Activation of the WNT/β-catenin pathway attenuates experimental emphysema.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available. OBJECTIVES: To characterize WNT/β-catenin signaling in COPD in humans and elucidate its potential role as a preventive and therapeutic target in experimental emphysema in mice. METHODS: The expression, localization, and activity of WNT/β-catenin signaling was assessed in 12 COPD and 12 transplant donor samples using quantitative RT-PCR, immunohistochemistry, and Western blotting. The role of WNT/β-catenin signaling was assessed in elastase- and cigarette smoke-induced emphysema and therapeutic modulation thereof in elastase-induced emphysema in TOPGAL reporter and wild type mice in vivo. MEASUREMENTS AND MAIN RESULTS: No differences in the mRNA expression profile of the main WNT/β-catenin signaling components were observed comparing COPD and donor lung homogenates. Immunohistochemical analysis revealed reduced numbers of nuclear !-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/β-catenin signaling was downregulated in both experimental emphysema models. Preventive, as well as therapeutic, WNT/β-catenin activation by lithium chloride attenuated experimental emphysema, as assessed by decreased airspace enlargement, improved lung function, reduced collagen content, and elevated expression of alveolar epithelial cell markers. CONCLUSION: Decreased WNT/β-catenin signaling is involved in parenchymal tissue destruction and impaired repair capacity in emphysema. These data indicate a crucial role of WNT/β-catenin signaling in lung repair mechanisms in vivo, and highlight WNT/β-catenin activation as a future therapeutic approach for emphysema

Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5.

Intrathecal IgM production in multiple sclerosis (MS) is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in MS, CSF from two independent cohorts, including MS patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS- related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of MS donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced and used to produce recombinant monoclonal antibodies for characterisation and antigen identification. We produced 5 cell-binding recombinant IgM antibodies, of which one, cloned from an HLA-DR + plasma-like B cell, mediated antigen-dependent complement activation. Immunoprecipitation and mass spectrometry, and biochemical and transcriptome analysis of the target cells identified the iron transport scavenger protein SCARA5 as the antigen target of this antibody. Intrathecal injection of a SCARA5 antibody led to an increased T cell infiltration in an EAE model. CSF IgM might contribute to CNS inflammation in MS by binding to cell surface antigens like SCARA5 and activating complement, or by facilitating immune cell migration into the brain

Caracterização fitossociológica do estrato arbóreo em um remanescente de floresta estacional semidecidual, em Montenegro, RS Phytosociological characterization of arboreal stratum in a remainder of a semidecidual seasonal forest in Montenegro, Rio Grande do Sul

O presente trabalho foi realizado em um remanescente de Floresta Estacional Semidecidual antropizado, localizada nas coordenadas 29&deg; 49'S e 52&deg; 25'W, nas proximidades do pólo petroquímico no município de Montenegro (RS), Brasil, com o objetivo de conhecer seus aspectos florísticos e fitossociológicos. A amostragem foi sistemática constituída de 21 faixas com 10m de largura e comprimento variável de acordo com a extensão da floresta, distantes entre si em 80m, onde foram distribuídas parcelas contíguas de 10 x 10m (100m²). Foram avaliados indivíduos que apresentavam circunferência à altura do peito (CAP)>15cm, totalizando 3.854 indivíduos (1,83ha), distribuídos em 81 espécies, 59 gêneros e 32 famílias. As famílias botânicas mais representativas na formação foram Myrtaceae (13 espécies), Fabaceae (7), Lauraceae (6), Meliaceae (5), Moraceae e Euphorbiaceae (4). As espécies mais características e importantes da floresta foram Sebastiania commersoniana, Casearia sylvestris, Myrsine umbellata, Mimosa bimucronata, Allophylus edulis e Syagrus romanzoffiana, representando 51,52 % do VI. A floresta apresentou média diversidade, com índice de Shannon de 1,9948 (nats.), indicando antropismo.<br>This research was developed in a Semideciduous Seasonal Forest located at coordinates (29&deg; 49'S; 52&deg; 25'W) in Montenegro Petrochemical pole, Rio Grande do Sul, Brazil, aiming at studying the floristic and phytossociological aspects of the forest. Sampling was systematic and composed of 21 strips (10m wide and variable length according to fragment extension located 80m apart. In the strips the distribution was in contiguous 10 X 10m plots (100m²). Individuals that presented circumference at breast height (CBH)>15cm, totaling 3.854 individuals (1,83ha), distributed in 81 species, 59 geneus and 32 families were appraised. The most representative botanic families in the forest formation were Myrtaceae (13 species); Fabaceae (7), Lauraceae (6); Meliaceae (5), Moraceae and Euphorbiaceae (4). The most valuable species were Sebastiania commersoniana, Casearia sylvestris, Myrsine umbellata, Mimosa bimucronata, Allophylus edulis e Syagrus romanzoffiana, representing 51.52 % of IV. The forest had been presented low diversity with Shannon index of 1.9948 (nats/individuals), indicating human impact

Tissue injuries of wistar rats treated with hydroalcoholic extract of Sonchus oleraceus L.

The use of plant species is emerging as an important alternative in the treatment of injuries. Therefore, the extract of Sonchus oleraceus 10% was employed in the repair of skin lesions. A total of 36 male Wistar rats were subjected to a punch injury and divided into three groups: a negative control, receiving no treatment, a positive control, treated with Dersani, and the experimental group treated with the extract. The injury was assessed macroscopically and microscopically. Morphometric data was collected at the 3rd, 5th and 7th postoperative day, and the experimental group showed greater changes in shrinkage of the lesion compared to control groups. On the 3rd postoperative day, the injury in the experimental group showed less necrotic tissue, lower slough and more granulation tissue in relation to the positive control group. On the 7th and 10th postoperative day, the injury in the experimental group showed lower slough compared to the positive control group. Microscopic analysis of lesions on the 5th postoperative day revealed increased fibroplasia in the experimental group compared to control groups, while on the 14th postoperative day less neovascularization was evident in the experimental group and increased formation of hair follicles in the negative control group. The extract of S. oleraceus provided tissue repair in accordance with normal physiological patterns thus confirming empirical evidence for its use.<br>O emprego de espécies vegetais vem surgindo como alternativa no tratamento de lesões. Dessa forma, foi utilizado o extrato hidroalcoólico de Sonchus oleraceus a 10% na reparação de lesões cutâneas. Trinta e seis ratos machos Wistar, foram submetidos a uma lesão com "punch" e distribuídos em três grupos: controle negativo, não recebeu tratamento; controle positivo, tratado com Dersani; e o experimental, tratado com extrato. A lesão foi avaliada macroscopicamente e microscopicamente. Os dados morfométricos mostraram que no 3º, 5º e 7º dia pós-operação (DPO), o grupo experimental apresentou maior evolução na retração da lesão em relação aos grupos controles. No 3° DPO a lesão do grupo experimental apresentou menor tecido necrótico, menor esfacelo e maior tecido de granulação em relação ao grupo controle positivo. No 7° e 10º DPO, a lesão do grupo experimental apresentou menor esfacelo em relação ao grupo controle positivo. A análise microscópica das lesões revelou no 5º DPO maior fibroplasia no grupo experimental em relação aos grupos controles; no 14º DPO ocorreu menor neovascularização no grupo experimental e maior formação de folículos pilosos no grupo controle negativo. O extrato hidroalcoólico de S. oleraceus propiciou reparo tecidual obedecendo a padrões fisiológicos normais e confirmando os dados empíricos de sua utilização