Search results for: Liver X receptor (LXR)

Authors: Ahsan Khan, Nazish Shah, Muhammad Salman

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The present study deals with the toxicological effects of copper, lead and chromium on brain and liver tissues of grass carp (Ctenopharyngodon idella). The average length of experimental fish was 8.5 ± 5.5 cm and weighed 9.5 ± 6.5 g. Grass carp was exposed to lethal concentration (LC₁₅) of copper, lead and chromium for 24, 48, 72 and 96 hours respectively. (LC₁₅) for copper was 1.5, 1.4, 1.2 and 1mgL⁻¹. Similarly, LC₁₅ of lead was 250, 235, 225 and 216mgL⁻¹ while (LC₁₅) for chromium was 25.5, 22.5, 20 and 18mgL⁻¹ respectively. During the time of exposure against various doses of heavy metals the grass carp showed some behavioral changes. In the initial stages of experiment, the rapid movements and gulping of air were observed. Several times the fish tried to jump to scat from the toxic median. In addition, the accumulation of heavy metals in different tissues of grass carp particularly in liver and brain tissues were observed. Lead was highly accumulated in brain tissue after the exposure of fish for 24 and 48 hours, while highly accumulated in liver tissues after the exposure of fish for 72 and 96 hours. Chromium was highly accumulated in the liver tissues after the exposure of fish for 24 hours while its accumulation was found highly in the brain tissues after the exposure of fish for 48, 72 and 96 hours. Similarly, accumulation of copper concentration was found highly in brain tissues after the exposure of 48 and 96 hours while its accumulation was high in liver tissues after the exposure of 24 and 72 hours. Comparatively maximum accumulation of lead was found in brain and liver tissues of grass carp followed by chromium and copper. Furthermore, accumulation of these metals caused many abnormalities like gliosis, destruction of cell, change in cell shape and shrinkage of cells in brain tissue while in liver tissues aggregation in hepatocytes, widen space between cells and also destruction of cell was observed. These experiments and observations can be useful to monitor the aquatic pollution and quality of aquatic environment system.

Keywords: brain, grass carp, liver, lethal concentration, toxicity

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Authors: Ahmedou Moulaye Idriss, Tfeil Yahya, Tamas Ungi, Gabor Fichtinger

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Image-guided therapy (IGT) plays a crucial role in minimally invasive procedures for liver interventions. Accurate segmentation of the liver and precise needle placement is essential for successful interventions such as needle aspiration. In this study, we propose a deep learning-based liver 3D slicer designed to enhance segmentation accuracy and facilitate needle aspiration procedures. The developed 3D slicer leverages state-of-the-art convolutional neural networks (CNNs) for automatic liver segmentation in medical images. The CNN model is trained on a diverse dataset of liver images obtained from various imaging modalities, including computed tomography (CT) and magnetic resonance imaging (MRI). The trained model demonstrates robust performance in accurately delineating liver boundaries, even in cases with anatomical variations and pathological conditions. Furthermore, the 3D slicer integrates advanced image registration techniques to ensure accurate alignment of preoperative images with real-time interventional imaging. This alignment enhances the precision of needle placement during aspiration procedures, minimizing the risk of complications and improving overall intervention outcomes. To validate the efficacy of the proposed deep learning-based 3D slicer, a comprehensive evaluation is conducted using a dataset of clinical cases. Quantitative metrics, including the Dice similarity coefficient and Hausdorff distance, are employed to assess the accuracy of liver segmentation. Additionally, the performance of the 3D slicer in guiding needle aspiration procedures is evaluated through simulated and clinical interventions. Preliminary results demonstrate the effectiveness of the developed 3D slicer in achieving accurate liver segmentation and guiding needle aspiration procedures with high precision. The integration of deep learning techniques into the IGT workflow shows great promise for enhancing the efficiency and safety of liver interventions, ultimately contributing to improved patient outcomes.

Keywords: deep learning, liver segmentation, 3D slicer, image guided therapy, needle aspiration

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Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Sohair Hassan, Olfat Hammam, Sahar Hussein, Wessam Magdi

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Objective: Acute liver failure (ALF) is a clinical condition with an unclear history of pathophysiology, making it a challenging task for scientists to reverse the disease in its initial phase and to help the liver re-function customary: this study aimed to estimate the hepatoprotective effects of Punica granatum Lpeel and Pistacia atlantica leaves as a multi-rich antioxidants ingredients either in their normal and/or in their nanoforms against thioacetamide induced acute liver failure in a rodent model. Method: Male Wistar rats (n=60) were divided into six equal groups, the first group employed as a control; The second group administered a dose of 350 mg /Kg/ b.w of thioacetamide (TAA)-IP, from the third to the sixth group received TAA + [2mls / 100 g b.w/d] of aqueous extracts of Punica granatum L and Pistacia atlantica either in their normal and/or Nano forms consecutively for (14 days) Results: Recorded significant elevation in liver enzymes, lipid profiles, LPO (p= 0.05) and NO with a marked significant decrease in GSH and SOD accompanied by an elevation in inflammatory cytokine (IL6, TNF-α, and AFP) in addition to a noticeable increase in HSP70 level & degradation in DNA respectively in TAA challenged group. However significant and subsequent amelioration of most of the impaired markers was observed with ip nano treatment of both extracts. Conclusion: The current results highlighted the high performance of both plant nano extracts and their hepatoprotective impact and their possible therapeutic role in the amelioration of TAA induced acute liver failure in experimental animals.

Keywords: acute liver failure HPLC, IL6, nano extracts, thioacetamide, TNF-α

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Authors: Prativa Das, Lay Poh Tan

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Three-dimensional microenvironment is a need to study the event cascades of liver fibrosis in vitro. Electrospun nanofibers modified with essential extracellular matrix proteins can closely mimic the random fibrous structure of native liver extracellular matrix (ECM). In this study, we fabricate a series of 3D electrospun scaffolds by wet electrospinning process modified with different ratios of collagen-I to fibronectin to achieve optimized distribution of these two ECM proteins on the fiber surface. A ratio of 3:1 of collagen-I to fibronectin was found to be optimum for surface modification of electrospun poly(lactic-co-glycolic acid) (PLGA) fibers by chemisorption process. In 3:1 collagen-I to fibronectin modified scaffolds the total protein content increased by ~2 fold compared to collagen-I modified and ~1.5 fold compared to 1:1/9:1 collagen-I to fibronectin modified scaffolds. We have cultured LX-2 cells on this scaffold over 14 days and found that LX-2 cells acquired more quiescent phenotype throughout the culture period and shown significantly lower expression of alpha smooth muscle actin and collagen-I. Thus, this system can be used as a model to study liver fibrosis by using different fibrogenic mediators in vitro.

Keywords: electrospinning, collagen-I and fibronectin, surface modification of fiber, LX-2 cells, liver fibrosis

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Ryan M. Monti, Bijal Mehta

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In cases of massive pulmonary embolism, defined as acute pulmonary embolism presenting with systemic hypotension or right ventricular dysfunction and impending failure, there is indication that unconventional therapies, such as phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs may decrease the morbidity and mortality. Based on the premise that dilating the pulmonary artery will decrease the pulmonary vascular pressure, while simultaneously decreasing the aggregation of platelets, it can be hypothesized that increased blood flow through the pulmonary artery will decrease right heart strain and subsequent morbidity and mortality. While this theory has yet to be formally studied, the recommendations for treating massive pulmonary embolism with phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs in conjunction with the current standards of care in massive pulmonary embolism should be formally studied. In particular, patients with massive PE who are unable to undergo thrombolysis/surgical intervention may be the ideal population to study the use of these treatments to determine any decrease in mortality and morbidity (short term and long term).

Keywords: acute pulmonary thromboembolism, treatment of pulmonary embolism, use of phosphodiesterase inhibitors, endothelin receptor antagonists, prostacyclin analogs in PE

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Authors: Alli Smith Yemisi Rufina, Adanlawo Isaac Gbadura

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Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity, and high mortality, its medical management is currently inadequate. This study was designed to evaluate the Hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced Wistar albino rats. Twenty-five male adult Wistar albino rats were divided into five (5) groups. Group I, was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV, and V were pre-treated with 100, 200 and 400 mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty-four hours after administration, the rats were sacrificed, and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and Conjugated Bilirubin, Glucose and Protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained with Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also, histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of the structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Keywords: hepatoprotective, liver damage, Garcinia kola, saponin, paracetamol

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Authors: Melkamu A., Woldu B., Sitotaw C., Seyoum M., Aynalem M.

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Background: Liver disease is any condition that affects the liver cells and their function. It is directly linked to coagulation disorders since most coagulation factors are produced by the liver. Therefore, this study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients. Methods: A cross-sectional study was conducted from August to October 2022 among 307 consecutively selected study participants at the University of Gondar Comprehensive Specialized Hospital. Sociodemographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 2.7 mL of venous blood was collected and analyzed by the Genrui CA51 coagulation analyzer. Data was entered into Epi-data and exported to STATA version 14 software for analysis. The finding was described in terms of frequencies and proportions. Factors associated with coagulation abnormalities were analyzed by bivariable and multivariable logistic regression. Result: In this study, a total of 307 study participants were included. Of them, the magnitude of prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were 68.08% and 63.51%, respectively. The presence of anemia (AOR = 2.97, 95% CI: 1.26, 7.03), a lack of a vegetable feeding habit (AOR = 2.98, 95% CI: 1.42, 6.24), no history of blood transfusion (AOR = 3.72, 95% CI: 1.78, 7.78), and lack of physical exercise (AOR = 3.23, 95% CI: 1.60, 6.52) were significantly associated with prolonged PT. While the presence of anaemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of vegetable feeding habit (AOR = 2.64; 95% CI: 1.34, 5.20), no history of blood transfusion (AOR = 2.28; 95% CI: 1.09, 4.79), and a lack of physical exercise (AOR = 2.35; 95% CI: 1.16, 4.78) were significantly associated with abnormal APTT. Conclusion: Patients with liver disease had substantial coagulation problems. Being anemic, having a transfusion history, lack of physical activity, and lack of vegetables showed significant association with coagulopathy. Therefore, early detection and management of coagulation abnormalities in liver disease patients are critical.

Keywords: coagulation, liver disease, PT, Aptt

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Authors: P. Strakos, M. Jaros, T. Karasek, T. Kozubek, P. Vavra, T. Jonszta

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In medical imaging, segmentation of different areas of human body like bones, organs, tissues, etc. is an important issue. Image segmentation allows isolating the object of interest for further processing that can lead for example to 3D model reconstruction of whole organs. Difficulty of this procedure varies from trivial for bones to quite difficult for organs like liver. The liver is being considered as one of the most difficult human body organ to segment. It is mainly for its complexity, shape versatility and proximity of other organs and tissues. Due to this facts usually substantial user effort has to be applied to obtain satisfactory results of the image segmentation. Process of image segmentation then deteriorates from automatic or semi-automatic to fairly manual one. In this paper, overview of selected available software applications that can handle semi-automatic image segmentation with further 3D volume reconstruction of human liver is presented. The applications are being evaluated based on the segmentation results of several consecutive DICOM images covering the abdominal area of the human body.

Keywords: image segmentation, semi-automatic, software, 3D volumetric reconstruction

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Authors: Cheng-Kuang Hsu, Chih-Hsiang Chang, Chi-Chih Wang

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Black soybeans contain high amount of antioxidants including polyphenols, anthocyanins and flavones. The protective function of black soybean against CCl4 (a strong oxidant) induced acute and chronic liver damage was investigated in vivo using SD rats or ICR mouse. The evaluation of CCl4 induced oxidative stress in the liver tissues included the measurements of the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the concentration of thiobarbituric acid reactive substances (TBARS), the activities of antioxidant enzymes (superoxide dismutase SOD, catalase, and glutathione peroxidase GPx), as well as the level of histological lesion in the liver tissues. For chronic experiment, a decoction at the concentration of 100 or 1000 mg/kg of body weight, produced by baking black soybean at 130°C for 5 min and followed by immerging in 100°C hot water for 20 min, showed the inhibitory effect against CCl4 induced liver damage in SD rats. Hot-water extract (80 °C for 30 min) from un-preheated black soybean at the concentration of 200 mg/kg of body weight could not reduce ALT and AST levels in CCl4 treated SD rats, but the hot-water extract from preheated black soybean did enhance antioxidant enzymes activities, decline ALT and AST levels. Specially, the hot-water extract from the seed cost of black soybean had the highest liver protective function since it can reduce vacuolization and necrosis in the liver tissues. For acute experiment, the hot-water extracts from black soybean and the seed coat, as well as pure cyanidin-3-glucoside (C3G) could reduce ALT and AST levels of CCl4 induced ICR mouse. The decoction and hot-water extract from the seed coat of black soybean had higher total polyphenols, anthocyanins and flavones contents than those extracts from whole black soybean. Such results agreed with high liver protective function in the decoction and hot-water from the seed coat of black soybean. Black soybean showed protective function only after preheating process (baking at 130°C for 5 to 10 min) because preheating treatment damaged the cell wall and made the extraction of the antioxidants more effectively.

Keywords: black soybean, liver protective function, antioxidant, antioxidative stress

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Authors: Mohamed Amine Aiche, Elkhansa Yahia, Leila Mallem, Mohamed Salah Boulakoud

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Exposure to endocrine disrupting (ED) during life may cause long-term health effects, the population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products. Previous research indicates that a wide range of pesticides may act as endocrine disrupters. The azole fungicides propiconazole and propineb have been shown to react through several endocrine disrupting mechanisms, and to induce various endocrine disrupting effects. The purpose of this study was to evaluate the effects of two fungicides; propiconazole and propineb tested separately and in combination, on liver function. The experimental was applied on male Wistar rats dosed orally with Propiconazole 60 mg/kg/day, Propineb 100 mg/kg/day and their mixture 30 mg Propiconazole/kg/day + 50 mg Propineb /kg/day for 4 weeks, for result, a significant increase in liver weights in both treated groups with propineb, propiconazole and their mixture by reference with controls group. Also, highly significant mean values of markers of liver function such as transaminases (ALT/AST) and the activity of alkaline phosphatase (ALP) in all treated groups. The antioxidant activity showed a significant decrease in the hepatic glutathione content (GSH) and glutathione peroxidase (GPX) in all treated groups.

Keywords: endocrine disrupting, pesticide mixture, propineb, propiconazole, liver, oxidative stress

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Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Latifeh Navidpour, Shabnam Shabani, Alireza Heidari, Manouchehr Bashiri, Azadeh Ebrahim-Habibi, Soraya Shahhosseini, Hamed Shafaroodi, Sayyed Abbas Tabatabai, Mahsa Toolabi

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A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABAA/ benzodiazepine receptor complex (IC50 values of 0.04–4.1 nM), relative to diazepam as the reference drug (IC50 value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLogP) and onset of action of studied analogues (r2 = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025–0.1 mg/kg, relative to diazepam (0.025 mg/kg).

Keywords: 1, 2, 4-triazole, flexible benzodiazepines, GABAA/bezodiazepine receptor complex, onset of action, PTZ induced seizure threshold

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Authors: Karim Adinehvand, Bakhtiar Azadbakht, Amin Sahebnasagh

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Relation to high absorption fraction of Tc SESTAMIBI by internal organs in heart scan, and these organs are near to generation organs (Ovaries and uterus). In this study, Liver is specified as source organ. Method: we have set amount of absorbed fraction radiopharmaceutical in position of Liver in RANDO-phantom in form of elliptical surfaces, then absorbed dose to ovaries and uterus measured by TLD-100 that had set at position of these organs in RANDO-phantom. Calculation had done by MIRD method. Results from direct measurement and MIRD method are too similar. The absorbed dose to uterus and ovaries for Rest are 26.05µGyMBq-1, 17.23µGyMBq-1 and for Stress are 2.04µGyMBq-1, 1.35µGyMBq-1 respectively.

Keywords: absorbed dose, TLD, MIRD, RANDO-phantom, Tc-99m

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Authors: Oluwafemi Ojo, Omotade Oloyede

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This study seeks to investigate the antioxidative properties and the ability of aqueous, ethanolic and ethyl acetate extracts from Ocimum gratissimum (OG) leaves to inhibit some pro-oxidants (Fe2+ and sodium nitroprusside) induced lipid peroxidation in rat’s liver homogenates in vitro. The ability of the extracts to inhibit 25 µM FeSO4 and 7.0 µM sodium nitroprusside induced lipid peroxidation in isolated rat’s liver was determined. The results of the study revealed that both pro-oxidants caused a significantly decrease in (p < 0.05) accumulation of lipid peroxides. However, aqueous extract of OG shows a high ability to inhibit lipid production in the liver induced with SNP than Fe2+. Ethanolic and ethyl acetate extract of OG which shows a high ability to inhibit lipid production more when induced with Fe2+ than SNP. However, ethyl acetate fraction of OG shows a higher inhibitory effect on both Fe2+ and SNP induced lipid peroxidation in rat’s liver. This applies to its significantly higher extractable phytochemicals. Therefore, Fe II and sodium nitroprusside induced oxidative stress could be managed by dietary intake of Ocimum gratissimum leaves.

Keywords: antioxidative, pro-oxidants, lipid peroxidation, Ocimum gratissimum

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Authors: Saeedeh Salimi, Farzaneh Farajian- Mashhadi, Ehsan Tabatabaei, Mahnaz Shahrakipoor, Minoo Yaghmaei, Mojgan Mokhtari

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Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore ERα gene could be a possible candidate for preeclampsia(PE) susceptibility. In the current study, we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: One hundred ninety-two pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by PCR-RFLP method. Results: The frequency of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; P = 0.02) and in severe PE compared to normotensive women [OR= 1.8(1.1-3), P=0.02] after adjusting for age, ethnicity and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.

Keywords: estrogen receptor-α, polymorphism, gene, preeclampsia

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Authors: Tugba Sevinc Gamsiz, Emine Koroglu, Ozcan Keskin

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Aim: Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease in the general population. The higher mortality and morbidity among NAFLD patients and lack of symptoms makes early detection and management important. In our study, we aimed to evaluate the relationship between noninvasive imaging and biochemical markers in diabetic and nondiabetic patients diagnosed with NAFLD. Materials and Methods: The study was conducted from (September 2017) to (December 2017) on adults admitted to Internal Medicine and Gastroenterology outpatient clinics with hepatic steatosis reported on ultrasound or transient elastography within the last six months that exclude patients with other liver diseases or alcohol abuse. The data were collected and analyzed retrospectively. Number cruncher statistical system (NCSS) 2007 program was used for statistical analysis. Results: 116 patients were included in this study. Diabetic patients compared to nondiabetics had significantly higher Controlled Attenuation Parameter (CAP), Liver Stiffness Measurement (LSM) and fibrosis values. Also, hypertension, hepatomegaly, high BMI, hypertriglyceridemia, hyperglycemia, high A1c, and hyperuricemia were found to be risk factors for NAFLD progression to fibrosis. Advanced fibrosis (F3, F4) was present in 18,6 % of all our patients; 35,8 % of diabetic and 5,7 % of nondiabetic patients diagnosed with hepatic steatosis. Conclusion: Transient elastography is now used in daily clinical practice as an accurate noninvasive tool during follow-up of patients with fatty liver. Early diagnosis of the stage of liver fibrosis improves the monitoring and management of patients, especially in those with metabolic syndrome criteria.

Keywords: diabetes, elastography, fatty liver, fibrosis, metabolic syndrome

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Authors: Roshika Tyagi, Shuvomoy Banerjee

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Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

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This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 µg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters and histopathological examination of various rabbits’ organs. Tissue distribution of AuNPs was evaluated at a dose of 300 µg/ kg in male rabbit. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions in lung and liver cells were induced in rabbits treated at the300 µg/ kg dose level. The highest gold levels were found in the spleen, followed by liver, lungs and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: gold nanoparticles, toxicity, pathology, hematology, liver function, kidney function

Procedia PDF Downloads 335

Authors: Yu-Chih Wang, Chia-Yu Lai, Hsiao-Tien Liu, Yi-Ju Chen, Shao-Bin Cheng

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Liver transplant has been one of the curative treatment options for hepatocellular carcinomaunder certain oncological conditions. Two of the most validated criteria are from Milan in1996 and USCF in 2001, suggesting number and size limits of tumor without vascularinvasion or distant metastasis. We performed a retrospective cohort study of hepatocellular carcinoma patients undergoing livertransplant between August 2003 and December 2020 in our institute. Clinical andpathological characteristic, survival outcome, and recurrent pattern were analysed.UCSF criteria was applied for living donor transplantation, and Milan criteria was applied for deceased donor transplantation. Of 180 total patients, 52 cases(28.8%) with diagnosis of hepatocellular carcinoma, including26 living donor(LD) and 26 deceased donor(DD) liver transplant. Complete pathologicalremission was significantly more in the DD group(p=0.009). Pathological reports showed that30.8% of DD group exceeded Milan criteria, and 19.2% of LD group exceeded UCSFcriteria.After a median follow-up of 52.2 months, the 1-year, 3-year and 5-year overall survival was 87.6%, 74.1%, and 71.8%, respectively.Meanwhile, progression-free survival was 93.1%, 85.7%, and 81.6% for 1, 3, and 5-year, respectively, similar to that in Mazzaferro et al, 1996. We concluded that Liver transplant could be applied cautiously in expanded criteria for patent withhepatocellular carcinoma.

Keywords: liver transplant, milan criteria, UCSF criteria, living donor transplantation, deceased donor transplantation

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Authors: W. Fatmi, F. Kriba, Z. Kechrid

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The aim of this study was to investigate the effect of vitamin C on blood biochemical parameters, tissue zinc, and antioxidants enzymes in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin C (1mg/l) for 27 days. Body weight and food intake were recorded regularly during 27 days. On day 28, animals were killed and glucose, total lipids, triglycerides, protein, urea, serum zinc , tissues zinc concentrations, liver glycogen, GSH, TBARS concentrations and serum GOT, GPT, ALP and LDH, liver GSH-Px, GST and Catalase activities were determined. Body weight gain and food intake of zinc deficient diabetic animals at the end of experimental period was significantly lower than that of zinc adequate diabetic animals. Dietary zinc intake significantly increased glucose, lipids, triglycerides, urea, and liver TBARS levels of zinc deficient diabetic rats. In contrast, serum zinc, tissues zinc, protein, liver glycogen and GSH levels were decreased. The consumption of zinc deficient diet led also to an increase in serum GOT, GPT and liver GST accompanied with a decrease in serum ALP, LDH and liver GSH-Px, CAT activities. Meanwhile, vitamin C treatment was ameliorated all the previous parameters approximately to their normal levels. Vitamin C supplementation presumably acting as an antioxidant, and it probably led to an improvement of insulin activity, which significantly reduced the severity of zinc deficiency in diabetes.

Keywords: antioxidant, experimental diabetes, liver enzymes, vitamin c, zinc deficiency

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Authors: Yuhua Wang, Mu Li, Jinggen Liu

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Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

Procedia PDF Downloads 389

Authors: Nasim Nosoudi, Amir Zadeh, Hunter White, Joshua Conrad, Joon W. Shim

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De novo Malignancy has become one of the major causes of death after transplantation, so early cancer diagnosis and detection can drastically improve survival rates post-transplantation. Most previous work focuses on using artificial intelligence (AI) to predict transplant success or failure outcomes. In this work, we focused on predicting de novo malignancy after liver transplantation using AI. We chose the patients that had malignancy after liver transplantation with no history of malignancy pre-transplant. Their donors were cancer-free as well. We analyzed 254,200 patient profiles with post-transplant malignancy from the US Organ Procurement and Transplantation Network (OPTN). Several popular data mining methods were applied to the resultant dataset to build predictive models to characterize de novo malignancy after liver transplantation. Recipient's bilirubin, creatinine, weight, gender, number of days recipient was on the transplant waiting list, Epstein Barr Virus (EBV), International normalized ratio (INR), and ascites are among the most important factors affecting de novo malignancy after liver transplantation

Keywords: De novo malignancy, bilirubin, data mining, transplantation

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Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

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Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea

Abstract:

Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studies

Keywords: anastrazole, letrozole, liver, rats

Procedia PDF Downloads 352

Authors: Sabine Danzinger, Nora Hielscher, Miriam Izso, Johanna Metzler, Carmen Trinkl, Christian Pfeifer, Kristina Tendl-Schulz, Christian F. Singer

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The objective of this study is to analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. Methods: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). Results: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (þ), have a lower proliferation rate (Ki67 <14%), and a higher patholog- ical T stage (pT2–4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ERþ, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1–3) was significantly more frequent with ILC versus IDC. Conclusions: Our data suggests that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

Keywords: breast cancer, lobular histology, tumor biology, hormone receptor, ki67

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Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

Abstract:

Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

Procedia PDF Downloads 78