Annexin A2 (ANXA2) expression is highly upregulated in many types of cancer. Although cell surface localization of ANXA2 has been reported to have a critical role in the progression and metastasis of ...a variety of tumors, including pancreatic cancer, the biological role of intracellular ANXA2 is not fully understood. Herein the role of intracellular ANXA2 was investigated in a pancreatic cancer cell line. We first determined whether ANXA2 is involved in NF-κB signaling pathways. ANXA2 bound to the p50 subunit of NF-κB in a calcium-independent manner, and the ANXA2-p50 complex translocated into the nucleus. Furthermore, ANXA2 increased the transcriptional activity of NF-κB in both the resting and activated states and upregulated the transcription of several target genes downstream of NF-κB, including that encoding interleukin (IL)-6, which contributes to anti-apoptotic signaling. In Mia-Paca2 cells, we determined the effects of wild-type ANXA2 and an ANXA2 mutant, Y23A, which suppresses the cell surface localization, on upregulation of NF-κB transcriptional activity and secretion of IL-6. Both wild-type and Y23A ANXA2 induced anti-apoptotic effects in response to treatment with tumor necrosis factor-α or gemcitabine. Based on these results, we suggest that ANXA2 mediates resistance to gemcitabine by directly increasing the activity of NF-κB. Collectively, these data may provide additional information about the biological role of ANXA2 in pancreatic cancer and suggest that ANXA2 is a potential biomarker for the drug resistance phenotype and a candidate therapeutic target for the treatment of pancreatic cancer.
Inorganic nanosized silicate nanoplatelets were incorporated into biodegradable poly(
l-lactic acid) (PLLA) for the purpose of tailoring mechanical stiffness of PLLA porous scaffold systems. ...Increasing the nucleation density around the foreign body surfaces, the montmorillonite (MMT) nanoplatelets modified with dimethyl dihydrogenated tallow ammonium cations decreased the glass transition temperature and the degree of PLLA crystallinity, which seemingly caused the accelerated biodegradation rate of PLLA nanocomposites due to the enhanced segmental mobility of backbone chains and the expanded amorphous region of PLLA matrix. The tensile modulus was increased from 121.2
MPa of pristine polymer scaffold to 170.1
MPa of MMT/PLLA nanocomposite scaffold (ca. 40% increment) by the addition of small amount of MMT platelets (5.79
vol%) acting as a mechanical reinforcement of polymer chains in the nanoscale molecular level. Overall, the nanotechnology used in this study may be applied to various scaffold systems of biodegradable polymers and hard/soft scaffold structures requiring critical control and design characteristics of mechanical stiffness and biodegradation rate.
Polyphenolic compounds present in green tea, particularly catechins, are known to have strong anti-influenza activity. The goal of this study was to determine whether green tea by-products could ...function as an alternative to common antivirals in animals compared to original green tea. Inhibition of viral cytopathic effects ascertained by neutral red dye uptake was examined with 50% effective (virus-inhibitory) concentrations (EC50) determined. Against the H1N1 virus A/NWS/33, we found the anti-influenza activity of green tea by-products (EC50 = 6.36 µg/mL) to be equivalent to that of original green tea (EC50 = 6.72 µg/mL). The anti-influenza activity of green tea by-products was further examined in mouse and chicken influenza infection models. In mice, oral administration of green tea by-products reduced viral titers in the lungs in the early phase of infection, but they could not protect these animals from disease and death. In contrast, therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001). We also demonstrated that unidentified hexane-soluble fractions of green tea by-products possessed strong anti-influenza activity, in addition to ethyl acetate-soluble fractions, including catechins. This study revealed green tea by-product extracts to be a promising novel antiviral resource for animals.
Abstract Purpose Previous studies have reported inconsistent findings regarding the association between the use of acid-suppressive drugs such as proton pump inhibitors (PPIs) and histamine 2 ...receptor antagonists (H2 RAs) and fracture risk. We investigated this association using meta-analysis. Methods We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library from inception through December 2010 using common key words. We included case-control, nested case-control, and cohort studies. Two evaluators independently reviewed and selected articles. We determined pooled effect estimates by using random-effects meta-analysis, because of heterogeneity. Results Of 1,809 articles meeting our initial inclusion criteria, 5 case-control studies, 3 nested case-control studies, and 3 cohort studies were included in the final analyses. The pooled odds ratio (OR) for fracture was 1.29 (95% confidence interval CI, 1.18–1.41) with use of PPIs and 1.10 (95% CI, 0.99–1.23) with use of H2 RAs when compared with nonuse of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30; 95% CI, 1.15–1.48) and hip fracture risk (adjusted OR = 1.34; 95% CI, 1.09–1.66), whereas long-term H2 RA use was not significantly associated with fracture risk. Conclusions We found possible evidence linking PPI use to an increased risk of fracture, but no association between H2 RA use and fracture risk. Widespread use of PPIs with the potential risk of fracture is of great importance to public health. Clinicians should carefully consider their decision to prescribe PPIs for patients already having an elevated risk of fracture because of age or other factors.
Three-phase bone scintigraphy (TPBS) is an established objective diagnostic method for complex regional pain syndrome (CRPS), but its validity remains controversial. The aims of this study were: (i) ...to re-evaluate the diagnostic performance of TPBS, and (ii) to suggest new TPBS criteria based on the proposed research criteria for CPRS in Budapest (the 2003 Budapest research criteria).
The medical records of 228 consecutive patients, evaluated using the Budapest research criteria, were retrospectively analysed. Of these, 116 patients were included in the present study, and 69 of 116 were diagnosed to have CRPS based on these criteria. The diagnostic performance of TPBS was assessed by determining its sensitivity, specificity, and positive and negative likelihood ratios, and new criteria for TPBS were identified by pattern analysis using the Budapest research criteria.
The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TPBS for the diagnosis of CRPS according to the Budapest research criteria were 40.0, 76.5, 1.73, and 0.78, respectively. Furthermore, D–D–D, D–D–S, and D–D–I patterns i.e. according to decreased (D), symmetrical (S), or increased (I) tracer uptake during Phases I, II, and III of TPBS were found to be positively predictive for CRPS.
The diagnostic value of a positive TPBS for CRPS is low from the view point of the Budapest research criteria. Our findings suggest that a diagnosis of CRPS using the Budapest research criteria should be considered when decreased patterns of TPBS are observed during Phases I and II.
The socioeconomic burden of cancer is growing rapidly in the Asian region, with a concentrated burden on low- and middle- income countries. The residents of this region, representing almost 60% of ...the global population, demonstrate an eclectic and complex nature, with huge disparities in ethnicity, sociocultural practices among others. The Asian National Cancer Centers Alliance (ANCCA) was established in 2005 by heads of several national cancer centers (NCCs) in the region to address common issues and concerns among Asian countries. During the first 13 years of ANCCA's existence, the participating NCCs' senior managers paved the way toward collaboration through transparent sharing of key facts and activities. Concrete achievements of the Alliance include the Asia Tobacco-Free Declaration, the establishment of the ANCCA Constitution in 2014 as well as the creation of an official website more recently. In November 2019, the most active ANCCA members (China, India, Indonesia, Japan, Korea, Mongolia, Singapore, Thailand, and Vietnam) strengthened the bonds of the entity with the clear aim to halt the increase in cancer and mortality rates in Asian countries by 2030. New opportunities including accelerated cooperation between members as well as collaboration with external and multidisciplinary stakeholders at local, regional and international levels are an essential step to most effectively tackle cancers in Asia.
Water-soluble chitosan (WSC) was used to increase the stability of chitosan in water and decrease the cytotoxicity induced by acetic acid. Lactobionic acid (LA) bearing galactose group was coupled ...with WSC for hepatocytes specificity. The composition of galactose in galactosylated chitosan (GC) was determined by NMR spectroscopy. The GC was complexed with plasmid DNA in various GC/DNA (N/P) charge ratios and the resulting complex was characterized by dynamic light scattering, gel retardation, and turbidity to determine the particle sizes, complex formation, and complex stability, respectively. Cytotoxicity and transfection efficiency of GC were also studied in cultured HepG2 human hepatoblastoma cell line and HeLa human cervix epithelial carcinoma cells. The complete GC/DNA complex was formed at the charge ratio of 5 and the GC/DNA complex to DNase I resistance was obtained. Particle sizes decreased with increasing charge ratio of GC to DNA and had a minimum value around 120
nm at the charge ratio of 5. And no significant difference in particle sizes from the charge ratio of 5–20 was found. The suspension of GC/DNA complexes exhibited no significant change in turbidity at the charge ratios of 10, indicating the complete shielding of DNA charge. Cytotoxicity study showed that GC prepared by the water-soluble chitosan had no cytotoxic effects on cells. And transfection efficiency into HepG2, which has asialoglycoprotein receptors (ASGP-R), was higher than that into HeLa without ASGP-R.
Over the past few decades, tetrafluoroethane (TFE, R134a Freon)-based gases have been widely used in the operation of phenolic resistive plate chambers (RPCs) in many high-energy experiments. ...However, TFE has a high global warming potential (GWP); therefore, a search for new eco-friendly gases to replace traditional TFE-based ones is now unavoidable. In this research, we present cosmic-ray test results of a prototype RPC for the SHiP (search for hidden particles) experiment using 1.6- and 1.4-mm-thick RPC electrodes containing mixtures of various gases, including 1,3,3,3-tetrafluoropropene (HFO1234ze), CO
2
,
i
C
4
H
10
and SF
6
. We compare the performance data gathered with these new gas mixtures with those gathered with a traditional TFE-based gas used for RPCs in compact muon solenoid (CMS) and a toroidal LHC apparatus (ATLAS) experiments. The addition of CO
2
to the HFO1234ze-based gas was found to be fairly effective in reducing the working-point high voltage (HV
WP
) for RPC operation. The results of our experiments lead us to the conclusion that adding 40% CO
2
or less, when combined with HFO1234ze-based gas, is conducive to reliable detector performance for SHiP single-gap phenolic RPCs.
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