• 제목/요약/키워드: translational research

검색결과 527건 처리시간 0.03초

1H-NMR Analysis of Metabolic Changes Induced by Snf1/AMP-Activated Protein Kinase During Environmental Stress Responses

  • Kim, Jiyoung;Oh, Junsang;Yoon, Deok-Hyo;Sung, Gi-Ho
    • Mycobiology
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    • 제47권3호
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    • pp.346-349
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    • 2019
  • AMP-activated protein kinase sucrose non-fermenting 1 (Snf1) is a representative regulator of energy status that maintains cellular energy homeostasis. In addition, Snf1 is involved in the mediation of environmental stress such as salt stress. Snf1 regulates metabolic enzymes such as acetyl-CoA carboxylase, indicating a possible role for Snf1 in metabolic regulation. In this article, we performed nuclear magnetic resonance (NMR) spectroscopy to profile the metabolic changes induced by Snf1 under environmental stress. According to our NMR data, we suggest that Snf1 plays a role in regulating cellular concentrations of a variety of metabolites during environmental stress responses.

Neoadjuvant Chemotherapy in Asian Patients With Locally Advanced Gastric Cancer

  • Xie Tong;Peng Zhi;Shen Lin
    • Journal of Gastric Cancer
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    • 제23권1호
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    • pp.182-193
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    • 2023
  • Presently, surgery is the only treatment approach for gastric cancer and improving the prognosis of locally advanced gastric cancer is one of the key factors in promoting gastric cancer survival benefit. The MAGIC study was the first to demonstrate the efficacy of neoadjuvant chemotherapy (NAC) in European countries. In recent years, several clinical trials have provided evidence for the use of NAC in Asian patients with locally advanced gastric cancer. However, clinical practice guidelines vary between Asian and non-Asian populations. Optimal NAC regimens, proper target populations, and predictors of NAC outcomes in Asian patients are still under investigation. Herein, we summarized the current progress in the administration of NAC in Asian patients with gastric cancer.

Computer-assisted horizontal translational osseous genioplasty: a simple method to correct chin deviation

  • Keyhan, Seied Omid;Azari, Abbas;Yousefi, Parisa;Cheshmi, Behzad;Fallahi, Hamid Reza;Valipour, Mohammad Amin
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제42권
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    • pp.36.1-36.5
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    • 2020
  • Background: Different genioplasty techniques are applied for the adjustment of chin area deformities such as chin deviation. Results: Thirty patients with simple facial asymmetry due to chin deviation underwent computer-assisted horizontal translational osseous genioplasty. In this technique, a surgical guide was used to cut a bone strip from the side where the chin should be transferred to; then, the same bone strip was used for the filling of the gap that was formed on the opposite side. Conclusion: According to the experience gained from this study, the authors believe that computer-assisted horizontal translational osseous genioplasty is a simple and reliable technique for patients with facial asymmetry due to chin deviation.

Regulation of post-translational modification in breast cancer treatment

  • Heo, Kyung-Sun
    • BMB Reports
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    • 제52권2호
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    • pp.113-118
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    • 2019
  • The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.

20(S)- Protopanaxadiol suppresses hepatic stellate cell activation via WIF1 demethylation-mediated inactivation of the Wnt/β-catenin pathway

  • Chunxue Li ;Yating Zhan ;Rongrong Zhang;Qiqi Tao ;Zhichao Lang ;Jianjian Zheng
    • Journal of Ginseng Research
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    • 제47권4호
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    • pp.515-523
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    • 2023
  • Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl4)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

Molecular docking study on the α3β2 neuronal nicotinic acetylcholine receptor complexed with α-Conotoxin GIC

  • Lee, Che-Wook;Lee, Si-Hyung;Kim, Do-Hyoung;Han, Kyou-Hoon
    • BMB Reports
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    • 제45권5호
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    • pp.275-280
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    • 2012
  • Nicotinic acetylcholine receptors (nAChRs) are a diverse family of homo- or heteropentameric ligand-gated ion channels. Understanding the physiological role of each nAChR subtype and the key residues responsible for normal and pathological states is important. ${\alpha}$-Conotoxin neuropeptides are highly selective probes capable of discriminating different subtypes of nAChRs. In this study, we performed homology modeling to generate the neuronal ${\alpha}3$, ${\beta}2$ and ${\beta}4$ subunits using the x-ray structure of the ${\alpha}1$ subunit as a template. The structures of the extracellular domains containing ligand binding sites in the ${\alpha}3{\beta}2$ and ${\alpha}3{\beta}4$ nAChR subtypes were constructed using MD simulations and ligand docking processes in their free and ligand-bound states using ${\alpha}$-conotoxin GIC, which exhibited the highest ${\alpha}3{\beta}2$ vs. ${\alpha}3{\beta}4$ discrimination ratio. The results provide a reasonable structural basis for such a discriminatory ability, supporting the idea that the present strategy can be used for future investigations on nAChR-ligand complexes.

Compromised extraction sockets: a new classification and prevalence involving both soft and hard tissue loss

  • Kim, Jung-Ju;Amara, Heithem Ben;Chung, Inna;Koo, Ki-Tae
    • Journal of Periodontal and Implant Science
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    • 제51권2호
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    • pp.100-113
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    • 2021
  • Purpose: Previous studies have solely focused on fresh extraction sockets, whereas in clinical settings, alveolar sockets are commonly associated with chronic inflammation. Because the extent of tissue destruction varies depending on the origin and the severity of inflammation, infected alveolar sockets may display various configurations of their remaining soft and hard tissues following tooth extraction. The aim of this study was to classify infected alveolar sockets and to provide the appropriate treatment approaches. Methods: A proposed classification of extraction sockets with chronic inflammation was developed based upon the morphology of the bone defect and soft tissue at the time of tooth extraction. The prevalence of each type of the suggested classification was determined retrospectively in a cohort of patients who underwent, between 2011 and 2015, immediate bone grafting procedures (ridge preservation/augmentation) after tooth extractions at Seoul National University Dental Hospital. Results: The extraction sockets were classified into 5 types: type I, type II, type III, type IV (A & B), and type V. In this system, the severity of bone and soft tissue breakdown increases from type I to type V, while the reconstruction potential and treatment predictability decrease according to the same sequence of socket types. The retrospective screening of the included extraction sites revealed that most of the sockets assigned to ridge preservation displayed features of type IV (86.87%). Conclusions: The present article classified different types of commonly observed infected sockets based on diverse levels of ridge destruction. Type IV sockets, featuring an advanced breakdown of alveolar bone, appear to be more frequent than the other socket types.

Titanium Ions Released from Oral Casting Alloys May Contribute to the Symptom of Burning Mouth Syndrome

  • Park, Yang Mi;Kim, Kyung-Hee;Lee, Sunhee;Jeon, Hye-Mi;Heo, Jun-Young;Ahn, Yong-Woo;Ok, Soo-Min;Jeong, Sung-Hee
    • Journal of Oral Medicine and Pain
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    • 제42권4호
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    • pp.102-108
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    • 2017
  • Purpose: Many metal ions released from dental casting alloys have been reported to influence the intraoral symptoms of oral lichen planus (OLP) and burning mouth syndrome (BMS). The aim of this study was to investigate the relationship between salivary metal ion levels and the prosthetic duration as well as to evaluate the time-dependent morbid effects of metal ions in OLP and BMS patients. Methods: Three study groups consist of the following subjects respectively: 17 OLP patients, 12 BMS patients, and 12 patients without oral symptoms. The salivary concentrations of 13 metal ions (copper, cobalt, zinc, chromium, nickel, aluminum, silver, iron, titanium [Ti], platinum, tin, palladium, and gold) were measured by Laser Ablation Microprobe Inductively coupled Plasma Mass Spectrometry. Results: The Ti ions had statistically significant differences among the groups with a prosthetic duration of less than 5 years. There were no significant differences between all ion levels among the groups wearing dental cast alloys for over 5 years. In the BMS group, the level of Ti ions in patients with prosthetic restorations less than 5 years old were significantly high (p<0.05). Conclusions: In the BMS group, 3-60 months during which salivary Ti levels were higher were matched with the duration of burning symptoms ($15.6{\pm}17.1months$). Furthermore, Ti ions were statistically high in the oral cavity of BMS patients fitted with dental casting alloys for 5 years. These results suggest that Ti ions released from dental implants and oral prostheses could attribute to burning sensation of BMS.

Advances in Systems Biology Approaches for Autoimmune Diseases

  • Kim, Ho-Youn;Kim, Hae-Rim;Lee, Sang-Heon
    • IMMUNE NETWORK
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    • 제14권2호
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    • pp.73-80
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    • 2014
  • Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.

The Protein Kinase 2 Inhibitor CX-4945 Induces Autophagy in Human Cancer Cell Lines

  • Kim, Jiyeon;Park, Mikyung;Ryu, Byung Jun;Kim, Seong Hwan
    • Bulletin of the Korean Chemical Society
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    • 제35권10호
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    • pp.2985-2989
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    • 2014
  • Autophagy is a self-digestion process in which intracellular structures are degraded in response to stress. Notably, prolonged autophagy leads to cell death. In this study, we investigated whether CX-4945, an orally available protein kinase 2 (CK2) inhibitor, induces autophagic cell death in human cervical cancer-derived HeLa cells and in human prostate cancer-derived LNCaP cells. CX-4945 treatment of both cell lines resulted in the formation of autophagosomes, in the conversion of microtubule-associated protein 1 light chain 3 (LC3), and in down-regulation of the Akt-mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (S6K) signaling cascade. Thus, pharmacologic inhibition of CK2 by CX-4945 induced autophagic cell death in human cancer cells by down-regulating Akt-mTOR-S6K. These results suggest that autophagy-inducing agents have potential as anti-cancer drugs.