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1.
Sci Rep ; 9(1): 12291, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444364

RESUMO

Buprofezin, a chitin synthesis inhibitor that can be used for the control of hemipteran pests, especially melon aphid, Aphis gossypii. The impact of low lethal concentrations of buprofezin on the biological parameters and expression profile of CHS1 gene were estimated for two successive generations of A. gossypii. The present result shows that the LC15 and LC30 of buprofezin significantly decreased the fecundity and longevity of both generations. Exposure of F0 individuals to both concentrations delay the developmental period in F1. Furthermore, the survival rate, intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) were reduced significantly in progeny generation at both concentrations. However, the reduction in gross reproductive rate (GRR) was observed only at LC30. Although, the mean generation time (T) prolonged substantially at LC30. Additionally, expression of the CHS1 gene was significantly increased in F0 adults. Significant increase in the relative abundance of CHS1 mRNA transcript was also observed at the juvenile and adult stages of F1 generation following exposure to LC15 and LC30. Therefore, our results show that buprofezin could affect the biological traits by diminishing the chitin contents owing to the inhibition of chitin synthase activity in the succeeding generation of melon aphid.

2.
Curr Opin Insect Sci ; 35: 27-33, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31302356

RESUMO

Abiotic and biotic factors affect plants in various ways which in turn affect associated arthropod communities through direct and/or indirect bottom-up interactions. Several review articles have synthesized studies examining the indirect effects of abiotic factors on plant-arthropod interactions, mainly focusing on soil nitrogen, soil water status, and climate change. However, these studies have mostly focused on bitrophic interactions, whereas most ecological systems are composed of at least three trophic levels. Lately, research on plant-mediated multitrophic interactions in plant-arthropod food web has received increasing interest. Both the intensification of agriculture and the global climate change have the potential to trigger bottom-up effects that cascade through trophic links. In this review article, we synthesize the most recent studies describing how abiotic changes could modulate plant-mediated bottom-up forces and how it could affect arthropod communities and associated biocontrol services. We discuss potential for increasing the sustainability of managed and natural ecosystems, and highlight road maps for future studies.

3.
Int J Surg ; 69: 68-76, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31356963

RESUMO

BACKGROUND: Many risk factors are associated with the growth of unruptured intracranial aneurysm; however, the effects of these risk factors on intracranial aneurysm growth remain poorly understood. Here, we performed a meta-analysis to evaluate the effects of these risk factors on intracranial aneurysm growth, incorporating different data types to provide comprehensive estimates of individual effects. METHODS: We searched the Cochrane Library, PubMed, Embase, and Web of Science for cohort studies analyzing risk factors for aneurysm growth prior to January 10, 2019. The hazard ratio (HR) and odds ratio (OR) with its 95% confidence interval (CI) were calculated to assess the effect of individual risk factors on intracranial aneurysm growth. Both univariate analysis (UVA) and multivariate analysis (MVA) were performed. Two reviewers independently assessed the quality of the trials and the associated data. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: We included 23 studies (N = 7208 participants) in this meta-analysis. A total of 944 patients (13.1%) experienced intracranial aneurysm growth during their follow-up times. Aneurysm size and smoking may have significant effects on the growth of intracranial aneurysm, with pooled ORs of 2.73 (95% CI 2.21-3.36; P < 0.00001) and 1.45 (95% CI 1.07-1.98; P = 0.02) respectively. However, our results indicated that subarachnoid hemorrhage (SAH) had a negative effect on the growth of intracranial aneurysm (OR 0.64; 95% CI 0.48-0.86; P = 0.003). Other risk factors such as irregular shape of intracranial aneurysm, female sex, and multiple aneurysms were inconsistent across studies due to differences in data types and effect estimates. CONCLUSIONS: Our meta-analysis identified aneurysm size and smoking as independent risk factors for the growth of intracranial aneurysm, while prior SAH had a negative effect on the growth of intracranial aneurysm. The roles of other risk factors for intracranial aneurysm growth were inconsistent, with further research necessary to assess fully the roles of these factors in disease outcomes.

4.
Int Immunopharmacol ; 75: 105752, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310910

RESUMO

BACKGROUND: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1ß (IL-1ß, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+Ad-GFP (n = 17); ACLT+Ad-HDAC4-GFP (n = 20); and sham+Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS: Overexpression of HDAC4 in chondrocytes stimulated by IL-1ß reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.

5.
Mol Med Rep ; 20(2): 1551-1560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257510

RESUMO

Circulating tumor cells (CTCs) are tumor cells present in the bloodstream, which originate from tumor sites, and are ultimately responsible for metastasis or relapse in several types of cancer. However, to the best of our knowledge, only a few studies have investigated these extremely rare cells in esophageal squamous cell carcinoma (ESCC). In the present study, 63 patients with ESCC and 50 healthy donors were recruited, and the potential clinical significance of CTCs was assessed using subtraction enrichment and immunostaining­fluorescence in situ hybridization. Blood samples were collected at the following times: At first diagnosis, following neoadjuvant chemoradiotherapy, 24 h and 13 days post­surgery, and every 3 months during follow­up. Cytokeratin (CK)­positive and clustered CTCs only accounted for 1% of total CTCs detected, whereas most CTCs were CK­negative aneuploid cells. Patients with ESCC (n=63) had higher CTC counts compared with healthy donors (control group; n=50) (area under curve=0.807, median CTC count, 2 vs. 0). However, there was no statistical association between CTC counts and sex, age, pathological stage, tumor location, tumor depth or lymph node involvement (P>0.05). The association of tumor development with CTC status and other circulating biomarkers was monitored in patients for a further 2 years. The results revealed that a change in CTC counts between first diagnosis and 13 days post­surgery (ΔCTC) of ≥2/7.5 ml peripheral blood could be applied for predicting progression­free survival (hazard ratio, 3.922; 95% confidence interval, 0.907­16.951; P<0.05) in patients with ESCC. In conclusion, ΔCTC evaluation may be a promising indicator for predicting tumor prognosis and the clinical efficacy of treatment in patients with ESCC.

6.
Nat Commun ; 10(1): 3260, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332187

RESUMO

The realization of ferromagnetism in semiconductors is an attractive avenue for the development of spintronic applications. Here, we report a semiconducting layered metal-organic framework (MOF), namely K3Fe2[(2,3,9,10,16,17,23,24-octahydroxy phthalocyaninato)Fe] (K3Fe2[PcFe-O8]) with spontaneous magnetization. This layered MOF features in-plane full π-d conjugation and exhibits semiconducting behavior with a room temperature carrier mobility of 15 ± 2 cm2 V-1 s-1 as determined by time-resolved Terahertz spectroscopy. Magnetization experiments and 57Fe Mössbauer spectroscopy demonstrate the presence of long-range magnetic correlations in K3Fe2[PcFe-O8] arising from the magnetic coupling between iron centers via delocalized π electrons. The sample exhibits superparamagnetic features due to a distribution of crystal size and possesses magnetic hysteresis up to 350 K. Our work sets the stage for the development of spintronic materials exploiting magnetic MOF semiconductors.

7.
Plant Cell Physiol ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165159

RESUMO

Apple ring rot is a severe disease that affects the yield and quality of apple fruits worldwide. However, the underlying molecular mechanism that involved in this process still remains largely unexplored. Here, we report that apple POZ/BTB CONTAINING-PROTEIN 1 (MdPOB1), a BTB-BACK domain E3 ligase protein, functions to suppress apple pathogen defense against Botryosphaeria dothidea (B. dothidea). Both in vitro and in vivo assays indicated that MdPOB1 interacted directly with and degraded apple U-box E3 ligase MdPUB29, a well-established positive regulator of plant innate immunity, through the ubiquitin/26S proteasome pathway. A series of transgenic analyses in apple fruits demonstrated that MdPOB1 affected apple pathogen defense against B. dothidea at least partially, if not completely, via regulating MdPUB29. Additionally, it was found that the apple pathogen defense against B. dothidea was correlated with the H2O2 contents and the relative expression of SA synthesis- and SA signaling-related genes, which might be regulated via degradation of MdPUB29 by MdPOB1. Overall, our findings provide new insights into the mechanism of the MdPOB1 modulation of apple ring rot resistance, which occur by directly regulating potential downstream target protein MdPUB29 for proteasomal degradation in apple.

8.
J Exp Clin Cancer Res ; 38(1): 254, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196210

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are being wildly used as target therapy in non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are primary resistant to EGFR-TKIs such as gefitinib. Curcumin has been known as a potential therapeutic agent for several major human cancers. In this study, we investigated the effect of curcumin on the reversal of gefitinib resistance in NSCLC cells as well as their molecular bases. METHODS: H157 (wild-type EGFR and KARS mutation) and H1299 (wild-type EGFR and HRAS mutation) cells were treated with gefitinib or curcumin alone, or the two combination, and then cell viability, EGFR activity, expressions of Sp1 and Sp1-dependent proteins and receptor tyrosine kinases, markers of autophagy and apoptosis were examined by using CCK-8, colony formation, immunoblot, quantitative PCR, immunofluoscence, and flow cytometry assays. Also xenograft experiments were conduced to test the synergism of curcumin to gefitinib. RESULTS: Our results showed that curcumin significantly enhanced inhibitory effect of gefitinib on primary gefitinib-resistant NSCLC cell lines H157 and H1299. Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells. Meanwhile, combination treatment of curcumin and gefitinib caused dramatic autophagy induction, autophagic cell death and autophagy-mediated apoptosis, compared to curcumin or gefitinib treatment alone, as evidenced by the findings that curcumin and gefitinib combination treatment-produced synergistic growth inhibition and apoptosis activation can be reversed by pharmacological autophagy inhibitors (Baf A1 or 3-MA) or knockdown of Beclin-1 or ATG7, also can be partially returned by pan-caspase inhibitor (Z-VAD-FMK) in H157 and H1299 cells. Xenograft experiments in vivo yielded similar results. CONCLUSIONS: These data indicate that the synergism of curcumin on gefitinib was autophagy dependent. Curcumin can be used as a sensitizer to enhance the efficacy of EGFR-TKIs and overcome the EGFR-TKI resistance in NSCLC patients with wild-type EGFR and/or KRAS mutation.

9.
Sci China Life Sci ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209800

RESUMO

Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.

10.
Mol Genet Genomic Med ; 7(7): e00748, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165590

RESUMO

BACKGROUND: Recently, increasing innovations improved the accuracy of next generation sequencing (NGS) data. However, the validation of all NGS variants increased the cost and turn-around time of clinical diagnosis, and therefore limited the further development of clinical applications. We aimed to comprehensively assess the necessity of validating NGS variants. METHODS: Validation data of 7,601 NGS variants involving 1,045 genes were collected from 5,190 clinical samples and sequenced by one of five targeted capture panels and two NGS chemistries, respectively. These genes and variants were widely distributed in 24 human chromosomes and mitochondrial genome. Variants validation was firstly processed by Sanger sequencing. If validation results were unavailable or inconsistent with NGS calls, another validation test would be performed by mass spectrometry genotyping. RESULTS: A total of 6,939 high quality NGS variants with ≥35 × depth coverage and ≥35% heterozygous ratio were 100% confirmed by a secondary methodology. 5,775 heterozygous variants were separated from 760 homozygous variants and 404 hemizygous variants by 80% heterozygous ratio. A total of 1.5% (98/6,939) of NGS variants were validated by mass spectrometry genotyping. CONCLUSION: Considering of the above comprehensive assessment, a new variant with high quality from a well-validated capture-based NGS workflow can be reported directly without validation.

11.
J Colloid Interface Sci ; 552: 312-318, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31132633

RESUMO

The electrochemical nitrogen reduction reaction (NRR) under mild conditions is significantly challenging, due to the extremely high stability of dinitrogen (N2) molecules. The NRR pathway also confronts the competitive water reduction reaction that takes places universally in an aqueous solution. Herein, a Fe2O3/Cu catalyst is demonstrated as an efficient NRR electrocatalyst. The electronic interactions elevate the d-state electron center, enabling strong back-bonding for N2 molecules. The altering of d-electron distribution promotes the adsorption of N2, leading to a high catalytic activity. As a result, the Fe2O3/Cu catalyst exhibits an outstanding ammonia production rate of 15.66 µg·h-1·mgcat.-1 at -0.1 V versus reversible hydrogen electrode (RHE), a Faradaic efficiency of 24.4%, and a good electrochemical stability.

12.
J Food Sci ; 84(6): 1288-1296, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31120570

RESUMO

The preservation effects of tartary buckwheat extract (T) and chitosan (C) coatings on the physicochemical (pH value, thiobarbituric acid value, Peroxide value (PV), total volatile basic nitrogen (TVB-N), K value, surface color and the texture profiles), bacteriological (total viable counts (TVC) and psychrotrophic bacteria counts (PBC)), and sensory characteristics of tilapia (Oreochromis niloticus) fillets storage at 0 °C for 18 days were evaluated. The fillets coated with 0.5% T + 1.0% C, 1.0% T + 1.0% C and 1.5% T + 1.0% C maintained better quality and had longer shelf life with respect to samples coated with chitosan alone and the control. Base on the limit values of TVB-N, K value, TVC and sensory preference scores, the shelf life of control fillets was 6 days. By contrast, shelf life of 9 days for 0.5% T + 1.0% C-coated fillets, 12 days for 1.0% T + 1.0% C treated-fillets, and 15 days for 1.5% T + 1.0% C-treated fillets were obtained. Therefore, TBE combined with chitosan coatings have the potential to extend the shelf life of tilapia fillets during storage at 0 °C. PRACTICAL APPLICATION: This study provides basic theory regarding the application of TBE to fish preservation. The edible coating of TBE combined with chitosan has potential use in developing activity food preservation coating.


Assuntos
Quitosana/química , Fagopyrum/química , Produtos Pesqueiros/análise , Conservação de Alimentos/métodos , Conservantes de Alimentos/química , Extratos Vegetais/química , Animais , Ciclídeos , Cor , Conservação de Alimentos/instrumentação , Armazenamento de Alimentos , Humanos , Paladar
13.
Cancer Med ; 8(6): 2886-2896, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31038847

RESUMO

OBJECTIVE: LncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) is a newly identified lncRNA to promote the sunitinib resistance of renal cell carcinoma (RCC), which may contribute to tumorigenesis and progression. This study aimed to explore the association of lncARSR tagSNPs with the risk and prognosis of RCC. METHODS: In this study, a 2-stage case-control study was performed to evaluate the association between 2 tagging SNPs (rs1417080 and rs7859384) and RCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analyses. Different survival time was estimated by the Kaplan-Meier method and compared by the Log-rank test. Hazard ratios (HRs) and their 95% CIs were calculated to determine predictive factors by Cox proportion hazards model. RESULTS: When combing discovery and validation sets together, rs7859384 was determined to be significantly associated with the decreased RCC risk with all P < 0.05 in 4 models (co-dominant model, additive model, dominant model and recessive model). stratified analyses showed prominent risk effect of SNP rs7859384 GA/GG genotypes was found in clinical subgroups of stage I and stage II (P = 0.009, OR = 0.77, 95% CI = 0.64-0.94) and individuals with clear cell RCC (P = 0.014, OR = 0.79, 95% CI = 0.65-0.95). A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with BMI > 24 (P = 0.025, OR = 0.74, 95% CI = 0.56-0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63-0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68-1.00). Survival analyses revealed individuals with GA/GG genotypes had higher survival rate compared with the corresponding AA wild genotypes in the dominant model (log-rank P = 0.005, adjusted HR = 0.34, 95% CI = 0.16-0.73). CONCLUSION: This study suggests that rs7859384 of lncARSR was associated with RCC susceptibility and may act as a prognostic biomarker for patients with RCC.

14.
Opt Express ; 27(8): 11137-11151, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31052962

RESUMO

We present a theoretical study of terahertz (THz) radiation induced by surface plasmon polaritons (SPPs) on a graphene layer under modulation by a surface acoustic wave (SAW). In our gedanken experiment, SPPs are excited by an electron beam moving on a graphene layer situated on a piezoelectric MoS2 flake. Under modulation by the SAW field, charge carriers are periodically distributed over the MoS2 flake, and this causes periodically distributed permittivity. The periodic permittivity structure of the MoS2 flake folds the SPP dispersion curve back into the center of the first Brillouin zone, in a manner analogous to a crystal, leading to THz radiation emission with conservation of the wavevectors between the SPPs and the electromagnetic waves. Both the frequency and the intensity of the THz radiation are tuned by adjusting the chemical potential of the graphene layer, the MoS2 flake doping density, and the wavelength and period of the external SAW field. A maximum energy conversion efficiency as high as ninety percent was obtained from our model calculations. These results indicate an opportunity to develop highly tunable and integratable THz sources based on graphene devices.

15.
Biomed Res Int ; 2019: 1341370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016184

RESUMO

A novel lectin (ABL) was purified from the dried fruiting bodies of Agaricus bitorquis. An efficient 3-step purification protocol involved two consecutive steps of ion exchange chromatography on Q-Sepharose and SP-Sepharose and gel filtration by FPLC on Superdex 75. ABL is a monomeric protein with the molecular mass of 27.6 kDa, which is different from other lectins from genus Agaricus. Its N-terminal amino acid sequence is EYTISIRVYQTNPKGFNRPV which is unique and sharing considerably high similarity of other mushroom lectins. The hemagglutinating activity of the lectin was inhibited by inulin. Based on hemagglutination tests, ABL prefers rabbit, human type A, and AB erythrocytes to human type B and O erythrocytes. The lectin inhibits the activity of HIV-1 reverse transcriptase and the proliferation of leukemia cell (L1210) with an IC50 value of 4.69 and 4.97 µM, respectively. Furthermore, ABL demonstrates the highest mitogenic activity with a response of 24177.7 ± 940.6 [3H-methyl] thymidine counts per minute (CPM) at a concentration of 0.91 µM.


Assuntos
Agaricales/química , Agaricus/química , Proliferação de Células/efeitos dos fármacos , Transcriptase Reversa do HIV/antagonistas & inibidores , Inulina/metabolismo , Lectinas/farmacologia , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemaglutinação/efeitos dos fármacos , Testes de Hemaglutinação/métodos , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Coelhos
16.
Int J Clin Oncol ; 24(9): 1042-1048, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31016429

RESUMO

BACKGROUND: Laryngeal carcinoma (LC) is one of common diagnosed head and neck malignancies. Telomere length has been reported involved in malignant transformation and tumorigenesis. We speculate that single nucleotide polymorphisms (SNPs) in telomere length-related gene oligonucleotide/oligosaccharide-binding folds containing 1 (OBFC1) may have an association with LC in Chinese Han male population. METHODS: To prove this hypothesis, we performed a case-control study to analyze the OBFC1 polymorphisms in 172 LC patients and 180 healthy controls. A total of five SNPs (i.e., rs9325507, rs3814220, rs12765878, rs11191865, rs9420707) were selected for further genotyping. RESULTS: There was a significant difference in rs9325507 T allele frequency (OR = 0.88, 95% CI 0.64-1.21, P = 0.036) and rs11191865 A allele frequency (OR = 0.86, 95% CI 0.62-1.18, P = 0.009) between patient and control groups. In addition, the rs9325507 T/C genotype, rs3814220 G/A genotype, rs12765878 C/T genotype and rs11191865 A/G genotype had a lower risk of LC based on the results of logistic regression model analysis. CONCLUSIONS: The results indicate a potential association between OBFC1 and LC risk in Chinese Han male population. Further work is required to confirm these results and explore the mechanisms of these effects.

17.
Ocul Immunol Inflamm ; : 1-4, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31013174

RESUMO

A 49-year-old male presented with a three-day onset of blurred vision and metamorphopsia in the left eye. Fundoscopy and OCT images identified multiple subretinal masses with associating serous retinal detachment in both eyes. Bilateral choroidal metastasis was suspected, and further evaluation revealed a mass in the lower left lobe of the lung with multiple metastatic loci. Ultimately, the patient was diagnosed with Stage IVB (T2aN2M1c) adenocarcinoma of the lung. Genetic analysis revealed an exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene. The patient was started on afatinib, a second-generation tyrosine kinase inhibitor. Drastic improvement in both tumor volume and visual acuity was observed after 1.5 months. The primary site and other metastatic loci also improved significantly during the observed period. Our report demonstrated the effectiveness of afatinib alone for the treatment of bilateral choroidal metastasis in a non-small cell lung cancer patient exhibiting EGFR mutation.

18.
Cell Death Dis ; 10(4): 307, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952838

RESUMO

Di-n-butyl phthalate (DBP) is a kind of ubiquitous chemical linked to hormonal disruptions that affects male reproductive system. However, the mechanism of DBP-induced germ cells toxicity remains unclear. Here, we demonstrate that DBP induces reduction of proliferation, increase of apoptosis and DNA damage dependent on the PTEN/AKT pathway. Mechanistically, DBP decreases PTEN promoter methylation and increases its transcriptional activity, leading to increased PTEN expression. Notably, DNMT3b is confirmed as a target of miR-29b and miR-29b-mediated status of PTEN methylation is involved in the effects of DBP treatment. Meanwhile, DBP decreases AKT pathway expression via increasing PTEN expression. In addition, the fact that DBP decreases the sperm number and the percentage of motile and progressive sperm is associated with downregulated AKT pathway and sperm flagellum-related genes. Collectively, these findings indicate that DBP induces aberrant PTEN demethylation, leading to inhibition of the AKT pathway, which contributes to the reproductive toxicity.

19.
Mol Med Rep ; 19(5): 3441-3448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30816533

RESUMO

Ataxia­telangiectasia (A­T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM serine/threonine kinase (ATM) gene. Typically, it presents in early childhood with progressive cerebellar dysfunction, accompanied by immunodeficiency and oculocutaneous telangiectasia. In the present study, the clinical and genetic findings of a Chinese family affected with A­T in two live siblings, the proband (II­2) and his elder brother (II­1), as well as a fetus (II­3) were reported. General health, clinical neurological, electrophysiological (motor and sensory nerve conduction) and magnetic resonance imaging evaluations revealed that patients II­1 and II­2 had similar symptoms of ataxia, dysarthria, conjunctival hyperemia and elevated serum α­fetoprotein, whereas patient II­1 had earlier A­T onset at 2 years old and more serious problems with movement and intelligence. Targeted sequencing followed by Sanger sequencing revealed that these two patients carried the compound heterozygotes of a novel nonsense mutation c.5170G>T (p.Glu1724Ter) and a known nonsense mutation c.748C>T (p.Arg250Ter) in the ATM gene. Each mutation was inherited from an asymptomatic parent, which therefore confirmed the diagnosis of A­T. Given this, proband's mother performed prenatal diagnosis in her third pregnancy. Unfortunately, the fetus had the same causal mutations as its siblings and the pregnancy was terminated. The findings of the present study expanded the mutation spectrum of the ATM gene and may help in understanding the genetic basis of A­T, in order to guide genetic counseling and prenatal diagnosis.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Estudos de Associação Genética , Aconselhamento Genético , Mutação , Fenótipo , Alelos , Grupo com Ancestrais do Continente Asiático , Ataxia Telangiectasia/fisiopatologia , Biomarcadores , Cerebelo/patologia , Biologia Computacional , Análise Mutacional de DNA , Eletromiografia , Feminino , Genótipo , Humanos , Imagem por Ressonância Magnética , Masculino , Linhagem , Avaliação de Sintomas
20.
Cell Mol Life Sci ; 76(13): 2633-2645, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30887099

RESUMO

The RNA-guided CRISPR-Cas9 technology has paved the way for rapid and cost-effective gene editing. However, there is still a great need for effective methods for rapid generation and validation of CRISPR/Cas9 gRNAs. Previously, we have demonstrated that highly efficient generation of multiplexed CRISPR guide RNA (gRNA) expression array can be achieved with Golden Gate Assembly (GGA). Here, we present an optimized and rapid method for generation and validation in less than 1 day of CRISPR gene targeting vectors. The method (LION) is based on ligation of double-stranded gRNA oligos into CRISPR vectors with GGA followed by nucleic acid purification. Using a dual-fluorescent reporter vector (C-Check), T7E1 assay, TIDE assay and a traffic light reporter assay, we proved that the LION-based generation of CRISPR vectors are functionally active, and equivalent to CRISPR plasmids generated by traditional methods. We also tested the activity of LION CRISPR vectors in different human cell types. The LION method presented here advances the rapid functional validation and application of CRISPR system for gene editing and simplified the CRISPR gene-editing procedures.


Assuntos
Mama/metabolismo , Sistemas CRISPR-Cas , Edição de Genes/métodos , Vetores Genéticos/administração & dosagem , Neoplasias Ovarianas/genética , RNA Guia , Neoplasias do Colo do Útero/genética , Células Cultivadas , Feminino , Marcação de Genes , Vetores Genéticos/genética , Células HEK293 , Humanos
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