Histology and histopathology Vol.26, nº3 (2011)
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- PublicationOpen AccessComparative pulmonary toxicity assessment of pristine and functionalized Multi-Walled Carbon Nanotubes intratracheally instilled in rats: morphohistochemical evaluations(Murcia: F. Hernández, 2011) Roda, E.; Coccini, T.; Acerbi, D.; Barni, Sergio; Vaccarone, R.; Manzo, L.. Increasing interest in safety evaluation of carbon nanotubes (CNTs) has risen in relation to their wide applications, together with the evidence of their cytotoxic effects. It has been shown that chemical functionalization extends the applications of CNTs, conferring them new functions that cannot otherwise be acquired by pristine CNTs, but also impacts on biological response to CNTs, modifying their toxicological profile. We assessed the onset of pulmonary toxic effects caused by pristine MW-CNTs and functionalized MWNH2 or MW-COOH, 16 days after intratracheal instillation (1 mg/kg b.w.); major endpoints tested included (i) histopathology of lung (Haematoxylin/Eosin Staining), (ii) apoptotic/proliferating features examined by TUNEL and PCNA immunostaining, and (iii) presence/distribution of (1) Transforming Growth Factor-beta1 (TGFß1), (2) Interleukin-6 (IL-6) and (3) Collagen (Type I) investigated by immunochemical methods, as markers of lung toxicity, inflammation, and fibrosis, respectively. Lung histopathology from exposed animals showed dark, particulate-laden macrophages, reflecting carbon nanomaterial engulfing, both at alveolar and bronchiolar levels, after treatment with all the tested CNTs. Alteration of lung architecture was also observed in several areas showing collapsed thick-walled alveoli and the presence of micro-haemorrhagic foci. TUNEL and PCNA, indicative of apoptosis and cell proliferation respectively, showed a significant increase of immunopositive cells at bronchiolar, alveolar and macrophagic levels, as expression of an improved cellular turnover. Increased immunoreactivity for pulmonary TGFß1 and IL-6 was observed in treated rats, particularly in bronchiolar areas, collapsed alveoli and at stromal level, while evident changes for collagen were not detected. Taken together these findings demonstrated the general pulmonary toxicity coupled with inflammatory response after in vivo exposure to CNTs, without overt signs of fibrosis and granuloma formation, irrespectively of nanotube functionalization
- PublicationOpen AccessMolecular regulation of articular chondrocyte function and its significance in osteoarthritis(Murcia: F. Hernández, 2011) Schroeppel, J.P.; Crist, J.D.; Anderson, H.C.; Wang, J.Osteoarthritis (OA) is the most common form of joint disease. Histopathologically, OA is characterized by a progressive loss of articular cartilage, osteophyte formation, thickening of subchondral bone, and subchondral cyst formation. All current therapies are aimed at symptomatic control and have limited impacts on impeding or reversing the histopathologic progression to advanced OA. Previous studies have shown that overexpression of matrix-degrading proteinases and proinflammatory cytokines is associated with osteoarthritic cartilage degradation. However, clinical trials applying an inhibitor of proteinases or proinflammatory cytokines have been unsuccessful. A more sophisticated understanding of the regulatory mechanisms that control the function of articular chondrocytes is paramount to developing effective treatments. Since multiple catabolic factors and pathological chondrocyte hypertrophy are involved in the development of OA, it is important to identify which upstream factors regulate the expression of catabolic molecules and/or chondrocyte hypertrophy in articular cartilage. This review summarizes the current studies on the molecular regulation, with a main focus on transcriptional regulation, of the function of adult articular chondrocytes and its significance in the pathogenesis and treatment of OA. Recent studies have discovered that transcription factor Nfat1 may play an important role in maintaining the physiological function of adult articular chondrocytes. Nfat1-deficient mice exhibit normal skeletal development but display most of the features of human OA as adults, including chondrocyte hypertrophy with overexpression of specific matrix-degrading proteinases and proinflammatory cytokines in adult articular cartilage. ß-catenin transcriptional signaling in articular chondrocytes may also be involved in the pathogenesis of OA. Activation of ß-catenin leads to OA-like phenotypes with overexpression of specific matrix-degrading proteinases in articular cartilage of adult mice. These and other regulatory mechanisms described in this review may provide new insights into the pathogenesis of OA and the development of novel therapeutic targets for the treatment of OA.
- PublicationOpen AccessEndosome-to-Golgi transport pathways in physiological processes(Murcia: F. Hernández, 2011) Zhao Lieu, Zi; Gleeson, Paul A.The trans-Golgi network (TGN) is a major traffic hub of the cell, as it regulates membrane transport in the secretory pathway as well as receiving protein cargo by retrograde transport from endocytic compartments. Retrograde transport between endosomes and the TGN is essential for the recycling of membrane proteins which regulate a range of cellular and development functions. In addition, retrograde transport pathways are exploited by many bacterial toxins to mediate cytotoxicity and by some viral proteins to promote pathogenicity. Recent advances using a range of molecular cell biological strategies have identified multiple retrograde transport pathways each regulated by a distinct set of molecular machinery. Here we review recent advances in this field and highlight the importance of these transport pathways in a range of physiological processes.
- PublicationOpen AccessMorphological characteristics and peptidergic innervation in the carotid body of spontaneously hypertensive rats(Murcia: F. Hernández, 2011) Takahashi, Masahiro; Matsuda, Hideki; Hayashida, Yoshiaki; Yamamoto, Yoshio; Tsukuda, Mamoru; Kusakabe, TatsumiWe examined morphological characteristics of the carotid body of spontaneously hypertensive rats (SHR), those of age-matched normotensive Wistar rats (NWR), and age-matched genetically comparable Wistar Kyoto rats (WKY). We examined the distribution and abundance of four different regulatory neuropeptides: substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the carotid bodies of these three strains of rats. The carotid bodies of SHR were larger than those of NWR and WKY. The values of the long axis of the carotid bodies of SHR were significantly larger (1.3 times) than those of NWR and WKY. In the carotid bodies of SHR, the percentage of relatively large vessels was similar to that of the carotid bodies of WKY, although the carotid bodies themselves were significantly larger than in WKY. The density of VIP varicose fibers in the carotid bodies of SHR was lower than in the carotid bodies of WKY, although the density of SP, CGRP and NPY fibers was similar to that of the carotid bodies of NWR and WKY. These findings suggested that VIP was unrelated to enlargement of the carotid body of SHR, but it might modify the sensitivity of chemoreceptors in the carotid body.
- PublicationOpen AccessHuman Leukocyte Antigen-G (HLA-G) as a marker for diagnosis, prognosis and tumor immune escape in human malignancies(Murcia: F. Hernández, 2011) Yie, Shang-mian; Hu, ZhenboHuman leukocyte antigen-G (HLA-G) is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main functions in physiological conditions are to abolish maternal immune cell activity against fetus and to establish immune tolerance at the maternal-fetal interface. In oncology, HLA-G molecules are aberrantly expressed in a variety of human neoplastic diseases and play an important role in the escape of tumor cells from immune surveillance. In the past few years, making use of HLA-G protein expression in tissues and circulating levels in body fluids as a tumor marker have been the focus of extensive research in the diagnosis and prognosis of several human malignancies. In addition, this molecule might be a promising target for future immune therapeutic approaches based on its immune tolerant functions and its highly specific expression for malignant transformation. In this review, we will summarize available literature data as well as our own works on HLA-G in cancer, and address some of the issues concerning its application in human neoplasia.
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