Publications by authors named "Yong Cheol Shin"

121 Publications

Anticancer Effects of JI017 on Two Prostate Cancer Cell Lines Involve Endoplasmic Reticulum Stress Mediated by Elevated Levels of Reactive Oxygen Species.

Front Pharmacol 2021 13;12:683575. Epub 2021 May 13.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

Prostate cancer is the second most commonly diagnosed cancer, and prostate cancer is the second most common cause of cancer death in United States men after lung cancer. Many therapies are used to treat prostate cancer, and chemotherapy is one of the most relevant treatments. However, chemotherapy has many side effects, and repeated administration of chemotherapeutic agents leads to acquired resistance. Thus, new drugs with few side effects are needed. We investigated the molecular mechanism of action of JI017 in human prostate cancer cells. We identified an endoplasmic reticulum (ER) stress pathway that depended on the reactive oxygen species (ROS) pathway and played a crucial role in JI017-induced apoptosis. We measured cell viability by the MTS assay to determine the effect of JI017. Analysis of apoptosis, mitochondrial dysfunction, and cell cycle features was performed by flow cytometry. We used western blot and RT-PCR to measure the levels of the proteins of the unfolded protein response (UPR) pathway and apoptosis markers. Immunoprecipitation assay and transfection were used to determine the expression levels of proteins interacting with the pathways influenced by JI017 in prostate cancer cells. The anticancer effects induced by JI017 were evaluated. JI017 induced cell death that regulated apoptotic molecules and caused cell cycle arrest that inhibited the proliferation of cancer cells. Moreover, JI017 generated ROS. Accumulation of ROS caused ER stress through the PERK-eIF2α-CHOP and IRE1α-CHOP pathways. Furthermore, persistent activation of the UPR pathway induced by JI017 treatment triggered mitochondrial dysfunction, including dissipation of mitochondrial membrane potential, which activated intrinsic apoptotic pathway in human prostate cancer cells. The data indicated that N-acetyl-L-cysteine diminished apoptosis. We demonstrated that JI017 induced ER stress and cell death. Anticancer properties of JI017 in prostate cancer cells and in a human prostate cancer model involved ROS-mediated ER stress. Thus, JI017 treatment provides a new strategy for chemotherapy of prostate cancer.
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http://dx.doi.org/10.3389/fphar.2021.683575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155384PMC
May 2021

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions.

Sci Adv 2021 Apr 28;7(18). Epub 2021 Apr 28.

Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.
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http://dx.doi.org/10.1126/sciadv.abe8873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081364PMC
April 2021

Bibliometric Analysis of Integrative Medicine Studies from 2000 to 2019.

Am J Chin Med 2021 7;49(4):829-841. Epub 2021 Apr 7.

Department of Global Public Health and Korean Medicine Management, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Integrative medicine has become a vital component of patient care. It provides patient-centered care that is focused on prevention and overall well-being. As there has been a growing number of patients favoring a blend of conventional, complementary and alternative approaches, integrative medicine has exceeded beyond the evaluation of complementary therapies. However, it is noteworthy that there has been a dilemma of providing substantial evidence supporting the efficacy of some complementary and alternative therapies. This study's goals were to analyze publication trends, most productive journals, most productive funding agencies, most productive authors, most relevant keywords, and countries in the field of integrative medicine research. Additionally, science mapping included country collaboration analysis and thematic evolution analysis. The findings from this study showed a constant rise in annual growth of publications from 2000 to 2019; the United States was dominant in various analysis categories. In conclusion, a comprehensive review of the evolution of research of integrative medicine will help healthcare providers understand an overview of the present status while encouraging more evidence-based research for the betterment of integrative patient care.
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http://dx.doi.org/10.1142/S0192415X21500397DOI Listing
April 2021

Adverse events from pharmacopuncture treatment in Korea: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Mar;100(11):e25107

Department of Global Public Health and Korean Medicine Management, Graduate School.

Background: Pharmacopuncture is a combination of acupuncture and herbal medicine, which involves the injection of herbal extracts into acupuncture points (acupoints). Pharmacopuncture has become one of the major therapeutic tools used in Korea; however, safety is one of the major concerns associated with it. We aim to systematically review clinical studies on the adverse events of pharmacopuncture in Korea.

Methods: To collect data on the incidence and characteristics of adverse events (AEs) and to evaluate pharmacopuncture safety, 2 or more researchers will conduct a comprehensive search of pertinent English and Korean databases using the keywords "pharmacopuncture" and "adverse events." Regardless of the participants' conditions or treatment types, we will include clinical studies on the AEs of pharmacopuncture. Studies that were not conducted in Korea, and acupoint injections containing Western medications, vitamins, or autologous serum will be excluded from this study. The severity of AEs will be classified using the common terminology criteria for adverse events, and the causality between pharmacopuncture and AEs will be assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality scale. The quality of identifying and reporting the AEs will be assessed using the McHarm scale. The risk of selection bias will be assessed using the Cochrane risk of bias and the risk of bias for non-randomized studies tools. Studies will be assessed for heterogeneity utilizing Higgins's I2 statistics, and the risk of publication bias will be assessed and expressed in the form of a contour-enhanced funnel plot.

Results And Conclusion: Comprehensive investigation of all types of clinical studies in Korea will provide clearer evidence of the safety of pharmacopuncture. The results of this study will be useful for traditional medical doctors and patients who use such treatments and interventions.Systematic Review Registration: Open Science Foundation (osf.io/umhyz).
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http://dx.doi.org/10.1097/MD.0000000000025107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982247PMC
March 2021

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Front Med Technol 2020 Aug 7;2. Epub 2020 Aug 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.
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http://dx.doi.org/10.3389/fmedt.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849371PMC
August 2020

Spatiotemporal Gradient and Instability of Wnt Induce Heterogeneous Growth and Differentiation of Human Intestinal Organoids.

iScience 2020 Aug 16;23(8):101372. Epub 2020 Jul 16.

Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton St., Austin, TX 78712, USA; Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA; Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:

In a conventional culture of three-dimensional human intestinal organoids, extracellular matrix hydrogel has been used to provide a physical space for the growth and morphogenesis of organoids in the presence of exogenous morphogens such as Wnt3a. We found that organoids embedded in a dome-shaped hydrogel show significant size heterogeneity in different locations inside the hydrogel. Computational simulations revealed that the instability and diffusion limitation of Wnt3a constitutively generate a concentration gradient inside the hydrogel. The location-dependent heterogeneity of organoids in a hydrogel dome substantially perturbed the transcriptome profile associated with epithelial functions, cytodifferentiation including mucin 2 expression, and morphological characteristics. This heterogeneous phenotype was significantly mitigated when the Wnt3a was frequently replenished in the culture medium. Our finding suggests that the morphological, transcriptional, translational, and functional heterogeneity in conventional organoid cultures may lead to a false interpretation of the experimental results in organoid-based studies.
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http://dx.doi.org/10.1016/j.isci.2020.101372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398973PMC
August 2020

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.

Micromachines (Basel) 2020 Jul 7;11(7). Epub 2020 Jul 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.
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http://dx.doi.org/10.3390/mi11070663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408321PMC
July 2020

Utilization of traditional medicine in primary health care in low- and middle-income countries: a systematic review.

Health Policy Plan 2020 Oct;35(8):1070-1083

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, Republic of Korea.

This paper reports the findings from the first systematic review of the utilization of traditional medicine (TM) in primary health care (PHC) in low- and middle-income countries (LMICs). PHC is an important component of health care and essential for achieving universal health coverage (UHC). For countries where there is a gap in PHC, TM plays a vital role. It is widely used and has the potential to increase the coverage of PHC and UHC. Hence in situations where TM is recognized in a considerable magnitude, there are scarce evidence and minimal regulation on it and TM practitioners (TMPs). This study aims to identify the current situation in the utilization of TM in PHC or UHC in LMICs. A systematic review and thematic synthesis of qualitative and quantitative studies have been conducted. A total of 56 articles met the criteria and were included in the review. In all, 14 analytic themes have been developed including the current use of TM in PHC, higher accessibility of TM, medical pluralism, national health system, national health policy and national health insurance to include TM, including TMPs in the referral system, utilizing TMPs as community health workers, the needs of scientific research on TM and the need for training both TMPs and conventional medical staffs for better collaboration. The study concluded that it is necessary to further focus on TM in the macro level on strengthening the referral system by including TM to establish a comprehensive service delivery network under UHC and in the micro level to focus on training the TMPs and conventional medicine health workers on both areas to attain more in-depth understanding of each other, which can lead to better collaboration and quality patient care.
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http://dx.doi.org/10.1093/heapol/czaa022DOI Listing
October 2020

Au nanozyme-driven antioxidation for preventing frailty.

Colloids Surf B Biointerfaces 2020 May 31;189:110839. Epub 2020 Jan 31.

Department of Chemistry, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address:

From senescence and frailty that may result from various biological, mechanical, nutritional, and metabolic processes, the human body has its own antioxidant defense enzymes to remove by-products of oxygen metabolism, and if unregulated, can cause several types of cell damage. Herein, an antioxidant, artificial nanoscale enzyme, called nanozyme (NZs), is introduced that is composed of Au nanoparticles (NPs) synthesized with a mixture of two representative phytochemicals, namely, gallic acid (GA) and isoflavone (IF), referred to as GI-Au NZs. Their unique antioxidant and anti-aging effects are monitored using Cell Counting Kit-8 and senescence-associated β-galactosidase assays on neonatal human dermal fibroblasts (nHDFs). Furthermore, alterations in epidermal thickness and SOD activity are measured under ultraviolet light to investigate the effects of the topical application of NZs on the histological structure and antioxidant activity in hairless mice skin. Then, hepatotoxicity and nephrotoxicity in the hairless mice are monitored. It is concluded that the NZs can effectively prevent serial passage-induced senescence in nHDFs, as well as oxidative stress in mice skin, suggesting a range of strategies to further develop novel therapeutics for acute frailty.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110839DOI Listing
May 2020

Synergistic anticancer effect of combined use of Trichosanthes kirilowii with cisplatin and pemetrexed enhances apoptosis of H1299 non-small-cell lung cancer cells via modulation of ErbB3.

Phytomedicine 2020 Jan 23;66:153109. Epub 2019 Oct 23.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, Republic of Korea. Electronic address:

Background: Lung cancer is one of the most common malignancies worldwide. To treat lung cancer, various anticancer drugs were developed and tested, but they failed because of drug resistance. In the present study, we tested herbal medicines, such as TK and CuD, as anticancer drugs to decrease side effects and resistance.

Methods: Cell viability was measured by an MTT assay. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by an annexin V-FITC/PI assay. We performed RTK kit analysis. Levels of p-ErbB3, p-STAT3, p-NF-κB, and caspases were measured by western blot analysis. Nuclear staining of ErbB3 was measured by immunocytochemistry. Transcriptional activity of STAT3 and NF-κB was detected by STAT3 and NF-κB luciferase reporter gene assays.

Results: We found a synergistic effect of TK with CDDP and PXD in primary culture of human NSCLC tumor cells. The combination of CDDP/PXD and TK or CuD inhibited the proliferation of H1299 cells. The combination of CDDP/PXD and TK or CuD induced sub-G1 and G2/M cell cycle arrest in H1299 cells. The combination of CDDP/PXD and TK or CuD induced apoptosis, regulated apoptotic molecules, caused morphological changes and inhibited colony formation in H1299 cells. We found that TK suppresses p-ErbB3 expression and signaling. The combination of CDDP/PXD and TK or CuD inhibited p-AKT, p-Erk, and p-JNK signaling and suppressed Stat3 and NF-κB transcriptional activity in H1299 cells. More importantly, the combination of CDDP/PXD and TK or CuD inhibited p-ErbB3 and downstream molecules in H1299 cells. The combination of CDDP/PXD and TK or CuD inhibited ErbB2/ErbB3 dimerization. Our results clearly demonstrate that the synergistic effect of CDDP/PXD and TK or CuD inhibits cell growth and induces apoptosis by inhibiting ErbB3 signaling.

Conclusion: The combination of CDDP/PXD and TK or CuD decreases cell proliferation and induces apoptosis by inhibiting ErbB3 signaling in H1299 lung cancer cells. TK or CuD could be useful as a compound to treat lung cancer. Additionally, targeting ErbB3 may also be useful for treating lung cancer.
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http://dx.doi.org/10.1016/j.phymed.2019.153109DOI Listing
January 2020

Nasolacrimal stent with shape memory as an advanced alternative to silicone products.

Acta Biomater 2020 01 7;101:273-284. Epub 2019 Nov 7.

Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address:

Epiphora is the overflow of tears typically caused by obstruction or occlusion of the nasolacrimal duct. More attention is required to address this global health issue owing to the increase in air pollution. Implantation of a silicone stent is the preferred treatment for epiphora; however, introducing a silicone stent into a narrow duct with complex geometry is challenging as it requires guidance by a sharp metal needle. Additionally, silicone can cause adverse reactions such as biofilm formation and tear flow resistance due to its extreme hydrophobicity. To overcome these problems, in this study we developed a new type of biocompatible shape memory polymer (SMP) stent with elasticity capacity for self-expansion. First, SMPs in the form of x%poly(ε-caprolactone)-co-y%poly(glycidyl methacrylate) (x%PCL-y%PGMA) were synthesized via ring opening polymerization by varying the molar ratio of PCL (x%) and PGMA (y%). Second, the shape memory and mechanical properties were tuned by controlling the crosslinking degree and concentration of x%PCL-y%PGMA solution to produce a test type of SMP stent. Lastly, this 94%PCL-06%PGMA stent exhibited more standout critical functions in a series of in vitro and in vivo experiments such as a cell growth-supporting level of biocompatibility with nasal epithelial cells without significant inflammatory responses, better resistance to biofilm formation, and more efficient capacity to drain tear than the silicone control. Overall, 94%PCL-06%PGMA can be suggested as a superior alternative to the currently used materials for nasolacrimal stents. STATEMENT OF SIGNIFICANCE: Silicone intubation (stenting) has been widely used to treat nasolacrimal duct obstruction, however, it can cause adverse clinical effects such as bacterial infection; presents procedural challenges because of the curved nasolacrimal duct structure; and shows poor drainage efficiency stemming from the highly hydrophobic nature of silicone. In this work, we describe an innovative shape memory polymer (SMP) as a superior alternative to conventional silicone-based materials for nasolacrimal duct intubation. We demonstrate the clear advantages of the SMP over conventional silicone, including a much higher drainage capacity and superior resistance to bacterial infection.
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http://dx.doi.org/10.1016/j.actbio.2019.11.001DOI Listing
January 2020

Topical Application of KAJD Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis Symptoms Through Regulation of IgE and MAPK Pathways in BALB/C Mice and Several Immune Cell Types.

Front Pharmacol 2019 19;10:1097. Epub 2019 Sep 19.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

Atopic dermatitis (AD) is a frequent skin complication that is caused by unknown reasons. KHU-ATO-JIN-D (KAJD) is a new drug aimed at AD composed of a mixture of extracts from six plants known to have anti-inflammatory and antiallergic effects. This study investigated whether KAJD alleviates 2,4-dinitrochlorobenzene (DNCB)-induced AD in BALB/c mice and several immune cell types. We applied KAJD to DNCB-induced AD-like skin lesions in BALB/c mice, phorbol myristate acetate/ionomycin-stimulated human mast cells (HMC-1), and lipopolysaccharide (LPS)-stimulated macrophages and splenocytes. Histological, ELISA, PCR, and Western blot experiments were performed. The application of KAJD significantly attenuated the lesion severity and skin thickness and inhibited the infiltration of inflammatory cells, mast cells, and CD4+ T cells into the sensitized skin of mice. Reduced leukocyte numbers and proinflammatory cytokine and IgE levels were also observed in the sera of KAJD-treated mice. Moreover, studies demonstrated that KAJD treatment reduced the LPS-induced expression of proinflammatory cytokines and nitric oxide (NO) production in RAW 264.7 cells. The regulation of IL-4 and IL-6 mRNA and MAPK pathways was also detected in agonist-induced isolated splenocytes and HMC-1 cells by the addition of KAJD. Taken together, our results demonstrate that KAJD inhibits the development of DNCB-induced AD in BALB/c mice and in several immune cell types, suggesting that KAJD might be a useful therapeutic drug for the treatment of AD.
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http://dx.doi.org/10.3389/fphar.2019.01097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761305PMC
September 2019

Development of a Shape-Memory Tube to Prevent Vascular Stenosis.

Adv Mater 2019 Oct 27;31(41):e1904476. Epub 2019 Aug 27.

Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.

Inserting a graft into vessels with different diameters frequently causes severe damage to the host vessels. Poor flow patency is an unresolved issue in grafts, particularly those with diameters less than 6 mm, because of vessel occlusion caused by disturbed blood flow following fast clotting. Herein, successful patency in the deployment of an ≈2 mm diameter graft into a porcine vessel is reported. A new library of property-tunable shape-memory polymers that prevent vessel damage by expanding the graft diameter circumferentially upon implantation is presented. The polymers undergo seven consecutive cycles of strain energy-preserved shape programming. Moreover, the new graft tube, which features a diffuser shape, minimizes disturbed flow formation and prevents thrombosis because its surface is coated with nitric-oxide-releasing peptides. Improved patency in a porcine vessel for 18 d is demonstrated while occlusive vascular remodeling occurs. These insights will help advance vascular graft design.
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http://dx.doi.org/10.1002/adma.201904476DOI Listing
October 2019

Contact Engineering High-Performance n-Type MoTe Transistors.

Nano Lett 2019 Sep 13;19(9):6352-6362. Epub 2019 Aug 13.

Department of Electrical Engineering , Stanford University , Stanford , California 94305 , United States.

Semiconducting MoTe is one of the few two-dimensional (2D) materials with a moderate band gap, similar to silicon. However, this material remains underexplored for 2D electronics due to ambient instability and predominantly p-type Fermi level pinning at contacts. Here, we demonstrate unipolar n-type MoTe transistors with the highest performance to date, including high saturation current (>400 μA/μm at 80 K and >200 μA/μm at 300 K) and relatively low contact resistance (1.2 to 2 kΩ·μm from 80 to 300 K), achieved with Ag contacts and AlO encapsulation. We also investigate other contact metals (Sc, Ti, Cr, Au, Ni, Pt), extracting their Schottky barrier heights using an analytic subthreshold model. High-resolution X-ray photoelectron spectroscopy reveals that interfacial metal-Te compounds dominate the contact resistance. Among the metals studied, Sc has the lowest work function but is the most reactive, which we counter by inserting monolayer hexagonal boron nitride between MoTe and Sc. These metal-insulator-semiconductor (MIS) contacts partly depin the metal Fermi level and lead to the smallest Schottky barrier for electron injection. Overall, this work improves our understanding of n-type contacts to 2D materials, an important advance for low-power electronics.
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http://dx.doi.org/10.1021/acs.nanolett.9b02497DOI Listing
September 2019

Virus-Incorporated Biomimetic Nanocomposites for Tissue Regeneration.

Nanomaterials (Basel) 2019 Jul 15;9(7). Epub 2019 Jul 15.

Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan 46241, Korea.

Owing to the astonishing properties of non-harmful viruses, tissue regeneration using virus-based biomimetic materials has been an emerging trend recently. The selective peptide expression and enrichment of the desired peptide on the surface, monodispersion, self-assembly, and ease of genetic and chemical modification properties have allowed viruses to take a long stride in biomedical applications. Researchers have published many reviews so far describing unusual properties of virus-based nanoparticles, phage display, modification, and possible biomedical applications, including biosensors, bioimaging, tissue regeneration, and drug delivery, however the integration of the virus into different biomaterials for the application of tissue regeneration is not yet discussed in detail. This review will focus on various morphologies of virus-incorporated biomimetic nanocomposites in tissue regeneration and highlight the progress, challenges, and future directions in this area.
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http://dx.doi.org/10.3390/nano9071014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669830PMC
July 2019

Clinical Effectiveness of Traditional and Complementary Medicine Interventions in Combination with Nicotine Replacement Therapy on Smoking Cessation: A Randomized Controlled Pilot Trial.

J Altern Complement Med 2019 May 23;25(5):526-534. Epub 2019 Apr 23.

4 Department of Preventive Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.

Smoking is associated with many preventable diseases and deaths. Globally, more than 6 million deaths per year are related to smoking. This study aimed to evaluate the pragmatic effectiveness of traditional and complementary medicine (T&CM) interventions for the smoking cessation treatment and to calculate the incremental cost-effectiveness ratio (ICER) of these interventions. The study design was a pragmatic, open-label randomized trial. The hypothesis of this trial was that the smoking cessation success rate increases with the addition of T&CM methods. The intervention group was provided T&CM interventions in addition to nicotine replacement therapy (NRT) and counseling, whereas the control group was treated with only NRT and counseling. Individuals received treatment for 4 weeks, then follow-up care for 20 weeks. Forty-one participants were enrolled and assigned to either an intervention group or a control group at a ratio of 1:1. The odds ratio values at 4 weeks were 1.96 (0.51-8.51) in intention-to-treat analysis and 3.27 (0.75-17.75) in per-protocol analysis. The amount of smoking (cigarettes) decreased in both groups: from 17.2 ± 10.31 (baseline) to 1.7 ± 3.02 (4 weeks) in the intervention group and from 12.9 ± 5.47 (baseline) to 3.3 ± 5.96 (4 weeks) in the control group. The total medical costs per patient were $212.20 USD in the intervention group and $170.80 in the control group. The adjusted ICER of T&CM interventions was $13,355. This pilot study evaluated the clinical feasibility of T&CM used in conjunction with NRT and counseling for the smoking cessation treatment. However, there was no statistically significant effectiveness of T&CM interventions to raise cessation success rate. This study demonstrates the necessity for further studies based on large-scale randomized controlled trials.
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http://dx.doi.org/10.1089/acm.2019.0009DOI Listing
May 2019

Enhanced osteogenic differentiation of human mesenchymal stem cells on Ti surfaces with electrochemical nanopattern formation.

Mater Sci Eng C Mater Biol Appl 2019 Jun 13;99:1174-1181. Epub 2019 Feb 13.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea. Electronic address:

Titanium (Ti) and its alloys are mainly used for dental and orthopedic applications due to their excellent biocompatibility and mechanical properties. However, their intrinsic bioinertness often quotes as a common complaint for biomedical applications. Herein, we produced nanopattern Ti surfaces with 10 nm nanopores in 120 nm dimples by electrochemical nanopattern formation (ENF), and evaluated the osteogenic differentiation of human mesenchymal stem cells (hMSCs) on the nanopattern Ti surfaces. The ENF surfaces were obtained by removing the TiO nanotube (NT) layers prepared by an anodization process. To determine the in vitro effects of the ENF surface, cell proliferation assay, alkaline phosphatase activity assay, alizarin red staining, western blotting, and immunocytochemistry were performed. Atomic force microscopy and scanning electron microscopy analysis show that the ENF surface has an ultrafine surface roughness with highly aligned nanoporous morphology. hMSCs on ENF surfaces exhibit increased proliferation and enhanced osteogenic differentiation as compared to the ordered TiO nanotubular and compact TiO surfaces. Surface modification with the ENF process is a promising technique for fabricating osteointegrative implant materials with a highly bioactive, rigid and purified nano surfaces.
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http://dx.doi.org/10.1016/j.msec.2019.02.039DOI Listing
June 2019

Flat Monolayer Graphene Cathodes for Li-Oxygen Microbatteries.

ACS Appl Mater Interfaces 2019 Jan 21;11(1):489-498. Epub 2018 Dec 21.

IBM Almaden Research Center , San Jose , California 95120 , United States.

Miniature batteries can accelerate the development of mobile electronics by providing sufficient energy to power small devices. Typical microbatteries commonly use thin-film inorganic electrodes based on Li-ion insertion reaction. However, they rely on the complicated thin-film synthesis method of inorganics containing many elements. Graphene, one atomic layer thick carbon sheet, has diverse physical and chemical properties and is compatible with conventional micron-scale device fabrication. Here, we study the use of chemical vapor deposition (CVD) grown monolayer graphene in a two-dimensional configuration, as a future Li-oxygen microbattery cathode. By maximizing the dissolution of discharge intermediates, we obtain 2610 Ah/g of capacity corresponding to 20% higher areal cathode energy density and 2.7 times higher cathode specific energy than that can be derived from the same volume or mass of conventional Li-ion battery cathode material. Furthermore, a clear observation on the discharge reaction on composite electrodes and their role in the charging reaction was made, thanks to the two-dimensional monolayer graphene Li-oxygen battery cathode. We demonstrate an easy integration of two-dimensional CVD graphene cathode into microscale devices by simply transferring or coating the target device substrate with flexible graphene layers. The ability to integrate and use monolayer graphene on arbitrary device substrates as well as precise control over a chemical derivation of the carbon interface can have a radical impact on future energy-storage devices.
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http://dx.doi.org/10.1021/acsami.8b12718DOI Listing
January 2019

Graphene-Functionalized Biomimetic Scaffolds for Tissue Regeneration.

Adv Exp Med Biol 2018;1064:73-89

Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, South Korea.

Graphene is a two-dimensional atomic layer of graphite, where carbon atoms are assembled in a honeycombed lattice structure. Recently, graphene family nanomaterials, including pristine graphene, graphene oxide and reduced graphene oxide, have increasingly attracted a great deal of interest from researchers in a variety of science, engineering and industrial fields because of their unique structural and functional features. In particular, extensive studies have been actively conducted in the biomedical and related fields, including multidisciplinary and emerging areas, as their stimulating effects on cell behaviors have been becoming an increasing concern. Herein, we are attempting to summarize some of recent findings in the fields of tissue regeneration concerning the graphene family nanomaterial-functionalized biomimetic scaffolds, and to provide the promising perspectives for the possible applications of graphene family nanomaterial.
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http://dx.doi.org/10.1007/978-981-13-0445-3_5DOI Listing
July 2019

Graphene-Based Nanocomposites as Promising Options for Hard Tissue Regeneration.

Adv Exp Med Biol 2018;1078:103-117

Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, South Korea.

Tissues are often damaged by physical trauma, infection or tumors. A slight injury heals naturally through the normal healing process, while severe injury causes serious health implications. Therefore, many efforts have been devoted to treat and repair various tissue defects. Recently, tissue engineering approaches have attracted a rapidly growing interest in biomedical fields to promote and enhance healing and regeneration of large-scale tissue defects. On the other hand, with the recent advances in nanoscience and nanotechnology, various nanomaterials have been suggested as novel biomaterials. Graphene, a two-dimensional atomic layer of graphite, and its derivatives have recently been found to possess promoting effects on various types of cells. In addition, their unique properties, such as outstanding mechanical and biological properties, allow them to be a promising option for hard tissue regeneration. Herein, we summarized recent research advances in graphene-based nanocomposites for hard tissue regeneration, and highlighted their promising potentials in biomedical and tissue engineering.
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http://dx.doi.org/10.1007/978-981-13-0950-2_6DOI Listing
July 2019

Application of black phosphorus nanodots to live cell imaging.

Biomater Res 2018 4;22:31. Epub 2018 Oct 4.

2Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, 46241 Republic of Korea.

Background: Black phosphorus (BP) has emerged as a novel class of nanomaterials owing to its unique optical and electronic properties. BP, a two-dimensional (2D) nanomaterial, is a structure where phosphorenes are stacked together in layers by van der Waals interactions. However, although BP nanodots have many advantages, their biosafety and biological effect have not yet been elucidated as compared to the other nanomaterials. Therefore, it is particularly important to assess the cytotoxicity of BP nanodots for exploring their potentials as novel biomaterials.

Methods: BP nanodots were prepared by exfoliation with a modified ultrasonication-assisted solution method. The physicochemical properties of BP nanodots were characterized by transmission electron microscopy, dynamic light scattering, Raman spectroscopy, and X-ray diffractometry. In addition, the cytotoxicity of BP nanodots against C2C12 myoblasts was evaluated. Moreover, their cell imaging potential was investigated.

Results: Herein, we concentrated on evaluating the cytotoxicity of BP nanodots and investigating their cell imaging potential. It was revealed that the BP nanodots were cytocompatible at a low concentration, although the cell viability was decreased with increasing BP nanodot concentration. Furthermore, our results demonstrated that the cells took up the BP nanodots, and the BP nanodots exhibited green fluorescence.

Conclusions: In conclusion, our findings suggest that the BP nanodots have suitable biocompatibility, and are promising candidates as fluorescence probes for biomedical imaging applications.
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http://dx.doi.org/10.1186/s40824-018-0142-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172722PMC
October 2018

Oral administration of Cervus nippon mantchuricus extract suppresses 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice and inflammatory effects in mast cells.

Int J Mol Med 2018 Nov 5;42(5):2961-2971. Epub 2018 Sep 5.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Cervus nippon mantchuricus extract, known as nok‑gol (NGE) in Korean, is useful for the treatment of various inflammatory diseases, including bone resorption and neutropenia. However, NGE has not been widely investigated, and its efficacy and safety remain to be fully elucidated. In the present study, histological analysis, blood analysis, reverse transcription‑semi-quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assays were performed to verify the inhibitory effect of NGE on atopic dermatitis (AD) in BALB/c mice and on inflammatory effects in HMC‑1 human mast cells. NGE suppressed the development of AD in mice, and decreased the infiltration of inflammatory cells, mast cells and CD4+ T cells into AD skin lesions. NGE also decreased leukocyte levels induced by 2,4‑dinitrochlorobenzene (DNCB). NGE alleviated AD‑like inflammatory symptoms in mice by suppressing the production of CD4+ T cells. NGE downregulated the mRNA expression of inflammatory cytokines induced by DNCB. It also decreased the serum immunoglobulin E concentration and inflammatory cytokine levels in DNCB‑treated BALB/c mice. The in vitro experiments demonstrated that NGE reduced the phorbol 12‑myristate 13‑acetate + ionomycin‑induced expression of pro‑inflammatory cytokines interleukin (IL)‑4, IL‑13, tumor necrosis factor‑α, and IL‑6 in HMC‑1 cells. Taken together, the results of the present study indicated that NGE suppressed the progression of DNCB‑induced AD in BALB/c mice and reduced inflammatory effects in HMC‑1 cells. This suggests that NGE may be a useful drug for the treatment of AD.
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http://dx.doi.org/10.3892/ijmm.2018.3856DOI Listing
November 2018

Corrigendum to "Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial".

Evid Based Complement Alternat Med 2018 30;2018:6162106. Epub 2018 Jul 30.

Department of Preventive Medicine, Korean Medical College, Kyung Hee University, Seoul, Republic of Korea.

[This corrects the article DOI: 10.1155/2017/8780325.].
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http://dx.doi.org/10.1155/2018/6162106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091375PMC
July 2018

Single-arm, open-label, dose-escalation phase I study to evaluate the safety of a herbal medicine SH003 in patients with solid cancer: a study protocol.

BMJ Open 2018 08 5;8(8):e019502. Epub 2018 Aug 5.

Department of Korean Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Introduction: Cancer is a major health problem worldwide and the leading cause of death in many countries. The number of patients with cancer and socioeconomic costs of cancer continues to increase. SH003 is a novel herbal medicine consisting of , and . Preclinical studies have shown that SH003 has therapeutic anticancer effects. The aim of this study is to determine the maximum tolerated dose of SH003 in patients with solid cancers.

Methods And Analysis: This study is an open-label, dose-escalation trial evaluating the safety and tolerability of SH003. The traditional 3+3 dose-escalation design will be implemented. Patients with solid cancers will be recruited. According to dose level, the patients will receive one to four tablets of SH003, three times a day for 3 weeks. Toxicity will be evaluated using common terminology criteria for adverse events (CTCAE). Dose-limiting toxicities are defined as grade 3 or higher adverse events based on CTCAE. The maximum tolerated dose will be determined by the highest dose at which no more than one of six patients experiences dose-limiting toxicity.

Ethics And Dissemination: This study has been approved by the institutional review board of the Ajou University Hospital (reference AJIRB-MED-CT1-16-311). The results of this study will be disseminated through a scientific journal and a conference.

Trial Registration Number: NCT03081819; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2017-019502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078237PMC
August 2018

Maekmoondong-tang in treatment of postoperative cough in patients with lung cancer: Study protocol for a randomized, double-blind, placebo-controlled, multicenter trial.

Medicine (Baltimore) 2018 Jul;97(29):e11541

Department of Preventive Medicine, College of Korean Medicine Department of Cardiovascular and Neurologic disease (Stroke Center), College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Background: Cough is a common symptom that occurs in 25% of patients after lung cancer surgery. It might last a long time and degrade the quality of life of patients. Maekmoondong-tang (Bakumondo-to in Japanese or Mai-Men-Dong-Tang in Chinese) is a herbal medicine which has been widely used for respiratory diseases with cough in Korea, China, and Japan.

Aims: The aim of the present study is to evaluate the efficacy and safety of Maekmoondong-tang for postoperative cough in patient with lung cancer.

Methods/design: This study is a randomized, double-blind, placebo-controlled, multicenter trial of Maekmoondong-tang. A total of 96 participants will be enrolled and allocated to 2 parallel groups: the Maekmoondong-tang group and the placebo group from 5 university hospitals. The participants will be administered either Maekmoondong-tang or a placebo 3 times a day for 4 weeks. The primary outcome measurement is the change in the Leicester Cough Questionnaire (LCQ) score. The secondary outcome measurements are the changes in the cough visual analog scale and Yin Deficiency Scale. The participants will visit 4 times in total for 4 weeks of trial period.

Discussion: The present study will be the first multicener study to evaluate the efficacy and safety of Maekmoondong-tang for postoperative cough in patient with lung cancer surgery. The results of this study will provide a new treatment for cough using herbal medicine and will be a reference for planning clinical trial of herbal medicine in patient with cough.
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http://dx.doi.org/10.1097/MD.0000000000011541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086514PMC
July 2018

The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo.

BMC Complement Altern Med 2018 Jul 13;18(1):215. Epub 2018 Jul 13.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447, South Korea.

Background: Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms.

Methods: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice.

Results: We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice.

Conclusion: These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.
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http://dx.doi.org/10.1186/s12906-018-2280-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045835PMC
July 2018

Sipjeondaebo-tang in patients with breast cancer with fatigue: a protocol for a pilot, randomised, double-blind, placebo-controlled, cross-over trial.

BMJ Open 2018 07 6;8(7):e021242. Epub 2018 Jul 6.

Department of Korean Preventive Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.

Introduction: Cancer-related fatigue is a frequent symptom in patients with cancer and one of the most distressing symptoms in patients with breast cancer. Sipjeondaebo-tang (Juzen-taiho-to in Japanese or Shi-Quan-Da-Bu-Tang in Chinese) is a widely used herbal medicine for the treatment of fatigue in Korea, China and Japan. The purpose of the present study is to evaluate the feasibility of Sipjeondaebo-tang for cancer-related fatigue.

Methods And Analysis: The present study is a randomised, double-blind, placebo-controlled, cross-over study. Forty-eight patients with breast cancer who are indicated for doxorubicin and cyclophosphamide will be recruited. The participants will receive 3 g of Sipjeondaebo-tang or a placebo three times a day for 56 days. The primary outcome measurement is the change in the Brief Fatigue Inventory scores. The secondary outcome measurements include the changes in the Visual Analogue Scale (VAS) of fatigue, and quality of life measured by the European Organization for Research and Treatment of Cancer-QLQ-C30 and QLQ-BR23. VAS of fatigue will be measured on every visit, and other outcomes will be measured on visits 2, 4, 6 and 7. The total study period is 14 weeks.

Ethics And Dissemination: This study has been approved by the Institutional Review Board of the Catholic Kwandong University International St Mary's Hospital (reference IS16MNSI0011). The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.

Trial Registration Number: NCT02858856; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2017-021242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042596PMC
July 2018

Dose- and Time-Dependent Cytotoxicity of Layered Black Phosphorus in Fibroblastic Cells.

Nanomaterials (Basel) 2018 Jun 6;8(6). Epub 2018 Jun 6.

Department of Mechanical Engineering, Sejong University, Seoul 05006, Korea.

Black phosphorus (BP) is a monolayer/multilayer two-dimensional (2D) nanomaterial, which has recently emerged as one of the most attractive 2D nanomaterials due to its fascinating physicochemical and optoelectronical properties. Layered BP may have promising applications in biomedical fields, such as drug delivery, photodynamic/photothermal therapy and bioimaging, although its intrinsic toxicity has not been fully elucidated yet. In the present study, the cytotoxicological effects of layered BP on both cell metabolic activity and membrane integrity were investigated. Layered BPs were prepared using a modified ultrasonication-assisted solution method, and their physicochemical properties were characterized. The dose- and time-dependent cytotoxicity of layered BP was assessed against L-929 fibroblasts. Our findings indicate that the cytotoxicity of BPs is proportionally dependent on their concentration and exposure time, which is affected by the oxidative stress-mediated enzyme activity reduction and membrane disruption. On the other hand, layered BPs did not exhibit significant cytotoxicity at concentrations lower than 4 μg/mL. Therefore, it is suggested that layered BPs can be effectively utilized as therapeutic delivery carriers and imaging agents.
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http://dx.doi.org/10.3390/nano8060408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027469PMC
June 2018

DSGOST regulates resistance via activation of autophagy in gastric cancer.

Cell Death Dis 2018 05 29;9(6):649. Epub 2018 May 29.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea.

Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST in Korean, Danggui-Sini-Jia-Wuzhuyu-Shengian-Tang in Chinese, and Tokishigyakukagoshuyushokyoto (TJ-38) in Japanese), a well-known traditional Korean/Chinese/Japanese medicine, has long been used to treat vascular diseases such as Raynaud's phenomenon (RP). However, anticancer effect of DSGOST remains elusive. In this study, we checked if DSGOST has an anticancer effect against gastric cancer cells, and investigated the mechanisms underlying DSGOST resistance. Moreover, DSGOST regulates chemoresistance in cisplatin-treated gastric cancer cells. Interestingly, DSGOST treatment induced the accumulation of GFP-LC3 puncta and increased the level of autophagy markers, such as LC3-II, ATG5, and Beclin-1, indicating activated autophagy. Furthermore, DSGOST could activate epithelial-to-mesenchymal transition (EMT) and exosomes via induction of autophagy. DSGOST in combination with TGFβ also induced autophagy and EMT. However, autophagy inhibition induces DSGOST-mediated cell death in gastric cancer cells. In addition, autophagy inhibition blocks the activation of DSGOST-mediated EMT markers including N-cadherin, Snail, Slug, vimentin, β-catenin, p-Smad2, and p-Smad3. Taken together, these findings indicated that prosurvival autophagy was one of the mechanisms involved in the resistance of gastric cancer to DSGOST. Targeting the inhibition of autophagy could be an effective therapeutic approach to overcome resistance to DSGOST in gastric cancer.
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http://dx.doi.org/10.1038/s41419-018-0658-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974125PMC
May 2018

Aligned laminin core-polydioxanone/collagen shell fiber matrices effective for neuritogenesis.

Sci Rep 2018 04 3;8(1):5570. Epub 2018 Apr 3.

Dental Life Science Research Institute, Seoul National University Dental Hospital, Seoul, 03080, Republic of Korea.

Neural tissue regeneration is a significant challenge, because severe nerve injury is quite difficult to regenerate spontaneously. Although, many studies have been devoted to promote nerve regeneration, there are still many technical challenges to achieve satisfactory results. In this study, we designed biomimetic matrices composed of aligned laminin core-polydioxanone/collagen shell (Lam-PDO/Col) fibers, which can provide both topographical and biochemical cues for promoting neuritogenesis. The aligned Lam-PDO/Col core-shell fiber matrices were fabricated by magnetic field-assisted electrospinning with the coaxial system, and their potential as biofunctional scaffolds for promoting neuritogenesis was explored. It was demonstrated that the aligned Lam-PDO/Col core-shell fibers were successfully fabricated, and the laminin in the core of fibers was steadily and continuously released from fibers. In addition, the cellular behaviors of hippocampal neuronal cells on the matrices were significantly enhanced. Moreover, the aligned Lam-PDO/Col fiber matrices effectively improved and guided neurite outgrowth as well as the neurogenic differentiation by providing both topographical and biochemical cues through aligned fiber structure and sustained release of laminin. Collectively, it is suggested that the aligned Lam-PDO/Col core-shell fiber matrices are one of the most promising approaches for promoting neuritogenesis and neural tissue regeneration.
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http://dx.doi.org/10.1038/s41598-018-23958-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882927PMC
April 2018
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