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Engineered probiotics (EPs) can be used to treat/manage chronic and congenital diseases. However, to the best of our knowledge, no systematic review has evaluated the effects of EPs on congenital metabolic disorders in murine models and human subjects. Thus, the present study systematically reviewed interventional studies that assessed the effects of EPs on congenital metabolic disorders. PubMed, Web of Science, and Scopus databases were searched up to February 2023 to retrieve related publications. Seventy-six articles were obtained in the primary step. After screening the titles/abstracts based on the inclusion and exclusion criteria, 11 papers were included. Finally, only seven articles were included after performing full-text evaluation. The included articles evaluated the effects of EPs on managing phenylketonuria (PKU, n=4) and hyperammonemia (n=3). Moreover, these studies examined mice and/or rats (n=6), monkeys (n=1), and humans (n=2). Studies on EPs and hyperammonemia revealed that some wild strains such as Lactobacillus plantarum have an innate ammonia-hyper-consuming potential; thus, there was no need to manipulate them. However, manipulation is needed to obtain a phenylalanine-metabolizing strain. In conclusion, EPs can be used to manage or treat congenital metabolic diseases including PKU.
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Pancreatic cancer (PC) is one of the leading causes of cancer mortality worldwide, and its incidence and mortality rate in several regions is higher in male patients. Although numerous efforts have been made to enhance the clinical outcomes of existing therapeutic regimens, their efficiency is still low, and drug resistance usually occurs in many patients. In addition, the exact underlying molecular basis that makes PC slightly more prevalent among males remains unknown. Providing information regarding the possible association between gender and PC tumorigenesis may offer important clues for how certain molecular cross-talks can affect PC initiation and/or progression. In this study, we used several microarray expression data to identify the common up- and downregulated genes within one specific gender, which were also specified to have binding sites for androgen and/or estrogen receptors. Using functional enrichment analysis among the others, for all the gene sets found in this study, we have shed light on the plausible importance of the androgenic effectors in tumorigenesis, such as the androgen-regulated expression of the GLI transcription factor and the potential role of testosterone in the extracellular matrix (ECM)-cell interaction, which are known for their importance in tumorigenesis. Moreover, we demonstrated that the biological process axon guidance was highlighted regarding the upregulated genes in male patients. Overall, identification of gene candidates as the possible link between gender and PC progression or survival rates may help in developing strategies to reduce the incidence of this cancer.
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Objectives: Juvenile idiopathic arthritis (JIA) is a childhood autoimmune rheumatoid disease. Past studies have confirmed that JIA is a complex disease, which means that genes and environmental factors affect the aetiology of the disease. In this study, we analysed the expression of interleukin 32, forkhead box P3 (FOXP3), methyl-CpG binding domain protein 1 (MBD1), and methyl-CpG-binding protein 2 (MECP2) in peripheral blood mononuclear cells of children with JIA in comparison with the expression of those in healthy children. Interleukin 32 is an inflammatory factor, FOXP3 is a transcription factor, and MBD1 and MECP2 are binding proteins that bind to the methylated deoxyribonucleic acid (DNA). Material and methods: We collected blood from JIA patients who had been diagnosed and classified into clinical subtypes by a rheumatologist from the division of paediatric rheumatology. Healthy children, whose clinical and preclinical analysis confirmed they had no disease and just came to the hospital for a check-up or minor surgical procedures were considered as a control group. Age and gender were matched in patients and the control group. Total ribonucleic acid was extracted from blood, and cDNA was synthesized. Eventually, the transcript levels were analysed by quantitative polymerase chain reaction, and statistical analysis was carried out. Results: Statistical analysis of gene expressions in young females affected by JIA demonstrated that MECP2 and FOXP3 were increased significantly (p-value = 0.002 and 0.05, respectively). Interleukin 32 gene expression was also increased (p-value = 0.14), whereas MBD1 gene expression was decreased (p-value = 0.06); however, these changes in the expression of all 4 genes were not significant in young males. Conclusions: Different expression levels of the mentioned genes between affected young females and males result from hormones in both gender and also methotrexate (MTX) drug. Also, the reason affected young females are more prone to JIA than males can be the lower level of FOXP3 expression in healthy females than healthy males.
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INTRODUCTION: Juvenile idiopathic arthritis (JIA) is an autoimmune rheumatic disease, which affects primarily the joints in children under 16 years old. The etiology of JIA is yet unknown but research has shown that JIA is a multifactorial disease implicating several genes and environmental factors. Environmental factors affect immune cells via epigenetic mechanisms. One of the most important epigenetic mechanisms is DNA methylation catalyzed by DNA methyltransferases (DNMTs) and usually associated with gene silencing. In this study, we analyzed the expression of three DNA methyltransferases namely DNMT1, DNMT3a and DNMT3b in peripheral blood mononuclear cells (PBMCs) of patients with JIA and compared it with the expression of these genes in healthy young individuals. MATERIALS AND METHODS: Peripheral blood mononuclear cells of 28 JIA patients and 28 healthy controls were isolated. Total RNA was extracted, cDNA was synthesized and the transcript levels of DNMTs were analyzed by quantitative PCR. RESULTS: Analysis of DNMT1, DNMT3a and DNMT3b relative gene expression in PBMCs of JIA patients and control individuals shows that the expression of DNMT1 and DNMT3a is reduced significantly by 7 folds and 5.5 folds, respectively, in JIA patients compared to healthy controls. Furthermore, the expression of all three DNMTs were significantly and drastically reduced in young affected males compared to healthy males. CONCLUSION: This study shows that the expression of DNMTs is reduced in JIA patients and this reduction is severe in male JIA patients.
