A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells

Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro- and anti-angiogenic effects in vitro and in vivo. the TSP-HepI peptide (2.3 kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells. We have previously shown that TSP-1 itself exhibits a dual effect on endothelial colony-forming cells (ECFC) by enhancing their adhesion through its TSP-HepI fragment while reducing their proliferation and differentiation into vascular tubes (tubulogenesis) in vitro. This effect is likely mediated through CD47 binding to the TSP-1 C-terminal domain. Here we investigated the effect of TSP-HepI peptide on the angiogenic properties of ECFC in vitro and in vivo. TSP-HepI peptide potentiated FGF-2-induced neovascularisation by enhancing ECFC chemotaxis and tubulogenesis in a Matrigel plug assay. ECFC exposure to 20 mu g/mL of TSP-HepI peptide for 18 h enhanced cell migration (p < 0.001 versus VEGF exposure), upregulated alpha 6-integrin expression, and enhanced their cell adhesion to activated endothelium under physiological shear stress conditions at levels comparable to those of SDF-1 alpha. the adhesion enhancement appeared to be mediated by the heparan sulfate proteoglycan (HSPG) syndecan-4, as ECFC adhesion was significantly reduced by a syndecan-4-neutralising antibody. ECFC migration and tubulogenesis were stimulated neither by a TSP-HepI peptide with a modified heparin-binding site (S/TSP-HepI) nor when the glycosaminoglycans (GAGS) moieties were removed from the ECFC surface by enzymatic treatment. Ex vivo TSP-HepI priming could potentially serve to enhance the effectiveness of therapeutic neovascularisation with ECFC. (C) 2012 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Groupe d'Etude et de Recherches sur l'Hemostase (GEHT)Region Ile-de-France (CORDDIM)Leducq TransAtlantic Network of ExcellenceUniv Estado Rio de Janeiro, Dept Biol Celular, Lab Biol Celula Endotelial & Angiogenese LabAngio, Inst Biol Roberto Alcantara Gomes, BR-20550011 Rio de Janeiro, RJ, BrazilINSERM, U765, Paris, FranceUniv Paris 05, Paris, FranceUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Ciencias Biomed, Rio de Janeiro, RJ, BrazilHop Europeen Georges Pompidou, AP HP, Dept Haematol, Paris, FranceINSERM, Paris Cardiovasc Res Ctr, U970, Paris, FranceUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilLeducq TransAtlantic Network of Excellence: 04CVD01-LENALeducq TransAtlantic Network of Excellence: 04CVD02 -LINATCNPq: E-26/110.780/2010CAPES: 629/09Web of Scienc

Review of Proxima DeLong & Freytag (Hemiptera: Cicadellidae: Gyponini) with description of two new species from Brazil and identification key to species

Laranjeira, Vanessa Cristina, Gonçalves, Clayton Corrêa, Domahovski, Alexandre Cruz, Takiya, Daniela Maeda (2022): Review of Proxima DeLong & Freytag (Hemiptera: Cicadellidae: Gyponini) with description of two new species from Brazil and identification key to species. Zootaxa 5091 (4): 573-586, DOI: https://doi.org/10.11646/zootaxa.5091.4.

FIGURES 13–25 in Review of Proxima DeLong & Freytag (Hemiptera: Cicadellidae: Gyponini) with description of two new species from Brazil and identification key to species

FIGURES 13–25. Proxima nigromaculata sp. nov., male holotype. 13, head and thorax, dorsal view. 14, head and thorax, lateral view. 15, head, ventral view. 16, forewing. 17–25, male terminalia: 17, sternite VIII, ventral view. 18, valve, ventral view. 19, pygofer, valve and subgenital plate, lateral view. 20, pygofer, apical portion. 21, subgenital plate, ventral view. 22, style and connective, dorsal view. 23, style, lateral view. 24, aedeagus, lateral view. 25, aedeagus, posterior view. Scale bars in mm.Published as part of Laranjeira, Vanessa Cristina, Gonçalves, Clayton Corrêa, Domahovski, Alexandre Cruz & Takiya, Daniela Maeda, 2022, Review of Proxima DeLong & Freytag (Hemiptera: Cicadellidae: Gyponini) with description of two new species from Brazil and identification key to species, pp. 573-586 in Zootaxa 5091 (4) on page 578, DOI: 10.11646/zootaxa.5091.4.5, http://zenodo.org/record/586423

Enterocyte ultrastructural alterations following intestinal obstruction in rats Alterações ultra-estruturais do enterócito após obstrução intestinal em ratos

PURPOSE: To analyze the small intestinal mucosa ultrastructure, and to characterize the enterocyte lesion severity caused by mechanical intestinal obstruction combined or not with an ischemia of the mesenteric marginal vessels arch. METHODS: It was used 47 Wistar rats divided into 4 groups as follows: Group 1- Control rats (C), Group 2- sham rats (S), Group 3- rats submitted to intestinal obstruction excluding marginal vessel (OEV), Group 4- Intestinal obstruction including marginal vessels (OIV). Rats of groups 3 and 4 were allotted into two subgroups for the removal of small intestinal tissue samples, one at the proximal (P), and the other at the distal (D) segments from the obstruction site. Samples of groups 2, 3, 4 were obtained 24, 48, and 72 hours after post operation care. Small intestinal tissue samples of group 1 were excised following laparotomy. Imaging in Light and Transmission Electronic Microscopy were used for morphological and morphometric studies. The results were analyzed by using the ANOVA and Newman-Keuls tests. RESULTS: No irreversible lesion was observed. In the 24 hours microvilli volume of group 3 turned down at the proximal site henceforth enlarging very slowly within the next 72 hours. At the distal site significant microvilli shrinkage was observed up to 48 hours. Then they recovered their volume after 72 hours. In the 24 hours microvilli volume of group 4 grew twice in comparison with the microvilli of group 1 rats but after 72 hours there was drastic volume shrinkage, shape alterations, and severe flatness, especially in the distal segments of the obstruction site. CONCLUSIONS: Terminal ileum mechanical obstruction with mesenteric marginal arch ischemia led to reversible ultrastructural alterations after 72 hours, and the injury is proportional to the persistence of the obstructive process. Furthermore the mesenteric vessels of the marginal arcade play an important role in the maintenance of mucosal integrity, when such obstructive disorder is present.<br>OBJETIVO: Analisar as alterações ultra-estruturais da mucosa do intestino delgado e caracterizar a severidade das lesões causadas por uma obstrução intestinal mecânica, associada ou não a isquemia da arcada marginal mesentérica. MÉTODOS: Foram utilizados 47 ratos, da linhagem Wistar, distribuídos em quatro grupos, da seguinte forma: Grupo 1 - Controle (C), Grupo 2- Simulação (S), Grupo 3- Ratos com obstrução intestinal sem inclusão de vaso marginal (OEV), Grupo 4 - Obstrução intestinal com inclusão de vaso marginal (OIV). Os animais dos grupos 3 e 4 foram redistribuídos em dois subgrupos com coleta de amostras do intestino delgado, à montante (P) e à jusante (D) do ponto de obstrução. Nos grupos 2, 3 e 4, as amostras foram colhidas com 24, 48 e 72 horas de pós-operatório. No grupo 1, este material foi retirado após laparotomia. Realizaram-se estudos morfológicos e morfométricos dos microvilos através das Microscopias Óptica e Eletrônica de Transmissão. Os resultados foram analisados mediante os testes estatísticos de ANOVA e Newman-Keuls. RESULTADOS: Não foram observadas lesões irreversíveis. No grupo 3 com 24 horas, o volume dos microvilos diminuiu, à montante, com discreto aumento em 72 horas. Á jusante, houve redução significante até 48 horas, com recuperação em 72 horas. No grupo 4, o volume dos microvilos quase dobrou em relação ao grupo 1, com 24 horas, mas reduziu-se, drasticamente, em especial à jusante, com 72 h de evolução, apresentando deformidade e achatamento severos, achados estes estatisticamente significantes. CONCLUSÕES: A obstrução intestinal mecânica do íleo terminal, associada ou não a isquemia da arcada mesentérica marginal, causa alterações ultra-estruturais reversíveis dos enterócitos, cuja gravidade é diretamente proporcional à duração do processo mórbido obstrutivo, até 72 horas de evolução. Aduz-se que, os vasos mesentéricos da arcada marginal exercem um papel relevante na preservação da mucosa intestinal, na presença destes quadros obstrutivos

Estudo da morfologia renal após a oclusão da aorta abdominal infra-renal em ratos

OBJETIVO: Relacionar as alterações morfológicas renais sob microscopia de luz, de ratos submetidos à oclusão de aorta, em modelo que simule a condição clínica de reparação cirúrgica de um aneurisma de aorta abdominal. MÉTODO: Ratos Wistar (N = 60), machos pesando entre 200 e 250g, foram distribuídos em três grupos: I (simulado); II (isquemia); III (isquemia + reperfusão); e cada grupo redistribuído em dois subgrupos: A (30 min); B (60 min). Foi realizada isquemia utilizando clamp vascular (8mm) na aorta abdominal infra-renal de acordo com o grupo estudado. Ao final de cada experimento os animais foram mortos e realizada análise histológica renal cortical e medular (descritiva e morfométrica) através de metodologia convencional (parafina-hematoxilinaeosina). A análise semiquantitativa de lesão tubular e intersticial foi realizada de acordo com o índice de lesão tubular e índice de lesão intersticial. Para a análise estatística foram aplicados os seguintes testes: Mann-Whitney, Kruskal-Wallis, Comparações múltiplas (p < 0,001). RESULTADOS: Observou-se no grupo III alterações histológicas tubulares e intersticiais significantes com relação aos outros grupos (p < 0,001). CONCLUSÕES: A oclusão da aorta abdominal infra-renal em ratos está associada a lesões estruturais renais tanto tubulares quanto intersticiais principalmente na fase de reperfusão

Presença da Proteína p53 como Prognóstico de Recidiva/Progressão de Neoplasia Intra-epitelial Vulvar III p53 Protein Overexpression as a Prognostic Marker for Vulvar Intraepithelial Neoplasia III Recurrence/Progression

Objetivo: avaliar o valor da presença da proteína p53 nos casos de recidiva/progressão da neoplasia intra-epitelial vulvar (VIN) III. Métodos: foram selecionadas 20 pacientes com VIN III indiferenciada, seguidas semestralmente por período de até quatro anos, divididas em dois grupos: quatorze sem e seis com recidiva/progressão da lesão. Os casos de recidiva/progressão foram distribuídos da seguinte forma: em três pacientes a recidiva ocorreu uma única vez, em duas, houve dupla recorrência e apenas uma evoluiu para carcinoma escamoso. Em ambos os grupos foram avaliados o sítio vulvar acometido e a presença da proteína p53 com análise do padrão de marcação imunohistoquímica. Estudo semelhante foi realizado nos casos de recidiva/progressão além da análise do intervalo de tempo para o surgimento de recidiva/progressão. Resultados: observou-se recidiva da VIN III em 25% dos casos e, em 5%, progressão para carcinoma. O tempo médio de recidiva foi de 24,5 meses. A localização multifocal da lesão primária foi a mais freqüente (50%) em ambos os grupos. Na maioria dos casos (87,5%), a recidiva/progressão ocorreu na mesma localização da lesão vulvar primária. A presença da proteína p53 mostrou-se positiva em 50% das lesões primárias de VIN III e em 75% dos casos de recidiva/progressão. Conclusões: a presença da proteína p53 parece desempenhar papel importante na gênese e na predição do curso clínico das VIN III. As recidivas/progressão das VIN III tendem a ocorrer na mesma área da doença inicial, sugerindo a presença de campo molecular alterado.<br>Purpose: to evaluate p53 overexpression value in vulvar intraepithelial neoplasia (VIN) III recurrence/progression. Methods: twenty patients with undifferentiated VIN III were selected and followed up every six months for four years and divided into two groups: fourteen without and six with recurrence/progression lesion. The recurrence/progression cases were distributed as follows: in three patients recurrence occurred only once; in two, twice, and only one progressed to squamous cancer. In both groups the site of vulvar lesion and p53 overexpression and immunostaining pattern were analyzed. A similar study was performed in recurrence/progression cases, besides the analysis of the time interval to occur the arise of recurrence/progression. Results: recurrence was observed in 25% of the cases and, in 5%, progression to carcinoma. The mean time interval for recurrence was 24.5 months. Multifocal location of the initial lesion was the predominant form (50%) in both groups. In the majority of the cases (87.5%) recurrence/progression occurred at the same site of the initial vulvar lesion. p53 overexpression was observed in 50% of the VIN III primary lesions and in 75% of the recurrence/progression cases. Conclusions: p53 overexpression seems to play an important role in VIN III pathogenesis and may predict the clinical course of the lesions. VIN III recurrence/progression has a tendency to occur in the same area of the initial lesion, suggesting the presence of molecular disturbance

Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors

The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms’ tumor protein antibody characteristics of Wilms’ tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms’ tumor development