Paper currency and coins may be a public health risk when associated with the simultaneous handling of food and could lead to the spread of nosocomial infections. Banknotes recovered from hospitals may be highly contaminated by Staphylococcus aureus. Salmonella species, Escherichia coli and S. aureus are commonly isolated from banknotes from food outlets. Laboratory simulations revealed that methicillin-resistant S. aureus can easily survive on coins, whereas E. coli, Salmonella species and viruses, including human influenza virus, Norovirus, Rhinovirus, hepatitis A virus, and Rotavirus, can be transmitted through hand contact. Large-scale, 16S rRNA, metagenomic studies and culturomics have the capacity to dramatically expand the known diversity of bacteria and viruses on money and fomites. This review summarizes the latest research on the potential of paper currency and coins to serve as sources of pathogenic agents.

Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-β1, TGF-βRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential.

Background. A crucial role for CD8⁺ cells in induction of crescentic anti-glomerular basement membrane (GBM) glomerulonephritis (GN) in WKY rats was demonstrated in studies showing that depletion of CD8⁺ cells completely suppressed glomerular accumulation of monocytes/macrophages (Mo/Mϕ), crescent formation and proteinuria. Because these studies did not definitively identify CD8⁺ cells as the cause of tissue injury, we examined the roles of Mo/Mϕ in the development of anti-GBM GN. Methods. We examined correlations between the amount of urinary protein and the numbers of glomerular CD8⁺ cells or Mo/Mϕ in rats after administrating different doses of anti-GBM antibody (5.0, 7.5, 10.0 and 25.0 μl/100 g body weight). The roles of Mo/Mϕ in induction of GN were examined in animals by depleting Mo/Mϕ in the glomerulus. To do this, rats were injected intravenously with liposome-encapsulated dichloromethylene diphosphonate (liposome-MDP) from day 3 to day 7 after anti-GBM antibody injection and they were then sacrificed at day 8. Results. Liposome-MDP treatment significantly reduced the number of ED-1⁺ Mo/Mϕ accumulated in glomeruli from 32.1±1.2 to 1.4±0.3/glomerular cross-section (mean±SD, P<0.01), and the amount of urinary protein from 103.8±19.8 to 31.8±15.9 mg/day (P<0.01), as well as the incidence of crescentic glomeruli from 91.3±2.7 to 23.3±7.6% (P<0.01) at day 8. This treatment also reduced the number of CD8⁺ cells accumulating in the glomeruli from 5.4± 0.7 to 0.5±0.1/glomerular cross-section (P<0.01). Upregulation of glomerular intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was suppressed by Mo/Mϕ depletion. Conclusion. These results indicate that Mo/Mϕ play an important role in the induction of crescentic anti-GBM GN and glomerular injury.

Vitamin D3 and its analogues have recently been shown to enhance the anti-tumour effects of 5- Fluorouracil (5-FU) both in vitro and in xenograft mouse model of colon cancer. This study measured the potential mechanism(s) by which vitamin D3 could synergise the tumouricidal activities of 5-FU in azoxymethane (AOM) rat model of colon cancer. Seventy-five male Wistar rats were divided equally into 5 groups: Control, AOM, AOM-treated by 5-FU (5-FU), AOM-treated by vitamin D3 (VitD3), and AOM-treated by 5-FU + vitamin D3 (5-FU/D). The study duration was 15 weeks. AOM was injected subcutaneously for 2 weeks (15 mg/kg/week). 5-FU was injected intraperitoneally in the 9th and 10th weeks post AOM (8 total injections were given: 12 mg/kg/day for 4 successive days, then 6 mg/kg every other day for another 4 doses) and oral vitamin D3 (500 IU/rat/day; 3 days/week) was given from week 7 post AOM till the last week of the study. The colons were collected following euthanasia for gross and histopathological examination. The expression of β-catenin, transforming growth factor-β1 (TGF-β1), TGF-β type 2 receptor (TGF-βR2), smad4, inducible nitric oxide synthase (iNOS), and heat shock protein-90 (HSP-90) proteins was measured by immunohistochemistry. In colonic tissue homogenates, quantitative RT-PCR was used to measure the mRNA expression of Wnt, β-catenin, Dickkopf-1 (DKK-1) and cyclooxygenase-2 (COX-2) genes, while ELISA was used to measure the concentrations of TGF-β1, HSP-90 and COX-2 proteins. Monotherapy with 5-FU or vitamin D3 significantly decreased the number of grown tumours induced by AOM (P < 0.05); however, their combination resulted in more significant tumouricidal effects (P < 0.05) compared with monotherapy groups. Mechanistically, vitamin D3/5-FU co-therapy significantly decreased the expression of Wnt, β-catenin, iNOS, COX-2 and HSP-90 and significantly increased the expression of DKK-1, TGF-β1, TGF-βR2, smad4 (P < 0.05), in comparison with their corresponding monotherapy groups. Vitamin D3 and 5-FU synergise together and exhibit better anticancer effects by modulating Wnt/β-catenin pathway, TGF-β1 signals, iNOS, COX-2 and HSP-90. Further studies are required to illustrate the clinical value of vitamin D supplementation during the treatment of colon cancer with 5-FU in human patients.

Gene-based virotherapy mediated by oncolytic viruses is currently experiencing a renaissance in cancer therapy. However, relatively little attention has been given to the potentiality of dual gene virotherapy strategy as a novel therapeutic approach to mediate triplex anticancer combination effects, particularly if the two suitable genes are well chosen. Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-12 (IL-12) have been emerged as promising pharmacological candidates in cancer therapy; however, the combined efficacy of TRAIL and IL-12 genes for treatment of human hepatocellular carcinoma (HCC) remains to be determined. Herein, we investigated the therapeutic efficacy of concurrent therapy with two armed oncolytic adenoviruses encoding human TRAIL gene (Ad-ΔB/TRAIL) and IL-12 gene (Ad-ΔB/IL-12), respectively, on preclinical models of human HCC, and also elucidated the possible underlying mechanisms. The effects of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy were assessed both in vitro on Hep3B and HuH7 human HCC cell lines and in vivo on HCC-orthotopic model established in the livers of athymic nude mice by intrahepatic implantation of human Hep3B cells. Compared to therapy with non-armed control Ad-ΔB, combined therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 elicited profound anti-HCC killing effects on Hep3B and HuH7 cells and on the transplanted Hep3B-orthotopic model. Efficient viral replication and TRAIL and IL-12 expression were also confirmed in HCC cells and the harvested tumor tissues treated with this combination therapy. Mechanistically, co-therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 exhibited an enhanced effect on apoptosis promotion, activation of caspase-3 and-8, generation of anti-tumor immune response evidenced by upregulation of interferon gamma (IFN-γ) production and infiltration of natural killer-and antigen presenting cells, and remarkable repression of intratumor vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and tumor microvessel density. Overall, our data showed a favorable therapeutic effect of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy against human HCC, and may therefore constitute a promising and effective therapeutic strategy for treating human HCC. However, further studies are warranted for its reliable clinical translation.

Background: Laboratory errors arise at any stage of testing. Detecting these inaccuracies before results are revealed might delay diagnosis and treatment, causing patient distress. Here, we studied the preanalytical errors in a hematology laboratory. Methods: This one-year retrospective analysis was conducted at the laboratory of a tertiary care hospital and included information on blood samples that were taken for hematology tests from both outpatients and inpatients. Laboratory records included sample collection and rejection information. The type and frequency of preanalytical errors were expressed as a proportion of total errors and sample number. Microsoft Excel was utilized to enter data. The results were presented in the form of frequency tables. Results: This research included 67,892 hematology samples. For preanalytical errors, 886 samples (1.3%) were discarded. The most common preanalytical error was insufficient sample (54.17%), and the least common was an empty/damaged tube (0.4%). Erroneous samples in the emergency department were mostly insufficient and clotted, whereas pediatric sample errors were caused by insufficient and diluted samples. Conclusion: Inadequate samples and clotted samples account for the vast majority of preanalytical factors. Insufficiency and dilutional errors were most frequent from pediatric patients. Adherence to best laboratory practices can drastically cut down on preanalytical errors.