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1.
Chem Biol Drug Des ; 103(1): e14419, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230792

RESUMO

Diabetic retinopathy (DR) is one of the most frequently occurring diabetic complications associated with inflammation and oxidative stress. Platycodin D (PLD) is a bio-active saponin that has been reported to exhibit anti-inflammation, anti-oxidative, and antidiabetic activities. Therefore, we speculated the protective effects of PLD on DR in the present study. Our results demonstrated that PLD attenuated high glucose (HG)-induced inflammation, as evidenced by decreased production of TNF-α, IL-1ß, IL-6. The HG-induced oxidative stress was prevented by PLD with decreased ROS production and malondialdehyde (MDA) level, as well as increased activities of superoxide dismutase and glutathione (GSH). In addition, treatment of PLD significantly decreased the apoptotic rate in HG-induced ARPE-19 cells. The HG-caused increases in expression of bax and cleaved capsase-3, as well a decrease in bcl-2 expression were attenuated by PLD. Furthermore, PLD suppressed the activation of TLR4/MyD88/NF-κB and enhanced the activation of Nrf2/HO-1 pathway in HG-induced ARPE-19 cells. Additionally, overexpression of TLR4 attenuated the anti-inflammatory, while knockdown of Nrf2 reversed the anti-oxidative and anti-apoptotic activities of PLD in HG-stimulated ARPE-19 cells. Furthermore, PLD attenuates retinal damage in DR rats. Finally, we demonstrated that PLD weakened the TLR4/MyD88/NF-κB p65 pathway and promoted the Nrf2/HO-1 pathway in vivo. Taken together, these findings indicated that PLD exerted protective effects against DR, which were attributed to the regulation of TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Saponinas , Triterpenos , Ratos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptor 4 Toll-Like/metabolismo , Retinopatia Diabética/tratamento farmacológico , Transdução de Sinais , Inflamação , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
2.
Front Neurosci ; 16: 925300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061613

RESUMO

Chronic neuropathic pain is commonly accompanied by cognitive impairment. However, the underlying mechanism in the occurrence of cognitive deficits under constant nociceptive irritation remains elusive. Herein, we established a chronic neuropathic pain model by chronic constriction injury (CCI) of the unilateral sciatic nerve in rats. Behavioral tests indicated that CCI rats with long-term nociceptive threshold decline developed significant dysfunction of working memory and recognitive memory starting at 14 days and lasting for at least 21 days. Afterward, circRNA expression profiles in the hippocampus of CCI and sham rats were analyzed via high-throughput sequencing to explore the potential key factors associated with cognitive impairment induced by ongoing nociception, which showed 76 differentially expressed circRNAs, 39 upregulated and 37 downregulated, in the CCI group. These differentially expressed circRNA host genes were validated to be primarily associated with inflammation and apoptotic signaling pathways according to GO/KEGG analysis and the circRNA-miRNA-mRNA network, which was also confirmed through the analysis of neuroinflammation and neuronal apoptosis. Consequently, we assumed that enhanced neuroinflammation and neuronal apoptosis might act as potential regulators of cognitive impairment induced by chronic neuropathic pain. The identification of the regulatory mechanism would provide promising clinical biomarkers or therapeutic targets in the diagnostic prediction and intervention treatment of memory deficits under neuropathic pain conditions.

3.
Front Microbiol ; 13: 947640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910610

RESUMO

Phages show promise in replacing antibiotics to treat or prevent bacterial diseases in the chicken breeding industry. Chicks are easily affected by their environment during early growth. Thus, this study investigated whether oral phages could affect the intestinal barrier function of chicks with a focus on the cecal microbiome. In a two-week trial, forty one-day-old hens were randomly divided into four groups: (1) NC, negative control; (2) Phage 1, 109 PFU phage/day (days 3-5); (3) Phage 2, 109 PFU phage/day (days 8-10); and (4) AMX, 1 mg/mL amoxicillin/day (days 8-10). High-throughput sequencing results of cecal contents showed that oral administration of phages significantly affected microbial community structure and community composition, and increased the relative abundance of Enterococcus. The number of different species in the Phage 1 group was much higher than that in the Phage 2 group, and differences in alpha and beta diversity also indicated that the magnitude of changes in the composition of the cecal microbiota correlated with the time of phage use. Particularly in the first stage of cecal microbiota development, oral administration of bacteriophages targeting Salmonella may cause substantial changes in chicks, as evidenced by the results of the PICRUSt2 software function prediction, reminding us to be cautious about the time of phage use in chicks and to avoid high oral doses of phages during the first stage. Additionally, the Phage 2 samples not only showed a significant increase in the relative abundance of Bifidobacterium and Subdoligranulum, but also improved the intestinal morphology (jejunum) and increased the mRNA expression level of occludin and ZO-1. We concluded that phages do not directly interact with eukaryotic cells. The enhancement of intestinal barrier function by phages in chicks may be related to changes in the intestinal flora induced by phages. This implies that phages may affect intestinal health by regulating the intestinal flora. This study provides new ideas for phage prevention of intestinal bacterial infections and promotes large-scale application of phages in the poultry industry.

4.
Front Microbiol ; 13: 940525, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875532

RESUMO

Salmonella enterica is not only the most common pathogen of poultry and poultry-derived products but is also a significant foodborne pathogen. In recent years, many S. enterica isolates have exhibited multi-drug resistance, which places huge pressure on global economy and health. Since phages are an attractive alternative to biocontrol pathogens, we isolated a total of 15 Salmonella phages from sewage effluent, sediment, and chicken manure. The GRNsp1, GRNsp3, GRNsp6, GRNsp21, GRNsp27, GRNsp30, GRNsp50, and GRNsp51 phages exhibited a wide host range against S. enterica serovars Enteritidis and Typhimurium in vitro. In particular, GRNsp51 exerted highly efficient lytic effects against a large proportion of S. Enteritidis and S. Typhimurium strains isolated from different regions of China. Meanwhile, GRNsp8 expanded the host range of GRNsp6 and GRNsp51. Based on their host ranges and lytic capacities, GRNsp6, GRNssp8, and GRNsp51 were selected for further investigation. Morphology, one-step growth curves, and stability assays revealed that GRNsp6, GRNsp8, and GRNsp51 all belong to the Caudovirales order and display relatively short latency periods with broad pH and thermal stability. Genomic analysis indicated that the genomes of these three phages contained no genes related to virulence, antibiotic resistance, or lysogeny. In addition, we tested the effectiveness of a cocktail composed of these three phages against S. Enteritidis in a chicken model. Treatment with the oral phage cocktail 24 h before or alongside Salmonella challenge significantly reduced colonization of the intestinal tract and decreased the mRNA expression of IL-6, IFN-γ, and IL-1ß in the duodenum. Together, these findings indicate that a cocktail of the GRNsp6, GRNsp8, and GRNsp51 phages could serve as an effective antimicrobial therapeutic agent against multidrug-resistant Salmonella in animal production to mitigate infections by multiple zoonotic Salmonella species.

5.
BMC Geriatr ; 22(1): 200, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287583

RESUMO

BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications of major surgery among elderly patients, remarkably decreasing patients' life quality. Platelet count has been proved to be an essential factor in inflammation. However, as far as we know, the relationship between platelet count and PND is not clear yet in the orthopedic area. PND could be a long-term disease, which sometimes lasts for several years, and it is meaningful to find a biomarker of PND at the early stage. Thus, we designed this study to find out the association between perioperative platelet count and occurrence of PND, and determine whether preoperative platelet count could be a biomarker of the early stage of PND. METHODS: A prospective observational study was performed on the patients who would take total knee arthroplasty or total hip arthroplasty. Their peripheral platelets were counted by blood routine examination 1 day before and 3 days after the surgery. And we assessed their neurocognitive functions 1 day before and 3 days after the surgery. These data were recorded and analyzed to find out the relationship between platelet count and the occurrence of PND. RESULTS: Eventually, 70 patients finished the whole process, and 14 of them developed PND. The median preoperative platelet count in the PND group was significantly higher than that in the non-PND group (239 vs 168 × 10^9/L, p = 0.009). Preoperative platelet count was an independent risk factor for PND (odds ratio = 1.014, 95% confidence interval [CI] 1.000-1.027, P = 0.043) in the logistic multivariable regression, while the area under the curve of the receiver operating characteristic curve of the prediction model was 0.796 (95% CI 0.676-0.916). CONCLUSIONS: The higher preoperative and postoperative level of platelet count in the peripheral blood were associated with the early stage of PND, and preoperative platelet count could be a potential predictor of the early stage of PND in patients undergoing major orthopedic surgeries. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033001 , registration date: 17 May 2020.


Assuntos
Transtornos Neurocognitivos , Procedimentos Ortopédicos , Idoso , Humanos , Transtornos Neurocognitivos/epidemiologia , Procedimentos Ortopédicos/efeitos adversos , Contagem de Plaquetas , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco
6.
Front Behav Neurosci ; 15: 646528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927600

RESUMO

Objective: Postoperative cognitive dysfunction (POCD) is a common and severe complication of cardiovascular surgery. Lymphocyte-to-monocyte ratio (LMR) has been reported to be an independent predictor of lots of diseases associated with inflammation, but the association between the LMR and POCD is not clear. The present study aimed to investigate the potential value of LMR level to predict POCD in patients undergoing cardiovascular surgery. Methods: A prospective observational study was performed on the patients diagnosed with heart diseases undergoing cardiovascular surgeries with cardiopulmonary bypass. The leukocyte counts were measured by blood routine examination preoperatively. Then we calculated the LMR by dividing the lymphocyte count by the monocyte count. Neurocognitive functions were assessed 1 day before and 7 days after surgery. Perioperative factors were recorded to explore the relationship between LMR and POCD. Results: In total, 75 patients finished the whole study, while 34 patients developed POCD. The preoperative LMR level in the POCD group was higher than that in the non-POCD group. A cutoff value of 4.855 was identified to predict POCD occurrence according to ROC curve. The perioperative dynamic change of LMR level in the POCD group was higher than those in the non-POCD group. A cutoff value of 2.255 was identified to predict POCD occurrence according to ROC curve and the dynamic LMR change had similar varying trend with preoperative LMR level. Conclusions: The dynamic change of LMR level in the peripheral blood is associated with occurrence of POCD, and preoperative LMR level seems to be a prognostic biomarker of postoperative cognitive dysfunction in patients after cardiovascular surgery.

7.
Am J Transl Res ; 12(8): 4594-4603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913533

RESUMO

This study aimed to evaluate the efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy. In this multicentered, blinded, randomized, active-controlled, non-inferior phase III trial, 384 eligible patients who were about to undergo colonoscopy were randomized as a ratio of 1:1 into remimazolam and propofol group. Procedure success was assessed and defined as the completion of colonoscopy without administration of rescue sedative agent or more than 5 top-ups of trial drug in any 15 minute-period after initial administration of trial drug. Sedation quality was evaluated by Modified Observer's Assessment of Alertness/Sedation score. Treatment-emergent adverse events were recorded. Procedure success rate was 96.91% (188/194) in remimazolam group and 100% (190/190) in propofol group, and the difference in rate was -3.09% with 95% confidence interval (CI) of -5.53%~-0.66%. Since the lower limit of 95% CI was greater than the non-inferiority margin of -8.00%, the efficacy of remimazolam tosylate was non-inferior to propofol. Besides, induction time of sedation was increased (P<0.001), while hypotension and respiratory depression was decreased in remimazolam group compared to propofol group; however, time to fully alert (P>0.05) or time to discharge (P>0.05) were unchanged. For safety assessment, total treatment-emergent adverse events were decreased in remimazolam group compared to propofol group (P<0.001); specifically, administration site pain (P<0.001), increased bilirubin (P=0.019), decreased respiratory rate (P<0.001) and decreased SpO2 (P<0.001) were less frequent in remimazolam group compared with propofol group. In conclusion, remimazolam tosylate is non-inferior in sedation efficacy while safer than propofol in patients undergoing colonoscopy.

8.
Front Med ; 14(6): 792-801, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32270434

RESUMO

Asthma is a serious health problem that involves not only the respiratory system but also the central nervous system. Previous studies identified either regional or network alterations in patients with asthma, but inconsistent results were obtained. A key question remains unclear: are the regional and neural network deficits related or are they two independent characteristics in asthma? Answering this question is the aim of this study. By collecting resting-state functional magnetic resonance imaging from 39 patients with asthma and 40 matched health controls, brain functional measures including regional activity (amplitude of low-frequency fluctuations) and neural network function (degree centrality (DC) and functional connectivity) were calculated to systematically characterize the functional alterations. Patients exhibited regional abnormities in the left angular gyrus, right precuneus, and inferior temporal gyrus within the default mode network. Network abnormalities involved both the sensorimotor network and visual network with key regions including the superior frontal gyrus and occipital lobes. Altered DC in the lingual gyrus was correlated with the degree of airway obstruction. This study elucidated different patterns of regional and network changes, thereby suggesting that the two parameters reflect different brain characteristics of asthma. These findings provide evidence for further understanding the potential cerebral alterations in the pathophysiology of asthma.


Assuntos
Asma , Imageamento por Ressonância Magnética , Asma/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos
9.
Eur J Ophthalmol ; 30(3): 500-505, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803266

RESUMO

AIM: The aim of this study was to investigate the expression of platelet-derived growth factor-C in aqueous humor of patients with neovascular glaucoma and its correlation with vascular endothelial growth factor. METHODS: This study involved 62 eyes of 62 patients with advanced neovascular glaucoma requiring transscleral cyclophotocoagulation. Aqueous humor was collected through paracentesis. Samples from 11 eyes of 11 patients with age-related cataract were collected as control. Concentrations of platelet-derived growth factor-C and vascular endothelial growth factor in aqueous humor were quantified by enzyme-linked immunosorbent assay. Meanwhile, the correlations between the concentrations of platelet-derived growth factor-C and vascular endothelial growth factor were analyzed. The elements including retinal photocoagulation treatment, iris neovascularization grade, and primary fundus disease were also studied to find out their roles in the concentrations of the two factors. RESULTS: The vascular endothelial growth factor and platelet-derived growth factor-C concentrations in aqueous humor from controls were (679.54 ± 49.81) pg/mL and (18.60 ± 1.85) pg/mL, respectively. Both of them were significantly lower than neovascular glaucoma patients (p < 0.001). The vascular endothelial growth factor and platelet-derived growth factor-C concentrations of neovascular glaucoma patients treated with retinal photocoagulation were (1095.99 ± 52.71) pg/mL and (28.55 ± 0.94) pg/mL, respectively, which were both significantly lower than those of untreated neovascular glaucoma patients, (1146.28 ± 69.57) pg/mL and (30.04 ± 1.64) pg/mL (p = 0.008, p = 0.034). There was a weak correlation between the expression level of vascular endothelial growth factor and platelet-derived growth factor-C in aqueous humor with neovascular glaucoma (r = 0.346, p = 0.006). However, iris neovascularization grade and primary fundus disease were not significant elements in the expression level of vascular endothelial growth factor and platelet-derived growth factor-C. CONCLUSION: Higher concentrations of vascular endothelial growth factor and platelet-derived growth factor-C were found in aqueous humor of patients with neovascular glaucoma compared with control, which could be lowered by retinal photocoagulation to some extent. Platelet-derived growth factor-C inhibitors may be another potential target for ocular neovascular diseases.


Assuntos
Humor Aquoso/metabolismo , Glaucoma Neovascular/metabolismo , Linfocinas/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Catarata/metabolismo , Corpo Ciliar/cirurgia , Ensaio de Imunoadsorção Enzimática , Feminino , Glaucoma Neovascular/cirurgia , Humanos , Pressão Intraocular , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Microscopia com Lâmpada de Fenda
10.
Brain Res ; 1724: 146463, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526800

RESUMO

A large body of evidence indicates that both the altered cytokines that mediate the immune-inflammatory process and abnormal gray matter are associated with schizophrenia. Whether peripheral cytokines are related to cerebral structural abnormality remains unclear. Therefore, we aimed to investigate the association of peripheral cytokine levels with gray matter abnormalities at the whole brain level in schizophrenia. Forty-four outpatients with schizophrenia and 44 controls were recruited. The serum levels of interleukin-1 beta (IL-1ß), IL-2, IL-6, IL-8, interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-ß), and IL-10 were measured using a quantitative chemiluminescence assay. High-resolution T1 weighted images were acquired from all subjects and processed using FreeSurfer software to obtain the cortical thickness, surface area, and cortical and subcortical gray matter volumes. The cytokines and cerebral structures were compared between patients and controls using analysis of covariance (ANCOVA). The association between the cytokines and whole cerebral structures was performed using stepwise linear regression. Patients had higher levels of IL-2, IL-6, IL-8, and IL-10 than controls. In patients, the IL-6 level was significantly associated with the cortical thickness in the left pars opercularis, right pars triangularis, left superior temporal gyrus, and right middle temporal gyrus, which showed structural differences between the two groups. Altered cytokine levels may be associated with particular but not all cortical abnormalities in schizophrenia, especially IL-6, which was significantly associated with the abnormal cortical thickness of the bilateral Broca's area and temporal gyrus, which provided neuroimaging evidence to support the relationship between peripheral cytokines and the cerebral cortex in schizophrenia.


Assuntos
Área de Broca/fisiopatologia , Citocinas/análise , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral , China , Citocinas/sangue , Citocinas/fisiologia , Feminino , Substância Cinzenta , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem , Esquizofrenia/metabolismo
11.
J Biomed Nanotechnol ; 15(9): 1897-1908, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387677

RESUMO

With the advance in nanomedicine, diagnostic and therapeutic nanoscale prodrugs have been rapidly developed in the field of cancer treatment. In this study, we constructed an enzyme-responsive polymer-paclitaxel (PTX) prodrug with a biocompatible saccharide-containing polymer backbone through the reversible addition-fragmentation chain transfer (RAFT) polymerization. A near-infrared fluorescent molecule (pheophorbide a) and magnetic resonance imaging (MRI) contrast agent (gadolinium-tetraazacyclododecanetetraacetic acid) were further conjugated onto the copolymer backbone to impart the ability of multimode imaging and tracing, forming the final diagnosis and treatment polymeric prodrug. This prodrug was amphiphilic and was able to self-assemble into uniform-size nanoparticles (80.1 nm). With the specific catalysis of enzymes, the anti-cancer drug, PTX, in the nanoparticles could be effectively released to kill cancer cells. The results of near-infrared fluorescence imaging and MRI showed that the diagnostic prodrug was preferentially concentrated at the tumor site compared with the free imaging reagents, suggesting improved and durable tumor imaging effects, which are beneficial for precise cancer diagnosis. The tumor growth in the mice could be effectively retarded after the administration of the prodrug. The tumor almost completely disappeared till the final treatment, and the tumor inhibition rate was as high as 96.4%. Immunohistochemical analysis indicated that the high anti-tumor effects might be attributed to the result that the prodrug not only induced the apoptosis of tumor cells, but also inhibited the formation of new blood vessels in the tumor environment. Therefore, this theranostic prodrug, which is based on the saccharide-containing polymer, holds potency for the development of a robust nanoscale platform for the diagnosis and treatment of cancer.


Assuntos
Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , Polímeros , Pró-Fármacos , Nanomedicina Teranóstica
12.
Respir Physiol Neurobiol ; 266: 89-94, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085322

RESUMO

Brain functional deficits had been reported in asthma patients. These deficits may be related to treatment resistance, inaccurate self-assessment and poor self-management. However, changes of the structural brain network in asthma patients remain largely unclear. Diffusion tensor imaging were acquired from 54 asthmatic patients and 44 controls. Then we calculated all the participants' structural network metrics. All the participants underwent the test of Hamilton Rating Scale for Depression and Anxiety as well as a lung function. Multiple linear correlation analyses were conducted. At the global level, asthma patients had a higher path length and lower global efficiency than controls, implying a shift toward regular networks. At the local level, asthma patients exhibited abnormal nodal connectivity with other nodes involved the fronto-limbic regions. Our findings highlight more locally segregated but less efficiently integrated structural networks, particularly involving frontal-limbic networks, in asthmatic patients. These findings provide important evidence to support the role of brain networks in the pathophysiology of asthma.


Assuntos
Asma/patologia , Depressão/patologia , Lobo Frontal/patologia , Sistema Límbico/patologia , Rede Nervosa/patologia , Adulto , Asma/diagnóstico por imagem , Conectoma , Depressão/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Sistema Límbico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem
13.
J Cell Biochem ; 120(4): 5644-5651, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30317656

RESUMO

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and is considered as a leading cause of blindness. Oxidative stress and inflammation are significant drivers for the development of DR. Eriodictyol, a flavonoid compound, was proved to possess anti-inflammatory, antioxidative, and antidiabetic activities. However, the role of eriodictyol in DR has not been unveiled. In the current study, we explored the protective effects of eriodictyol on high glucose (HG)-induced rat retinal ganglial cells (RGCs). The results suggested that eriodictyol improved cell viability of HG-induced rat RGC-5 cells in a dose-dependent manner. Eriodictyol reduced the reactive oxygen species production and increased the activities of superoxide dismutase, glutathione peroxidase and catalase in rat RGC-5 cells in response to HG stimulation. The production of proinflammatory cytokines including tumor necrosis factor alpha and interleukin-8 was diminished after eriodictyol treatment. Eriodictyol also suppressed cell apoptosis induced HG in rat RGC-5 cells. Furthermore, eriodictyol enhanced the nuclear translocation of nuclear factor erythroid-2 (E2)-related factor 2 (Nrf2) and elevated the expression of antioxidant enzyme heme-oxygenase-1 (HO-1). These findings suggested that eriodictyol protects the RGC-5 cells from HG-induced oxidative stress, inflammation, and cell apoptosis through regulating the activation of Nrf2/HO-1 pathway.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Flavanonas/farmacologia , Glucose/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Animais , Linhagem Celular , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Ratos , Células Ganglionares da Retina/patologia
14.
PLoS One ; 13(9): e0202772, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30212490

RESUMO

Studies have established that oxidative stress plays an important role in the pathology of myocardial ischemia/reperfusion injury (MIRI). Vascular endothelial growth factor receptor 1 (VEGFR1) activation was reported to reduce oxidative stress and apoptosis. In the present study, we tested the hypothesis that the activation of VEGFR1 by placental growth factor (PlGF) could reduce MIRI by regulating oxidative stress. Mouse hearts and neonatal mouse cardiomyocytes were subjected to ischemia/reperfusion (I/R) and oxygen glucose deprivation (OGD), respectively. PlGF pretreatment markedly ameliorated I/R injury, as demonstrated by reduced infarct size and improved cardiac function. The protection was associated with a reduction of cardiomyocyte apoptosis. Similarly, our in vitro study showed that PlGF treatment improved cell viability and reduced cardiomyocyte apoptosis. Also, activation of VEGFR1 by PlGF suppressed intracellular and mitochondrial reactive oxygen species (ROS) generation. However, VEGFR1 neutralizing monoclonal antibody, which preventing PlGF binding, totally blocked this protective effect. In conclusion, activation of VEGFR1 could protect heart from I/R injury by suppression of oxidative stress and apoptosis.


Assuntos
Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/citologia , Fator de Crescimento Placentário/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator de Crescimento Placentário/farmacologia , Resultado do Tratamento
15.
Biomed Opt Express ; 9(7): 3153-3166, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29984089

RESUMO

The segmentation and classification of retinal arterioles and venules play an important role in the diagnosis of various eye diseases and systemic diseases. The major challenges include complicated vessel structure, inhomogeneous illumination, and large background variation across subjects. In this study, we employ a fully convolutional network to simultaneously segment arterioles and venules directly from the retinal image, rather than using a vessel segmentation-arteriovenous classification strategy as reported in most literature. To simultaneously segment retinal arterioles and venules, we configured the fully convolutional network to allow true color image as input and multiple labels as output. A domain-specific loss function was designed to improve the overall performance. The proposed method was assessed extensively on public data sets and compared with the state-of-the-art methods in literature. The sensitivity and specificity of overall vessel segmentation on DRIVE is 0.944 and 0.955 with a misclassification rate of 10.3% and 9.6% for arteriole and venule, respectively. The proposed method outperformed the state-of-the-art methods and avoided possible error-propagation as in the segmentation-classification strategy. The proposed method was further validated on a new database consisting of retinal images of different qualities and diseases. The proposed method holds great potential for the diagnostics and screening of various eye diseases and systemic diseases.

16.
Front Neurosci ; 12: 318, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867329

RESUMO

Introduction: There are still uncertainties about the true nature of age related changes in topological properties of the brain functional network and its structural connectivity during various developmental stages. In this cross- sectional study, we investigated the effects of age and its relationship with regional nodal properties of the functional brain network and white matter integrity. Method: DTI and fMRI data were acquired from 458 healthy Chinese participants ranging from age 8 to 81 years. Tractography was conducted on the DTI data using FSL. Graph Theory analyses were conducted on the functional data yielding topological properties of the functional network using SPM and GRETNA toolbox. Two multiple regressions were performed to investigate the effects of age on nodal topological properties of the functional brain network and white matter integrity. Result: For the functional studies, we observed that regional nodal characteristics such as node betweenness were decreased while node degree and node efficiency was increased in relation to increasing age. Perversely, we observed that the relationship between nodal topological properties and fasciculus structures were primarily positive for nodal betweenness but negative for nodal degree and nodal efficiency. Decrease in functional nodal betweenness was primarily located in superior frontal lobe, right occipital lobe and the global hubs. These brain regions also had both direct and indirect anatomical relationships with the 14 fiber bundles. A linear age related decreases in the Fractional anisotropy (FA) value was found in the callosum forceps minor. Conclusion: These results suggests that age related differences were more pronounced in the functional than in structural measure indicating these measures do not have direct one-to-one mapping. Our study also indicates that the fiber bundles with longer fibers exhibited a more pronounced effect on the properties of functional network.

17.
Zhongguo Zhong Yao Za Zhi ; 42(11): 2068-2071, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28822149

RESUMO

The study aims at predicting ecological suitability of Ephedra intermedia in China by using maximum entropy Maxent model combined with GIS, and finding the main ecological factors affecting the distribution of E. intermedia suitability in appropriate growth area. Thirty-eight collected samples of E. intermedia and E. intermedia and 116 distribution information from CVH information using ArcGIS technology were analyzed. MaxEnt model was applied to forecast the E. intermedia in our country's ecology. E. intermedia MaxEnt ROC curve model training data and testing data sets the AUC value was 0.986 and 0.958, respectively, which were greater than 0.9, tending to be 1.The calculated E. intermedia habitat suitability by the model showed a high accuracy and credibility, which indicated that MaxEnt model could well predict the potential distribution area of E. intermedia in China.


Assuntos
Ecossistema , Ephedra/crescimento & desenvolvimento , China , Ecologia
18.
Med Sci Monit ; 23: 114-120, 2017 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-28064304

RESUMO

BACKGROUND Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)-guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. MATERIAL AND METHODS Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. RESULTS No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ²=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ²=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ²=0.25, P=0.88). CONCLUSIONS The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach.


Assuntos
Procedimentos Endovasculares/métodos , Artéria Oftálmica/cirurgia , Oclusão da Artéria Retiniana/terapia , Angiografia Digital/métodos , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Papaverina/uso terapêutico , Terapia Trombolítica/métodos , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Acuidade Visual
19.
Sci Rep ; 6: 34603, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27698369

RESUMO

Retinal vasculature analysis is important for the early diagnostics of various eye and systemic diseases, making it a potentially useful biomarker, especially for resource-limited regions and countries. Here we developed a smartphone-based retinal image analysis system for point-of-care diagnostics that is able to load a fundus image, segment retinal vessels, analyze individual vessel width, and store or uplink results. The proposed system was not only evaluated on widely used public databases and compared with the state-of-the-art methods, but also validated on clinical images directly acquired with a smartphone. An Android app is also developed to facilitate on-site application of the proposed methods. Both visual assessment and quantitative assessment showed that the proposed methods achieved comparable results to the state-of-the-art methods that require high-standard workstations. The proposed system holds great potential for the early diagnostics of various diseases, such as diabetic retinopathy, for resource-limited regions and countries.


Assuntos
Bases de Dados Factuais , Retinopatia Diabética , Processamento de Imagem Assistida por Computador , Aplicativos Móveis , Sistemas Automatizados de Assistência Junto ao Leito , Vasos Retinianos/diagnóstico por imagem , Smartphone , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/diagnóstico por imagem , Feminino , Humanos , Masculino
20.
Radiology ; 279(3): 867-75, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27007945

RESUMO

Purpose To determine whether the brain functional abnormalities of drug-naive first-episode schizophrenia are reduced after 1 year of undergoing antipsychotic treatment and whether pretreatment resting-state functional magnetic resonance (MR) imaging parameters are associated with longitudinal changes in clinical symptoms. Materials and Methods This prospective study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty antipsychotic-naive first-episode patients with schizophrenia and 16 healthy individuals were recruited and underwent resting-state functional MR imaging at baseline and again at 1-year follow-up, by which time significant clinical improvement was seen. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were analyzed with analysis of covariance. Results The amount of ALFF in the right inferior parietal lobule (IPL) and orbitofrontal cortex (OFC) and the amount of FC between the bilateral IPLs significantly increased over the follow-up period, and the amount of ALFF in the right occipital gyrus was reduced (P < .050, AlphaSim corrected [ http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf ]), returning toward normal levels. Furthermore, the degree of alteration in ALFF values in the right OFC (P = .037) and occipital gyrus (P = .002) at baseline was significantly correlated with the magnitude of the normalization in those regions at 1-year follow-up. In contrast, abnormalities of ALFF in the bilateral thalamus, ventral medial prefrontal cortex, precuneus, and right amygdala and of FC between the right OFC and the dorsal medial prefrontal cortex at baseline did not improve in patients at 1-year follow-up. Conclusion These findings show that some, but not all, neurophysiologic alterations that occur during the acute phase of schizophrenia are normalized in the context of clinical improvement and suggest therapeutic implications for exploration of which alterations in regional and network-level brain function evolve over time in patients with schizophrenia and which reflect persistent pathologic traits. Online supplemental material is available for this article.


Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico por imagem , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Estudos Prospectivos , Esquizofrenia/fisiopatologia , Adulto Jovem
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