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1.
Endocr Relat Cancer ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33974557

RESUMO

Prolactinomas have harmful effects on human health, and 25% of prolactinoma patients do not respond to the therapy of dopamine receptor agonist in the clinic. Thus, it is important to reveal the pathogenesis and develop new therapeutic methods for prolactinomas. Herein, two animal models of prolactinomas, namely oestrogen-treated rats and transgenic D2 dopamine receptor-deficient mice, were used. PET/CT imaging detection showed that translocator protein-mediated microglia activation and inflammation significantly increased in the pituitary glands of prolactinomas rats. Messenger ribonucleic acid microarrays showed that the innate immune response genes were up-regulated in the pituitary glands of prolactinoma rats. We found that the expressions of NLRP3, Caspase-1, apoptosis-associated speck-like, interleukin (IL)-1ß and IL-18 proteins of pituitary glands in prolactinomas rats were increased considerably compared with those in control rats. This suggested the activation of the NLRP3 inflammasome during the emergence and evolution of prolactinomas. Immunohistochemistry results also confirmed that the NLRP3 expression was elevated in human prolactinoma tissues, and the microglia marker IBA-1 was co-located with the NLRP3 protein in prolactinomas by immunofluorescence assay. Finally, compared with the wild type mice, NLRP3-/- mice had smaller pituitary glands (weight/body weight) and diminished prolactin (PRL) expressions and secretions. Furthermore, MCC950 decreased the PRL expression and secretion following the inhibition of NLRP3 inflammasome activation in GH3 cells stimulated with lipopolysaccharide and nigericin and in prolactinoma rats. Our findings showed that microglial NLRP3 inflammasome activation-mediated IL-1ß-related inflammation promoted the development of prolactinomas and identified the inflammasome as a new therapeutic target for prolactinomas.

2.
Sci Total Environ ; 783: 146976, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33866162

RESUMO

An aerosol mass spectrometer (AMS) was used to measure the chemical composition of non-refractory submicron particles (NR-PM1) in Beijing from 2012 to 2013. The average concentration of NR-PM1 was 56 µg·m-3, with higher value of 106 µg·m-3 when Beijing was influenced by air masses from south in winter. Organics was the primary chemical component with a concentration of 26 µg·m-3, accounting for 46% of the total NR-PM1. The ratio of NO3-/SO42- was utilized to identify the relative contribution of stationary and traffic related resource to PM pollution. When NR-PM1 concentration was between 50 and 200 µg·m-3, NO3-/SO42-was larger than 1, indicating traffic resource contributed more than stationary resource during the aerosol growth. A new method was developed to calculate aerosol extinction coefficient (σ) as a function of aerosol optical depth (AOD) and the mixing layer height (MLH). σ derived from the new method showed a statistically significant correlation with that obtained from traditional method, which was calculated using visibility (y = 0.99x + 85 R2 = 0.69). Multiple linear regressions in dependence of chemical component were performed to evaluate light extinction apportionment. Under the overall condition, NR-PM1 contributed about 88% to the whole aerosol light extinction; organics, ammonium chloride, ammonium nitrate, ammonium sulfate, black carbon contributed 30%, 6%, 24%, 26% and 6% of the NR-PM1 light extinction, respectively. By further comparing the light extinction apportionment under the different dominated air masses, we concluded that the organics and ammonium sulfate contributed more in polluted days (36% and 23%) than that in clean days (21% and 21%). Mass ratio (MR) between NR-PM1 and black carbon (MR = massNR-PM1/massBC) was used to identify black carbon aging degree, and the result showed that aerosol mass extinction efficiency increased rapidly after MR reached about 7 in the process of black carbon aging.

3.
Gen Physiol Biophys ; 40(2): 115-126, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33880998

RESUMO

Emerging evidence proposes that circular RNAs (circRNAs) are involved in epileptogenesis. This study aimed to investigate the role and the function mechanism of circ_0003170 in epilepsy models in vitro. Epilepsy models were established in human hippocampal neurons treated by magnesium-free (Mg2+-free) solution. The expression of circ_003170, miR-421 and C-C motif chemokine ligand 2 (CCL2) was detected by qRT-PCR. The putative interaction between miR-421 and circ_003170 or CCL2 was validated by dual-luciferase reporter assay and RIP assay. The protein level of CCL2 was detected by Western blot. Cell viability was detected by CCK-8 assay, and cell cycle and apoptosis were monitored by flow cytometry. The content of superoxide dismutase (SOD) and malondialdehyde (MDA) and the activity of caspase-3 were assessed using commercial kits. The results showed that circ_0003170 and CCL2 expression was enhanced, while miR-421 expression was declined in temporal lobe epilepsy serum specimens and Mg2+-free-induced neurons. circ_0003170 knockdown ameliorated Mg2+-free-induced cell cycle arrest, oxidative stress and apoptosis in neurons by enriching miR-421. Further analysis presented that miR-421 overexpression alleviated Mg2+-freeinduced cell injuries by depleting CCL2. CCL2 overexpression reversed the effects of circ_0003170 knockdown. Overall, circ_0003170 knockdown ameliorated Mg2+-free-induced human hippocampal neuron injuries by mediating the miR-421/CCL2 axis.


Assuntos
Epilepsia , MicroRNAs , RNA Circular/genética , Quimiocina CCL2 , Quimiocinas , Epilepsia/genética , Hipocampo , Humanos , Ligantes , MicroRNAs/genética , Neurônios
4.
J Nanosci Nanotechnol ; 21(10): 5207-5214, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875108

RESUMO

A small aliquot (10-14 µL) of ZnO nanoparticles dispersed in deionized water was deposited by evaporation to produce a dry residue on the working area of a screen-printed electrode. An electrochemical test solution containing K3Fe(CN)6 and KCl was added to the electrode surface for analysis by electrochemical impendence spectroscopy (EIS). Using this deposition analysis technique, a new relationship between the charge transfer resistance (Rct) and the amount of ZnO nanoparticles has been explored. Based on the trend of increasing Rct value with an increase of ZnO nanoparticles, a quantitative analysis method can be established to determine the mass of nanoparticles (0.01-1.00 µg) deposited from an unknown dispersion. To study the matrix effect, addition of Nafion solution to the aqueous dispersion resulted in a change of the linear range to 0.3-0.5 µg nanoparticles. Addition of methanol (10% by volume) to the aqueous dispersion changes the analysis range to 0.2-0.6 µg nanoparticles, while additional methanol (50% by volume) changes the analysis range to 0.06-1.00 µg nanoparticles. The analytical sensitivity, as indicated by the slope of each standard calibration curve, ranked as: aqueous dispersion > Nafion/aqueous dispersion > 10% methanol/aqueous dispersion > 50% methanol/aqueous dispersion. Altogether these results verify that deionized water is the best dispersion medium for EIS analysis of ZnO nanoparticles.

5.
Toxicology ; 456: 152770, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823232

RESUMO

Extensive health studies had declared that exposure to particulate matter (PM) was closely associated with neurodegenerative diseases, i.e. Parkinson's disease (PD). Our aim was to clarify the potential molecular mechanism by which PM2.5 aggravated PD symptoms using in vitro and in vivo PD models. In this study, PC12 cells treated with rotenone (1 µM) and/or PM2.5 (50 µg/mL) for 4 days was used as the in vitro model. C57BL/6 J mice expored to PM2.5 (inhalation, 2.5 mg/kg) and rotenone (intraperitoneal injection, 30 mg/kg) for 28 days was used as the in vivo model. Rapamycin was used to promote the level of autophagy. The results showed that after exposure to PM2.5, the apoptosis of rotenone-treated PC12 cells were increased by increasing the ROS levels and decreasing the levels of mitochondrial membrane potential. In rotenone-treated PC12 cells, exposure to PM2.5 could decrease the expression levels of LC3II and Atg5, and increase the expression level of mTOR, suggesting that PM2.5 exposure inhibited autophagy. Furthermore, the mitophagy related genes, including PINK1 and Parkin, were decreased. At the same time, inhalation of PM2.5 could relieve the behavioral abnormalities of PD mouse induced by rotenone. The levels of inflammatory factors (TNF-α, IL-1ß, and IL-6) were significantly increased. Inhalation of PM2.5 could induce the oxidative stress and apoptosis in the substantia nigra of PD mouse, as well as the key markers of autophagy and mitophagy were also changed, which was consistent with the cell model. Besides, rapamycin would relieve the damaging effect of PM2.5 by triggering autophagy and mitophagy in rotenone-induced PD models. These results indicated that exposure to PM2.5 aggravated the behavioral abnormalities of PD symptoms through increasing oxidative stress, decreasing autophagy and mitophagy, and inducing mitochondria-mediated neuronal apoptosis. These findings not only revealed the effects and mechanism of PM2.5 exposure on PD, but also provided fundamental data that can be exploited to develop environmental safety policies.

6.
Nat Commun ; 12(1): 2177, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846355

RESUMO

The recent advancements in single-cell technologies, including single-cell chromatin accessibility sequencing (scCAS), have enabled profiling the epigenetic landscapes for thousands of individual cells. However, the characteristics of scCAS data, including high dimensionality, high degree of sparsity and high technical variation, make the computational analysis challenging. Reference-guided approaches, which utilize the information in existing datasets, may facilitate the analysis of scCAS data. Here, we present RA3 (Reference-guided Approach for the Analysis of single-cell chromatin Accessibility data), which utilizes the information in massive existing bulk chromatin accessibility and annotated scCAS data. RA3 simultaneously models (1) the shared biological variation among scCAS data and the reference data, and (2) the unique biological variation in scCAS data that identifies distinct subpopulations. We show that RA3 achieves superior performance when used on several scCAS datasets, and on references constructed using various approaches. Altogether, these analyses demonstrate the wide applicability of RA3 in analyzing scCAS data.


Assuntos
Epigênese Genética , Análise de Célula Única , Análise por Conglomerados , Células HEK293 , Humanos , Padrões de Referência
7.
Appl Opt ; 60(4): 942-948, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690403

RESUMO

A double seed curve extension (DSCE) method is proposed to design a freeform surface directly in an off-axis reflective imaging system. Compared with the basic seed curve extension (SCE) method, the DSCE can effectively reduce the error of freeform surface construction and improve the imaging quality of the off-axis reflective imaging system. In addition, the method can be employed to design an off-axis reflective imaging system consisting of multiple freeform surfaces with several virtual image points set in advance. In order to verify the DSCE method, three examples are given. One is the off-axis freeform one-mirror system, one is a compact off-axis three-mirror imaging system with two freeform surfaces, and the other is an off-axis reflective system with three freeform surfaces. The modulation transfer function (MTF) of the one-mirror system is greater than 0.9 at 20 lp/mm, which is close to the diffraction limit. The average of the sagittal and tangential MTFs of the second system designed by the SCE and DSCE methods are 0.26 and 0.74 at spatial frequency of 20 lp/mm, respectively. And the MTF of the last system designed by the DSCE method is greater than 0.9 at 20 lp/mm, which is better than that of the SCE method.

8.
Medicine (Baltimore) ; 100(12): e25213, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761707

RESUMO

ABSTRACT: Poststroke pneumonia (PSP) is a common complication of stroke and an important cause of death following stroke. However, the treatment of PSP remains inadequate due to severe impairment to the respiratory system by PSP. Thus, it is crucial to focus on preventing PSP to improve the prognosis of patients with stroke.This prospective single-center Cohort study aimed to investigate the risk factors for pulmonary infection following an ischemic stroke and identify whether PSP significantly influences the prognosis of patients after stroke.Altogether, 451 patients who were treated for acute ischemic stroke in the First Affiliated Hospital of Chongqing Medical University in China between April 2017 and April 2018 were enrolled. Clinical data from the patients from admission to 3 months after discharge were collected. PSP was the primary outcome and poor prognosis or death at 3 months following discharge was the secondary outcome observed in this study. We performed logistic regression analyses to identify the risk factors for PSP and test an association between pneumonia and poor prognosis or death after stroke.Our findings revealed the following risk factors for PSP: atrial fibrillation odds ratio (OR) = 2.884, 95% confidence intervals (CI) = 1.316-6.322), being bedridden (OR = 2.797, 95%CI = 1.322-5.921), subject to an invasive procedure (OR = 12.838, 95%CI = 6.296-26.178), massive cerebral infarction (OR = 3.994, 95%CI = 1.496-10.666), and dysphagia (OR = 2.441, 95%CI = 1.114-5.351). Pneumonia was a risk factor for poor prognosis (OR = 2.967, 95%CI = 1.273-6.915) and death (OR = 5.493, 95%CI = 1.825-16.53) after stroke.Hence, since pneumonia increases the risk of poor prognosis and death following acute ischemic stroke, preventing, and managing the risk factors for PSP may improve the prognosis and reduce the mortality after stroke.


Assuntos
Fibrilação Atrial , Transtornos de Deglutição , Pneumonia , Fatores Etários , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Pessoas Acamadas/estatística & dados numéricos , China/epidemiologia , Estudos de Coortes , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Feminino , Humanos , /mortalidade , Masculino , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/prevenção & controle , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
9.
Sci Rep ; 11(1): 2820, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531576

RESUMO

Enlarged perivascular spaces (EPVS) are widely considered as a feature of cerebral small vessel diseases (SVD), but its underlying pathology is still under active investigation. The aim of this study was to explore the association between hemoglobin level and the severity of EPVS. Consecutive patients with acute ischemic stroke who underwent baseline MRI scan and hemoglobin testing were evaluated. EPVS in basal ganglia (BG) and central semiovale (CS) were rated with a validated 4-point semiquantitative scale (0 = none; 1 = 1-10; 2 = 11-20; 3 = 21-40; and 4 ≥ 40). Bivariate logistic regression models were used to identify the associations of hemoglobin with predefined high-degree (score > 1) CS-EPVS and BG-EPVS. Multinomial logistic regression models were used to analyze the associations between hemoglobin and CS-/BG-EPVS predominance patterns. A total of 401 patients were included in the final analysis, 94 patients (23.4%) had a high degree of CS-EPVS and 45 patients (11.2%) had a high degree of BG-EPVS. Compared with tertile 1 of hemoglobin, tertile 3 of hemoglobin was independently associated with high degree of CS-EPVS after adjusting for other features of SVD (odds ratio [OR] 2.399, 95% confidence interval [CI] 1.315-4.379, P = 0.004) and potential confounding factors (OR 2.611, 95% CI 1.346-5.066, P = 0.005). In multinomial logistic regression models, compared with tertile 1 of hemoglobin, tertile 2 (OR 2.463, 95% CI 1.195-5.075, P = 0.015) and tertile 3 (OR 2.625, 95% CI 1.102-6.251, P = 0.029) of hemoglobin were associated with higher odds of BG-EPVS = CS-EPVS pattern, and tertile 3 of hemoglobin (OR 2.576, 95% CI 1.004-6.608, P = 0.049) was associated with higher odds of BG-EPVS < CS-EPVS pattern. Elevated hemoglobin level was independently associated with high degree of CS-EPVS and higher odds of CS-EPVS predominance pattern, but not with BG-EPVS, which support that the topography of EPVS is characteristic. However, the pathogenesis linking hemoglobin and CS-EPVS is unclear and still needs further investigation.

10.
Proc Natl Acad Sci U S A ; 118(6)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526666

RESUMO

Gene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored since most previous studies have focused on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than the long-term rate. Comparisons with single-nucleotide polymorphism distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression levels of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load has been highly underestimated in natural populations. This has additional implications for strategies of disease allele detection in humans.

11.
J Ethnopharmacol ; 271: 113879, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33524509

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora Tonkinensis Gagnep. (STG) has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, cervical cancer, liver cancer, stomach cancer, lung cancer and leukemia in China. However, the main chemical composition and anticancer mechanism of chloroform extract of STG (CESTG) were still not very clear. AIM OF STUDY: This work was carried out to investigate the anticancer effects and mechanisms of chloroform extract of STG (CESTG) on NPC. METHODS: Cultured NPC CNE1, CNE2 and Np69 cells were treated with CESTG. Cells were subjected to cell proliferation, colony-forming, migration and invasion assays. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and morphological analysis were also performed. Tumor xenografts and drug treatments were made in BALB/c nude mice. The main compounds of CESTG was separated by HPLC. RESULTS: CESTG inhibited cell viability, clonal growth and induced cell apoptosis in a dose-dependent manner by silencing the PI3K/AKT/mTOR signaling pathway, which is associated with upregulation of cleaved PARP, caspase 3/7/8/9, cleaved caspase 3/7/8/9, Bax and downregulation of PARP, P-PI3K, PI3K, P-AKT, AKT, P-mTOR, mTOR and Bcl-2. In addition, CESTG arrested cell cycle in the G1/S phase, correlating with decreased levels of cyclin D1/B1, CDK 4 and 6. CESTG decreased cell migration and invasion which correlated with decreased expression of ß-catenin, vimentin and snail. CESTG significantly inhibited the tumor growth without toxicity. CONCLUSION: The results presented here suggest that CESTG could be use as a potential source of NPC therapeutic drug.

12.
J Environ Sci (China) ; 102: 53-63, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33637265

RESUMO

A distinctive kind of organic carbon aerosol that could absorb ultraviolet-visible radiation is called brown carbon (BrC), which has an important positive influence on radiative budget and climate change. In this work, we reported the absorption properties and potential source of BrC based on a seven-wavelength aethalometer in the winter of 2018-2019 at an urban site of Sanmenxia in Fenwei Plain in central China. Specifically, the mean value of BrC absorption coefficient was 59.6 ± 36.0 Mm-1 at 370 nm and contributed 37.7% to total absorption, which made a significant impact on visibility and regional environment. Absorption coefficients of BrC showed double-peak pattern, and BrC had shown small fluctuations under haze days compared with clean days. As for the sources of BrC, BrC absorption coefficients expressed strong correlations with element carbon aerosols and primary organic carbon aerosols, indicating that most of BrC originated from primary emissions. The linear correlations between trace metal elements (K, As, Fe, Mn, Zn, and Pb) and BrC absorption coefficients further referred that the major sources of BrC were primary emissions, like coal burning, biomass burning, and vehicle emissions. The moderate relationship between BrC absorption coefficients and secondary organic aerosols suggested that secondary production of BrC also played an important role. The 120 hr backward air mass trajectories analysis and concentration-weighted trajectories analysis were also used to investigate potential sources of BrC in and around this area, which inferred most parts of BrC were derived from local emissions.


Assuntos
Poluentes Atmosféricos , Carbono , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , China , Monitoramento Ambiental , Material Particulado/análise
13.
Sci Total Environ ; 772: 145464, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571768

RESUMO

Assimilatory and dissimilatory sulfate reduction (ASR and DSR) are the core bacterial sulfate-reducing pathways involved in wastewater treatment. It has been reported that sulfate-reducing activities could happen within biofoulants of membrane bioreactors during wastewater treatment. Biofoulants are mainly microbial products contributing membrane fouling and subsequent rising energy consumption in driving membrane filtration. Biofoulants from a full-scale biofilm-membrane bioreactor (biofilm-MBR) treating textile wastewater were investigated in this study. During a 10-month operation, sulfate concentrations in the effluent of the biofilm-MBR gradually decreased alongside with the creeping up sulfite concentrations when biofoulants were also building up on membrane modules. Sulfide had no apparent increases in the effluent during this period. Metagenomic analysis revealed diverse microbial communities residing in the biofoulants. Further analysis on their genetic traits revealed abundant ASR's and DSR's functional genes. A plethora of sulfate-reduction bacteria (SRB), including the well-known Desulfovibrio, Desulfainum, Desulfobacca, Desulfobulbus, Desulfococcus, Desulfonema, Desulfosarcina, Desulfobacter, Desulfobacula, Desulfofaba, Desulfotigum, Desulfatibacillum, Desulfatitalea, Desulfobacterium, were detected in the biofoulants. They were believed to play some important carbon and sulfur-cycling roles in our study. Based on metagenomic analysis, we also deduced that ASR was a functionally more important sulfate-reducing route because of the high abundance of assimilatory sulfate reductases detected. Also, the "AMP (adenosine monophosphate)→sulfite" step was a key reaction shared by both ASR and DSR in the biofoulant. This step might be responsible for the sulfite accumulation in the biofilm-MBR effluent. Overall, ASR functional genes in the biofoulants were more abundant. But the bacteria possessing complete DSR pathways caused the sulfide production in the biofilm-MBR.


Assuntos
Reatores Biológicos , Purificação da Água , Bactérias/genética , Biofilmes , Sulfatos , Têxteis , Águas Residuárias
14.
Eur J Obstet Gynecol Reprod Biol ; 259: 26-31, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33561585

RESUMO

OBJECTIVE: Vaginal childbirth is an established main aetiological factor in the pathogenesis of female pelvic floor dysfunction. However, pregnancy itself is also likely to have an effect. This study investigated the effect of pregnancy on pelvic floor functional anatomy. STUDY DESIGN: This was a retrospective observational study involving vaginally nulliparous women who presented to a tertiary urogynaecology unit with symptoms and signs of pelvic floor dysfunction between 2006 and 2014. Nulliparous women were compared with those who delivered exclusively by Caesarean Section (CS). All had undergone a standardised clinical interview, ICS POP-Q assessment and 3D/4D translabial pelvic floor ultrasound. Main outcome measures included sonographically determined pelvic organ position and hiatal dimensions on Valsalva and pelvic floor muscle contraction (PFMC). RESULTS: Of 2930 women seen during the study period, 242 had never given birth vaginally. One hundred and twenty-nine (53 %) were nulliparous, and 113 (47 %) were delivered by CS only. The CS group demonstrated significantly higher pelvic organ mobility in the anterior compartment (all P < 0.05) and a larger hiatal area on Valsalva (P = 0.004). All sonographic measures of pelvic floor muscle function demonstrated greater tissue displacement on PFMC in the CS group (all P < 0.05). CONCLUSIONS: Compared to nulliparas, women who delivered exclusively by CS showed increased pelvic organ descent on Valsalva and tissue displacement on PFMC, implying increased tissue elasticity/ compliance or reduced stiffness, consistent with a small permanent hormonal and/or mechanical effect of pregnancy.

15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(1): 54-60, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33441229

RESUMO

Objective To detect the expression of long non-coding RNA (lncRNA) actin filament-related protein 1 antisense RNA1 (AFAP1-AS1) in papillary thyroid carcinoma tissue, and to investigate the effects of the knockdown of AFAP1-AS1 in TPC-1 papillary thyroid carcinoma cells on cell epithelial-mesenchymal transition (EMT) and related molecular mechanism in TPC-1 cells. Methods Real-time quantitative PCR was used to detect the expression of lncRNA AFAP1-AS1 in 60 cases of papillary thyroid carcinoma tissues. RNA interfering (RNAi) was used to knockdown AFAP1-AS1 in TPC-1 cells. TPC-1 cells were divided into AFAP1-AS1 knockdown (shAFAP1-AS1) group, negative control RNA (shNC) group and untransfected control group. The colony-formation assay, TranswellTM invasion and scratch healing assays were employed to detect the colony-forming ability, cell invasion ability and cell migration ability of TPC-1 cells, respectively. After knockdown of AFAP1-AS1, real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein levels of E-cadherin, vimentin, ß-catenin and snail2, respectively. Results Compared with the paracancerous tissue, the expression level of AFAP1-AS1 mRNA in the papillary thyroid carcinoma tissue significantly increased. Knockdown of AFAP1-AS1 significantly reduced the colony-forming ability, invasion and migration ability of TPC-1 cells. Compared with shNC group and control group, knockdown of AFAP1-AS1 significantly reduced the mRNA and protein expression of snail2, vimentin and ß-catenin. In contrast, the mRNA and protein expression of E-cadherin increased considerably. Conclusion The lncRNA AFAP1-AS1 is highly expressed in papillary thyroid carcinoma tissue. After knockdown of AFAP1-AS1 in TPC-1 cells, the colony-forming ability, invasion and migration ability of cancer cells are significantly down-regulated, which may be related to the inhibition of EMT.


Assuntos
RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Citoesqueleto de Actina , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas dos Microfilamentos , RNA Bacteriano , RNA Longo não Codificante/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética
16.
Curr Biol ; 31(5): 1092-1098.e6, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417882

RESUMO

Organismal phenotypes usually have a quantitative distribution, and their genetic architecture can be studied by genome-wide association (GWA) mapping approaches. In most of such studies, it has become clear that many genes of moderate or small effects contribute to the phenotype.1-4 Hence, the attention has turned toward the loci falling below the GWA cut-off, which may contribute to the phenotype through modifier interactions with a set of core genes, as proposed in the omnigenic model.5 One can thus predict that both moderate effect GWA-derived candidate genes and randomly chosen genes should have a similar likelihood to affect a given phenotype when they are analyzed via gene disruption assays. We have tested this hypothesis by using an automated phenotyping system for Drosophila pupal phenotypes.6,7 We first identified candidate genes for pupal length in a GWA based on the Drosophila Genetic Reference Panel (DGRP)8,9 and showed that most of these candidate genes are indeed involved in the phenotype. We then randomly chose genes below a GWA significance threshold and found that three-quarters of them had also an effect on the trait with comparable effect sizes as the GWA candidate genes. We further tested the effects of these knockout lines on an independent behavioral pupal trait (pupation site choice) and found that a similar fraction had a significant effect as well. Our data thus confirm the implication that a large number of genes can influence independent quantitative traits.

17.
Hum Genet ; 140(5): 791-803, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33392778

RESUMO

PIGK gene, encoding a key component of glycosylphosphatidylinositol (GPI) transamidase, was recently reported to be associated with inherited GPI deficiency disorders (IGDs). However, little is known about the specific downstream effects of PIGK on neurodevelopment due to the rarity of the disease and the lack of in vivo study. Here, we described 2 patients in a Chinese family presented with profound global developmental delay, severe hypotonia, seizures, and postnatal progressive global brain atrophy including hemisphere, cerebellar and corpus callosum atrophy. Two novel compound heterozygous variants in PIGK were identified via genetic analysis, which was proved to cause significant decrease of PIGK protein and reduced cell surface presence of GPI-APs in the patients. To explore the role of Pigk on embryonic and neuronal development, we constructed Pigk knock-down zebrafish and knock-in mouse models. Zebrafish injected with a small dose of morpholino oligonucleotides displayed severe developmental defects including small eyes, deformed head, curly spinal cord, and unconsumed yolk sac. Primary motor neuronal dysplasia and extensive neural cell apoptosis were further observed. Meanwhile, the mouse models, carrying the two variants respectively homologous with the patients, both resulted in complete embryonic lethality of the homozygotes, which suggested the intolerable effect caused by amino acid substitution of Asp204 as well as the truncated mutation. Our findings provide the in vivo evidence for the essential role of PIGK during the embryonic and neuronal development. Based on these data, we propose a basis for further study of pathological and molecular mechanisms of PIGK-related neurodevelopmental defects.


Assuntos
Encefalopatias/genética , Moléculas de Adesão Celular/genética , Glicosilfosfatidilinositóis/deficiência , Malformações do Sistema Nervoso/genética , Neurogênese/genética , Convulsões/genética , Anormalidades Múltiplas/genética , Animais , Apoptose/genética , Linhagem Celular , Pré-Escolar , Modelos Animais de Doenças , Desenvolvimento Embrionário/genética , Técnicas de Introdução de Genes , Glicosilfosfatidilinositóis/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Peixe-Zebra
18.
Artigo em Inglês | MEDLINE | ID: mdl-33498934

RESUMO

The non-stationarity, nonlinearity and complexity of the PM2.5 series have caused difficulties in PM2.5 prediction. To improve prediction accuracy, many forecasting methods have been developed. However, these methods usually do not consider the importance of data preprocessing and have limitations only using a single forecasting model. Therefore, this paper proposed a new hybrid decomposition-ensemble learning paradigm based on variation mode decomposition (VMD) and improved whale-optimization algorithm (IWOA) to address complex nonlinear environmental data. First, the VMD is employed to decompose the PM2.5 sequences into a set of variational modes (VMs) with different frequencies. Then, an ensemble method based on four individual forecasting approaches is applied to forecast all the VMs. With regard to ensemble weight coefficients, the IWOA is applied to optimize the weight coefficients, and the final forecasting results were obtained by reconstructing the refined sequences. To verify and validate the proposed learning paradigm, four daily PM2.5 datasets collected from the Jing-Jin-Ji area of China are chosen as the test cases to conduct the empirical research. The experimental results indicated that the proposed learning paradigm has the best results in all cases and metrics.


Assuntos
Algoritmos , Baleias , Animais , China , Previsões , Aprendizado de Máquina , Material Particulado/análise
19.
J Clin Pharm Ther ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462825

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Acarbose can efficiently block glucose absorption in the intestine as an alpha-glucosidase inhibitor. It is currently manufactured in several oral dosage forms, with the most common types being tablets and chewable tablets. The acarbose tablet (Glucobay® , 50 mg, Bayer) package insert gives instructions for either directly swallowing or chewing then swallowing. This study compared the pharmacodynamic effects of a single formulation of acarbose tablets under these two different administration routes. METHODS: This randomized, crossover study enrolled 24 healthy subjects who were instructed to chew (C group) or swallow (S group) the acarbose tablet. Glucose levels were monitored in subjects for up to 4 h following administration of 75 g of sucrose to establish a baseline firstly, after which subjects in the C and S groups were administered 50- or 100- mg of acarbose along with 75 g of sucrose. Then, subjects entered a 1-week washout period before being crossed over to the alternate dosing route. RESULTS AND DISCUSSION: Compared with the S group, the C group had a lower maximum concentration of serum glucose (Cmax ) and areas under the concentration-time curve (AUC0-2 , AUC0-1.5 ). In addition, the maximum reduction in serum glucose (ΔCmax ) and the reduction in the AUC (AUEC0-1.5 ) were both increased in the S group. This occurred at both the 50 mg and 100 mg dosages. These results indicate that fluctuations in blood glucose were lower following chewing of the acarbose tablet. Both administration routes exhibited similar safety and tolerance profiles. WHAT IS NEW AND CONCLUSION: In summary, chewing acarbose tablets appears to induce a superior glycaemic-controlling effect compared with swallowing them directly, at least with a single dose. It will be important to inform both clinicians and patients about these differences between the two administrations so that informed clinical decisions can be made, as numerous patients with diabetes are inclined to directly swallow acarbose tablets for convenience.

20.
Plant Dis ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439037

RESUMO

Alfalfa (Medicago sativa L.) is one of the most important perennial leguminous forages in many countries, known by its high feed value and yield potential. With the increasing demand for feed, alfalfa has been planted all over China. However, an increasingly serious alfalfa disease was observed and may restrict the development of the alfalfa industry in North China. In August 2019, an emerging alfalfa disease with symptoms resembling southern blight was observed in Jiaozhou experimental base (Jiaozhou Modern Agricultural Science and Technology Demonstration Park) of Qingdao Agricultural University (Qindao, Shandong province, China). The infected plants showed dark brown lesions on the stems and yellowing and wilting of the leaves. The pathogen produced white fluffy mycelia, and later sclerotia on stems and roots; the disease affected up to 25% of the plants and causes bare spots filled with weeds (Figure S1). Typical symptomatic tissues were brought back to the laboratory for pathogen isolation and identification. Fragments (3-5mm2) of root tissues were excised from lesions on the symptomatic roots and their surfaces were disinfested by sequential dipping in 70% ethanol for 30 s and in 2% NaClO for 3 min, then the fragments were rinsed in sterile water five times and cultured on potato dextrose (PDA) medium amended with streptomycin sulfate (0.1mg/mL). Cultures were incubated at 28°C in the dark and purified in PDA medium for three times. A representative strain (coded as CZL1) was isolated from the root rot of the diseased plant. After four days incubation on PDA, CZL1 formed white fluffy aerial mycelium 5.6-6 cm in diameter typical of S. rolfsii. After 15 to 20 days, abundant round sclerotia approximately1-3 mm in diameter were produced on the surface of the culture (Figure S2). The sclerotia were white at first and then gradually turned dark brown. To confirm the identity of the causal fungus, the complete internal transcribed spacer (ITS) rDNA region of the fungus was amplified using the primers ITS1/ITS4 (White et al.1990), and the elongation factor-1a gene (EF1a) was amplified using primers EF1-983F/EF1-2218R (Rehner and Buckley 2005). Then the PCR amplicons were cloned into the pCE2 TA/Blunt-Zero vector. The isolate was determined to contain two distinct sequence types for each gene. The results of ITS (MT812692, MT812693) and EF1a (MT846496 and MT846497) sequences were deposited in GenBank. DNA analysis revealed that the two ITS sequences were more than 99% identical to Athelia rolfsii (MN872304) in the NCBI GenBank database, and two EF1a sequences were 99% identical to the A. rolfsii EF1a sequence MN702789 and KP982854. To fulfill Koch's postulates, infected sorghum grain was placed near the roots of 15 40-day-old healthy alfalfa seedlings split into 3 pots with the same number of seedlings receiving a control treatment of sterilized sorghum grain. All plants were incubated in growth chamber at 24±1°C with 14-h-photoperiod (85% relative humidity). After 10-15 days, blight symptoms identical to those in the field were observed on inoculated plants, whereas those control plants were symptomless (Figure S2). S. rolfsii was successfully re-isolated from the inoculated plants and molecularly characterized as described above. Based on disease symptoms, fungal colonies, the ITS and EF1a sequence, and pathogenicity to the host, this fungus was identified as S. rolfsii (teleomorph Athelia rolfsii). To our knowledge, this is the first report of S. rolfsii as the causal agent of southern blight of alfalfa in North China, and it is also the first report of southern blight on alfalfa caused by S. rolfsii in China since 1996 observed in Guizhou province (Mo and Luo 1996).

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