627 research outputs found

    Early MicroRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection

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    It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease. © 2014 Yeruva et al

    Molecular mechanism of methyl jasmonate induced apoptosis in human cancer cells

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    This study investigated the cytotoxic activity of four plant derived compounds including perillic acid (PA), Perillyl alcohol (POH), cis jasmone (CJ) and methyl jasmonate (MJ) on a variety of human cancer cell lines: Breast (MDA-MB-435, MDA-MB-231, DC4, DB46, T47D, SKBR3 and ZR75-1), Prostate (PC-3 and DU-145) and Lung (A549, H520 and H2170). It was demonstrated that these compounds induce cell cycle arrest and apoptosis by themselves or in combination with other agents. Specifically, MJ decreases membrane fluidity resulting in an activation of tumor necrosis factor receptor 1 (TNFR1) which signals apoptosis via caspase 8 and 2. Combination studies demonstrated that POH, MJ and cisplatin decreased viability, induced cell cycle arrest and activated TNFR1. These results indicate that plant compounds show promise as an alternate treatment option and the combination of these compounds with chemotherapeutic drugs may decrease toxicity and improve efficacy over single agent therapy

    Microscopic Image Retrieval Scheme Using Neural Network For Multi Image Queries

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    In this paper, we describe the plan and advancement of a neural network based image retrieval framework for microscopic images using a reference information base that contains images of more than one information. Such an extraction requires a point by point assessment of retrieval execution of image highlights. This paper presents a survey of crucial parts of content based image retrieval including highlight extraction of color and surface highlights. The proposed neural network based image retrieval framework utilizes a multitier way to deal with arrange and recover microscopic images including their particular subtypes, which are generally hard to separate and characterize. Broad examinations on neural network based image retrieval frameworks show that low-level image highlights can't generally depict elevated level semantic ideas in the clients mind. This framework empowers multi-image inquiry to ensure the semantic consistency among the recovered images. New weighting terms, roused from information retrieval hypothesis, are characterized for multiple-image inquiry and retrieval. The multi-image inquiry calculation with the proposed weighting technique accomplishes about normal order exactness at the main position retrieval, beating the image-level retrieval precision by about ideal rate focuses for different infections separately. Utilizing low level highlights just does exclude human insight. In the event that human mediation is permitted in the image retrieval framework the proficiency supports up

    Influence of NFκB inhibitors on IL-1β-induced chemokine CXCL8 and -10 expression levels in intestinal epithelial cell lines: glucocorticoid ineffectiveness and paradoxical effect of PDTC

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    Activation of intestinal epithelial cell (IEC) nuclear factor kappa B (NF kappa B) and the consequent chemokine upregulation are crucial events in inflammatory bowel disease (IBD) pathogenesis. Not much is known about the consequences of NF kappa B inhibition in terms of chemokine expression in intestinal cells. Therefore, we aimed to evaluate the efficacy of compounds known to disrupt the NF kappa B pathway on NF kappa B transcriptional activity and CXCL8 and CXCL10 gene expression in intestinal cell lines. The influence of NF kappa B inhibitors (dexamethasone, pyrrolidine dithiocarbamate (PDTC) and BAY 11-7082) on IL-1 beta-induced NF kappa B transcriptional activity was investigated by transient transfection of Caco-2 cells with an NF kappa B-secreted alkaline phosphatase reporter plasmid. Il-1 beta stimulated CXCL8 and CXCL10 mRNA and protein expression and was studied in Caco-2 and HT29 cells in the presence and absence of the NF kappa B inhibitors by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent serologic assay, respectively. To reveal alternative signalling cascades, experiments were also performed in the presence of the p38MAPK inhibitor SB 203580 and the ERK inhibitor PD 98059. Dexamethasone did not downregulate chemokine expression sufficiently, probably due to a lack of glucocorticoid receptors in these cells. While BAY11-7082 inhibited chemokine expression, PDTC led to a paradoxical upregulation of CXCL8 in Caco-2 cells, which could be prevented by inhibition of p38MAPK. These data explain the frequent unresponsiveness of IBD to glucocorticoid treatment and suggest that alternative NF kappa B inhibition in IECs might be of use in IBD therapy. Drug development based on measuring anti-NF kappa B activity might be misleading and should therefore also include studies on relevant gene products

    Fast Nearest Neighbor Search with Keywords in Spatial Databases

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    In these days, many modern purposes name for novel varieties of queries that purpose to find objects pleasing both a spatial predicate, and a predicate on their related texts. Present answer for such queries has a couple of deficiencies that critically influence its effectivity. Prompted by way of this, in this venture, development of a new entry process called the spatial inverted index that extends the conventional inverted index to cope with multidimensional data, and is derived with algorithms that may reply nearest neighbor queries with key words in actual time. As tested via experiments, the proposed approaches outperform the IR2-tree in question response time tremendously, more commonly through a factor of orders of magnitude. DOI: 10.17762/ijritcc2321-8169.15080

    Smart hydrogel for enzyme responsive vaginal delivery of anti-HIV peptide therapeutics

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    Title from PDF of title page viewed December 16, 2021Dissertation advisor: Chi H. LeeVitaIncludes bibliographical references (pages 150-181)Thesis (Ph.D.)--School of Pharmacy and Department of Chemistry. University of Missouri--Kansas City, 2021In response to an urgent need for advanced formulations for the delivery of anti-retrovirals, a stimuli sensitive hydrogel formulation that intravaginally delivers HIV-1 entry inhibitor upon being exposed to a specific protease was developed. The hydrogel formulation consists of PEG-azide and PEG-DBCO covalently linked to the entry inhibitor peptide, Enfuvirtide via substrate linker. The substrate linker is designed to undergo proteolysis by prostate specific antigen (PSA) present in seminal fluid and release innate Enfuvirtide. Of the tested PSA substrate linkers (HSSKLQYY, GISSFYSSK, AYLMYY and AYLMGRR), HSSKLQ was found to be an ideal candidate for PEG-based hydrogel with kcat/KM of 2.2 M-1 s-1. The PEG-based hydrogel displayed a pseudoplastic, thixotropic behavior with overall viscosity varying between 1516 Pa. s to 2.2 Pa. s, within the biologically relevant shear rates of 0.01-100 s-1. It also exhibited viscoelastic properties appropriate for uniform spreading and being retained in vagina. PEG-based hydrogels were loaded with N3-HSSKLQ-Enfuvirtide (HF42) that is customarily synthesized Enfuvirtide prodrug with its N-terminus connected to HSSKLQ linker. The stimuli sensitive PEG-based hydrogel formulations released 31.3 ± 8.7% of Enfuvirtide upon being exposed to PSA at pH 7.4 and 45.5 ± 6.5 % of Enfuvirtide at pH 8.6 over 24 hr., both of which are significantly greater than its IC50. The PEG-based hydrogel was non-cytotoxic to vaginal epithelial cells (VK2/E6E7) and murine macrophages (RAW 264.7) and did not significantly induce production of nitric oxide, an inflammatory mediator. The PEG-based hydrogel is found to have suitable physicochemical properties for an intravaginal formulation of the PSA substrate linked anti-retrovirals and is safe towards vaginal epithelium. It is capable of delivering Enfuvirtide with effective concentrations and has the potential to be used in clinical setting for effective prevention of HIV-1.Introduction -- Biomedical strategies to prevent vaginal transmission of HIV in women -- Current state of stimuli sensitive microbicide -- Development and evaluation of Smart Hydrogel for HIV-1 -- Summary, scope and recommendations -- Appendi

    STATISTICS OF CANCER, 2020 IN INDIAN STATES: A REVIEW ON THE REPORT FROM NATIONAL CANCER REGISTRY PROGRAMME

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    The deliberate assortment of information on cancer growth was performed by different populace-based disease vaults (population-based cancer registries [PBCRs]) and clinic-based cancer growth libraries (hospital-based cancer registries [HBCRs]) across India under the National Cancer Registry Program–National Center for Disease Informatics and Research of Indian Council of Medical Research since 1982. This survey analyzed the malignant growth occurrence, designs, patterns, projections, and mortality from 28 PBCRs and furthermore the stage at introduction and kind of therapy of patients with disease from 58 HBCRs (n=667,666) from the pooled investigation for the composite time frame 2012–2016. Time patterns in cancer growth rate were created as yearly percent change from 16 PBCRs (those with at least 10 years of consistent great information accessible) utilizing Joinpoint relapse. Aizawl locale (269.4) and Papumpare region (219.8) had the most elevated age changed occurrence rates among guys and females, separately. The extended number of patients with disease in India is 1,392,179 for the year 2020, and the basic five driving destinations are cancer, lung, mouth, cervix uteri, and tongue. Patterns in disease frequency rate showed an expansion on the whole locales of cancer in both genders and were high in Kamrup Metropolitan (yearly percent change, 3.8%; p<0.05). Most of the patients with cancer were analyzed at the privately progressed stage for cancer (57.0%), cervix uteri (60.0%), head and neck (66.6%), and stomach (50.8%) disease, while in cellular breakdown in the lungs, far off metastasis was dominating among guys (44.0%) and females (47.6%). This audit gives a system to surveying the status and patterns of cancer growth in India. It will manage proper help for activity to fortify endeavors to improve cancer growth avoidance and control to accomplish the public non-communicable illness targets and the reasonable advancement objectives
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