Solid lipid nanoparticles of anticancer drug andrographolide: formulation,in vitro and in vivo studies

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (C_max), area under the curve (AUC), etc. There was an improvement in C_max and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The t_max was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.     

Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury

Background and Aims: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4^−/− mice with deficiency of the hepatobiliary phospholipid transporter. Methods: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4⁻/⁻ (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. Results: Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. Conclusions: The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1.     

Influence of short dispersed and short integral glass fibres on the mechanical behaviour of textile-reinforced concrete

This article addresses the influence of the addition of short dispersed and short integral fibres made of alkali-resistant (AR) glass on the fracture behaviour of textile-reinforced concrete (TRC) subject to tensile loading. A series of uniaxial, deformation-controlled tension tests was performed to study the strength, deformation, and fracture behaviour of thin, narrow plates made of TRC, both with and without the addition of short fibres. Additionally, uniaxial tension tests on specimens reinforced with only short fibres were performed to figure out the difference in behaviour in the absence of textile reinforcement. Furthermore, multifilament-yarn and single-fibre pullout tests were carried out to gain a better understanding of bonding properties and crack-bridging behaviour. While pronounced enhancement of first-crack stress was achieved due to the addition of short dispersed fibres (the value increased by a factor of 2), a significant improvement in tensile strength was recorded for TRC specimens with the addition of integral glass fibres; the value increased by approximately 30 %. Moreover, TRC specimens reinforced with short dispersed glass fibres showed formation of more and finer cracks in comparison to the specimens with integral fibres. It was also found that short integral fibres can improve the bond between multifilament-yarns and the surrounding matrix by means of “special” cross-links. In TRC with short dispersed fibres this phenomenon was less pronounced. The investigations were accompanied by microscopical investigations which provided additional basis for an in-depth discussion of the decisive working mechanisms of hybrid reinforcement.     

TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.     

An experimental analysis of a flaring process for tube ends using a novel spinning tool

The flaring of tube ends are typically performed using electromagnetic forming, or punch-and-die method, both of which cost time and effort. In this work, a new method of tube flaring using a metal spinning process is proposed. An experimental study was carried out to flare the end of aluminium tubes. A multifunction tool was designed based on the flaring ratio to widen the tube end. Several flared specimens were conducted at different working conditions. The effects of working conditions such as flaring ratio, axial feed rate (mm/rev), and rotating speed (rpm) on the flaring loads were investigated. An experimental analysis was carried out to illustrate the effect of the working conditions on the characteristics of the formed part. The analysis showed that these working conditions have a clear influence on wall thickness, surface hardness, and flaring loads.     

The effect of angiotensin II on myosin heavy chain expression in cultured myocardial cells

Angiotensin II (AII), the principal mediator of the renin-angiotensin system, is an important regulator of vascular and cardiac homeostasis. AII has also been shown to be a regulator of cardiac hypertrophy and of the corresponding changes in amount and composition of certain tissue proteins. We examined the trophic effects of AII on cultured myocytes derived from neonatal rat ventricles and followed, by Northern blot analysis and polyacrylamide gel electrophoresis, the expression of alpha- and beta-myosin heavy chain iso-mRNAs and isoproteins. Our findings show that a single administration of AII is sufficient to induce a trophic response in cultured beating myocytes and to enhance the expression of beta-myosin heavy chain iso-mRNA and isoprotein, having no effect on alpha-myosin heavy chain. Induction of alpha-myosin heavy chain expression by thyroid hormone before AII was administered showed that AII could not potentiate a shift from alpha- to beta-myosin heavy chain predominance. We suggest that the potency of AII to regulate the expression of myosin heavy chain isogenes is restricted to the beta isoform and is overridden by thyroid hormone.     

The impact of seismic interpretation on the hydrocarbon trapping at Falak field,Meleiha, Western Desert,Egypt

The object from this study is to find ways to develop field and discover the possible reservoirs and appropriate solutions to avoid the problems we have faced before in the drilled wells that led to drilling dry wells close to producing wells. A set of twenty reflection sections have been used to highlight the subsurface structural setting and the hydrocarbons entrapment styles in Falak field in the northern Western Desert, this is achieved through an integrated geological and geophysical studies utilizing a number of maps and cross sections, all of that for demonstrating all the chances for exploring or developing the field. The reflectors are Ras-Qattara formation, Khatatba-2D member, Masajid formation, Alam El Beuib 3G member, AEB 3F member, AEB 3E member, AEB 3D member, AEB 2A member, AEB 1 member, Alamein Dolomite formation, Dahab Shale member, Kharita formation, Bahariya 5 member, Bahariya 4 member, Bahariya 1 member, Abu Roash “G” member, Abu Roash “E” member, Abu Roash “A” member, and the Apollonia formation. The N-S and E-W trending seismic sections revealed normal faults forming shape seems to be horsts all over the mapped field, these faults led to thin Cretaceous section in the up thrown block area compared to thick section on the downthrown block of the two main faults, for some instances dry hole conditions occur due to missing of structural closure on both the up thrown block and the downthrown. The TWT maps on the top of the traced reflectors reveal different structural closures with set of normal faults constructing three way dip closure in most of these faults and big shape like horst.     

Effects of Arbuscular Mycorrhiza on Plant Chemistry and the Development and Behavior of a Generalist Herbivore

Arbuscular mycorrhiza (AM) formed between plants and AM fungi (AMF) can alter host plant quality and thus influence plant-herbivore interactions. While AM is known to affect the development of generalist chewing-biting herbivores, AM-mediated impacts on insect behavior have been neglected until now. In this study, the effects of Rhizophagus irregularis, a generalist AMF, on phenotypic and leaf metabolic traits of Plantago major plants were investigated. Further, the influence of AM-mediated host plant modifications on the development and on seven behavioral traits of larvae of the generalist Mamestra brassicae were recorded. Tests were carried out in the third (L3) and fourth (L4) larval instar, respectively. While shoot water content, specific leaf area, and foliar concentrations of the secondary metabolite aucubin were higher in AM-treated compared to non-mycorrhized (NM) plants, lower concentrations of the primary metabolites citric acid and isocitric acid were found in leaves of AM plants. Larvae reared on AM plants gained a higher body mass and tended to develop faster than individuals reared on NM plants. However, plant treatment had no significant effect on any of the behavioral traits. Instead, differences between larvae of different ages were detected in several behavioral features, with L4 being less active and less bold than L3 larvae. The results demonstrate that AM-induced modifications of host plant quality influence larval development, whereas the behavioral phenotype seems to be more fixed at least under the tested conditions.     

Investigating the antigraffiti properties of a polyurethane clearcoat containing a silicone polyacrylate additive

In this study, a polyurethane clearcoat was modified using a silicone polyacrylate antigraffiti additive and its surface free energy and mechanical properties were evaluated by various analytical techniques. The results showed that surface free energy decreased by replacing the polyol resin with the additive up to 10 mol%. Dynamic mechanical thermal analysis (DMTA) showed that the presence of the additive increased the storage modulus of the samples at ambient temperature. Evaluation of stainability of the coatings containing the additive revealed that a spray paint would be repelled from the surface showing a proper antigraffiti behavior. The additive did not affect the surface roughness of the films, indicating that the antigraffiti properties resulted from changes in surface chemistry due to migration of the additive to the surface.