Comparison of the gene expression profiles of endometrial and trophoblastic cells in women with recurrent miscarriage: A bioinformatics approach.

Background: Recurrent miscarriage (RM) remains unsolved in > 50% of patients and causes physical and psychological problems in women without specific risk factors for miscarriage. For a successful pregnancy, acceptance of the endometrium and invasion of trophoblast cells into the endometrium is necessary. Objective: This study aimed to use computational analysis to identify key genes and related pathways in endometrial and trophoblast cells derived from RM samples. Materials and Methods: In this bioinformatics study, we explored the differential expression of genes in endometrial and trophoblast cells by analyzing the GSE165004 and GSE76862 datasets, respectively with the limma package in R software. Subsequently, overlapped genes between 2 datasets were selected, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. The overlapped genes were integrated to construct a protein-protein interaction network and hub genes selection. Results: We observed 41 overlapped genes between endometrial and trophoblast cells, and future analysis was accomplished in overlapped and nonoverlapped genes. Kyoto Encyclopedia of Genes and Genomes analysis indicated that overlapped genes were significantly enriched in the complement and coagulation cascades, pluripotency of stem cells, and synthesis and degradation of ketone bodies. Gene ontology analysis suggested that the genes were enriched in the cell cycle, apoptosis, and cell division. The top 10 genes included: IRS1, FGF2, MAPK6, MAPK1, MAPK3, MAPK8, MAPK9, PLK1, PRKACA, and PRKCA were identified from the PPI network. Conclusion: This study identified the key genes and potential molecular pathways underlying the development of RM. This could provide novel insights to determine the possible mechanisms and interventional strategies associated with miscarriage.

Bioinformatics analysis of a disease-specific lncRNA-miRNA-mRNA regulatory network in recurrent spontaneous abortion (RSA).

BACKGROUND: This study investigated the molecular mechanisms of long non-coding RNAs (lncRNAs) in RSA using the lncRNA-miRNA-mRNA regulatory network. METHODS: The present study obtained expression datasets of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) from blood samples of individuals with unexplained recurrent spontaneous abortion (RSA) and healthy controls. Differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEmiRs) were identified. A regulatory network comprising lncRNA, miRNA, and mRNA was constructed, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEM. Also, a protein-protein interaction (PPI) network was made and key genes were identified. RESULTS: A total of 57 DELs, 212 DEmiRs, and 301 DEMs regarding RSA were identified. Later analysis revealed a lncRNA-miRNA-mRNA network comprising nine lncRNAs, 14 miRNAs, and 65 mRNAs. Then, the ceRNA network genes were subjected to functional enrichment and pathway analysis, which showed their association with various processes, such as cortisol and thyroid hormone synthesis and secretion, human cytomegalovirus infection, and parathyroid hormone synthesis. In addition, ten hub genes (ITGB3, GNAI2, GNAS, SRC, PLEC, CDC42, RHOA, RAC1, CTNND1, and FN1) were identified based on the PPI network results. CONCLUSION: In summary, the outcomes of our study provided some data regarding the alteration genes involved in RSA pathogenic mechanism via the lncRNA-miRNA-mRNA network and reveal the possibility of identifying new lncRNAs and miRNAs as promising molecular biomarkers.

Objective Bayesian Estimation for the Differential Entropy Measure Under Generalized Half-Normal Distribution.

The evaluation of the information entropy content in the data analysis is an effective role in the assessment of fatigue damage. Due to the connection between the generalized half-normal distribution and fatigue extension, the objective inference for the differential entropy of the generalized half-normal distribution is considered in this paper. The Bayesian estimates and associated credible intervals are discussed based on different non-informative priors including Jeffery, reference, probability matching, and maximal data information priors for the differential entropy measure. The Metropolis-Hastings samplers data sets are used to estimate the posterior densities and then compute the Bayesian estimates. For comparison purposes, the maximum likelihood estimators and asymptotic confidence intervals of the differential entropy are derived. An intensive simulation study is conducted to evaluate the performance of the proposed statistical inference methods. Two real data sets are analyzed by the proposed methodology for illustrative purposes as well. Finally, non-informative priors for the original parameters of generalized half-normal distribution based on the direct and transformation of the entropy measure are also proposed and compared.

The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS. METHODS: This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study. RESULTS: The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p < 0.05). Flaxseed supplementation also led to a significant reduction in insulin concentration, HOMA-IR, TG, hs-CRP, Interleukin 6 (IL- 6), and leptin and an increase in QUICKI, HDL, and adiponectin compared to the control group (p < 0.05). No significant changes were observed in other parameters. CONCLUSIONS: Flaxseed supplementation plus lifestyle modification was more effective compared to lifestyle modification alone in biochemical and anthropometric variables in patients with PCOS. TRIAL REGISTRATION: The trial protocol was approved by the Ethics Board at Ahvaz Jundishapur University of Medical Sciences and was registered at Iranian Registry of Clinical Trials (code: IRCT20120704010181N11).

Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial.

Elevated levels of reactive oxygen species under diabetic condition lead to vascular complications and inflammation. This study aimed to examine the effects of hesperidin supplement on blood pressure and inflammatory markers in type 2 diabetes. In this research, 64 patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on systolic blood pressure (SBP), diastolic blood pressure, serum total antioxidant capacity (TAC), tumor necrosis factor alpha, interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were collected at the baseline and at the end of the study. In the hesperidin group, SBP (122.7 ± 8.5 vs. 119.0 ± 7.4; p = .005), mean arterial blood pressure (94.2 ± 5.5 vs. 91.8 ± 5.5; p = .009), IL-6 (8.3 ± 2.1 vs. 7.4 ± 1.8; p = .001), and hs-CRP (1.9 ± 1.2 vs. 1.1 ± 0.9; p < .000) decreased whereas TAC increased (0.74 ± 0.1 vs. 0.82 ± 0.1; p < .000) in comparison to the baseline values. There was a significant difference in mean percent change of SBP, diastolic blood pressure, mean arterial blood pressure, serum TAC, and inflammatory markers (tumor necrosis factor alpha, IL-6, and hs-CRP) between hesperidin and control groups following intervention in adjusted models (p < .05). These results suggest that hesperidin may have antihypertensive and anti-inflammatory effects in type 2 diabetes.

Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

This study aimed to examine the effects of hesperidin supplement on the glycemic parameters, oxidative DNA damage, and lipid peroxidation in patients with type 2 diabetes. Sixty-four patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on glycemic parameters, total antioxidant capacity (TAC), 8-hydroxydeoxyguanosine (8-OHDG), and malondialdehyde (MDA) were collected at the baseline and at the end of the study. In hesperidin group, TAC increased (0.74 ± 0.16 vs. 0.82 ± 0.18), while serum froctoseamin (5.79 ± 5.86 vs. 5.01 ± 4.95; p = 0.001), 8-OHDG (14.32 ± 6.4 vs. 11.00 ± 7.0; p = 0.000), and MDA (5.78 ± 1.76 vs. 4.60 ± 0.75; p = 0.000) decreased in comparison with the baseline values. There was a significant difference in percent change of TAC (13.35 ± 19.21 vs. 3.13 ± 10.02; p = 0.043), froctoseamin (-10.10 ± 16.84 vs. 4.27 ± 34.646), 8-OHDG (-25.11 ± 28.23 vs. 8.69 ± 35.41; p = 0.000), and MDA (-16.46 ± 18.04 vs. -1.82 ± 22.63; p = 0.007) between hesperidin and control groups following intervention in adjusted models. These results suggest that hesperidin may improve TAC and alleviate serum froctoseamin, 8-OHDG, and MDA levels in type 2 diabetes. Copyright © 2017 John Wiley & Sons, Ltd.

Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue

Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 µm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression.

Association of Mood Disorders with Serum Zinc Concentrations in Adolescent Female Students.

Among various factors influencing mood disorders, the impact of micronutrient deficiencies has attracted a great attention. Zinc deficiency is considered to play a crucial role in the onset and progression of mood disorders in different stages of life. The main objective of this study was to assess the correlation between serum zinc levels and mood disorders in high school female students. This cross-sectional study was conducted on a random sample of 100 representative high school female students. The participants completed 24-h food recall questionnaires to assess the daily zinc intakes. Serum zinc status was assessed using flame atomic absorption spectrometry, and zinc deficiency was defined accordingly. Mood disorders were estimated by calculating the sum of two test scores including Beck's depression inventory (BDI) and hospital anxiety depression scale (HADS) tests. General linear model (GLM) and Pearson's regression test were applied to show the correlation of serum zinc levels and mood disorder scores and the correlation between zinc serum levels and BDI scores, respectively. Dietary zinc intake was higher in subjects with normal zinc concentrations than that of zinc-deficient group (p = 0.001). Serum zinc levels were inversely correlated with BDI and HADS scores (p < 0.05). Each 10 µg/dL increment in serum zinc levels led to 0.3 and 0.01 decrease in depression and anxiety scores, respectively (p < 0.05). Serum zinc levels were inversely correlated with mood disorders including depression and anxiety in adolescent female students. Increasing serum levels of zinc in female students could improve their mood disorders.

Occult hepatitis B virus among the patients with abnormal alanine transaminase.

BACKGROUND: The occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the sera or in the liver biopsy and the absence of hepatitis B surface antigen (HBsAg) by serological test. OBJECTIVES: The current study aimed to evaluate the occult HBV infection by polymerase chain reaction (PCR) and determine HBV genotyping among the patients with abnormal alanine transaminase (ALT) in Ahvaz city, Iran. PATIENTS AND METHODS: The sera of 120 patients, 54 (45%) females and 66 (55%) males, with abnormal ALT 40-152 IU were collected. All the patients were negative for HBsAg for more than one year. The patients` sera were tested by PCR using primers specified for the S region of HBV. Then the positive PCR products were sequenced to determine HBV genotyping and phylogenic tree. RESULTS: Of these 120 subjects, 12 (10%) patients including 6 (5%) males and 6 (5%) females were found positive for HBV DNA by PCR, which indicated the presence of occult HBV infection among these patients. The sequencing results revealed that genotype D was predominant with sub-genotyping D1 among OBI patients. CONCLUSIONS: Occult hepatitis B infection is remarkably prevalent in Ahvaz, Iran, and should be considered as a potential risk factor for the transmission of Hepatitis B Virus throughout the community by the carriers.

Flavonoid-rich beverage effects on lipid profile and blood pressure in diabetic patients.

AIM: To compare freeze-dried strawberry (FDS) beverage and strawberry-flavored drink effects on lipid profile and blood pressure in type 2 diabetic (T2D) patients. METHODS: In a randomized, double-blind, controlled trial, 36 subjects with T2D (23 females; mean ± SE age: 51.57 ± 10 years) were randomly divided into two groups. Participants consumed two cups of either pure FDS beverage (each cup containing 25 g freeze-dried strawberry powder equivalent to one serving of fresh strawberries; intervention group) or an iso-caloric drink with strawberry flavoring (similar to the FDS drink in fiber content and color; placebo group) daily for 6 wk. Anthropometric measurements, 3 d, 24 h dietary recall, and fasting blood samples were collected at baseline and at weeks 6 intervention. After lying down and relaxing for approximately 10 min, each participant's blood pressure was recorded in triplicate with 5 min intervals; recordings were made at baseline and the trial end-point. Each participant's lipid profile was assessed before and after intervention. RESULTS: Assessment at the weeks 6 intervention showed a significant reduction from baseline in total cholesterol levels and total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio in the intervention group (179.01 ± 31.86 to 165.9 ± 32.4 mg/L; P = 0.00 and 3.9 ± 0.88 to 3.6 ± 0.082 mg/L; P = 0.00 respectively), but the change was not significantly different between the two groups (P = 0.07, P = 0.29 respectively). Systolic blood pressure levels were significantly reduced from baseline in both the FDS and placebo drink groups (129.95 ± 14.9 to 114.3 ± 27.5 mmHg; P = 0.02 and 127.6 ± 15.6 to 122.9 ± 14.47 mmHg; P = 0.00 respectively), but the reduction was not significantly different between the two groups. Diastolic blood pressure was significantly reduced post-intervention in the FDS drink group compared to placebo group (78.7 ± 7.2 vs 84.4 ± 5.8; P = 0.01), the reduction was also significant within the FDS drink group (84.2 ± 8.03 to 78.7 ± 7.2; P = 0.00). Triglycerides, HDL-C concentrations and anthropometric indices showed no significant differences between or within groups. CONCLUSION: Short-term FDS supplementation improved selected cardiovascular risk factors in subjects with T2D. Long-term effects on other metabolic biomarkers need to be investigated in future trials.

A climatological study of scorpion sting incidence from 2007 to 2011 in the Dezful area of southwestern Iran, using a time series model.

Scorpion stings are a public health problem in south and southwest Iran. There is little information regarding climatological effects on incidence of scorpion stings in Iran. Therefore, the present systemic survey of scorpion sting data was conducted from the point of view of entomo-meteorological relationships and analyzed statistically for the Dezful area in Khuzestan, southwest of Iran. The time series analysis was implemented using MINITAB version 16 statistical software packages. In total, 3,755 scorpion sting files from the Dezful health centers were monitored from April 2007 to September 2011 in a time series analysis. The results showed that temperature had significant effects on scorpion sting. From the data of this study, it is concluded that the scorpion activity in Dezful County is a climatological-dependent phenomenon.

Assessing the Autoantibody levels in Relation to Recurrence of Pemphigus: Joint Modeling of Longitudinal Measurements and Recurrent Event Times.

BACKGROUND: Pemphigus is an autoimmune bullous disease and it is unclear what triggers and deteriorates it. The current study aimed to evaluate whether increasing the IgG antibody titer represents a good indicator of the pemphigus recurrence. OBJECTIVES: The current study aimed to evaluate whether increasing IgG titer is an indicator of the expected recurrence. PATIENTS AND METHODS: The current study was conducted at the Department of Dermatology, Imam Khomeini Hospital, Tehran University of Medical Sciences, between March 2007 and December 2012. A total of 112 patients with confirmed diagnosis of pemphigus based on clinical, histological and immuno-histological criteria were engaged in the study. The primary outcomes of the study were recurrent event times and IgG (Immunoglobulin G) antibody titer at each attendance. Joint model with shared random-effects was applied to assess the association between the two processes and investigate the affective factors. RESULTS: Up to 8 recurrences were observed during the study time, but only 10% of the patients experienced more than 5 recurrences. A significant linear increasing trend in IgG antibody titer over time was found, IgG antibody titer increased 2.43% each month (P < 0.0001). The results showed positive correlation between IgG antibody titer and recurrence of pemphigus (P < 0.0001). CONCLUSIONS: The patients with higher IgG antibody titer were more likely to experience pemphigus recurrence. Therefore it can be concluded that titer of IgG and its increase may provide information regarding the progression of the pemphigus and the hazard of its recurrence.

Serotype determination of adenoviruses in children with respiratory infection.

OBJECTIVE: To determine adenovirus serotypes among children with acute respiratory infection (ARI) in Khoozestan province, Iran during years 2010-2011. METHODS: One hundred sixty three nasopharyngeal swabs were collected from children between 1 and 15 y who were hospitalized for the acute respiratory infection. The viral DNA was extracted from the nasopharyngeal swabs and adenoviruses were detected by Nested PCR. Positive PCR samples were sequenced in order to confirm the adenovirus serotypes. RESULTS: Out of 163 samples, 30 (18.4 %) were positive for adenoviruses by nested PCR. Twenty two PCR products were sequenced and recognized as Ad5 and Ad2 serotypes including 19 (86.3 %) Ad5 and 3 (13.7 %) Ad2. CONCLUSIONS: This study reveals that adenoviruses with Ad5 predominance are important cause of respiratory tract infection in children.

Modeling the recurrent failure to thrive in less than two-year children: recurrent events survival analysis.

BACKGROUND: This study aimes to evaluate the failure to thrive (FTT) recurrent event over time. METHODS: This longitudinal study was conducted during February 2007 to July 2009. The primary outcome was growth failure. The analysis was done using 1283 children who had experienced FTT several times, based on recurrent events analysis. RESULTS: Fifty-nine percent of the children had experienced the FTT at least one time and 5.3% of them had experienced it up to four times. The Prentice-Williams-Peterson (PWP) model revealed significant relationship between diarrhea (HR=1.26), respiratory infections (HR=1.25), urinary tract infections (HR=1.51), discontinuation of breast-feeding (HR=1.96), teething (HR=1.18), initiation age of complementary feeding (HR=1.11) and hazard rate of the first FTT event. CONCLUSIONS: Recurrence nature of the FTT is a main problem, which taking it into account increases the accuracy in analysis of FTT event process and can lead to identify different risk factors for each FTT recurrences.

Effects of freeze-dried strawberry supplementation on metabolic biomarkers of atherosclerosis in subjects with type 2 diabetes: a randomized double-blind controlled trial.

BACKGROUND: To our knowledge there has been no study investigating the impact of freeze-dried strawberry (FDS) supplementation on metabolic biomarkers of atherosclerosis in subjects with type 2 diabetes (T2D). OBJECTIVE: This study was carried out to determine the effects of FDS supplementation on glycemic control, biomarkers of oxidative stress, inflammation and serum total antioxidant status in subjects with T2D compared to matched control subjects. METHODS: Thirty-six subjects with T2D (23 females; mean body mass index 27.90 ± 3.7; mean age 51.57 ± 10 years) were randomly divided into two groups. The treatment group consumed 2 cups of FDS beverage (50 g of FDS is equivalent to 500 g of fresh strawberries) or macronutrient matched placebo powder with strawberry flavor daily for 6 weeks in a randomized double-blind controlled trial. Anthropometric measurements, dietary intakes, hemoglobin (Hb)A1c, antioxidant status, C-reactive protein and malondialdehyde (MDA) levels were assessed at baseline and 6 weeks post-intervention. RESULTS: FDS supplementation significantly decreased C-reactive protein levels as a biomarker of inflammation (2.5 vs. 2.04 mg/l, p < 0.05) and lipid peroxidation in the form of MDA (3.36 vs. 2.7 nmol/ml, p < 0.05) at 6 weeks compared to the baseline. Moreover, supplementation led to a decreasing trend in HbA1c (-5.7%, p < 0.05) and significant increase in total antioxidant status in the FDS group (1.44 vs. 1.26 mmol/l, p < 0.01) compared to the placebo group. No significant changes were observed in serum glucose concentrations and anthropometric indices. CONCLUSIONS: FDS improved glycemic control and antioxidant status, and reduced lipid peroxidation and inflammatory response in patients with T2D. Supplementation with freeze-dried berry products, as natural sources of antioxidants with low glycemic index, could be considered as an adjunctive therapy in ameliorating metabolic complications of T2D.