Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production.

Improving the cellular capacity of Chinese hamster ovary (CHO) cells to produce large amounts of therapeutic proteins remains a major challenge for the biopharmaceutical industry. In previous studies, we observed strong correlations between the performance of CHO cells and expression of two transcription factors (TFs), MYC and XBP1s. Here, we have evaluated the effective of overexpression of these two TFs on CHO cell productivity. To address this goal, we generated an EPO-producing cell line (CHOEPO) using a targeted integration approach, and subsequently engineered it to co-overexpress MYC and XBP1s (a cell line referred to as CHOCXEPO). Cells overexpressing MYC and XBP1s increased simultaneously viable cell densities and EPO production, leading to an enhanced overall performance in cultures. These improvements resulted from the individual effect of each TF in the cell behaviour (i.e., MYC-growth and XBP1s-productivity). An evaluation of the CHOCXEPO cells under different environmental conditions (temperature and media glucose concentration) indicated that CHOCXEPO cells increased cell productivity in high glucose concentration. This study showed the potential of combining TF-based cell engineering and process optimisation for increasing CHO cell productivity.

Strengthening data collection and use for quality improvement in primary care: the case of Costa Rica.

Costa Rica is a bright spot of primary healthcare (PHC) performance, providing first-contact accessibility and continuous, comprehensive, coordinated, and patient-centered care to its citizens. Previous research hypothesized that strong data collection and use for quality improvement are central to Costa Rica's success. Using qualitative data from 40 interviews with stakeholders across the Costa Rican healthcare system, this paper maps the various data streams at the PHC level and delineates how these data are used to make decisions around insuring and improving the quality of PHC delivery. We describe four main types of PHC data: individual patient data, population health data, national healthcare delivery data, and local supplementary healthcare delivery data. In particular, we find that the Healthcare Delivery Performance Index-a ranking of the nation's 106 Health Areas using 15 quality indicators-is utilized by Health Area Directors to create quality improvement initiatives, ranging from education and coaching to optimization of care delivery and coordination. By ranking Health Areas, the Index harnesses providers' intrinsic motivation to stimulate improvement without financial incentives. We detail how a strong culture of valuing data as a tool for improving population health and robust training for personnel have enabled effective data collection and use. However, we also find that the country's complex data systems create unnecessary duplication and can inhibit efficient data use. Costa Rica's experience with data collection, analysis, and use for quality improvement hold important lessons for PHC in other public sector systems.

Aqueous leaf extract of Passiflora alata Curtis promotes antioxidant and anti-inflammatory effects and consequently preservation of NOD mice beta cells (non-obese diabetic).

Passiflora alata Curtis (P. alata) leaves have anti-inflammatory properties; the present study aimed to investigate the anti-diabetogenic properties of P. alata aqueous leaf extract. HPLC analysis identified the phenolic compounds catechin, epicatechin and rutin. The aqueous extract was administered for 30weeks to non-obese diabetic (NOD) mice presenting a decrease of 28.6% in diabetes incidence and the number of inflammatory cells in pancreatic islets, when compared with the control group (water). The P. alata group presented an antioxidant effect and decreased lipid peroxidation in the serum of NOD mice. Increased numbers of insulin-positive cells were also observed in the pancreatic islets of the treated group. The diabetic group exhibited higher levels in the glucose tolerance test and glycemic index, in comparison to the P. alata-treated group and non-diabetic control BALB/c mice. In addition, the P. alata extract reduced the percentage and the proliferation index of NOD mice lymphocytes submitted to in vitro dose/response mitogenic stimulation assays. These results suggest that the aqueous extract of P. alata has anti-inflammatory properties, contributing to the protection of beta cells in pancreatic islets in NOD mice, and presents potential for use a supporting approach to treat type 1 diabetes.

Survey of aphid population in a yellow passion fruit crop and its relationship on the spread Cowpea aphid-borne mosaic virus in a subtropical region of Brazil.

BACKGROUND: Passion fruit woodiness may be caused by Cowpea aphid-borne mosaic virus (CABMV) and is currently the major passion fruit disease in Brazil. To assess the virus-vector-host interactions, a newly introduced golden passion fruit plantation located in eastern region of São Paulo State, Brazil, was monitored. METHODS: Dissemination of CABMV was determined analyzing golden passion fruit plants monthly for 18 months by PTA-ELISA. Seasonality and aphid fauna diversity was determined by identification of the captured species using yellow sticky, yellow water-pan and green tile traps. Population composition of the aphid species was determined using the descriptive index of occurrence, dominance and general classification and overlap of species in the R program. RESULTS: Analyses of species grouping afforded to recognize 14 aphid species. The genus Aphis represented 55.42 % of the species captured. Aphid species formed two distinct clusters, one of which was characterized by the diversity of polyphagous species that presented high potential to spread CABMV. CONCLUSION: The low abundance and diversity of aphid species did not interfere negatively in the CABMV epidemiology. The genus Aphis, particularly Aphis fabae/solanella and A. gossypii, was crucial in the spread of CABMV in passion fruit orchards in the eastern State of São Paulo.

Identification and Antioxidant Activity of the Extracts of Eugenia uniflora Leaves. Characterization of the Anti-Inflammatory Properties of Aqueous Extract on Diabetes Expression in an Experimental Model of Spontaneous Type 1 Diabetes (NOD Mice).

Medical and folklore reports suggest that Eugenia uniflora (E. uniflora) is a functional food that contains numerous compounds in its composition, with anti-inflammatory, antioxidant and anti-diabetic effects. In the present study, we investigated the best solvents (water, ethanol and methanol/acetone) for extracting bioactive compounds of E. uniflora leaves, assessing total phenols and the antioxidant activity of the extracts by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and Oxygen Radical Absorbance Capacity (ORAC) assays, identifying hydrolysable tannins and three phenolic compounds (ellagic acid, gallic acid and rutin) present in the leaves. In addition, we evaluated the incidence of diabetes, degree of insulitis, serum insulin, hepatic glutathione and tolerance test glucose in non-obese diabetic (NOD) mice. Our results suggest that the aqueous extract presents antioxidant activity and high total phenols, which were used as a type 1 diabetes mellitus (DM-1) treatment in NOD mice. We verified that the chronic consumption of aqueous extract reduces the inflammatory infiltrate index in pancreatic islets, maintaining serum insulin levels and hepatic glutathione, and reducing serum lipid peroxidation as well as the risk for diabetes.