Knockdown of SLC39A4 Expression Inhibits the Proliferation and Motility of Gallbladder Cancer Cells and Tumor Formation in Nude Mice.

PURPOSE: Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies. MATERIALS AND METHODS: Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo. RESULTS: Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC. CONCLUSION: SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.

Paroxysmal nocturnal haemoglobinuria (PNH) manifesting on CT as a pathologic segment of small bowel.

Paroxysmal nocturnal haemoglobinuria, a rare, acquired, life-threatening disease of the blood, is characterised by a triad of haemolysis previously believed to occur mainly at night, bone marrow dysfunction, and thrombophilia. Paroxysmal nocturnal haemoglobinuria is customarily regarded to manifest clinically as haemolytic anaemia and haemoglobinuria experienced as reddened urine in the morning, pancytopenia, and thrombosis. We describe a case in which an abnormal segment of small bowel as visualised on computed tomography was the principal sign of the disease process on presentation.

Improving access to City and Hackney adult mental health services.

City and Hackney Adult Mental Health Referral and Assessment Service (CHAMHRAS) is the single point of entry for all mental health referrals to secondary services, with the exception of perinatal referrals, in the City and Hackney region of London, UK. CHAMHRAS was established in 2013 with the objective of providing a one-stop point of referral which screens urgent and non-urgent referrals of adults aged 18-65 to mental health services. This single point of entry simplifies the referral process to secondary mental health services-something service users have requested. It also enables rapid feedback on all referrals taken from general practitioners as well as other sources. The centralised nature of CHAMHRAS has also facilitated the monitoring of waiting times from receipt of referral to first face-to-face assessment across services. It was noted that the waiting time for the majority of patients was exceeding the 28-day target set by local commissioners. Indeed, in December 2014, only 30% of patients were being seen within this time frame. The aim of this quality improvement project has been to decrease the average waiting time from referral to first face-to-face assessment, and concomitantly increase the proportion of patients being assessed within the 28-day target period. The team identified potential sources of delay in the process of handling referrals, from receipt and triage, to forwarding to the relevant secondary service, and have tested change ideas such as the implementation of daily meetings to review referrals and the centralisation of appointment bookings to streamline the processes and minimise delays. The average waiting time from referral to first face-to-face assessment decreased by 34% and the proportion of patients being assessed within 28 days increased accordingly, exceeding 95% in the case of referrals from general practitioners (GP). We have listed changes that we intend to introduce with the aim of bringing waiting times down further.

Overexpression of a Brassica campestris HSP70 in tobacco confers enhanced tolerance to heat stress.

Heat shock proteins (HSPs) exist extensively in eukaryotes and are conserved molecular chaperones with important contribution to plant's survival under environmental stresses. Here, the cloning and characterization of one complementary DNA (cDNA) designated as BcHSP70 from young seedlings of Brassica campestris were reported in the present work. Bioinformatic analysis revealed that BcHSP70 belongs to the plant HSP gene family and had the closest relationship with HSP70-4 from Arabidopsis thaliana. Constitutive overexpression of BcHSP70 in tobacco obviously conferred tolerance to heat stress by affecting different plant physiological parameters. In our study, transgenic tobaccos exhibited higher chlorophyll content than wild-type control when exposed to heat stress. Superoxide dismutase (SOD) and peroxidase (POD) activities, which were helpful to decrease the damage to the membrane system, were significantly higher in transformants compared to wild-type lines. Meanwhile, lower comparative electrical conductivity and malondialdehyde (MDA) content and higher proline and soluble sugar accumulation were found in transgenic tobaccos than in wild-type lines. All these above results indicated that this isolated BcHSP70 cDNA owned the ability to improve the tolerance to heat stress in transgenic tobacco, which provides helpful information and good basement to culture new robust B. campestris variety resistant to high-temperature stress by molecular breeding in the future.

Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila.

Camptothecin (CPT) belongs to a group of monoterpenoidindole alkaloids (TIAs) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. Genes from Catharanthus roseus encoding strictosidine synthase (STR) and geraniol 10-hydroxylase (G10H), were separately and simultaneously introduced into Ophiorrhiza pumila hairy roots. Overexpression of individual G10H (G lines) significantly improved CPT production with respect to non-transgenic hairy root cultures (NC line) and single STR overexpressing lines (S lines), indicating that G10H plays a more important role in stimulating CPT accumulation than STR in O. pumila. Furthermore, co-overexpression of G10H and STR genes (SG Lines) caused a 56% increase on the yields of CPT compared to NC line and single gene transgenic lines, showed that simultaneous introduction of G10H and STR can produce a synergistic effect on CPT biosynthesis in O. pumila. The MTT assay results indicated that CPT extracted from different lines showed similar anti-tumor activity, suggesting that transgenic O. pumila hairy root lines could be an alternative approach to obtain CPT. To our knowledge, this is the first report on the enhancement of CPT production in O. pumila employing a metabolic engineering strategy.

WITHDRAWN: Metabolic engineering and biotechnological approaches for production of bioactive diterpene tanshinones in Salvia miltiorrhiza.

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