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1.
Brain Imaging Behav ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478055

RESUMO

Unilateral temporal lobe epilepsy (TLE) is the most common type of focal epilepsy characterized by foci in the unilateral temporal lobe grey matters of regions such as the hippocampus. However, it remains unclear how the functional features of white matter are altered in TLE. In the current study, resting-state functional magnetic resonance imaging (fMRI) was performed on 71 left TLE (LTLE) patients, 79 right TLE (RTLE) patients and 47 healthy controls (HC). Clustering analysis was used to identify fourteen white matter networks (WMN). The functional connectivity (FC) was calculated among WMNs and between WMNs and grey matter. Furthermore, the FC laterality of hemispheric WMNs was assessed. First, both patient groups showed decreased FCs among WMNs. Specifically, cerebellar white matter illustrated decreased FCs with the cerebral superficial WMNs, implying a dysfunctional interaction between the cerebellum and the cerebral cortex in TLE. Second, the FCs between WMNs and the ipsilateral hippocampus (grey matter foci) were also reduced in patient groups, which may suggest insufficient functional integration in unilateral TLE. Interestingly, RTLE showed more severe abnormalities of white matter FCs, including links to the bilateral hippocampi and temporal white matter, than LTLE. Taken together, these findings provide functional evidence of white matter abnormalities, extending the understanding of the pathological mechanism of white matter impairments in unilateral TLE.

2.
Curr Opin Pharmacol ; 60: 291-297, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34507029

RESUMO

Nicotinamide adenine dinucleotide (NAD) is essential for cellular physiological processes, directly or indirectly affecting metabolism and gene expression. The decline of NAD+ levels in the heart is accompanied by aging, causing cardiac pathological remodeling and dysfunction. Niacinamide mononucleotide (NMN) has emerged as a precursor to alleviate age-related cardiac pathophysiological changes by improving cardiac NAD+ homeostasis. Preclinical trials on the efficacy and safety of intaking NMN have shown encouraging results, revealing a cardioprotective effect without significant side effects. Strategies for improving the effectiveness of NMN are also evolving. The present review aimed to summarize the potentials of NMN as a nutraceutical against cardiac aging and highlight the relationship between NMN supplementation and cardiac protection.

3.
Water Res ; 204: 117602, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34481283

RESUMO

Selenate and sulfide are both contaminants which severely pollute water bodies. Respective bioremediation of selenate- and sulfide-contaminated wastewaters requires abundant electron donors and acceptors. Here, we present a novel concept coupling biological selenate to selenite (shortcut deselenization) and chemical sulfide-driven selenite reduction, to remove multiple pollutants simultaneously. Vial tests showed that shortcut deselenization could save at least two thirds of operation time and one third of carbon source, compared to the complete deselenization to elemental selenium. Subsequent co-removal of sulfide and selenite was optimized at reaction pH of ∼10 and reactant molar ratio of ∼4. Using a newly-designed continuous flow system, >95% removal of both selenate and sulfide was achieved by coupling shortcut deselenization to sulfide oxidation. A series of characterization tools revealed that the final collected precipitates were comprised of high-purity hexagonal selenium (97.4%, wt) and inconsiderable sulfur (2.6%, wt). Superior over selenate-reducing solutions generally producing selenium mixed with reagents or microorganisms, the selenium products generated here were highly purified thus very favorable for further recovery and reuse. Overall, this proof-of-concept study provided a promising technology not only for co-removal of multiple pollutants, but also for substantial costs saving, as well as for valuable products recovery.

4.
J Transl Med ; 19(1): 379, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488791

RESUMO

BACKGROUND: Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC. METHODS: Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples. RESULTS: Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages. CONCLUSIONS: On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.

5.
J Ethnopharmacol ; 282: 114609, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508802

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in "Zhulinsi fuke mifang" in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. AIM OF THE STUDY: In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. MATERIALS AND METHODS: Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. RESULTS: Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. CONCLUSIONS: Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation.

6.
Front Immunol ; 12: 725587, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512655

RESUMO

With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment. In recent years, the wide application of whole-exome sequencing/whole-genome sequencing has tremendously promoted the discovery and further studies of new IEI. The number of discovered IEI is growing rapidly, followed by numerous studies of their pathogenesis and therapy. In this review, we focus on novel discovered primary immune dysregulation diseases, including deficiency of SLC7A7, CD122, DEF6, FERMT1, TGFB1, RIPK1, CD137, TET2 and SOCS1. We discuss their genetic mutation, symptoms and current therapeutic methods, and point out the gaps in this field.

7.
J Diabetes Res ; 2021: 5445349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513999

RESUMO

The present study was designed to detect possible biomarkers associated with diabetic foot ulcer (DFU) incidence in an effort to develop novel treatments for this condition. The GSE7014 and GSE29221 gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, after which differentially expressed genes (DEGs) were identified between DFU and healthy samples. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were performed to explore the functional roles of these genes. In total, 1192 DEGs were identified in the GSE7014 dataset (900 upregulated, 292 downregulated), while 1177 were identified in the GSE29221 dataset (257 upregulated, 919 downregulated). GO analyses revealed these DEGs to be significantly enriched in biological processes including sarcomere organization, muscle filament sliding, and the regulation of cardiac conduction, molecular functions including structural constituent of muscle, protein binding, and calcium ion binding, and cellular components including Z disc, myosin filament, and M band. These DEGs were also enriched in the adrenergic signaling in cardiomyoctes, dilated cardiomyopathy, and tight junction KEGG pathways. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with DFU development.

8.
Nat Commun ; 12(1): 5377, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508089

RESUMO

Beyond the scope of Hermitian physics, non-Hermiticity fundamentally changes the topological band theory, leading to interesting phenomena, e.g., non-Hermitian skin effect, as confirmed in one-dimensional systems. However, in higher dimensions, these effects remain elusive. Here, we demonstrate the spin-polarized, higher-order non-Hermitian skin effect in two-dimensional acoustic higher-order topological insulators. We find that non-Hermiticity drives wave localizations toward opposite edges upon different spin polarizations. More interestingly, for finite systems with both edges and corners, the higher-order non-Hermitian skin effect leads to wave localizations toward two opposite corners for all the bulk, edge and corner states in a spin-dependent manner. We further show that such a skin effect enables rich wave manipulation by configuring the non-Hermiticity. Our study reveals the intriguing interplay between higher-order topology and non-Hermiticity, which is further enriched by the pseudospin degree of freedom, unveiling a horizon in the study of non-Hermitian physics.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34510347

RESUMO

Improving the logistics ecological efficiency (LEE) has become a significant part of ensuring a sustainable development and tackling environmental pollution. Previous studies in the logistics industry seldom considered air pollutants and the association of spatial information. Therefore, innovatively considering SO2, NOx, and PM, this study adopted the super-SBM-undesirable model to calculate the LEE of 30 provinces in China from 2005 to 2019 and, thereafter, developed information-based matrix to explore its influencing factors by using the spatial Dubin model. The results indicated that (1) the overall LEE was low with the average of 0.657, presenting a three-stage trend of "decreasing first, then rising, and later stable," and significant regional differences with the decreasing gradient pattern of the "Eastern-Central-Western." (2) A spatial directionality distributed from the northeast to southwest and a significant spatial autocorrelation were observed. (3) The LEE had a significant positive spillover effect. Industrial structure, urbanization level, environmental regulation, and technological innovation level had a positive impact on the local LEE, and industrial structure displayed the most promoting effects. Energy intensity, economic level, energy structure, and opening level had a significant effect on the local LEE with varying degree of inhibition. Local energy intensity and environmental regulation had a positive influence on the LEE in neighboring areas, while local opening level had inhibiting effects. In addition, policy recommendations for enhancing the LEE were made.

10.
Med Sci Monit ; 27: e928512, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34511593

RESUMO

BACKGROUND Coronavirus disease 2019 (COVID-19) has emerged as a global threat. This study was performed to gain an understanding of COVID-19-related knowledge, attitudes, and practices among susceptible individuals. MATERIAL AND METHODS Patients who had been diagnosed with old myocardial infarction were followed up via telephone survey based on an established follow-up system at the beginning of the COVID-19 outbreak (January 2020) in Chongqing, Southwest China. RESULTS A total of 631 eligible patients participated in this survey, and 40.6% of the rural respondents did not know the transmission routes of SARS-CoV-2, which was higher than the proportion of urban respondents (40.6% vs 31.0). Rural residents had a lower rate of adopting preventive measures than urban residents, such as wearing masks (76.7% vs 90.1%), avoiding meetings and gatherings (58.6% vs 68.5%), and hand washing (56.0% vs 63.8%). A higher percentage of women than men did not take any preventive measures (11.3% vs 7.6%), while a lower percentage of women than men wore masks (77.7% vs 84.5%). Multiple logistic regression revealed that rural patients were more likely to lack knowledge about transmission (odds ratio (OR): 1.51). Rural patients had an increased risk of failing to implement protective measures. CONCLUSIONS Female and rural populations lacked knowledge and failed to adopt protective measures during the beginning of the COVID-19 epidemic. Therefore, these populations may benefit from health education campaigns and policies.

11.
Analyst ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514481

RESUMO

To overcome obstacles such as low response and poor selectivity of pure ZnO and SnO2 gas sensors, the ZnO@SnO2 sensor was synthesized by hydrothermal synthesis. The samples were characterized by XRD, XPS, SEM, HRTEM, N2 adsorption-desorption and other techniques. The results show that ZnO@SnO2 forms an n-n-type heterostructure and presents a double-layer capsule with a size of 0.5-4 µm. The results show that compared with pure ZnO and SnO2, the ZnO@SnO2 sensor exhibits a higher response (138.9) to 50 ppm triethylamine (TEA) at 152°C, which is 19.56 times that of the pure ZnO sensor and 21.7 times that of the SnO2 sensor. It has a short response/recovery time (11/11 s), excellent selectivity and cycling stability. Compared with other volatile organic compounds or gases, it has higher selectivity for TEA detection.

12.
J Sep Sci ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34514725

RESUMO

Red and yellow pigments are the major ingredients of safflower, often used to color food and cosmetics. Carthamin, the main component of red pigment, and hydroxysafflor yellow A, anhydrosafflower yellow B were representative components of yellow pigment. Plant metabolomics and semi-quantitative analysis were used to analyze the changes of pigment composition during blooming period, especially these characteristic components. Carthamin, hydroxysafflor yellow A, anhydrosafflower yellow B and other components were screened out as differential metabolites based on plant metabolomics. Then semi-quantitative analysis was used to quantify these three representative components of pigments. Experimental results showed that: content of pigments has dynamic changes along with flowering, in the early blooming period, yellow pigment accumulated much and red pigment was low in content. In the middle period, the accumulation rate of the yellow pigment slowed down and content was stabilized. In the next step, the content of yellow pigment gradually decreased, and the content of red pigments gradually increased. Later, the level of yellow pigment decreased significantly, and accumulation rate of red pigment increased significantly. Lastly, the appearance color of safflower was red, with yellow parts barely visible, and accumulation of red pigment was highest, yellow pigment was lowest in content. This article is protected by copyright. All rights reserved.

13.
Kidney Blood Press Res ; : 1-8, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34515147

RESUMO

BACKGROUND: Previous studies have reported that disturbance of endogenous circadian rhythms enhances the chance of hypertension and suggested that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was aimed to investigate the association of the mRNA expression of aryl hydrocarbon receptor nuclear translocator like (Arntl), clock circadian regulator (Clock), and period circadian regulators 1 and 2 (Per1 and Per2) with hypertension and blood pressure levels. METHODS: A total of 172 subjects were recruited in this study, including 86 hypertension and 86 nonhypertension controls. The mRNA expression levels in peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction. The differences in Arntl, Clock, Per1, and Per2 mRNA expression were compared between the 2 groups, and the relationship between mRNA expression and cardiometabolic risk profiles was also assessed. RESULTS: We found that the mRNA expression of Arntl was downregulated in the hypertension cases compared with controls in women (1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06], p = 0.031). There was a significant negative correlation between the Arntl mRNA expression and SBP (r = -0.301, p = 0.004) and DBP (r = -0.222, p = 0.034) in women. In men, a negative correlation between the Per1 mRNA expression and SBP (r = -0.247, p = 0.026) was found. CONCLUSIONS: The Arntl mRNA expression may play an important role in progression of hypertension in women.

14.
Pharmacol Res ; : 105869, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481973

RESUMO

Advanced osteosarcoma (OSA) is highly aggressive and can lead to distant metastasis or recurrence. Here, a novel small-molecule inhibitor / antagonist of DNA methyltransferase 1 (DNMT-1) named DI-1 (inhibitor of DNMT-1) was explored to enhance the antitumor effect of a molecular-targeted agent, cabozantinib, on OSA cell lines. In patients with OSA, expression of DNMT-1 was negatively related with that of microRNA (miR)-34a and associated with a poor prognosis. In OSA cell lines (OSA cell line U2OS and an OSA cell line U2OSR resistance to cabozantinib), DI-1 treatment enhanced miR-34a expression by inhibiting hypermethylation of the promoter region of miR-34a mediated by DNMT-1. DI-1 enhanced the sensitivity of OSA cells (U2OS, 143B and MG63) to cabozantinib and other molecular-targeted agents by enhancing miR-34a expression and repressing activation of the Notch pathway. Mechanistically, DI-1 repressed recruitment of DNMT-1 to the promoter region of miR-34a and, in turn, decreased the methylation rate in the promoter region of miR-34a in OSA cells. These results suggest that repressing DNMT-1 activation by DI-1 enhances miR-34a expression in OSA cells and could be a promising therapeutic strategy for OSA.

15.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4252-4264, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467740

RESUMO

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.


Assuntos
Medicamentos de Ervas Chinesas , Influenza Humana , Antivirais , Teorema de Bayes , Humanos , Influenza Humana/tratamento farmacológico , Medicina Tradicional Chinesa , Metanálise em Rede
16.
J Synchrotron Radiat ; 28(Pt 5): 1333-1342, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34475282

RESUMO

In the method of X-ray footprinting mass spectrometry (XFMS), proteins at micromolar concentration in solution are irradiated with a broadband X-ray source, and the resulting hydroxyl radical modifications are characterized using liquid chromatography mass spectrometry to determine sites of solvent accessibility. These data are used to infer structural changes in proteins upon interaction with other proteins, folding, or ligand binding. XFMS is typically performed under aerobic conditions; dissolved molecular oxygen in solution is necessary in many, if not all, the hydroxyl radical modifications that are generally reported. In this study we investigated the result of X-ray induced modifications to three different proteins under aerobic versus low oxygen conditions, and correlated the extent of damage with dose calculations. We observed a concentration-dependent protecting effect at higher protein concentration for a given X-ray dose. For the typical doses used in XFMS experiments there was minimal X-ray induced aggregation and fragmentation, but for higher doses we observed formation of covalent higher molecular weight oligomers, as well as fragmentation, which was affected by the amount of dissolved oxygen in solution. The higher molecular weight products in the form of dimers, trimers, and tetramers were present in all sample preparations, and, upon X-ray irradiation, these oligomers became non-reducible as seen in SDS-PAGE. The results provide an important contribution to the large body of X-ray radiation damage literature in structural biology research, and will specifically help inform the future planning of XFMS, and well as X-ray crystallography and small-angle X-ray scattering experiments.

17.
Lab Chip ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34476431

RESUMO

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.

18.
Arch Gynecol Obstet ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476599

RESUMO

PURPOSE: Sirtuin 2 (SIRT2) is functionally important in cancer progression and treatment resistance as an NAD+-dependent deacetylase, whereas its role in endometrial cancer (EC) is limitedly investigated. This study aimed to evaluate the regulatory role of SIRT2 on cell stemness and chemosensitivity in EC. METHODS: SIRT2 expression was detected in human EC cell lines, including Ishikawa, AN3CA, HEC1A, KLE, and normal human endometrial (uterine) epithelial cells (served as controls). Then, SIRT2 overexpression plasmids (constructed with pcDNA3.1 vector) and knock-down plasmids (constructed with pGPH1 vector) were transfected in Ishikawa cells and KLE cells, respectively to assess the influence of SIRT2 on EC cell stemness and chemosensitivity to cisplatin and paclitaxel. RESULTS: SIRT2 mRNA and protein were both overexpressed in EC cell lines (including Ishikawa cells, AN3CA cells, HEC1A cells, and KLE cells) compared with controls. Upregulation of SIRT2 increased the sphere formation capacity (by sphere formation assay and extreme limiting dilution analysis) and CD133+ cells rate in Ishikawa cells, whereas knock-down of SIRT2 reduced the sphere formation capacity and CD133+ cells rate in KLE cells. As for chemosensitivity, upregulation of SIRT2 increased relative cell viability in cisplatin-treated and paclitaxel-treated Ishikawa cells. In contrast, SIRT2 knock-down suppressed relative cell viability in cisplatin-treated but not in paclitaxel-treated KLE cells. In addition, SIRT2 overexpression increased, while SIRT2 knock-down reduced p-MEK and p-ERK1/2 levels in EC cells. CONCLUSION: SIRT2 promotes cell stemness and activates the MEK/ERK signaling pathway while represses chemosensitivity in EC.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34477493

RESUMO

Chloropropanols such as 3-monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) have drawn increasing attention due to their release from food contact paper and their potential carcinogenic effects. In this study, the effects were investigated of water extraction conditions on release of chloropropanols from food contact paper, and the extraction efficiencies of chloropropanols by water extract and migration method were compared. Cold water was found to be more severe than hot water for extraction of chloropropanols, with the highest water extraction value obtained at 23°C. Two hours of extraction was sufficient as the chloropropanols can be fully extracted from food contact paper within a short period of time. Increase of temperature in the range of 10°C-60°C had little impact on release of chloropropanols, however, the extraction of chloropropanols decreased when high temperatures (80°C or above) were applied due to volatilisation losses. Hence, attention should be paid when choosing extract conditions representing the worst-case scenario. The water extraction value using EN 645 method gives higher results compared to migration test described in GB 31604.1 and GB 5009.156, suggesting that the water extract method was probably more severe. For migration test, aqueous-based simulants were found to be more conservative than oil-based simulants, suggesting the conventional experiment conditions applicable for compliance test of chloropropanols migration can be simplified and optimised.

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