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Cossu A.,University of Massachusetts Amherst | Sechi L.A.,University of Sassari | Bandino E.,Experimental Zooprophylactic Institute of Sardinia | Zanetti S.,University of Sassari | Rosu V.,Experimental Zooprophylactic Institute of Sardinia
Microbial Pathogenesis | Year: 2013

Several studies regarding the transcriptome of Mycobacterium tuberculosis following the exposure to various invitro simulated phagosomal stressors, have already tried to elucidate the bacterium behavior during the intracellular infection. An invitro acid-nitrosative multi-stress was carried out for M. tuberculosis H37Rv and Mycobacterium smegmatis MC2155 in order to analyze by DNA-microarray the gene expression changes associated respectively to pathogenic and non-pathogenic mycobacterial species. During acid-nitrosative multi-stress both mycobacteria shift their transcriptome to allow the anaerobic respiratory state and energy pathways characteristic of starvation. M. tuberculosis counteracts the combined acid-nitrosative stress more efficiently than M. smegmatis as also shown by the up-regulation of glbN and hmp genes, that are specifically directed to NO detoxification. Moreover, the down-regulation of some virulence factors involved in phthiocerol dimycocerosates synthesis strengthens the hypothesis that these major virulence determinants may be attenuated by M. tuberculosis in the presence of reactive nitrogen species. In fact, it down-regulates other genes implicated in the synthesis of membrane structural lipids but in contrast to M. smegmatis, M. tuberculosis up-regulates many genes annotated for the synthesis of peptidoglycan. Results suggest a gene regulation of M. tuberculosis which reveals a distinctive expression pattern under stressful environment. © 2013 Elsevier Ltd. Source

Polo M.F.,University of Sassari | Mastrandrea S.,University of Sassari | Santoru L.,University of Sassari | Arcadu A.,University of Sassari | And 6 more authors.
Microbes and Infection | Year: 2015

A 58-year-old man was admitted because of respiratory failure, episodic fever with chilling, cough, malaise, fatigue, myalgia and weight loss lasting for at least one month. Chest x-rays and CT scan of the chest showed bilateral pulmonary consolidations in upper lobes, the left lower lobe, and mediastinal lymphadenopathy. Bronchoscopy with cytology was unremarkable. A needle CT-guided lung biopsy documented an inflammatory pseudotumor, lymphoplasmacytic type. Serology showed high titer antibodies to phase II Coxiella burnetii infection. Therapy with doxycycline and hydroxychloroquine for three months led to a complete resolution of symptoms and radiological findings, and a marked decrease in titers to Q fever. © 2015 . Source

Varoni M.V.,University of Sassari | Palomba D.,University of Sassari | MacCiotta N.P.,University of Sassari | Antuofermo E.,University of Sassari | And 4 more authors.
Drug and Chemical Toxicology | Year: 2010

In order to elucidate the involvement of the brain renin-angiotensin system (RAS) in cadmium intracerebroventricular (ICV) hypertension, we evaluated the effects of a pretreatment with different drugs: clonidine, an α2 adrenergic agonist, enalapril and captopril, both ACE inhibitors, and saralasin, a competitive nonselective AT1 and AT2 receptor antagonist. We used a rat strain with low levels of kallikrein (LKR) that was more sensitive to ICV cadmium hypertension, compared with normal kallikrein rats (NKRs), the control strain. The interplay between the kallikrein-kinin system and the RAS in the LKR strain caused various hemodynamic alterations, which we believe were the result of elevated RAS activity in these animals. Moreover, we suggest that the defective kallikrein-kinin system in LKR may also cause an alteration in the activation of brain RAS in these animals. The LKR displayed elevated concentrations of plasma AII, hypertrophy of the myocardium, and initial alterations in the renal glomerulotubular system. With the exception of clonidine, all of the other drugs showed greater antihypertensive effects of differing statistical significance in LKR, compared with NKR. Both ACE inhibitors were able to significantly reduce pressor response to cadmium ICV in LKR throughout the experiment, whereas in NKR, they were only able to reduce the hypertensive peak of cadmium. A significant protective effect was also observed in LKR pretreated with saralasin, while no effect was observed in NKR. These findings confirm the presence of brain RAS activation in LKR and its contribution to the central control of pressor response to cadmium ICV. © 2010 Informa UK Ltd. Source

Cossu A.,University of Sassari | Sechi L.A.,University of Sassari | Zanetti S.,University of Sassari | Rosu V.,University of Sassari | Rosu V.,Experimental Zooprophylactic Institute of Sardinia
BMC Microbiology | Year: 2012

Background: Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools. Results: In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures. Conclusions: These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health. © 2012 Cossu et al.; licensee BioMed Central Ltd. Source

Frau M.,University of Sassari | Ladu S.,University of Sassari | Calvisi D.F.,University of Sassari | Simile M.M.,University of Sassari | And 6 more authors.
Journal of Hepatology | Year: 2011

Background & Aims: MYBL2 is implicated in human malignancies and over expressed in hepatocellular carcinoma (HCC). We investigated Mybl2 role in the acquisition of susceptibility to HCC and tumor progression. Methods: MYBL2 mRNA and protein levels were evaluated by quantitative RT-PCR and immunoblotting, respectively. MYBL2 expression in HCC cell lines was controlled through MYBL2 cDNA or anti-MYBL2 siRNA transfection. Gene expression profile of cells transfected with MYBL2 was analyzed by microarray. Results: Low induction of Mybl2 and its target Clusterin mRNAs, in low-grade dysplastic nodules (DN), progressively increased in fast growing high-grade DN and HCC of F344 rats, susceptible to hepatocarcinogenesis, whereas no/lower increases occurred in slow growing lesions of resistant BN rats. Highest Mybl2 protein activation, prevalently nuclear, occurred in F344 than BN lesions. Highest Mybl2, Clusterin, Cdc2, and Cyclin B1 expression occurred in fast progressing DN and HCC of E2f1 transgenics, compared to c-Myc transgenics, and anti-Mybl2 siRNA had highest anti-proliferative and apoptogenic effects in cell lines from HCC of E2f1 transgenics. MYBL2 transfected HepG2 and Huh7 cells exhibited increased cell proliferation and G1-S and G2-M cell cycle phases. The opposite occurred when MYBL2 was silenced by specific siRNA. MYBL2 transfection in Huh7 cells led to upregulation of genes involved in signal transduction, cell proliferation, cell motility, and downregulation of oncosuppressor and apoptogenic genes. Conclusions: mybl2 expression and activation are under genetic control. Mybl2 upregulation induces fast growth and progression of premalignant and malignant liver, through cell cycle deregulation and activation of genes and pathways related to tumor progression. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

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