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Peroxisome proliferator-activated receptor-gamma (PPARγ) has been shown to have therapeutic promise in the treatment of ischemic stroke and is supported by several studies. To identify possible PPARγ activators, the current study used an in silico technique in conjunction with molecular simulations and in vivo validation. FDA-approved drugs were evaluated using molecular docking to determine their affinity for PPARγ. The findings of molecular simulations support the repurposing of rabeprazole and ethambutol for the treatment of ischemic stroke. Adult Sprague Dawley rats were subjected to transient middle cerebral artery occlusion (t-MCAO). Five groups were made as a sham-operated, t-MCAO group, rabeprazole +t-MCAO, ethambutol +t-MCAO, and pioglitazone +t-MCAO. The neuroprotective effects of these drugs were evaluated using the neurological deficit score and the infarct area. The inflammatory mediators and signaling transduction proteins were quantified using Western blotting, ELISA, and immunohistochemistry. The repurposed drugs mitigated cerebral ischemic injury by PPARγ mediated downregulation of nods like receptor protein 3 inflammasomes (NLRP3), tumor necrosis factor-alpha (TNF-α), cyclooxygenase 2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-kB), and c-Jun N-terminal kinase (p-JNK). Our data demonstrated that rabeprazole and ethambutol have neuroprotective potential via modulating the cytoprotective stress response, increasing cellular survival, and balancing homeostatic processes, and so may be suitable for future research in stroke therapy.
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Isquemia Encefálica , AVC Isquêmico , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Encéfalo , Isquemia Encefálica/metabolismo , Etambutol/farmacologia , Etambutol/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Simulação de Acoplamento Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , PPAR gama/metabolismo , Rabeprazol/farmacologia , Rabeprazol/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
The unipolar/bipolar pacing mode of pacemaker is related to its circuit impedance, which affects the battery life. In this study, the in vitro experiment scheme of pacemaker circuit impedance test was constructed. The human blood environment was simulated by NaCl solution, and the experimental environment temperature was controlled by water bath. The results of in vitro experiments showed that under the experimental conditions similar to clinical human parameters, the difference between the circuit impedance of bipolar mode and unipolar mode is 120~200 Ω. The results of the in vitro experiment confirmed that the circuit impedance of bipolar circuit was larger than that of unipolar mode, which was found in clinical practice. The results of this study have reference value to the optimization of pacing mode and the reduction of pacemaker power consumption.
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Marca-Passo Artificial , Estimulação Cardíaca Artificial/métodos , Impedância Elétrica , Humanos , Próteses e ImplantesRESUMO
OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.
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Apoptose/genética , Células Endoteliais/patologia , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/genética , Transdução de Sinais/genética , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Estresse Oxidativo/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologiaRESUMO
Cardiac lipomyomas are tumors that may produce various signs and symptoms, including life threatening ventricular tachycardia (VT), often requiring surgical resection and/or catheter ablation. Here we report on a 35-year-old female patient with longstanding repetitive VT in the setting of a large cardiac lipomyoma. Diagnostic testing included non-invasive approaches including ECG, echocardiography and CMR. She then underwent electroanatomic mapping, which provided additional information. The patient ultimately underwent partial resection of the tumor. Postoperatively, long term ambulatory ECG showed VT suppression without anti-arrhythmic or catheter ablation for VT.
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Ablação por Cateter , Taquicardia Ventricular , Adulto , Eletrocardiografia , Feminino , Coração , Ventrículos do Coração/cirurgia , Humanos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Syncope is a perplexing challenge that often receives thorough evaluation, yet the diagnosis remains unclear. Usually, the emergency department is the first point at which patients present with syncope. However, diverse medical factors, including low diagnostic rates and inconsistent management by doctors, add to healthcare costs and delay diagnosis for syncope patients. METHODS: Patients who had been to the emergency department at least once but were not given a clear diagnosis of syncope were recruited into our study at the time they visited syncope clinic staffed by a multidisciplinary team. Complete medical histories and clinical examinations were conducted by both experienced cardiologists and neurologists. If patients were not given a conclusive diagnosis at the syncope clinic on the basis of outpatient examinations, they were admitted for further evaluation. RESULTS: A total of 209 consecutive patients claiming "syncope" visited the syncope clinic, yet only 167 patients were formally diagnosed with syncope. For these 167 patients, the mean age was 55.93 ± 17.40 years old, and 41.3% were male. The proportions of cardiac syncope, reflex syncope, orthostatic hypotension (OH), and syncope of uncertain etiology were 19.8%, 64.1%, 7.8%, and 8.4%, respectively. The diagnostic rate was 91.6%, and the hospitalization rate was 23.4%. Patients with reflex syncope and OH were younger than patients with cardiac syncope. Cardiac syncope tends to occur more frequently in males, while reflex syncope is more likely in females. CONCLUSIONS: The cooperation of professional cardiologists and neurologists will play an important role in improving diagnostic rates, lowering admission rates, and reducing medical costs.
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Equipe de Assistência ao Paciente , Síncope/diagnóstico , Cardiologistas , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Neurologistas , Exame FísicoRESUMO
BACKGROUND/AIMS: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. METHODS: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. RESULTS: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-ß expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. CONCLUSIONS: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.
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Síndrome Cardiorrenal/patologia , Estresse do Retículo Endoplasmático/fisiologia , Coração/fisiopatologia , Rim/patologia , Sirtuína 1/metabolismo , Animais , Síndrome Cardiorrenal/etiologia , Síndrome Cardiorrenal/metabolismo , Creatinina/sangue , Desmina/metabolismo , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Rim/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Miocárdio/patologia , Nefrectomia , Sirtuína 1/deficiência , Sirtuína 1/genética , Fator de Transcrição CHOP/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: To compare the diagnostic yield and safety of 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in the diagnosis of pancreatic solid lesions. METHODS: Between April 2014 and September 2015, 36 patients with pancreatic solid lesions were included for endoscopic ultrasound test. Patients were randomly divided into two groups: EUS-FNA (n = 18) and EUS-FNB (n = 18). Each nidus was punctured three times (15 ~ 20 insertions for each puncture) with a 22G needle. The core specimens were analyzed, and the diagnostic yields of FNA and FNB were evaluated. RESULTS: The procedure success rate was 100% with no complications. Cytological and histological examinations found that the diagnostic yield of FNB and FNA were both 83.3%. To get a definitive diagnosis, FNB needed fewer punctures than FNA (1.11 vs. 1.83; P â< â0.05). CONCLUSIONS: 22G EUS-FNB is a safe and effective way to diagnose pancreatic solid lesions. FNB required a lower number of needle passes to achieve a diagnosis compared with FNA.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pancreatopatias/diagnóstico por imagem , Pancreatopatias/patologia , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Agulhas , Avaliação de Resultados em Cuidados de Saúde , Estudos ProspectivosRESUMO
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This study aimed to investigate the role of miR-138 in human coronary artery endothelial cell (HCAEC) injury and inflammatory response and the involvement of the PI3K/Akt/eNOS signalling pathway. Oxidized low-density lipoprotein (OX-LDL)-induced HCAEC injury models were established and assigned to blank, miR-138 mimic, miR-138 inhibitor, LY294002 (an inhibitor of the PI3K/Akt/eNOS pathway), miR-138 inhibitor + LY294002 and negative control (NC) groups. qRT-PCR and Western blotting were performed to detect the miR-138, PI3K, Akt and eNOS levels and the protein expressions of PI3K, Akt, eNOS, p-Akt, p-eNOS, Bcl-2, Bax and caspase-3. ELISAs were employed to measure the expressions of TNF-α, IL-4, IL-6, IL-8, IL-10 and nitric oxide (NO) and the activities of lactate dehydrogenase (LDH) and eNOS. MTT and flow cytometry were performed to assess the proliferation and apoptosis of HCAECs. Compared to the blank group, PI3K, Akt and eNOS were down-regulated in the miR-138 mimic and LY294002 groups but were up-regulated in the miR-138 inhibitor group. The miR-138 mimic and LY294002 groups showed decreased concentrations of TNF-α, IL-6, IL-8 and NO and reduced activities of LDH and eNOS, while opposite trends were observed in the miR-138 inhibitor group. The concentrations of IL-4 and IL-10 increased in the miR-138 mimic and LY294002 groups but decreased in the miR-138 inhibitor group. The miR-138 mimic and LY294002 groups had significantly decreased cell proliferation and increased cell apoptosis compared to the blank group. These findings indicate that up-regulation of miR-138 alleviates HCAEC injury and inflammatory response by inhibiting the PI3K/Akt/eNOS signalling pathway.
Assuntos
Células Endoteliais/metabolismo , Lipoproteínas LDL/farmacologia , MicroRNAs/genética , Óxido Nítrico Sintase Tipo III/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Antagomirs/genética , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Vasos Coronários/citologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Interleucinas/genética , Interleucinas/metabolismo , MicroRNAs/metabolismo , Morfolinas/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
This study investigated roles of serum ST2, IL-33 and BNP in predicting major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Blood samples were collected from the included AMI patients (n = 180) who underwent PCI. All patients were divided into the MACEs and MACEs-free groups. Enzyme-linked immunosorbent assay was performed to measure serum levels of ST2, IL-33 and BNP. Severity of coronary artery lesion was evaluated by Gensini score. Pearson correlation analysis was used. A receiver operating characteristics curve was drawn to evaluate the potential roles of ST2, IL-33 and BNP in predicting MACEs, and Kaplan-Meier curve to analyse the 1-year overall survival rate. Logistic regression analysis was conducted to analyse the independent risk factors for MACEs. Compared with the MACEs-free group, the serum levels of ST2, IL-33 and BNP were significantly higher in the MACEs group. Serum levels of ST2, IL-33 and BNP were positively correlated with each other and positively correlated with Gensini score. The area under curves of ST2, IL-33 and BNP, respectively, were 0.872, 0.675 and 0.902. The relative sensitivity and specificity were, respectively, 76.27% and 85.92%, 69.49% and 58.68%, as well as, 96.61% and 77.69%. Serum levels of ST2, IL-33 and BNP were independent risk factors for MACEs. The 1-year overall survival rate was higher in AMI patients with lower serum levels of ST2, IL-33 and BNP. In conclusion, serum levels of ST2, IL-33 and BNP have potential value in predicting MACEs in AMI patients undergoing PCI.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Interleucina-33/sangue , Infarto do Miocárdio/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Intervenção Coronária Percutânea/efeitos adversos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Idoso , Área Sob a Curva , Biomarcadores/sangue , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Feminino , Expressão Gênica , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-33/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Peptídeo Natriurético Encefálico/genética , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Índice de Gravidade de DoençaRESUMO
Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Complexo I de Transporte de Elétrons/metabolismo , Insulina/administração & dosagem , Mitocôndrias Cardíacas/patologia , Chaperonas Moleculares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Células HeLa , Humanos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Regulação para Cima/efeitos dos fármacosRESUMO
To investigate interference, and how to avoid it, by high-frequency electromagnetic fields (EMFs) of Global System for Mobile Communications (GSM) mobile phone with communication between cardiac rhythm management devices (CRMs) and programmers, a combined in vivo and in vitro testing was conducted. During in vivo testing, GSM mobile phones interfered with CRM-programmer communication in 33 of 65 subjects tested (50.8%). Losing ventricle sensing was representative in this study. In terms of clinical symptoms, only 4 subjects (0.6%) felt dizzy during testing. CRM-programmer communication recovered upon termination of mobile phone communication. During in vitro testing, electromagnetic interference by high-frequency (700-950 MHz) EMFs reproducibly occurred in duplicate testing in 18 of 20 CRMs (90%). During each interference, the pacing pulse signal on the programmer would suddenly disappear while the synchronous signal was normal on the amplifier-oscilloscope. Simulation analysis showed that interference by radiofrequency emitting devices with CRM-programmer communication may be attributed to factors including materials, excitation source distance, and implant depth. Results suggested that patients implanted with CRMs should not be restricted from using GSM mobile phones; however, CRMs should be kept away from high-frequency EMFs of GSM mobile phone during programming.
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Telefone Celular , Campos Eletromagnéticos/efeitos adversos , Marca-Passo Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Comunicação , Simulação por Computador , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos TeóricosRESUMO
Non-small cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. The aim of the present study was to test the antitumour effects of short-hairpin RNA targeting aquaporin 3 (AQP3) in experimental NSCLC. Expression of AQP3 was suppressed in human A549 and H1299 NSCLC cell lines by short-hairpin RNA-mediated silencing. Therapeutic effects were assessed by examining tumorigenicity using a subcutaneous xenograft mouse model of NSCLC. Aquaporin 3 knockdown inhibited tumour growth and prolonged survival of mice with tumours. Aquaporin 3 knockdown suppressed tumour proliferation, marked by enhanced expression of p53, an increased ratio of cleaved caspase 3 to pro-caspase 3 and reduced expression of proliferating cell nuclear antigen and B-cell lymphoma-2 (bcl-2). Aquaporin 3 knockdown inhibited tumour angiogenesis, marked by decreased CD31 immunostaining and reduced expression of hypoxia-inducible factor-2α and vascular endothelial growth factor. Aquaporin 3 knockdown reduced cellular glycerol content and suppressed mitochondrial ATP formation. Aquaporin 3 knockdown in vitro significantly suppressed activities of matrix metalloproteinases MMP2 and MMP9, reduced AKT phosphorylation and decreased cell invasiveness of A549 and H1299 cells. In conclusion, AQP3 knockdown suppressed tumour growth and reduced angiogenesis in human NSCLS xenografts. Aquaporin 3 could thus be envisaged as a novel therapeutic target for NSCLC.
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Aquaporina 3/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , RNA Interferente Pequeno/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Camundongos Nus , Terapia de Alvo Molecular , Transplante de Neoplasias , Neovascularização Patológica/prevenção & controle , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: The generalized tonic-clonic seizure (GTCS) is the most usual variety of epileptic seizure. It is mainly characterized by strong body muscle rigidity, loss of consciousness, a disorder of plant neurofunction, and significant damage to cognitive function. The effect of antiepileptic drugs on cognition should also be considered. At present, there is no effective treatment for patients with epilepsy, but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should, therefore, be considered for the therapy means of epilepsy with cognitive dysfunction. AIM: To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment. METHODS: This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups (experimental and control) using random number table method. The control group was treated with sodium valproate, and the experimental group was Baijin pills and sodium valproate for three months. The frequency and duration of each seizure, the Montreal Cognitive Assessment Scale (MoCA), and the Quality of Life Rating Scale (QOLIE-31) were recorded before and after treatment. RESULTS: There were 85 patients included (42 in the control group and 43 in the experimental group). After treatment, the seizure frequency in the experimental group was significantly reduced (P < 0.05), and seizure duration was shortened (P < 0.01). The total MoCA score in the experimental group significantly increased compared to before treatment (P < 0.01), and the sub-item scores, except naming and abstract generalization ability, significantly increased (P < 0.05), whereas the total MoCA score in the control group significantly decreased after treatment (P < 0.05). The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment (P < 0.01). CONCLUSION: Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.
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OBJECTIVES: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20-30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. DESIGN: Employing a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. SETTING: Older adults aged 60 and above in the United States. PARTICIPANTS: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. MEASUREMENTS: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. RESULTS: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. CONCLUSION: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.
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Cognição , Dieta , Inquéritos Nutricionais , Pontuação de Propensão , Humanos , Masculino , Feminino , Estudos Transversais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Dieta/estatística & dados numéricos , Dieta/métodos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estados Unidos , ÁcidosRESUMO
BACKGROUND: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. METHODS: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. RESULTS: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. CONCLUSIONS: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.
Assuntos
Doença de Alzheimer , Demência Vascular , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Análise da Randomização Mendeliana , Cirrose Hepática/complicações , Cirrose Hepática/genética , CogniçãoRESUMO
Objective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.
RESUMO
OBJECTIVE: The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM). METHODS: Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for cc RESULTS: The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p<0.001). CONCLUSION: Age, education, diabetic dietary pattern, WC, overweight, obesity, hypoglycaemic episode in 3 months and CVD may be potential influencing factors for the occurrence of CI in hospitalised middle-aged population with T2DM. The combination of BMI and WC may represent a good predictor for early screening of CI in this population. Nevertheless, more relevant prospective studies are still needed.
Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Pessoa de Meia-Idade , Humanos , Lactente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Transversais , Sobrepeso , Fatores de Risco , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico , Obesidade/complicações , Obesidade/epidemiologia , Circunferência da Cintura , Índice de Massa Corporal , HipoglicemiantesRESUMO
Reactive oxygen species (ROS) is generated by oxidative stress and plays an important role in various cardiac pathologies. The SIRT1 signaling pathway and mitochondrial biogenesis play essential roles in mediating the production of ROS. SIRT1 activated by resveratrol protects cardiomyocytes from oxidative stress, but the exact mechanisms by which SIRT1 prevents oxidative stress, and its relationship with mitochondrial biogenesis, remain unclear. In this study, it was observed that after stimulation with 50µMH2O2 for 6h, H9C2 cells produced excessive ROS and downregulated SIRT1. The mitochondrial protein NDUFA13 was also downregulated by ROS mediated by SIRT1. Resveratrol induced the expression of SIRT1 and mitochondrial genes NDUFA1, NDUFA2, NDUFA13 and Mn-SOD. However, the production of these genes was reversed by SIRT1 inhibitor nicotinamide. These results suggest that resveratrol inhibits ROS generation in cardiomyocytes via SIRT1 and mitochondrial biogenesis signaling pathways.
Assuntos
Mitocôndrias/metabolismo , Renovação Mitocondrial , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular , Peróxido de Hidrogênio/farmacologia , NADH Desidrogenase/fisiologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Transdução de SinaisRESUMO
Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.