• BMB Reports
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• 제51권5호
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• pp.209-210
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• 2018

NAFLD induces the development of advanced liver diseases such as NASH and liver cancer. Therefore, understanding the mechanism of NAFLD development is critical for its prevention and treatment. Ablation of PTEN or Hippo pathway components induces liver cancer in a murine model by hyperactive AKT or YAP/TAZ, respectively. Although the regulation of these two pathways occurs in the same hepatocyte, the details of crosstalk between Hippo-YAP/TAZ and PTEN-AKT pathways in liver homeostasis and tumorigenesis still remain unclear. Here, we found that depletion of both PTEN and SAV1 in liver promotes spontaneous NAFLD and liver cancer through hyperactive AKT via YAP/TAZ-mediated up-regulation of IRS2 transcription. Conversely, NAFLD is rescued by both ablation of YAP/TAZ and activation of the Hippo pathway. Furthermore, human HCC patients with NAFLD showed strong correlation between YAP/TAZ and IRS2 or phospho-AKT expression. Finally, the inhibition of AKT by MK-2206 treatment attenuates NAFLD development and tumorigenesis. Our findings indicate that Hippo pathway interacts with AKT signaling during the intervention with IRS2 to prevent NAFLD and liver cancer.

• BMB Reports
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• 제55권6호
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• pp.251-258
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• 2022

Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5069-5073
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• 2015

The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.

• Toxicological Research
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• 제7권1호
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• pp.51-59
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• 1991

The purpose of the present study was to investigate the effects of non-watering, fasting and non-watering fasting for 16-17 hrs on haematological and biochemical parameters in SD rats. 1. Liver weight was decreased in the order of in the fasting group, non-watering fasting group and non-watering group in both sexes. 2. In fasting group and non-watering fasting group, haematologic parameters of male (HGB and MCH) and femal (MCHC) were trends to decrease compared with normal feeding & watering group. 3. In the differential leucocyte counts, there were no significant differences compared with noraml feeding % watering group.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.367-373
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• 2017

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine. Circulating miR-146a and miR-206 were increased in cisplatin-induced nephrotoxicity and bupivacaine-induced myotoxicity, respectively. Taken together, these results indicate that circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.

• Journal of Nutrition and Health
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• 제8권2호
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• pp.15-18
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• 1975

In man, ornithine carbamyl transferase is localized mainly in the liver and to a lesser extent in the smll intestine. Because of these findings, one might expect damage only to the liver or perhaps the small intestine to cause elevated ornithine carbamyl transferase activity in serum $(_S-OCT)$. Serum ornithine carbamyl transferase activity was determined in thirty normal subjects, and fifteen patients with viral hepatitis and fifteen patients with liver cirrhosis. The correlation of $_S-OCT$ with $_S-GPT$ and $_S-GOT$ was studied. The mean $_S-OCT$ activity in thirty normal Korean subjects was $0.094{\pm}0.043$I.U./L of serum. Elevated $_S-OCT$ activity was observed in patients with liver disease. The correlation coefficient was 0.18 for $_S-OCT$ and $_S-GPT$, ana 0.40 for $_S-OCT$ and $_S-GOT$.

• Archives of Pharmacal Research
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• 제13권1호
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• pp.113-116
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• 1990

People in some tropical countries used to use some plant extracts in folklore medicine as treatment of diabetes melitus. Of these plants is Calligonum comsum ("orta"). The present work deals with the biochemical effects of the whole plant water extract given orally to the albino rats, normals and alloxan diabetics, as to fulfil its hypoglycemic effects on rats. The results showed that "orta" extract produced a hypoglycemic effect indicated by the decrease in blood sugar level. It was observed that the diabetic state in rats treated with 300 mg/kg body weight of "orta" extract, was alleviated, showeing normal levels of blood glucose, liver fat and cholesterol contents. Liver proteins were still below the normal level in the rats. Gibenclamide, a hypoglycemic drug, was used for comparison with "ora" extract. Although it did alleviate the diabetic state, yet the liver fat and cholesterol contents were still higher than those of normal. Also the liver proteins were lower than the control levels.

• BMB Reports
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• 제56권2호
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• pp.65-70
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• 2023

Prominin-1 (PROM1), also called CD133, is a penta-span transmembrane protein that is localized in membrane protrusions, such as microvilli and filopodia. It is known to be expressed in cancer stem cells and various progenitor cells of bone marrow, liver, kidney, and intestine. Accumulating evidence has revealed that PROM1 has multiple functions in various organs, such as eye, tooth, peripheral nerve, and liver, associating with various molecular protein partners. PROM1 regulates PKA-induced gluconeogenesis, TGFβ-induced fibrosis, and IL-6-induced regeneration in the liver, associating with Radixin, SMAD7, and GP130, respectively. In addition, PROM1 is necessary to maintain cancer stem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain, peripheral nerves, and tooth. Here, we discuss recent findings of PROM1-mediated signal transduction.

• Toxicological Research
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• 제34권3호
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• pp.231-239
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• 2018

Bisphenol A, an everywhere chemical, is applied as a plasticizer in polycarbonate plastics, which often used in our everyday products and in epoxy resins as protective coatings and linings for food and beverage cans for decades. Human exposure to BPA may lead to adverse effects by interfering with oestrogen receptors. Our present study was conducted to investigate the protective effects of selenium (Se) and vitamin E (Vit E) on BPA-induced damage in the liver of male rats. Animals were randomly divided into four groups: the first group received olive oil and served as control. The second group received both (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet). The third one treated orally by (10 mg/kg b.w.) of BPA. The last group received (Se + Vit E) (0.5 mg/kg diet; 100 mg/kg of diet) concomitantly with (10 mg/kg b.w.) BPA. Exposure to BPA for three weeks engendered a hepatic disorder. An increased AST and ALT enzymatic activity was noticed in BPA-treated group as compared to other groups. Furthermore, a change in glucose, cholesterol, LDL-C, HDL-C, albumin, and bilirubin level was remarkable. Moreover, exposure to BPA increased malondialdehyde levels while reduced gluthatione content was decreased in the liver homogenate. A decrease in glutathione peroxidase, glutathione s-transferase and catalase activities was observed in the same group. Administration of selenium and vitamin E through the diet in BPA treated rats ameliorated the biochemical parameters cited above. In addition, an improvement in activities of liver enzymes was recorded. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between BPA-induced hepatotoxicity and its alleviation by natural antioxidants like selenium and vitamin E.

• Asian-Australasian Journal of Animal Sciences
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• 제25권9호
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• pp.1229-1236
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• 2012

Our previous studies showed that kisspeptin-10 (Kp-10) injected in vivo can markedly increase lipid anabolism in liver of quails. In order to investigate the direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp-10, respectively. The results showed that after 24 h treatment, cells viability was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10 compared to the control cells. Based on the results of the cell viability, 100 nM dosage of Kp-10 was selected for the further study and analysis. Compared with control cells, total cholesterol (Tch) contents in 100 nM treated cells were increased by 51.23%, but did not reach statistical significance, while the level of triglyceride (TG), high density of lipoprotein-cholesterol (HDL-C) and low density of lipoprotein-cholesterol (LDL-C) were significantly increased. Real-time PCR results showed that ApoVLDL-II mRNA expression had a tendency to increase, genes including sterol regulatory element-binding protein-1 (SREBP-1), acetyl coenzyme A carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT1), 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR) and stearyl coenzyme A dehydrogenase-1 (SCD1) mRNA in hepatocytes were significantly down-regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1 protein expression was significantly up-regulated by 100 nM Kp-10. Some of the significant correlations in mRNA expression were found between genes encoding hepatic factors or enzymes involved in lipid metabolism in liver of birds. These results indicate that Kp-10 stimulates lipid synthesis directly in primary cultured hepatocytes of chickens.