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Intracellular Calcium Disturbances Induced by Arsenic and Its Methylated Derivatives in Relation to Genomic Damage and Apoptosis Induction

Arsenic and its methylated derivatives are contaminants of air, water, and food and are known as toxicants and carcinogens. Arsenic compounds are also being used as cancer chemotherapeutic agents. In humans, inorganic arsenic is metabolically methylated to mono-, di-, and trimethylated forms. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In recent years, the correlation between arsenic exposure, cytotoxicity and genotoxicity, mutagenicity, and tumor promotion has been established, as well as the association of arsenic exposure with perturbation of physiologic processes, generation of reactive oxygen species, DNA damage, and apoptosis induction. Trivalent forms of arsenic have been found to induce apoptosis in several cellular systems with involvement of membrane-bound cell death receptors, activation of caspases, release of calcium stores, and changes of the intracellular glutathione level. It is well known that calcium ion deregulation plays a critical role in apoptotic cell death. A calcium increase in the nuclei might lead to toxic effects in the cell. In this review, we highlight the relationship between induced disturbances of calcium homeostasis, genomic damage, and apoptotic cell death caused by arsenic and its organic derivatives

Differential Analysis of Pregnancy Outcomes After Treatment of HIFU and LEEP in Patients with Cervical High-Grade Squamous Intraepithelial Lesions

Xiao-Ling Shen,1,* Zhuo-Yi Li,1,* Qing Li,1 Kai Wang2 1Department of Women Health Care, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China; 2Department of Aristogenesis, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Wang; Qing Li, Email [email protected]; [email protected]: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age.Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher’s exact test or the Kruskal–Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification.Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P 0.05).Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.Keywords: cervical high-grade squamous intraepithelial lesions, high-intensity focused ultrasound, loop electrosurgical excision procedure, pregnancy outcom

A parametric description of the 3D structure of the Galactic bar/bulge using the VVV survey

© 2017 The Authors. We study the structure of the inner Milky Way using the latest data release of the VISTA Variables in the Via Lactea (VVV) survey. The VVV is a deep near-infrared, multi-colour photometric survey with a coverage of 300 square degrees towards the bulge/bar. We use red clump (RC) stars to produce a high-resolution dust map of the VVV's field of view. From dereddened colour-magnitude diagrams, we select red giant branch stars to investigate their 3D density distribution within the central 4 kpc. We demonstrate that our best-fitting parametric model of the bulge density provides a good description of the VVV data, with a median percentage residual of 5 per cent over the fitted region. The strongest of the otherwise lowlevel residuals are overdensities associated with a low-latitude structure as well as the so-called X-shape previously identified using the split RC. These additional components contribute only ~5 per cent and ~7 per cent respectively to the bulge mass budget. The best-fitting bulge is 'boxy' with an axial ratio of [1:0.44:0.31] and is rotated with respect to the Sun-Galactic Centre line by at least 20°. We provide an estimate of the total, full sky, mass of the bulge of MbulgeChabrier= 2.36 × 1010M⊙for a Chabrier initial mass function. We show that there exists a strong degeneracy between the viewing angle and the dispersion of the RC absolute magnitude distribution. The value of the latter is strongly dependent on the assumptions made about the intrinsic luminosity function of the bulge

Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer

Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. © 2012 The Author(s).published_or_final_versio

Screening of Diagnostic Biomarkers and Immune Infiltration Characteristics Linking Rheumatoid Arthritis and Rosacea Based on Bioinformatics Analysis

Yun Wang,1 Jun Chen,1 Zheng-Yu Shen,1 Jie Zhang,2 Yu-Jie Zhu,1 Xu-Qiong Xia1 1Department of Dermatology, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai, 200080, People’s Republic of China; 2The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Yu-Jie Zhu; Xu-Qiong Xia, Email [email protected]; [email protected]: Both rheumatoid arthritis (RA) and rosacea represent common chronic systemic autoimmune conditions. Recent research indicates a heightened RA risk among individuals with rosacea. However, the molecular mechanisms linking these diseases remain largely unknown. This study aims to uncover shared molecular regulatory networks and immune cell infiltration patterns in both rosacea and RA.Methods: The gene expression profiles of RA (GSE12021, GSE55457), and the rosacea gene expression profile (GSE6591), were downloaded from Gene Expression Omnibus (GEO) databases, and obtained to screen differentially expressed genes (DEGs) by using “limma” package in R software. Various analyses including GO, KEGG, protein–protein interaction (PPI) network, and weighted gene co-expression network analyses (WGCNA) were conducted to explore potential biological functions and signaling pathways. CIBERSORT was used to assess the abundance of immune cells. Pearson coefficients were used to calculate the correlations between overlapped genes and the leukocyte gene signature matrix. Flow cytometry (FCM) analysis confirmed the most abundant immune cells detected in rheumatoid arthritis and rosacea. Receiver operator characteristic (ROC) analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to confirm biomarkers and functions.Results: Two hundred seventy-seven co-expressed DEGs were identified from these datasets. Functional enrichment analysis indicated that these DEGs were associated with immune processes and chemokine-mediated signaling pathways. Fourteen and 17 hub genes overlapped between cytoHubba and WGCNA were identified in RA and rosacea, respectively. Macrophages and dendritic cells were RA and rosacea’s most abundant immune cells, respectively. The ROC curves demonstrated potential diagnostic values of CXCL10 and CCL27, showing higher levels in the serum of patients with RA or rosacea, and suggesting possible regulation in the densities and functions of macrophages and dendritic cells from RA and rosacea, which were validated by FCM and qRT-PCR.Conclusion: Importantly, our findings may contribute to the scientific basis for biomarkers and therapeutic targets for patients with RA and rosacea in the future.Keywords: autoimmune disease, immune infiltration, macrophage, chemokine, diagnostic biomarker

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A Piezoelectric Immunosensor Using Hybrid Self-Assembled Monolayers for Detection of Schistosoma japonicum

BACKGROUND: The parasite Schistosoma japonicum causes schistosomiasis disease, which threatens human life and hampers economic and social development in some Asian countries. An important lesson learned from efforts to reduce the occurrence of schistosomiasis is that the diagnostic approach must be altered as further progress is made towards the control and ultimate elimination of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Using mixed self-assembled monolayer membrane (mixed SAM) technology, a mixture of mercaptopropionic acid (MPA) and mercaptoethanol (ME) was self-assembled on the surface of quartz crystals by gold-sulphur-bonds. Soluble egg antigens (SEA) of S. japonicum were then cross-linked to the quartz crystal using a special coupling agent. As compared with the traditional single self-assembled monolayer immobilization method, S. japonicum antigen (SjAg) immobilization using mixed self-assembled monolayers exhibits much greater immunoreactivity. Under optimal experimental conditions, the detection range is 1:1500 to 1:60 (infected rabbit serum dilution ratios). We measured several infected rabbit serum samples with varying S. japonicum antibody (SjAb) concentrations using both immunosensor and ELISA techniques and then produced a correlation analysis. The correlation coefficients reached 0.973. CONCLUSIONS/SIGNIFICANCE: We have developed a new, simple, sensitive, and reusable piezoelectric immunosensor that directly detects SjAb in the serum. This method may represent an alternative to the current diagnostic methods for S. japonicum infection in the clinical laboratory or for analysis outside the laboratory

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al