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Background With the significant growth of migration and expatriation, facilitated by increased global mobility, the number of Koreans living abroad as of 2016 is approximately 7.4 million (15% of the Korean population). Healthcare utilization or health problems, especially among expatriates in developing countries, have not been well researched despite the various health risks these individuals are exposed to. Consequently, we identified the health utilization patterns and healthcare needs among Korean expatriates in Vietnam, Cambodia, and Uzbekistan. Methods This cross-sectional survey examined 429 Korean expatriates living in Vietnam (n = 208), Cambodia (n = 60), and Uzbekistan (n = 161) who had access to the Internet and were living abroad for at least 6 months. A 67-item questionnaire was used, and feedback was received via an online survey program. Stepwise logistic regression analyses were performed to evaluate factors associated with unmet healthcare needs and preferences of certain type of telemedicine. Results We found that 45.5% (195/429) of respondents had used medical services in their country of stay. Among those who visited health institutions > 3 times, the most popular choice was general hospitals (39.4%, 15/38); however, they initially visited Korean doctors’ or local doctors’ offices. The most essential criteria for healthcare service facilities was a “skilled professional” (39.3%, 169/429), 42% wanted a health program for chronic disease management, and 30% wanted specialized internal medicine. A substantial number wanted to access telemedicine services and were willing to pay for this service. They were particularly interested in experts’ second opinion (61.5%, 264/429) and quick, 24-h medical consultations (60.8%, 261/429). Having unmet healthcare needs and being younger was strongly associated with all types of telemedicine networks. Conclusions Nearly half of the expatriates in developing countries had unmet healthcare needs. Telemedicine is one potential solution to meet these needs, especially in developing countries.

High molecular weight water-soluble chitosan(WSC), having an average molecular weight of 300,000 Da and a degree of deacethylation over 90%, can be produced using a simple multi-step membrane separation process. In this study, the trabecular bone area and thickness in ovariectomized(OVX) rats decreased by almost 50% from those in sham-operated rats. WSC was evaluated for inhibition of the progress of bone loss induced by OVX rats. We measured bone histomorphometry in sham, OVX or WSC-administered OVX rats. From light microscopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in OVX rats, whereas those of the same bone in sham-operated rats were composed of fine particles. The trabecular bone area and trabecular thickness in OVX rats decreased by 50% from those in sham rats, these decreases were completely inhibited by administration of WSC at a concentration of 15 mg/kg/daily for 7 weeks. In this study, the mechanical strength in femur neck was significantly enhanced by the treatment of WSC for 7 weeks. In OVX rats, free T(3) was normal in all cases, whereas free T(4) was significantly increased. Although there was no difference between OVX and WSC-administered rats in T(3) level, we have found significant difference between them in T(4) level. These results strongly suggest that WSC is effective in preventing the development of bone loss induced by OVX in rats.

Background Carbon monoxide (CO) and nitric oxide (NO) each have unique roles for various inflammatory states, including inflammatory bone resorption. Although it is known that NO can induce the expression of the cytoprotective enzyme HO-1, there is no information as to whether the protective effect of CO requires NO production or whether CO must induce the expression of HO-1 to exert its functional effects. Methods Murine osteoblast cells, MC3T3E1 osteoblasts, were cultured for CO and NO-associated HO-1 experiments and were transfected with pcDNA 3, pcDNA 3-HO-1, control siRNA or HO-1 siRNA using Nucleofector. For cell death measurement, MTT and annexin V assays were used. We performed Western blotting to check the expressions of HO-1 and iNOs and measured the HO-1 enzyme activity. We also measured the amounts of nitrite and nitrate using Griess reagents. Results The increased expression of HO-1 is required for the protective effect of NO and a single treatment of CO can increase the expression of HO-1, and this is also important for the protective effect of CO in MC3T3E1 osteoblasts. CO as well as NO attenuates the TNF-α-induced apoptosis in osteoblasts. The anti-apoptotic effect of CO or NO is not mediated by cGMP, and CO has no effect on the release of NO. The inhibition of HO-1 with using the HO-1 inhibitor ZnPP or HO-1 siRNA resulted in a striking increase of apoptosis in the CO/TNF-α-treated cells. Furthermore, HO-1 overexpression showed resistance against the TNF-α-induced cytotoxicity in the MC3T3E1 osteoblasts. Conclusions There is a need for HO-1 expression to mediate the protection provided by exogenous CO or NO in osteoblasts.

Ge-Jee-Bok-Ryung-Hwan (GJBRH), a commonly used herb formulation in Korea, Japan and China, caused a decrease of viability in HeLa human cervical carcinoma cells. The treatment of GJBRH resulted in genomic DNA fragmentation as well as the increase of Sub-G1 portion in cell cycle analysis. In this study, GFP-Bax over-expression system showed that Bax, pro-apoptotic Bcl-2 family protein, was translocated to mitochondria by the presence of GJBRH. The treatment of BAPTA-AM, permeable endogenous calcium chelator, inhibited GJBRH-induced caspase-3 and -9 activations, the release of cytochrome c and Smac/DIABLO into cytoplasm and the resultant cell death in HeLa human cervical carcinoma cells. The treatment of BAPTA-AM increased the expression of XIAP, which mediates binding to and inhibiting caspases and showed protective effect, in GJBRH-treated cells. GJBRH induced the expression of Glucose Response Protein 78 (GRP 78), a positive ER stress marker protein. However, BAPTA-AM did not interfere with the ER-stress response pathway that triggers the expression of GRP 78. This study showed that GJBRH induces cell death, which occurs downstream of or parallel to this point in the ER-stress pathway linked to apoptosis. In conclusion, GJBRH induces apoptosis in HeLa cells via ER stress-pathway associated mitochondria-dependent apoptosis mechansim.

The purpose of this study was to identify the DNA methylation status of the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual-specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and serpin peptidase inhibitor A member 5 (SERPINA5) in thyroid cancer.Using 76 papillary thyroid cancer(PTC) tissues and three thyroid cancer cell lines (TPC1, WRO82-1 and XTC), the expression of three genes and DNA methylation were determined by reverse transcription-PCR and methylation-specific PCR.In all cell lines, the expression of DUSP4 and DUSP6 increased; the corresponding gene promoters were unmethylated. However, SERPINA5 gene expression decreased and SERPINA5 DNA was methylated in the TPC1 cell line. With the de-methylating agent 5'-aza-2'-deoxycytidine, SERPINA5 gene expression was restored. In 82.9% of PTC tissues (63/76), the SERPINA5 DNA promoter was methylated, which was associated with a higher v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation rate in PTC tissues based on multivariate regression (odds ratio=3.573; 95% confidence interval=1.122-11.379; p=0.031).The expression of the MAPK signal-inhibiting gene SERPINA5 decreased in the TPC1 cell line, SERPINA5 expression was regulated by DNA methylation, which was associated with a higher BRAF mutation rate in PTC.

Previous studies have suggested that cathepsin B participates in the joint destruction associated with rheumatoid arthritis (RA). This study examined the activity of cathepsin B (a lysosomal cysteine protease) in human osteoblasts along with its regulation by cyclic AMP and Interleukin-6 (IL-6). Cyclic AMP elevating agents activate cathepsin B and stimulate the secretion of cathepsin B via the secretion of IL-6, a potent mediator of RA. This study investigated the induction of cathepsin B using the proinflammatory cytokine in human osteoblasts (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B transcription factor. When added to MG-63 cells, IL-6 stimulated the production of cathepsin B, which was reduced significantly by the addition of SB203580, a specific p38 MAPK inhibitor. In addition, the release of IL-6 was also inhibited by either pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which are potent NF-kappaB inhibitors. Both NF-kappaB inhibitors had a larger inhibitory effect on the activity of cathepsin B in the presence of SB203580. IL-6 stimulated the NF-kappaB binding affinity as well as the activation of p38 MAP kinase, leading to the release of cathepsin B. However, SB203580 had no effect on the IL-6-induced activation of NF-kappaB, and neither of the NF-kappaB inhibitors decreased the level of p38 MAPK activation in the IL-6-stimulated osteoblasts. Moreover, IL-6 increased the activity of urokinase type plasminogen activator (uPA) in MG-63 cells, which was inhibited by SB203580, PDTC and NF-kappaB SN50. This strongly suggests that p38 MAPK and NF-kappaB are essential to the IL-6-induced activation of cathepsin B or uPA and that these two IL-6-activated pathways can act independently.

Background: The epidermal growth factor receptor (EGFR) has been reported to be overexpressed in anaplastic thyroid carcinoma (ATC). In vitro studies have shown that EGFR tyrosine kinase inhibitors (TKIs) greatly inhibit cellular growth and induced apoptosis in the ATC cell lines, while somatic mutations in the tyrosine kinase domain or an increased gene copy number are associated with increased sensitivity to TKIs in non-small cell lung cancer. Aim: To investigate the prevalence of EGFR overexpression, gene amplification and activating mutation in the tyrosine kinase domain in patients with ATC. Methods: The EGFR gene status and protein expression were investigated by direct DNA sequencing of the hot-spot regions in exons 18, 19 and 21, fluorescence in situ hybridisation (FISH), and immunohistochemistry in tumour tissues from 23 patients with ATC. Results: On mutational analysis and FISH, neither mutations in the hot-spots nor gene amplification was observed. However, high polysomy was identified in 14/23 (60.9%) patients with ATC. All cases with immunohistochemistry (IHC) positivity (n = 6) had high polysomy, whereas 8/17 (47.1%) cases with IHC negativity had high polysomy (p = 0.048). High polysomy was observed in all 10 cases with giant cell subtype, but in only 4/11 (36.3%) with squamoid and 0/2 with spindle cell sarcomatoid subtype. There was no statistically significant correlation between FISH positivity of ATC tumour and presence of well-differentiated component. Conclusion: Despite the low incidence of somatic EGFR gene mutation and amplification in the study samples, in view of the fact that high polysomy was often identified by FISH, as well as the current lack of therapeutic options, EGFR TKIs are worth investigating for treating the patients with ATC who have at least giant cell subtype.

Background Between 10 and 30% of the fine needle aspiration biopsies (FNABs) of thyroid nodules are diagnosed as 'indeterminate'. A molecular diagnostic method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is the classic papillary type and the BRAF(V600E) mutation is highly prevalent. Aim To evaluate the role of pre-operative detection of BRAF(V600E) mutation in the FNAB specimens of thyroid nodules in a BRAF(V600E) mutation-prevalent geographical area. Patients and methods In 137 specimens of FNAB (107 papillary thyroid carcinomas (PTC); 3 follicular thyroid carcinomas (FTC); 2 undifferentiated thyroid carcinomas; 25 benign lesions), both direct DNA sequencing and PCR-RFLP were used for detecting the BRAF(V600E) mutation. The sensitivity and specificity were calculated. We analysed the association between BRAF(V600E) mutation and the clinico-pathological parameters. Results The BRAF(V600E) mutation was present in 93 (83%) of 112 thyroid cancers. Direct DNA sequencing showed a sensitivity of 83.0% and a specificity of 96.0%. The sensitivity and specificity of PCR-RFLP were 78.6% and 80.0%, respectively. Among 25 cases with indeterminate FNAB cytology, 8 patients had malignant lesions (5 PTC and 3 FTC). Three (60%) of 5 PTCs and 1 out of 17 benign lesions had BRAF(V600E) mutation (only one false positive case and the definitive pathology showed atypical nodular hyperplasia that could be a premalignant lesion). The diagnostic accuracy of this molecular method in only the 25 indeterminate nodules was 76% (19/25). No mutation was found in 3 FTCs. Among 107 PTCs, there was no significant association of the BRAF(V600E) mutation with the known risk factors. Conclusion Detection of the BRAF(V600E) mutation in FNAB specimens refines the FNAB-cytology diagnosis, especially in a BRAF(V600E) mutation-prevalent area. Direct DNA sequencing was a more reliable method than PCR-RFLP for detecting the BRAF(V600E) mutation with a high sensitivity and specificity.

Ge-Jee-Bok-Ryung-Hwan (GJBRH), a commonly used herb formulation in Korea, Japan and China, caused a decrease of viability in HeLa human cervical carcinoma cells. The treatment of GJBRH resulted in genomic DNA fragmentation as well as the increase of Sub-G1 portion in cell cycle analysis. In this study, GFP-Bax over-expression system showed that Bax, pro-apoptotic Bcl-2 family protein, was translocated to mitochondria by the presence of GJBRH. The treatment of BAPTA-AM, permeable endogenous calcium chelator, inhibited GJBRH-induced caspase-3 and -9 activations, the release of cytochrome c and Smac/DIABLO into cytoplasm and the resultant cell death in HeLa human cervical carcinoma cells. The treatment of BAPTA-AM increased the expression of XIAP, which mediates binding to and inhibiting caspases and showed protective effect, in GJBRH-treated cells. GJBRH induced the expression of Glucose Response Protein 78 (GRP 78), a positive ER stress marker protein. However, BAPTA-AM did not interfere with the ER-stress response pathway that triggers the expression of GRP 78. This study showed that GJBRH induces cell death, which occurs downstream of or parallel to this point in the ER-stress pathway linked to apoptosis. In conclusion, GJBRH induces apoptosis in HeLa cells via ER stress-pathway associated mitochondria-dependent apoptosis mechansim.