1,720,995 research outputs found
Interleukin-15 as a potential new target in Sjögren's syndrome-associated inflammation.
Full text linkIL-15 is a key regulatory cytokine that shares many biological properties with IL-2. Recently, it has been shown that IL-15 could be up-regulated in T cell-mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in the inflammatory autoimmune disease Sjögren's syndrome (SS) has not been investigated. In the present study we evaluated the expression of IL-15 mRNA and protein in minor salivary gland (MSG) biopsy specimens and in human salivary gland epithelial cell (SGEC) cultures obtained from patients with primary SS (pSS) and compared their expression with that seen in normal healthy control subjects. IL-15 gene and protein analysis revealed that SGEC are able to produce IL-15. Results obtained demonstrated that the number of IL-15+ cultured SGEC was significantly higher in cells derived from patients with pSS in comparison with SGEC from healthy subjects; similar results were obtained for IL-15 immunoreactivity by using immunohistochemistry that revealed a strong expression both in acinar and in ductal cells from pSS MSG. These studies could provide a rational basis to determine whether IL-15 could be a good candidate for anti-cytokine therapy in chronic inflammatory pSS diseases
X-linked ectodermal dysplasia receptor (XEDAR) gene silencing prevents caspase-3-mediated apoptosis in Sjögren's syndrome
No full textDespite recent advancements in the knowledge of the etiology and pathogenic mechanisms, treatment of the autoimmune disease Sjögren’s syndrome (SS) remains mostly empiric and symptom-based, indicating the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the expression and the biological activity of EDA-A2 in human salivary gland epithelial cells (SGEC) from primary Sjögren’s syndrome (pSS) patients. We report that EDA-A2 and its receptor XEDAR are overexpressed in pSS SGEC in comparison with healthy individuals and that the EDA-A2/XEDAR system in these cells is involved in the induction of apoptosis via caspases activation. Collectively, our results suggest that EDA-A2/XEDAR system may be a promising agent for the gene therapy of pS
Carcinoma tiroideo e gravidanza.
No full textLa gestione del carcinoma tiroideo in gravidanza comporta scelte terapeutiche importanti in considerazione dei potenziali rischi per la paziente e per il feto. La maggior parte delle donne in gravidanza affette da carcinoma tiroideo differenziato può effettuare il trattamento chirurgico dopo il parto. In questi casi è opportuno monitorare il nodulo mediante l’ecografia del collo e la funzionalità tiroidea ed eseguire terapia con L-tiroxina. Qualora si decida di intervenire durante la gravidanza, è opportuno che l’intervento venga eseguito nel secondo trimestre
TLR2 signals via NF-κB to drive IL-15 production in salivary gland epithelial cells derived from patients with primary Sjögren's syndrome
No full textToll-like receptors (TLRs) are pattern recognition receptors linking innate and adaptive immune responses, which resulted overexpressed in primary Sjögren's syndrome (pSS). Interleukin-15 (IL-15) is a pro-inflammatory cytokine which was recently demonstrated to be involved in pSS pathogenesis. The study was undertaken to clarify whether TLR2 is involved in the production of IL-15 in human salivary gland epithelial cells (SGEC) from pSS patients. SGEC primary cell cultures were established from pSS minor salivary gland tissues explanted from patients with a sure diagnosis of SS. After neutralization of TLR2 with a blocking monoclonal antibody, IL-15 production was assayed by immunoblotting and flow cytometry, IL-15 in the culture supernatants was measured by ELISA, and mRNA levels were assessed by RT-PCR and real-time PCR. The production of IL-15 by pSS SGEC decreased in culture supernatants and in protein lysates (p < 0.01) when TLR2 signaling was inhibited in pSS SGEC. In addition, a control at the transcriptional level was also detected; in fact, inhibition of nuclear factor (NF)-κB through the transfection of pSS SGEC with the dominant-negative inhibitory κBα proteins (IκBα) vector (IκBαDN) abrogated the stimulatory effect of TLR2 on IL-15 production. These data suggest that TLR2 activation is involved in the induction of IL-15 production by pSS SGEC and promotes inflammation through NF-κB activation. Therefore, therapeutic strategies that target TLR2/IL-15 pathway might be strong candidates for preventing or treating pSS
Immunohistochemical characterization of axon terminals of the adult rat cerebellar cortex
Full text linkThe study was carried out on adult rat using immunohistochemical techiques for demonstration of VGLUT1 and VGLUT2 and their co-localization with synaptophysin.
In the molecular layer (ML): VGLUT1 terminals were distributed throughout the layer with a pattern resembling that of the parallel fiber terminals; VGLUT2 terminals were displaced along distinct spiral lines extending from deep to superficial layer, likely corresponding to terminals of climbing fibers. No colocalization of VGLUT1 and VGLUT2 was observed; on the contrary, terminals co-localizing GLUT1 and synaptophysin and VGLUT2 and synaptophysin, respectively, were detected, according to terminal nature of the immunolabelled elements. In the granular layer (GL): VGLUT1 and VGLUT2 terminals displayed similar distribution pattern, being clustered
in restricted regions of the layer among granules (glomeruli). Most of them showed colocalization of VGLUT1 and VGLUT2, some showing positivity for VGLUT2 and negativity for VGLUT1, and all showing positivity for synaptophysin. Finally, some terminals were synaptophysin positive, but VGLUT1 and VGLUT2 negative.
The results indicate that the glutamatergic terminals in the cerebellar cortex may be differentiated by combining immunohistochemistry for VGLUT1 and VGLUT2. Moreover, they identify different subpopulations of terminals of parallel, climbing and mossy fibers. In particular, a subpopulation of mossy fiber terminals, displaying positivity for VGLUT2 and negativity for VGLUT1, differently from the vast majority of mossy fiber terminals, displaying positivity for both VGLUT1 and VGLUT2, but similarily to climbing fiber terminals. It is intriguing to hypothesize that these mossy fibers may constitute a contingent of mossy fiber originated in the inferior olivary nuclear complex
EXOCRINE GLAND MORPHOGENESIS: INSIGHTS INTO THE ROLE OF AMPHIREGULIN FROM DEVELOPMENT TO DISEASE
No full textAmphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current
advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of
AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjo ̈gren’s syndrome
Double Immunohistochemical Staining on Formalin-Fixed Paraffin-Embedded Tissue Samples to Study Vascular Co-option
No full text: Vascular co-option is a non-angiogenic mechanism whereby tumor growth and progression move on by hijacking the pre-existing and nonmalignant blood vessels and is employed by various tumors to grow and metastasize.The histopathological identification of co-opted blood vessels is complex, and no specific markers were defined, but it is critical to develop new and possibly more effective therapeutic strategies. Here, in glioblastoma, we show that the co-opted blood vessels can be identified, by double immunohistochemical staining, as weak CD31+ vessels with reduced P-gp expression and proliferation and surrounded by highly proliferating and P-gp- or S100A10-expressing tumor cells. Results can be quantified by the Aperio Colocalization algorithm, which is a valid and robust method to handle and investigate large data sets
Systemic treatment of advanced, metastatic, medullary thyroid carcinoma
No full textMedullary thyroid carcinoma (MTC) is a rare endocrine tumor, which arises from thyroid parafollicular C cells. Through its ability to metastasize by blood and lymphatic vessels, it can show a more aggressive clinical behavior than differentiated thyroid cancers. Mutation of RET gene is the main molecular alteration involved in MTC origin. In the case of germline RET mutation, MTC can be inherited in an autosomal dominant way and show three different phenotypes: familial medullary thyroid carcinoma and multiple endocrine neoplasia types IIA and IIB. In addition, in sporadic cases, somatic RET mutation remains the key molecular alteration in most of cases. Total thyroidectomy with prophylactic or therapeutic central compartment lymph nodes dissection is the surgical treatment of choice. Further surgical treatments and local therapies should be used in the case of single or few local or distant metastasis. However, in cases with large metastatic spread of the disease, particularly in those with significant tumor progression, additional systemic treatments are needed. In this review, we discuss the key points of systemic treatment in advanced, metastatic MTC. We provide an update on the main aspects (from biological rationale to clinical experience) of each treatment, focusing our attention on the drugs used in clinical practice in the last years. Finally, we give insights about the emerging treatments from highly selective RET inhibitors to new radionuclide therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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