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1.
J Immunother Cancer ; 10(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35379737

RESUMO

OBJECTIVE: This study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy. METHODS: Initially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis. RESULTS: In 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb-IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions. CONCLUSION: Perioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients' recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions. TRIAL REGISTRATION NUMBER: NCT04297202.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia , Período Perioperatório , Proteômica , Piridinas , Microambiente Tumoral
2.
Bioengineered ; 13(3): 4786-4797, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35139763

RESUMO

Chemoresistance in hepatocellular carcinoma (HCC) has been found to be influenced by exosomal transport of circRNAs. However, the role of circZFR in HCC chemoresistance still remains unclear. In the present study, circZFR was highly expressed in cisplatin (DDP)-resistant HCC cell lines and could regulate DDP resistance of the HCC cells. Also, circZFR was highly expressed in cancer-associated fibroblast (CAFs) and the exosome of CAFs. In addition, supplementation of CAFs in culture medium could promote DDP resistance of HCC cells. In vivo tumor xenograft experiments showed that knockdown of circZFR inhibited tumor growth and weakened DDP resistance, while CAFs-derived exosomes incubation increased the expression of circZFR, inhibited the STAT3/NF-κB pathway, promoted tumor growth, and enhanced DDP resistance. In general, CAFs-derived exosomes deliver circZFR to HCC cells, inhibit the STAT3/NF-κB pathway, and promote HCC development and chemoresistance. The results provided a new sight for the prevention and treatment of chemoresistance in HCC.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , RNA Circular , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Circular/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdutores
3.
J Med Virol ; 94(2): 521-530, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34761827

RESUMO

Measles is one of the most infectious diseases of humans. It is caused by the measles virus (MeV) and can lead to serious illness, lifelong complications, and even death. Whole-genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The noncoding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Although the nucleotide substitution rate of H1 WGS was around 0.75 × 10-3 substitution per site per year, the M/F NCR had an evolutionary rate three times higher, with 2.44 × 10-3 substitution per site per year. Phylogenetic analysis identified three distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by two other genetic groups in 1999-2002. Bayesian skyline plot showed that the genetic diversity of the H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52 628) and 2020 (993). The current coronavirus disease 2019 (COVID-19) pandemic might have some effect on the measles epidemic and further studies will be necessary to assess the genetic diversity of the H1 genotype in a post-COVID area.


Assuntos
Evolução Molecular , Genoma Viral/genética , Vírus do Sarampo/genética , China/epidemiologia , Genes Virais/genética , Variação Genética , Genômica , Genótipo , Humanos , Sarampo/epidemiologia , Sarampo/virologia , Vírus do Sarampo/classificação , Filogenia , RNA Viral/genética
4.
Front Cell Dev Biol ; 9: 775462, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869376

RESUMO

Immune associated cells in the microenvironment have a significant impact on the development and progression of hepatocellular carcinoma (HCC) and have received more and more attention. Different types of immune-associated cells play different roles, including promoting/inhibiting HCC and several different types that are controversial. It is well known that immune escape of HCC has become a difficult problem in tumor therapy. Therefore, in recent years, a large number of studies have focused on the immune microenvironment of HCC, explored many mechanisms worth identifying tumor immunosuppression, and developed a variety of immunotherapy methods as targets, laying the foundation for the final victory in the fight against HCC. This paper reviews recent studies on the immune microenvironment of HCC that are more reliable and important, and provides a more comprehensive view of the investigation of the immune microenvironment of HCC and the development of more immunotherapeutic approaches based on the relevant summaries of different immune cells.

5.
J Am Chem Soc ; 143(10): 3881-3888, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33683868

RESUMO

Selective carbon-carbon (C-C) bond formation in chemical synthesis generally requires prefunctionalized building blocks. However, the requisite prefunctionalization steps undermine the overall efficiency of synthetic sequences that rely on such reactions, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without prefunctionalized building blocks. In this transformation several classes of unactivated internal acceptor alkynes can be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. This method is facilitated by a tailored P,N-ligand that enables regioselective addition and suppresses secondary E/Z-isomerization of the product. The reaction is scalable and can operate effectively with as low as 0.5 mol % catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.


Assuntos
Alcinos/química , Alcinos/síntese química , Carbono/química , Catálise , Oxirredução , Paládio/química , Propanóis/química , Estereoisomerismo
6.
Sci Rep ; 11(1): 6517, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753770

RESUMO

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy.


Assuntos
Antraquinonas/farmacologia , Interferon gama/genética , Meduloblastoma/tratamento farmacológico , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/genética , Sulfonamidas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Xenoenxertos , Humanos , Interleucina-6/genética , Meduloblastoma/genética , Meduloblastoma/patologia , Camundongos , Fosforilação/efeitos dos fármacos
7.
Cell Death Discov ; 7(1): 47, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723252

RESUMO

Growing evidence demonstrates that MicroRNAs (miRNAs) play an essential role in contributing to tumor development and progression. However, the underlying role and mechanisms of miR-23b-5p in hepatocellular carcinoma (HCC) formation remain unclear. Our study showed that miR-23b-5p was downregulated in the HCC tissues and cell lines, and lower expression of miR-23b-5p was associated with more severe tumor size and poorer survival. Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in HCC specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p. In addition, miR-23b-5p could regulate cyclin D1 and c-MYC expression by directly targeting FOXM1. Further study revealed that restoration of FOXM1 neutralized the cell cycle arrest and cell proliferation inhibition caused by miR-23b-5p. Taken together, our findings suggest that miR-23b-5p acted as a tumor suppressor role in HCC progression by targeting FOXM1 and may serve as a potential novel biomarker for HCC diagnosis and prognosis.

8.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 26-31, 2021 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33723933

RESUMO

OBJECTIVES: This study aimed to investigate the effects of microRNA-146a (miR-146a) on the production of cytokines in lymphocytes stimulated by Porphyromonas gingivalis (P.gingivalis) lipopolysaccharide (LPS). METHODS: Lymphocytes were harvested from mouse spleen and cultured in vitro. The cells were treated with P. gingivalis LPS, miR-146a mimic, or miR-146a inhibitor. Scramble RNA served as the negative control of mimic and inhibitor. The production of inflammatory cytokines was detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Compared with non-LPS-stimulated group, P. gingivalis LPS could increase the levels of interleukin (IL)-1ß, IL-6, receptor activator NF-κB ligand (RANKL), and IL-10 (P<0.05) and decrease the mRNA level of osteoprotectin (OPG) (P<0.05). However, it did not significantly change the secretion of OPG. Compared with the negative control group, miR-146a mimic upregulated the levels of IL-10 and OPG (P<0.05), downregulated IL-1ß, IL-6, and RANKL (P<0.05). Meanwhile, miR-146a inhibitor had a reverse effect on these cytokines (P<0.05) in P.gingivalis LPS-treated-lymphocytes. CONCLUSIONS: MiR-146a can provide a suitable microenvironment for bone formation by preventing the inflammatory effects of P.gingivalis LPS through the inhibition of IL-1ß, IL-6, and RNAKL, thereby enhancing IL-10 and OPG.


Assuntos
Lipopolissacarídeos , MicroRNAs , Animais , Citocinas , Linfócitos , Camundongos , Porphyromonas gingivalis
9.
J Dent ; 107: 103599, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33561513

RESUMO

OBJECTIVES: The purpose of this study was to prepare carboxymethyl chitosan (CMC) and lysozyme nanogels that could encapsulate amorphous calcium phosphate (ACP) for achieving its controlled delivery, thus forming an aprismatic enamel-like layer on the demineralized enamel surface. METHODS: CMC/LYZ-ACP nanogels were developed, and the controlled delivery of ACP from the nanogels was induced by the presence of NaCl. The nanogel morphologies at various NaCl concentrations was measured by transmission electron microscopy (TEM). The particle sizes and zeta potentials (ζ-potential) of the samples were determined using a combined dynamic light scattering/particle electrophoresis instrument. Comparing the remineralization effect of the CMC/LYZ-ACP nanogels on the demineralized enamel surface with that of a fluoride treatment, the remineralization effect was examined by nanoindentation tests, X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). RESULTS: CMC/LYZ-ACP nanogels were negatively charged spherical structures with a particle size of approximately 300 nm. At high concentrations of NaCl (0.15 M), ACP was dissociated from the disassembled nanogels and transformed into hydroxyapatite (HAP). Groups treated with the CMC/LYZ-ACP nanogels showed the regeneration of an aprismatic enamel-like layer on an acid-etched enamel surface, which provided increased mechanical properties (P < 0.05) and a high impermeability (P < 0.01) compared to those of the fluoride-treated group. CONCLUSIONS: This research provides a new idea for the stable and controllable delivery of ACP from CMC/LYZ-ACP nanogels, which can form an aprismatic enamel-like layer in situ on the surface of demineralized enamel. In regard to further clinical development, this material and method may be promising for treating early enamel caries.


Assuntos
Quitosana , Fosfatos de Cálcio , Caseínas , Esmalte Dentário , Muramidase , Nanogéis , Remineralização Dentária
10.
JCI Insight ; 6(4)2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33411696

RESUMO

Reestablishing an appropriate balance between T effector cells (Teff) and Tregs is essential for correcting autoimmunity. Multiple sclerosis (MS) is an immune-mediated chronic CNS disease characterized by neuroinflammation, demyelination, and neuronal degeneration, in which the Teff:Treg balance is skewed toward pathogenic Teffs Th1 and Th17 cells. STAT3 is a key regulator of Teff:Treg balance. Using the structure-based design, we have developed a potentially novel small-molecule prodrug LLL12b that specifically inhibits STAT3 and suppresses Th17 differentiation and expansion. Moreover, LLL12b regulates the fate decision between Th17 and Tregs in an inflammatory environment, shifting Th17:Treg balance toward Tregs and favoring the resolution of inflammation. Therapeutic administration of LLL12b after disease onset significantly suppresses disease progression in adoptively transferred, chronic, and relapsing-remitting experimental autoimmune encephalomyelitis. Disease relapses were also significantly suppressed by LLL12b given during the remission phase. Additionally, LLL12b shifts Th17:Treg balance of CD4+ T cells from MS patients toward Tregs and increases Teff sensitivity to Treg-mediated suppression. These data suggest that selective inhibition of STAT3 by the small molecule LLL12b recalibrates the effector and regulatory arms of CD4+ T responses, representing a potentially clinically translatable therapeutic strategy for MS.


Assuntos
Autoimunidade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Fator de Transcrição STAT3/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Animais , Antraquinonas/farmacologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/imunologia , Encefalomielite Autoimune Experimental/imunologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sulfonamidas/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/imunologia
11.
Emerg Infect Dis ; 27(1): 275-277, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33350918

RESUMO

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/epidemiologia
12.
J Clin Microbiol ; 58(11)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32878947

RESUMO

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution. Infants and children of ages 8 to 23 months were the main population of VARI. VARI mainly occurred within 14 days after measles vaccination. The number of VARI cases peaked on the 8th day after measles vaccination, which was later than that of genotype H1 wild-type measles cases with a measles vaccination history. VARI presents clinical symptoms similar to those of measles. The frequencies of the "3Cs" (cough, coryza, and conjunctivitis), Koplik spots, and complications in VARI cases were significantly lower than those in wild-type measles cases. In total, 94.06% of sequences from VARI cases were identical to measles vaccine strain S191 in the C-terminal 450-nucleotide sequence of the nucleoprotein (N-450) gene. A few substitutions were found in N-450 sequences of the VARI cases. The confirmation of VARI has become an emerging issue in the process of measles elimination. Rapid confirmation of VARI is critical for measles surveillance and will help to determine the response measures for measles, especially in measles preelimination and elimination settings. The suspected measles cases with measles-containing vaccine (MCV) vaccination were recommended to be tested by the laboratory to identify wild-type measles or VARI.


Assuntos
Exantema , Sarampo , China/epidemiologia , Surtos de Doenças , Exantema/epidemiologia , Humanos , Lactente , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo/efeitos adversos , Vírus do Sarampo/genética , Vacinação
13.
Vasc Endovascular Surg ; 54(7): 565-572, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32677549

RESUMO

OBJECTIVES: To investigate the safety and efficacy of a stent combined with a linear strand of 125I seeds to treat malignant cancer-associated venous obstruction. METHODS: We retrospectively analyzed the data of 57 patients with malignant cancer-associated venous obstruction. Nineteen patients underwent the placement of a stent combined with a linear strand of 125I seeds (group A), and 38 patients underwent the placement of a bare stent (group B). The following parameters were compared between the 2 groups of patients: symptom relief rate, duration of venous patency, survival time, quality of life, and adverse events. RESULTS: A total of 34 stents and 527 seeds were implanted in group A, while a total of 57 stents were implanted in group B. The surgery success rate was 96.5%, and no serious complication related to the surgery was reported. Symptoms of venous obstruction improved significantly after surgery. The score of group A decreased from 14.74 ± 0.562 points before surgery to 2.79 ± 1.357 points after surgery(P < .001), and the score of group B decreased from 13.79 ± 1.398 points before surgery to 5.55 ± 3.674 points after surgery (P < .001). The patency rate of group A was significantly higher than that of group B at 1 to 6 months after surgery (100%, 84.2%, 68.4%, 63.2%, 36.8%, 21.1% vs 68.4%, 23.7%, 18.4%, 7.9%, 5.3%, 2.6%, respectively; P < .05). Before treatment, there was no statistically significant difference in the Karnofsky Performance Status (KPS) score between the groups (P = .791). After 1 to 6 months of treatment, the KPS score was significantly higher in group A than in group B (P = .013). The median patency duration in groups A and B was 125 days (95% CI: 80.018-169.982) and 35 days (95% CI: 20.501-49.499), respectively (P < .001). The median survival time of group A was 155 days (95% CI: 110.406-199.594), and that of group B was 98 days (95% CI: 55.712-140.288; P = .325). Multivariate analysis showed that the implantation of a stent combined with a linear strand of 125I seeds and the KPS score (≥80 points) were independent factors of long-term patency after stent placement. CONCLUSIONS: The placement of a stent combined with a linear strand of 125I seeds is a safe and effective treatment for venous obstruction caused by malignant tumors. This treatment provides prolonged patency compared with the placement of bare stent, and while it does not significantly improve the survival time of patients, it can improve their quality of life.


Assuntos
Procedimentos Endovasculares/instrumentação , Radioisótopos do Iodo/administração & dosagem , Neoplasias/terapia , Células Neoplásicas Circulantes/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Stents , Doenças Vasculares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/patologia , Desenho de Prótese , Qualidade de Vida , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Doenças Vasculares/patologia , Grau de Desobstrução Vascular
14.
Arch Virol ; 165(8): 1895-1898, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462283

RESUMO

We previously reported genotype D11 strains of measles virus that were first isolated from a measles outbreak associated with imported cases in Yunnan province of China by Zhang et al. (Emerg Infect Dis 16(6):943-7, 2010). Genotype D11 has been identified as the 24th genotype of the WHO reference strains. In this study, we sequenced the whole genome of a D11 strain. Phylogenetic analysis using the complete genome sequences of D11 and other reference strains showed that the D11 strain formed a distinct branch that was distant from the other genotypes and was most closely related to the reference strain D7. The M-F non-coding region (NCR) and the N450 coding region sequence (CDS) were found to be the most variable regions. This report provides basic genetic data on genotype D11 for further study of measles evolution and the support for measles elimination.


Assuntos
Genoma Viral/genética , Vírus do Sarampo/genética , China , Surtos de Doenças , Genótipo , Humanos , Sarampo/virologia , Filogenia , Análise de Sequência de DNA/métodos
15.
Vaccine ; 38(22): 3832-3838, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32280040

RESUMO

Measles incidence has decreased dramatically in China due to the implement of measles-containing vaccine (MCV). However, a measles epidemic caused resurgence recently, even among vaccinated individuals. To evaluate the effectiveness of current immunization programs and discuss initiatives for the next step in measles elimination in mainland China, the characteristics of 121,969 laboratory-confirmed measles cases reported in the measles surveillance system (MSS) during 2014-2018 were analyzed according to the vaccination status of the cases in this study. Children under 2 years of age without MCV vaccination (44,424, 36.42% of all cases) and adults over 20 years of age with an unknown vaccination history (37,564, 30.80% of all cases) accounted for the majority of measles cases from 2014 to 2018. 42,425 (34.78%) of the 77,384 cases with available vaccination information were categorized as programmatically preventable. 38,840 (91.55%) of the 42,425 cases were aged ≥8 months without the MCV vaccination history. 34,959 (28.66%) cases were categorized as programmatically non-preventable, of whom 22,611 (64.68%) were too young to receive their first MCV dose, 6857 (19.61%) received their first dose and were too young to receive their second dose, 5491 (15.71%) received at least two doses of MCV. 15,933 (13.06%) of the 121,969 cases had a history of MCV vaccination. Measles virus infection in cases with an MCV vaccination history mainly occurred within the first month after MCV vaccination, especially in those who received a one-dose measles vaccination. MCV vaccination could reduce the frequencies of clinical symptoms and complications of measles cases. Our study confirmed that the current measles immunization programs used in mainland China is effective in reducing the measles incidence in China. Unvaccinated infants/children aged 8-23 months and high risk susceptible adults over 20 years of age with unknown vaccination histories should be the focus groups of measles immunization activities in China in the future.


Assuntos
Vacina contra Sarampo/administração & dosagem , Sarampo , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Criança , China/epidemiologia , Humanos , Programas de Imunização , Incidência , Lactente , Sarampo/epidemiologia , Sarampo/prevenção & controle , Adulto Jovem
16.
Org Lett ; 21(22): 8952-8956, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31647668

RESUMO

A Cu-catalyzed enantioselective aminoboration of E-vinylarenes with pivZPhos as a ligand is reported. Enantioenriched aminoborates are prepared with excellent regio- and enantioselectivities up to >99:1 er under the optimized conditions. The utility of the current method was further established by rapid conversion of an adduct to a chiral benzo[f][1,4]oxazepine. A model for the stereochemistry of the asymmetric aminoboration process, which agrees with the experimental outcomes, was generated by computational analysis of the systems.

17.
Anal Biochem ; 586: 113413, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479631

RESUMO

The Hippo signaling pathway controls cell-cell contact, cell proliferation, as well as organ size by integrating changes in the cellular microenvironment. In recent years, the pivotal role of Hippo signaling in cancers has been well recognized. Inhibition of the pathway promotes the translocation of the major Hippo pathway effectors, the yes-associated protein (YAP) and its paralog TAZ, to the nucleus, where they interact with the transcription factor family transcriptional enhancer associate domain (TEAD), thus coactivating the expression of downstream genes, leading to cell transformation, tissue overgrowth, and tumor development. Therefore, the interruption of the YAP-TEAD transcriptional complex represents a novel opportunity for the treatment of cancer. Here, we established a fluorescence polarization (FP)-based assay for the identification and evaluation of YAP-TEAD protein-protein interface (PPI) inhibitors at the YAP Ω-loop binding region of TEAD, which is also called interface 3 at the YAP-TEAD binding surface. Furthermore, a patented small molecule (Patent-22) was evaluated by the FP assay, which confirmed that it was a YAP-TEAD PPI inhibitor at interface 3. Possessing great application value, this FP method is reliable, robust, and economical for inhibitor assessment and drug discovery.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Peptídeos , Bibliotecas de Moléculas Pequenas , Fatores de Transcrição/antagonistas & inibidores , Cristalografia por Raios X , Polarização de Fluorescência , Humanos , Modelos Moleculares , Estrutura Molecular , Peptídeos/análise , Peptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/análise , Bibliotecas de Moléculas Pequenas/farmacologia
18.
Data Brief ; 25: 103737, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31304204

RESUMO

In this article, we presented the detailed measurements and comparisons of skeletal muscle perfusion parameters in a canine hind limb ischemia model. Data presented here is related to and supportive to the research article "Evaluation of skeletal muscle perfusion in canine hind limb ischemia model using color-coded digital subtraction angiography" [1], where interpretation of the research data presented here is available.

19.
PLoS One ; 14(6): e0218782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220172

RESUMO

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.


Assuntos
Vírus do Sarampo/genética , Sarampo/epidemiologia , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Doenças Endêmicas , Feminino , Genótipo , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/prevenção & controle , Vírus do Sarampo/classificação , Vírus do Sarampo/imunologia , Tipagem Molecular , Filogenia , Análise de Sequência de DNA , Vacinação , Adulto Jovem
20.
Chem Sci ; 10(15): 4339-4345, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057761

RESUMO

We report the synthesis of enantiomerically enriched 1,4-benzodioxanes containing alkyl, aryl, heteroaryl, and/or carbonyl substituents at the 2-position. The starting 1,4-benzodioxines were readily synthesized via ring closing metathesis using an efficient nitro-Grela catalyst at ppm levels. Excellent enantioselectivities of up to 99:1 er were obtained by using the versatile catalyst system [Ir(cod)Cl]2/BIDIME-dimer in the asymmetric hydrogenation of 2-substituted 1,4-benzodioxines. Furthermore, DFT calculations reveal that the selectivity of the process is controlled by the protonation step; and coordinating groups on the substrate may alter the interaction with the catalyst, resulting in a change in the facial selectivity.

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