RESUMO
Human periodontal ligament cells (hPDLCs) cultured from periodontal ligament (PDL) tissue contain postnatal stem cells that can be differentiated into PDL fibroblasts. We obtained PDL fibroblasts from hPDLCs by treatment with low concentrations of TGF-ß1. Since the extracellular matrix and cell surface molecules play an important role in differentiation, we had previously developed a series of monoclonal antibodies against PDL fibroblast-specific cell surface molecules. One of these, the anti-PDL51 antibody, recognized a protein that was significantly upregulated in TGF-ß1-induced PDL fibroblasts and highly accumulated in the PDL region of the tooth root. Mass spectrometry revealed that the antigen recognized by the anti-PDL51 antibody was leucine-rich repeat containing 15 (LRRC15), and this antibody specifically recognized the extracellular glycosylated moiety of LRRC15. Experiments presented here show that as fibroblastic differentiation progresses, increased amounts of LRRC15 localized at the cell surface and membrane. Inhibition of LRRC15 by siRNA-mediated depletion and by antibody blocking resulted in downregulation of the representative PDL fibroblastic markers. Moreover, following LRRC15 inhibition, the directed and elongated cell phenotypes disappeared, and the long processes of the end of the cell body were no longer found. Through a specific interaction between integrin ß1 and LRRC15, the focal adhesion kinase signaling pathway was activated in PDL fibroblasts. Furthermore, it was shown that increased LRRC15 was important for the activation of the integrin-mediated cell adhesion signal pathway for regulation of cellular functions, including fibroblastic differentiation, proliferation, and cell migration arising from the expression of PDL-related genes in TGF-ß1-induced PDL fibroblastic differentiation.
Assuntos
Ligamento Periodontal , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Adesão Celular , Leucina/metabolismo , Proliferação de Células , Diferenciação Celular , Transdução de Sinais , Fibroblastos/metabolismo , Integrinas/metabolismo , Células Cultivadas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.
RESUMO
Type 2 diabetes (T2D) is caused by genetic and environmental factors as well as gene-environment interactions. However, these interactions have not been systematically investigated. We analyzed these interactions for T2D and fasting glucose levels in three Korean cohorts, HEXA, KARE, and CAVAS, using the baseline data with a multiple regression model. Two polygenic risk scores for T2D (PRST2D ) and fasting glucose (PRSFG ) were calculated using 488 and 82 single nucleotide polymorphisms (SNP) for T2D and fasting glucose, respectively, which were extracted from large-scaled genome-wide association studies with multiethnic data. Both lifestyle risk factors and T2D-related biochemical measurements were assessed. The effect of interactions between PRST2D -triglyceride (TG) and PRST2D -total cholesterol (TC) on fasting glucose levels was observed as follows: ß ± SE = 0.0005 ± 0.0001, p = 1.06 × 10-19 in HEXA, ß ± SE = 0.0008 ± 0.0001, p = 2.08 × 10-8 in KARE for TG; ß ± SE = 0.0006 ± 0.0001, p = 2.00 × 10-6 in HEXA, ß ± SE = 0.0020 ± 0.0004, p = 2.11 × 10-6 in KARE, ß ± SE = 0.0007 ± 0.0004, p = 0.045 in CAVAS for TC. PRST2D -based classification of the participants into four groups showed that the fasting glucose levels in groups with higher PRST2D were more adversely affected by both the TG and TC. In conclusion, blood TG and TC levels may affect the fasting glucose level through interaction with T2D genetic factors, suggesting the importance of consideration of gene-environment interaction in the preventive medicine of T2D.
Assuntos
Diabetes Mellitus Tipo 2 , Glicemia/genética , Colesterol , Diabetes Mellitus Tipo 2/genética , Jejum , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Glucose , Humanos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , República da Coreia , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Although survival based outcomes of lung cancer patients have been well developed, institutional transition of cancer care, that is, when patients transfer from primary visiting hospitals to other hospitals, and mortality have not yet been explored using a large-scale representative population-based sample. METHODS: Data from the Korean National Elderly Sampled Cohort survey were used to identify patients with lung cancer who were diagnosed during 2005-2013 and followed up with for at least 1 year after diagnosis (3738 patients with lung cancer aged over 60 years). First, the authors examined the distribution of the study population by mortality, and Kaplan-Meier survival curves/log-rank test were used to compare mortality based on institutional transition of cancer care. Survival analysis using the Cox proportional hazard model was conducted after controlling for all other variables. RESULTS: Results showed that 1-year mortality was higher in patients who underwent institutional transition of cancer care during 30 days after diagnosis (44.2% vs. 39.7%, p = .027); however, this was not associated with 5-year mortality. The Cox proportional hazard model showed that patients who underwent institutional transition of cancer care during 30 days after diagnosis exhibited statistically significant associations with high mortality for 1 year and 5 years (1-year mortality, Hazard ratio [HR]: 1.279, p = .001; 5-year mortality, HR: 1.158, p = .002). CONCLUSION: This study found that institutional transition of cancer care was associated with higher mortality among elderly patients with lung cancer. Future consideration should also be given to the limitation of patients' choice when opting for institutional transition of care since there are currently no control mechanisms in this regard. Results of this study merit health policymakers' attention.
Assuntos
Neoplasias Pulmonares , Idoso , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data. METHODS: From a nationwide sampled cohort database, we identified National Health Insurance beneficiaries diagnosed with gastric cancer (ICD-10: C16) in South Korea during 2005-2013. We analyzed the results of a multiple logistic regression analysis using the generalized estimated equation model to investigate which patient and institution characteristics affected fragmented cancer care during the first year after diagnosis. Then, survival analysis using the Cox proportional hazard model was conducted to investigate the association between fragmented cancer care and five-year mortality. RESULTS: Of 2879 gastric cancer patients, 11.9% received fragmented cancer care by changing their most visited medical institution during the first year after diagnosis. We found that patients with fragmented cancer care had a higher risk of five-year mortality (HR: 1.310, 95% CI: 1.023-1.677). This association was evident among patients who only received chemotherapy or radiotherapy (HR: 1.633, 95% CI: 1.005-2.654). CONCLUSIONS: Fragmented cancer care was associated with increased risk of five-year mortality. Additionally, changes in the most visited medical institution occurred more frequently in either patients with severe conditions or patients who mainly visited smaller medical institutions. Further study is warranted to confirm these findings and examine a causal relationship between fragmented cancer care and survival.
Assuntos
Seguro , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Estudos Retrospectivos , Análise de Sobrevida , Modelos de Riscos ProporcionaisRESUMO
This paper reports a concise and scalable method for the synthesis of the phytoestrogen 7,2'-dihydroxy-4',5'-dimethoxyisoflavanone 1 via an optimized synthetic route. Compound 1 was readily obtained in 11 steps and 11% overall yield on a gram scale from commercially available 3,4-dimethoxyphenol. The key features of the synthesis include the construction of the deoxybenzoin unit through a sequence of Claisen rearrangement, oxidative cleavage, and aryllithium addition and the efficient synthesis of the isoflavanone architecture from highly functionalized 2-hydroxyketone.
Assuntos
Fitoestrógenos , Fitoestrógenos/farmacologia , EstereoisomerismoRESUMO
Pumps and motors are essential components of the world as we know it. From the complex proteins that sustain our cells, to the mechanical marvels that power industries, much we take for granted is only possible because of pumps and motors. Although molecular pumps and motors have supported life for eons, it is only recently that chemists have made progress toward designing and building artificial forms of the microscopic machinery present in nature. The advent of artificial molecular machines has granted scientists an unprecedented level of control over the relative motion of components of molecules through the development of kinetically controlled, away-from-thermodynamic equilibrium chemistry. We outline the history of pumps and motors, focusing specifically on the innovations that enable the design and synthesis of the artificial molecular machines central to this Perspective. A key insight connecting biomolecular and artificial molecular machines is that the physical motions by which these machines carry out their function are unambiguously in mechanical equilibrium at every instant. The operation of molecular motors and pumps can be described by trajectory thermodynamics, a theory based on the work of Onsager, which is grounded on the firm foundation of the principle of microscopic reversibility. Free energy derived from thermodynamically non-equilibrium reactions kinetically favors some reaction pathways over others. By designing molecules with kinetic asymmetry, one can engineer potential landscapes to harness external energy to drive the formation and maintenance of geometries of component parts of molecules away-from-equilibrium, that would be impossible to achieve by standard synthetic approaches.
Assuntos
Proteínas Motores Moleculares/metabolismo , Trifosfato de Adenosina/metabolismo , Catálise , Hidrólise , Cinética , Luz , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , ATPases Translocadoras de Prótons/metabolismo , TermodinâmicaRESUMO
Layered transition metal oxides, in particular P2-type ones, are considered as promising cathode materials for sodium-ion batteries on account of their high specific capacity and rate capability. Nevertheless, conventional layered compounds involve detrimental phase transformation throughout repeated cycles, which results in electrochemical performance degradation. Therefore, finding structurally stable layered compounds, featuring minimal phase transition has been a key theme of the sodium-ion battery research. Here lithium substituted Fe/Mn-based P2/O3 layered oxide-Na0.67 Li0.2 Fe0.2 Mn0.6 O2 -that overcomes the inherited structural instability, is reported. In situ synchrotron-based diffraction measurements and DFT calculations are utilized, in order to identify the association between P2/O3 biphasic structure and electrochemical performances. The lithium honeycomb ordering within the P2/O3 biphasic layered compound effectively constrains the undesirable phase transitions; more specifically, both P2-Z phase transition and Jahn-Teller distortion are suppressed throughout wide potential range of 1.5-4.5 V. The DFT calculation further discovers that the presence of honeycomb ordering is crucial for achieving the structural stability by forming Na-vac-Li and Na-Li-Na pairing at highly charged state. The results highlight that the synergetic effect of P2/O3 biphasic structure and lithium substitution can provide an effective strategy toward achieving electrochemically stable layered cathode material for sodium-ion batteries.
RESUMO
The battery safety and cost remain major challenges for developing next-generation rechargeable batteries. All-solid-state sodium (Na)-ion batteries are a promising option for low-cost as well as safe rechargeable batteries by using abundant resources and solid electrolytes. However, the operation of solid-state batteries is limited due to the low ionic conductivity of solid electrolytes. Therefore, it is essential to develop new compounds that feature a high ionic conductivity and chemical stability at room temperature. Herein, we report a potassium-substituted sodium superionic conductor solid electrolyte, Na3-xKxZr2Si2PO12 (0 ≤ x ≤ 0.2), that exhibits an ionic conductivity of 7.734 × 10-4 S/cm-1 at room temperature, which is more than 2 times higher than that of the undoped sample. The synchrotron powder diffraction patterns with Rietveld refinements revealed that the substitution of large K-ions resulted in an increased unit cell volume, widened the Na diffusion channel, and shortened the Na-Na distance. Our work demonstrates that substituting a larger cation on the Na site effectively widens the ion diffusion channel and consequently increases the bulk ionic conductivity. Our findings will contribute to improving the ionic conductivity of the solid electrolytes and further developing safe next-generation rechargeable batteries.
RESUMO
BACKGROUND: In Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality. METHODS: The Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated with the survival probability of HCC patients. RESULTS: From 2004 to 2008, there were 4658 new HCC cases among males and 2667 new cases among females. The 5-year survival proportion of males was 68%, and the incidence per person-year was 0.768; the female survival proportion was 78%, and the incidence per person-year was 0.819. Lower income was associated with higher hazard ratio (HR), and HCC patients with hepatitis B (HBV), alcoholic liver cirrhosis, and other types of liver cirrhosis had higher HRs than those without these conditions. Subgroup analyses showed that middle-aged men were most vulnerable to the effects of low income on 5-year mortality, and community-level characteristics were associated with survival of HCC patients. CONCLUSION: Having a low income significantly affected the overall 5-year mortality of Korean adults who were newly diagnosed with HCC from 2004 to 2008. Middle-aged men were the most vulnerable. We believe our findings will be useful to healthcare policymakers in Korea as well as to healthcare leaders in countries with NHI programs who need to make important decisions about allocation of limited healthcare resources according to a consensually accepted and rational framework.
Assuntos
Carcinoma Hepatocelular , Disparidades nos Níveis de Saúde , Renda , Neoplasias Hepáticas , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Renda/estatística & dados numéricos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , República da Coreia/epidemiologiaRESUMO
The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1ß and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , NF-kappa B/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Linhagem Celular , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Lactonas/síntese química , Macrolídeos/síntese química , Estrutura Molecular , NF-kappa B/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
PURPOSE: This study was performed to investigate the prevalence of and factors associated with depressive symptoms in the Korean adult population. METHODS: 10,710 participants in the 2014 and 2016 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed in this study. Assessment of depressive symptoms was performed using the self-administered nine-item Patient Health Questionnaire (PHQ-9). RESULTS: The weighted prevalence of clinically relevant depression (PHQ-9 score ≥ 10) in the Korean adult population was 6.1% [5.5-6.8%]. Female sex, adults aged 19-29 years, elementary school graduation, living alone were significantly associated with clinically relevant depression. Having a household income ≤ 24th percentile was associated with a 2.26 (CI 1.49-3.45, p < 0.001)-fold higher prevalence of clinically relevant depression compared to having a household income ≥ 75th percentile. Regarding occupation, treating managers and professionals as controls, we found that unemployed individuals (OR 2.36, 95% CI 1.52-3.65, p < 0.001) had an increased risk of clinically relevant depression. Alcohol consumption < 30 g/day was reversely associated with clinically relevant depression (OR 0.75, 95% CI 0.62-0.93, p = 0.007), when abstain from alcohol was treated as control. Current smokers (OR 3.42, 95% CI 2.54-4.60, p < 0.001) and ex-smokers (OR 1.73, 95% CI 1.24-2.42, p = 0.001) had a higher risk of clinically relevant depression than never-smokers. CONCLUSIONS: The estimated prevalence of depressive symptoms in a representative sample of the Korean adult population was 6.1%. This study suggests that younger age, female sex, elementary school graduation, living alone, low household income, current smoking, and being unemployed are associated with depressive symptoms.
Assuntos
Depressão , Adulto , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Inquéritos Nutricionais , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
Coupling of spin and heat currents enables the spin Nernst effect, the thermal generation of spin currents in nonmagnets that have strong spin-orbit interaction. Analogous to the spin Hall effect that electrically generates spin currents and associated electrical spin-orbit torques (SOTs), the spin Nernst effect can exert thermal SOTs on an adjacent magnetic layer and control the magnetization direction. Here, the thermal SOT caused by the spin Nernst effect is experimentally demonstrated in W/CoFeB/MgO structures. It is found that an in-plane temperature gradient across the sample generates a magnetic torque and modulates the switching field of the perpendicularly magnetized CoFeB. The W thickness dependence suggests that the torque originates mainly from thermal spin currents induced in W. Moreover, the thermal SOT reduces the critical current for SOT-induced magnetization switching, demonstrating that it can be utilized to control the magnetization in spintronic devices.
RESUMO
Aqueous rechargeable zinc batteries (ZBs) have received considerable attention recently for large-scale energy storage systems in terms of rate performance, cost, and safety. Nevertheless, these ZBs still remain a subject for investigation, as researchers search for cathode materials enabling high performance. Among the various candidate cathode materials for ZBs, quinone compounds stand out as candidates because of their high specific capacity, sustainability, and low cost. Quinone-based cathodes, however, suffer from the critical limitation of undergoing dissolution during battery cycling, leading to a deterioration in battery life. To address this problem, we have introduced a redox-active triangular phenanthrenequinone-based macrocycle (PQ-Δ) with a rigid geometry and layered superstructure. Notably, we have confirmed that Zn2+ ions, together with H2O molecules, can be inserted into the PQ-Δ organic cathode, and, as a consequence, the interfacial resistance between the cathode and electrolytes is decreased effectively. Density functional theory calculations have revealed that the low interfacial resistance can be attributed mainly to decreasing the desolvation energy penalty as a result of the insertion of hydrated Zn2+ ions in the PQ-Δ cathode. The combined effects of the insertion of hydrated Zn2+ ions and the robust triangular structure of PQ-Δ serve to achieve a large reversible capacity of 210 mAh g-1 at a high current density of 150 mA g-1, along with an excellent cycle-life, that is, 99.9% retention after 500 cycles. These findings suggest that the utilization of electron-active organic macrocycles, combined with the low interfacial resistance associated with the solvation of divalent carrier ions, is essential for the overall performance of divalent battery systems.
RESUMO
The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 (PFKFB3) catalyzes the first committed rate-limiting step of glycolysis and is upregulated in cancer cells. The mechanism of PFKFB3 expression upregulation in cancer cells has not been fully elucidated. The PFKFB3 3'-UTR is reported to contain AU-rich elements (AREs) that are important for regulating PFKFB3 mRNA stability. However, the mechanisms by which PFKFB3 mRNA stability is determined by its 3'-UTR are not well known. We demonstrated that tristetraprolin (TTP), an ARE-binding protein, has a critical function regulating PFKFB3 mRNA stability. Our results showed that PFKFB3 mRNA contains three AREs in the 3'-UTR. TTP bound to the 3rd ARE and enhanced the decay of PFKFB3 mRNA. Overexpression of TTP decreased PFKFB3 expression and ATP levels but increased GSH level in cancer cells. Overexpression of PFKFB3 cDNA without the 3'-UTR rescued ATP level and GSH level in TTP-overexpressing cells. Our results suggested that TTP post-transcriptionally downregulated PFKFB3 expression and that overexpression of TTP may contribute to suppression of glycolysis and energy production of cancer cells in part by downregulating PFKFB3 expression.
Assuntos
Regulação para Baixo , Neoplasias/patologia , Fosfofrutoquinase-2/metabolismo , Tristetraprolina/fisiologia , Elementos Ricos em Adenilato e Uridilato , Glicólise , Humanos , Neoplasias/metabolismo , Fosfofrutoquinase-2/genética , Estabilidade de RNA , RNA Mensageiro , Transcrição Gênica , Tristetraprolina/metabolismo , Células Tumorais CultivadasRESUMO
Recent research revealed that doxorubicin (DOX) decreased expression of programmed death-ligand 1 (PD-L1) in cancer cells. However, the detailed mechanisms underlying this effect are not well established. Here, we demonstrate that doxorubicin down-regulates PD-L1 expression through induction of AU-rich element (ARE) binding protein tristetraprolin (TTP) in cancer cells. PD-L1 mRNA contain three AREs within its 3'UTR. Doxorubicin induced expression of TTP, increased TTP binding to the 3rd ARE of the PD-L1 3'UTR, and increased decay of PD-L1 mRNA. Inhibition of TTP abrogates the inhibitory effect of doxorubicin on PD-L1 expression. Our data suggest that TTP plays a key role in doxorubicin-mediated down-regulation of PD-L1 by enhancing degradation of PD-L1 mRNA in cancer cells.
Assuntos
Antígeno B7-H1/genética , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Estabilidade de RNA/efeitos dos fármacos , Tristetraprolina/metabolismo , Regiões 3' não Traduzidas/genética , Elementos de Resposta Antioxidante/genética , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/genética , Humanos , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
This study examined the control of nosemosis caused by Nosema ceranae, one of the hard-to-control diseases of honey bees, using RNA interference (RNAi) technology. Double-stranded RNA (dsRNA) for RNAi application targeted the mitosome-related genes of N. ceranae. Among the various mitosome-related genes, NCER_100882, NCER_101456, NCER_100157, and NCER_100686 exhibited relatively low homologies with the orthologs of Apis mellifera. Four gene-specific dsRNAs were prepared against the target genes and applied to the infected A. mellifera to analyze Nosema proliferation and honey bee survival. Two dsRNAs specifics to NCER_101456 and NCER_100157 showed high inhibitory effects on spore production by exhibiting only 62% and 67%, respectively, compared with the control. In addition, these dsRNA treatments significantly rescued the honey bees from the fatal nosemosis. It was confirmed that the inhibition of Nosema spore proliferation and the increase in the survival rate of honey bees were resulted from a decrease in the expression level of each target gene by dsRNA treatment. However, dsRNA mixture treatment was no more effective than single treatments in the rescue from the nosemosis. It is expected that the four newly identified mitosome-related target genes in this study can be effectively used for nosemosis control using RNAi technology.
Assuntos
Abelhas/microbiologia , Microsporidiose/prevenção & controle , Nosema/genética , Interferência de RNA , Animais , Inativação Gênica , Microsporidiose/mortalidade , RNA de Cadeia Dupla , Taxa de SobrevidaRESUMO
AIM: To assess the efficacy and safety of add-on therapy with the dipeptidyl peptidase-4 inhibitor teneligliptin compared with sitagliptin in patients with type 2 diabetes (T2DM) inadequately controlled with metformin and glimepiride. MATERIALS AND METHODS: This was a phase 3, randomized, double-blind, non-inferiority study of adult Korean subjects with T2DM (n = 201), with HbA1c ranging from 7.0% to 11.0%, on stable doses of metformin plus glimepiride. Subjects were randomized in a 1:1 fashion to receive either oral teneligliptin 20 mg or sitagliptin 100 mg for 24 weeks. The primary endpoint was change from baseline in HbA1c. RESULTS: At baseline, mean age was 60.56 ± 9.41 years, body mass index was 25.23 ± 2.85 kg/m2 and HbA1c was 8.11% ± 0.79%. At 24 weeks, both groups achieved significant reductions from baseline in HbA1c (teneligliptin, -1.03% ± 0.10% [P < 0.0001]; sitagliptin, -1.02% ± 0.10% [P < 0.0001]). The inter-group difference was -0.01% (95% confidence interval [CI]: -0.28, 0.26; P = 0.9497); the upper limit of the 95% CI was within the preset limit for non-inferiority (0.4%). There were no significant differences between groups in the proportion of patients achieving HbA1c targets, or changes from baseline in fasting plasma glucose, body weight or lipid levels at 24 weeks. Rates of adverse events (teneligliptin, n = 63 [61.76%]; sitagliptin, n = 61 [62.24%]; P = 0.9442) and hypoglycaemia (teneligliptin, n = 32 [31.37%]; sitagliptin, n = 28 [28.57%]; P = 0.6656) were similar. CONCLUSION: Teneligliptin was non-inferior to sitagliptin in the context of triple therapy for T2DM and is an important option in this setting.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/administração & dosagem , Pirazóis/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Compostos de Sulfonilureia/administração & dosagem , Tiazolidinas/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , República da Coreia , Compostos de Sulfonilureia/efeitos adversos , Falha de TratamentoRESUMO
Potato is an important source of food in South Korea, and viruses represent a significant threat to sustainable and profitable potato production. However, information about viruses affecting the potato crop in South Korea is limited. In 2017, potato plants of five cultivars exhibiting foliar mosaic, crinkling, and mottle were collected in two seed potato production areas, in Gangwon-do and Jeollabuk-do Provinces, and subjected to virus testing and characterization. Potato virus Y (PVY) was found associated with mosaic symptoms, and samples were characterized using reverse transcription polymerase chain reaction (RT-PCR) and whole genome sequencing. All analyzed PVY-positive samples were found to represent the same recombinant PVY strain: PVYNTN. Three PVY isolates were subjected to whole genome sequencing using overlapping RT-PCR fragments and Sanger methodology, and all three were confirmed to represent strain PVYNTNa after a recombination analysis of the complete genomes. In phylogenetic analysis, the three South Korean isolates were placed most closely to several PVYNTNa isolates reported from Japan and Vietnam, suggesting a common source of infection. This is the first report and complete molecular characterization of a PVYNTN strain present in the country, and because this strain induces tuber necrotic ringspot disease in susceptible cultivars of potato, appropriate management tools need to be implemented to mitigate potential tuber quality losses.
Assuntos
Potyvirus , Solanum tuberosum , Japão , Filogenia , Doenças das Plantas , República da Coreia , VietnãRESUMO
Arthritis is not only a chronic disease but also causes physical inactivity. We investigated the association between arthritis and quality of life and psychological problems, as measured by suicidal ideation. We used data from the 2013 Community Health Survey, and 162,598 persons aged 40 years and older were included as study subjects. Our main focus was to investigate association of arthritis with suicidal ideation and quality of life. Multivariate survey logistic regression analysis was used to estimate the odds ratio for suicidal ideation, and multivariate survey linear regression analysis used to identify associations between variables and scores on the EuroQol Visual Analogue Scale(EQ-VAS). 8.30% of male and 13.90% of female experienced suicidal ideation, and 16.17% of and 21.23% of female suffered from arthritis. Individuals with arthritis were more likely to report suicidal ideation and have lower health-related quality of life (HRQOL) scores. Furthermore, higher rates of suicidal ideation and lower HRQOLs were also associated with older age, low income and less education. Arthritis was associated with higher rates of suicidal ideation and lower HRQOL scores. These results should contribute to the development and implementation of polices and management strategies to alleviate suicidal ideation and increase HRQOL scores among arthritis patients.