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1.
J Environ Sci (China) ; 109: 102-113, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34607659

RESUMO

Antibiotics are widely used in humans and animals, but their transformation from surface water to groundwater and the impact of land uses on them remain unclear. In this study, 14 antibiotics were systematically surveyed in a complex agricultural area in Central China. Results indicated that the selected antibiotic concentrations in surface waters were higher in winter (average: 32.7 ng/L) than in summer (average: 17.9 ng/L), while the seasonal variation in groundwaters showed an opposite trend (2.2 ng/L in dry winter vs. 8.0 ng/L in summer). Macrolides were the predominant antibiotics in this area, with a detected frequency of over 90%. A significant correlation between surface water and groundwater antibiotics was only observed in winter (R2 = 0.58). This study further confirmed the impact of land uses on these contaminants, with optimal buffer radii of 2500 m in winter and 500 m in summer. Risk assessment indicated that clarithromycin posed high risks in this area. Overall, this study identified the spatiotemporal variability of antibiotics in a typical agricultural area in Central China and revealed the impact of land uses on antibiotic pollution in aquatic environments.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Animais , Antibacterianos/análise , China , Monitoramento Ambiental , Humanos , Estações do Ano , Água , Poluentes Químicos da Água/análise
2.
Artigo em Inglês | MEDLINE | ID: mdl-34542824

RESUMO

Stroke remains a highly deadly and disabling disease with limited treatment tragedies due to the limitations of available treatments; novel therapies for stroke are needed. In this article, the synergistic results of dual bone marrow mesenchymal stem cells (BMSC) and fasudil treatment in rat models of ischemic stroke still require further identification. Sprague-Dawley rats were used to construct the middle cerebral artery, occlusion models. BMSCs were incubated with fasudil, and MTT was performed to evaluate cell proliferation. The rats were treated with fasudil + BMSC, BMSC, fasudil, and saline. Blood samples were collected for complete blood count analysis and measurement of serum TNF-α levels. The neurological functions were evaluated. After the rats were sacrificed, immunohistochemical staining and TTC staining was performed. Fasudil promoted the proliferation of BMSCs and induced their differentiation into neuron-like cells. BMSCs increased the proportion of neutrophils; nevertheless, fasudil counteracted the neutrophil increase. The TUJ-1/MAP2/VIII factor expression in the fasudil + BMSC group was significantly higher than that in the other groups. The number of GFAP-positive cells decreased in the fasudil + BMSC and BMSC alone groups. The infarct volume in the fasudil + BMSC and BMSC alone groups was significantly lower than in the fasudil alone and control groups. Both BMSCs and fasudil exert neurorestorative effects in rat models of cerebral ischemia. Fasudil neutralizes the pro-inflammatory effects of BMSCs, while BMSCs and fasudil together had synergistic effects promoting neurovascular remodeling and neurological function recovery in stroke. A combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke.

3.
Acta Cytol ; 65(5): 393-402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343999

RESUMO

OBJECTIVE: The aim of the study was to investigate the mutation status of multiple driver genes by RT-qPCR and their significance in advanced lung adenocarcinoma using cytological specimens. MATERIALS AND METHODS: 155 cytological specimens that had been diagnosed with lung adenocarcinoma in the Fourth Hospital of Hebei Medical University were selected from April to November 2019. The cytological specimens included serous cavity effusion and fine-needle aspiration biopsies. Among cytological specimens, 108 cases were processed by using the cell block method (CBM), and 47 cases were processed by the disposable membrane cell collector method (MCM) before DNA/RNA extraction. Ten drive genes of EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET were combined detected at one step by the amplification refractory mutation system and ABI 7500 RT-qPCR. RESULTS: The purity of RNA (p = 0.005) and DNA (p = 0.001) extracted by using the MCM was both significantly higher than that extracted by using the CBM. Forty-seven cases of fresh cell specimens processed by the MCM all succeeded in multigene detections, while of 108 specimens processed by the CBM, 6 cases failed in multigene detections. Among 149 specimens, single-gene mutation rates of EGFR, ALK, ROS1, RET, HER2, MET, KRAS, NRAS, BRAF, and PIK3CA mutations were 57.71%, 6.04%, 3.36%, 2.68%, 2.01%, 2.01%, 1.34%, 0.67%, 0% and 0% respectively, and 6 cases including 2 coexistence mutations. We found that mutation status was correlated with gender (p = 0.047), but not correlated with age (p = 0.141) and smoking status (p = 0.083). We found that the EGFR mutation status was correlated with gender (p = 0.003), age (p = 0.015) and smoking habits (p = 0.007), and ALK mutation status was correlated with age (p = 0.002). CONCLUSION: Compared with the CBM, the MCM can improve the efficiency of DNA/RNA extraction and PCR amplification by removing impurities and enriching tumor cells. And we speculate that the successful detection rate of fresh cytological specimens was higher than that of paraffin-embedded specimens. EGFR, ALK, and ROS1 mutations were the main driver mutations in patients with advanced lung adenocarcinoma. We speculate that EGFR and ALK are more prone to concomitant mutations, respectively. Targeted therapies for patients with coexisting mutations need further study.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adulto , Idoso , Quinase do Linfoma Anaplásico/genética , Biópsia por Agulha Fina , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética
4.
Ying Yong Sheng Tai Xue Bao ; 32(7): 2397-2406, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34313057

RESUMO

To clarify the effects of alternation of drying and wetting on the formation of soil preferential flow in arid valley, taking the wasteland in the arid valley of Honghe River as the research object, we analyzed the soil preferential flow characteristics before and after the simulation of drying and wetting alternation based on dyeing tracer method, water breakthrough curve, and image processing technology. The results showed that, under the simulated alternation of drying and wetting, the matrix flow occurred in the 0-10 cm soil layer, the dyeing depth reached 35 cm, the horizontal width of the preferred path was only 3-10 cm, and the dyeing area curve fluctuated little. Simulated alternation of drying and wetting led to significant increases in the steady effluent, macropores number, and macroporosity. In the 0-20 cm soil layer, the steady effluent after alternation of drying and wetting was about 0.27 cm3·s-1 higher than that non-alternation of drying and wetting, macropores number in dyeing area was about 1.4 times higher, and the macroporosity was 13.4% higher. The macropores number was positively correlated with stable flow rate. After simulated alternation of drying and wetting, the number of macropores from large to small was 0.6-0.8 mm>0.8-1.0 mm>1.0-1.5 mm>1.5-2.0 mm>2.0-3.7 mm, while under non-alternation of drying and wetting, it was 0.8-1.0 mm>0.6-0.8 mm>1.0-1.5 mm>2.0-3.7 mm>1.5-2.0 mm. The macropores number in each pore size range was significantly correlated with the dyeing area ratio. After simulated alternation of drying and wetting, the correlation increased, and the dominant factor affecting the occurrence of preferential flow changed from the macropores number in the pore size range of 1.5-2.0 mm to that of 0.8-1.0 mm. Therefore, the alternation of drying and wetting would affect the characteristics of macropores, which caused the soil to be more prone to preferential flow and with higher magnitude.


Assuntos
Solo , Movimentos da Água , Dessecação , Rios , Água/análise
5.
Artigo em Inglês | MEDLINE | ID: mdl-34299692

RESUMO

The surface urban heat island (SUHI) effect poses a significant threat to the urban environment and public health. This paper utilized the Local Climate Zone (LCZ) classification and land surface temperature (LST) data to analyze the seasonal dynamics of SUHI in Wuhan based on the Google Earth Engine platform. In addition, the SUHI intensity derived from the traditional urban-rural dichotomy was also calculated for comparison. Seasonal SUHI analysis showed that (1) both LCZ classification and the urban-rural dichotomy confirmed that Wuhan's SHUI effect was the strongest in summer, followed by spring, autumn and winter; (2) the maximum SUHI intensity derived from LCZ classification reached 6.53 °C, which indicated that the SUHI effect was very significant in Wuhan; (3) LCZ 8 (i.e., large low-rise) had the maximum LST value and LCZ G (i.e., water) had the minimum LST value in all seasons; (4) the LST values of compact high-rise/midrise/low-rise (i.e., LCZ 1-3) were higher than those of open high-rise/midrise/low-rise (i.e., LCZ 4-6) in all seasons, which indicated that building density had a positive correlation with LST; (5) the LST values of dense trees (i.e., LCZ A) were less than those of scattered trees (i.e., LCZ B) in all seasons, which indicated that vegetation density had a negative correlation with LST. This paper provides some useful information for urban planning and contributes to the healthy and sustainable development of Wuhan.


Assuntos
Monitoramento Ambiental , Temperatura Alta , China , Cidades , Estações do Ano
6.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 43(3): 306-313, May-June 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249200

RESUMO

Objective: To evaluate the efficacy and safety of Morinda officinalis oligosaccharide (MOO) capsules for depressive disorder. Methods: Eight electronic databases were searched for relevant studies from inception to April 19, 2020. Randomized controlled trials comparing MOO capsules with antidepressants were included. Data analysis was conducted using Review Manager 5.3 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality of the studies was evaluated by two researchers using the Grading of Recommendation, Assessment, Development and Evaluations (GRADE) software. Results: Seven studies involving 1,384 participants were included in this study. The effect of MOO capsules for moderate depressive disorder was not different from that of antidepressants (risk ratio [RR] = 0.99, 95%CI 0.92-1.06). Regarding adverse events, no significant difference was found between MOO capsules and antidepressants (RR = 0.84, 95%CI 0.65-1.07). In addition, the quality of evidence related to these adverse events was rated as low. Conclusion: This systematic review suggests that the efficacy of MOO capsules in the treatment of mild to moderate depression is not inferior to that of conventional antidepressants, which may provide a new direction for clinical alternative selection of antidepressants. However, more high-quality research and detailed assessments are needed.

7.
J Psychosom Res ; 147: 110528, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34034140

RESUMO

OBJECTIVES: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting. METHODS: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2. RESULTS: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant. CONCLUSION: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively.

9.
Comput Methods Programs Biomed ; 204: 106061, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33819821

RESUMO

BACKGROUND AND OBJECTIVE: Computer-aided cervical cancer screening based on an automated recognition of cervical cells has the potential to significantly reduce error rate and increase productivity compared to manual screening. Traditional methods often rely on the success of accurate cell segmentation and discriminative hand-crafted features extraction. Recently, detector based on convolutional neural network is applied to reduce the dependency on hand-crafted features and eliminate the necessary segmentation. However, these methods tend to yield too much false positive predictions. METHODS: This paper proposes a global context-aware framework to deal with this problem, which integrates global context information by an image-level classification branch and a weighted loss. And the prediction of this branch is merged into cell detection for filtering false positive predictions. Furthermore, a new ground truth assignment strategy in the feature pyramid called soft scale anchor matching is proposed, which matches ground truths with anchors across scales softly. This strategy searches the most appropriate representation of ground truths in each layer and add more positive samples with different scales, which facilitate the feature learning. RESULTS: Our proposed methods finally get 5.7% increase in mean average precision and 18.5% increase in specificity with sacrifice of 2.6% delay in inference time. CONCLUSIONS: Our proposed methods which totally avoid the dependence on segmentation of cervical cells, show the great potential to reduce the workload for pathologists in automation-assisted cervical cancer screening.


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos , Redes Neurais de Computação , Neoplasias do Colo do Útero/diagnóstico por imagem
10.
Biochem Pharmacol ; 186: 114502, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33684391

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality. Apnea-induced chronic intermittent hypoxia (CIH) is a primary pathophysiological manifestation of OSA that promotes various cardiovascular alterations, such as aortic vascular remodeling. In this study, we investigated the association between angiopoietin-like proteins 8 (ANGPTL8) and CIH-induced aortic vascular remodeling in mice. METHODS: C57BL/6J male mice were divided into four groups: Normoxia group, ANGPTL8-/- group, CIH group, CIH + ANGPTL8-/- group. Mice in the normoxia group and ANGPTL8-/- group received no treatment, while mice in the CIH and CIH + ANGPTL8-/- group were subjected to CIH (21%-5% O2, 180 s/cycle, 10 h/day) for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization, and aortic wall collagen abundance were assessed in vivo. Immunohistochemistry and Western-blot were used to detect endoplasmic reticulum stress (ERS) and aortic vascular smooth muscle cell proliferation. ANGPTL8 shRNA and ANGPL8 overexpression were used in aortic vascular smooth muscle cells to investigate the mechanism of ANGPTL8 in CIH. RESULTS: Compared to the control group, CIH exposure significantly increased intima-media thickness (IMT), elastic fibers disorganization, and aortic wall collagen abundance. CIH also significantly increased blood pressure, induced hyperlipidemia, as well as the expression of ERS protein activating transcription factor-6 (ATF6) and aortic vascular smooth muscle cell proliferation. Contrary, ANGPTL8-/- significantly mitigated the CIH-induced vascular remodeling; ANGPTL8-/- decreased CIH-induced hypertension and hyperlipidemia, inhibited the protein expression of ATF6, and aortic vascular smooth muscle cell proliferation. Moreover, our in vitro study suggested that CIH could induce ANGPTL8 expression via hypoxia-inducible factor (HIF-1α); ANGPTL8 induced proliferation of aortic vascular smooth muscle cells via the ERS pathway. CONCLUSION: ANGPTL8-/- can prevent CIH-induced aortic vascular remodeling, probably through the inhibition of the ERS pathway. Therefore, ANGPTL8 might be a potential target in CIH-induced aortic vascular remodeling.


Assuntos
Proteínas Semelhantes a Angiopoietina/deficiência , Modelos Animais de Doenças , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Remodelação Vascular/fisiologia , Proteínas Semelhantes a Angiopoietina/genética , Animais , Células Cultivadas , Feminino , Humanos , Hipóxia/complicações , Hipóxia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/genética
11.
J Agric Food Chem ; 69(8): 2501-2511, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33599481

RESUMO

The iridoids and their derivatives monoterpene indole alkaloids (MIAs) are two broad classes of plant-derived natural products with valuable pharmaceutical properties. However, the poor source limited their application. Nepetalactol, a common iridoid scaffold of MIAs, was heterologously produced in Saccharomyces cerevisiae. Although the optimization of nepetalactol production in S. cerevisiae was achieved by metabolic engineering, the inherent metabolic constraints impose a restriction on the production. Herein, we developed a high nepetalactol-producing Aspergillus oryzae platform strain. First, the co-expression of 5 nepetalactol biosynthetic genes, in a high isopentenyl pyrophosphate (IPP)-producing strain A. oryzae AK2, succeeded in the biosynthesis of nepetalactol. Second, the improvement of the IPP supply and the suppression of the byproduct citronellol formation were simultaneously achieved. Finally, the highest titer of nepetalactol of 7.2 mg/L was obtained with the engineered strain, after the optimization of the carbon source. To the best of our knowledge, this is the highest reported titer of nepetalactol in microbial cells. The developed A. oryzae strain represents an attractive biosynthetic platform host for the de novo production of iridoids and MIAs.


Assuntos
Aspergillus oryzae , Iridoides , Aspergillus oryzae/genética , Engenharia Metabólica , Monoterpenos , Saccharomyces cerevisiae/genética
12.
Acta Cytol ; 65(3): 235-241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33631757

RESUMO

PURPOSE: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection. MATERIALS AND METHODS: CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results. RESULTS: The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed. CONCLUSIONS: Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.


Assuntos
Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/genética , Separação Celular/instrumentação , Equipamentos Descartáveis , Fusão Gênica , Neoplasias Pulmonares/genética , Membranas Artificiais , Derrame Pleural Maligno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/patologia , Centrifugação , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Inclusão em Parafina , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/enzimologia , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes , Fixação de Tecidos
13.
Lancet Digit Health ; 3(2): e88-e97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33509389

RESUMO

BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.


Assuntos
Algoritmos , Simulação por Computador , Aprendizado Profundo , Doenças do Sistema Digestório/diagnóstico , Olho , Programas de Rastreamento/métodos , Modelos Biológicos , Adulto , Área Sob a Curva , China , Túnica Conjuntiva/diagnóstico por imagem , Doenças do Sistema Digestório/complicações , Olho/diagnóstico por imagem , Fundo de Olho , Humanos , Iris/diagnóstico por imagem , Fígado , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Prospectivos , Curva ROC , Esclera/diagnóstico por imagem , Microscopia com Lâmpada de Fenda/métodos
14.
Oncol Rep ; 45(2): 459-468, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416163

RESUMO

Studies have shown that suppression of both the JAK/STAT3 pathway and epithelial­mesenchymal transition (EMT) may overturn the resistance of non­small cell lung cancer (NSCLC) cells to gefitinib. Zoledronic acid (ZA) injection is used to treat and prevent multiple forms of osteoporosis, hypercalcemia and bone metastasis­related complications of malignancy. Clinical research has shown that ZA may exert antitumour effects and delay the progression of NSCLC. In the present study, we investigated whether ZA combined with gefitinib could re­sensitise NSCLC cells to gefitinib in vitro and in vivo through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The results revealed that ZA potently increased the sensitivity of gefitinib­resistant lung cancer cells to gefitinib. ZA decreased activation of JAK/STAT3 signalling and reversed EMT in the H1975 and HCC827GR cell lines. Furthermore, addition of IL­6 to ZA­pretreated gefitinib­resistant cell lines abrogated the effect of ZA and restored the cellular resistance to tyrosine kinase inhibitors. Finally, ZA­based combinatorial therapy effectively inhibited the growth of xenografts derived from gefitinib­resistant cancer cells, which was correlated with the inhibition of the JAK/STAT3 signalling pathway and EMT reversal. In conclusion, ZA re­sensitised gefitinib­resistant lung cancer cells through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The combination of ZA and gefitinib may be a promising therapeutic strategy to reverse gefitinib resistance and prolong the survival of patients with NSCLC.

15.
BMC Immunol ; 22(1): 6, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430765

RESUMO

BACKGROUD: It is important to expound the opposite clinical outcomes between children and adulthood for eradicate malaria. There remains unknown about the correlation between adaptive immune response and age-related in malaria. METHODS: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. RESULTS: The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group. CONCLUSIONS: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

16.
Acta Pharmacol Sin ; 42(3): 491-498, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32661351

RESUMO

N-methyl-D-aspartate receptors (NMDARs) play critical roles in the physiological function of the mammalian central nervous system (CNS), including learning, memory, and synaptic plasticity, through modulating excitatory neurotransmission. Attributed to etiopathology of various CNS disorders and neurodegenerative diseases, GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs. Herein, we report the synthesis and preclinical evaluation of two 11C-labeled GluN2B-selective negative allosteric modulators (NAMs) containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography (PET) imaging. Two PET ligands, namely [11C]31 and [11C]37 (also called N2B-1810 and N2B-1903, respectively) were labeled with [11C]CH3I in good radiochemical yields (decay-corrected 28% and 32% relative to starting [11C]CO2, respectively), high radiochemical purity (>99%) and high molar activity (>74 GBq/µmol). In particular, PET ligand [11C]31 demonstrated moderate specific binding to GluN2B subtype by in vitro autoradiography studies. However, because in vivo PET imaging studies showed limited brain uptake of [11C]31 (up to 0.5 SUV), further medicinal chemistry and ADME optimization are necessary for this chemotype attributed to low binding specificity and rapid metabolism in vivo.

17.
Braz J Psychiatry ; 43(3): 306-313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32997072

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Morinda officinalis oligosaccharide (MOO) capsules for depressive disorder. METHODS: Eight electronic databases were searched for relevant studies from inception to April 19, 2020. Randomized controlled trials comparing MOO capsules with antidepressants were included. Data analysis was conducted using Review Manager 5.3 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and the quality of the studies was evaluated by two researchers using the Grading of Recommendation, Assessment, Development and Evaluations (GRADE) software. RESULTS: Seven studies involving 1,384 participants were included in this study. The effect of MOO capsules for moderate depressive disorder was not different from that of antidepressants (risk ratio [RR] = 0.99, 95%CI 0.92-1.06). Regarding adverse events, no significant difference was found between MOO capsules and antidepressants (RR = 0.84, 95%CI 0.65-1.07). In addition, the quality of evidence related to these adverse events was rated as low. CONCLUSION: This systematic review suggests that the efficacy of MOO capsules in the treatment of mild to moderate depression is not inferior to that of conventional antidepressants, which may provide a new direction for clinical alternative selection of antidepressants. However, more high-quality research and detailed assessments are needed.


Assuntos
Transtorno Depressivo , Morinda , Antidepressivos/efeitos adversos , Cápsulas/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Humanos , Oligossacarídeos/efeitos adversos
18.
Microb Cell Fact ; 19(1): 224, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287814

RESUMO

BACKGROUND: Monascus azaphilone pigments (MonAzPs), which were produced by Monascus species, have been used as important food colorant and food supplements for more than one billion people during their daily life. Moreover, MonAzPs recently have received more attention because of their diverse physiological activities. However, the high microbial production of MonAzPs is still not always guaranteed. Herein, the aim of this study was to develop an efficient biotechnological process for MonAzPs production. RESULTS: In this study, exogenous cyclic adenosine monophosphate (cAMP) treatment not only induced MonAzPs production, but also stimulated the expression of a cAMP phosphodiesterase gene, named as mrPDE, in M. purpureus HJ11. Subsequently, MrPDE was identified as a cAMP phosphodiesterase by in vitro enzymatic reaction with purified enzyme. Further, a gene knockout mutant of mrPDE was constructed to verify the activation of cAMP signalling pathway. Deletion of mrPDE in M. purpureus HJ11 improved cAMP concentration by 378% and enhanced PKA kinase activity 1.5-fold, indicating that activation of cAMP signalling pathway was achieved. The ΔmrPDE strain produced MonAzPs at 8563 U/g, with a 2.3-fold increase compared with the WT strain. Moreover, the NAPDH/NADP+ ratio of the ΔmrPDE strain was obviously higher than that of the wild type strain, which led to a higher proportion of yellow MonAzPs. With fed-batch fermentation of the ΔmrPDE strain, the production and yield of MonAzPs achieved 332.1 U/mL and 8739 U/g. CONCLUSIONS: A engineered M. purpureus strain for high MonAzPs production was successfully developed by activating the cAMP signalling pathway. This study not only describes a novel strategy for development of MonAzPs-producing strain, but also provides a roadmap for engineering efforts towards the production of secondary metabolism in other filamentous fungi.

19.
J Am Chem Soc ; 142(52): 21938-21947, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33320668

RESUMO

A dual experimental/theoretical investigation of the Ireland-Claisen rearrangement of tetrasubstituted α-phthalimido ester enolates to afford α-tetrasubstituted, ß-trisubstituted α-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z- and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of α,α-disubstituted allyl esters. Density functional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determination of quantum mechanical energies.


Assuntos
Aminoácidos/química , Aminoácidos/síntese química , Alcenos/química , Técnicas de Química Sintética , Teoria da Densidade Funcional , Cetonas/química , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
20.
Int J Clin Exp Pathol ; 13(8): 2106-2114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922607

RESUMO

OBJECTIVE: To explore the significance of a DNA quantitative analysis of lung cancer cells with different pathological types taken from bronchial brush specimens and its relationship with the clinicopathological features. METHODS: 903 bronchial brush cytological specimens taken in the Cytology Department of the Fourth Hospital of Hebei Medical University were collected from March 2017 to December 2019 and divided into three groups: the squamous carcinoma (SC) group, the adenocarcinoma (AC) group, and the small-cell carcinoma (SCC) group. The maximum DNA index (DI) value, the percentage of cells with a DI larger than 2.5, the mean DI, and the peaks of the aneuploid cells of the three groups were compared. A single factor analysis was used to analyze the relationship between the DNA content, aneuploidy, and the clinico pathological features of the patients who had surgery. RESULTS: The peaks of the aneuploid cells in the SC group, the AC group, and the SCC group had no significant differences (P=0.57). The maximum DI, the percentage of cells with a DI larger than 2.5, and the mean DI of the three groups showed statistically significant differences (P<0.001). The clinicopathological features of the AC patients and the SC patients, such as gender, age, tumor type, the maximum tumor diameter, clinical stage, vascular invasion, nerve invasion, pleural invasion, tracheal spread, and lymph node metastasis were not independent factors that influence the DNA content and have no statistical significance (P > 0.05). CONCLUSION: The reason why the DNA content of small-cell lung cancer is lower than SC and AC remains to be further studied.

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