• Journal of Life Science
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• v.31 no.9
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• pp.849-855
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• 2021

Recently, as nanotechnology has been introduced and used in various fields, the development of new drugs has been accelerating. Nanoparticles have maintained blood drug concentration for extended periods of time with a single administration of the drug. The drug can then be selectively released only at the pathological site, thereby reducing side effects to other non-pathological sites. In addition, nanoparticles can be modified for selective target sites delivery for other specific diseases, with polymers being widely used in the manufacture of these nanoparticles. Poly (D,L-lactic-co-glycolic acid ) (PLGA) is one of the most extensively developed biodegradable polymers. PLGA is widely used in drug delivery for a variety of applications. It has also been approved by the FDA as a drug delivery system and is widely applied in controlled release formulations, such as in gene therapy treatments. PLGA nanoparticles have been developed as delivery systems with high efficiency to specific cell types by using passive and active targeting methods. After the development of a drug delivery system using PLGA nanoparticles, the drug is selectively delivered to the target site, and the effective blood concentration for extended periods of time is optimized according to the disease. In this review paper, we focus on ways to improve cell-specific treatment outcomes by examining the development of astrocyte selective nanoparticles based on PLGA nanomaterials for gene therapy.

• Journal of Life Science
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• v.31 no.4
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• pp.430-441
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• 2021

Sesquiterpene lactones (STLs) are terpenoids found mostly in the Asteraceae family and are known for their strong cytotoxic properties, among other notable bioactivities. Some STLs, such as artemisinin and mipsagargin, are already commercially available and are used to fight malaria and tumor growth, respectively. Although the interest in STLs was low for a time after their discovery due to their toxic nature, past decades have witnessed a soar in STL-based studies focused on developing novel pharmaceuticals via chemical diversification. These studies have reported several promising physiological effects for STLs, including lower toxicity and diverse modes of action, and have demonstrated the antimicrobial, antioxidant, hepatoprotective, antiviral, antiprotozoal, phytotoxic, antitumor, and antiaging properties of STLs. STLs are mainly considered as valuable natural molecules for the fight against cancer since most STLs induce death of different types of cancer cells, as shown by in vitro and in vivo studies. Some STLs can also enhance the effects of drugs that are already in clinical use. Medicinal chemists use various STLs as starting molecules for the synthesis of new STLs or different bioactive compounds. All these developments warrant future research to provide more information on STLs, their bioactivities, and their mode of action. In this context, this review has summarized the bioactivities of some of the widely studied STLs, namely artemisinin, costunolide, thapsigargin, arglabin, parthenolide, alantolactone, cynaropicrin, helenalin, and santonin.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.617-630
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• 2021

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

• Journal of Life Science
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• v.31 no.7
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• pp.677-685
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• 2021

Cannabis sativa L. belongs to the Cannabaceae family and is an annual herbaceous flowing plant. The plants can be classified into narcotic marijuana and nonnarcotic hemp. Different parts of C. sativa L. have been used as food, medicine, cosmetics, fiber and textile. However, the use of leaf, flower, and seed of C. sativa L was forbidden in Korea in January 1977 as a result of the Cannabis Control Act due to the narcotic properties. The plant's mature stems have limited uses for the production of fiber and sheets. Recently, various cannabinoids, terpenes and essential fatty acids were identified from C. sativa L., and their safety and useful bio-activities, such as neuroprotective, anti-inflammation, antithrombosis, antiepileptic, and antimicrobial activities, and the relief of pain, have been highlighted. Furthermore, the process of reduction of tetrahydrocannabinol, a representative narcotic compound, and the isolation of cannabidiol, a nonnarcotic active compound in C. sativa L., have been determined. These findings resulted in the legalization of C. sativa L. in Korea for medical use in December 2018 and the exclusion of C. sativa L. from the narcotic list of the UN Commission on Narcotics Drugs (UNCND) in December 2020. Therefore, developments of various high-value added products have commenced worldwide. Additionally, in 2021, the Korean government deregulated special zones based on hemp. In this study, the current status and the prospect of the hemp industry, as well as essential techniques for developing new hemp products, are provided for the activation of the Korea Green-Rush.

• Journal of Dairy Science and Biotechnology
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• v.36 no.4
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• pp.208-219
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• 2018

Emergence of drug resistant strains of Salmonella enterica threatens milk processing and related dairy industries, thereby increasing the need for development of new anti-bacterials. Developments of antibacterial drugs are largely aimed to target the bacterial envelope, but screening their efficacy on bacterial envelope is laborious. This study presents a potential biosensor for envelope-specific stress in which a gfp reporter gene fused to spy gene encoding a periplasmic chaperone protein Spy (spheroplast protein y) that can sense envelope stress signals transduced by two major two-component signal transduction systems BaeSR and CpxAR in Salmonella enterica serovars Enteritidis and S. Gallinarum. Using spy-gfp operon fusions in S. Enterititis and S. Gallinarum, we found that spy transcription in both serovars was greatly induced when Salmonella cells were forming the spheroplast and were treated with ethanol or a membrane-disrupting antibiotic polymyxin B. These envelope stress-specific inductions of spy transcription were abrogated in mutant Salmonella lacking either BaeR or CpxR. Results illustrate that induction of Spy expression can be efficiently triggered by two-component signal transduction systems sensing envelope stress conditions, and thereby suggest that monitoring the spy transcription by spy-gfp operon fusions would be helpful to determine if developing antimicrobials can damage envelopes of S. Enteritidis and S. Gallinarum.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.166-174
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• 2021

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

• The Korean Journal of Applied Statistics
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• v.35 no.2
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• pp.251-263
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• 2022

Phase I clinical trial is called 'Dose finding study'. It is first step of experimenting on humans with new drugs developed through animal experiments or vitro experiments. The important area of interest in designing Phase I clinical trial is determining the dose that acceptable level to the patients and provides the greatest efficacy. In this paper, we explain about methods to determine the maximum tolerated dose using various stopping rules. The SM3, NM, Rim, J3, BSM methods are compared through simulation. And we consider how the methods might be reformed. As a result of the simulation, BSM estimated the MTD closest to the target toxicity probability. J3 method required the least number of subjects. These results are due to the feature of the stopping rules of both methods. The BSM adds 2 or 1 subject at the same dose level when there is a toxic reaction. In addition, the J3 method has a smaller number of subjects than the other methods. If the methods are improved by combining these features, MTD can be estimated more efficiently. If the total number of subjects can be reduced while using the stopping rule of the BSM, accurate estimation is possible for a small number of subjects.

• Korean Chemical Engineering Research
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• v.60 no.2
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• pp.300-307
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• 2022

Time-resolved serial femtosecond crystallography (TR-SFX) is a powerful technique for determining temporal variations in the structural properties of biomacromolecules on ultra-short time scales without causing structure damage by employing femtosecond X-ray laser pulses generated by an X-ray free electron laser (XFEL). The mixing rate of reactants and biomolecule samples, as well as the hit rate between crystal samples and x-ray pulses, are critical factors determining TR-SFX performance, such as accurate image acquisition and efficient sample consumption. We here develop two distinct sample delivery systems that enable ultra-fast mixing and on-demand droplet injecting via pneumatic application with a square pulse signal. The first strategy relies on inertial mixing, which is caused by the high-speed collision and subsequent coalescence of droplets ejected through a double nozzle, while the second relies on on-demand pneumatic jetting embedded with a 3D-printed micromixer. First, the colliding behaviors of the droplets ejected through the double nozzle, as well as the inertial mixing within the coalesced droplets, are investigated experimentally and numerically. The mixing performance of the pneumatic jetting system with an integrated micromixer is then evaluated by using similar approaches. The sample delivery system devised in this work is very valuable for three-dimensional biomolecular structure analysis, which is critical for elucidating the mechanisms by which certain proteins cause disease, as well as searching for antibody drugs and new drug candidates.

• Journal of Life Science
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• v.32 no.7
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• pp.550-566
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• 2022

Stroke is among the leading causes of death and long-term physical and cognitive disabilities worldwide, affecting an estimated 15 million people annually. The pathophysiological process of stroke is complicated by multiple and coordinated events. The breakdown of the blood-brain barrier (BBB) in people with stroke can significantly contribute to the development of ischemic brain injury. Therefore, BBB disruption is recognized as a hallmark of stroke; thus, it is important to develop novel therapeutic strategies that can protect against BBB dysfunction in ischemic stroke. Traditional medicines are composed of natural products, which represent a promising source of new ingredients for the development of conventional medicines. Indeed, several studies have shown the effectiveness of Korean medicine on stroke, highlighting the value of Korean medicinal treatment for ischemic stroke. This review summarizes the current information and underlying mechanisms regarding the ameliorating effects of the formula, decoction, herbs, and active components of traditional Korean medicine on cerebral ischemia-induced BBB disruption. These traditional medicines were shown to have protective effects on the BBB in many cellular and animal ischemia models of stroke, and experiments in various animal species, such as mice and rats. In addition, they showed brain-protective effects by protecting the BBB through the regulation of tight junction proteins and matrix metalloproteinase-9, reducing edema, neuroinflammation, and neuronal cell death. We hope that this review will help promote further investigation into the neuroprotective effects of traditional Korean medicines and stimulate the performance of clinical trials on Korean herbal medicine-derived drugs in patients with stroke.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.541-556
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• 2022

Myocardial fibrosis is a key link in the occurrence and development of diabetic cardiomyopathy. Its etiology is complex, and the effect of drugs is not good. Cardiomyocyte apoptosis is an important cause of myocardial fibrosis. The purpose of this study was to investigate the effect of gaseous signal molecule sulfur dioxide (SO₂) on diabetic myocardial fibrosis and its internal regulatory mechanism. Masson and TUNEL staining, Western-blot, transmission electron microscopy, RT-qPCR, immunofluorescence staining, and flow cytometry were used in the study, and the interstitial collagen deposition, autophagy, apoptosis, and changes in phosphatidylinositol 3-kinase (PI3K)/AKT pathways were evaluated from in vivo and in vitro experiments. The results showed that diabetic myocardial fibrosis was accompanied by cardiomyocyte apoptosis and down-regulation of endogenous SO₂-producing enzyme aspartate aminotransferase (AAT)_1/2. However, exogenous SO₂ donors could up-regulate AAT_1/2, reduce apoptosis of cardiomyocytes induced by diabetic rats or high glucose, inhibit phosphorylation of PI3K/AKT protein, up-regulate autophagy, and reduce interstitial collagen deposition. In conclusion, the results of this study suggest that the gaseous signal molecule SO₂ can inhibit the PI3K/AKT pathway to promote cytoprotective autophagy and inhibit cardiomyocyte apoptosis to improve myocardial fibrosis in diabetic rats. The results of this study are expected to provide new targets and intervention strategies for the prevention and treatment of diabetic cardiomyopathy.