Yeon-Cheol Park

WIN-34B, a new herbal medicine, inhibits the inflammatory response by inactivating IκB-α phosphorylation and mitogen activated protein kinase pathways in fibroblast-like synoviocytes.

ETHNOPHARMACOLOGICAL RELEVANCE The dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE have been used for the treatment of a variety of inflammatory diseases in traditional Korean medicine. OBJECTIVE The aim of the study is to evaluate the anti-inflammatory effects of WIN-34B, a new herbal medicine, in fibroblast-like synoviocytes (FLS) obtained from patients with osteoarthritis (OA). MATERIALS AND METHODS WIN-34B is isolated from the n-butanol fraction of dried flowers of L. japonica and dried roots of A. asphodeloides. The anti-inflammatory effects of WIN-34B on cell viability, the production and release of inflammatory mediators, matrix metalloproteinases (MMPs), aggrecanases, tissue inhibitor of matrix proteinases (TIMP) is compared with celecoxib in IL-1β-stimulated human OA FLS. Furthermore, the effect of WIN-34B on inhibitory kappa B-α (IκB-α) phosphorylation and mitogen-activated protein kinases (MAPK) in the IL-1β-stimulated OA FLS was also evaluated. RESULTS WIN-34B significantly inhibited the IL-1β-induced cell viability in human OA FLS without cytotoxicity. Compared to celecoxib, WIN-34B exhibited similar or better anti-inflammatory effects through significant suppression of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO), MMPs (MMP-1, MMP-3 and MMP-13) and aggrecanases (ADAMTS-4 and ADAMTS-5), and enhancement of TIMPs (TIMP-1 and TIMP-3). Moreover, WIN-34B reduced the phosphorylation of IκB-α, ERK1/2, p38 and JNK1/2 in IL-1β-stimulated OA FLS. CONCLUSIONS WIN-34B exhibited similar or better anti-inflammatory properties in IL-1β-stimulated OA FLS compared to celecoxib. The anti-inflammatory effects of WIN-34B are due to inhibition of inflammatory mediators (IL-1β, TNF-α, PGE2 and NO) and regulation of MMPs, ADAMTSs and TIMPs via the inhibition of IκB-α and MAPK phosphorylation in IL-1β-stimulated OA FLS.

Current Studies of Acupuncture in Cancer-Induced Bone Pain Animal Models

Acupuncture is generally accepted as a safe and harmless treatment option for alleviating pain. To explore the pain mechanism, numerous animal models have been developed to simulate specific human pain conditions, including cancer-induced bone pain (CIBP). In this study, we analyzed the current research methodology of acupuncture for the treatment of CIBP. We electronically searched the PubMed database for animal studies published from 2000 onward using these search terms: (bone cancer OR cancer) AND (pain OR analgesia) AND (acupuncture OR pharmacopuncture OR bee venom). We selected articles that described cancer pain in animal models. We analyzed the methods used to induce cancer pain and the outcome measures used to assess the effects of acupuncture on CIBP in animal models. We reviewed articles that met our inclusion criteria. Injection of mammary cancer cells into the cavity of the tibia was the most frequently used method for inducing CIBP in the animal models. Among the eight selected studies, five studies demonstrated the effects of electroacupuncture on CIBP. The effects of acupuncture were assessed by measuring pain-related behavior. Future researches will be needed to ascertain the effectiveness of acupuncture for treating CIBP and to explore the specific mechanism of CIBP in animal models.

Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone.

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

Dual effect of WIN-34B on osteogenesis and osteoclastogenesis in cytokine-induced mesenchymal stem cells and bone marrow cells.

ETHNOPHARMACOLOGICAL RELEVANCE As an n-butanol fractionated extracted mixture of Lonicera japonica Thunb, dried flowers and Anemarrhena asphodeloides Bunge, root, WIN-34B has been reported the analgesic, anti-inflammatory, cartilage-repairing and protective effects in previous studies. AIM OF THE STUDY To investigate the effect of WIN-34B on osteogenesis and osteoclastogenesis in cytokine-induced mesenchymal stem cells and bone marrow cells. MATERIALS AND METHODS To examine the effect of WIN-34B on osteogenic differentiation, human mesenchymal stem cells (hMSCs) were treated with WIN-34B (1μg/mL and 10μg/mL). Alkaline phosphatase (ALP) activity was evaluated and Von Kossa staining was conducted. Mice bone marrow macrophages (BMMs) were obtained and treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony stimulating factor (m-CSF) to induce osteoclastogenesis. To investigate osteoclast differentiation, tartrate-resistant acid phosphatase (TRAP) staining was conducted after treatment with WIN-34B. Osteoclastogenic conditions were induced by stimulating the cells with interleukin (IL)-1α, IL-17, and tumor necrosis factor (TNF-α) in hMSCs and BMMs co-culture systems. The expression levels of osteoprotegerin (OPG), RANKL, runt-related transcription factor 2 (RUNX2), IL-17, c-Fos, TNF-α, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured by reverse transcription polymerase chain reaction (RT-PCR). The expression levels of nuclear factor-kappaB (NF-κB), inhibitory kappa B-α (IκBα), phospho-NF-κB, phospho-IκBα, β-actin, p38 MAPK, phospho-c-Jun N-terminal kinase (JNK), phospho-extracellular-signal regulated kinase (ERK), phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, and phospho-ERK were measured by western blot analysis. RESULTS WIN-34B promoted ALP activity and mineralization of hMSCs. In TRAP-stained BMMs, the number of multinucleated cells decreased after WIN-34B treatment. WIN-34B increased the OPG/RANKL ratio and the expression of RUNX2, and suppressed the expression of IL-17, c-Fos, and TNF-α. It also suppressed the activation of NF-κB, IκBα, p38 MAPK, and JNK in a dose-dependent manner. CONCLUSIONS These results demonstrated that WIN-34B increased osteogenesis and decreased osteoclastogenesis in cytokine-induced mesenchymal stem cells and bone marrow cells via inhibition of the NF-κB, JNK, and p38 MAPK pathways.

Medical service use and usual care of common shoulder disorders in Korea: a cross-sectional study using the Health Insurance Review and Assessment Service National Patient Sample

Objectives This study examined National Health Insurance claims data to investigate the epidemiology of shoulder disorders in Korea. Detailed information on medical services and related costs was assessed by major shoulder disorder category. Design and setting The 2014 National Patient Sample dataset provided by the Health Insurance Review and Assessment Service was analysed. Among shoulder-related diagnosis codes, adhesive capsulitis of the shoulder (ACS), rotator cuff syndrome (RCS) and shoulder impingement syndrome (SIS) categories were of highest prevalence. Sociodemographic characteristics and medical service use, frequency and medical costs regarding common shoulder disorders were evaluated. Results The majority of patients with shoulder disorder received ambulatory care (97%). Total and per-patient expenses were highest in patients with RCS. The number of inpatients with RCS was more than twice that of the other two groups, and patients with RCS were more likely to receive surgical management compared with patients with ACS and SIS. Prevalence of shoulder disorders was highest among subjects in their 50s for all three groups. Primary care physicians treated 75.80% of patients with ACS, 56.99% of patients with RCS and 48.06% of patients with SIS, respectively, outlining the difference in medical institution usage patterns. In all three groups, the highest proportion of patients visited orthopaedic surgeons out of medical departments. In the ACS and SIS groups, cost of visits (consultations) took up the largest part of total expenses at 32.30% and 18.88%, respectively, while cost of procedure/surgery constituted the largest portion in patients with RCS (37.77%). The usage proportion of subcutaneous or intramuscular and intra-articular injections ranged between 20% and 30% for outpatients in all three groups. Conclusions Medical service use, frequency and cost distributions relating to major shoulder disorders in Korea were assessed using nationwide claims data. These findings are expected to aid policy-makers as well as researchers and practitioners as basic healthcare data.

Association between temporomandibular disorders, chronic diseases, and ophthalmologic and otolaryngologic disorders in Korean adults: A cross-sectional study

Introduction Temporomandibular disorders (TMDs) are common musculoskeletal conditions in the maxillofacial area. Although strong relationships between TMDs and other pain and diseases exist, few studies have comprehensively assessed the association between chronic diseases, ophthalmologic and otolaryngologic disorders and TMD. Methods Of 25,534 individuals included in the fifth Korea National Health and Nutrition Examination Survey (2010–2012), 17,575 aged ≥20 years who completed survey items on TMD symptoms were included for cross-sectional analysis. Logistic regression analysis was performed to assess the association between chronic diseases, ophthalmologic and otolaryngologic disorders and examination findings, and TMD symptoms after adjusting for various confounding variables. Results Out of 17,575 participants, 2,059 (11.75%) reported experience of ≥1 TMD symptom(s). Compared to individuals without chronic disease, those with asthma (odds ratio (OR) 1.46; 95% confidence interval (CI) 1.09–1.96), migraine (1.44; 1.26–1.65), osteoarthritis (1.51; 1.20–1.89), thyroid dysfunction (1.49; 1.13–1.96), and depressive symptoms (1.51; 1.29–1.77) had higher ORs for TMD prevalence. Participants with tinnitus (1.97; 1.70–2.27), hearing difficulties (1.55; 1.29–1.87), dizziness (1.52; 1.27–1.82), rhinitis (1.46; 1.28–1.65), and xerophthalmia (1.82; 1.57–2.12) also displayed higher ORs for TMD prevalence. Patients diagnosed with chronic rhinosinusitis upon otolaryngologic examination exhibited an OR of 1.44 (95% CI 1.11–1.87) for TMD prevalence, while that for individuals with abnormal laryngoscopic results was 0.57 (95% CI 0.36–0.90). Conclusions These findings imply that TMDs, chronic diseases, and ophthalmologic and otolaryngologic disorders hold various correlations, suggesting the need for multitarget approaches to effectively address this phenomenon.

Effectiveness and safety of moxibustion treatment for non-specific lower back pain: protocol for a systematic review

Introduction Many patients experience acute lower back pain that becomes chronic pain. The proportion of patients using complementary and alternative medicine to treat lower back is increasing. Even though several moxibustion clinical trials for lower back pain have been conducted, the effectiveness and safety of moxibustion intervention is controversial. The purpose of this study protocol for a systematic review is to evaluate the effectiveness and safety of moxibustion treatment for non-specific lower back pain patients. Methods and analysis We will conduct an electronic search of several databases from their inception to May 2017, including Embase, PubMed, Cochrane Central Register of Controlled Trial, Allied and Complementary Medicine Database, Wanfang Database, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure Database, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, Oriental Medicine Advanced Searching Integrated System, the Korea Institute of Science and Technology, and KoreaMed. Randomised controlled trials investigating any type of moxibustion treatment will be included. The primary outcome will be pain intensity and functional status/disability due to lower back pain. The secondary outcome will be a global measurement of recovery or improvement, work-related outcomes, radiographic improvement of structure, quality of life, and adverse events (presence or absence). Risk ratio or mean differences with a 95% confidence interval will be used to show the effect of moxibustion therapy when it is possible to conduct a meta-analysis. Ethics and dissemination This review will be published in a peer-reviewed journal and will be presented at an international academic conference for dissemination. Our results will provide current evidence of the effectiveness and safety of moxibustion treatment in non-specific lower back pain patients, and thus will be beneficial to patients, practitioners, and policymakers. Trial registration number CRD42016047468 in PROSPERO 2016