ENU-exposure at E15 in subsequent pregnancies lead to an increase in glioma and PNST incidence. However, consecutive generational ENU-exposure (E15) decreased the animals’ survival due to an early onset of both types of tumors. Moreover, PNST presented an inheritable component because progeny, which were not themselves exposed to ENU but whose progenitors were, developed PNSTs. Our results suggest that repeated exposure to ENU later in pregnancy and in successive generations favours the development of intracranial gliomas and PNSTs in the offspring.The Clp protease is an AAA+ protease that executes abnormally folded or malfunctioning proteins, and has an important role in producing virulence factors, forming biofilms or persisters and developing methicillin-resistant Staphylococcus aureus (MRSA). Recent studies showed that Clp protease controls virulence via agr signaling and degrades antitoxins of the toxin-antitoxin system to modulate the formation of persisters and biofilms. In this review, we focus on recent developments concerning the virulence and persistence regulatory pathways and resistance-related mechanism of Clp protease in S. ML390 aureus, with an overview of the Clp modulators developed to treat MRSA infection.Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expression patterns might be a quick, cheap, and interesting approach to predict the biological activity of investigated molecules.In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, a panel of assays has been developed and applied to screen collections of approved and investigational drugs for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity in a quantitative high-throughput screening (qHTS) format. In this review, we applied data-driven approaches to evaluate the ability of each assay to identify potential anti-SARS-CoV-2 leads. Multitarget assays were found to show advantages in terms of accuracy and efficiency over single-target assays, whereas target-specific assays were more suitable for investigating compound mechanisms of action. Moreover, strict filtering with counter screens might be more detrimental than beneficial in identifying true positives. Thus, developing novel HTS assays acting simultaneously against multiple targets in the SARS-CoV-2 life cycle will benefit anti-COVID-19 drug discovery.Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that affects 3.8-9.2% of the world population. It affects the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development. Presently, a large number of studies have shown that compared to healthy individuals, the composition and diversity of gut microbiota in IBS patients have changed, and the proteolytic activity (PA) in fecal supernatant and colonic mucosa of IBS patients has also increased. These findings indicate that the imbalance of intestinal microecology and intestinal protein hydrolysis is closely related to IBS. Furthermore, the intestinal flora is a key substance that regulates the PA and is associated with IBS. The current review described the intestinal microecology and intestinal proteolytic activity of patients with IBS and also discussed the effect of intestinal flora on PA. In summary, this study proposed a pivotal role of gut microbiota and PA in IBS, respectively, and provided an in-depth insight into the diagnosis and treatment targets of IBS as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

We investigated the biomarkers, immune responses and cellular changes in vaccinated and non-vaccinated goats experimentally challenged with M. haemolytica serotype A2 under rainy and hot tropical conditions. A total of twenty-four clinically healthy, non-pregnant, female goats randomly allocated to 2 groups of 12 goats each were used for the study. The 12 goats in each season were subdivided into three groups (n=4), which served as the control (G-NEG), non-vaccinated (G-POS), and vaccinated (G-VACC). In week-1, the G-VACC received 2mL of alum-precipitated pasteurellosis vaccine while G-POS and G-NEG received 2ml of sterile PBS. In week 2, the G-POS and G-VACC received 1mL intranasal spray containing 10

CFU of M. haemolytica serotype A2. Inoculation was followed by daily monitoring and weekly bleeding for eight weeks to collect data and serum for biomarkers and immune responses using commercial ELISA test kits. The goats were humanely euthanised at the end of the experiments to collect lungs and the submandmental humidity recorded in the rainy season. Increased relative humidity in the rainy season is a significant stress factor for the higher susceptibility and severity of pneumonic mannheimiosis of goats in the tropics. Vaccination of goats using the alum precipitated Pasteurella multocida vaccine before the onset of the rainy season is recommended to minimise mortality due to potential outbreaks of pneumonia during the rainy season.Acinetobacter baumannii is Gram-negative, an opportunistic pathogen responsible for life-threatening ventilator-associated pneumonia. World Health Organization (WHO) enlisted it as a priority pathogen for which therapeutic options need speculations. Biofilm further benefits this pathogen and aids 100-1000 folds more resistant against antimicrobials and the host immune system. In this study, ursolic acid (1) and its amide derivatives (2-4) explored for their antimicrobial and antibiofilm potential against colistin-resistant A. baumannii (CRAB) reference and clinical strains. Viability, crystal violet, microscopic, and gene expression assays further detailed the active compounds’ antimicrobial and biofilm inhibition potential. Compound 4 [N-(2′,4′-dinitrophenyl)-3β-hydroxyurs-12-en-28-carbonamide)], a synthetic amide derivate of ursolic acid significantly inhibits bacterial growth with MIC in the range of 78-156 μg/mL against CRAB isolates. This compound failed to completely kill the CRAB isolates even at 500 μg/mL concentration, suggesting the compound’s anti-virulence and bacteriostatic nature.