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Front Immunol ; 12: 648754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790913


Background and Aims: Emerging evidence has revealed that innate lymphoid cells (ILCs) play a key role in regulating metabolic disorders. Here, we investigated the role of group 3 ILCs (ILC3s) in the modulation of Non-alcoholic fatty liver disease (NAFLD). Methods: RORγ gfp/gfp (RORgt KI/KI) and Rag2-/- mice with the administration of A213, RORgt antagonist, fed with a high-fat-diet (HFD) for 12 weeks, were used. We performed flow cytometry, real time PCR, and lipidomics analysis of serum and liver, and used RAW264.7 cells and murine primary hepatocytes in vitro. Results: HFD increased ILC3s and M1 macrophages in the liver, and RORgt KI/KI mice deficient in ILC3 showed significant fatty liver, liver fibrosis and significantly increased palmitic acid levels in serum and liver. In addition, administration of A213 to Rag2-/- mice caused significant fatty liver, liver fibrosis, and a significant increase in serum and liver palmitate concentrations, as in RORgt KI/KI mice. Addition of palmitc acid stimulated IL-23 production in cell experiments using RAW264.7. IL-22 produced by ILC3s inhibited the palmitate-induced apoptosis of primary hepatocytes. Conclusions: HFD stimulates IL-23 production by M1 macrophages, thus promoting ILC3 proliferation, whereas IL-22 secreted by ILC3s contributes to the upregulation of hepatic lipid metabolism and has anti-apoptosis activity.

Fígado Gorduroso/imunologia , Imunidade Inata/imunologia , Fígado/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Animais , Apoptose/imunologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Hepatócitos/citologia , Hepatócitos/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ácido Palmítico/sangue , Ácido Palmítico/imunologia , Ácido Palmítico/metabolismo , Substâncias Protetoras/metabolismo , Células RAW 264.7
Am J Physiol Gastrointest Liver Physiol ; 318(6): G989-G999, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32363890


Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.

Estradiol/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Testosterona/farmacologia , Aminoácidos , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Cromo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Estradiol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Insulina , Cirrose Hepática , Neoplasias Hepáticas , Masculino , Camundongos , Camundongos Knockout , Ácidos Nicotínicos , Hepatopatia Gordurosa não Alcoólica/patologia , Orquiectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
Endocr J ; 67(7): 733-740, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32213726


We have previously reported that the creatinine (Cre) to cystatin C (CysC) ratio is associated with height-adjusted skeletal muscle mass index (SMI). However, weight-adjusted SMI is reported to be a more useful marker of insulin sensitivity than height-adjusted SMI. Thus, we hypothesized that the creatinine to (cystatin C × body weight [BW]) relationship (Cre/[CysC × BW]) might be associated with weight-adjusted SMI. In this cross-sectional study of 169 males and 132 females, a body composition analyzer was used and the weight-adjusted SMI was calculated as (absolute muscle mass [kg]/BW [kg]) × 100. The cut-off of low muscle mass was defined as weight-adjusted SMI <37.0% for males and <28.0% for females. The Cre/(CysC × BW) was correlated with weight-adjusted SMI in both males (r = 0.484, p < 0.001) and females (r = 0.538, p < 0.001). In addition, Cre/(CysC × BW) was associated with weight-adjusted SMI in both males (standardized ß = 0.493, p < 0.001) and females (standardized ß = 0.570, p < 0.001) after adjusting for covariates. According to the receiver operator characteristic (ROC) curve analysis, the optimal cut-off point of Cre/(CysC × BW) for low muscle mass was 0.0145 (area under the ROC curve [AUC] 0.756 [95% confidence interval {95% CI} 0.644-0.842], sensitivity = 0.96, specificity = 0.47, p < 0.001) in males and 0.0090 (AUC 0.976 [95% CI 0.894-0.995], sensitivity = 1.00, specificity = 0.93, p < 0.001) in females. There is a correlation between Cre/(CysC × BW) and weight-adjusted SMI. The Cre/(CysC × BW) could be a practical screening marker for low muscle mass.

Peso Corporal/fisiologia , Creatinina/sangue , Cistatina C/sangue , Músculo Esquelético/anatomia & histologia , Sarcopenia/diagnóstico , Idoso , Composição Corporal/fisiologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Retrospectivos , Sarcopenia/sangue , Sarcopenia/patologia
J Hazard Mater ; 355: 154-161, 2018 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-29787967


The adsorption behavior of Sr2+ over alginate (Alg) fibers prepared by wet spinning was investigated. Different grades of sodium alginate (Alg-Na) were chosen. The Alg fibers were obtained by coagulation of 1% H2SO4 (Alg-acid) or 5% CaCl2 (Alg-Ca) solutions. In addition, the Sr2+ adsorption percentages of the spherical Alg-Ca beads with a 0.672-mm-diameter was 70.64% which was significantly lower than that Alg-Ca fibers (79.49%). These results suggested that the fibrous shape is more suitable than the spheres as an adsorbent from sea water. For Sr2+ adsorption capacities using different Alg fibers, the Alg-acid fibers obtained from 12% IL-2 and 8% I-2 grade solutions reached adsorption equilibrium at 99.88 and 99.27%, respectively, within 3 min. However, the Alg-Ca fiber obtained from 8% I-2 grade solution reached equilibrium at 80.01% within 30 min. Moreover, the Alg-acid fiber obtained from 8% I-2 grade solution adsorbed up to 34 mg/g of Sr2+ at an initial concentration of 1700 mg/L solutions. However, when Sr2+ co-existing cations (Ca2+, Na+, and mixtures of them) the adsorption capacity of the Alg-Ca fiber obtained from 8% I-2 grade solution slightly decreased since the egg-box structure of Alg-Ca fiber favored the selective Sr2+ adsorption and subsequent ion exchange with Ca2+.

Int J Biol Macromol ; 104(Pt B): 1509-1516, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28315442


Rayon fiber coated with chitosan (CTS) that contained immobilized Prussian blue (KFe) (KFe/CTS/rayon) were investigated for the removal of cesium ion (Cs+) from contaminated water. The morphology and mechanical strength of the fibers were observed using scanning electron microscopy (SEM) and a universal testing machine, respectively. The Cs+ concentration was determined by inductively coupled plasma-atomic emission spectroscopy. SEM images revealed that the surface of the KFe/CTS/rayon fiber showed the most roughness. It was found that Cs+ was absorbed from the water by the KFe on the fibers in a molar ratio of 1:1 (Cs+:KFe). After treating the KFe/CTS/rayon fiber with 1% HNO3 for 3h, 48.8% Cs+ desorption was observed. Woven fibers were interlaced with either 2 or 4 lines of the KFe/CTS/rayon fiber from 16 bobbins. The tensile strengths of those fibers were 19.06 and 14.25MPa, respectively. When silver cotton was used as the core axis of the woven fiber, the tensile strength of the fibers interlaced with 2 and 4 lines increased to 27.18 and 25.17MPa, respectively. Moreover, the results of hot tests using radioactive Cs+ showed that the woven KFe/CTS/rayon fibers could absorb up to 1000Bqg-1 from an initial concentration of 8000Bqkg-1.

Celulose/química , Césio/química , Quitosana/química , Ferrocianetos/química , Adsorção , Eletroquímica , Concentração de Íons de Hidrogênio
Nihon Rinsho ; 75(4): 567-572, 2017 04.
Artigo em Japonês | MEDLINE | ID: mdl-30549858


Elderly people are at a high risk of experiencing problems with drug therapy due to age- related changes in the body, as well as exposure to many medications owing to multiple health problems. Medication-related adverse events are common amongst the elderly. Pharmacotherapy for benign prostatic hyperplasia or overactive bladder can generally im- prove lower urinary tract symptoms, whilst also improving the quality of life. However,;these drugs also have the potential to cause dangerous adverse events. For this reason, a great deal of caution should be taken when prescribing medication for elderly patients who are suffer- ing from lower urinary tract symptoms.

Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/terapia , Idoso , Humanos , Masculino