Acute toxicity and biodegradability of N-alkyl-N-methylmorpholinium and N-alkyl-DABCO based ionic liquids

N-Alkyl-N-methylmorpholinium and N-alkyl substituted 1,4-diazabicyclo[2.2.2]octane (DABCO) based ionic liquids (ILs), N-alkyl-DABCO, bearing short alkyl chains are characterised by a low toxicity to Vibrio fischeri, although toxicity significantly increases on increasing the alkyl chain length. Alkyl chain length affects also biodegradability in the 28 days tests; the higher level of biodegradation was found in both the series in the case of the ethyl (C2) derivatives. In the case of N-ethyl DABCO based IL, although biodegradability is still around 40%, and consequently this IL cannot be classified as “readily biodegradable”, this value is similar to the more biodegradable functionalized imidazolium based ILs.     

Computational models for 5αR inhibitors for treatment of prostate cancer: review of previous works and screening of natural inhibitors of 5αR2

Taking into consideration the high importance of the drug target 5-α-reductase (5αR) in prostate cancer in this work we are going first to review previous works and discuss works related to the computer aided drug design of 5αR inhibitors. We report new results in the in silico screening of natural 5αR inhibitors. Traditionally, drugs were discovered by testing compounds synthesized in time consuming multi-step processes against a battery of in vivo biological screens. Promising compounds were then further studied in development, where their pharmacokinetic properties, metabolism and potential toxicity were investigated. Here we present a study on herbal lead compounds and their potential binding affinity to the effectors molecules of major disease like Prostate Cancer. Clinical studies demonstrate a positive correlation between the extent of 5αR type 2 (5αR2) and malignant progression of precancerous lesions in prostate. Therefore, identification of effective, well-tolerated 5αR inhibitors represents a rational chemo preventive strategy. This study has investigated the effects of naturally occurring non-protein compounds berberine and monocaffeyltartaric acid that inhibits 5αR type2. Our results reveal that these compounds use less energy to bind to 5αR and inhibit its activity. Their high ligand binding affinity to 5αR introduce the prospect for their use in chemopreventive applications; in addition they are freely available natural compounds that can be safely used to prevent prostate cancer.     

The hexosamine biosynthetic pathway can mediate myocardial apoptosis in a rat model of diet-induced insulin resistance

Aims: Type 2 diabetes is characterized by deranged metabolic pathways that may result in cardiovascular complications. For example, hyperglycaemia promotes flux through the hexosamine biosynthetic pathway (HBP) leading to greater O‐GlcNAcylation of target proteins, with pathophysiological outcomes. This study investigated mechanisms whereby increased HBP flux elicits myocardial apoptosis in a rat model of diet‐induced hyperglycaemia/insulin resistance. Methods: Four‐week‐old male Wistar rats were fed a high‐fat diet (86 days) after which insulin resistance was assessed vs. matched controls. Oxidative stress was evaluated, and apoptotic peptide levels, BAD phosphorylation and overall O‐GlcNAcylation assessed by immunoblotting. Protein‐specific O‐GlcNAcylation and BAD‐Bcl‐2 dimerization were determined by immunoprecipitation and Western blotting. Results: Rats consuming the high‐fat diet exhibited a moderate elevation in body weight, higher fasting insulin and glucose levels, and insulin resistance vs. controls. Overall protein O‐GlcNAcylation was increased in hyperglycaemic/insulin‐resistant hearts. In parallel, myocardial peptide levels of apoptotic markers (caspase‐3, cytochrome‐c, BAD) were significantly higher with insulin resistance. To gain mechanistic insight into our findings, we evaluated O‐GlcNAcylation of BAD, a pro‐apoptotic Bcl‐2 homolog. Here we found increased BAD O‐GlcNAcylation and decreased BAD phosphorylation (Ser136) in hyperglycaemic/insulin‐resistant rat hearts. These data are in agreement with competition by phosphorylation and O‐GlcNAcylation for the same or neighbouring site(s) on target proteins. Moreover, we observed increased BAD‐Bcl‐2 dimerization in hyperglycaemic/insulin‐resistant hearts. Conclusion: The main finding of this study is that increased apoptosis in hyperglycaemic/insulin‐resistant hearts can also be mediated through HBP‐induced BAD O‐GlcNAcylation and greater formation of BAD‐Bcl‐2 dimers (pro‐apoptotic).     

Recent advances in gelatin-based therapeutics

Introduction: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules.

Areas covered: The most relevant properties of gelatin as biomaterial are presented together with its main therapeutic applications. The latter includes drug delivery systems, tissue engineering approaches, potential uses as ink for 3D/4D Bioprinting, and its relevance in organ-on-a-chip platforms.

Expert opinion: Advances in polymer chemistry, mechanobiology, imaging technologies, and 3D biofabrication techniques have expanded the application of gelatin in multiple biomedical research applications ranging from bone and cartilage tissue engineering, to wound healing and anti-cancer therapy. Here, we highlight the latest advances in gelatin-based approaches within the fields of biomaterial-based drug delivery and tissue engineering together with some of the most relevant challenges and limitations.