Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: new insight into the anticancer effect of TAK-242 (Resatorvid)

Cancer Chemotherapy and Pharmacology - Despite all advances in the treatment of ovarian cancer (OC), it remains the most lethal gynecological malignancy worldwide. There are growing amounts of...     

Effect of Thermomechanical Treatment of Al-Zn-Mg-Cu with Minor Amount of Sc and Zr on the Mechanical Properties

In this study, the mechanical and microstructural properties of Al-Zn-Mg-Cu-Zr cast alloy with 0.1% Sc under homogeneous, dissolution, and T6 and thermomechanical treatments with the aim of increasing the volume fraction of MgZn₂. Al₃(Sc,Zr) reinforcing precipitates were examined by hardness, microscopic examinations, tensile tests and software analysis. The results showed that, firstly, the hardness results are well proportional to the results of the tensile properties of alloys and, secondly, the strength of the alloy with thermomechanical treatments compared to T6 treatments increased from 492 MPa to 620 MPa and the elongation increased from 8% to 17% and was 100% upgraded. Microstructural and fracture cross section investigations showed that Al₃(Sc,Zr) nanosize dispersoids were evenly distributed among MgZn₂ dispersoids and the alloy fracture was of semi-ductile type and nanosize dispersoids less than 10 nm were observed at the end of the dimples in the fracture section. The volume fraction of nanosize dispersoids in the whole microstructure of thermomechanical treatment samples was also much higher than that of T6 heat treated samples, so that the percentage of Al₃(Sc,Zr) precipitates arrived from less than 1% in T6 operation to 8.28% in the quench-controlled thermomechanical operation (with 50% deformation). The quality index (QI) in thermomechanical treatment samples is 19% higher than T6 samples, so that this index has increased from 641 in T6 operation to 760 in samples under thermomechanical treatment due to precipitate morphology, volume fraction of precipitates, their uniform distribution in the matrix, and nano sized precipitates in samples under thermomechanical treatment.     

Graphene oxide based crosslinker for simultaneous enhancement of mechanical toughness and self-healing capability of conventional hydrogels

Extraordinary self-healing efficiency is rarely observed in mechanically strong hydrogels, which often limits the applications of hydrogels in biomedical engineering. We have presented an approach to utilize a special type of graphene oxide-based crosslinker (GOBC) for the simultaneous improvement of toughness and self-healing properties of conventional hydrogels. The GOBC has been prepared from graphene oxide (GO) by surface oxidation and further introduction of vinyl groups. It has been designed in such a way that the crosslinker is able to form both covalent bonds and noncovalent interactions with the polymer chains of hydrogels. To demonstrate the efficacy of GOBC, it was incorporated in a conventional polyacrylamide (PAM) and polyacrylic acid (PAA) hydrogel matrix, and the mechanical and self-healing properties of the prepared hydrogels were investigated. In PAM-GOBC hydrogels, it has been observed that the mechanical properties such as tensile strength, Young''s modulus, and toughness are significantly improved by the incorporation of GOBC without compromising the self-healing efficiency. The PAM-GOBC hydrogel with a modulus of about 0.446 MPa exhibited about 70% stress healing efficiency after 40 h. Whereas, under the same conditions a PAM hydrogel with commonly used crosslinker N,N′-methylene-bis(acrylamide) of approximately the same modulus demonstrated no self-healing at all. Similar improvement of self-healing properties and toughness in PAA-GOBC hydrogel has also been observed which demonstrated the universality of the crosslinker. This crosslinker-based approach to improve the self-healing properties is expected to offer the possibility of the application of commonly used hydrogels in many different sectors, particularly in developing artificial tissues.

Introduction of a two-dimensional graphene oxide-based crosslinker simultaneously improve the mechanical and self-healing properties of hydrogels by offering an interesting combination of covalent and reversible hydrogen bonds to polymer backbones.     

Concrete by Preplaced Aggregate Method Using Silica Fume and Polypropylene Fibres

Preplaced aggregate concrete (PAC) is prepared in two steps, with the coarse aggregate being initially laid down in the formwork, after which a specialised grout is injected into it. To enhance the properties of concrete and to reduce the emission of CO₂ produced during the production of cement, supplementary cementitious materials (SCMs) are used to partially substitute ordinary Portland cement (OPC). In this study, 100 mm × 200 mm (diameter x height) PAC cylinders were cast with 10 per cent of cement being substituted with silica fume; along with that, 1.5% dosage of Macro polypropylene fibres were also introduced into the coarse aggregate matrix. Compressive strength test, splitting tensile strength test, mass loss at 250 °C, and compressive strength at 250 °C were performed on the samples. PAC samples with 10% of cement replaced with Silica Fume (SPAC) were used as control samples. The primary objective of this study was to observe the effect of the addition of Polypropylene fibres to PAC having Silica fume as SCM (FRPAC). The aforementioned tests showed that FRPAC had a lower compressive strength than that of the control mix (SPAC). FRPAC had greater tensile strength than that of NPAC and SPAC. Mass loss at 250 °C was greater in SPAC compared to FRPAC. The compressive strength loss at 250 °C was significantly greater in FRPAC compared to SPAC. FRPAC exhibited a greater strain for the applied stress, and their stress-strain curve showed that FRPAC was more ductile than SPAC.     

Coadministration of liposomal methylglyoxal increases the activity of amphotericin B against Candida albicans in leukopoenic mice

Abstract

In this study, we investigated the therapeutic efficacy of a combination of liposomal amphotericin B (Lip-Amp B) and Methylglyoxal (Lip-MG) against Candida albicans in the leukopoenic mice. The antifungal efficacy of Lip-Amp B or Lip-MG or a combination of Lip-Amp B and Lip-MG was evaluated by the analysis of the survival rate and the fungal load in the treated mice. The immune-stimulatory effect of Lip-MG on macrophages was evaluated by analysing the secretion of proinflammatory cytokines. C. albicans infected mice treated at the doses of 1 and 2?mg/kg of Lip-Amp B showed 20% and 50% survival rates, respectively. Whereas the mice treated with free Amp B at the same doses died within 40?days of treatment. Interestingly, C. albicans infected mice treated with a combination of Lip-Amp B and Lip-MG had 70% survival rate on day 40 postinfection. Moreover, treatment of macrophages with Lip-MG increased their fungicidal activity and the secretion of proinflammatory cytokines, including TNF-α and IL-1β. These findings suggested that co-treatment with Lip-Amp B and Lip-MG had a synergistic effect and could be effective against C. albicans in immunocompromised subjects.     

Biological Activities of 2-Mercaptobenzothiazole Derivatives: A Review

2-Mercaptobenzothiazoles are an important class of bioactive and industrially important organic compounds. These compounds are reported for their antimicrobial and antifungal activities, and are subsequently highlighted as a potent mechanism-based inhibitor of several enzymes like acyl coenzyme A cholesterol acyltransferase, monoamine oxidase, heat shock protein 90, cathepsin D, and c-Jun N-terminal kinases. These derivatives are also known to possess antitubercular, anti-inflammatory, antitumor, amoebic, antiparkinsonian, anthelmintic, antihypertensive, antihyperlipidemic, antiulcer, chemoprotective, and selective CCR3 receptor antagonist activity. This present review article focuses on the pharmacological profile of 2-mercaptobenzothiazoles with their potential activities.     

Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines

Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 μg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.     

Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons

Many behavioral effects of nicotine result from activation of nigrostriatal and mesolimbic dopaminergic systems. Nicotine regulates dopamine release not only by stimulation of nicotinic acetylcholine receptors (nAChRs) on dopamine cell bodies within the substantia nigra and ventral tegmental area (SN/VTA), but also on presynaptic nAChRs located on striatal terminals. The nAChR subtype(s) present on both cell bodies and terminals is still a matter of controversy. The purpose of this study was to use double-labeling in situ hybridization to identify nAChR subunit mRNAs expressed within dopamine neurons of the SN/VTA, by using a digoxigenin-labeled riboprobe for tyrosine hydroxylase as the dopamine cell marker and (35)S-labeled riboprobes for nAChR subunits. The results reveal a heterogeneous population of nAChR subunit mRNAs within midbrain dopamine neurons. Within the SN, almost all dopamine neurons express alpha2, alpha4, alpha5, alpha6, beta2, and beta3 nAChR mRNAs, with more than half also expressing alpha3 and alpha7 mRNAs. In contrast, less than 10% express beta4 mRNA. Within the VTA, a similar pattern of nAChR subunit mRNA expression is observed except that most subunits are expressed in a slightly lower percentage of dopamine neurons than in the SN. Within the SN, alpha4, beta2, alpha7, and beta4 mRNAs are also expressed in a significant number of nondopaminergic neurons, whereas within the VTA this only occurs for beta4. The heterogeneity in the expression of nAChR subunits within the SN/VTA may indicate the formation of a variety of different nAChR subtypes on cell bodies and terminals of the nigrostriatal and mesolimbic pathways.