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Drug resistance is a major problem in the treatment of non-small-cell lung cancer (NSCLC). In this study, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to identify the differentially expressed genes in Adriamycin (ADR)-resistant NSCLC A549/ADR cells compared with parental A549 cells. Among the tested phytochemicals, nobiletin (NBT) is able to overcome the ADR resistance of A549/ADR cells. NBT treatment decreased the expression of a neuroblastoma-derived MYC (MYCN) and multidrug resistance-associated protein 1 (MRP1) as well as downregulating Akt, GSK3β, and β-catenin. Consistent with these results, NBT treatment resulted in the accumulation of intracellular ADR. A combination index (CI) assay confirmed the synergistic effect of combined treatment with NBT and ADR in reducing the viability of A549/ADR cells (CI = 0.152). Combined treatment with NBT and ADR enhanced apoptosis in A549/ADR cells, as evidenced by increased caspase-3 activation, poly (ADP-ribose) polymerase (PARP) cleavage, and sub-G1 population compared to treatment with ADR alone. In vivo experiments using a mouse xenograft model revealed that combination therapy with NBT and ADR significantly reduced tumor volume by 84.15%. These data suggest that NBT can sensitize ADR-induced cytotoxicity against A549/ADR cells by inhibiting MRP1 expression, indicating that NBT could serve as an effective adjuvant agent for ADR-based chemotherapy in lung cancer.

Objectives Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015–16 in Vietnam using AMR testing, WGS and detection of AMR determinants. Methods Two hundred and twenty-nine gonococcal isolates cultured in 2015–16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq. Results Resistance among the 2015–16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2–8 mg/L. Among the 2015–16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q. Conclusions From 2011 to 2015–16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.

With a view to developing therapeutic strategies against hepatocellular carcinoma (HCC), we have recently shown that co-expression of c-myc and the X protein of hepatitis B virus (HBx) resulted in the development of HCC in the X-myc transgenic mice [Lakhtakia et al., J. Gastroenterol. Hepatol. 18 (2003) 80^91]. We now show in cell culture-based studies that small interfering RNA (siRNA) corresponding to HBx and cmyc can regulate expression and transactivation of the target genes. Expression vectors for small hairpin RNAs (shRNAs) against two di¡erent regions each of the HBx and c-myc open reading frames were constructed and their regulatory e¡ects were investigated in COS-1 cells. A dose-dependent speci¢c inhibition in the expression levels of HBx and c-myc was observed with individual shRNAs. Further, the recombinantly expressed shRNAs also blocked the transactivation functions of their cognate genes. Though each shRNA worked at a di¡erent e⁄-ciency, the inhibitory e¡ects with two di¡erent shRNAs were cumulative. These results appear promising for developing a siRNA-based therapy for HCC. ß 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

I. The double Thiry-Vella loop operation was successfully performed in the rat with the formation of two zoo mm jejunal segments, thus isolating one-half of the small intestine. z. Using this preparation a comparative in vivo study of the effects of pantothenic acid on glucose absorption was carried out. 3. Pantothenic acid increased glucose absorption by local action on the mucous surface of the intestine. This vitamin appears to be part of a glucose carrier system, in a labile form different from coenzyme A.