Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted

Small Angle X-Ray and Neutron Scattering - Its Application to Supramolecular Solutions

Contains reports on five research projects

Small Angle X-Ray and Neutron Scattering - Its Application to Supramolecular Solutions

Contains reports on seven research projects

Microfluidic assisted synthesis of silver nanoparticle–chitosan composite microparticles for antibacterial applications

AbstractSilver nanoparticle (Ag NP)-loaded chitosan composites have numerous biomedical applications; however, fabricating uniform composite microparticles remains challenging. This paper presents a novel microfluidic approach for single-step and in situ synthesis of Ag NP-loaded chitosan microparticles. This proposed approach enables obtaining uniform and monodisperse Ag NP-loaded chitosan microparticles measuring several hundred micrometers. In addition, the diameter of the composites can be tuned by adjusting the flow on the microfluidic chip. The composite particles containing Ag NPs were characterized using UV–vis spectra and scanning electron microscopy-energy dispersive X-ray spectrometry data. The characteristic peaks of Ag NPs in the UV–vis spectra and the element mapping or pattern revealed the formation of nanosized silver particles. The results of antibacterial tests indicated that both chitosan and composite particles showed antibacterial ability, and Ag NPs could enhance the inhibition rate and exhibited dose-dependent antibacterial ability. Because of the properties of Ag NPs and chitosan, the synthesized composite microparticles can be used in several future potential applications, such as bactericidal agents for water disinfection, antipathogens, and surface plasma resonance enhancers

Small Angle X-Ray and Neutron Scattering - Its Application to Supramolecular Solutions

Contains reports on seven research projects.Argonne National LaboratoryU.S. Department of Energy DE-FG01-90ER45429National Science FoundationUniversity of Florence, ItalyExxon FellowshipNational Science Foundation Grant INT 87-508

Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis

Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis

Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan

Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase–polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus–based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection

The impact of the synergistic effect of SO2 and PM2.5/PM10 on obstructive lung disease in subtropical Taiwan

BackgroundChronic Obstructive lung diseases (COPD) are complex conditions influenced by various environmental, lifestyle, and genetic factors. Ambient air pollution has been identified as a potential risk factor, causing 4.2 million deaths worldwide in 2016, accounting for 25% of all COPD-related deaths and 26% of all respiratory infection-related deaths. This study aims to evaluate the associations among chronic lung diseases, air pollution, and meteorological factors.MethodsThis cross-sectional study obtained data from the Taiwan Biobank and Taiwan Air Quality Monitoring Database. We defined obstructive lung disease as patients with FEV1/FVC < 70%. Descriptive analysis between spirometry groups was performed using one-way ANOVA and the chi-square or Fisher’s exact test. A generalized additive model (GAM) was used to evaluate the relationship between SO2 and PM2.5/PM10 through equations and splines fitting.ResultsA total of 2,635 participants were enrolled. Regarding environmental factors, higher temperature, higher relative humidity, and lower rainfall were risk factors for obstructive lung disease. SO2 was positively correlated with PM10 and PM2.5, with correlation coefficients of 0.53 (p < 0.0001) and 0.52 (p < 0.0001), respectively. Additionally, SO2 modified the relative risk of obstructive impairment for both PM10 [β coefficient (β) = 0.01, p = 0.0052] and PM2.5 (β = 0.01, p = 0.0155). Further analysis per standard deviation (per SD) increase revealed that SO2 also modified the relationship for both PM10 (β = 0.11, p = 0.0052) and PM2.5 (β = 0.09, p = 0.0155). Our GAM analysis showed a quadratic pattern for SO2 (per SD) and PM10 (per SD) in model 1, and a quadratic pattern for SO2 (per SD) in model 2. Moreover, our findings confirmed synergistic effects among temperature, SO2 and PM2.5/PM10, as demonstrated by the significant associations of bivariate (SO2 vs. PM10, SO2 vs. PM2.5) thin-plate smoothing splines in models 1 and 2 with obstructive impairment (p < 0.0001).ConclusionOur study showed high temperature, humidity, and low rainfall increased the risk of obstructive lung disease. Synergistic effects were observed among temperature, SO2, and PM2.5/PM10. The impact of air pollutants on obstructive lung disease should consider these interactions

Small-Molecule Synthetic Compound Norcantharidin Reverses Multi-Drug Resistance by Regulating Sonic Hedgehog Signaling in Human Breast Cancer Cells

Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells