to the appearance of overt clinical symptoms. Method In this review, we describe the analytical techniques and workflow used in untargeted metabolomics. We also identify several case studies that highlight the use of untargeted metabolomics in cardiovascular research. Results Five case studies that employ untargeted metabolomics approaches to identify biomarkers for cardiovascular risk, myocardial ischemia, transient ischemic attack, incident coronary heart disease, and myocardial infarction risk prediction are described. The use of the untargeted metabolomics is still relatively new in cardiovascular research. As such, there remains a need for future advancement in metabolomic technologies. Conclusion Early diagnosis of CVDs and identification of patients at high risk of developing adverse events would allow for timely intervention that prevents serious consequences or death. There is a need to establish sensitive and non-invasive CV biomarkers, and novel therapeutic targets for the prevention and treatment of CVDs.

Abstract: Background The developments of new parenteral approaches to target PCSK-9 for the treatment of LDL-Cholesterol has yielded impressive results; and have shown significant decreases in the risk of mortality associated with hypercholesterolemia. However improved and convenient alternate approaches that exploit the beneficial drug target properties of PCSK-9 also need to be explored and developed. One such approach is the oral administration of Berberine using nanotechnology. Methods Nanoprecipitation encapsulation and physiochemical characterization of Berberine Chloride in PLGA-PEG-PLGA block copolymer has been developed and characterized in Hep-G2 cells using Berberine Chloride encapsulated nanoparticle (Bc-NP). Evaluation of PCSK-9, SREBP- 1, LDL-r, HNF-1alpha mRNAs and PCSK-9 protein expression was performed using quantitative real-time PCR (qPCR) and median fluorescence intensity (MFI) of flow cytometric studies respectively. Pearson's correlation analysis of PCSK-9 mRNA and protein levels in Berberine chloride delivery was performed. Results The PCSK-9 mRNA and protein expression shows a relationship to the release of Berberine from the encapsulating PLGA-PEG-PLGA polymer in a time dependent manner. Conclusion PCSK-9 modulation by oral administration of Berberine using nanotechnology approach can improve its pharmacokinetic profile. Further studies are needed to maximize its delivery efficiency.

Abstract: Objective Exosomes are small secreted membrane vesicles formed in the late endocytic compartments by inward budding. Interest in these extracellular vesicles and their role in atherosclerosis is growing, as they can affect multiple cellular processes that lead to lipid overload, cytokine secretion and cellular adhesion. Exosomes protect and transport lipids, proteins, and RNAs, fostering intercellular communication among different cell types involved in atherogenesis such as macrophages, endothelium and smooth muscle. Their molecular composition reflects their cell type of origin, but they share attributes because they are enriched in proteins of their endosomal source. Conclusion This review will describe the current state of our knowledge of exosome involvement in the development of atherosclerosis. The transfer of signaling molecules, lipids, mRNAs, and microRNAs via exosomes with effects on monocyte and macrophage cholesterol metabolism, endothelial cell and platelet activation and smooth muscle proliferation will be discussed. Finally, therapeutic potential of exosomes and clinical application will be explored.

Abstract: Background SGLT-2 inhibitors are a novel class of antidiabetic drugs, recently approved for the treatment of patients with T2DM. Their cardioprotective and renoprotective action, along with their beneficial effects on metabolic parameters, makes them an attractive therapeutic option. Since 2015, when the US FDA issued warning regarding the increased risk of euDKA in the setting of SGLT-2 inhibitors administration, a vivid discussion upon the direct connection between this novel class and the major metabolic complication of diabetes mellitus is still ongoing. Objectives To present the underlying pathophysiology, associating SGLT-2 inhibitors and euDKA, and clinical data both in T1DM and in T2DM patients, in order to understand the clinical background which favors the development of euDKA. Method We conducted a comprehensive research of the relevant literature regarding the association between SGLT-2 inhibitors in clinical practice and the events of diabetic ketoacidosis, mainly euglycemic. Results Randomized controlled trials, meta-analyses, case series and case reports shed light on this possible connection, the background that favors euDKA, and the mediating pathophysiologic mechanisms. Many of those euDKA events developed in patients with T1DM, due to off-label use of SGLT-2 inhibitors, or in patients previously misdiagnosed as having T2DM, who in fact suffered from LADA. Conclusion SGLT-2 inhibitors certainly predispose to euDKA, but it is unclear if, as certain precipitating factors are usually recognized on the background, DKA would also occur in the absence of an SGLT-2 inhibitor. Further investigation is required in order to establish or not SGLT- 2 inhibitors as causative factors of euDKA.

Abstract: Background & objective Acute Myeloid Leukemia (AML) is characterized by the accumulation of ≥20% myeloid premature blast cells in the bone marrow and they are most often found in the peripheral blood. AML is generally classified based on either French-American-British (FAB) or World Health Organization (WHO) systems. For better clinical management, cytogenetic finding in AML is necessary and in patients with normal karyotypes - molecular, epigenetic and proteomic biomarkers are very important in choosing which drugs to prescribe. Mutations of certain genes like NPM1, FLT3, CEBPA, RUNX1 and MLL play a crucial role in the risk management and clinical stratification of AML patients. We reviewed the literature for the current trends of clinical practice based on laboratory based diagnostic tests in AML. Outcome and Result: We listed in AML chromosomal aberrations (translocations, fusions or RUNX1, CBFB, MYHI1, MLL, EVI1, PML-RARA), genes and mutations (NPM1, FLT3, CEPBA, MLL) epigenetic factors (DNMT34, TET2) and proteomic biomarkers (PTP, PTK, PIP) and analysed how on the basis of these factors medical risk was stratified and accordingly managed. Conclusion AML is genetically and functionally a heterogenous malignant disease. In the western world, leukemia is one of the most common among all cancers. India is ranked 3rd in cancer disease after United States of America and China. Cytogenetic analysis, molecular/proteomic biomarkers and epigenetic factors assist in determining the management strategies and prognosis of the disease. A number of targeted drugs in pre-clinical and clinical trials based on molecular factors and epigenetic mechanisms have been reported to have promising results in AML patients.

Abstract: The effects of hypoxia on the human organism has been considered doubly fascinating by the scientific community. The knowledge of the discrete mechanisms allowing the acclimatization both at genetic level or through the cell mediators production in addition to the macroscopic responses of the cardio-circulatory and ventilatory systems to a hypoxic environment has been progressively developed since the last century; moreover granting a safer stay in hypoxic conditions not only for the residents but also for the different cathegories of workers, sportsmen and tourists has been considered a worthy aim of the medical activity. The effects of hypoxia were simulated in laboratory by means of an induced low pressure environment (normobaric hypoxia) or tested on the subjects at different levels of altitude (hypobaric hypoxia). Far from describing all the physiological and pathological responses of the organism, in this review, the authors expose the state of the art in the knowledge of the responsiveness of the pulmonary circle to the acute or chronic hypoxic condition, its possible progression to the pulmonary arterial hypertension, the latter being more appropriately named High-Altitude Pulmonary Hypertension. The currently available therapeutic options in the treatment of High-Altitude Pulmonary Hypertension are also reviewed.

Abstract: Background Myeloproliferative neoplasms (MPNs) are chronic blood disorders caused by clonal expansion in one or more myeloid lineages and include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and chronic myeloid leukemia (CML). Cardiovascular events are a main challenge for patients with MPN and can lead to their death. Objective JAK2V617F mutation is observed in Philadelphia-negative MPNs such as ET and PV, increasing the risk of cardiovascular complications in these patients. JAK2 mutation can affect cardiac arteries and veins in ET and PV, which results in thrombosis, ischemia and other cardiovascular events. JAK/STAT signaling pathway plays an important role in heart diseases. In this review, we will survey the cardiovascular events in JAK2-positive MPN patients. Method Relevant English-language literature were searched and retrieved from PubMed search engine (1995-2017). The following keywords were used: "Cardiovascular Events", "JAK2" and "Myeloproliferative Neoplasms". Forty three articles were selected by using the key words. Results JAK2 phosphorylates the signal transducers and activators of transcription (STAT). Various factors like angiotensin II (ANG II) and cardiotrophin-1 (CT-1) can bind their receptors on myocytes and increase the expression of angiotensinogen (Ao) gene by binding of STAT proteins to these factors in myocytes, causing different cardiovascular complications through autocrine mechanisms. Conclusion JAK2 mutation is observed in patients with thrombosis, ischemia and other cardiovascular complications having abnormal increase in cell count even without definite clinical diagnosis of MPN. Therefore, identification of this mutation in these patients contributes to definite diagnosis of cardiovascular events. Also, cardiovascular complications in MPN patients can be prevented by targeting the factors involved in JAK/STAT signaling pathway.

Abstract: 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.

Abstract: Introduction Adult People With Hemophilia (PWH) mainly use Factor VIII/Factor IX (FVIII/FIX) to lessen chronic articular pain, followed in frequency by nonsteroidal antiinflammatory drugs. Analgesics are used by only one-third of adult PWH. Limitations in activities of daily living are encountered in the large majority of PWH, and most describe pain as affecting their state of mind. A review of the literature on their treatment is important because the chronic pain in adult PWH is often undertreated or wrongly treated, causing psychological problems for these patients. Aim To determine the optimal treatment for chronic articular pain in adult PWH. Methods A review of the literature has been performed. Results There are three main strategies to alleviate chronic pain secondary to hemophilic arthropathy: pharmacologic treatment (including intra-articular injections of corticosteroids and hyaluronic acid), physical medicine and rehabilitation. Pharmacologic treatment of chronic articular pain is inadequate in many PWH. The optimal pharmacologic treatment for chronic articular pain in these patients is paracetamol and COX-2 inhibitors (celecoxib and rofecoxib). Intra-articular injections of hyaluronic acid and corticosteroids should be second-line therapy. Conclusion Most adult PWH experience limitations in activities of daily living, and chronic articular pain affects their mental health. Pharmacologic treatment of pain in adult PWH has frequently proven to be inadequate. The optimal pharmacologic treatment of chronic articular pain in these patients is the use of paracetamol and COX-2 inhibitors. Physical medicine, rehabilitation and intra-articular injections of hyaluronic acid and corticosteroids should be second-line therapy.

Abstract: BACKGROUND The impact of diet strategies to manage cardiovascular disease has been focused in recent years. The food ingredients, such as flavonoids, are known as cardioprotective agents; however, it is not fully understood how these compounds are effective against cardiovascular problems. Catechins are polyphenolic compounds exhibiting several biological activities in the human body, potentially in the treatment of cardiovascular disease. The present study indicates that catechins may be effective against cardiovascular problems through modulating blood lipid metabolism, protecting vascular endothelial, and decreasing blood pressure. CONCLUSION The current review has evaluated various studies on the role of catechins in the prevention and treatment of cardiovascular disorders by focusing on oxidative stress and inflammatory responses.

Abstract: Background In the general population the leading cause of cardioembolic stroke is atrial fibrillation (AF). A silent AF is also the possible cause of many cryptogenic strokes. P wave dispersion (PWD), a predictor of AF, has been proposed as a marker of silent AF occurrence in these strokes. PWD correlates with high-sensitive C-reactive protein levels reflecting the role of inflammation in promoting a slowed and inhomogeneous atrial conduction. Statins have a multitude of additional effects beyond lipid lowering, in particular anti-inflammatory effects that may influence atrial conduction. Objective The aim of this study was to evaluate the effects of previous statin use on PWD in patients with cryptogenic stroke, in order to highlight a possible role for statins in preventing atrial conduction alterations that predispose to AF. Method We enrolled 131 patients (67 males, 64 females; mean age 69±13 years) with cryptogenic stroke. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. PWD was measured in all subjects. Results Patients previously treated with statins (n: 34) had lower PWD and P index values in comparison with no-statin group (41.7±12.2 vs 48.7±15.2 ms, p=0.01, and 14.2±3.7 vs 16.5±5.3 ms, p=0.02, respectively). Conclusions Our results show lower PWD values in cryptogenic stroke patients previously treated with statins. These findings provide support to the hypothesis that statins may play a role in modulating atrial electrophysiological and structural properties, preventing the occurrence of a slowed and heterogeneous atrial conduction and finally, reducing the occurrence of AF.

Abstract: Background Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The recent class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect. Objective In the present review, the pleiotropic actions of SGLT-2 inhibitors are summarized and their potential implications on ischemic stroke prevention are discussed. Methods We performed a comprehensive search of the literature in terms of SGLT-2 inhibitors efficacy on ischemic stroke and traditional risk factors of cerebrovascular disease. Results Several studies consistently showed that SGLT-2 inhibitors reduce blood pressure, induce weight loss, increase high-density lipoprotein cholesterol levels and reduce triglyceride levels. In addition, they improve several emerging cardiovascular risk factors, most notably arterial stiffness, albuminuria and oxidative stress. However, in the only trial that evaluated the effects of these agents on the incidence of ischemic stroke, empagliflozin did not reduce the risk of first or recurrent stroke despite a significant reduction in cardiovascular and all-cause mortality. Conclusion Despite the multiple pleiotropic effects of SGLT-2 inhibitors, these agents do not appear to affect stroke risk. Ongoing large trials with longer follow-up will evaluate whether the pleiotropic effects of this class will translate into benefits in ischemic stroke prevention.

Abstract: INTRODUCTION Buxus sempervirens L. is used in Morocco as a plant with some medicinal properties including treatment of diabetes and cardiovascular diseases. METHODS The objective of the study was to assess the effect of the aqueous extract of Buxus sempervirens L. (Boxwood) leaves on the blood lipid parameters including total cholesterol, triglycerides, High-Density Lipoprotein Cholesterol (HDL-C), Low-Density Lipoprotein Cholesterol (LDL-C) and Very Low-Density Lipoprotein Cholesterol (VLDL-C) in normal and streptozotocininduced diabetic rats. In addition, antioxidant activity of aqueous Buxus sempervirens extract was evaluated by DPPH and FRAP assays. RESULTS The results indicated a significant decrease in serum total cholesterol and LDL-C levels, while, no change was observed on triglycerides and VLDL-C values in diabetic rats. Lipid profile of normal animals did not reveal any modification. In addition the aqueous extract of Buxus sempervirens exerted a significant antioxidant activity. Therefore, the results suggest that the aqueous extract of Buxus sempervirens exhibits lipid lowering activity which could be due partially to its antioxidant ability. CONCLUSION In conclusion, Buxus sempervirens leaf extract may be helpful in controlling the development of hyperlipidemia as well as atherosclerosis in diabetic animals.

Abstract: Background and objective ADAMTS13 (A Disintegrin-like and Metalloproteases with Thrombospondin type-1 repeats, member-13) plays an important role in vascular hemostasis by cleaving the von Willebrand Factor (vWF). ADAMTS13 and vWF are involved in the development of ischemic heart disease. In this review paper, we examine the effects of Single Nucleotide Polymorphisms (SNPs) and mutations in the vWF and ADAMTS13 genes and their contribution to the development of thrombosis. Methods Relevant English-language literature was searched and retrieved from PubMed search engine (2001-2017). The following keywords were used: "ADAMTS13", "vWF", "Polymorphism", and Thrombosis". Results SNPs in the ADAMTS13 and vWF genes cause genetic variability and affect the plasma levels of these genes. Moreover, environmental (such as age, smoking, hypertension) and genetic factors (like ABO blood groups) play a role in the development of different polymorphisms in ADAMTS13 and vWF genes. Conclusion The increased or decreased activity of these two genes as a result of genetic changes and the development of thrombosis are a challenging and contradictory matter, and the study of genetic variability in ADAMTS13 and vWF genes may be helpful in the diagnosis of thrombotic disorders.

Abstract: Background The treatment of diabetes remains challenging over the decades, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes require a combination of multiple agents and eventually the use of insulin. The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney. Objective The purpose of this review is to critically discuss the beneficial effect of SGLT-2i on glycemic control as monotherapy or in combination with other hypoglycemic agents. Methods A systematic review of randomised clinical trials on SGLT-2i vs placebo, other glucoselowering drugs or insulin was performed, and studies assessing glycemic control, mainly expressed through glycated hemoglobin and fasting plasma glucose levels (FPG) were included in the review. Electronic and manual searches on MEDLINE, EMBASE and Cochrane Library were performed. Results In our review, we mainly focused on dapagliflozin, empaglifozin and canagliflozin. All agents exhibited a sufficient reduction of HbA1c as well as FPG. Conclusions SGLT-2i are a reliable second-line therapy of T2DM, since they can be combined safely with metformin, sulfonylures, incretin mimetics, insulin as well as in triple combinations. In many studies, they were prioritised as monotherapy with satisfying effects regarding HbA1c and FPG level reductions.

Abstract: Background Viscoelastic tests (VETs) such as thromboelastography, rotational thromboelastography, and the Sonoclot Analyzer assess the entire process of clot formation through dissolution in real-time, and may provide additional therapeutic value to conventional laboratory coagulation tests. With the ability to obtain rapid results and identify specific coagulopathies, VETs has been examined in a variety of clinical scenarios, including cardiac surgery, trauma, obstetric emergencies, and liver transplant. Conclusion This review provides a summary of clinical trials utilizing VETs in the aforementioned clinical scenarios, and suggests that VETs have demonstrated a capability to identify coagulopathies, utility in guiding algorithms to reduce the amount of transfusions, and a limited ability to predict bleeding events or mortality.

Abstract: Background Diabetic nephropathy is a crucial microvascular complication of diabetes mellitus that is associated with elevated cardiovascular risk. SGLT-2 inhibitors are a new class of hypoglycemic drugs that positively affect several risk factors of cardiorenal damage. Objectives The study aimed to review and critically discuss available data on the association of SGLT-2 inhibitors treatment with kidney function, progress of diabetic kidney disease, and renal related outcomes, as well to unveil potential mechanisms of action that mediate such effects. Method We conducted a comprehensive search of the literature on the renal related effects of SGLT-2 inhibitors, to compose a narrative mini-review. Results The administration of SGLT-2 inhibitors was observed to exert beneficial effects on a wide cluster of risk factors of chronic kidney disease, such as hyperglycemia, blood pressure, serum uric acid, and body weight. Data from the first two large, randomized, clinical trials of SGLT-2 inhibitors conducted to address the renal related outcomes of SGLT-2 inhibitors suggest substantial benefits on estimated glomerular filtration rate decline and albuminuria. Conclusion The initial data suggest clinically meaningful benefits of the SGLT-2 inhibitors in diabetic patients in relevance with chronic kidney disease. Future, well-designed randomised clinical trials need to be further investigated such as nephroprotective outcomes, that if confirmed, could lead to new perspectives in the management of diabetic nephropathy.

Abstract: OBJECTIVE Infective endocarditis due to Enterococus Gallinarum is a rare clinical condition. We present a case of an 85 years old male with a history of the valvular disease and permanent pace maker with past medical history of repetitive urinary tract infections in the previous months, who presented to the emergency department with fever, urinary disturbances, general malaise and positive blood cultures for Enterococcus Gallinarum. METHODS Echocardiography was a useful diagnostic method in the present case, showing the vegetation on the tricuspid valve. RESULTS This case is notable because tricuspid valve endocarditis due to Enterococcus Gallinarum is a rare clinical condition and improves knowledge of disease and management in patients with endocarditis.

Abstract: BACKGROUND Previous studies have shown that metabolism of adenosine 5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. OBJECTIVE To investigate the acute effect of high dose of doxorubicin (DOX) on adenosine and ATP catabolism in systemic blood in vivo. METHOD Sprague Dawley (SD) rats were each given either 10 mg/kg of DOX (n = 8) or normal saline (1 mL/kg, n = 11) twice daily for 4 doses by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measuring circulating concentrations of ATP, adenosine and their metabolites. Hemodynmic recording was obtained continuously after the last injection. The difference in response between groups was considered significant at p < 0.05 (t-test). RESULTS Diastolic blood pressure (DBP) was significantly lower in the DOX treated rats than in the control before the final injection (87 ± 12 vs. 104 ± 11 mmHg, p < 0.05). Blood pressure fell gradually after the last injection and the decrease was significantly greater in the DOX treated group (p < 0.05). Plasma concentration of adenosine was significantly lower in the DOX treated group. In contrast, plasma concentrations of uric acid and hypoxanthine, as well as Red Blood Cell (RBC) concentrations of AMP, were significantly higher (p < 0.05). CONCLUSION Acute cardiotoxicity induced by DOX may be measured by the increased breakdown of ATP to AMP in the RBC and also breakdown of adenosine to hypoxanthine and uric acid in plasma.

Abstract: Aims Atrial fibrillation (AF) ablation is associated with increased circulating markers of inflammation. Innate immune or inflammation pathways up-regulate mononuclear cell responses and may increase the risk for recurrent arrhythmia. Chemokines and serine protease coagulation pathways both activate innate immune responses. Here, we measured inflammatory markers in peripheral blood samples from patients after cryoballoon and/or radiofrequency pulmonary vein isolation and assessed the capacity for the inhibition of chemokine and serine protease pathways to block cell activation. Methods Markers of inflammation were measured in 55 patients immediately before and one day after AF ablation. Peripheral blood mononuclear cells (PBMCs) isolated from 19 patients were further tested for responsiveness to two anti-inflammatory proteins ex vivo using fluorescence assays and RT-qPCR analysis of gene expression. Results White blood cells (WBC), C-reactive protein, fibrinogen and troponin T levels were significantly elevated after ablation. PBMCs isolated from the circulating blood had increased activation with Phorbol 12-myristate 13-acetate. Cell activation, as measured by membrane fluidity, was blunted after treatment with a broad-spectrum chemokine modulating protein, M-T7, which interferes with chemokine/glycosaminoglycan (GAG) interactions, but not by Serp-1, a serine protease inhibitor (serpin) that targets both thrombotic and thrombolytic pathway proteases. Differential gene expression changes in the apoptotic pathway were identified with M-T7 and Serp-1. Conclusions Patients undergoing AF ablation have significantly increased inflammatory markers. Inhibition of chemokine signaling, but not serine proteases, reduced the activation of monocytes isolated from patients, in vitro. Targeting chemokines have the potential to reduce post-ablation activation of circulating leukocytes.

Abstract: INTRODUCTION In coronary bypass surgery, after cardiopulmonary bypass is initiated by arterial cannulation in the ascending aorta and venous cannulation through a single vein generally in the right atrium, the process of cooling the patient is started. OBJECTIVE There is a relation between cooling the patient and irisin, which is responsible for releasing heat. Therefore, the main objective of the present study is to explore how irisin concentrations and some other panel of myocardium injury in patients undergoing coronary artery bypass surgery. METHODS The blood samples collected before induction (T1), before bypass (T2), before (T3) and after (T4) removing the cross-clamp, upon admission to intensive care (T5), and at the postoperative 24 (T6) and 72 (T7) hours, and whether these concentrations are correlated with lactate levels classically used in monitoring this surgery. A total of biological samples, 23 from control individuals and 105 from bypass patients (14-16 samples for each timeframe) were analyzed to determine irisin, CK-MB, TnT and BNP levels by ELISA and lactate levels by lactate assay kit. Both lactate and irisin were seen to increase gradually from the time of induction to the removal of the cross-clamp. After the cross-clamp was removed and the patient was started to be warmed, both parameters began to decrease gradually and were restored to normal levels on the second and third post-operative days. The increase and decrease in irisin were found correlated with lactate levels. CK-MB, TnT and BNP alteration were similar to each other. RESULTS Based on these results, it is estimated that measurement of irisin along with lactate may prove to be a useful parameter in monitoring the coronary bypass surgery and irisin may be a significant marker of hypothermia. Beside CK-MB, TnT and BNP, measurements of irisin concentration in open heart surgery may also be useful parameters for the panel of myocardium injury.

Abstract: Background Sodium-glucose co-transporters 2 inhibitors have emerged as a novel antidiabetic class of drugs offering significant ameliorating effects on a variety of cardiovascular risk factors, secondary to their mechanism of action, including blood pressure and body weight Objective The purpose of this article is to discuss available data on the impact of SGLT-2 inhibitors on blood pressure and body weight compared with other available anti-diabetic drugs and to present potential mechanisms mediating these effects Methods A comprehensive review of the literature was performed to identify studies examining the effects of SGLT-2 inhibitors on blood pressure and body weight Results SGLT-2 inhibition has been related with a mild decrease in blood pressure of approximately 3-5mmHg in systolic and 1-2mmHg in diastolic blood pressure These data have been confirmed with 24h ambulatory measurements, as well Furthermore, given the loss of calories in the urine, a mild decrease in body weight is anticipated, as well Studies with this class of drugs noted a reduction in body weight of 2 to 3 kg, similar to the loss noted with the use of glucagon-like peptide 1 analogues, the only class of drugs that has offered significant reductions in body weight so far Consclusion: The beneficial effects of the SGLT-2 inhibition on an abundance of cardiovascular risk factors, including blood pressure and body weight, have created great expectations for potential benefits from the cardiovascular events standpoint, a theory that was confirmed in the two available cardiovascular studies of this promising class of drugs

Abstract: Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a new class of oral antidiabetic drugs. So far, there are three agents approved for use in Europe and in the USA, two in Japan and another four agents under testing. Objective The purpose of this study is to describe the mechanism of action and the favorable and adverse effects of SGLT-2 inhibitors. Method A thorough review of literature indexed in PubMed, Scopus and Cochrane databases were conducted. Original papers, review papers and their relevant references in English, from 2005 to February 2017, were included. Results The main mechanism of action is the glycosuria induced by the inhibition of SGLT-2, located in the early segment of the proximal convoluted tubule. Along with large amounts of glucose, sodium, water and uric acid are also excessively excreted in urine. These actions have various, both desired and adverse, consequent implications in kidneys, blood pressure, cardiovascular system and other systems. Moreover, SGLT-2 inhibitors act directly to organs other than the kidneys, as SGLT-2 can be expressed there. Conclusion The underlying mechanisms responsible for the SGLT-2 inhibitor actions, are pleiotropic and occur in the kidneys, as well as in other target organs. The comprehension of these mechanisms, not only permits us to understand their actions better, but it could also help us to predict more of their undisclosed favorable actions, as well as their rare adverse effects.

Abstract: Background The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. Objectives To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus. Method We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects. Results In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy. Conclusion The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes.

Abstract: Background In exploring the cause of Imatinib Mesylate (IM) resistance among Chronic Myeloid Leukemia (CML) patients who do not harbor BCR-ABL dependent mechanism, BCR-ABL independent pathways are the most probable pathways that should be explored. In BCR-ABL independent pathway, SOCS1 plays an important role as it helps in regulating optimal JAK/STAT activity. Objective To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance. Method The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific-High Resolution Melt (MS-HRM) analysis. Results Both primers used to amplify promoter region from -333 to -223 and from -332 to -188 showed less than 10% methylation in all CML and normal samples. Consequently, there was no significant difference in SOCS1 promoter methylation level between IM resistant and IM good response patients. Conclusion SOCS1 promoter methylation level is not suitable to be used as one of the biomarkers for predicting the possibility of acquiring resistance among CML patients treated with IM.

Abstract: Background Transient Receptor Potential Vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. Method Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Results HFD increased body weight, heart weight, and levels of fasting glucose, insulin, and leptin in both strains, with no differences between two strains. HFD impaired glucose tolerance in both strains with a more profound effect on Trpv1-/- than WT mice. HFD increased left ventricular (LV) internal diameter in diastole in both strains, while increased LV posterior wall thickness in diastole in Trpv1-/- but not in WT mice. HFD increased LV end-diastolic pressure in both strains with a further increase in Trpv1-/- mice, while decreased -dP/dt in Trpv1-/- but not in WT mice. HFDinduced cardiac collagen deposition and superoxide production were enhanced in Trpv1-/- mice. HFD upregulated cardiac p22phox in both strains, while increased p47phox in Trpv1-/- but not in WT mice. Conclusion In summary, TRPV1 knockout exacerbates HFD-induced glucose intolerance, cardiac oxidative stress and collagen deposition, leading to aggravated LV diastolic dysfunction.

Abstract: Background Available hypoglycemic-agents enable physicians to achieve consistent glycemic-control, but effects on cardiovascular-outcomes have been marginal or questionable. SGLT-2 inhibitors emerged as a novel antidiabetic drug class with remarkable cardiovascular benefits, and significant improvement in the prevention and progression of HF. Objective The purpose of this article is to critically review the effect of SGLT-2 inhibitors on HFoutcomes and the potential underlying mechanisms. Method We conducted a thorough review of the literature. The studies addressing the impact of SGLT-2 inhibitors on HF and potential underlying mechanisms were identified. Additionally, we reviewed the references of the identified original papers. Results The EMPA-REG OUTCOME trial was the first cardiovascular safety study of this drug class that assessed among other outcomes, the impact of SGLT-2 inhibition on HF. Empagliflozin was associated with significant reductions of the risks for hospitalization or death from HF in patients with- and without-HF. Similar benefits were noted from a large-cohort study assessing the effect of SGLT-2 inhibitors on HF-outcomes in real-life. Potential mechanisms include the SGLT-2 inhibitors-induced lowering of blood pressure, the decrease in visceral obesity and the amelioration of arterial stiffness. Improvements of left ventricular mass and diastolic dysfunction may also be implicated in the manifestation of HF-benefits. Lastly, the SGLT-2 inhibitors-related higher ketones bioavailability might offer a better "fuel" to the myocardium. Conclusion The pleiotropic effects of SGLT-2 inhibitors seem to be translated in significant improvement of HF-related outcomes. On-going trials will provide further information on the impact of these agents in various high- and low-risk populations.

Abstract: Background Recently, the treatment and prevention of ischemic cardiomyopathy is one of the emerging research topics in the cardiovascular field. Gap junction is the basic structure of cardiac electrophysiology. Connexin is the basic unit of gap junctions. Connexin43(CX43) is the most abundant member of Cx family in the heart, the normal expression of Cx43 is important for heart development, electrically coupled cardiomyocytes activities and coordination of myocardial function. The connection between Cx43 and myocardial ischemia/reperfusion or reperfusion injury has become the focus of current research. Methods We undertook a structured search of bibliographic database for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to analyze the interventions and findings of included studies using a conceptual framework. Results Twenty-one papers were included in the review, eight papers outlined the relationship of Cx43 and reperfusion arrhythmias. Eight papers pointed out the effect on the infarct size of Cx43. Conclusion The findings of this review confirm that Cx43 is the most abundant member of Cx family in the heart and is vital for myocardial protection during ischemia/reperfusion process and for ischemia/reperfusion injury. Many of its mechanism are still not very clear and require future research in the future.