A series of 2-arylbenzo[c]furan-chalcone hybrids 3a–y have been synthesized and evaluated for antiproliferative effects against the human breast cancer (MCF-7) cell line and for its potential to induce apoptosis and also to inhibit tubulin polymerization and/or epidermal growth factor receptor-tyrosine kinase (EGFR-TK) phosphorylation. Most of these compounds exhibited moderate to significant antigrowth effects in vitro against the MCF-7 cell line when compared to the reference standard actinomycin D. The capabilities of the most cytotoxic benzofuran-chalcone hybrids 3b and 3i, to induce apoptosis, have been evaluated by Annexin V-Cy3 SYTOX staining and caspase-3 activation. The experimental and molecular docking results suggest that the title compounds have the potential to exhibit inhibitory effects against tubulin polymerization and epidermal growth factor receptor tyrosine kinase (EGFR-TK) phosphorylation. The modeled structures of representative compounds displayed hydrophobic interactions as well as hydrogen and/or halogen bonding with the protein residues. These interactions are probably responsible for the observed increased binding affinity for the two receptors and their significant antigrowth effect against the MCF-7 cell line.

The 37/67 kDa high-affinity laminin receptor (laminin receptor precursor/laminin receptor, LRP/LR) is a multi-faceted cellular receptor. It plays a vital role in the malignancy of various cancer types where it is seen to contribute to invasion, adhesion, apoptosis evasion and angiogenesis. Furthermore, it has been found to play an important role in facilitating the processes leading to neurotoxicity in Alzheimer's disease (AD). Various therapeutic options targeting this receptor have been patented with the outlook on application for the treatment/prevention of these diseases. The various roles that LRP/LR plays in cancer, AD and infectious diseases caused by viruses and bacteria have been examined in detail and an overview of the current patented therapeutic strategies targeting this receptor is given. Molecular tools directed against LRP/LR, such as antibodies and small interfering RNA, could prove to be effective in the prevention of metastasis and angiogenesis while inducing apoptosis in cancers. Moreover, these strategies could also be applied to AD where LRP/LR is seen to facilitate the production and internalization of the neurotoxic Aβ peptide. This review provides a comprehensive overview of the mechanisms by which LRP/LR is involved in eliciting pathogenic events, while showing how the use of patented approaches targeting this receptor could be used to treat them.

Cancer has become a major problem worldwide due to its increasing incidence and mortality rates. Both the 37kDa/67kDa laminin receptor (LRP/LR) and telomerase are overexpressed in cancer cells. LRP/LR enhances the invasiveness of cancer cells thereby promoting metastasis, supporting angiogenesis and hampering apoptosis. An essential component of telomerase, hTERT is overexpressed in 85–90% of most cancers. hTERT expression and increased telomerase activity are associated with tumor progression. As LRP/LR and hTERT both play a role in cancer progression, we investigated a possible correlation between LRP/LR and telomerase. LRP/LR and hTERT co-localized in the perinuclear compartment of tumorigenic breast cancer (MDA_MB231) cells and non-tumorigenic human embryonic kidney (HEK293) cells. FLAG^® Co-immunoprecipitation assays confirmed an interaction between LRP/LR and hTERT. In addition, flow cytometry revealed that both cell lines displayed high cell surface and intracellular LRP/LR and hTERT levels. Knock-down of LRP/LR by RNAi technology significantly reduced telomerase activity. These results suggest for the first time a novel function of LRP/LR in contributing to telomerase activity. siRNAs targeting LRP/LR may act as a potential alternative therapeutic tool for cancer treatment by (i) blocking metastasis (ii) promoting angiogenesis (iii) inducing apoptosis and (iv) impeding telomerase activity.

37 kDa LRP::FLAG enhances telomerase activity and reduces senescent markers in vitro 37 kDa LRP::FLAG enhances telomerase activity and reduces senescent markers in vitro

Background: Ezetimibe is used to treat cardiovascular disease as it blocks the sterol transporter Niemann-Pick C1-Like 1 (NPC1CL1) protein. However, recent evidence indicates that Ezetimibe inhibits several cancers indirectly by reducing circulating cholesterol or via specific signalling pathways. Methods and Results: Our in silico studies indicate that Ezetimibe binds to the Tp53 binding domain in Mdm2, forming a more thermodynamically stable complex than nutlin3a. Furthermore, a docking study of the newly developed inhibitors—RG7388 and RG7112—was conducted. This further showed lower binding energies of −6.337 kcal/mol and −6.222 kcal/mol, respectively, when compared to the −7.919 kcal/mol exhibited by Ezetimibe. We show that Ezetimibe inhibits the growth of several cancer cell lines at concentrations that are not toxic to a normal cell line. Conclusions: Thus, Ezetimibe is probably active against cancers that overexpress Mdm2. Moreover, inhibitors of RBBP6 may be combined with Ezetimibe for effective anticancer activity. Due to poor oral bioavailability, Ezetimibe must be administered parenterally for cancer treatment.

This study investigated the particle number concentrations (PNCs) and particle size distributions (PSDs) of chalk particles released during writing with dust‐free and normal chalkands when the chalkboard was wiped with different materials. A standard paragraph was written alongside a pie chart using dust‐free and normal chalk sticks, which was then erased with a chalkboard duster. A chalkboard duster, dry cloth, wet cloth and paper towels were also used to wipe the standard paragraph and pie chart written using dust‐free and normal chalk. The chalk particles were measured using a TSI 3330 optical particle sizer at a flow rate of 1 L/min. The mean PNC was numerically higher when writing with dust‐free chalk (2.13 ± 0.37 #/cm ³ ) than when writing with normal chalk (2.08 ± 0.35 #/cm ³ ); however, this difference was not statistically significant ( p = 0.70). The mean PNC was numerically higher when wiping a paragraph written with normal chalk (14.15 ± 1.15 #/cm ³ ) compared with dust‐free chalk (13.00 ± 1.32 #/cm ³ ); however, this difference was not statistically significant ( p = 0.14). Paper towels showed the highest PNC when wiping paragraphs written with dust‐free (18.68 ± 2.01 #/cm ³ ) and normal chalk (19.08 ± 1.27 #/cm ³ ), whereas a dry cloth recorded the lowest PNC for dust‐free (5.76 ± 0.51 #/cm ³ ) and normal chalk (5.22 ± 0.94 #/cm ³ ). Writing with and wiping off dust‐free and normal chalk mainly released fine particles (< 4.5 μ m), with peaks between 1.562 and 3.752 μ m. The various wiping materials also released fine particles, with most peaks occurring between 1.562 and 4.672 μ m for both dust‐free and normal chalk. Transitioning to alternative teaching tools, such as whiteboards or digital devices, is necessary to protect teachers′ health.