Oleanolic acid arrests cell cycle and induces apoptosis via ROS‐mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti‐tumor activity against many tumor cell lines. This study aims to examine the anti‐tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc‐28 cells was inhibited by OA in a concentration‐dependent manner, with an IC₅₀ (The half maximal inhibitory concentration) value of 46.35 µg ml^?1, as determined by MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis‐correlated proteins was also affected in cells treated with OA, including activation of caspases‐3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc‐28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS‐mediated mitochondrial and a lysosomal pathway in Panc‐28 cells. Copyright © 2012 John Wiley & Sons, Ltd.     

MMRdb: Measles,mumps, and rubella viruses database and analysis resource

Measles, mumps, and rubella viruses are well known human pathogens that cause mild to severe illnesses. Despite the existence of MMR vaccines since 1971, outbreaks have been largely documented even in highly vaccinated populations. There is a pressing need to develop a resource to monitor genetic and antigenic variations among these viruses. Here, we introduced MMRdb, a web central database and analysis resource for measles, mumps, and rubella viruses. Users can search viruses at gene level and obtain sequence information based on gene product, geographic location, year, or host. The MMRdb also catalogs experimentally verified B cells and T cells antigenic epitopes data. A set of computation tools such as multiple sequence alignment, Geo Chart, and sequence similarity BLAST search has been implemented in a user-friendly database. The main features of this database will assist researchers in monitoring genetics and antigenic variations, tracking geographic spread with regards of sequence information, and facilitate the development of diagnostics, vaccines, and immunotherapeutics. Database URL: http://mmrdb.org     

Analysis of risk factors for multiple primary oral squamous cell carcinoma: a cohort study

Clinical Oral Investigations - Chewing betel quid (CBQ) is popular in Southeast Asia, resulting in a high incidence of oral squamous cell carcinoma (OSCC). The incidence of multiple primary oral...     

Identification of immunogenic proteins and evaluation of four recombinant proteins as potential vaccine antigens from Vibrio anguillarum in flounder (Paralichthys olivaceus)

Vibrio anguillarum is a severe bacterial pathogen that can infect a wide range of fish species. Identification of immunogenic proteins and development of vaccine are essential for disease prevention. In this study, immunogenic proteins were screened and identified from V. anguillarum, and then protective efficacy of the immunogenic proteins was evaluated. Immunogenic proteins in V. anguillarum whole cell were detected by Western blotting (WB) using immunized flounder (Paralichthys olivaceus) serum, and then identified by Mass spectrometry (MS). The recombinant proteins of four identified immunogenic proteins were produced and immunized to fish, and then percentages of surface membrane immunoglobulin-positive (sIg+) cells in peripheral blood lymphocytes (PBL), total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were measured, respectively. The results showed that five immunogenic proteins, VAA, Groel, OmpU, PteF and SpK, were identified; their recombinant proteins, rOmpU, rGroel, rSpK and rVAA, could induce the proliferation of sIg+ cells in PBL and production of total antibodies, antibodies against V. anguillarum and antibodies against the recombinant proteins; their protection against V. anguillarum showed 64.86%, 72.97%, 21.62% and 78.38% RPS, respectively. The results revealed that the immunoproteomic technique using fish anti-V. anguillarum serum provided an efficient way to screen the immunogenic protein for vaccine antigen. Moreover, the rVAA, rGroel and rOmpU had potential to be vaccine candidates against V. anguillarum infection.     

TPGS-stabilized NaYbF4:Er upconversion nanoparticles for dual-modal fluorescent/CT imaging and anticancer drug delivery to overcome multi-drug resistance

Multi-drug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively investigated for overcoming MDR in cancer therapy because of its ability to inhibit P-glycoprotein (P-gp). In this work, TPGS was for the first time used as a new surface modifier to functionalize NaYbF₄:Er upconversion nanoparticles (UNCPs) and endowed the as-prepared products (TPGS-UCNPs) with excellent water-solubility, P-gp inhibition capability and imaging-guided drug delivery property. After the chemotherapeutic drug (doxorubicin, DOX) loading, the as-formed composites (TPGS-UCNPs-DOX) exhibited potent killing ability for DOX-resistant MCF-7 cells. Flow-cytometric assessment and Western blot assay showed that the TPGS-UCNPs could potently decrease the P-gp expression and facilitate the intracellular drug accumulation, thus achieving MDR reversal. Moreover, considering that UCNPs process efficient upconversion emission and Yb element contained in UCNPs has strong X-ray attenuation ability, the as-obtained composite could also serve as a dual-modal probe for upconversion luminescence (UCL) imaging and X-ray computed tomography (CT) imaging, making them promising for imaging-guided cancer therapy.     

Ambient ionization coupled with a miniature mass spectrometer for rapid identification of unauthorized adulterants in food

Considerably simplified workflows based on a miniature mass spectrometer combined with versatile ambient ionization methods were developed for rapid, on-site identification of illicit adulterants in select food (medicinal liquor, chili powder, hotpot seasoning and watermelon). The labor- and time-intensive procedures of sample pretreatment and chromatographic separation, traditionally required for mass spectrometry analysis, have been bypassed using capillary nano-electrospray ionization, paper spray ionization, or syringe spray ionization. A miniature ion trap mass spectrometer with a continuous atmospheric pressure interface and tandem mass spectrometry capability was employed for the analysis of adulterated additives. Key experimental parameters were carefully optimized in order to achieve the optimal performance of the integrated system. Maintaining the ease of analytical protocol, limits of detection as low as 30–40 μg/L for sex stimulants in medicinal liquor, 20–50 μg/kg for illegal dyes in chili powder and hotpot seasoning, and 15 μg/kg for plant growth regulator in watermelon were obtained. The capability of conducting quantitative analysis with an isotopic internal standard was demonstrated. The developed methodologies coupling ambient ionization and miniature mass spectrometry represent promising potential for fast and in situ screening of food adulteration.     

Reprint of “Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum”

High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk.     

Hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves on Streptococcus mutans biofilm and tooth demineralization

ObjectivesThis study evaluated the effect of the hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves (alone or combined) on the viability of Streptococcus mutans biofilm and on the prevention of enamel demineralization.MethodsStrain of S. mutans (ATCC 21175) was reactivated in BHI broth. Minimum inhibitory concentration, minimum bactericidal concentration, minimum inhibition biofilm concentration and minimum eradication biofilm concentration were determined in order to choose the concentrations to be tested under biofilm model. S. mutans biofilm (5 × 10⁵ CFU/ml) was produced on bovine enamel, using McBain saliva under 0.2% sucrose exposure, for 3 days. The biofilm was daily treated with the extracts for 1 min. The biofilm viability was tested by fluorescence and the enamel demineralization was measured using TMR.ResultsMyracrodruon urundeuva All. (Isolated or combined) at the concentrationsc ≥0.625 mg/ml was able to reduce bacteria viability, while Qualea Grandflora Mart. alone had antimicrobial effect at 5 mg/ml only (p < 0.05). On the other hand, none of the extracts were able to reduce enamel demineralization.ConclusionsThe hydroalcoholic extracts of Myracrodruon urundeuva All. and Qualea grandiflora Mart. leaves (isolated or combined) have antimicrobial action; however, they do not prevent enamel caries under S. mutans biofilm model.