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1.
Org Biomol Chem ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605502

RESUMO

This paper reports a convenient copper-catalyzed three-component conversion of arylhydrazine hydrochlorides to arenesulfonyl fluorides in good yields under mild conditions, using 1,4-diazabicyclo [2.2.2]octane bis(sulfur dioxide) (DABSO) as a sulfonyl source and N-fluorobenzenesulfonimide (NFSI) as a fluorine source based on a radical sulfur dioxide insertion and fluorination strategy. Notably, arylhydrazine hydrochloride is used as a safe precursor of aryl radicals.

2.
Front Immunol ; 12: 673693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408744

RESUMO

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.


Assuntos
COVID-19/tratamento farmacológico , Síndrome do Desconforto Respiratório/epidemiologia , Timalfasina/efeitos adversos , Adulto , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Timalfasina/administração & dosagem , Resultado do Tratamento
3.
Clin Microbiol Infect ; 27(10): 1488-1493, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34020032

RESUMO

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

4.
Org Lett ; 23(10): 3975-3980, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33969691

RESUMO

Herein we report a practical and efficient copper-catalyzed approach for the conversion of various arenediazonium salts to the corresponding N-protected sulfonimidoyl fluorides. This operationally simple protocol tolerates a wide range of functional groups and can be applied to the late-stage modification of complex bioactive molecules. Furthermore, pharmaceutically important primary sulfonamides and sulfonimidamides derived from these valuable N-protected sulfonimidoyl fluoride units were prepared in minimal synthetic steps.

5.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
6.
Chemosphere ; 262: 127793, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799142

RESUMO

Currently, few studies have investigated the joint toxicity mechanism of azole fungicides at different exposure times and mixed at the relevant environmental concentrations. In this study, three common azole fungicides, namely, myclobutanil (MYC), propiconazole (PRO), and tebuconazole (TCZ), were used in studying the toxic mechanisms of a single substance and its ternary mixture exposed to ambient concentrations of Chlorella pyrenoidosa. Superoxide dismutase (SOD), catalase (CAT), chlorophyll a (Chla), and total protein (TP), were used as physiological indexes. Results showed that three azole fungicides and ternary mixture presented obvious time-dependent toxicities at high concentrations. MYC induced a hormetic effect on algal growth, whereas PRO and TCZ inhibit algal growth in the entire range of the tested concentrations. The toxicities of the three azole fungicides at 7 days followed the order PRO > TCZ > MYC. Three azole fungicides and their ternary mixture induced different levels of SOD and CAT activities in algae at high concentrations. The ternary mixture showed additive effects after 4 and 7 days exposure, but no effect was observed at actual environmental concentrations. The toxic mechanisms may be related to the continuous accumulation of reactive oxygen species, which not only affected protein structures and compositions but also damaged thylakoid membranes, hindered the synthesis of proteins and chlorophyll a, and eventually inhibited algal growth. These findings increase the understanding of the ecotoxicity of azole fungicides and use of azole fungicides in agricultural production.


Assuntos
Antioxidantes/metabolismo , Azóis/toxicidade , Chlorella/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Catalase/metabolismo , Chlorella/enzimologia , Chlorella/crescimento & desenvolvimento , Clorofila A/metabolismo , Relação Dose-Resposta a Droga , Nitrilas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Triazóis/toxicidade
7.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141117

RESUMO

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/mortalidade , Idoso , COVID-19/complicações , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
8.
Respir Med ; 173: 106159, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010731

RESUMO

BACKGROUND: The outbreak of COVID-19 caused by SARS-CoV-2 has been a pandemic. The objective of our study was to explore the association between sex and clinical outcomes in patients with COVID-19. METHODS: Detailed clinical data including clinical characteristics, laboratory tests, imaging features and treatments of 1190 cases of adult patients with confirmed COVID-19 were retrospectively analyzed. Associations between sex and clinical outcomes were identified by multivariable Cox regression analysis. RESULTS: There were 635 (53.4%) male and 555 (46.6%) female patients in this study. Higher rates of acute kidney injury (5.5% vs. 2.9%, p = 0.026), acute cardiac injury (9.1% vs. 4.3%, p = 0.001), and disseminated intravascular coagulation (2.5% vs. 0.7%, P = 0.024) were observed in males. Compared with female patients, male patients with COVID-19 had a higher inhospital mortality rate (15.7% vs. 10.3%, p = 0.005). However, Cox regression analysis showed that sex did not influence inhospital mortality of COVID-19 patients. CONCLUSIONS: Male sex was associated with a worse prognosis of COVID-19, but it seems not to be an independent prognostic factor.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , China , Infecções por Coronavirus/terapia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais
9.
Ann Intensive Care ; 10(1): 99, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737627

RESUMO

BACKGROUND: Since December 2019, an outbreak of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) initially emerged in Wuhan, China, and has spread worldwide now. Clinical features of patients with COVID-19 have been described. However, risk factors leading to in-hospital deterioration and poor prognosis in COVID-19 patients with severe disease have not been well identified. METHODS: In this retrospective, single-center cohort study, 1190 adult inpatients (≥ 18 years old) with laboratory-confirmed COVID-19 and determined outcomes (discharged or died) were included from Wuhan Infectious Disease Hospital from December 29, 2019 to February 28, 2020. The final follow-up date was March 2, 2020. Clinical data including characteristics, laboratory and imaging information as well as treatments were extracted from electronic medical records and compared. A multivariable logistic regression model was used to explore the potential predictors associated with in-hospital deterioration and death. RESULTS: 1190 patients with confirmed COVID-19 were included. Their median age was 57 years (interquartile range 47-67 years). Two hundred and sixty-one patients (22%) developed a severe illness after admission. Multivariable logistic regression demonstrated that higher SOFA score (OR 1.32, 95% CI 1.22-1.43, per score increase, p < 0.001 for deterioration and OR 1.30, 95% CI 1.11-1.53, per score increase, p = 0.001 for death), lymphocytopenia (OR 1.81, 95% CI 1.13-2.89 p = 0.013 for deterioration; OR 4.44, 95% CI 1.26-15.87, p = 0.021 for death) on admission were independent risk factors for in-hospital deterioration from not severe to severe disease and for death in severe patients. On admission D-dimer greater than 1 µg/L (OR 3.28, 95% CI 1.19-9.04, p = 0.021), leukocytopenia (OR 5.10, 95% CI 1.25-20.78), thrombocytopenia (OR 8.37, 95% CI 2.04-34.44) and history of diabetes (OR 11.16, 95% CI 1.87-66.57, p = 0.008) were also associated with higher risks of in-hospital death in severe COVID-19 patients. Shorter time interval from illness onset to non-invasive mechanical ventilation in the survivors with severe disease was observed compared with non-survivors (10.5 days, IQR 9.25-11.0 vs. 16.0 days, IQR 11.0-19.0 days, p = 0.030). Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39-6.01, p < 0.001). Administration of antiviral drugs especially oseltamivir or ganciclovir is associated with a decreased risk of death in severe patients (OR 0.17, 95% CI 0.05-0.64, p < 0.001). CONCLUSIONS: High SOFA score and lymphocytopenia on admission could predict that not severe patients would develop severe disease in-hospital. On admission elevated D-dimer, leukocytopenia, thrombocytopenia and diabetes were independent risk factors of in-hospital death in severe patients with COVID-19. Administration of oseltamivir or ganciclovir might be beneficial for reducing mortality in severe patients.

10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(5): 618-621, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32576358

RESUMO

Continuous renal replacement therapy (CRRT) has become an effective multiple organ support therapy instead of single renal replacement as initially expected, and it is widely used in intensive care unit (ICU). After the outbreak of coronavirus disease 2019 (COVID-19), a series of expert recommendation or consensus have been developed to diagnose and treat the disease, including CRRT in acute kidney injury (AKI) and hyper inflammatory response. However, CRRT in COVID-19 is extraordinarily different from regular one due to different pathophysiology and infectious clinical scenarios. Accordingly, the paper aims to elaborate the similarities and differences between CRRT in COVID-19 and routine treatment in terms of safety and accessibility, indications and timing, clinical operation, anticoagulation, fluid management, prevention and control of infectious diseases, etc.


Assuntos
Injúria Renal Aguda , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Terapia de Substituição Renal Contínua , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2
11.
J Cell Mol Med ; 24(12): 6731-6740, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383354

RESUMO

Sepsis is a life-threatening syndrome with a high risk of mortality, which is caused by the dysregulated host response to infection. We examined significant roles of circDMNT3B and miR-20b-5p in the intestinal mucosal permeability dysfunction of rats with sepsis. SD rats were randomly divided into 6 groups (n = 10/group): sham group, sepsis group, si-negative control group, circDNMT3B-si1 group, circDNMT3B-si2 group and circDNMT3B-si1 + anti-miR-20b-5p group. The level of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin (IL)-6 and IL-10 levels were measured through ELISA assay kits. Cell survival rate and cell apoptosis were evaluated by Cell-Counting Kit-8 Assay and flow cytometry, respectively. Luciferase reporter assays were used to investigate interactions between miR-20b-5p circDMNT3B in HEK-293T cells. Silencing circDNMT3B can significantly increase the level of d-lactic acid, FD-40, MDA, diamine oxidase, IL-10 and IL-6, compared with sepsis group, while the SOD activity was lower. Silencing circDNMT3B leads to oxidative damage and influence inflammatory factors level in intestinal tissue. CircDNMT3B was identified as a target gene of miR-20b-5p. Silencing circDNMT3B decreased cell survival and induced apoptosis in Caco2 cells treated with LPS, which was reversed by anti-miR-20b-5p. MiR-20b-5p inhibitor remarkably down-regulated mentioned-above levels, in addition to up-regulate SOD activity, which may relieve the damage of intestinal mucosal permeability caused by silencing circDNMT3B in sepsis rats. Down-regulation of circDMNT3B was conducive to the dysfunction of intestinal mucosal permeability via sponging miR-20b-5p in sepsis rats, which may provide the novel strategy for sepsis treatment in the future.


Assuntos
Regulação para Baixo/genética , Mucosa Intestinal/fisiopatologia , MicroRNAs/metabolismo , RNA Circular/genética , Sepse/genética , Sepse/fisiopatologia , Animais , Apoptose/genética , Sequência de Bases , Células CACO-2 , Proliferação de Células/genética , Sobrevivência Celular/genética , Inativação Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Mucosa Intestinal/patologia , Lipopolissacarídeos , Masculino , MicroRNAs/genética , Estresse Oxidativo/genética , Permeabilidade , RNA Circular/metabolismo , Ratos Sprague-Dawley
12.
Org Lett ; 22(6): 2281-2286, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32115957

RESUMO

We report herein a general and practical copper-catalyzed fluorosulfonylation reaction of a wide range of abundant arenediazonium salts to smoothly prepare various arenesulfonyl fluorides using the 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct as a convenient sulfonyl source in combination with KHF2 as an ideal fluorine source and without the need for additional oxidants. Interestingly, the electronic character of the arene ring in the starting arenediazonium salts has a significant impact on the reaction mechanistic pathway.

13.
J Hazard Mater ; 362: 451-457, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30265976

RESUMO

Toxicological evidence indicates that exposure to drinking water trihalomethanes (THMs) can impair neural development. However, no epidemiologic study to date has evaluated the relation of trihalomethanes exposure with neonatal neurobehavioral development. Here we aimed to evaluate if prenatal exposure to THMs during early pregnancy is associated with neonatal neurobehavioral development in 451 Chinese mother-child pairs. First trimester blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] were determined by solid phase micro-extraction gas chramatography. Neonatal neurobehavioral development was assessed using neonatal behavioral neurological assessment (NBNA) on the third day after birth. Multivariable linear regression models and restricted cubic spline models were constructed to evaluate the associations between blood THMs and neonatal neurological development scores. Blood concentrations of BDCM, whether modeled as continuous or categorical variables, were inversely associated with total NBNA score of newborns based on the multivariable linear regression. The association was further confirmed in the cubic spline model, and a linear dose-response relationship was observed. Stratified analysis showed that the inverse association between blood BDCM and total NBNA score was more evident in male infants than females. Our findings suggest that exposure to THMs during early pregnancy may be associated with impaired neonatal neurobehavioral development.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Água Potável/química , Exposição Materna , Primeiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Trialometanos/sangue , Poluentes Químicos da Água/sangue , Adulto , China/epidemiologia , Desinfecção , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Complicações na Gravidez , Fatores Sexuais , Trialometanos/efeitos adversos , Poluentes Químicos da Água/efeitos adversos
14.
Chemistry ; 25(7): 1824-1828, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30444035

RESUMO

A versatile and general zinc-mediated intermolecular reductive radical fluoroalkylsulfination of unsaturated C-C bonds has been developed using readily available fluoroalkyl bromides and 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct (DABSO) with wide substrate scope and excellent functional group tolerance. Sulfur dioxide anion radical generated in situ from the reduction of sulfur dioxide with zinc may be involved in the reaction mechanism.

15.
J Org Chem ; 83(10): 5836-5843, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29658711

RESUMO

An efficient oxidative radical intermolecular trifluoromethylthioarylation of styrenes with arenediazonium salts and copper(I) trifluoromethylthiolate under mild conditions is described for the first time. The reactions provide good yields of the corresponding trifluoromethylthioarylation products with broad substrate scope and excellent functional group compatibility.

16.
Angew Chem Int Ed Engl ; 56(48): 15432-15435, 2017 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-29094795

RESUMO

Presented is a novel intermolecular radical trifluoromethylfluorosulfonylation of unactivated alkenes under mild reaction conditions with good functional-group tolerance in the most atom-economic manner by using readily available Ag(O2 CCF2 SO2 F) and N-fluorobenzenesulfonimide (NFSI). Both the trifluoromethyl and sulfonyl groups in the products originate from Ag(O2 CCF2 SO2 F).

17.
Infect Genet Evol ; 44: 228-233, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27431332

RESUMO

Haemophilus parasuis is the etiological agent of Glässers disease, which causes high morbidity and mortality in swine herds. Although H. parasuis strains can be classified into 15 serovars with the Kielstein-Rapp-Gabrielson serotyping scheme, a large number of isolates cannot be classified and have been designated 'nontypeable' strains. In this study, multilocus sequence typing (MLST) of H. parasuis was used to analyze 48 H. parasuis field strains isolated in China and two strains from Australia. Twenty-six new alleles and 29 new sequence types (STs) were detected, enriching the H. parasuis MLST databases. A BURST analysis indicated that H. parasuis lacks stable population structure and is highly heterogeneous, and that there is no association between STs and geographic area. When an UPGMA dendrogram was constructed, two major clades, clade A and clade B, were defined. Animal experiments, in which guinea pigs were challenged intraperitoneally with the bacterial isolates, supported the hypothesis that the H. parasuis STs in clade A are generally avirulent or weakly virulent, whereas the STs in clade B tend to be virulent.


Assuntos
Haemophilus parasuis/classificação , Haemophilus parasuis/genética , Haemophilus parasuis/patogenicidade , Animais , Austrália , Técnicas de Tipagem Bacteriana , China , Feminino , Frequência do Gene , Cobaias , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/isolamento & purificação , Tipagem de Sequências Multilocus , Filogenia , Sorotipagem , Suínos/microbiologia , Virulência
18.
Iran J Immunol ; 13(2): 89-99, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27350630

RESUMO

BACKGROUND: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. OBJECTIVE: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. METHODS: Firefly luciferase reporter plasmids pEZX-MT01-wild-type-BTLA and pEZX-MT01-mutant-BTLA were constructed. Lymphocytes were nucleofected with miR-155 inhibitor or negative control (NC). Then, naïve CD4+ CD62L+ helper T cells purified from lymphocytes were stimulated with immobilized antibody to CD3 and soluble antibody to CD28. miR-155 and BTLA expression were examined by real-time RT-PCR. Cell surface CD69 expression and IL-2 secretion were measured by ELISA and flowcytometry, respectively. RESULTS: Luciferase reporter assay showed that miR-155 targeted the BTLA 3'UTR region. Compared with non-stimulated condition, both miR-155 and BTLA mRNA expression were upregulated after T cell activation. Similar results were observed for BLTA protein expression. Compared with NC, the miR-155 inhibitor decreased miR-155 by about 45%, but did not influence BTLA mRNA expression. Compared with NC, the miR-155 inhibitor decreased the surface BTLA expression by about 60%. Upregulation of BTLA in miR-155 knockdown CD4+ T cells did not influence the cell surface expression of CD69, an early activation marker (p=0.523). Similarly, IL-2 production was not changed. CONCLUSION: miR-155 is involved in the inhibition of BTLA during CD4+ T cell activation. These results might serve as a basis for an eventual therapeutic manipulation of this pathway to treat inflammatory and autoimmune diseases.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos B/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Lectinas Tipo C/metabolismo , MicroRNAs/metabolismo , Receptores Imunológicos/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Anticorpos/imunologia , Antígenos CD28/imunologia , Complexo CD3/imunologia , Células Cultivadas , Interleucina-2/metabolismo , Ativação Linfocitária/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Mutação/genética , RNA Interferente Pequeno/genética , Receptores Imunológicos/genética
19.
Dongwuxue Yanjiu ; 35(4): 262-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25017744

RESUMO

Food restriction (FR) and refeeding (Re) have been suggested to impair body mass regulation and thereby making it easier to regain the lost weight and develop over-weight when FR ends. However, it is unclear if this is the case in small mammals showing seasonal forging behaviors. In the present study, energy budget, body fat and serum leptin level were measured in striped hamsters that were exposed to FR-Re. The effects of leptin on food intake, body fat and genes expressions of several hypothalamus neuropeptides were determined. Body mass, fat content and serum leptin level decreased during FR and then increased during Re. Leptin supplement significantly attenuated the increase in food intake during Re, decreased genes expressions of neuropepetide Y (NPY) and agouti-related protein (AgRP) of hypothalamus and leptin of white adipose tissue (WAT). Hormone-sensitive lipase (HSL) gene expression of WAT increased in leptin-treated hamsters that were fed ad libitum, but decreased in FR-Re hamsters. This indicates that the adaptive regulation of WAT HSL gene expression may be involved in the mobilization of fat storage during Re, which partly contributes to the resistance to FR-Re-induced overweight. Leptin may be involved in the down regulations of hypothalamus orexigenic peptides gene expression and consequently plays a crucial role in controlling food intake when FR ends.


Assuntos
Privação de Alimentos/fisiologia , Leptina/metabolismo , Animais , Cricetinae , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Regulação da Expressão Gênica , Hipotálamo , Masculino , Ganho de Peso , Perda de Peso
20.
Horm Behav ; 65(4): 355-62, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24631583

RESUMO

Physiological and behavioral adjustments of small mammals are important strategies in response to variations in food availability. Although numerous of studies have been carried out in rodents, behavioral patterns in response to food deprivation and re-feeding (FD-RF) are still inconsistent. Here we examined effects of a 24h FD followed by RF on general activity, serum leptin concentrations and gene expression of orexigenic and anorexigenic hypothalamic neuropeptides in striped hamsters (Cricetulus barabensis) with/without leptin supplements. The time spent on activity was increased by 2.5 fold in FD hamsters compared with controls fed ad libitum (P<0.01). Body mass, fat mass as well as serum leptin concentrations were significantly decreased in FD hamsters in comparison with ad libitum controls, which were in parallel with hyperactivity. During re-feeding, leptin concentrations increased rapidly to pre-deprivation levels by 12h, but locomotor activity decreased gradually and did not return to pre-deprivation levels until 5days after re-feeding. Leptin administration to FD hamsters significantly attenuated the increased activity. Gene expression of hypothalamic neuropeptide Y (NPY) was upregulated in FD hamsters and fell down to control levels when hamsters were re-fed ad libitum, similar to that observed in activity behavior. Leptin supplement induced increases in serum leptin concentrations (184.1%, P<0.05) in FD hamsters and simultaneously attenuated the increase in activity (45.8%, P<0.05) and NPY gene expression (35%, P<0.05). This may allow us to draw a more generalized conclusion that decreased leptin concentrations function as a starvation signal in animals under food shortage; to induce an increase in activity levels, leading animals to forage and/or migrate, and consequently increasing the chance of survival. Decreased concentrations of serum leptin in animals subjected to food shortage may induce an upregulation of gene expression of hypothalamus NPY, consequently driving a significant increase in foraging behavior.


Assuntos
Cricetulus/metabolismo , Privação de Alimentos/fisiologia , Regulação da Expressão Gênica/fisiologia , Leptina/sangue , Atividade Motora/fisiologia , Neuropeptídeo Y/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Leptina/farmacologia , Atividade Motora/efeitos dos fármacos , Distribuição Aleatória
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