The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

Administration of stem cells against cardiovascular diseases with a focus on molecular mechanisms: Current knowledge and prospects.

Cardiovascular diseases (CVDs) are a serious global concern for public and human health. Despite the emergence of significant therapeutic advances, it is still the leading cause of death and disability worldwide. As a result, extensive efforts are underway to develop practical therapeutic approaches. Stem cell-based therapies could be considered a promising strategy for the treatment of CVDs. The efficacy of stem cell-based therapeutic approaches is demonstrated through recent laboratory and clinical studies due to their inherent regenerative properties, proliferative nature, and their capacity to differentiate into different cells such as cardiomyocytes. These properties could improve cardiovascular functioning leading to heart regeneration. The two most common types of stem cells with the potential to cure heart diseases are induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). Several studies have demonstrated the use, efficacy, and safety of MSC and iPSCs-based therapies for the treatment of CVDs. In this study, we explain the application of stem cells, especially iPSCs and MSCs, in the treatment of CVDs with a focus on cellular and molecular mechanisms and then discuss the advantages, disadvantages, and perspectives of using this technology in the treatment of these diseases.

Association Analysis of GSTP1-rs1695 Polymorphism with the Risk of Oral Cancer: A Literature Review, an Updated Meta- Analysis, and a Structural Assessment.

BACKGROUND: This study aimed to investigate the association of rs1695 polymorphism in glutathione S-transferase P1 (GSTP1) with risk of oral cancer in a meta-analysis which was followed by a bioinformatics approach. MATERIALS AND METHODS: Related articles were collected through a systematic search in PubMed, Google Scholar, and EMBASE databases up to June 2022 and then screened. Finally, seven studies, including 1249 cases of oral cancer and 1861 healthy individuals, were included in our meta-analysis. Seven different genetic models including G vs. A, GG+GA vs. AA, GG vs. GA+AA, GA vs. GG+AA, GG vs. GA, GG vs. AA, and GA vs. AA were used for the calculation of odds ratio and 95% confidence interval in order to assess the association between GSTP1-rs1695 polymorphism and oral cancer risk. Also, the ethnicity-based stratified analyses were performed using the seven mentioned models. Some bioinformatics software was used to investigate the effect of rs1695 polymorphism on the primary, secondary, and three-dimensional structure of GSTP1. RESULTS: Our results showed that rs1695 polymorphism was not associated with the risk of oral cancer in any seven genetic models (G vs. A: OR= 0.9331, 95%CI= 0.6339-1.3737, P= 0.726; GG vs. GA+AA: OR= 0.9112 , 95%CI= 0.6865-1.2093, P= 0.520; GG+GA vs. AA: OR= 0.9006, 95%CI= 0.5522-1.4690, P= 0.675; GA vs. GG+AA: OR= 0.8732, 95%CI= 0.5763-1.3230, P= 0.522; GG vs. AA: OR= 0.9516, 95%CI= 0.5503-1.6456, P= 0.859; GG vs. GA: OR= 1.0645, 95%CI= 0.7891-1.4359, P= 0.683; GA vs. AA: OR= 0.8825, 95%CI= 0.5499-1.4162, P= 0.604). Also, we did not observe any significant associations in ethnicity-based stratified analyses. But bioinformatics studies have shown that this polymorphism can alter the physicochemical properties and secondary structure of the protein. CONCLUSIONS: Based on results, the rs1695 polymorphism could not be considered a risk factor for oral cancer.

Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data.

BACKGROUND: Although cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO). METHODS: We searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist. RESULTS: A total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76-2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91-3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6-0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO. CONCLUSIONS: According to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.

Risk factors prediction, clinical outcomes, and mortality in COVID-19 patients.

Preventing communicable diseases requires understanding the spread, epidemiology, clinical features, progression, and prognosis of the disease. Early identification of risk factors and clinical outcomes might help in identifying critically ill patients, providing appropriate treatment, and preventing mortality. We conducted a prospective study in patients with flu-like symptoms referred to the imaging department of a tertiary hospital in Iran between March 3, 2020, and April 8, 2020. Patients with COVID-19 were followed up after two months to check their health condition. The categorical data between groups were analyzed by Fisher's exact test and continuous data by Wilcoxon rank-sum test. Three hundred and nineteen patients (mean age 45.48 ± 18.50 years, 177 women) were enrolled. Fever, dyspnea, weakness, shivering, C-reactive protein, fatigue, dry cough, anorexia, anosmia, ageusia, dizziness, sweating, and age were the most important symptoms of COVID-19 infection. Traveling in the past 3 months, asthma, taking corticosteroids, liver disease, rheumatological disease, cough with sputum, eczema, conjunctivitis, tobacco use, and chest pain did not show any relationship with COVID-19. To the best of our knowledge, a number of factors associated with mortality due to COVID-19 have been investigated for the first time in this study. Our results might be helpful in early prediction and risk reduction of mortality in patients infected with COVID-19.

Surgical left atrial appendage closure: Success rate and its relationship with cerebrovascular accident.

Background: Several surgical procedures such as excision or exclusion are recommended for the closure of the left atrial appendage (LAA). This study was conducted with the aim to evaluate the success rate of different surgical techniques for LAA closure, their respective complications, and the rate of post-surgical cerebrovascular accident (CVA). Methods: This retrospective study included 150 consecutive patients who underwent LAA closure most commonly after mitral valve surgery within 3 to 6 months after surgery. An expert echocardiographic fellow collected the data on patients' surgical LAA closure methods and history of CVA, types of prosthetic valves, mortality, and bleeding. Results: The failure rate for complete LAA closure was 36.7% (55 patients) in our study. The greatest success rate of complete LAA closure was seen in purse-string method (75.5%), followed by resection method (71.4%), while the lowest success rate (≈ 33.3%) was observed in ligation method. A significant relationship was observed between clots on the surface of metallic valve and postoperative CVA (P = 0.001; likelihood ratio: 32).In multivariate analysis, there was also no statistically significant relationship between partial LAA closure and the incidence of post-surgical CVA (P > 0.050). Conclusion: We observed the highest success rate of complete LAA closure in purse-string method followed by resection method. Interestingly, our results showed that despite the higher rate of residual LAA clot in cases of partial LAA closure, the occurrence of post-surgical CVA was mostly related to the presence of clots on the surface of metallic mitral prostheses rather than the presence of partial LAA closure.

Non diagnosed PAPVC induce large reverse venovenous shunt after modified Fontan surgery: A case report of a rare anomaly and embolization therapy.

Fontan operation is a reliable palliative surgery for patients with single ventricle physiology. Still, the development of complication is common; one of these complications that need to interventional approach is veno-venous collaterals between systemic and pulmonary veins. A 16-yearoldgirl with a history of modified Fontan operation at 9 years ago was referred with progressive cyanosis and dyspnea on exertion. In contrast trans-thoracic echocardiography (TTE), no fenestration was seen in Fontan circulation. Cardiac magnetic resonance revealed partial anomalous pulmonary vein connection (PAPVC) from left upper pulmonary vein to vertical vein and then into the in nominate vein and SVC with the reverse flow from superior vena cava (SVC) to left upper pulmonary vein(LUPV). This anomalous vein became severe engorged and tortuous. Possibly, LUPV and the verticalvein was dilated gradually as a result of increased pressure in the Fontan circuit. Finally, she underwent successful coil embolization in the midpart of the vertical vein. The oxygen saturation increased from80% to 93%.

Large pericardial mesothelial cyst coexisting with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Pericardial mesothelioma cyst occurs rarely, and is often found incidentally. The coexistence between large pericardial mesothelial cyst and hypertrophic obstructive cardiomyopathy (HOCM) can make difficulties in medical management. CASE REPORT: Our case was a 33-year-old man presented with dizziness and pallor while standing since four years before, and recent syncope. On admission, transthoracic echocardiography reveled presence of hypertrophic cardiomyopathy in association with relatively small right ventricular and atrium due to compression effect by a large echo-free space at the right side of heart suggestive of pericardial cyst. Cardiac computed tomography confirmed presence of HOCM and large pericardial cyst. Patient underwent surgical septal myectomy and large mesothelial pericardial cyst excision because of persistent symptoms and compression effect of cyst on the right chambers despite beta-blocker therapy. CONCLUSION: To best of our knowledge, the coexistence of the large pericardial mesothelial cyst and HOCM has not been reported before.

The survivin molecule as a double-edged sword in cellular physiologic and pathologic conditions and its role as a potential biomarker and therapeutic target in cancer.

Survivin is a member of the family of apoptosis inhibitory proteins with increased expression level in most cancerous tissues. Evidence shows that survivin plays regulatory roles in proliferation or survival of normal adult cells, principally vascular endothelial cells, T lymphocytes, primitive hematopoietic cells, and polymorphonuclear neutrophils. Survivin antiapoptotic role is, directly and indirectly, related to caspase proteins and shows its role in cell division through the chromosomal passenger complex. Survivin contains many genetic polymorphisms that the role of some variations has been proven in several cancers. The -31G/C polymorphism is one of the most important survivin mutations which is located in the promoter region on a CDE/CHR motif. This polymorphism can upregulate the survivin messenger RNA. In addition, its allele C can increase the risk of cancers in 1.27-fold than allele G. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment. For this purpose, various strategies have been designed including the prevention of survivin expression through inhibition of mRNA translation using antagonistic molecules, inhibition of survivin gene function through small inhibitory molecules, gene therapy, and immunotherapy. In this study, we describe the structure, played roles in physiological and pathological states and genetic polymorphisms of survivin. Finally, the role of survivin as a potential target in cancer therapy given challenges ahead has been discussed.

Evaluation of SEPP1 and Selenoprotein S Gene Polymorphisms (rs7579 and rs34713741) in Relation to Colorectal Cancer Susceptibility in Subset of Iranian Population: A Case-control Study.

BACKGROUND: Colorectal cancer (CRC) is rated as the second cause of cancer death worldwide. Selenium (Se) has antioxidant activity and antitumor effect, especially in colon cancer. This important role occurs through selenoproteins. Low Se intake or low plasma Se and selenoproteins concentrations are associated with higher risk of CRC. rs7579 polymorphism in 3' untranslated region of the SEPP1 gene can effect on selenocysteine incorporation during protein synthesis and also effect on microRNA -messengerRNA interaction and sequentially change in SEPP1 expression. rs34713741 polymorphism as a promoter variant in selenoprotein S (SELS) gene can effect on SElS expression and finally lead to increased CRC risk. METHODS: A case-control study using 60 CRC patients and 74 noncancerous counterparts were undertaken in order to determine rs7579 and rs34713741 genotypes using real-time polymerase chain reaction high-resolution melting method. RESULTS: We found an association of borderline statistical significance between allele A for rs7579 in SEPP1 and CRC risk (adjusted odds ratio = 1.63; confidential interval = 0.99-2.07; P = 0.05). The frequency of genotypes rs34713741 of the mentioned polymorphisms was not significantly different between case and control groups (P = 0.23 and P = 0.93, respectively). CONCLUSIONS: The results suggest that these polymorphisms probably has not a substantial role in Iranian CRC risk and is not a serious potential factor in risk assessment of mentioned disease among Iranians.

Coronary CT angiography by modifying tube voltage and contrast medium concentration: Evaluation of image quality and radiation dose.

BACKGROUND: Currently, there is an increasing interest in noninvasive imaging of cardiovascular system such as computed tomography coronary angiography (CCTA). The risks of radiation-induced cancer and contrast-induced nephropathy (CIN) have always been regarded as concerns which increased demand for CCTA using reduced radiation dose and iodine intake. We aimed to evaluate the image quality and radiation dose of CCTA by modifying tube voltage and concentration of contrast media. METHODS: The present study includes 105 patients who underwent CCTA for clinical indications. Specific inclusion and exclusion criteria in terms of patient's weight, body mass index, calcium score, and stenting were used. First group of patients scanned by 120 kV and 370 mg I/mL contrast medium, compared with second and third groups for which scanning was performed using 100 kV and 370 mg I/mL and 100 kV and 300 mg I/mL, respectively. Image quality was evaluated both subjectively and objectively. The effective dose and iodine intake were also measured. RESULTS: Using low kV protocols led to radiation dose reduction up to 38% and applying low contrast medium concentration with consequent reduced iodine intake up to 21%. Moreover, there were significant differences in image quality of new scanning protocols. CONCLUSION: Reduction in tube voltage with lowering of contrast medium concentration can reduce radiation dose and iodine intake with acceptable image quality.

A Comparison Between Full-COLD PCR/HRM and PCR Sequencing for Detection of Mutations in Exon 9 of PIK3CA in Breast Cancer Patients.

One of the most common somatic mutations in breast cancer is found in PIK3CA with a prevalence rate of 18-45%. Different variants of this gene are considered as resistance markers for treatment with HER2-targeted medicines. Conventional molecular methods such as Sanger sequencing are not able to detect mutations with low abundance in a mixture of wild-type DNA, especially in the early stages of cancer development. In this study, two methods of co-amplification at lower denaturation temperature PCR (COLD-PCR) and high-resolution melting (HRM) were combined for detection of mutations in exon 9 of PIK3CA; DNA, therefore, was extracted from MCF-7 and BT-474 as mutant and wild-type cell lines respectively. Thereafter, serial dilutions of extracted DNA were used to determine sensitivity of full-COLD PCR/HRM in comparison with conventional PCR sequencing as the gold standard method. Cell line experiments resulted in almost 30 fold increase in sensitivity by use of full-COLD PCR/HRM. In addition, 40 patients with primary breast cancer were investigated with the mentioned methods. As a result of this part of study, four mutations were detected by conventional PCR sequencing including E542K and E545K mutations in three and one samples respectively. Whereas, full-COLD PCR/HRM was able to detect one E542K mutation more than gold standard method which caused the percentage of sensitivity to get improved by 2.5% (10 to 12.5%). Our results clearly demonstrated that full-COLD PCR/HRM could detect lower levels of mutations in wild-type background as a sensitive method with simple and cost-effective procedure; therefore, it can prospectively be used in screening of patients with early-stage breast cancers.

Isolated Congenital Dysgenesia of a Pulmonary Valve Cusp Presenting as a Pulmonary Artery Aneurysm.

Pulmonary artery aneurysm is a rare disorder, with the underlying pathology remaining obscure in many instances. More common causes include pulmonary hypertension, poststenotic dilation, or vasculitis. In this case series, we report 3 patients presenting with isolated pulmonary artery aneurysms in whom multimodality imaging revealed the dysgenesia of a single pulmonary valve cusp as the cause of the huge pulmonary aneurysm.

Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis.

BACKGROUND: The Arg399Gln polymorphism in the X-ray repair cross-complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1-Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta-analysis and an in silico analysis. METHODS: In a case-control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1-Arg399Gln genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, 14 eligible studies were included to which our case-control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein. RESULTS: Our case-control study revealed a significant association between the XRCC1-Arg399Gln polymorphism and PCa risk. The data from overall meta-analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein. CONCLUSIONS: Based on these results, the XRCC1-Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.

Association between (GT)n Repeats in Heme Oxygenase-1 Gene Promoter and 3-Year Survival of Patients with Acute Leukemia: a Controlled, Cross-Sectional Study.

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. The levels of HO-1 expression are related to (GT)n microsatellite polymorphisms in the location of its promoter. This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Methods: Sixty-three patients with acute leukemia and seventy healthy infants were included in this study. We used the medical records of patients to collect information about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n ≥ 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P<0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of "LL" genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy.

Evaluation of Energy Balance on Human Telomerase Reverse Transcriptase (hTERT) Alternative Splicing by Semi-quantitative RT-PCR in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Decreased high-energy phosphate level is involved in endothelial cell injury and dysfunction. Reduced telomerase activity in endothelial cells in parallel with reduced energy levels might be due to altered direction of alternative splicing machine as a complication of depleted energy during the process of atherosclerosis. MATERIALS AND METHODS: Isolated human umbilical vein endothelial cells (HUVECs) were treated for 24 hours by oligomycine (OM) and 2-deoxy glucose (2-DG). After 24 hours, the effect of energy depletion on telomerase splicing pattern was evaluated using RT-PCR. Indeed, in both treated and untargeted cells, nitric oxide (NO) and von Willebrand factor (vWF) were measured. RESULTS: ATP was depleted in treated cells by 43.9% compared with control group. We observed a slight decrease in NO levels (P = 0.09) and vWF (P = 0.395) in the setting of 49.36% ATP depletion. In both groups, no telomerase gene expression was seen. Telomerase and housekeeping gene expression were found in positive control group (colon cancer tissue) and sample tissue. CONCLUSIONS: The absence of telomerase gene expression in HUVECs might be due to the mortality of these cells or the low level of telomerase gene expression in these cells under normal circumstances.

Paternal or maternal history of hypertension is more important in increasing the risk of hypertension inoffspring?

BACKGROUND: Along with tripartiteclose relationship of socioeconomic level, smoking, and prevalence of hypertension, the present study aimed to assess the relationship between socioeconomic status (SES) and hypertension based on habitual smoking in Iranian population. METHODS: The present study analyzed the individuals subsample consisted of 9623 subjects, out of all people resident in Isfahan province in Iran of the wave of the Isfahan Heart Health Project (IHHP) in three cities in Iran: Isfahan, Najafabad and Arak. Systolic and diastolic blood pressures were measured in supine position using an automated blood pressure monitor. Smokers were defined as persons who were smoked prior to the survey and never smokers were defined as a person who had never smoked. RESULTS: Those individuals who experienced cigarette smoking, SES class was significantly lower in hypertensive patients compared with normotensive subject so 7.8% of hypertensive patients and 92.2% of normotensive ones classified in SES class IV (p<0.001). Univariate analysis showed hypertension was related to lower SES class when compared with normotension status in both smoker and nonsmoker groups (p<0.001). In stepwise logistic regression models adjusting sex, age, global dietary index and leisure time physical activity, hypertension could be predicted by lower SES in nonsmoker group, while this predictive role for SES could not be reveal in smoker group. CONCLUSION: The significant SES-smoking association may determinate in the increasing blood pressure even adjusted for other covariates such as demographics as well as dietary behaviors and leisure time physical activity.

Transient expression of recombinant ACKR4 (CCRL1) gene, an atypical chemokine receptor in human embryonic kidney (HEK 293) cells.

ACKR4 also called CCX-CKR, CCRL1 as a member of atypical chemokine receptors, regulates the biological responses by clearance or transporting homeostatic chemokines such as CCL19, CCL21, CCL25, and CXCL13. Since these chemokines are involved in cancer development and metastasis, ACKR4 could have inhibition roles in cancer cell proliferation and invasion. Forming complexes with chemokine receptors by ACKR4 as in the case of hCXCR3 which lead to chemotaxis prevention is the other function of this protein is. However, as an atypical chemokine receptor, ACKR4 is less well-characterized compared to other members. Here, as the first step in understanding the molecular mechanisms of ACKR4 action, transfectants in HEK293T cell, was generated. In this study, ACKR4 coding sequence was cloned and human embryonic kidney 293T cells were used for recombinant production of ACKR4 protein. The liposome-mediated transfection with ACKR4 CDs, were detected in ACKR4 positive cells as early as 48 h post-transfection. The production of ACKR4 protein was confirmed using RT-PCR, dot blot, western blot, and flow cytometry. ACKR4 may represent a novel molecular target in cancer therapy, which might provide a chance for new therapeutic strategy. Therefore, the first step in the understanding of the molecular mechanisms of ACKR4 action is generation ACKR4-HEK293T recombinant cells.

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls.

BACKGROUND: Aberrant immune responses are evident in the pathogenesis of multiple sclerosis (MS) and it has been proposed that the spectrum of cytokines influence disease outcomes. Leptin and lipopolysaccharide (LPS) of Gram-negative bacteria are both potent cellular stimulators for production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to compare the TNF-α production by peripheral blood monocytes from MS patients with healthy controls. METHODS: Peripheral blood samples were stimulated with LPS or leptin. After blocking the Golgi apparatus, intracellular cytokine production was assessed using a monoclonal antibody against human TNF-α by the flow cytometry technique. Moreover, plasma level measurement of cytokines was performed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracellular levels of TNF-α were 16.80 ± 8.21 and 16.52 ± 8.23in MS patients and healthy controls which showed no statistically significant difference between them (p = 0.850). Leptin-stimulated and LPS-stimulated TNF-α production showed no significant difference between MS patients and the control group (p = 0.263 and p = 0.191, respectively). However, after treatment with leptin, a weak significant difference was shown between cases and control group (p = 0.049). There were significant differences between cases and controls regarding serum levels of IL-6 and Toll-like receptor-4 (TLR-4) before and after stimulation with leptin and LPS, separately (p < 0.05). CONCLUSION: Taken together, we cannot definitely conclude that TNF-α does not play an important role in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS pathogenesis.

N-acetylcysteine, Ascorbic Acid, and Methylene Blue for the Treatment of Aluminium Phosphide Poisoning: Still Beneficial?

OBJECTIVES: Intentional and accidental intoxication with aluminium phosphide (ALP) remains a clinical problem, especially in the Middle East region. Considering the high mortality rate besides lack of any recommended first option drug for its treatment, this study was aimed to compare the therapeutic effects of N-acetylcysteine (NAC), vitamin C (Vit C), and methylene blue; both in isolate and also in combination, for the treatment of ALP intoxication in a rat model. MATERIALS AND METHODS: In this experimental animal study, 80 male Wistar rats in eight groups were intoxicated with ALP (12.5 mg/kg) and treated with a single dose of NAC (100 mg/kg) or Vit C (500-1,000 mg/kg) or methylene blue (1 mg/kg/5 min, 0.1%) or two of these agents or all three of them (controls were not treated). Rats were monitored regarding the parameters of drug efficacy as increased survival time and reduced morbidity and mortality rate for 3 consecutive days to ensure toxin neutralization. Macroscopic changes were recorded and biopsy sections were taken from brain, cerebellum, kidney, liver, and heart for microscopic evaluation regarding cellular hypoxia. RESULTS: The mean survival times of rats exposed to ALP and treated with VitC + NAC was 210.55±236.22 minutes. In analysis of survival times, there was a significant difference between Group 5 which received VitC + NAC and the other groups (P < 0.01). Serum magnesium levels after death were higher than normal (P = 0.01). CONCLUSIONS: Despite the higher survival rate of antioxidant-treated rats compared with controls, this difference was not statistically significant.