• 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.

• BMB Reports
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• v.56 no.11
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• pp.612-617
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• 2023

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.692-699
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• 2023

The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.

• Journal of Microbiology and Biotechnology
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• v.33 no.10
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• pp.1376-1383
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• 2023

Recent studies have confirmed that gut microbiota differs according to race or country in many diseases, including mild cognitive impairment (MCI) and Alzheimer's disease. However, no study has analyzed the characteristics of Korean MCI patients. This study was performed to observe the association between gut microbiota and MCI in the Korean elderly and to identify potential markers for Korean MCI patients. For this purpose, we collected fecal samples from Korean subjects who were divided into an MCI group (n = 40) and control group (n = 40) for 16S rRNA gene amplicon sequencing. Although no significant difference was observed in the overall microbial community profile, the relative abundance of several genera, including Bacteroides, Prevotella, and Akkermansia, showed significant differences between the two groups. In addition, the relative abundance of Prevotella was negatively correlated with that of Bacteroides (r = 0.733). This study may provide Korean-specific basic data for comparing the characteristics of the gut microbiota between Korean and non-Korean MCI patients.

• Korean Journal of Veterinary Research
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• v.63 no.4
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• pp.41.1-41.6
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• 2023

Many viruses can infect different types of birds, with poultry being the most susceptible. These viral diseases have a direct negative impact on the poultry industry, with significant economic losses. This study examined a group of the most important viruses that infect backyard chickens in 2 specific areas of Basrah Governorate, south of Iraq. The study analyzed avian influenza viruses (AIVs), Newcastle disease virus (NDV), and infectious bronchitis virus (IBV). Two hundred and ninety oropharyngeal swabs, 150 from Abu Al-Khasib and 140 from Shatt Al-Arab regions in the Basrah governorate, were obtained from backyard chickens with clear respiratory signs. The samples were subjected to viral RNA extraction, and the viral nucleic acids were detected using a reverse transcriptase polymerase chain reaction technique. The overall rate of viral infections was 74.8%, which varied depending on the type of virus: 15.8%, 31.3%, and 27.5% for AIV, NDV, and IBV, respectively. The NDV and IBV had much higher infection rates than that of AIV. In addition, the prevalence of AIV in the Shatt Al Arab district was significantly higher than in the Abul Khasib district. Moreover, there were no significant differences between the NDV and the IBV distributions in either of the targeted regions in this study.

• Journal of Integrative Natural Science
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• v.17 no.1
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• pp.31-41
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• 2024

Calcium ions play an important role in development and intracellular signaling. Dictyostelium discoideum has 14 genes encoding calcium -binding proteins (CBPs), but the function of most CBPs during development has not yet been studied. In this study, we investigated the specific functions of CBP7, one of 14 CBPs, in development using RNA interference cell lines of CBP7, cell lines overexpressing CBP7, cell lines with point mutations in the EF-hand domain, and cell lines expressing fragment proteins. was intended to reveal. CBP7 consists of 169 amino acids and contains 4EF-hand domains. The CBP7-overexpressing cells showed complete loss of developmental process. These cells remained in the single-cell growth stage under development -inducing conditions, while wild-type cells formed aggregations within 6-8h of development and eventually formed fruiting bodies. The experiments using point-mutated CBP7 protein showed that all EF-hand domains of CBP7 were important for CBP7 to function during developmental process. These results suggest that CBP7 plays an important role in developmental processes across all EF-hand domains.

• International Journal of Oral Biology
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• v.49 no.3
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• pp.79-86
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• 2024

Periodontal disease (PD) is strongly linked to increased risk of oral squamous cell carcinoma (OSCC); however, the specific mechanism through which the development of PD and OSCC is simultaneously promoted remains unclear. This study explored the impact of periodontal pathogens on OSCC progression and the contribution of periodontal pathogen-stimulated OSCC to PD development. The expression of osteoclastogenesis-inducing factors was assessed using quantitative reverse transcription polymerase chain reaction analysis following stimulation of OSCC with lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas gingivalis (Pg), a pathogen commonly responsible for PD. The cell counting kit-8 assay was used to determine the effects of Pg-LPS on OSCC proliferation and drug resistance to cisplatin and 5-fluorouracil. The effects of conditioned medium (CM) derived from Pg-LPS-stimulated OSCC on osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining on bone marrow-derived macrophages (BMMs). Pg-LPS administration in SCC-25 and YD-8 OSCC cell lines induced a significant increase in receptor activator of nuclear factor kappa-B ligand mRNA expression; however, it did not affect cell proliferation. Treatment with CM derived from Pg-LPS-stimulated SCC-25 or YD-8 cells markedly enhanced the formation of TRAP-positive multinucleated cells during osteoclast differentiation of BMMs. Altogether, these findings demonstrate that Pg-LPS-stimulated OSCC promoted osteoclastogenesis through a paracrine mechanism.

• Oncology Letters
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• v.41 no.6
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• pp.3305-3312
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• 2019

Histone H2B monoubiquitination has been shown to play critical roles in diverse cellular processes including DNA damage response. Although recent data indicate that H2B monoubiquitination is strongly connected with tumor progression and regulation, the implications of this modification in lung adenocarcinoma are relatively unknown. In the present study, we demonstrated the clinical implication of H2B monoubiquitination and the potential role of tumor necrosis factor receptor-associated factor-interacting protein (TRAIP) in regulating its modification in lung adenocarcinoma. Immunohistochemical analysis showed that H2B monoubiquitination was significantly downregulated in 68 human lung adenocarcinoma patient samples compared to their normal adjacent tissues. Depletion of TRAIP by specific siRNA treatment markedly decreased ionizing radiation (IR)-induced H2B monoubiquitination. In addition, deletion mutants without RING domain or C-terminus of TRAIP diminished the ability to induce H2B monoubiquitination at lysine 120. Notably, the nuclear expression of TRAIP was positively related with H2B monoubiquitination levels in patients with lung adenocarcinoma. Furthermore, statistical analysis indicated that low levels of both TRAIP and H2B monoubiquitination, not each alone, in patients with lung adenocarcinoma were strongly correlated with poor survival. Taken together, these results suggest that TRAIP is a novel regulator of H2B monoubiquitination in DNA damage response and cancer development in lung adenocarcinoma.

• International Journal of Oncology
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• v.54 no.2
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• pp.665-672
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• 2019

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a dynamic cytokine that initiates the apoptosis of cancer cells, but exhibits little or no toxicity in normal cells. Luteolin is a flavonoid compound frequently used in the treatment of cancer. In the current study, we demonstrate that treatment with luteolin and TRAIL exerts a synergistic effect and the mechanisms on TRAIL-resistant Huh7 cells. The results demonstrated that luteolin induced an autophagic flux in human liver cancer cells. The attenuation of the autophagic flux by applying the specific inhibitor of autophagy, chloroquine, significantly suppressed DR5 expression. Treatment with genetically modified autophagy-related 5 siRNA abrogated the luteolin-mediated sensitizing effect of TRAIL. Furthermore, pre-treatment with the c-Jun N-terminal kinase (JNK) inhibitor, SP600125, significantly attenuated the luteolin-induced upregulation of DR5 expression, thereby suggesting that JNK activation promotes DR5 expression. Our findings also revealed that Akt phosphorylation was required for TRAIL sensitization. On the whole, the findings of this study indicated that luteolin effectively enhanced TRAIL-initiated apoptosis, and that these effects were likely to be mediated by autophagy and JNK-mediated DR5 expression.

• Clinical Nutrition Research
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• v.11 no.3
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• pp.159-170
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• 2022

Ischemic stroke and Alzheimer's disease (AD) are representative geriatric diseases with a rapidly increasing prevalence worldwide. Recent studies have reported an association between ischemic stroke neuropathology and AD neuropathology. Ischemic stroke shares some similar characteristics with AD, such as glia activation-induced neuroinflammation, amyloid beta accumulation, and neuronal cell loss, as well as some common risk factors with AD progression. Although there are considerable similarities in neuropathology between ischemic stroke and AD, no studies have ever compared specific genetic changes of brain cortex between ischemic stroke and AD. Therefore, in this study, I compared the cerebral cortex transcriptome profile of 5xFAD mice, an AD mouse model, with those of middle cerebral artery occlusion (MCAO) mice, an ischemic stroke mouse model. The data showed that the expression of many genes with important functional implications in MCAO mouse brain cortex were related to synaptic dysfunction and neuronal cell death in 5xFAD mouse model. In addition, changes in various protein-coding RNAs involved in synaptic plasticity, amyloid beta accumulation, neurogenesis, neuronal differentiation, glial activation, inflammation and neurite outgrowth were observed. The findings could serve as an important basis for further studies to elucidate the pathophysiology of AD in patients with ischemic stroke.