• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.4
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• pp.342-349
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• 2023

Backgrounds/Aims: Liver organoids have emerged as a powerful tool for studying liver biology and disease and for developing new therapies and regenerative medicine approaches. For organoid culture, Matrigel, a type of extracellular matrix, is the most commonly used material. However, Matrigel cannot be used for clinical applications due to the presence of unknown proteins that can cause immune rejection, batch-to-batch variability, and angiogenesis. Methods: To obtain human primary hepatocytes (hPHs), we performed 2 steps collagenase liver perfusion protocol. We treated three small molecules cocktails (A83-01, CHIR99021, and HGF) for reprogramming the hPHs into human chemically derived hepatic progenitors (hCdHs) and used hCdHs to generate liver organoids. Results: In this study, we report the generation of liver organoids in a collagen scaffold using hCdHs. In comparison with adult liver (or primary hepatocyte)-derived organoids with collagen scaffold (hALO_C), hCdH-derived organoids in a collagen scaffold (hCdHO_C) showed a 10-fold increase in organoid generation efficiency with higher expression of liver- or liver progenitor-specific markers. Moreover, we demonstrated that hCdHO_C could differentiate into hepatic organoids (hCdHO_C_DM), indicating the potential of these organoids as a platform for drug screening. Conclusions: Overall, our study highlights the potential of hCdHO_C as a tool for liver research and presents a new approach for generating liver organoids using hCdHs with a collagen scaffold.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2257-2261
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• 2012

Pinocembrin (5, 7-dihydroxyflavanone) is a flavanone extracted from the rhizome of Boesenbergia pandurata. Our previous studies demonstrated that pinocembrin had no toxicity or mutagenicity in rats. We here evaluated its effects on the initiation and promotion stages in diethylnitrosamine-induced rat hepatocarcinogenesis, using short- and medium-term carcinogenicity tests. Micronucleated hepatocytes and liver glutathione-S-transferase placental form foci were used as end point markers. Pinocembrin was neither mutagenic nor carcinogenic in rat liver, and neither inhibited nor prevented micronucleus formation as well as GST-P positive foci formation induced by diethylnitrosamine. Interestingly, pinocembrin slightly increased the number of GST-P positive foci when given prior to diethylnitrosamine injection.

• Food Science and Biotechnology
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• v.14 no.1
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• pp.102-107
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• 2005

In this study, the ameliorating effect of soybean embryos on the impact of alcohol consumption was investigated on rat hepatocytes and in reducing total serum cholesterol levels and total serum lipid levels. Liver histology and two clinically important enzyme markers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), of rats administered with both alcohol and soybean embryo were compared with a control group. The treatment regimen of soybean embryo significantly reduced the serum ALT and AST levels of the subjects, demonstrating the hepato-protective effects of soybean embryo. Electron microscopy indicated that the administration of soybean embryo preserved the important hepatocyte structures and prevented the presence of lipid droplets and secondary lysosomes. Furthermore, total cholesterol and total lipid levels were significantly reduced. These results indicate that treatment with soybean embryo can positively mediate the effects of alcohol on hepatocytes and general liver functions.

• BMB Reports
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• v.56 no.7
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• pp.374-384
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• 2023

Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.5
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• pp.700-711
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• 2017

Objective: The current study aimed to investigate the impact of high-fat diets composed of different animal and vegetable fat sources on serum metabolic health markers in Japanese quail, as well as the overall lipid content and fatty acid profiles of the edible bird tissues following significantly increased dietary lipid supplementation. Methods: Fifty seven male quail were divided into six groups and fed either a standard diet or a diet enriched with one of five different fats (22% coconut oil, lard, palm oil, soybean oil, or sunflower oil) for 12 weeks. The birds were subjected to an oral glucose tolerance test following the feeding period, after which they were euthanized and blood, liver, breast, and thigh muscle samples collected. Total fat content and fatty acid profiles of the tissue samples, as well as serum uric acid, triglyceride, cholesterol, total protein, albumin, aspartate transaminase, and total bilirubin concentrations were assessed. Results: High-fat diet feeding had no significant effects on the glucose tolerance of the birds. Dietary fatty acid profiles of the added fats were reflected in the lipid profiles of both the liver and breast and thigh muscle tissues, indicating successful transfer of dietary fatty acids to the edible bird tissues. The significantly increased level of lipid inclusion in the diets of the quail used in the present study was unsuccessful in increasing the overall lipid content of the edible bird tissues. Serum metabolic health markers in birds on the high-fat diets were not significantly different from those observed in birds on the standard diet. Conclusion: Thus, despite the various high-fat diets modifying the fatty acid profile of the birds' tissues, unlike in most mammals, the birds maintained a normal health status following consumption of the various high-fat diets.

• Journal of the Korea Safety Management & Science
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• v.14 no.1
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• pp.43-51
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• 2012

This study was carried out to observe the impacts of a mouse's inhalation of toxic gas SO2 generated from combustion on its organs by different concentrations. As for research methods: First, after concentrations of SO2 generation from combustion had been set to three: low (10.4 ppm), middle (24.9 ppm) and high (122 ppm) through Gas Toxicity Testing Method (KS F 2271) and SO2 combustion gas was exposed to eight mice in each concentration. Five mice that were able to move based on LD50, a criterion, which sets the down time of a mouse's average behaviors to over 9 minutes, were randomly selected in each concentration, and they were set up as the subjects of the study on toxicity bio-markers. Second, tissues were taken from heart, liver, lungs, spleen and the thymus gland of the mice selected in each concentration and a pathological examination of them was carried out. As a result, microvascular congestion appeared in the heart, and cell necrosis, cortex congestion and tubule medulla congestion, etc. in each concentration were observed in addition to vascular congestion in liver, lungs, spleen and the thymus gland. Also, it was found that the higher the concentrations of SO2 exposure is, the greater, the changes in the organs get. Through this study, SO2 of various toxic gases generated from fire turned out to affect the tissues of each organ of a mouse, it is expected that the toxic gases may greatly affect human body in case of actual fire, and this study is evaluated as having a significance as a basic data on inhalation toxicity assessment of toxic substances generated in combustion.

• Journal of Korean Traditional Oncology
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• v.24 no.1
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• pp.19-28
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• 2019

Objective : The purpose of this study is to report and observe effects of Integrative Cancer Treatment (ICT) on metastatic breast cancer patient. Method : A left breast cancer patient diagnosed with recurrence on liver and bones April 2018. The patient had received paclitaxel chemotherapy for two months and discontinued it because of tumor progression and side effects. The patient has been treated with ICT since March 2018 and has been taking capecitabine since October 2018. The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (CEA, CA15-3). The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (CEA, CA15-3), liver function test (AST, ALT), Eastern Cooperative Oncology Group performance status (ECOG PS), and numeric rating scales (NRS). Results : After the ICT, tumor size was partially decreased accompanying by reducing the levels of tumor markers. Major clinical symptoms induced by paclitaxel chemotherapy were improved. There were no severe adverse events induced by ICT based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Conclusion : This case suggests that ICT may have synergistic effect for the treatment of metastatic breast cancer patient in conjunction with capecitabine.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1597-1599
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• 2013

Since renal failure causes decrease in tumor marker excretion, use of these markers in cancer care and treatment in patients with renal insufficiency or hemodialysis is controversial. The aim of this study was to investigate differences of serum levels of tumor markers CA15-3, AFP, CA19-9 and CEA in patients with impaired renal function. A total of 100 patients referred to the Tabriz Immam Reza and Amiralmomenin hospital from June 2010 to November 2011 were selected for study. Subjects were divided to 3 groups of healthy, dialysis and renal failure but non hemodialysis cases, the last category being re-grouped based on creatinine clearance. No significant relationship between different groups in serum levels of CEA (P=0.99) and CA19-9 (P=0.29) tumor markers was found. A significant correlation was observed between serum levels of AFP (P<0.001) and CA15-3 (P<0.001) and also a tendency between creatinine clearance and CEA (r=0.05, P=0.625). Creatinine clearance significantly correlated with AFP (P<0.001, r=0.53) and CA15-3 (p=0.00, r=-0.412), but not CA19-9 (P=0.089, r=-0.171). According to results of this study it appears that use of tumor markers in patients with impaired renal function should be performed with special precautions.

• Nutrition Research and Practice
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• v.13 no.1
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• pp.3-10
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• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• Toxicological Research
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• v.32 no.2
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• pp.133-140
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• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.