Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

The impacts of C1q/TNF-related protein-15 and adiponectin on Interleukin-6 and tumor necrosis factor-α in primary macrophages of patients with coronary artery diseases.

Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays a key role in the pathogenesis of atherosclerosis and some previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages. METHODS: THP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15. RESULTS: Adiponectin and CTRP15 have reduced IL-6 and TNF-α secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines' expressions and secretions in primary macrophages of both patient and control groups. However, CTRP15 has only reduced cytokines' expressions and secretions in controls and it was not able to ameliorate inflammation in macrophages of CAD patients. CONCLUSION: The results of the present study indicate anti-inflammatory impact of adiponectin and CTRP15, while this property was stronger for CTRP15. In addition, it seems likely that anti-inflammatory CTRP15's impact on macrophages in the CAD patients was weaker than macrophages from the controls.

Klotho, FOXO1 and cytokines associations in patients with coronary artery disease.

INTRODUCTION: Atherosclerosis is one of the main reasons for adult mortality in advanced populations and countries with high stress levels. Klotho family are single-pass trans-membrane proteins that involve in the genesis and progression of various diseases, including acardiovascular disease, apoptosis and stress oxidative imbalance. Present study, investigates the pattern of changes in Klotho and FOXO1 gene expressions and levels in atherosclerosis. METHODS: Present case control study consisted of 79 patients with atherosclerosis and 78 healthy controls. PBMC (peripheral mono-nuclear blood cells) expression levels of Klotho and FOXO1 were assayed, using qPCR method. Serum concentration of Klotho and FOXO1 were measured by ELISA method. RESULTS: A significant reduction was found in PBMC genes expression levels of Klotho (P < 0.01) of patients as comparison with controls. PBMC Gene expression of FOXO1 in patients was increased significantly (P < 0.01) when compared with controls. Pearson analysis showed a positive correlation between PBMC Klotho gene expression and Klotho levels of patients (P < 0.01). The correlation between serum concentrations of Klotho and FOXO1 of patients was also positive significantly (P < 0.01). AUC of ROC for gene expression and serum concentration of Klotho in patients were 0.701 and 0.737 respectively. CONCLUSION: Investigating the PBMC gene expression and serum concentration of Klotho in patients with atherosclerosis is suggested could be a convenient novel biomarker for predicting, prognosis, monitoring the disease progression and designing a suitable drug for patients with atherosclerosis.

Epigenetic Modification of MicroRNA-219-1 and Its Association with Glioblastoma Multiforme.

MicroRNA-219-1 (miR-219-1) acts as a tumor suppressor in a variety of cancers but, the regulatory epigenetic mechanism involved in its gene expression level has not been studied. Using real-time polymerase chain reaction (real-time PCR) and bisulfite genomic sequencing technology, promoter methylation level of miR-219-1 and gene expression levels of miR-219-5p and miR-219-1-3p were determined respectively, in glioblastoma multiforme (GBM) (n = 31), their adjacent normal tissues (n = 31), and GBM U87 cell line. Following treatment of GBM U87 cells with 5-aza-2'-deoxycitidine (5-aza-dC), miR-219-1 promoter methylation, their target mRNA, and protein levels were determined by genomic bisulfite modification, real-time-PCR, and ELISA techniques, respectively. Our results showed that gene expression levels of miR-219-5p and miR-219-1-3p were significantly lower in GBM patients relative to their adjacent normal tissues (p < 0.01). MiR-219-1 promoter had a high level of methylation in GBM tissues (p < 0.01) and a negative correlation was observed between the miRNAs gene expression and methylation levels in GBM tissues (p < 0.01). Treatment of GBM U87 cells by 5-aza-dC decreased the level of miR-219-1 methylation, amount of target mRNA, and levels of cyclin A2 and mucin 4 (MUC4) proteins, and increased the expression levels of miR-219-5p and miR-219-1-3p (p < 0.01). Using external miR-219-5p and miR-219-1-3p, the expression of cyclin A2 and MUC4 were suppressed and proliferative activity of the U87MG cell line was reduced (p < 0.01). These findings suggested that DNA methylation has a crucial role in the regulation of miR-219-1 gene expression and that hypermethylated miR-219-1 may be involved in GBM pathogenesis.

Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines.

BACKGROUND: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. METHODS: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn's disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. RESULTS: Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. CONCLUSIONS: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.

The effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Our study aimed to determine the effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active RA. In this randomized, double-blind, placebo-controlled trial, 66 women older than 18 years old received 100 mg/day either saffron supplement in the intervention group (n = 33) or matched placebo in the placebo group (n = 33) for a period of 12 weeks. Sixty-one patients (30 in the control and 31 in the saffron group) remained for the final analysis. No adverse effects were reported by the patients. Saffron supplementation significantly decreased the number of tender (-1.38 ± 1.66 vs. 0.10 ± 0.40, p < .001) and swollen (-2.12 ± 2.34 vs. 0.63 ± 2.79, p < .001) joints, pain intensity based on visual analogue scale (-18.36 ± 15.07 vs. -2.33 ± 5.04), p < .001), and disease activity score (DAS28) (-0.75 ± 0.67 vs. 0.26 ± 0.77, p < .001) at the end of intervention between the two groups and in saffron group compared with baseline values. Physician Global Assessment (p = .002) and erythrocyte sedimentation rate were significantly improved after intervention (24.06 ± 12.66 vs. 32.00 ± 14.75, p = 0.028). High-sensitivity C-reactive protein reduced at the end of the intervention in the saffron group compared with baseline values (12.00 ± 7.40 vs. 8.82 ± 7.930, p = .004). Tumor necrosis factor alpha, interferon gamma, and malondialdehyde were decreased, and total antioxidant capacity were increased, but their differences between the two groups were not significant (p > .05). According to the results, saffron supplements could positively and significantly improve clinical outcomes in RA patients.

Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance.

Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis as the main underlying mechanism of CAD is associated with inflammation and adipose tissue dysfunction. C1q/TNF-related protein12 (CTRP12) is a newly discovered adipokine which is a paralog of adiponectin. CTRP12 has anti-inflammatory and insulin sensitizing effects. Circulating levels of this adipokine have been reported to be lower in patients with type 2 diabetes and women with polycystic ovarian syndrome. The present study was undertaken for the first time to evaluate serum levels of CTRP12 in CAD patients and its association with anthropometric and biochemical parameters. Serum levels of CTRP12 were measured using ELISA kit in 188 CAD patients (angiography confirmed) and 70 controls. The serum levels of adiponectin, TNF-α and IL-6 were measured using ELISA kits. Serum levels of CTRP12 were found to be lower in CAD patients (585.48 ±â€¯201.67 pg/mL) than in the controls (814.86 ±â€¯247.85 pg/mL; p < 0.001). CTRP12 also showed an independent association with the risk of CAD (OR [CI] = 0.998 [0.996-0.999]; p = 0.019). Moreover, it showed an inverse correlation with HOMA-IR (r = -0.298; p = 0.012) and TNF-α (r = -0.269; p = 0.023) and a positive correlation with adiponectin (r = 0.344; p = 0.003) in the controls. In CAD patients, CTRP12 was inversely correlated with BMI (r = -0.181, p = 0.013), HOMA-IR (r = -0.199; p = 0.006), TNF-α (r = -0.259; p < 0.001) and IL-6 (r = -320; p < 0.001) and a positive correlation with high density lipoprotein-cholesterol(r = 0.342; p < 0.001) and adiponectin (r = 0.398; p < 0.001). The present study showed for the first time that serum levels of CTRP12 are independently associated with CAD and that CTRP12 is associated with several CAD risk factors. The results suggest a possible link between CTRP12 and pathogenic mechanisms of atherosclerosis, such as inflammation and high density lipoprotein-cholesterol metabolism; however, more study is required in this regard.

The effect of Cornus mas fruit extract consumption on lipid profile, glycemic indices, and leptin in postmenopausal women- A randomized clinical trial.

Menopause, which occurs following a declined ovarian activity and reduced estrogen levels, can lead to long-term changes in lipid and glycemic profiles and increases the risk of cardiovascular disease and osteoporosis. Cornelian cherry (Cornus mas) is rich in phytochemicals and antioxidants, which appears to be useful in reducing the postmenopausal complications. This interventional, double-blinded, randomized clinical trial carried out on 84 menopaused women aged 45-60 years old. They were randomly divided into two groups. The treatment group received three capsules of 300 mg of Cornus mas extract (CME), and control group received three capsules of 300 mg of starch powder per day for 8 weeks. Then, BMI, waist circumference, glycemic indices, lipid profile, serum apoproteinase, apoprotein B100, fibrinogen, and leptin were measured. The dietary intakes were evaluated using 24-hr dietary recall questionnaire. The consumption of CME in comparison with the control group resulted in a significant reduction in weight, body mass index, waist circumference, LDL to HDL ratio, total cholesterol to HDL ratio, and fibrinogen. There was also a significant increase in HDL and ApoA1 levels in the treatment group. Furthermore, there was a significant decrease in BMI, waist circumference, fasting insulin, and insulin resistance index after 8 weeks of using CME. Summing up the results, it can be concluded that CME can have possible effects on decreasing BMI, waist circumference, and improving some aspects of lipid profile and glycemic indices in postmenopausal women.

Lower Expression of miR-10a in Coronary Artery Disease and its Association with Pro/Anti-Inflammatory Cytokines.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. Atherosclerosis, the main underlying cause of CAD, is a progressive inflammatory disease. microRNAs play a substantial role in the inflammatory process and pathogenesis of atherosclerosis. miR-155, a widely studied microRNA, is associated with inflammation but there are conflicting data regarding expression of miR-155 in CAD. miR-10a is also one of the key regulators of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway which have not been evaluated in peripheral blood mononuclear cells (PBMCs) of CAD patients. METHODS: This is a case-control study conducted on 69 angiography confirmed CAD patients and 65 controls. PBMC expressions of miR-155, miR-10a, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were evaluated by real-time PCR in the study population. Also, serum levels of IL-6, TNF-α, interleukin-10 (IL10), and adiponectin were measured by ELISA. RESULTS: No significant differences in miR-155 expression was found between CAD and control group (p = 0.059), while lower expression of miR-10a was observed in CAD individuals compared to controls (p < 0.001). An independent association of miR-10a expression with risk of CAD was also demonstrated. Higher serum levels and PBMC expressions of IL-6 and TNF-α were observed in the CAD group compared to controls (p = 0.002 and p = 0.001). However, serum concentrations of IL-10 and adiponectin were lower in CAD individuals compared to controls (p < 0.001 and p = 0.005, respectively). We found a negative association of miR-10a expression with miR155, TNF-α and IL-6 gene expression as well as serum TNF-α and IL-6 levels. A positive correlation between miR10a and serum IL-10 concentrations was also shown. CONCLUSIONS: Our findings suggested a potential role of miR-10a in the inflammatory process underlying atherosclerosis; however, more studies are needed to support these finding.

miR-342-5p Expression Levels in Coronary Artery Disease Patients and its Association with Inflammatory Cytokines.

BACKGROUND: Atherosclerosis is a progressive inflammatory disease and is the main underlying mechanism of coronary artery disease (CAD). Immune system cells and cytokines play pivotal roles in the development of atherosclerosis. Several studies have shown the role of microRNA in the inflammatory processes of atherosclerosis, and miR-342-5p has been shown to be involved in macrophage activation during atherosclerosis and cytokine secretion. But until now, there has been no data regarding the association of miR-342-5p with CAD and inflammatory cytokines. METHODS: This case control study was conducted on 82 CAD patients and 80 controls. Peripheral blood mononuclear cell (PBMC) miR-342-5p expression and gene expression of IL-6 and TNF-α were evaluated using real timePCR. Also, the serum levels of IL-6 and TNF-α were measured using ELISA kits. RESULTS: The results demonstrated a higher expression of miR-342-5p in CAD patients compared to controls (p < 0.001). Moreover, logistic regression revealed an increased risk of CAD according to the expression of miR342-5p after adjusting for CAD risk factors (OR [CI] = 6.1 [1.0 - 37.2], p = 0.048). Also, serum IL-6 and TNF-α showed higher levels in CAD patients (p = 0.003 and p = 0.004, respectively). Furthermore, there were positive correlations of miR-342-5p with gene expressions and serum levels of IL-6 and TNF-α. CONCLUSIONS: The present study demonstrated higher levels of miR-342-5p in CAD patients and showed positive correlation with inflammatory cytokines. This result is in accordance with a previous study, and suggested a regulatory role for miR-342-5p in atherosclerosis and cytokine secretion, although more studies are required in this direction.

Epigenetic Modification of MicroRNA-205 and its Association with Glioblastoma Multiform.

BACKGROUND: Deregulated expressions of tumor-suppressive microRNAs (miRNAs) by epigenetic aberrations has a critical role in tumorigenesis. The aim of the present study was to investigate the epigenetic aberrations of miR205 and to understand how this modification may contribute to molecular events in glioblastoma multiform (GBM). METHODS: Quantitative RT-PCR and bisulfite genomic sequencing techniques were used to investigate gene expression and methylation levels of miR-205 in GBM tissues (n = 23), their matched adjacent normal tissues (n = 23) and glioblastoma U87MG cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), DNA methylation and gene expression levels of miR-205 gene and protein expressions of its target mRNA were investigated. RESULTS: Our study showed that gene expression level of miR-205 decreased in GBM tissues compared to controls (p < 0.01) and lower expression was significantly correlated with this miRNA promoter hypermethylation (r = -78; p < 0.01). Cell treatment with 5-aza-dC restored the hypermethylated promoter and gene expression of the miR205 and decreased target mRNA and proteins levels (p < 0.01). CONCLUSIONS: In summary, our results offered that miR-205 is an epigenetically silenced tumor suppressive miRNA in GBM, suppresses enhanced target mRNA when induced by DNA demethylating agents.

MicroRNA-149 is epigenetically silenced tumor-suppressive microRNA, involved in cell proliferation and downregulation of AKT1 and cyclin D1 in human glioblastoma multiforme.

Aberrant DNA methylation has been shown to inactivate tumor suppressor genes during carcinogenesis. MicroRNA-149 (miR-149) was recently demonstrated to function as a tumor suppressor gene in glioblastoma multiforme (GBM). However, the potential linkage of miR-149 levels and the underlying epigenetic regulatory mechanism in human GBM has not been studied. We used quantitative real-time polymerase chain reaction to investigate the levels of miR-149 in GBM tissues, their matched adjacent normal tissues, and glioblastoma U87MG cell line. Using bisulfite genomic sequencing technology, DNA methylation status of upstream region of miR-149 was evaluated in study population groups and the U87MG cell line. After treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), the DNA methylation status, gene expression, and target protein levels of miR-149 were investigated. Our studies revealed that methylation and expression levels of miR-149 were significantly increased and decreased, respectively in GBM patients relative to the adjacent normal tissues (P < 0.01). MiR-149 suppressed the expression of AKT1 and cyclin D1 and reduced the proliferative activities of the U87MG cell line. Treatment of U87MG cells with 5-aza-dC reversed the hypermethylation status of miR-149, enhanced the expression of its gene, and decreased target mRNA and proteins levels (P < 0.01). These findings suggest that the methylation mechanism is associated with decreased expression levels of miR-149, which may in turn lead to the increased levels of its oncogenic target proteins.

MiR-153 as a Tumor Suppressor in Glioblastoma Multiforme is Downregulated by DNA Methylation.

BACKGROUND: Aberrant DNA hypermethylation contributes to many cancers by silencing structurally normal tumor suppressive genes. MicroRNA-153 (miR-153) exerts a tumor suppressive function in glioblastoma multiforme (GBM) by silencing oncogenic targets. However, the mechanism underlying miR-153 regulation in glioma cells has not been studied. METHODS: The expression levels of miR-153 were determined by real-time PCR and genomic bisulfite modification technique was used to detect the DNA methylation status in the upstream region of miR-153 in GBM, their matched normal adjacent tissues, and the glioblastoma U87 cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), the DNA methylation, gene expression and target proteins levels of miR-153 were determined. RESULTS: This study confirmed that miR-153 is significantly downregulated and hypermethylated in GBM tissues compared to their matched normal adjacent tissues. Increased methylation level of miR-153 was significantly correlated with reduced miR-153 expression in GBM tissue specimens. Demethylation of cells by 5-aza-dC treatment led to reduction of miR-153 methylation level, re-expression of candidate microRNA, and downregulation of its target proteins levels. CONCLUSIONS: Our data indicated that miR-153 acts as a tumor suppressor in GBM and is down-regulated by DNA methylation, suggesting that miR-153 may serve as a potential diagnostic or therapeutic target of GBM. (Clin. Lab. 2016;62:573-580. DOI: 10.7754/Clin.Lab.2015.150738)

Association Between Genetic Variants of Akt1 and Endometrial Cancer.

Akt isoforms have critical roles in the cause and regulation of cancer cells invasive, migration, and metastatic dissemination. In the present study, the association between Akt1 polymorphisms and endometrial cancer was investigated in patients with endometrial cancer and controls. Thirty premenopaused patients diagnosed with endometrial cancer and 30 premenopaused women with no clinically documented abnormalities of the endometrium undergoing hysterectomy were included in this study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. There was no significant difference between Akt1 gene polymorphisms of patients (SNP1, SNP2 and SNP3) with endometrial cancer and controls (p > 0.05). Difference between alleles frequency of SNP1, SNP2, SNP3 of patients with endometrial cancer and controls was not significant (p > 0.05). SNPs (rs72715985), (rs2494750), and (rs74090038) of Akt1 gene are not associated with endometrial cancer in Iranian subjects.

Evaluation of autophagy related ATG4B gene, protein and miR-655-3p expression levels in endometrial cancer and hyperplasia.

OBJECTIVE: The pathogenesis of endometrial cancer (EC) and hyperplasia is complex and poorly understood. Autophagy has emerged as a crucial aspect of this process. METHODS: This study examines the role of autophagy in the pathogenesis of EC and hyperplasia by investigating the expression of the autophagy-related 4B cysteine peptidase (ATG4B) gene, protein, and miR-665-3p levels in patients compared to a control group. This cross-sectional case control study analyzed 90 endometrial tissues, including 30 tumors, 30 normal controls, and 30 hyperplasia, using quantitative reverse transcription polymerase chain reaction and Western blot to assess ATG4B gene and protein levels. RESULTS: Higher ATG4B gene expression levels were found in the endometrial tissue of EC patients than in hyperplasia patients and controls. Furthermore, protein levels of ATG4B were also higher in EC and hyperplasia patients than in controls. ATG4B gene expression and protein levels were positively correlated in EC patients. However, in EC patients, miR-655-3p showed a significant negative correlation with the ATG4B gene and protein levels. CONCLUSION: ATG4B gene and protein expression is elevated in EC tissue, suggesting their role as a tumor promoter. Evaluating their levels could serve as markers for monitoring EC progression and prognosis.

The effect of purslane supplementation on clinical outcomes, inflammatory and antioxidant markers in patients with rheumatoid arthritis: A parallel double-blinded randomized controlled clinical trial.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder that results in joint dysfunction, inflammation, and increased mortality. HYPOTHESIS/PURPOSE: The aim of this study was to evaluate the efficacy of purslane supplements on clinical outcomes, as well as inflammation and antioxidant markers in patients with RA. STUDY DESIGN: A double-blinded randomized controlled clinical trial. METHODS: In this 12-week trial, 86 participants aged between 20 and 79 were divided into two groups. The intervention group (n = 43) received a 500 mg purslane capsule twice a day, while the control group (n = 43) received a placebo capsule of the same shape and dosage. RESULTS: Seventy-seven patients (37 from the control group and 40 from the purslane group) completed the study. Purslane capsule intake significantly declined visual analog scale (53.38 ± 23.81 vs. 26.25 ± 17.27, p ≤ 0.001), swollen joint count (4.42 ± 3.36 vs. 1.60 ± 1.64, p ≤ 0.001), tender joint count (8.20 ± 5.93 vs. 2.78± 2.15, p ≤ 0.001), High-sensitivity C-reactive protein (p ≤ 0.001), disease activity score (DAS28) (5.17 ± 1.30 vs. 3.48 ± 1.20, p ≤ 0.001) and increased Superoxide dismutase (p = .037), and total antioxidant capacity (p ≤ 0.001) changes. Furthermore, Morning stiffness (p=.002) and Physician Global Assessment (p = .026) significantly decreased in the purslane group compared to the placebo group at the end of the trial. There was a significant decrease in tumor necrosis factor-α (2.885 ± 2.068 vs. 2.330 ± 1.121, p = .046), and erythrocyte sedimentation rate (36.52 ± 20.04 vs. 26.70 ± 22.59, p = .007) levels in the purslane group. CONCLUSION: Therefore, supplementation with purslane could lead to improved clinical outcomes, and inflammatory and antioxidant indicators in RA patients.

Association of the apolipoprotein E variants with susceptibility to pregnancy with preeclampsia.

BACKGROUND: Apolipoprotein E (ApoE) polymorphism plays a significant role in the development of several diseases, but its role in the preeclampsia disease incidence is not clear. Therefore, the purpose of this study was to investigate the susceptibility of some pregnant women to preeclampsia. METHODS: In a comparative cross-sectional study, the ApoE polymorphism genotypes were investigated in 100 patients with preeclampcia and 100 normal pregnant, using the polymerase chain reactions (PCR) analysis. Serum lipids and lipoproteins concentrations were also evaluated using the commercially available kits. RESULTS: The difference in distribution of the epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon3, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes between patient subjects and controls was not significantly (p = 0.266). The data obtained for Apo epsilon4, epsilon2 and epsilon3 alleles in the patient group was not different significantly from those obtained for the control group (p = 0.220). The VLDL and TG levels of the patient group were higher significantly than controls (p < 0.01, p < 0.01 respectively). The data obtained for HDL concentration (52.2 +/- 16.1 g/dL) of the patient group was not different significantly from controls (49.4 +/- 12.5 g/dL). The difference between LDL concentration of patients with preeclampsia and controls was not significant. The cholesterol concentration of control subjects was not different significantly from patient subjects. CONCLUSIONS: The observed profiles of ApoE alleles and genotypes frequencies suggest that Apo E polymorphism does not play a major role in the development of preeclampsia. Nonetheless, the abnormal lipid profiles that we found in patients with preeclampsia may have a genetic explanation and/or contribution.

Mutations of the connexin 37 and 40 gap-junction genes in patients with acute myocardial infarction.

BACKGROUND: There is evidence showing the association between connexin 37 (Cx37) C1019T polymorphism and acute myocardial infarction (AMI). Since there has been no study that takes the polymorphisms of Cx37 and connexin 40 (Cx40) into consideration at the same time, we investigated the association between AMI and the polymorphism gene of two gap junction proteins Cx 37 and Cx40 which are important in the electrical coupling between arterial myocytes. METHODS: 200 patients with acute myocardial infarction (AMI) and 185 healthy controls were included in this study. Cx37 and Cx40 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: We identified that single nucleotide polymorphism (SNP) of Cx37 was significantly associated with AMI disease. Significant differences between cases and controls were observed for Cx37 genotype frequencies (p < 0.001, Chi2 = 16.528). The T allele of Cx37 had more frequency in the AMI group compared to the control group. (53.75% vs. 40%; p < 0.05). Subsequent analysis identified that, in contrast to the previous studies, there is a significant difference in women (p < 0.01) but not in men. We also found that the SNP of Cx40 was not significantly associated with AMI disease (p > 0.05). Our study showed that the -44A allele and -44AA genotype were not significantly different in the AMI and control groups (p > 0.05). CONCLUSIONS: It is suggested that the polymorphism in the Cx37 gene (but not Cx40 gene) potentially plays a significant role in the manifestation of AMI disease in Iranian population.

The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer.

BACKGROUND: The current study was designed to explore the changes of the mRNA levels of the YT521, Forkhead box protein O1 (FOXO1), and Krüppel-like factor 9 (KLF9) proteins in human normal and cancerous endometrial tissue. METHODS: The study was conducted in 30 premenopausal patients diagnosed with endometrial cancer and 20 premenopausal women with no clinically documented abnormalities of the endometrium undergoing hysterectomy. Gene expression levels were assayed using quantitative real-time PCR. RESULTS: The endometrial tissue FOXO1 mRNA level (0.82 +/- 0.27) of patients with endometrial cancer was significantly lower (p < 0.001) than controls (4.51 +/- 2.68). In subjects with endometrial cancer the KLF9 mRNA level (1.12 +/- 0.38) was lower (p < 0.001) when compared to controls (3.11 +/- 1.52). A remarkable (not significant, p = 0.069) increase was found in the YT521 mRNA level of patients' endometrial tissue (11.19 +/- 3.99) in comparison with the control subjects (8.82 +/- 5.01). No significant difference was detected for the FOXO1, KLF9 and YT521 mRNA levels of the endometrial tissue of patients with cancer at different stages. CONCLUSIONS: It is suggested that the alteration of the gene expression profiles of FOXO1, KLF9 and YT521, which occur in human endometrial cancers likely play a crucial role in initiation of cancer.

Prostaglandin E2 alteration in contraceptive consumers: as a risk factor for inflammatory diseases.

PURPOSE: The aim of this study was to evaluate the effect of oral combined contraceptive pills on Prostaglandin E2 levels and lipid profiles. METHODS: The enzyme-linked immune absorbent assay method and spectrophotometric assay were used for the evaluation of PGE2 levels and lipid profiles, respectively, in 50 healthy women with normal menstrual cycles who served as the control group and 50 women taking contraceptive pill. RESULTS: The data obtained for serum Prostaglandin E2, LDL-C, and cholesterol concentrations in contraceptive pill consumers were significantly upper (P = 0.04, 0.002, and 0.05, respectively) than control group. The age of contraceptive pill consumption and the duration of pill intake beyond 36 months had no significant effect on the prostaglandin E2 concentration. CONCLUSION: It is suggested that the increase of Prostaglandin E2 and atherogenic lipid levels may be related to their probable effects in response to various pathological and physiological properties of COCs.