1,721,043 research outputs found
Endothelial-mesenchymal transition represents a key process during atherosclerotic plaque calcification
No full textStudy objective
The endothelial-mesenchymal transition (End-MT) has been recently proposed as a key process during plaque evolution and calcification. In our hypothesis, microenvironment cues stimulate the endothelial cell conversion into MSC-like cells that lately differentiate toward the osteogenic lineage, contributing to the calcium accumulation within the intima. The main objective of the present study was to investigate the expression of SLUG, a key transcription factor regulating the End-MT, in human atherosclerotic lesions of abdominal aortic aneurysms (AAA) and carotid plaques (CP). Then we addressed the End-MT in endothelial cells, investigating its possible association with the calcification process in presence of inflammatory soluble mediators and in co-culture models with vascular resident cells.
Methods
SLUG was analysed in FFPE tissues of AAA and CP patients. End-MT was explored in Human Umbilical Vein Endothelial Cells (HUVEC) in presence of the inflammatory cytokine TNF-α and the members of the TGF- β superfamily (the canonical TGF-β1 and TGF-β3) for 7 days. Mesenchymal Stem Cells (MSCs) were ex-vivo isolated from AAA and CP biopsies, characterized and used for transwell co-culture assays with HUVEC. After 7-days, HUVEC were tested for osteogenic differentiation by calcium stain with Alizarin Red and by mRNA levels of SLUG, MMP-9, CD31 and RUNX-2. Considering that SLUG is a potential target of miR-30 family, we also detected miR-30a/d variations in HUVEC after each culture conditions.
Results
SLUG analysis by IHC revealed intense stain in AAA and CP tissues, mostly within inflammatory infiltrates and in endothelial cells. TNF-α and TGF-β3 effectively promoted End-MT, as supported by the spindle-shape morphology and by the increase of SLUG and MMP-9 mRNA. TNF-α also stimulated RUNX-2 expression in HUVEC. In addition, HUVEC demonstrated osteogenic property as shown by mineralization assay and RUNX-2 expression, especially after culture with AAA- and CP-MSC. Interestingly, the HUVEC osteogenic phenotype was accompanied by SLUG up-regulation and slight decrease of CD31. Finally, End-MT and osteogenic differentiation decreased miR-30a and miR-30d expression in HUVEC.
Conclusions
Our results support the occurrence of the End-MT process in human atherosclerotic disease and highlight that the endothelial cells actively govern the plaque formation as well as the late calcification, by switching into the mesenchymal cell intermediate. Future investigations will address the potential therapeutic strategies targeting the main End-MT mediators in order to inhibit the calcification of the atherosclerotic plaque
Unusual lamellar calcifications in two rare cases of splenic aneurysms associated with fibromuscular dysplasia
No full textFibromuscular dysplasia (FMD) of the splenic artery is a rare underdiagnosed condition. Here, we report two cases of FMD affecting the splenic artery: one alone and one concomitantly with the renal artery. Histology revealed fibromuscular thickening of the media layer alternating with a circumferential calcification of the whole artery thickness. Ultrastructurally, FMD showed matrix vesicles and dense bodies in the extracellular matrix. A diagnosis of FMD with calcification was made. This is the first report to document circumferential lamellar calcifications alternating with the more typical fibrotic medial areas in the rare FMD localized to splenic artery
Immunohistochemical and Ultrastructural Characterization of Telocytes in Normal and Diabetic Human Kidneys
Full text linkBackground: Telocytes are interstitial stromal cells identified in various human organs, including the kidney. Their presence and role in human diabetic kidney disease remain unknown. Methods: To identify and localize telocytes in glomerular and tubule-interstitial compartments, both normal and diabetic human renal tissues were examined using immunohistochemistry, immunofluorescence, and transmission electron microscopy. Results: Renal telocytes are elongated interstitial cells with long, thin telopodes, showing alternating thin and thick segments. They expressed CD34, Nestin, α-SMA, and Vimentin markers. Occasionally, c-Kit expression was observed in some rounded and spindle cells, while no positivity was detected for PDGFR-β and NG2. Telocytes were identified around Bowman's capsule, tubules, and peritubular capillaries in both normal and diabetic conditions. In diabetic renal samples, there was a significant increase in α-SMA expressing telocytes, leading to periglomerular fibrosis. These telocytes also exhibited a synthetic phenotype with proteoglycan deposition in the extracellular matrix and, in some cases, showed pre-adipocytic differentiation. Conclusions: Telocytes were identified in normal and diabetic human kidneys. These cells form an elastic mechanical scaffold in the interstitium and are present in all renal cortical compartments. In diabetic samples, their increased α-SMA expression and synthetic phenotype suggest their potential role in the pathogenesis of diabetic nephropathy
State-of-the-art review on the correlations between pathological and magnetic resonance features of cirrhotic nodules
No full textHepatocellular carcinoma (HCC) has become the second greatest cause of cancer-related mortality worldwide and the newest advancements in liver imaging have improved the diagnosis of both overt malignancies and premalignant lesions, such as cirrhotic or dysplastic nodules, which is crucial to improve overall patient survival rate and to choose the best treatment options. The role of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) has grown in the last 20 years. In particular, the introduction of hepatospecific contrast agents has strongly increased the definition of precursor nodules and detection of high-grade dysplastic nodules and early HCCs. Nevertheless, the diagnosis of liver tumours in cirrhotic patients sometimes remains challenging for radiologists, thus, in doubtful cases, biopsy and histological analysis become critical in clinical practice. This current review briefly summarizes the history of imaging and histology for HCC, covering the newest techniques and their limits. Then, the article discusses the links between radiological and pathological characteristics of liver lesions in cirrhotic patients, by describing the multistep process of hepatocarcinogenesis. Explaining the evolution of pathologic change from cirrhotic nodules to malignancy, the list of analyzed lesions provides regenerative nodules, low-grade and high-grade dysplastic nodules, small HCC and progressed HCC, including common subtypes (steatohepatitic HCC, scirrhous HCC, macrotrabecular massive HCC) and more rare forms (clear cell HCC, chromophobe HCC, neutrophil-rich HCC, lymphocyte-rich HCC, fibrolamellar HCC). The last chapter covers the importance of the new integrated morphological-molecular classification and its association with radiological features
Unusual asymptomatic presentation of bladder cancer metastatic to the penis
No full textPenile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer
Case report: Histological findings of peri-appendicitis in three children with SARS-CoV-2 – related multisystem inflammatory syndrome: A mark for systemic inflammation?
Full text linkBACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy. METHODS: We retrospectively collected the clinical features and histological findings of three previously healthy children who underwent appendectomy for clinical suspicion of acute appendicitis but were later diagnosed with MIS-C. FINDINGS: The three children presented with prominent abdominal manifestations and fever leading to the suspicion of acute abdomen. Histological findings showed transmural and perivascular inflammation. Notably, CD68(+) macrophages were predominant in the child with milder abdominal symptoms without cardiac injury, while CD3(+) lymphocytes in the patient presented with more severe abdominal pain and cardiovascular involvement at admission. INTERPRETATION: Gastrointestinal symptoms of children with MIS-C improve after proper immunomodulatory therapy, conversely showing inadequate response to surgical appendectomy. Histological findings revealed different inflammatory cell infiltration that primarily involved perivisceral fat and vessels, and subsequently mucosal tissue, in contrast to other forms of acute appendicitis. Our findings suggest that this kind of peri-appendicitis in MIS-C could represent a focal sign of systemic inflammation, with different histological patterns compared to other forms of acute appendicitis
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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