Type 1 diabetes (T1D) is a chronic autoimmune disorder that results from destruction of the insulin‐producing pancreatic β‐cells. The disease mainly affects juveniles. Changes in the composition of the gut microbiota (dysbiosis) and changes in the properties of the gut barrier have been documented in T1D subjects. Because these factors affect immune system functions, they are likely to play a role in disease pathogenesis. However, their exact role is currently not fully understood and is under intensive investigation. In this article we discuss recent advancements depicting the role of intestinal dysbiosis on immunity and autoimmunity in T1D. We also discuss therapies aimed at maintaining a healthy gut barrier as prevention strategies for T1D.
The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafbfl/fl CAG-CreER™ (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells.
Buffaloes represent a major source of milk production, especially in developing countries including Egypt. The buffalo foot is frequently involved in a large proportion of lameness cases. The relatively small size and complexity of its structures often render the radiographic evaluation of the foot challenging. Magnetic resonance imaging (MRI) is a noninvasive imaging technique that is regarded as both safe and accurate for assessment of the foot disorders in both man and animals. The purpose of the current investigation was to describe the MRI anatomy of buffalo foot using cadaveric hind feet. The feet were subjected to consecutive MRI scanning using a 0.3 Tesla scanner. Both T1-weighted (T1-W) and T2-weighted (T2-W) spin-echo pulse sequences were applied in dorsal, sagittal and transverse planes. The heterogeneity of signal intensities noted amongst foot components allowed for clear differentiation of bones, tendons, ligaments, adipose tissue and synovial fluid. The T1-W images provided an excellent overview of the foot. They were valuable for visualizing the bones and the alignment of tendons and ligaments. The T2-W images were particularly useful for the evaluation of synovial structures such as tendon sheaths and joint cavities. A communication between the two plantar sacs of the metatarsophalangeal (fetlock) joints was evident in T2-W images. MRI findings were further confirmed using relevant gross anatomical sections. The present study establishes a detailed MRI anatomic reference of buffalo foot that could help veterinary researchers, clinicians and surgeons for increasing the accuracy of interpretation of foot MRI scans of both healthy and diseased animals.
The transcription factor c-Maf is a member of the large Maf family, members of which possess transactivation and bZIP domains. c-Maf plays an important role in lens formation, Tlymphocyte differentiation, hypertrophic chondrocyte differentiation, and kidney development in mouse embryos. However, because homozygous deletion of c-Maf in C57BL/6J mice causes embryonic lethality, the functions of c-Maf in adult mice remain largely uninvestigated. To address this issue, we generated c-Maf floxed (c-Maf fl/fl) C57BL/6J mice and established tamoxifen-inducible c-Maf knockout mice (c-Maf fl/fl ; CAG-Cre-ER TM mice, c-Maf ΔTAM). After tamoxifen injection, adult c-Maf ΔTAM mice showed successful deletion of c-Maf protein and developed severe cataracts; cataracts are also seen in human patients who have mutations in the c-MAF DNA binding domain. Furthermore, adult c-Maf ΔTAM mice exhibited abnormal lens structure and impaired differentiation of lens fiber cells. In summary, we established c-Maf fl/fl and c-Maf ΔTAM C57BL/6J mice, which can be useful animal models for the investigation of c-Maf function in various developmental stages and can also be used as a disease model for cataracts.
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