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1.
BMC Emerg Med ; 23(1): 32, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949386

RESUMO

BACKGROUND: Anaemia is highly prevalent in critically ill patients; however, the long-term effect on mortality remains unclear. METHODS: We retrospectively included patients admitted to the medical intensive care units (ICUs) during 2015-2020 at the Taichung Veterans General Hospital. The primary outcome of interest was one-year mortality, and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined to assess the association. We used propensity score matching (PSM) and propensity score matching methods, including inverse probability of treatment weighting (IPTW) as well as covariate balancing propensity score (CBPS), in the present study. RESULTS: A total of 7,089 patients were eligible for analyses, and 45.0% (3,189/7,089) of them had anaemia, defined by mean levels of haemoglobin being less than 10 g/dL. The standardised difference of covariates in this study were lower than 0.20 after matching and weighting. The application of CBPS further reduced the imbalance among covariates. We demonstrated a similar association, and adjusted HRs in original, PSM, IPTW and CBPS populations were 1.345 (95% CI 1.227-1.474), 1.265 (95% CI 1.145-1.397), 1.276 (95% CI 1.142-1.427) and 1.260 (95% CI 1.125-1.411), respectively. CONCLUSIONS: We used propensity score-based analyses to identify that anaemia within the first week was associated with increased one-year mortality in critically ill patients.


Assuntos
Anemia , Estado Terminal , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Hemoglobinas
2.
Acta Neurol Taiwan ; 32(1): 16-24, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36474450

RESUMO

PURPOSE: The three-dimensional (3D) measurement of vessel wall volume (VWV) and plaque volume is sensitive for predicting cardiovascular risk. We established the normal norms of carotid VWV. METHODS: We retrospectively enrolled 352 patients with normal findings of the carotid ultrasound studies. Two-dimensional carotid intima-media thickness (IMT) was measured online. Grayscale 3D images of both sides of the carotid arteries were analyzed offline for measurement of IMT (QIMT) and VWV. RESULTS: The median age of the enrollees was 59 years. The median carotid IMT, QIMT, and VWV was 0.61 mm, 0.72 mm, and 90 mm3, respectively. No differences in IMT and VWV were observed between men and women or between the right and left side. We stratified participants into four groups, namely young adults (≤50 years), middle-aged adults (51-65 years), older adults (66-75 years), and senior adults (≥75 years). All the values of measured variables increased with advancing age. The median VWV of each group was 84, 90, 100, and 112 mm3, respectively. The increment percentage from young to senior adults was similar in terms of IMT and VWV. Nevertheless, the difference in the value of VWV (28 mm3) was much larger than that in IMT (0.18 mm). All three measured variables exhibited a positive linear correlation with age. CONCLUSION: Both IMT and VWV have positive linear correlations with age. The application of QIMT measurements was limited by its inconsistent accuracy. VWV not only has a strong correlation with IMT but also enables observation of dynamic vessel wall changes, which is valuable for clinical observational studies.


Assuntos
Artérias Carótidas , Espessura Intima-Media Carotídea , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Artérias Carótidas/diagnóstico por imagem
3.
Biochem Biophys Res Commun ; 616: 49-55, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35636255

RESUMO

Obesity drives nonalcoholic fatty liver disease (NAFLD). This study investigated the effects of dietary brewers' spent grain (BSG) supplementation on obesity-induced NAFLD. Mice fed a high-fat diet supplemented with 30% BSG (HFD30) had reduced body weight and decreased plasma total cholesterol (TC) concentrations compared with HFD-fed mice. Retroperitoneal white adipose tissue (RWAT) and liver weights were reduced. Consistent with reduced hepatic triacylglycerol, TC, and non-esterified fatty acid concentrations, HFD30-fed mice showed reduced hepatic steatosis. 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor genes were increased, whereas carnitine palmitoyltransferase 1 alpha, ATP-binding cassette subfamily A member 1 (Abca1), and cholesterol 7 alpha-hydroxylase genes were upregulated in the liver of HFD30-fed mice. Abca1 gene expression was also increased in epididymal WAT and RWAT of HFD30-fed mice. BSG supplementation increased and decreased fecal fat and bile acid concentrations, respectively. Taken together, BSG supplementation reduced HFD-induced hepatic lipid accumulation by increasing fatty acid oxidation and bile acid synthesis in the liver as well as decreasing lipid absorption in the intestine.


Assuntos
Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Animais , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Triglicerídeos/metabolismo
4.
Chem Rec ; 22(10): e202200098, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35686885

RESUMO

Owing to the abundant resources of potassium resources, potassium ion batteries (PIBs) hold great potential in various energy storage devices. However, the poor lifespan of PIBs anodes limit their merchant applications. The exploitation of anode materials with high performance is one of the critical factors to the development of PIBs. Metallic Sn-, Sb-, and Bi-based materials, show promising future thanks to their high theoretical capacities and safe working voltage. However, the rapid capacity decay caused by the large K+ is still a pivotal challenge. In this review, recent progresses on alloying anodes were summarized. Schemes, such as ultra-small nanoparticles, hetero-element doping, and electrolyte optimization are effective strategies to improve their electrochemical properties. This review provides an outlook on the nanostructures and their synthesis methods for the alloying-type materials, and will stimulate their intensive study for practical application in the near future.

5.
Acta Pharmacol Sin ; 43(4): 811-828, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34183754

RESUMO

Intracerebral hemorrhage (ICH) is a devastating disease, in which neuroinflammation substantially contributes to brain injury. Uncoupling protein 2 (UCP2) is a member of the mitochondrial anion carrier family, which uncouples oxidative phosphorylation from ATP synthesis by facilitating proton leak across the mitochondrial inner membrane. UCP2 has been reported to modulate inflammation. In this study we investigated whether and how UCP2 modulated neuroinflammation through microglia/macrophages following ICH in vitro and in vivo. We used an in vitro neuroinflammation model in murine BV2 microglia to mimic microglial activation following ICH. ICH in vivo model was established in mice through collagenase infusion into the left striatum. ICH mice were treated with anetholetrithione (ADT, 50 mg· kg-1 ·d-1, ip) or the classical protonophoric uncoupler FCCP (injected into hemorrhagic striatum). We showed that the expression and mitochondrial location of microglial UCP2 were not changed in both in vitro and in vivo ICH models. Knockdown of UCP2 exacerbated neuroinflammation in BV2 microglia and mouse ICH models, suggesting that endogenous UCP2 inhibited neuroinflammation and therefore played a protective role following ICH. ADT enhanced mitochondrial ROS production thus inducing mitochondrial uncoupling and activating UCP2 in microglia. ADT robustly suppressed neuroinflammation, attenuated brain edema and improved neurological deficits following ICH, and these effects were countered by striatal knockdown of UCP2. ADT enhanced AMP-activated protein kinase (AMPK) activation in the hemorrhagic brain, which was abrogated by striatal knockdown of UCP2. Moreover, striatal knockdown of AMPK abolished the suppression of neuroinflammation by ADT following ICH. On the other hand, FCCP-induced mitochondrial uncoupling was independent of UCP2 in microglia; and striatal knockdown of UCP2 did not abrogate the suppression of neuroinflammation by FCCP in ICH mice. In conclusion, the uncoupling activity is essential for suppression of neuroinflammation by UCP2. We prove for the first time the concept that activators of endogenous UCP2 such as anetholetrithione are a new class of uncouplers with translational significance.


Assuntos
Anetol Tritiona , Anetol Tritiona/metabolismo , Anetol Tritiona/farmacologia , Animais , Hemorragia Cerebral/tratamento farmacológico , Camundongos , Microglia , Doenças Neuroinflamatórias , Proteína Desacopladora 2/metabolismo
6.
Acta Neurol Taiwan ; 31(4): 179-185, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35470412

RESUMO

PURPOSE: Takotsubo syndrome (TTS) is characterized angiographically by transient left ventricular systolic dysfunction sparing the basal segments of the left ventricle and absence of obstructive coronary artery disease. Epileptic seizures as triggering events for TTS are uncommon, having only been described in approximately 100 previous cases Case report: A 64-year-old woman with a history of recent stroke-related seizures was admitted for an acute onset of right hemiparesis with dull response. Neurological examination revealed a forced deviation of the eyeballs to the left side and quadriplegia. No large intracranial artery occlusion was disclosed through computed tomography angiography, but an acute infarction at the right corona radiata was identified through magnetic resonance imaging. Electroencephalography showed frequent spike-and-wave complexes over the right cerebral hemisphere indicating subtle status epilepticus. Her consciousness deteriorated to a stuporous state, and her eyeballs were forced deviated to the right side with persistent twitching of the right limbs 10 hours later. The convulsive status epilepticus (CSE) subsided after intravenous infusion of midazolam. However, atrial flutter with inverted T-wave and elevated high-sensitivity troponin I were observed 12 hours after CSE. Arrhythmia was soon alleviated through appropriate treatment. A further coronary angiography did not show significant coronary artery stenosis but indicated that the midsection and the apex of the left ventricle ballooned out during systole as the base contracted normally, indicating a Takotsubo syndrome. CONCLUSION: Physicians need to monitor unusual arrhythmias, particularly atrial and ventricular arrhythmias, for the possibility of TTS in patients with epileptic seizure.


Assuntos
Estado Epiléptico , Cardiomiopatia de Takotsubo , Eletroencefalografia/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Pessoa de Meia-Idade , Convulsões/etiologia , Estado Epiléptico/etiologia , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/diagnóstico por imagem
7.
J Neurosci ; 40(6): 1355-1365, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31882402

RESUMO

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.


Assuntos
Disfunção Cognitiva/metabolismo , Espinhas Dendríticas/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Regulação da Expressão Gênica/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Disfunção Cognitiva/genética , Espinhas Dendríticas/patologia , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/genética , Masculino , Camundongos , Camundongos Knockout , Neurogênese/genética
8.
Int J Mol Sci ; 22(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922657

RESUMO

BRCA mutation, one of the most common types of mutations in breast and ovarian cancer, has been suggested to be synthetically lethal with depletion of RAD52. Pharmacologically inhibiting RAD52 specifically eradicates BRCA-deficient cancer cells. In this study, we demonstrated that curcumin, a plant polyphenol, sensitizes BRCA2-deficient cells to CPT-11 by impairing RAD52 recombinase in MCF7 cells. More specifically, in MCF7-siBRCA2 cells, curcumin reduced homologous recombination, resulting in tumor growth suppression. Furthermore, a BRCA2-deficient cell line, Capan1, became resistant to CPT-11 when BRCA2 was reintroduced. In vivo, xenograft model studies showed that curcumin combined with CPT-11 reduced the growth of BRCA2-knockout MCF7 tumors but not MCF7 tumors. In conclusion, our data indicate that curcumin, which has RAD52 inhibitor activity, is a promising candidate for sensitizing BRCA2-deficient cells to DNA damage-based cancer therapies.


Assuntos
Proteína BRCA2/deficiência , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Dano ao DNA , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Recombinação Homóloga , Proteína Rad52 de Recombinação e Reparo de DNA/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Apoptose , Proteína BRCA2/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Reparo do DNA , Feminino , Humanos , Irinotecano/farmacologia , Camundongos , Camundongos Nus , Mutação , Inibidores da Topoisomerase I/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Acta Neurol Taiwan ; 30(4): 128-140, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34841498

RESUMO

PURPOSE: Occlusion of both internal carotid arteries (ICAs) is rare. Clinical manifestations of stroke vary widely. We conducted a retrospective review to compare acute and chronic bilateral ICA occlusion. METHODS: We retrospectively reviewed records of inpatients with acute ischemic stroke and carotid duplex sonography (CDS) during the period from February 2006 to February 2021. RESULTS: Bilateral ICA occlusion and acute bilateral ICA occlusion accounted for 0.3% and less than 0.1% of all ischemic stroke cases, respectively. All five patients with acute bilateral ICA occlusion presented with consciousness disturbance. Three patients died within 1 week, and two patients had a vegetative outcome. Pituitary apoplexy with bilateral ICA occlusion was observed in one patient. Forward bilateral ophthalmic arterial flow (OAF) was detected in all three patients who received CDS. Among 13 patients with chronic bilateral ICA occlusion, five and six had modified Rankin Scale (mRS) scores upon discharge of more than 5 and less than 2, respectively; two patients did not have a stroke. Of the 13 patients, 11 had reversed bilateral OAF. Patients with acute bilateral ICA occlusion had a higher rate of initial consciousness disturbance, Glasgow Coma Scale score of less than 9, National Institute of Health Stroke Scale score of more than 20, and mRS score of more than 5. than that of patients with chronic bilateral ICA occlusion. CONCLUSION: Patients with acute bilateral ICA occlusion had higher initial stoke severity, poorer collateral circulation, and worse clinical outcomes than did those with chronic bilateral ICA occlusion. Physicians must pay attention to rare causes of acute bilateral ICA occlusion, including pituitary apoplexy.


Assuntos
Isquemia Encefálica , Estenose das Carótidas , Acidente Vascular Cerebral , Isquemia Encefálica/etiologia , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
10.
J Neuroinflammation ; 17(1): 202, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631435

RESUMO

BACKGROUND: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. METHODS: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. RESULTS: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. CONCLUSION: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.


Assuntos
Mediadores da Inflamação/metabolismo , Proteínas dos Microfilamentos/antagonistas & inibidores , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Células Cultivadas , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia
11.
Neuroradiology ; 62(4): 439-445, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31853589

RESUMO

PURPOSE: Differential diagnosis between central neurocytoma and ependymoma is very important for making preoperative scheme. We explored the application of diffusion-weighted imaging (DWI) combined with apparent diffusion coefficient (ADC) in differential diagnosis between both. METHODS: The data of preoperative MR plain and contrast-enhanced scan, DWI and ADC values of neoplastic solid parts from 18 cases with central neurocytoma and 19 cases with lateral ventricular ependymoma, were retrospectively analyzed. Mann-Whitney test was used for the comparison of ADC values between central neurocytoma and ependymoma. The application of ADC values in the differential diagnosis between central neurocytoma and ependymoma was evaluated by ROC curve. RESULTS: The lesions showed hyperintensity-dominant mixed signal intensity on DWI and mean ADC was (0.65 ± 0.13) × 10-3 mm2/s in the 18 cases with central neurocytoma. In the 19 cases with ependymoma, 13 had hyperintensity-dominant mixed signal intensity on DWI and 6 had hypointensity-dominant mixed signal intensity on DWI, and mean ADC was (1.20 ± 0.23) × 10-3 mm2/s. The mean ADC value was significantly higher in the 19 cases with ependymoma than in the 18 cases with central neurocytoma (P < 0.001). The ADC of 0.87 × 10-3 mm2/s might be used as a threshold for differential diagnosis between central neurocytoma and ependymoma with an area under ROC curve of 0.98 ± 0.02 and a 95% confidence interval of 0.95-1.00. Its sensitivity, specificity, and accuracy were 90%, 100%, and 90%, respectively. CONCLUSION: There is a certain overlap in MRI imaging features between central neurocytoma and ependymoma. DWI combined with ADC value can improve peoperative diagnostic accuracy.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Ependimoma/diagnóstico por imagem , Neurocitoma/diagnóstico por imagem , Adolescente , Adulto , Criança , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Acta Neurol Taiwan ; 29(4): 103-113, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34018169

RESUMO

OBJECTIVE: Chronic inflammatory processes involving the vascular wall may induce atherosclerosis. Immune-inflammatory processes proceed throughout all stages of acute stroke. We investigated the association of three immune-inflammatory markers, namely systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and neutrophil count (NC), with prehospital delay and clinical features in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 2543 inpatients admitted within 4 days of symptom onset from May 2010 to February 2020. Patients were stratified into three groups: Group A, comprising 161 patients with tissue plasminogen activator (tPA) treatment; Group B, comprising 415 patients who were eligible for tPA treatment; and Group C, comprising all 2543 patients. RESULTS: The levels of all three immune-inflammatory markers had positive linear correlations with onsetto- emergency room time, initial National Institutes of Health Stroke Scale (NIHSS) scores, and discharge modified Rankin Scale scores. In Group B, levels of follow-up, but not initial, immuneinflammatory markers were higher in patients with unfavorable outcomes. Common significant predictors of in-hospital complications and unfavorable outcomes were age > 72 years, female sex, NIHSS > 4, diabetes mellitus, and all three immune-inflammatory markers. When combined with other predictors, NC > 7.2 × 103/mL achieved optimal predictive performance (0.794) for in-hospital complications, and SII > 651, NLR > 2.9, and NC > 7.2 × 103/mL had equal predictive performance up to 0.859 for unfavorable outcomes. CONCLUSIONS: Immune-inflammatory markers dynamically increased from symptom onset of acute ischemic stroke in patients eligible for thrombolytic therapy. Higher levels of immune-inflammatory markers suggest more in-hospital complications and unfavorable short-term outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
13.
Gastroenterology ; 155(6): 1971-1984.e4, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30213555

RESUMO

BACKGROUND & AIMS: Transmembrane protein 173 (TMEM173 or STING) signaling by macrophage activates the type I interferon-mediated innate immune response. The innate immune response contributes to hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). We investigated whether STING regulates diet-induced in hepatic steatosis, inflammation, and liver fibrosis in mice. METHODS: Mice with disruption of Tmem173 (STINGgt) on a C57BL/6J background, mice without disruption of this gene (controls), and mice with disruption of Tmem173 only in myeloid cells were fed a standard chow diet, a high-fat diet (HFD; 60% fat calories), or a methionine- and choline-deficient diet (MCD). Liver tissues were collected and analyzed by histology and immunohistochemistry. Bone marrow cells were isolated from mice, differentiated into macrophages, and incubated with 5,6-dimethylxanthenone-4-acetic acid (DMXAA; an activator of STING) or cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Macrophages or their media were applied to mouse hepatocytes or human hepatic stellate cells (LX2) cells, which were analyzed for cytokine expression, protein phosphorylation, and fat deposition (by oil red O staining after incubation with palmitate). We obtained liver tissues from patients with and without NAFLD and analyzed these by immunohistochemistry. RESULTS: Non-parenchymal cells of liver tissues from patients with NAFLD had higher levels of STING than cells of liver tissues from patients without NAFLD. STINGgt mice and mice with disruption only in myeloid cells developed less severe hepatic steatosis, inflammation, and/or fibrosis after the HFD or MCD than control mice. Levels of phosphorylated c-Jun N-terminal kinase and p65 and mRNAs encoding tumor necrosis factor and interleukins 1B and 6 (markers of inflammation) were significantly lower in liver tissues from STINGgt mice vs control mice after the HFD or MCD. Transplantation of bone marrow cells from control mice to STINGgt mice restored the severity of steatosis and inflammation after the HFD. Macrophages from control, but not STINGgt, mice increased markers of inflammation in response to lipopolysaccharide and cGAMP. Hepatocytes and stellate cells cocultured with STINGgt macrophages in the presence of DMXAA or incubated with the medium collected from these macrophages had decreased fat deposition and markers of inflammation compared with hepatocytes or stellate cells incubated with control macrophages. CONCLUSIONS: Levels of STING were increased in liver tissues from patients with NAFLD and mice with HFD-induced steatosis. In mice, loss of STING from macrophages decreased the severity of liver fibrosis and the inflammatory response. STING might be a therapeutic target for NAFLD.


Assuntos
Imunidade Inata/genética , Cirrose Hepática/genética , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Hepatite/genética , Hepatite/metabolismo , Humanos , Interferon Tipo I/imunologia , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL
14.
Hepatology ; 68(1): 48-61, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29315766

RESUMO

Adenosine 2A receptor (A2A R) exerts protective roles in endotoxin- and/or ischemia-induced tissue damage. However, the role for A2A R in nonalcoholic fatty liver disease (NAFLD) remains largely unknown. We sought to examine the effects of global and/or myeloid cell-specific A2A R disruption on the aspects of obesity-associated NAFLD and to elucidate the underlying mechanisms. Global and/or myeloid cell-specific A2A R-disrupted mice and control mice were fed a high-fat diet (HFD) to induce NAFLD. In addition, bone marrow-derived macrophages and primary mouse hepatocytes were examined for inflammatory and metabolic responses. Upon feeding an HFD, both global A2A R-disrupted mice and myeloid cell-specific A2A R-defcient mice revealed increased severity of HFD-induced hepatic steatosis and inflammation compared with their respective control mice. In in vitro experiments, A2A R-deficient macrophages exhibited increased proinflammatory responses, and enhanced fat deposition of wild-type primary hepatocytes in macrophage-hepatocyte cocultures. In primary hepatocytes, A2A R deficiency increased the proinflammatory responses and enhanced the effect of palmitate on stimulating fat deposition. Moreover, A2A R deficiency significantly increased the abundance of sterol regulatory element-binding protein 1c (SREBP1c) in livers of fasted mice and in hepatocytes upon nutrient deprivation. In the absence of A2A R, SREBP1c transcription activity was significantly increased in mouse hepatocytes. CONCLUSION: Taken together, our results demonstrate that disruption of A2A R in both macrophage and hepatocytes accounts for increased severity of NAFLD, likely through increasing inflammation and through elevating lipogenic events due to stimulation of SREBP1c expression and transcription activity. (Hepatology 2018;68:48-61).


Assuntos
Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor A2A de Adenosina/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Feminino , Hepatócitos/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo
15.
J Cardiovasc Nurs ; 33(6): 551-558, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29851660

RESUMO

BACKGROUND: Urinary tract infection (UTI) during acute ischemic stroke is associated with a longer hospital length of stay and unfavorable functional outcomes. OBJECTIVE: We investigated the benefits of portable bladder ultrasound (PBU) scanning during acute ischemic stroke. METHODS: We retrospectively reviewed patients with acute ischemic stroke from January 2011 to February 2017. Patients were divided into group 1 (PBU not available) and group 2 (PBU available), before or after the split date, April 9, 2014. Portable bladder ultrasound scanning was conducted by nurses to measure postvoid residual urine volume in patients with impaired consciousness and/or dependent ambulation. RESULTS: In total, 1928 patients were enrolled, of whom 109 (5.7%) had UTI and 901 (46.7%) experienced unfavorable outcomes (modified Rankin scale score ≥ 3). Multivariate analysis revealed that factors that influenced UTI were age of 75 years or older, female gender, initial total National Institutes of Health Stroke Scale (NIHSS) score of 5 or higher, initial NIHSS conscious score of 1 or higher, initial NIHSS leg score of 2 or higher, and urinary catheterization. Factors influencing unfavorable outcomes were similar to those influencing UTI but further comprised UTI. C-statistic for UTI detection was 0.864 for model fitting, including significant factors in logistic regression. Compared with group 1, group 2 had a higher incidence of urinary catheterization (13.1% vs 8.2%), a lower incidence of UTI (4.0% vs 6.9%), and a shorter length of stay (11.9 vs 13.6 days). CONCLUSIONS: Portable bladder ultrasound scanning reduced the incidence of UTI and shortened length of stay. We suggest routine PBU procedures for patients with acute ischemic stroke who fulfill the AGN3 criteria for a high risk of UTI.


Assuntos
Tempo de Internação/estatística & dados numéricos , Monitorização Ambulatorial , Bexiga Urinária/diagnóstico por imagem , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controle , Idoso , Isquemia Encefálica/complicações , Feminino , Humanos , Incidência , Masculino , Monitorização Ambulatorial/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Ultrassonografia , Infecções Urinárias/etiologia
16.
Bioprocess Biosyst Eng ; 41(4): 501-510, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29279999

RESUMO

Based on the Prussian blue spectrophotometric method, one high-throughput screening strategy for screening lignin-degrading microorganisms was built on 24-well plate at room temperature. One high activity of alkali lignin-degrading strain Rhodococcus pyridinivorans CCZU-B16 was isolated from soil. After the optimization of biodegradation, 30.2% of alkali lignin (4 g/L) was degraded under the nitrogen-limited condition (30/1 of C/N ratio; g/g) at 30 °C for 72 h. It was found that syringyl (S) units and guaiacyl (G) in lignin decreased after biodegradation. Moreover, the accumulated lipid in cells had a fatty acid profile rich in C16 and C18 with four major constituent fatty acids including palmitic acid (C16:0; 22.4%), palmitoleic acid (C16:1; 21.1%), stearic acid (C18:0; 16.2%), and oleic acid (C18:1; 23.1%). In conclusion, Rhodococcus pyridinivorans CCZU-B16 showed high potential application in future.


Assuntos
Lignina/metabolismo , Rhodococcus/metabolismo , Microbiologia do Solo , Rhodococcus/isolamento & purificação
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(3): 455-459, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-28616925

RESUMO

OBJECTIVES: To investigate the perceptions and attitudes of Chengdu residents toward "medical and aged care" integrated models and associated factors. METHODS: A cross-sectional questionnaire survey was conducted in 935 residents who were 45 years or older in 8 communities in Chengdu. Descriptive analyses and logistic binary regression analyses were performed. RESULTS: About 91.1% of respondents preferred self-care and family support, and only 8.9% preferred community and institutional care. About 84.9% of respondents reported no knowledge about the "medical and aged care" integrated models, and 15.1% had some basic understanding of the integrated care models. Middle-aged respondents were more likely to understand the integrated care models than their older counterparts, with 21.7% willing to endorse the integrated care models. The logistic regression analyses showed that age, educational attainment, marital status, chronic illness, available financial support, and knowledge and awareness were associated with the choice. CONCLUSIONS: Chengdu residents have low level of knowledge and awareness of the "medical and aged care" integrated models. Public education is needed to promote the new aged care models.


Assuntos
Envelhecimento , Prestação Integrada de Cuidados de Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 263-267, 2017 Mar.
Artigo em Zh | MEDLINE | ID: mdl-28612539

RESUMO

OBJECTIVES: To investigate social support for elderly in urban and rural settings, and determine its role in physical and psychological health of the elderly populations. METHODS: Data were extracted from the 2013 China Health and Retirement Longitudinal Study (CHARLS). Physical health was measured by the ADL/IADL scale. Mental health was measured by the CES-D scale. Family support included financial support, daily care and emotional care. Binary logistic models were established to test the associations between family support and physical and mental health. RESULTS: For the rural elderly people, financial support from children was positively associated with physical health (P <0.05); whereas, emotional comfort from children was associated with better mental health (P <0.01). Daily care from children was associated with physical and mental health of the elderly in both urban and rural settings (P <0.01). CONCLUSION: An urban-rural difference exists in the role of family support in physical and mental health of the elderly. Rural elderly people are more dependent on family support than their urban counterparts. Social support needs to be strengthened to reduce the urban-rural gap. Meanwhile, family support will continue to play a role in improving the health of elderly populations.


Assuntos
Saúde Mental , População Rural , Apoio Social , População Urbana , Idoso , Criança , China , Família , Humanos , Estudos Longitudinais
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 268-271, 2017 Mar.
Artigo em Zh | MEDLINE | ID: mdl-28612540

RESUMO

OBJECTIVES: To determine the prevalence of arthritis in middle- and old-aged populations in China and associated factors. METHODS: Data were drawn from the 2013 China Health and Retirement Longitudinal Study (CHARLS). Binary logistic regression analyses were performed to examine the associations of arthritis with social economic status (age, gender, areas, education), comorbidity (hypertension, dyslipidaemia, diabetes, cancer, chronic lung disease, liver disease, heart disease, stroke, kidney disease, digestive disease, asthma), lifestyle (smoking, drinking, sleeping) and mental health (depression symptoms). RESULTS: About 30.8% of respondents reported arthritis. Those who resided in rural areas, drank regularly, and had depression symptoms, hypertension, chronic lung disease, liver disease, heart disease, stroke, kidney disease, digestive disease and asthma had higher prevalence of arthritis than others. CONCLUSION: The prevalence of arthritis is high in middle- and old-aged populations in China, which deserves increasing attention.


Assuntos
Artrite/epidemiologia , Idoso , China/epidemiologia , Comorbidade , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(4): 584-588, 2017 Jul.
Artigo em Zh | MEDLINE | ID: mdl-28752979

RESUMO

OBJECTIVE: To determine the relationship between sleep duration and abdominal obesity in elderly in china. METHODS: Data were drawn from the 2013 China Health and Retirement National Investigation (China Health and Retirement Longitudinal Study, CHARLS). The prevalence of abdominal obesity in the elderly who had a normal range of sleep duration was compared with those who had a shorter or longer sleep duration using Chi-square tests and binary logistic regression models. RESULTS: Higher odds of abdominal obesity were found in the elderly male with a shorter (OR=1.627, 95%CI: 1.286-2.060, P<0.05) or longer (OR=1.499, 95%CI: 1.009-2.228, P<0.001) sleep duration, compared with those with a normal range of sleep duration. Statistical significances were found in the prevalence of abdominal obesity among those with different characteristics in education, smoking, chronic conditions, and social participation. CONCLUSION: Both long and short sleep durations are associated with increased risk of obesity, which is more evident in older men. Bad living habits and mental state will increase the risk of abdominal obesity.


Assuntos
Obesidade Abdominal , Sono , Idoso , China , Humanos , Estudos Longitudinais , Masculino , Fatores de Tempo
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