Chemistry/Biochemistry

Le syndrome d'Alport est une néphropathie héréditaire qui s'accompagne de surdité et d'anomalies oculaires. Les ponctuations rétiniennes représentent la manifestation ophtalmologique la plus fréquente au cours de ce syndrome. Observation. -Les auteurs rapportent le cas d'un enfant de 13 ans atteint de ces lésions rétiniennes caractéristiques, associées à un syndrome d'Alport. Conclusion. -La présence des ponctuations rétiniennes au cours du syndrome d'Alport est d'une aide considérable au diagnostic et s'accompagne souvent d'une atteinte rénale sévère. © 2000 Éditions scientifiques et médicales Elsevier SAS Alport (syndrome d') / ponctuations rétiniennes Summary -Retinal flecks in Alport's syndrome. Alport's syndrome is a familial disorder characterized by progressive renal failure, sensorineural hearing loss and ocular manifestations. Case report. -The authors report a case of a 13-year-old child with Alport's syndrome associated with retinal flecks. Conclusion. -Retinal flecks are the most frequent ocular manifestation in Alport's syndrome and are a considerable help to diagnosis. They are often associated with severe renal failure. © 2000 Éditions scientifiques et médicales Elsevier SAS nephritis, hereditary / Alport's syndrome / retinal diseases / ophthalmology / child

Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor ...

Elevated Src family kinase (SFK) activity is associated with tumor invasion and metastasis. The SFK inhibitor saracatinib (AZD0530) is currently in phase II trials in patients including those with colorectal cancer (CRC), where links between SFK activity and poor prognosis are particularly striking. Saracatinib is likely to be used clinically in combination regimens, specifically with 5-fluorouracil (5-FU) and oxaliplatin, in CRC. The aim of this study was to determine the effect of saracatinib on oxaliplatin and 5-FU efficacy in CRC cells. Saracatinib did not modulate 5-FU efficacy but antagonized oxaliplatin in a schedule-specific manner through reduced oxaliplatin uptake via an SFK-independent mechanism. Saracatinib resembles the pharmacophore of known organic cation transporter (OCT) inhibitors and reduced oxaliplatin efficacy maximally in cells overexpressing OCT2. These data suggest that oxaliplatin uptake in CRC is attenuated by saracatinib via inhibition of OCT2, a potential consideration for the clinical development of this SFK inhibitor.

End-stage renal disease (ESRD) is a state of chronic inflammation. DNA methylation is a major epigenetic modification that has the potential to silence gene expression. IFN-γ and suppressor of cytokine signaling (SOCS) are essential modulators of inflammation. The current study aimed to determine the methylation status of IFN-γ, SOCS1 and SOCS3 promoter regions in DNA isolated from peripheral blood of ESRD patients and controls, in order to correlate this methylation status with the clinical features of ESRD. Ninety six ESRD patients and 96 healthy ethnically, age and gender matched controls were included in the study. The promoter methylation of the studied genes was assessed using the methylation-specific polymerase chain reaction (MSP). Most of our samples were positive for IFN-γ promoter methylation. Full unmethylation was observed only in the ESRD group (7.3%), and statistical difference was observed among groups (P=0.02). IFN-γ unmethylation was associated to a decrease in estimated glomerular filtration rate (eGFR) and an increase in both serum creatinine and total cholesterol levels. For SOCS1 promoter methylation, partial and full methylation were observed only in ESRD patients (5.2% and 2.1%, respectively); however no methylation was detected in controls (P=0.014). SOCS3 promoter methylation was not detected in either the patient or control group. In conclusion, the methylation profile of IFN-γ and SOCS1 promoter regions play an important role in the pathogenesis of ESRD. The present study highlights the role of epigenetics in disease progression. proteins: cytokine-inducible SH 2 protein (CIS) and SOCS1-SOCS7.

Objectives: Among tropical diseases, schistosomiasis caused by Schistosoma mansoni is the second major cause of morbidity and mortality worldwide. Inflammation was considered as an adverse event that contributes to the pathology associated with schistosomiasis. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) have been implicated in the process of angiogenesis. The current study aimed to evaluate the effect of S. mansoni infection on HO-1 gene expression, IL-4, IL-12, and VEGF to address the role of these factors in the pathogenesis of schistosomiasis. Methods: Thirty mice divided equally into three groups comprised a non-infected control group and two S. mansoni-infected groups. Infected animals were studied at 8 and 12 weeks post-infection. Serum IL-4, IL-12, and VEGF were measured. HO-1 mRNA was detected by RT-PCR of liver homogenates and HO activity was assessed as percentage of carboxy hemoglobin. Results: S. mansoni-infected mice showed a progressive incre...

Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR-RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a signi cant association between the VEGFA rs25648 C allele and breast cancer risk (OR = 2.5, 95% CI = 1.7-3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically signi cantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (P = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically signi cantly higher in breast cancer patients vs. control (P = 0.001). There was no signi cant difference in genotypes and allele frequencies of HIF-1A rs11549465 polymorphism between breast cancer cases and control individuals (P > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (P < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a signi cant association with increased breast cancer risk in Egyptian patients.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins:

Objective The study aimed to investigate the over expression of IFITM3 in hepatocellular carcinoma Egyptian patients. Background Hepatocellular carcinoma (HCC) continues to be a serious disease burden. Interferon Induced Transmembrane protein 3 (IFITM3) is a protein that encoded in humans by the IFITM3 gene. It plays a critical role in the immune system's defense, responsible for a large portion of the antiviral activity. In this study, we showed that IFITM3 rs 12252-CC was over expressed in HCC patients compared to control group with HCV infection. Method DNA sequencing was applied for detection of IFITM3 rs 12252-CC and IFITM3 protein level was measured by ELISA to 50 patients with HCC with cirrhosis and 50 with Hepatitis C virus infection. Results The obtained results of this study indicated that IFITM3 rs 12252-CC was significantly elevated in HCC group, the codominant model of CC genotype of IFITM3 gene had high association with risk of hepatocellular carcinoma with odd ratio (OR) = 2.70, p = 0.041. Conclusion IFITM3 play an important role in progression of hepatocellular carcinoma. Results revealed that IFITM3 rs 12252-CC among Hepatocellular carcinoma patients would allow diagnosis and starting intervention.

Worldwide mortality from hepatic fibrosis remains high, due to hepatocellular carcinoma and end stage liver failure. The progressive nature of hepatic fibrosis from inflammation to cicatrized tissues warrants subtle intervention with pharmacological agents that hold potential. Empagliflozin (Empa), a novel hypoglycemic drug with antioxidant and anti-inflammatory properties, has lately been proposed to have additional antifibrotic activities. In the current study, we examined the antifibrotic effect of the Empa through modulating the activity of hepatic stellate cells by hedgehog (Hh) pathway. We also assessed the markers of inflammatory response and endoplasmic reticulum (ER) stress. Male Albino rats were treated with either CCl 4 (0.4 mg/kg twice/week) and/or Empa (10 mg/kg/day) for eight weeks. In this study, CCl 4 rats had active Hh signaling as indicated by overexpression of Patched 1, Smoothened and Glioblastoma-2. CCl 4 induced ER stress as CHOP expression was upregulated and ERAD was downregulated. CCl 4-induced inflammatory response was demonstrated through increased levels of TNF-α, IL-6 and mRNA levels of IL-17 while undetectable expression of IL-10. Conversely, Empa elicited immunosuppression, suppressed the expression of Hh markers, and reversed markers of ER stress. In conclusion, Empa suppressed CCl 4-induced Hh signaling and proinflammatory response, meanwhile embraced ER stress in the hepatic tissues, altogether provided hepatoprotection.

Mono, bis and tris complexes of rhodium(III) oxine (systematic name 8-hydroxy-7-quinolinecarboxaldehyde) and mixed ligand have been prepared. The amine exchange reaction of coordinated Schiff base in these complexes has also been carried out, which gives symmetrical tetradentate Schiff base complexes. The complexes are characterized by elemental and thermal analysis, IR, magnetic and electronic spectral analysis methods were also employed as well as conductivity measurements. An octahedral structure is proposed for all the new complexes in which chloride is attached to the metal ion in 1:1; 1:2 (metal:ligand) ratio. The spectral data were utilized to compute the important ligand field parameter B, i and Dq. The B-values suggest a strong covalency in the metal-ligand s-bond and the Dq-values indicate a medium strong ligand field. 1 H NMR spectra show that the tris (ligand) complex is cis isomer. IR spectra show that the ligand is mono-basic bidentate.

New polymeric complexes of Cu(II), Co(II), Ni(II) and UO 2 (II) with 5-(2 1 -carboxyphenylazo)-8-hydroxyquinoline (LH 2 ) have been prepared and characterized on the basis of analytical, magnetic, 1 H NMR, EPR and electronic spectral studies. Tentative structures for the polymeric complexes are proposed. The important infrared (IR) bands and the main 1 H NMR signals are assigned and discussed relative to the molecular structure. EPR spectrum of copper(II) complex has been studied with a view to assigning their stereochemistries. Various EPR parameters have been calculated. Each metal has six-coordinates in an octahedral environment. The ligand acts as a dibasic (bis-bidentate chelating agent coordinating through CN, N=N, COOH and OH groups by replacement of a proton from the two latter groups. Considerable interest has also been focused on the synthesis of the azo compounds and its polymeric metal complex due to its wide potential applications. The thermal decomposition behavior of the complexes is also discussed. ଝ This article has been abstracted from the M.Sc. thesis of M.A. Hussien. (A.Z. El-Sonbati).

We use (PAN/AC) composite as adsorbent for the removal of textile dyes. XRD and FRIR studies have been carried out for characterization of the composite. Langmuir and Freundlich isotherms have been used to find out the best fit model. Kinetic and thermodynamic studies of the surfactant adsorption have been investigated. Results are of marked significance to the water treatment industries. g r a p h i c a l a b s t r a c t Effect of initial dye concentration on adsorption of AR57 on to (PAN/AC) composite at dye concentration 60 mg/L, pH 1 and 25°C. 15 30 45 60 75 90 105 120 65 70 75 80 85 90 95 100 40 mg/L 120 mg/L 70 mg/L Removal (%) t (min.) 150 mg/L a b s t r a c t