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1.
Hum Genet ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020363

RESUMO

Secretory carrier membrane proteins (SCAMPs) play an important role in exocytosis in animals, but the precise function of SCAMPs in human disease is unknown. In this study, we identified a homozygous mutation, SCAMP5 R91W, in a Chinese consanguineous family with pediatric epilepsy and juvenile Parkinson's disease. Scamp5 R91W mutant knock-in mice showed typical early-onset epilepsy similar to that in humans. Single-neuron electrophysiological recordings showed that the R91W mutation significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) at a resting state and also increased the amplitude of evoked EPSCs. The R91W mutation affected the interaction between SCAMP5 and synaptotagmin 1 and may affect the function of the SNARE complex, the machinery required for vesicular trafficking and neurotransmitter release. Our work shows that dysfunction of SCAMP5 shifted the excitation/inhibition balance of the neuronal network in the brain, and the deficiency of SCAMP5 leads to pediatric epilepsy.

2.
Bioorg Med Chem Lett ; 30(4): 126951, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926784

RESUMO

The incidence of invasive fungal infections has dramatically increased for several decades. In order to discover novel antifungal agents with broad spectrum and anti-Aspergillus efficacy, a series of novel triazole derivatives containing 1,2,3-benzotriazin-4-one was designed and synthesized. Most of the compounds exhibited stronger in vitro antifungal activities against tested fungi than fluconazole. Moreover, 6m showed comparable antifungal activity against seven pathogenic strains as voriconazole and albaconazole, especially against Aspergillus fumigatus (MIC = 0.25 µg/ml), and displayed moderate antifungal activity against fluconazole-resistant strains of Candida albicans. A clear SAR study indicated that compounds with groups at the 7-position resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum.

3.
Chemistry ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965665

RESUMO

Acridinium benzoate was developed as a unique ICT-based fluorescent scaffold for both ratiometric and turn-on fluorescence imaging through decaging of the phenolic hydroxyl groups. Two fluorescent probes, Acr1-H2O2 and Acr1-ß-gal , were developed for the fluorescence imaging of H2O2 and ß-galactosidase in vivo.

4.
Antimicrob Agents Chemother ; 64(2)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31791946

RESUMO

In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described a leading compound, NT-a9, an analogue of isavuconazole, that showed strong antifungal activities in vitro and in vivo NT-a9 showed a wide range of activities against several pathogenic fungi in vitro, including Cryptococcus neoformans, Cryptococcus gattii, Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, with MICs ranging from 0.002 to 1 µg/ml. In particular, NT-a9 exhibited excellent efficacy against C. neoformans, with a MIC as low as 0.002 µg/ml. NT-a9 treatment resulted in changes in the sterol contents in C. neoformans, similarly to fluconazole. In addition, NT-a9 possessed relatively low cytotoxicity and a high selectivity index. The in vivo efficacy of NT-a9 was assessed using a murine disseminated-cryptococcosis model. Mice were infected intravenously with 1.8 × 106 CFU of C. neoformans strain H99. In the survival study, NT-a9 significantly prolonged the survival times of mice compared with the survival times of the control group or the isavuconazole-, fluconazole-, or amphotericin B-treated groups. Of note, 4 and 8 mg/kg of body weight of NT-a9 rescued all the mice, with a survival rate of 100%. In the fungal-burden study, NT-a9 also significantly reduced the fungal burdens in brains and lungs, while fluconazole and amphotericin B only reduced the fungal burden in lungs. Taken together, these data suggested that NT-a9 is a promising antifungal candidate for the treatment of cryptococcosis infection.

5.
Nanotechnology ; 31(12): 125405, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31751972

RESUMO

By exploiting the storage performance of supercapacitors, iron has the potential to be used as a new anode material. However, this potential is limited by unsatisfactory electrical conductivity and poor cycling stability which impact the energy and power density. Consequently a foundation for improving the electrical conductivity and cycling stability of iron materials to obtain good storage performance is needed. In this work, Ag-modified Fe2O3 nanoparticles on carbon cloth were synthesized as an anode material for supercapacitors. The specific capacitance of the composite material reaches 10.39 F cm-2 (2734.2 F g-1) at a current density of 1 mA cm-2 and remains at 83% of this value after 12 000 cycles. The energy density is 379.8 Wh kg-1 at a power density of 131.6 W kg-1 and remains at 123.9 Wh kg-1 at a power density of 2631.6 W kg-1. The electrical conductivity and interfacial effect created between Ag@Fe2O3 is confirmed with density functional theory calculations. The packaged asymmetric supercapacitor devices have flexibility and can light ten LEDs for 2 min 30 s, with an energy density of 60.3 Wh kg-1 that can be reached at a power density of 1063.8 W kg-1 and remain at 16 Wh kg-1 even at a power density of 4255.3 W kg-1.

6.
Microb Pathog ; 139: 103912, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816402

RESUMO

BACKGROUND AND AIMS: Recent available treatment guidelines are pointing up clearance or seroconversion of hepatitis B e-antigen (HBeAg) as a valuable endpoint in treating HBeAg-positive chronic hepatitis B (CHB) patients. To evaluate the effect of combination therapy [interferon (IFN) plus nucleos(t)ide analogues (NAs)] versus IFN monotherapy on HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. METHODS: All available controlled clinical studies, published from Jan 2000 to Sep 2018, with CHB receiving IFN and NA combination therapy or IFN monotherapy were included. Risk ratio (RR) and their 95% confidence intervals (CIs) was estimated with a fixed-effects model when I2 <50% for the test for heterogeneity. Publication bias was measured using Egger's test. RESULTS: Twelve studies were included. Our meta-analysis demonstrated that IFN and NA combination therapy had a superior HBeAg seroconversion rate or clearance rate compared with IFN monotherapy at the end of treatment (EOT). Sub-analysis showed IFN plus adefovir dipivoxi (ADV) therapy had a better HBeAg seroconversion or seroclearance rate at EOT or at the end of follow-up (EOF). CONCLUSION: Compared with IFN monotherapy, the combined therapy had a higher e-antigen serological response at EOT, but failed to improve the sustained response at EOF. Only combination therapy with IFN and ADV is superior to IFN monotherapy at the EOT or EOF for HBeAg seroconversion or seroclearance in HBeAg-positive CHB patients. The effect of other combination therapies is not superior to IFN monotherapy.

7.
Ann Hepatol ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31884016

RESUMO

INTRODUCTION AND OBJECTIVE: The aim of the present study was to investigate the significance of serum HBsAg levels in treatment cessation of nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) infection. METHODS: In 158 CHB patients with long-term NAs treatment, 74 patients were in HBeAg negative and had a HBsAg level <1500IU/mL, 36 of whom were informed and consented to cease NAs. HBsAg, HBV DNA and liver function were examined in the 1st, 3rd, 6th, 9th and 12th month after treatment cessation. RESULTS: The sustained response rate was 88.89% (32/36) within one year after NAs cessation. Sub-group analysis was based on HBsAg levels of patients with NAs cessation, there was no relapse case in 11 patients whose HBsAg <50IU/mL, and the negative predictive value (NPV) was 100%. Seroconversion of HBsAg occurred in 3 patients. 2 patients from 21 cases whose HBsAg was between 50IU/mL and 1000IU/mL relapsed. 2 of 4 patients whose in HBsAg >1000IU/mL relapsed. HBsAg of patients with a sustained response decreased slowly. In contrast, HBsAg levels increased gradually in relapsed patients, and the increase of HBsAg was precedent to relapses of HBV DNA and ALT. Multivariate analysis suggested that only HBsAg level showed a close correlation with HBV DNA relapses. ROC curve analysis suggested that the increase of HBsAg level in the 3rd and 6th month after NAs cessation had a great predictive value for relapses. CONCLUSION: Monitoring of base line HBsAg level can predict outcomes of NAs cessation in HBeAg-negative chronic hepatitis B. HBsAg <50IU/mL has higher predictive values of better sustained responses in HBeAg-negative CHB patients.

8.
Chin Med J (Engl) ; 132(22): 2647-2656, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725459

RESUMO

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

9.
Chem Commun (Camb) ; 55(78): 11802-11805, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31524901

RESUMO

Introduction of a heteroatom into a fluorophore was carried out for coumarin through a replacement of its bridging oxygen atom with a silicon atom. The maximum-emission wavelength of Si-coumarin (SiC B) bathochromically shifted from 426 nm in cyclohexane to 626 nm in water. The adipogenic differentiation processes in mesenchymal stem cells were monitored using SiC B.


Assuntos
Cumarínicos/química , Silício/química , Adipogenia/efeitos dos fármacos , Animais , Linhagem Celular , Teoria da Densidade Funcional , Ligações de Hidrogênio , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Microscopia Confocal
10.
J Assist Reprod Genet ; 36(9): 1957-1962, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428887

RESUMO

PURPOSE: To identify the disease-causing gene in a family with female infertility and fertilization failure. METHODS: Whole-exome sequencing and Sanger sequencing were used to identify the disease-causing gene in a female with infertility and fertilization failure. Subcellular localization and western blot analysis were used to check the effect of mutations. RESULTS: We identified novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female with infertility and fertilization failure. The p.Arg200Ter mutant WEE2 gene produce truncated protein and mainly located in the nucleus, the same as the wild protein, while the p.Trp440Ser mutant WEE2 proteins are located in the nucleus and cytoplasm and the expression level of p.Trp440Ser mutant WEE2 protein is reduced significantly compared with that of wild-type WEE2. CONCLUSIONS: We discovered novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection (ICSI). Moreover, mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure.

11.
Biomed Res Int ; 2019: 3962785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218224

RESUMO

Background and Aims: Liver transplantation is one of the most effective treatments for end-stage liver disease as well as for cases of acute liver failure. Facing organ donor shortage, liver transplant teams had to use marginal organs. Thus, increasing availability is a key concern of donor liver grafts including steatotic livers. However, the use of steatotic liver is still controversial. The aim of this systematic review and meta-analysis was to analyze the impact of steatosis on the outcome of liver transplantation. Methods: We searched PubMed, Cochrane Library, Embase, Web of knowledge, and so on for studies published through May 31, 2018, in which patients experienced liver transplantation using fatty liver. All studies extracted outcome indicators, and we draw conclusions by contrasting outcome indicators in different groups of steatosis. Odds ratios and 95% confidence intervals were calculated. P<0.05 was considered as statistically significant difference. Results: 19 publications were included. There was no significant difference between the group of no steatosis and mild group in primary nonfunction rate (P=0.605) or early graft dysfunction rate (P=0.44). The PNF rate was significantly higher in moderate group (P=0.003) and severe group (P <0.001) compared with that in no steatosis group. The same results were seen in early graft dysfunction rate. However, graft survival rate and patient survival rate did not differ between groups. Conclusions: Livers with mild steatosis, even with moderate or severe steatosis, could be suitable donor under strict control of transplant conditions.


Assuntos
Fígado Gorduroso , Sobrevivência de Enxerto , Transplante de Fígado , Disfunção Primária do Enxerto/mortalidade , Humanos , Disfunção Primária do Enxerto/metabolismo , Taxa de Sobrevida
12.
BMC Gastroenterol ; 19(1): 65, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046700

RESUMO

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Resposta Viral Sustentada , Adulto , Antivirais/administração & dosagem , China , Feminino , Seguimentos , Hepatite B Crônica/sangue , Humanos , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
13.
Virol J ; 16(1): 47, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992019

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is one of the leading causes of liver cancer, creating enormous economic and social burdens. The Chinese government recommends routine screening of inpatients for HCV before invasive procedures to prevent iatric infections. However, the diagnosis and treatment rates for HCV remain low. The aim of this study was to use available routine screening data to understand the HCV screening of inpatients in different regions of China. METHODS: Inpatient information and HCV screening results were collected from January 2016 to December 2016 at eight tertiary hospitals in different regions of China to compare the HCV-positivity of hospitalized patients among different regions and age groups. RESULTS: The HCV screening rate of inpatients was more than 50%. A total of 467,008 inpatients were enrolled in the study (51.20% were male), and the HCV antibody (anti-HCV) -positive rate was 0.88% (95% confidence interval [CI], 0.85-0.91%) among the total population. This rate was significantly higher among all males compared with all females (0.91% vs 0.85%). Moreover, the HCV antibody-positive rate increased with age and was highest for the 60-64-year age group. Notably, 90.14% (3722/4129) of the anti-HCV seropositive patients were 40 years of age or older. HCV screening for people over 40 years old is recommended. CONCLUSIONS: This study highlights the key role of routine examination for HCV infection in hospitalized patients. Full use of inpatient screening results to manage HCV antibody-positive patients and a screening strategy targeting inpatients 40 years and older were found to be low-cost and effective, which will help to find the missing millions of yet unaware patients and also accelerate the elimination of HCV in China.


Assuntos
Hepatite C/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Hepatite B/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Hospitalização/estatística & dados numéricos , Hospitais , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
14.
PLoS One ; 14(4): e0215648, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30998751

RESUMO

Mendelian Susceptibility to Mycobacterial Diseases (MSMD) is a primary immunodeficiency disease (PID) characterized by variable susceptibility to weakly virulent mycobacteria (Bacille Calmette-Guerin, BCG) and various intramacrophagic bacteria, fungi, parasites. Mycobacterial disease generally begins in childhood, more rarely during adolescence and adulthood. The pathogenesis of MSMD is the inherited impaired production of interferon gamma (IFN-γ) or inadequate response to it. Autosomal recessive IL12RB1 deficiency is the most common genetic etiology of MSMD. Here we identified three novel compound heterozygous mutations in IL12RB1 gene (c.635G>A, c.765delG; c.632G>C, c.847C>T; c.64G>A, c.1673insGAGCTTCCTGAG) in three Chinese families with MSMD.


Assuntos
Predisposição Genética para Doença , Heterozigoto , Infecções por Mycobacterium/genética , Mutação Puntual , Receptores de Interleucina-12/genética , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Lactente , Interferon gama/genética , Interferon gama/imunologia , Masculino , Infecções por Mycobacterium/imunologia , Receptores de Interleucina-12/imunologia
15.
Nanotechnology ; 30(33): 335401, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30836342

RESUMO

One-dimensional tunnel and layer frame crystal structure materials are extremely attractive for energy storage in electrode materials. The energy storage properties of the electrode materials depend on their conductivity. Furthermore, the conductivity of electrode materials can be tailored through combination or doping with other materials, which transforms their properties from semiconductor to semimetallic or metallic and allow them to show unequaled performance for storage devices. In this work, heterostructures of manganese oxide (MnO) and modified sodium titanate (Na2Ti6O13) (MnO@Na2Ti6O13) nanowires are attained by the in situ thermal decomposition method. The heterojunction between MnO and Na2Ti6O13 allows the semiconductor properties of pure Na2Ti6O13 to show remarkable metallic behavior for improving the electrochemical performance. The capacitance of MnO@Na2Ti6O13 heterojunction nanowires can reach 272.3 F g-1, a power intensity of 250 W kg-1 at the energy density of 37.83 Wh kg-1 and retain 5000 W kg-1 at 6.67 Wh kg-1 as well. The energy storage mechanism of the MnO@Na2Ti6O13 heterostructure is studied by density functional theory. All of the results show that the MnO@Na2Ti6O13 heterostructure material has the potential to be an excellent supercapacitor material in the future.

16.
Chemistry ; 25(11): 2675-2683, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30264413

RESUMO

Desilication has been proven an effective approach for the construction of well-defined hierarchical porosities inside zeolites with an optimal framework Al content (Si/Al=25-50). However, for the Al-rich aluminosilicate zeolites, desilication is constrained by the excess and extensive shielding effects from high Al-contents. The developments in the desilication of siliceous zeolites convey a simplified principle of controlled dissolution of the microporous matrix for the construction of hierarchical porosities, which benefits the innovation of synthetic approaches for Al-rich zeolites. The perturbations to the environments of framework Al species may alleviate the excess shielding effects. This review highlights two corresponding protocols of sequential "fluorination-desilication" and "steaming-desilication" for the construction of hierarchical porosities inside Al-rich ZSM-5 zeolites. The success of these two protocols revitalizes the prevailing understanding of the interplay between dealumination and desilication, and implies the necessity of investigating the overlooked roles of extra-framework Al species. Despite the long history and significant achievements in the last decade, fundamental understandings at the molecule level are still limited for the desilication-based top-down approaches. In particular, the investigations on Al-rich zeolites just find their growing. The bridging of dealumination and desilication is essential for other industrially relevant Al-rich zeolites (e.g., faujasite zeolites). The complexities in the inherent characters (topology, spatial distribution, proximity, etc.) and apparent parameters (morphology, crystal/particle size, etc.) demand constructive synthetic toolboxes and further fundamental understanding.

17.
Diving Hyperb Med ; 48(4): 235-240, 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30517956

RESUMO

BACKGROUND: Recent studies indicated that ketone ester R,S-1,3-butanediol acetoacetate diester (BD-AcAc2) may be effective in preventing central nervous system oxygen toxicity (CNS-OT) and concomitant acute lung injury, a serious medical problem to be faced when breathing hyperbaric oxygen (HBO). This study aimed to further investigate the protective effects of BD-AcAc2 against CNS-OT and concomitant acute lung injury (ALI) in mice. METHODS: Mice were treated with BD-AcAc2 in peanut oil vehicle (2.5, 5.0 or 10.0 g·kg⁻² body weight) by gavage 20 minutes before 600 kPa HBO exposure. Control mice received the vehicle only. Seizure latency was recorded. Malondialdehyde content in brain and lung tissues, total protein level in bronchoalveolar lavage fluid (BLF) and lung water content were measured 60 minutes after the hyperbaric exposure. Histopathology of lung tissue was undertaken. RESULTS: Compared with the vehicle alone, BD-AcAc2 prolonged seizure latency in a dose-dependent manner (P < 0.01). The HBO-induced increase in brain malondialdehyde, BLF protein and lung water were significantly reduced by BD-AcAc2 (P < 0.01). CONCLUSION: Oral administration of the ketone ester BD-AcAc2 significantly protected against CNS-OT and concomitant ALI. Alleviation of oxidative stress may be one underlying mechanism providing this effect.


Assuntos
Acetoacetatos/uso terapêutico , Lesão Pulmonar Aguda , Encéfalo/efeitos dos fármacos , Butileno Glicóis/uso terapêutico , Oxigenação Hiperbárica , Acetoacetatos/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Oxigenação Hiperbárica/efeitos adversos , Camundongos , Oxigênio , Ratos Sprague-Dawley , Convulsões/tratamento farmacológico
18.
Chemistry ; 24(54): 14506-14512, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30019781

RESUMO

Replacement of the bridging oxygen atom in rhodamine with phosphorus is one of the most efficient ways for bright near-infrared (NIR) fluorophores with wavelengths over 700 nm. However, the organophosphorus bridge is more versatile than just being a spectrum tuner, it is also a profound solubility booster and photostability enhancer, as proved by a series of phosphorus-substituted rhodamines (PRBs). A unique bridge-caging strategy for efficiently manipulating fluorescence has further been innovated in example PRB2. Consistent with theoretical calculations, the formation of organophosphinate by a caging group as a fluorescence-controller locks the spirolactone into a colorless and nonfluorescent form, whereas decaging, a process induced by a specific stimulus, results in a ring-opened form, which yields strong fluorescence. The bridge-caging strategy is feasible for the modular development of NIR probes. Efficient in vivo imaging of photoillumination, hydrogen peroxide, and enzyme have been achieved on the PRB2 scaffold as a photoactivatable fluorophore, PRB2-hν; fluorescent indicator, PRB2-H2 O2 ; and fluorogenic enzyme substrate, PRB2-NTR, respectively.

19.
Ophthalmic Genet ; 39(4): 473-476, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29947569

RESUMO

PURPOSE: To identify the disease-causing gene of a four-generation Chinese family with congenital cataract. METHODS: To screen the disease-causing gene of the family, six disease genes of congenital cataract are screened by direct DNA sequencing, the cDNA of wild-type (WT) MIP gene, and P191R mutant MIP gene (MT) were constructed into pEGFP-C1 vector and pGH19 vector. The recombinant plasmids of pEGFP-C1, WT, and mutant MIP were transfected into Hela cell to check the localization and HEK293T cells to detect expression level of protein. The cRNA of WT and MT MIP gene were injected into Xenopus oocytes to measure the swelling rate. RESULTS: A novel missense mutation c.572C>G(p.P191R)at exon 3 of the MIP gene was identified and co-segregated with disease in the Chinese family. The same amount of pEGFP-WT MIP and pEGFP- P191R MIP plasmids were transfected in Hela cells. Confocal microscopy imaging showed that WT MIP protein predominantly localized on the plasma membrane, the mutant protein was rich in the cytoplasm in Hela cells. Western blot results show that the expression level of P191R mutant MIP was significantly lower than WT MIPincell membrane enriched lysates in HEK293T cells. Xenopus oocytes swelling assay showed that the P191R mutation reduces the swelling rate of Xenopus oocytes. CONCLUSIONS: The novel missense mutation c.572C>G(p.P191R)at exon 3 of the MIP gene was identified in a Chinese family of congenital cataract. The mutation affects the traffic of MIP protein in the cells and reduces the expression level of MIP protein in the cell membrane. The mutation of MIP gene reduces the swelling ratio of Xenopus oocytes.


Assuntos
Aquaporinas/genética , Grupo com Ancestrais do Continente Asiático/genética , Catarata/congênito , Catarata/genética , Proteínas do Olho/genética , Mutação de Sentido Incorreto , Animais , Western Blotting , Pré-Escolar , China/epidemiologia , Éxons/genética , Feminino , Células HeLa , Humanos , Masculino , Oócitos/patologia , Linhagem , Plasmídeos , Análise de Sequência de DNA , Transfecção , Xenopus laevis
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