Hanan Hassan Fouad

Sodium silicate (Na2SiO) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO exposure. This study investigates the role of Na2SiO exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO suspension, respectively. Na2SiO was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats.

Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the homogentisate 1,2-dioxygenase (HGD) gene. This leads to a deficient HGD enzyme with the consequent accumulation of homogentisic acid (HGA) in different tissues causing complications in various organs, particularly in joints, heart valves and kidneys. The genetic basis of AKU in Egypt is completely unknown. We evaluated the clinical and genetic spectrum of six pediatric and adolescents AKU patients from four unrelated Egyptian families. All probands had a high level of HGA in urine by qualitative GC/MS before genetic confirmation by Sanger sequencing. Recruited AKU patients were four females and two males (median age 13 years). We identified four different pathogenic missense variants within HGD gene. Detected variants included a novel variant c.1079G > T;p.(Gly360Val) and three recurrent variants; c.1078G > C;p.(Gly360Arg), c.808G > A;p.(Gly270Arg) and c.473C > T;p.(Pro158Leu). All identified variants were properly segregating in the four families consistent with autosomal recessive inheritance. In this study, we reported the phenotypic and genotypic spectrum of alkaptonuria for the first time in Egypt. We further enriched the HGD-variant database with another novel pathogenic variant. The recent availability of nitisinone may promote the need for genetic confirmation at younger ages to start therapy earlier and prevent serious complications.

Many studies have reported the influence of hormonal drugs on gut microbiota composition. However, the underlying mechanism of this interaction is still under study. Therefore, this study aimed to evaluate the possible changes in selected members of gut bacteria exposed to oral hormonal drugs used for years. Selected members of gut bacteria were , representing the four main phyla in the gut. Selected hormonal drugs used for a long time were estradiol, progesterone, and thyroxine. The effect of intestinal concentrations of these drugs on the selected bacterial growth, biofilm formation, and adherence to Caco-2/HT-29 cell line was assessed. Short-chain fatty acids (SCFAs) have been included in host functions including the gut, immune and nervous functions; thus, the drug's effects on their production were assayed using High- Performance Liquid Chromatography. Sex steroids significantly increased the growth of all tested bacteria except , similarly, thyroxine increased the growth of tested Gram-negative bacteria however reducing that of tested Gram-positive bacteria. The effect of drugs on biofilm formation and bacterial adherence to cell lines cocultures was variable. Progesterone decreased the biofilm formation of tested Gram-positive bacteria, it nevertheless increased adherence to Caco-2/HT-29 cell line cell lines coculture. By contrast, progesterone increased biofilm formation by Gram-negative bacteria and increased adherence of to the cell lines coculture. Moreover, thyroxine and estradiol exhibited antibiofilm activity against , while thyroxine increased the ability of to form a biofilm. Moreover, hormones affected bacterial adherence to cell lines independently of their effect on hydrophobicity suggesting other specific binding factors might contribute to this effect. Tested drugs affected SCFAs production variably, mostly independent of their effect on bacterial growth. In conclusion, our results showed that the microbiota signature associated with some hormonal drug consumption could be the result of the direct effect of these drugs on bacterial growth, and adherence to enterocytes besides the effect of these drugs on the host tissue targets. Additionally, these drugs affect the production of SCFAs which could contribute to some of the side effects of these drugs.

We investigated whether a high-fat/high-sugar (HF/HS) diet alters the lipidomic profile of the oviductal epithelium (OE) and studied the patterns of these changes over time. Female outbred Swiss mice were fed either a control (10% fat) or HF/HS (60% fat, 20% fructose) diet. Mice ( = 3 per treatment per time point) were sacrificed and oviducts were collected at 3 days and 1, 4, 8, 12 and 16 weeks on the diet. Lipids in the OE were imaged using matrix-assisted laser desorption ionisation mass spectrometry imaging. Discriminative / values and differentially regulated lipids were determined in the HF/HS versus control OEs at each time point. Feeding the obesogenic diet resulted in acute changes in the lipid profile in the OE already after 3 days, and thus even before the development of an obese phenotype. The changes in the lipid profile of the OE progressively increased and became more persistent after long-term HF/HS diet feeding. Functional annotation revealed a differential abundance of phospholipids, sphingomyelins and lysophospholipids in particular. These alterations appear to be not only caused by the direct accumulation of the excess circulating dietary fat but also a reduction in the de novo synthesis of several lipid classes, due to oxidative stress and endoplasmic reticulum dysfunction. The described diet-induced lipidomic changes suggest alterations in the OE functions and the oviductal microenvironment which may impact crucial reproductive events that take place in the oviduct, such as fertilization and early embryo development.