Orexin-A exerts equivocal role in atherosclerosis process depending on the duration of exposure : in vitro study

Orexin-A is a peptide hormone that plays a crucial role in feeding regulation and energy homeostasis. Diurnal intermittent fasting (DIF) has been found to increase orexin-A plasma levels during fasting hours, while Ramadan fasting which resembles DIF, has led to beneficial effects on endothelial function. Herein, we aimed to investigate the effects of orexin-A on the expression of molecules involved in the atherogenesis process: Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase-1 and 2 (TIMP-1 and TIMP-2), in human aortic endothelial cells (HAECs). HAECs were incubated with orexin-A at concentrations of 40 ng/mL, 200 ng/mL and 400 ng/mL for 6, 12 and 24 h. The mRNA levels of MCP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 and orexin-1 receptor were measured by real-time qPCR. We also evaluated the MMP-2, p38, phospho-p38, NF-κΒ/p65 as well as TIMP-1 protein levels by Western blot and ELISA, respectively. MMP-2 activity was measured by gelatin zymography. Short-term 6-h incubation of HAECs with orexin-A at a high concentration (400 ng/mL) decreased MCP-1, MMP-2 expression, MMP-2/TIMP-1 ratio (p < 0.05), and MMP-2 activity, while incubation for 24 h increased MCP-1, MMP-2 expression (p < 0.05), MMP-2/TIMP-1 and MMP-2/TIMP-2 ratio (p < 0.01 and p < 0.05, respectively) as well as MMP-2 activity. The dual effects of orexin-A are mediated, at least in part, via regulation of p38 and NF-κΒ pathway. Orexin-A may have an equivocal role in atherosclerosis process with its effects depending on the duration of exposure

Infantile Neuroaxonal Dystrophy in Two Cases: Siblings with Different Presentations

&nbsp; Infantile neuroaxonal dystrophy (INAD) is a rare recessive neurodegenerative disorder manifested by symptoms, including hypotonia, extrapyramidal signs, spastic tetraplegia, vision problems, cerebellar ataxia, cognitive complications, and dementia, before the age of three. Various reports evaluated the relationship with the incidence of INAD and different mutations in the PLA2G6 gene. We describe cases of two children with INAD whose diagnoses were challenging due to misleading findings and had a mutation in the position C.2370 T&gt;G (p. Y790X) in the PLA2G6 gene based on NM_001349864 which has been reported previously

Antibiotic Self-Medication and Risk Factors among Medical Students in an Iranian University: a Cross Sectional Study

Background: Self-medication with antibiotic is a widely prevalent practice all over the world especially among medical students. This study was aimed to evaluate the prevalence and the pattern of self-medication among medical students in Tehran, Iran. Materials and Methods: A cross-sectional questionnaire-based study was conducted among the undergraduate medical students from a referral university in Tehran, Iran. All data obtained were analyzed using the statistical package for social sciences program (SPSS) version 20. Results: A total of 201 students were enrolled in the current study. According to the analysis, 129 (64.1%) of the study population reported that they have self-medicated with antibiotics at least once in their student life. The principal morbidities for seeking self-medication include cough and common cold (23.4%) followed by fever (14.9%). The most frequent antibiotics used to self-medicate the mentioned morbidities were: amoxicillin (62%), co-amoxiclav (19.4%), penicillin (17%), cefixime (16%), azithromycin (14%) and tetracycline (9%). The majority of the participants stated cost saving, convenience and lack of confidence as their reasons for self-medication. The drug selection was mostly based on opinion of family members (31.8%), their own experience (27.4%) and the least commonly reported was selection based on recommendation by net citizens (0.5%). Conclusion: Our study indicates that self-medication is widely practiced among students of the college. In this situation, the health care system should create as effective awareness and educate their students regarding advantages and disadvantages of self-medication

Can laboratory tests at the time of admission guide us to the prognosis of patients with COVID-19?

Introduction: To enhance the COVID-19 patients’ care and to optimize utilizing medical resources during the pandemic, relevant biomarkers are needed for prediction of the disease’s progression, the current study was aimed to determine the factors that effect on mortality of COVID-19 patients who admitted in Baharloo hospital in Iran. Methods: in the current retrospective study, 56 patients who were died because of COVID-19 infection were randomly selected from those who were admitted to Baharloo hospital. One patient who was diagnosed with COVID-19 and had recovered from it matched with each non-survived patient in the term of age. Laboratory tests of all these patients at the time of admission were recorded and compared. All analyses performed using spss version 22 by considering α:0.05 as a significant level. Results: There was no statistical difference in the age and gender distribution between the two groups (p&gt;0.05). The prevalence of diabetes among survived patients was 37.5% and among non-survived patients was 26.8% and there was no statistical difference between two groups about this comorbidity (p:0.22). Also, there was no statistical difference in the prevalence of hypertension and coronary heart diseases between two groups (p&gt;0.05). Lymphocyte percentage, Blood oxygen level, and platelet (PLT) count was significantly higher in patients who had recovered (P&lt;0.05).&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Conclusions: LDH level, Lymphocyte percentage, PLT count, and blood Oxygen saturation have associations with severe forms of COVID-19 infection and can be used as predictors to assess the patients who are suspected of infection with COVID-19 at the time of admission

Estrogen Receptor Subtypes Elicit a Distinct Gene Expression Profile of Endothelial-Derived Factors Implicated in Atherosclerotic Plaque Vulnerability

In the presence of established atherosclerosis, estrogens are potentially harmful. MMP-2 and MMP-9, their inhibitors (TIMP-2 and TIMP-1), RANK, RANKL, OPG, MCP-1, lysyl oxidase (LOX), PDGF-β, and ADAMTS-4 play critical roles in plaque instability/rupture. We aimed to investigate (i) the effect of estradiol on the expression of the abovementioned molecules in endothelial cells, (ii) which type(s) of estrogen receptors mediate these effects, and (iii) the role of p21 in the estrogen-mediated regulation of the aforementioned factors. Human aortic endothelial cells (HAECs) were cultured with estradiol in the presence or absence of TNF-α. The expression of the aforementioned molecules was assessed by qRT-PCR and ELISA. Zymography was also performed. The experiments were repeated in either ERα- or ERβ-transfected HAECs and after silencing p21. HAECs expressed only the GPR-30 estrogen receptor. Estradiol, at low concentrations, decreased MMP-2 activity by 15-fold, increased LOX expression by 2-fold via GPR-30, and reduced MCP-1 expression by 3.5-fold via ERβ. The overexpression of ERα increased MCP-1 mRNA expression by 2.5-fold. In a low-grade inflammation state, lower concentrations of estradiol induced the mRNA expression of MCP-1 (3.4-fold) and MMP-9 (7.5-fold) and increased the activity of MMP-2 (1.7-fold) via GPR-30. Moreover, p21 silencing resulted in equivocal effects on the expression of the abovementioned molecules. Estradiol induced different effects regarding atherogenic plaque instability through different ERs. The balance of the expression of the various ER subtypes may play an important role in the paradoxical characterization of estrogens as both beneficial and harmful

Motor neuron diseases caused by a novel VRK1 variant – A genotype/phenotype study

Background: Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia- related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly. Results: Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsensemediated decay machinery and results in a premature termination codon. Conclusions: Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases

Use of Complementary Medicine in SARS-CoV-2 and MERS-CoV: a Narrative Review

Severe acute respiration syndrome coronavirus 2 (SARS-CoV-2) is characterized by severe cytokine storm syndrome following inflammation. SARS-CoV-2 is the 7th coronavirus that causes infection in human bodies; SARS-CoV, MERS-CoV, and SARS-CoV-2 can purpose severe diseases. SARS-CoV-2 at once interacts with angiotensin-converting enzyme 2 (ACE-2) receptors inside the body and causes respiratory problems. Interestingly, complementary medicines and herbal drugs affect the expression of IgE and IgG antibodies and improve the immune system; for that reason, complementary medicine could be beneficial for infectious diseases like SARS-COV-2. In this review, we assessed some related articles to evaluate the effect of complementary medicine on SARS-COV2 and MERS-COV

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection?

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment

Endothelial cell dysfunction and nonalcoholic fatty liver disease (NAFLD) : a concise review

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. It is strongly associated with obesity, type 2 diabetes (T2DM), and other metabolic syndrome features. Reflecting the underlying pathogenesis and the cardiometabolic disorders associated with NAFLD, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has recently been proposed. Indeed, over the past few years, growing evidence supports a strong correlation between NAFLD and increased cardiovascular disease (CVD) risk, independent of the presence of diabetes, hypertension, and obesity. This implies that NAFLD may also be directly involved in the pathogenesis of CVD. Notably, liver sinusoidal endothelial cell (LSEC) dysfunction appears to be implicated in the progression of NAFLD via numerous mechanisms, including the regulation of the inflammatory process, hepatic stellate activation, augmented vascular resistance, and the distortion of microcirculation, resulting in the progression of NAFLD. Vice versa, the liver secretes inflammatory molecules that are considered pro-atherogenic and may contribute to vascular endothelial dysfunction, resulting in atherosclerosis and CVD. In this review, we provide current evidence supporting the role of endothelial cell dysfunction in the pathogenesis of NAFLD and NAFLD-associated atherosclerosis. Endothelial cells could thus represent a “golden target” for the development of new treatment strategies for NAFLD and its comorbid CVD

Genetic and Diet-Induced Animal Models for Non-Alcoholic Fatty Liver Disease (NAFLD) Research

A rapidly increasing incidence of non-alcoholic fatty liver disease (NAFLD) is noted worldwide due to the adoption of western-type lifestyles and eating habits. This makes the understanding of the molecular mechanisms that drive the pathogenesis of this chronic disease and the development of newly approved treatments of utmost necessity. Animal models are indispensable tools for achieving these ends. Although the ideal mouse model for human NAFLD does not exist yet, several models have arisen with the combination of dietary interventions, genetic manipulations and/or administration of chemical substances. Herein, we present the most common mouse models used in the research of NAFLD, either for the whole disease spectrum or for a particular disease stage (e.g., non-alcoholic steatohepatitis). We also discuss the advantages and disadvantages of each model, along with the challenges facing the researchers who aim to develop and use animal models for translational research in NAFLD. Based on these characteristics and the specific study aims/needs, researchers should select the most appropriate model with caution when translating results from animal to human