Ionotropic and metabotropic proton-sensing receptors involved in airway inflammation in allergic asthma

An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases

Effect of resistance exercise intensity on delayed onset muscle soreness

O objetivo do presente estudo foi verificar o efeito da intensidade do exercício de força sobre a percepção de dor muscular de início tardio (DMIT). A fim de investigar a hipótese que a intensidade determina o nível de DMIT, foram selecionados 40 homens saudáveis, iniciantes no treinamento de força, que, posteriormente, foram submetidos a duas sessões de treinamento realizadas com intensidades distintas (50%-1RM (n=20) e 75%-1RM (n=20)). A DMIT foi analisada por meio da escala analógica visual, 24, 48 e 72h após cada sessão de treinamento. A DMIT apresentou aumento significante em ambas as sessões (50%-1RM e 75%-1RM) (p<0,05), atingindo o pico em 48h (p<0,05). Entretanto, a DMIT não apresentou diferença entre as sessões (50%-1RM vs. 75%-1RM) (p>0,05). Os resultados desse estudo sugerem que a intensidade não parece ser um fator determinante para a magnitude da DMIT, quando o volume total de carga levantada na sessão de treinamento é equalizado.The aim of the study was to assess the effect of resistance exercise intensity on the perceived DOMS. In order to investigate the hypothesis that the intensity determines the magnitude of DOMS, 40 healthy, untrained men were subjected to two bouts of resistance exercise performed at different intensities (50%-1RM (n=20) and 75%-1RM (n=20)). DOMS was assessed using visual analogue scale, 24, 48 and 72 hours after each training bout. DOMS increased after both exercise bouts (50%-1RM and 75%-1RM) (p<0.05), peaking at 48 hours (p<0.05). However, DOMS did not differ between exercise sessions (50%-1RM and 75%-1RM) (p>0.05). The results suggested that the intensity does not seem to influence the magnitude of DOMS when the total volume of load lifted during the exercise bout is equalized.Agradecemos o apoio do Prof. Reginaldo Ghilardi, Coordenador do Departamento de Musculação da Academia Competition (Unidade Oscar Freire, São Paulo). Também agradecemos o apoio financeiro do CNPq (Processo 470758/2012-0)

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.ArticleNANOMATERIALS. 10(7):1374 (2020)journal articl

Effect of resistance exercise intensity on delayed onset muscle soreness

The aim of the study was to assess the effect of resistance exercise intensity on the perceived DOMS. In order to investigate the hypothesis that the intensity determines the magnitude of DOMS, 40 healthy, untrained men were subjected to two bouts of resistance exercise performed at different intensities (50%-1RM (n=20) and 75%-1RM (n=20)). DOMS was assessed using visual analogue scale, 24, 48 and 72 hours after each training bout. DOMS increased after both exercise bouts (50%-1RM and 75%-1RM) (p<0.05), peaking at 48 hours (p<0.05). However, DOMS did not differ between exercise sessions (50%-1RM and 75%-1RM) (p&gt;0.05). The results suggested that the intensity does not seem to influence the magnitude of DOMS when the total volume of load lifted during the exercise bout is equalized.O objetivo do presente estudo foi verificar o efeito da intensidade do exercício de força sobre a percepção de dor muscular de início tardio (DMIT). A fim de investigar a hipótese que a intensidade determina o nível de DMIT, foram selecionados 40 homens saudáveis, iniciantes no treinamento de força, que, posteriormente, foram submetidos a duas sessões de treinamento realizadas com intensidades distintas (50%-1RM (n=20) e 75%-1RM (n=20)). A DMIT foi analisada por meio da escala analógica visual, 24, 48 e 72h após cada sessão de treinamento. A DMIT apresentou aumento significante em ambas as sessões (50%-1RM e 75%-1RM) (p<0,05), atingindo o pico em 48h (p<0,05). Entretanto, a DMIT não apresentou diferença entre as sessões (50%-1RM vs. 75%-1RM) (p&gt;0,05). Os resultados desse estudo sugerem que a intensidade não parece ser um fator determinante para a magnitude da DMIT, quando o volume total de carga levantada na sessão de treinamento é equalizado.253259Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Lipocalin function of E.coli zinT (yodA) protein.

重金属やアミトロール(AT)で発現誘導され、大腸菌ストレス応答タンパク質の一種であるzinT (yodA)は、一次構造比較やX線結晶構造解析による三次元立体構造などから、C末端領域に金属結合部位を持つこと、ABC transporter やlipocalinファミリーと一部相同なアミノ酸配列を持つことが明らかとなっているが、zinTの金属以外の低分子結合能については報告がない。そこで本研究では、大腸菌zinTタンパク質の種々の物質との結合能を、野生型zinTおよびN末端22残基欠損体(ΔN22)を用いて検討した。 まず、zinTの分子内TyrまたはTrp蛍光を指標として、種々の物質を添加に伴う蛍光強度の減少を測定した。低分子化合物としては、(1)ATおよびdNTP(2) 脂肪酸および脂質5種、(3) 複素式化合物3種、(4)芳香族化合物3種を検討し、zinTに対しそれぞれ添加し、30℃、10分間保温後、蛍光スペクトルを測定した。その結果、化合物添加によりzinTの最大蛍光強度は濃度依存的に減少し、特にdNTP, Qurcetinおよび8-ANSで顕著に見られた。また、野生型とΔN22において、蛍光減少の濃度依存性に顕著な差異は見られなかった。以上より、zinTは疎水性低分子化合物結合能(lipocalin活性)を有し、N末端領域のlipocalin活性に対する寄与は少ないことが明らかとなった

Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFN gamma for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFN gamma increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.ArticleBMC CANCER. 20(1):25 (2020)journal articl

Leucine supplementation improves skeletal muscle regeneration after cryolesion in rats

This study was undertaken in order to provide further insight into the role of leucine supplementation in the skeletal muscle regeneration process, focusing on myofiber size and strength recovery. Young (2-month-old) rats were subjected or not to leucine supplementation (1.35 g/kg per day) started 3 days prior to cryolesion. Then, soleus muscles were cryolesioned and continued receiving leucine supplementation until 1, 3 and 10 days later. Soleus muscles from leucine-supplemented animals displayed an increase in myofiber size and a reduction in collagen type III expression on post-cryolesion day 10. Leucine was also effective in reducing FOXO3a activation and ubiquitinated protein accumulation in muscles at post-cryolesion days 3 and 10. In addition, leucine supplementation minimized the cryolesion-induced decrease in tetanic strength and increase in fatigue in regenerating muscles at post-cryolesion day 10. These beneficial effects of leucine were not accompanied by activation of any elements of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin signalling pathway in the regenerating muscles. Our results show that leucine improves myofiber size gain and strength recovery in regenerating soleus muscles through attenuation of protein ubiquitination. In addition, leucine might have therapeutic effects for muscle recovery following injury and in some muscle diseases.FAPESP, 2010/52520-0FAPESP, 2012/15276-