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1.
Dysphagia ; 36(2): 183-191, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32347417

RESUMO

Small flexible force-sensing resistor (FSR) sensors can detect laryngeal excursion during swallowing, but the detected laryngeal excursion has not been correlated with videofluoroscopic swallowing study (VFSS) results. Here, we tested the correlation of temporal parameters between the laryngeal excursion recording by FSR sensor and the hyoid motion recording by VFSS under simultaneously swallowing test recordings. Swallowing measurements were recorded in a radiological suite by simultaneously using VFSS and FSR sensors to detect hyoid motion and laryngeal excursion, respectively. Volunteers sat with their head vertical to the Frankfort plane. Two FSR sensors, each for detecting thyroid cartilage excursion and thumb pressing, were placed. VFSS images and FSR sensor signals during single 5-mL barium liquid (30% wt/volume %) bolus swallowing were collected and analyzed for four swallows per participant. In total, 15 men (28.0 ± 4.1 years old); 14 women (28.4 ± 4.2 years old) were recruited. Temporal parameters between VFSS and noninvasive system demonstrated a strong correlation by Pearson's correlation analysis: in men (R = 0.953-0.999) and in women (R = 0.813-0.982), except for VT1-V1 compared with FT1-F1, which demonstrated a moderate correlation in women (R = 0.648; all p < 0.001). Only VT1-V1 and FT1-F1 in women displayed a significant difference (p = 0.001). Therefore, this is the first study to simultaneous record VFSS and noninvasive signals by FSR sensor. The correlation of temporal parameters between these two tests was strong. This finding is valuable for future applications of this noninvasive swallowing study tool.


Assuntos
Transtornos de Deglutição , Deglutição , Adulto , Fenômenos Biomecânicos , Transtornos de Deglutição/diagnóstico por imagem , Feminino , Humanos , Osso Hioide/diagnóstico por imagem , Masculino , Cartilagem Tireóidea , Adulto Jovem
2.
Chemistry ; 22(30): 10620-6, 2016 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-27346677

RESUMO

Herein, mesoporous sodium vanadium phosphate nanoparticles with highly sp(2) -coordinated carbon coatings (meso-Na3 V2 (PO4 )3 /C) were successfully synthesized as efficient cathode material for rechargeable sodium-ion batteries by using ascorbic acid as both the reductant and carbon source, followed by calcination at 750 °C in an argon atmosphere. Their crystalline structure, morphology, surface area, chemical composition, carbon nature and amount were systematically explored. Following electrochemical measurements, the resultant meso-Na3 V2 (PO4 )3 /C not only delivered good reversible capacity (98 mAh g(-1) at 0.1 A g(-1) ) and superior rate capability (63 mAh g(-1) at 1 A g(-1) ) but also exhibited comparable cycling performance (capacity retention: ≈74 % at 450 cycles at 0.4 A g(-1) ). Moreover, the symmetrical sodium-ion full cell with excellent reversibility and cycling stability was also achieved (capacity retention: 92.2 % at 0.1 A g(-1) with 99.5 % coulombic efficiency after 100 cycles). These attributes are ascribed to the distinctive mesostructure for facile sodium-ion insertion/extraction and their continuous sp(2) -coordinated carbon coatings, which facilitate electronic conduction.

3.
Nutrients ; 14(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36432627

RESUMO

This cross-sectional study aimed to explore the influence of the COVID-19 pandemic on physical activity (PA) and dietary habits, and their impact on body weight changes during the Level 3 alert period that resulted in the lockdown in Taiwan. The study was conducted between 1 July 2021 and 15 July 2021, using a Google Forms online survey platform. Personal data, anthropometric information, PA information, and dietary habit information were collected before and during the alert period. Exactly 374 respondents, aged between 20 and 66, were included in the study. The results indicate that the lockdown during the alert period negatively impacted all levels of PA, including vigorous and moderate activities and walking. Additionally, respondents showed a sedentary lifestyle, with an increased daily sitting time of 22%. However, body weight and dietary behavior were not significantly affected, and some dietary questions achieved significant differences, including eating three meals less regularly, among others. During the pandemic, exercise was still one of the most important ways to maintain health; therefore, we hope to bring more attention to the prevention of sedentary lifestyles and dietary abnormalities in Taiwan during a pandemic.


Assuntos
COVID-19 , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Pandemias , Taiwan/epidemiologia , Controle de Doenças Transmissíveis , Exercício Físico , Inquéritos e Questionários , Peso Corporal , Dieta
4.
Biomed Res Int ; 2022: 6496382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586817

RESUMO

Objectives: The texture of the autologous platelet-rich plasma (PRP) that is used in treating degenerative joint diseases such as knee osteoarthritis (OA) is usually in liquid form. However, the turnover rate of protein metabolism in the knee synovial fluid (SF) is less than one hour. This study examined the feasibility of the thermal oscillation technique in converting the liquid-form PRP into an injectable viscous paste-like PRP that may delay the degradation of PRP and continuously release growth factors in the knee joint for a longer period of time. Methods: This study was conducted in the rehabilitation department of a tertiary hospital. A total of 10 elderly patients with an average age of greater than 65 years and diagnosed with moderate degree of knee OA were recruited. The RegenPRP (RegenLab, Le Mont-sur-Lausanne, Switzerland) test tube chamber was used for PRP generation. A total of 60 milliliters (mL) of blood was drawn from each patient. 10 mL of blood was injected into each PRP test tube chamber. As a result, a total of 6 test tube chambers were obtained and each chamber was centrifuged for 15 minutes. Approximately 5 mL of PRP supernatant (the liquid-form end product) was aspirated and sent for thermal oscillation treatment. Five temperatures were tested: 55, 65, 75, 85, and 95 degrees Celsius. Oscillation was set at 200 revolutions per minute (rpm) for 15 minutes. The enzyme-linked immunosorbent assay (ELISA) was applied in measuring the concentration of platelet-derived growth factor (PDGF) in picogram/milliliter (pg/mL). Repeated measures ANOVA followed by the Bonferroni post hoc test was used to compare the PDGF concentrations between each testing condition. Results: Under 75 degrees Celsius of heating, the resultant paste-like PRP end product had the highest concentration of PDGF in picograms per milliliter (pg/mL) as compared with other heating conditions (p < 0.05). The viscosity of the paste-like PRP was measured to be 70,000 centipoise (cP), which is similar to the viscosity of a toothpaste. The paste-like PRP end product was able to release PDGF continuously for about 14 days, with the highest concentration achieved on the 8th day with an average of 35646 ± 2499 pg/mL. In nonthermally treated liquid-form PRP sample, the highest number of PRP was observed on the 4th day with an average value of 8444 ± 831 pg/mL. Under the heating conditions of 55 and 95 degrees Celsius, the highest concentration of PDGF was observed on the 5th day (13346 ± 764 pg/mL and 3440 ± 303 pg/mL, respectively). Under the heating conditions of 65 and 85 degrees Celsius, the highest concentration of PDGF was observed on the 7th day (15468 ± 744 pg/mL and 20432 ± 1118 pg/mL, respectively). Conclusion: Through thermal oscillation, liquid-form PRP can be converted to paste-like PRP end product with a viscosity similar to that of a toothpaste. The best heating condition was discovered to be 75 degrees Celsius. The paste-like PRP was able to release PDGF continuously for about 2 weeks, with the highest concentration obtained on the 8th day. The findings in this study suggested that paste-like PRP may be a viable option in treating degenerative knee joint diseases.


Assuntos
Osteoartrite do Joelho , Plasma Rico em Plaquetas , Idoso , Humanos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Plasma Rico em Plaquetas/metabolismo , Cremes Dentais
5.
Front Med (Lausanne) ; 9: 1069654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561715

RESUMO

Background: No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication. Methods: We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated. Results: A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups. Conclusion: Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.

6.
Am J Chin Med ; 50(6): 1617-1643, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35850642

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-[Formula: see text]-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1[Formula: see text], IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1[Formula: see text], IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.


Assuntos
Chifres de Veado , Artrite Experimental , Artrite Reumatoide , Cervos , Sinoviócitos , Animais , Anti-Inflamatórios/farmacologia , Chifres de Veado/metabolismo , Chifres de Veado/patologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Cervos/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-6 , Interleucina-8 , Camundongos , Camundongos Endogâmicos DBA , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa
7.
Front Pharmacol ; 12: 762829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955833

RESUMO

Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2'-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34444491

RESUMO

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Taiwan. Chronic obstructive pulmonary disease (COPD) is associated with CRC mortality in several population-based studies. However, this effect of COPD on CRC shows no difference in some studies and remains unclear in Taiwan's population. Methods: We conducted a retrospective cohort study using Taiwan's nationwide database. Patients newly diagnosed with CRC were identified from 2007 to 2012 via the Taiwan Cancer Registry dataset and linked to the National Health Insurance research database to obtain their medical records. Propensity score matching (PSM) was applied at a ratio of 1:2 in COPD and non-COPD patients with CRC. The 5-year overall survival (OS) was analyzed using the Cox regression method. Results: This study included 43,249 patients with CRC, reduced to 13,707 patients after PSM. OS was lower in the COPD group than in the non-COPD group. The adjusted hazard ratio (aHR) for COPD was 1.26 (95% confidence interval (CI), 1.19-1.33). Moreover, patients with CRC plus preexisting COPD showed a higher mortality risk in all stage CRC subgroup analysis. Conclusions: In this 5-year retrospective cohort study, patients with CRC and preexisting COPD had a higher mortality risk than those without preexisting COPD, suggesting these patients need more attention during treatment and follow-up.


Assuntos
Neoplasias Colorretais , Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Humanos , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
9.
Front Pharmacol ; 11: 572009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162887

RESUMO

This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

10.
Life (Basel) ; 10(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260891

RESUMO

BACKGROUND: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. METHODS: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund's adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and a hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. RESULTS: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1ß, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. CONCLUSIONS: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.

11.
J Ethnopharmacol ; 246: 112246, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31539577

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kan-Lu-Hsiao-Tu-Tan (KLHTT) is a popular traditional Chinese medicine for treating various inflammatory diseases. AIM OF THE STUDY: The aim of the present study was to investigate the anti-inflammatory effects of KLHTT on human neutrophils and its therapeutic potential in treating imiquimod (IMQ)-induced psoriasis-like skin inflammation. MATERIALS AND METHODS: Spectrophotometry, flow cytometry, and microscopy with immunohistochemical staining were used to evaluate superoxide anion generation, elastase release, CD11b expression, adhesion, and neutrophil extracellular trap (NET) formation in activated human neutrophils. Reactive oxygen species (ROS) and reactive nitrogen species in cell-free systems were measured using a multi-well fluorometer or a spectrophotometer. A psoriasis-like skin inflammation was induced in mice using the IMQ cream. RESULTS: KLHTT suppressed superoxide anion generation, ROS production, CD11b expression, and adhesion in activated human neutrophils. In contrast, KLHTT failed to alter elastase release in activated human neutrophils. Additionally, KLHTT had an ROS-scavenging effect in the AAPH assay, but it did not scavenge superoxide anions directly in the xanthine/xanthine oxidase assay. Protein kinase C (PKC)-induced NET formation most commonly occurs through ROS-dependent mechanisms. KLHTT significantly inhibited phorbol 12-myristate 13-acetate, a PKC activator, inducing NET formation. Furthermore, topical KLHTT treatment reduced the area affected by psoriasis area and severity index (PASI) score and ameliorated neutrophil infiltration in IMQ-induced psoriasis-like skin inflammation in mice. CONCLUSIONS: Our data show that KLHTT has anti-neutrophilic inflammatory effects in inhibiting ROS generation and cell adhesion. KLHTT also mitigated NET formation, mainly via an ROS-dependent pathway. In addition, KLHTT reduced neutrophil infiltration and improved the severity of IMQ-induced psoriasis-like skin inflammation in mice. Therefore, KLHTT may prove to be a safe and effective psoriasis therapy in the future.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Imiquimode/toxicidade , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Psoríase/induzido quimicamente , Animais , Células Cultivadas , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Medicina Tradicional Chinesa , Camundongos , Psoríase/tratamento farmacológico
12.
Front Immunol ; 10: 2376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649677

RESUMO

Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a chronic systemic inflammatory disease affecting ~2-3% of the world population. The abundant presence of neutrophils in the psoriatic skin lesions serves as a typical histopathologic hallmark of psoriasis. Recent reports indicated that oxidative stress, granular components, and neutrophil extracellular traps from psoriatic neutrophils are related to the initial and maintenance phases of psoriasis. This review provides an overview on the recent (up to 2019) advances in understanding the role of neutrophils in the pathophysiology of psoriasis, including the effects of respiratory burst, degranulation, and neutrophil extracellular trap formation on psoriatic immunity and the clinical relationships.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata , Neutrófilos/imunologia , Psoríase/imunologia , Explosão Respiratória/imunologia , Humanos , Neutrófilos/patologia , Psoríase/patologia
13.
Medicine (Baltimore) ; 98(24): e15890, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192922

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disease of reproductive-age women, accounting for about 9% to 18% of all women in this age group. Hyperandrogenemia, oligomenorrhea, or amenorrhea or anovulation, and polycystic ovary morphology are the 3 main criteria used to diagnose PCOS currently. Substantial scientific evidence and consensus on treating Taiwanese PCOS was lacking. The aim of this study is to investigate the characteristics and utilization of traditional Chinese medicine (TCM) among Taiwanese women with PCOS.The data used in this study were derived from the Longitudinal Health Insurance Database (LHID 2000 and LHID 2005). Demographic characteristics, TCM usage, the frequency, as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with PCOS, were analyzed. Chinese herbal formulas and the single herbs prescribed for PCOS women during 1999 to 2013 were extracted to build up Chinese Herbal Medicine prescription database.In our study, 66.43% (n = 8205) women sought TCM treatment because of PCOS for infertility or menstrual disorders. The most commonly prescribed Chinese herbal formula was Jia-wei-xiao-yao-san (Supplemented Free Wanderer Powder). The most commonly prescribed single herb was Yi-mu-cao (Leonuri herba). Among top 20 Chinese herbal formulas, Si-wu-tang has the largest average daily dosage (9.60 g).Our study identified the characteristics and prescription patterns of TCM for patients with PCOS in Taiwan. We may need do further longitudinal research for TCM and its long-term response for improvement of pregnancy rate and reduction of metabolic disease rate.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Padrões de Prática Médica , Adulto , Distribuição por Idade , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Seguro Saúde , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Projetos de Pesquisa , Taiwan , Adulto Jovem
14.
Redox Biol ; 26: 101273, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325723

RESUMO

Neutrophil infiltration plays a significant pathological role in inflammatory diseases. NADPH oxidase type 2 (NOX2) is a respiratory burst oxidase that generates large amounts of superoxide anion (O2•-) and subsequent other reactive oxygen species (ROS). NOX2 is an emerging therapeutic target for treating neutrophilic inflammatory diseases. Herein, we show that 4-[(4-(dimethylamino)butoxy)imino]-1-methyl-1H-benzo[f]indol-9(4H)-one (CYR5099) acts as a NOX2 inhibitor and exerts a protective effect against complete Freund's adjuvant (CFA)-induced inflammatory arthritis in mice. CYR5099 restricted the production of O2•- and ROS, but not the elastase release, in human neutrophils activated with various stimulators. The upstream signaling pathways of NOX2 were not inhibited by CYR5099. Significantly, CYR5099 inhibited NOX2 activity in activated human neutrophils and in reconstituted subcellular assays. In addition, CYR5099 reduced ROS production, neutrophil infiltration, and edema in CFA-induced arthritis in mice. Our findings suggest that CYR5099 is a NOX2 inhibitor and has therapeutic potential for treating neutrophil-dominant oxidative inflammatory disorders.


Assuntos
Artrite/metabolismo , Inibidores Enzimáticos/farmacologia , NADPH Oxidase 2/antagonistas & inibidores , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Artrite/patologia , Biomarcadores , Cálcio/metabolismo , Células Endoteliais , Inibidores Enzimáticos/química , Espaço Extracelular/metabolismo , Adjuvante de Freund , Humanos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADPH Oxidase 2/química , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
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