Design and evaluation of a biosynthesized cellulose drug releasing duraplasty.

Decompressive craniectomy (DC) is a standard surgical procedure performed on stroke patients in which a portion of a skull is removed and a duraplasty membrane is applied onto the brain. While DC can significantly reduce the risk of death, it does not reverse the stroke damage. In this study, a novel biosynthesized cellulose (BC)-based drug releasing duraplasty was developed and studied. The BC duraplasty fabrication process allowed readily incorporation of growth factors (GFs) in a sterile manner and control of physical and mechanical properties of the resulting duraplasty. Our results showed that BC duraplasty containing the highest amount of dry cellulose presented swelling ratio of 496 ± 27%, Young's modulus of 0.37 ± 0.02 MPa, ultimate tensile strength of 0.96 ± 0.02 MPa, while releasing GFs for over 10 days. In addition, neural stem/progenitor cell (NSPC) cultures demonstrated that the GFs released from the BC duraplasty promoted NSPC proliferation and differentiation in vitro. Finally, animal studies revealed that the BC duraplasty did not cause any inflammatory reactions after the DC procedure in vivo. In summary, this newly developed GF loaded BC membrane demonstrates a promising potential as drug releasing duraplasty, not only for stroke treatments but also for traumatic brain injuries and spinal cord injuries.

In situ and ex situ modifications of bacterial cellulose for applications in tissue engineering.

Bacterial cellulose (BC) is secreted by a few strains of bacteria and consists of a cellulose nanofiber network with unique characteristics. Because of its excellent mechanical properties, outstanding biocompatibilities, and abilities to form porous structures, BC has been studied for a variety of applications in different fields, including the use as a biomaterial for scaffolds in tissue engineering. To extend its applications in tissue engineering, native BC is normally modified to enhance its properties. Generally, BC modifications can be made by either in situ modification during cell culture or ex situ modification of existing BC microfibers. In this review we will first provide a brief introduction of BC and its attributes; this will set the stage for in-depth and up-to-date discussions on modified BC. Finally, the review will focus on in situ and ex situ modifications of BC and its applications in tissue engineering, particularly in bone regeneration and wound dressing.

Activity of chalcones derived from 2,4,5-trimethoxybenzaldehyde against Meloidogyne exigua and in silico interaction of one chalcone with a putative caffeic acid 3-O-methyltransferase from Meloidogyne incognita.

Meloidogyne exigua is a parasitic nematode of plants that causes great losses to coffee farmers. In an effort to develop parasitic controls, 154 chalcones were synthesized and screened for activity against this nematode. The best results were obtained with (2E)-1-(4'-nitrophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one (6) with a 50% lethal concentration (LC50) of 171 µg/ml against M. exigua second-stage juveniles, in comparison to the commercially-available nematicide carbofuran which had an LC50 of 260 µg/ml under the same conditions. When coffee plants were used, 6 reduced the nematode population to ~50% of that observed in control plants. To investigate the mechanism of action of 6, an in silico study was carried out, which indicated that 6 may act against M. exigua through inhibition of a putative caffeic acid 3-O-methyltransferase homodimer, the amino acid sequence of which was determined by examining the genome of Meloidogyne incognita.

Acylhydrazones contribute to serum glucose homeostasis through dual physiological targets.

In this study the in vivo and in vitro antidiabetic effects of four acylhydrazone derivatives were investigated in rats. The secretagogue action, oral glucose tolerance, insulinogenic index and mechanism of action of these acylhydrazones in relation to calcium uptake in pancreatic islets were studied. Also, the insulinomimetic effect on glycemia in diabetic rats was verified. Of the acylhydrazones studied, 1 and 4 were able to increase glucose tolerance in an acute time-course. A powerful secretagogue effect was exhibited by 1 and glibenclamide with an insulinogenic index around 3.9 and 1.3-fold higher than that of the hyperglycemic group, respectively. Moreover, an acute and dose-dependent effect of glibenclamide and 1 on calcium uptake in pancreatic islets was observed. The rapid stimulatory effect of 1 on calcium uptake seems to be mediated, at least in part, by ATP-dependent K+ channels (K+-ATP) since the stimulatory effect of 1 was similar to that observed for glibenclamide but was not potentiated by sulphonylurea. Furthermore, both extracellular and calcium from stocks mediate the signal transduction of stimulatory effect of 1 on calcium uptake which may contribute to insulin secretion. In addition, the insulinomimetic effect of 1 was evidenced through the level of serum glucose lowering in alloxan-induced diabetic rats. Also, 1 induced a significant increase in glycogen content in vivo and glucose uptake in soleus muscle in vitro. The results of this study indicate dual physiological targets for the acylhydrazone 1, i.e., pancreatic islets and skeletal muscle, as a result of insulin secretagogue and insulinomimetic action.

Trimethoxy-chalcone derivatives inhibit growth of Leishmania braziliensis: synthesis, biological evaluation, molecular modeling and structure-activity relationship (SAR).

In this work we described the synthesis, the antileishmanial activity and the molecular modeling and structure-activity relationship (SAR) evaluations of a series of chalcone derivatives. Among these compounds, the methoxychalcones 2h, 2i, 2j, 2k and 2l showed significant antileishmanial activity (IC(50)<10 µM). Interestingly 2i (IC(50)=2.7 µM), 2j (IC(50)=3.9 µM) and 2k (IC(50)=4.6 µM) derivatives presented better antileishmanial activity than the control drug pentamidine (IC(50)=6.0 µM). Our SAR study showed the importance of methoxy di-ortho substitution at phenyl ring A and the relationship between the frontier orbital HOMO coefficients distribution of these molecules and their activity. The most active compounds 2h, 2i, 2j, 2k, and 2l fulfilled the Lipinski rule-of-five which theoretically is important for good drug absorption and permeation through biological membranes. The potential profile of 2j (IC(50)=3.9 µM and CC(50)=216 µM) pointed this chalcone derivative as a hit compound to be further explored in antileishmanial drug design.