Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 118
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Orthop Sci ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061466

RESUMO

PURPOSE: The effects of different combination of surgical techniques for recurrent patella dislocation (RPD) remain unclear. Thus, aim of this study was to investigate the surgical outcomes of different combination of surgical techniques for RPD. METHODS: The clinical data of 79 patients with RPD from August 2014 to October 2016 were analysed retrospectively. Knee joint was assessed according to measurements of the congruence angle (CA), patellar tilt angle (PTA) and lateral patellofemoral angle (LPFA). Knee function was evaluated by Kujala patellofemoral score, Lysholm knee score and Tegner score. Patients were followed up by out-patient examination and telephone till October 2018. RESULTS: Preoperative clinical characteristics were similar across groups. It was statistically insignificant among three groups in CA, PTA, LPFA and redislocation rate. In term of knee functions, the MPFL reconstruction and LPR release group had the highest score (Lysholm score: 91.82 ± 4.64, Kujala score: 94.22 ± 4.26, Tegner score: 5.80 ± 1.00, respectively) and the LPR release and MPR plication had the lowest score (Lysholm score: 78.10 ± 6.90, Kujala score: 80.91 ± 4.30, Tegner score: 4.98 ± 1.22, respectively). CONCLUSION: Three combinations of surgical methods were similar in terms of postoperative joint congruence and redislocation rate, but MPFL reconstruction combined with LPR release is worthy to be promoted with the highest knee function scores.

2.
J Chin Med Assoc ; 83(3): 266-271, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31990819

RESUMO

BACKGROUND: Acute Stanford type A aortic dissection is a lethal disease requiring surgery. Evidence regarding the effects of preoperative creatinine in mortality is limited, and few studies have evaluated the effect of postoperative dialysis treatment on it. METHODS: In this cohort study, we continuously recruited 632 surgical patients who were treated for acute type A aortic dissection in our hospital between January 2015 and May 2017. The preoperative level of serum creatinine was measured. All patients were followed up after surgery for 30 days to determine early mortality. RESULTS: The 30-day mortality after surgery increased with elevated levels of preoperative serum creatinine. Median (interquartile range) serum creatinine levels in survivors were 9.61 µmol/dL (7.28-12.62 µmol/dL) versus 13.41 µmol/dL (10.28-20.63 µmol/dL) in death (p < 0.01). Adjusted odds ratios for increasing per µmol/dL serum creatinine were 1.09 (95% confidence interval, 1.03-1.15). We also found that the effect of preoperative creatinine on 30-day mortality was diminished by dialysis treatment after surgery. CONCLUSION: Preoperative serum creatinine predicts outcome in patients undergoing surgery for Stanford type A aortic dissection, and postoperative dialysis treatment can reduce its hazard.

4.
Parasitol Res ; 119(2): 465-471, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845021

RESUMO

Blastocystis is a highly prevalent eukaryotic parasite of many animals and humans worldwide. It can compromise the gastrointestinal tract and cause gastrointestinal symptoms, constituting a serious threat to human health and animal growth. Many animals are potential sources of Blastocystis infection in humans. However, limited data are available regarding the prevalence and subtype distribution of Blastocystis infection among zoo animals in China. Therefore, the present study examined the prevalence and subtypes of Blastocystis in zoo animals in Hangzhou, Dalian, and Suzhou cities, China. Of 450 fecal samples from zoo animals, 27 (6.0%) were PCR-positive for Blastocystis, with 7.7% (8/104), 11.3% (7/62), 16.7% (3/18), 1.8% (2/114), 6.3% (1/16), 9.5% (2/21), and 3.6% (4/109) in artiodactyla, aves, rodentia, nonhuman primates, perissodactyla, marsupialia, and carnivora, respectively. Significant differences in the prevalence of Blastocystis were found among different animal groups (P < 0.05). Sequence analysis showed 7 known subtypes (ST2, ST4, ST5, ST7, ST8, ST10, and ST14) of Blastocystis in the present study, with ST10 (10/27) as the predominant subtype in all three of the examined zoos. To our knowledge, this is the first report of Blastocystis infection in Damaliscus dorcas, Cervus elaphus, Macropus rufogriseus, Grus japonensis, Trichoglossus haematodus, Panthera tigris ssp. tigris (white), Panthera tigris ssp. altaica, Lycaon pictus, Suricata suricatta, and Dolichotis patagonum in China. These results demonstrate the presence of Blastocystis infection in zoo animals and provided baseline data for preventing and controlling Blastocystis infection in zoo animals and humans in China.

5.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4975-4984, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872608

RESUMO

Databases including CNKI,Wan Fang,CBM,VIP,PubMed and Cochrane Library were searched to collect qualified researches,and the quality of articles was evaluated according to scales. Meta-analysis including subgroup analysis was performed by using Rev Man 5. 3 software and Meta-regression test was performed by using Stata 12. 0 software. All of these methods were used to systematically evaluate the safety and clinical efficacy of Qili Qiangxin Capsules in treatment of ischemic heart failure under two circumstances( with or without syndrome differentiation). A total of 22 randomized controlled trials( RCTs) involving 1 942 patients were included,with generally low quality. RESULTS: of Meta-analysis showed that as compared with the routine Western treatment alone,additional use of Qili Qiangxin Capsules could improve the clinical efficacy( RR = 1. 21,95%CI[1. 16,1. 27],P<0. 000 01) in treatment of ischemic heart failure,with its combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 03,I~2= 78. 9%),Meta-regression( sig = 0. 9,P = 0. 057); left ventricular ejection fraction( WMD = 7. 28,95% CI[5. 18,9. 38],P<0. 000 01),with combined effect of syndrome differentiation group greater than that of non-syndrome differentiation group( P= 0. 01,I2= 83. 2%),Meta-regression( I~2= 81. 09%,R2= 29. 08%,sig = 0. 47,P = 0. 029); 6-minute walk test( WMD = 33. 20,95%CI[24. 70,41. 70 ],P < 0. 000 01); left ventricular end diastolic diameter( WMD =-4. 61,95% CI[-5. 38,-3. 84 ],P <0. 000 01); left ventricular end diastolic volume( WMD =-34. 43,95%CI[-38. 81,-30. 05],P< 0. 000 01); and left ventricular end systolic volume( WMD =-9. 60,95% CI[-13. 16,-6. 05],P < 0. 000 01). Adverse effects were reported in 11 patients taking Qili Qiangxin Capsules and in 20 patients with routine treatment group,tolerable in both groups. None of the patients had obvious abnormality in liver and kidney function. Qili Qiangxin Capsules were effective and safe in the treatment of ischemic heart failure,which can further improve clinical efficacy as compared with routine treatment alone. Qili Qiangxin Capsules with syndrome differentiation showed more significant effects than those without syndrome differentiation,indicating better efficacy of clinical syndrome differentiation. However,these conclusions still need to be verified with more high-quality and large-sample literature.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Cápsulas , Humanos , Masculino , Síndrome
6.
Vet Microbiol ; 237: 108390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31585652

RESUMO

Parvovirosis is a highly contagious disease in dogs, often causing acute hemorrhagic enteritis and altering the intestinal microflora. In this study, real-time PCR was used to detect the viral copy numbers in dogs diagnosed with the disease. Hematological and hemobiochemical parameters were also determined. The species and abundances of the fecal microbial flora in both sick and healthy dogs were determined and compared via metagenomic sequencing. The viral copy numbers in the sick dogs were infected with little difference in the positive samples. The blood coagulation time was significantly shorter and the number of white blood cells was significantly greater in the sick dogs. The serum calcium content was slightly increased and the phosphorus content was reduced in the sick dogs. The LDH and CK activities were significantly elevated in the sick dogs. Metagenomic sequencing and analysis revealed relatively more Escherichia, Lachnoclostridium, gnavus group (Ruminococcus), and uncultured_bacterium_f_lachnospiraceae in the infected dogs, whereas the abundance of Collinsella was relatively reduced. Alloprevotella and Sutterella were absent among the fecal microorganisms of the infected dogs. The relative abundances of Romboutsia, Erysipelatoclostridium, Anaerotruncus, and Blautia were significantly increased in the infected dogs. Functional analysis of the metagenomes of the samples indicated a significant enrichment of the 'replication, recombination and repair', 'nucleotide transport and metabolism', 'transcription', and 'defense metabolism' functions in the fecal microbial flora of the infected dogs. In summary, this study provides a scientific theoretical basis for preventing and controlling diarrhea caused by the canine parvovirus.


Assuntos
Bactérias/classificação , Doenças do Cão/virologia , Fezes/microbiologia , Infecções por Parvoviridae/veterinária , Animais , Cães , Metagenômica , Infecções por Parvoviridae/virologia , Parvovirus Canino , Reação em Cadeia da Polimerase em Tempo Real
8.
Drug Dev Res ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397505

RESUMO

The proteolytic enzyme ß-secretase (BACE1) plays a central role in the synthesis of the pathogenic ß-amyloid peptides (Aß) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+• ) assay, which could be used as a lead compound for further study.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31202083

RESUMO

The shell color of marine bivalves shows great diversity and is considered as an economic trait. In China, the hard clam, Mercenaria mercenaria, commonly has three shell colors in the wild: red, white, and mottled. The genetic mechanisms controlling color segregation are not fully understood. In this study, RNA-seq was performed to exploit the related shell color genes and determine the genetic basis of the different shell colors. Nine sequence libraries with those three shell colors of hard clam were constructed; 406,377 transcripts and 248,251 unigenes were obtained with N50 values of 1365 and 1682 base pairs, respectively. Cluster analysis identified 363, 392, and 220 genes exclusively highly expressed in red, white, and mottled clams, respectively. We further classified differentially expressed genes (DEGs), the genes involved in lipid binding and transport, signal transduction, ATP synthesis, and other processes in the red vs white comparison were found, which may participate in red shell formation. DEGs related to signal transduction, particularly G protein-coupled receptor activity, were found in the red vs mottled comparison, suggesting that these genes might be important in mottled shell formation. In the white vs mottled comparison, DEGs involved in zinc ion binding were found. Our results provide new insights into shell color formation mechanisms in molluscs. This information could be used in selective breeding and marker-assisted breeding of this economically important clam species.


Assuntos
Exoesqueleto/metabolismo , Mercenaria/genética , Transcriptoma , Exoesqueleto/anatomia & histologia , Animais , Análise por Conglomerados , Perfilação da Expressão Gênica , Mercenaria/anatomia & histologia , Anotação de Sequência Molecular , Pigmentação
10.
Biochem Biophys Res Commun ; 512(4): 779-785, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30928098

RESUMO

3-oxoacid CoA-transferase 1 (OXCT1) is a key enzyme in ketone body metabolism that is expressed in adipose and other tissues. The present study addressed the function of OXCT1 in adipose tissue from Tan sheep. The 1563 bp ovine OXCT1 coding sequence was cloned from ovine adipose tissue. The OXCT1 protein sequence was highly homologous to OXCT1 from other species. OXCT1 was highly expressed in kidney and at lower levels in small intestine, lung, spleen, heart, stomach, liver, tail adipose, and cartilage, but not in longissimus muscle. OXCT1 was expressed at higher levels in perirenal and tail adipose tissues than in subcutaneous adipose tissue. OXCT1 expression levels increased during the in vitro differentiation of adipocytes, but decreased dramatically at day 8. OXCT1 knockdown in ovine adipocytes promoted lipid accumulation, whereas overexpression did the converse. This study demonstrates that OXCT1 may play a role in adipogenesis and provides new insight on adipose deposition in sheep.

11.
Molecules ; 24(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669620

RESUMO

Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.


Assuntos
Betaína/farmacologia , Lipopolissacarídeos/imunologia , Microglia/efeitos dos fármacos , Microglia/fisiologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Biomarcadores , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Óxido Nítrico , Fenótipo
12.
RNA Biol ; 16(3): 282-294, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30663934

RESUMO

Long-term memory formation requires gene expression and new protein synthesis. MicroRNAs (miRNAs), a family of small non-coding RNAs that inhibit target gene mRNA expression, are involved in new memory formation. In this study, elevated miR-151-5p (miR-151) levels were found to be responsible for hippocampal contextual fear memory formation. Using a luciferase reporter assay, we demonstrated that miR-151 targets APH1a, a protein that has been identified as a key factor in γ-secretase activity, namely APH1a. Blocking miR-151 can upregulate APH1a protein levels and subsequently impair hippocampal fear memory formation. These results indicate that miR-151 is involved in hippocampal contextual fear memory by inhibiting APH1a protein expression. This work provides novel evidence for the role of miRNAs in memory formation and demonstrates the implication of APH1a protein in miRNA processing in the adult brain.


Assuntos
Endopeptidases/genética , Medo , Regulação da Expressão Gênica , Memória , MicroRNAs/genética , Interferência de RNA , Animais , Ansiedade/genética , Comportamento Animal , Hipocampo/metabolismo , Proteínas de Membrana , Camundongos
13.
Ann Hum Genet ; 83(1): 46-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30191965

RESUMO

The genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci were analyzed in 449 individuals of the Uygur population from Ili Kazakh Autonomous Prefecture, Northwestern China. Phylogenetic analysis was performed among the Ili Uygur population and other relevant populations. The neighbor-joining tree and multidimensional scaling plot were generated based on the Nei's standard genetic distance. We found a total of 173 alleles with corresponding frequencies ranging from 0.5022 to 0.0011. The combined powers of discrimination and exclusion for the 15 autosomal STR loci were 0.99999999985 and 0.99999880065, respectively. Population comparisons indicated that the Ili Uygur population had a relatively close genetic relationship with the Uygur populations from other regions of China. The pairwise genetic distance and P-values between Ili Uygur and 10 published populations showed that no statistically significant differences existed between the Ili Uygur population and the Kashi, Kashgar, and Kotan Uygur. Therefore, the Ili Uygur population has its own unique Uygur genetic characteristics that were different from the other ethnic populations of China.


Assuntos
Grupos Étnicos/genética , Repetições de Microssatélites , Filogenia , Polimorfismo Genético , Alelos , Grupo com Ancestrais do Continente Asiático/etnologia , China/etnologia , Frequência do Gene , Humanos
14.
Asian J Androl ; 21(4): 360-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30460934

RESUMO

We aimed to establish a novel rat model of seminal vesiculitis that would provide an effective approach to investigate the pathogenesis of this disease in the future. Eight male rats received the same operation, during which the root of one of the two seminal vesicles was partly ligatured with sutures and the other vesicle was left intact. The samples of seminal vesicles were harvested on the 8th day following the operation. Hematoxylin and eosin and Masson's trichrome stains were used to observe the histopathology and the presence of fibrous tissue in seminal vesicles, respectively. Immunoblotting and immunohistochemistry were applied to determine the tumor necrosis factor-alpha and cyclooxygenase-2 levels in seminal vesicle tissues. Real-time fluorescence quantitative polymerase chain reaction was performed to measure the gene expression levels of proinflammatory cytokines. H2O2levelsin the seminal plasma from the seminal vesicle were also measured. Hematoxylin and eosin staining suggested that there was inflammatory cell infiltration into the seminal vesicles treated by partial root ligation. The tumor necrosis factor-alpha and cyclooxygenase-2 proteins were significantly upregulated in the treated seminal vesicles. The tumor necrosis factor-alpha, cyclooxygenase, interleukin 6, and inducible nitric oxide synthase mRNA expression levels were also upregulated in the treated seminal vesicles. The H2O2 levels in the seminal plasma from seminal vesicles with partial root ligation were significantly elevated compared with those from vesicle left intact. In conclusion, partially ligating the root of the seminal vesicle via sutures in rats is an effective method to establish a seminal vesiculitis rat model.

15.
Transbound Emerg Dis ; 66(2): 852-864, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30520567

RESUMO

African swine fever (ASF) is a transcontinental, contagious, fatal virus disease of pig with devastating socioeconomic impacts. Interaction between infected wild boar and domestic pig may spread the virus. The disease is spreading fast from the west of Eurasia towards ASF-free China. Consequently, prediction of the distribution of ASF along the Sino-Russian-Korean borders is urgent. Our area of interest is Northeast China. The reported ASF-locations in 11 contiguous countries from the Baltic to the Russian Federation were extracted from the archive of the World Organization for Animal Health from July 19, 2007 to March 27, 2017. The locational records of the wild boar were obtained from literature. The environmental predictor variables were downloaded from the WorldClim website. Spatial rarefication and pair-wise geographic distance comparison were applied to minimize spatial autocorrelation of presence points. Principal component analysis (PCA) was used to minimize multi-collinearity among predictor variables. We selected the maximum entropy algorithm for spatial modelling of ASF and wild boar separately, combined the wild boar prediction with the domestic pig census in a single map of suids and overlaid the ASF with the suids map. The accuracy of the models was assessed by the AUC. PCA delivered five components accounting for 95.7% of the variance. Spatial autocorrelation was shown to be insignificant for both ASF and wild boar records. The spatial models showed high mean AUC (0.92 and 0.97) combined with low standard deviations (0.003 and 0.006) for ASF and wild boar, respectively. The overlay of the ASF and suids maps suggests that a relatively short sector of the Sino-Russian border has a high probability entry point of ASF at current conditions. Two sectors of the Sino-Korean border present an elevated risk.


Assuntos
Vírus da Febre Suína Africana/isolamento & purificação , Febre Suína Africana/epidemiologia , Doenças dos Suínos/epidemiologia , Animais , China/epidemiologia , Probabilidade , República da Coreia/epidemiologia , Federação Russa/epidemiologia , Análise Espacial , Sus scrofa/virologia , Suínos
16.
Biomed Pharmacother ; 109: 751-761, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551528

RESUMO

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) represents an aggressive malignancy often accompanied with a poor prognosis. Owing to the poor mortality and morbidity rates associated with this malignancy, a deeper understanding of the finer molecular changes that occur in ESCC is required in order to identify novel potential targets for early detection and therapy. At present the mechanism by which ESCC functions on a molecular level is not fully understood. Hence, the aim of the present study was to ascertain as to whether microRNA-384 (miR-384) influences the progression of ESCC. MATERIAL AND METHODS: Bioinformatics analysis was initially conducted to identify ESCC-related differentially expressed genes and predict regulatory miRs. After the target relationship between miR-384 and LIMK1 had been verified, the expression of miR-384 and LIMK1 in the EC9706 cell line was altered in an attempt to investigate the regulatory roles of miR-384 in the expression of the LIMK1/cofilin signaling pathway-related genes, cell proliferation, invasion, cell cycle distribution and apoptosis, in addition to lymph node metastasis (LNM) and tumor growth in nude mice. RESULTS: Microarray-based gene expression profiling indicated that miR-384 affected the progression of ESCC through the LIMK1-mediated LIMK1/cofilin signaling pathway. Furthermore, miR-384 and Bax were observed to be poorly expressed, while LIMK1, cofilin and Bcl-2 were highly expressed in ESCC. The obtained evidences indicating that miR-384 targeted and negatively regulated LIMK1. Upregulation of miR-384 or LIMK1 inhibition was determined to block the LIMK1/cofilin signaling pathway, repress cell proliferation, invasion, cell cycle, LNM and tumor growth, while promote cell apoptosis in ESCC. CONCLUSION: Collectively, based on the key findings of the study, miR-384 could sequester LIMK1, which acts to suppress activation of the LIMK1/cofilin signaling pathway, thus ultimately inhibiting the development and progression of ESCC.


Assuntos
Cofilina 1/metabolismo , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Quinases Lim/metabolismo , MicroRNAs/biossíntese , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Cofilina 1/antagonistas & inibidores , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/prevenção & controle , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/prevenção & controle , Feminino , Humanos , Quinases Lim/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ligação Proteica/fisiologia , Ratos , Ratos Nus , Transdução de Sinais/fisiologia
17.
FASEB J ; 33(1): 1151-1166, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30148675

RESUMO

Metastatic growth is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC). Metastasis is believed to be initiated by an increase in cell motility mediated by the loss of cell-cell adhesion because of the suppression of E-cadherin [encoded by cadherin 1 ( CDH1)]. However, very little is known about the molecular mechanism of CDH1 regulation. Therefore, we hypothesized that non-small cell lung cancer-associated transcript-1 (NSCLCAT1) suppresses functional CDH1 and mediates the Hippo signaling pathway, resulting in increased cell migration and invasion, and reduced apoptosis. Initially, microarray profiling and target prediction programs were employed to identify whether NSCLCAT1 targets CDH1. Next, quantitative PCR was used to determine the expression pattern of NSCLCAT1 in 114 specimens. The biologic functions of NSCLCAT1 in NSCLC were assessed through the up-regulation and down-regulation of the levels of endogenous NSCLCAT1 with the use of NSCLCAT1 vector or small interfering RNA against NSCLCAT1 in NSCLC cells. Furthermore, the Hippo signaling pathway in NSCLC cells was blocked by applying the verteporfin treatment to have a better understanding on the pivotal role of the Hippo signaling pathway in NSCLC. Microarray expression profiles of long noncoding RNAs, GSE19804 and GSE27262), revealed that NSCLCAT1 was up-regulated in NSCLC. Among patients with NSCLC, we determined that the NSCLCAT1 was robustly induced, whereas CDH1 was suppressed. The luciferase activity determination identified CDH1 as a NSCLCAT1 target. NSCLCAT1 was found to increase cell viability, migration, and invasion and to reduce apoptosis in NSCLC cells. The results from the quantitative PCR and Western blot analysis revealed that NSCLCAT1 modulated the Hippo signaling pathway. Furthermore, the inhibition of the Hippo signaling pathway by verteporfin treatment led to the loss of the effect of NSCLCAT1 on NSCLC cells. In summary, our findings suggested that NSCLCAT1 potentially has a role in NSCLC and NSCLCAT1-mediated regulation of the Hippo signaling pathway through the transcriptional repression of CDH1; therefore, the functional suppression or inhibition of NSCLCAT1 could be used as a novel therapeutic pathway in the control of aggressive and metastatic NSCLC.-Zhao, W., Zhang, L.-N., Wang, X.-L., Zhang, J., Yu, H.-X. Long noncoding RNA NSCLCAT1 increases non-small cell lung cancer cell invasion and migration through the Hippo signaling pathway by interacting with CDH1.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/fisiopatologia , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/fisiologia , Transdução de Sinais , Adulto , Idoso , Animais , Antígenos CD/genética , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Xenoenxertos , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Fármacos Fotossensibilizantes/farmacologia , RNA Longo não Codificante/genética , Regulação para Cima , Verteporfina/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-30472607

RESUMO

The veined rapa whelk, Rapana venosa, a poikilotherm that is susceptible to temperature, is an important and valuable fishery resource in China but a major invader around the world. We studied the effects of abnormal temperature on the digestive tract microflora of R. venosa to investigate how temperature impacts its digestion and ingestion. We characterized the microflora in nine samples by sequencing the 16S rRNA gene. To assess the species diversity within the samples, effective tags were clustered at 97% similarity by default. Mycoplasma was the most abundant genus among the three groups, and the Proteobacteria phylum had the highest diversity. However, the microflora structure in the digestive tract was significantly different at different temperatures. The top five most abundant genera in the samples housed at 16 °C were Mycoplasma, Phyllobacterium, Aliivibrio, Psychromonas, and Delftia, whereas those in the samples housed under 22 °C were Mycoplasma, Phyllobacterium, Delftia, Spirochaeta_2, and Sphingomonas, and those in the samples housed at 28 °C were Mycoplasma, Phyllobacterium, Vibrio, Delftia, and Aliivibrio. The family Flavobacteriaceae was more abundant in R. venosa housed at 22 °C and 28 °C, whereas a significant decrease in Flavobacteriaceae abundance and a substantial increase in Mycoplasmataceae abundance were observed in R. venosa housed at 16 °C. The alteration in the digestive tract microflora might further affect the function of the R. venosa digestive tract. The results presented herein might provide further insight into investigations on the effects of temperature on the digestion and ingestion of gastropods.


Assuntos
Sistema Digestório/microbiologia , Gastrópodes/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de RNA/métodos , Temperatura Ambiente , Animais
19.
Molecules ; 23(12)2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513790

RESUMO

: The judicious application of ligand or binding efficiency (LE) metrics, which quantify the molecular properties required to obtain binding affinity for a drug target, is gaining traction in the selection and optimization of fragments, hits and leads. Here we report for the first time the use of LE based metric, fit quality (FQ), in virtual screening (VS) of MDM2/p53 protein-protein interaction inhibitors (PPIIs). Firstly, a Receptor-Ligand pharmacophore model was constructed on multiple MDM2/ligand complex structures to screen the library. The enrichment factor (EF) for screening was calculated based on a decoy set to define the screening threshold. Finally, 1% of the library, 335 compounds, were screened and re-filtered with the FQ metric. According to the statistical results of FQ vs activity of 156 MDM2/p53 PPIIs extracted from literatures, the cut-off was defined as FQ = 0.8. After the second round of VS, six compounds with the FQ > 0.8 were picked out for assessing their antitumor activity. At the cellular level, the six hits exhibited a good selectivity (larger than 3) against HepG2 (wt-p53) vs Hep3B (p53 null) cell lines. On the further study, the six hits exhibited an acceptable affinity (range of Ki from 10² to 10³ nM) to MDM2 when comparing to Nutlin-3a. Based on our work, FQ based VS strategy could be applied to discover other PPIIs.


Assuntos
Descoberta de Drogas , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/química , Relação Quantitativa Estrutura-Atividade , Proteína Supressora de Tumor p53/química , Linhagem Celular Tumoral , Descoberta de Drogas/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Reprodutibilidade dos Testes , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/metabolismo
20.
Ann Transl Med ; 6(20): 405, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30498732

RESUMO

Background: Evaluation of the clinical efficacy and safety of icotinib in advanced nonsquamous non-small cell lung cancer (NSCLC) patients with an unknown EGFR mutation who failed to respond to second-line chemotherapy. Methods: Seventy-six cases of advanced nonsquamous NSCLC were involved in this study from seven hospitals from the Hubei province of China. Patients with an unknown EGFR mutation status were treated with Icotinib, at an oral dosage of 125 mg three times daily. All patients were followed up for at least 1 year to observe the efficacy, adverse reactions, and 1-year survival. Results: The patients' overall objective response rate (ORR) was 34.2%, the disease control rate (DCR) was 75.0%, the clinical benefit rate (CBR) was 80.2%, the median progression-free survival (PFS) was 11.0 months, the median overall survival (OS) was 16.9 months, and the 1-year OS rate was 63.2%. Gender and smoking history were associated with the DCR (P<0.05). Both PFS and OS were significantly higher in groups that had pre-accepted ≤6 cycles of chemotherapy than in groups that had pre-accepted >6 cycles. Conclusions: Our results demonstrated that icotinib had a better DCR or clinical benefits for treating the patients with unknown EGFR mutation who failed to respond to second-line chemotherapy in advanced nonsquamous NSCLC, and the adverse effects are tolerable.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA