RESUMO
BACKGROUND AND AIMS: In obesity and type 2 diabetes mellitus, leptin promotes insulin resistance and contributes to the progression of NASH via activation of hepatic stellate cells (HSCs). However, the pathogenic mechanisms that trigger HSC activation in leptin-deficient obesity are still unknown. This study aimed to determine how HSC-targeting lipocalin-2 (LCN2) mediates the transition from simple steatosis to NASH. APPROACH AND RESULTS: Male wild-type (WT) and ob/ob mice were fed a high-fat diet (HFD) for 20 weeks to establish an animal model of NASH with fibrosis. Ob/ob mice were subject to caloric restriction or recombinant leptin treatment. Double knockout (DKO) mice lacking both leptin and lcn2 were also fed an HFD for 20 weeks. In addition, HFD-fed ob/ob mice were treated with gadolinium trichloride to deplete Kupffer cells. The LX-2 human HSCs and primary HSCs from ob/ob mice were used to investigate the effects of LCN2 on HSC activation. Serum and hepatic LCN2 expression levels were prominently increased in HFD-fed ob/ob mice compared with normal diet-fed ob/ob mice or HFD-fed WT mice, and these changes were closely linked to liver fibrosis and increased hepatic α-SMA/matrix metalloproteinase 9 (MMP9)/signal transducer and activator of transcription 3 (STAT3) protein levels. HFD-fed DKO mice showed a marked reduction of α-SMA protein compared with HFD-fed ob/ob mice. In particular, the colocalization of LCN2 and α-SMA was increased in HSCs from HFD-fed ob/ob mice. In primary HSCs from ob/ob mice, exogenous LCN2 treatment induced HSC activation and MMP9 secretion. By contrast, LCN2 receptor 24p3R deficiency or a STAT3 inhibitor reduced the activation and migration of primary HSCs. CONCLUSIONS: LCN2 acts as a key mediator of HSC activation in leptin-deficient obesity via α-SMA/MMP9/STAT3 signaling, thereby exacerbating NASH.
Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Masculino , Camundongos , Dieta Hiperlipídica , Células Estreladas do Fígado/metabolismo , Leptina , Lipocalina-2/metabolismo , Fígado/patologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/metabolismoRESUMO
Lipocalin-2 (LCN2) is an acute phase protein used as a biomarker for acute lung injury (ALI). Although the innate immune functions of LCN2 have been studied, how LCN2 contributes to ALI induced by lipopolysaccharide (LPS) remains unknown. In this study, we investigated the effect of LCN2 deletion on LPS-induced ALI using RNA-sequencing. LPS-treated LCN2 knockout (KO) mice had a decreased histopathological score and reduced neutrophil and macrophage infiltration in lung tissue compared with LPS-treated WT mice. RNA-sequencing analysis identified 38 differentially expressed genes (DEGs), including Cxcl5, Cxcl13, Xcl1, Saa1, and Cd14. In particular, Gene Ontology analysis of DEGs revealed a significant reduction in the inflammatory response, neutrophil chemotaxis, and chemokine-mediated signaling in LPS-treated LCN2KO mice compared with LPS-treated WT mice. Thus, these results suggest that LCN2 deletion alleviates LPS-induced ALI and that LCN2 may be involved in chemotaxis-related gene expression.
Assuntos
Lipopolissacarídeos , Pneumonia , Animais , Camundongos , Lipocalina-2/genética , Lipopolissacarídeos/efeitos adversos , Quimiotaxia , RNA , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Camundongos KnockoutRESUMO
Type 2 diabetes is associated with a risk factor for Alzheimer's disease (AD). Activation of glial cells, such as microglia and astrocytes, is crucial for the development of neuroinflammation in both diabetes and AD. The role of amyloid-beta oligomer (AßO) in the hippocampus of diabetic mice has been investigated; however, the effect of galectin-3 and lipocalin-2 (LCN2) on amyloid toxicity-related glial activation in diabetic mice is not known. To fill this knowledge gap, we fed mice a high-fat diet (HFD) for 20 weeks to induce a diabetic state and then injected the hippocampus with AßO. Sholl analysis of iba-1-positive microglia showed retraction of microglial ramifications in the hippocampus of HFD-fed diabetic mice. AßO treatment caused more retraction of microglial process in HFD-fed mice. In particular, microglial galectin-3 levels and astrocytic LCN2 levels were increased in the hippocampus of HFD-fed mice with AßO treatment. These findings suggest that galectin-3 and LCN2 are involved in amyloid toxicity mechanisms, especially glial activation under diabetic conditions.
Assuntos
Doença de Alzheimer , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Microglia/metabolismo , Peptídeos beta-Amiloides/metabolismo , Galectina 3 , Astrócitos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lipocalina-2/farmacologia , Doença de Alzheimer/etiologia , Hipocampo/metabolismoRESUMO
The purpose of this study was to assess the utility of a picture archiving and communication systems (PACS)-integrated refer function for improving collaboration between radiologists and radiographers during daily reading sessions. Retrospective analysis was conducted on refers sent by radiologists using a PACS-integrated refer system from March 2020 to December 2021. Refers were categorized according to receiver: radiologists in the same division (intra-division), radiologists in a different division (inter-division), and radiographers. The proportions of answered refers, content of refers, and timing of refer posts were evaluated. Additionally, time intervals in minutes from initial refer post to refer response were assessed to assess the efficiency of the refer system and compared according to receivers using the Mann-Whitney U test. Among a total of 691 refers posted by radiologists, 579 (83.8%) were answered directly using the refer function in PACS. Of the answered refers, 346 refers (59.8%) were made between radiologists, and 173 (50%) were intra-division refers. About the content of refers, about 82.6% of radiologists' refers were about imaging interpretation consultation, and about 98.9% of refers from radiologists to radiographers were for image quality control. The median time interval until refer response was 9 min, and this response time did not differ between intra-division and inter-division refers (p = 0.998). Of the refers that got responses, 74.3% (257/346) were sent among radiologists before official reports were made, and the median time until refer response was 9-10 min. The proportion of refers answered by radiographers was 85.7% (233/272). The median time interval until refer response by radiographers was 87 min for all refers, and 63% were made within 6 h. Therefore, the PACS-integrated refer function can facilitate communication between radiologists for image interpretation and quality control.
Assuntos
Sistemas de Informação em Radiologia , Humanos , Estudos Retrospectivos , Radiologistas , Eficiência , ComunicaçãoRESUMO
Doxorubicin (DOX) is an effective anticancer drug with the side effect of irreparable cardiomyopathy. Lipocalin-2 (LCN2) has been identified as an important regulator of oxidative stress and inflammation in cardiovascular disease pathophysiology. Here, we demonstrate that LCN2 deletion increases autophagic flux in the DOX-treated hearts. Mice were injected intraperitoneally six times with 30 mg/kg DOX. Echocardiography showed that DOX-treated wild-type (WT) mice had markedly weaker cardiac function compared to saline-treated WT mice. In DOX-treated LCN2 knockout (KO) mice, cardiac function was partially restored. Histological analysis showed a reduction in cardiomyocyte diameter in DOX-treated WT mice that was ameliorated in DOX-treated LCN2KO mice. Cardiac levels of phosphorylated signal transducer and activator of transcription 3, LCN2, heme oxygenase-1, and NAD (P) H dehydrogenase were markedly greater in DOX-treated WT mice than in DOX-treated LCN2KO mice. Light chain 3B (LC3B)II expression was higher in DOX-treated WT mice, but lower in DOX-treated LCN2KO mice when compared to saline-treated WT mice. Less co-localization of LC3B and lysosomal-associated membrane protein 1 was observed in DOX-treated WT mice than in DOX-treated LCN2KO mice. LCN2 co-localized with LC3B-stained cells in the DOX-treated WT mouse heart, but not in the DOX-treated LCN2KO mouse heart. These findings indicate that the cardiotoxic effect of DOX is due to autophagosome accumulation mediated by LCN2 upregulation and that LCN2 may inhibit autophagic flux, leading to DOX-induced cardiomyopathy.
Assuntos
Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Doxorrubicina/efeitos adversos , Lipocalina-2/deficiência , Animais , Autofagossomos/metabolismo , Autofagia , Feminino , Deleção de Genes , Lipocalina-2/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo , Fosforilação , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Diabetic individuals have increased circulating inflammatory mediators which are implicated as underlying causes of neuroinflammation and memory deficits. Tonicity-responsive enhancer-binding protein (TonEBP) promotes diabetic neuroinflammation. However, the precise role of TonEBP in the diabetic brain is not fully understood. METHODS: We employed a high-fat diet (HFD)-only fed mice or HFD/streptozotocin (STZ)-treated mice in our diabetic mouse models. Circulating TonEBP and lipocalin-2 (LCN2) levels were measured in type 2 diabetic subjects. TonEBP haploinsufficient mice were used to investigate the role of TonEBP in HFD/STZ-induced diabetic mice. In addition, RAW 264.7 macrophages were given a lipopolysaccharide (LPS)/high glucose (HG) treatment. Using a siRNA, we examined the effects of TonEBP knockdown on RAW264 cell' medium/HG-treated mouse hippocampal HT22 cells. RESULTS: Circulating TonEBP and LCN2 levels were higher in experimental diabetic mice or type 2 diabetic patients with cognitive impairment. TonEBP haploinsufficiency ameliorated the diabetic phenotypes including adipose tissue macrophage infiltrations, neuroinflammation, blood-brain barrier leakage, and memory deficits. Systemic and hippocampal LCN2 proteins were reduced in diabetic mice by TonEBP haploinsufficiency. TonEBP (+ / -) mice had a reduction of hippocampal heme oxygenase-1 (HO-1) expression compared to diabetic wild-type mice. In particular, we found that TonEBP bound to the LCN2 promoter in the diabetic hippocampus, and this binding was abolished by TonEBP haploinsufficiency. Furthermore, TonEBP knockdown attenuated LCN2 expression in lipopolysaccharide/high glucose-treated mouse hippocampal HT22 cells. CONCLUSIONS: These findings indicate that TonEBP may promote neuroinflammation and cognitive impairment via upregulation of LCN2 in diabetic mice.
Assuntos
Disfunção Cognitiva/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Lipocalina-2/sangue , Fatores de Transcrição NFATC/sangue , Doenças Neuroinflamatórias/sangue , Animais , Cognição/fisiologia , Disfunção Cognitiva/etiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Dieta Hiperlipídica , Aprendizagem em Labirinto/fisiologia , Camundongos , Doenças Neuroinflamatórias/etiologia , Células RAW 264.7RESUMO
OBJECTIVES: To evaluate the outcome of staging chest CT and to identify clinicoradiological factors predictive of lung metastasis in patients with hepatoblastoma based on the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system. METHODS: This bi-center study retrospectively identified patients diagnosed with hepatoblastoma between January 1998 and September 2019 in two tertiary hospitals. The primary outcome was the proportion of the patients who had lung metastasis at staging chest CT. The diagnostic accuracy of staging chest CT was calculated based on the 2017 PRETEXT criteria. The secondary outcome was the identification of factors predictive of lung metastasis using multivariable logistic regression. RESULTS: In total, 123 patients (median age, 1 year; interquartile range, 0-4 years; 59 female) were included. Among those, 28% (35/123; 95% confidence interval [CI], 21-37%) had lung metastasis at staging chest CT. The overall accuracy of staging chest CT was 96.8%. The proportion of lung metastasis in patients with stage I, II, III, and IV was 0%, 24% (12 of 49; 95% CI, 14-38%), 23% (9 of 40; 95% CI, 12-38%), and 56% (14 of 25; 95% CI, 37-73%), respectively. Multifocality (adjusted odds ratio, 6.7; 95% CI, 2.7-17.5; p < .001) and male sex (adjusted odds ratio, 3.1; 95% CI, 1.2-8.6; p = .02) were associated with the presence of lung metastasis. CONCLUSIONS: Twenty-eight percent of the patients with hepatoblastoma had lung metastasis at staging chest CT. Multifocality and male sex were predictive factors for lung metastasis on staging chest CT. KEY POINTS: ⢠The proportion of lung metastasis in patients with hepatoblastoma was 28%. ⢠The overall accuracy of staging chest CT was 97% based on the 2017 PRETEXT system. ⢠Hepatic tumor multifocality and male sex were predictors of lung metastasis.
Assuntos
Hepatoblastoma , Neoplasias Hepáticas , Neoplasias Pulmonares , Criança , Feminino , Hepatoblastoma/diagnóstico por imagem , Hepatoblastoma/patologia , Humanos , Lactente , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD. METHODS: A cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD. RESULTS: The adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS. CONCLUSION: Our results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.
Assuntos
Hipopituitarismo , Hepatopatia Gordurosa não Alcoólica , Adolescente , Criança , Estudos Transversais , Hormônio do Crescimento , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Fator de Crescimento Insulin-Like I , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Adulto JovemRESUMO
BACKGROUND: In neonatal intensive care unit (NICU) patients with intubation status, fluoroscopic evaluation for the bowel is limited. This study was to evaluate the utility of bedside upper gastrointestinal (UGI) series with delayed radiographs (DR) for assessing duodenojejunal junction (DJJ) and small bowel passage in NICU patients with nonspecific bowel ultrasonography and contrast enema findings. METHODS: We reviewed clinical and imaging data for bedside UGI with DR of NICU patients from 2014 to 2019. Five abdominal radiographs were obtained at fixed time intervals of immediately after, 1 min, 5 min, 1 h, and 2 h following the administration of 5 cc/kg isotonic water-soluble contrast agent via the nasogastric tube. RESULTS: Twenty bedside UGI with DR were performed in 17 patients (weight range: 520-3620 g, age range: 0-4 months). Confidence identifying the DJJ was either good (n = 7) or equivocal (n = 8) at immediate or 1 min radiographs. The DJJ could not be evaluated in five from four delayed passage (including two meconium plug syndrome and one gastric volvulus) and one inadequate timing. There was only one case of intestinal malrotation, which was not detected on ultrasonography, but detected at the first UGI examination with good DJJ confidence. CONCLUSIONS: Bedside UGI with DR can evaluate intestinal malrotation using immediate and 1 min delay and small bowel passage using 1 and 2 h delay images in NICU patients with nonspecific ultrasonographic and contrast enema findings. The majority with delayed contrast passages can have bowel pathology. Because of a small number of patients in this study, further studies with more infants are needed.
Assuntos
Anormalidades do Sistema Digestório , Volvo Intestinal , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Volvo Intestinal/diagnóstico por imagem , Radiografia , UltrassonografiaRESUMO
PURPOSE: To evaluate elasticity and perfusion change associated with fibrosis in a rabbit model of unilateral ureter obstruction using shear wave elastography (SWE) and contrast-enhanced ultrasonography (CEUS). METHODS: Complete unilateral ureter obstruction by ligation was performed in the left kidney of 15 rabbits. Renal elasticity on SWE and perfusion change on CEUS at the renal cortex were measured before and after the operation. Histopathological renal fibrosis was quantified by the stained area ratio with Masson trichrome and Picrosirius red using ImageJ analysis. Renal elasticity and perfusion values were compared by the Mann-Whitney U test and Proc Mixed as a function of time. Spearman's correlation was used to analyze differences between imaging values and fibrosis. RESULTS: The duration of imaging follow-up was up to 49 days, with interval imaging performed 1-3 times. Renal elasticity values were higher in obstructed kidneys compared to contralateral kidneys (31.0 kPa vs 16.4 kPa, p < 0.001) and increased according to postoperative time (0.46 kPa/day). With respect to renal fibrosis, SWE values were positively correlated with Masson trichrome (ρ = 0.651, p < 0.001) and Picrosirius red (ρ = 0.514, p = 0.007). Among CEUS parameters, mean transit time was negatively correlated with renal fibrosis by Masson trichrome (ρ = - 0.639, p = 0.001) and Picrosirius red (ρ = - 0.625, p = 0.001). Rise time and time to peak were positively correlated with renal fibrosis. CONCLUSION: Obstructive uropathy resulted in changes to both renal elasticity and perfusion. Renal fibrosis was moderately associated with increased renal cortical stiffness and both delayed and decreased cortical perfusion. KEY POINTS: ⢠Obstructive uropathy causes changes in elasticity and perfusion in a rabbit model. ⢠Renal fibrosis from obstructive uropathy increases renal cortical stiffness, and both delay and decrease cortical perfusion.
Assuntos
Fibrose/diagnóstico , Nefropatias/diagnóstico , Rim/diagnóstico por imagem , Ultrassonografia/métodos , Obstrução Ureteral/diagnóstico , Animais , Modelos Animais de Doenças , Elasticidade , Fibrose/etiologia , Humanos , Rim/fisiopatologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Coelhos , Obstrução Ureteral/complicaçõesRESUMO
OBJECTIVES: To evaluate the implications of hepatic subcapsular and capsular flows using ultrasonography (US) in children after Kasai operation. METHODS: Children who underwent liver US including color Doppler US and microvascular imaging (MVI) from May 2017 to October 2017 were retrospectively included. Children who underwent the Kasai operation for biliary atresia were included in the Kasai group and children with normal liver were included in the control group. Using US results, the number of intrahepatic biliary cysts and the maximum diameter of the spleen were evaluated in the Kasai group. Liver stiffness values were included when patients in the Kasai group had transient elastography (TE) or shear wave elastography (SWE) results. Hepatic subcapsular and capsular flows on color Doppler US and MVI were compared between the two groups using the following scores: 0, no flow reaching the hepatic capsule; 1, any flow reaching the hepatic capsule; and 2, contiguous hepatic capsular flow. The logistic regression test was used to identify associations between age, intrahepatic biliary cysts, spleen size, SWV, TE results, and flow scores measured on Doppler US and MVI in the Kasai group using the odds ratio (OR) and 95% confidence interval (CI). RESULT: A total of 65 children (mean 7.6 ± 5.3 years), 44 in the Kasai group and 21 in the control group, were included. In the control group, one child had score 1 on MVI and others had score 0 on both Doppler US and MVI. Among the Kasai group, 28 children (63.6%) had score 1, while others had score 0 using Doppler US. Using MVI, 24 children (54.5%) had score 2, 18 children had score 1, and one child had score 0. In the Kasai group, increased liver stiffness on TE was the only factor significantly associated with the presence of subcapsular flow on color Doppler US (OR 1.225, 95% CI 1.020-1.470) and increased spleen size was the only factor significantly associated with increased flow scores on MVI (OR 1.397, 95% CI 1.002-2.724). CONCLUSION: Detection of hepatic subcapsular, capsular flows on US would be meaningful for children after receiving the Kasai operation. KEY POINTS: ⢠Hepatic subcapsular or capsular flows can be useful not only for the diagnosis but also for the postoperative follow-up in patients with biliary atresia. ⢠Increased liver stiffness and splenomegaly after the Kasai operation were associated with presence of subcapsular or capsular flow on ultrasonography. ⢠Evaluation of hepatic subcapsular and capsular flows could be needed to assess disease progression after receiving the Kasai operation.
Assuntos
Atresia Biliar/fisiopatologia , Atresia Biliar/cirurgia , Circulação Hepática , Microcirculação , Doenças dos Ductos Biliares/complicações , Doenças dos Ductos Biliares/diagnóstico por imagem , Atresia Biliar/complicações , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Criança , Pré-Escolar , Cistos/complicações , Cistos/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Baço/diagnóstico por imagem , Esplenomegalia , Ultrassonografia Doppler em CoresRESUMO
Obesity-induced adipocyte apoptosis promotes inflammation and insulin resistance. Src homology domain-containing inositol 5'-phosphatase 1 (SHIP1) is a key factor of apoptosis and inflammation. However, the role of SHIP1 in obesity-induced adipocyte apoptosis and autophagy is unclear. We found that diet-induced obesity (DIO) mice have significantly greater crown-like structures and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive cells than ob/ob or control mice. Using RNA sequencing (RNA-seq) analysis, we identified that the apoptosis- and inflammation-related gene Ship1 is upregulated in DIO and ob/ob mice compared with control mice. In particular, DIO mice had more SHIP1-positive macrophages and lysosomal-associated membrane protein 1 (LAMP1) as well as a higher B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio compared with ob/ob or control mice. Furthermore, caloric restriction attenuated adipose tissue inflammation, apoptosis, and autophagy by reversing increases in SHIP1-associated macrophages, Bax/Bcl2-ratio, and autophagy in DIO and ob/ob mice. These results demonstrate that DIO, not ob/ob, aggravates adipocyte inflammation, apoptosis, and autophagy due to differential SHIP1 expression. The evidence of decreased SHIP1-mediated inflammation, apoptosis, and autophagy indicates new therapeutic approaches for obesity-induced chronic inflammatory diseases.
Assuntos
Inflamação/genética , Obesidade/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/crescimento & desenvolvimento , Tecido Adiposo/patologia , Animais , Apoptose/genética , Autofagia/genética , Dieta Hiperlipídica , Humanos , Inflamação/patologia , Resistência à Insulina/genética , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Obesos , Obesidade/patologiaRESUMO
Hypothalamic inflammation has been known as a contributor to high-fat diet (HFD)-induced insulin resistance and obesity. Myeloid-specific sirtuin 1 (SIRT1) deletion aggravates insulin resistance and hypothalamic inflammation in HFD-fed mice. Neurogranin, a calmodulin-binding protein, is expressed in the hypothalamus. However, the effects of myeloid SIRT1 deletion on hypothalamic neurogranin has not been fully clarified. To investigate the effect of myeloid SIRT1 deletion on food intake and hypothalamic neurogranin expression, mice were fed a HFD for 20 weeks. Myeloid SIRT1 knockout (KO) mice exhibited higher food intake, weight gain, and lower expression of anorexigenic proopiomelanocortin in the arcuate nucleus than WT mice. In particular, KO mice had lower ventromedial hypothalamus (VMH)-specific neurogranin expression. However, SIRT1 deletion reduced HFD-induced hypothalamic neurogranin. Furthermore, hypothalamic phosphorylated AMPK and parvalbumin protein levels were also lower in HFD-fed KO mice than in HFD-fed WT mice. Thus, these findings suggest that myeloid SIRT1 deletion affects food intake through VMH-specific neurogranin-mediated AMPK signaling and hypothalamic inflammation in mice fed a HFD.
Assuntos
Hipotálamo/metabolismo , Células Mieloides/metabolismo , Neurogranina/metabolismo , Sirtuína 1/deficiência , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Sinalização do Cálcio , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos , Expressão Gênica , Inflamação/metabolismo , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pró-Opiomelanocortina/metabolismo , Sirtuína 1/genética , Núcleo Hipotalâmico Ventromedial/metabolismoRESUMO
BACKGROUND: Controlled attenuation parameter (CAP) is a recently introduced, non-invasive and quantitative method to evaluate hepatic steatosis demonstrated in adults, but limited in obesity and not well evaluated in children. The aim of this study was to investigate the diagnostic performance for assessing hepatic steatosis grades using CAP in children based on MR proton density fat fraction (PDFF). METHODS: Children evaluated for non-alcoholic fatty liver disease (NAFLD) who were assessed for PDFF and CAP were enrolled retrospectively. Hepatic steatosis grades 0-3 were classified according to PDFF using cutoff values of 6, 17.5, and 23.3%. Subgroup analyses were performed in non-obese and obese groups using the 95th percentile body mass index (BMI) as a cutoff and BMI30 group when BMI > 30 kg/m2. Pearson's correlations between variables were also analyzed. RESULTS: In a total of 86 children, there were 53 in the obese group including 17 of the BMI30 group. CAP demonstrated 98.7% sensitivity and 80% specificity for diagnosing grades 1-3 vs. grade 0 using a cutoff value of 241 dB/m (area under the curve = 0.941, p < 0.001). The diagnostic performance for higher steatosis grades was suboptimal. CAP correlated with abdominal wall thickness in both obese (r = 0.549, p = 0.001) and non-obese (r = 0.386, p = 0.004) groups and did not correlate with PDFF in BMI30 group. CONCLUSION: In children with NAFLD, CAP showed excellent diagnostic performance for differentiating presence and absence of hepatic steatosis using a cutoff value of 241 dB/m. However, CAP was limited in evaluating grades of steatosis, especially in children with BMI > 30 kg/m2.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Índice de Massa Corporal , Fígado Gorduroso/diagnóstico , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/normas , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.
RESUMO
OBJECTIVES: To evaluate MRI findings and to generate a decision tree model for diagnosis of biliary atresia (BA) in infants with jaundice. METHODS: We retrospectively reviewed features of MRI and ultrasonography (US) performed in infants with jaundice between January 2009 and June 2016 under approval of the institutional review board, including the maximum diameter of periportal signal change on MRI (MR triangular cord thickness, MR-TCT) or US (US-TCT), visibility of common bile duct (CBD) and abnormality of gallbladder (GB). Hepatic subcapsular flow was reviewed on Doppler US. We performed conditional inference tree analysis using MRI findings to generate a decision tree model. RESULTS: A total of 208 infants were included, 112 in the BA group and 96 in the non-BA group. Mean age at the time of MRI was 58.7 ± 36.6 days. Visibility of CBD, abnormality of GB and MR-TCT were good discriminators for the diagnosis of BA and the MRI-based decision tree using these findings with MR-TCT cut-off 5.1 mm showed 97.3 % sensitivity, 94.8 % specificity and 96.2 % accuracy. CONCLUSIONS: MRI-based decision tree model reliably differentiates BA in infants with jaundice. MRI can be an objective imaging modality for the diagnosis of BA. KEY POINTS: ⢠MRI-based decision tree model reliably differentiates biliary atresia in neonatal cholestasis. ⢠Common bile duct, gallbladder and periportal signal changes are the discriminators. ⢠MRI has comparable performance to ultrasonography for diagnosis of biliary atresia.
Assuntos
Atresia Biliar/complicações , Atresia Biliar/diagnóstico por imagem , Icterícia/complicações , Imageamento por Ressonância Magnética/métodos , Ductos Biliares/diagnóstico por imagem , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To investigate consistency in shear wave velocities (SWVs) on ultrasound elastography using different machines, transducers and acquisition depths. METHODS: The SWVs were measured using an elasticity phantom with a Young's modulus of 16.9 kPa, with three recently introduced ultrasound elastography machines (A, B and C from different vendors) and two transducers (low and high frequencies) at four depths (2, 3, 4 and 5 cm). Mean SWVs from 15 measurements and coefficient of variations (CVs) were compared between three machines, two transducers and four acquisition depths. RESULTS: The SWVs using the high frequency transducer were not acquired at 5 cm depth in machine B, and a high frequency transducer was not available in machine C. The mean SWVs in the three machines were different (p ≤ 0.002). The CVs were 0-0.09 in three machines. The mean SWVs between the two transducers were different (p < 0.001) except at 4 and 5 cm depths in machine A. The SWVs were affected by the acquisition depths in all conditions (p < 0.001). CONCLUSION: There is considerable difference in SWVs on ultrasound elastography depending on different machines, transducers and acquisition depths. Caution is needed when using the cutoff values of SWVs in different conditions. KEY POINTS: ⢠The shear wave velocities (SWVs) are different between different ultrasound elastography machines ⢠The SWVs are also different between different transducers and acquisition depths ⢠Caution is needed when using the cutoff SWVs measured under different conditions.
Assuntos
Módulo de Elasticidade , Técnicas de Imagem por Elasticidade/instrumentação , Imagens de Fantasmas , Transdutores , HumanosRESUMO
OBJECTIVE: To suggest a simple method that can quantify air trapping from chest CT in children with graft-versus-host disease (GVHD)-related bronchiolitis obliterans (BO). METHODS: This institutional review board-approved retrospective study included eight GVHD-related BO patients (age, 6 - 17 years) who underwent both 31 CTs of variable settings and pulmonary function tests (PFT). The attenuation values of lung parenchyma in normal (An) and air trapping (Aa) areas were obtained. Individualized threshold [(An + Aa)/2] and fixed threshold of -950 HU were set for air trapping quantification. Spearman correlation analysis and generalized linear mixed models were used for statistical analysis. RESULTS: The mean value of individualized threshold was -830.2 ± 48.3 HU. The mean air trapping lung volume percentage with individualized threshold and -950 HU were 45.4 ± 18.9% and 1.4 ± 1.9%, respectively. The air trapping lung volume percentage with individualized threshold showed a significant negative correlation with the PFT of FEV1/FVC% in all data (γ = -0.795, P < .001) and in the correction of repetition (γ = -0.837, P = .010). CONCLUSIONS: We suggest a simple and individualized threshold attenuation setting method for air trapping quantification insusceptible to CT imaging protocols or respiratory phase control in children with GVHD-related BO. KEY POINTS: ⢠Simple and individualized threshold attenuation setting for air trapping quantification is possible. ⢠Individualized threshold attenuation setting is insusceptible to CT imaging protocols or respiratory phase control. ⢠CT air trapping quantification correlates with PFT of pulmonary obstruction.
Assuntos
Bronquiolite Obliterante/diagnóstico por imagem , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Adolescente , Ar , Criança , Estudos de Viabilidade , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Masculino , Projetos Piloto , Testes de Função Respiratória , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVES: To evaluate clinical and sonographic features of testicular teratomas and epidermoid cysts in children and to assess differential points of immature teratomas from benign counterparts. METHODS: We retrospectively reviewed testicular teratomas and epidermoid cysts in children. Age at surgery, α-fetoprotein (AFP) level, and sonographic findings, including components (mainly cystic, mainly solid, or mixed), presence of calcification, and size, were reviewed. RESULTS: Nineteen cases were included, with 10 mature teratomas, 3 immature teratomas, and 6 epidermoid cysts. On sonography, most of the teratomas (n = 9) had mixed components, with 2 mainly cystic and 2 mainly solid lesions. The 2 mainly cystic teratomas underwent follow-up sonography and showed component changes to mainly solid. Compared to epidermoid cysts, teratomas were larger (P = .029) with less cystic components (P = .046). All 3 immature teratomas showed mixed components with calcification. In differentiating immature from benign teratomas, immature teratomas were larger (P= .047) in younger children (P= .008) with higher AFP levels (P= .023). The optimal cutoff values for diagnosing immature teratomas were 8 months of age, 23 ng/mL in AFP level, and 2.5 cm in size, with 100% sensitivity and 89.5% accuracy rates. However, sonographic features, including tumor components and presence of calcification, were not helpful for differentiating immature teratomas. CONCLUSIONS: Testicular masses in children younger than 8 months with AFP levels higher than 23 ng/mL and size larger than 2.5 cm need to be considered for orchiectomy rather than testis-sparing tumorectomy because of the increased frequency of immature teratomas versus mature teratomas or epidermoid cysts.
Assuntos
Cisto Epidérmico/diagnóstico , Teratoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Ultrassonografia/métodos , Pré-Escolar , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Masculino , Exame Físico/métodosRESUMO
OBJECTIVES: The purpose of this study was to evaluate the normal thickness of the filum terminale on sonography and suggest an optimal cutoff value for filum terminale lipoma screening in young children. METHODS: We retrospectively reviewed lumbosacral sonograms and magnetic resonance images from children younger than 36 months that were obtained between January 2013 and June 2014. The filum terminale thickness on sonography and the presence of fat in the filum terminale on magnetic resonance imaging were evaluated. RESULTS: From 111 children (mean age ± SD, 3.6 ± 3.0 months), 49 did not have abnormal lesions (normal group), and 62 had fat infiltration in the filum terminale (lipoma group). The filum terminale was thicker in the lipoma group than the normal group (1.5 ± 0.5 versus 0.9 ± 0.2 mm; P < .001). Filum terminale thickness also showed significance in a multivariable analysis with sex and age (odds ratio per 0.1-mm unit, 2.754; P < .001) and in propensity score matching for age (P < .001). The optimal cutoff value for filum terminale lipoma screening was 1.1 mm, with 94% sensitivity and 86% specificity. CONCLUSIONS: The conventional cutoff value of 2 mm for a thickened filum terminale on sonography can be too thick. We suggest an optimal cutoff value of 1.1 mm for lipoma screening in young children.