ability by reducing intratumoral microvessel leakiness. Finally, we demonstrated that CAF-derived microfibrilla-associated protein 5 (MFAP5) can upregulate LPP in MECs via a calcium-dependent MFAP5/FAK/ERK/LPP signaling pathway.
Our findings suggest the feasibility of using novel multicellular systems biology modeling to identify and repurpose known drugs targeting cancer-stroma crosstalk networks, potentially leading to faster and more effective cures for cancers.
Research on the subjective experience of suffering has typically focussed on older clinical samples living in Western, educated, industrialised, rich, and democratic (WEIRD) countries. To further extend the existing body of empirical research on suffering to less WEIRD contexts, we use three waves of data (Wave 1: December 2020; Wave 2: January 2021; Wave 3: February 2021) from a sample of nonclinical Indonesian adults (n = 594) to examine associations between suffering, two indices of psychological distress, and 10 facets of well‐being. In our primary analysis, we estimated a series of multiple regression models that adjusted for a range of sociodemographic characteristics, financial and material stability, religious/spiritual factors, prior values of overall suffering, and prior values of each outcome assessed in Wave 1. Results indicated that overall suffering assessed in Wave 2 was associated with an increase in both indices of psychological distress and a decrease in eight facets of well‐being assessed in Wave 3. Using a similar analytic approach, results from a secondary analysis indicated that higher scores on both indices of psychological distress and lower scores on seven of the well‐being facets assessed in Wave 2 were associated with worse subsequent overall suffering assessed in Wave 3. These findings contribute to empirical literature on the implications of suffering for well‐being.
SARS-CoV-2 is a newly discovered virus which causes COVID-19 (coronavirus disease of 2019), initially documented as a human pathogen in 2019 in the city of Wuhan China, has now quickly spread across the globe with an urgency to develop effective treatments for the virus and emerging variants. Therefore, to identify potential therapeutics, an antiviral catalogue of compounds from the CAS registry, a division of the American Chemical Society was evaluated using a pharmacoinformatics approach. A total of 49,431 compounds were initially recovered. After a biological and chemical curation, only 23,575 remained. A machine learning approach was then used to identify potential compounds as inhibitors of SARS-CoV-2 based on a training dataset of molecular descriptors and fingerprints of known reported compounds to have favorable interactions with SARS-CoV-2. This approach identified 178 compounds, however, a molecular docking analysis revealed only 39 compounds with strong binding to active sites. Downstream molecular analysis of four of these compounds revealed various non-covalent interactions along with simultaneous modulation between ligand and protein active site pockets. The pharmacological profiles of these compounds showed potential drug-likeness properties. Our work provides a list of candidate anti-viral compounds that may be used as a guide for further investigation and therapeutic development against SARS-CoV-2.
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