Cellular and Biochemical Effects of Sparstolonin B on Endothelial Cells to Inhibit Angiogenesis

Angiogenesis is the process of new blood vessel development by endothelial cells from pre-existing vasculature; however, abnormal angiogenesis contributes to the pathogenesis of many disorders such as cardiovascular diseases, cancer, and chronic inflammation. Angiogenesis in atherosclerotic plaques contributes to their instability and therefore increases the risk of plaque rupture and thrombus formation. Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb that has been used historically in the Chinese herbal medicine SanLeng as an herbal remedy for the treatment of several inflammatory diseases. In this study, we have explored the anti-angiogenic properties of SsnB in vitro. In cell culture, SsnB induced rapid changes in the morphology of human umbilical vein endothelial cells (HUVECs). After 6 hours, SsnB induced endothelial cell actin stress fibers, increased cell perimeter/area ratio, and enhanced formation of focal adhesions. These effects occurred in a dose-dependent manner in which the maximum effect was at 100M SsnB. In addition, we have also analyzed early response gene expression in response to 100 M SsnB. Our data show that SsnB blocked the up-regulation c-Myc and c-Fos, which occurred in response to addition of vehicle control (DMSO). These results imply that alteration of endothelial cell morphology and change of early response genes regulation may play a role in the anti-angiogenic effects induced by SsnB

Does call centers operators’ introjected regulation impact their skill variety and task significance? Evidence from Morocco

Purpose – The aim of this paper was to empirically examine the impact of work motivation represented by introjected regulation on job satisfaction, which was illustrated by skill variety and task significance. This study was conducted relatedly to Moroccan call center operators, in the post-COVID-19 era in which motivational and satisfactory issues are still strongly faced by managers, mainly due to the operated hybrid working systems. Research methodology – The chosen methodology was a quantitative one, based on the administration of a questionnaire to 158 call center operators, working in various Moroccan districts. The data analysis consisted of an exploratory factor analysis (EFA), followed by a full structural equation modelling (SEM). Findings – The findings display that introjected regulation positively and significatively impacts skill variety, but not task significance, in a way that permitted to partly confirm the conceptual model built upon the central hypothesis, claiming that work motivation positively affects job satisfaction. Indeed, avoiding to experience feelings of shame and guilt in addition to seeking for conformity and approbation in a work context turned out to lead individuals to execute the assigned tasks by implementing their personal configuration of skills and talents in this regard. Research limitations – This study admits methodological limitations as for instance the restricted sample size, and the adopted quantitative approach rather than a qualitative one, or even a mixed approach that could have opened more research tracks to be explored regarding the investigated relationship. Practical implications – This study comes out with appealing practical implications willing to help managers to understand better the causality link between work motivation and job satisfaction. The main implication of this study is the illustration of how introjected regulation can predict and foster skill variety in a professional context, as the correspondent research hypothesis was empirically verified. Originality/Value – Morocco is admittedly one of the poorest targeted populations for International Business and Management studies, hopefully this study can contribute in enriching the pre-existent studies in this regard. Also, work motivation and job satisfaction are usually seen as qualitative variables (using interviews, case studies…), hence a quantitative methodology is not commonly adopted in this perspective

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Enhancements in Alginate Microencapsulation Technology & Impacts on Cell Therapy Development

Biodegradable alginate microcapsules (MC) are recently becoming widely used in the biomedical field, and have shown effectiveness as a drug delivery system. Alginate has been used in microencapsulation due to its simple gelling process, biodegradability, excellent biocompatibility, and its stability under in-vivo conditions. Alginate polymer is a natural polysaccharide derived from brown seaweed and has the ability to polymerize rapidly in the presence of cations to form a porous matrix. In order to advance the previous system for efficient protein and peptide delivery, we further lyophilized the peptide-filled microcapsules and we were able to rehydrate, and test them for sustained release. Electrospray method, as a microencapsulation technique, has been previously used to encapsulate peptides and proteins successfully using alginate. A second coating of poly-l-ornithine (PLO) polymer can be used to increase the integrity of alginate microcapsules. Alpha-carboxy terminus 1 (αCT1) peptide, Human platelet lysate (HPL), and bovine serum albumin (BSA) were examples of peptides and proteins that were successfully encapsulated by our lab. Cell-based therapies represent a revolutionary bio-technique that has been applied widely in medicine. Recently, they have been successfully applied in treatment of neurodegenerative diseases, eye diseases, cardiovascular disease, diabetes, liver disease and cancer. Suppression of the host immune system is considered the main challenge in such therapies. In order to avoid the side effects of immunosuppressive drugs, encapsulating cells into polymeric matrices is considered a promising strategy. Encapsulation systems utilize permeable materials that allow diffusion of nutrients, waste and therapeutic factors into and out of cells, while masking the cells from the host immune response. In our model, we have been encapsulating ARPE-19, human immortal cell line, that was genetically designed to express and secret CR2-fH protein to test them for safe and effective long term inhibition in vivo. CR2-fH is a complement inhibitor molecule that has been recently found to express promising therapeutic effects in both in vivo and in vitro models of Age-related Macular degeneration (AMD). Furthermore, human skeletal muscle differentiating cells (skMDC) that were recently used in biomedical research to investigate skeletal muscle behavior, function, and ability to be implemented in tissue regeneration field for further applications of disease advanced therapies. In this study we hypothesize that alginate encapsulation using high voltage method can be enhanced and advanced further to use it in different clinical approaches and applications. The present study shows the successful formation of alginate-poly-Lornithine microcapsules using the above-mentioned method, according to specific parameters, to produce microcapsules about 200 mm in diameter. The microcapsules derived from this encapsulation technique according to our hypothesis can be freeze dried without harming the shape of the microcapsules in which they retain the original shape after hydration. The main purpose of lyophilization is to increase the shelf-life storage of encapsulated biomaterials as well as preserve its activity to be used for treatment. Moreover, the technique has the ability to preserve the metabolic activity of genetically engineered ARPE-19 cells and skMDC cells resulting in effective and safe long-term drug delivery for treatment. In addition, hydrogel systems have been utilized in combination with the previous approaches, lyophilized microcapsules and encapsulated cells, for more improvements in regenerative medicine and targeted delivery therapy field

Variance Gamma process for predictive maintenance of mechanical systems

International audienceRemaining Useful Life (RUL) prediction is important for the prognosis and the maintenance of expensive systems. High reliability is an indispensable requirement for advanced systems. Correspondingly, reliability practitioners attempt to investigate the system behaviour in order to mitigate risk as much as possible. The study of the behaviour is insured by collecting the real data of degradation, which is considered as a challenged task. Based on the retrieved data, one can propose a good stochastic process to model the system degradation. In this study, the Variance Gamma process is proposed to model the degradation of the water tank pump. The estimation of the data parameters and their fitting to the model is considered. In addition, the study of the First hitting time (FT) and its distribution is treated. Finally, a good prognostic is conducted based on the FT results