Immunoinformatic Analysis of Leishmania Major gp46 Protein and Potential Targets for Vaccination against Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is a parasitic disease with a significant burden in the Old World countries. OBJECTIVE: In the current study, some of the primary biochemical properties and IFN-γ inducing epitopes with specific binding capacity to human and mouse MHC alleles were predicted for Leishmania major gp46 antigenic protein. METHODS: Several online servers were used to predict physico-chemical traits, allergenicity, antigenicity, transmembrane domain and signal peptide, subcellular localization, post-translational modifications (PTMs), secondary and tertiary structures, tertiary model refining with validations. Also, IEDB web server was used to predict mouse/human cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes. RESULTS: The 33.25 kDa protein was stable, hydrophilic, antigenic, while non-allergenic, with enhanced thermotolerance and 45 PTM sites. The secondary structure encompassed a random coil, followed by extended strands and helices. Ramachandran-based analysis of the refined model showed 73.1%, 21.6%, 3.4% and 1.9% of residues in the most favored, additional allowed, generously-allowed and disallowed regions, respectively. Epitope screening demonstrated 4 HTL epitopes against seemingly protective HLA alleles, 5 HTL epitopes against the HLA reference set, 3 human CTL epitopes and a number of mouse MHC-restricted epitopes. CONCLUSION: This paper provides insights into the bioinformatics characteristics of the L. major gp46 protein as a promising vaccine candidate.

Epidemiology of gastroesophageal reflux disease in Iran: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD), which leads to acid reflux into the esophagus, is a common gastrointestinal disorder. Several studies have shown the prevalence of GERD in Iranian population, but their evidence is contradictory. Therefore, the present study was conducted to investigate the epidemiology of GERD in Iran. METHODS: The entire steps of this systematic review and meta-analysis were based on the MOOSE protocol, and the results were reported accordance with the PRISMA guideline. This review is registered on PROSPERO (registration number: CRD42020142861). To find potentially relevant published articles, comprehensive search was done on international online databases Scopus, Science Direct, EMBASE, PubMed/Medline, CINAHL, EBSCO, Cochrane Library, Web of Science, Iranian online databases and the Google Scholar search engine in June 2019. Cochran test and I2 index were used to assess the heterogeneity of the studies. Data were analyzed using Comprehensive Meta-Analysis software ver. 2. The significance level of the test was considered to be P <  0.05. RESULTS: The daily, weekly, monthly, and overall prevalence of GERD symptoms in Iranian population was 5.64% (95%CI [confidence interval]: 3.77-8.35%; N = 66,398), 12.50% (95%CI: 9.63-16.08%; N = 110,388), 18.62% (95%CI: 12.90-26.12%; N = 70,749) and 43.07% (95%CI: 35.00-51.53%; N = 73,189), respectively. The daily, weekly, monthly, and overall prevalence of heartburn in Iranian population was 2.46% (95%CI: 0.93-6.39%; N = 18,774), 9.52% (95%CI: 6.16-14.41%; N = 54,125), 8.19% (95%CI: 2.42-24.30%; N = 19,363) and 23.20% (95%CI: 13.56-36.79%; N = 26,543), respectively. The daily, weekly, monthly, and overall prevalence of regurgitation in Iranian population was 4.00% (95%CI: 1.88-8.32%; N = 18,774), 9.79% (95%CI: 5.99-15.60%; N = 41,140), 13.76% (95%CI: 6.18-44.31%; N = 19,363) and 36.53% (95%CI: 19.30-58.08%; N = 21,174), respectively. The sensitivity analysis for prevalence of all types GERD, heartburn and regurgitation symptoms by removing a study showed that the overall estimate is still robust. CONCLUSION: The present meta-analysis provides comprehensive and useful information on the epidemiology of GERD in Iran for policy-makers and health care providers. This study showed a high prevalence of GERD in Iran. Therefore, effective measures on GERD-related factors such as lifestyle can be among the health policies of Iran.

Effect of Yoga on Lipid Profile and C-reactive Protein in Women.

BACKGROUND: Few scientific studies have been conducted about the effect of yoga on biochemical variables such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and C-reactive protein (CRP) to lay a scientific foundation regarding benefits of yoga, but its effect is not clearly detected yet. This study was conducted to assess the effect of yoga on lipid profile and CRP in women. METHODS: This research was designed as an interventional study. After reviewing inclusion and exclusion criteria, selected biochemical variables such as TC, HDL-C, LDL-C, TG, and CRP were measured for each participant. Yoga instruction was done three times a week for 26 weeks by an experienced yoga instructor. After 26 weeks of yoga intervention, the above-mentioned dependent variables were assessed. SPSS Ver. 16 was used for data analysis. RESULTS: After a 26-week follow-up for participants, only 24 women had the necessary criteria to be included in the study. The mean TG was 157.33 ± 68.416 mg/dL and 134.33 ± 58.80 mg/dL before and after the intervention (P = 0.108), respectively. The mean TC was 234.83 ± 48.47 mg/dL and 183.33 ± 55.09 mg/dL before and after the intervention (P = 0.014), respectively. The mean HDL-C was 31.58 ± 14.22 mg/dL and 38.25 ± 13.5 mg/dL before and after the intervention (P = 0.118), respectively. The mean LDL-C was 171.75 ± 42.69 mg/dL and 142.91 ± 36.4 mg/dL before and after the intervention (P = 0.030), respectively. The mean CRP was 0.57 ± 0.22 mg/L and 0.71 ± 0.77 mg/L before and after the intervention (P = 0.779), respectively. CONCLUSIONS: The result showed that yoga reduced TC and LDL-C significantly, but had no significant effect on TG, HDL-C, and CRP.

Total Calcium (Dietary and Supplementary) Intake and Prostate Cancer: a Systematic Review and Meta-Analysis

Background: Controversial results have been reported concerning the influence of calcium intake on prostate cancer risk. The aim of this study was to determine any association between total calcium (in the diet and in supplements) intake and prostate cancer. Materials and Methods: The present systematic review and meta-analysis study was carried out following a PRISMA guidelines. Two reviewers independently using MeSH keywords searched international databases including PubMed, Science Direct, Cochrane, EMBASE, Web of Science, CINAHL, EBSCO and search engines such as Google Scholar. The searches were performed without any time limit until May 2016. The results were pooled using a random effects model and homogeneity was confirmed using the Q test and I2 index. Subgroup analyses was performed according to continents and study designs. The data were analyzed using STATA software version 3.2, with p<0.05 considered significant. Result: Overall, 12 studies with a total sample size of 905,046 were entered into the final meta-analysis. The main age range of the participants was 50 to 70 years. The relative risks (RR) for total calcium with total prostate cancer, localized prostate cancer, and advance prostate cancer were estimated to be 1.15 (95% CI: 1.04-3.46), 1.05 (95% CI: 0.96-1.14), and 1.15 (95% CI: 0.89-1.50), respectively. Only the relationship between total calcium and total prostate cancer was significant (P<0.05). Conclusions: High calcium intake can be considered as a risk factor for total prostate cancer. Therefore, calcium intake might be a target for prevention.

Cúrcuma em combinação com os regimes de terapia tríplice melhora o estresse oxidativo e as alterações histopatológicas em gastrite crônica associada à infecçäo por Helicobacter pylori / Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis-associated helicobacter pylori infection

ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

RESUMO CONTEXTO A infecção gástrica pelo Helicobacter pylori (H. pylori) é principal causa de alterações inflamatórias e de câncer gástrico. OBJETIVO O objetivo deste estudo foi encontrar os efeitos da cúrcuma no estresse oxidativo e as alterações histológicas na gastrite crônica associada ao H. pylori. MÉTODOS Em um estudo randomizado clínico experimental, pacientes foram divididos em dois grupos: um grupo de terapia tríplice padrão e outro com terapia tríplice com e cúrcuma. Exames endoscópicos e histológicos foram analisados para todos os pacientes antes e depois de 8 semanas de tratamento. RESULTADOS A terapia tríplice com grupo de tratamento de cúrcuma diminuiu significativamente os marcadores de malondialdeído, de peróxidos de glutationa, com aumento da capacidade antioxidante total da mucosa gástrica ao final do estudo em comparação com grupos de regime basal e tríplice. Além disso, o dano oxidativo ao DNA diminuiu significativamente em terapia tríplice com grupo de cúrcuma no final do estudo em comparação com a linha de base e comparado à terapia tríplice (P<0,05 para ambos). No grupo de terapia tríplice em combinação com cúrcuma houve diminuição significativa de todas os escores ativos de inflamação crônica e endoscópica dos pacientes em relação ao grupo de terapia de base e tríplice (P<0,05 para ambos). A taxa de erradicação por terapia tríplice + cúrcuma aumentou significativamente em relação à terapia tríplice isolada (P<0,05). CONCLUSÃO A cúrcuma pode ser um complemento útil para melhorar a inflamação crônica e prevenção de alterações cancerígenas em pacientes com gastrite crônica associada ao H.pylori.

CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI INFECTION.

BACKGROUND: Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE: The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS: In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS: Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION: Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

Effects of Nigella sativa Extract on Markers of Cerebral Angiogenesis after Global Ischemia of Brain in Rats.

BACKGROUND: Reduction of permanent or transient cerebral blood flow may lead to some structural and functional changes of the brain, causing high mortality and morbidity. The aim of this experimental study was to investigate the effects of hydroalcoholic extract of Nigella sativa (NS) on markers of cerebral angiogenesis in rats induced by global brain ischemia. METHODS: Thirty-two male Wistar rats (250 ± 20 g) were randomly divided into 4 groups: group 1, control group receiving only normal saline; group 2, sham group undergoing surgery and stroke induction without treatment; and groups 3 and 4 treated with 10 and 20 mg/kg NS, respectively, after induction of stroke. Global ischemia was induced by ligation of the right carotid artery for 20 minutes. RESULTS: According to the results of this study, brain edema and infarct volume were significantly decreased in the group treated with 20 mg/kg NS compared with the group treated with 10 mg/kg NS (P < .05). Global ischemia caused a significant reduction in gene expression of vasoactive endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) in the sham group compared with the control group (P < .05), but NS groups, in led to a significant increase in gene expression of VEGF and HIF compared with the sham group (P < .05). In addition, the activity level of matrix metallopeptidase-9 was decreased among NS groups compared with the control group (P < .05). CONCLUSIONS: Application of NS extract among rats with brain ischemia is associated with increase of VEGF and HIF as angiogenic markers and inhibition of matrix metallopeptidase-9 activities.

The evaluation of hepatoma-derived growth factor in determining of prognosis and estimating of invasive probability of tumoral cells, recurrent, and metastasis of lymphatic glands in breast carcinoma.

INTRODUCTION: Recently, hepatoma-derived growth factor (HDGF) has been considered as a significantly important factor in determining the prognosis and estimating the probability of tumor cell invasions, recurrence, and lymph node metastasis in different cancers, including breast malignancies. MATERIALS AND METHODS: Immunohistochemistry (IHC) study for HDGF was performed on paraffin-embedded blocks of patients with breast carcinoma in Modarres hospital, Tehran, Iran, since 1387-1390 (74 cases); three separate pathologists read the slides after complete IHC staining. Thereafter, necessary information was recorded from patient files, and eventually, findings were analyzed by SPSS program. RESULTS: Expression of nuclear HDGF has significant statistical correlation with tumor grade according to Nottingham grading scheme; this correlation is also seen with nuclear pleomorphism of tumor cells and mitotic count. No correlation between age and tumor size with expression of HDGF is found. Lymph node metastasis is in inverse ratio to nuclear HDGF staining. CONCLUSION: Nuclear expression of HDGF in tumor cells is increased concordantly to tumor grade, which implies us to the role of this marker in determining the prognosis and choosing the most suitable treatment plan.

Correlation of Homocysteine with Cerebral Hemodynamic Abnormality, Endothelial Dysfunction Markers, and Cognition Impairment in Patients with Traumatic Brain Injury.

OBJECTIVE: This study aimed to assess any correlation between serum levels of homocysteine (Hcy) and markers of cerebral hemodynamics, endothelial dysfunction, and cognition impairment in patients with traumatic brain injury (TBI). METHODS: By a cross-sectional study, all clinical data and serum levels of homocysteine of 85 TBI patients were collected. The pulsatility indices (PIs) of the middle cerebral artery were recorded by transcranial color-coded Doppler ultrasonography and cerebrovascular reactivity was measured by the increase in middle cerebral artery flow velocity in response to 5% inhaled CO2. Serum levels of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), cognition status by Montreal Cognitive Assessment, and Mini-Mental State Examination were measured in all participants. RESULTS: Totally, 85 patients including 51.76% male and the mean age of 54.48 years were studied. The level of Hcy in patients who died in the hospital or during 6 months after TBI was significantly higher than in survivors (P = 0.045, P = 0.020, respectively). Also, the levels of ICAM-1, VCAM-1, and PI in deceased patients were higher than their figures in survivors in both hospital and 6-month follow-ups (P = 0.450, P = 0.000; P = 0.072, P = 0.000, P = 0.090, and P = 0.000, respectively). Cerebrovascular reactivity in deceased patients was significantly lower than that in alive individuals (P = 0.008 and P = 0.000, respectively). A significant correlation was found between Hcy with cognition impairment according to Montreal Cognitive Assessment, Mini-Mental State Examination, and cerebral hemodynamic status according to PI (P = 0.000 for all). Also, this correlation was shown between Hcy with ICAM-1 and VCAM-1 in hospital and 6-month follow-ups (P = 0.000 for both). CONCLUSION: Hcy has a significant correlation with markers of cerebrovascular, endothelial, and cognition abnormality in TBI patients.

Detraining-induced alterations in adipokines and cardiometabolic risk factors after nonlinear periodized resistance and aerobic interval training in obese men.

This study compared the effects of nonlinear resistance training (NRT), aerobic interval training (AIT), and detraining on adipokines and cardiometabolic risk factors in middle-aged obese men. Thirty-three obese men were randomly allocated to NRT (n = 12), AIT (n = 10), and control (CON, n = 11) groups. Subjects in experimental groups performed exercise protocols 3 days per week for 12 weeks followed by a 4-week detraining period. The NRT involved 55 min of weight training with flexible periodization. The AIT consisted of running on a treadmill (4 × 4-min intervals at 90% of maximal heart rate, with each interval separated by 3 min at 65%). Peak oxygen consumption increased significantly after training compared with CON (P < 0.01), but it increased more in the AIT group than in the NRT group (P = 0.004). After detraining, peak oxygen consumption decreased significantly in both training groups (P < 0.001); however, the value in the AIT group was still higher than that in the CON group (P = 0.003). No significant changes were observed in serum levels of omentin-1 and interleukin (IL)-18 after training (P > 0.05), but omentin-1 decreased significantly in both training groups and IL-18 increased significantly in the NRT group after detraining (P < 0.05). High-density lipoprotein cholesterol (HDL-C) increased significantly after training in the AIT group compared with the CON group (P < 0.05) and returned to the pre-training level after detraining. Conversely, apelin-13 increased significantly in response to training, compared with baseline (P < 0.05), and remained unchanged after detraining. Both training regimens had similar effects on most markers; however, AIT seems to have stronger anti-coronary disease effects (as indicated by HDL-C and peak oxygen consumption) than NRT.

Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

BACKGROUND: Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. METHODS: Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. RESULTS: Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p < 0.01) was significant. A significant relationship between dysplasia and hs-CRP (p < 0.04) was revealed. A significant relationship between age and hs-CRP was detected (p < 0.05). CONCLUSION: Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.

Precancerous histopathologic lesions of upper gastrointestinal tract among dyspeptic patients upon endoscopic evaluations.

PURPOSE: Gastric cancer is one of the most important causes of morbidity and mortality worldwide which is influenced by different risk factors. This study aimed to investigate the effects of various factors associated with precancerous lesions among dyspeptic patients. METHODS: Among dyspeptic patients admitted to gastrointestinal clinics in Ilam city, west of Iran, 1123 were investigated during 2008 to 2011. All patients were evaluated by endoscopy and their biopsy samples were examined for histological differentiations and their pathology reports were classified according to Sydney criteria. RESULTS: One thousand out of 1123 admitted dyspeptic patients were finally analyzed. The mean age of participants was 48 years (ranged 21-84 years), and 64.8% of patients were male. The frequency of patients with atrophy, metaplasia, or both was 14.4%, adenocarcinoma 1.2%, and polyp hyperplasia 0.7%, respectively. The highest frequency was related to those with chronic gastritis accompanied by Helicobacter pylori infection with a figure of 80.8%. The frequency of precancerous lesions among smokers compared to non-smokers was higher significantly (p < 0.03). Though non-significant, BMI was associated with the higher risk of premalignant lesions among dyspeptic patients by an increasing manner. CONCLUSION: Chronic gastritis accompanied with H. pylori infection was revealed as the most prevalent variable among dyspeptic patients. Also, higher BMI compared to normal and smokers compared to non-smokers were more involved by precancerous lesions.

Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring.

Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats' offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats. By a dose-dependent manner, the body weight (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and their heart rate and blood pressure were conversely increased compared to the control group. Also, the wall thickness, cross-sectional area of the aorta and septal branch of the descending left coronary artery were significantly increased in the intervention group. In addition, PA significantly increased the level of malondialdehyde and decreased the level of superoxide dismutase and glutathione peroxidase, compared to the control group. This study revealed that prenatal exposure of rats to PA causes vascular dysfunction, increasing oxidative stress, and reduction in cardiac nitric oxide synthetase activity among offspring rats.

Coenzyme Q10 in combination with triple therapy regimens ameliorates oxidative stress and lipid peroxidation in chronic gastritis associated with H. pylori infection.

Chronic gastritis associated with H. pylori infection causes oxidative stress in the stomach. This study aimed to evaluate the therapeutic effects of coenzyme q10 among gastric patients infected by H. pylori. By a clinical trial, chronic gastric patients infected by H. pylori were randomly divided into 2 groups: intervention and placebo. The placebo group received a standard triple therapy regimen, and the intervention group received the triple regimen + coenzyme Q10 (CoQ10). Mean inflammation score; serum levels of 3 serum markers were then compared. A total of 100 participants of whom 67% were female were evaluated. The mean age of participants was 59.4 ± 11.4 years. The mean inflammation score was considerably decreased at the end of the study, in the intervention group. The mean levels of total antioxidant capacity (TAC) and glutathione peroxidase (GPx) at the end of the study were reduced among the triple therapy group (P < .05, P =.03 respectively). The mean levels of TAC and GPx were significantly higher among the intervention group at the end of the study compared with those at the start of the study. The combination of triple therapy with CoQ10 demonstrated an effective outcome on the mucosal inflammation, and stress oxidative in patients with chronic gastritis.