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This study aimed to determine the earliest markers of diabetic nephropathy (DN) onset with discriminative potentials from controlled diabetes (CD).Sixty male Wistar rats were allocated into three groups (20/group), the two diabetic groups CD and DN received 45 and 65 mg/kg STZ in 0.1 mole/L citrate buffer, respectively, while the control group received only the vehicle. Serum/urinary levels of glomerular, tubular, oxidative and proinflammatory markers were weekly monitored.Each diabetic group showed a different pattern of inflammatory, oxidative and signs of nephropathy along the study period, but none had a discriminative power until the fourth week. At this time point, levels of urinary transferrin, serum/urinary IL-6 and TNF-α as well as urinary IL-18 were significantly higher in DN group compared to CD (Urinary transferrin and the inflammatory endpoints proposed in this study might represent promising biomarkers for the early DN onset.

The Eremobium aegyptiacum (Spreng.) Schweinf.et Asch.ex Boiss aqueous extract (EAAE) was subjected to phytochemical investigation using LC–ESI–MS analysis. Twenty-seven compounds (one organic acid, two phenolic acids and twenty-four flavonoids) were characterized and tentatively identified. Among the detected compounds, acyl triglycoside derivatives of kaempferol and isorhamnetin are identified in the current study by using LC–MS technique for the first time from this species. EAAE was evaluated for its anti-Alzheimer activity. EAAE dose (156 mg/kg bw/day) was administrated for 6 weeks orally to female adult rats prior treated with AlCl3 (50 mg/Kg b.wt) to induce Alzheimer disease. AChE level, lipid profile (TC, TG and LDL-C) levels, reduced glutathione (GSH) and malondialdehyde (MDA) levels were investigated. EAAE exhibited significant reduction in AChE level (58.57 ± 9 µMSH/min/mg protein) in comparison with AlCl3 group (97.88 ± 9.87 µMSH/min/mg protein). Also, GSH level was increased to 100.09 ± 25.51 mg/g tissue and MDA level was decreased to 1.26 ± 0.1 µmol/g tissue, compared to AlCl3 rats (57.05 ± 12.56 mg/g tissue and 1.96 ± 0.29 µmol/g tissue, respectively). Additionally, lipid profile (TC, TG, LDL-C) levels were significantly reduced to 35.15 ± 4.74, 18.16 ± 3.07 and 35.75 ± 4.17 µmol/g tissue, in comparison with AlCl3 group (65.20 ± 5.54, 27.93 ± 3.51 and 63.84 ± 6.98, respectively). Briefly, EAAE succeeded in amelioration of the increased AChE activity and the antioxidant activity which considered as an important defense mechanism to control the brain injury in AlCl3 rats. This amelioration was parallel to its effect on total cholesterol triglycerides and LDL levels.

Curcuma longa (Family, Zingiberaceae) is rich in polyphenolic compounds; curcuminoids which is used in traditional medicine as antioxidant, anti-tumor, antimicrobial, anti-inflammatory, wou...

The expedient fungi Candida albicans (C. albicans) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by C. albicans (1.5 × 106 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. Candida albicans significantly elevated serum MDA. On the other hand, C. albicans injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersۥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent. Keywords: Candida albicans, Diflucan, α-SMA, COX-2, Total antioxidant, Acetylcholinestrase

Introduction — Egypt has the highest prevalence of hepatitis C virus (HCV) infection which is reported to be associated with autoimmune manifestations. Aim — There is a need for markers that enable differentiation between viral and non-infected-autoimmune patients. Material and Methods — Levels of the B-cell activation factor (BAFF), IL6, IL10 and TNF-α were quantified by ELISA in sera from HCV-infected-autoimmune patients (HCV-AI), HCV-infected patients with no autoimmune diseases (HCV-NAI), non-infected autoimmune patients (NIAI) and healthy control humans (C). Results — HCV-infected patients were 12.96, 8.33, 69.44 and 36.11% positive for the auto-antibodies ANA, AMA, ASMA and AGPCA respectively. The BAFF level was significantly (P

Background/aim Alzheimer’s disease (AD) is a chronic neurodegenerative disease. The AD incidence is rising and is becoming a heavy economic burden on society and patients’ families. The present study was directed to investigate the protective and therapeutic effects of Hyphaene thebaica fruit extract (HTE) on AD in an animal model. Materials and methods A total of 90 adult albino male rats were involved in this study and were classified into six groups (15 each). Two negative control groups were used: one did not take any supplementation (G1) and a second negative control group in which normal rats were supplemented with HTE (G2). AD induction was performed by orally injecting the animals with 50 mg AlCl3/kg body weight for 6 weeks. Four groups took AlCl3. First group served as a positive control (G3). Two groups were used to investigate the effect of the orally injected HTE on AD rats either as a therapeutic (G4) or preventive (G5) agent. The last group was treated with the reference drug donepezil (G6). After treatment with HTE for 4 weeks, biochemical analyses of acetylcholinesterase activity, lipid peroxidation (malondialdehyde), and reduced glutathione were done in the brain tissue homogenate. Lipid profile was determined in sera. Expression level assessments of genes encoding microtubule-associated protein tau and amyloid precursor protein were carried out as well as DNA adducts were measured in brain tissues. Histopathological investigations of brain tissues were also performed. Results The results showed that brain samples of AD group exhibited significant changes in biochemical, molecular, and histopathological parameters. The samples of the groups treated with HTE showed improvements in the studied parameters. The treatment of induced AD group with HTE showed better results than supplementing the extract after occurrence of the signs of Alzheimer. Conclusion It was concluded that HTE acts as a promising candidate natural product to ameliorate and protect brain injury in AD-induced rats.

Graphical abstract, Highlights • The current study interested by treatment of Candida albicans in case of invading the fungi into brain and kidney. • Investigating novel synthesized compounds as antifungal agents then determining their efficiency and safety margin. • Assessment molecular biochemical parameters specific for inflammation. • Comparing their antifungal effect to Diflucan in case of invading the fungi to kidney and brain tissue., The expedient fungi Candida albicans (C. albicans) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by C. albicans (1.5 × 106 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. Candida albicans significantly elevated serum MDA. On the other hand, C. albicans injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersۥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent.

Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU). Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed. Candida albicans significantly elevated serum alanine aminotransferase (ALT) and butrylcholinesterase (BCHE) as well as hepatic malondialdehyde (MDA). Molecular analysis confirmed a significant up-regulation in mRNA gene expression of Agglutinin-like sequence (ALS1), hepatic cytochrome p450 (Cyp450). Vaginal COX-2 gene expression was also elevated. Nevertheless, a significant down-regulation was apparent in mice treated with the aforementioned compounds. Meanwhile, administration of 14b in a high dose noticeably down-regulated the altered parameters expression showing a significant effect in comparison to animals treated with the variable doses of the tested compounds. Histopathological finding confirmed the obtained results. The current work investigated the efficiency of new synthetic pyrimidine derivatives 14bas anti-microbial agents and recommended to be improved and evaluated as a novel antifungal drug to overcome the emergence of resistance problem.

Despite effective chemotherapy, schistosomiasis remains the second major public health problem in the developing world, second to malaria. The present study was undertaken to explore the therapeutic effect of the micronutrients (vitamin E and selenium) and chloroform extract of Citharexylum quadrangular leaves and their mixture against the deleterious pathological impacts induced in mice livers by Schistosoma mansoni infection. Parasitological markers showed that oral ingestion of the different supplements to S. mansoni infected mice was effective in reducing the worm burden with concomitant decrease in the egg burden, granuloma count and its diameter as well as total area of infection in their livers versus untreated ones. Parasitological parameters were reflected by the improvement of the histopathological pictures of livers of infected-treated mice. The current investigation also showed that the used agents and their mixture successfully modulated liver fibrosis of infected mice which was documented by a marked decrease of liver hydroxyproline level ( as biomarker of liver fibrosis) as well as the serum levels of inflammatory fibrogenic mediators namely, fructosamine, tumor necrosis factor alpha (TNFα) and total immunoglobin E (IgE). In addition, the used agents showed ameliorative action on the elevated liver oxidative stress- nitric oxide (NO) and malondialdehyde (MDA) and the decreased antioxidant biomarkers, reduced glutathione (GSH), glutathione reductase (GR), thioredoxin reductase (TrxR) and catalase (CAT) which may have a role in liver damage and fibrosis due to S mansoni infection. In conclusion, treatment with the used micronutrients and plant extract either alone or in combination attenuated the deleterious impacts of S. mansoni infection on mice livers. The combination of all supplements was more effective as it greatly modified the inflammatory mediators and oxidative stress responsible for schistosomal liver fibrosis. Key words: Citharexylum quadrangular; Vitamin E, selenium, Shistosoma mansoni, antioxidants.

Objective: The objective of this study is to investigate the efficacy of microalgae Dunaliella salina to improve apelin, oxidative damage, inflammatory, and apoptotic function implicated in high-fat diet (HFD)-induced obesity in rats.Methods: Fifty male Westar albino rats weighing 150–160 g were fed on HFD for 12 weeks. Treatment of obese rats with D. salina was carried out in a dose 150 mg/kg body weight as compared to orlistat as anti-obesity standard drug. Blood nuclear factor kappa-B cells (NF-kB), apelin, apoptosis regulator (B-cell lymphoma 2 [BCl2]), monocytes chemo attractant protein-1, paraoxonase-1 (PON1) were determined in serum of different groups. Besides, lipid peroxidation (malondialdehyde [MDA]), glutathione (GSH) levels as well as histopathological examination were investigated in liver tissue of obese rats.Results: Serum apelin, MDA, and NF-kB levels were significantly high, reached to 97.25, 158.18, 511.433, and 170.73%, respectively. While significant decrease in PON1 (47.82%), BCl2 (74.88%), and GSH (63.54 %), levels were detected in the obese rats compared to controls. Obviously improvement in all biomarkers under investigation upon treated obese rats with ethanol extract of D. salina. Histopathological examination of obese hepatic tissue showed dilatation in the central portal veins associated with inflammatory cells infiltration in the portal area and congestion. However, treatment of obese rats with D. salina confirmed biochemical analysis and declared less diffuse inflammatory cells infiltration as well as less focal infiltration in both hepatic parenchyma and portal area with higher improvement in D. salina than drug.Conclusion: It could be concluded that D. salina has a great ability to improve inflammation associated with obesity as well as damaged hepatic architectures which can be used as a promising anti-obesity nutraceuticals.

Praziquantel (PZQ), the drug of choice according to the World Health Organization (WHO), causes some side effects. The appearance of drug resistance against PZQ in Schistosoma mansoni infected species leads to must introduce new effective compounds and/or suppress its side effects. The aim of present work is a trial to solve this problem. Chloroform extract of Citharexylum quadrangular jacq leaves was used as a medicinal plant, which affect the Schistosoma mansoni adults. Prophylactic and therapeutic treatment of Schistosoma mansoni infected mice with the plant extract and/or the antioxidants vitamin E and selenium in combination with PZQ was studied. The study revealed that the combination of the chloroform extract together with vitamin E and selenium improved the efficiency of PZQ. These supplementations are very effective in ameliorating the oxidative insult as well as other parameters: glutathione reductase (GR), thioredoxin reductase (TrxR), catalase (CAT) and reduced glutathione (GSH), nitric oxide (NO) and lipid peroxidation (MDA), hepatic hydroxyproline content, Alanine aminotransferase (ALT), Gamma-glutamyltransferase (γ-GT), tumor necrosis factor-alpha (TNFα), interleukin- 10 (IL-10) and total immunoglobulin E (total IgE) associated with Schistosoma mansoni infection.