• Journal of Korean Neurosurgical Society
• /
• 제62권2호
• /
• pp.166-174
• /
• 2019

Objective : Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson's disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. Methods : Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. Results : Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. Conclusion : Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

• BMB Reports
• /
• 제52권3호
• /
• pp.202-207
• /
• 2019

Keloids are the most common pathological form of trauma healing, with features that seriously affect appearance and body function, are difficult to treat and have a high recurrence rate. Emerging evidence suggests that miRNAs are involved in a variety of pathological processes and play an important role in the process of fibrosis. In this study, we investigated the function and regulatory network of miR-152-5p in keloids. The miRNA miR-152-5p is frequently downregulated in keloid tissue and primary cells compared to normal skin tissue and fibroblasts. In addition, the downregulation of miR-152-5p is significantly associated with the proliferation, migration and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibits the progression of fibrosis in keloids. Smad3 is a direct target of miR-152-5p, and knockdown of Smad3 also inhibits fibrosis progression, consistent with the overexpression of miR-152-5p. The interaction between miR-152-5p and Smad3 occurs through the Erk1/2 and Akt pathways and regulates collagen3 production. In summary, our study demonstrates that miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권3호
• /
• pp.191-201
• /
• 2019

The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or $GTP{\gamma}S$. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.

• Journal of Gynecologic Oncology
• /
• 제29권6호
• /
• pp.93.1-93.11
• /
• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

• Journal of Ginseng Research
• /
• 제43권4호
• /
• pp.692-698
• /
• 2019

Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

• BMB Reports
• /
• 제54권2호
• /
• pp.124-129
• /
• 2021

In current times, obesity is a major health problem closely associated with metabolic disease such as diabetes, dyslipidemia, and cardiovascular disease. The direct cause of obesity is known as an abnormal increase in fat cell size and the adipocyte pool. Hyperplasia, the increase in number of adipocytes, results from adipogenesis in which preadipocytes differentiate into mature adipocytes. Adipogenesis is regulated by local and systemic cues that alter transduction pathways and subsequent control of adipogenic transcription factors. Therefore, the regulation of adipogenesis is an important target for preventing obesity. Myonectin, a member of the CTRP family, is a type of myokine released by skeletal muscle cells. Although several studies have shown that myonectin is associated with lipid metabolism, the role of myonectin during adipogenesis is not known. Here, we demonstrate the role of myonectin during adipocyte differentiation of 3T3-L1 cells. We found that myonectin inhibits the adipogenesis of 3T3-L1 preadipocytes with a reduction in the expression of adipogenic transcription factors such as C/EBPα, β and PPARγ. Furthermore, we show that myonectin has an inhibitory effect on adipogenesis through the regulation of the p38 MAPK pathway and CHOP. These findings suggest that myonectin may be a novel therapeutic target for the prevention of obesity.

• 동의생리병리학회지
• /
• 제34권4호
• /
• pp.177-183
• /
• 2020

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

• Journal of Microbiology and Biotechnology
• /
• 제31권2호
• /
• pp.250-258
• /
• 2021

Among various species of marine bacteria, those belonging to the genus Halomonas have several promising applications and have been studied well. However, not much information has been available on their antibiotic resistance. In our efforts to learn about the antibiotic resistance of strain Halomonas socia CKY01, which showed production of various hydrolases and growth promotion by osmolytes in previous study, we found that it exhibited resistance to multiple antibiotics including kanamycin, ampicillin, oxacillin, carbenicillin, gentamicin, apramycin, tetracycline, and spectinomycin. However, the H. socia CKY01 resistance pattern to kanamycin, gentamicin, apramycin, tetracycline, and spectinomycin differed in the presence of 10% NaCl and 1% NaCl in the culture medium. To determine the mechanism underlying this NaCl concentration-dependent antibiotic resistance, we compared four aminoglycoside resistance genes under different salt conditions while also performing time-dependent reverse transcription PCR. We found that the aph2 gene encoding aminoglycoside phosphotransferase showed increased expression under the 10% rather than 1% NaCl conditions. When these genes were overexpressed in an Escherichia coli strain, pETDuet-1::aph2 showed a smaller inhibition zone in the presence of kanamycin, gentamicin, and apramycin than the respective control, suggesting aph2 was involved in aminoglycoside resistance. Our results demonstrated a more direct link between NaCl and aminoglycoside resistance exhibited by the H. socia CKY01 strain.

• Journal of Microbiology and Biotechnology
• /
• 제32권3호
• /
• pp.387-395
• /
• 2022

Deciphering the metabolites of human diseases is an important objective of biomedical research. Here, we aimed to capture the core metabolites of Fanconi anemia (FA) using the bioinformatics method of a multi-omics composite network. Based on the assumption that metabolite levels can directly mirror the physiological state of the human body, we used a multi-omics composite network that integrates six types of interactions in humans (gene-gene, disease phenotype-phenotype, disease-related metabolite-metabolite, gene-phenotype, gene-metabolite, and metabolite-phenotype) to procure the core metabolites of FA. This method is applicable in predicting and prioritizing disease candidate metabolites and is effective in a network without known disease metabolites. In this report, we first singled out the differentially expressed genes upon different groups that were related with FA and then constructed the multi-omics composite network of FA by integrating the aforementioned six networks. Ultimately, we utilized random walk with restart (RWR) to screen the prioritized candidate metabolites of FA, and meanwhile the co-expression gene network of FA was also obtained. As a result, the top 5 metabolites of FA were tenormin (TN), guanosine 5'-triphosphate, guanosine 5'-diphosphate, triphosadenine (DCF) and adenosine 5'-diphosphate, all of which were reported to have a direct or indirect relationship with FA. Furthermore, the top 5 co-expressed genes were CASP3, BCL2, HSPD1, RAF1 and MMP9. By prioritizing the metabolites, the multi-omics composite network may provide us with additional indicators closely linked to FA.

• Molecules and Cells
• /
• 제45권4호
• /
• pp.202-215
• /
• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.