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Aims: To assess the anti-atherosclerotic effects of Myricetin (pharmaceutical) in human THP-1 macrophages following IFN-γ or MCP-1 stimulation. Study Design: The protective effects of myricetin against atherosclerosis was evaluated using the humanTHP-1 macrophages and studying the following parameters namely, cell viability, cell proliferation, cell migration, inflammation related gene expression and cholesterol efflux in vitro. Place and Duration of Study: THP-1 cell line: Department of biochemistry (faculty of science), Cell Culture Unit, Experimental Biochemistry Unit (King Fahad Medical Research Centre), King Abdul Aziz University, between September 2019 and September 2020. Methodology: The THP-1 cell lines were differentiated into macrophages by incubation with PMA (160 nM) for 24 hours. The viability percentage was determined using Pierce LDH cytotoxicity assay kit, the percentage change in macrophages proliferation was evaluated by crystal violet dye, the RNA was extracted then the cDNA was synthesized and the quantitative real time polymerase chain reaction (qRT-PCR) was done for inflammation-related genes, ICAM-1 and MCP-1. The percentage of monocyte migration and cholesterol efflux were also calculated. Results: Cytotoxicity assays demonstrated no significant toxicity with myricetin at 25μM and 50 μM concentrations on THP-1 macrophages. The quantitative real-time RT-PCR (qRT-PCR) demonstrated a significant increase in interferon gamma (IFN-γ) mediated expression of both intercellular adhesion molecule (ICAM-1) and monocyte chemo-attractant protein-1 (MCP-1) by 2.1 and 7.1 fold respectively, compared to the control. Treatment with myricetin (25 μM and 50 μM) significantly inhibited the IFN-γ induced overexpression of ICAM-1 by 42.86% & 71.34% and MCP-1 by 53.52% & 87.32% respectively. Myricetin (25 μM) significantly reduced the migration of monocytes by 33.66% compared to MCP-1. The cholesterol efflux from THP-1 macrophages treated with myricetin was significantly increased by 47% and 57% in the absence and presence of IFN-γ, respectively compared to the control. Conclusion: Myricetin has anti-inflammatory effects and supports cholesterol efflux, which can help in prevention of atherosclerosis. Furthermore, myricetin did not exhibit any cytotoxic effects and therefore is a safe phytochemical which can complement conventional therapeutics.

Although there are numerous drugs available for the treatment of gastric ulcers (GU), these drugs are not always effective. Antidepressant medications have been used for a variety of non-psychiatric indications, including antiulcer activity in various ulcer models. The purpose of this study was to compare the antiulcer effects of fluvoxamine and mirtazapine in two rat GU experimental models and to determine their relationship to antioxidant and antisecretory mechanisms.The antiulcer activities of various doses of fluvoxamine and mirtazapine on water immersion restraint stress (WIRS) and pyloric ligation-induced GU in rats have been studied against the positive control antiulcer drug famotidine. Various oxidative stress markers were evaluated.Fluvoxamine and mirtazapine significantly protected against WIRS and pyloric ligation-induced gastric lesions, as evidenced by a dose-dependent decrease in ulcer index, myeloperoxidase (MPO) activity, lipid peroxidation, and an increase in prostaglandin E2, nitric oxide (NO), and reduced glutathione levels, as well as increased antioxidant enzyme activity. In the pyloric ligation model, fluvoxamine and mirtazapine improved GU more than famotidine. Furthermore, a 30 mg/kg dose of mirtazapine significantly improves both NO levels and MPO activity compared to famotidine.The results highlighted the relationship in correlating the antiulcer effect of drugs from different antidepressant classes across two animal GU models, implying that antidepressants that affected both norepinephrine and serotonin levels (mirtazapine) had a more potent antiulcer effect in WIRS-induced gastric model than drugs that only affected serotonin levels (fluvoxamine).

Background: Viral hemorrhagic fevers (VHF) refers to a group of febrile illnesses caused by different viruses that result in high mortality in animals and humans. Many risk factors like increased human-animal interactions, climate change, increased mobility of people and limited diagnostic facility have contributed to the rapid spread of VHF. Materials: The history of VHFs in the Saudi Arabian Peninsula has been documented since the 19th century, in which many outbreaks have been reported from the southwestern region of Saudi Arabia. Despite presence of regional network of experts and technical organizations, which expedite support and respond during outbreaks, there are some more challenges that need to be addressed immediately. Gaps in funding, exhaustive and inclusive response plans and improved surveillance systems are some areas of concern in the region which can be dealt productively. This review primarily focusses on the hem- orrhagic fevers that are caused by three most common viruses namely, the Alkhurma hemorrhagic fever virus, Rift valley fever virus, and Dengue fever virus. Conclusion: In summary, effective vector control, health education, possible use of vaccine and concerted synchronized efforts between different government organizations and private research institutions will help in planning effective out- break-prevention and response strategies in future. Keywords: Viral fever; hemorrhagic fever (VHF); Saudi Arabia; challenges; management; future considerations.

Backgroud: Polycystic ovary syndrome (PCOS) is considered as a common cause of hormonal disturbance and obesity. The diagnosis of PCOS was done by different methods including clinical signs as anovulation, hyperandrogenism, biochem- ical markers and ultrasounographic investigation. This study investigated comparative outcomes of ultrasonographic and biochemical markers for early prediction of PCOS in obese women. Subjects and methods: Seventy-five patients were clinically diagnosed with obese, PCOS and obese with PCOS and twen- ty-five normal age matched subjects were enrolled as control. Abdominal and transvaginal ultrasonographic for assessment of ovarian properties. In addition, BMI, serum free testosterone, dehydroepiandrosterone (DHEA), insulin, glycosylated hemoglobin (HbA1c) and LDL-c levels were evaluated. Results: In obese patients with PCOs (20%) ovaries revealed normal appearance in morphology while the rest (80%) showed PCOs in the form of cysts of 2–8 mm in diameter peripherally arranged around stroma. A significant elevation of free testosterone, DHEA and insulin in obese with or without PCOS compared with obese group (p

Alzheimer’s disease (AD) is atrophy of brain cells that lead to decline in the mental capacity and memory. This study investigated the mechanism which postulates that intraneuronal accumulation of ...

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent. Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Background: Worldwide, breast cancer is a main cause of morbidity and mortality in females. Doxorubicin (DOX) is an anthracycline anticancer drug and most commonly employed in polychemotherapy protocols in the treatment of solid and hematological tumors. Unfortunately, its optimal clinical benefit is limited secondary to the rapid development of DOX resistance and therapeutic failure. Aim: Therefore, the current study has been initiated to investigate the possible mechanisms whereby the calcium channel blocker Verapamil (VER) could decrease DOX resistance and enhance the cytotoxic activity of DOX against the growth of human breast cancer cells. Methodology: To achieve the ultimate goal of this study, we have examined DOX-induced cytotoxicity, apoptosis, alteration in the function of multidrug resistance proteins and cell cycle phase distribution against MCF-7 cell line in presence and absence of Verapamil. Results: Addition of VER enhanced the cytotoxic effect of DOX against the growth of MCF-7 cells which manifested as a significant decrease in the IC50 from 36 µg/ml for DOX alone to 13 µg/ml for DOX plus VER. Moreover, combined treatment with VER and DOX significantly increased percentage of early apoptosis and cells arrested in G0/G1 phase when compared to DOX alone. In addition, VER significantly increased DOX cellular uptake through inhibition of the function of multidrug resistant proteins. Conclusion: VER treatment enhanced the cytotoxic activity of DOX against the growth of MCF-7 cells secondary to increase its cellular accumulation. The observed increase in DOX uptake by VER was parallel to increased accumulation of Rho-123 dye which my point to the contribution of inhibition of multidrug resistant proteins by VER in the enhancement of DOX cytotoxicity.

Background: L-carnitine and vitamin E have antioxidant properties. This study aimed to assess the effectiveness of L-carnitine, vitamin E and their combination in protection against isoproterenol (ISO)-induced biochemical and histopathological changes in rat heart. Materials and methods: Fifty male Wistar rats assigned to five groups; control, ISO-treated group (100 mg/kg), ISO + vitamin E-treated group (100 IU/kg), ISO + L-carnitine (100 mg/kg) and ISO + vitamin E + L-carnitine treated group. At the end of the experiment, serum cardiac enzyme as well as the cardiac level malondi- aldehyde (MDA), antioxidant enzymes and inflammatory cytokines interleukin-6, tumour necrosis factor alpha (TNF- a ) were assessed. Histopathological changes in the left ventricle wall were assessed using the light and electron microscopy. Results: Treating rats with vitamin E and L-carnitine could alleviate ISO-induced changes as it significantly reduced the serum level cardiac enzymes, MDA and IL-6, TNF- a and improved the antioxidants enzymes (SOD, GSPxase and GSRase). Histopathologically, they improved cardiac fibres atrophy, haemorrhages between cardiac fibres, lost striations, and disturbed sarcomere structure. The combined ef- fect of vitamin E and L-carnitine was more superior compared to the other groups. Conclusions: Combined administration of vitamin E, L-carnitine ameliorated the biochemical and histopathological cardiac injury induced by ISO. The effect seemed to be mediated through the antioxidant and anti-inflammatory effect of vitamin E, L-carnitine. Administration of these two elements is recommended for patient at risk for myocardial infarction.

Background: Oxidative stress is defined as imbalance between oxidant and antioxidant ratio, that lead to oxidative damage of biologically active molecules, finally lead to different disease and initiate carcinogenesis. The drug discovery using natural products as medicinal plants or marine organism still an important target for recent research. This study investigated anticancer activity of algae extract obtained from Red sea at Jeddah. Materials and Methods: Aqueousand methanol extracts ofDictyotaciliolata(DC) were tested on HCT-116 and HepG2 cell lines using WST-1. Aqueous extract (AEDC) and methanol extract (MEDC) at doses 0.05, 0.1, 0.5, 1 mg/ml and positive control 0.3% H2O2 at doses 0.5 mg/ml for 24,48 and 72 h (for two cell lines). Results: AEDC showed the mosteffective antitumor activity against HCT116 and HePG2, the IC50 dose for HCT116 cells was 0.05 mg/ml at 72 h, while for the HePG2 it was 0.01 mg/ml at 72 h. These results showed that HePG2cells was more sensitive to the AEDC. However, IC50 for MEDC were 0.01 mg/ml for HCT116 and 0.05 for HepG2 at 48 Hrs. The algae extracts contain sulfated polysaccharides and different pigments as chlorophylls, carotenoids and phycobiliproteins. These pigments were approved as biological active biomolecules that exert different biological activities as antioxidants, antitumor and rich source of micronutrients. In addition, AEDC or MEDC exert apoptotic activity by increase activity of caspase 3 and 9 in HepG2. Conclusıon: The antitumor effect of AEDC or MEDC is promising for development of chemotherapeutic agent as effective with no side effects.

Backgound: The generation of oxidative stress can be referred to Aluminium toxic effect in animals and humans. This study aimed to evaluate the role of broccoli (Br) and beetroot (Be) extarcts as antioxidant that prevents oxidative stress that associated with aluminum toxicity. Materials and Methods: Fifty Wister female rats were grouped into five groups (each 10 rats): Group 1: control group, administered drinking water only. Group 2: (Neurogenerative) which were induced by oral administration of aluminum chloride (20 mg/kg b.w) daily for one month. Group 3: Rats given aluminum chloride were treated with Rivastigmine (Ri) (1 mg/kg b.w) as a reference drug daily for five weeks. Group 4: Rats given aluminum chloride were treated with beet root extract (50 mg/kg b.w) daily for six weeks. Group 5. Rats given aluminum chloride were treated with broccoli extract (50 mg/kg b.w) daily for five weeks. Results: (AlCl3) group showed a significant increase in Ach level (P

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 increase in serum IL-4 and VEGF and decrease in IL-12 levels. In addition, HO-1 expression and activity were increased in infected mice compared to control group with the maximum increase at egg deposition stage. Conclusion: Our results suggested that the body response to acute stage of S. mansoni infection by elevating the expression of the stress gene HO-1 and that VEGF may serve as a new indicator of progression of S. mansoni associated angiogenesis which regulates granuloma and/or fibrosis development in the liver of infected mice. Understanding the role of HO-1 and VEGF in pathogenesis of S. mansoni may provide a new pharmacological target.

Background Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells. Methods Cytotoxic activity of DOX alone and combined with either 1 mM EUG or 40 μM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1 mM EUG or 40 μM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 μM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

In this study, we investigated the inhibitory effects of m-coumaric acid on the glycosylation of proteins in the retinas of diabetic rats. Male rats were divided into two main groups, Group I (normal control) and Group II (diabetic); Group II was further divided into four subgroups: Group IIa (diabetic control), Group IIb (diabetic rats were given m-coumaric acid orally [150 mg/kg, body weight (bw)/day]), Group IIc (diabetic rats were given HCA m-coumaric acid orally [300 mg/kg bw/day]), and Group IId (diabetic rats were given insulin [10 units/kg bw/day]) as a positive control). The treatment lasted for six weeks, and the data obtained suggested that m-coumaric acid reduced glucose and glycated hemoglobin levels, which further decreased the formation of glucose-derived advanced glycation end products. Hence, it protected the tissues from the detrimental effects of hyperglycemia and enhanced antioxidant activity. In conclusion, m-coumaric acid could be a potential candidate to prevent the onset and progression of retinopathy in diabetic patients.

Mesenchymal stem cells (MSCs) from various sources have been used in cartilage differentiation with variable success. Therefore, it is of interest to evaluate the in vitro differentiation potential of the hWJSCs derived from the human umbilical cords into chondrocytes at the stem cell research facility at the King Abdulaziz University. hWJSCs are an attractive choice for tissue engineering and regenerative medical applications including cartilage regeneration. We evaluated the hWJSCs using classical histological and cartilage related gene expression studies. Some of the known parameters were re-examined for consistency at the current laboratory conditions. Early passages (P1-P4) showed short fibroblastic morphology and high expression of MSC related surface markers namely CD29 (99.9%), CD44 (97.8%), CD73 (99.6%), CD90 (95.1%) and CD105 (98.9%). MTT assay showed time dependent increase in hWJSCs proliferation by 61.06% and 206.31% at 48h and 72h respectively. Toluidine blue histology showed that hWJSCs were successfully differentiated into chondrocytes in chondrocytic differentiation medium for 21 days. Differentiated hWJSCs also showed significantly increased expression of collagen type II, aggrecan and SOX9 compared to the undifferentiated control. It should be noted that the determination of the average cell yield, the population doubling time and histological staining wtih alcian blue and/or safronin O is required in future studies for improved evaluation of differentiation. Painless derivation, abundance of stem cells that are hypo-immunogenic and safety issues makes this method advantages to MSCs derived from other sources.

Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ± 0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P

Discovery of new urease inhibitors is an important approach towards the treatment of diseases caused by ureolytic bacteria. Urease has an important role in several pathologies, such as urolithiasis, peptic and duodenal ulcers, etc. In this regard, urease inhibitory activity of heterocyclic synthetic compounds 1–14, belonging to different chemical classes was evaluated by employing in vitro biochemical assay, and saturation transfer difference-NMR technique. Compounds 1, 3–5, 7, 10, and 12 have shown urease inhibitory potential in vitro. Among them, compound 1 was found to be more potent (IC50 of 12.90 ± 0.63 µM) than a clinical drug, acetohydroxamic acid (IC50 = 41.5 ± 1.50 µM) (Standard). Compounds 3 (IC50 = 15.0 ± 1.10 µM), 4 (IC50 = 24.67 ± 2.87 µM), and 5 (IC50 = 25.50 ± 0.63 µM) were also identified as potent inhibitors of urease enzyme. These compounds showed strong interactions with the urease enzyme (receptor) in saturation transfer difference-NMR spectra. Specifically, aromatic protons of active compounds received maximum Rf saturation from the receptor protein, thus were inferred to be as in close proximity to the protein. New inhibitors identified through biochemical assay and saturation transfer difference-nuclear magnetic resonance techniques were then subjected to kinetic and molecular docking studies to investigate their mode of inhibition, and production of their interactions with the protein at atomic level, respectively. Active compounds were found to be non-cytotoxic against mouse fibroblast (3T3) cell line MTT assay. Present study thereby identifies new inhibitors of urease enzyme in vitro as leads for further investigation towards the development of novel mechanism-based urease inhibitors.

Background: Borage (Borago officinal L.) is an annual herbaceous plant of great interest because its oil contains a high percentage of -linolenic acid (GLA). The present work was carried out to detect fatty acids composition of the oil extracted from borage seeds (BO) and its potential effectiveness against γ-irradiation- induced hepatotoxicity in male rats. Materials and Methods: GC-MS analysis of fatty acids methyl esters of BO was performed to identify fatty acids composition. Sixty rats were divided into five groups (12 rats each): Control, irradiated; rats were exposed to (6.5 Gy) of whole body γ-radiation, BO (50 mg/kg b.wt), irradiated BO post-treated and irradiated BO prepost-treated. Six rats from each group were sacrificed at two time intervals 7 and 15 days post-irradiation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) levels, lipids profile, as well as serum and hepatic reduced glutathione (GSH) and lipid peroxide (malondialdehyde) (MDA) levels were assessed. Histopathological examination of liver sections were also carried out. Results: The results showed that the high contents of BO extracted by cold pressing, were linoleic acid (34.23%) and GLA (24.79%). Also, oral administration of BO significantly improved serum levels of liver enzymes, lipids profile, as well as serum and hepatic GSH and MDA levels (p

Background: The goal of this study was identification signaling molecules mediated the formation of AGEs in brain of rats injected with CdCl2 and the role of camel whey proteins and Brassicaceae extract on formation of AGEs in brain.Methods: Ninety male rats were randomly grouped into five groups; Normal control (GpI) and the other rats (groups II-V) were received a single dose of cadmium chloride i.p (5 μg/kg/b.w) for induction of neurodegeneration. Rats in groups III-V were treated daily with whey protein (1g/kg b.w) or Brassicaceae extract (1mg/kg b.w) or combined respectively for 12 weeks.Results: It was found that whey protein combined with Brassicaceae extract prevented the formation of AGEs and enhance the antioxidant activity compared with untreated group (p

Background: Hemophilia is an inherited genetic disease characterized by the inability to coagulate blood after injury. The rationale of the current study was to evaluate serum proteins S and C and correlate to kidney function test in hemophilic patients for early diagnosis of abnormality in renal function. Subjects and Methods: This study was conducted on 80 males subjects divided into four groups. Group I: Control: Healthy subjects. Group II: Renal dysfunction (serum Creatinine >2mg/dl): Group III: Hemophilic patients. Group IV: Hemophilic patients with renal disorder. Serum urea, creatinine, sodium, potassium, protein C and protein S level were determined. Resuts: Protein C and S levels showed a significant decrease in hemophilic/and with renal dysfunction (P < 0.001,p

Background: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P 450 mixed function oxidase system. Materials and methods: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P 450 mixed function oxidase) analysis Results: The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (p

Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As such, in the present study we evaluated the beneficial effects of punicalagin, a phytochemical against an atherosclerotic cell model in vitro. Cytotoxicity assays were examined for 10 &micro, M concentration of punicalagin on THP-1 macrophages. Real-time-polymerase chain reaction (RT-PCR) was used to analyze monocyte chemoattractant protein-1 (MCP-1) and Intercellular adhesion molecule (ICAM-1) expressions. Monocyte migration and cholesterol efflux assays were performed to investigate punicalagin's further impact on the key steps of atherosclerosis. Cytotoxicity assays demonstrated no significant toxicity for punicalagin (10 &micro, M) on THP-1 macrophages. Punicalagin inhibited the IFN-&gamma, induced overexpression of MCP-1 and ICAM-1 in macrophages by 10 fold and 3.49 fold, respectively, compared to the control. Punicalagin also reduced the MCP-1- mediated migration of monocytes by 28% compared to the control. Percentages of cellular cholesterol efflux were enhanced in presence or absence of IFN-&gamma, by 88% and 84% compared to control with 58 %and 62%, respectively. Punicalagin possesses anti-inflammatory and anti-atherosclerotic effects. Punicalagin also did not exhibit any cytotoxicity and therefore can be considered a safe and potential candidate for the treatment and prevention of atherosclerosis.

The monoclonal antibodies 6E10 and 4G8 are among the first anti-amyloid monoclonal antibodies against Aβ and the most widely used antibodies in Alzheimer's disease research. Although the epitopes for 6E10 and 4G8 have been reported to correspond to residues 1-16 and 17-24, a more recent high-resolution mapping approach indicates that 6E10 maps to residues 4-10 while 4G8 maps to residues 18-23. To characterize the binding specificity of both antibodies in greater detail, we used immunoselection of random sequences from phage display library followed by deep sequencing and analysis of resulting patterns from thousands of immunoselected sequences. We found that the minimum sequence required for 6E10 binding is R-x-D with over half (53%) of the immunoselected sequences conforming to this pattern. The vast majority of these sequences contain an H at position x (R-H-D), corresponding to residues 5-7 of the Aβ target sequences, but Y is also permitted at this position in a minority of sequences. For 4G8 we found that the most frequent pattern is F-x-A contained in approximately 30% of the sequences, followed by F-A, L-x(3)-A, L-x-F, and F-F each accounting for approximately 18% of the sequences. The F-x-A motif also occurs in islet amyloid poly peptide which may explain why 4G8 also recognizes amyloid fibrils of this peptide. Immunoselection of random sequences and deep sequencing may also be a facile and efficient means of determining residues critical for antibody binding and validating the specificity of monoclonal antibodies and polyclonal antisera.

Background: Red grape juice (RGJ) and dark raisins (DR) are rich in polyphenols and antioxidants. This study aimed to assess the efficacy of RGJ and DR in protec- ting the renal tubules against hypercholesteraemic-induced pathological changes. Materials and methods: Forty albino rats divided into four groups (n = 10) were utilised in this study. They included the control, high cholesterol diet (HCD)-fed, HCD+RGJ-fed, and HCD+DR-fed groups. Body weight gain, food and water in- take, blood and insulin levels, lipid profile and kidney functions were assessed at the start of the experiment and after 12 weeks. The right kidney was dissected out and processed for both light and electron microscopic examination. Desmin and cytokeratin antibodies were utilised as histologic markers to assess the integrity of the proximal (PTs) and distal tubules (DTs) of the kidney. Results: Administration of HCD resulted in hypercholesterolaemia in rats as evi- denced by the lipid profile. The PTs of hypercholesteraemic rats appeared dilated with hyaline casts and mitochondria in most of the tubular cells were affected. Immunohistochemical assessment revealed affection of both PTs and DTs. Both RGJ and DR, when administered along with the HCD for 12 weeks, improved the lipid profile, kidney functions as well as the histologic and cellular changes-induced by hypercholesterolaemia in the rats. The effect of raisins was superior to RGJ which might be due to its high contents of fibres and proteins. Conclusions: This study highlighted the importance of supplementation of red grape and raisins in protection against the harmful effects induced by deposition of fat on the renal tubules’ structure and function.

Background : Studies have shown that Na + -K + ATPase activity was altered in disrupted red blood cell membranes and this enzyme is believed to be the site of active transport of Na + and K + in intact red blood cells. The enzyme is often referred to as Na + - K + pump because it pumps Na + out and K + into the cell against gradients with the concomitant hydrolysis of intracellular ATP. Objective: The aim of this study was to find out the possibility of using Na + -K + -ATPase activity as a biomarker for the diagnosis of individuals with different physiological conditions. Materials and methods: The activity of Na + -K + ATPase was determined in blood samples collected from different pathological and physiological conditions such as pregnancy, smoking, diabetes and renal dysfunction compared with healthy subjects matched for age and sex. Results: The Na + -K + ATPase activity in pregnancy (0.094 ± 0.0051 μM Pi/min. mg protein), smoking (0.064 ± 0.0011 μM), diabetes (0.047 μM 0.002 μM) and kidney disease (0.069 ± 0.0014 μM) was higher compared to the measurements in healthy individuals (0.0081 ± 0.0031 μM). Conclusion : Na + - K + ATPase specific activity is a biomarker for the diagnosis of individuals with different physiological diseases. Keywords: Na + -K + ATPase, red blood cell, pregnancy, smoking, diabetes, kidney diseases.

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have, therefore, investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies, therefore, reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages.

Background: Body overweight and obesity were considered as a risk factor for many systemic diseases as diabetic hypertension, cardiovascular diseases, and some cancers. The lipoic acid and Co Q are considered as coenzymes needed for enhancement metabolic rate. The goal of this study is to evaluate the anti-obese effect of lipoic acid alone or combined with Co-Q in rats.Materials and Methods: Ninety male albino rats (100–150g) were used in this study, divided into six groups (15 each). Group I: Normal rats fed normal diet. Group II: Rats fed high fat diet (HFD). Group III: Rats fed HFD were given lipoic acid (10 μg/kg b w /day) intra-gastric by stomach tube. Group IV: Rats fed HFD were given Co-Q (10 μg/kg b.w/day) intra-gastric. Group V: Rats fed HFD were given lipoic acid (50 mg/kg b w /day) and Co-Q (10 μg /kg b. w/day). Group VI: Rats were given orlistat intra-gastric (10 mg/kg b w/day) as positive control for 6 weeks. Serum was subjected for determination of lipid profile, liver function tests atherogenic factor and lipoprotein lipase.Results: It was found that treatment with lipoic acid or Co-Q or combined showed increase in the activity of lipoprotein lipase (P < 0.001) and reduction of atherogenic effect and obesity index (P

Background: The current study aimed to evaluate the role of carnitine in combination with vitamin E in protection against myocardial infarction induced by isoproterenol (ISO) in rats.Materials and Methods: Rats were grouped into 5 (each 10 rats): Group I. Control fed a standard diet. Group III: Rats were injected with vitamin E (100 IU/kg bw, i.p) daily. Group IV: Rats were given carnitine (20 mg/kg bw, i.p) daily .Group V: Rats were injected with both vitamin E (100 IU/kg bw, i.p) and carnitine (20 mg/kg bw, i.p) daily. On 7th, 8th, and 9th day, rats in groups (II-V) were injection i.p with ISO (55mg/kg b.w for successive three days). The treatment with carnitine and vitamin E were continuous for 21 days.Results: Canirine combined with vitamin E significantly increased coronary flow (CF) (P

Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder characterized by dysmorphic features, cardiovascular defects, cognitive deficits and developmental delay. WBS is caused by a segmental aneuploidy of chromosome 7 due to heterozygous deletion of contiguous genes at the long arm of chromosome 7q11.23. We aimed to apply array-CGH technique for the detection of copy number variants in suspected WBS patients and to determine the size of the deleted segment at chromosome 7q11.23 in correlation with the phenotype. The study included 24 patients referred to the CEGMR with the provisional diagnosis of WBS and 8 parents. The patients were subjected to conventional Cytogenetic (G-banding) analysis, Molecular Cytogenetic (Fluorescent In-Situ Hybridization), array-based Comparative Genomic Hybridization (array-CGH) and quantitative Real time PCR (qPCR) Techniques. No deletions were detected by Karyotyping, however, one patient showed unbalanced translocation between chromosome 18 and 19, the karyotype was 45,XX, der(19) t(18;19)(q11.1;p13.3)-18. FISH technique could detect microdeletion in chromosome 7q11.23 in 10/24 patients. Array-CGH and qPCR confirmed the deletion in all samples, and could detect duplication of 7q11.23 in three patients and two parents. Furthermore, the size of the deletion could be detected accurately by both array-CGH and qPCR techniques. Three patients not showing the 7q11.23 deletion were diagnosed by array-CGH to have deletion in chr9p13.1-p11.2, chr18p11.32-p11.21 and chr1p36.13. Both FISH and array-CGH are reliable methods for the diagnosis of WBS; however, array-CGH has the advantage of detection of genome deletions/ duplications that cannot otherwise be detected by conventional cytogenetic techniques. Array-CGH and qPCR are useful for detection of deletion sizes and prediction of the interrupted genes and their impact on the disease phenotype. Further investigations are needed for studying the impact of deletion sizes and function of the deleted genes on chromosome 7q11.23. ISRCTN ISRCTN73824458 . MOCY-D-16-00041R1. Registered 28 September 2014. Retrospectively registered.

Liver X receptors (LXRs) are ligand-dependent transcription factors that are activated by metabolites of cholesterol, oxysterols, and a number of synthetic agonists. LXRs play potent anti-atherogenic roles in part by stimulating the efflux of cholesterol from macrophage foam cells. The LXR-induced expression of ATP-binding cassette transporter (ABC)-A1 and Apolipoprotein E (ApoE) in macrophages is essential for the stimulation of cholesterol efflux and the prevention of atherosclerotic development. Unfortunately, the signaling pathways underlying such regulation are poorly understood and were therefore investigated in human macrophages. The expression of ApoE and ABCA1 induced by synthetic or natural LXR ligands [TO901317, GW3965, and 22-(R)-hydroxycholesterol (22-(R)-HC), respectively] was attenuated by inhibitors of c-Jun N-terminal kinase (JNK) (curcumin and SP600125) and phosphoinositide 3-kinase (PI3K) (LY294002). Similar results were obtained with ABCG1 and LXR-α, two other LXR target genes. LXR agonists activated several components of the JNK pathway (SEK1, JNK and c-Jun) along with AKT, a downstream target for PI3K. In addition, dominant negative mutants of JNK and PI3K pathways inhibited the LXR-agonists-induced activity of the ABCA1 and LXR-α gene promoters in transfected cells. LXR agonists also induced the binding of activator protein-1 (AP-1), a key transcription factor family regulated by JNK, to recognition sequences present in the regulatory regions of the ApoE and ABCA1 genes. These studies reveal a novel role for JNK and PI3K/AKT signaling in the LXR-regulated expression in macrophages of several key genes implicated in atherosclerosis.

Objective : This study aimed to analyze the agricultural soils from different regions in Saudi Arabia for cobalt and related metals as Cu 2+ , Ni 2+ ,Cr 3+ +, Zn 2+ and Pb 2+ . Materlais and methods : Liver and muscle tissues of livestock grazing on the selected areas were analyzed for the content of Co and vitamin B 12 . Results : Our results indicated that the levels of Co in surface soil (0-15 cm) were higher than in sub-surface soil (>15 cm- 45 cm). In contrast, Pb and Zn were higher in sub-surface soil than in surface soil. A significant positive correlation existed between the levels of Co and vitamin B 12 in the liver of livestock. However, Co was not detected in muscle tissues while vitamin B 12 was present at very low levels in comparison with the levels found in the liver. The results indicated that Zn 2+ , Pb 2+ compete with Co in soil, which eventually affected the levels of vitamin B 12 in liver. Conclusion : It was recommended that survey of heavy metals in grazing fields of cattle should consider inclusion of multiple elements that compete with the bioavailability of essential elements in plants and animals for the prevention of deficiency of essential elements such as Co. Keywords : Soil, vitamin B 12 , cobalt, cattle, uptake, transfer

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have therefore investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies therefore reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages. This article is protected by copyright. All rights reserved.

Materials and methods We used SurePrint G3 human CGH+SNP, 2×400K, microarrays to assess gains and losses in 47 PTCs in comparison to male and female human reference DNA. Interpretation of results was accomplished by using the HG19 version of the design file and the default analysis method of the Cytogenomics 2.7 research software [1]. To compare BRAF mutant (BRAF) PTCs with BRAF wild type (BRAF) PTCs, the BRAF mutational status was established in 42 cases by direct sequencing the mutational hotspot region in exon 15 [2].

Objective: Coronary artery diseases including atherosclerosis is considered as commonest problem worldwide. Ergosterols are the main components of vegetable oils and nuts. The objective of this study was to evaluate the potential hypoplipidemic and hypocholesterolemic effects of ergosterol in combination with niacin in rats fed high fat diet (HFD). Methods: Eighty male albino rats were included in this study divided into two main groups: Group I: Normal rats fed standard diet treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/Kg b.w) or both. Group II; rats fed HFD treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/Kg b.w) or both The feeding and treatment lasted for 8 weeks. Results: A significant elevation in the levels of total cholesterol, triacylglycerol, VLDL-c, LDL-c and atherogenic factor (p

BackgroundWilliam’s Syndrome (WS) is one of the most powerfulmodels of human cognition and rare genetic disorder, theincidence of WS range between 1/7500 and 50,000 and isconsidered to be a segmental aneuploidy due to heterozy-gous deletion of a contiguous gene at the long arm ofchromosome7atq11.23[1].The deletion size usuallyranges between 1.5-1.8 Mb. At least 26 genes have beendetected in the deletion region in WS patients [2,3]. Theaim of this study was to determine the efficient methodfor detection of the microdeletion at chromosome 7q11.23in patients with WS. This comparative study will help todetermine the effective methods to detect the microdele-tion at chromosome 7q11.23 in William’ssyndrome.Materials and methodsThe study included 29 patients referred to the DGMU withthe provisional diagnosis of WS. Peripheral blood sampleswere taken after obtaining informative consent from theparents or patients’ guardian. We applied conventionalCytogenetic (G-banding technique), Molecular Cytogenetic(Fluorescent In-Situ Hybridization) and Real time PCRTechniques for detection of segmental Aneuploidy inWilliams-Beuren Syndrome.ResultsNo deletions were detected by Karyotyping, however onepatient had translocation chromosomes (18; 19)(q11.1;p13.3). FISH technique could detect microdeletion inchromosome 7q11.23 in 6/23 patients. However, qPCRcould detect deletion in 9/23 samples. Furthermore, thesize of deletion could be detected accurately using theqPCR technique.ConclusionsReal time PCR could be used to confirm the FISH resultsand to detect small deletions or duplications that couldnot be detected by FISH.

Background Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs. Methods Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15. Results We identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set. Conclusions The expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect important canonical pathways. The identified gene set adds to our understanding of the tumor biology of BRAFwt and BRAFmut PTCs and contains genes/biomarkers of interest.

Materials and methods Affymetrix HuGene 1.0 ST microarrays were used to generate whole transcript expression profiles in 11 BRAF and 14 BRAF PTCs. A p-value with a false discovery rate (FDR) ≤ 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Spearman’s correlation as a similarity matrix was utilized for unsupervised two dimensional hierarchical clustering. The BRAF mutational status was surveyed by direct sequencing the hotspot region of BRAF exon 15.