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1.
Oxid Med Cell Longev ; 2021: 8836355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211634

RESUMO

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague-Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial-osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

2.
Mater Sci Eng C Mater Biol Appl ; 127: 112204, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225856

RESUMO

Alginate fibrous materials have been applied as wound dressing to enhance wound healing due to its nontoxic, biodegradable, and hemostatic nature. Conventional nonwoven fabrication tactics, however, showed weakness in inflammation, degradation stability and mechanical properties. Herein, the wet-spun alginate fibers were prepared by a novel wheel spinning technique, then knitted into wound dressing. Benefiting from optimized wet spinning parameters and the agglomeration of alginate multimers, the fibers were endowed with elevated mechanical performances and biodegradability, which allowed for the feasibility of knitting wound-care materials. Using the new wheel spinning technique, high strength alginate fibers with 173 MPa were produced with breaking strain up to 18% and toughness of 16.16 MJ*m-3. Meanwhile, alginate fibers with high breaking strain reaching 35% were produced with tensile strength of 135 MPa and toughness of 37.47 MJ*m-3. The overall mechanical performances of these alginate fibers with high breaking strain are significantly higher (up to 2 times) than those published in the literature in term of toughness. In vitro degradation evaluation revealed that this wet spun fibrous dressing had good aqueous absorbency (50%) and sustained biodegradation properties. Furthermore, the consequent cell viability study also proved that this alginate knitted fabric is biocompatible for being applied as wound dressing.


Assuntos
Alginatos , Materiais Biocompatíveis , Bandagens , Materiais Biocompatíveis/farmacologia , Hidrogéis , Cicatrização
3.
J Environ Sci (China) ; 106: 124-135, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210428

RESUMO

Heterogeneous reactions of NO2 on different surfaces play an important role in atmospheric NOx removal and HONO formation, having profound impacts on photochemistry in polluted urban areas. Previous studies have suggested that the NO2 uptake on the ground or aerosol surfaces could be a dominant source for elevated HONO during the daytime. However, the uptake behavior of NO2 varies with different surfaces, and different uptake coefficients were used or derived in different studies. To obtain a more holistic picture of heterogeneous NO2 uptake on different surfaces, a series of laboratory experiments using different flow tube reactors was conducted, and the NO2 uptake coefficients (γ) were determined on inorganic particles, sea water and urban grime. The results showed that heterogeneous reactions on those surfaces were generally weak in dark conditions, with the measured γ varied from <10-8 to 3.2 × 10-7 under different humidity. A photo-enhanced uptake of NO2 on urban grime was observed, with the obvious formation of HONO and NO from the heterogeneous reaction. The photo-enhanced γ was measured to be 1.9 × 10-6 at 5% relative humidity (RH) and 5.8 × 10-6 at 70% RH on urban grime, showing a positive RH dependence for both NO2 uptake and HONO formation. The results demonstrate an important role of urban grime in the daytime NO2-to-HONO conversion, and could be helpful to explain the unknown daytime HONO source in the polluted urban area.


Assuntos
Ácido Nitroso , Água do Mar , Aerossóis
4.
Oxid Med Cell Longev ; 2021: 6644238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221235

RESUMO

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

5.
J Med Chem ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251202

RESUMO

Breast cancer remains a leading cause of cancer death in women, representing a significant unmet medical need. Here, we disclose our discovery efforts culminating in a clinical candidate, 35 (GDC-9545 or giredestrant). 35 is an efficient and potent selective estrogen receptor degrader (SERD) and a full antagonist, which translates into better antiproliferation activity than known SERDs (1, 6, 7, and 9) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing of 35 in preclinical species and humans. 35 exhibits low drug-drug interaction liability and demonstrates excellent in vitro and in vivo safety profiles. At low doses, 35 induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1Y537S mutant PDX or a wild-type ERα tumor model. Currently, 35 is being evaluated in Phase III clinical trials.

6.
J Fish Dis ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34227114

RESUMO

White spot syndrome virus (WSSV) is a serious pathogen threatening global crustacean aquaculture with no commercially available drugs. Herbal medicines widely used in antiviral research offer a rich reserve for drug discovery. Here, we investigated the inhibitory activity of 13 herbal medicines against WSSV in crayfish Procambarus clarkii and discovered that naringenin (NAR) has potent anti-WSSV activity. In the preliminary screening, the extracts of Typha angustifolia displayed the highest inhibitory activity on WSSV replication (84.62%, 100 mg/kg). Further, NAR, the main active compound of T. angustifolia, showed a much higher inhibition rate (92.85%, 50 mg/kg). NAR repressed WSSV proliferation followed a dose-dependent manner and significantly improved the survival of WSSV-challenged crayfish. Moreover, pre- or post-treatment of NAR displayed a comparable inhibition on the viral loads. NAR decreased the transcriptional levels of vital genes in viral life cycle, particularly for the immediately early-stage gene ie1. Further results showed that NAR could decrease the STAT gene expression to block ie1 transcription. Besides, NAR modulated immune-related gene Hsp70, antioxidant (cMnSOD, mMnSOD, CAT, GST), anti-inflammatory (COX-1, COX-2) and pro-apoptosis-related factors (Bax and BI-1) to inhibit WSSV replication. Overall, these results suggest that NAR may have the potential to be developed as preventive or therapeutic agent against WSSV.

7.
Phys Med Biol ; 66(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34225262

RESUMO

Metallic implants can heavily attenuate x-rays in computed tomography (CT) scans, leading to severe artifacts in reconstructed images, which significantly jeopardize image quality and negatively impact subsequent diagnoses and treatment planning. With the rapid development of deep learning in the field of medical imaging, several network models have been proposed for metal artifact reduction (MAR) in CT. Despite the encouraging results achieved by these methods, there is still much room to further improve performance. In this paper, a novel dual-domain adaptive-scaling non-local network (DAN-Net) is proposed for MAR. We correct the corrupted sinogram using adaptive scaling first to preserve more tissue and bone details. Then, an end-to-end dual-domain network is adopted to successively process the sinogram and its corresponding reconstructed image is generated by the analytical reconstruction layer. In addition, to better suppress the existing artifacts and restrain the potential secondary artifacts caused by inaccurate results of the sinogram-domain network, a novel residual sinogram learning strategy and non-local module are leveraged in the proposed network model. Experiments demonstrate the performance of the proposed DAN-Net is competitive with several state-of-the-art MAR methods in both qualitative and quantitative aspects.

8.
Small ; : e2102558, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34293248

RESUMO

The additive strategy is widely used in optimizing the morphology of organic solar cells (OSCs). The majority of additives are liquid with high boiling points, which will be trapped within device and consequently deteriorate performance during operation. In this work, solid but volatile additives 2-(4-fluorobenzylidene)-1H-indene-1,3(2H)-dione (INB-F) and 2-(4-chlorobenzylidene)-1H-indene-1,3(2H)-dione (INB-Cl) are designed to replace the common 1,8-diiodooctane (DIO) in nonfullerene OSCs. These additives present during solution casting but evaporate after moderate heating. Molecular dynamics simulations show that they can reduce the adsorption energy to improve π-π stacking among nonfullerene acceptor (NFA) molecules, an effect that enhances light absorption and electron mobility. Both INB-F and INB-Cl enhance efficiency, with INB-F achieving a maximum efficiency of 16.7% from 15.1% of the reference PBDB-T-2F (PM6):BTP-BO-4F (Y6-BO) cell, and outperforming DIO. Remarkably, they can simultaneously enhance the operational stability, with the INB-F-treated OSC maintaining over 60% of the initial efficiency after 1000 h operation, demonstrating a T80 lifetime of 523 h, which is a significant improvement over T80 values of 66.2 h for the reference and 6.6 h for DIO-treated OSC. The simultaneously enhanced efficiency and operational lifetime are also effective in PM6:BTP-BO-4Cl (Y7-BO) OSCs, demonstrating a universal strategy to improve the performance of OSCs.

9.
Br J Cancer ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290392

RESUMO

BACKGROUND: Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. METHODS: A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. RESULTS: A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. DISCUSSION: The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.

10.
Environ Int ; 156: 106732, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34197974

RESUMO

Severe episodic air pollution blankets entire cities and regions and have a profound impact on humans and their activities. We compiled daily fine particle (PM2.5) data from 100 cities in five continents, investigated the trends of number, frequency, and duration of pollution episodes, and compared these with the baseline trend in air pollution. We showed that the factors contributing to these events are complex; however, long-term measures to abate emissions from all anthropogenic sources at all times is also the most efficient way to reduce the occurrence of severe air pollution events. In the short term, accurate forecasting systems of such events based on the meteorological conditions favouring their occurrence, together with effective emergency mitigation of anthropogenic sources, may lessen their magnitude and/or duration. However, there is no clear way of preventing events caused by natural sources affected by climate change, such as wildfires and desert dust outbreaks.

11.
Bioinformatics ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302462

RESUMO

MOTIVATION: Microbiome data have proven extremely useful for understanding microbial communities and their impacts in health and disease. Although microbiome analysis methods and standards are evolving rapidly, obtaining meaningful and interpretable results from microbiome studies still requires careful statistical treatment. In particular, many existing and emerging methods for differential abundance analysis fail to account for the fact that microbiome data are high-dimensional and sparse, compositional, negatively and positively correlated, and phylogenetically structured. To better describe microbiome data and improve the power of differential abundance testing, there is still a great need for the continued development of appropriate statistical methodology. RESULTS: In this paper, we propose a model-based approach for microbiome data transformation, and a phylogenetically informed procedure for differential abundance (DA) testing based on the transformed data. First, we extend the Dirichlet-tree multinomial (DTM) to zero-inflated DTM (ZIDTM) for multivariate modeling of microbial counts, addressing data sparsity, and correlation and phylogeny among bacterial taxa. Then, within this framework and using a Bayesian formulation, we introduce posterior mean transformation to convert raw counts into nonzero relative abundances that sum to one, accounting for the compositionality nature of microbiome data. Second, using the transformed data, we propose adaptive analysis of composition of microbiomes (adaANCOM) for DA testing by constructing log-ratios adaptively on the tree for each taxon, greatly reducing the computational complexity of ANCOM in high dimensions. Finally, we present extensive simulation studies, an analysis of HMP data across 18 body sites and 2 visits, and an application to a gut microbiome and malnutrition study, to investigate the performance of posterior mean transformation and adaANCOM. Comparisons with ANCOM and other DA testing procedures show that adaANCOM controls the false discovery rate well, allows for easy interpretation of the results, and is computationally efficient for high-dimensional problems. AVAILABILITY: The developed R package is available at https://github.com/ZRChao/adaANCOM. For replicability purposes, scripts for our simulations and data analysis are available at https://github.com/ZRChao/Papers_supplementary. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

12.
Fish Physiol Biochem ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313912

RESUMO

The regulation mechanism of the hybrid yellow catfish "Huangyou-1" was assessed under conditions of hypoxia and reoxygenation by examination of oxygen sensors and by monitoring respiratory metabolism, oxidative stress, and apoptosis. The expressions of genes related to oxygen sensors (HIF-1α, HIF-2α, VHL, HIF-1ß, PHD2, and FIH-1) were upregulated in the brain and liver during hypoxia, and recovered compared with control upon reoxygenation. The expressions of genes related to glycolysis (HK1, PGK1, PGAM2, PFK, and LDH) were increased during hypoxia and then recovered compared with control upon reoxygenation. The mRNA levels of CS did not change during hypoxia in the brain and liver, but increased during reoxygenation. The mRNA levels of SDH decreased significantly only in the liver during hypoxia, but later increased compared with control upon reoxygenation in both tissues. Under hypoxic conditions, the expressions of genes related to oxidative stress (SOD1, SOD2, GSH-Px, and CAT) and the activity of antioxidant enzymes (SOD, CAT, and GSH-Px) and MDA were upregulated compared with control. The expressions of genes related to apoptosis (Apaf-1, Bax, Caspase 3, Caspase 9, and p53) were higher than those in control during hypoxic exposure, while the expressions of Bcl-2 and Cyt C were decreased. The findings of the transcriptional analyses will provide insights into the molecular mechanisms of hybrid yellow catfish "Huangyou-1" under conditions of hypoxia and reoxygenation. Overall, these findings showed that oxygen sensors of "Huangyou-1" are potentially useful biomarkers of environmental hypoxic exposure. Together with genes related to respiratory metabolism, oxidative stress and apoptosis occupy a quite high position in enhancing hypoxia tolerance. Our findings provided new insights into the molecular regulatory mechanism of hypoxia in "Huangyou-1."

13.
Transbound Emerg Dis ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314096

RESUMO

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease with high morbidity and mortality in domestic pigs. Although adaptation of ASFV to Vero cells has been investigated, the phenotypic changes and the corresponding genomic variations during adaptation of ASFV to other cell lines remain unclear. To obtain a cell-adapted ASFV strain, different cell lines were tested to determine whether they support ASFV infection. Interestingly, the ASFV wild-type strain ASFV-HLJ/18 can infect HEK293T cells and replicate at a low level. After continuous passaging, the adapted ASFV strain can replicate efficiently in both HEK293T and Vero cells. However, the adapted ASFV strain displayed reduced infectivity in primary porcine alveolar macrophages compared to the corresponding wild-type strain. Furthermore, stepwise losses at the left variable end of the MGF genes and accumulative mutations were identified during passaging, indicating that the ASFV strain gradually adapted to HEK293T cells. Comparison of MGF deletions in other cell culture-adapted ASFV strains revealed that the deletions of MGF300 (1L, 2R and 4L) and MGF360 genes (8L, 9L, 10L and 11L) play an important role for the adaptation of ASFV to HEK293T cells at the early stage. The biological functions of the deletions and mutants associated with ASFV infection in HEK293T cells and pigs warrant further study. Overall, our findings provide new targets to elucidate the molecular mechanism of adaptation of ASFV to cell lines.

14.
Clin Cancer Res ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210685

RESUMO

PURPOSE: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives. EXPERIMENTAL DESIGN: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors. RESULTS: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC. CONCLUSIONS: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches.

15.
Neural Plast ; 2021: 4516133, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221001

RESUMO

The modulation of attentional load on the perception of auditory and visual information has been widely reported; however, whether attentional load alters audiovisual integration (AVI) has seldom been investigated. Here, to explore the effect of sustained auditory attentional load on AVI and the effects of aging, nineteen older and 20 younger adults performed an AV discrimination task with a rapid serial auditory presentation task competing for attentional resources. The results showed that responses to audiovisual stimuli were significantly faster than those to auditory and visual stimuli (AV > V ≥ A, all p < 0.001), and the younger adults were significantly faster than the older adults under all attentional load conditions (all p < 0.001). The analysis of the race model showed that AVI was decreased and delayed with the addition of auditory sustained attention (no_load > load_1 > load_2 > load_3 > load_4) for both older and younger adults. In addition, AVI was lower and more delayed in older adults than in younger adults in all attentional load conditions. These results suggested that auditory sustained attentional load decreased AVI and that AVI was reduced in older adults.

16.
Artigo em Chinês | MEDLINE | ID: mdl-34304466

RESUMO

Objective:To investigate the curative effect of the auricular defect repaired by the autologous concha cartilage. Methods:Seven cases with the auricular defect were repaired using the autologeous concha cartilage which combined with the retroauricular flap or retroauricular fascia with skin graftin. Results:Total 7 patients were followed up for 6 months after the surgery. The shape and size of the repaired ears were similar to the healthy ears. The teansplanted cartilages were not absorbed or deformed. Conclusion:This method is harmless and simple,which has reliable and satisfactory effects on auricle defect. We can operate under local anethesia and avoid cutting the rib cartilage.


Assuntos
Pavilhão Auricular , Procedimentos Cirúrgicos Reconstrutivos , Cartilagem , Pavilhão Auricular/cirurgia , Orelha Externa , Humanos , Transplante de Pele , Retalhos Cirúrgicos
17.
Sci Total Environ ; 797: 149127, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34311350

RESUMO

It is a concern whether the effect of soil type on N2O emissions has to be considered for regional mitigation strategies and emission estimates in mountainous areas with inherent spatial heterogeneities of soil type. To date, there were few field experiments which investigated soil type effects on N2O emissions. Thus a 2-year field study was conducted to measure N2O emissions and soil environmental variables from three different soils that were formed from similar parental rock under the same climate. Seasonal N2O fluxes ranged from 0.18 to 0.40 kg N ha-1 for wheat seasons and 0.40 to 1.50 kg N ha-1 for maize seasons across different experimental soils. The intra- and inter-annual variations in N2O emissions were mainly triggered by temporal dynamics of soil temperature and moisture conditions. On average, seasonal N2O fluxes for acidic soils were significantly lower than for neutral and alkaline soils in cold-dry wheat seasons while significantly greater than for neutral and alkaline soils in warm-wet maize seasons. These determined differences of N2O emissions were mainly caused by differences of initial soil properties across different soils. Moreover, seasonal N2O fluxes were positively correlated with soil pH in wheat seasons, but negatively correlated in maize seasons. The temperature sensitivity coefficient (Q10) of soil N2O emissions for acidic soil (4.06) were significantly greater than those for neutral (1.82) and alkaline (1.15) soils. Overall, N2O emissions for acidic soils were not only higher than those for neutral and alkaline soils but also more sensitive to changing temperature. The present study highlights that soil type is needed to be carefully considered for regional estimate and proposing mitigation strategy of N2O emissions especially in subtropical mountain regions with inherent great heterogeneity of soil type.

18.
Pathol Res Pract ; 224: 153511, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34214845

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory intestinal disease. Genetic susceptibility, gut microbiota and mucosal immune dysfunction play important roles in the pathogenesis and development of UC. We investigate the effect of Mist1 in model of colitis and its underlying mechanism. The expressions of Mist1 in patients with colitis tissue were up-regulated. Meanwhile, Mist1 mRNA and protein expressions in DSS-induced colitis mice model were also induced and Mist1 mRNA and protein expressions of LPS induced THP-1 cell were also up-regulated. we found Mist1 human protein promoted inflammation in DSS-induced colitis mice by NLRP3. So, we up-regulated Mist1 expression and over-expression of Mist1 promoted IL-1ß and NLRP3 protein expression levels in vitro model. However, down-regulation of Mist1 suppressed IL-1ß and NLRP3 protein expression levels in vitro model. Next, SNAI1 is a shooting point of Mist1 in the effects of Mist1 in colitis. The inhibition of SNAI1 reduced the effects of Mist1 on NLRP3 inflammasome in vitro model. Activation of SNAI1 induced the effects of Mist1 on NLRP3 inflammasome in vitro model. Lastly, anti-SNAI1 human protein lowered the effects of Mist1 human protein on NLRP3 inflammasome in DSS-induced colitis mice. We demonstrated that Mist1 promoted inflammation in colitis model via NLRP3 inflammasome by SNAI1, whereas the absence of these macrophages led to a significant improvement in colitis treatment.

19.
Respir Med ; 186: 106522, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34229289

RESUMO

BACKGROUND: We conducted the first real-world study of treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E antibody, in Chinese patients with severe allergic asthma. OBJECTIVE: The primary objective was the steroid-sparing effect of omalizumab after 12 and 16 weeks of treatment. Characteristics of the patient population, treatment patterns, response rate, and other measures of therapeutic effectiveness were also reported. METHODS: This nationwide, retrospective, real-world study was conducted in patients with severe allergic asthma who were treated with omalizumab in China. Data, including demographics, Asthma Control Test (ACT) and laboratory and lung function test results, and omalizumab use information, were extracted from patient records collected as part of a previously conducted real-world survey (Asthma Group of the Respiratory Disease Society of the Chinese Medical Association). RESULTS: In total, 139 patient records were included; 131 and 118 patients remained on treatment at the ≥12- and ≥16-week time points, respectively. The mean ± standard deviation age and median asthma duration (interquartile range) were 47.4 ± 14.3 and 7 (4, 15) years, respectively; 75.6% of patients had a history of allergic disease. Reductions (versus baseline) in inhaled corticosteroid/long-acting ß2 agonists or oral corticosteroids were reported in 61.1% and 63.6% of patients at ≥12 and ≥ 16 weeks, respectively. There were significant improvements in ACT scores (6.08, P < .001) and nitric oxide fraction in exhaled air (-13.0, P = .01) from baseline. Multivariate analysis revealed that age and allergic medical history were predictors of omalizumab treatment response. No serious adverse events were reported. CONCLUSION: Real-world omalizumab treatment was efficacious and well-tolerated in Chinese patients with severe allergic asthma.

20.
Infect Dis Poverty ; 10(1): 100, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284821

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an international public health threat, and people's participation in disease-related preventive behaviours is the key to controlling infectious diseases. This study aimed to assess the differences in adopting preventive behaviours among populations to explore potential individual and household factors and inequalities within families. METHODS: This online survey was conducted in April 2020. The directional stratified convenient sampling method was used to select 4704 participants from eight provinces in eastern, central, and western China. The questionnaire included demographic information, household variables, and five target prevention behaviours. The chi-squared test, binary multilevel model, and Mantel-Haenszel hierarchical analysis were used for data analysis in the study. RESULTS: Approximately 71.2% of the participants had appropriate outdoor prevention, and 32.9% of the participants had indoor protection in place. Sharing behaviours (P < 0.001) and education level (P < 0.001) were positively associated with adopting preventive measures. The inhibiting effect of household crowding and stimulating effect of high household income on preventive behaviours were determined in this study. Household size was negatively associated with living area (ß = -0.057, P < 0.05) and living style (ß = -0.077, P < 0.05). Household income was positively associated with age (ß = 0.023, P < 0.05), and relationship with friends (ß = 0.053, P < 0.05). Vulnerable groups, such as older adults or women, are more likely to have inadequate preventive behaviours. Older adults (OR = 1.53, 95% CI 1.09-2.15), women (OR = 1.37, 95% CI 1.15-1.64), and those with more than 2 suspected symptoms (OR = 1.85, 95% CI 1.07-3.19) were more likely to be affected by the inhibiting effect of household crowding, while the stimulating effect of high household income was limited in these groups. CONCLUSIONS: Inequalities in COVID-19 prevention behaviours exist between families and inadequate adoption of prevention by vulnerable groups are noteworthy. This study expands the research perspective by emphasizing the role of household factors in preventive behaviours and by focusing on family inequalities. The government should use traditional media as a platform to enhance residents' public health knowledge. Targeted additional wage subsidies, investments in affordable housing, financial support for multigenerational households, and temporary relocation policies may deserve more attention. Communities could play a critical role in COVID-19 prevention.


Assuntos
COVID-19/prevenção & controle , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , COVID-19/epidemiologia , Criança , China/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Aglomeração , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Saúde Pública , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Adulto Jovem
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