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1.
Sci Total Environ ; 689: 743-753, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31280156

RESUMO

In order to provide an overall evaluation and characterization of the comfort sensation and performance of face mask related to breathing resistance for healthcare in fog and haze weather, and address the influence of structural features on breathing resistance properties, an experimental set-up was developed, which was able to continuously change the direction and rate of air flow and the breathing frequency to simulate the dynamic breathing process during the actual wearing of face mask. The dynamic changes of airflow rate and the breathing resistance were acquired by a virtual instrument (VI) system and a microelectronics system. Six evaluation indices were defined for the dynamic performance and comfort sensation of face mask, derived from the source data of dynamic breathing resistance. Twelve types of face masks from different department stores with different features such as shape, respiratory valve, brand, main materials and protection level were tested using the experimental set-up. The one-way ANOVA analysis was carried out to identify the significance of the differences of the indices among the test masks. The results showed that each evaluation index was significantly different (P < 0.05) among different test masks. The change rate of breathing resistance could be obtained using the dynamic measurement of breathing resistance and could be applied for the dynamic performance evaluation of face mask compared with the static measurement of breathing resistance under constant airflow rate. The influences of structural features such as respiratory valve, shape and main materials on breathing resistance were evaluated and analyzed. The face masks with respiratory valve had lower change rate of breathing resistance. Moreover, the cup type mask had lower change rate of breathing resistance than the folding mask. Furthermore, the cotton mask had lower change rate of breathing resistance than the nonwoven fabric mask.

2.
Chem Commun (Camb) ; 55(26): 3789-3792, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30864584

RESUMO

A facile and efficient method to form a chiral multi-substituted 3H-spiro[benzofuran-2,1'-cyclopentane] structural unit has been developed via a one-pot [3+2] cyclization/semipinacol rearrangement cascade. A catalysis system of Cu(ii)/BOX has been used to efficiently construct a key stereogenic center via a cyclization between substituted benzoquinones and allylic alcohols affording the desired products in good yields and with excellent enantioselectivities and diastereoselectivities (21 examples; up to 67% yields; up to 92% ee and up to >20 : 1 dr). This method provides an alternative strategy for the synthesis of the corresponding bioactive molecules containing spiro[benzofurancyclopentane] skeleton units.

3.
Int J Mol Med ; 43(4): 1866-1878, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720049

RESUMO

Beclin1, a key regulator of autophagy, has been demonstrated to be associated with cancer cell resistance to chemotherapy. Paclitaxel is a conventional chemotherapeutic drug used in the clinical treatment of breast cancer. However, the function and mechanism of Beclin1 in paclitaxel­mediated cytotoxicity in breast cancer are not well defined. The present study demonstrated that paclitaxel suppressed cell viability and Beclin1 expression levels in BT­474 breast cancer cells in a dose­ and time­dependent fashion. Compared with the control, the knockdown of Beclin1 significantly enhanced breast cancer cell death via the induction of caspase­dependent apoptosis following paclitaxel treatment in vitro (P<0.05). In a BT­474 xenograft model, paclitaxel achieved substantial inhibition of tumor growth in the Beclin1 knockdown group compared with the control group. Furthermore, analysis of the publicly available Gene Expression Omnibus datasets revealed a clinical correlation between Beclin1 levels and the response to paclitaxel therapy in patients with breast cancer. Collectively, the present results suggest that Beclin1 protects breast cancer cells from apoptotic death. Thus, the inhibition of Beclin1 may be a novel way to improve the effect of paclitaxel. Additionally, Beclin1 may function as a favorable prognostic biomarker for paclitaxel treatment in patients with breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Proteína Beclina-1/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Paclitaxel/farmacologia , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Sci Rep ; 7: 45952, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28383024

RESUMO

Salt-sensitive hypertension (SSHT) leads to kidney interstitial fibrosis. However, the potential mechanisms leading to renal fibrosis have not been well investigated. In present study, Dahl salt-sensitive (DS) rats were divided into three groups: normal salt diet (DSN), high salt diet (DSH) and high salt diet treated with hydrochlorothiazide (HCTZ) (DSH + HCTZ). A significant increase in systolic blood pressure (SBP) was observed 3 weeks after initiating the high salt diet, and marked histological alterations were observed in DSH rats. DSH rats showed obvious podocyte injury, peritubular capillary (PTC) loss, macrophage infiltration, and changes in apoptosis and cell proliferation. Moreover, Wnt/ß-catenin signaling was significantly activated in DSH rats. However, HCTZ administration attenuated these changes with decreased SBP. In addition, increased renal and urinary Wnt4 expression was detected with time in DSH rats and was closely correlated with histopathological alterations. Furthermore, these alterations were also confirmed by clinical study. In conclusion, the present study provides novel insight into the mechanisms related to PTC loss, macrophage infiltration and Wnt/ß-catenin signaling in SSHT-induced renal injury and fibrosis. Therefore, multi-target therapeutic strategies may be the most effective in preventing these pathological processes. Moreover, urinary Wnt4 may be a noninvasive biomarker for monitoring renal injury after hypertension.

5.
Expert Rev Vaccines ; 16(5): 515-524, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28277801

RESUMO

BACKGROUND: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup A and C-tetanus toxoid conjugate vaccine (Hib-MenAC). METHODS: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3-5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint. RESULTS: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination. CONCLUSIONS: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months.


Assuntos
Vacinas Anti-Haemophilus/imunologia , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Anticorpos Antibacterianos/sangue , China , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Humanos , Lactente , Masculino , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis Sorogrupo A/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Placebos/administração & dosagem , Método Simples-Cego , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/efeitos adversos , Toxoide Tetânico/imunologia , Resultado do Tratamento , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
6.
Mil Med Res ; 3: 37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27980800

RESUMO

BACKGROUND: People rapidly ascending to high altitudes (>2500 m) may suffer from acute mountain sickness (AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk. METHODS: The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the PubMed and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios (ORs) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P < 0.05. We also computed 95% confidence intervals (CIs). Data extracted from the articles were analyzed with Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). RESULTS: We used seven case-control studies including 694 smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking (OR = 0.71, 95% CI 0.52-0.96, P = 0.03). CONCLUSIONS: We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.


Assuntos
Doença da Altitude/complicações , Doença da Altitude/epidemiologia , Fumar/epidemiologia , Adulto , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Fatores de Risco , Adulto Jovem
7.
Sci Rep ; 6: 32610, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27600466

RESUMO

Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury.


Assuntos
Túbulos Renais/lesões , Túbulos Renais/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteína Wnt4/metabolismo , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Adulto , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Creatinina/sangue , Feminino , Imunofluorescência , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/fisiopatologia , Regulação para Cima , Proteína Wnt4/urina
8.
Expert Rev Vaccines ; 15(7): 803-13, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27206811

RESUMO

INTRODUCTION: Enterovirus A71 (EV71) is the predominant causative agent of hand, foot, and mouth disease (HFMD), which is often associated with severe cases and even deaths. EV71-associated epidemics have emerged as a serious threat to public health, particularly in the Asia-Pacific region. AREAS COVERED: We searched PubMed using the terms 'enterovirus 71', 'hand, foot, and mouth disease', and 'vaccine', with no date or language restrictions for all publications before April 27, 2016. Among various vaccine candidates, the alum-adjuvant inactivated EV71 vaccines are most promising. Three alum-adjuvant inactivated EV71 vaccines developed by mainland China showed high efficacy, good immunogenicity persistence and acceptable safety profiles in clinical trials. Recently, two of these EV71 vaccines have been approved for marketing in China and the other one is undergoing the review process of licensure. In this manuscript, we summarized previous study results as well as discussed the regulatory affairs and post-market surveillances issues. Expert commentary: The marketing of EV71 vaccines is a milestone in the controlling of HFMD. International clinical trials are needed to further assess the efficacy and cross-immunogenicity. Establishing a sensitive pathogen monitoring system would be essential to monitor the variation of genotypes and control HFMD epidemics.


Assuntos
Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Ásia , China , Ensaios Clínicos como Assunto , Aprovação de Drogas , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos
9.
Am J Nephrol ; 43(2): 129-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27058841

RESUMO

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. METHODS: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA2R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA2R was assessed by immunofluorescence. RESULTS: Most patients with IMN displayed both gPLA2R and sPLA2R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA2R or sPLA2R-Ab positive. The sPLA2R-Ab titre, not gPLA2R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA2R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA2R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA2R intensity and outcome. CONCLUSIONS: These data indicate that sPLA2R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA2R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.


Assuntos
Anticorpos/sangue , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/metabolismo , Glomérulos Renais/química , Receptores da Fosfolipase A2/análise , Receptores da Fosfolipase A2/imunologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
10.
PLoS One ; 11(1): e0147084, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26765329

RESUMO

Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1) is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG) mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO) model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT) mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/ß-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/ß-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis.


Assuntos
Expressão Gênica , Heme Oxigenase-1/genética , Nefrite Intersticial/etiologia , Nefrite Intersticial/patologia , Obstrução Ureteral/complicações , Animais , Apoptose/genética , Proliferação de Células , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica , Camundongos , Miofibroblastos/metabolismo , Regulação para Cima , Via de Sinalização Wnt
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 31(6): 517-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27215019

RESUMO

OBJECTIVE: Highland natives adapt well to the hypoxic environment at high altitude (HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial ni- tric oxide synthase (ENOS) G894T polymorphism contributed to the physiology and pathophysiology of hu- mans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894T polymorphism and HA adaptation through analyzing the published data. METHODS: We searched all relevant literature about the ENOS G894T polymorphism and HA adaptation in PubMed, Med- line, and Embase before Step 2015. A random-effects model was applied (Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. RESULTS: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups (OR = 1.85; 95% Cl, 1.47-2.33; P < 0.0001). In addition, the GG genotype was significantly associated with HA adaptation (OR = 1.99; 95% Cl, 1.54-2.57; P < 0.0001). CONCLUSION: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.


Assuntos
Adaptação Fisiológica/genética , Altitude , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Genótipo , Humanos
12.
Huan Jing Ke Xue ; 33(10): 3489-94, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23233978

RESUMO

The carrier is the key influencers in moving bed biofilm reactor( MBBR), in this paper, a pilot scale apparatus was set up for treating municipal wastewater using modified cubic polyurethane carriers. For MBBR, the capacity of 3-3.5 t x d(-1), hydraulic residence time of 7-8 h, under the condition of continuous feed water (COD:140-280 mg x L(-1), NH4+ -N:30-50 mg x L(-1), TN: 45-65 mg x L(-1), TP:2.5-4.0 mg x L(-1)), the speed of biofilm formation and removal effects of COD, nitrogen and phosphorus were studied. After 140 days, the results showed that the formation of biofilm on the carrier was very quickly under 24-28 degrees C, and obtained stable treatment effect about 6 days. The COD, NH4+ -N, TN, TP average removal rates were 70%, 97%, 70%, 39%, respectively. As the temperature gradually decreased to about 12 degrees C, a high NH4+ -N removal rate (97%) could still be maintained, which indicating that the modified carrier can be achieved a high nitrification rate at low temperature.


Assuntos
Compostos de Amônio/isolamento & purificação , Biofilmes , Nitrogênio/isolamento & purificação , Poliuretanos/química , Eliminação de Resíduos Líquidos/métodos , Compostos de Amônio/metabolismo , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos/microbiologia , Cidades , Nitrogênio/metabolismo , Oxigênio/química , Oxigênio/isolamento & purificação , Projetos Piloto , Esgotos/química , Águas Residuárias/química
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 28(7): 718-21, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22768862

RESUMO

AIM: To optimize the expression and purification protocol for human scFv antibody against-amyloid peptide. METHODS: Expression of E3 scFv was induced by different concentrations of IPTG under the fixed condition of time period and temperature, and the optimal concentration of IPTG was determined by SDS-PAGE analysis on E3 scFv expression level. Furthermore, elution buffer with different concentrations of imidazole was used for pre-eluting to determine the optimal pre-eluting condition by Western blotting against E3 scFv. RESULTS: We obtained the highest expression of E3 scFv after 18 h induction with 0.1 mmol/L IPTG under 20 Degrees Celsius. In addition, Western blotting indicated the highest purity of E3 scFv when the resin was pre-eluted with the buffer containing 10 mmol/L imidazole. CONCLUSION: Through optimizing the above mentioned conditions, we established an improved strategy for high expression and efficient purification of E3 scFv, which paves the way for further research.


Assuntos
Peptídeos beta-Amiloides/imunologia , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/isolamento & purificação , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/isolamento & purificação , Anticorpos de Cadeia Única/imunologia
14.
Radiat Oncol ; 5: 70, 2010 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-20704701

RESUMO

BACKGROUND: Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. METHODS: DNA-PKcs epitopes were predicted and cloned. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA damage repair was analyzed by comet assay and immunofluorescence detection of gammaH2AX foci. The radiosensitization in vivo was determined on Balb/c athymic mice transplanted tumours of HeLa cells. RESULTS: Four epitopes of DNA-PKcs have been predicted and expressed as the antigens, and a specific human anti-DNA-PKcs scFv antibody gene, anti-DPK3-scFv, was obtained by screening the phage antibody library using the DNA-PKcs peptide DPK3. The specificity of anti-DPK3-scFv was verified, in vitro. Transfection of HeLa cells with the anti-DPK3-scFv gene resulted in an increased sensitivity to IR, decreased repair capability of DNA double-strand breaks (DSB) detected by comet assay and immunofluorescence detection of gammaH2AX foci. Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. Measurement of the growth and apoptosis rates showed that anti-DPK3-scFv enhanced the sensitivity of tumours transplanted in Balb/c athymic mice to radiation therapy. CONCLUSION: The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential.


Assuntos
Proteína Quinase Ativada por DNA/antagonistas & inibidores , Neoplasias/genética , Neoplasias/terapia , Tolerância a Radiação/genética , Anticorpos de Cadeia Única/uso terapêutico , Animais , Especificidade de Anticorpos , Proliferação de Células , Ensaio Cometa , Quebras de DNA de Cadeia Dupla , Reparo do DNA/fisiologia , Terapia Genética/métodos , Células HeLa , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Nus , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/genética , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(3): 250-2, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20230690

RESUMO

AIM: To clone human anti-soman transition state analogues antibodies from a large single-chain phage antibody library. METHODS: An organophosphorus hapten P6 [O1-methyl-O2-(1, 2, 2-trimethylpropyl)-2-hydroxy-5-nitrophenyl methylphosphonic acid] was synthesized. Its chemical conjugate with bovine serum albumin (BSA) was used as antigen (P6-BSA) to screen antibodies against soman. Panning of a large single-chain phage antibody library was conducted to select specific antibodies against soman. The antigen binding characteristics were analyzed by ELISA. RESULTS: After 4 rounds of panning, 14 clones had specific binding ability to P6. DNA fingerprinting showed that diverse specific human scFvs against P6 was obtained from the library by biopanning. CONCLUSION: Human anti-soman transition state analogues scFvs have been cloned from large phage antibody library.


Assuntos
Clonagem Molecular , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/genética , Soman/imunologia , Humanos , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/isolamento & purificação , Soman/análogos & derivados
16.
Opt Lett ; 34(16): 2471-3, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19684819

RESUMO

The ultrafast third-order nonlinear optical properties of ZnPc(OBu)(6)(NCS)/dimethyl sulfoxide solution are investigated by optical Kerr effect (OKE) and pump-probe techniques with femtosecond pulses. Using CS(2) as the reference, the third-order susceptibility of the sample solution is obtained as about 1.40x10(-14) esu at a concentration of 3.00x10(-5) M. The second hyperpolarizability for the sample solution is deduced to be as large as 2.35x10(-31) esu. The dynamic characteristics of the nonlinear optical response and the origins of the OKE signal can be attributed to excited singlet state populations.

17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 24(9): 878-80, 2008 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-18782521

RESUMO

AIM: To clone human anti-TNF-alpha scFv from large phage antibody library. METHODS: Panning of large phage library against TNF-alpha was conducted to select specific antibodies. The antigen binding activity and DNA sequence were determined and analyzed by ELISA, restriction enzyme map. RESULTS: After 4 rounds of panning, 62 positive clones were obtained and 27 clones had specific binding ability to TNF-alpha. DNA fingerprinting of the 27 clones showed 7 different stripes indicated 7 different positive clones. 5 of the 7 clones expressed soluble anti-TNF-alpha activity. DNA sequence analysis showed that the variable regions of these scFvs belonged to different subgroups. CONCLUSION: Human TNF-alpha scFv have been successfully obtained from large phage antibody library.


Assuntos
Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Biblioteca de Peptídeos , Fator de Necrose Tumoral alfa/imunologia , Anticorpos/genética , Anticorpos/imunologia , Humanos , Fator de Necrose Tumoral alfa/genética
18.
J Comb Chem ; 10(1): 79-87, 2008 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18062672

RESUMO

Glycoconjugates can be artificially synthesized by combinatorial biocatalysis. An example is given in this paper describing the construction of glycoconjugates array by using glycosidase and lipase in nonaqueous media. This array was started from glucose, with three aryl alcohols as the aglycone moiety of glycosides and five acids or esters as acyl donors for combinatorial acylation of glycosides, affording a three-dimensional array containing about 30 members with diverse structures. The array would be more abundant if more aglycones and acyl donors with other structures were filled in. Indeed, diverse classes of carbohydrates besides glucose can also be employed for generating diverse glycoconjugates due to their different roles in numerous physiological responses. The composition and distribution of the demonstration glycoconjugates array was detected and evaluated by HPLC-MS with electrospray ionization. And also, the distribution of the artificial array can be adjusted by changing the molar ratio of the auxiliary materials.


Assuntos
Técnicas de Química Combinatória/métodos , Glicoconjugados/síntese química , Glicosídeo Hidrolases/química , Glicosídeos/química , Lipase/química , Acilação , Catálise , Cromatografia Líquida de Alta Pressão , Glicoconjugados/química , Modelos Moleculares , Estrutura Molecular
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 25(7): 1088-91, 2005 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16241062

RESUMO

The interaction of water-soluble p-(N, N-dimethylaminomethyl) calix [8] arene (CX8) with DNA was studied using adriamycin(ADM) as a probe by fluorescent spectrometry. The effect factors such as, pH of solution, salt effect and unlinking DNA on the spectra were also investigated. The interaction mechanism was proposed. The authors observed that the fluorescence of ADM was quenched by calf thymus DNA, and the fluorescence intensity of DNA-ADM enhanced with the increasing of the CX8 gradually. The result indicates that the strong electrostatic interaction between the oxyphosphate anion of DNA and the CX8 existed. According to the plot of scatchard, the results imply that the influence of CX8 on interaction of DNA-ADM belongs to mixed model, on the one hand, in the condition of neutral and acidity, the oxyphosphate anion of DNA can be neutralized by CX8 partially, which induced the contraction of DNA and the conformational change of DNA, which led to release ADM from DNA partially, on the other hand, the CX8 can also compete the electrostatic sites with ADM directly.


Assuntos
Calixarenos/química , DNA/química , Espectrometria de Fluorescência , Algoritmos , Animais , Bovinos , Doxorrubicina/química , Fluorescência , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , Solubilidade , Água/química
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 25(4): 591-3, 2005 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16097694

RESUMO

The inclusion interaction of water-soluble p-(N,N-dimethylaminomethyl)-calix[8]arene with diphenylamine-4-sulfonic acid sodium salt was investigated by fluorimetric method. When diphenylamine-4-sulfonic acid sodium salt was added into the p-(N,N-dimethylaminomethyl)-calix[8]arene solution, the emission spectrum of diphenylamine-4-sulfonic acid sodium salt occurred to a blue shift with the enhancement of the fluorescent intensity. The results show that the formation of the inclusion complex of the p-(N,N-dimethylaminomethyl)-calix[8]arene with diphenylamine-4-sulfonic acid sodium salt. The influence factors such as the pH value of solutions, solvents on the emission and excitation spectra of the inclusion complex were studied. It indicates that diphenylamine-4-sulfonic acid sodium salt penetrated the cavity of the calix[8]arene via the static action between the sulphonyl group of diphenylamine-4-sulfonic acid sodium salt and nitrogen atom of p-(N,N-dimethylaminomethyl)-calix[8]arene and the hydrophobic interaction of the aromatic rings.


Assuntos
Benzenossulfonatos/química , Calixarenos/química , Difenilamina/análogos & derivados , Difenilamina/química , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Solubilidade , Espectrometria de Fluorescência/métodos , Água/química
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