There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal. Contrary to the conventional model, the cytotoxic effects of CQ were found to be autophagy-independent, as genetic targeting of ATG7 or the ULK1/2 complex could not sensitise cells, like CQ, to serum depletion. Interestingly, although CQ combined with serum starvation was robustly cytotoxic, further glucose starvation under these conditions led to a full rescue of cell viability. Inhibition of hexokinase using 2-deoxyglucose (2DG) similarly led to CQ resistance. As this form of cell death did not resemble classical caspase-dependent apoptosis, we hypothesised that CQ-mediated cytotoxicity was primarily via a lysosome-dependent mechanism. Indeed, CQ treatment led to marked lysosomal swelling and recruitment of Galectin3 to sites of membrane damage. Strikingly, glucose starvation or 2DG prevented CQ from inducing lysosomal damage and subsequent cell death. Importantly, we found that the related compound, amodiaquine, was more potent than CQ for cell killing and not susceptible to interference from glucose starvation. Taken together, our data indicate that CQ effectively targets the lysosome to sensitise towards cell death but is prone to a glucose-dependent resistance mechanism, thus providing rationale for the related compound amodiaquine (currently used in humans) as a better therapeutic option for cancer.

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Antioxidant and antimicrobial activity of thyme has been well established against various microorganisms. This study was carried out to investigate the effect of aqueous and alcoholic extract of thyme on beef mincemeat quality. Three differential concentrations (0.4, 0.8, and 1.2 mg/ml) of both thyme extracts were used for the beef mincemeat preservation. Untreated meat samples were considered as the control group while the extracts treated beef mincemeat are stored at 4°C for 7 to 14 days. To validate the extract's ability to prolong the storage period at 4 °C, various bacteriological indicators like total plate count, presence of total coliform, Salmonella, Shigella, and Staphylococcus aureus count were assessed. The results of the antimicrobial assay of aqueous and alcoholic extracts of thyme at different concentrations showed that the aqueous extract had significant inhibitory action on the growth of a wide range of bacteria compared to the alcoholic extract. Thus, the thyme aqueous extracts can be efficient and promising as preservatives for meat and its products, especially at high concentrations to inhibit bacterial growth.

The oral cavity is habitat to a wide variety of commensal flora, which may act as a reservoir of factors that influence drug resistance. Bacteria in the oral cavity create biofilms, which makes it easier for horizontal gene transfer to result in the accumulation of antibiotic resistance genes. Methicillin-resistant Staphylococcus aureus (MRSA) carriage rates in the oral cavity are high, according to recent studies. The widespread use of antibiotic prophylaxis among at-risk dental procedure applicants may facilitate MRSA establishment in the mouth.  These modifications in the epidemiology of MRSA have significant ramifications for clinical practice, methodological approaches to MRSA carriage studies, and MRSA prevention efforts.

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