• Molecules and Cells
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• 제45권12호
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• pp.869-876
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• 2022

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

• Molecules and Cells
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• 제42권10호
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• pp.687-692
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• 2019

Transfer RNA-derived small RNAs (tsRNAs) play a role in various cellular processes. Accumulating evidence has revealed that tsRNAs are deeply implicated in human diseases, such as various cancers and neurological disorders, suggesting that tsRNAs should be investigated to develop novel therapeutic intervention. tsRNAs provide more complexity to the physiological role of transfer RNAs by repressing or activating protein synthesis with distinct mechanisms. Here, we highlight the detailed mechanism of tsRNA-mediated dual regulation in protein synthesis and discuss the necessity of novel sequencing technology to learn more about tsRNAs.

• Medical Lasers
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• 제10권2호
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• pp.61-67
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• 2021

Advances in nanobiotechnology have presented numerous possibilities of more effective diagnostic and therapeutic options. In particular, gold nanoparticles have demonstrated the potential for application in molecular imaging and treatment of cancers, including drug delivery system of certain target molecules, enhancement of radiation therapy, and photothermal treatment. This review discusses the properties, mechanism of action, and clinical application of gold nanoparticles. Although the safety of nanoparticles is yet to be ascertained, there is no doubt that in the future, nanotechnology will play an important role in the development and enhancement of a wide range of diagnostic and treatment modalities.

• Journal of Ginseng Research
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• 제37권1호
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• pp.8-29
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• 2013

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.15-24
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• 2022

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H₃R₉ exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H₃R₉ showed a better rescue action compared to that of MTS-H₃R₉. GA-MTS-H₃R₉ dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H₃R₉ towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H₃R₉ alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H₃R₉ showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H₃R₉. We showed that GA-MTS-H₃R₉ can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

• BMB Reports
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• 제48권12호
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• pp.685-690
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• 2015

The eukaryotic genome is packed into chromatin, which is important for the genomic integrity and gene regulation. Chromatin structures are maintained through assembly and disassembly of nucleosomes catalyzed by histone chaperones. Asf1 (anti-silencing function 1) is a highly conserved histone chaperone that mediates histone transfer on/off DNA and promotes histone H3 lysine 56 acetylation at globular core domain of histone H3. To elucidate the role of Asf1 in the modulation of chromatin structure, we screened and identified small molecules that inhibit Asf1 and H3K56 acetylation without affecting other histone modifications. These pyrimidine-2,4,6-trione derivative molecules inhibited the nucleosome assembly mediated by Asf1 in vitro, and reduced the H3K56 acetylation in HeLa cells. Furthermore, production of HSV viral particles was reduced by these compounds. As Asf1 is implicated in genome integrity, cell proliferation, and cancer, current Asf1 inhibitor molecules may offer an opportunity for the therapeutic development for treatment of diseases.

• Journal of Microbiology and Biotechnology
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• 제16권5호
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• pp.651-660
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• 2006

Natural products are a rich source of biologically active small molecules and a fertile area for lead discovery of new drugs [10, 52]. For instance, 5% of the 1,031 new chemical entities approved as drugs by the US Food and Drug Administration (FDA) were natural products between 1981 and 2002, and another 23% were natural product-derived molecules [53]. These molecules have evolved through millions of years of natural selection to interact with biomolecules in the cells or organisms and offer unrivaled chemical and structural diversity [14, 37]. Nonetheless, a large percentage of nature remains unexplored, in particular, in the marine and microbial environments. Therefore, natural products are still major valuable sources of innovative therapeutic agents for human diseases. However, even when a natural product is found to exhibit biological activity, the cellular target and mode of action of the compound are mostly mysterious. This is also true of many natural products that are currently under clinical trials or have already been approved as clinical drugs [11]. The lack of information on a definitive cellular target for a biologically active natural product prevents the rational design and development of more potent therapeutics. Therefore, there is a great need for new techniques to expedite the rapid identification and validation of cellular targets for biologically active natural products. Chemical genomics is a new integrated research engine toward functional studies of genome and drug discovery [40, 69]. The identification and validation of cellular receptors of biologically active small molecules is one of the key goals of the discipline. This eventually facilitates subsequent rational drug design, and provides valuable information on the receptors in cellular processes. Indeed, several biologically crucial proteins have already been identified as targets for natural products using chemical genomics approach (Table 1). Herein, the representative case studies of chemical genomics using natural products derived from microbes, marine sources, and plants will be introduced.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.346-351
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• 1999

Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In order to investigate whether the major histocompatibility complex (MHC) class I-mediated antigen processing machinery is preserved in human lung cancer cell lines, we examined the expression of multiple components of the MHC class I antigen processing pathway, including transporter associated with antigen processing (TAP), $\beta_2$-microglobulin, MHC class I molecules, and chaperones which have not been previously examined in this context. Row cytometry analysis showed that the cell surface expression of MHC class I molecules was downregulated in all of the cell lines. While some cell lines showed no detectable expression of MHC class I molecules, pulse-chase experiments showed that MHC class I molecules were synthesized in the other cell lines but not transported from the endoplasmic reticulum to the cell surface. Low or nondetectable levels of TAP1 and/or TAP2 expression were demonstrated by Western blot analysis in all of the cell lines, representing a variety of lung tissue types. In some cases, this was accompanied by loss of tapasin expression. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. This study provides further information for designing the potential therapeutic applications such as immunotherapy and gene therapy against cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6197-6208
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• 2013

Cancers will continue to be a threat to health unless they can be controlled by combinations of treatment modalities. In this review, evaluate the role of resveratrol (RSV) as a radiosensitizing agent was evaluated and underlying mechanisms holistically explored in different cancer models focusing on therapeutic possibilities. The ability of RSV to modify the effect of radiation exposure in normal and cancer cells has indeed been shown quite convincingly, the combination of RSV and IR exhibiting synergistic effects on different cancer cells. This is relevant since controlled exposure to IR is one of the most frequently applied treatments in cancer patients. However, radiotherapy (XRT) treatment regimes are very often not effective in clinical practice as observed in patients with glioma, prostate cancer (PCa), melanoma, for example, largely due to tumour radioresistant properties. Sensitization of IR-induced apoptosis by natural products such as RSV is likely to be relevant in cancer control and treatment. However, all cancers do not respond to RSV+IR in a similar manner. Therefore, for those such as the radioresistant PCa or melanoma cells, the RSV+IR regime has to be very carefully chosen in order to achieve effective and desirable outcomes with minimum toxicity to normal cells. They are reports that the highest concentration of 100 ${\mu}M$ RSV and highest dose of 5 Gy IR are sufficient to kill cells by induction of apoptosis, indicating that RSV is effective in radiosensitizing otherwise radioresistant cells. In general, it has been shown in different cancer cells that RSV+XRT effectively act by enhancing expression of anti-proliferative and pro-apoptotic molecules, and inhibiting pro-proliferative and anti-apoptotic molecules, leading to induction of apoptosis through various pathways, and cell death. If RSV+XRT can suppress the signature of cancer stemness, enhance the radiosensitivity by either targeting the mitochondrial functionality or modulating the tumour necrosis factor-mediated or Fas-FasL-mediated pathways of apoptosis in different cancers, particularly in vivo, its therapeutic use in the control of cancers holds promise in the near future.

• Journal of Ginseng Research
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• 제46권5호
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• pp.621-627
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• 2022

Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb₁ from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb₁ from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl₂ to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.