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The results demonstrated the strong antimuscarinic action of HBB whereas the nicotinic antagonism at higher concentrations plays at most a moderate modulatory role. The muscle relaxing effect of HBB and its inhibition of muscarinic nerve activation likely explain its clinical use as an antispasmodic drug. Our results further highlight a so far unknown antisecretory action of HBB which warrants further clinical studies on its use in secretory disorders.

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PurposeOver the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar®), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula.Materials and methodsSorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model).ResultsThe in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers.ConclusionOur results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.

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Summary The majority of power utilities have targeted pretentious clean and efficient energy plans. These plans are accompanied in driving down the cost of biomass distributed generation units (BDGs). This paper proposes an optimal allocation procedure of BDGs to enhance the performance of the distribution systems and to reduce the related environmental emissions. The proposed procedure aims to maximize the power utilities' benefits in terms of power loss reduction, energy sales excess, and pollutant emission reduction. It also takes into consideration the minimization of the annual operational and maintenance costs of the BDGs. The load growth with several loading levels over the BDGs planning period is presented. For achieving this target, an adaptive equilibrium optimizer (EO) technique is developed which is characterized by simple structure and dynamic control parameters. The proposed procedure is applied to IEEE 33‐bus and practical large‐scale 141‐bus system of AES‐Venezuela in the metropolitan area of Caracas. The simulation results declare the effectiveness and capability of the employed EO technique in achieving great benefits in terms of energy sales and environmental emissions with a high improvement of the voltage profile and minimizing power losses. In addition, a comparative and statistical analysis is executed with several recent techniques to show the superior capability of the proposed procedure using the EO technique.

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