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Aim: Coronary artery calcification (CAC) is a predictor of atherosclerosis. However, the association of osteoprotegerin (OPG) with CAC is still controversial. Methods: Prospective cohort studies that provided odds ratios with 95% CIs were included from PubMed, Embase, Web of Science and Scopus through July 2022. Results: Out of 14 studies included in the systematic review, three studies with 7642 participants were included in the meta-analysis. The pooled odds ratio indicated a significant association between higher OPG levels and accelerated risk of CAC (1.15; 95% CI: 1.03–1.30; p 2 = 0%; p = 0.43). Conclusion: The results indicated that increased concentrations of OPG are positively associated with a 15% elevated odds of CAC after adjustment of major covariates.

Visceral adipose tissue (VAT) has an important role in the incidence of cardiovascular disease (CVD) than obesity by itself. The visceral adiposity index (VAI) and lipid accumulation product (LAP) are surrogate indices for measuring VAT. The aimed of this study was to investigate the association of these markers with cardiovascular events among populations with different BMI category in Mashhad, northeast of Iran.The present study comprised a prospective cohort of 9685 men and women (35-65 years) who were recruited from MASHAD study. BMI category was defined as normal weight (BMI25), over weight (25 ≤ BMI30) and obese (BMI≥30). Demographic, laboratory evaluations, anthropometric and metabolic parameters were performed. Logistic and Cox regression analyses were used to determine the association and risk of cardiovascular events with VAT and LAP.The mean VAI and LAP in CVD patients were significantly higher than in healthy ones in all 3 groups. In terms of CVD event prediction, VAI and LAP had significant association with the incidence of CVD in the second (RR (95% CI): 2.132 (1.047-4.342) and 2.701 (1.397-5.222), respectively) and third tertiles (RR (95% CI): 2.541 (1.163-5.556) and 2.720 (1.159-6.386), respectively) in the normal group, but this association was only found in the third tertiles (RR (95% CI): 2.448 (1.205-4.971) and 2.376 (1.086-5.199), respectively) in the overweight group. The result couldn't find this association for the obese group.In this study, we found that there was a significant association between LAP and VAI and cardiovascular events in normal weight and over-weight groups; however, no significant relationship was found in the obese group.

Loads of new therapeutic regimes have been turned up to manage Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly in elderly patients who are unfit for intensive chemotherapy. Despite accumulating research, the best MDS and AML management approach is indeterminate. Myelodysplastic syndrome implies a group of various hematopoietic stem cell disorders that may progress to acute myeloid leukemia. These disorders are more frequent in older adults. To the high rate of morbidity and abundant toxicities related to the therapeutic approaches, also, the treatment would be challenging. The clinical effectiveness of valproic acid, a histone deacetylase inhibitor, in MDS and AML patients is unknown, even though it has demonstrated positive activities to promote differentiation and apoptosis in cancer cells. We investigated the clinical research on the effects of valproic acid in conjunction with various drugs, including low-dose cytarabine, all-trans retinoic acid, DNA-hypomethylating agents, hydrazine, and theophylline. We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine. However, more randomized clinical studies are required to identify an ideal regimen.

Background Non-high-density lipoprotein-cholesterol (non-HDL-C) has been identified as a potential biomarker for metabolic syndrome (MetS). However, its predictive capability for MetS varies among different ethnic groups, indicating the need for further clarification. This study aimed to investigate the potential role of non-HDL-C in the early diagnosis of MetS in the Iranian population using a longitudinal study with a 10-year follow-up period.Methods Our study included 4684 individuals from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorder) cohort, followed for 10 years to investigate the association between non-HDL-C and the incidence of MetS. We also assessed the contribution of individual components of MetS to the overall burden.Results Out of 7561 individuals, who completed 10-years follow-up, 3085 subjects developed MetS. Non-HDL-C levels ≥ 130 had a 28% higher risk of developing MetS (relative risk (RR),1.27; 95% confidence interval (CI), 1.14–1.41). Elevated waist circumference (WC) had the strongest association with MetS incidence (RR,1.51; 95% CI, 1.45–1.58), whereas triglyceride (TG) levels ≥ 150 mg/dl demonstrated the weakest association (RR,1.07; 95% CI, 1.01–1.15). Fasting blood glucose (FBG) levels ≥ 100 mg/dl were not significantly linked to MetS burden. Conversely, higher HDL-C levels show protective effect against the risk of MetS (RR, 0.87; 95% CI: 0.76-1.00), while blood pressure (BP) levels ≥ 130 mmHg or diastolic BP levels ≥ 85 mmHg increased the risk of MetS incidence (RR, 1.081; 95% CI: 1.037–1.127).Conclusions Elevated non-HDL-C and increased WC are significant predictors of MetS in our population. To reduce the risk of MetS development, strategies targeting non-HDL-C levels and weight loss should be emphasized.

Background\ud Cervical cancer is one of the most prevalent cancers among women and is associated with high morbidity and mortality. Several factors are involved in the pathogenesis of cervical cancer including viral infections and/or genetic modifications that include single nucleotide polymorphisms (SNPs). \ud \ud Methods\ud We aimed to investigate the association of genetic variants in ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs1128503) and Fc Gamma Receptor IIIa (FCGR3A) (rs396991) genes and susceptibility to cervical cancer in 263 individuals with or without this form of cancer. DNA samples were isolated and genotyped using a TaqMan based real-time (RT-) PCR method. \ud \ud Results\ud The rs1128503 was found to be associated with an increased risk of cervical cancer (recessive model: OR=2.6, CI: 1.1-5.8, p=0.02). whilst there was no association between the rs396991 and susceptibility to cervical cancer.\ud \ud Conclusion\ud Our results showed that there is an association between the ABCB1 polymorphism and susceptibility for cervical cancer suggesting its potential as a risk stratification marker for cervical neoplasia.

A randomized clinical trial high-density lipoprotein (HDL) cholesterol uptake capacity (CUC) is reduced in patients with metabolic syndrome (MetS). We have assessed the effect of crocin supplementation on HDL CUC in patients with MetS. Forty-four subjects with MetS were randomly allocated to one of two groups: one group received placebo and the other group received crocin at a dose of 30 mg (two tablets of 15 mg per day) for 8 weeks. Serum biochemical parameters were measured using an AutoAnalyzer BT3000 (BioTechnica). The modified CUC method is a cell free, simple, and high-throughput assay that used to evaluate HDL CUC of serum samples. The decision tree analysis was undertaken using JMP Pro (SAS) version 13. The mean age of the crocin and placebo groups were 38.97 ± 13.33 and 43.46 ± 12.77 years, respectively. There was a significant increase in serum HDL CUC in the crocin group compared to that of the placebo group in patients with MetS (p-value< 0.05). The decision tree analysis showed that serum HDL functionality was more important variable than HDL-C level in predicting patients with hypertension at baseline (p-value < 0.05). Crocin administration (30 mg for a period of 8 weeks) was found to improve serum HDL CUC in patients with MetS. Trial registration: IRCT2013080514279N1.

Background Angiopoietin-like 3 (ANGPTL3)-deficiency due to loss-of-function variants are being reported to have a link with triglyceride (TG) level, and high-density lipoprotein cholesterol (HDL-C), and thereby affecting the risk of cardiovascular disease (CVD). Objective In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the group of Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. Method 1002 cases with/without CVD following 10 years follow-up were recruited from the MASHAD cohort, followed by DNA extraction and genotyping. The association of the variant with CVD even and lipid profile was assessed using Univariate and Multivariate analysis. Result our data showed that CVD patients after 10 years follow up with AC/CC genotypes have been related to higher risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01–2.02, P = 0.041) as well as its C allele with CVD risk (OR = 1.32, 95%CI = 1.06–1.72, P value = 0.038). Moreover, we realized that significant association between the variant and serum TG and HDL-C. Conclusion We demonstrated the potential value of g.14079A > C in ANGPTL3 in CVD, indicating further investigations of the emerging biomarker in a multi-center setting as a risk stratification biomarker in cardiovascular disease.

Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity.Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments.Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias.Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.

Introduction: Coronary heart disease (CHD) is the leading cause of morbidity and mortality globally, and specially in Iran. An accurate assessment of the incidence of coronary heart disease (CHD) is very important for public health. In current study we aimed to investigate the incidence of CHD and importance of several classical modifiable and un-modifiable risk factors for CHD among an urban population in eastern Iran after 6 years follow-up. Methods: The population of MASHAD cohort study were followed up for 6 years, every 3 years initially by phone and those who reported symptoms of cardiovascular disease (CVD) were asked to attend for a cardiac examination. An estimate of the incidence of CHD was determined with 95% confidence interval (95% CI) and multiple logistic regression analysis was performed to assess the association of several baseline characteristics with the incidence of a CHD event. Evaluation of goodness-of-fit was undertaken using ROC analysis. CHD cases were divided into four different categories: stable angina, unstable angina pectoris, myocardial infarction and sudden cardiac death. Results: In the six years of follow-up of the Mashhad study participants, the incidence density of CHD events in men and women in 1000 person-year with 95% confidence intervals were 19.20 (8.10-30.30) and 11.60 (7.30-15.90), respectively. The areas under ROC curve (AUC), based on multiple logistic regression model of CHD outcome, was determined to be 0.783. Conclusion: Our findings indicated that the incidence rate of coronary heart diseases in MASHAD cohort study increases with age, and our final model was able to predict approximately 78% of CHD events in this Iranian population.

Background: Ulcerative colitis (UC) is one of the chronic diseases which is increasing in prevalence and patients suffer from illness flare-ups. UC standard regimen treatment has various side effects besides the efficacy, so there is an interest in administering complementary medicine to reduce adverse effects and increase the efficacy, as well. The aim of this study was to evaluate the efficacy and anti-inflammatory effect of Thymus kotschyanus as an additive treatment in a randomized double-blind placebo-controlled trial of UC patients. Methods: Thirty UC out-patients with mesalazine regimen treatment that fulfilled the inclusion criteria were participated in a 12-week trial and were randomly chosen for the treatment and control group. Fifteen patients were administered a placebo as a control and 15 patients were administered received Thymus kotschyanus extract by a dose of 0.5 grams in a day in the treatment group. Laboratory tests were performed at baseline and week 12. The primary outcome was reduction in fecal calprotectin as the main intestine inflammatory marker. Likewise, reduction in SCCAI, SIDBQ, and SEO indices were considered as the secondary aims. The primary outcome was a reduction in SCCAI as the main intestine inflammatory marker. Likewise, reduction in fecal calprotectin, SIDBQ, and SEO indices were the secondary aims. Results: Fecal calprotectin Comparing the treatment and placebo groups at week 12 indicated a was decreased in fecal calprotectin by 54.74% in the treatment group, as compared with placebo group at week 12 (p=0.02). and alsoA significant difference reduction was shown in SCCAI was also shown between two study groups (p=0.01). Thymus kotschyanus extract was safe and no severe side effects were reported. Conclusion: Administration of Thymus kotschyanus revealed improvement in UC symptoms by the intestinal anti-inflammation effect of the plant and could be suggested as a potential additive treatment in UC patients. The study protocol has been registered under the identification code: IRCT20200406046965N2.

Background and Aim. Disseminated intravascular coagulation (DIC) is a critical clinical condition that is expressed by systemic activation of the homeostatic system, leading to elevation of thrombin deposition and result in microvascular thrombi. Heparin makes a good effect on hypercoagulability states through inhibition of thrombin. The present study aimed to summarize and discuss the results of randomized clinical trials and cohort studies regarding the effect of heparin and its preparations on DIC mortality and duration of hospitalization. Methods. The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to November 2021. The quality of RCTs was assessed by Cochrane Collaboration’s tool and the risk of bias was assessed for cohort studies through NOS score. Results. Out of 3288 articles, eight studies were eligible to be included in this study. Our review retrieved six RCTs and two retrospective cohort studies consisting of 950 participants diagnosed by DIC. A significant effect of heparin on DIC mortality was identified in four studies. Furthermore, heparin was used as a control group in three studies. Conclusions. We concluded that administration of heparin and its preparations in DIC patients could reduce the mortality rate and duration of hospitalization, especially in the earlier stages of DIC.

Background Scavenger receptor class B type 1 (SR-BI) encoded by SCARB1 gene serves as a multifunctional HDL receptor, facilitating the uptake of cholesteryl esters from HDL to the liver. Recent studies have identified the association between the P376L missense mutation of the SCARB1 gene with increased serum HDL-Cholesterol level. However, the contribution of this variant to the development of cardiovascular disease (CVD) remains unclear. Objective We have investigated the association between the P376L polymorphism with the properties of HDL and CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. Methods Six hundred and fifteen individuals who had a median follow-up period of 7 years were recruited as part of the MASHAD cohort. Anthropometric, biochemical parameters and HDL lipid peroxidation (HDLox) were assessed. Genotyping was performed using TaqMan-real-time-PCR based method. The association of P376L-rs74830766 with cardiovascular-risk-factors and CVD events were evaluated. Results Carriers of the P376L variant were significantly more likely than non-carriers to develop CVD using multivariate analyses adjusted for traditional CVD risk factors defined as: age, sex, BMI, presence of diabetes, or hypertension, positive smoking habit, and total cholesterol (OR: 3.75, 95%CI: 1.76–7.98, p = 0.001). In an adjusted model, there was a two fold increase in cardiovascular endpoints among individuals who were heterozygous for the P376L variant (hazard ratio, 2.08; 95% CI, 1.12-to 3.84, p = 0.02). Although there was no association between the presence of the P376L variant and HDL-C level, serum HDLox, measured as dysfunctional HDL, was 13% higher among carriers of the P376L variant than non-carriers. Conclusion We have found that carriers of the P376L variant possessed higher HDLox and were at increased risk of CVD in a representative population-based cohort, as compared to non-carriers.

Background The efficiency of high‐density lipoprotein (HDL) to efflux cholesterol contributes to the reverse cholesterol transport (RCT) pathway as one of HDL’s proposed functions and depends on the ability of HDL to uptake cholesterol. We aimed to investigate cholesterol uptake capacity (CUC) by a newly developed assay in samples from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorders) cohort study. Method The study population comprised 153 individuals developed CVD diagnosed by a specialist cardiologist, over 6 years of follow‐up, and 350 subjects without CVD. We used a modified CUC method to evaluate the functionality of HDL in serum samples. Result The CUC assay was highly reproducible with values for inter‐ and intra‐assay variation of 13.07 and 6.65, respectively. The mean serum CUC was significantly lower in the CVD group compared to control (p = 0.01). Although, there were no significant differences in serum HDL‐C between the groups and there was no significantly association with risk of progressive CVD. Multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.57, 95% CI = 0.38–0.87, p = 0.009). The CUC was also inversely and independently associated with the risk of CVD event using Cox proportional hazards models analysis (HR = 0.62; 95% CI = 0.41–0.94, p = 0.02). We determined the optimum cutoff value of 1.7 a.u for CUC in the population. Furthermore, the CUC value was important in determining the CVD risk stratification derived from data mining analysis. Conclusions Reduced HDL functionality, as measured by CUC, appears to predict CVD in population sample from north‐eastern Iran., Mashhad‐Stroke and Heart‐Atherosclerotic‐Disorders (MASHAD) cohort; 530 healthy individuals, over 6 years of follow‐up,350 individuals without CVD, 153 individuals with CVD. A modified CUC method was used to evaluate the HDL functionality of serum samples. The mean value of serum CUC was significantly lower in the group developed CVD compared to healthy individuals (p = 0.01). multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.62, 95% CI = 0.41–0.94, p = 0.02). The CUC was also independently inversely associated with the risk of a CVD event using Cox proportional hazards models analysis (HR, 0.62; 95% CI, 0.41–0.94, p = 0.02). The CUC value was important in assigning the CVD risk stratification derived from data mining analysis. Reduced HDL functionality, as measured by CUC, appears to predict CVD in our population sample from north‐eastern Iran. CEC: Cholesterol Efflux Capacity; CUC: Cholesterol Uptake Capacity. ​

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and specifically in Iran. Generally, diabetes mellitus is the result of impaired glucose tolerance which together with dyslipidemia are considered as important risk factors of CVD. The aim of this study was to determine the relationship between fasting serum glucose (FSG), lipid profile and CVD endpoints, and to establish an optimal FSG cut-off in the MASHAD cohort study after nearly 6 years of follow-up. METHODS: All the participants of MASHAD study were followed up for 6 years to determine their cardiovascular status. FSG, fasting lipids, and physical examinations were all recorded. To identify the optimal cut- off point of FSG, we carried out receiver operating curve (ROC) analysis RESULTS: We determined MASHAD cutoff point of blood glucose as 90 mg/dl predicting the CVD outcome. The sensitivity and specificity of the FSG criterion were 54.34% and 71.68%, respectively. The AUC was 0.665 (95% CI 0.656-0.675, P< 0.0001). The adjusted hazard ratio show that FSG is associated with 2.34 increase in CVD risk using MASHAD cutoff point (HR 2.34, 95% 1.73–3.17, P< 0.001). CONCLUSION: These findings suggest that not only FSG and lipid profile are related to CVD outcome in the MASHAD study, but also elevated fasting glucose levels is strongly associated with cardiovascular events in this population. Besides, the fasting glucose at a threshold of 90 mg/dl can be used for screening cardiovascular events among the Iranian population.

Fondazione Italiana per la Ricerca sul Cancro FIRC 18112 Sina Atashpaz.Fondazione Umberto Veronesi Sina Atashpaz Associazione Italiana per la Ricerca sul Cancro AIRC 5xmille METAMECH program Vincenzo Costanzo Giovanni Armenise-Harvard Foundation Vincenzo Costanzo European Research Council Consolidator grant 614541 Vincenzo Costanzo Associazione Italiana per la Ricerca sul Cancro Fellowship 23961 Negar ArghavanifarDanish Cancer Society KBVU-2014 Andres Joaquin Lopez-Contreras Danish Council for Independent Research Sapere Aude, DFF Starting Grant 2014 Andres Joaquin Lopez-Contreras European Research Council ERC-2015-STG-679068 Andres Joaquin Lopez-Contreras Danish National Research Foundation DNRF115 Andres Joaquin Lopez-Contreras The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response to replication stress (RS) in mouse embryonic stem cells (ESCs) that induces genes expressed in totipotent two-cell (2C) stage embryos and 2C-like cells. This response is mediated by Dux, a multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals. In response to RS, DUX triggers the transcription of 2C-like markers such as murine endogenous retrovirus-like elements (MERVL) and Zscan4. This response can also be elicited by ETAA1-mediated ATR activation in the absence of RS. ATR-mediated activation of DUX requires GRSF1-dependent post-transcriptional regulation of Dux mRNA. Strikingly, activation of ATR expands ESCs fate potential by extending their contribution to both embryonic and extra-embryonic tissues. These findings define a novel ATR dependent pathway involved in maintaining genome stability in developing embryos by controlling ESCs fate in response to RS. Sí

Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high-density lipoprotein (HDL)-cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.

Gap junctions (GJs) are intercellular channels consisting of connexin proteins that allow the communication/cross-talk of molecules between neighboring cells. Connexins play an important role in various cellular processes including proliferation, cell signaling, homeostasis, differentiation, invasion, and metastasis. Connexins are involved in the development of several cancers that include breast cancer (BC). There is evidence that genetic variations of the GJs gene that encode connexin 37 (Cx37), are associated with susceptibility to several malignancies. Here we aimed to investigate the relationship between the Cx37 1019 C > T polymorphism, and the risk of BC. One hundred and fifty-seven women were recruited and genotyping was conducted using a Taqman® based assay. The frequency of the minor allele was 0.4. The Cx37 1019 C > T polymorphism was associated with an increased risk of BC (e.g., recessive model (TT + TC vs. CC), OR = 3.37, 95%CI = 1.51–7.49, P = 0.003; co-dominant model (TC vs. TT + CC), OR = 3.10, 95%CI = 1.57–6.13, P = 0.001). Further studies in more diverse populations are required to determine the value of the emerging marker as a risk stratification biomarker for breast cancer.

Solid extraction process, using the supercritical fluid, is a modern science and technology, which has come in vogue regarding its considerable advantages. In the present article, a new and comprehensive model is presented for predicting the performance and separation yield of the supercritical extraction process. The base of process modeling is partial differential mass balances. In the proposed model, the solid particles are considered twofold: (a) particles with intact structure, (b) particles with destructed structure. A distinct mass transfer coefficient has been used for extraction of each part of solid particles to express different extraction regimes and to evaluate the process accurately (internal mass transfer coefficient was used for the intact-structure particles and external mass transfer coefficient was employed for the destructed-structure particles). In order to evaluate and validate the proposed model, the obtained results from simulations were compared with two series of available experimental data for extraction of chamomile extract with supercritical carbon dioxide, which had an excellent agreement. This is indicative of high potentiality of the model in predicting the extraction process, precisely. In the following, the effect of major parameters on supercritical extraction process, like pressure, temperature, supercritical fluid flow rate, and the size of solid particles was evaluated. The model can be used as a superb starting point for scientific and experimental applications.

High-density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three-hundred andthirty individuals who had a median follow-up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41-1.86; p 2.5-fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox > 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88-3.94). HigherHDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population-based cohort.

Cardiovascular disease (CVD) is the leading cause of mortality globally. There are few useful markers available for CVD risk stratification that has proven clinical utility. Scavenger receptor B type I (SR-BI) is a cell surface protein that plays a major role in cholesterol homeostasis through its interaction with high-density lipoprotein-cholesterol (HDL-C) esters (CE). HDL delivers CE to the liver through selective uptake by the SR-BI. SR-BI also regulates the inflammatory response. It has been shown that SR-BI overexpression has beneficial, protective effects in atherogenesis, and there is considerable interest in developing antiatherogenic strategies that involve SR-BI-mediated increases in reverse cholesterol transport through HDL and/or low-density lipoprotein. Further investigations are essential to explore the clinical utility of this approach. Moreover, there is growing evidence showing associations between genetic variants with modulation of SR-BI function that may, thereby, increase CVD risk. The aim of the current review was to provide an overview of the possible molecular mechanisms by which SR-BI may affect CVD risk, and the clinical implications of this, with particular emphasis on preclinical studies on genetic changes of SR-BI and CVD risk.

Confirming the constructive effects of reading comprehension on critical thinking, this paper attempted to investigate the impact of story structures on critical thinking of Iranian EFL learners. In doing so, the researcher utilized a quasi–experimental design with 60 intermediate students who were divided into two embedded story structures and sequential story structures groups (experimental groups). After taking PET, a critical thinking questionnaire was employed as a pre-test. The two groups received 16 sessions of treatment. All participants received similar amount of instruction but one group was given embedded short stories and the other group sequential short stories. To compare the two groups, they were received the parallel critical thinking questionnaire as a post-test. The two null hypotheses in this study were rejected due to different performance of the two groups. Statistical results did not support the superiority of neither structures. Therefore, the researcher was not able to suggest which structure caused a better or higher impact on critical thinking. However, the findings reveal that teaching story structures in EFL context can develop critical thinking of intermediate EFL learners. The study have some implications for test-designers, teachers, and students.

Background: Coronary artery disease (CAD) cannot be sufficiently explained by the presence of traditional risk factors. Cathepsin D has been proposed to serve as a surrogate marker of atherosclerosis but its alterations in CAD patients have not been studied. Objective: To evaluate serum cathepsin D concentrations in relation to the presence and severity of CAD. Materials and methods: A total of 104 subjects were recruited; 71 patients with suspected CAD and 33 healthy subjects. Thirty-four patients had >50% coronary stenosis of at least one artery (CAD+); the remaining 37 patients had

HMGB1 orchestrates leukocyte recruitment and their induction to secrete inflammatory cytokines by switching between mutually exclusive redox states., Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to sulfonates by reactive oxygen species abrogates both activities. We show that leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1 mutant in which serines replace all cysteines (3S-HMGB1) does not promote cytokine production, but is more effective than wild-type HMGB1 in recruiting leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte recruitment but not with activation. We detected the different redox forms of HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states.

Introduction: Today, with the tremendous potential of genomics and other recent advances in science, the role of science to improve reliable DNA extraction methods is more relevant than ever before. The ideal process for genomic DNA extraction demands high quantities of pure, integral and intact genomic DNA (gDNA) from the sample with minimal co-extraction of inhibitors of downstream processes. Here, we report the development of a very rapid, less-hazardous, and high throughput protocol for extracting of high quality DNA from blood samples. Methods: Dried, clotted and ethylene diamine tetra-acetic acid (EDTA) treated fresh and frozen blood samples were extracted using this method in which the quality and integrity of the extracted DNA were corroborated by agarose gel electrophoresis, PCR reaction and DNA digestion using restricted enzyme. The UV spectrophotometric and gel electrophoresis analysis resulted in high A260/A280 ratio (>1.8) with high intactness of DNA. Results: PCR and DNA digestion experiments indicated that the final solutions of extracted DNA contained no inhibitory substances, which confirms that the isolated DNA is of good quality. Conclusion: The high quality and quantity of current method, no enzymatic processing and accordingly its low cost, make it appropriate for DNA extraction not only from human but also from animal blood samples in any molecular biology labs., BioImpacts; ISSN 2228-5660

Introduction: Recent report on existence of a stem region of hemagglutinin has arisen new hopes for vaccination of influenza A as it consist of a conserve fusion peptide shared across several influenza subtypes and can be targeted by human immune system. Methods: Given that traditional vaccination based on live attenuated viruses often fails to surpass such viral infection, a great deal of attention has been devoted to develop a safe yet efficient system for vaccination influenza A. We believe that a natural bioshuttle can be recruited for spontaneous mass vaccination. Results: Thus, here, we hypothesize that a bioengineered transgenic Hirudo medicinalis can be considered as an alive bioshuttle for in-situ vaccination against influenza A virus. By introducing the designated gene(s) encoding the target fragment (i.e., stem region of hemagglutinin), this microsurgeon can act as a rapid microproducer of viral proteins for in-house mass vaccination through imparting the necessary proteins such as those, naturally presented in leech's saliva. Conclusion: This peculiar bioshuttle can be easily exploited as a medical modality choice at home resulting in greater patient compliance., BioImpacts; ISSN 2228-5660

The pathogenicity and genetic characterizations of six Newcastle disease virus (NDV) isolates obtained from chicken farms in six different regions in Iran were carried out using conventional and molecular techniques. Based on the pathogenicity indices (MDT, ICPI, and IVPI), all of these isolates were found to be velogenic (highly virulent) strains. A sequence analysis of the full-length mRNA encoding the fusion glycoprotein precursor (F0) of the NDV's fusion proteins F1 and F2 in these six isolates showed the presence of point mutations in form of nucleic acid substitutions at positions 82((C→T)), 83((T→C)), 736((A→G)), and 1,633((G→A)). However, the nucleic acid residues at positions 330-347 of the precursor F0 gene, corresponding to the cleavage site of the F0 protein, were found to have remained conserved among the six NDV isolates. A phylogenetic comparison between the six Iranian isolates and the NDVs whose F0 gene sequences were previously deposited in GenBank Database showed that all of the newly characterized Iranian NDV isolates belonged to genotype VII.