RESUMO
Phase shifting fringe projection profilometry is a widely used optical 3D surface measurement method due to its high resolution, high speed, and full-field inspection. However, the measurement accuracy decreases in regions with a reflectivity or distance discontinuity. To this end, first, a general continuous quasi-one-dimensional phase error model is proposed for discontinuity representation. Second, the discontinuities are further divided into degenerate and nondegenerate discontinuities to improve the computational speed. Third, a phase error compensation algorithm is proposed with a parameter estimation method to improve the measurement accuracy. Simulations and experiments demonstrate that the proposed methods are effective.
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Multisystem inflammatory syndrome in children (MIS-C) is a type of hyperinflammatory symptoms similar to Kawasaki disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is commonly observed in children aged 8-10 years. Primary therapeutic medications for MIS-C are intravenous immunoglobulins and glucocorticoids. It has been reported that biologics, such as IL-1 receptor antagonist anakinra, IL-6 receptor antagonist tocilizumab, and TNF-α receptor antagonist infliximab, can be used as an option for critically ill patients. This article elaborates on the mechanism of action of the above biologics and discusses the efficacy and safety biologics in the treatment of MIS-C after SARS-CoV-2 infection, in order to provide methods for the treatment of MIS-C with severe symptoms.
Assuntos
Produtos Biológicos , COVID-19 , COVID-19/complicações , Criança , Humanos , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
BACKGROUND: The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. METHODS: We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People's Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. RESULTS: In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = - 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. CONCLUSIONS: Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.
Assuntos
COVID-19 , Proteína D Associada a Surfactante Pulmonar , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
BACKGROUND: We have previously reported that the long-term exposure of organophosphorus induces vascular dementia (VD) in rats. As a coenzyme, vitamin B6 is mainly involved in the regulation of metabolisms. Whether vitamin B6 improves VD remains unknown. METHODS: The model of VD was induced by feeding rats with isocarbophos (0.5 mg/kg per two day, 12 weeks). The blood flow of the posterior cerebral artery (PCA) in rat was assessed by transcranial Doppler (TCD). The learning and memory were evaluated by the Morris Water Maze (MWM) test. RESULTS: Administration of vitamin B6 increased the blood flow in the right and left posterior cerebral arteries and improved the functions of learning and memory in isocarbophos-treated rats. Vitamin B6 increased the protein levels of N-methyl-D-aspartate receptor (NMDAR) 2B, postsynaptic densities (PSDs) protein 95, and calmodulin-dependent protein kinase II (CaMK-II) in the hippocampus, which were decreased by isocarbophos in rats. Morphological analysis by light microscope and electronic microscope indicated disruptions of the hippocampus caused by isocarbophos were normalized by vitamin B6. Importantly, the antagonist of NMDAR signaling by eliprodil abolished these beneficial effects produced by vitamin B6 on PCA blood flow, learning, memory, and hippocampus structure in rats, as well as the protein expression of NMDAR 2B, PSDs protein 95, and CaMK-II in the hippocampus. CONCLUSION: Vitamin B6 activates NMDAR signaling to prevent isocarbophos-induced VD in rats.
Assuntos
Demência Vascular/metabolismo , Demência Vascular/prevenção & controle , Receptores de N-Metil-D-Aspartato/metabolismo , Vitamina B 6/farmacologia , Complexo Vitamínico B/farmacologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Demência Vascular/induzido quimicamente , Proteína 4 Homóloga a Disks-Large/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Hipertensão/fisiopatologia , Malation/análogos & derivados , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Piperidinas/farmacologia , Artéria Cerebral Posterior/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Ultrassonografia DopplerRESUMO
BACKGROUND: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressing c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells. In this present study, we aimed to investigate whether there is a negative feedback regulation between microRNA let-7g and LOX-1 in hypoxia-induced proliferation of PASMCs. METHODS: SD Rats were exposed to hypoxia (10% O2, 3 weeks) to induce PH. HE staining was used to evaluate pulmonary artery remodeling. in situ hybridization and immunohistochemistry were performed to assess the expression and distribution of let-7g and LOX-1, respectively. MTS, EDU and flow cytometry were performed to evaluate PASMCs proliferation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess the expression of let-7g, LOX-1, calpain-1,-2,-4, and OCT-1. RESULTS: The expression of let-7g was significantly down-regulated in pulmonary arteries of hypoxia-induced PH rats accompanied by pulmonary vascular remodeling, whereas let-7g mimic inhibited hypoxia-induced proliferation of PASMCs and up-regulation of LOX-1 expression. LOX-1 blocking reversed hypoxia-induced down-regulation of let-7g expression. Calpains, protein kinase C and OCT-1 were involved in negative feedback regulation between let-7g and LOX-1. CONCLUSION: Negative feedback regulation between let-7g and LOX-1 mediated hypoxia-induced proliferation of in PASMCs.
Assuntos
Retroalimentação Fisiológica , Hipóxia , MicroRNAs/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Artéria Pulmonar/citologia , Receptores Depuradores Classe E/metabolismo , Animais , Proliferação de Células , Regulação para Baixo , Masculino , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Receptores Depuradores Classe E/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg). Typical lesions of diabetic pulmonary fibrosis were observed 8 weeks after STZ injection by hematoxylin-eosin (HE) and Masson staining. Human bronchial epithelial cells (HBECs) and A549 cells were treated by high glucose. Gene or protein expression was measured by real-time PCR, Western blot, immunohistochemistry or immunofluorescence. The knockdown of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) or transforming growth factor-ß1 (TGF-ß1) was conducted by siRNA. RESULTS: Activation of EMT was observed in lung tissues of STZ-induced diabetic rats, exhibiting a loss in the epithelial cell marker E-cadherin and an increase in the mesenchymal marker Vimentin. The protein and mRNA levels of LOX-1, TGF-ß1 and krüppel-like factor 6 (KLF6) in the lung tissues were increased. Incubation of HBECs and A549 cells with high glucose activated EMT and induced an increase in LOX-1, TGF-ß1 and KLF-6 expression. LOX-1 siRNA inhibited high glucose-induced EMT in HBECs and A549 cells, which correlated with the reduction of TGF-ß1. TGF-ß1 siRNA decreased the expression of LOX-1 and KLF6. CONCLUSIONS: EMT was involved in the pathological process of diabetic pulmonary fibrosis, which was activated by LOX-1/TGF-ß1/KLF6 signaling pathway.
Assuntos
Diabetes Mellitus Experimental/complicações , Transição Epitelial-Mesenquimal/fisiologia , Pulmão/patologia , Fibrose Pulmonar/etiologia , Células A549 , Animais , Western Blotting , Caderinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Fator 6 Semelhante a Kruppel/genética , Fator 6 Semelhante a Kruppel/metabolismo , Pulmão/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/metabolismo , Transdução de Sinais/fisiologia , Estreptozocina , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Vimentina/metabolismoRESUMO
Recent studies revealed that sirtuin 1 (SIRT1) is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM-0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet (HFD)-induced obese mice were intragastrically administered with BTM-0512 (5, 10, and 20 mg/kg/day) or resveratrol (10 mg/kg/day). It was found that the body weight, Lee's index, ratio of visceral adipose tissue (VAT) to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol. BTM-0512 up-regulated the expressions of SIRT1, full length PRDM16 (fPRDM16), total PRDM16 (tPRDM16, including fPPRDM16 and other PRDM16 isoforms), and uncoupling protein 1 (UCP1) in both brown and subcutaneous adipose tissues. Although BTM-0512 and resveratrol also up-regulated SIRT1 and tPRDM16 levels in VAT of HFD-induced obese mice, the expressions of fPRDM16, UCP1, and TMEM26 were down-regulated. In mouse primary subcutaneous preadipocytes cultured with or without adipogenic medium, BTM-0512 up-regulated fPRDM16, tPRDM16, and UCP1 expressions, which was reversed by SIRT1 antagonists. But in cultured brown and visceral adipocytes, the UCP1 protein level showed no significant change after treatment with 1 µM of BTM-0512. Moreover, transfection with human SIRT1 plasmid reduced lipid deposit, as well as the mRNA levels of fPRDM16, UCP1, and TMEM26, in cultured human visceral adipose-derived stem cells. In conclusion, BTM-0512 has stronger anti-obesity effect than resveratrol, which might be associated with activation of beige remodeling in subcutaneous adipose tissue.
Assuntos
Adipócitos/efeitos dos fármacos , Tecido Adiposo Bege/efeitos dos fármacos , Obesidade/prevenção & controle , Estilbenos/farmacologia , Gordura Subcutânea/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Bege/citologia , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/etiologia , Obesidade/metabolismo , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estilbenos/química , Gordura Subcutânea/citologia , Gordura Subcutânea/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction.
Assuntos
Disfunção Cognitiva/induzido quimicamente , Hipocampo/efeitos dos fármacos , Malation/análogos & derivados , Artéria Cerebral Média/efeitos dos fármacos , Praguicidas/toxicidade , Artéria Cerebral Posterior/efeitos dos fármacos , Acetilcolina/antagonistas & inibidores , Acetilcolina/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Circulação Cerebrovascular , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Expressão Gênica , Hipocampo/irrigação sanguínea , Hipocampo/metabolismo , Hipocampo/patologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Malation/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Artéria Cerebral Média/metabolismo , Artéria Cerebral Média/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Artéria Cerebral Posterior/metabolismo , Artéria Cerebral Posterior/patologia , Cultura Primária de Células , Ratos , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND: Endothelial cell apoptosis contributes to cardiovascular diseases such as hypertension, atherosclerosis. MicroRNA regulates endothelial cell function but its role in endothelial cell apoptosis remains to be fully elucidated. This study aims to investigate the role of miR-590-5p in endothelial cell apoptosis and dissect the underlying mechanisms. METHODS: Flow cytometric analysis, Hoechst 33258 staining and Western blotting were performed to evaluate human umbilical vein endothelial cell (HUVEC) apoptosis induced by Angiotensin (Ang) II. Western blotting and real-time quantitative PCR were conducted to assess the expression of LOX-1. DCFH-DA staining was carried out to measure the generation of reactive oxygen species (ROS). RESULTS: Ang II-induced HUVEC apoptosis was accompanied by downregulation of miR-590-5p; administration of miR-590-5p mimics attenuated HUVEC apoptosis and decreased ROS generation, as indicated by reduced fraction of apoptotic HUVECs and decreased caspase-3 activity. LOX-1 expression was increased by Ang II, and miR-590-5p mimics reduced LOX-1 expression in HUVECs in the absence or presence of Ang II. Pharmacologic or genetic block of LOX-1 with small interference RNA or TS92 (LOX-1 neutralizing antibody) significantly ameliorated HUVEC apoptosis, as evidenced by reduced number of apoptotic HUVECs, inhibited caspase-3 activation and suppressed mitochondrial cytochrome C release. Moreover, LOX-1 siRNA or TS92 treatment dramatically reduced ROS production in HUVECs treated with Ang II. CONCLUSION: Our data demonstrated that miR-590-5p downregulation promoted Ang II-induced endothelial cell apoptosis by elevating LOX-1 expression and consequently increasing ROS generation. Thus, restoration of miR-590-5p or block of LOX-1 could be therapeutically exploited to alleviate endothelial cell apoptosis.
Assuntos
Angiotensina II/metabolismo , Apoptose/fisiologia , MicroRNAs/metabolismo , Receptores Depuradores Classe E/metabolismo , Angiotensina II/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe E/genética , Regulação para Cima/efeitos dos fármacosRESUMO
We have found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-ß1 is mediated via the ERK1/2 pathway. Whether ERK1/2 - eIF3a signal pathway is involved in calcitonin gene-related peptide (CGRP)-mediated pathogenesis of bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. Sensory CGRP depletion by capsaicin exacerbated bleomycin-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-ß1, eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. Exogenous application of CGRP significantly inhibited TGF-ß1-induced proliferation and differentiation of pulmonary fibroblasts concomitantly with decreased expression of eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. These effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK1/2 - eIF3a signaling pathway.
Assuntos
Bleomicina/toxicidade , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Animais , Antibióticos Antineoplásicos/toxicidade , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Células Cultivadas , Regulação para Baixo/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Fibrose Pulmonar/tratamento farmacológico , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To explore the role of calpain in pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension and the underlying mechanisms.â© METHODS: Sprague-Dawley rats were randomly divided into the hypoxia group and the normoxia control group. Right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored by a method with right external jugular vein cannula. Right ventricular hypertrophy index was presented as the ratio of right ventricular weight to left ventricular weight (left ventricle plus septum weight). Levels of calpain-1, -2 and -4 mRNA in pulmonary artery were determined by real-time PCR. Levels of calpain-1, -2 and -4 protein were determined by Western blot. Primary rat pulmonary arterial smooth muscle cells (PASMCs) were divided into 4 groups: a normoxia control group, a normoxia+MDL28170 group, a hypoxia group and a hypoxia+MDL28170 group. Cell proliferation was detected by MTS and flow cytometry. Levels of Ki-67 and proliferating cell nuclear antigen (PCNA) mRNA were determined by real-time PCR.â© RESULTS: RVSP, mPAP and right ventricular remodeling index were significantly elevated in the hypoxia group compared to those in the normoxia group. In the hypoxia group, pulmonary vascular remodeling was significantly developed, accompanied by up-regulation of calpain-1, -2 and -4. MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs concomitant with the suppression of Ki-67 and PCNA mRNA expression.â© CONCLUSION: Calpain mediates vascular remodeling via promoting proliferation of PASMCs in hypoxia-induced pulmonary hypertension.
Assuntos
Calpaína/fisiologia , Hipertensão Pulmonar/fisiopatologia , Remodelação Vascular/genética , Remodelação Vascular/fisiologia , Animais , Calpaína/genética , Proliferação de Células , Dipeptídeos/fisiologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertrofia Ventricular Direita , Hipóxia , Antígeno Ki-67/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
Long non-coding RNA (lncRNA) is a type of DNA transcript that is longer than 200 nucleotides (nt). They do not encode proteins, but they control gene expression on various levels. Long non-coding RNA metastasis-associated urothelial carcinoma associated 1 (UCA1) was confirmed to play an important role in the occurrence and development of many tumor and non-tumor diseases. UCA1 mainly interacts with proteins in the nucleus, regulating gene expression in transcription and post-transcription. UCA1 is highly expressed in tumor tissue, and therefore can be related to clinical parameters. It may regulate tumor cell proliferation, invasion, apoptosis, and migration, so UCA1 can be applied in clinical prognosis and targeted therapy. This review mainly elaborates the roles of UCA1 in tumor diseases of the respiratory, digestive, reproductive, and urinary systems; and in non-tumor diseases.
Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Humanos , PrognósticoRESUMO
The risk of cardiovascular complications in diabetic patients is mainly associated with endothelial dysfunction. Reduced number of EPCs and impaired function of EPCs in diabetes result in imbalance of endothelial homeostasis and dysfunction of vessels. In patients with diabetes mellitus, plasma levels of asymmetric dimethylarginine (ADMA) were elevated, while the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) were reduced. In the present study, we investigated the role of the DDAH2/ADMA pathway in the senescence of EPCs in type 2 diabetic patients and cultured EPCs treated with high glucose. The results showed that the percentage of senescent EPCs increased while the expression of DDAH2 decreased concomitantly with an increase in the plasma levels of ADMA in patients with type 2 diabetes mellitus (T2DM). Similar results were seen in cultured EPCs treated with high glucose. Exogenous application of ADMA accelerated the senescence of EPCs in a dose-dependent manner, and overexpression of DDAH2 inhibited high glucose-induced EPCs senescence. In addition, it has also been reported that DDAH/ADMA pathway is regulated by silent information regulator 1 (SIRT1) in endothelial cell. In the present study, we found decreased expression of SIRT1 both in T2DM patients and EPCs pretreated with high glucose. And resveratrol (activating SIRT1) inhibited high glucose-induced EPCs senescence by upregulating the expression of DDAH2 and decreasing the levels of ADMA. Taken together, we concluded that DDAH2/ADMA is involved in the accelerated senescence of EPCs in diabetes, which is associated with the activation of SIRT1.
Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/patologia , Células Progenitoras Endoteliais/patologia , Arginina/sangue , Arginina/metabolismo , Senescência Celular , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sirtuína 1/metabolismoRESUMO
Recent studies demonstrated that NADPH oxidase 2 (NOX2) expression in myocardium after ischemia-reperfusion (IR) is significantly upregulated. However, the underlying mechanisms remain unknown. This study aims to determine if nuclear cardiac myosin light chain 2 (MYL2), a well-known regulatory subunit of myosin, functions as a transcription factor to promote NOX2 expression following myocardial IR in a phosphorylation-dependent manner. We examined the phosphorylation status of nuclear MYL2 (p-MYL2) in a rat model of myocardial IR (left main coronary artery subjected to 1 h ligation and 3 h reperfusion) injury, which showed IR injury and upregulated NOX2 expression as expected, accompanied by elevated H2O2 and nuclear p-MYL2 levels; these effects were attenuated by inhibition of myosin light chain kinase (MLCK). Next, we explored the functional relationship of nuclear p-MYL2 with NOX2 expression in H9c2 cell model of hypoxia-reoxygenation (HR) injury. In agreement with our in vivo findings, HR treatment increased apoptosis, NOX2 expression, nuclear p-MYL2 and H2O2 levels, and the increases were ameliorated by inhibition of MLCK or knockdown of MYL2. Finally, molecular biology techniques including co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), DNA pull-down and luciferase reporter gene assay were utilized to decipher the molecular mechanisms. We found that nuclear p-MYL2 binds to the consensus sequence AGCTCC in NOX2 gene promoter, interacts with RNA polymerase II and transcription factor IIB to form a transcription preinitiation complex, and thus activates NOX2 gene transcription. Our results demonstrate that nuclear MYL2 plays an important role in IR injury by transcriptionally upregulating NOX2 expression to enhance oxidative stress in a phosphorylation-dependent manner.
Assuntos
Miosinas Cardíacas/fisiologia , Glicoproteínas de Membrana/genética , Miocárdio/metabolismo , Cadeias Leves de Miosina/fisiologia , NADPH Oxidases/genética , Animais , Miosinas Cardíacas/análise , Núcleo Celular/química , Células Cultivadas , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Cadeias Leves de Miosina/análise , Quinase de Cadeia Leve de Miosina/antagonistas & inibidores , NADPH Oxidase 2 , Estresse Oxidativo , Fosforilação , Ratos , Ratos Sprague-DawleyRESUMO
Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase-domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.
Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Diferenciação Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Amidoidrolases/antagonistas & inibidores , Amidoidrolases/genética , Arginina/farmacologia , Células Cultivadas , Senescência Celular , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Recent studies show that resveratrol exerts beneficial effects on prevention of pulmonary hypertension. This study is performed to explore the effects of trimethoxystilbene, a novel resveratrol analog, on rat pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary arterial hypertension (PAH) and the underlying mechanisms. Sprague-Dawley rats were placed in a chamber and exposed to 10% O(2) continuously for 4 weeks to induce PAH. The effects of trimethoxystilbene (5 or 10 mg/kg per day, intragastric [i.g.]) and resveratrol (as a positive control, 25 mg/kg per day, i.g.) on hypoxia-induced PAH vascular remodeling and right ventricle hypertrophy were evaluated. At the end of experiments, the index for pulmonary vascular remodeling and right ventricle hypertrophy, inflammatory cell infiltration in lung tissue, the plasma levels and lung tissue contents of hydrogen peroxide (H(2)O(2)), the mRNA and protein levels for NADPH oxidases (NOX2, NOX4) and vascular peroxidase 1 (VPO1) in pulmonary artery or right ventricle were measured. The results showed that trimethoxystilbene treatment significantly attenuated hypoxia-induced pulmonary vascular remodeling (such as decrease in the ratio of wall thickness to vessel external diameter) and right ventricle hypertrophy (such as decrease in the ratio of right ventricle weight to the length of the tibia), accompanied by downregulation of NOX2, NOX4, and VPO1 expression in pulmonary artery or right ventricle, decrease in H(2)O(2) production and inflammatory cell infiltration in lung tissue. Trimethoxystilbene is able to prevent pulmonary vascular remodeling and right ventricle hypertrophy in hypoxia-induced rat model of PAH, which is related to inhibition of the NOX/VPO1 pathway-mediated oxidative stress and the inflammatory reaction.
Assuntos
Hemeproteínas/antagonistas & inibidores , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , NADPH Oxidases/antagonistas & inibidores , Peroxidases/antagonistas & inibidores , Estilbenos/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Hemeproteínas/metabolismo , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Hipóxia/enzimologia , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Masculino , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Peroxidases/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Estilbenos/química , Estilbenos/uso terapêutico , Remodelação Ventricular/fisiologiaRESUMO
Fluorofenidone (AKF-PD) is a novel pyridone derivate that targets transforming growth factor-ß1 (TGF-ß1) signaling. Previous studies have proven that AKF-PD functions as an antifibrotic agent in pulmonary fibrosis and renal fibrosis models. Activated TGF-ß1 signaling is thought to be a major feature of pulmonary hypertension (PH). TGF-ß1 exerts powerful pro-proliferation effects on pulmonary arterial smooth muscle cells (PASMCs), and hence, prompts vascular remodeling. This study is designed to investigate the effect of AKF-PD on vascular remodeling in a rat model of hypoxia-induced PH. PH was induced in rats by 4 weeks of hypoxia. The expression of TGF-ß1, collagen I, and collagen III was analyzed by ELISA, immunohistochemistry, real-time PCR, or Western blot. Proliferation of cultured PASMCs was determined by the BrdU incorporation method and flow cytometry. The results showed that AKF-PD treatment (0.5 or 1.0 g·(kg body mass)·d(-1)) for 4 weeks attenuated pulmonary vascular remodeling and improved homodynamic parameters. TGF-ß1 level was significantly down-regulated by AKF-PD both in vivo and in vitro. Furthermore, hypoxia- and TGF-ß1-induced PASMC proliferation and collagen expression were both significantly suppressed by AKF-PD. These results suggest that AKF-PD ameliorates the progression of PH induced by hypoxia in rats through its regulation of TGF-ß1 expression, PASMC proliferation, and the extracellular matrix.
Assuntos
Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Piridonas/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Matriz Extracelular/metabolismo , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin II (Ang II) plays a vital role in the pathogenesis of arteriosclerosis and restenosis. In the present study, the effect of reinioside C, a main active ingredient of Polygala fallax Hemsl, on proliferation of VSMCs induced by Ang II was investigated. It was found that Ang II (1 microM) markedly stimulated proliferation of VSMCs. Pretreatment of reinioside C (3, 10 or 30 microM) concentration-dependently inhibited the proliferative effect of Ang II. To determine the possible mechanism, NADPH oxidase subunits (Nox-1, Nox-4) mRNA expression, intracellular ROS level, phosphorylation of ERK1/2, NF-kappaB activity, and mRNA expression of AP-1 subunits (c-fos, c-jun) and c-myc were measured. The results demonstrated that reinioside C attenuated Ang II-induced NADPH oxidase mRNA expression, generation of ROS, ERK1/2 phosphorylation, activation of NF-kappaB, and mRNA expression of AP-1 and c-myc in VSMCs in a concentration-dependent manner. The effects of Ang II were also inhibited by diphenyleneiodonium (DPI, the NADPH oxidase inhibitor), PD98059 (the ERK1/2 inhibitor) and pyrrolidine dithiocarbamate (PDTC, the NF-kappaB inhibitor). These results suggest reinioside C attenuates Ang II-induced proliferation of VSMCs by inhibiting NADPH oxidase-ROS-ERK1/2-NF-kappaB-AP-1 pathway.
Assuntos
Angiotensina II/fisiologia , Proliferação de Células/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , NADPH Oxidases/metabolismo , NF-kappa B/efeitos dos fármacos , Saponinas/farmacologia , Fator de Transcrição AP-1/efeitos dos fármacos , Animais , Western Blotting , Ensaio de Desvio de Mobilidade Eletroforética , Fosforilação , Polygala/química , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Saponinas/química , Saponinas/isolamento & purificaçãoRESUMO
This review addresses the issues of low consumer engagement and market development difficulties in intangible cultural heritage (ICH) products. Dietary ICH products are selected as research materials to discover contemporary commercial survival paths for ICH through the psychological effects of advertising. Firstly, this study examines the respective advantages of rational and emotional ICH advertisement in terms of emotional responses, cognitive responses, attitudes, recall, and recognition. Then, it explores the effects of different ICH advertisement types (rational advertisement, emotional advertisement) and different degrees of situational involvement (purchasing for oneself, purchasing gifts for others) on the advertising effectiveness, aiming to identify factors influencing the psychological effects of ICH advertisement. Through statistical analysis, the main conclusions are as follows: (1) Rational ICH advertisement prompts consumers to consider the actual attributes of ICH products, leading to a more positive purchasing attitude. (2) Emotional ICH advertisement is more effective in eliciting positive emotions from consumers and enhancing brand memory. (3) Under the scenario of purchasing a gift for others, emotional ICH advertisement has a more positive impact on consumers' attitudes towards advertising. (4) Under different degrees of situational involvement, rational ICH advertisement has a more positive impact on consumers' purchasing attitudes. This study not only provides guidance for optimizing ICH advertising strategies but also offers new directions for market expansion, contributing valuable insights into cultural heritage preservation, as well as the development and protection of ICH.
RESUMO
BACKGROUND: Atherosclerosis is associated with macrophage accumulation. LOX-1 has been shown to induce macrophage attachment, and its deletion (LOX-1 knockout, KO) reduces atherosclerosis in LDLr KO mice fed a high cholesterol diet. We examined differences in macrophage trafficking in age-matched wild type, LOX-1 KO, LDLr KO, and LDLr/LOX-1 double KO mice. METHODS: Sections of aortas of mice fed high cholesterol diet were collected at weeks 0, 4, 8, 12 and 19 and analyzed by immunohistochemistry and flow cytometry. RESULTS: In the LDLr KO mice aorta, CD68 positivity (macrophage accumulation) increased over time up to 12 weeks, and then the accumulation fell modestly but significantly. The periaortal fat and adventitia showed more CD68 positivity than the media and intima. This pattern was also evident in the non-atherosclerotic areas. Importantly, LOX-1 KO and LDLr-LOX-1 double KO mice showed diminished CD68 positivity in comparison to wild type and LDLR KO mice, respectively. Further, macrophages from LOX-1 KO mice revealed a marked reduction in migration (vs. macrophages from wild type mice) in in vitro migration assay. CONCLUSIONS: LOX-1 deletion translates into reduction in macrophage trafficking in the aorta of LDLr KO mice. Most of the macrophage trafficking appears in the subadventitial regions.