RESUMO
To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.
Assuntos
Infecções por Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Criança , Humanos , Lactente , Pré-Escolar , Idoso , Rhinovirus/genética , Prevalência , Infecções por Picornaviridae/epidemiologia , Infecções Respiratórias/epidemiologia , China/epidemiologia , Variação GenéticaRESUMO
Under high relative humidity (RH) conditions, the release of volatile components (such as acetate) has a significant impact on the aerosol hygroscopicity. In this work, one surface plasmon resonance microscopy (SPRM) measurement system was introduced to determine the hygroscopic growth factors (GFs) of three acetate aerosols separately or mixed with glucose at different RHs. For Ca(CH3COO)2 or Mg(CH3COO)2 aerosols, the hygroscopic growth trend of each time was lower than that of the previous time in three cyclic humidification from 70% RH to 90% RH, which may be due to the volatility of acetic acid leading to the formation of insoluble hydroxide (Ca(OH)2 or Mg(OH)2) under high RH conditions. Then the third calculated GF (using the Zdanovskii-Stokes-Robinson method) for Ca(CH3COO)2 or Mg(CH3COO)2 in bicomponent aerosols with 1:1 mass ratio were 3.20% or 5.33% lower than that of the first calculated GF at 90% RH. The calculated results also showed that the hygroscopicity change of bicomponent aerosol was negatively correlated with glucose content, especially when the mass ratio of Mg(CH3COO)2 to glucose was 1:2, the GF at 90% RH only decreased by 4.67% after three cyclic humidification. Inductively coupled plasma atomic emission spectrum (ICP-AES) based measurements also indicated that the changes of Mg2+concentration in bicomponent was lower than that of the single-component. The results of this study reveal thatduring the efflorescence transitions of atmospheric nanoparticles, the organic acids diffusion rate may be inhibited by the coating effect of neutral organic components, and the particles aging cycle will be prolonged.
Assuntos
Microscopia , Ressonância de Plasmônio de Superfície , Molhabilidade , Aerossóis , Acetatos , GlucoseRESUMO
Human rhinovirus (RV) is an important viral pathogen associated with severe acute respiratory tract infection. The present study retrospectively identified RV types in hospitalized patients with severe acute respiratory infection (SARI) from October 2017 to June 2019 in Henan Province, China. Real-time PCR was used to screen pharyngeal swab samples for RV. Then, the VP1 gene sequences of RV-positive samples were amplified and sequenced with nested primer PCR; subsequently, analyses of the molecular epidemiology and genetic diversity characteristics of the RV types were performed. Seventy-three out of 1015 respiratory samples were identified as RV-positive, from which 65 complete VP1 sequences were successfully sequenced. These RVs were classified into 41 different types, including 26 RV-A types, 2 RV-B types, and 13 RV-C types. The RVs showed an obvious seasonal distribution, with peaks in summer and autumn. The epidemic peak of RV-C was later than that of RV-A. In addition, two new types of species, B and C, were proposed, Bpat107 and Cpat58, respectively. Compared with other types in the same RV species, the pairwise nucleotide p-distances of the two novel RV types were 0.262~0.402 and 0.251~0.508, respectively. This study analyzed the seasonal and genetic characteristics of RV associated with SARI cases in Henan Province, China. Two novel RV types were proposed.
Assuntos
Infecções por Picornaviridae , Infecções Respiratórias , Humanos , Rhinovirus/genética , Estudos Retrospectivos , Infecções por Picornaviridae/epidemiologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
When exposed to different relative humidities (RHs), the optical properties of atmospheric aerosols will change because of changes in the aerosol particle size and complex refractive index (RI), which will affect haze formation and global climate change. The potential contributions of ultrafine particles to the atmospheric optical characteristics and to haze spreading cannot be ignored because of their high particle number concentrations and strong diffusibility; measurement of the optical properties of wet ultrafine particles is thus highly important for environmental assessment. Therefore, a surface plasmon resonance microscopy with azimuthal rotation illumination (SPRM-ARI) system is designed to determine the RIs of single particle aerosols with diameters of less than 100 nm in the hygroscopic growth process. Measurements are taken using mixed single particles with different mass ratios. The RIs of mixed single aerosols at different RHs are retrieved by measuring the scattering light intensity using the SPRM-ARI system and almost all the RIs of the bicomponent particles with different mass ratios decrease with increasing water content under high RH conditions. Finally, for each of the bicomponent particles, the maximum standard deviations for the retrieved RI values are only 2.06×10-3, 3.08×10-3 and 3.83×10-3, corresponding to the NaCl and NaNO3 bicomponent particles with a 3:1 mass ratio at 76.0% RH, the NaCl and glucose particles with a 1:3 mass ratio at 89.0% RH, and the NaCl and OA particles with a 1:1 mass ratio at 78.0% RH, respectively; these results indicate that the high-sensitivity SPRM-ARI system can measure the RI effectively and accurately.
Assuntos
Refratometria , Ressonância de Plasmônio de Superfície , Microscopia , Material Particulado , Peptídeos e Proteínas de Sinalização Intercelular , BismutoRESUMO
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis. DESIGN: C57BL/6 mice were 'educated' by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models. RESULTS: Pex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis. CONCLUSION: The Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC.
Assuntos
Carcinoma Ductal Pancreático/secundário , Proteínas de Transporte/fisiologia , Receptores de Hialuronatos/fisiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/secundário , Proteínas Mitocondriais/fisiologia , Neoplasias Pancreáticas/patologia , Animais , Carcinoma Ductal Pancreático/mortalidade , China , Exossomos/fisiologia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/etiologia , Neoplasias Hepáticas/mortalidade , Modelos Logísticos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Microambiente TumoralRESUMO
Human metapneumovirus (HMPV) plays an important role in acute respiratory tract infections (ARTIs), especially in children. We investigated the epidemiology of HMPV associated with ARTIs among pediatric inpatients and identified HMPV genetic variations in Qingdao, China, from January 2018 to June 2019. HMPV-positive samples were identified from throat swabs by multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR). The G gene sequences of HMPV were obtained, followed by phylogenetic analysis. As a result, 71 out of 1051 (6.76%) patients were HMPV positive, and the HMPV-positive rate in children under 5 years of age was three times higher than that in those aged 5-17 years. The epidemic season of HMPV was in spring, with a peak mainly in March. Thirty-two nucleotide sequences of the HMPV G gene successfully obtained were clustered into three genotypes, A2c (25/32, 78.13%), B1 (3/32, 9.38%) and B2 (4/32, 12.50%). In addition, 76% (19/25) of A2c viruses were identified as the emerging A2c111nt-dup variants, which were predominantly circulating among pediatric inpatients with ARTIs between January 2018 and June 2019 in Qingdao. The emerging A2c111nt-dup variants have spread between countries and cities and might spread more widely in the future. Further prevalence monitoring of this duplication variant is needed to clarify the potentially expanding transmission and to provide a scientific basis for disease control and vaccine development.
Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Pré-Escolar , China/epidemiologia , Genótipo , Humanos , Lactente , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , Filogenia , Infecções Respiratórias/epidemiologiaRESUMO
A comparative analysis of confirmed cases of human influenza virus (HIFV), human respiratory syncytial virus (HRSV), and human metapneumovirus (HMPV) was conducted to describe their clinical and epidemiological characteristics. During 2009-2021, active surveillance of acute respiratory infections (ARIs) was performed in nine provinces of China. Clinical and epidemiological information and laboratory testing results of HIFV, HRSV, and HMPV were analyzed. Among 11591 ARI patients, the single-infection rates of HIFV, HRSV, and HMPV were 15.00%, 9.59%, and 2.24%, respectively; the coinfection rate of these three viruses was 0.64%. HIFV infection was mainly in adults aged 15-59 years, accounting for 39.10%. HRSV and HMPV infections were mainly in children under 5 years old, accounting for 87.13% and 83.46%, respectively. Patients with HRSV infection were younger than HMPV. HRSV and HMPV had high similarities in clinical manifestations, presenting with lower respiratory symptoms. HIFV mainly presented with an upper respiratory infection. The epidemic peak of HRSV was earlier than that of HIFV, and that of HMPV was later than those of HRSV and HFIV. A total of 85.14% of coinfection cases were children under 5 years old. Coinfection might increase the risk of pneumonia in HIFV cases. During 2020-2021, the positive rates and seasonal patterns of these three viruses changed due to the impact of the COVID-19 pandemic. Certain clinical and epidemiological features were observed in HIFV, HRSV, and HMPV infections, which could be beneficial for guiding clinical diagnosis, treatment, and prevention of these three viruses in China.
Assuntos
COVID-19 , Coinfecção , Influenza Humana , Metapneumovirus , Infecções por Paramyxoviridae , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Adulto , Criança , Pré-Escolar , China/epidemiologia , Coinfecção/epidemiologia , Humanos , Lactente , Influenza Humana/epidemiologia , Pandemias , Infecções Respiratórias/epidemiologiaRESUMO
We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017-2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.
Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Pré-Escolar , China/epidemiologia , Duplicação Gênica , Humanos , Lactente , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/epidemiologiaRESUMO
OBJECTIVE: To compare the efficacy and safety between drug-coated devices (DCDs) and bypass surgery with saphenous vein graft (BSV) in femoropopliteal arterial occlusive disease. METHODS: A Bayesian network meta-analysis and indirect comparison were performed. Randomized controlled trials of BSV, bypass surgery with prosthetic graft, bare metal stents, endoluminal bypass (covered stent), percutaneous transluminal angioplasty, and DCDs treating femoropopliteal arterial occlusive disease were collected. The primary end point was target lesion revascularization/target vessel revascularization, and secondary end points were all-cause mortality, limb salvage, and early complications (PROSPERO registry number: CRD42019136530). RESULTS: Forty-two trials and 6867 patients were included. The comparison of DCDs and BSV revealed no significant difference in the 1-year target lesion revascularization/target vessel revascularization (DCDs vs BSV: odds ratio [OR], 0.60; 95% credible interval [CrI], 0.16-2.39). Total early complications from BSV were significantly higher than those from DCDs (DCDs vs BSV: OR, 0.14; 95% CrI, 0.05-0.45), and the main complications of BSV were not death related. There was also no significant difference in systemic early complications (DCDs vs BSV: OR, 0.19; 95% CrI, 0.00-7.82) and 1-year amputation rate (DCDs vs BSV: OR, 2.81; 95% CrI, 0.16-89.53). The 30-day (DCDs vs BSV: OR, 0.38; 95% CrI, 0.00-110.46), 1-year (DCDs vs BSV: OR, 0.96; 95% CrI, 0.24-3.29), 2-year (DCDs vs BSV: OR, 1.60; 95% CrI, 0.64-4.95), and 5-year all-cause mortality rates (DCDs vs BSV: OR, 2.05; 95% CrI, 0.92-4.39) showed no significant differences between DCDs and BSV, although there was a noticeable tendency toward significant results of a higher 5-year mortality rate. CONCLUSIONS: There is no significant difference between DCDs and BSV in short-term efficacy or short- and long-term mortality. Despite traditional BSV remaining the gold standard, DCDs provide a reasonable alternative therapy. In addition, the DCDs have a lower short-term morbidity associated with the procedure at the cost of the possible risk of higher long-term mortality. Clinical trials with more validity are required for a direct comparison between BSV and DCDs.
Assuntos
Materiais Revestidos Biocompatíveis , Stents Farmacológicos , Procedimentos Endovasculares/instrumentação , Artéria Femoral/cirurgia , Doença Arterial Periférica/terapia , Artéria Poplítea/cirurgia , Veia Safena/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Functionalized multi-walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP-1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP-1-conjugated functionalized multi-walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP-1-conjugated functionalized multi-walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi-walled carbon nanotubes, cellular uptake of LyP-1-functionalized multi-walled carbon nanotubes was shown to be increased. Compound of LyP-1-functionalized multi-walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP-1-fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Nanotubos de Carbono/química , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Peptídeos Cíclicos/química , RNA Interferente Pequeno/administração & dosagem , Fatores de Transcrição/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/ultraestrutura , Neoplasias Pancreáticas/genética , TransfecçãoRESUMO
Aerosol particle hygroscopicity is an important factor in visibility reduction, cloud formation, radiation forcing, and the global climate. The high number concentration of nanoparticles (defined as particles with diameters below 100 nm) means that their hygroscopic growth abilities and potential contributions to the climate and environment are significant. Therefore, a rapid and accurate in situ analysis method for single nanoparticle hygroscopic growth in an atmospheric environment is important to characterize the effects of the particle's physical and chemical properties in this process. In this work, surface plasmon resonance microscopy with azimuthal rotation illumination (SPRM-ARI) is used to observe the hygroscopic growth and water content of single nanoparticles in situ. The hygroscopic growth results of a single-component nanoparticle are well matched with the extended aerosol inorganic model (E-AIM) results, and the proposed method remains reliable even when the relative humidity (RH) exceeds 90%. For a bicomponent nanoparticle (with NaCl as the primary content), the presence of a component without deliquescence phase transitions under increasing humidity conditions causes the measured data to differ from both the Zdanovskii-Stokes-Robinson (ZSR) model and E-AIM predictions in the low RH range. However, because of their complete liquefaction, the growth factor (GF) variation of the bicomponent nanoparticle is close to the model predictions in the high RH range. Finally, based on the positive correlation between particle volume and the gray intensity of SPRM-ARI, GF values can be obtained from the cube root of the gray intensity and the actual water content of single nanoparticles can then be derived.
RESUMO
Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients' nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.
Assuntos
Carcinoma Ductal Pancreático/mortalidade , Dieta Saudável/estatística & dados numéricos , Avaliação Nutricional , Neoplasias Pancreáticas/mortalidade , Medição de Risco/métodos , Idoso , Área Sob a Curva , Carcinoma Ductal Pancreático/cirurgia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Prognóstico , Pontuação de Propensão , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
In order to realize accurate dynamic control of supersaturation and to study condensation growth characteristics of nanoparticles through different levels of supersaturation, a series of parametric analyses and systematic comparisons between two-stage and three-stage operating temperature designs were simulated with COMSOL Multiphysics. The simulation results showed that the three-stage operating temperature did not change peak supersaturation compared with two operating temperatures, and the three-stage operating temperature was superior in decreasing the amount of water vapor and the temperature, thus lowering particle loss and variation in detection and collection. The peak supersaturation level increased by 0.3 as the flow rate increased from 0.6 to 2.0 L/min, but the supersaturation peak moved from 0.0027 z0 to 0.08 z0 (i.e., the growth time and the final size decreased by 40%). Peak supersaturation increased as the temperature difference increased or the temperature difference window was shifting left, and minimum activation size decreased. Shifting the 70°C temperature difference window from 9°C, 79°C-1°C, 71°C for the condenser and initiator temperatures resulted in peak supersaturation in the centerline being above 5.8, and the activation size changed as low as 1 nm. Experiments with flow rates varying by a factor of 2.5 (from 0.6 to 1.5 L/min) resulted in a final size decrease of 43% (from 3.2 to 1.8 µm), and experimental results of outlet particle size distributions were equivalent with theoretical analysis as the operating temperature was changed.
Assuntos
Modelos Químicos , Nanopartículas/química , Temperatura , ÁguaRESUMO
Low temperature NH3 selective catalytic reduction (NH3-SCR) technology is an efficient and economical strategy for cutting NO x emissions from power-generating equipment. In this study, a novel and highly efficient NH3-SCR catalyst, tourmaline-modified FeMnTiO x is presented, which was synthesized by a simple one-step sol-gel method. We found that the amount of tourmaline has an important impact on the catalytic performance of the modified FeMnTiO x-based catalysts, and the NO x conversion exceeded 80% from 160 to 380 °C with the addition of 5 wt % tourmaline. Compared with the pure FeMnTiO x, the catalytic efficiency at a temperature below 100 °C was increased by nearly 18.9%, and the operation temperature window was broadened significantly. The enhanced catalytic performance of the FeMnTiO x catalyst was mainly attributed to the small spherical nanoparticles structure around the tourmaline powders, resulting in the increased content of Mn3+, Mn4+, and chemical oxygen on the catalytic surface. These as-developed tourmaline-modified FeMnTiO x materials have been demonstrated to be promising as a new type highly efficient low temperature NH3-SCR catalyst.
Assuntos
Amônia , Temperatura Baixa , Catálise , Silicatos , TemperaturaRESUMO
Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing ß cell apoptosis, CD68-cell infiltration, ROS production, and caspase-3 expression. The siRNA-knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor-2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking-induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking-related diabetes, and the therapeutic regimens are absent currently.
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Insulina/metabolismo , Glicogênio Hepático/biossíntese , Melatonina/farmacologia , Fumar/efeitos adversos , Animais , Hiperglicemia/etiologia , Secreção de Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pâncreas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor MT2 de Melatonina/metabolismoAssuntos
Apoio Social , Pessoas Transgênero , China , Feminino , Direitos Humanos , Humanos , Masculino , Sexismo/prevenção & controleRESUMO
This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromonas , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Nus , Morfolinas , Reação em Cadeia da Polimerase , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Hepatectomy in hepatocellular carcinoma (HCC) patients lead to postoperative hepatitis B virus (HBV) reactivation (PHR) as well as immunosuppression. METHODS: This prospective study involved 135 HBV-related HCC patients and 42 control hepatic hemangioma patients. RESULTS: Among HCC patients, 26 (19.3%) suffered PHR. Risk factors for PHR were HBV-cAg S1 positivity [hazard ratio (HR) = 404.82, P = 0.004], high preoperative total bilirubin level (HR = 186.38, P = 0.036), small preoperative proportions of CD3-CD16 + CD56 + cells (HR = 0.01, P = 0.014) and CD19 + B cells (HR = 0.02, P = 0.016), blood transfusion (HR = 157.03, P = 0.006) and high liver cirrhosis S score (HR = 270.45, P = 0.004). On postoperative day (POD) 3, PHR patients showed much greater immunosuppression than non-PHR patients based on proportions of T cells (CD3+, CD3 + CD4+, CD3 + CD8+), B cells (CD19+) and on levels of IgG, IgA antibodies, complement proteins C3, and C4. By POD 7, PHR patients had partially recovered but not as quickly as non-PHR patients: PHR patients still showed deficits in T cells (CD3+, CD3 + CD4+), CD3-CD16 + CD56+ cells and in levels of IgM, C3, C4, and C-reactive protein. CONCLUSION: PHR may be associated with resection-induced immunosuppression in patients with HBV-related HCC.
Assuntos
Carcinoma Hepatocelular/virologia , Hepatectomia/efeitos adversos , Vírus da Hepatite B/fisiologia , Hepatite B/complicações , Neoplasias Hepáticas/virologia , Complicações Pós-Operatórias , Ativação Viral , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Hepatite B/diagnóstico , Hepatite B/virologia , Humanos , Terapia de Imunossupressão , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carga ViralRESUMO
AIM: Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB-TACE compares with cTACE. METHODS: MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database and clinical trial registries were searched through June 2014. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: The analysis included four randomized controlled trials, one uncontrolled prospective study and one prospective case-control study, altogether involving 652 patients. Overall survival benefit was similar between cTACE and DEB-TACE patients (HR = 1.07, 95% CI = 0.82-1.40, P = 0.875). However, DEB-TACE was associated with a significantly higher objective tumor response rate (RR = 1.14, 95% CI = 1.01-1.29, P = 0.03) and a slightly lower incidence of adverse events. CONCLUSION: Though the available evidence suggests that although DEB-TACE is associated with better tumor response and potentially fewer adverse events, it does not provide greater survival benefit than cTACE. These results need to be validated in high-quality trials with large sample size.
RESUMO
Transarterial chemoembolization (TACE) and transarterial embolization (TAE) are commonly used as first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and have been shown to improve overall survival (OS). However, there remain concerns regarding whether the benefit of the prolonged survival achieved with TACE is superior to the maximum cytotoxic effect of the associated chemotherapeutics. This systematic review aims to compare the efficiency of TACE and TAE based on randomized controlled trials (RCTs). MEDLINE, EMBASE, the Cochrane library, the Science Citation Index, and the Chinese National Knowledge Infrastructure databases were systematically searched through the end of April 2014. Risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated. Meta-analysis of the RCTs was conducted to estimate the mortality and survival rate between the TACE and TAE groups. The analysis included five RCTs involving 582 patients. For all-cause mortality, TACE did not result in a statistically significant reduced incidence of adverse events than TAE with a pooled RR of 1.21 (95 % CI = 0.74-1.98, P = 0.16). In addition, 6-, 9-, 12-, 24-, and 36-month OS of the TACE group were not significantly higher than that of the TAE group (all P > 0.05). Interestingly, TACE resulted in a significantly higher rate of advanced events. The efficacy of TACE is not superior to TAE in advanced HCC patients. Moreover, TACE was associated with an increased rate of adverse events than TAE. Improved strategies are needed to reduce the risk of post-TACE complications.