Genetically modified organisms (GMOs) have emerged as an integral component of a sustainable bioeconomy, with an array of applications in agriculture, bioenergy, and biomedicine. However, the rapid development of GMOs and associated synthetic biology approaches raises a number of biosecurity concerns related to environmental escape of GMOs, detection thereof, and impact upon native ecosystems. A myriad of genetic safeguards have been deployed in diverse microbial hosts, ranging from classical auxotrophies to global genome recoding. However, to realize the full potential of microbes as biocatalytic platforms in the bioeconomy, a deeper understanding of the fundamental principles governing microbial responsiveness to biocontainment constraints, and interactivity of GMOs with the environment, is required. Herein, we review recent analytical biotechnological advances and strategies to assess biocontainment and microbial bioproductivity, as well as opportunities for predictive systems biodesigns towards securing a viable bioeconomy.

Concerning the link between copper excess and the pathogenesis of chronic liver diseases, its retention is reckoned to develop as a complication of cholestasis. Recently, it has been found that cholestatic liver injury involves largely inflammatory cell-mediated liver cell necrosis, with consequent reduced hepatic mass, more than occurring through direct bile acid-induced apoptosis. On the other hand, interference with protein synthesis could be expected to result, ending in an altered ability of the liver to retain copper. Little is known about the association between serum copper and clotting factors in cirrhotics. We aimed at studying a possible relationship between increased levels of copper and an aspect of the haemostatic process in liver cirrhosis patients, assessing an index of protein synthesis (albumin) and parameters of protein synthesis/coagulation/fibrinolysis, such as prothrombin time (PT), antithrombin (AT) III and fibrinogen.

Records from 85 patients suffering from liver cirrhosis of variorelationship of copper to coagulation/hypercoagulation parameters (mainly AT III) in our research could find a plausible interpretation.Trapping assays are conducted at lead optimization stages to detect reactive metabolites (RMs) that can contribute to drug toxicity. The commonly used dansyl glutathione (dGSH) provides a sensitive analysis owing to the fluorescent label, however, it captures only soft electrophilic RMs. TRs for hard electrophilic RMs, few of which are labeled fluorescently, can detect hard electrophilic aldehydes only by forming unstable imine derivatives. In this study, we aimed to develop novel fluorescently labeled TRs that detect both soft and hard electrophilic RMs and form stable ring structures with aldehydes. We designed four dansylated TRs based on cysteine, which has both soft and hard nucleophilic groups. To evaluate the reactivity of the TRs, we incubated them with several substrates and found that one of the TRs (CysGlu-Dan) detected all the soft and hard electrophilic RMs. We also examined the inhibition potential of each TR for seven major CYPs involved in drug metabolism and found that CysGlu-Dan showed an inhibitory profile similar to that of dGSH. In conclusion, CysGlu-Dan can be used to evaluate the risk of RMs in drug discovery.Lung cancer is the leading cause of cancer related deaths worldwide. The present study investigated the effects of naproxen (NSAID) on lung adenocarcinoma in spontaneous lung cancer mouse model. Six-week-old transgenic KrasG12V mice (n = 20; male + female) were fed modified AIN-76A diets containing naproxen (0/400 ppm) for 30 wk and euthanized at 36 wk of age. Lungs were evaluated for tumor incidence, multiplicity, and histopathological stage (adenoma and adenocarcinoma). Lung tumors were noticeable as early as 12 wk of age exclusively in the KrasG12V mice. By 36 wk age, 100% of KrasG12V mice on control diet developed lung tumors, mostly adenocarcinomas. KrasG12V mice fed control diet developed 19.8 ± 0.96 (Mean ± SEM) lung tumors (2.5 ± 0.3 adenoma, 17.3 ± 0.7 adenocarcinoma). Administration of naproxen (400 ppm) inhibited lung tumor multiplicity by ∼52% (9.4 ± 0.85; P less then 0001) and adenocarcinoma by ∼64% (6.1 ± 0.6; P less then 0001), compared with control-diet-fed mice. However, no significant difference was observed in the number of adenomas in either diet, suggesting that naproxen was more effective in inhibiting tumor progression to adenocarcinoma. Biomarker analysis showed significantly reduced inflammation (COX-2, IL-10), reduced tumor cell proliferation (PCNA, cyclin D1), and increased apoptosis (p21, caspase-3) in the lung tumors exposed to naproxen. Decreased serum levels of PGE2 and CXCR4 were observed in naproxen diet fed KrasG12V mice. Gene expression analysis of tumors revealed a significant increase in cytokine modulated genes (H2-Aa, H2-Ab1, Clu), which known to further modulate the cytokine signaling pathways. Overall, the results suggest a chemopreventive role of naproxen in inhibiting spontaneous lung adenocarcinoma formation in KrasG12V mice.

Up to 30% of severely injured patients on prophylactic anticoagulation experience venous thromboembolism (VTE). Our previous work shows that acquired antithrombin (AT) deficiency [AT<80%] occurs in approximately 20% of trauma patients upon admission and drives poor responsiveness to enoxaparin. DL-Alanine datasheet However, changes in AT over time and its association with VTE remain unknown. The aim of this study was to determine the relationship between acquired AT deficiency and VTE in severely injured patients.

A secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) clinical trial was performed. Patients who died within 24h of hemorrhage were excluded from analysis. Demographics, mechanism and severity of injury, transfusions volumes, and outcomes were compared between patients who did and did not develop VTE. Non-parametric statistical tests were used to compare patients with and without VTE. Logistic regression analyses were performed to identify predictors of VTE risk, controlling for AT deficiency (over first 72h), age, gender, race, body mass index, study site, randomization group and injury severity.