• BMB Reports
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• 제56권2호
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• pp.114-119
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• 2023

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

• BMB Reports
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• 제56권2호
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• pp.120-125
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• 2023

Karyopherin-α3 (KPNA3), a karyopherin-α isoform, is intimately associated with metastatic progression via epithelial-mesenchymal transition (EMT). However, the molecular mechanism underlying how KPNA3 acts as an EMT inducer remains to be elucidated. In this report, we identified that KPNA3 was significantly upregulated in cancer cells, particularly in triple-negative breast cancer, and its knockdown resulted in the suppression of cell proliferation and metastasis. The comprehensive transcriptome analysis from KPNA3 knockdown cells indicated that KPNA3 is involved in the regulation of numerous EMT-related genes, including the downregulation of GATA3 and E-cadherin and the up-regulation of HAS2. Moreover, it was found that KPNA3 EMT-mediated metastasis can be achieved by TGF-β or AKT signaling pathways; this suggests that the novel independent signaling pathways KPNA3-TGF-β-GATA3-HAS2/E-cadherin and KPNA3-AKT-HAS2/E-cadherin are involved in the EMT-mediated progress of TNBC MDA-MB-231 cells. These findings provide new insights into the divergent EMT inducibility of KPNA3 according to cell and cancer type.

• Parasites, Hosts and Diseases
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• 제61권1호
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• pp.24-32
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• 2023

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the polymorphic var multigene family, is a highly polymorphic antigen that plays a crucial role in the pathology of malaria. The contribution of the genetic diversity of var toward the immune escape of P. falciparum has not yet been fully elucidated. This study aimed to characterize the diversity of var repertoires by screening P. falciparum Duffy-binding-like α domain (PfDBLα) among field isolates from central Myanmar. Genetic analysis revealed that the D-H segments of var in Myanmar populations have an extensive polymorphic repertoire, with high numbers of unique sequence types in each individual. However, var genes from the global population, including Myanmar, shared close genetic lineages regardless of their geographic origins, indicating that they have not undergone rapid evolutionary changes.

• Fisheries and Aquatic Sciences
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• 제26권2호
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• pp.158-168
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• 2023

The global output of Pyropia yezoensis (dried seaweed or laver, also called 'Gim' in Korea) has been reduced over the half-decade due to the wide spread of red rot disease, a serious algal disease affecting P. yezoensis. Recently, Gold 1 (G1), which is a resistant strain of P. yezoensis to red rot disease, was developed and commercialized in South Korea, yet its physiological activity has not been investigated. In this study, a comparative study was performed on G1 and commercially available strain of P. yezoensis (CP) for their antioxidative activities. Aqueous extract of G1 showed more marked 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity compared to that of CP. In 293T cells, antioxidant activity against H₂O₂-induced reactive oxygen species (ROS) formation was only observed in G1 extract. In addition, G1 extract showed more potent inhibitory effect on H₂O₂-induced apoptotic cell death than CP extract, as examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence microscopy. Expression levels of various apoptosis-related genes, including B-cell lymphoma 2-associated X protein, p53, capase-3, and inflammatory cytokines, in H₂O₂-treated cells were significantly decreased by the treatment of G1. Taken together, the present study suggests that a new strain of red seaweed G1 can recover oxidative stress effectively by improving the imbalance of ROS generation and has a potential to be used a functional ingredient as an antioxidant source.

• Animal Bioscience
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• 제36권5호
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• pp.692-703
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• 2023

Objective: The main goals of this investigation were to i) assess the population structure and genetic diversity and ii) determine the efficiency of the ongoing breeding program in a closed flock of Angora rabbits through pedigree analysis. Methods: The pedigree records of 6,145 animals, born between 1996 to 2020 at NTRS, ICAR-CSWRI, Garsa were analyzed using ENDOG version 4.8 software package. The genealogical information, genetic conservation index and parameters based on gene origin probabilities were estimated. Results: Analysis revealed that, 99.09% of the kits had both parents recorded in the whole dataset. The completeness levels for the whole pedigree were 99.12%, 97.12%, 90.66%, 82.49%, and 74.11% for the 1st, 2nd, 3rd, 4th, and 5th generations, respectively, reflecting well-maintained pedigree records. The maximum inbreeding, average inbreeding and relatedness were 36.96%, 8.07%, and 15.82%, respectively. The mean maximum, mean equivalent and mean completed generations were 10.28, 7.91, and 5.51 with 0.85%, 1.19%, and 1.85% increase in inbreeding, respectively. The effective population size estimated from maximum, equivalent and complete generations were 58.50, 27.05, and 42.08, respectively. Only 1.51% of total mating was highly inbred. The effective population size computed via the individual increase in inbreeding was 42.83. The effective numbers of founders (f_e), ancestors (f_a), founder genomes (f_g) and non-founder genomes (f_ng) were 18, 16, 6.22, and 9.50, respectively. The fe/fa ratio was 1.12, indicating occasional bottlenecks had occurred in the population. The six most influential ancestors explained 50% of genes contributed to the gene pool. The average generation interval was 1.51 years and was longer for the sire-offspring pathway. The population lost 8% genetic diversity over time, however, considerable genetic variability still existed in the closed Angora population. Conclusion: This study provides important and practical insights to manage and maintain the genetic variability within the individual flock and the entire population.

• Journal of Ginseng Research
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• 제47권3호
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• pp.440-447
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• 2023

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/β-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/β-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of β-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/β-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.

• 대한한의학회지
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• 제43권4호
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• pp.52-73
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• 2022

Objectives: The anti-inflammatory and anti-oxidative activities of LCVC (Lonicerae Flos, Citri Pericarpium and Violae Herba Complex) have not been fully elucidated. The purpose of this study was to investigate the mechanisms underlying these effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Methods: The evaluation of the anti-oxidative activity of LCVC was completed via DPPH and ABTS radical scavenging capacity, FRAP assay, measurement of polyphenol and flavonoid, assessment of ROS and NO levels in LPS-induced RAW 264.7 cells. The anti-inflammatory activity was defined by measuring the production of biomarkers (PGE2, IL-1B, IL-6 and TNF-𝛼), proteins (ERK, JNK, P38, Nrf2, Keap1, HO-1 and NQO1) and expressions of genes (iNOS, COX-2, IL-1𝛽, IL-6, TNF-𝛼, Nrf2, Keap1, HO-1 and NQO1) in LPS-induced RAW 264.7 cells. Results: LCVC have polyphenol and flavonoid contents. The results of DPPH and ABTS free radical scavenging capacity and FRAP assay showed that the anti-oxidative activity was increased. Production of ROS, NO, IL-6, TNF-𝛼, mRNA expressions of IL-1𝛽, IL-6, TNF-𝛼, Keap1, iNOS and COX-2 were decreased, and NQO1, Nrf2, and HO-1 were increased. In protein expression, JNK and Keap1 were decreased, NQO1, Nrf2 and HO-1 were increased, and no relationships were observed with the ERK and P38 by LCVC. Conclusions: These results suggest that LCVC may offer protective effects against LPS-induced inflammatory and oxidative responses through attenuating Nrf2/HO-1 pathway and MAPKs pathway. Therefore, we propose that LCVC has anti-inflammatory and anti-oxidative activities that have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by the over-activation of macrophages.

• 환경생물
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• 제40권4호
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• pp.398-404
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• 2022

본 연구는 플라스틱 가소제인 DEHP가 식물 병원균 중 하나인 P. carotovorum SCC1 균주에 미치는 영향을 조사하였다. DEHP가 균주 생장과 대사에 미치는 영향을 조사한 결과, 개체군 변화에 유의한 영향을 주지 않았으며, 세포막 투과성, ATPase 활성에 유의한 변화가 없었지만 TCA cycle 에서 DEHP 첨가에 따라 Succinyl-CoA synthase 활성이 유의적으로 감소하였다. 병원성 관련 유전자 발현량을 관찰한 결과 pectate lyase 유전자 발현량이 상대적으로 증가한 반면, pectinase 유전자는 상대적으로 발현량이 감소하였다. 따라서 DEHP는 P. carotovorum SCC1의 개체군 변화나 대사에는 유의미한 영향을 미치지 않지만 병원성 관련 유전자 발현에 영향을 미치므로 본 연구 결과는 향후 실제 식물 재배 조건에서 DEHP가 존재할 때 P. carotovorum의 특성에 관한 기초연구 자료로 활용할 수 있을 것이라 사료된다.

• 공업화학
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• 제34권3호
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• pp.318-325
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• 2023

The detection of antibiotics in treated wastewater is a global concern as it enters water bodies and causes the development of antibiotic resistance genes in humans and marine life. The study specifically aims to explore the potential of ferrate (VI) in eliminating tetracycline (TCL). The degradation of TCL is optimized with parametric studies, viz., the effect of pH and concentration, which provide insights into TCL elimination. The increase in pH (from 7.0 to 10.0) favors the percentage removal of TCL; however, the increase in TCL concentrations from 0.02 to 0.3 mmol/L caused a decrease in percentage TCL removal from 97.4 to 29.1%, respectively, at pH 10.0. The time-dependent elimination of TCL using ferrate (VI) followed pseudosecond-order rate kinetics, and an apparent rate constant (kapp) was found at 1978.8 L² /mol² /min. Coexisting ions, i.e., NaNO₃, Na₂HPO₄, NaCl, and oxalic acid, negligibly affect the oxidation of TCL by ferrate (VI). However, EDTA and glycine significantly inhibited the elimination of TCL using ferrate (VI). The mineralization of TCL using ferrate (VI) was favored at higher pH, and it increased from 18.57 to 32.52% when the solution pH increased from pH 7.0 to 10.0. Additionally, the real water samples containing a relatively high level of inorganic carbon spiked with TCL revealed that ferrate (VI) performance in the removal of TCL was unaffected, which further inferred the potential of ferrate (VI) in real implications.

• International Journal of Oral Biology
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• 제48권1호
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• pp.1-7
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• 2023

Oral squamous cell carcinoma (OSCC), which accounts for approximately 90% of oral cancers, has a high rate of local recurrence and a poor prognosis despite improvements in treatment. Exosomes released from OSCC cells promote cell proliferation and metastasis. Although it is clear that the biogenesis of exosomes is mediated by the endosomal sorting complex required for transport (ESCRT) machinery, the gene expression pattern of ESCRT, depending on the cell type, remains elusive. The exosomal release from the human OSCC cell lines, HSC-3 and HSC-4, and their corresponding gefitinib-resistant sub-cell lines, HSC-3/GR and HSC-4/GR, was assessed by western blot and flow cytometry. The levels of ESCRT machinery proteins, including Hrs, Tsg101, and Alix, and whole-cell ubiquitination were evaluated by western blot. We observed that the basal level of exosomal release was higher in HSC-3/GR and HSC-4/GR cells than in HSC-3 and HSC-4 cells, respectively. Long-term gefitinib exposure of each cell line and its corresponding gefitinib-resistant sub-cell line differentially induced the expression of the ESCRT machinery. Furthermore, whole-cell ubiquitination and autophagic flux were shown to be increased in gefitinib-treated HSC-3 and HSC-4 cells. Our data indicate that the expression patterns of the ESCRT machinery genes are differentially regulated by the characteristics of cells, such as intracellular energy metabolism. Therefore, the expression patterns of the ESCRT machinery should be considered as a key factor to improve the treatment strategy for OSCC.