The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.

The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO T cells reside in the fetal intestine. Here we combined functional assays with mass cytometry, single-cell RNA sequencing and high-throughput T cell antigen receptor (TCR) sequencing to characterize the CD4 T cell compartment in the human fetal intestine. We identified 22 CD4 T cell clusters, including naive-like, regulatory-like and memory-like subpopulations, which were confirmed and further characterized at the transcriptional level. Memory-like CD4 T cells had high expression of Ki-67, indicative of cell division, and CD5, a surrogate marker of TCR avidity, and produced the cytokines IFN-γ and IL-2. Pathway analysis revealed a differentiation trajectory associated with cellular activation and proinflammatory effector functions, and TCR repertoire analysis indicated clonal expansions, distinct repertoire characteristics and interconnections between subpopulations of memory-like CD4 T cells. Imaging mass cytometry indicated that memory-like CD4 T cells colocalized with antigen-presenting cells. Collectively, these results provide evidence for the generation of memory-like CD4 T cells in the human fetal intestine that is consistent with exposure to foreign antigens.

Introduction: Phoenix dactylifera L. (date palm) is one of the most valued crops worldwide for its economical and nutraceutical applications of its date fruit (pericarp). Currently date pits, considered as a waste product, is employed as coffee substitute post roasting. Whereas, pollen represents another valuable by-product used as a dietary supplement. Objectives: In this study, a large-scale comparative metabolomics approach was performed for the first characterization and standardization of date palm by-products viz., date pits and pollen. Moreover, roasting impact on date pit metabolite composition was also assessed. Methods: Metabolites profiling of pits and pollen was determined via a multiplex approach of UPLC–MS and NMR, coupled to multivariate analysis, in relation to its antioxidant activities. Results: Chemical analyses led to the identification of 67 metabolites viz., phenolic acids, flavonols, fatty acids, sphingolipids, steroids and saponins of which 10 are first time to be reported. The enrichment of steroids in date pollen accounts for its fertility promoting properties, whereas date pit was found a rich source for antioxidant polyphenols using metabolomics. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

INTRODUCTION: Phoenix dactylifera L. (date palm) is one of the most valued crops worldwide for its economical and nutraceutical applications of its date fruit (pericarp). Currently date pits, considered as a waste product, is employed as coffee substitute post roasting. Whereas, pollen represents another valuable by-product used as a dietary supplement.

OBJECTIVES: In this study, a large-scale comparative metabolomics approach was performed for the first characterization and standardization of date palm by-products viz., date pits and pollen. Moreover, roasting impact on date pit metabolite composition was also assessed.

METHODS: Metabolites profiling of pits and pollen was determined via a multiplex approach of UPLC-MS and NMR, coupled to multivariate analysis, in relation to its antioxidant activities.

RESULTS: Chemical analyses led to the identification of 67 metabolites viz., phenolic acids, flavonols, fatty acids, sphingolipids, steroids and saponins of which 10 are first time to be reported. The enrichment of steroids in date pollen accounts for its fertility promoting properties, whereas date pit was found a rich source for antioxidant polyphenols using metabolomics.

Ziziphus plants are well recognized for their nutritive and medicinal value worldwide, albeit their chemical profile has yet to be fully reported. The secondary metabolites profile of three traditionally used Ziziphus leaf accessions was investigated via ultra-high performance liquid chromatography coupled to photodiode array and electrospray ionization mass detectors (UHPLC/PDA/ESI-MS). A total of 102 metabolites were characterized revealing the first holistic approach onto Ziziphus leaf metabolome and to include the first report of several novel flavonoids and cyclopeptide alkaloids. Fragmentation pattern for cyclopeptide alkaloids was proposed via ESI-MS. Principal component analysis (PCA) revealed close metabolite resemblance among Z. spina-christi and Z. mauritiana leaf specimens found enriched in saponins and distinct from that of Z. jujuba in which quercetin-3-O-(2-pentosyl)-rhamnoside was most abundant. Further, in-vitro antioxidant, anti-inflammatory and antidiabetic assays revealed for Z. spina-christi and Z. mauritiana strong effects compared to Z. jujuba and in correlation with their metabolites repertoire.

The potential inhibitory effect of the antidiabetic and anti-inflammatory drug, metformin on thioacetamide (TAA)-induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)-hypoxia-inducible factor-1α (HIF-1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group). Using light and electron microscopy examinations, we observed in the model group substantial damage to the hepatocytes and liver tissue such as collagen deposition, infiltration of inflammatory cells, and degenerative cellular changes with ballooned mitochondria that were substantially ameliorated by metformin. Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1α, mTOR, the profibrogenic biomarker α-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples. In addition, a significant ( p < 0.01) positive correlation between hypoxia scoring (HIF-1α) and the serum levels of TNF-α ( r = 0.797), IL-6 ( r = 0.859), and ALT ( r = 0.760) was observed. We conclude that metformin protects against TAA-induced hepatic injuries in rats, which is associated with the inhibition of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.

The potential inhibitory effect of the antidiabetic and anti-inflammatory drug, metformin on thioacetamide (TAA)-induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)-hypoxia-inducible factor-1α (HIF-1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group). Using light and electron microscopy examinations, we observed in the model group substantial damage to the hepatocytes and liver tissue such as collagen deposition, infiltration of inflammatory cells, and degenerative cellular changes with ballooned mitochondria that were substantially ameliorated by metformin. Metformin also significantly ( p < 0.05) inhibited TAA-induced HIF-1α, mTOR, the profibrogenic biomarker α-smooth muscle actin, tissue inhibitor of metalloproteinases-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase in harvested liver homogenates and blood samples. In addition, a significant ( p < 0.01) positive correlation between hypoxia scoring (HIF-1α) and the serum levels of TNF-α ( r = 0.797), IL-6 ( r = 0.859), and ALT ( r = 0.760) was observed. We conclude that metformin protects against TAA-induced hepatic injuries in rats, which is associated with the inhibition of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers; thus, may offer therapeutic potential in humans.

BACKGROUND: MHC class II deficiency leads to defective CD4 T-cell function that results from impaired antigen presentation. A genetic disorder in 1 of 4 genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency.

OBJECTIVE: To describe the clinical, immunological, and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC class II deficiency between 2012 and 2017.

METHODS: An initial diagnosis based on the combination of clinical features and low HLA-DR expression by flow cytometry was confirmed by genetic analyses.

RESULTS: Symptoms included failure to thrive (n = 9), persistent diarrhea (n = 5), and pneumonia (n = 8). Septicemia due to coagulase-negative staphylococci (n = 1) and Candida krusei (n = 1) was diagnosed. Nine patients orally received the live attenuated polio vaccine, of whom 3 developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, 1 carried a CIITA gene mutation, and none carried RFXAP gene mutations. Six of the 7 detected mutations were previously unreported mutations: c.431T>C, c.247_250delTCAG, and c.600delG in the RFXANK gene; c.116+1G>A and c.715C>T in the RFX5 gene; and c.929delA in the CIITA gene.

CONCLUSIONS: Given that Egypt is a North African country with a high rate of consanguinity, MHC class II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based on suspicious clinical signs and laboratory diagnosis because the defect can be missed by T-cell receptor excision circles based on neonatal screening.