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1.
Neurocrit Care ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480608

RESUMO

BACKGROUND: In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. RESULTS: A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. CONCLUSIONS: Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

2.
J Neurosci ; 42(13): 2662-2677, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35165175

RESUMO

Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity. Our results showed that global palmitoylation level, palmitoylation of PSD-95 and glutamate receptors, postsynapse density localization of PSD-95, surface expression of AMPARs, and synaptic strength of cultured hippocampal neurons were all enhanced by TTX pretreatment, and these can be reversed by inhibition of palmitoylation with palmitoyl acyl transferases inhibitors, 2-bromopalmitate and N-(tert-butyl) hydroxylamine hydrochloride. Importantly, we also found that acyl-protein thioesterase 1 (APT1)-mediated depalmitoylation is involved in palmitoylation of PSD-95 and glutamatergic synaptic transmission. Knockdown of APT1, not protein palmitoyl thioesterase 1, with shRNA, or selective inhibition, significantly increased AMPAR-mediated synaptic strength, palmitoylation levels, and synaptic or surface expression of PSD-95 and AMPARs. Results from hippocampal tissues and fear-conditioned rats showed that palmitoylation is required for synaptic strengthening and fear memory formation. These results suggest that palmitoylation and APT1-mediated depalmitoylation have critical effects on the regulation of glutamatergic synaptic plasticity, and it may serve as a potential target for learning and memory-associated disorders.SIGNIFICANCE STATEMENT Fear-related anxiety disorders, including post-traumatic stress disorder, are prevalent psychiatric conditions, and fear memory is associated with hyperexcitability in the hippocampal CA1 region. Palmitoylation is involved in learning and memory, but mechanisms coupling palmitoylation with fear memory acquisition remain poorly understood. This study demonstrated that palmitoylation is essential for postsynapse density-95 clustering and hippocampal glutamatergic synaptic transmission, and APT1-mediated depalmitoylation plays critical roles in the regulation of synaptic plasticity. Our study revealed that molecular mechanism about downregulation of APT1 leads to enhancement of AMPAR-mediated synaptic transmission, and that palmitoylation cycling is implicated in fear conditioning-induced synaptic strengthening and fear memory formation.


Assuntos
Hipocampo , Sinapses , Animais , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Ratos , Sinapses/metabolismo , Transmissão Sináptica/fisiologia
3.
Nature ; 543(7645): 385-390, 2017 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-28273060

RESUMO

Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.


Assuntos
Regulação do Apetite/fisiologia , Osso e Ossos/metabolismo , Lipocalina-2/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Osso e Ossos/citologia , AMP Cíclico/metabolismo , Ingestão de Alimentos/fisiologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Glucose/metabolismo , Homeostase , Hipotálamo/citologia , Hipotálamo/metabolismo , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Masculino , Camundongos , Neurônios/metabolismo , Obesidade/metabolismo , Osteoblastos/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , Magreza/metabolismo
5.
J Nurs Care Qual ; 38(3): E42-E49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36827597

RESUMO

BACKGROUND: To prevent recurrent stroke, patients need to follow evidence-based practices following discharge; however, adherence to these practices is suboptimal. PURPOSE: To evaluate whether a smartphone mobile application can improve medication adherence and stroke awareness in secondary stroke prevention. METHODS: A retrospective study design was used. Patients with ischemic stroke registered in a database between August 2018 and January 2019 were enrolled. Propensity score matching was used to match patients managed with the mobile application compared with regular practice in a 1:2 ratio. RESULTS: Sixty-five patients were paired with 123 controls. Three-month medication adherence was 93.8% in the application group versus 82.9% in the control group ( P = .036). Patients in the application group were more likely to know stroke warning signs ( P = .003) and when to call an ambulance for stroke symptoms (87.7% vs 72.4%, P = .016). CONCLUSIONS: Using a mobile application may increase medication adherence and stroke awareness in secondary stroke prevention.


Assuntos
Telefone Celular , Acidente Vascular Cerebral , Telemedicina , Humanos , Estudos de Coortes , Estudos Retrospectivos , Pontuação de Propensão , Acidente Vascular Cerebral/complicações , Assistência ao Paciente
6.
Osteoporos Int ; 33(9): 1957-1967, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35583602

RESUMO

The widely recommended fracture prediction tool FRAX was developed based on and for the general population. Although several adjusted FRAX methods were suggested for type 2 diabetes (T2DM), they still need to be evaluated in T2DM cohort. INTRODUCTION: This study was undertaken to develop a prediction model for Chinese diabetes fracture risk (CDFR) and compare its performance with those of FRAX. METHODS: In this retrospective cohort study, 1730 patients with T2DM were enrolled from 2009.08 to 2013.07. Major osteoporotic fractures (MOFs) during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Multivariate Cox regression with backward stepwise selection was used to fit the model. The performances of the CDFR model, FRAX, and adjusted FRAX were compared in the aspects of discrimination and calibration. RESULTS: 6.3% of participants experienced MOF during a median follow-up of 10 years. The final model (CDFR) included 8 predictors: age, gender, previous fracture, insulin use, diabetic peripheral neuropathy (DPN), total cholesterol, triglycerides, and apolipoprotein A. This model had a C statistic of 0.803 (95%CI 0.761-0.844) and calibration χ2 of 4.63 (p = 0.86). The unadjusted FRAX underestimated the MOF risk (calibration χ2 134.5, p < 0.001; observed/predicted ratio 2.62, 95%CI 2.17-3.08), and there was still significant underestimation after diabetes adjustments. Comparing FRAX, the CDFR had a higher AUC, lower calibration χ2, and better reclassification of MOF. CONCLUSION: The CDFR model has good performance in 10-year MOF risk prediction in T2DM, especially in patients with insulin use or DPN. Future work is needed to validate our model in external cohort(s).


Assuntos
Diabetes Mellitus Tipo 2 , Fraturas do Quadril , Insulinas , Osteoporose , Fraturas por Osteoporose , Densidade Óssea , Diabetes Mellitus Tipo 2/complicações , Fraturas do Quadril/epidemiologia , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
7.
Eur J Neurol ; 29(6): 1643-1651, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35143095

RESUMO

BACKGROUND AND PURPOSE: DIRECT-MT showed that endovascular thrombectomy was noninferior to thrombectomy preceded by intravenous alteplase with regard to functional outcome in patients with acute ischemic stroke. In this post hoc analysis, we examined whether infarct size modified the effect of alteplase. METHODS: All patients with baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) grades were included. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Multivariate ordinal logistic regression analysis was used to calculate the adjusted common odds ratio (OR) for better functional outcome based on the mRS for thrombectomy alone versus combination therapy. An interaction term was entered to test for an interaction with baseline ASPECTS subgroups: 0-4 versus 5-7 versus 8-10. RESULTS: Of 649 patients, 323 (49.8%) were in the thrombectomy-alone group and 326 (50.2%) in the combination-therapy group. There was no significant treatment-by-trichotomized ASPECTS interaction with alteplase prior to endovascular treatment for the primary endpoint of ordinal mRS (p-value interaction term relative to ASPECTS 8-10: ASPECTS 0-4, p = 0.386; ASPECTS 5-7, p = 0.936). Adjusted common ORs for improvement in the 90-day mRS with thrombectomy alone compared with combination therapy were 1.99 (95% confidence interval = 0.72-5.46) for ASPECTS 0-4, 1.07 (0.62-1.86) for ASPECTS 5-7, and 1.03 (0.74-1.45) for ASPECTS 8-10. There was no significant difference in the safety outcomes between the two groups. CONCLUSIONS: Baseline infarct size may not modify the effect of alteplase prior to endovascular thrombectomy with regard to favorable functional outcomes and adverse events.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Procedimentos Endovasculares/métodos , Fibrinolíticos/efeitos adversos , Humanos , Infarto/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
8.
Exp Cell Res ; 404(2): 112593, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33961841

RESUMO

AIMS: Acute lung injury (ALI) is a leading cause of mortality as a result of inflammatory cytokine overexpression and increased rates of apoptosis. Therapies for ALI are yet to be thoroughly investigated. Recent evidence has shown that irisin exerts protective effects against many types of pathologies. The present study aimed to determine the function of irisin in an ALI mouse model induced by lipopolysaccharide (LPS) and the corresponding underlying mechanisms at the tissue, cellular, and molecular levels. MAIN METHODS: We assessed irisin function in A549 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The cell apoptosis was evaluated by flow cytometry. Western blotting and RT-PCR were used to test expression level. Animal models of ALI was established. KEY FINDINGS: We found that irisin treatment maintained lung weight, significantly reduced inflammatory cytokine expression, and alleviated lung injury by downregulating miR-199a. In LPS-stimulated cells, forced miR-199a expression downregulated Rad23b expression by targeting its 3' untranslated region, indicating that Rad23b is a direct target of miR-199a. SIGNIFICANCE: These findings reveal that irisin can alleviate ALI by inhibiting miR-199a and upregulating Rad23b expression, suggesting that irisin has clinical potential for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fibronectinas/farmacologia , MicroRNAs/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação a DNA/efeitos dos fármacos , Modelos Animais de Doenças , Fibronectinas/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
9.
BMC Pregnancy Childbirth ; 21(1): 576, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34420520

RESUMO

BACKGROUND: There is no consensus or management algorithm for primary hyperparathyroidism (PHPT) in pregnancy. METHODS: This study comprises a retrospective case series. From August 2014 to December 2020, 9 cases of PHPT in pregnancy were diagnosed by a multidisciplinary team (MDT) consultation center of obstetrics in our hospital. Their clinical manifestations, treatment strategies, and maternal and infant outcomes were analyzed. RESULTS: The median onset age of the patients was 32 (25 ~ 38) years. PHPT was diagnosed in two cases before pregnancy, in six cases during pregnancy and in one case postpartum. The main clinical manifestations were nausea, vomiting, and other nonspecific symptoms, with anemia as the most common maternal complication. Hypercalcemia crisis was developed in one case. The median levels of preoperative serum calcium and parathyroid hormone (PTH) were 3.08 (2.77 ~ 4.21) mmol/L and 300.40 (108.80 ~ 2603.60) pg/ml, respectively. The parathyroid ultrasonography tests were positive in eight cases and negative in one patient who had an ectopic lesion localized by 99mTc-MIBI. Parathyroidectomy was conducted in 7 cases during the 2nd trimester, including 2 patients diagnosed before pregnancy who refused surgery, 1 patient during the 1st trimester, and 1 patient postpartum, with a significant reduction in serum concentrations of calcium and PTH. A management algorithm was developed. CONCLUSION: This case series suggests that pregnant women with PHPT should be managed by MDT according to the algorithm. If PHPT is confirmed in fertile women before pregnancy, parathyroidectomy should be strongly suggested and performed. If PHPT is diagnosed during pregnancy, even in its mild form, surgical treatment, optimally during the 2nd trimester, is effective and safe for pregnancy and neonatal outcome.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Comunicação Interdisciplinar , Paratireoidectomia , Resultado da Gravidez/epidemiologia , Adulto , Algoritmos , China/epidemiologia , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico , Paratireoidectomia/estatística & dados numéricos , Equipe de Assistência ao Paciente , Gravidez , Estudos Retrospectivos
10.
Korean J Physiol Pharmacol ; 25(2): 119-129, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33602882

RESUMO

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

11.
Neuroradiology ; 62(7): 867-876, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32242265

RESUMO

PURPOSE: Data on posterior circulation tandem occlusions in acute ischemic stroke are scarce: recognition may be challenging and little is known about optimal treatment strategy. We report our endovascular treatment strategy for posterior circulation tandem occlusion. METHODS: Consecutive patients with posterior circulation tandem occlusions in our centre were enrolled retrospectively. The preferred strategy was "distal-to-proximal" strategy, which means opening the distal occlusion first followed by treatment of the proximal pathology. The imaging characteristics, treatment strategy, clinical outcomes, and complications of patients with posterior circulation tandem occlusions were analyzed. RESULTS: In total, 21 patients with posterior circulation tandem occlusions were enrolled in the study, which accounted for 23.6% of patients with posterior circulation stroke in our centre. The mean age was 60 years (range 32 to 80), and median pre-procedure NIHSS score was 28 (interquartile range: 13-31). Eighteen patients (85.7%) had vertebrobasilar artery tandem occlusions and 3 (14.3%) had basilar artery to basilar artery tandem occlusions. All distal occlusions were successfully recanalized (modified TICI 2b/3). Two (9.5%) of the proximal lesions were not treated. A total of 57.1% of the patients had stents implanted on the proximal occlusions. The rate of mRS 0-3 at 3 months was 57.1% and the mortality rate was 19.0%. CONCLUSION: In patients with acute ischaemic stroke caused by posterior circulation tandem occlusions, we favor "distal-to-proximal" strategy based on the positive results in this small series. Nevertheless, a more extensive study is required to explore the optimal treatment strategy further.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Neuroimagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Beilstein J Org Chem ; 16: 233-247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180842

RESUMO

A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (K i = 0.011 µM) and I23 (K i = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (K i = 0.013 µM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.

13.
Endocr Pract ; 25(6): 534-544, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30865546

RESUMO

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width.


Assuntos
Diabetes Insípido Neurogênico , Hipopituitarismo , Doenças da Hipófise , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Hipófise
14.
Cytokine ; 102: 123-130, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28969944

RESUMO

AIMS: Inflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor 1α (SDF-1α), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1α expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1α and its correlation with aneurysm remodeling. METHODS: Saccular aneurysms were induced by porcine pancreatic elastase in New Zealand White rabbits. Aneurysm size was measured by digital subtraction angiography. Endothelial-like cells on the aneurysm wall were assessed on postoperative days 1, 3, 7, 14, 21, and 30. SDF-1α levels in the aneurysmal wall and serum were examined at several follow-up time points. Adherent molecule expression was examined, and migration assays were performed in vitro. After SDF-1α stimulation, the mobilization of endothelial-lineage cells and its role in the reendothelialization of the aneurysm wall were investigated in a saccular aneurysm rabbit model. RESULTS: After the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1α levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1α expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1α stimulation and down-regulated by the SDF-1α ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1α and blocked by AMD3100. The in vivo administration of SDF-α to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall. CONCLUSIONS: The SDF-1α expression level in the peripheral blood and local aneurysm wall correlated with the aneurysm remodeling process in rabbits with elastase-induced saccular aneurysms. We conclude that SDF-1α may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial-lineage cells.


Assuntos
Quimiocina CXCL12/fisiologia , Aneurisma Intracraniano/etiologia , Remodelação Vascular/fisiologia , Angiografia Digital , Animais , Antígenos CD/metabolismo , Benzilaminas , Caderinas/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quimiocina CXCL12/administração & dosagem , Quimiocina CXCL12/sangue , Ciclamos , Modelos Animais de Doenças , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Compostos Heterocíclicos/farmacologia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Masculino , Microscopia Eletrônica de Varredura , Elastase Pancreática/toxicidade , Coelhos , Remodelação Vascular/efeitos dos fármacos
15.
Diabetes Obes Metab ; 20(8): 1817-1828, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29687585

RESUMO

Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.


Assuntos
Osso e Ossos/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Modelos Biológicos , Estado Pré-Diabético/tratamento farmacológico , Animais , Depressores do Apetite/metabolismo , Depressores do Apetite/farmacologia , Depressores do Apetite/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/prevenção & controle , Metabolismo Energético/efeitos dos fármacos , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Secreção de Insulina/efeitos dos fármacos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Lipocalina-2/farmacologia , Lipocalina-2/uso terapêutico , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/farmacologia , Neuropeptídeo Y/uso terapêutico , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteocalcina/farmacologia , Osteocalcina/uso terapêutico , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/patologia , Estado Pré-Diabético/prevenção & controle , Ligante RANK/genética , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Ligante RANK/uso terapêutico , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Secretagogos/metabolismo , Secretagogos/farmacologia , Secretagogos/uso terapêutico
16.
Endocr Pract ; 24(4): 334-341, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29658832

RESUMO

OBJECTIVE: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture [MOF] and hip fracture [HF]) was assessed using the fracture risk assessment tool (FRAX). RESULTS: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH ( r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard ß = 0.073, P = .010) and HF (standard ß = 0.094, P = .004). CONCLUSION: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels. ABBREVIATIONS: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2/complicações , Fraturas por Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/complicações , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Vitamina D/análogos & derivados , Vitamina D/sangue
17.
World J Surg Oncol ; 15(1): 46, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28196488

RESUMO

BACKGROUND: Pilocytic astrocytomas (PAs) are slow growing neoplasms and usually located at the cerebellum. There has been certainty regarding the truthful benefit of surgical resection for patients with PA. Gross total resection (GTR) of PAs, especially those being situated in deep regions, remains a surgical challenge. Generally, they are considered as benign and usually develop in young patients. PAs, belonging to WHO I can be cured by radical resection. The patients with PA have excellent prognosis if complete resection can be conducted. The use of fluorescein in vermis PA surgery has not been yet reported. Our data presents fluorescein facilitates surgical resection of vermis PA. METHODS: Five milligrams per kilogram of fluorescein sodium was intravenously injected directly before general anesthesia for the three patients with PA. The yellow 560 filter was employed for microsurgical tumor resection. Surgical outcomes were assessed concerning the extent of resection. RESULTS: Most portion of PA in the three cases was found to be highly fluorescent after intravenous fluorescein sodium injection, which markedly enhanced tumor visibility. Gross total resection in all of the patients was achieved without further neurological deficits. No adverse effects and complications resulting from fluorescein sodium were observed over the postoperative course. CONCLUSIONS: Intraoperative guidance by fluorescein sodium as a new, simple, safe, and practical procedure can enhance the fidelity of tumor tissue and increase the possibility of completely resecting PAs.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Vermis Cerebelar/cirurgia , Meios de Contraste/metabolismo , Fluoresceína/metabolismo , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Vermis Cerebelar/diagnóstico por imagem , Vermis Cerebelar/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Procedimentos Neurocirúrgicos , Prognóstico
18.
World J Surg Oncol ; 15(1): 186, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29041974

RESUMO

BACKGROUND: We investigated the functional status of adult supratentorial superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant factors to guide the therapeutic strategy and improve the life quality of these patients. METHODS: Clinical materials from January 2008 to December 2010 in 104 adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged from 6 months to 1.5 years. The logistic regression was used to evaluate the preoperative and postoperative variation of functional status in patients to disclose the relevant factors affecting postoperative functional status, such as age, gender, the duration of symptom, size and location of the tumor, hemisphere, resection degree, and tumor pathologic grade and preoperative Karnofsky performance status (Pre-KPS). RESULTS: Four out of nine candidate factors are related to the postoperative functional status. They are age less than 40 years, the size of tumor less than 5 cm in diameter, tumor located in the right hemisphere, and limited resection of tumor in the eloquent area. CONCLUSIONS: It seems more meaningful to evaluate the functional status of the patients with ASS-LGG on the basis of these clinical features, involving age, tumor size, location, and extent of resection.


Assuntos
Glioma/cirurgia , Avaliação de Estado de Karnofsky , Procedimentos Neurocirúrgicos/efeitos adversos , Qualidade de Vida , Neoplasias Supratentoriais/cirurgia , Adulto , Fatores Etários , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Gradação de Tumores , Procedimentos Neurocirúrgicos/métodos , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Neoplasias Supratentoriais/patologia
19.
Eur Radiol ; 26(2): 351-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26007603

RESUMO

OBJECTIVES: We performed this study to report our experience using a stepwise stent deployment technique for the treatment of tandem intracranial aneurysms. METHODS: Patients with intracranial tandem aneurysms that were treated with a stepwise stent deployment technique between May 2009 and June 2013 were retrospectively reviewed. RESULTS: Twenty-one patients with 42 tandem aneurysms were identified (11 men, 10 women), with a mean age of 53.7 years (range, 17-82 years). Subarachnoid haemorrhage was confirmed in 12 patients using computed tomography at onset. Complete occlusion was achieved in 20 of the aneurysms (47.6%) after the procedure, neck remnant in 9 (21.4%), and aneurysm remnant in 13 (31.0%). The perioperative complications included in-stent thrombosis in one case and vasospasm in two cases, none of which left a permanent neurological deficit. The modified Rankin Scale (mRS) score at discharge was 0-2 in 20 cases and 3 in one case. The follow-up angiograms available for 17 patients showed complete occlusion in 26 aneurysms, improved in 4, and stable in 4. All of the patients had mRS scores of 0-1 during the clinical follow-up period. CONCLUSIONS: The stepwise stent deployment technique is feasible and helpful in the treatment of intracranial tandem aneurysms. KEY POINTS: • Treating wide-necked intracranial aneurysms with stent-assisted coiling is preferable. • Tandem wide-necked intracranial aneurysms can be treated with a single stent. • Stepwise stent deployment is technically feasible for embolizing tandem intracranial aneurysms.


Assuntos
Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/terapia , Stents , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral/métodos , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
20.
J Cardiovasc Pharmacol ; 67(6): 474-81, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26485210

RESUMO

Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.


Assuntos
Células Endoteliais/metabolismo , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Células Progenitoras Endoteliais/metabolismo , Músculo Liso Vascular/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais , Sirtuínas/metabolismo
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