• Toxicological Research
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• v.14 no.3
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• pp.293-300
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• 1998

Previous studies have shown that the heterocycles including thiazoles are efficacious in inducing phase phase II metabolizing enzyme as well as certain cytochrome P450s and that the inductin of these matabolizing enzymes by the heterocyclic agents is highly associated with their hepatotoxicity. In the present study, the effects of benzylisothiazole (BIT), which has a isothiazole moiety, on the expression of microsomal epoxide hydrolase (mEH), major glutathione S-transerases and cytochrome P450s were studied in the rat liver in association with its hepatotoxicity. Treatment of rats with BIT(1.17 mmol/kg, 1~3d) resulted in substantial increases in the mEH. rGSTA2, rGSTA2, rGSTM1 and rGSTM2 mRNA levels, whereas rGSTA3 and rGSTA5 mRNA levels were increased to much lesser extents. A time-course study showed that the mRNA levels of mEH and rGSTs were greater at 24hr after treatment than those after 3 days of consecutive treatment. Relative changes in mEH and rGST mRNA levels were consistent with those in the proteins, as assessed by Western immunoblot analysis. Hepatic cytochrom P450 levels were monitored after BIT treatment under the assumption that metabolic activation of BIT may affect expression of the enzymes in conjunction with hepatotoxicity. Immunoblot analysis revealed that cytochrome P450 2B1/2 were 3-to 4-fold induced in rats teatd with BIT(1.17 mmol/kg/day.3days), whereas P450 1A2, 2C11 and 3A1/2 levels were decreased to 20~30% of those in unteatd rats. P450 2E1 was only slightly decreased by BIT. Thus, the levels of several cytochrome P450s were suppressed by BIT treatment. Rats treated with BIT at the dose of 1.17mmol/kg for 3 days exhibited extensive multifocal nodular necrosis with moderate to extensive diffuse liver cell degeneration. No notable toxicity was observed in the kidney. These results showed that BIT induces mEH and rGSTs in the liver with increases in the mRNA levels, whereas the agent significantly decreased major cytochrome P450s. The changes in the detoxifying enzymes might be associated with the necrotic liver after consecutive treatment.

• Journal of Life Science
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• v.21 no.4
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• pp.529-533
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• 2011

Metallothioneins (MT) are a group of low-molecular weight, cysteine-rich, intracellular proteins that are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins is associated with protection against DNA damage, oxidative stress, and apoptosis. Many studies have shown increased expression of MT in various human tumors, whereas MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. Using Northern blot analysis, we found that laminin induced expression of MT-1 in HSG and PC12 cells, which can be differentiated by laminin, but had no effect on MB-231, MDA-435, and PC-3 cells, which cannot be differentiated by laminin. In addition, we analyzed the expression level of the MT-1 gene in five prostate cancer cell lines possessing different metastatic potential. The expression of MT-1 in normal and less malignant cells (RWPE-1 and WPE1-NA22) was high and up-regulated by laminin, whereas the expression of MT-1 in WPE1-NB14, WPE1-NB11, and WPE1-NB26 cells (malignant) was extremely low and not elevated by laminin. These results suggest that the MT-1 gene is involved in laminin-mediated differentiation and affects the metastatic potential of tumor cells.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.233-239
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• 2024

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferase-like (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

• Journal of dental hygiene science
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• v.24 no.3
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• pp.181-189
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• 2024

Background: Focal adhesions (FAs) is the most important process in the first step of osseointegration between preosteoblasts and titanium (Ti). FAs improvement and pre-osteoblasts cell proliferation leads to successful Ti-based dental implants. This study aimed to confirm the applicability of rosmarinic acid (RA) as a functional substance for improving FAs and cell proliferation of MC3T3-E1 preosteoblasts on Ti surfaces during the first stage of osseointegration for successful Ti-based dental implants. Methods: We used MC3T3-E1 preosteoblasts on Ti discs incubated in a medium supplemented with or without 14 ㎍/ml to decipher the effects of RA on FAs and cell proliferation. FAs and proliferation of MC3T3-E1 cells on Ti discs were assessed via MTT assay. Actin-labeled cells and paxillin contacts were observed and imaged by fluorescent microscopy, and the associated signaling pathways were revealed through western blot analysis. Results: In RA-treated MC3T3-E1 cells on Ti discs, FAs between MC3T3-E1 preosteoblasts and Ti surfaces and the expression of focal adhesion kinase (FAK), phosphorylated FAK and paxillin proteins and filamentous-actin formation increased. RA increased the proliferation of MC3T3-E1 preosteoblasts on the Ti surface as well as the expression of Grab2, Ras, pERK1/2, and ERK1/2. In addition, the expression of secretory leukocyte protease inhibitor and thymosin b4, known as nanomolecules that enhance the interaction between implanted Ti materials and preosteoblasts in the RA-treated MC3T3-E1 preosteoblasts, increased. RA not only increased the FAs of MC3T3-E1 preosteoblasts on the Ti surface through the FAK/Paxillin signaling pathway, but also increased cell proliferation and mitosis through the FAK/Grab2/Ras/ERK1/2 signaling pathway. Conclusion: RA can be applied as an effective functional substrate to improve the FAs and proliferation of MC3T3-E1 preosteoblats on Ti surfaces, which are essential in the first step of osseointegration between implanted Ti and bone tissue for the clinical success of Ti based dental implants.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3287-3291
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• 2014

Background: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between $1^{st} $January 2005 and $31^{st}$ December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ${\geq}50$-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5925-5928
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• 2013

Objective: This study aimed to examine the relationship between expression of mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and relatiuonships with clinical factors. Methods: Immunohistochemistry was used to detect the expression of the associated proteins mTOR, p-mTOR, and phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40 cases of gastrointestinal stromal tumors, with division into a very low and low risk group as well as a moderate and high risk group. Results: The positive rate of mTOR and p-mTOR was significantly increased in the moderate and high risk group compared with the very low and low risk group. The difference was statistically significant (P<0.05). When grouped according to size, the positive mTOR expression rate exhibited a statistical difference (P<0.05), which was significantly increased in the group of tumors larger than 5 cm. The difference in the positive mTOR and p-mTOR expression rate exhibit no statistical significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05). Conclusion: The different expressions of mTOR and p-mTOR in the signal transduction pathway of gastrointestinal stromal tumor in the different degree-of-risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway serve an important function in the occurrence and development of gastrointestinal stromal tumors.

• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.846-853
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• 2024

Adzuki bean (Vigna angularis), which provides plant-based proteins and functional substances, requires a long soaking time during processing, which limits its usefulness to industries and consumers. To improve this, ultrasonic treatment using high pressure and shear force was judged to be an appropriate pretreatment method. This study aimed to determine the optimal conditions of ultrasound treatment for the improved hydration of adzuki beans using the response surface methodology (RSM). Independent variables chosen to regulate the hydration process of the adzuki beans were the soaking time (2-14 h, X₁), treatment intensity (150-750 W, X₂), and treatment time (1-10 min, X₃). Dependent variables chosen to assess the differences in the beans post-immersion were moisture content, water activity, and hardness. The optimal conditions for treatment deduced through RSM were a soaking time of 12.9 h, treatment intensity of 600 W, and treatment time of 8.65 min. In this optimal condition, the values predicted for the dependent variables were a moisture content of 58.32%, water activity of 0.9979 a_w, and hardness of 14.63 N. Upon experimentation, the results obtained were a moisture content of 58.28 ± 0.56%, water activity of 0.9885 ± 0.0040 a_w, and hardness of 13.01 ± 2.82 g, confirming results similar to the predicted values. Proper ultrasound treatment caused cracks in the hilum, which greatly affects the water absorption of adzuki beans, accelerating the rate of hydration. These results are expected to help determine economically efficient processing conditions for specific purposes, in addition to solving industrial problems associated with the low hydration rate of adzuki beans.

• Journal of Microbiology and Biotechnology
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• v.16 no.8
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• pp.1262-1268
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• 2006

In the search for a novel cytotoxic substance from medicinal plants, HY53 ($C_{17}H_{32}O_2N_2$; molecular weight 296) was isolated from the leaves of Pata de Vaca (Bauhinia forficata). The growth of the HepG2 cells was inhibited in a dose-dependent manner when treated with 0.07 to 0.40 mM HY53 for 24 h (IC$_{50}$: 0.13 mM). Furthermore, nuclear DAPI staining revealed the typical nuclear features of apoptosis in the HepG2 cells exposed to 0.27 mM HY53, whereas a flow cytometric analysis of the HepG2 cells using propidium iodide showed that the apoptotic cell population increased gradually from 8% at 0 mM to 23% at 0.14 mM and 45% at 0.40 mM after being exposed to each concentration of HY53 for 24 h. Moreover, a TUNEL assay also exhibited the apoptotic induction of the HepG2 cells treated with HY53. To obtain further information on the HY53-induced apoptosis, the expression level of certain apoptosis-associated proteins was examined using a Western blot analysis. Treatment of the HepG2 cells with HY53 resulted in the activation of caspase-3, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Consequently, the results confirmed that the apoptosis in the HepG2 cells was induced by HY53 and the involvement of caspase-3-mediated PARP cleavage in the apoptotic process.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.217-225
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• 2021

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

• The Korea Journal of Herbology
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• v.37 no.4
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• pp.17-29
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• 2022

Objective : The present study comparatively analyzed the anti-obesity effect of Arctium lappa L. roots with and without microwave processing. Methods : Four HFD groups except for the Normal group (n=8) were allocated: Control, microwave-processed dried Arctium lappa L. roots (MAL) extract 400 mg/kg/d (MAL400), MAL extract 800 mg/kg/d (MAL800), and the dried Arctium lappa L. roots (DAL) extract 800 mg/kg/d (DAL800). The efficacy of MAL and DAL was confirmed in terms of the serum biochemical index, protein expressions related to the synthesis of triglyceride (TG) and total cholesterol (TC) and 𝛽-oxidation, and histopathological staining. Results : Both MAL and DAL treatments significantly reduced final body weight and body weight gain. MAL800 treatment significantly reduced serum TG, TC, low-density lipoprotein cholesterol, and leptin levels, but the serum high-density lipoprotein cholesterol and adiponectin concentrations were dramatically increased. In particular, leptin in the MAL800 group was reduced by 14.1% compared with the DAL800 group. Moreover, the MAL800 treatment showed an effect superior to the DAL800 treatment in the reduction of serum TC, the sirtuin 1 (Sirt1) activation, and the inhibition of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) gene expression. In particular, unlike the DAL800 treatment, MAL treatment significantly led to the activation of peroxisome proliferator-activated receptor alpha (PPAR𝛼). Subsequently, PPAR𝛼 meaningfully regulated downstream proteins associated with 𝛽-oxidation. Conclusion : These findings suggest that Arctium lappa L. roots with microwave processing effectively ameliorate obesity through the regulation of leptin and TC and the promotion of 𝛽-oxidation compared with Arctium lappa L. roots without microwave processing.