Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving heterogeneous clinical manifestations and numerous susceptibility genes. Several findings evidence the critical role of ...inflammasomes in the predisposition to autoimmune diseases and in SLE. We investigated whether inflammasome polymorphins could affect susceptibility to develop and/or severity SLE. Moreover, differences in inflammasome activation in peripheral blood were also evaluated in SLE patients and controls. The distribution of 13 SNPs in eight inflammasome genes was evaluated. To assess inflammasome priming in peripheral blood monocytes of SLE and controls, differential expression of selected inflammasome genes and IL-1ß production was analyzed in resting condition as well as after LPS and ATP stimulation. Results showed that the gain-of-function variant rs10754558 (
NLRP3)
was significantly more frequent in SLE patients with nephritis, reinforcing the concept of a key role of
NLRP3
inflammasome not only in SLE but also especially in kidney disease. SLE monocytes in resting condition showed a higher level of IL-1ß expression and produced higher levels of IL-1ß when stimulated with LPS+ATP comparing to controls. The stimulation induced a significant expression of
NLRP1
,
AIM2
,
CASP1
, and
IL1B
genes, suggesting that the
NLRP1
inflammasome is responsible for the IL-1ß production observed in monocytes. These data emphasized once more the important contribution of inflammasome in SLE-associated inflammation.
Objective
In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)’s development and severity in the Brazilian population.
...Materials and methods
Thirteen single nucleotide polymorphisms within six inflammasome genes (
NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1
) as well as
IL1B
and
IL18
genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS + ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR.
Results
Our results showed that rs10754558
NLRP3
and rs2043211
CARD8
polymorphisms are associated with RA development (
p
value = 0.044, OR = 1.77, statistical power = 0.999) and severity measured by Health Assessment Questionnaire (HAQ) (
p
value = 0.03), respectively. Gene expression analyses showed that RA patients display activation of
CASP1, IL1B
and
IL1R
genes independently of LPS + ATP activation. In LPS + ATP-treated monocytes,
NLRP3
and
NLRC4
expressions were also significantly higher in patients compared with controls.
Conclusions
The first reported results in Brazilian populations support the role of inflammasome in the development of RA.
Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic ...protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH.
Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 10
adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial-mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68
and CD163
macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated.
In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68
macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial-mesenchymal transition.
In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the M1 phenotype.
Background and Purpose
Pulmonary arterial hypertension (PAH) is a progressive disease associated with high morbidity and mortality, despite advances in medical therapy. We compared the effects of ...infigratinib (NVP‐BGJ398), a new FGF receptor‐1 inhibitor, with or without the PDE‐5 inhibitor sildenafil, on vascular function and remodelling as well as on gene expression of signal transducers for receptors of TGF‐β (Smads‐1/2/4) and transcription factor of endothelial–mesenchymal transition (Twist‐1) in established experimental PAH. Types I and III pro‐collagen and TGF‐β expressions in lung fibroblasts were analysed in vitro after the different treatments.
Experimental Approach
PAH was induced in male Wistar rats with monocrotaline. 14 days later, treatments sildenafil (SIL), infigratinib (INF) or their combination (SIL+INF) were given for another 14 days. On Day 28, echocardiography and haemodynamic assays were performed, and lungs and pulmonary vessels were removed for analysis by histology, immunohistochemistry and RT‐PCR. Fibroblasts prepared from PAH lungs were also analysed for TGF‐β and pro‐collagen.
Key Results
Only the combination of infigratinib and sildenafil significantly improved right ventricular systolic pressure and vascular remodelling parameters (right ventricular hypertrophy, smooth muscle α‐actin, vessel wall thickness, and vascular collagen content). Infigratinib may act by reducing gene expression of Smads‐1/4 and Twist‐1 in lung tissue, as well as TGF‐β and types I and III pro‐collagen in lung fibroblasts.
Conclusions and Implications
In this model of monocrotaline‐induced PAH, the combination of the new inhibitor of FGF receptor‐1, infigratinib, and sildenafil effectively improved haemodynamics and decreased vascular remodelling.
Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, which leads to a spectrum of clinical presentations that range from asymptomatic to severe cardiac involvement. The host immune ...response plays a pivotal role in disease progression. Ig isotypes may contribute to disease pathogenesis. Investigating these components can provide insights into the immunopathogenic mechanisms underlying CD. This cross-sectional study aims to establish a correlation between the Ig profile of individuals infected with T. cruzi with the clinical forms of chronic CD. Serum samples were collected from partner institutions in different states of Brazil. Individuals diagnosed with chronic CD were categorized based on the clinical form of the disease. The indirect ELISA method using the recombinant chimeric Molecular Biology Institute of Paraná membrane protein 8.4 as the antigen was used to determine the Ig profile, including total IgG, IgG1, IgG2, IgG3, and IgG4. Ninety-seven serum samples from patients classified as negative (NEG, n = 38), indeterminate (IND, n = 24), mild cardiac (MC, n = 20), and severe cardiac (SC, n = 15) forms were analyzed. IgG1 exhibited greater levels compared with the other isotypes, showing a significant difference between the MC and IND groups. IgG3 levels were greater in individuals from the MC group compared with the SC group. IgG1 and IgG3 isotypes can serve as biomarkers to evaluate the progression of CD because they exhibit variations across clinical groups. Additional longitudinal studies are necessary to explore the relationship between antibody kinetics and the development of tissue damage.
Objetivo do estudo: Descrever o cuidado do enfermeiro ao individuo hospitalizado, que apresenta uma ferida traumática por esmagamento. Metodologia: O método utilizado consiste em um relato de caso ...que contém informações organizadas sobre um paciente vítima de acidente automobilístico. Resultados: Para análise dos dados foram definidos quatro momentos: primeiro momento (inflamatório), segundo momento (proliferativo), terceiro momento (cuidado com o enxerto) e quarto momento (remodelagem/maturação). Conclusão: O relato de caso revelou que o enfermeiro é imprescindível no cuidado de feridas e que o constante movimento dialógico com a equipe interdisciplinar é de suma importância para recuperação e reabilitação do paciente hospitalizado que possui uma lesão cutânea proveniente de um trauma.
Transgenic technology is an excellent alternative for improvement of crop production and disease free crops such as potato, which is one of the most important crops worldwide. One of the first steps ...to apply the transgenic technique is the establishment of an efficient plant regeneration protocol. This is a limiting step in this kind of study, since most protocols are species-specific and some of them do not adequately respond to in vitro culture or present low regeneration rates. The objective of this study was to stablish an efficient regeneration protocol of Solanum tuberosum cv. Monalisa from internodes explants. This work is important since most in vitro protocols are based on shoots. Twenty five treatments were performed, with each treatment being composed of six internodes in flasks containing MS medium supplemented with a fixed concentration of zeatin riboside (3 mg.L-1) (ZEA), varying concentrations of naphthaleneacetic acid (0 to 1 mg. L-1) (NAA), and gibberellic acid (0 to 3 mg.L -1) (GA3). The treatment composed of ZEA, 0.05 mg.L-1 of NAA, and 0.10 mg.L-1 of GA3 was considered the best for shoot regeneration from potato internodes. The study was able to establish a specific regeneration protocol for Monalisa cultivar. This result can be very useful since it is possible to obtain plants from internode, without the requirement of meristematic regions, enabling the obtainment of a higher number of plants.
Este estudo teve como objetivo identificar quais as contas mais frequentes nos pareceres da auditoria com ressalvas das companhias listadas na BM&FBovespa. A técnica metodológica utilizada foi a ...pesquisa documental, por meio de um estudo de caráter descritivo, bibliográfico e com abordagem predominantemente qualitativa. A população abrangeu os pareceres de auditoria das empresas listadas na Bolsa de Valores de São Paulo, no período de 2015 a 2017, sendo a amostra composta por 728 pareceres. Os resultados demonstraram que a conta de Lucros/Prejuízos Acumulados foi a conta mais frequente nos pareceres de auditoria com ressalvas dessas companhias, vindo em seguida, com o mesmo percentual de incidência, as contas de Investimento e de Empréstimos e Financiamentos e, por fim, também com o mesmo percentual cada uma, as contas de Crédito a Receber, Provisões Fiscais e Imobilizado e Intangível. A incidência maior da conta de Lucros/Prejuízos Acumulados nestas empresas, pode trazer implicações no que diz respeito à distribuição de lucros, à destinação de reservas ou ao prejuízo que ela possa ter resultado.
Este estudo teve como objetivo identificar quais as contas mais frequentes nos pareceres da auditoria com ressalvas das companhias listadas na BM&FBovespa. A técnica metodológica utilizada foi a ...pesquisa documental, por meio de um estudo de caráter descritivo, bibliográfico e com abordagem predominantemente qualitativa. A população abrangeu os pareceres de auditoria das empresas listadas na Bolsa de Valores de São Paulo, no período de 2015 a 2017, sendo a amostra composta por 728 pareceres. Os resultados demonstraram que a conta de Lucros/Prejuízos Acumulados foi a conta mais frequente nos pareceres de auditoria com ressalvas dessas companhias, vindo em seguida, com o mesmo percentual de incidência, as contas de Investimento e de Empréstimos e Financiamentos e, por fim, também com o mesmo percentual cada uma, as contas de Crédito a Receber, Provisões Fiscais e Imobilizado e Intangível. A incidência maior da conta de Lucros/Prejuízos Acumulados nestas empresas, pode trazer implicações no que diz respeito à distribuição de lucros, à destinação de reservas ou ao prejuízo que ela possa ter resultado.
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