Search results for: liver foci

Authors: Marina Lazar Chandy, N. Kannan, Rajendra Patil, Vinod Mathew, Ajmal Mohamed, P. K. Sreeja, Renju Jose

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Introduction- Arecoline, a major constituent of arecanut has shown to have some effect on liver. The use of arecanut is found to be the most common etiological factor for the development of Oral Submucous fibrosis (O.S.M.F). The effect of arecanut usage on liver in patients with O.S.M.F needs to be assessed. Lipids play a role in structural maintenance of cell. Alterations of lipid profile were noted in cancer patients. O.S.M.F being a precancerous lesion can have some effect on the level of lipids in the body. Objectives: This study was done to assess the alterations in liver enzymes (Serum Glutamic Pyruvic Transaminase(S.G.P.T ,Serum Glutamic Oxaloacetic Transaminase(S.G.O.T)) and lipid metabolism (High Density Lipoprotien(H.D.L) and Apo Lipoprotien A1 (Apo A1)) in patients with O.S.M.F. Methods-130 patients were taken for the study,100 patients with O.S.M.F and 30 as control group without O.S.M.F. Fasting blood sugar levels were taken, centrifuged and analyzed for S.G.P.T,S.G.O.T, H.D.L and Apo A1 using semi automated spectrophotometer. Results: After statistical analysis, it was concluded that there is an elevation of levels of S.G.P.T, S.G.O.T, and decreased levels of H.D.L, Apo A1 for O.S.M.F group when compared with control group. With increased grade of O.S.M.F. and duration of habit, S.G.P.T. & S.G.O.T. increased whereas, H.D.L. & Apo A1 decreased. All the values were statistically significant at p<0.01.

Keywords: apolipoprotien A1, high density lipoprotien, oral submucous fibrosis, serum glutamic oxaloacetic transaminase

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Authors: Isaac Gbadura Adanlawo, Olusola Olalekan Elekofehinti

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This work investigated the antihyperglycemic, antioxidant and antihyperlipidemic effects of saponins from the fruit of Solanum anguivi, a plant generally used in folk medicine to treat diabetes and hypertension and to compare its effect with metformin in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in albino rats by administration of STZ (65 mg/kg) intraperitoneally. Saponin (40 and 100 mg/kg) was administered by oral gavage once daily for 21 days. Metformin (200 mg/kg b.w.) was administered as the positive control. The effect of saponin on blood glucose, serum lipids and enzymatic antioxidants defense systems, like superoxide dismutase (SOD), catalase (CAT), as well as MDA levels in serum, liver and pancreas were studied. Saponins from S. anguivi fruits reduced the blood glucose, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) levels in STZ-diabetic rats. They also significantly abolished the increase in MDA level in serum, liver and pancreas of diabetic rats. The activities of SOD and CAT in serum, liver and pancreas were significantly increased as well as concentration of HDL in the serum. Metformin had the same effect as saponin but saponins seems to be more potent in reducing serum TC, TG, LDL, and MDA, and increasing SOD and CAT. Conclusions: These results suggest that saponins from S. anguivi fruits have anti-diabetic and antihypercholesterolemic, antihypertriglyceridemic antiperoxidative activities mediated through their antioxidant properties. Also, saponins appeared to have more hypolipidemic, antiperoxidative and antioxidant activity than metformin.

Keywords: saponin, diabetes, metformin, streptozotocin, Solanum anguivi

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Magdalena B. Kaziuk, Waldemar Kosiba, Marek J. Kuzniewski

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Introduction: Adipose tissue is a typical place for storage water-insoluble toxins in the body. It's connective tissue, where the intercellular substance consist of fat, which level in people with low physical activity should be 18-25% for women and 13-18% for men. Due to the fat distribution in the body we distinquish two types of obesity: android (visceral, abdominal) and gynoidal (gluteal-femoral, peripheral). Abdominal obesity increases the risk of complications of the cardiovascular system diseases, and impaired renal and liver function. Through the influence on disorders of metabolism, lipid metabolism, diabetes and hypertension, leading to emergence of the metabolic syndrome. So thus, obesity will especially overload kidney function in patients after transplantation. Aim: An attempt was made to estimate the impact of amount fat tissue on transplanted kidney function and excretory function of the liver in patients after Ktx. Material and Methods: The study included 108 patients (50 females, 58 male, age 46.5 +/- 12.9 years) with active kidney transplant after more than 3 months from the transplantation. An analysis of body composition was done by using electrical bioimpedance (BIA) and anthropometric measurements. Estimated basal metabolic rate (BMR), muscle mass, total body water content and the amount of body fat. Information about physical activity were obtained during clinical examination. Nutritional status, and type of obesity were determined by using indicators: Waist to Height Ratio (WHR) and Waist to Hip Ratio (WHR). Excretory functions of the transplanted kidney was rated by calculating the estimated renal glomerular filtration rate (eGFR) using the MDRD formula. Liver function was rated by total bilirubin and alanine aminotransferase levels ALT concentration in serum. In our patients haemolitic uremic syndrome (HUS) was excluded. Results: In 19.44% of patients had underweight, 22.37% of the respondents were with normal weight, 11.11% had overweight, and the rest were with obese (49.08%). People with android stature have a lower eGFR compared with those with the gynoidal stature (p = 0.004). All patients with obesity had higher amount of body fat from a few to several percent. The higher amount of body fat percentage, the lower eGFR had patients (p <0.001). Elevated ALT levels significantly correlated with a high fat content (p <0.02). Conclusion: Increased amount of body fat, particularly in the case of android obesity can be a predictor of kidney and liver damage. Due to that obese patients should have more frequent control of diagnostic functions of these organs and the intensive dietary proceedings, pharmacological and regular physical activity adapted to the current physical condition of patients after transplantation.

Keywords: obesity, body fat, kidney transplantation, glomerular filtration rate, liver function

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Authors: Ibrahim I. Elshahawy

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The objective of the present study was to investigate the effect of green tea extract on serum oxidant and antioxidant profile, liver and kidney function. 40 Friesian calves are included in this study and allocated into two groups: Group I (n=20) clinically healthy calves showing no clinical abnormalities, not receiving any treatment and served as control; group II (n=20) received green tea extract (GTE) for 30 days. Non-significant changes in blood urea nitrogen (BUN) were detected between groups, on contrary, serum creatinine and activities of liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) were significantly different between two groups. There were significant increases in the mean values of serum antioxidative parameters (total antioxidant capacity, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase) in group II. Whereas, the activity of lipid peroxidase significantly decreased in GTE treated calves when compared to control.

Keywords: green tea extract, antioxidants, oxidants, calves

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Authors: Baki Aydin, Erkan Gumus

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The aim of the present study was to investigate the effects of replacing dietary soybean meal by dried grains with solubles (DDGS) on liver histology of rainbow trout, Oncorhynchus mykiss. Five isoproteic (∼45% crude protein) and isocaloric (∼3570 kcal/kg digestible energy) diets were formulated: Conrol-1 (Fish meal control), Control-2, DDGS33, DDGS66 and DDGS100 which included 0%, 0%, 10%, 20% and 30% DDGS, respectively. Triplicate groups of fish with an average weight of 20.46 g were fed three times a day until apparent satiation during 84 days. The obtained results showed that diameters of hepatocyte nuclei were not statistically different among the groups. The histological examination of liver sections from the fish fed the Control-1 diet showed normal histology, mild cytoplasm vacuoles and appears to be central to hepatocyte nuclei. Fish fed diets containing soybean meal and DDGS presented variable levels of cytoplasmic vacuolization and some with eccentric hepatocyte nuclei. But, fish fed diet soybean meal based control (Control-2) showed the highest hepatocyte nuclei displacement, and cytoplasm vacuoles compared the DDGS30 diet. DDGS20 and DDGS30 fish also showed more regular hepatocytes than in Control-2 fish. The results of this study demonstrated that fish fed diets containing increasing DDGS levels exhibited less histomorphological changes compared the Control-2 diet.

Keywords: DDGS, soybean meal, rainbow trout, hepatocyte

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Authors: Zahra Khoshnood, Mehdi Kazaie, Sajedeh Neisi

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In 2013, 24 fish samples were taken from two fishery regions in the north of Persian Gulf near the Iranian coastal lines. The two flatfishes were Yellofin seabream (Acanthopagrus latus) and Longtail tuna (Thannus tonggol). We analyzed total Hg concentration of liver and muscle tissues by Mercury Analyzer (model LECO AMA 254). The average concentration of total Hg in edible Muscle tissue of deep-Flounder was measured in Bandar-Abbas and was found to be 18.92 and it was 10.19 µg.g-1 in Bandar-Lengeh. The corresponding values for Oriental sole were 8.47 and 0.08 µg.g-1. The average concentration of Hg in liver tissue of deep-Flounder, in Bandar-Abbas was 25.49 and that in Bandar-Lengeh was 12.52 µg.g-1.the values for Oriental sole were 11.88 and 3.2 µg.g-1 in Bandar-Abbas and Bandar-Lengeh, respectively.

Keywords: mercury, Acanthopagrus latus, Thannus tonggol, Persian Gulf

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Authors: Abder-Rahman Ali, Adélaïde Albouy-Kissi, Manuel Grand-Brochier, Viviane Ladan-Marcus, Christine Hoeffl, Claude Marcus, Antoine Vacavant, Jean-Yves Boire

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In this paper, we present a new segmentation approach for focal liver lesions in contrast enhanced ultrasound imaging. This approach, based on a two-cluster Fuzzy C-Means methodology, considers type-II fuzzy sets to handle uncertainty due to the image modality (presence of speckle noise, low contrast, etc.), and to calculate the optimum inter-cluster threshold. Fine boundaries are detected by a local recursive merging of ambiguous pixels. The method has been tested on a representative database. Compared to both Otsu and type-I Fuzzy C-Means techniques, the proposed method significantly reduces the segmentation errors.

Keywords: defuzzification, fuzzy clustering, image segmentation, type-II fuzzy sets

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Authors: Uchenna Nkiruka Umeononihu, Adenike Kuku, Oludele Odekanyin, Olubunmi Babalola, Femi Agboola, Rapheal Okonji

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In this study, a lectin from the bulb of Dioscorea bulbifera was purified, characterised, and its acute and sub-acute toxicity was investigated with a view to evaluate its toxic effects in mice. The protein from the bulb was extracted by homogenising 50 g of the bulb in 500 ml of phosphate buffered saline (0.025 M) of pH 7.2, stirred for 3 hr, and centrifuged at the speed of 3000 rpm. Blood group and sugar specificity assays of the crude extract were determined. The lectin was purified in a two-step procedure- gel filtration on Sephadex G-75 and affinity chromatography on Sepharose 4-B arabinose. The degree of purity of the purified lectin was ascertained by SDS-polyacrylamide gel electrophoresis. Detection of covalently bound carbohydrate was carried out with Periodic Acid-Schiffs (PAS) reagent staining technique. Effects of temperature, pH, and EDTA on the lectin were carried out using standard methods. This was followed by acute toxicity studies via oral and subcutaneous routes using mice. The animals were monitored for mortality and signs of toxicity. The sub-acute toxicity studies were carried out using rats. Different concentrations of the lectin were administered twice daily for 5 days via the subcutaneous route. The animals were sacrificed on the sixth day; blood samples and liver tissues were collected. Biochemical assays (determination of total protein, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), catalase (CAT), and superoxide dismutase (SOD)) were carried out on the serum and liver homogenates. The collected organs (heart, liver, kidney, and spleen) were subjected to histopathological analysis. The results showed that lectin from the bulbs of Dioscorea bulbifera agglutinated non-specifically the erythrocytes of the human ABO system as well as rabbit erythrocytes. The haemagglutinating activity was strongly inhibited by arabinose and dulcitol with minimum inhibitory concentrations of 0.781 and 6.25, respectively. The lectin was purified to homogeneity with native and subunit molecular weights of 56,273 and 29,373 Daltons, respectively. The lectin was thermostable up to 30 0C and lost 25 %, 33.3 %, and 100 % of its heamagglutinating activity at 40°C, 50°C, and 60°C, respectively. The lectin was maximally active at pH 4 and 5 but lost its total activity at pH eight, while EDTA (10 mM) had no effect on its haemagglutinating activity. PAS reagent staining showed that the lectin was not a glycoprotein. The sub-acute studies on rats showed elevated levels of ALT, AST, serum bilirubin, total protein in serum and liver homogenates suggesting damage to liver and spleen. The study concluded that the aerial bulb of D. bulbifera lectin was non-specific in its heamagglutinating activity and dimeric in its structure. The lectin shared some physicochemical characteristics with lectins from other Dioscorecea species and was moderately toxic to the liver and spleen of treated animals.

Keywords: Dioscorea bulbifera, heamagglutinin, lectin, toxicity

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Authors: Hyun-Kyung Lee, Jehyung Oh, Young Eun Jeong, Hyun-Shik Lee

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Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in the human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in the ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8-11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs) and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated [perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using the whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects.

Keywords: PFC, xenopus, fetax, development

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Authors: Asmaa F. Hamouda, Randa M Shrourou

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Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) constitute apportion of regular human diet. The effect of Cabbage(CE) and Ginger extracts(GE) separately on liver nitric oxide (NO), malondialdehyde (MDA), as well as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, total cholesterol(TC), triglyceride(T.G), high density lipoprotein(HDL cholesterol), low density lipoprotein (LDL cholesterol), thyroid-stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) in rats treated and untreated with carbon tetrachloride (CCl4) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDLand TSH showed an elevation and decline in HDL, T3, and T4 in rats treated with CCl4 as compared to control. Treatment of rats with GE pre, during, and post CCl4 administration improved NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CCl4, indicates that GE improve thyroid function and reduced oxidative stress as well as injuries induced by CCl4. Treatment of rats with CE pre, during, and post CCl4 administration did not improved in the thyroid hormones and lipid profile levels as compared to CCl4. These findings suggest that ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.

Keywords: liver injuries, carbon tetrachloride (CCl4), cabbage (Brassica oleracea), ginger (Zingiber officinale), thyroid function

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Authors: Moushira Zaki, Wafaa Ezzat, Yasser Elhosary, Omnia Saleh

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Nonalcoholic fatty liver disease (NAFLD) has increased in conjunction with obesity. The accuracy of risk factors for detecting NAFLD in obese adolescents has not undergone a formal evaluation. The aim of this study was to evaluate predictors of NAFLD among Egyptian female obese adolescents. The study included 162 obese female adolescents. All were subjected to anthropometry, biochemical analysis and abdominal ultrasongraphic assessment. Metabolic syndrome (MS) was diagnosed according to the IDF criteria. Significant association between presence of MS and NAFLD was observed. Obese adolescents with NAFLD had significantly higher levels of ALT, triglycerides, fasting glucose, insulin, blood pressure and HOMA-IR, whereas decreased HDL-C levels as compared with obese cases without NAFLD. Receiver–operating characteristic (ROC) curve analysis shows that ALT is a sensitive predictor for NAFLD, confirming that ALT can be used as a marker of NAFLD.

Keywords: obesity, NAFLD, predictors, adolescents, Egyptians, risk factors, prevalence

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Authors: Syeda Hira, Muhammad Gulfraz

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Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: M. A. Hamza, H. A. Bosila, M. A. Zewil, I. M. Harridy

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Silymarin is one active component extracted from milk thistle Silybum marianum; it is flavonoid recognized for its ability to benefit people with liver disorders and as a protective compound against liver damaging agents. For this reason, this research aims to study the effect of growth regulators (BA+NAA) and explant type (cotyledon, hypocotyl, and root) to increase the growth and active ingredients (silymarin) in callus of S. mariaum plant. The results showed that cotyledon explant which have been cultured in MS medium supplemented with BA 0.4 mg/l. +NAA 0.25 mg/l. Led to obtain the best results in callus fresh weight (1.847a) and callus dry weight (0.155a). On the other hand, the same explant (cotyledon) cultured in MS medium supplemented with BA 1.6 mg/l. + NAA 0.5 mg/l. The suitable condition to silymarin content (0.132 mg/100 mg dry weight). And also, it turned out, lack of importance of the use of hypocotyl and root in the production of callus and silymarin compared to cotyledon.

Keywords: silybum, callus, tissue culture, cotyledon

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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Authors: Karthyayani Rajamani, Yi-Chun Lin, Tung-Chou Wen, Jeanne Hsieh, Yi-Maun Subeq, Jen-Wei Liu, Po-Cheng Lin, Horng-Jyh Harn, Shinn-Zong Lin, Tzyy-Wen Chiou

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Assuring cell quality is an essential parameter for the success of stem cell therapy, utilization of various components to improve this potential has been the primary goal of stem cell research. The aim of this study was not only to demonstrate the capacity of trans-cinnamaldehyde (TC) to reverse stress-induced senescence but also improve the therapeutic abilities of stem cells. Because of the availability and the promising application potential in regenerative medicine, adipose-derived stem cells (ADSCs) were chosen for the study. We found that H2O2 treatment resulted in the expression of senescence characteristics in the ADSCs, including decreased proliferation rate, increased senescence-associated- β-galactosidase (SA-β-gal) activity, decreased SIRT1 (silent mating type information regulation 2 homologs) expression and decreased telomerase activity. However, TC treatment was sufficient to rescue or reduce the effects of H2O2 induction, ultimately leading to an increased proliferation rate, a decrease in the percentage of SA-β-gal positive cells, upregulation of SIRT1 expression, and increased telomerase activity of the senescent ADSCs at the cellular level. Further recently it was observed that the ADSCs were treated with TC without induction of senescence, all the before said positives were observed. Moreover, a chemically induced liver fibrosis animal model was used to evaluate the functionality of these rescued cells in vivo. Liver dysfunction was established by injecting 200 mg/kg thioacetamide (TAA) intraperitoneally into Wistar rats every third day for 60 days. The experimental rats were separated into groups; normal group (rats without TAA induction), sham group (without ADSC transplantation), positive control group (transplanted with normal ADSCs); H2O2 group (transplanted with H2O2 -induced senescent ADSCs), H2O2+TC group (transplanted with ADSCs pretreated with H2O2 and then further treated with TC) and TC group (ADSC treated with TC without H2O2 treatment). In the transplantation group, 1 × 106 human ADSCs were introduced into each rat via direct liver injection. Based on the biochemical analysis and immunohistochemical staining results, it was determined that the therapeutic effects on liver fibrosis by the induced senescent ADSCs (H2O2 group) were not as significant as those exerted by the normal ADSCs (the positive control group). However, the H2O2+TC group showed significant reversal of liver damage when compared to the H2O2 group 1 week post-transplantation. Further ADSCs without H2O2 treatment but with just TC treatment performed much better than all the groups. These data confirmed that the TC treatment had the potential to improve the therapeutic effect of ADSCs. It is therefore suggested that TC has potential applications in maintaining stem cell quality and could possibly aid in the treatment of senescence-related disorders.

Keywords: senescence, SIRT1, adipose derived stem cells, liver fibrosis

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Authors: Rebeca V. Tholen, Elaine Bundy

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Background: Liver transplantation (LT) is considered the only curative treatment for end-stage liver disease Background: Liver transplantation (LT) is considered the only curative treatment for end-stage liver disease (ESLD). The effects of alcoholism can cause irreversible liver damage, cirrhosis and subsequent liver failure. Alcohol relapse after transplant occurs in 20-50% of patients and increases the risk for recurrent cirrhosis, organ rejection, and graft failure. Alcohol relapse after transplant has been identified as a problem among liver transplant recipients at a large urban academic transplant center in the United States. Transplantation will reverse the complications of ESLD, but it does not treat underlying alcoholism or reduce the risk of relapse after transplant. The purpose of this quality improvement project is to implement and evaluate the effectiveness of a High-Risk Alcoholism Relapse (HRAR) Scale to screen and identify patients at high-risk for alcohol relapse after receiving an LT. Methods: The HRAR Scale is a predictive tool designed to determine the severity of alcoholism and risk of relapse after transplant. The scale consists of three variables identified as having the highest predictive power for early relapse including, daily number of drinks, history of previous inpatient treatment for alcoholism, and the number of years of heavy drinking. All adult liver transplant recipients at a large urban transplant center were screened with the HRAR Scale prior to hospital discharge. A zero to two ordinal score is ranked for each variable, and the total score ranges from zero to six. High-risk scores are between three to six. Results: Descriptive statistics revealed 25 patients were newly transplanted and discharged from the hospital during an 8-week period. 40% of patients (n=10) were identified as being high-risk for relapse and 60% low-risk (n=15). The daily number of drinks were determined by alcohol content (1 drink = 15g of ethanol) and number of drinks per day. 60% of patients reported drinking 9-17 drinks per day, and 40% reported ≤ 9 drinks. 50% of high-risk patients reported drinking ≥ 25 years, 40% for 11-25 years, and 10% ≤ 11 years. For number of inpatient treatments for alcoholism, 50% received inpatient treatment one time, 20% ≥ 1, and 30% reported never receiving inpatient treatment. Findings reveal the importance and value of a validated screening tool as a more efficient method than other screening methods alone. Integration of a structured clinical tool will help guide the drinking history portion of the psychosocial assessment. Targeted interventions can be implemented for all high-risk patients. Conclusions: Our findings validate the effectiveness of utilizing the HRAR scale to screen and identify patients who are a high-risk for alcohol relapse post-LT. Recommendations to help maintain post-transplant sobriety include starting a transplant support group within the organization for all high-risk patients. (ESLD). The effects of alcoholism can cause irreversible liver damage, cirrhosis and subsequent liver failure. Alcohol relapse after transplant occurs in 20-50% of patients, and increases the risk for recurrent cirrhosis, organ rejection, and graft failure. Alcohol relapse after transplant has been identified as a problem among liver transplant recipients at a large urban academic transplant center in the United States. Transplantation will reverse the complications of ESLD, but it does not treat underlying alcoholism or reduce the risk of relapse after transplant. The purpose of this quality improvement project is to implement and evaluate the effectiveness of a High-Risk Alcoholism Relapse (HRAR) Scale to screen and identify patients at high-risk for alcohol relapse after receiving a LT. Methods: The HRAR Scale is a predictive tool designed to determine severity of alcoholism and risk of relapse after transplant. The scale consists of three variables identified as having the highest predictive power for early relapse including, daily number of drinks, history of previous inpatient treatment for alcoholism, and the number of years of heavy drinking. All adult liver transplant recipients at a large urban transplant center were screened with the HRAR Scale prior to hospital discharge. A zero to two ordinal score is ranked for each variable, and the total score ranges from zero to six. High-risk scores are between three to six. Results: Descriptive statistics revealed 25 patients were newly transplanted and discharged from the hospital during an 8-week period. 40% of patients (n=10) were identified as being high-risk for relapse and 60% low-risk (n=15). The daily number of drinks were determined by alcohol content (1 drink = 15g of ethanol) and number of drinks per day. 60% of patients reported drinking 9-17 drinks per day, and 40% reported ≤ 9 drinks. 50% of high-risk patients reported drinking ≥ 25 years, 40% for 11-25 years, and 10% ≤ 11 years. For number of inpatient treatments for alcoholism, 50% received inpatient treatment one time, 20% ≥ 1, and 30% reported never receiving inpatient treatment. Findings reveal the importance and value of a validated screening tool as a more efficient method than other screening methods alone. Integration of a structured clinical tool will help guide the drinking history portion of the psychosocial assessment. Targeted interventions can be implemented for all high-risk patients. Conclusions: Our findings validate the effectiveness of utilizing the HRAR scale to screen and identify patients who are a high-risk for alcohol relapse post-LT. Recommendations to help maintain post-transplant sobriety include starting a transplant support group within the organization for all high-risk patients.

Keywords: alcoholism, liver transplant, quality improvement, substance abuse

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Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

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Authors: Abdolghani Ebrahimi, Diego Klabjan, Chenxi Ge, Daniela Ladner, Parker Stride

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In this work, we use machine learning and novel data analysis techniques to predict the one-year mortality of cirrhotic patients. Data from 2,322 patients with liver cirrhosis are collected at a single medical center. Different machine learning models are applied to predict one-year mortality. A comprehensive feature space including demographic information, comorbidity, clinical procedure and laboratory tests is being analyzed. A temporal pattern mining technic called Frequent Subgraph Mining (FSM) is being used. Model for End-stage liver disease (MELD) prediction of mortality is used as a comparator. All of our models statistically significantly outperform the MELD-score model and show an average 10% improvement of the area under the curve (AUC). The FSM technic itself does not improve the model significantly, but FSM, together with a machine learning technique called an ensemble, further improves the model performance. With the abundance of data available in healthcare through electronic health records (EHR), existing predictive models can be refined to identify and treat patients at risk for higher mortality. However, due to the sparsity of the temporal information needed by FSM, the FSM model does not yield significant improvements. To the best of our knowledge, this is the first work to apply modern machine learning algorithms and data analysis methods on predicting one-year mortality of cirrhotic patients and builds a model that predicts one-year mortality significantly more accurate than the MELD score. We have also tested the potential of FSM and provided a new perspective of the importance of clinical features.

Keywords: machine learning, liver cirrhosis, subgraph mining, supervised learning

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Authors: Elidrissi Laila, El Rhaoussi Fatima-Zahra, Haddad Fouad, Tahiri Mohamed, Hliwa Wafaa, Bellabah Ahmed, Badre Wafaa

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Introduction: Metabolic Dysfunction Associated with Non-Alcoholic Fatty Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the leading cause of chronic liver disease. The cardiometabolic risk factors associated with MASLD represent common health issues and significant public health challenges. Medical students, being active participants in the healthcare system and a young demographic, are particularly relevant for understanding this entity to prevent its occurrence on a personal and collective level. The objective of our study is to assess the level of knowledge among medical students regarding MASLD, its risk factors, and its long-term consequences. Materials and Methods: We conducted a descriptive cross-sectional study using an anonymous questionnaire distributed through social media over a period of 2 weeks. Medical students from various faculties in Morocco answered 22 questions about MASLD, its etiological factors, diagnosis, complications, and principles of treatment. All responses were analyzed using the Jamovi software. Results: A total of 124 students voluntarily provided complete responses. 59% of our participants were in their 3rd year, with a median age of 21 years. Among the respondents, 27% were overweight, obese, or diabetic. 83% correctly answered more than half of the questions, and 77% believed they knew about MASLD. However, 84% of students were unaware that MASLD is the leading cause of chronic liver disease, and 12% even considered it a rare condition. Regarding etiological factors, overweight and obesity were mentioned in 93% of responses, and type 2 diabetes in 84%. 62% of participants believed that type 1 diabetes could not be implicated in MASLD. For 83 students, MASLD was considered a diagnosis of exclusion, while 41 students believed that a biopsy was mandatory for diagnosis. 12% believed that MASLD did not lead to long-term complications, and 44% were unaware that MASLD could progress to hepatocellular carcinoma. Regarding treatment, 85% included weight loss, and 19% did not consider diabetes management as a therapeutic approach for MASLD. At the end of the questionnaire, 89% of the students expressed a desire to learn more about MASLD and were invited to access an informative sheet through a hyperlink. Conclusion: MASLD represents a significant public health concern due to the prevalence of its risk factors, notably the obesity pandemic, which is widespread among the young population. There is a need for awareness about the seriousness of this emerging and long-underestimated condition among young future physicians.

Keywords: MASLD, medical students, obesity, diabetes

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Authors: Shahriar Sepahvand, Mohammad Ali Davarpanah

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Infections caused by Acinetobacter baumannii are among the common hospital-acquired infections that have seen an increase in antibiotic resistance in recent years. Colistin is the last treatment option against this pathogen. The aim of this study is to investigate the histopathology of BALB/C mice receiving sensitive and resistant strains of Acinetobacter baumannii to colistin. A total of 68 female laboratory mice weighing 30 to 40 grams of the BALB/C breed were studied in this research for three weeks under appropriate laboratory conditions in terms of food and environment. The experimental groups included: control group, second group, third group, fourth group. Lung, liver, spleen, and kidney tissues were removed from anesthetized mice and, after washing in physiological serum, were fixed in 10% formalin for 14 days. For dehydration, alcohol with ascending degrees of 70, 80, 90, and 100 was used. After clearing and soaking in paraffin, the samples were embedded in paraffin. Then, sections with a thickness of 5 microns were prepared and, after staining by hematoxylin-eosin, the samples were ready for study with a light microscope. In liver, spleen, lung, and kidney tissues of mice receiving the colistin-sensitive strain of Acinetobacter baumannii, infiltration of inflammatory cells and hyperemia were observed compared to control group mice. Liver and lung tissues of mice receiving strains of Acinetobacter baumannii resistant to colistin showed tissue destruction in addition to infiltration of inflammatory cells and hyperemia, with more destruction observed in lung tissue.

Keywords: acinetobacter baumannii, colistin antibiotic, histopathological examination, resistant

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Authors: Ali Bagherpour, Masoud Soltanialvar

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Campylobacter species are common bacterial pathogens associated with human gastroenteritis which are generally transmitted through foods of animal origin. This study was carried out to determine the prevalence of Campylobacter species in poultry meat and by products in the city of Dezful in Iran. Since April 2012 to July 2013, a total of 400 samples including meat (n = 100), liver (n = 100), gizzard (n = 100), and poultry heart (n = 100), were randomly collected from Dezful industrial poultry abattoir and were experimented in order to investigate presence of Campylobacter species. According to culture test, 251 samples out of 400 samples under study (69%) were contaminated with Campylobacter species. The highest prevalence of Campylobacter species was observed in poultry's liver (78.3%) and then in gizzard (75.8%), heart (65%) and meat (56.7%). The most common isolated Campylobacter were C. jejuni (90.9%) and the rest were C. coli (9.1%). There was a significant difference (P < 0.05) in the prevalence of Campylobacter species between the meat samples taken in the summer (86.7%). The results of this study indicate the importance of edible offal of poultries as the potential source of Campylobacter infections.

Keywords: Campylobacter jejuni, Campylobacter coli, poultry, meat, products

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

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We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

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Authors: Deepak Kumar Mittal, Alok Kumar Jena, Deepmala Joshi

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The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the aqueous extract of the roots of Polygonum bistorta (PB) (200 mg/kg) and Zingiber roseum (ZR) (250 mg/kg) in rats treated with carbon tetrachloride (0.15 ml/kg, i.p.). Extract of PB and ZR at the tested doses restored the levels of liver homogenate enzymes, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymes, significantly. The activities of MTT assay significantly recovered the damage and supported the biochemical observations. This study suggests that Zingiber roseum has a higher protective effect on liver, compared to Polygonum bistorta, against carbon tetrachloride-induced hepatotoxicity and possesses antioxidant activities. Also, extracts exhibited moderate anticancer activity towards cell viability at higher concentration.

Keywords: Polygonum bistorta, Zingiber roseum, hepatoprotective effect, carbon tetrachloride, anti-cancerous

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Authors: M. Zehtabian, Z. Molaiemanesh, Z. Shafahi, M. Papie, M. Zahraie Moghaddam, M. Mehralizadeh, M. R. Vahidi, S. Sina

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The introduction of CT scans has been a great improvement in diagnosis of different diseases. However, this imaging modality can expose the patients to cumulative radiation doses which may increase the risks of some health problems like cancer. In this study, the dose delivered to different organs in lumbar-abdominal imaging was measured by putting the TLD-100, and TLD-100H chips inside the Alderson Rando phantom. The lumbar-abdominal image of the phantom was obtained, while TLD chips were inside the holes of the phantom. According to the results obtained in this study using TLD-100 chips, the average dose received by liver, bladder, rectum, kidneys, and uterus were found to be 12.9 mSv, 8.9 mSv, 10.1 mSv, 11.0 mSv, 11.2 mSv, and 10.5 mSv respectively, while the measurements performed by TLD-100H show that the average dose to liver, bladder, rectum, kidneys, and uterus were found to be 12.4 mSv, 9.2 mSv, 9.5 mSv, 10.5 mSv, 10.7 mSv, and 9.9 mSv respectively. The results of this study indicates that the dose measured by the TLD-100H chips are in close agreement with those obtained by TLD-100.

Keywords: CT scan, dose, TLD-100, diagnosis

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Authors: Awad G. Abdellatif, Huda M. Gargoum, Abdelkader A. Debani, Mudafara Bengleil, Salmin Alshalmani, N. El Zuki, Omran El Fitouri

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In this study, the administration of 660 mg/kg of the ethanolic extract of the Alhgigraecorum (camel thorn) to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. The histopathological investigation also confirmed that camel thorn extract protects the liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand, the cardiac toxicity produced by adriamycin was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with an unexpected increase in the cardiac toxicity–induced by adriamycin in rodents.

Keywords: ethanolic, alhgigraecorum, tetrachloride, acetaminophen

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Authors: Muhammad Shahzad Tufail, Iram Liaqat

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Silver nanoparticles (AgNPs) have wider biomedical applications due to their intensive antimicrobial activities. However, toxicity and side effects of nanomaterials like AgNPs is a subject of great controversy towards the further studies in this direction. In this study, biogenically synthesized AgNPs, previously characterized via ultraviolet (UV) visible spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR), were subjected to toxicity evaluation using mice model. Albino male mice (BALB/c) were administered with 50 mgkg-1, 100 mgkg-1 and 150 mgkg-1 of AgNPs, respectively, except for control for 30 days. Log-probit regression analysis was used to measure the dosage response to determine the median lethal dose (LD50). Exposure to AgNPs caused significant changes in the levels of serum AST (P ˂ 0.05) at the 100mgkg-1 and 150mgkg-1 of AgNPs exposure, while ALT and serum creatinine (P ˃ 0.05) levels remained normal. Histopathology of male albino mice liver and kidney was studied after 30 days experimental period. Results revealed that mice exposed to heavy dose (150 mgkg-1) of AgNPs showed cell distortion, necrosis and detachment of hepatocytes in the liver. Regarding kidney, at lower concentration, normal renal structure with normal glomeruli was observed. However, at higher concentration (150 mgkg-1), kidneys showed smooth surface and dark red colour with proliferation of podocytes. It can be concluded from present study that biologically synthesized AgNPs are small to be eliminated easily by kidney and therefore the liver and kidney did not show toxicity at low concentrations.

Keywords: silver nanoparticles, pseudomonas aeruginosa, male albino mice, toxicity assessment

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Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

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Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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