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BACKGROUND: Recently, a new type of pulmonary nodule positioning needle has been adopted clinically. We aimed to evaluate the efficacy and safety of a new type of localization needles compared with coils for the simultaneous localization of multiple pulmonary nodules guided by computed tomography (CT) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From January 2021 to March 2022, 87 pulmonary nodules from 40 patients were localized using the new localization needle. From January 2020 to December 2020, 68 pulmonary nodules in 31 patients were localized using coils. The relative outcomes were compared. RESULTS: The success rate of pulmonary nodule localization in the needle group was 97.7% while that in the coil group was 98.5%. In the needle group, the time needed to locate the first nodule was significantly shorter than in the coil group (10.9 min vs. 17.2 min, P = 0.001). Moreover, the time needed per patient was also significantly shorter for the needle group compared with the coil group (23.7 min vs. 30 min, P = 0.017). The incidence of pneumothorax in the needle group was 25.0% vs. 12.9% in the coil group (P = 0.204). The rate of pulmonary hemorrhage in the needle group was 40.0% vs. 32.3% in the coil group (P = 0.502). The success rate of VATS wedge resection was 100% in both groups. CONCLUSION: Both disposable pulmonary nodule localization needles and coils are safe and effective for CT-guided localization of multiple pulmonary nodules of the same stage prior to VATS. However, the use of needles is time-saving compared with the use of coils. The coil localization may exhibit better safety than needle localization.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Nódulos Pulmonares Múltiplos/cirurgia , Agulhas , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Pulmão/cirurgiaRESUMO
PURPOSE: To assess the effectiveness of I-125 seeds (IS) insertion with transcatheter arterial chemoembolization (TACE) in treating patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: An extensive search was conducted for relevant randomized controlled trials (RCTs) from the establishment date of each database to November 2020. RESULTS: A total of nine RCTs were included in this study. Our analysis showed no significant changes in the pooled Δalpha-fetoprotein values (p = .06), incident rates of myelosuppression (p = .46), vomit occurrence (p = .27), and abnormal liver function (p = .42) between the two treatment groups. However, the complete response (p < .00001), total response (p < .00001), and disease control (p < .00001) rates were significantly higher in patients who underwent TACE with IS insertion, as opposed to patients who received TACE alone. Furthermore, patients who underwent TACE with IS insertion experienced markedly longer pooled overall survival (OS) time (p < .0001), with better OS rates at the six-month (p = .0002), one-year (p < .0001), and three-year (p = .0003) follow-ups than patients who received TACE alone. CONCLUSION: TACE with IS insertion can significantly improve clinical response and prolong the survival of advanced HCC patients.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Humanos , Radioisótopos do Iodo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Phosphofurin Acidic Cluster Sorting Protein 2 (PACS2)-related early infantile developmental and epileptic encephalopathy (EIDEE) is a rare neurodevelopmental disorder. EIDEE is characterized by seizures that begin during the first three months of life and are accompanied by developmental impairment over time. In this article, we present three patients with EIDEE who experienced neonatal-onset seizures that developed into intractable seizures during infancy. Whole exome sequencing revealed a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene. We conducted a literature review and found 29 cases to characterize the seizure patterns, neuroimaging features, the usage of anticonvulsants, and the clinical neurodevelopmental outcomes of PACS2-related EIDEE. The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. Neuroimaging abnormalities were observed in the posterior fossa region, including mega cisterna magna, cerebellar dysplasia, and vermian hypoplasia. The long-term prognosis ranges from low-average intelligence to severe developmental retardation, emphasizing the importance of early recognition and accurate diagnosis by pediatric neurologists to provide personalized patient management.
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AIMS: The purpose of this study was to explore the predictive value of wall thickness measured by cardiac magnetic resonance (CMR) for all-cause mortality in dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: DCM patients who underwent CMR and completed the regular follow-up were included in this study. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular ejection fraction, and left ventricular mass (LVM) were measured by CMR. The presence and extent of late gadolinium enhancement (LGE) were also assessed. The relative posterior wall thickness (RWTPW ) and relative interventricular septum wall thickness (RWTIVS ) were defined by the following equations: RWTPW = (2 × PWT)/LVDd, and RWTIVS = (2 × IVST)/LVDd. All patients received regular telephone and outpatient follow-up. The primary endpoint was all-cause mortality. A total of 161 patients were enrolled in this study, including 126 (78.3%) males. The mean age was 52.3 ± 13.6 years. During the median follow-up of 47 months (interquartile range 32-57 months), 41 (24.8%) patients died. Compared with the non-death group, LVDd (75.2 ± 11.9 vs. 70.5 ± 8.8 mm; P = 0.025) was greater in the death group, while PWT [5.2 mm (3.7-6.8) vs. 6.9 mm (5.3-8.6); P < 0.001], IVST [8.2 mm (6.5-9.5) vs. 9.3 mm (7.4-10.5); P = 0.005], RWTPW [0.15 (0.11-0.19) vs. 0.20 (0.15-0.25); P < 0.001], RWTIVS [0.22 (0.17-0.26) vs. 0.26 (0.22-0.31); P < 0.001], and LVM/LVEDV ratio (0.5 ± 0.2 vs. 0.7 ± 0.2 g/mL; P < 0.001) were lower. The presence of LGE [LGE(+)] was more frequent in the death group (75.6% vs. 58.3%; P = 0.048). However, the LGE extent was not significantly different between the two groups [4 (1-7) vs. 2 (0-6); P = 0.096]. Multivariate Cox regression analysis showed that PWT [hazard ratio (HR) 0.086, 95% confidence interval (CI) 0.665-0.976; P < 0.05] and RWTPW (HR 0.001, 95% CI 0.000-0.502; P < 0.05) were independent predictors of all-cause death. In contrast, IVST, RWTIVS , and the presence of LGE were not clearly associated with death. CONCLUSIONS: PWT measured by CMR is an independent predictor of all-cause mortality in DCM patients. However, there was no significant correlation between septum wall thickness and mortality.
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Cardiomiopatia Dilatada , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Cardiomiopatia Dilatada/diagnóstico por imagem , Volume Sistólico , Função Ventricular Esquerda , Meios de Contraste , GadolínioRESUMO
The Omicron variant BA.2 is the dominant form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in many countries, including those that have already implemented the strictest quarantine mandates that effectively contained the spread of the previous variants. Although many individuals were partially or fully vaccinated, confirmed Omicron infections have far surpassed all other variants combined in just a couple of months since the Omicron variant emerged. The ChAdOx1-S (AstraZeneca), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines offer protection against the severe illness of SARS-CoV-2 infection; however, these currently available vaccines are less effective in terms of preventing Omicron infections. As a result, a booster dose of BNT162b2 or mRNA-1273 is recommended for individuals >12 years old who had received their second dose of the approved vaccines for >5 months. Herein, we review the studies that assessed the clinical benefits of the booster dose of vaccines against Omicron infections. We also analyzed public data to address whether early booster vaccination effectively prevented the surge of the Omicron infections. Finally, we discuss the consideration of a fourth dose of vaccine as a way to prevent possible upcoming infections.
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Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Humanos , Criança , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2RESUMO
Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.
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Doença da Artéria Coronariana , MicroRNAs , Placa Aterosclerótica , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , MicroRNAs/genética , Insuficiência Renal Crônica/genética , Doença da Artéria Coronariana/diagnóstico , Calcificação Vascular/genéticaRESUMO
BACKGROUND: The clinical presentations of abusive head trauma can abruptly worsen, so the occurrence of seizures and changes of EEG can be variable according to patients' conditions. Since the changes of EEG background waves reflect the cortical function of children, we aimed to find out whether the timing of EEG background, epileptiform discharges and seizure patterns were associated with the outcomes of patients with AHT. MATERIAL AND METHODS: Using seizure type and acute stage electroencephalographic (EEG) characteristics to assess adverse neurological outcomes in children with seizures secondary to abusive head trauma (AHT). Children who were hospitalized with AHT at a tertiary referral hospital from October 2000 to April 2010 were evaluated retrospectively. A total of 50 children below 6 years of age admitted due to AHT were included. KOSCHI outcome scale was used to evaluate the primary outcome and neurological impairment was used as secondary outcome after 6 months discharge. RESULTS: Children with apnea, cardiac arrest, reverse blood flow and skull fracture in clinic had a higher mortality rate even in the no-seizure group (3/5 [60%] vs. 3/45 [6.7%], odds ratio [OR] = 11; 95% CI = 2.3-52; p = 0.025). Seizure occurrence reduced mostly at the second day after admission in seizure groups; but children with persistent seizures for 1 week showed poor neurological outcomes. The occurrence of initial seizure was frequency associated with younger age; focal seizure, diffuse cortical dysfunction in acute-stage EEG, and low Glasgow Coma Scale (GCS) score were significantly related to poor outcomes after 6 months. Diffuse cortical dysfunction was also associated with motor, speech, and cognitive dysfunction. CONCLUSIONS: Diffuse cortical dysfunction in acute-stage EEG combined with low GCS score and focal seizure may related to poor outcomes and neurological dysfunctions in children with AHT.
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OBJECTIVE: Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) is a potent anticancer agent, which could specifically target cancerous cells. Nutlin-3, a small-molecular inhibitor of murine double minute 2 (MDM2), shows oncogenic potential in a variety of human cancers. It has also been found to promote the TRAIL-induced apoptosis of cancer cells in esophageal squamous cancer, but its potential role and underlying mechanisms in the TRAIL-treated hepatocellular carcinoma (HCC) remains to be elucidated. METHODS: HSS cell line (Huh7) cells were used as an in vitro model of HCC. TRAIL (100 ng/ml) was used to induce cell apoptosis. Cell viability was measured by CCK-8 assay. Cell apoptosis was detected using TUNEL staining. Mitochondrial activity was evaluated by measuring caspase 3/7 and 9 levels. P53 expression at protein and mRNA level were measured by Western blotting and RT-qPCR, respectively. RESULTS: The combination of Nutlin-3 and TRAIL facilitated the apoptosis and increased the levels of mitochondrial cleaved-caspase3/7 and 9 in HCC cells compared with TRAIL treatment alone, both in a concentration-dependent way. Nutlin-3 also upregulated the expression of p53 and DR5, while knockdown of p53 significantly hindered the pro-apoptotic effect of Nutlin-3. Further studies revealed that Nutlin-3 downregulated the expression of survivin and bcl-2, both of which could be reversed by p53 knockdown. Moreover, survivin suppressant YM155 and bcl-2 inhibitor YM155 further enhanced the apoptosis of HCC cells in the presence of Nutlin-3 and TRAIL. CONCLUSION: These results suggested that Nutlin-3 facilitated TRAIL-induced apoptosis of HCC cells by activating the p53-survivin/bcl-2 pathway, which provided novel insights into the mechanism of Nutlin-3 and confirmed the potential of combination of Nutlin-3 and TRAIL as an adjuvant in HCC therapy.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Antineoplásicos/farmacologia , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Imidazóis , Ligantes , Neoplasias Hepáticas/patologia , Camundongos , Piperazinas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Mensageiro , Survivina/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy.
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BACKGROUND: Splenectomy is the life-saving treatment for high-grade spleen trauma. Splenectomized patients are at a significant infection risk. However, the trauma-induced splenectomy results in less incidence of postsplenectomy infection than the hematologic disorder. We conducted a large-scale study to identify the infection rate and management strategy in trauma-related splenic injuries. METHODS: We included patients with the diagnosis of spleen injury in Taiwan from January 2003 to December 2013 by using the National Health Insurance Database and divided them into spleen preserved and splenectomized groups. The demographic factors including age, sex, hospital level, year of injury, trauma mechanism, associated injuries, whether injury severity score â§16, and comorbidities were extracted. A 1:1 propensity score match was performed, and we analyzed the long-term outcome as the presence of infection-related disease (septicemia, pneumonia, and meningitis) after spleen trauma. The multivariate logistic regression analysis was used to identify the risk factor for each outcome. RESULTS: During the 11 years included in this study, a total of 8,897 patients with spleen trauma were identified. A total of 3,520 (39.6%) patients were splenectomized, and 5,377 (60.4%) were spleen preserved. After propensity score matching, 3,099 pairs of patients were enrolled for further analysis. In univariate analysis, the incidence of pneumonia is significantly higher in the splenectomized group (8.5% vs 7.0%, P = .037). There was no significant difference in septicemia and meningitis between the 2 groups. In multivariate analysis, splenectomy is an independent risk factor for pneumonia in long-term follow-up. CONCLUSION: Compared with the spleen preserved group, splenectomy is related to an increased likelihood of long-term pneumonia onset but not to an increase in the possibility of other infections.
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Traumatismos Abdominais/epidemiologia , Pneumonia/epidemiologia , Pneumonia/etiologia , Esplenectomia/efeitos adversos , Traumatismos Abdominais/complicações , Traumatismos Abdominais/cirurgia , Adulto , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância da População , Pontuação de Propensão , Medição de Risco , Fatores de Risco , Esplenectomia/métodos , Esplenectomia/estatística & dados numéricos , Adulto JovemRESUMO
ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically. Aiming to explore new potent inhibitors, a series of 2-amino-4-(1-piperidine) pyridine derivatives that stabilized a novel DFG-shifted conformation in the kinase domain of ALK were designed and synthesized on the base of lead compound A. Biological evaluation highlighted that most of these new compounds could also potently inhibit ROS1 kinase, leading to the promising inhibitors against both ROS1 and ALK. Among them, the representative compound 2e stood out potent anti-proliferative activity against ALK-addicted H3122 and ROS1-addicted HCC78â¯cell lines (IC50â¯=â¯6.27⯵M and 10.71⯵M, respectively), which were comparable to that of Crizotinib. Moreover, 2e showed impressive enzyme activity against clinically Crizotinib-resistant ALKL1196M with an IC50 value of 41.3â¯nM, which was about 2-fold more potent than that of Crizotinib. 2e also showed potent inhibitory activity in about 6-fold superior to Crizotinib (IC50: 104.7â¯nM vs. 643.5â¯nM) in Ba/F3 cell line harboring ROS1G2032R. Furthermore, molecular modeling disclosed that all the representative inhibitors could dock into the active site of ALK and ROS1, which gave a probable explanation of anti Crizotinib-resistant mutants. These results indicated that our work has established a path forward for the generation of anti Crizotinib-resistant ALK/ROS1 dual inhibitors.
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Quinase do Linfoma Anaplásico/antagonistas & inibidores , Antineoplásicos/farmacologia , Crizotinibe/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Piridinas/farmacologia , Células A549 , Quinase do Linfoma Anaplásico/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Crizotinibe/química , Relação Dose-Resposta a Droga , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Piperidinas/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Piridinas/química , Relação Estrutura-AtividadeRESUMO
his study demonstrates the feasibility of coastal water quality mapping using satellite remote sensing images. Water quality sampling campaigns were conducted over a coastal area in northern Taiwan for measurements of three water quality variables including Secchi disk depth, turbidity, and total suspended solids. SPOT satellite images nearly concurrent with the water quality sampling campaigns were also acquired. A spectral reflectance estimation scheme proposed in this study was applied to SPOT multispectral images for estimation of the sea surface reflectance. Two models, univariate and multivariate, for water quality estimation using the sea surface reflectance derived from SPOT images were established. The multivariate model takes into consideration the wavelength-dependent combined effect of individual seawater constituents on the sea surface reflectance and is superior over the univariate model. Finally, quantitative coastal water quality mapping was accomplished by substituting the pixel-specific spectral reflectance into the multivariate water quality estimation model.
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With the aim of discovering potential and selective inhibitors targeting ROS1 kinase, we rationally designed, synthesized and evaluated two series of novel 2-amino-pyridine derivatives with 1-phenylethoxy at C-3 and C-4 position. The enzymic assays results indicated that six of the new compounds 13b-13d and 14a-14c showed remarkably higher inhibitory activities against ROS1 kinase. The most promising compounds, 13d and 14c displayed the most desired ROS1 inhibitory activity with IC50 values of 440 nM and 370 nM respectively. Furthermore, 13d and 14c displayed ROS1 inhibitory selectivity of about 7-fold and 12-fold, relative to that of ALK sharing about 49% amino acid sequence homology in the kinase domains. They also showed good anti-proliferative effects against ROS1-addicted HCC78 cell lines with the IC50 values of 8.1 µM and 65.3 µM, respectively. Moreover, molecular docking and molecular dynamics simulation studies disclosed that compound 14c and 13d shared similar binding poses with Crizotinib except the selective binding site of ROS1. It also gave a probable molecular explanation for their activity and selectivity, which the methoxyl group in benzene ring was the crucial to the selectivity to ROS1 versus ALK.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Piridinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Piridinas/síntese química , Piridinas/química , Relação Estrutura-AtividadeRESUMO
Parkinson's disease (PD) is a progressive neurological disease, one of the pathological characteristics is a gradual loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNpc). In animals, PD-like symptoms can be induced by genetic mutations or by neurotoxins such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). It has been reported that deletion of autophagy-related gene 5 (Atg5) in the brain can disrupt neural function and is accompanied by the accumulation of cytoplasmic inclusions. However, the exact role of autophagy in PD etiology has not fully been asserted. In this study, we used tyrosine hydroxylase (TH)-Cre mice to generate conditional knockouts (CKO) with the specific deletion of Atg5 in mDA neurons, and found that adult Atg5 CKO mice contained ubiquitin- and p62-positive inclusions and fewer TH-positive mDA neurons compared with wild-type controls. Interestingly, MPTP-induced loss of mDA neurons was not observed in Atg5 CKO mice. Thus, Atg5-associated autophagy is required for the survival of mDA neurons, and may be involved in MPTP-induced neuronal degeneration.
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Proteína 5 Relacionada à Autofagia/genética , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Intoxicação por MPTP/genética , Mesencéfalo/efeitos dos fármacos , Animais , Sobrevivência Celular , Neurônios Dopaminérgicos/metabolismo , Intoxicação por MPTP/patologia , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Camundongos Knockout , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The genetic susceptibility to and vaccine effectiveness against rotavirus gastroenteritis were different in distinct ethnic groups. The case-control study was aimed to evaluate the effectiveness of rotavirus vaccines and associations between the histo-blood group antigens and susceptibility to rotavirus infections in a Taiwanese population. Cases were children <18 years old who were hospitalized because of laboratory-confirmed rotavirus infection. Controls were healthy children matched to cases by age and gender. The secretor status and Lewis antigen and ABO types were determined by molecular methods. A total of 68 cases and 133 controls were included. Rotavirus immunization was recorded in 8 (12%) cases and 77 (58%) controls, indicating a vaccine effectiveness of 90.3% (95% confidence interval [CI], 78.1% - 95.7%). The secretor and Lewis-positive genotypes were independently associated with increased risk of rotavirus infections (matched odds ratio [mOR] 28.5, 95% CI 2.94-277, P = 0.003 and mOR 16.8, 95% CI 1.08-2601, P = 0.04, respectively). The distribution of ABO blood types did not differ significantly between cases and controls (P = 0.47). In conclusion, Taiwanese children with the secretor genotype and Lewis-positive genotype were at increased risk of moderate-to-severe rotavirus infections. The illness can be effectively prevented by immunization in this population.
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Gastroenterite/virologia , Infecções por Rotavirus/genética , Vacinas contra Rotavirus/uso terapêutico , Sistema ABO de Grupos Sanguíneos/genética , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fucosiltransferases/genética , Gastroenterite/genética , Gastroenterite/prevenção & controle , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único , Infecções por Rotavirus/prevenção & controle , Taiwan , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
To explore the source of heavy metals in lake sediments and their hazard to environment on Tibetan Plateau, China, heavy metal (Cu, Zn, Cd, Pb, Cr, Co, Ni and As) levels in surface sediments of 18 lakes were investigated. Inductively Coupled Plasma Mass Spectrometry (ICP-MS, X-7 series) was used to determine the contents of heavy metals and the concentrations of carbon and nitrogen in sediment samples were analyzed by element analyzer (Vario Max CN, Elementar, Germany). The average concentrations for Cu, Zn, Cd, Pb, Cr, Co, Ni and As were 24.61 mg x kg(-1), 70.14 mg x kg(-1), 0.26 mg x kg(-1), 25.43 mg x kg(-1), 74.12 mg x kg(-1), 7.93 mg x kg(-1), 33.85 mg x kg(-1), 77.69 mg x kg(-1). It was found that heavy-metal concentrations in Tibet sediments were higher than those in Antarctic, but lower than those in the regions affected by anthropogenic activities. The contents of Cu, Zn, Pb, Cr and Co in the samples were lower than the background values of Tibet. Correlation analysis and principal components analysis (PCA) were used to analyze the origins of heavy metals. The result showed that Cu, Zn, Cd, Pb, Co, Ni and As came from soil in drainage basin and atmospheric deposition. Cr was mainly affected by human activities. Assessment on ecological risk of heavy metals was carried out using Hakanson's method and cluster analysis (CA). Assessment on ecological risk indicated that Pumoyum Co, Longmo Co and Bangong Co were at low risks, Bieruoze Co was at high ecological risk level and the other lakes were at different risk levels.
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Monitoramento Ambiental , Sedimentos Geológicos/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , Carbono/análise , Lagos/química , Medição de Risco , Solo/química , TibetRESUMO
Three series of novel quinazoline and pyrido[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and a panel of five human cancer cell lines (MCF-7, A549, BT-474, SK-BR-3, and MDA-MB-231). Bioassay results indicated that five of these prepared compounds (12c-12e and 13c-13d) exhibited remarkably higher inhibitory activities against EGFR and SK-BR-3 cell line. Compounds 12c and 12e displayed the most potent EGFR inhibitory activity (IC50 = 2.97 nM and 3.58 nM, respectively) and good anti-proliferative effect against SK-BR-3 cell with the IC50 values of 3.10 µM and 5.87 µM, respectively. Furthermore, molecular docking and molecular dynamics simulation studies verified that compound 12c and 12e shared similar binding pattern with gefitinib in the binding pocket of EGFR. MM-GBSA binding free energy revealed that the compound 12c and 12e have almost the same inhibitory activity against EGFR as gefitinib, and that the dominating effect of van der Waals interactions drives the binding process.
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Desenho de Fármacos , Receptores ErbB/antagonistas & inibidores , Simulação de Acoplamento Molecular , Pirimidinas/síntese química , Pirimidinas/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Conformação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/química , Pirimidinas/metabolismo , Quinazolinas/química , Quinazolinas/metabolismo , Relação Estrutura-AtividadeRESUMO
Parkinson's disease (PD) is a neurodegenerative disease caused by a gradual loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNpc) during aging. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is one of the neurotoxins used widely to induce PD-like symptoms in PD animal models, including rodents and non-human primates. It has been reported that deletion of autophagy-related gene 7 (Atg7) in the brain results in a reduction of mDA neurons in adulthood. In this study, we used tyrosine hydroxylase (TH)-Cre mice to generate conditional knockout (CKO) mice with the specific deletion of Atg7 in mDA neurons. Consistent with previous reports, adult Atg7 CKO mice contained fewer TH-positive mDA neurons compared with wild-type (WT) controls. TH-expressing neurons containing puncta-like structures with p62 and ubiquitin immunoreactivity were observed in the midbrain of Atg7 CKO mice but were not detected in control mice. However, MPTP-induced loss of mDA neurons was not observed in Atg7 CKO mice. Our results indicate that Atg7-involved autophagy is required not only for the survival of mDA neurons in the mouse brain, but also for MPTP-induced mDA neuron degeneration.
Assuntos
Proteína 7 Relacionada à Autofagia/deficiência , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Intoxicação por MPTP/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Neurônios Dopaminérgicos/patologia , Marcha/efeitos dos fármacos , Marcha/fisiologia , Intoxicação por MPTP/patologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Mesencéfalo/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuroproteção/efeitos dos fármacos , Neuroproteção/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismo , Ubiquitina/metabolismoAssuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Glioma/patologia , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Sesquiterpenos/administração & dosagem , Fatores de TempoRESUMO
ABSTRACT Effects of leached amylose (AM) and amylopectin (AP) on textural and morphological properties of cooked rice were investigated separately by replacing cooking liquid with AM and AP separated from pouring cooking liquid. The pouring of cooking water reduced the hardness (from 28.45 to 19.42N) and stickiness (from 1.74 to 1.19N·s) significantly. However, the addition of AM and AP enhanced the hardness (27.63N) and stickiness (1.71N·s).Scanning electron microscopy show that the leached short-chain AM entered the surface hollows in the cooked rice after water evaporation. Meanwhile, the Long-chain AM cross-linked to formed a three-dimensional network structures, which covered on the filled hollows. This distribution led to a harder texture of cooked rice. The leached AP absorbed water and swelledto form masses. Atthe gelatinization temperature,theAPmassesagglomeratedtoformafilmlayer,whichcoveredtheunevenstructure, the thicker and smoother film contributed to the sticky texture.