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1.
Health Qual Life Outcomes ; 18(1): 75, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188480

RESUMO

BACKGROUND: Proxy respondent-someone who assists the intended respondent or responds on their behalf-are widely applied in the measurement of health-related quality of life (HRQL). However, proxies may not provide the same responses as the intended respondents, which may bias the findings. OBJECTIVES: To determine whether the use of proxies is related to socio-demographic characteristics of the intended respondent, and to assess the possible proxy response bias of Chinese version of EQ-5D-3 L in general population. METHODS: A cross-sectional study based on a provincially representative sample from 2013 National Health Service Survey (NHSS) in Shaanxi, China was performed. HRQL was measured by Chinese version of EQ-5D-3 L. Propensity score matching (PSM) was used to get matched pairs of self-reports and proxy-reports. Before and after PSM, univariate logistic and linear models including the indicator of proxy response as the only independent variable, were employed to assess the possible proxy response bias of the dimensional and overall health status of EQ-5D-3 L respectively. RESULTS: 19.9% of the responses involved a proxy. Before PSM, the proxy-report group was younger in age and reported less unhealthy lifestyle, lower prevalence of disease, and less hospitalization than the self-report group. After PSM, it showed that the proxy-report group was statistically more likely to report health problem on each dimension of EQ-5D-3 L, with odds ratios larger than one comparing with self-report group. The means of EQ-5D-3 L index and EQ VAS of proxy-report group were 0.022 and 0.834 lower than self-report group. CONCLUSIONS: Significantly negative proxy response bias was found in Chinese EQ-5D-3 L in general population, and the magnitude of the bias was larger in physical dimensions than psychological dimensions after using PSM to control confounders.

2.
Crit Rev Biotechnol ; 40(2): 265-281, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928250

RESUMO

As a host for therapeutic protein expression, Chinese hamster ovary (CHO) cells are widely utilized in the mainstream biopharmaceutical industry. Cell culture process development plays an important role in transitioning laboratory research to manufacturing. Among different mathematic tools, kinetic modeling is commonly achieved through analyzing cell culture data to design process parameters, optimize media, and scale up bioreactors. In this review, we examine key factors for upstream process development, and summarize currently used kinetic modeling strategies. In addition, two original examples of kinetic modeling application optimizing cell culture performance are presented. A comprehensive understanding is provided for the kinetic modeling and its applications in cell culture process development.

3.
Trials ; 21(1): 47, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915038

RESUMO

BACKGROUND: It is very important for clinicians and dieticians to explore reasonable weight management strategies for obese people that address both short-term weight loss and subsequent weight maintenance. We hypothesized that resistance training combined with a high-protein diet would result in similar short-term weight loss but better long-term weight maintenance than either a conventional low-fat diet control or a high-protein diet alone. METHODS/DESIGN: This is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The study will be conducted between June 2019 and October 2020. The 90 overweight or obese participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group. Primary outcomes are body weight change at week 8 and week 24 compared with the baseline level. DISCUSSION: High-quality research on the effect of a high-protein diet combined resistance training on weight loss and weight maintenance is limited in the Chinese population. Our study will provide a basis for obesity management in China and will promote the development of exercise- and diet-related studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023841. Registered on 14 June 2019.

4.
J Neurointerv Surg ; 12(1): 55-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300535

RESUMO

BACKGROUND: The main surgical techniques for spontaneous basal ganglia hemorrhage include stereotactic aspiration, endoscopic aspiration, and craniotomy. However, credible evidence is still needed to validate the effect of these techniques. OBJECTIVE: To explore the long-term outcomes of the three surgical techniques in the treatment of spontaneous basal ganglia hemorrhage. METHODS: Five hundred and sixteen patients with spontaneous basal ganglia hemorrhage who received stereotactic aspiration, endoscopic aspiration, or craniotomy were reviewed retrospectively. Six-month mortality and the modified Rankin Scale score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of different surgical techniques on patient outcomes. RESULTS: For the entire cohort, the 6-month mortality in the endoscopic aspiration group was significantly lower than that in the stereotactic aspiration group (odds ratio (OR) 4.280, 95% CI 2.186 to 8.380); the 6-month mortality in the endoscopic aspiration group was lower than that in the craniotomy group, but the difference was not significant (OR=1.930, 95% CI 0.835 to 4.465). A further subgroup analysis was stratified by hematoma volume. The mortality in the endoscopic aspiration group was significantly lower than in the stereotactic aspiration group in the medium (≥40-<80 mL) (OR=2.438, 95% CI 1.101 to 5.402) and large hematoma subgroup (≥80 mL) (OR=66.532, 95% CI 6.345 to 697.675). Compared with the endoscopic aspiration group, a trend towards increased mortality was observed in the large hematoma subgroup of the craniotomy group (OR=8.721, 95% CI 0.933 to 81.551). CONCLUSION: Endoscopic aspiration can decrease the 6-month mortality of spontaneous basal ganglia hemorrhage, especially in patients with a hematoma volume ≥40 mL.

5.
Huan Jing Ke Xue ; 40(9): 3990-3999, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854861

RESUMO

In order to explore the pollution levels and characteristics of perfluorinated alkyl substances (PFASs), seawater, sediment, and Ruditapes philippinarum samples were collected near the Jiaozhou Bay coast in April 2018. All samples were analyzed by using the high performance liquid chromatography-mass spectrometry method to determine the content of 35 types of PFASs. The results showed that 12 different PFASs were tested in the seawater with ∑PFASs concentrations of 21.1-38.0 ng·L-1; 10 types of PFASs were detected in sediments, with ∑PFASs content (dry weight) ranging from 0.459 to 1.20 µg·kg-1; 19 types of PFASs were measured in Ruditapes philippinarum, with ∑PFASs content (dry weight) of 15.5-27.5 µg·kg-1. Compared with other areas reported in the literature, the total pollution of Jiaozhou Bay was at medium or high levels. In addition, perfluorooctanoic acid (PFOA) was the dominant PFAS in the seawater, sediments, and Ruditapes philippinarum with a detection rate of 100%. 6:2 fluorotelomer phosphate diester (6:2 diPAP) was observed for the first time in seawater and sediments from Jiaozhou Bay and had the highest detection frequency and concentration of the precursor. Perfluorooctanesulfonamide (PFOSA) was the main precursor in Ruditapes philippinarum, of which the detection rate was 93.8%. Moreover, the organic carbon normalized sediment-water distribution coefficient (lg KOC) values were 5.24-6.37 and increased with an increase in carbon chain length. The bioaccumulation factors (lg BAF) and field-based biota-sediment accumulation factors (lg BSAF) were 2.53-4.32 and 1.30-2.50, respectively. The lg BAF values positively correlated with the carbon chain length, whereas the lg BSAF values decreased with an increase in the carbon chain length (C8-C13).


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Animais , Baías , China , Monitoramento Ambiental , Sedimentos Geológicos , Água do Mar
6.
J Surg Res ; 243: 371-379, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31277014

RESUMO

BACKGROUND: Segmentectomy and wedge resection have been recommended as appropriate surgical treatments for patients with poor pulmonary function or major comorbidities. However, for stage I non-small cell lung cancer (NSCLC), it is still undecided whether survival is better with segmentectomy or with wedge resection. METHODS: A meta-analysis was performed of studies examining survival outcomes after sublobar resection in patients with stage I NSCLC. Three electronic databases were searched to identify studies that investigated overall survival, cancer-specific survival, and disease-free survival between patients receiving segmentectomy versus wedge resection. A total of 19 relevant studies published before 31 April 2018 that satisfied the inclusion criteria were included in this meta-analysis. RESULTS: The 19 studies involved a total of 14,197 patients with stage I NSCLC. Overall survival was significantly better after segmentectomy than after wedge resection (hazard ratio [HR] = 0.82; 95% confidence interval [CI], 0.77-0.88; P < 0.00001). This was also true of cancer-specific survival (HR = 0.71; 95% CI, 0.64-0.79; P < 0.00001) and disease-free survival (HR = 0.73, 95% CI, 0.54-0.98; P = 0.04). A fixed-model was applied for the analysis as there was no significant heterogeneity between the studies. CONCLUSIONS: Survival after lobar resection for stage I NSCLC is significantly better with segmentectomy than with wedge resection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade
7.
BMC Cardiovasc Disord ; 19(1): 139, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182031

RESUMO

BACKGROUND: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality. METHODS: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. CTRP3 and CTRP9 levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Both CTRP3 and CTRP9 concentrations were significantly decreased in the HFrEF group compared to the control group (p < 0.001). Moreover, patients with higher New York Heart Association class had significantly lower CTRP3 or CTRP9 concentrations. Correlation analysis revealed that CTRP3 and CTRP9 levels were positively related with LVEF% (CTRP3, r = 0.556, p < 0.001; CTRP9, r = 0.526, p < 0.001) and negatively related with NT-proBNP levels (CTRP3, r = - 0.454, p < 0.001; CTRP9, r = - 0.483, p < 0.001). After a follow up for 36 months, after adjusted for age, LVEF and NT-proBNP, we observed that CTRP3 or CTRP9 levels below the 25th percentile was a predictor of total mortality (CTRP3,HR:1.93,95%CI1.03~3.62,P = 0.042;CTRP9,HR:1.98,95%CI:1.02~3.85,P = 0.044) and hospitalizations (CTRP3,HR:2.34,95% CI:1.43~3.82,P = 0.001;CTRP9,HR:2.67,95%CI:1.58~4.50,P < 0.001). CONCLUSIONS: CTRP3 and CTRP9 are decreased in patients with HFrEF, proportionate to disease severity, and each is associated with increased morbidity and mortality. TRIAL REGISTRATION: NCT01372800 . Registered May 2011.

8.
Exp Ther Med ; 17(5): 3965-3970, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31007739

RESUMO

The aim of the present study was to evaluate the impact of donor age on liver function and regeneration following living donor liver transplantation. Donors were divided into an elderly donor group (age >50 years old; n=8) and a young donor group (age <30 years old; n=35). The recipients were also divided into an elderly group (age >50 years old; n=5) and a young group (age <30 years old; n=25). Alanine aminotransferase, aspartate aminotransferase, total bilirubin (TB) and prothrombin time were recorded 1-5 days postoperatively. The liver regeneration ratio (LRR) was recorded 7 and 15 days postoperatively in donors and at 0.5, 1, 3 and 6 months postoperatively in recipients by contrast-enhanced multi-slice spiral computed tomography. Notably, the LRR in the young donor group was significantly increased compared with that in the elderly donor group at 7 days postoperatively (P<0.05). Among recipients, TB in the elderly group was significantly increased compared with that in the young group at 1-5 days postoperatively (P<0.05). The residual liver regeneration rate was decreased and the time of jaundice was prolonged in recipients in the elderly group 7 days postoperatively, but donor age had little impact on the short-term outcome of the residual liver and graft.

9.
Appetite ; 138: 146-152, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30917942

RESUMO

The aim of this study was to explore the relationship between caregivers' feeding behaviors and children's eating behaviors among preschoolers in China. From April to July 2016, a cross-sectional survey was administered to 912 preschoolers' caregivers in China. The Chinese Preschooler's Caregiver Feeding Behavior Scale (CPCFBS) and Chinese Preschooler's Eating Behavior Questionnaire (CPEBQ) were used to assess caregivers' feeding behaviors and children's eating behaviors, respectively. Pearson correlation and canonical correlation analysis (CCA) based on principal component analysis were performed to explore the relationships between them. Two interpretable canonical variables and structures were yielded through CCA. The first canonical variable could explain 35.1% and 29.0% of the total variance of the caregivers' feeding behaviors and the children's eating behaviors variable groups, respectively, with a canonical correlation coefficient of 0.659 (rU1,V1 = 0.659, P < 0.001). The second canonical variable could explain 17.6% and 14.9% of the total variance of the caregivers' feeding behaviors and the children's eating behaviors variable groups, respectively, with a canonical correlation coefficient of 0.309 (rU2,V2 = 0.309, P < 0.001). According to the canonical structure, higher performance behaviors of the caregiver, such as encouragement of healthy eating, responsibility for feeding, supervision of eating, behavior restricted feeding, content restricted feeding and lower weight concerns, were associated with reasonable behaviors of children, including lower emotional eating, food responsiveness, unhealthy eating habits and higher initiative eating. Our results demonstrated that caregivers' feeding behaviors were the major influencing factors of children's eating behaviors, and caregivers' encouragement of healthy eating, responsibility for feeding, supervision of eating, restricted feeding and lower weight concerns were associated with reasonable children's eating behaviors, especially low children's emotional eating, low food responsiveness, infrequent unhealthy eating habits, frequent initiative eating, infrequent satiety responsiveness and food fussiness behaviors.

10.
J Mol Histol ; 50(2): 155-166, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783857

RESUMO

Sweat gland regeneration is important for patients with an extensive deep burn injury. In previous study, we reported that bone marrow-mesenchymal stem cells (BM-MSCs) could differentiate into sweat gland-like cells (SGLCs), but the underlying molecular mechanism remains unclear. Recently, microRNAs (miRNAs or miRs) are reported to manipulate many biological processes. However, whether the process of MSCs differentiation into sweat gland cells (SGCs) is regulated by miRNAs has not been reported. In this study, BM-MSCs were induced into SGLCs by co-culturing with SGCs. Differential expressions of miRNAs between BM-MSC and SGLCs were determined through miRNAs microarray and 68 miRNAs were found significantly changed in miRNA profile including hsa-miR-138-5p. Bioinformatics analysis showed that hsa-miR-138-5p targeted a group of nuclear factor-κB (NF-κB) related genes which play an important role in skin appendage development. As expected, hsa-miR-138-5p inhibitor transfected into BM-MSCs partly mimicked the effects of co-culture and increased the number of SGLCs by increasing the expression of NF-κB related genes. These results suggest that hsa-miR-138-5p and NF-κB are involved in the regulation of BM-MSCs differentiation into SGLCs. This study may also offer a new approach to yield SGCs for burn patients.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , MicroRNAs/fisiologia , Glândulas Sudoríparas/citologia , Células Cultivadas , Técnicas de Cocultura , Humanos , MicroRNAs/análise , MicroRNAs/farmacologia , NF-kappa B/genética , NF-kappa B/farmacologia , Regeneração , Glândulas Sudoríparas/fisiologia
11.
J Sep Sci ; 42(7): 1423-1431, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30667151

RESUMO

Okadaic acid is a marine biotoxin that primarily occurs in shellfish and can cause diarrheic shellfish poisoning in humans. When analyzing biological samples using liquid chromatography with tandem mass spectrometry, the presence of complex matrices is a major issue. Thus, it is crucial to selectively and simply extract the target analyte from samples and minimize matrix effects simultaneously. To meet this need, an immunomagnetic-bead-based liquid chromatography with tandem mass spectrometry method was developed to detect okadaic acid in shellfish. Magnetic beads bound to monoclonal antibody against okadaic acid were used as affinity probes to specifically enrich okadaic acid in samples, which effectively eliminated matrix effects. A magnetic separator was used to aggregate and separate magnetic particles from sample matrices, and methanol was used to elute okadaic acid from the magnetic beads. Standard solution prepared with methanol was employed directly for quantitative analysis. Several experimental conditions were optimized to improve performance. The method is of interest as a rapid (10 min) sample clean-up and selective enrichment tool, and it showed good linearity and sensitivity, with reported limits of detection and quantitation of 3 and 10 µg/kg, respectively. Fifty-three shellfish samples from an aquatic products market were tested using this method, and four samples positive for okadaic acid were found.


Assuntos
Separação Imunomagnética , Ácido Okadáico/análise , Frutos do Mar/análise , Anticorpos Monoclonais/imunologia , Reações Antígeno-Anticorpo , Cromatografia Líquida , Ácido Okadáico/imunologia , Espectrometria de Massas em Tandem
12.
J Environ Sci Health B ; 54(4): 271-280, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30628846

RESUMO

Perfluorinated alkyl substances (PFASs) are emerging persistent organic pollutants, which pose a threat to human health primarily by dietary exposure, especially through seafood. Bohai Sea (a semi-closed sea located north of China) is an important shellfish aquaculture area that is possibly highly-polluted with PFASs. In this study, we first evaluated contamination by PFASs in a total of 230 samples of marine shellfish from the Bohai Sea. Samples included five important shellfish species, collected from important aquaculture spots distributed around the Bohai Sea. Samples were analyzed by an ultra-fast liquid chromatography-tandem mass spectrometry method, which could simultaneously detect 23 PFASs in shellfish. Our research verified that PFASs have become a threat to the safety of shellfish products in this area. Furthermore, contamination by PFASs in shellfish changed depending on the components of PFASs, the species of shellfish, and the sampling sites. Many of the 23 target compounds contributed to the high detection ratio (>50%) as follows: perfluorooctanoic acid (PFOA) > perfluorononanoic acid > perfluorodecanesulfonic acid > perfluorooctanesulfonic acid (PFOS). Compared with other dominant components, PFOA not only had the highest detection percentage in shellfish samples (98.3%), but its detection level contributed to 87.2% of total PFASs concentrations, indicating that PFOA is the major threat to the safety of shellfish products. The highest level of PFAS was found in clams (62.5 ng g-1 wet weight of PFOA). The concentration of total PFAS in different shellfish species showed the following trend: clams > mussels > scallops > whelks > oysters. The maximum concentration of total PFAS or PFOA was found in Shouguang. The total concentration of PFOS and its precursor were highest in Cangzhou, possibly due to local industrial activities. The results presented in this paper provide new data on the contamination of marine shellfish along the Bohai Sea coasts in China, and constitute a reference for future monitoring of contamination by emerging contaminants in Bohai coast.


Assuntos
Fluorcarbonetos/análise , Frutos do Mar/análise , Poluentes Químicos da Água/análise , Ácidos Alcanossulfônicos/análise , Caprilatos/análise , China , Cromatografia Líquida , Monitoramento Ambiental/métodos , Humanos , Oceanos e Mares , Espectrometria de Massas em Tandem
13.
MAbs ; 11(1): 205-216, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30602334

RESUMO

Controlling acidic charge variants is critical for an industrial bioprocess due to the potential impact on therapeutic efficacy and safety. Achieving a consistent charge variant profile at manufacturing scale remains challenging and may require substantial resources to investigate effective control strategies. This is partially due to incomplete understanding of the underlying causes for charge variant formation during the cell culture process. To address this gap, we examined the effects of four process input factors (temperature, iron concentration, feed media age, and antioxidant (rosmarinic acid) concentration) on charge variant profile. These factors were found to affect the charge profile by modulating the cell culture oxidative state. Process conditions with higher acidic peaks corresponded to elevated supernatant peroxide concentration, intracellular reactive oxygen species (ROS) levels, or both. Changes in glycation level were the primary cause of the charge heterogeneity, and for the first time, supernatant peroxide was found to positively correlate with glycation levels. Based on these findings, a novel mathematical model was developed to demonstrate that the rate of acidic species formation was exponentially proportional to the concentrations of supernatant peroxide and protein product. This work provides critical insights into charge variant formation during the cell culture process and highlights the importance of modulating of cell culture oxidative stress for charge variant control.


Assuntos
Anticorpos Monoclonais/química , Técnicas de Cultura de Células/métodos , Modelos Teóricos , Estresse Oxidativo/fisiologia , Animais , Reatores Biológicos/normas , Células CHO , Cricetinae , Cricetulus
14.
Mar Pollut Bull ; 135: 1198-1204, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30301019

RESUMO

The North Yellow Sea is a major aquaculture production area for the scallop Patinopecten yessoensis. In this study, the temporal and spatial variation of phycotoxins in scallops, phytoplankton, and their cysts were analyzed during a survey conducted from June 2011 to April 2012 around Zhangzi Island. The study area is a semi-enclosed epicontinental sea surrounded by the Shandong Peninsula, the Liaodong Peninsula and the Korean Peninsula. The three main results of the study were as follows: (1) The saxitoxin-group toxins, okadaic acid and analogues, and pectenotoxins were the major phycotoxin residues found in scallops; (2) Six kinds of toxic microalgae were identified, Protoperidinium spp., Gonyaulax spp., and Alexandrium spp. were the dominant taxa; Seven types of potential marine toxin-producing dinoflagellates, A. tamarense, A. catenella, Dinophysis fortii, G. catenatum, Gambierdiscus toxicus, Azadinium poporum, and Pseudo-nitzschia pungen were identified as the primary source of phycotoxins and were present at relatively high density from June to October; and (3) azaspiracids and domoic acid might be new potential sources of toxin pollution. This study represents the first assessment to phycotoxins around Zhangzi Island in the North Yellow Sea.


Assuntos
Contaminação de Alimentos/análise , Toxinas Marinhas/análise , Pectinidae/química , Fitoplâncton , Frutos do Mar/análise , Animais , Aquicultura/métodos , China , Diatomáceas , Dinoflagelados , Microalgas , Oceanos e Mares , Fitoplâncton/química , Saxitoxina/análise , Estações do Ano , Análise Espaço-Temporal , Compostos de Espiro/análise
15.
Cancer Lett ; 426: 98-108, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29653269

RESUMO

The transcription factor c-Myc is a key driver for hepatocellular carcinomas (HCCs), while the polycombrepressive complex 2 (PRC2) subunit EZH2 is an essential biomarker of HCC. c-Myc epigenetically silences tumor suppressors by recruiting PRC2 and inducing methylation of histone H3 lysine 27. However, it remains elusive how they are regulated in HCC. We found here that microRNA-26a (miR-26a) suppresses c-Myc, a classical Wnt pathway target gene, by targeting the Wnt pathway coactivator, cyclin-dependent kinase 8 (CDK8); miR-26a also directly targets and inhibits EZH2. The expression of MIR26A2, a predominant origin of miR-26a transcripts in hepatic cells, is repressed by c-Myc/PRC2, thereby forming a c-Myc/miR-26a/CDK8 regulatory circuit in HCC. Meanwhile, miR-26a suppresses migration of HCC by targeting p21-activated kinase 2 (PAK2), a critical kinase linking Rho GTPases to cytoskeleton reorganization. Consequently, in vivo delivery of miR-26a remarkably suppressed the development of xenograft HCC and metastasis of orthotopic HCC by downregulating c-Myc, CDK8 and PAK2. These findings unraveled a novel mechanism of c-Myc and Wnt/ß-catenin interplay that dictates HCC pathogenesis, and have implications for the potential applicability of miRNA delivery in targeting the newly identified signaling axis and treating metastatic HCCs.


Assuntos
Carcinoma Hepatocelular/patologia , Quinase 8 Dependente de Ciclina/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/genética , Quinases Ativadas por p21/genética , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Via de Sinalização Wnt
16.
Int J Equity Health ; 17(1): 32, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540183

RESUMO

BACKGROUND: In advanced economies, economic factors have been found to be associated with many health outcomes, including health-related quality of life (HRQL), and people's health is affected more by income inequality than by absolute income. However, few studies have examined the association of income inequality and absolute income with HRQL in transitional economies using individual data. This paper focuses on the effects of county or district income inequality and absolute income on the HRQL measured by EQ-5D and the differences between rural and urban regions in Shaanxi province, China. METHODS: Data were collected from the 2008 National Health Service Survey conducted in Shaanxi, China. The EQ-5D index based on Japanese weights was employed as a health indicator. The income inequality was calculated on the basis of self-reported income. The special requirements for complex survey data analysis were considered in the bivariate analysis and linear regression models. RESULTS: The mean of the EQ-5D index was 94.6. The EQ-5D index of people with low income was lower than that in the high-income group (for people in the rural region: 93.2 v 96.1, P < 0.01; for people in the urban region: 95.5 v 96.8, P < 0.01). Compared with people with moderate inequality, the EQ-5D index of those with high inequality was relatively lower (for people living in the rural region: 91.1 v 95.8, P < 0.01; for people living in the urban region: 95.6 v 97.3, P < 0.01). Adjusted by age, gender, education, marital status, employment, medical insurance, and chronic disease, all the coefficients of the low-income group and high income inequality were significantly negative. After stratifying by income group, all the effects of high income inequality remained negative in both income groups. However, the coefficients of the models in the high income group were not statistically significant. CONCLUSION: Income inequality has damaging effects on HRQL in Shaanxi, China, especially for people with low income. In addition, people living in rural regions were more vulnerable to economic factors.


Assuntos
Doença Crônica/epidemiologia , Renda/estatística & dados numéricos , Qualidade de Vida , Fatores Socioeconômicos , Adulto , Idoso , China , Doença Crônica/economia , Estudos Transversais , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Programas Nacionais de Saúde , População Rural/estatística & dados numéricos , Autorrelato , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , Adulto Jovem
17.
Biotechnol Bioeng ; 115(7): 1646-1665, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29532901

RESUMO

Controlling the charge profile of therapeutic protein is a critical challenge in the current quality-by-design (QbD) paradigm, throughout all phases of biologics process development (PD): cell line development, upstream cell culture, recovery process, downstream purification, and analytical characterization. Charge variant profiles may influence efficacy and/or lead to unintended side-effects. Thus, maintaining a consistent charge profile is of tremendous importance, and increasingly, researchers have focused efforts toward developing strategies to mitigate variability during cell culture and to improve separation and detection of charge variants. Current understanding of factors affecting charge variant formation during manufacturing remains inadequate, and sometimes, even substantial commitment of resources may still not fully achieve the desired or consistent profiles. As such, this review attempts to provide a comprehensive resource for the biologics community by summarizing the impact of charge variants and CQA management, analytical methods for charge variant detection, as well as strategies in downstream and upstream PD for controlling charge variant profiles.


Assuntos
Produtos Biológicos/química , Biotecnologia/métodos , Processamento de Proteína Pós-Traducional , Proteínas/química , Eletricidade Estática , Tecnologia Farmacêutica/métodos , Produtos Biológicos/normas , Proteínas/normas , Controle de Qualidade
18.
MAbs ; 10(3): 500-510, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29336721

RESUMO

During large-scale monoclonal antibody manufacturing, disulfide bond reduction of antibodies, which results in generation of low molecule weight species, is occasionally observed. When this happens, the drug substance does not meet specifications. Many investigations have been conducted across the biopharmaceutical industry to identify the root causes, and multiple strategies have been proposed to mitigate the problem. The reduction is correlated with the release of cellular reducing components and depletion of dissolved oxygen before, during, and after harvest. Consequently, these factors can lead to disulfide reduction over long-duration storage at room temperature prior to Protein A chromatography. Several strategies have been developed to minimize antibody reduction, including chemical inhibition of reducing components, maintaining aeration before and after harvest, and chilling clarified harvest during holding. Here, we explore the use of hydrogen peroxide in clarified harvest bulk or cell culture fluid as a strategy to prevent disulfide reduction. A lab-scale study was performed to demonstrate the effectiveness of hydrogen peroxide in preventing antibody reduction using multiple IgG molecules. Studies were done to define the optimal concentration of hydrogen peroxide needed to avoid unnecessary oxidization of the antibody products. We show that adding a controlled amount of hydrogen peroxide does not change product quality attributes of the protein. Since hydrogen peroxide is soluble in aqueous solutions and decomposes into water and oxygen, there is no additional burden involved in removing it during the downstream purification steps. Due to its ease of use and minimal product impact, we demonstrate that hydrogen peroxide treatment is a powerful, simple tool to quench reducing potential by simply mixing it with harvested cell culture fluid.


Assuntos
Anticorpos Monoclonais , Dissulfetos/química , Peróxido de Hidrogênio/química , Imunoglobulina G , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Células CHO , Cromatografia de Afinidade/métodos , Cricetulus , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificação , Oxirredução , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteína Estafilocócica A/química
19.
Biotechnol Bioeng ; 115(4): 900-909, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29205285

RESUMO

Process control for manufacturing biologics is critical for ensuring product quality, safety, and lot to lot consistency of therapeutic proteins. In this study, we investigated the root cause of the pink coloration observed for various in-process pools and drug substances in the antibody manufacturing process. Vitamin B12 is covalently bound to mAbs via a cobalt-sulfur coordinate bond via the cysteine residues. The vitamin B12 was identified to attach to an IgG4 molecule at cysteine residues on light chain (Cys-214), and heavy chain (Cys-134, Cys-321, Cys-367, and Cys-425). Prior to attachment to mAbs, the vitamin B12 needs to be in its active form of hydroxocobalamin. During culture media preparation, storage and cell culture processing, cyanocobalamin, the chemical form of vitamin B12 added to media, is converted to hydroxocobalamin by white fluorescence light (about 50% degradation in 11-14 days at room temperature and with room light intensity about 500-1,000 lux) and by short-wavelength visible light (400-550 nm). However, cyanocobalamin is stable under red light (wavelength >600 nm) exposure and does not convert to hydroxocobalamin. Our findings suggests that the intensity of pink color depends on concentrations of both free sulfhydryl groups on reduced mAb and hydroxocobalamin, the active form of vitamin B12 . Both reactants are necessary and neither one of them is sufficient to generate pink color, therefore process control strategy can consider limiting either one or both factors. A process control strategy to install red light (wavelength >600 nm) in culture media preparation, storage and culture processing areas is proposed to provide safe light for biologics and to prevent light-induced color variations in final products.


Assuntos
Anticorpos Monoclonais/química , Hidroxocobalamina/química , Imunoglobulina G/química , Vitamina B 12/química , Anticorpos Monoclonais/análise , Produtos Biológicos/análise , Produtos Biológicos/química , Cobalto/análise , Cobalto/química , Qualidade de Produtos para o Consumidor , Meios de Cultura/análise , Meios de Cultura/química , Cisteína/análise , Cisteína/química , Dissulfetos/análise , Dissulfetos/química , Humanos , Hidroxocobalamina/análise , Imunoglobulina G/análise , Luz , Vitamina B 12/análise
20.
Harmful Algae ; 67: 119-130, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28755714

RESUMO

The genus Pseudo-nitzschia has attracted attention because of production of the toxin, domoic acid (DA), causing Amnesic Shellfish Poisoning (ASP). Pseudo-nitzschia blooms occur frequently in Chinese coastal waters, and DA has been detected in several marine organisms, but so far no Pseudo-nitzschia strains from Chinese waters have been shown to produce DA. In this study, monoclonal Pseudo-nitzschia strains were established from Chinese coastal waters and examined using light microscopy, electron microscopy and molecular markers. Five strains, sharing distinct morphological and molecular features differentiating them from other Pseudo-nitzschia species, represent a new species, Pseudo-nitzschia simulans sp. nov. Morphologically, the taxon belongs to the P. pseudodelicatissima group, cells possessing a central nodule and each stria comprising one row of poroids. The new species is characterized by the poroid structure, which typically comprises two sectors, each sector located near opposite margins of the poroid. The production of DA was examined by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of cells in stationary growth phase. Domoic acid was detected in one of the five strains, with concentrations around 1.05-1.54 fg cell-1. This is the first toxigenic diatom species reported from Chinese waters.


Assuntos
Diatomáceas/metabolismo , Ácido Caínico/análogos & derivados , Água do Mar , China , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Geografia , Ácido Caínico/metabolismo , Ácido Caínico/toxicidade , Conformação de Ácido Nucleico , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Subunidades Ribossômicas Maiores/metabolismo
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