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Microglia-induced inflammatory signaling and neuronal oxidative stress are mutually reinforcing processes central to the pathogenesis of neurodegenerative diseases. Recent studies have shown that extracts of dried Pheretima aspergillum (Lumbricus) can inhibit tissue fibrosis, mitochondrial damage, and asthma. However, the effects of Lumbricus extracts on neuroinflammation and neuronal damage have not been previously studied. Therefore, to evaluate the therapeutic potential of Lumbricus extract for neurodegenerative diseases, the current study assessed the extract's anti-inflammatory and antioxidant activities in BV2 microglial cultures stimulated with lipopolysaccharide (LPS) along with its neuroprotective efficacy in mouse hippocampal HT22 cell cultures treated with excess glutamate. Lumbricus extract dose-dependently inhibited the LPS-induced production of multiple proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß) and reversed the upregulation of proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Lumbricus also activated the antioxidative nuclear factor erythroid 2-relayed factor 2/heme oxygenase-1 pathway and inhibited LPS-induced activation of the nuclear factor-κB/mitogen-activated protein kinases/NOD-like receptor family pyrin domain containing 3 inflammatory pathway. In addition, Lumbricus extract suppressed the glutamate-induced necrotic and apoptotic death of HT22 cells, effects associated with upregulated expression of antiapoptotic proteins, downregulation of pro-apoptotic proteins, and reduced accumulation of reactive oxygen species. Chromatography revealed that the Lumbricus extract contained uracil, hypoxanthine, uridine, xanthine, adenosine, inosine, and guanosine. Its effects against microglial activation and excitotoxic neuronal death reported herein support the therapeutic potential of Lumbricus for neurodegenerative diseases.
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Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.
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Linfócitos T CD8-Positivos , Neoplasias , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Receptor de Morte Celular Programada 1RESUMO
Before 2014, the only test used for anonymous voluntary human immunodeficiency virus (HIV) screening at public health centers (PHCs) in the Republic of Korea was an enzyme-linked immunosorbent assay (ELISA), which takes around 3 days to obtain results. In 2014, to encourage voluntary anonymous HIV screening tests, the Seoul Metropolitan Government adopted a rapid HIV screening test at PHCs. The rapid HIV screening test was introduced at four PHCs in 2014 and all 25 PHCs after 2015. We compared the numbers of HIV screening tests and confirmed positive individuals before and after introduction of the rapid HIV screening test. In 2012-2013, before the introduction of rapid HIV screening test, an average of 330 HIV screening tests were performed monthly (355 in 2012 and 305 in 2013) and 69 individuals were confirmed to have HIV in 2012 and 93 in 2013. After the introduction of the rapid HIV screening test, anonymous voluntary HIV screening increased to a monthly average of 447 tests in 2014, 2099 in 2015, and 2409 in 2016. These identified 38 new cases in 2014, 116 in 2015, and 143 in 2016. Adoption of the rapid HIV screening test has increased the number of HIV screening tests and confirmed cases.
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Sorodiagnóstico da AIDS/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Teste de HIV/métodos , Programas de Rastreamento/estatística & dados numéricos , Sorodiagnóstico da AIDS/estatística & dados numéricos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV/estatística & dados numéricos , Humanos , Projetos Piloto , Saúde Pública , República da Coreia , SeulRESUMO
Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl acetate (EtOAc) fraction more significantly enhanced myoblast proliferation and differentiation than the other fractions. Ten bioactive compounds were isolated from the EtOAc fraction and characterized by GC-MS and NMR. Of these compounds (4-hydroxybenzoic acid, liquiritigenin, (R)-(-)-vestitol, isoliquiritigenin, medicarpin, tetrahydroxymethoxychalcone, licochalcone B, liquiritin, liquiritinapioside, and ononin), liquiritigenin, tetrahydroxymethoxychalcone, and licochalcone B were found to enhance myoblast proliferation and differentiation, and myofiber diameters in injured muscles were wider with the liquiritigenin than the non-treated one. Computational analysis showed these compounds are non-toxic and possess good drug-likeness properties. These findings suggest that G. uralensis-extracted components might be useful therapeutic agents for the management of muscle-associated diseases.
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Glycyrrhiza uralensis/química , Atrofia Muscular/tratamento farmacológico , Extratos Vegetais/química , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Chalconas/química , Chalconas/farmacologia , Chalconas/uso terapêutico , Flavanonas/química , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Miostatina/genética , Miostatina/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Six lignols (1-6), including two new compounds (+)-(7R,8R)-palmitoyl alatusol D (1) and (+)-(7R,8R)-linoleyl alatusol D (2), along with four phenolics (7-10), a neolignan (11), three alkyl aryl ether-type lignans (12-14), two furofuran-type lignans (15-16), three benzofuran-type lignans (17-19), a tetrahydrofuran-type lignan (20), and a dibenzylbutane-type lignan (21) were isolated from the ethyl acetate-soluble fraction of the methanol extract of Platycodon grandiflorum (Jacq.) A. DC. root. The chemical structures of the obtained compounds were elucidated via high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy analyses. The obtained spectroscopic data agreed well with literature. Among the isolated compounds, eighteen (1-7 and 11-21) were isolated from P. grandiflorum and the Campanulaceae family for the first time. This is the first report on lignol and lignan components of P. grandiflorum. The anti-inflammatory effects of the isolated compounds were examined in terms of their ability to inhibit the production of pro-inflammatory cytokines IL-6, IL-12 p40, and TNF-α in lipopolysaccharide-stimulated murine RAW264.7 macrophage cells. Nine compounds (4-6, 12, and 15-19) exhibited inhibitory effects on IL-12 p40 production, eleven compounds (1-6, 12, 15-17, and 19) exhibited inhibitory activity on IL-6 production, and eleven compounds (1-6 and 15-19) exhibited inhibitory effects against TNF-α. These results warrant further investigation into the potential anti-inflammatory activity and general benefits of the phenolic constituents of P. grandiflorum root.
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Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Lignanas/farmacologia , Macrófagos/imunologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Platycodon/química , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Citocinas/antagonistas & inibidores , Lignanas/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Fenóis/química , Extratos Vegetais/química , Células RAW 264.7RESUMO
Calcium (Ca2+) dependent signaling circuit plays a critical role in influenza A virus (IAV) infection. The 8-O-(E-p-methoxycinnamoyl)harpagide (MCH) exhibits pharmacological activities that exert neuroprotective, hepatoprotective, anti-inflammatory and other biological effects. However, not have reports of antiviral effects. To investigate the antiviral activity of MCH on IAV-infected human lung cells mediated by calcium regulation. We examined the inhibitory effect of MCH on IAV infections and measured the level of viral proteins upon MCH treatment using Western blotting. We also performed molecular docking simulation with MCH and IAV M2 protein. Finally, we analyzed MCH's suppression of intracellular calcium and ROS (reactive oxygen species) in IAV-infected human lung cells using a flow cytometer. The results shown that MCH inhibited the infection of IAV and increased the survival of the infected human lung cells. The levels of IAV protein M1, M2, NS1 and PA were inhibited in MCH-treated human lung cells compared to that in infected and untreated cells. Also, docking simulation suggest that MCH interacted with M2 on its hydrophobic wall (L40 and I42) and polar amino acids (D44 and R45), which formed intermolecular contacts and were a crucial part of the channel gate along with W41. Lastly, MCH inhibited IAV infection by reducing intracellular calcium and mitochondrial Ca2+/ROS levels in infected human lung cells. Taken together, these data suggest that MCH inhibits IAV infection and increases the survival of infected human lung cells by suppressing calcium levels. These results indicate that MCH is useful for developing IAV treatments.
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Antivirais/farmacologia , Cálcio/metabolismo , Vírus da Influenza A/efeitos dos fármacos , Espaço Intracelular/metabolismo , Glicosídeos Iridoides/farmacologia , Piranos/farmacologia , Células A549 , Antivirais/uso terapêutico , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Canais Iônicos/metabolismo , Glicosídeos Iridoides/química , Glicosídeos Iridoides/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Simulação de Acoplamento Molecular , Piranos/química , Piranos/uso terapêutico , Proteínas da Matriz ViralRESUMO
The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.
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A dibenzylbutane-type lignan (16), along with eight furofuran-type (1-8), five furan-type (9-13), two dibenzylbutane-type (14 and 15), two bibenztetrahydronaphthalene-type lignans (17 and 18), two neolignans (19 and 20), and six phenolic derivatives (21-26) were isolated from an MeOH extract of the stem bark of Albizia julibrissin Durazz. The chemical structures of the obtained compounds were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. Of the evaluated compounds, 14 were isolated from A. julibrissin and the Fabaceae family for the first time. Anti-inflammatory effects of the isolated analogs were investigated in terms of the inhibition of the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells. Ten compounds (10-12, 14, and 17-22) displayed significant dose-dependent inhibitory effects against the NO production, with IC50 values ranging from 5.4 to 19.2 µM. Moreover, eight compounds (1-4, 9, 13, 15, and 16) exhibited moderate inhibitory activities, with IC50 values ranging from 21.0 to 62.5 µM.
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Albizzia/química , Furanos/farmacologia , Lignanas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Fenóis/farmacologia , Casca de Planta/química , Animais , Relação Dose-Resposta a Droga , Desenho de Fármacos , Furanos/química , Concentração Inibidora 50 , Lignanas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Óxido Nítrico/metabolismo , Fenóis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
To identify new potential anti-influenza compounds, we isolated six flavonoids, 2'-hydroxyl yokovanol (1), 2'-hydroxyl neophellamuretin (2), yokovanol (3), swertisin (4), spinosin (5), and 7-methyl-apigenin-6-C-ß-glucopyranosyl 2â³-O-ß-d-xylopyranoside (6) from MeOH extractions of Ohwia caudata. We screened these compounds for antiviral activity using green fluorescent protein (GFP)-expressing H1N1 (A/PR/8/34) influenza A-infected RAW 264.7 cells. Compounds 1 and 3 exhibited significant inhibitory effects against influenza A viral infection in co-treatment conditions. In addition, compounds 1 and 3 reduced viral protein levels, including M1, M2, HA, and neuraminidase (NA), and suppressed neuraminidase (NA) activity in RAW 264.7 cells. These findings demonstrated that 2'-hydroxyl yokovanol and yokovanol, isolated from O. caudate, inhibit influenza A virus by suppressing NA activity. The moderate inhibitory activities of these flavonoids against influenza A virus suggest that they may be developed as novel anti-influenza drugs in the future.
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Antivirais/farmacologia , Fabaceae/química , Flavonoides/farmacologia , Vírus da Influenza A Subtipo H1N1/metabolismo , Infecções por Orthomyxoviridae , Animais , Antivirais/química , Antivirais/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Células RAW 264.7RESUMO
BACKGROUND: Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells. METHODS: Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed. RESULTS: ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation. CONCLUSION: These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.
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Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Chrysanthemum/química , Neoplasias do Colo/fisiopatologia , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Extratos Vegetais/isolamento & purificação , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismoRESUMO
This study examined factors associated with the intention to take an HIV test among men who have sex with men (MSM) in South Korea. An internet website-based survey was conducted among users of the only and largest online MSM website between 20 July 2016, and 20 August 2016. A total of 2915 participants completed the survey and answered questions related to sociodemographic information, health behaviors, sexual behaviors, and HIV testing history. Of these, 2587 (88.7%) participants responded as having an intention to take an HIV test. A multivariable logistic regression analysis revealed the following as having reduced the intention to undergo HIV testing: very good subjective health status and no sexual interactions during the last 6 months (Adjusted odds ratios [AOR] 0.45 and 0.54, respectively). In contrast, increased intention to take an HIV test was associated with being 20-29 years old, 30-39 years old, not paying or receiving money for sex, having a history of HIV testing, and taking an HIV test once per 12 months (AOR 2.64, 2.13, 1.54, 1.81, and 2.17, respectively). In conclusion, HIV testing among MSM in this study was associated with age, subjective health status, sex(es) of one's sexual partner(s) during the last 6 months, sexual risk behaviors, HIV testing history, and undergoing regular HIV testing.
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Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Intenção , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Parceiros Sexuais , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Infecções por HIV/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Assunção de Riscos , Comportamento Sexual , Inquéritos e Questionários , Adulto JovemRESUMO
This study aimed to identify the factors associated with medication adherence in human immunodeficiency virus (HIV) patients in South Korea. A cross-sectional study was conducted from six hospitals participating in the Nationwide Specialized Counseling Program for HIV infected patients from 22 February to 10 May 2010. A total of 300 HIV patients have completed a self-administered questionnaire. Among 300 patients, 230 patients had above 95% medication adherence. Binary logistic regression analysis revealed that having medical insurance (p = .003) and a good relationship with the medical team (p = .046) were the main factors affecting medication adherence in HIV patients. In conclusion, medical insurance through the National Health Insurance Service and a good relationship between HIV infected patients and physicians are the main influencing factors that impact medication adherence in countries with low economic barriers to treatment.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cobertura do Seguro , Adesão à Medicação/psicologia , Relações Profissional-Paciente , Adulto , Idoso , Antirretrovirais/administração & dosagem , Antirretrovirais/economia , Estudos Transversais , Feminino , Infecções por HIV/etnologia , Infecções por HIV/psicologia , Humanos , Seguro Saúde , Masculino , Adesão à Medicação/etnologia , Pessoa de Meia-Idade , Programas Nacionais de Saúde , República da Coreia/epidemiologia , Inquéritos e QuestionáriosRESUMO
Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax ), area under the curve (AUC0 â 480 min ), and relative bioavailability (Frel ) of ciprofloxacin (p < 0.05). The rhodamine 123 accumulation assay revealed that treatment with baicalein for 48 h markedly reduced the intracellular accumulation of rhodamine 123. Taken together, these findings suggest that baicalein may result in the therapeutic failure of ciprofloxacin or other quinolone-based antibiotics used for chemotherapy in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.
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Antibacterianos/farmacocinética , Ciprofloxacina/farmacocinética , Flavanonas/química , Flavonoides/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Flavanonas/farmacologia , Flavonoides/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In traditional oriental medicine, Angelica dahurica Radix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg), blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (Tmax) of imperatorin and isoimperatorin was significantly delayed (p < 0.05). Lower peak plasma concentrations (Cmax) and longer mean residence times for all furanocoumarins were also observed (p < 0.05) compared with normal rats. There was no significant difference in the area under the plasma concentration-time curve or elimination half-lives. Thus, the delayed Tmax and decreased Cmax, with no influence on the elimination half-life, could be colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention.
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Colite/patologia , Furocumarinas/química , Furocumarinas/farmacocinética , Angelica/química , Animais , Cromatografia Líquida de Alta Pressão , Colite/tratamento farmacológico , Colite/etiologia , Modelos Animais de Doenças , Estabilidade de Medicamentos , Furocumarinas/administração & dosagem , Masculino , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em TandemRESUMO
BACKGROUND: In January 2015, US FDA approved secukinumab, a human interleukin-17A (IL-17A) antagonist, for the treatment of plaque psoriasis. OBJECTIVE: To provide unbiased drug information about the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis by performing meta-analysis. METHODS: PubMed and EMBASE database searches were conducted. Among the literatures retrieved, relevant Phase III clinical trials were analyzed. Statistical analysis of the data was performed by RevMan. RESULTS: Four pivotal and three non-pivotal Phase III clinical trials were retrieved. All the trials evaluated the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis with two co-primary endpoints: proportions of Psoriasis Area and Severity Index (PASI) responders and Investigator's Global Assessment (IGA) responders. The overall odd ratios for proportions of PASI responders and IGA responders in secukinumab-containing arm were 65.6 and 62.5 compared to the placebo arm, respectively. Secukinumab was superior to etanercept resulting in both of the odd ratios being 3.7 compared to the etanercept. Secukinumab was generally well tolerated during the one year trial. However, as with other monoclonal antibody medications, vulnerability of respiratory infection (especially nasopharyngitis) was reported as most common adverse event. CONCLUSIONS: Meta-analysis of the seven Phase III clinical trials resulted in superiority of secukinumab over etanercept in terms of the efficacy and safety. However, long-term safety data is lacking at this time so post-marketing surveillance should be performed for any adverse events associated with the use of this new biological medication.
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Anticorpos Monoclonais/uso terapêutico , Interleucina-17/antagonistas & inibidores , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase III como Assunto , Etanercepte/uso terapêutico , HumanosRESUMO
The accumulation and infiltration of mast cells are found in osteoarthritic lesions in humans and rodents. Nonetheless, the roles of mast cells in osteoarthritis are almost unknown. Although Viscum coloratum has various beneficial actions, its effect on allergic and osteoarthritic responses is unknown. In this study, we established an in vitro model of mast cell-mediated osteoarthritis and investigated the effect of the ethanol extract of Viscum coloratum (VEE) on IgE/antigen (IgE/Ag)-activated mast cells and mast cell-derived inflammatory mediator (MDIM)-stimulated chondrocytes. The anti-allergic effect of VEE was evaluated by degranulation, inflammatory mediators, and the FcεRI signaling cascade in IgE/Ag-activated RBL-2H3 cells. The anti-osteoarthritic action of VEE was evaluated by cell migration, and the expression, secretion, and activity of MMPs in MDIM-stimulated SW1353 cells. VEE significantly inhibited degranulation (IC50: 93.04 µg/mL), the production of IL-4 (IC50: 73.28 µg/mL), TNF-α (IC50: 50.59 µg/mL), PGD2 and LTC4, and activation of the FcεRI signaling cascade in IgE/Ag-activated RBL-2H3 cells. Moreover, VEE not only reduced cell migration but also inhibited the expression, secretion, and/or activity of MMP-1, MMP-3, or MMP-13 in MDIM-stimulated SW1353 cells. In conclusion, VEE possesses both anti-allergic and anti-osteoarthritic properties. Therefore, VEE could possibly be considered a new herbal drug for anti-allergic and anti-osteoarthritic therapy. Moreover, the in vitro model may be useful for the development of anti-osteoarthritic drugs.
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Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Condrócitos/imunologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Osteoartrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Viscum/química , Animais , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Metaloproteinase 1 da Matriz/imunologia , Metaloproteinase 13 da Matriz/imunologia , Metaloproteinase 3 da Matriz/imunologia , Osteoartrite/patologia , Ratos , Receptores de IgE/imunologia , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Academic interest in athletic performance is ongoing. To examine the correlation between athletic performance and athletes' personality types, data extraction in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was completed in October 2021, and a meta-analysis was performed using 180 data from 18 selected papers using the "meta" package version 4.8-4 of R Studio 3.3.3. As a result, these selected studies proved to have reliable quality in proceeding with this study via quality assessment. The overall effect of personality on athletic performance (AP) was ESr = 0.124, p < 0.01. Furthermore, only conscientiousness (ESr = 0.178, p < 0.001) and extroversion (ESr = 0.145, p < 0.01), among the five personality types, showed statistically significant results, and these two personality types had a positive correlation with performance. In the publication bias test, this study found that (a) agreeableness had a publication bias; but, with an additional test using trim-and-fill, (b) the effect was not significant enough to be considered. In addition, the analysis of the moderating effects was conducted in four aspects, and all moderating effect analyses showed statistically significant differences between the groups, demonstrating the heterogeneity of this study. Therefore, this study found a significant relationship between personality and athletic performance and showed the importance of conscientiousness and extroversion.
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This study investigated the differences in amateur golfers' perceptions of instructor expertise, instructor credibility, and lesson participation intention depending on the golf instructor's certification level to investigate whether placebo and nocebo effects exist depending on the certification level. Accordingly, the study analyzed 153 amateur golfers with at least 1 year of playing experience, and the results were as follows: First, there was a difference in the perception of instructor expertise among amateur golfers depending on the golf instructor's certification level. Specifically, there were significant differences in perceived performance and teaching skills but no differences in personality and emphasis on basic principles. Second, the participants reported significant differences in their perceptions of instructor credibility depending on the instructor's certification level. Instructor credibility of the tournament professional group was the highest, whereas that of the amateur group was the lowest. Third, the results showed differences in lesson participation intention among amateur golfers depending on the instructor's certification level. Lesson participation intention was higher for semi-professional and tournament professional instructors than for amateur instructors. These results verified the presence of psychological biases, such as placebo/nocebo effects, that result in differences in the perception of instructor expertise, instructor credibility, and lesson participation intention depending on the certification level of instructors. Additionally, based on the data obtained from this study, further research is required to improve the performance of golf instructors and create an efficient teaching environment.
RESUMO
Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase α1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of α1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.
RESUMO
Previous studies have shown that burnout negatively affects athletes' mental health. To further explore this subject, we conducted a systematic review and meta-analysis by combining data from previous studies. This study followed the PRISMA guidelines for systematic and reliable research and completed data extraction using 10 databases and 8 keywords in December 2021. There were 93 cases of initially extracted data from the selected articles (n = 14) and the meta-analysis was conducted using the "meta" package, version 4.8-4 of R Studio 3.3.3, with data (k = 77) excluding other-oriented perfectionism data (k = 16). The results showed that self-oriented perfectionism had a negative effect on sports devaluation (SD) (ESr = -0.246, p < 0.001), and socially prescribed perfectionism had a positive effect on emotional/physical exhaustion (ESr = 0.150, p < 0.05) and SD (ESr = 0.138, p < 0.05). Furthermore, the test for publication bias showed that no groups had asymmetrical data, and four moderator analyses were conducted to prove the heterogeneity (I2) of the total effect size; however, there was no difference among groups (QB), thereby resulting in unexplained variance. Consequently, this study presents variable data that determine the effects of perfectionism and burnout on elite athletes.