50 research outputs found

    Differences in proteolytic activity and gene profiles of fungal strains isolated from the total parenteral nutrition patients

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    Fungal infections constitute a serious clinical problem in the group of patients receiving total parenteral nutrition. The majority of species isolated from infections of the total parenteral nutrition patients belong to Candida genus. The most important factors of Candida spp. virulence are the phenomenon of “phenotypic switching,” adhesins, dimorphism of fungal cells and the secretion of hydrolytic enzymes such as proteinases and lipases, including aspartyl proteinases. We determined the proteolytic activity of yeast-like fungal strains cultured from the clinical materials of patients receiving total parenteral nutrition and detected genes encoding aspartyl proteinases in predominant species Candida glabrata—YPS2, YPS4, and YPS6, and Candida albicans—SAP1–3, SAP4, SAP5, and SAP6. C. albicans released proteinases on the various activity levels. All C. glabrata strains obtained from the clinical materials of examined and control groups exhibited secretion of the proteinases. All 13 isolates of C. albicans possessed genes SAP1–3. Gene SAP4 was detected in genome of 11 C. albicans strains, SAP5 in 6, and SAP6 in 11. Twenty-six among 31 of C. glabrata isolates contained YPS2 gene, 21 the YPS4 gene, and 28 the YPS6 gene. We observed that clinical isolates of C. albicans and C. glabrata differed in SAPs and YPSs gene profiles, respectively, and displayed differentiated proteolytic activity. We suppose that different sets of aspartyl proteinases genes as well as various proteinase-activity levels would have the influence on strains virulence

    Nicotine Promotes Tumor Growth and Metastasis in Mouse Models of Lung Cancer

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    Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7) nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens

    Crk and CrkL adaptor proteins: networks for physiological and pathological signaling

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    The Crk adaptor proteins (Crk and CrkL) constitute an integral part of a network of essential signal transduction pathways in humans and other organisms that act as major convergence points in tyrosine kinase signaling. Crk proteins integrate signals from a wide variety of sources, including growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic cells. Mounting evidence indicates that dysregulation of Crk proteins is associated with human diseases, including cancer and susceptibility to pathogen infections. Recent structural work has identified new and unusual insights into the regulation of Crk proteins, providing a rationale for how Crk can sense diverse signals and produce a myriad of biological responses

    Clearance of apoptotic cells: implications in health and disease

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    Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies

    Organic remains of tentaculitids: New evidence from Upper Devonian of Poland

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    Organic remains of tentaculitids have been recovered during palynological research on archival samples from the Dobrzyca 2 borehole (Western Pomerania). Until now tentaculitids are widely known from their abundant mineralised shells. As organic remains, on the other hand, they have only been known since 2004. The present discovery is currently the second one of this kind found in Upper Devonian strata. The shape and morphology of some recognized tentaculitid organic remains are similar to embryonic and juvenile forms of dacryoconarids belonging to orders Nowakiida and Stylionida. Based on palynomorphs, the age of the two samples investigated has been established as Frasnian, RB and RD local miospore zones

    Preliminary results of the palaeobotanical investigations of the Studzianna well cores (Triassic-Jurassic) from the northern part of the Holy Cross Mts margin

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    Studzianna well core (Triassic-Jurassic) from the Holy Cross Mts region were investigated. Fossil plants from the genus Neocalamites (Equisetales) were found mainly in the Triassic sediments. Fragments of Ginkgoales and Czekanowskiales and Coniferales were determined mainly from the Lower Jurassic. The Lower Jurassic microflora consists of sporomorphs from Bryophyta, Equisetales, Lycopodiales, Filicales from the family Cyatheaceae or Dicsoniaceae, Pteridospermophyta from Caytoniales, Ginkgoales or Cycadales or Bennettitales, Coniferales from the families Taxodiaceae, Pinaceae and Cheirolepidiaceae. Palynofacies have mainly terrestrial character and confirms earlier opinion (Karaszewski 1962, Pieńkowski 2004) of the prevailed terrestrial origin of the Lower Jurassic (Hettangian-Sinemurian) sediments from the Holy Cross Mts region
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