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1.
Mol Reprod Dev ; 91(1): e23728, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282314

RESUMO

Infertility has become a global disease burden. Although assisted reproductive technologies are widely used, the assisted reproduction birth rate is no more than 30% worldwide. Therefore, understanding the mechanisms of reproduction can provide new strategies to improve live birth rates and clinical outcomes of enhanced implantation. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in various biological processes and diseases in many species. In this review, we especially focus on the role of lncRNAs in human reproduction. We summarize the function and mechanisms of lncRNAs in processes vital to reproduction, such as spermatogenesis and maturation, sperm motility and morphology, follicle development and maturation, embryo development and implantation. Then, we highlight the importance and diverse potential of lncRNAs as good diagnostic molecular biomarkers and therapeutic targets for infertility treatment.


Assuntos
Infertilidade , RNA Longo não Codificante , Humanos , Masculino , RNA Longo não Codificante/genética , Motilidade dos Espermatozoides , Reprodução/genética , Espermatogênese/genética
2.
Int Wound J ; 21(4): e14613, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38158647

RESUMO

There is much controversy about the application of abdominal irrigation in the prevention of wound infection (WI) and intra-abdominal abscess (IAA) in the postoperative period. Therefore, we performed a meta-analysis of the effect of suctioning and lavage on appendectomy to assess the efficacy of either suctioning or lavage. Data were collected and estimated with RevMan 5.3 software. Based on our research, we found 563 publications in our database, and we eventually chose seven of them to analyse. The main results were IAA after the operation and WI. Inclusion criteria were clinical trials of an appendectomy with suctioning or lavage. In the end, seven trials were chosen to meet the eligibility criteria, and the majority were retrospective. The results of seven studies showed that there was no statistically significant difference between abdominal lavage and suctioning treatment for post-operative WI (OR, 1.82; 95% CI, 0.40, 2.61; p = 0.96); There was no statistically significant difference between the two groups in the risk of postoperative abdominal abscess after operation (OR, 1.16; 95% CI, 0.71, 1.89; p = 0.56). No evidence has been found that the use of abdominal lavage in the treatment of postoperative infectious complications after appendectomy is superior to aspiration.


Assuntos
Abscesso Abdominal , Apendicite , Laparoscopia , Humanos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Sucção/efeitos adversos , Sucção/métodos , Irrigação Terapêutica , Apendicite/cirurgia , Estudos Retrospectivos , Abscesso Abdominal/etiologia , Abscesso Abdominal/prevenção & controle , Abscesso Abdominal/cirurgia , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Complicações Pós-Operatórias/etiologia , Laparoscopia/métodos
3.
Reprod Biomed Online ; 46(3): 511-518, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36621365

RESUMO

RESEARCH QUESTION: Are QL1012 and Gonal-f® equivalent in women undergoing ovarian stimulation for assisted reproductive technology (ART)? DESIGN: This multicentre, randomized, assessor-blinded, phase-three trial was conducted at 13 centres in China. Eligible patients were infertile women; age 20-39 years; body mass index 18-30 kg/m2; regular menstrual cycles; and indication for ART. After successful pituitary downregulation, patients were randomly assigned (1:1) to receive QL1012 or Gonal-f®, stratified by age (initial dose of 75-150 IU for women younger than 30 years, 150-225 IU for women aged 30-34 years and 225-300 IU for women aged ≥35 years, subcutaneously, once daily). The primary end point was the number of oocytes retrieved. RESULTS: Between October 2018, and June 2019, 341 patients were included in the per-protocol set. The mean numbers of oocytes retrieved were 14.7 ± 7.0 in the QL1012 group (n = 169) and 13.4 ± 6.1 in the Gonal-f® group (n = 172). Adjusted by analysis of covariance model, the least-squares mean difference was 1.3 oocytes (95% CI -0.1 to 2.7; P = 0.0650), within the pre-defined equivalence margins of ±3.0. Similar results were observed in the full analysis set. Additionally, no statistical differences were found in secondary end points except oestradiol concentration (median 3948.0 pg/ml versus 3545.3 pg/ml; P = 0.0015). Ovarian hyperstimulation syndrome (12.4% versus 13.1 %) and other adverse events were similar between the two groups. CONCLUSIONS: Therapeutic equivalence and similar safety profiles were demonstrated between QL1012 and Gonal-f® in women undergoing ovarian stimulation for ART.


Assuntos
Medicamentos Biossimilares , Infertilidade Feminina , Feminino , Humanos , Hormônio Foliculoestimulante Humano , Medicamentos Biossimilares/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/métodos , Proteínas Recombinantes , Hormônio Foliculoestimulante/uso terapêutico , Fertilização in vitro/métodos
4.
Environ Sci Technol ; 57(14): 5633-5645, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36972473

RESUMO

Microplastics (MPs) and oil pollution are major concerns in oceans. Although their coexistence in oceans and the associated MP-oil-dispersant agglomerates (MODAs) have been reported, limited attention is given to the behavior of the co-contaminants. This study investigated MODA transport in a simulated ocean system and explored related mechanisms under various oil types, salinities, and mineral concentrations. We found that more than 90% of the heavy oil-formed MODAs stayed at the seawater surface, while the light oil-formed MODAs were widely distributed throughout the seawater column. The increased salinity promoted MODAs formed by 7 and 90 µm MPs to transport from the seawater surface to the column. This was elucidated by the Derjaguin-Landau-Verwey-Overbeek theory as more MODAs formed under higher salinities and dispersants kept them stable in the seawater column. Minerals facilitated the sinking of large MP-formed MODAs (e.g., 40 µm) as minerals were adsorbed on the MODA surface, but their impact on small MP-formed MODAs (e.g., 7 µm) was negligible. A MODA-mineral system was proposed to explain their interaction. Rubey's equation was recommended to predict the sinking velocity of MODAs. This study is the first attempt to reveal MODA transport. Findings will contribute to the model development to facilitate their environmental risk evaluation in oceans.


Assuntos
Poluição por Petróleo , Petróleo , Poluentes Químicos da Água , Plásticos , Microplásticos , Poluentes Químicos da Água/análise , Tensoativos , Água do Mar , Minerais
5.
BMC Pregnancy Childbirth ; 23(1): 607, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620792

RESUMO

BACKGROUND: It is still urgent and challenge to develop a simple risk assessment scale for venous thromboembolism (VTE) in puerperium in Chinese women. METHODS: The study, a retrospective case-control study, was conducted in 12 hospitals in different cities in China. A total of 1152 pregnant women were selected, including 384 cases with VTE and 768 cases without VTE. A logistic regression method was conducted to determine the risk factors of VTE. RESULTS: Age, BMI before delivery, gestational diabetes mellitus, family history (thrombosis, diabetes, cardiovascular disease), and assisted reproductive technology were independent risk factors (P<0.05). The difference between the high-risk group and the low-risk group was statistically significant(P<0.001) with a sensitivity of 0.578, specificity of 0.756, Yuden index o.334, and area under the ROC curve of 0.878. CONCLUSIONS: The age (≥ 35 years), BMI before delivery (≥ 30 kg/m2), gestational diabetes mellitus, family history of related diseases and assisted reproductive technology are more likely to cause VTE after full-time delivery. The simple and rapid assessment scale of VTE in women after full-term delivery has perfect discrimination (P < 0.001), which can be applied to predict the risk of VTE in Chinese full-term postpartum women.


Assuntos
Diabetes Gestacional , Tromboembolia Venosa , Gravidez , Feminino , Humanos , Adulto , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Diabetes Gestacional/diagnóstico , Estudos de Casos e Controles , População do Leste Asiático , Estudos Retrospectivos , Período Pós-Parto
6.
Ecotoxicol Environ Saf ; 259: 115015, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37201423

RESUMO

BACKGROUND: Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. METHODS: This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015-2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. RESULTS: Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. CONCLUSIONS: Our results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , China , Fertilização in vitro , Conceitos Meteorológicos , Material Particulado/efeitos adversos , Material Particulado/análise
7.
J Assist Reprod Genet ; 40(12): 2913-2923, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770818

RESUMO

PURPOSE: Infertility remains a human health burden globally. Only a fraction of embryos produced via assisted reproductive technologies (ARTs) develop to the blastocyst stage in vitro. lncRNA abundance changes significantly during human early embryonic development, indicating vital regulatory roles of lncRNAs in this process. The aim of this study is to obtain insights into the transcriptional basis of developmental events. METHODS: scRNA-seq data and SUPeR-seq data were used to investigate the lncRNA profiles of human preimplantation embryos. The top 50 highly expressed unique and shared lncRNAs in each stage of preimplantation development were identified. Comparative analysis of the two datasets was used to verify the consistent expression patterns of the lncRNAs. Differentially expressed lncRNAs were identified and subjected to functional enrichment analysis. RESULTS: The lncRNA profiles of human preimplantation embryos in the E-MTAB-3929 dataset were similar to those in the GSE71318 dataset. The ratios of overlap among the top 50 highly expressed lncRNAs between two pairs of stages (2-cell stage vs. 4-cell stage and 8-cell stage vs. morula) were aberrantly low compared with those between other stages. Each stage of preimplantation development exhibited unique and shared lncRNAs among the top 50 highly expressed lncRNAs. Among the between-group comparisons, the 2-cell stage vs. 4-cell stage showed the highest number of differentially expressed lncRNAs. Functional enrichment analysis revealed that differentially expressed lncRNAs and their associated super enhancers and RNA binding proteins (RBPs) are closely involved in regulating embryonic development. These lncRNAs could function as important cell markers for distinguishing fetal germ cells. CONCLUSIONS: Our study paves the way for understanding the regulation of developmental events, which might be beneficial for improved reproductive outcomes.


Assuntos
RNA Longo não Codificante , Transcriptoma , Gravidez , Feminino , Humanos , Transcriptoma/genética , RNA Longo não Codificante/genética , Desenvolvimento Embrionário/genética , Blastocisto/metabolismo , Mórula/metabolismo , Perfilação da Expressão Gênica
8.
J Obstet Gynaecol ; 43(1): 2152660, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36534044

RESUMO

Heterotopic pregnancy (HP) is a rare but potentially life-threatening event with a high risk of maternal death, which also jeopardise the coexisting intrauterine pregnancy (IUP), thus an early accurate diagnosis and prompt treatment can decrease adverse complications. We aimed to explore the early predictors for pregnancy outcomes of HP. We reviewed patients with HP following assisted reproductive technology in our institution between January 2013 and December 2020. The relationships between pregnancy outcomes and clinical features were analysed by logistic regression. We found that 29 patients (72.5%) of HP were accurately diagnosed by transvaginal ultrasonography (TVS). Eighteen patients in the surgery group had live births, three of whom delivered preterm. Additionally, the miscarriage rate was lower for patients with IUP cardiac activity than those without (16.7% vs. 90.0%, p < .001). Further by logistic regression analysis, an IUP with cardiac activity at HP diagnosis was identified as favourable independent predictor of live birth (p < .001). Therefore, early diagnosis and prompt surgical intervention are recommended to prevent the development of HP.Impact of statementWhat is already known on this subject? Heterotopic pregnancy (HP) has long been thought to be a rare but potentially life-threatening event with a high risk of complications. The early diagnosis of HP is challenging due to the co-existence of a viable intrauterine pregnancy (IUP) and the absence of typical clinical symptoms.What do the results of this study add? This stduy showed that symptoms combined with routine transvaginal ultrasonography (TVS) scans reduce the rates of misdiagnosis of HP and prompt surgical intervention after diagnosis may minimise the incidence of miscarriage of the IUP.What are the implications of these findings for clinical practice and/or further research? An IUP with cardiac activity at HP diagnosis is a predictor of a favourable prognosis of HP, and laparoscopy under general anaesthesia is effective and safe during the first trimester of pregnancy. Awareness, assessment and early interventions in view of symptoms combined with routine TVS is recommended to reduce the risk of miscarriage and ensure a favourable live birth rate.


Assuntos
Aborto Espontâneo , Gravidez Heterotópica , Feminino , Humanos , Recém-Nascido , Gravidez , Aborto Espontâneo/etiologia , Transferência Embrionária , Fertilização in vitro , Gravidez Heterotópica/diagnóstico por imagem , Gravidez Heterotópica/terapia , Estudos Retrospectivos
9.
Environ Res ; 212(Pt E): 113602, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35660568

RESUMO

The challenge from pathogenic infections still threatens the health and life of people in developing areas. An efficient, low-cost, and abundant-resource disinfection method is desired for supplying safe drinking water. This study aims to develop a novel Ti3+ doping TiO2 nanoparticle decorated ceramic disk filter (Ti3+/TiO2@CDF) for point-of-use (POU) disinfection of drinking water. The production of Ti3+/TiO2@CDF was optimized to maximize disinfection efficiency and flow rate. Under optimal conditions, the log reduction value (LRV) could reach up to 7.18 and the flaw rate was 108 mL/h. The influences of environmental factors were also investigated. Natural or slightly alkaline conditions, low turbidity, and low concentration of humic acid were favorable for the disinfection of Ti3+/TiO2@CDF, while co-existing HCO3- ions and diatomic cations (Ca2+ and Mg2+) exhibited the opposite effect. Furthermore, the practicability and stability of Ti3+/TiO2@CDF was demonstrated. Ti3+/TiO2@CDF showed high disinfection efficiency for E. coli and S. aureus under a range of concentrations. Long-term experiment indicated that Ti3+/TiO2@CDF was stable. The underlying disinfection mechanisms were investigated and concluded as the combination of retention, adsorption, and photocatalytic disinfection. The developed Ti3+/TiO2@CDF can provide an effective and reliable disinfection tool for POU water treatment in remote area.


Assuntos
Água Potável , Nanopartículas , Purificação da Água , Catálise , Cerâmica , Desinfecção/métodos , Escherichia coli , Humanos , Staphylococcus aureus , Titânio , Purificação da Água/métodos
10.
J Obstet Gynaecol Res ; 48(2): 440-447, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34889489

RESUMO

AIM: Intrauterine device (IUD) is a commonly used contraceptive method worldwide. Abnormal uterine bleeding (AUB) is one of the most common side effects of Cu-IUDs. Since AUB varies among Cu-IUD users, changes in the bleeding-related genetic factors may contribute to AUB. This study aimed to determine the genetic risk factors of AUB after Cu-IUD insertion. METHODS: We conducted a case-control study on women who experienced AUB after Cu-IUD insertion (case:control = 62:59). Six candidate variants were genotyped using the Sequenom MassARRAY. Genotype and allele frequencies were analyzed using SHEsisPlus. We performed Pearson's Chi-squared test to analyze categorical data, and ESEfinder to predict the impact on splicing regulation. RESULTS: MCM8 coding sequence variants: rs3761873-A>C was in Exon 7 and rs16991617 A>G was in Exon 12 of all 19 exons, both of which were significantly different between cases and controls (pallele  = 0.039 and pgenotype  = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R2 > 0.8). ESEfinder indicated that the variants of MCM8 may affect the splicing regulation. CONCLUSIONS: MCM8 rs376187 and rs16991617 were associated with AUB in Cu-IUDs users. MCM8 may play a role in AUB by regulating functions of reproductive organs and primary ovarian insufficiency. Our findings may improve the understanding of the genetic basis of AUB caused by Cu-IUDs.


Assuntos
Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Estudos de Casos e Controles , Feminino , Humanos , Levanogestrel , Proteínas de Manutenção de Minicromossomo , Hemorragia Uterina
11.
Protein Expr Purif ; 178: 105786, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33157199

RESUMO

Protein A, Protein L and KappaSelect affinity resins have been widely used for antibody purification. Elution of antibody bound to these resins is typically achieved by acidic pH. In addition, elution can be moderately adjusted by tuning the salt concentration in mobile phase as hydrophobic interactions play a major role in binding. In this study, we assessed the impact of salt concentration in mobile phase on antibody retention in these three types of affinity chromatography. The data suggest that salt concentration has a bigger impact on retention in the two light chain-binding affinity columns (i.e., Protein L and KappaSelect) than in Protein A column. In particular, lowering salt concentration in mobile phase for Protein L and KappaSelect columns allows elution become feasible at higher pH. In addition, this finding suggests that wash in these two types of column aimed at removing weakly-bound byproducts can also be performed at increased pH by lowering salt concentration in the wash buffer. Rendering wash and elution feasible at higher pH has practical value for cases where the target antibodies are sensitive to stringent conditions.


Assuntos
Anticorpos/isolamento & purificação , Proteínas de Bactérias/química , Cromatografia de Afinidade , Cloreto de Sódio/química , Proteína Estafilocócica A/química , Anticorpos/química , Humanos
12.
BMC Pregnancy Childbirth ; 21(1): 814, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879850

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the critical causes of adverse perinatal outcomes. A reliable estimate of GDM in early pregnancy would facilitate intervention plans for maternal and infant health care to prevent the risk of adverse perinatal outcomes. This study aims to build an early model to predict GDM in the first trimester for the primary health care centre. METHODS: Characteristics of pregnant women in the first trimester were collected from eastern China from 2017 to 2019. The univariate analysis was performed using SPSS 23.0 statistical software. Characteristics comparison was applied with Mann-Whitney U test for continuous variables and chi-square test for categorical variables. All analyses were two-sided with p < 0.05 indicating statistical significance. The train_test_split function in Python was used to split the data set into 70% for training and 30% for test. The Random Forest model and Logistic Regression model in Python were applied to model the training data set. The 10-fold cross-validation was used to assess the model's performance by the areas under the ROC Curve, diagnostic accuracy, sensitivity, and specificity. RESULTS: A total of 1,139 pregnant women (186 with GDM) were included in the final data analysis. Significant differences were observed in age (Z=-2.693, p=0.007), pre-pregnancy BMI (Z=-5.502, p<0.001), abdomen circumference in the first trimester (Z=-6.069, p<0.001), gravidity (Z=-3.210, p=0.001), PCOS (χ2=101.024, p<0.001), irregular menstruation (χ2=6.578, p=0.010), and family history of diabetes (χ2=15.266, p<0.001) between participants with GDM or without GDM. The Random Forest model achieved a higher AUC than the Logistic Regression model (0.777±0.034 vs 0.755±0.032), and had a better discrimination ability of GDM from Non-GDMs (Sensitivity: 0.651±0.087 vs 0.683±0.084, Specificity: 0.813±0.075 vs 0.736±0.087). CONCLUSIONS: This research developed a simple model to predict the risk of GDM using machine learning algorithm based on pre-pregnancy BMI, abdomen circumference in the first trimester, age, PCOS, gravidity, irregular menstruation, and family history of diabetes. The model was easy in operation, and all predictors were easily obtained in the first trimester in primary health care centres.


Assuntos
Diabetes Gestacional/diagnóstico , Aprendizado de Máquina , Modelos Estatísticos , Primeiro Trimestre da Gravidez , Adulto , China , Feminino , Humanos , Gravidez , Atenção Primária à Saúde , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade
13.
Biochem Cell Biol ; 98(2): 277-283, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31608649

RESUMO

Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM), which results in vision loss. This study explored the role of miR-126 in high-glucose-induced human retinal endothelial cells (HRECs) and its underlying molecular mechanisms. The results showed that the expression levels of miR-126 and interleukin-17A (IL-17A) in high-glucose-induced HRECs were downregulated and upregulated, respectively. Functionally, overexpression of miR-126 promoted proliferation and suppressed apoptosis in high-glucose-induced HRECs, while IL-17A reversed the effects induced by miR-126. However, overexpression of IL-17A inhibited the proliferation and induced apoptosis, while knockdown of IL-17A accelerated the proliferation and repressed apoptosis. In addition, miR-126 repressed the expression of IL-17A, Bax, and caspase-3, while promoting the expression of survivin and phosphorylation of PI3K and AKT; restoration of IL-17A rescued these effects. Furthermore, IL-17A was identified as a target of miR-126. This indicates that miR-126 enhances proliferation and inhibits apoptosis in high-glucose-induced HRECs by activating the PI3K-AKT pathway, increasing survivin levels, and decreasing Bax and caspase-3 expression by targeting IL-17A, suggesting that miR-126 could be a novel target for preventing DR.


Assuntos
Apoptose , Retinopatia Diabética/metabolismo , Células Endoteliais/citologia , Interleucina-17/metabolismo , MicroRNAs/metabolismo , Sítios de Ligação , Proliferação de Células , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retina/citologia , Transdução de Sinais/efeitos dos fármacos , Survivina/metabolismo , Proteína X Associada a bcl-2/metabolismo
14.
Protein Expr Purif ; 172: 105635, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268171

RESUMO

Half antibody (one half of an antibody which comprises a heavy chain and a light chain) is a common byproduct in bispecific antibody (bsAb) production and in many cases it represents the major product-related impurity. As half antibody contains only one Fc-domain, it binds Protein A resin weaker than the target bsAb, which contains the full Fc-region. Indeed, Protein A chromatography provides certain resolution between half antibody and the intact bsAb under linear pH gradient elution. Nevertheless, separation between these two species is far from complete under this condition. In this study, we demonstrated that adding salt additive to Protein A mobile phase can significantly improve resolution between half antibody and the intact bsAb, allowing most of the half antibody impurity in the load to be removed by this capture step. Having the majority of half antibody byproduct removed at this early stage is a big advantage as it improves the overall robustness of the downstream process.


Assuntos
Anticorpos Biespecíficos , Cromatografia de Afinidade , Proteína Estafilocócica A/química , Animais , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/isolamento & purificação , Células CHO , Cricetulus , Humanos , Fragmentos Fc das Imunoglobulinas/química
15.
Protein Expr Purif ; 175: 105711, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738435

RESUMO

Asymmetric IgG-like bispecific antibodies (bsAbs) are normally derived from two parental mAbs with different origin. Despite the implementation of heterodimerization-promoting strategy in the design, homodimerization can still occur at a low level during the recombinant production of these molecules. In general, monitoring and removal of homodimers pose great challenges to analytical and purification teams, respectively, as these byproducts share high similarity in physicochemical properties with the target heterodimeric bsAb. Protein L is a bacterial surface protein that binds to the variable region of kappa light chain without interfering with the antigen binding site. In this work, we first showed that different antibodies bind Protein L-conjugated resin with varied strength, and then based on this observation we further demonstrated that Protein L chromatography can be a useful tool for monitoring/separating homodimers during the purification of asymmetric bsAbs.


Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais , Proteínas de Bactérias/química , Proteínas de Ligação a DNA/química , Imunoglobulina G , Multimerização Proteica , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/isolamento & purificação , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Cromatografia Líquida , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificação
16.
Protein Expr Purif ; 175: 105713, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738439

RESUMO

For IgG-like bispecific antibodies (bsAbs) whose construction involves sequence engineering to promote desired heavy chain-light chain pairing, ¾ antibody (antibody lacking one light chain) is a frequent byproduct during their recombinant production. As this byproduct shares high similarity in physicochemical properties with the target bsAb, its removal poses a challenge to downstream purification. Capto L is an affinity resin based on Protein L, which binds to the variable region of kappa light chain without interfering with the antigen binding site. In this work, we demonstrated that Capto L provides a convenient means for separating ¾ antibody from the bsAb product.


Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais , Proteínas de Bactérias/química , Cromatografia de Afinidade , Proteínas de Ligação a DNA/química , Imunoglobulina G , Multimerização Proteica , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/isolamento & purificação , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificação
17.
BMC Cardiovasc Disord ; 20(1): 120, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138681

RESUMO

BACKGROUND: Atherosclerosis (AS) is the basis of cardiovascular diseases, characterized by chronic inflammatory and lipid metabolism disorders. Although the anti-inflammatory effect of Klotho in AS has been clearly shown, its lipid-lowering effect is unclear. In this study, we examined the effects of recombinant Klotho (Re-KL) protein on lipid accumulation in foam cells. METHODS: THP-1 cells were exposed to 100 nM phorbol myristate acetate for 24 h and then to oxidized low-density lipoprotein (ox-LDL; 80 mg/mL) to induce foam cell formation. Subsequently, the foam cells were incubated with Re-KL and/or DKK1, an inhibitor of the Wnt/ß-catenin pathway. RESULTS: Oil red O staining and cholesterol intake assay revealed that the foam cell model was constructed successfully. Pre-treatment of the foam cells with Re-KL decreased total cholesterol level, up-regulated the expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1), and down-regulated the expression of acyl coenzyme a-cholesterol acyltransferase 1 (ACAT1) and members of the scavenger family (SR-A1 and CD36). In addition, the expression of Wnt/ß-catenin pathway-related proteins in foam cells was significantly decreased by the stimulus of Re-KL. Interestingly, the effect of Re-KL was similar to that of DKK1 on foam cells. CONCLUSIONS: The Re-KL-induced up-regulation of reverse cholesterol transport capacity promotes cholesterol efflux and reduces lipid accumulation by suppressing the Wnt/ß-catenin pathway in foam cells.


Assuntos
Anticolesterolemiantes/farmacologia , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Glucuronidase/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Transporte Biológico , Células Espumosas/metabolismo , Humanos , Proteínas Klotho , Metabolismo dos Lipídeos/genética , Lipoproteínas LDL/farmacologia , Proteínas Recombinantes/farmacologia , Células THP-1
18.
J Environ Manage ; 275: 111232, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829266

RESUMO

Spilled oil frequently reaches the shorelines and affects coastal biota and communities. The application of surface washing agents is an important shoreline cleanup technique that can help remove stranded oil from substrate surfaces with the advantages of high removal efficiency, low toxicity, and strong economic viability. In this study, the investigation into the oil removal from contaminated sand using a surface washing agent under variable environmental conditions was conducted. A preliminary test was conducted to obtain the optimal combination of operating factors of surface washing agent-to-oil ratio (SOR) 2:1, mixing speed 150 rpm, and mixing time 30 min. The results of single-factor experiments showed that high temperature and humic acid concentration of flush water contributed to the performance of a surface washing agent, while salinity and kaolinite concentration could inhibit its performance. The factorial analysis revealed the main effects of temperature and salinity, and the interactive effects of temperature and salinity as well as salinity and humic acid concentration that were significant to the washing efficiency of the surface washing agent. In addition, the comprehensive assessment of a surface washing agent from the aspects of toxicity, detergency, dispersion properties, and field trials was conducted. The results have significant implications for future application of surface washing agents in the shoreline cleanup.


Assuntos
Petróleo , Poluentes Químicos da Água , Salinidade , Areia , Temperatura , Poluentes Químicos da Água/análise
19.
Reprod Biomed Online ; 38(6): 917-925, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928300

RESUMO

RESEARCH QUESTION: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China? DESIGN: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy. RESULTS: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy. CONCLUSION: The prevalence of infertility in China is high, but the uptake of treatment is relatively low.


Assuntos
Infertilidade Feminina/psicologia , Infertilidade Feminina/terapia , Infertilidade Masculina/psicologia , Infertilidade Masculina/terapia , Adulto , Índice de Massa Corporal , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inseminação Artificial/métodos , Masculino , Medicina Tradicional Chinesa , Participação do Paciente , Gravidez , Prevalência , Análise de Regressão , Técnicas de Reprodução Assistida , Risco , Adulto Jovem
20.
J Environ Manage ; 235: 350-356, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703649

RESUMO

In this paper, the typical organic component of humic acid (HA) was studied to explore its effect on the co-metabolic biodegradation of Tetrabromobisphenol A (TBBPA) in bioelectrochemical systems (BES). The degradation efficiency, intermediate metabolites and microbial diversity were investigated to demonstrate the impact of HA on the biodegradation of TBBPA in BES-HA-T (Bioelectrochemical system with TBBPA as substrate and HA as a stimulating factor). The highest biodegradation rate (93.2%) for TBBPA were obtained, which illustrated that HA played a positive role in the biodegradation of TBBPA. According to the analysis of the intermediate metabolites, it can be concluded that HA has changed the biodegradation pathway of TBBPA. The analysis of microbial diversity showed that the interaction of microorganisms had great effects on the anaerobic biodegradation of TBBPA, especially Trichococcus and Anaerolineaceae. Meanwhile, the abundance of Desulfobulbus in the BES-HA (Bioelectrochemical system with HA as a stimulating factor) had a positive effect on the improvement of electrochemical system performance.


Assuntos
Substâncias Húmicas , Bifenil Polibromatos , Biodegradação Ambiental
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