Enhancing computational enzyme design by a maximum entropy strategy.

Although computational enzyme design is of great importance, the advances utilizing physics-based approaches have been slow, and further progress is urgently needed. One promising direction is using machine learning, but such strategies have not been established as effective tools for predicting the catalytic power of enzymes. Here, we show that the statistical energy inferred from homologous sequences with the maximum entropy (MaxEnt) principle significantly correlates with enzyme catalysis and stability at the active site region and the more distant region, respectively. This finding decodes enzyme architecture and offers a connection between enzyme evolution and the physical chemistry of enzyme catalysis, and it deepens our understanding of the stability-activity trade-off hypothesis for enzymes. Overall, the strong correlations found here provide a powerful way of guiding enzyme design.

Analyzing the Reaction of Orotidine 5'-Phosphate Decarboxylase as a Way to Examine Some Key Catalytic Proposals.

This study analyzes the origin of enzyme catalysis by focusing on the reaction of orotidine 5'-phosphate decarboxylase (ODCase). This reaction involves an enormous catalytic effect of 23 kcal/mol that has been attributed to reactant state destabilization associated with the use of binding energy through the so-called Circe effect. However, our early studies and subsequent key experiments have shown that the presumed effect of the binding energy (namely, the strain exerted by a bond to a phosphate group) does not contribute to the catalysis. In this study, we perform quantitative empirical valence bond calculations that reproduce the catalytic effect of ODCase and the effect of removing the phosphate side chain. The calculations demonstrate that the effect of the phosphate is due to a change in reorganization energy and should not be described as an induced fit effect. Similarly, we show that the overall catalytic effect is due to electrostatic transition state stabilization, which again reflects the smaller reorganization energy in the enzyme than in water. We also elaborate on the problems with the induced fit proposal, including the fact that it does not serve to tell us what the actual origin of the action of the catalytic effect is. In addition to the above points, we use this paper to discuss misconceptions about the meaning of the preorganization effect, as well as other misunderstandings of what is being done in consistent calculations of enzyme catalysis.

Metformin and long non-coding RNAs in breast cancer.

Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical and pathological features. Recent studies also investigated the roles of metformin treatment as the firstline treatment for type 2 diabetes (T2D) played in lncRNAs expression/regulation or BC incidence, outcome, mortality and survival, separately. This comprehensive study aimed to review lncRNAs associated with BC features and identify metformin-regulated lncRNAs and their mechanisms of action on BC or other types of cancers. Finally, metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, by several molecular mechanisms have been described in this review. In addition, metformin action on other types of cancers by regulating ten lncRNAs including AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, H19, MALAT1, AFAP1-AS1, AC026904.1 is described.

Association of ACE gene polymorphisms with in-stent restenosis by stent type (biomime, supraflex, xience).

INTRODUCTION: Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE gene polymorphism (I/D) affects enzyme activity and the risk of coronary artery disease or CAD. AIMS: To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) the Ace gene allele and genotype frequencies were determined in patients who underwent angioplasty. MATERIAL & METHODS: Patients with in-stent restenosis (ISR+) (N = 53) and patients as non-ISR group (ISR-) (N = 68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR). RESULTS: The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR + groups observed (p-Values > 0.005). CONCLUSION: In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. The results showed that the number of patients who received Clopidogrel in the ISR + group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.

Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis.

OBJECTIVE: This study aimed to examine the association between the interleukin-1 receptor antagonist gene (IL-1RN) and coronary in-stent restenosis (ISR) through the analysis of the VNTR variant based on the previously reported results. MATERIALS AND METHODS: The samples were classified into two clearly defined groups: the case group, which comprised 45 patients diagnosed with in-stent restenosis (ISR+), and the control group, which included 60 patients without ISR (ISR-). Polymerase chain reaction (PCR) was performed to examine the 86-bp VNTR variant of the IL-1RN gene. RESULTS: In the analysis of six identified groups consisting of variant alleles of 86 base pairs of VNTR of the IL-1RN gene statistically significant difference was observed for the presence of IL1RN*2 allele between cases and controls (p = 0.04, OR; 0.045). CONCLUSION: Individuals with allele 2 of the IL-1Ra gene may be more predisposed to ISR. This could be due to an imbalance between IL-1Ra and IL-1ß which is crucial in preventing the initiation or advancement of inflammatory diseases in specific organs. The observed phenomenon can be characterized by increased production of IL-1ß and potential reduction of IL-1Ra as a result of functional VNTR variation in IL-RN gene.

Zinc supplementation ameliorates type 2 diabetes markers through the enhancement of total antioxidant capacity in overweight patients.

BACKGROUND: Evidence show that the recommended dose of zinc may not be sufficient for controlling pathological conditions such as type 2 diabetes mellitus (T2DM). AIM: This study aimed to evaluate the effects of zinc supplementation on the oxidative status in overweight T2DM. In addition, the routine glycaemic parameters were determined and compared in zinc-treated and placebo groups. METHODS: In this randomised, double-blind, placebo-controlled trial, 70 patients with T2DM were selected. They were divided into two groups for supplementation of 50 mg zinc gluconate or placebo (zinc group, n=35; placebo group, n=35) per day for 8 weeks. Blood samples were collected from all the individuals in the zinc group and controls for analysis. RESULTS: The results showed that zinc supplementation to patients with T2DM for 8 weeks significantly inhibited serum levels of lipid peroxidation (25%), nitrotyrosine (30%) and total oxidant status levels (25%, p<0.05). Nevertheless, the total antioxidant capacity was significantly elevated (16%) following zinc intake by patients with T2DM. CONCLUSIONS: These data, together with our previous report, may suggest that the control in the glycaemic condition in overweight patients with T2DM is correlated with the antioxidative/oxidative balance following intake of 50 mg zinc supplementation for 8 weeks. Under these circumstances, the clinical and glycaemic indices, including fasting blood glucose, insulin, haemoglobin A1c and homeostasis model of assessment-insulin resistance, were controlled. TRIAL REGISTRATION NUMBER: IRCT2015083102.

Effect of Environmental Factors on the Catalytic Activity of Intramembrane Serine Protease.

The cleavage of protein inside cell membranes regulates pathological pathways and is a subject of major interest. Thus, the nature of the coupling between the physical environment and the function of such proteins has recently attracted significant experimental and theoretical efforts. However, it is difficult to determine the nature of this coupling uniquely by experimental and theoretical studies unless one can separate the chemical and the environmental factors. This work describes calculations of the activation barriers of the intramembrane rhomboid protease in neutral and charged lipid bilayers and in detergent micelle, trying to explore the environmental effect. The calculations of the chemical barrier are done using the empirical valence bond (EVB) method. Additionally, the renormalization method captures the energetics and dynamical effects of the conformational change. The simulations indicate that the physical environment around the rhomboid protease is not a major factor in changing the chemical catalysis and that the conformational and substrate dynamics do not exhibit long-time coupling. General issues about the action of membrane-embedded enzymes are also considered.

Exploring the Role of Chemical Reactions in the Selectivity of Tyrosine Kinase Inhibitors.

A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult to design selective covalent inhibitors. The present study explores the contribution of the chemical reaction steps to the selectivity of the commercialized inhibitor acalabrutinib over the Bruton's tyrosine kinase (BTK) and the interleukin-2-inducible T-cell kinase (ITK). Ab initio and empirical valence bond (EVB) simulations of the two kinases indicate that the most favorable reaction path involves a water-assisted mechanism of the 2-butynamide reactive group of acalabrutinib. BTK reacts with acalabrutinib with a substantially lower barrier than ITK, according to our calculated free-energy profile and kinetic simulations. Such a difference is due to the microenvironment of the active site, as further supported by a sequence-based analysis of specificity determinants for several commercialized inhibitors. Our study involves a new approach of simulating directly the IC50 and inactivation efficiency keff, instead of using the standard formulas. This new strategy is particularly important in studies of covalent inhibitors with a very exothermic bonding step. Overall, our results demonstrate the importance of understanding the chemical reaction steps in designing selective covalent inhibitors for tyrosine kinases.

The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress.

INTRODUCTION: To date, numerous disorders have been linked to vitamin D deficiency. Several lines of evidence indicate a relationship between vitamin D deficiency and the risk of developing type 2 diabetes. It has been postulated that vitamin D may influence insulin activity, which can predispose individuals to develop type 2 diabetes. MATERIALS AND METHODS: In this case-control study, 262 patients with definite type 2 diabetes were enrolled, considering whether they were being affected by diabetic foot ulcers or not. The plasma levels of vitamin D and homocysteine were measured using ELISA, and the PCR-RFLP technique was utilized to determine allele and genotype frequencies. The antioxidant capacity of plasma samples of diabetic patients was analyzed using the thiobarbituric acid reactive substance (TBARS) and ferric reducing ability of plasma (FRAP) assays. RESULTS: The obtained results demonstrated no significant difference in the frequency of TaqI and BsmI polymorphisms between the case and control groups. However, the frequency of genotypes and alleles of the ApaI polymorphism in the VDR gene significantly differed between the case and control groups. A significant correlation was found between ApaI polymorphism and oxidative stress, as patients with the GG genotype had lower levels of TBARS than those with other genotypes. Furthermore, in the case group, patients with the CC genotype of BsmI showed a significant decrease in TBARS levels. DISCUSSION: It seems that the plasma levels of vitamin D do not differ between patients with or without diabetic foot ulcers; however, the presence of some VDR gene polymorphisms is thought to be involved in the development of diabetic foot ulcers via increasing oxidative stress.

Circulating amino acids and acylcarnitines correlated with different CAC score ranges in diabetic postmenopausal women using LC-MS/MS based metabolomics approach.

BACKGROUND: Diabetes mellitus (DM) and its cardiovascular disease (CVD) complication are among the most frequent causes of death worldwide. However, the metabolites linking up diabetes and CVD are less understood. In this study, we aimed to evaluate serum acylcarnitines and amino acids in postmenopausal women suffering from diabetes with different severity of CVD and compared them with healthy controls. METHODS: Through a cross-sectional study, samples were collected from postmenopausal women without diabetes and CVD as controls (n = 20), patients with diabetes and without CVD (n = 16), diabetes with low risk of CVD (n = 11), and diabetes with a high risk of CVD (n = 21) referred for CT angiography for any reason. Metabolites were detected by a targeted approach using LC-MS/MS and metabolic -alterations were assessed by applying multivariate statistical analysis. The diagnostic ability of discovered metabolites based on multivariate statistical analysis was evaluated by ROC curve analysis. RESULTS: The study included women aged from 50-80 years with 5-30 years of menopause. The relative concentration of C14:1, C14:2, C16:1, C18:1, and C18:2OH acylcarnitines decreased and C18 acylcarnitine and serine increased in diabetic patients compared to control. Besides, C16:1 and C18:2OH acylcarnitines increased in high-risk CVD diabetic patients compared to no CVD risk diabetic patients. CONCLUSION: Dysregulation of serum acylcarnitines and amino acids profile correlated with different CAC score ranges in diabetic postmenopausal women. (Ethic approval No: IR.TUMS.EMRI.REC.1399.062).

Association of circulating omega 3, 6 and 9 fatty acids with gestational diabetes mellitus: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM. METHODS: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies. RESULTS: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles. CONCLUSIONS: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO ( www.crd.york.ac.uk/PROSPERO ) as CRD42020196122.

Liquid Calibration Phantoms in Ultra-Low-Dose QCT for the Assessment of Bone Mineral Density.

INTRODUCTION: Cortical bone is affected by metabolic diseases. Some studies have shown that lower cortical bone mineral density (BMD) is related to increases in fracture risk which could be diagnosed by quantitative computed tomography (QCT). Nowadays, hybrid iterative reconstruction-based (HIR) computed tomography (CT) could be helpful to quantify the peripheral bone tissue. A key focus of this paper is to evaluate liquid calibration phantoms for BMD quantification in the tibia and under hybrid iterative reconstruction-based-CT with the different hydrogen dipotassium phosphate (K2HPO4) concentrations phantoms. METHODOLOGY: Four ranges of concentrations of K2HPO4 were made and tested with 2 exposure settings. Accuracy of the phantoms with ash gravimetry and intermediate K2HPO4 concentration as hypothetical patients were evaluated. The correlations and mean differences between measured equivalent QCT BMD and ash density as a gold standard were calculated. Relative percentage error (RPE) in CT numbers of each concentration over a 6-mo period was reported. RESULTS: The correlation values (R2 was close to 1.0), suggested that the precision of QCT-BMD measurements using standard and ultra-low dose settings were similar for all phantoms. The mean differences between QCT-BMD and the ash density for low concentrations (about 93 mg/cm3) were lower than high concentration phantoms with 135 and 234 mg/cm3 biases. In regard to accuracy test for hypothetical patient, RPE was up to 16.1% for the low concentration (LC) phantom for the case of high mineral content. However, the lowest RPE (0.4 to 1.8%) was obtained for the high concentration (HC) phantom, particularly for the high mineral content case. In addition, over 6 months, the K2HPO4 concentrations increased 25% for 50 mg/cm3 solution and 0.7 % for 1300 mg/cm3 solution in phantoms. CONCLUSION: The excellent linear correlations between the QCT equivalent density and the ash density gold standard indicate that QCT can be used with submilisivert radiation dose. We conclude that using liquid calibration phantoms with a range of mineral content similar to that being measured will minimize bias. Finally, we suggest performing BMD measurements with ultra-low dose scan concurrent with iterative-based reconstruction to reduce radiation exposure.

Comparison common equations for LDL-C calculation with direct assay and developing a novel formula in Iranian children and adolescents: the CASPIAN V study.

BACKGROUND: Hypercholesterolemia is a common dyslipidemia that leads to atherosclerosis. It is proved that early stages of atherosclerosis begins in early stages of life. In several studies, widespread prevalence of dyslipidemia in children is reported. So, assessment of lipid profile in children and adolescence is necessary for early diagnosis of dyslipidemia. Laboratory methods for measuring LDL are not available and economical. So, in some laboratories Friedwald method is used to determine LDL level. But, the preciseness of this method is not acceptable. Further, the preciseness of this method was not assayed in children and adolescence. So, it seems that assaying the preciseness of different methods is necessary. METHODS: The methodology of this work is on the basis of findings of the Caspian V study. This study was conducted in 30 provinces of Iran during 2015. The population of this work was rural and urban students aged 7-18 years old. The level of total cholesterol (TC), HDL, LDL, and TG were measured using laboratory methods. The average and variances values were determined for each group of data using SPSS. Further, LDL values were calculated with a new formula introduced in this work. A comparison was made between the new formula and the other methods. RESULTS: In the present study, we found that compare to four common formulas, Friedwald was the best equation to estimate LDL-C concentrations in Iranian children and adolescents and the new formula was the next accurate equation. The strongest correlation between Friedwald and the new equation was found for those with 15-18 years old. CONCLUSION: Considering the cut-off points of TG (100 mg/dL), we observed the strongest correlation between Friedwald equation and direct assay and the weakest one was for Ahmadi formula in subjects with either greater or lower TG concentrations. Furthermore, we found that Anandraja equation had the most sensitivity (89.5%), while the most specificity was dedicated to the new formula (98.9%).

Association of screen time and physical activity with health-related quality of life in Iranian children and adolescents.

BACKGROUND: Health-related quality of life (HRQoL) is a multidimensional concept with significant effects and children and adolescence; while physical activity (PA) and screen time (ST) have been suggested as its probable predictors. Present study aims to investigate the association of PA, ST and their combination, with HRQoL in a nationally-representative sample of Iranian children and adolescents. METHODS: As for the estimated sample size, 25,000 students aged 6-18 years were selected via multi-stage cluster sampling from 30 provinces of Iran. Sociodemographic data was obtained by using the questionnaire of the World Health Organization-Global school based student health survey (GSHS). Persian Pediatric Quality of Life inventory (PedsQL) and Physical Activity Questionnaire for the pediatric age group (PAQ-A) were applied for evaluating HRQoL and PA, respectively. PA scores 1-1.9 and 2-5 were respectively considered as low and high PA. The average duration of time spent on watching TV and leisure time computer use were considered as ST behaviors. ST of less than 2 h was considered low. RESULTS: Out of 25,000 invited individuals, 23,043 students (mean age: 12.5) completed the study (response rate: 92.17%). In linear regression models, ST duration had significant inverse association with total QoL (ß: - 0.49, p < 0.05). PA showed positive significant associations with HRQoL total score (ß: 1.8, p < 0.05). Joint association of PA and ST revealed the strongest association of "high PA-low ST" category with total HRQoL (ß: 2.2, p < 0.05); while "high PA-high ST" showed better total HRQoL score (ß: 1.3) compared to "low PA-low ST" subgroup. CONCLUSION: Both PA and ST are significantly and independently associated with HRQoL in Iranian children and adolescents; while the adverse effect of prolonged ST could be diminished by a high PA.

MDCT-QCT, QUS, and DXA in healthy adults: An intermodality comparison.

Background: Cortical deceleration is the main reason for bone loss at peripheral sites. It was suggested that when peripheral bones were assessed for osteoporosis, management and therapy can be administered early. The main aim of this study was to assess the relationships between the central and peripheral measurements at different skeleton bone sites (spine, femur, forearm, tibia, and calcaneus) with available modalities: DXA, QUS, and MDCT-QCT. Methods: The volunteers recruited in this study did not have any history or evidence of metabolic bone disease. Blood test and DXA measurements were used as inclusion criteria to select 40 healthy participants. The selected volunteers underwent 3 imaging modalities: QCT, DXA, and QUS. DXA-based measurements were made on 3 sites, including spine, femur, and forearm. QCT and QUS measurements were done for distal of tibia and calcaneus bones, respectively. The extracted parameters from the 3 modalities were analyzed using a bivariate (Pearson) correlation (r) in statistical software. Results: The results showed moderate to good correlations between spongy bones in central and peripheral sites from all the modalities. However, there was no correlation between MDCT measures and central bone values. According to correlations between different peripheral sits, aBMD of 33% radius and trabecular vBMD in 38% distal tibia showed weak but significant relationship between peripheral bones (r=-0.342, p=0.044). Conclusion: The findings demonstrated how bones in central and peripheral sites were correlated. Multimodality imaging was used in this group of healthy volunteers. Also, it was found that QCT-based MDCT needs more optimization and requires further investigations.

Comparison of citalopram and venlafaxine's role in treating sleep disturbances in menopausal women, a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Sleep disturbance is a common complaint in postmenopausal women. Few studies compared symptom improvement taking antidepressants versus placebo. This study aims to evaluate the efficacy of venlafaxine and Citalopram compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. METHOD: This randomized, double-blind, placebo-controlled clinical trial was conducted in three groups of 20 postmenopausal women. The patients took venlafaxine 75 mg/daily (group I) or citalopram 20 mg/d (group II) or placebo (group III). Each patient filled Pittsburgh sleep quality index (PSQI) and Pittsburgh and Beck depression questionnaires. The frequency of hot flashes in a day and its severity were measured through diaries. Somatic symptoms and adverse side effects were evaluated. Follow-up visit was conducted after 3 months. The prior and the later results were compared. RESULTS: The PSQI scores in three placebo, venlafaxine, and citalopram groups before treatment were 14.25 ± 3.85, 11.55 ± 3.96, and 13.50 ± 3.56, respectively (p = 0.076). These values after treatment reached 9.95 ± 5.07, 8 ± 3.06, and 6.95 ± 1.84, respectively. PSQI score in citalopram and venlafaxine group was not significantly different (p = 0.19) but the score in both groups was significantly lower compared with placebo group after treatment (p = 0.01). The frequency of hot flashes in a day was reduced significantly by both citalopram and venlafaxine (p < 0.05), although it was more reduced by citalopram than venlafaxine (p = 0.03). Severity of hot flashes in both venlafaxine and citalopram was significantly lower in comparison with placebo group (p = 0.02), and there was no significant difference between two drugs, though (p = 0.84). Beck score decreased more in venlafaxine group in comparison with other groups but it did not reach significant (p = 0.06). CONCLUSION: Citalopram and venlafaxine are equally more effective than placebo in reducing sleep disturbance and severity of hot flashes, while citalopram is more effective in reducing frequency of hot flashes than venlafaxine. Meanwhile, venlafaxine is more effective than citalopram in treatment of depression in postmenopausal women. TRIAL REGISTRATION: Iranian Registry of Clinical Trials 201210152576N6.

Clinical performance of seven prescreening tools for osteoporosis in Iranian postmenopausal women.

This study was designed to evaluate seven prescreening osteoporosis models in postmenopausal Iranian women. This study was performed on 8644 postmenopausal women who have been referred for bone mineral densitometry (BMD) in BMD center of Shariati hospital in Tehran between 2001 and 2011. Diagnostic properties of seven prescreening instruments were evaluated. With regard to area under curve (AUC), these models have low accuracy (AUC ≤ 0.65). Considering only femoral neck or total femur area, these models had low accuracy but were more sensitive. Except for three models with sensitivities of ≤65 % in both osteoporosis and fracture threshold, other models were around 70 % sensitive. However, these models were not considered clinically useful regarding their positive predictive values (PPV) especially in BMDs ≤02.5. With regard to different measures of diagnostic property, none of these models were good screening tools for osteoporosis or fracture threshold. Although some of them are sensitive, considering other measures such as PPV indicates that they are not completely useful for clinical use. Attempts should be made for developing newer prescreening methods and calibration of the existing models with regard to the studied population.

Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.

PURPOSE: To determine whether administration of vitamin D affects the success rates of intra uterine insemination (IUI) in infertile polycystic ovarian syndrome (PCOS) women and their endometrial thickness. METHODS: This randomized, double-blind, placebo-controlled trial was conducted in an infertility clinic of Women's Hospital, and 110 infertile PCOS patients undergoing IUI were randomly divided to receive vitamin D or placebo. Endometrial thickness, IUI results, number of dominant follicles, duration of IUI cycle, and dose of HMG used in IUI were determined. RESULTS: The endometrial thickness was significantly different in the group treated with vitamin D versus the placebo group (p = 0.003). There was no statistical difference in pregnancy out come between the two groups (RR = 1.167, CI 95 % 0.70-1.93). No statistical difference was found in number of dominant follicles (p = 0.96), duration of IUI cycles (p = 0.70) and dose of HMG used for IUI (p = 0.95). CONCLUSIONS: It seems that administration of vitamin D induces endometrial proliferation in PCOS women during IUI cycle. The study was recorded in Iranian Registry of Clinical Trials(IRCT201104216246N1).

Association analysis between the VDR gene variants and type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial. We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population. Methods: A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping. Results: The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918). Conclusion: Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01323-0.

ACE I/D gene polymorphisms and polycystic ovary syndrome manifestations.

Objective: Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder affecting women of reproductive age. ACE enzyme is involved in the physiopathology of the ovarian system, and there are inconsistencies between studies regarding the association between ACE gene variants and PCOS. The objective of this study is to evaluate the association between ACE I/D gene polymorphisms and PCOS, as well as its clinical manifestations, in Iranian women with PCOS. Design: This study included 140 patients with PCOS and 153 controls without the disease. Samples were collected from Yas Hospital Complex in Tehran-Iran during 2018 to 2022. Genomic DNA was obtained from whole blood samples using salt extraction, and genotyping was carried out using polymerase chain reaction (PCR). Results: Variants of DD, ID, and II were observed in 31.4, 44.3, and 24.3% of PCOS, and 38.6, 44.1, and 17.2% of control group, respectively. The frequency of ACE gene variants did not differ between PCOS patients and control group. A significant difference was observed between the frequency of elevated LH to FSH ratio > 2 and ACE gene polymorphisms in patients with PCOS (OR: 0.32 (0.12-0.88), P value 0.024) with lower frequency observed in D allele carriers. Conclusion: This study indicate that although ACE I/D variants frequency in PCOS women is similar to non-PCOS women, it may be involved in the pathogenesis of the disease through mechanisms regulating steroidogenesis in the ovary and suggests that ACE might be related to exacerbated clinical manifestations of PCOS which requires further investigations.