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Threonyl-tRNA synthetase (TRS) is an aminoacyl-tRNA synthetase that catalyzes the aminoacylation of tRNA by transferring threonine. In addition to an essential role in translation, TRS was extracellularly detected in autoimmune diseases and also exhibited pro-angiogenetic activity. TRS is reported to be secreted into the extracellular space when vascular endothelial cells encounter tumor necrosis factor-α. As T helper (Th) type 1 response and IFN-γ levels are associated with autoimmunity and angiogenesis, in this study, we investigated the effects of TRS on dendritic cell (DC) activation and CD4 T cell polarization. TRS-treated DCs exhibited up-regulated expression of activation-related cell-surface molecules, including CD40, CD80, CD86, and MHC class II. Treatment of DCs with TRS resulted in a significant increase of IL-12 production. TRS triggered nuclear translocation of the NF-κB p65 subunit along with the degradation of IκB proteins and the phosphorylation of MAPKs in DCs. Additionally, MAPK inhibitors markedly recovered the degradation of IκB proteins and the increased IL-12 production in TRS-treated DCs, suggesting the involvement of MAPKs as the upstream regulators of NF-κB in TRS-induced DC maturation and activation. Importantly, TRS-stimulated DCs significantly increased the populations of IFN-γ+CD4 T cells, and the levels of IFN-γ when co-cultured with CD4+ T cells. The addition of a neutralizing anti-IL-12 mAb to the cell cultures of TRS-treated DCs and CD4+ T cells resulted in decreased IFN-γ production, indicating that TRS-stimulated DCs may enhance the Th1 response through DC-derived IL-12. Injection of OT-II mice with OVA-pulsed, TRS-treated DCs also enhanced Ag-specific Th1 responses in vivo. Importantly, injection with TRS-treated DC exhibited increased populations of IFN-γ+-CD4+ and -CD8+ T cells as well as secretion level of IFN-γ, resulting in viral clearance and increased survival periods in mice infected with influenza A virus (IAV), as the Th1 response is associated with the enhanced cellular immunity, including anti-viral activity. Taken together, these results indicate that TRS promotes the maturation and activation of DCs, DC-mediated Th1 responses, and anti-viral effect on IAV infection.

Objective: The purpose of this study was to investigate the impact of wearing various types of shoes on gait ability in stroke survivors and in order to gain information in regards to shoes that could possibly replace ankle orthosis. Design: Cross-sectional study. Methods: Eight hemiplegic survivors diagnosed with stroke participated in the study. Gait was analyzed using the GAITRite Electronic Walkway (CIR System Inc., USA) when subjects walked with no showed, walked with non-ankle-covered shoes, and walked with ankle-covered shoes. This study collected gait variables, including velocity, cadence, step length, stride length, single support time, and double support time, respectively. Results: In the comparison of walking with no shoes, non-ankle-covered shoes, and ankle-covered shoes, there were significant differences in gait velocity, step length, stride length, and the less affected side single support time (p

Interleukin (IL)-33 is an alarmin factor that is highly secreted in a variety of autoimmune diseases, induces maturation of dendritic cells (DCs) and differentiation of T helper 17 (Th17) cells. As the balance between Th17 cells and regulatory T cells (Tregs) is important to maintain immune homeostasis, in this study, we investigated the effects of IL-33 on Treg cell response. We observed that direct treatment with IL-33 had no effect on Treg differentiation, whereas IL-33-matured DCs (IL33-matDCs) inhibited the differentiation of CD4

CD4+ T cell activation and adequate differentiation into effector T helper (Th) cells are crucial for mediating adaptive immune responses to cope with foreign pathogens. Despite the significant role of Th cells, excessive increases in their numbers result in inflammatory and autoimmune diseases. In this study, we investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating Th cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation. Furthermore, costunolide inhibited the expression level of Th subset-polarizing master genes such as T-bet, GATA3, and RORγt, indicating that costunolide inhibits the differentiation of CD4+ T cells into Th subsets. Additionally, costunolide suppressed the proliferative activity of CD4+ T cells and the expression of CD69 activation marker on CD4+ T cells. When the molecular targets of costunolide were investigated, phosphorylation of ERK and p38 was found to be decreased under Th subset-polarizing conditions, whereas activity of JNK remained unchanged. U0126, an ERK inhibitor, and SB203580, a p38 inhibitor, decreased the expression of CD69 upon TCR stimulation and inhibited CD4+ T cell differentiation, indicating that both ERK and p38 are suggested to be critical molecular targets of costunolide. Taken together, these results suggest that costunolide inhibits the differentiation of CD4+ T cells by suppressing ERK and p38 activities and can be an effective therapeutic agent for T cell-mediated immune diseases.

Focal dystonia is a neurological condition affecting a muscle or group of muscles in a specific part of the body, leading to involuntary muscular contractions. This condition is often treated with medications including muscle relaxants and injections of botulinum toxin. However, some cases do not respond to normal modes of treatment. Deep brain stimulation (DBS) can be a therapeutic option for patients who are resistant to medical treatment. We report a case of fibromyalgia accompanied by focal hand dystonia, where unilateral DBS improved the patient’s focal dystonic movement. We also present a review of the relevant literature. (Korean J Med 2016;90:270-273)

The optical properties of InGaP/GaAs double-junction solar cells (DJSCs) grown by metalorganic chemical vapor deposition were investigated using temperature- and excitation power-dependent photoluminescence (PL) measurements. The InGaP/GaAs DJSC samples studied were the same structures; however, the corresponding tunnel junctions were grown at different growth rates (1.0 and 1.5 A/s). The PL spectrum measured at 10 K for both samples exhibited a strong main peak at ∼1.97 eV with a weak shoulder peak at ∼1.94 eV, which could be attributed to the emissions of disordered and ordered InGaP, respectively. A PL peak located at ∼1.91 eV was observed under a low excitation power, originating from the donor–acceptor pair (DAP) transition. With the increase in the temperature, the emission related to the DAP of the sample grown at a growth rate of 1.0 A/s was found to be less dominant compared with the sample grown at a growth rate of 1.5 A/s. The power-conversion efficiency of the sample grown at a growth rate of 1.0 A/s was improved compared to that of the sample grown at a growth rate of 1.5 A/s, owing to fewer defect states. Our results help understand the luminescence properties of InGaP/GaAs DJSCs, which could be a crucial factor in fabricating high-efficiency solar cells.

In millimeter-wave (mm-wave) cellular systems, beamforming antennas are necessary at both the base station (BS) and mobile station (MS) to compensate for high attenuation in mm-wave frequency bands and to extend the transmission range. In space-division multiple access (SDMA) systems, the challenge is the inter-beam interference (IBI) caused by adjacent beams that are formed by the BS in the same cell and BSs in neighboring cells. The beams that are formed toward MSs in each cell may generate significant interference to MSs in neighboring cells, especially for MSs at the cell boundary. In this paper, we propose four different digital precoding techniques (Type-1, Type-2, Type-3, and Type-4) to reduce IBI in mm-wave cellular systems with a hybrid beamformer.

Current treatment for leukemia largely depends on chemotherapy. Despite the progress in treatment efficacy of chemotherapy, a poor outcome consequent upon chemoresistance against conventional anti-cancer drugs still remains to be solved. In this study, we report 5-diphenylacetamido-indirubin-3′-oxime (LDD398) as a novel mitochondria-targeting anti-leukemic agent, which is a derivative of indirubin used in traditional medicine. Treatment with LDD398 resulted in caspase activation, cell death, and growth arrest at G2/M phases in leukemia cells. Interestingly, LDD398 quickly collapsed mitochondrial membrane potential (MMP) within 1 h, accompanied by cytochrome c release into cytosol and severe depletion of cellular ATP. However, the LDD398-induced cellular events was significantly mitigated by blockage of mitochondrial permeability transition pore (MPTP) opening with chemical and genetic modifications, strongly supporting that LDD398 executes its anti-leukemic activity via an inappropriate opening of MPTP and a consequent depletion of ATP. The most meaningful finding was the prominent effectiveness of LDD398 on primary leukemia cells and also on malignant leukemia cells resistant to anticancer drugs. Our results demonstrate that, among a series of indirubin derivatives, LDD398 induces leukemia cell death via a different mode from indirubin or conventional chemotherapeutics, and can be employed as a potent anti-cancer agent in the treatment for newly diagnosed and relapsed leukemia. © 2015 Wiley Periodicals, Inc.

In millimeter-wave (mm-wave) cellular systems, beamforming antennas are necessary at both the base station (BS) and mobile station (MS) to compensate for high attenuation in mm-wave frequency bands and to extend the transmission range. The beamforming antennas also allow each BS to serve a number of MSs simultaneously, providing a substantial gain in system capacity. In space-division multiple access (SDMA) systems, the challenge is the inter-beam interference (IBI) caused by adjacent beams that are formed by the BS in the same cell and BSs in neighboring cells. The beams that are formed toward MSs in each cell may generate significant interference to MSs in neighboring cells, especially for MSs at the cell boundary. In this paper, we propose four different digital precoding techniques (Type-1, Type-2, Type-3, and Type-4) to reduce IBI in mm-wave cellular systems with a hybrid beamformer. Simulation results show that the proposed techniques can reduce the IBI in mm-wave cellular systems effectively, compared with a single-cell multiuser case.

IL-33 is associated with a variety of autoimmune diseases, such as sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Although IL-33 is mainly involved in the induction of Th2 cells, however, the relationship between IL-33 and Th17 cells is still largely unknown. In this study, we investigated the effects of IL-33 on DC-mediated CD4+ T cell activation and Th17 cell differentiation because DCs are essential cells for presenting self-antigens to CD4+ T cells in autoimmune disease conditions. OT-II mice were injected with IL-33-treated DCs or untreated DCs that were primed by OVA323-339 peptide, and their Th17 cell responses were compared. Th17 cell population and IL-17 expression levels were significantly increased in draining lymph nodes of mice injected with IL-33-treated DCs, compared with those in mice injected with untreated DCs. IL-33 treatment maturated DCs to present self-antigens and to increase production of proinflammatory cytokines such as IL-1β and IL-6, which have a crucial role in Th17 cell differentiation. We found that the IL-33-matured DCs enhanced the expression of an early T cell activation marker (CD69) and the Th17 master transcription factor (RORγt), but IL-33 did not directly affect CD4+ T cell differentiation or increase Th17 polarization. Notably, neutralizing IL-1β and/or IL-6 significantly decreased IL-17 expression levels and Th17 cell population which were increased by the coculture of CD4+ T cells with IL-33-matured DCs, indicating that IL-33 may induce Th17 cell responses via IL-1β and IL-6 derived from IL-33-matured DCs.

Matrix metalloproteinase 9 (MMP-9) and interleukin-8 (IL-8) play major roles in tumor progression and invasion of breast cancer cells. The present study was undertaken to investigate the inhibitory mechanism of cell invasion by luteolin 8-C-β-fucopyranoside (named as LU8C-FP), a C-glycosylflavone, in human breast cancer cells. We investigated whether LU8C-FP would inhibit MMP-9 activation and IL-8 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. LU8C-FP suppressed TPA-induced MMP-9 and IL-8 secretion and mRNA expression via inhibition of the MAPK signaling pathway and down-regulation of nuclear AP-1 and NF-κB. TPA-induced phosphorylation of ERK 1/2 was suppressed by LU8C-FP, whereas JNK and p38 MAPK phosphorylation were unaffected. In addition, LU8C-FP blocked the ERK 1/2 pathways following expression of MMP-9 and IL-8. These results suggest LU8C-FP may function to suppress invasion of breast cancer cells through the ERK/AP-1 and ERK/NF-κB signaling cascades.

In this study, the shape memory behavior of Ti–50.9 at.% Ni alloys with time gradient annealing (TGA) was investigated via differential scanning calorimetry (DSC) and thermal cycling tests under constant load. The ingot was prepared using a high-frequency induction vacuum furnace. The as-cast ingot was hot forged and extruded, followed by cold-drawing and intermediate annealing to produce wires of 1.0 mm in diameter, with a final cold-drawing of 30% reduction in cross-section. For the TGA treatment, a new type of radiant furnace was designed to maintain a constant temperature and create a time gradient along the length of the specimen. According to DSC measurements, a 34 K variation in the R-phase transformation interval (i.e., R s − R f ) was obtained along the length of the specimen (80 mm) that was time-gradient annealed from 3 min to 20 min at 773 K. The results of thermal cycling tests under constant load revealed that the temperature dependence of transformation elongation ( dɛ / dT ) of the TGA specimen is smaller than that of the isochronously annealed specimen at every heat-treatment temperature (673–773 K). The lowest dɛ / dT of R-phase transformation (0.0031%/K) was obtained for the specimen that was TGA-treated at 673 K. The difference in dɛ / dT of R-phase and the martensitic transformation of the TGA-treated and isochronously annealed specimen was largest at 773 K and increased with increasing stress. Such behavior provides superior controllability for actuation applications.

Purpose: Regular cancer screening for workers can help prevent cancer or allow early treatment, and is thus beneficial in improving health, reducing costs, and increasing companies` productivity. However, there has been little research on cancer screening rates of workers and related factors. The purpose of this study was to identify cancer screening rates and relevant factors among manufacturing workers. Methods: Using a questionnaire, data were collected from 335 workers aged over 40 years recruited from seven manufacturing companies. The collected information included cancer screenings (stomach, colorectal, breast, and cervical), attitude towards cancer screening, and demographic and job characteristics. Results: 72.5% of workers received stomach cancer screening (SCS), and 43% received colorectal cancer screening (CRCS). Among 86 women, 68.6% received breast cancer screening and cervical cancer screening. The attitude towards cancer screening was . Workers aged over 51, married, and those working in mobile manufacturing were more likely to have undergone SCS. Workers aged over 51, married, those working in mobile manufacturing, those in workplaces with more than 1,001 employees, and those with more positive attitudes toward cancer screening were more likely to have undergone CRCS. Finally, attitude affected cervical cancer screening. Conclusion: Workers in small-sized workplaces had lower cancer screening rates. Thus, follow-up research should assess the health environment of workplaces and develop educational programs on cancer screening that reflect attitudes towards screening.

The current status of needlestick or sharp injuries of hospital nurses and factors associated with the injuries have not been systematically examined with representative registered nurse samples in South Korea.To examine the incidence to needlestick or sharp injuries and identify the factors associated with such injuries among hospital nurses in South Korea.A cross-sectional survey of hospital nurses in South Korea. Data were collected from 3079 registered nurses in 60 acute hospitals in South Korea by a stratified random sampling method based on the region and number of beds.The dependent variable was the occurrence of needlestick or sharp injuries in the last year, and the independent variables were protective equipment, nurse characteristics, and hospital characteristics. This study employed logistic regression analysis with generalized estimating equation clustering by hospital to identify the factors associated with needlestick or sharp injuries.The majority (70.4%) of the hospital nurses had experienced needlestick or sharp injuries in the previous year. The non-use of safety containers for disposal of sharps and needles, less working experience as a registered nurse, poor work environments in regards to staffing and resource adequacy, and high emotional exhaustion significantly increased risk for needlestick or sharp injuries. Working in perioperative units also significantly increased the risk for such injuries but working in intensive care units, psychiatry, and obstetrics wards showed a significantly lower risk than medical-surgical wards.The occurrence of needlestick or sharp injuries of registered nurses was associated with organizational characteristics as well as protective equipment and nurse characteristics. Hospitals can prevent or reduce such injuries by establishing better work environments in terms of staffing and resource adequacy, minimizing emotional exhaustion, and retaining more experienced nurses. All hospitals should make safety-engineered equipment available to registered nurses. Hospitals as well as specific units showing higher risk for needlestick and sharp injuries should implement organizational strategies to prevent such injuries. It is also necessary to establish a monitoring system of needlestick and sharp injuries at a hospital level and a reporting system at the national level in South Korea.

Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)

CD4

Purpose: This study was done to identify the relationship among Critical Thinking Disposition (CTD), stress of clinical practice and clinical competence in Korean nursing students. Methods: Participants were 407 baccalaureate nursing students (3rd and 4th grades) in Korea. Variables included CTD, stress of clinical practice, clinical competence, and demographic variables. Data was analyzed by frequencies, t-test, ANOVA, Pearson`s correlation and multiple regression. Results: Clinical competence positively correlated with CTD, but negatively correlated with stress of clinical practice. The regression model explained 25.6% of clinical competence. The significant predictors of clinical competence were intellectual eagerness, intellectual fairness in CTD, conflict with patients, and clinical environment in stress of clinical practice. Conclusions: CTD and stress of clinical practice contribute to nursing student`s clinical competence. Therefore, efforts to encourage nursing student`s CTD, increase stress management skills, especially in conflict with patients, and build a supportive clinical environment should be made to strengthen clinical competence.

Objective: This study was conducted to explore the possible influence of risk notification regarding breast cancer on the intention of women to undergo mammography. Methods: This study employed an uncontrolled before–after design. A baseline survey was conducted in a random sample of 1000 women to examine the sociodemographic variables, breast cancer risk factors, and screening-related variables. All subjects received the findings of a personalized health-risk appraisal (HRA) following the baseline interview. After 2 months of the baseline survey, a survey was conducted in 855 women to assess whether the intention of undergoing mammography had changed. Thus, the modification in the intention by communicating the individual risk status was assessed. Results: There was an overall increase from baseline to post-intervention in the number of subjects with the intention of undergoing mammography. Women in the contemplation and action stages who had intention toward mammography utilization at baseline showed decreased intention regarding mammography. After intervention in the form of HRA to promote mammography utilization, it was determined that young age, being married, being in neither the precontemplation nor the relapse stage, and having one or more risk factors of breast cancer were the predictors of intention to undergo mammography. Conclusions: Our findings indicate that communicating the risk status by HRA service can have a negative effect in the promotion of health-conscious behavior. The selection of the appropriate type of intervention using HRA to promote mammography utilization in the target group will be enhanced by taking into account the risk status of each client. Copyright © 2009 John Wiley & Sons, Ltd.

Current treatment for leukemia largely depends on chemotherapy. Despite the progress in treatment efficacy of chemotherapy, a poor outcome consequent upon chemoresistance against conventional anti-cancer drugs still remains to be solved. In this study, we report 5-diphenylacetamido-indirubin-3'-oxime (LDD398) as a novel mitochondria-targeting anti-leukemic agent, which is a derivative of indirubin used in traditional medicine. Treatment with LDD398 resulted in caspase activation, cell death, and growth arrest at G2/M phases in leukemia cells. Interestingly, LDD398 quickly collapsed mitochondrial membrane potential (MMP) within 1 h, accompanied by cytochrome c release into cytosol and severe depletion of cellular ATP. However, the LDD398-induced cellular events was significantly mitigated by blockage of mitochondrial permeability transition pore (MPTP) opening with chemical and genetic modifications, strongly supporting that LDD398 executes its anti-leukemic activity via an inappropriate opening of MPTP and a consequent depletion of ATP. The most meaningful finding was the prominent effectiveness of LDD398 on primary leukemia cells and also on malignant leukemia cells resistant to anticancer drugs. Our results demonstrate that, among a series of indirubin derivatives, LDD398 induces leukemia cell death via a different mode from indirubin or conventional chemotherapeutics, and can be employed as a potent anti-cancer agent in the treatment for newly diagnosed and relapsed leukemia.

Luteolin, a flavonoid extracted from a number of plants with recognized anticancer, anti-inflammatory and anti-oxidative activities, inhibits angiogenic processes and modulates multidrug resistance. However, the efficacy and mechanisms of action of this flavonoid agent are still undergoing study. In order to elucidate whether luteolin exhibits an anticancer effect in cervical cancer cells, HeLa cells were incubated with luteolin and apoptosis was assessed by observing nuclear morphological changes, and performing Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Cell cycle analysis, western blotting, RT-PCR and mitochondrial membrane potential measurements were also carried out. Luteolin showed a significant dose-dependent cytotoxic effect only in human papillomavirus (HPV)-positive cervical cancer cells, when compared to its effect on HPV-negative cervical cancer C33A cells. Expression levels of human papilloma virus E6 and E7 oncogenes were suppressed, those of related factors pRb and p53 were recovered and E2F5 was increased by luteolin treatment. Furthermore, luteolin enhanced the expression of death receptors and death receptor downstream factors such as Fas/FasL, DR5/TRAIL and FADD in HeLa cells, and activated caspase cascades. In particular, luteolin enhanced the activity of caspase-3 and -8 in a dose-dependent manner. Activation of caspase-3 induced caspase-8 activity and vice versa. Luteolin also induced mitochondrial membrane potential collapse and cytochrome c release, and inhibited Bcl-2 and Bcl-xL expression. In conclusion, luteolin exerts anticarcinogenic activity through inhibition of E6 and E7 expression and cross-activation of caspase-3 and -8. Taken together, these results suggest that luteolin induces inactivation of HPV-18 oncogene expression and apoptosis by activating the intrinsic and extrinsic pathways.

IL-32 has been studied for its pleiotropic effects ranging from host immune responses to cell differentiation. Although several IL-32 isoforms have been characterized for their effects on cells, the roles of the others remain unclear. We previously reported that IL-32δ interacted with IL-32β and inhibited IL-32β-mediated IL-10 production. Thus, we performed comprehensive analyses to reveal more interactions between IL-32 isoforms in this study. We screened the interactions of 81 combinations of nine IL-32 isoforms by using a yeast two-hybrid assay, which identified 13 heterodimeric interactions. We verified these results by using reciprocal immunoprecipitation assays and reconfirmed 10 interactions, and presented the interaction network map between IL-32 isoforms. Our data suggest that IL-32 may have diverse intracellular effects through the interactions with its different isoforms.

There is growing evidence for multifunctional properties of IL-32. We previously demonstrated that IL-32β upregulates IL-10 production through the association with PKCδ. In this study, we examined the effects of other IL-32 isoforms on IL-10 production. We found that IL-32δ decreased IL-10 production and investigated the inhibitory mechanism of IL-32δ. We showed that IL-32δ suppressed IL-32β binding to PKCδ by interacting with IL-32β. The inhibitory effect of IL-32δ on IL-32β association with PKCδ was further verified by immuno-fluorescence staining. The co-localization of IL-32β and PKCδ around the nuclear membrane was disrupted by IL-32δ. Our data therefore indicate that IL-32δ plays an inhibitory role against IL-32β function, which also suggests that IL-32 may be regulated by its own isoform.

BACKGROUND Early detection is important for reducing mortality by colorectal cancer. Workplaces have access to a large number of people, approximately half of the Korean population. For cancer prevention, it is necessary to approach cancer screening through the workplace. OBJECTIVE In this cross-sectional study, we aimed to identify colorectal cancer screening (CRCS) stages and to predict factors that affect the respective stages. METHODS Data were collected from 314 manual workers at 32 medium-sized and small workplaces located in Korea. The dependent variable was the stage of CRCS, and independent variables were intrapersonal, interpersonal, and organizational levels. RESULTS At the intrapersonal level, workers who increased work hours per week or who felt stress were less likely to be in the acting/maintenance stage than in the decided to act stage of CRCS. At the organizational level, workers in medium-sized workplaces, those whose administrators secured health checkup and cancer screening budget for their workplace, and those considering health checkup and cancer screening were more likely to be in the acting/maintenance stage, compared with the decided to act stage. CONCLUSIONS Our findings suggest that the respective stages are affected by different intrapersonal, interpersonal, and organizational factors. IMPLICATION FOR PRACTICE The workplace environment and organizational predictors before the implementation of CRCS promotion programs may produce better results.

The effects of MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], a novel synthetic compound derived from epothilone, was investigated for its effects on the expression of proinflammatory mediators in lipopolysaccharide-stimulated BV-2 microglia. MMHD attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA and protein without affecting cell viability. Moreover, MMHD suppressed nuclear factor-κB (NF-κB) activation via the translocation of p65 into the nucleus. These results indicate that MMHD exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes through the NF-κB signaling pathway. Keywords:: microglia, lipopolysaccharide, nuclear factor-κB (NF-κB), MMHD [(S,E)-2-methyl-1-(2-methylthiazol-4-yl) hexa-1,5-dien-ol], neurodegenerative disease

Tedanolide (1), an 18-membered macrolide, was isolated by Schmitz et al. in 1984 from the Caribbean sponge Tedania ignis and structurally related 13-deoxytedanolide (2) was isolated from a Japanese sea sponge, Mycale adhaerens, by Fusetani et al. in 1991. Both tedanolide (1) and 13-deoxytedanolide (2) exhibit very potent biological activities against certain tumor cell lines. Their complex structures and distinctive biological properties make them extremely attractive targets for synthetic chemists. Recently Kalesse and Smith have reported successful total syntheses of tedanolide (1). As shown in Scheme 1, our retrosynthetic strategy for tedanolide (1) was the disconnection to two subunits 4 and 5 via cleavage at ester C-O bond and the aldol condensation transformation. The subunit 5 was envisioned to be obtained from the coupling between precursors 6 and 7. Herein we disclose our efforts in the construction of the C1-C7 fragment 6 of tedanolide (1). At first stage, we have utilized the Roush protocol as a key methodology toward fragment 6. The synthesis began with the known aldehyde 9. The Roush asymmetric crotylation upon 9 with 10 gave the desired product in 80% yield as a 92:8 mixture of two diastereomers, which was methylated to the methyl ether 11 in good yield. Ozonolysis of 11 furnished aldehyde 12. The second Roush crotylation on 12 did not yield the desired product. Instead we obtained a mixture of diastereomers (Scheme 2). Because of the observed lability of aldehyde 12 during the second crotylation, we considered the modification of the synthetic pathway. As a replacing measurement for the second Roush crotylation, we devised the combined application of Sharpless asymmetric epoxidation and Gilman cuprate reaction. As shown in Scheme 3, we established a highly stereoselective synthesis of precursor 6 via epoxide ring-opening and Mitsunobu reaction. The oxidative cleavage of the terminal vinyl group of 11 followed by immediate HornerWadsworth-Emmons reaction provided α,β-unsaturated ester 15 in 75% yield over two steps (trans:cis = 96:4). Subsequent reduction of ester 15 using DIBAL-H gave the intermediate allylic alcohol and Sharpless epoxidation upon this alcohol with Ti(OPr)4, L-DET and TBHP afforded stereoselectively epoxide 8 in nearly quantitative yield (β/α ≥ 30). Epoxide ring opening of 8 by the treatment with MeLi and CuI furnished the intermediate 1,3-diol (1,3-diol:1,2diol = 88:12) and the exposure of the resulting 1,3-diol to 16 with PPTS yielded p-methoxyphenyl acetal 17 in 70% yield. To introduce the requisite stereochemistry at C2, the

The macrolide (+)-sorangicin A (1), isolated by Hofle and co-workers from the gliding myxobacterium Sorangium cellulosum, has highly effective biological activity against a broad panel of both Gram-positive and Gram-negative bacteria, displaying average MIC values of 10 ng/mL and 10 μg/mL, respectively. The mechanism of action has been shown to be the inhibition of RNA polymerase in both Escherichia coli and Staphylococcus aureus. In addition, sorangicin A is active in vitro against several cancer cell lines. This fact motivated us to be interested in the synthesis toward sorangicin A. One of key steps in our synthetic plan is the successful preparation of dihydropyran. There have been numerous synthetic efforts reported in the literature. In general, dihydropyran units has been elegantly constructed by reactions such as Claisen rearrangement, Ferriertype reaction, radical, hetero Diels-Alder cyclizations and a few other reactions. We sought new and concise synthetic methods for this ring. Herein, we describe two new and simple preparations of the dihydropyran moiety based on olefinic ring-closing metathesis (RCM) reaction employing Grubbs catalyst. We planned two pathways according to retrosynthetic concept included formation of the C11-C12 double bond by RCM reaction (Scheme 1). First route A is employing oxazolidinone to yield the syn-aldol product. This methodology was implemented by Crimmins and She. The second route B is utilizing enantiospecific rhodium-catalyzed allylic etherification with the copper(I) alkoxide as a nucleophile. In the first reaction pathway A according to our synthetic plan (Scheme 2), the alcohol 5 was reacted with sodium salt of bromoacetic acid in refluxing THF to give glycolic acid, which was converted to its mixed pivalic anhydride and treated with (R)-3-lithio-4-benzyl-2-oxazolidinone to generate the N-glycolyloxazolidinone 7 in 81% yield over two steps. The addition reaction of 7 with acrolein furnished hydroxy compound 8 in good yield and high diastereoselectivity (73%, 93:7 dr by H NMR analysis). Protection of the resulting alcohol 8 as its TBS ether 3 and reductive removal of the chiral auxiliary group afforded primary alcohol 9 in 83% yield. The olefinic RCM reaction in the presence of Grubbs’ catalyst in CH2Cl2 transformed 9 to the desired dihydropyran compound 2. In the more convenient second synthetic approach B to dihydropyran 2 (Scheme 3), the stereospecificity in the reaction of rhodium-catalyzed allylic etherification could be maintained by suppressing the rate of isomerization. The copper(I) alkoxide as a nucleophile served to promote the etherification. Thus, this reaction allows for net retention of the absolute configuration through the alkylation of a rhodium-enyl complex. We began the second pathway with an aldol addition of chiral oxazolidinone 10 to acrolein to give syn-aldol adduct (84%, 92:8 dr by H NMR analysis). Protection of the resulting secondary hydroxy group as its TBS ether 11 and reductive removal of the chiral auxiliary group afforded an intermediate primary alcohol in 92% yield. Then, silylation of the hydroxy group as the TBS ether and removal of the MPM group yielded the alcohol 12 in 93% yield. Treatment of the allylic carbonate 13 with the trimethylphosphitemodified Wilkinson catalyst and the copper(I) alkoxide derived from the alkenyl alcohol 12, afforded the diene 4 in 67% yield with excellent diastereoselectivity (98:2 dr by H NMR analysis). The high selectivity observed can be explained using the reported proposed mechanism. Desilylation of the primary hydroxyl group with CSA gave alcohol 14 in 76% isolated yield. Finally, The RCM reaction was

in order to find the optimum reaction condition for theconstruction of C13-C15 homoallylic alcohol unit oflaulimalide. Also, we examined the stereoselective effects ofindium metal in the presence of Lewis acids and chiralligands on allylation. We successfully demonstrated that theindium-mediated allylation reaction of (2

Purpose: This study was performed to identify the relationship between optimistic bias about health crisis and health behavior of Korean adults in a crisis of health, and to prepare baseline data for developing a health education and promotion program. Methods: Study subjects were 595 adults aged from 19 to 64 who live in Korea. Data were collected through questionnaires administered by one interviewer. Descriptive statistics and Pearson’s correlation coefficient were calculated using the SPSS program. Results: The average score for optimistic bias about health crisis was 2.69, and that for health behavior was 107.05. The optimistic bias about health crisis showed a significantly positive correlation with health behavior (r=.187, p=.000). Conclusion: To make our results more useful, it is necessary to identity the causal relationship between health attitudes as an explanatory variable and optimistic bias as an outcome variable. In addition, a relatively low score in optimistic bias from this research compared to other studies must be explained through further studies considering unique Korean cultural background. Moreover, research of the relationship between optimistic bias about health crisis and health behavior looking at people who don’t have good health behaviors is needed.

Objective. Although previous trials suggested a relationship between neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic inflammatory response, clinical utility of NLR and PLR in rheumatoid arthritis (RA) is not well defined. This study was conducted to assess the efficiency of NLR and PLR as an inflammatory index in patients with RA. Methods. A total of 107 patients with newly diagnosed RA who had never used steroid and a control group of 50 age- and gender-matched healthy subjects whose high sensitive C-reactive protein (hsCRP) was within normal range were included. Those with cere- brovascular diseases, diabetes, malignancies, or any cardiovascular diseases were excluded from both groups. The patients were divided into two groups according to the Disease Activity Score of 28 joints (DAS28). Group 1 included patients with a DAS28 score of 3.2 and lower (low disease activity) and group 2 included patients with a score higher than 3.2 (moderate to high disease activity). Results. NLR and PLR in the patient group were 2.99±2.04, 170.90±86.49, significantly higher than that of the control group. NLR and PLR in group 2 were 4.16±2.50, 225.23±93.21, significantly higher than those of group 1 pa- tients (2.26±1.22, 137.15±61.92). NLR and PLR both showed correlation with rheumatoid factor, hsCRP, serum albumin, Korean Heath Assesment Questionnaire, and DAS28. Conclusion. These data showed a positive correlation between NLR or PLR level and RA disease activity, suggesting that NLR or PLR can be used as an additional inflammatory marker in patients with RA. (J Rheum Dis 2016;23:96-100)