Search results for: liver

Authors: Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O Saleh, Manal Badawi

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Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P<0.05) lowered serum glucose, AST, ALT, triglyceride, cholesterol, IL-6, TNF-α and IL-1β. Moreover, the treated diabetic rats showed higher levels of reduced glutathione (P<0.05) in the liver compared to the diabetic control rats and inhibited diabetes-induced elevation in the levels of malondialdehyde in liver. The results of this study clearly demonstrated that diosmin and chrysin possess several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects and anti-inflammatory effects. Conclusion: Considering these observations, it appears that diosmin and chrysin may be a useful supplement to delay the developmentof diabetes and its complications.

Keywords: diabetes, streptozocin, chrysin, rat, diosmin, cytokines

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Authors: Laura Acevedo-Pacheco, Janet Alejandra Gutierrez-Uribe, Lucia Elizabeth Cruz-Suarez, Segio Othon Serna-Saldivar

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Seaweeds can generate changes in the metabolism of lipids; as a consequence, this may diminish cholesterol and other lipids in the blood. However, the consumption of marine algae may also alter the functions of other organs. Therefore, the objective of this research was to study the effect of two different sorts of algae (Ecklonia arborea and Silvetia compressa) in the metabolism of lipids, as well as, in the physiology of the liver. Wistar male rats were fed for two months with independent diets composed of 20% of fat and 2.5% of E. arborea and S. compressa each. Blood parameters (cholesterol, lipoproteins, triglycerides, hepatic enzymes) and triglycerides in the liver were quantified, and also hepatic histology analyses were performed. While S. compressa reduced 18% total cholesterol compared to the positive control, E. arborea increased it 5.8%. Animals fed with S. compressa presented a decrement, compared to the positive control, not only in low density lipoproteins levels (53%) but also in triglycerides (67%). The presence of steatosis in the histologies and the high levels of triglycerides showed an evident lipid accumulation in hepatic tissues of rats fed with both algae. These results indicate that even though S. compressa showed a promising resource to decrease total cholesterol and low-density lipoproteins in blood, a detrimental effect was observed in liver physiology. Further investigations should be made to find out if toxic compounds associated with these seaweeds may cause liver damage especially in terms of heavy metals.

Keywords: brown algae, Eisenia arborea, hepatic metabolism, lipidemic metabolism, Pelvetia compressa, steatosis

Procedia PDF Downloads 100

Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

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Authors: Nondumiso Lushozi, Busisani Lembede, Eliton Chivandi

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Consumption of fructose increases the risk of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome in children. Zingerone which is found in ginger has antidiabetic and antiobesogenic properties. Therefore, the aim of the study was to investigate the potential of orally administered zingerone to protect growing Sprague-Dawley rats (mimicking growing children) against high-fructose diet-induced metabolic derangements. Forty, 21-day old female Sprague-Dawley rats were randomly allocated and administered the following four treatments for 12 weeks: group I: standard rat chow (SR) + plain water (PW) + plain gelatine cube (PC). group II: SR + 20% (w/v) fructose solution (FS) + PC. group III: SR + FS + 100 mg/kg/day of fenofibrate in gelatine cube. group IV: SR+ FS + 20 mg/kg/day of zingerone in gelatine cube. The rats’ triglyceride, cholesterol, insulin & adiponectin concentration, visceral fat liver lipid content, homoeostasis model assessment of insulin resistance (HOMA-IR) and ability to handle glucose were determined. Oral administration of zingerone significantly increased (P<0.001) visceral fat and liver lipid content (P<0.001), respectively. Results from the study revealed that administration of 20% fructose solution did not induce metabolic dysfunction, however the zingerone treatment increased visceral fat and liver lipid content, all these lipid abnormalities are typical features of the metabolic syndrome, therefore the current study suggests that zingerone has no effect on metabolic dysfunction in adolescent females.

Keywords: antidiabetic, metabolic syndrome, zingerone, antiobesogenic

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Authors: Maryam Rafraf, Aida Ghaffari

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Objectives: Nonalcoholic fatty liver disease (NAFLD) is considered as an independent risk factor for cardiovascular disease (CVD). Dyslipidemia contributes to the enhanced risk of CVD in persons with NAFLD. This study aimed to investigate the effects of turmeric supplementation on serum lipids levels in patients with NAFLD. Methods: In this double-blind, randomized, controlled clinical trial, 46 NAFLD patients (21 males and 25 females; age range, 20 – 60 years) were randomly assigned in the two groups. The intervention and control groups received 3g of turmeric (n = 23) and placebo (n = 23), daily for 12 weeks. Fasting blood samples were collected at baseline and at the end of the trial. Results: Turmeric supplementation significantly increased serum levels of HDL-C compared with the placebo group at the end of the study (by 12.73%, P < 0.05). Serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced within turmeric group at the end of the study (P < 0.05). Conclusions: Turmeric consumption had beneficial effects on serum lipids levels of subjects and may be useful in controlling of CVD risk factors in NAFLD patients.

Keywords: nonalcoholic fatty liver, serum lipids, supplementation, turmeric

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Authors: Magda I. Hassan

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This paper aims to investigate the health effects of aspartame on weanling male hamsters. 20 Golden Syrian hamsters drank only water (control) or water with 6, 11, and 18 mg aspartame/kg of body weight per day for 42 days. Food intake, weight gain, glucose blood level, and lipid profile were determined at the end of the experiment. The animals were sacrificed and histopathological examination of organs (liver, brain and heart) was done. Results revealed that animals in Asp.groups consumed significantly larger amount of food than the control (13.4±5.9, 8.6±2.5 and 8.8±3.0 vs 4.2±2.5 g/day, in succession). Hamsters in the control group showed higher total cholesterol and HDL levels than hamsters in aspartame 6, 11, 18 groups (160±19 vs 101±13, 130±22, 141±15 mg/dl & 144±9 vs 120±12, 118±13, 99±17 respectively (P<0•05)). The control group showed a glucose concentration below those of aspartame groups, indicating no effect of aspartame on glucose blood level. While, there were no significant differences in the triglycerides and LDL levels between control group and Asp.groups. Histopathological changes were observed, especially in brain and liver cells. Aspartame increases appetite and weight gain of young hamsters. Therefore, FDA should reconsider the acceptable daily intake (ADI) of aspartame for children.

Keywords: aspartame, brain, food intake, hamsters

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Oluwatosin Adetola Arojojoye, Olajumoke Olufunlayo Alao, Philip Odigili

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This study investigated the extent of pollution in Eleyele River in Oyo State, Nigeria by investigating the antioxidant status and malondialdehyde levels (index of lipid peroxidation) in the organs of African Catfish, Clarias gariepinus from the river. Clarias gariepinus weighing between 250g-400g were collected from Eleyele River (a suspected polluted river) and Clarias gariepinus from a clean fish farm (Durantee fisheries) were used as the control. Levels of malondialdehyde, glutathione concentration (GSH) and activities of antioxidant enzymes - superoxide dismutase, catalase and glutathione-S-transferase (GST) were evaluated in the post-mitochondrial fractions of the liver, kidney and gills of the fishes. From the results, there were increases in malondialdehyde level and GSH concentration in the liver, kidney and gills of Clarias gariepinus from Eleyele River when compared with control. Glutathione-S-transferase activity was induced in the liver and kidney of Clarias gariepinus from Eleyele River when compared with control. However, the activity of this enzyme was depleted in the gills of fishes from Eleyele River compared with control. Also there was an induction in SOD activity in the liver of Clarias gariepinus from Eleyele River when compared with control but there was a decrease in the activity of this enzyme in the kidney and gills of fishes from Eleyele River compared with control. Increase in lipid peroxidation and alterations in antioxidant system in Clarias gariepinus from Eleyele River show that the fishes were under oxidative stress. These suggest that the river is polluted probably as a result of industrial, domestic and agricultural wastes frequently discharged into the river. This could pose serious health risks to consumers of water and aquatic organisms from the river.

Keywords: antioxidant, lipid peroxidation, Clarias gariepinus, Eleyele River

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Authors: Muhammad Waqar Ashraf, Atiq A. Mian

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In the present study, accumulation of eight heavy metals, lead (Pb), cadmium (Cd), manganese (Mn), copper (Cu), zinc (Zn), iron (Fe), nickel (Ni) and chromium (Cr)was determined in kidney, heart, liver and muscle tissues of Lethrinus miniatus fish caught from Arabian Gulf. Metal concentrations in all the samples were measured using Atomic Absorption Spectroscopy. Analytical validation of data was carried out by applying the same digestion procedure to standard reference material (NIST-SRM 1577b bovine liver). Levels of lead (Pb) in the liver tissue (0.60µg/g) exceeded the limit set by European Commission (2005) at 0.30 µg/g. Zinc concentration in all tissue samples were below the maximum permissible limit (50 µg/g) as set by FAO. Maximum mean cadmium concentration was found 0.15 µg/g in the kidney tissues. Highest content of Mn in the studied tissues was seen in the kidney tissue (2.13 µg/g), whereas minimum was found in muscle tissue (0.87 µg/g). The present study led to the conclusion that muscle tissue is the least contaminated tissue in Lethrinus miniatus and consumption of organs should be avoided as much as possible.

Keywords: lethrinus miniatus, arabian gulf, heavy metals, atomic absorption spectroscopy

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Authors: Turan Yaman, Zabit Yener, Ismail Celik

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The aim of this study was to investigate the antioxidant properties and protective role of honey, considered a part of traditional medicine, against carcinogen chemical aflatoxin (AF) exposure in rats, which were evaluated by histopathological changes in liver and kidney, measuring level of serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamil transpeptidase (GGT)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)], and lipid peroxidation content in liver, erythrocyte, brain, kidney, heart and lungs. For this purpose, a total of eighteen healthy Sprague-Dawley rats were randomly allocated into three experimental groups: A (Control), B (AF-treated) and C (AF+honey-treated). While rats in group A were fed with a diet without AF, B, and C groups received 25 µg of AF/rat/day, where C group additionally received 1 mL/kg of honey by gavage for 90 days. At the end of the 90-day experimental period, we found that the honey supplementation decreased the lipid peroxidation and the levels of enzyme associated with liver damage, increased enzymatic and non-enzymatic antioxidants in the AF+honey-treated rats. Hepatoprotective and nephroprotective effects of honey is further substantiated by showing almost normal histological architecture in AF+honey-treated group, compared to degenerative changes in the liver and kidney of AF-treated rats. Additionally, honey supplementation ameliorated antioxidant defense systems and lipid peroxidation content in other tissues of AF+honey-treated rats. In conclusion, the present study indicates that honey has a hepatoprotective and nephroprotective effect in rats with experimental aflatoxicosis due to its antioxidant activity.

Keywords: aflatoxicosis, honey, histopathology, malondialdehyde, antioxidant, rat

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

Procedia PDF Downloads 32

Authors: Muhammad Waqar Ashraf

Abstract:

In the present study, accumulation of eight heavy metals, lead (Pb), cadmium (Cd), manganese (Mn), copper (Cu), zinc (Zn), iron (Fe), nickel (Ni) and chromium (Cr)was determined in kidney, heart, liver and muscle tissues of Lethrinus Miniatus fish caught from Arabian Gulf. Metal concentrations in all the samples were measured using Graphite Furnace Atomic Absorption Spectroscopy (GF-AAS). Analytical validation of data was carried out by applying the same digestion procedure to standard reference material (NIST-SRM 1577b bovine liver). Levels of lead (Pb) in the liver tissue (0.60µg/g) exceeded the limit set by European Commission (2005) at 0.30 µg/g. Zinc concentration in all tissue samples were below the maximum permissible limit (50 µg/g) as set by FAO. Maximum mean cadmium concentration was found to be 0.15 µg/g in the kidney tissues. Highest content of Mn in the studied tissues was seen in the kidney tissue (2.13 µg/g), whereas minimum was found in muscle tissue (0.87 µg/g). The present study led to the conclusion that muscle tissue is the least contaminated tissue in Lethrinus Miniatus and consumption of organs should be avoided as much as possible.

Keywords: Arabian gulf, Lethrinus miniatus, heavy metals, atomic absorption spectroscopy

Procedia PDF Downloads 230

Authors: Mohammed A. Arishy, Sultan M. Alharbi, Mohammed A. Hakami, Farid M. Abualsail, Mohammad A. Attafi, Riyadh M. Tobaiqi, Hussain M. Alsalem, Ibraheem M. Attafi

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Lidocaine is the most common local anesthetics used for para cervical block to reduce pain associated with surgical abortion. A 25-year-old pregnant woman who. She died before reaching hospital, and she was undergoing criminal abortion during the first trimester. In post-mortem investigations and autopsy shows no clear finding; therefore, toxic substances must be suspected and searched for routinely toxicology analysis. In this case report, the postmortem concentration of lidocaine was detected blood, brain, liver, kidney, and stomach. For lidocaine identification and quantification, sample was extracted using solid phase extraction and analyzed by GC-MS (Shimadzu, Japan). Initial screening and confirmatory analysis results showed that only lidocaine was detected in all collected samples, and no other toxic substances or alcohol were detected. The concentrations of lidocaine in samples were 19, 17, 14, 7, and 3 ug/m in the brain, blood, kidney, liver, and stomach, respectively. Lidocaine blood concentration (17 ug/ml) was toxic level and may result in death. Among the tissues, brain showed the highest level of lidocaine, followed by the kidney, liver, and stomach.

Keywords: forensic toxicology, GC-MS, lidocaine, postmortem

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Authors: Zakia Alioua, Amira Soumia, Zerouali-Khodja Fatiha

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In spite of a wide variety of contaminants such as heavy metals and organic compounds in addition to the importance of extended pollution, the deep-sea and its species are not in haven and being affected through contaminants exposure. This investigation is performed in order to provide data on the presence of pathological changes in the liver and gonads of the greater forkbeard. A total of 998 specimens of the teleost fish Phycis blennoides Brünnich, 1768 ranged from 5,7 to 62,7 cm in total length, were obtained from the commercial fisheries of Algerian ports. The sampling has been carried out monthly from December 2013 to June 2015 and from January to June 2016 caught by trawlers and longlines between 75 and 600 fathoms in the coast of Algeria. Individuals were sexed their gonads, and their livers were removed and processed for light microscopy and one case of atresia was identified. In whole, overall 0,002% of the specimens presented some degree of liver steatosis. For the gastric section, 442 selected stomachs contents were observed looking for parasitic infestation and enumerate 212 nematodes. A prospecting survey for metal contaminant was performed on the liver by atomic absorption spectrophotometry analysis.

Keywords: atresia, coast of Algeria, histopathology, nematode, Phycis blennoides, steatosis

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Belgherbi Aicha, Hadjidj Ismahen, Bessaid Abdelhafid

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Accurate Liver, spleen and kidneys segmentation in abdominal CT images is one of the most important steps for computer aided abdominal organs pathology diagnosis. In this paper, we have proposed a new semi-automatic algorithm for Liver, spleen and kidneys area extraction in abdominal CT images. Our proposed method is based on hierarchical segmentation and watershed algorithm. In our approach, a powerful technique has been designed to suppress over-segmentation based on mosaic image and on the computation of the watershed transform. The algorithm is currency in two parts. In the first, we seek to improve the quality of the gradient-mosaic image. In this step, we propose a method for improving the gradient-mosaic image by applying the anisotropic diffusion filter followed by the morphological filters. Thereafter we proceed to the hierarchical segmentation of the liver, spleen and kidney. To validate the segmentation technique proposed, we have tested it on several images. Our segmentation approach is evaluated by comparing our results with the manual segmentation performed by an expert. The experimental results are described in the last part of this work.

Keywords: anisotropic diffusion filter, CT images, morphological filter, mosaic image, multi-abdominal organ segmentation, mosaic image, the watershed algorithm

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: M. Chaichanyut, S. Tungjitkusolmun

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This research is presented with microwave (MW) ablation by using the T-Prong monopole antennas. In the study, three-dimensional (3D) finite-element methods (FEM) were utilized to analyse: the tissue heat flux, temperature distributions (heating pattern) and volume destruction during MW ablation in liver cancer tissue. The configurations of T-Prong monopole antennas were considered: Three T-prong antenna, Expand T-Prong antenna and Arrow T-Prong antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The microwave power deliveries were 10 W; the duration of ablation in all cases was 300s. Our numerical result, heat flux and the hotspot occurred at the tip of the T-prong antenna for all cases. The temperature distribution pattern of all antennas was teardrop. The Arrow T-Prong antenna can induce the highest temperature within cancer tissue. The microwave ablation was successful when the region where the temperatures exceed 50°C (i.e. complete destruction). The Expand T-Prong antenna could complete destruction the liver cancer tissue was maximized (6.05 cm³). The ablation pattern or axial ratio (Widest/length) of Expand T-Prong antenna and Arrow T-Prong antenna was 1, but the axial ratio of Three T-prong antenna of about 1.15.

Keywords: liver cancer, T-Prong antenna, finite element, microwave ablation

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Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

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The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w.day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation.

Keywords: antioxidants, doxorubicin, hepatotoxicity, purslane

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Authors: Aya Gamal Khattab

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Chronic infection with the hepatitis C virus (HCV) is now the leading cause of liver-related morbidity and mortality; Currently, alanine aminotransferase ALT measurement is not only widely used in detecting the incidence, development, and prognosis of liver disease with obvious clinical symptoms, but also provides reference on screening the overall health status during health check-ups. Exercise is a low-cost, reliable and sustainable therapy for many chronic diseases. Low-volume high intensity interval training HIT is time efficient while also having wider application to different populations including people at risk for chronic inflammatory diseases. Purpose of this study was to investigate the effect of low volume high intensity interval training on ALT, AST in HCV patients. All practical work was done in outpatient physiotherapy clinic of Suez Canal Authority Hospitals. Forty patients both gender (27 male, 13 female), age ranged (40-60) years old submitted to low volume high intensity interval training on treadmill for two months three sessions per week. Each session consisting of five min warming up, two bouts for 10 min each bout consisting of 30 sec - 1 min of high intensity (75%-85%) HRmax then two to four min active recovery at intensity (40%-60%) HRmax, so the sum of high intensity intervals was one to two min for each session and four to eight min active recovery, and ends with five min cooling down. ALT and AST were measured before starting exercise session and 2 months later after finishing the total exercise sessions through blood samples. Results showed significant decrease in ALT, AST with improvement percentage (18.85%), (23.87%) in the study, so the study concluded that low volume high intensity interval training had a significant effect in lowering the level of circulating liver enzymes (ALT, AST) which means protection of hepatic cells and restoration of its function.

Keywords: alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C (HCV), low volume high intensity interval training

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Authors: Alireza Barari, Maryam Firozi-Niyaki, Maryam Kamarlouei

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Background: Herbs have a strong anti-cancer effect. Also, exercise is one of several lifestyle factors known to lower the risk of developing cancer. The aim of this study was to investigate the effect of endurance training and taxol on cyclooxygenase-2 and prostaglandin E2 in the liver tissue of mice with cervical cancer. Materials and Methods: In this experimental study, 35 female C57 mice were randomly divided into 5 groups (n=7 in each group): control (healthy), control (cancer), complement (cancer), training-supplementary (cancer) and training (cancer). The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/kg/day of pure taxol was injected intra peritoneally. The dependent variables of this study were measured 24 hours after the last training session by ELISA. Results: The results showed that the use of taxol and endurance training reduced the levels of cyclooxygenase-2 and prostaglandin E2 in the liver tissues of C57 mice with cervical cancer. Conclusion: Induction of the cancerous tissue in mice with cervical cancer increases the levels of cyclooxygenase-2 and prostaglandin E2 and endurance training along with taxol may reduce these levels.

Keywords: cervical cancer, taxol, endurance training, cyclooxygenase-2, prostaglandin E2

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Authors: Y. A. Shettima, M. A. Tijjani, S. Modu, F. I. Abdulrahman, B. M. Abubakar

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The toxicity profile of the methanolic extract of Punica granatum L. fruit rind was studied in normal rats. The rats were administered orally by intubating graded doses of 150, 250, 500 and 750 mg/kg body weight of the extract for 28 days and the effects on biochemical parameters and histology of the liver and kidney were evaluated. There was a significant increase (P<0.05) in the levels of liver enzymes of the rats that received the highest dose of 750 mg/kg body weight. The AST and ALT levels were 41.59±0.18 ALP and 9.25±0.29 IU/L, respectively, while the ALP level was 15.68±10 IU/L.There was a significant difference in the albumin and globulin levels; 3.72±0.05 and 4.05±0.13 g/dl, respectively. Serum urea and creatinine levels remained normal, as well as the electrolyte levels. The increase in sodium concentration observed was not statistically significant (P≥0.05) when the control group (131.50±3.11) was compared with the experimental groups (132.25±3.86, 132.75±3.86, 133.50±3.11 and 134.00±1.83). The increase in potassium concentration was not statistically significant (P≥0.05) when the control group with a value of 95.50±3.51 mmol/L was compared with the experimental groups 98.00±3.16, 99.25±2.22, 99.79±0.36 and 99.99±0.02 mmol/L. The increase observed in bicarbonate concentration was not statistically significant (P≥0.05) when the control group with a value of 20.75±1.71 mmol/L was compared with the experimental groups 21.68±0.62, 24.25±2.99, 24.50±3.42, 25.50±2.65 mmol/L.

Keywords: punical granatum, methanolic, ALT, AST, electrolytes, histology

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Authors: Hatem A. El-Mezayen, Hossam Darwesh

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Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. Methods: VEGF was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score)=1.26 (numerical constant) + 0.05 ×AFP (U L-1)+0.038 × VEGF(ng ml-1)+0.004× INR –1.02 × Albumin (g l-1)–0.002 × Platelet count × 109 l-1 was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 4.4 (ie less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, tumor markers

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Authors: Aml M. El-Sharkawy, Hossam M. Darwesh

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Abstract— Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between tumor associated trypsin inhibitor (TATI) and HCC progression, we aimed to develop a novel score based on combination of TATI and routine laboratory tests for early prediction of HCC. Methods: TATI was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-TATI score) = 3.1 (numerical constant) + 0.09 ×AFP (U L-1) + 0.067 × TATI (ng ml-1) + 0.16 × INR – 1.17 × Albumin (g l-1) – 0.032 × Platelet count × 109 l-1 was developed. HCC-TATI score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 6.5 (ie less than 6.5 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-TATI score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, TATI

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Chi V. Phan, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le

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Wilson’s disease is an autosomal recessive disorder of copper metabolism, which is caused by mutation in copper- transporting P-type ATPase (ATP7B). The mechanism of this disease is a failure of hepatic excretion of copper to the bile, and it leads to copper deposits in the liver and other organs. Most clinical symptoms of Wilson’s disease can present as liver disease and/or neurologic disease. Objective: The goal of the study is prenatal diagnosis for pregnant women at high risk of Wilson’s disease in Northern Vietnam. Material and method: Three probands with clinically diagnosed liver disease were detected in the mutations of 21 exons and exon-intron boundaries of the ATP7B gene by direct Sanger-sequencing. Prenatal diagnoses were performed by amniotic fluid sampling from pregnant women in the 16th-18th weeks of pregnancy after the genotypes of parents with the probands were identified. Result: A total of three different mutations of the probands, including of S105*, P1052L, P1273G, were detected. Among three fetuses which underwent prenatal genetic testing, one fetus was homozygote; two fetuses were carriers. Conclusion: Genetic testing provided a useful method for prenatal diagnosis, and is a basis for genetic counseling.

Keywords: ATP7B gene, genetic testing, prenatal diagnosis, pedigree, Wilson disease

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Authors: Khaled S. Al Salhen

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Aldehyde oxidase is molybdo-flavoenzyme involved in the oxidation of hundreds of endogenous and exogenous and N-heterocyclic compounds and environmental pollutants. Uncharged N-heterocyclic aromatic compounds such phenanthridine are commonly distributed pollutants in soil, air, sediments, surface water and groundwater, and in animal and plant tissues. Phenanthridine as uncharged N-heterocyclic aromatic compound was incubated with partially purified aldehyde oxidase from rainbow trout fish liver. Reversed-phase HLPC method was used to separate the oxidation products from phenanthridine and the metabolite was identified. The 6(5H)-phenanthridinone was identified the major metabolite by partially purified aldehyde oxidase from fish liver. Kinetic constant for the oxidation reactions were determined spectrophotometrically and showed that this substrate has a good affinity (Km = 78 ± 7.6 µM) for hepatic aldehyde oxidase, coupled with a relatively high oxidation rate (0.77± 0.03 nmol/min/mg protein). In addition, the kinetic parameters of hepatic fish aldehyde oxidase towards the phenanthridine substrate indicate that in vitro biotransformation by hepatic fish aldehyde oxidase will be a significant pathway. This study confirms that partially purified aldehyde oxidase from fish liver is indeed the enzyme responsible for the in vitro production 6(5H)-phenanthridinone metabolite as it is a major metabolite by mammalian aldehyde oxidase.

Keywords: aldehyde oxidase, fish, phenanthridine, specificity

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: David Tanujaya Kurniawan

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Background: Liver injury caused by paracetamol is marked by increased serum transaminase levels. Turmeric is a local herb that is available in large quantities and inexpensive in contradiction to its substantial benefits, including its potency to increase glutathione production and regenerate hepatocyte into normal condition. Aim: The aim of this study was to analyze the potencial treatment effect of turmeric rhizome extract to reduce serum transaminase level on paracetamol induced liver toxicity in rats. Methods: This study was a laboratory experimental research with post-test only controlled group design. A group of 24 Wistar white male rats was induced with paracetamol 360 mg/kg body weight for 10 days. The group was then separated into four groups: the first and the second was treated with 100 mg/kg body weight and 150 mg/kg body weight of turmeric rhizome extract, subsequently, the third as positive control was given 27 mg/kg body weight of lesichol, while the fourth as negative control was given CMC-Na 1%. Each of this treatment was given for seven days. At the end of the study, the blood samples were taken to measure SGOT and SGPT levels. The one-way Anova test revealed significant difference in mean of SGPT level (p=0,001). The LSD test showed significant differences of SGPT levels in both treatment groups and negative control group. However, there was no sgnificant difference between positive control and both treatment groups. Conclusion: Curcuma domestica Val. rhizome extract could not reduce SGOT level, but it reduced SGPT level significantly.

Keywords: Curcuma domestica val., SGOT, SGPT, paracetamol, liver toxicity

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Fakhrosadat Sajjadian

Abstract:

The majority of deaths in cancer patients are caused by distant metastasis. Breast cancer shows a unique spread pattern, often affecting bone, liver, lung, and brain. Breast cancer can be categorized into various subtypes according to gene expression patterns, and these subtypes exhibit specific preferences for organs where metastasis occurs. Breast tumors with luminal characteristics have a preference for spreading to the bone, whereas basal-like breast cancer (BLBC) shows a tendency to metastasize to the lungs. Still, the mechanisms behind this particular pattern of metastasis in organs have yet to be fully understood. In this evaluation, we will outline the latest progress in molecular signaling pathways and treatment methods for breast cancer lung metastasis.

Keywords: lung cancer, liver cancer, diagnosis, BLBC, metastasis

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