Development of a coupled modeling for tumor growth, angiogenesis, oxygen delivery, and phenotypic heterogeneity.

Analysis of the evolution and growth dynamics of tumors is crucial for understanding cancer and the development of individually optimized therapies. During tumor growth, a hypoxic microenvironment around cancer cells caused by excessive non-vascular tumor growth induces tumor angiogenesis that plays a key role in the ensuing tumor growth and its progression into higher stages. Various mathematical simulation models have been introduced to simulate these biologically and physically complex hallmarks of cancer. Here, we developed a hybrid two-dimensional computational model that integrates spatiotemporally different components of the tumor system to investigate both angiogenesis and tumor growth/proliferation. This spatiotemporal evolution is based on partial diffusion equations, the cellular automation method, transition and probabilistic rules, and biological assumptions. The new vascular network provided by angiogenesis affects tumor microenvironmental conditions and drives individual cells to adapt themselves to spatiotemporal conditions. Furthermore, some stochastic rules are involved besides microenvironmental conditions. Overall, the conditions promote some commonly observed cellular states, i.e., proliferative, migrative, quiescent, and cell death, depending on the condition of each cell. Altogether, our results offer a theoretical basis for the biological evidence that regions of the tumor tissue near blood vessels are densely populated by proliferative phenotypic variants, while poorly oxygenated regions are sparsely populated by hypoxic phenotypic variants.

Construction of a three-component regulatory network of transcribed ultraconserved regions for the identification of prognostic biomarkers in gastric cancer.

Altered expression and functional roles of the transcribed ultraconserved regions (T-UCRs), as genomic sequences with 100% conservation between the genomes of human, mouse, and rat, in the pathophysiology of neoplasms has already been investigated. Nevertheless, the relevance of the functions for T-UCRs in gastric cancer (GC) is still the subject of inquiry. In the current study, we first used a genome-wide profiling approach to analyze the expression of T-UCRs in GC patients. Then, we constructed a three-component regulatory network and investigated potential diagnostic and prognostic values of the T-UCRs. The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was used as a resource for the RNA-sequencing data. FeatureCounts was utilized to quantify the number of reads mapped to each T-UCR. Differential expression analysis was then conducted using DESeq2. In the following, interactions between T-UCRs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were combined into a three-component network. Enrichment analyses were performed and a protein-protein interaction (PPI) network was constructed. The R Survival package was utilized to identify survival-related significantly differentially expressed T-UCRs (DET-UCRs). Using an in-house cohort of GC tissues, expression of two DET-UCRs was furthermore experimentally verified. Our results showed that several T-UCRs were dysregulated in TCGA-STAD tumoral samples compared to nontumoral counterparts. The three-component network was constructed which composed of DET-UCRs, miRNAs, and mRNAs nodes. Functional enrichment and PPI network analyses revealed important enriched signaling pathways and gene ontologies such as "pathway in cancer" and regulation of cell proliferation and apoptosis. Five T-UCRs were significantly correlated with the overall survival of GC patients. While no expression of uc.232 was observed in our in-house cohort of GC tissues, uc.343 showed an increased expression, although not statistically significant, in gastric tumoral tissues. The constructed three-component regulatory network of T-UCRs in GC presents a comprehensive understanding of the underlying gene expression regulation processes involved in tumor development and can serve as a basis to investigate potential prognostic biomarkers and therapeutic targets.

Corona Virus Disease 2019 (COVID-19) as a System-Level Infectious Disease With Distinct Sex Disparities.

The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.

A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression.

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA (trimethylamine), as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

Identification of a novel HEXB Mutation in an Iranian Family with suspected patient to GM2-gangliosidoses.

Sandhoff disease is one of the GM2-gangliosidoses which is caused by a mutation in the HEXB preventing the breakdown of GM2-ganglioside. We report a novel HEXB variant in a family with a history of a dead girl with Sandhoff disease which was not found in controls.

Predicting the most deleterious missense nsSNPs of the protein isoforms of the human HLA-G gene and in silico evaluation of their structural and functional consequences.

BACKGROUND: The Human Leukocyte Antigen G (HLA-G) protein is an immune tolerogenic molecule with 7 isoforms. The change of expression level and some polymorphisms of the HLA-G gene are involved in various pathologies. Therefore, this study aimed to predict the most deleterious missense non-synonymous single nucleotide polymorphisms (nsSNPs) in HLA-G isoforms via in silico analyses and to examine structural and functional effects of the predicted nsSNPs on HLA-G isoforms. RESULTS: Out of 301 reported SNPs in dbSNP, 35 missense SNPs in isoform 1, 35 missense SNPs in isoform 5, 8 missense SNPs in all membrane-bound HLA-G isoforms and 8 missense SNPs in all soluble HLA-G isoforms were predicted as deleterious by all eight servers (SIFT, PROVEAN, PolyPhen-2, I-Mutant 3.0, SNPs&GO, PhD-SNP, SNAP2, and MUpro). The Structural and functional effects of the predicted nsSNPs on HLA-G isoforms were determined by MutPred2 and HOPE servers, respectively. Consurf analyses showed that the majority of the predicted nsSNPs occur in conserved sites. I-TASSER and Chimera were used for modeling of the predicted nsSNPs. rs182801644 and rs771111444 were related to creating functional patterns in 5'UTR. 5 SNPs in 3'UTR of the HLA-G gene were predicted to affect the miRNA target sites. Kaplan-Meier analysis showed the HLA-G deregulation can serve as a prognostic marker for some cancers. CONCLUSIONS: The implementation of in silico SNP prioritization methods provides a great framework for the recognition of functional SNPs. The results obtained from the current study would be called laboratory investigations.

Design and evaluation of biological gate circuits and their therapeutic applications in a model of multidrug resistant cancers.

OBJECTIVES: Synthetic biology is primarily an emerging research field that consists of designing new synthetic gene circuits dedicated to targeted functions and therapies such as cancer therapy. In this study, a genetic logic NOT-IF gate is used to reduce the multidrug resistance and facilitate the malignant cancer therapy. MCF7 cancer cells were cultured in RPMI-1640 medium and transfected with lentiviral vectors including MDR1 gene and the corresponding shRNA against MDR1 with controllable promoters. Transcript levels and protein levels of MDR1 gene were quantified. RESULTS: Our results showed that when doxycycline (DOX) and sodium butyrate were present and IPTG was absent, these led to a 74,354-fold increase in MDR1 gene expression. Upon IPTG treatment, the MDR1 gene expression was not detected due to the lack of the inducer. In addition, following IPTG induction in the presence of DOX and sodium butyrate and expressing shRNA, there was a 75% reduction in MDR1 gene expression compared to those cells treated only with sodium butyrate and DOX. CONCLUSIONS: We successfully designed and implemented the genetic logic NOT-IF gate at the transcriptional level using the inducible expression of both MDR1 drug resistance pump and its specific shRNA in MCF7 cancer cells, using the third generation lentiviral vectors.

Synthetic Biology Based on Genetic Logic Circuit, Using the Expression of Drug Resistance, BCRP Pump in MCF-7 Cancer Cell Line.

Biological circuits are developed as biological parts within a cell to carry out logical functions resembling those studied in electronics circuits. These circuits can be performed as a method to vary cellular functions, to develop cellular responses to environmental conditions, or to regulate cellular developments. This research explored the possibility of synthetic biology based on the genetic logic circuit A and (not B) using the inducible expression of the both BCRP drug resistance pump and its specific shRNA in MCF-7 cancer cell line utilizing the third generation of lentiviral vectors. The accuracy of the output of the proposed circuit for living cells, was confirmed by the results of the Real-Time PCR and flow cytometry at the RNA and protein levels. At the RNA level, the effect of the inducers on the BCRP gene expression and silencing were investigated by real-time PCR. Furthermore, at the protein level, induction of the expression of the BCRP pump resulted in driving out of the substrate from inside the cells leading to the decrease of the fluorescent emission from the transfected cells. We successfully designed and implemented the genetic logic circuit A and (not B) using the inducible expression of the both BCRP drug resistance pump and its specific shRNA in MCF-7 cancer cells.

Bioinformatics prediction and experimental validation of a novel microRNA: hsa-miR-B43 within human CDH4 gene with a potential metastasis-related function in breast cancer.

As a class of short noncoding RNAs, microRNAs (miRNAs) play a key role in the modulation of gene expression. Although, the regulatory roles of currently identified miRNAs in various cancer types including breast cancer have been well documented, there are many as yet undiscovered miRNAs. The aim of the current study was to bioinformatically reanalyze a list of 189 potentially new miRNAs introduced in a previously published paper (PMID: 21346806) and experimentally explore the existence and function of a candidate one: hsa-miR-B43 in breast cancer cells. The sequences of 189 potential miRNAs were re-checked in the miRbase database. Genomic location and conservation of them were assessed with the University of California Santa Cruz (UCSC) genome browser. SSC profiler, RNAfold, miRNAFold, MiPred, and FOMmiR bioinformatics tools were furthermore utilized to explore potential hairpin structures and differentiate real miRNA precursors from pseudo ones. hsa-miR-B43 was finally selected as one of the best candidates for laboratory verification. The expression and function of hsa-miR-B43 were examined by real-time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and wound-healing assays. DIANA-microT, RNAhybrid and Enrichr tools were used to predict the miRNA target genes and for further enrichment analysis. We could detect the exogenous and endogenous expression of hsa-miR-B43, as a real novel miRNA, in cancer cell lines. Gene Ontology enrichment, pathway analysis and wound-healing assay results furthermore confirmed that a metastasis-related function may be assigned to hsa-miR-B43. Our results introduced hsa-miR-B43, as a novel functional miRNA, which might play a role in the metastatic process. Further studies will be necessary to completely survey the existence and function of hsa-miR-B43 in other cancer types.

Down-regulation of circular RNA ITCH and circHIPK3 in gastric cancer tissues

Background/aim: Gastric cancer (GC) is one of the major causes of cancer mortality worldwide. As a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) are formed by a covalent link between 5' and 3' ends. They are very stable and abundant in eukaryotes. As there were no reported studies on the expression profiles of circular RNA ITCH (cir-ITCH) and circHIPK3 in GC, in the current study, we aimed to delineate the expression profiles and clinicopathological relevance of these two circRNAs in GC tissues compared to their paired adjacent noncancerous tissues. Materials and methods: Quantitative real-time polymerase chain reaction was performed to evaluate cir_ITCH and circHIPK3 expression in 30 paired gastric cancer tissues. The clinicopathological relevance of these two circular RNAs' expression levels with gastric cancer was further examined. Results: Our results showed that the expression of cir_ITCH and circHIPK3 were significantly downregulated in GC tumoral tissues compared with their paired adjacent nonneoplastic counterparts. Further analyses showed that cir_ITCH and circHIPK3 expression levels were related with numerous clinicopathological features of tumoral tissues. Conclusion: Cir_ITCH and circHIPK3 may have imperative roles in GC and serve in the future as potential prognostic biomarkers in GC.

Hypothesis: A Challenge of Overexpression Zfp521 in Neural Tendency of Derived Dental Pulp Stem Cells.

Neurodegenerative diseases have now become a major challenge, especially in aged societies. Most of the traditional strategies used for treatment of these diseases are untargeted and have little efficiency. Developments in stem cell investigations have given much attention to cell therapy as an alternative concept in the regeneration of neural tissues. Dental pulp stem cells (DPSCs) can be readily obtained by noninvasive procedures and have been shown to possess properties similar to well-known mesenchymal stem cells. Furthermore, based on their neural crest origin, DPSCs are considered to have a good potential to differentiate into neural cells. Zfp521 is a transcription factor that regulates expression of many genes, including ones involved in the neural differentiation process. Therefor based on neural crest origin of the cell and high expression of neural progenitor markers, we speculate that sole overexpression of Zfp521 protein can facilitate differentiation of dental stem cells to neural cells and researchers may find these cells suitable for therapeutic treatment of neurodegenerative diseases.

Gene Expression Analysis of Two Epithelial-mesenchymal Transition-related Genes: Long Noncoding RNA-ATB and SETD8 in Gastric Cancer Tissues.

BACKGROUND: Cancer is the second cause of death after cardiovascular diseases worldwide. Tumor metastasis is the main cause of death in patients with cancer; therefore, unraveling the molecular mechanisms involved in metastasis is critical. Epithelial-mesenchymal transition (EMT) is believed to promote tumor metastasis. Based on the critical roles of long noncoding RNA-ATB (lncRNA-ATB) and SETD8 genes in cancer pathogenesis and EMT, in this study, we aimed to assess expression profile and clinicopathological relevance of these two genes in human gastric cancer. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction was performed to assess these gene expressions in gastric cancer tissues and various cell lines. The associations between these gene expressions and clinicopathological characteristics were also analyzed. RESULTS: Insignificant downregulation of lncRNA-ATB and significant upregulation of SETD8 in cancerous versus noncancerous gastric tissues were observed. Among different examined cell lines, all displayed both genes expression. Except for a significant inverse correlation between the expression levels of lncRNA-ATB and depth of invasion (T) and a direct association between SETD8 levels and advanced tumor grades, no significant association was found with other clinicopathological characteristics. CONCLUSION: lncRNA-ATB and SETD8 genes may play a critical role in gastric cancer progression and may serve as potential diagnostic/prognostic biomarkers in cancer patients.

Lack of Evidence of the Role of APOA5 3'UTR Polymorphisms in Iranian Children and Adolescents with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a complex and multifactorial disorder characterized by insulin resistance, dyslipidaemia, hyperglycemia, abdominal obesity, and elevated blood pressure. The apolipoprotein A5 (APOA5) gene variants have been reported to correlate with two major components of MetS, including low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglyceride. In the present study, we explored the associations between five single nucleotide polymorphisms (SNPs) of APOA5 gene and the MetS risk. METHODS: In a case-control design, 120 Iranian children and adolescents with/without MetS were genotyped by polymerase chain reaction-sequencing for these SNPs. Then, we investigated the association of SNPs, individually or in haplotype constructs, with MetS risk. RESULTS: The rs34089864 variant and H1 haplotype (harboring the two major alleles of rs619054 and rs34089864) were associated with HDL-C levels. However, there was no significant association between different haplotypes/individual SNPs and MetS risk. CONCLUSION: These results presented no association of APOA5 3'UTR SNPs with MetS. Further studies, including other polymorphisms, are required to investigate the involvement of APOA5 gene in the genetic susceptibility to MetS in the pediatric age group.

Augmented expression levels of lncRNAs ecCEBPA and UCA1 in gastric cancer tissues and their clinical significance.

OBJECTIVES: As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation. This lncRNA reduces CEBPA promoter methylation by interacting with DNA methyltransferase 1. lncRNA UCA1 (urothelial carcinoma-associated 1) elevates cell proliferation through the PI3K/Akt signaling pathway which has a critical role in cell growth and apoptosis. The aim of this study was to examine the expression of ecCEBPA and UCA1 genes in GC tissues as well as their clinical significance. MATERIALS AND METHODS: Total RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed for cells and 80 paired GC tissues. Furthermore, clinical relevance of UCA1 expression was investigated in TCGA cohort data. RESULTS: Our results showed ecCEBPA and UCA1 over-expression in GC tissues. Furthermore, lncRNAs associations with clinicopathological features were demonstrated both in the current and TCGA cohort. Kaplan-Meier analysis indicated that patients with higher UCA1 expression had a worse overall survival in the case of pancreatic and lung adenocarcinomas but not other solid cancer types including GC. CONCLUSION: These data demonstrate UCA1 and ecCEBPA involvement in GC and suggest that these lncRNAs might be useful as diagnostic/ prognostic biomarkers in cancer.

Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric cancer diagnosis and clinically monitoring cancer progression.

AIM: To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. PATIENTS & METHODS: Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. RESULTS: Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. CONCLUSION: In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.

Pseudogenes in gastric cancer pathogenesis: a review article.

Cancer burden rises globally at an alarming pace. According to GLOBOCAN 2012, gastric cancer (GC) is regarded as the fifth most common malignancy in the world. Being twice as high in men as in women, GC is the third leading cause of cancer mortality in both sexes globally. Being labeled as 'junk DNA', pseudogenes were considered as nonfunctional 'trash', which contribute nothing to survival of the organism; therefore, a number of strategies have been developed to circumvent their accidental detection. Recent progresses have confirmed that pseudogenes can have broad and multifaceted spectrum of activities in human cancers in general and GC in particular. Furthermore, the mentioned functions are parental gene-dependent and/or -independent. Therefore, pseudogenes can be regarded as the emerging class of elaborate modulators of gene expression involved in pathogenesis of human cancers including gastric adenocarcinoma.

Identification of a New Single-nucleotide Polymorphism within the Apolipoprotein A5 Gene, Which is Associated with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a common disorder which is a constellation of clinical features including abdominal obesity, increased level of serum triglycerides (TGs) and decrease of serum high-density lipoprotein-cholesterol (HDL-C), elevated blood pressure, and glucose intolerance. The apolipoprotein A5 (APOA5) is involved in lipid metabolism, influencing the level of plasma TG and HDL-C. In the present study, we aimed to investigate the associations between four INDEL variants of APOA5 gene and the MetS risk. MATERIALS AND METHODS: In this case-control study, we genotyped 116 Iranian children and adolescents with/without MetS by using Sanger sequencing method for these INDELs. Then, we explored the association of INDELs with MetS risk and their clinical components by logistic regression and one-way analysis of variance analyses. RESULTS: We identified a novel insertion polymorphism, c. *282-283 insAG/c. *282-283 insG variant, which appears among case and control groups. rs72525532 showed a significant difference for TG levels between various genotype groups. In addition, there were significant associations between newly identified single-nucleotide polymorphism (SNP) and rs72525532 with MetS risk. CONCLUSIONS: These results show that rs72525532 and the newly identified SNP may influence the susceptibility of the individuals to MetS.

Long noncoding RNAs in gastric cancer carcinogenesis and metastasis.

Recent studies of the human transcriptome, most prominently by the ENCyclopedia Of DNA Elements project, have revealed an unexpected number of noncoding RNAs (ncRNAs). Long noncoding RNAs (lncRNAs) are typically referred to a heterogeneous group of polyadenylated long ncRNAs, with a length of > 200 nt. LncRNAs constitute an integral part of tumor biology, with many lncRNAs discovered to be aberrantly expressed in various cancer types. They are involved in many aspects of cancer pathogenesis from its initiation to progression, metastasis and treatment response. Gastric cancer (GC) is the third leading cause of cancer death worldwide. Despite the current improvements of life expectancy and survival rate, most of the patients are diagnosed when their cancer has been progressed to advanced stages. Therefore, unraveling the molecular mechanisms of GC to find early-stage biomarkers is urgent. As the list of lncRNAs with deregulated expression in GC is steadily expanding, these molecules offer a source for developing GC-specific biomarkers. In this review, we will present and discuss those lncRNAs whose expression has been shown to be deregulated in GC.

Clinical and metabolic response to probiotic supplementation in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to determine the effects of probiotic supplementation on clinical and metabolic status of patients with rheumatoid arthritis (RA). METHODS: Sixty patients with RA aged 25-70 years were assigned into two groups to receive either probiotic capsules (n = 30) or placebo (n = 30) in this randomized, double-blind, placebo-controlled trial. The patients in the probiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) colony-forming units [CFU]/g), Lactobacillus casei (2 × 10(9) CFU/g) and Bifidobacterium bifidum (2 × 10(9) CFU/g) for 8 weeks. The placebo group took capsules filled with cellulose for the same time period. Fasting blood samples were taken at the beginning and the end of the study to quantify related markers. RESULTS: After 8 weeks of intervention, compared with the placebo, probiotic supplementation resulted in improved Disease Activity Score of 28 joints (DAS-28) (-0.3 ± 0.4 vs. -0.1 ± 0.4, P = 0.01). In addition, a significant decrease in serum insulin levels (-2.0 ± 4.3 vs. +0.5 ± 4.9 µIU/mL, P = 0.03), homeostatic model assessment-B cell function (HOMA-B) (-7.5 ± 18.0 vs. +4.3 ± 25.0, P = 0.03) and serum high-sensitivity C-reactive protein (hs-CRP) concentrations (-6.66 ± 2.56 vs. +3.07 ± 5.53 mg/L, P < 0.001) following the supplementation of probiotics compared with the placebo. Subjects who received probiotic capsules experienced borderline statistically significant improvement in total- (P = 0.09) and low-density lipoprotein-cholesterol levels (P = 0.07) compared with the placebo. CONCLUSION: Overall, the results of this study indicated that taking probiotic supplements for 8 weeks among patients with RA had beneficial effects on DAS-28, insulin levels, HOMA-B and hs-CRP levels.

Analysis of the T354P mutation of the sodium/iodide cotransporter gene in children with congenital hypothyroidism due to dyshormonogenesis.

BACKGROUND: Congenital hypothyroidism (CH) due to the thyroid dyshormonogenesis is more prevalent in Iran in comparison to other countries. Sodium iodide symporter (NIS) is one of the plasma membrane glycoproteins that is located on the basolateral side of thyroid follicular cells and mediates active I(-) trapping into these cells. Playing a prominent role in thyroid hormone synthesis, NIS gene mutations can be a cause of permanent CH with the etiology of dyshormonogenesis. The aim of this study was to investigate the occurrence of T354P mutation of the NIS gene, in a group of children affected with permanent CH in Isfahan. MATERIALS AND METHODS: Thirty-five patients with the etiology of dyshormonogenesis, and 35 healthy children, collected between 2002 and 2011 in Isfahan Endocrine and Metabolism Research Center, were examined for T354P mutation of the NIS gene by direct polymerase chain reaction-sequencing method. RESULTS: No T354P mutation was detected in any of the studied children. CONCLUSIONS: More subjects with confirmed iodide transport defects should be screened for detecting the frequency of different reported NIS gene mutations in our population.