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1.
Ann Thorac Surg ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626616

RESUMO

BACKGROUND: The aim of this study was to evaluate the survival benefits of adjuvant chemotherapy in patients with positive lymph nodes after esophagectomy for esophageal squamous cell carcinoma. METHODS: Patients who underwent esophagectomy for esophageal cancer in the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) from 2013 to 2017 were selected for this retrospective cohort study. Patients with positive lymph nodes were grouped into the surgery alone group and adjuvant chemotherapy group. Propensity score matching (1:1) was used to minimize baseline differences. RESULTS: Among the 5118 patients who underwent esophagectomy, 792 patients were enrolled in the study. After matching, 253 (of 476) patients (adjuvant chemotherapy group) and 253 (of 316) patients (surgery alone group) were included. The median overall survival was significantly prolonged in the adjuvant chemotherapy group (54.0 months, 95% CI, 41.1-66.9 months) compared with the surgery alone group (28.0 months, 95% CI, 22.4-33.6 months) (P <0.001). A significant difference was also observed in median disease-free survival between the two groups (adjuvant chemotherapy group, 33.0 months, 95% CI, 20.8-45.2 months compared with the surgery alone group, 22.0 months, 95% CI, 17.0-27.0 months; P = 0.007). In a multivariable analysis, receiving adjuvant chemotherapy (P <0.001) was significantly associated with a reduced risk of death and dissection of more than six lymph node stations (P = 0.05) was marginally associated with a reduced risk of death. CONCLUSIONS: Postoperative adjuvant chemotherapy improves the overall survival and disease-free survival of patients with resected esophageal squamous cell carcinoma with positive lymph nodes.

2.
Sci Total Environ ; 806(Pt 3): 150736, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600985

RESUMO

Humic-reducing microorganisms (HRMs) can utilize humic substance as terminal electron mediator promoting the bioremediation of contaminate, which is ubiquitous in composts. However, the impacts of HRMs on antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in composts and different HRMs community composition following the types of biowastes effected the spread of ARGs have not been investigated. Herein, the dynamics and mobility of ARGs and HRMs during protein-, lignocellulose- and lignin-rich composting were investigated. Result show that ARGs change significantly at the thermophilic phase, and the relative abundance of most ARGs increase during composting. Seven groups of HRMs communities are classified as primary host HRMs of ARGs, and most host HRMs groups from protein-rich composts. Conclusively, regulating methods for inhibiting ARGs spread for different composts are proposed. HRMs show a higher ARGs dissemination capacity in protein-rich composts than lignocellulose- and lignin-rich composts, but the spread of ARGs can be inhibited by regulate physicochemical parameters in protein-rich composts. In contrary, most HRMs have inhibitory effects on ARGs spread in lignocellulose- and lignin-rich composts, and those HRMs can be used as a new agent that inhibits the spread of ARGs. Our results can help in understanding the potential risk spread of ARGs by inoculating functional bacteria derived from different biowastes composts for environmental remediation, given their expected importance to developing a classification-oriented approach for composting different biowastes.

3.
Breast Cancer Res Treat ; 189(2): 533-539, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34196900

RESUMO

PURPOSE: Mutations in hereditary breast cancer genes play an important role in the risk for cancer. METHODS: Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. RESULTS: A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). CONCLUSIONS: Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.


Assuntos
Neoplasias da Mama , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Genes BRCA2 , Células Germinativas , Guatemala , Humanos
5.
BMC Public Health ; 21(1): 1225, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172040

RESUMO

AIMS: This study aimed to analyze the relationship between diet and overweight and obesity in Jiangsu Province by using structural equation modeling (SEM), and to determine dietary differences between genders in the model. METHODS: Data from 1739 individuals (53.8% female, n = 935) were analyzed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to classify dietary patterns. SEM and multivariate logistic regression were used to explore the relationship between dietary patterns and overweight and obesity. RESULTS: Overweight and obesity was found in 49.1%, and no difference was found in gender (51.2% of men and 47.2% of women, respectively; P = 0.090). Three dietary patterns: the traditional dietary pattern (i.e., poultry, light-colored vegetables, red meat and its products, cereals and tubers products, condiment, oils and dark-colored vegetables), the fruit-egg dietary pattern (i.e., fruit, whole grains, pickled vegetables and eggs and eggs products) and nut-wine dietary pattern (i.e., nut, wine and pastry snacks) were established by using EFA and CFA. It was found that the traditional dietary pattern for adult male was positively associated with the overweight and obesity in Jiangsu Province of China through multivariate logistic regression and SEM (OR = 1.954; 95%CI: 1.258 ~ 3.036; ß =0.121, P < 0.05, respectively). CONCLUSION: The traditional dietary pattern only have positive association with overweight and obesity in men in Jiangsu Province, China.


Assuntos
Obesidade , Sobrepeso , Adulto , China/epidemiologia , Estudos Transversais , Dieta , Comportamento Alimentar , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Verduras
6.
Cancer Immunol Immunother ; 70(11): 3249-3258, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33835222

RESUMO

Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected. Median survival after surgery was significantly shorter with complete dLN resection at the time of surgery (49 days (95%CI)) compared to when lymph nodes remained intact (> 88 days; p < 0.05). Survival was partially restored with incomplete lymph node resection and CD8 T cell dependent. Treatment with aCTLA4 whilst effective against the primary tumour was ineffective for metastatic lung disease. Conversely, aPD-1/aCD40 treatment was effective in both the primary and metastatic disease settings and restored the detrimental effects of complete dLN resection on survival. In this pre-clinical lung metastatic disease model that closely reflects the clinical setting, we observe decreased frequency of survival after complete lymphadenectomy, which was ameliorated with partial lymph node removal or with early administration of aPD-1/aCD40 therapy. These findings have direct relevance to surgical lymph node resection and adjuvant immunotherapy in lung cancer, and perhaps other cancer, patients.

7.
Microorganisms ; 9(3)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673613

RESUMO

Nosema ceranae (Opisthosporidia: Microsporidia) is an emergent intracellular parasite of the European honey bee (Apis mellifera) and causes serious Nosema disease which has been associated with worldwide honey bee colony losses. The only registered treatment for Nosema disease is fumagillin-b, and this has raised concerns about resistance and off-target effects. Fumagillin-B is banned from use in honey bee colonies in many countries, particularly in Europe. As a result, there is an urgent need for new and effective therapeutic options to treat Nosema disease in honey bees. An RNA interference (RNAi)-based approach can be a potent strategy for controlling diseases in honey bees. We explored the therapeutic potential of silencing the sequences of two N. ceranae encoded spore wall protein (SWP) genes by means of the RNAi-based methodology. Our study revealed that the oral ingestion of dsRNAs corresponding to SWP8 and SWP12 used separately or in combination could lead to a significant reduction in spore load, improve immunity, and extend the lifespan of N. ceranae-infected bees. The results from the work completed here enhance our understanding of honey bee host responses to microsporidia infection and highlight that RNAi-based therapeutics are a promising treatment for honey bee diseases.

8.
J Med Genet ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397747

RESUMO

High-quality interpretation of BRCA1/2 variants plays a critical role in the clinical practice of precision medicine. However, a comprehensive system to evaluate the quality and accuracy of variant interpretation has yet to be established. This study investigates the performance of an interpretation system in evaluating the capacities of BRCA1/2 interpretation among distinct laboratories in China. The evaluation system is based on a reference database that contains 750 different variants in BRCA1/2 Evaluation was performed among 41 laboratories in China. We classified their performance into five levels. Only level A was considered qualified. This level allows for a 0.3% error rate for clinical decision-related misinterpretation; 26 of 41 laboratories (63%) met the qualified standard, while 7 laboratories were at levels D and E, which indicated egregious mistakes and systemic problems in variant interpretation. Due to strict quality demands, the interpretation of several variants was amended, which largely influenced the quality rate. The number of qualified laboratories would decrease from 26 to 17 if those incorrect recommended interpretations were not corrected. This evaluation system provides a potential approach for standardisation of variant interpretation and lowers the discordance of variant interpretation between different laboratories. A well-designed interpretation ability evaluation is essential to evaluate the interpretation level of laboratories before they provide service in real-world clinical settings.

9.
Huan Jing Ke Xue ; 42(1): 403-410, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372493

RESUMO

Nitrogen deposition may affect forest soil traits and metabolic activity. We would like to further understand the mechanisms of soil biochemical processes and habitat interactions under conditions of nitrogen deposition in forests and to investigate the characteristics of soil enzyme activities and soil environmental factors in response to nitrogen deposition in Picea schrenkiana forests in the Tianshan Mountains. In this study, nitrogen application tests were carried out using the nitrogen sedimentation gradient method on Picea schrenkiana forest soils in the Tianshan Mountains. We analyzed the characteristics of soil enzyme activity and soil environmental factors at different nitrogen application levels and discussed the correlation between soil enzyme activity and soil environmental factors in conjunction with a redundancy analysis. The study showed that:① Soil enzyme activities showed a tendency to increase and then decrease with the increase in nitrogen application. With the exception of soil acid phosphatase, all enzyme levels reached maximums in the low nitrogen treatment. ② Exogenous nitrogen addition led to low soil pH values, and in the low or medium nitrogen treatments, soil conductivity and the content of organic carbon, ammonium nitrogen, ammonium nitrogen, and total phosphorus increases, along with the C/N ratio, while the N/P ratio showed an irregular decline. ③ Soil enzymes and their correlation with soil environmental factors showed that soil water content, organic carbon content, ammonium nitrogen content, total phosphorus content, and the C/N ratio were all significantly correlated with soil enzymes activity. Only the C/N ratio was negatively correlated with soil enzyme activity, while all other environmental factors were positively correlated with soil enzyme activity. There was no significant correlation between pH and the N/P ratio and soil enzyme activity. The important factors influencing soil enzyme activity were soil organic carbon and ammonium nitrogen with nitrogen application in Picea schrenkiana, Xinjiang.


Assuntos
Picea , Solo , Carbono/análise , China , Florestas , Nitrogênio/análise
10.
Cancer Manag Res ; 12: 11783-11791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33235506

RESUMO

Purpose: To develop and validate a nomogram model to predict the occurrence of acute kidney disease (AKD) after nephrectomy. Patients and Methods: A retrospective cohort including 378 patients with renal cell carcinoma (RCC) who had undergone radical or partial nephrectomy between March 2013 and December 2017 at the First Affiliated Hospital of Zhengzhou University was analyzed. Of these, patients who had undergone surgery in an earlier period of time formed the training cohort (n=265) for nomogram development, and those who had undergone surgery thereafter formed the validation cohort (n=113) to confirm the model's performance. The incidence rate of AKD was measured. Univariate and multivariate logistics regression analysis was used to estimate the independent risk factors associated with AKD. The independent risk factors were incorporated into the nomogram. The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis, respectively. Results: Overall, AKD occurred in 27.5% and 28.3% of patients in the training and validation cohorts, separately. The final nomogram included surgery approach, Charlson comorbidity index (CCI), and the decrement of eGFR. This model achieved good concordance indexes of 0.78 (95% CI=0.71-0.84) and 0.76 (95% CI=0.67-0.86) in the training and validation cohorts, respectively. The calibration curves and decision curve analysis (DCA) demonstrated the accuracy and the clinical usefulness of the proposed nomogram, separately. Conclusion: The nomogram accurately predicts AKD after nephrectomy in patients with RCC. The risk for patients' progress into AKD can be determined, which is useful in guiding clinical decisions.

11.
Huan Jing Ke Xue ; 41(8): 3804-3810, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124357

RESUMO

The impact of exogenous carbon input changes on forest soil respiration provides the basis for an intensive analysis of the forest carbon cycle. Based on a plant residue addition and removal control experiment, this study investigated the short-term soil respiration response to carbon input changes of Picea schrenkiana on the Tianshan Mountains during their growing season with five different carbon input treatments:control, double litter, no root, no litter, and no input. The results revealed that, during the entire observation period, the cumulative soil respiration rates were 3.38, 3.94, 2.65, 2.87, and 2.01 µmol·(m2·s)-1 in the double litter, control, no litter, no root, and no input treatments, respectively. Compared with the control treatment, the cumulative soil CO2 efflux increased by 402.65 g·m-2 in the double litter treatment, whereas it decreased by 515.00, 354.73, and 967.15 g·m-2 in the no litter, no root, and no input treatments, respectively. The mineral soil respiration, litterfall respiration, and root respiration contributed 59.46%, 21.49%, and 14.79%, respectively, to the total soil respiration rate. PCA analysis revealed that the soil respiration rate was positively correlated with the soil temperature, soil moisture, soil total phosphorus content, pH, and soil organic carbon content, and negatively correlated with the soil bulk density, while the soil total nitrogen content, carbon nitrogen ratio, and soil electrical conductivity had no effect on the soil respiration rate.


Assuntos
Picea , Solo , Carbono/análise , Ciclo do Carbono , China , Florestas
12.
Oncol Rep ; 44(5): 1787-1798, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000238

RESUMO

Cervical, ovarian and endometrial cancer are the three most common types of malignant tumor and the leading causes of cancer­associated death in women. Tumor debulking surgery followed by platinum and paclitaxel chemotherapy is the current treatment regime of choice. However, as a result of late diagnosis and chemoresistance, the survival rates of patients with advanced gynecological cancers remains unsatisfactory. Circular RNAs (circRNAs) are stable noncoding RNAs that are present in a wide variety of tissue and cell types. With the enhancement of RNA sequencing methods, increasing numbers of circRNAs have been identified, and their functions are gradually being revealed. In recent years, circRNAs have received increasing attention for their regulatory roles in cervical, ovarian and endometrial cancer. The aim of the present review was to summarize the possible mechanisms of recently identified circRNAs; we hypothesize that a novel diagnostic and therapeutic biomarker may be identified to prolong the survival time of patients with gynecological malignancies.

13.
IUCrJ ; 7(Pt 5): 934-948, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32939285

RESUMO

In Pseudomonas aeruginosa, an important opportunistic pathogen that causes numerous acute and chronic infections, the hybrid two-component system (TCS) regulates the swarming ability and biofilm formation with a multistep phospho-relay, and consists of hybrid-sensor histidine kinase (HK), histidine-containing phospho-transfer protein (Hpt) and response regulator (RR). In this work, two crystal structures of HptB and the receiver domain of HK PA1611 (PA1611REC) of P. aeruginosa have been determined in order to elucidate their interactions for the transfer of the phospho-ryl group. The structure of HptB folds into an elongated four-helix bundle - helices α2, α3, α4 and α5, covered by the short N-terminal helix α1. The imidazole side chain of the conserved active-site histidine residue His57, located near the middle of helix α3, protrudes from the bundle and is exposed to solvent. The structure of PA1611REC possesses a conventional (ß/α)5 topology with five-stranded parallel ß-sheets folded in the central region, surrounded by five α-helices. The divalent Mg2+ ion is located in the negatively charged active-site cleft and interacts with Asp522, Asp565 and Arg567. The HptB-PA1611REC complex is further modeled to analyze the binding surface and interactions between the two proteins. The model shows a shape complementarity between the convex surface of PA1611REC and the kidney-shaped HptB with fewer residues and a different network involved in interactions compared with other TCS complexes, such as SLN1-R1/YPD1 from Saccharomyces cerevisiae and AHK5RD/AHP1 from Arabidopsis thaliana. These structural results provide a better understanding of the TCS in P. aeruginosa and could potentially lead to the discovery of a new treatment for infection.

14.
ACS Omega ; 5(34): 21570-21578, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32905426

RESUMO

Metallo-ß-lactamase (MBL)-producing bacteria resistant to ß-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4-6). Inhibitor 6 showed the best binding affinity (K d ≈ 2.3 ± 0.3 µM), followed by 4 (K d = 11 ± 11 µM) and 5 (K d = 34 ± 43 µM), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1-3) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.

15.
Sensors (Basel) ; 20(17)2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32842485

RESUMO

Action recognition has gained great attention in automatic video analysis, greatly reducing the cost of human resources for smart surveillance. Most methods, however, focus on the detection of only one action event for a single person in a well-segmented video, rather than the recognition of multiple actions performed by more than one person at the same time for an untrimmed video. In this paper, we propose a deep learning-based multiple-person action recognition system for use in various real-time smart surveillance applications. By capturing a video stream of the scene, the proposed system can detect and track multiple people appearing in the scene and subsequently recognize their actions. Thanks to high resolution of the video frames, we establish a zoom-in function to obtain more satisfactory action recognition results when people in the scene become too far from the camera. To further improve the accuracy, recognition results from inflated 3D ConvNet (I3D) with multiple sliding windows are processed by a nonmaximum suppression (NMS) approach to obtain a more robust decision. Experimental results show that the proposed method can perform multiple-person action recognition in real time suitable for applications such as long-term care environments.


Assuntos
Identificação Biométrica/instrumentação , Aprendizado Profundo , Atividades Humanas , Sistemas Computacionais , Humanos
16.
Sensors (Basel) ; 20(15)2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32722044

RESUMO

Accurate estimation of 3D object pose is highly desirable in a wide range of applications, such as robotics and augmented reality. Although significant advancement has been made for pose estimation, there is room for further improvement. Recent pose estimation systems utilize an iterative refinement process to revise the predicted pose to obtain a better final output. However, such refinement process only takes account of geometric features for pose revision during the iteration. Motivated by this approach, this paper designs a novel iterative refinement process that deals with both color and geometric features for object pose refinement. Experiments show that the proposed method is able to reach 94.74% and 93.2% in ADD(-S) metric with only 2 iterations, outperforming the state-of-the-art methods on the LINEMOD and YCB-Video datasets, respectively.

17.
Eur J Nucl Med Mol Imaging ; 47(11): 2525-2532, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666395

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. METHODS: A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. RESULTS: CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. CONCLUSION: Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Aprendizado Profundo , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Pandemias , Pneumonia Viral/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Software , Adulto Jovem
18.
Onco Targets Ther ; 13: 5605-5616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606775

RESUMO

Purpose: It is well known that diet Eicosapentaenoic acid (EPA) is beneficial to colon cancer (CC). However,  the underlying molecular mechanisms of EPA-relating miRNAs on genesis and development of this area is still unclear. Materials and Methods: This study tries to find the function and specific role of EPA in CC through quantitative PCR (qPCR), Western blotting, immunofluorescence (IF), mass spectrometry, and immunohistochemistry (IHC) assays. By these methods, the enrichment of 15-LOX-1 metabolites of EPA, the expression of miR-101 and Cox2, and the relationship among them in CC are measured. Results: The quantity of miR-101 was obviously suppressed in CC tissues and SW480 cells. After application of miR-101 mimics in CC cell lines, the Cox2 expression was inhibited too. Next, we confirmed that EPA could increase the expression of miR-101 induced by 15-LOX-1. Finally, we tested whether EPA functions as a regulator of miR-101 via the production of resolvin E3. Conclusion: Our data demonstrate that the EPA-15-LOX-1-miR-101-Cox2 signaling pathway owns a crucial position in the pathogenesis and development of diet-related CC. These findings exert exciting meanings for presenting new therapeutic angles in CC.

20.
Pharm Biol ; 58(1): 438-446, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32432963

RESUMO

Context: Hypoxia-inducible factor-1α (HIF-1α)-induced genes can improve blood circulation.Objective: To investigate brain protective effect of recombinant adenovirus-mediated HIF-1α (AdHIF-1α) expression and its mechanism.Materials and methods: Male SD rats were used to establish focal cerebral ischaemia-reperfusion (CIR) injury models and randomly divided into normal, sham, CIR, Ad and AdHIF-1α groups. Ad or AdHIF-1α (108 pfu/10 µL) were administered into lateral ventricle of rats in Ad and AdHIF-1α groups. Modified neurological severity score (mNSS), brain water content (BWC) and cerebral infarct volumes (CIVs) were analyzed, and HE staining was performed using the brain tissues. Furthermore, the expression of caspase-3 and HSP90 was analyzed using qRT-PCR and Western blotting.Results: Compared to CIR (mNSS, 8.52 ± 0.52; CIV, 0.22 ± 0.01) and Ad groups (mNSS, 8.83 ± 0.41; CIV, 0.22 ± 0.02), mNSS and CIV were significantly decreased in AdHIF-1α group (mNSS, 6.03 ± 0.61; CIV, 0.11 ± 0.01) at 72 h (p < 0.05). With prolonged reperfusion time (6 h to 72 h), BWC of all rats increased gradually, although the increase was markedly less in AdHIF-1α group (78.15 ± 0.16 to 87.01 ± 0.31) compared to that in CIR (78.77 ± 0.60 to 89.74 ± 0.34) and Ad groups (78.77 ± 0.35 to 89.71 ± 0.27) (p < 0.01). There were significantly greater pathological changes in the neurons in AdHIF-1α group at 72 h following CIR. Furthermore, expression of caspase-3 (p < 0.01) down-regulated and HSP90 up-regulated (p < 0.05) at mRNA and protein levels in AdHIF-1α group.Discussion and conclusions: HIF­1α gene therapy is neuroprotective towards the CIR rat model. HIF-1α may be a candidate gene for the treatment of ischaemic brain injury.


Assuntos
Adenoviridae/genética , Isquemia Encefálica/genética , Terapia Genética/métodos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neuroproteção/genética , Traumatismo por Reperfusão/genética , Animais , Isquemia Encefálica/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/administração & dosagem , Infusões Intraventriculares , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/terapia
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