Versican maintains the homeostasis of adipose tissues and regulates energy metabolism.

Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix. It plays a pivotal role in the formation of the provisional matrix. S100a4, previously known as fibroblast-specific protein, functions as a calcium channel-binding protein. To investigate the role of versican expressed in fibroblasts, we generated conditional knockout mice in which versican expression is deleted in cells expressing S100a4. We found that S100a4 is expressed in adipose tissues, and these mice exhibit obesity under a normal diet, which becomes apparent as early as five months. The white adipose tissues of these mice exhibited decreased expression levels of S100a4 and versican and hypertrophy of adipocytes. qRT-PCR showed a reduced level of UCP1 in their white adipose tissues, indicating that the basic energy metabolism is diminished. These results suggest that versican in adipose tissues maintains the homeostasis of adipose tissues and regulates energy metabolism.

Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1.

Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of -10.4, -10.1, and -9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.

EEG based stress analysis using rhythm specific spectral feature for video game play.

BACKGROUND AND OBJECTIVE: For the emerging significance of mental stress, various research directives have been established over time to understand better the causes of stress and how to deal with it. In recent years, the rise of video gameplay has been unprecedented, further triggered by the lockdown imposed due to the COVID-19 pandemic. Several researchers and organizations have contributed to the practical analysis of the impacts of such extended periods of gameplay, which lacks coordinated studies to underline the outcomes and reflect those in future game designing and public awareness about video gameplay. Investigations have mainly focused on the "gameplay stress" based on physical syndromes. Some studies have analyzed the effects of video gameplay with Electroencephalogram (EEG), Magnetic resonance imaging (MRI), etc., without concentrating on the relaxation procedure after video gameplay. METHODS: This paper presents an end-to-end stress analysis for video gaming stimuli using EEG. The power spectral density (PSD) of the Alpha and Beta bands is computed to calculate the Beta-to-Alpha ratio (BAR). The Alpha and Beta band power is computed, and the Beta-to-Alpha band power ratio (BAR) has been determined. In this article, BAR is used to denote mental stress. Subjects are chosen based on various factors such as gender, gameplay experience, age, and Body mass index (BMI). EEG is recorded using Scan SynAmps2 Express equipment. There are three types of video gameplay: strategic, puzzle, and combinational. Relaxation is accomplished in this study by using music of various pitches. Two types of regression analysis are done to mathematically model stress and relaxation curve. Brain topography is rendered to indicate the stressed and relaxed region of the brain. RESULTS: In the relaxed state, the subjects have BAR 0.701, which is considered the baseline value. Non-gamer subjects have an average BAR of 2.403 for 1 h of strategic video gameplay, whereas gamers have 2.218 BAR concurrently. After 12 minutes of listening to low-pitch music, gamers achieved 0.709 BAR, which is nearly the baseline value. In comparison to Quartic regression, the 4PL symmetrical sigmoid function performs regression analysis with fewer parameters and computational power. CONCLUSION: Non-gamers experience more stress than gamers, whereas strategic games stress the human brain more. During gameplay, the beta band in the frontal region is mostly activated. For relaxation, low pitch music is the most useful medium. Residual stress is evident in the frontal lobe when the subjects have listened to high pitch music. Quartic regression and 4PL symmetrical sigmoid function have been employed to find the model parameters of the relaxation curve. Among them, quartic regression performs better in terms of Akaike information criterion (AIC) and R2 measure.

Accumulation of versican and lack of versikine ameliorate acute colitis.

Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan that plays a key role in the formation of the provisional matrix. Here, we generated dextran sulfate sodium-induced colitis in knockin-mice, R/R, expressing ADAMTS-resistant versican, and investigated the impact of accumulating versican and its turnover in the inflammatory colon mucosa. Histologically, R/R colon showed decreased levels of tissue destruction and an increased number of myofibroblasts and macrophages. Characterization of inflammatory cells revealed an increase in F4/80+ macrophages in R/R colon, compared with wildtype, without a clear shift between M1 and M2 populations. Intestinal stroma exhibited a higher number of myofibroblasts in R/R, suggesting increased levels of tissue regeneration. Coculture of macrophages and stromal fibroblasts obtained from inflammatory colon showed that wild-type macrophages inhibited myofibroblastic differentiation of R/R fibroblasts but not wild-type. This inhibitory effect was due to an increased level of versikine, a cleaved fragment of versican by ADAMTS proteinases. Taken together, our results demonstrate versikine as the direct regulator that inhibits repair of inflamed tissue.