A comparative study of the traditional medicine systems of South Korea and Taiwan: Focus on administration, education and license.

BACKGROUND: Traditional medicine (TM) is widely used in South Korea and Taiwan, and both societies have similar systems for the management of TM. This study aimed to compare the TM systems in South Korea and Taiwan. METHODS: We searched for studies on the TM systems and collected statistical data from the websites of relevant government agencies in both countries. Interviews were conducted with experts on TM and officials from government agencies. The two TM systems were described and examined in terms of policies, resources, utilization, licensing, and educational systems. RESULTS: Both South Korea and Taiwan have a dual system that separates the administration, licensing and educational systems between TM and Western Medicine (WM), and the TM systems are well established and highly standardized. Comparing with South Korea, however, Taiwan has a more flexible dual medical system in which education courses for producing dual licensure are provided. Additionally, in the system in Taiwan, dual license holders can use both TM and WM methods without limitations and WM doctors can apply acupuncture under some circumstances. Because of the strict dual medical system in South Korea, TM and WM conflict with each other on most health issues. CONCLUSION: Both South Korea and Taiwan have the advantages of preserving TM, as TM and WM are systemically independent and together provide a more holistic approach. The institutionalization of TM in South Korea and Taiwan may be a good reference for countries considering modernization of their TM.

Senescent fibroblasts in melasma pathophysiology.

It has been proposed that melasma is a photoageing skin disorder. The photoaged fibroblasts have been suggested as an important source of melanogenic factors which are involved in the regulation of pigmentation. To investigate whether melasma includes senescent cells, lesional and perilesional normal skin from 38 melasma patients was assessed using a cell senescence marker, p16INK4A . The results showed that lesional dermal skin had more p16INK4A -positive senescent cells than perilesional skin. The impact of senescent fibroblasts was further investigated in a pilot study using radiofrequency (RF) intervention for melasma. It showed that the RF therapy decreased the number of senescent cells with increased expression of procollagen-1, which were associated with reduced epidermal pigmentation. This leads us to the speculation that senescent fibroblasts may contribute to drive melasma and might be considered as a potential therapeutic target.

Senescent fibroblasts drive ageing pigmentation: ​A potential therapeutic target for senile lentigo.

Cutaneous ageing is an important extrinsic process that modifies the pigmentary system. Because cellular senescence is a fundamental ageing mechanism, we examined the role of senescent cells in ageing pigmentation. Methods: Biopsies obtained from senile lentigo and perilesional normal skin were assayed for a marker of cellular senescence, p16INK4A. To determine the secretory phenotypes of senescent fibroblasts, we performed microarray, RNA sequencing and methylation array analyses in senile lentigo and senescent fibroblasts. To further investigate the impact of senescent cells on ageing-related pigmentation, an intervention that targeted senescent cells using radiofrequency was performed. Results:In vivo, senescent fibroblasts accumulated at the sites of age-related pigmentation. Phenotype switching of the cells resulted in the repression of stromal-derived factor 1 (SDF1) by promoter methylation. SDF1 induced melanocyte differentiation via stromal-epithelial interactions, ultimately driving skin pigmentation. Furthermore, the elimination of senescent fibroblasts from pigmented skin using radiofrequency was accompanied by skin lightening, rendering it a potential target for treatment. Conclusion: Aged pigmented skin contains an increasing proportion of senescent fibroblasts. Cells with phenotype switching exhibited a loss of SDF1, which stimulates the melanogenic process and thereby contributes to aging pigmentation. These data may promote the development of new therapeutic paradigms, such as a stroma-targeting therapy for pigmentary disorders.

Targeted Delivery of Cyclotides via Conjugation to a Nanobody.

Many naturally occurring peptides have poor proteolytic stability, which limits their therapeutic applications. Cyclotides are plant-derived cyclic peptides that resist proteolysis due to their highly constrained structure, comprising a head-to-tail cyclic backbone and three disulfide bonds that form a cystine-knotted core. This structure makes them useful as scaffolds onto which peptide sequences (epitopes) can be grafted. In this study, VHH7, an alpaca-derived nanobody that targets murine class II MHC molecules, was used for the targeted delivery of cyclotides to antigen-presenting cells (APCs). The cyclotides MCoTI-I, and MCoTI-I with a HA-tag (YPYDVPDYA) grafted into loop 6 (MCoTI-HA), were tested for immunogenic properties. To produce the requisite VHH7-peptide conjugates, a site-specific sortase A-catalyzed reaction in combination with a copper-free strain-promoted cycloaddition reaction was used. MCoTI-I alone did not display any obvious antibody response, thus showing the capacity of cyclotides as immunologically silent scaffolds. By contrast, MCoTI-I conjugated to VHH7 elicited antibodies against cyclic or linear MCoTI-I, thus suggesting a simple and robust approach for targeting cyclotides to APCs, and potentially to other cell types. A similar antibody response was observed when MCoTI-HA was conjugated to VHH7, but there was no reactivity toward a linear HA-tag itself, suggesting differences in conformational constraint between cyclotide-presented and linear epitopes. Studies of commercially available HA antibodies applied to MCoTI-HA confirmed that the conformation of peptide immunogens affects their reactivity. Thus, the production of antibodies that recognize constrained epitopes may benefit from engraftment onto scaffolds such as cyclotides. More broadly, this study validates that a prototypic cyclotide, a member of a peptide family that has proven to be useful as drug design scaffolds in many other studies, can efficiently reach a specific target in vivo.

Ultraviolet-irradiated endothelial cells secrete stem cell factor and induce epidermal pigmentation.

Ultraviolet (UV)-associated hyperpigmented skins are characterized with increased vasculature underlying pigmentation, suggestive of the possible biological role of endothelial cells in the regulation of skin pigmentation during UV irradiation. In this study, we showed that UV-irradiated endothelial cells significantly increased the pigmentation of melanocytes through epithelial-mesenchymal crosstalk. The stimulatory effect of endothelial cells was further demonstrated using ex vivo human skin. RNA sequence analysis and enzyme-linked immunosorbent assay showed that endothelial cells secrete more stem cell factor (SCF) upon UV irradiation than non-irradiated cells. The increased pigmentation elicited by endothelial cells was abrogated following inhibition of SCF/c-KIT signaling. Together these results suggest that endothelial cells are activated upon UV exposure to release melanogenic factors such as SCF, which contributes to the development of skin hyperpigmentation during chronic sun exposure.

Changes in trust and the use of Korean medicine in South Korea: a comparison of surveys in 2011 and 2014.

BACKGROUND: Korean medicine (KM) has been widely used in Korea. This study aimed to assess the general perceptions of KM, to investigate the patterns of its usage in 2014, and to compare the results with those of an earlier survey from 2011. METHODS: A cross-sectional study was conducted with 1000 Korean people. The questionnaire included items regarding trust in KM, reasons for distrust of KM, and visit frequency to KM clinics. This study used methods consistent with those of a 2011 survey to examine changes in attitudes over 3 years. RESULTS: Despite high rates of trust in KM, the visit frequency decreased from 69.3% in 2011 to 63.2% in 2014. Usage among young adults (in their 20s and 30s) was significantly reduced compared to all other age groups. The KM modality most commonly used by participants was acupuncture, whereas the use of moxibustion and cupping therapies has decreased since 2011. Men and women were most likely to distrust KM due to a "lack of scientific evidence" (59.3%) and "suspicion of KM safety" (47.4%), respectively. CONCLUSIONS: The findings suggested that KM use and trust in KM were slightly lower in 2014 than in 2011. The decreases were most notable among individuals in their 30s and in the use of moxibustion in KM therapy. This study aimed to produce practical insights by reviewing patterns of KM use and perceptions over time. Additional surveys must be considered to produce a more in-depth analysis.

Efficient enzymatic cyclization of an inhibitory cystine knot-containing peptide.

Disulfide-rich peptides isolated from cone snails are of great interest as drug leads due to their high specificity and potency toward therapeutically relevant ion channels and receptors. They commonly contain the inhibitor cystine knot (ICK) motif comprising three disulfide bonds forming a knotted core. Here we report the successful enzymatic backbone cyclization of an ICK-containing peptide κ-PVIIA, a 27-amino acid conopeptide from Conus purpurascens, using a mutated version of the bacterial transpeptidase, sortase A. Although a slight loss of activity was observed compared to native κ-PVIIA, cyclic κ-PVIIA is a functional peptide that inhibits the Shaker voltage-gated potassium (Kv) channel. Molecular modeling suggests that the decrease in potency may be related to the loss of crucial, but previously unidentified electrostatic interactions between the N-terminus of the peptide and the Shaker channel. This hypothesis was confirmed by testing an N-terminally acetylated κ-PVIIA, which shows a similar decrease in activity. We also investigated the conformational dynamics and hydrogen bond network of cyc-PVIIA, both of which are important factors to be considered for successful cyclization of peptides. We found that cyc-PVIIA has the same conformational dynamics, but different hydrogen bond network compared to those of κ-PVIIA. The ability to efficiently cyclize ICK peptides using sortase A will enable future protein engineering for this class of peptides and may help in the development of novel therapeutic molecules. Biotechnol. Bioeng. 2016;113: 2202-2212. © 2016 Wiley Periodicals, Inc.

Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus.

The superior colliculus (SC) is a midbrain center involved in controlling head and eye movements in response to inputs from multiple sensory modalities. Visual inputs arise from both the retina and visual cortex and converge onto the superficial layer of the SC (sSC). Neurons in the sSC send information to deeper layers of the SC and to thalamic nuclei that modulate visually guided behaviors. Presently, our understanding of sSC neurons is impeded by a lack of molecular markers that define specific cell types. To better understand the identity and organization of sSC neurons, we took a systematic approach to investigate gene expression within four molecular families: transcription factors, cell adhesion molecules, neuropeptides, and calcium binding proteins. Our analysis revealed 12 molecules with distinct expression patterns in mouse sSC: cadherin 7, contactin 3, netrin G2, cadherin 6, protocadherin 20, retinoid-related orphan receptor ß, brain-specific homeobox/POU domain protein 3b, Ets variant gene 1, substance P, somatostatin, vasoactive intestinal polypeptide, and parvalbumin. Double labeling experiments, by either in situ hybridization or immunostaining, demonstrated that the 12 molecular markers collectively define 10 different sSC neuronal types. The characteristic positions of these cell types divide the sSC into four distinct layers. The 12 markers identified here will serve as valuable tools to examine molecular mechanisms that regulate development of sSC neuronal types. These markers could also be used to examine the connections between specific cell types that form retinocollicular, corticocollicular, or colliculothalamic pathways. J. Comp. Neurol. 524:2300-2321, 2016. © 2016 Wiley Periodicals, Inc.

Perspectives on the Market Globalization of Korean Herbal Manufacturers: A Company-Based Survey.

The growth of herbal markets has increased substantially in South Korea, but the worldwide market share remains small despite significant governmental efforts. This study aimed to characterize manufacturing employment and identify employees' general perceptions of market expansion. A survey study covering 567 companies was conducted using face-to-face interviews in 2012. Data were analyzed using comparisons among three manufacturing groups (i.e., the herbal dietary supplement manufacturing group, the herbal medicine manufacturing group, and the personal care product manufacturing group) or among the manufacturers themselves. We found that the majority of the manufacturing employee respondents were regular permanent and production workers. The domestic distributors were primarily chain stores/direct outlets or retailers/wholesalers, and the dominant product was red ginseng (hongsam). Although the responding companies exhibited a variety of perspectives, "advertisement/public relations" was cited as the most important factor in the development of the herbal industry. In contrast, "low manpower/seeking business partners" were the most crucial limiting and challenging factors for market globalization. Our results can be used to design a proper national plan by reducing the gaps in perspective between herbal product producers and policy makers.

Changes in attitudes toward and patterns in traditional Korean medicine among the general population in South Korea: a comparison between 2008 and 2011.

BACKGROUND: Traditional Korean medicine (TKM) is acknowledged to be prevalent among the Korean public, but few follow-up studies are available to confirm this commonly held belief. Whereas most survey studies have focused on the demographic factors influencing the usage of TKM, only a few studies have conducted a pattern or trend analysis over time. The purpose of this paper is to observe and document recent trends in the usage of TKM in South Korea and to compare overall patterns of TKM use over a period of several years. METHODS: A cross-sectional survey was conducted in 2011 to assess TKM usage patterns and public perceptions regarding TKM. An online questionnaire was administered to consenting respondents that focused upon individual preferences between TKM and current Western medicine, respondents' reasons for using TKM, the frequency of respondents' visits to TKM clinics, the reasons respondents visited TKM clinics, and respondents' perceived satisfaction. RESULTS: The results revealed that 66.6% of the respondents showed a positive attitude toward TKM. In addition, 69.3% of the respondents had visited TKM clinics one to four times during the previous year. Patients used TKM with the intentions of receiving acupuncture (95.3%), moxibustion (40.1%), and cupping (36.0%) treatments or to take herbal medicines (35.7%). Most respondents who had visited TKM clinics were largely satisfied with the clinics' effectiveness (56.1%). The factors most commonly associated with TKM usage included sex (female), age (50s), and education (college or higher), but the within-factor differences were not significant. Compared with a previous survey of other groups, TKM usage was found to have increased from 45.8% in 2008 to 69.3% in 2011. With the exception of acupuncture and physical therapy, most usage doubled or more than doubled. CONCLUSIONS: The attitudes toward and usage of TKM in South Korea have improved between 2008 and 2011. This result will be used to explain outcomes of certain social phenomena and to argue for national support in the promotion of TKM.

Semienzymatic cyclization of disulfide-rich peptides using Sortase A.

Disulfide-rich cyclic peptides have generated great interest in the development of peptide-based therapeutics due to their exceptional stability toward chemical, enzymatic, or thermal attack. In particular, they have been used as scaffolds onto which bioactive epitopes can be grafted to take advantage of the favorable biophysical properties of disulfide-rich cyclic peptides. To date, the most commonly used method for the head-to-tail cyclization of peptides has been native chemical ligation. In recent years, however, enzyme-mediated cyclization has become a promising new technology due to its efficiency, safety, and cost-effectiveness. Sortase A (SrtA) is a bacterial enzyme with transpeptidase activity. It recognizes a C-terminal penta-amino acid motif, LPXTG, and cleaves the amide bond between Thr and Gly to form a thioacyl-linked intermediate. This intermediate undergoes nucleophilic attack by an N-terminal poly-Gly sequence to form an amide bond between the Thr and N-terminal Gly. Here, we demonstrate that sortase A can successfully be used to cyclize a variety of small disulfide-rich peptides, including the cyclotide kalata B1, α-conotoxin Vc1.1, and sunflower trypsin inhibitor 1. These peptides range in size from 14 to 29 amino acids and contain three, two, or one disulfide bond, respectively, within their head-to-tail cyclic backbones. Our findings provide proof of concept for the potential broad applicability of enzymatic cyclization of disulfide-rich peptides with therapeutic potential.

Discovery and applications of disulfide-rich cyclic peptides.

Cyclic peptides typically have much higher stability and improved biopharmaceutical properties over their linear counterparts. Our work focuses on the discovery of naturally occurring disulfide-rich cyclic peptides and their applications in drug design. These peptides provide a design basis for re-engineering natural acyclic peptides to improve their biopharmaceutical properties by chemically linking their termini. Here we describe examples of the discovery of the cyclotide family of peptides, their chemical re-engineering to introduce desired pharmaceutical activities, studies of their biopharmaceutical properties and applications of cyclization technologies to naturally occurring toxins, including conotoxins and scorpion toxins. In the case of the conotoxin Vc1.1, we produced an orally active peptide with potential for the treatment of neuropathic pain by cyclising the native peptide. In the case of the scorpion toxin chlorotoxin, a cyclised derivative had improved biopharmaceutical properties as a tumour imaging agent over the naturally occurring linear chlorotoxin. Ongoing chemical and structural studies of these classes of disulfide-rich peptides promise to increase their value for use in dissecting biological processes in plants and mammals while also providing leads to new classes of biopharmaceuticals.