Sang Keun Ha

Bio: Sang Keun Ha is an academic researcher from Korea University of Science and Technology. The author has contributed to research in topics: Glycation & Nitric oxide. The author has an hindex of 24, co-authored 70 publications receiving 1784 citations. Previous affiliations of Sang Keun Ha include Kyung Hee University & Concordia University Wisconsin.

Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues

Abstract: Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with α-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of α-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

Microfluidic Gut-liver chip for reproducing the first pass metabolism

Abstract: After oral intake of drugs, drugs go through the first pass metabolism in the gut and the liver, which greatly affects the final outcome of the drugs' efficacy and side effects. The first pass metabolism is a complex process involving the gut and the liver tissue, with transport and reaction occurring simultaneously at various locations, which makes it difficult to be reproduced in vitro with conventional cell culture systems. In an effort to tackle this challenge, here we have developed a microfluidic gut-liver chip that can reproduce the dynamics of the first pass metabolism. The microfluidic chip consists of two separate layers for gut epithelial cells (Caco-2) and the liver cells (HepG2), and is designed so that drugs go through a sequential absorption in the gut chamber and metabolic reaction in the liver chamber. We fabricated the chip and showed that the two different cell lines can be successfully co-cultured on chip. When the two cells are cultured on chip, changes in the physiological function of Caco-2 and HepG2 cells were noted. The cytochrome P450 metabolic activity of both cells were significantly enhanced, and the absorptive property of Caco-2 cells on chip also changed in response to the presence of flow. Finally, first pass metabolism of a flavonoid, apigenin, was evaluated as a model compound, and co-culture of gut and liver cells on chip resulted in a metabolic profile that is closer to the reported profile than a monoculture of gut cells. This microfluidic gut-liver chip can potentially be a useful platform to study the complex first pass metabolism of drugs in vitro.

An Updated Review of Tyrosinase Inhibitors

Abstract: Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed.

Systemic inflammation and microglial activation: systematic review of animal experiments

Abstract: Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain. We searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions. Fifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels. Animal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.

Numerical methods for engineers

Abstract: The fifth edition of "Numerical Methods for Engineers" continues its tradition of excellence. Instructors love this text because it is a comprehensive text that is easy to teach from. Students love it because it is written for them--with great pedagogy and clear explanations and examples throughout. The text features a broad array of applications, including all engineering disciplines. The revision retains the successful pedagogy of the prior editions. Chapra and Canale's unique approach opens each part of the text with sections called Motivation, Mathematical Background, and Orientation, preparing the student for what is to come in a motivating and engaging manner. Each part closes with an Epilogue containing sections called Trade-Offs, Important Relationships and Formulas, and Advanced Methods and Additional References. Much more than a summary, the Epilogue deepens understanding of what has been learned and provides a peek into more advanced methods. Approximately 80% of the end-of-chapter problems are revised or new to this edition. The expanded breadth of engineering disciplines covered is especially evident in the problems, which now cover such areas as biotechnology and biomedical engineering. Users will find use of software packages, specifically MATLAB and Excel with VBA. This includes material on developing MATLAB m-files and VBA macros.

Neuroinflammation in Parkinson’s disease and its potential as therapeutic target

Abstract: Parkinson’s disease (PD), the second most common age-associated neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons and the presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc). Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Post-mortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain. Chronic release of pro-inflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc. Besides, peripheral immune system is also implicated in the pathogenesis of PD. Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients. Moreover, inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases. A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies. In this review, we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.

Modelling cancer in microfluidic human organs-on-chips.

Abstract: One of the problems that has slowed the development and approval of new anticancer therapies is the lack of preclinical models that can be used to identify key molecular, cellular and biophysical features of human cancer progression. This is because most in vitro cancer models fail to faithfully recapitulate the local tissue and organ microenvironment in which tumours form, which substantially contributes to the complex pathophysiology of the disease. More complex in vitro cancer models have been developed, including transwell cell cultures, spheroids and organoids grown within flexible extracellular matrix gels, which better mimic normal and cancerous tissue development than cells maintained on conventional 2D substrates. But these models still lack the tissue-tissue interfaces, organ-level structures, fluid flows and mechanical cues that cells experience within living organs, and furthermore, it is difficult to collect samples from the different tissue microcompartments. In this Review, we outline how recent developments in microfluidic cell culture technology have led to the generation of human organs-on-chips (also known as organ chips) that are now being used to model cancer cell behaviour within human-relevant tissue and organ microenvironments in vitro. Organ chips enable experimentalists to vary local cellular, molecular, chemical and biophysical parameters in a controlled manner, both individually and in precise combinations, while analysing how they contribute to human cancer formation and progression and responses to therapy. We also discuss the challenges that must be overcome to ensure that organ chip models meet the needs of cancer researchers, drug developers and clinicians interested in personalized medicine.