Jamal (2020) Design of experiment (DoE)-driven invitro and invivo uptake studies of exosomes for pancreatic cancer delivery enabled by copper-free click chemistry-based labelling,

The global transcriptional response of Escherichia coli to styrene and the potential influence of the exposure source was determined by performing RNA sequencing (RNA-seq) analysis on both styrene-producing and styrene-exposed cells. Relative to an unexposed control, 1,574 and 755 genes showed significant changes in differential expression when styrene was exogenously added versus endogenously produced. Taken together, in both cases, styrene exposure appears to cause both cell envelope and DNA damage, to which cells respond by down-regulating key genes and pathways involved in DNA replication, protein production, and cell wall biogenesis. Among the most significantly up-regulated genes under both exposure modes were those involved in the phage shock protein response (e.g. pspABCDE/G), general stress regulators (e.g. marA, rpoH), and several membrane-altering genes (notably, bhsA, ompR, ldtC), whereas most efflux transporters were, surprisingly, unaffected. Subsequent studies performed with styrene addition, meanwhile, demonstrate how strains lacking ompR (involved in controlling outer membrane (OM) composition/osmoregulation) or any of tolQ, tolA, or tolR (all involved in OM constriction) each displayed over 40 per cent reduced growth relative to wild-type E. coli; differences pointing to the likely importance of these OM-associated processes in native styrene tolerance. Conversely, despite reducing the basal fitness of unexposed cells, overexpression of plsX (involved in phospholipid biosynthesis) led to 70 per cent greater growth when styrene exposed; further suggesting the importance of OM properties in controlling tolerance. Overall, the collective behaviors suggest that, regardless of its source, prolonged exposure to inhibitory styrene levels causes cells to shift from a 'growth mode’ to ‘survival mode’, redistributing cellular resources to fuel native tolerance mechanisms.

Chalcones and their derivatives are becoming increasingly popular due to their various pharmacological effects. Chalcone molecules may be extracted from natural resources, entirely synthesised, or biosynthesised by modifying the natural ones. In this study, five pyrazole based adamantyl heterocyclic compounds were synthesised by condensation of 1-adamantyl chalcone with substituted phenylhydrazine. The products were characterised by using ¹HNMR, ¹³CNMR and FT-IR spectroscopy. The microbiological activity of these compounds was investigated against bacteria and fungi. The new compounds showed good to moderate activity against the microbial species used for screening. All developed molecules showed antibacterial activity against gram-negative and gram-positive. These molecules showed antifungal activities against Fusarium oxysporum fungus and in a dose-dependent manner, apart from RS-1 molecules which showed compromised antifungal activity and even at a high dose.

Clinical applications of oral protein therapy for the treatment of various chronic diseases are limited due to the harsh conditions encounter the proteins during their journey in the Gastrointestinal Tract. Although nanotechnology forms a platform for the development of oral protein formulations, obtaining physiochemically stable formulations able to deliver active proteins is still challenging because of harsh preparation conditions. This study proposes the use of poly (D, L-lactic-co-caprolactone)-based polymeric nanocapsules at different monomers’ ratios for protein loading and oral delivery. All formulations had a spherical shape and nano-scale size, and lysozyme encapsulation efficiency reached 80% and significantly affected by monomers’ ratio. Trehalose and physical state of lysozyme had a significant effect on its biological activity (P < 0.05). Less than 10% of the protein was released in simulated gastric fluid, and 73% was the highest recorded accumulative release percentage in simulated intestinal fluid (SIF) over 24 h. The higher caprolactone content, the higher encapsulation efficiency (EE) and the lower SIF release recorded. Therefore, the formulation factors were optimised and the obtained system was PEGylated wisely to attain EE 80%, 81% SIF release within 24 h, and 98% lysozyme biological activity. The optimum formulation was prepared to deliver DNase, and similar attributes were obtained.