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1.
Environ Int ; 158: 106913, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624590

RESUMO

BACKGROUND: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. OBJECTIVES: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. METHODS: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. RESULTS: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. CONCLUSIONS: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

2.
Alzheimers Dement ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569690

RESUMO

Speech comprehension in noisy environments depends on central auditory functions, which are vulnerable in Alzheimer's disease (AD). Binaural processing exploits two ear sounds to optimally process degraded sound information; its characteristics are poorly understood in AD. We studied behavioral and electrophysiological alterations in binaural processing among 121 participants (AD = 27; amnestic mild cognitive impairment [aMCI] = 33; subjective cognitive decline [SCD] = 30; cognitively normal [CN] = 31). We observed impairment of binaural processing in AD and aMCI, and detected a U-shaped curve change in phase synchrony (declining from CN to SCD and to aMCI, but increasing from aMCI to AD). This improvement in phase synchrony accompanying more severe cognitive stages could reflect neural adaptation for binaural processing. Moreover, increased phase synchrony is associated with worse memory during the stages when neural adaptation apparently occurs. These findings support a hypothesis that neural adaptation for binaural processing deficit may exacerbate cognitive impairment, which could help identify biomarkers and therapeutic targets in AD.

3.
Int J Biol Sci ; 17(13): 3413-3427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512156

RESUMO

Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In the late stages of atherosclerosis, the atherosclerotic plaque gradually expands in the blood vessels, resulting in vascular stenosis. When the unstable plaque ruptures and falls off, it blocks the vessel causing vascular thrombosis, leading to strokes, myocardial infarctions, and a series of other serious diseases that endanger people's lives. Therefore, regulating plaque stability is the main means used to address the high mortality associated with CVDs. The progression of the atherosclerotic plaque is a complex integration of vascular cell apoptosis, lipid metabolism disorders, inflammatory cell infiltration, vascular smooth muscle cell migration, and neovascular infiltration. More recently, emerging evidence has demonstrated that non-coding RNAs (ncRNAs) play a significant role in regulating the pathophysiological process of atherosclerotic plaque formation by affecting the biological functions of the vasculature and its associated cells. The purpose of this paper is to comprehensively review the regulatory mechanisms involved in the susceptibility of atherosclerotic plaque rupture, discuss the limitations of current approaches to treat plaque instability, and highlight the potential clinical value of ncRNAs as novel diagnostic biomarkers and potential therapeutic strategies to improve plaque stability and reduce the risk of major cardiovascular events.

4.
JCI Insight ; 6(17)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494552

RESUMO

Mitochondrial dysfunction is a major pathophysiological contributor to the progression of Parkinson's disease (PD); however, whether it contributes to epigenetic dysregulation remains unknown. Here, we show that both chemically and genetically driven mitochondrial dysfunctions share a common mechanism of epigenetic dysregulation. Under both scenarios, lysine 27 acetylation of likely variant H3.3 (H3.3K27ac) increased in dopaminergic neuronal models of PD, thereby opening that region to active enhancer activity via H3K27ac. These vulnerable epigenomic loci represent potential transcription factor motifs for PD pathogenesis. We further confirmed that mitochondrial dysfunction induces H3K27ac in ex vivo and in vivo (MitoPark) neurodegenerative models of PD. Notably, the significantly increased H3K27ac in postmortem PD brains highlights the clinical relevance to the human PD population. Our results reveal an exciting mitochondrial dysfunction-metabolism-H3K27ac-transcriptome axis for PD pathogenesis. Collectively, the mechanistic insights link mitochondrial dysfunction to epigenetic dysregulation in dopaminergic degeneration and offer potential new epigenetic intervention strategies for PD.

5.
Molecules ; 26(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361800

RESUMO

Thin-layer chromatography (TLC) bioautography is an evolving technology that integrates the separation and analysis technology of TLC with biological activity detection technology, which has shown a steep rise in popularity over the past few decades. It connects TLC with convenient, economic and intuitive features and bioautography with high levels of sensitivity and specificity. In this study, we discuss the research progress of TLC bioautography and then establish a definite timeline to introduce it. This review summarizes known TLC bioautography types and practical applications for determining antibacterial, antifungal, antitumor and antioxidant compounds and for inhibiting glucosidase, pancreatic lipase, tyrosinase and cholinesterase activity constitutes. Nowadays, especially during the COVID-19 pandemic, it is important to identify original, natural products with anti-COVID potential compounds from Chinese traditional medicine and natural medicinal plants. We also give an account of detection techniques, including in situ and ex situ techniques; even in situ ion sources represent a major reform. Considering the current technical innovations, we propose that the technology will make more progress in TLC plates with higher separation and detection technology with a more portable and extensive scope of application. We believe this technology will be diffusely applied in medicine, biology, agriculture, animal husbandry, garden forestry, environmental management and other fields in the future.


Assuntos
Cromatografia em Camada Delgada/métodos , Descoberta de Drogas/métodos , Medições Luminescentes/métodos , Animais , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Sensibilidade e Especificidade
6.
Nutr Rev ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432056

RESUMO

CONTEXT: Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of homocysteine levels can benefit cognitive function. OBJECTIVE: To investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia. DATA SOURCES: The PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for articles published from the inception dates to March 1, 2020. Randomized controlled trials (RCT) were included if B vitamins were supplied to investigate their effect on the rate of cognitive decline. Cohort studies investigating dietary intake of B vitamins and the risk of incident dementia were eligible. Cross-sectional studies comparing differences in levels of B vitamins and Hcy were included. DATA EXTRACTION: Two reviewers independently performed data extraction and assessed the study quality. DATA ANALYSIS: Random-effect or fixed-effect models, depending on the degree of heterogeneity, were performed to calculate mean differences (MDs), hazard ratios (HRs), and odds ratios (ORs). RESULTS: A total of 95 studies with 46175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included in this meta-analysis. This meta-analysis supports that B vitamins can benefit cognitive function as measured by Mini-Mental State Examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline. For the > 12 months interventional period stratum, B vitamin supplementation decreased cognitive decline (3814 participants; MD, 0.15, 95%CI 0.05 to 0.26) compared to placebo; no such outcome was detected for the shorter interventional stratum (806 participants; MD, 0.18, 95%CI -0.25 to 0.61). In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75). Lower folate levels (but not B12 or B6 deficiency) and higher Hcy levels were significantly associated with higher risks of dementia (folate: 6654 participants; OR, 1.76, 95%CI 1.24 to 2.50; Hcy: 12665 participants; OR, 2.09, 95%CI 1.60 to 2.74) and cognitive decline (folate: 4336 participants; OR, 1.26, 95%CI 1.02 to 1.55; Hcy: 6149 participants; OR, 1.19, 95%CI 1.05 to 1.34). Among the population without dementia aged 50 years and above, the risk of incident dementia was significantly decreased among individuals with higher intake of folate (13529 participants; HR, 0.61, 95%CI 0.47 to 0.78), whereas higher intake of B12 or B6 was not associated with lower dementia risk. CONCLUSIONS: This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.

7.
Water Res ; 202: 117491, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34358911

RESUMO

The addition of nano zero-valent iron (nZVI) has been proven to improve the efficiency of the anammox process, however, the mechnism is not clear. Here, the effect of nZVI on anammox microbial community was studied by metagenomic sequencing methods. It was found that 50 mg/L nZVI indeed promoted the removal of NH4+ and NO2- of the anammox reactor and significantly improved the relative abundance of AnAOB (Ca. Brocadia) from 42.1% to 52.5%. What's more, 50 mg/L nZVI increased the abundance of c-di-GMP synthesized protein from 148 rpmr to 252 rpmr in the microbial community and decreased the abundance of c-di-GMP degradation protein from 238 rpmr to 204 rpmr, which indirectly led to the enrichment of c-di-GMP in the microbial community. The enrichment of c-di-GMP reduced the motility of microorganisms in the reactor and promoted the secretion of extracellular polymers by bacteria, which is beneficial to the formation of sludge particles in the anammox reactor. In conclusion, this research clarified the mechanism of nZVI promoting the anammox process and provided theoretical guidance for the engineering application of anammox.


Assuntos
Reatores Biológicos , Ferro , Bactérias/genética , Nitrogênio , Oxirredução , Percepção de Quorum , Esgotos
8.
Front Immunol ; 12: 690653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394084

RESUMO

Although vaccine resources are being distributed worldwide, insufficient vaccine production remains a major obstacle to herd immunity. In such an environment, the cases of re-positive occurred frequently, and there is a big controversy regarding the cause of re-positive episodes and the infectivity of re-positive cases. In this case-control study, we tracked 39 patients diagnosed with COVID-19 from the Jiaodong Peninsula area of China, of which 7 patients tested re-positive. We compared the sex distribution, age, comorbidities, and clinical laboratory results between normal patients and re-positive patients, and analysed the correlation between the significantly different indicators and the re-positive. Re-positive patients displayed a lower level of serum creatinine (63.38 ± 4.94 U/L vs. 86.82 ± 16.98 U/L; P =0.014) and lower albumin (34.70 ± 5.46 g/L vs. 41.24 ± 5.44 g/L, P =0.039) at the time of initial diagnosis. In addition, two positive phases and the middle negative phase in re-positive patients with significantly different eosinophil counts (0.005 ± 0.005 × 109/L; 0.103 ± 0.033 × 109/L; 0.007 ± 0.115 × 109/L; Normal range: 0.02-0.52 × 109/L). The level of eosinophils in peripheral blood can be used as a marker to predict re-positive in patients who once had COVID-19.


Assuntos
COVID-19/patologia , Creatinina/sangue , Eosinófilos/citologia , Reinfecção/sangue , Albumina Sérica/análise , Biomarcadores/sangue , Estudos de Casos e Controles , China , Eosinófilos/imunologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Reinfecção/imunologia , Reinfecção/virologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
9.
Microb Pathog ; 159: 105121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343655

RESUMO

The emergence of multidrug resistance (MDR) and extensive drug resistance (XDR) in Klebsiella pneumoniae strains has posed great threats to conventional antibiotics. Previous studies have shown that plant-derived flavonoids have inhibitory functions against pathogens. However, in K. pneumoniae, the antibacterial activity of different flavonoids against growth and biofilm formation remains a mystery. The aim of the present study was to evaluate the antioxidant abilities of different flavonoids, to screen active ingredients and to identify their inhibitory effects on K. pneumoniae growth and biofilm formation. In total, 10 flavonoids representing 4 major categories were screened and used in this study. The antioxidant capacity of each flavonoid was evaluated through a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Rutin showed the highest level of free radical scavenging capacity, followed by kaempferol, luteolin, quercetin, apigenin, hesperidin, sinensetin, naringenin, naringin and 3,5,6,7,8,3',4'-heptamethoxyflavone. The inhibitory effects of rutin and naringin on bacterial growth were also compared. The lowest MICs of rutin were found against K. pneumoniae ATCC700603 (1024 µg/mL) and E. coli ATCC25922 (512 µg/mL). However, the MBICs were not found. Rutin showed strong inhibitory ability against both the growth curve and biofilm production. The expression profiles of 15 biofilm-related genes were analyzed in biofilm cells both with and without rutin treatment. The luxS gene and wabG gene were downregulated significantly by rutin treatment. Correlation analysis showed that mrkA gene expression was positively correlated with biofilm biomass accumulation. Our study indicated that biofilm production is correlated with the expression of several genes rather than one. MrkA gene expression was positively correlated with biofilm biomass accumulation. Our study screened rutin as a potential agent to inhibit K. pneumoniae biofilm formation.


Assuntos
Antioxidantes , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Escherichia coli , Flavonoides/farmacologia , Humanos , Rutina/farmacologia
10.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3422-3428, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396763

RESUMO

The effect of Danhong Injection on the endogenous metabolites of rabbit platelets was analyzed by the liquid chromatography-mass spectrometry( LC-MS) based metabonomic approach. Anti-platelet aggregation was detected after Danhong Injection treatment and the changes of platelet metabolites were analyzed by metabonomics. Principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) were performed to investigate the effect of Danhong Injection on endogenous metabolites of platelets,characterize the biomarkers,and explore the relevant pathways and the underlying mechanism. As demonstrated by the pharmacodynamic results,Danhong Injection of different doses and concentrations antagonized platelet aggregation in a dose-and concentration-dependent manner. In contrast to the control group,25 differential metabolites such as nicotinic acid,nicotinic acid riboside,and hypoxanthine were screened out after platelets were treated by Danhong Injection. These metabolites,serving as important biomarkers,were mainly enriched in the nicotinic acid-niacinamide metabolic pathway and purine metabolic pathway. This study explored the therapeutic mechanism of Danhong Injection from a microscopic perspective by metabonomics,which is expected to provide a new idea for the investigation of platelet-related mechanisms.


Assuntos
Plaquetas , Medicamentos de Ervas Chinesas , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Coelhos , Tecnologia
11.
Gene Ther ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34404916

RESUMO

While generally referred to as "non-integrating" vectors, adenovirus vectors have the potential to integrate into host DNA via random, illegitimate (nonhomologous) recombination. The present study provides a quantitative assessment of the potential integration frequency of adenovirus 5 (Ad5)-based vectors following intravenous injection in mice, a common route of administration in gene therapy applications particularly for transgene expression in liver. We examined the uptake level and persistence in liver of first generation (FG) and helper-dependent (HD) Ad5 vectors containing the mouse leptin transgene. As expected, the persistence of the HD vector was markedly higher than that of the FG vector. For both vectors, the majority of the vector DNA remained extrachromosomal and predominantly in the form of episomal monomers. However, using a quantitative gel-purification-based integration assay, a portion of the detectable vector was found to be associated with high molecular weight (HMW) genomic DNA, indicating potential integration with a frequency of up to ~44 and 7000 integration events per µg cellular genomic DNA (or ~0.0003 and 0.05 integrations per cell, respectively) for the FG and HD Ad5 vectors, respectively, following intravenous injection of 1 × 1011 virus particles. To confirm integration occurred (versus residual episomal vector DNA co-purifying with genomic DNA), we characterized nine independent integration events using Repeat-Anchored Integration Capture (RAIC) PCR. Sequencing of the insertion sites suggests that both of the vectors integrate randomly, but within short segments of homology between the vector breakpoint and the insertion site. Eight of the nine integrations were in intergenic DNA and one was within an intron. These findings represent the first quantitative assessment and characterization of Ad5 vector integration following intravenous administration in vivo in wild-type mice.

12.
Turk J Gastroenterol ; 32(5): 422-430, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34231471

RESUMO

BACKGROUND: This systematic review and meta-analysis were carried out on well-conducted and adequately powered studies to explore whether arterial stiffness was associated with inflammatory bowel disease (IBD). METHODS: The search for potential literature was conducted on PubMed, MEDLINE, Cochrane Library, and Embase from inception to February 15, 2020. The studies assessing arterial stiffness in IBD were reviewed and included. RESULTS: Conclusively, 17 eligible trials with a total of 2188 participants were in compliance with the inclusion criteria. Of the included 2188 participants, the cases for ulcerative colitis (UC) and Crohn's disease (CD) were 558 and 693, respectively. Altogether 10 studies were conducted to evaluate the carotid-femoral pulse wave velocity (CPWV) in overall IBD patients, which was significantly increased with the mean difference (MD) and 95% CI as 0.70 (0.48-0.92, P < .01). The pooled results for CPWV in patients with CD and UC were also faster than that of control groups with MD and 95% CI as 1.09 (0.45-1.72) and 0.57 (0.57-1.24), respectively. The CPWV in CD and UC groups was comparable with a MD of 0.07 (P = .74, 95% CI: -0.32 to 0.45). CONCLUSION: Arterial stiffness had associations with the overall IBD, UC, and CD with a similar strength of association between UC and CD.

13.
Bioengineered ; 12(1): 3772-3786, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34281459

RESUMO

Esophageal carcinoma (ESCA) is one of the most aggressive malignancies with extremely high morbidity and mortality. At present, limited advancement in ESCA treatment has achieved. Therefore, it is urgent to explore the pathogenesis and progression mechanism of ESCA to provide the basis for the formulation of novel therapeutic strategies. Previous studies have found that long non-coding RNA (lncRNA) DDX11-AS1 expression enhances the paclitaxel resistance of ESCA cells. However, the mechanisms underlying the drug resistance conferred by lncRNA DDX11-AS1 in ESCA remains to be elucidated. Our research aims to clarify the role and mechanism of lncRNA DDX11-AS1 in regulating the progression of ESCA. We found that the expression of lncRNA DDX11-AS1 in ESCA tissues and cell lines was significantly upregulated. Subsequently, silencing lncRNA DDX11-AS1 significantly inhibited the proliferation, migration and invasion of ESCA cells, and induced the level of cell apoptosis. In terms of mechanism, our data showed that miR-514b-3p/RING box protein 1 (RBX1) axis played a crucial role in the oncogenic function of lncRNA DDX11-AS1. LncRNA DDX11-AS1 expression impaired the inhibitory function of miR-514b-3p on RBX1 through sponging effect. Taken together, our data support the notion that lncRNA DDX11-AS1 promotes the progression of ESCA through miR-514b-3p/RBX1 axis. Our research uncovers the novel regulatory role of lncRNA DDX11-AS1 in ESCA and lays a theoretical basis for developing novel treatment strategy of ESCA.

14.
Medicine (Baltimore) ; 100(22): e25889, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087833

RESUMO

BACKGROUND: With the attention paid to the heritability of breast cancer, the search for the genetic susceptibility gene of breast cancer has become a hot spot. At present, a number of studies have explored the relationship between rs13347 polymorphism of cluster of differentiation 44 (CD44) gene and breast cancer, but the research conclusions are inconsistent. Therefore, we will use this meta-analysis to explore the role of this gene polymorphism in breast cancer susceptibility. METHODS: The search time is set from the establishment of the database in March 2021 in this study. The search database include China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and China Biology Medicine disc, PubMed, EMBASE, Web of Science and the Cochrane Library. The subjects are observational studies on the relationship between rs13347 polymorphism of CD44 gene and breast cancer (including case-control study, cross-sectional study and a cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by two researchers independently. The data are statistically analyzed by Stata 16.0 software. RESULTS: Based on the existing studies, this study will systematically evaluate the relationship between CD44 gene rs13347 polymorphism and breast cancer. CONCLUSION: This study will provide evidence-based medical evidence to clarify the role of CD44 gene polymorphism in breast cancer, and provide help for the early detection and preventive intervention of breast cancer. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WBC7F.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores de Hialuronatos/genética , Feminino , Humanos , Metanálise como Assunto , Recidiva Local de Neoplasia , Polimorfismo de Nucleotídeo Único , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
15.
J Biomed Mater Res A ; 109(11): 2101-2110, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34060692

RESUMO

Decellularized (DC) kidney scaffold shows great potential for renal recovering. Our study explored the effect of the DC kidney scaffolds treating on chronic renal failure (CRF) through grafting them on 5/6 nephrectomized (5/6 Nx) rat kidneys compared with gelatin sponges covered the incision edges. Blood urea nitrogen and angiotensin II were significantly lower in most time in scaffold-grafted groups. Remnant kidney tumor necrosis factor-α and fibroblast growth factor in scaffold-grafted groups significantly reduced in majority of time points compared with controls. But platelet-derived growth factor-BB showed a different varied tendency, first higher in scaffold groups on week 2, 4, 6, but lower on week 8, finally no difference on week 12 compared with gelatin-sponge groups. In addition, the index of glomerular sclerosis was significantly lesser in scaffold-grafted groups, and, the accumulation of collagen III and collagen IV decreased in scaffold-grafted groups on week 6, 8, 12 compared with gelatin-sponge groups. Moreover, DC scaffolds enhanced the expression of CD133 on week 2, 6, 8, 12. In conclusion, DC kidney scaffold altered the healing response after 5/6 nephrectomy and ameliorated renal injury to some degree. Therefore, DC kidney scaffold could be a promising therapeutic method on CRF.

16.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068366

RESUMO

Magnaporthe oryzae (M. oryzae) is a typical cause of rice blast in agricultural production. Isobavachalcone (IBC), an active ingredient of Psoralea corylifolia L. extract, is an effective fungicide against rice blast. To determine the mechanism of IBC against M. oryzae, the effect of IBC on the metabolic pathway of M. oryzae was explored by transcriptome profiling. In M. oryzae, the expression of pyruvate dehydrogenase E1 (PDHE1), part of the tricarboxylic acid (TCA cycle), was significantly decreased in response to treatment with IBC, which was verified by qPCR and testing of enzyme activity. To further elucidate the interactions between IBC and PDHE1, the 3D structure model of the PDHE1 from M. oryzae was established based on homology modeling. The model was utilized to analyze the molecular interactions through molecular docking and molecular dynamics simulation, revealing that IBC has π-π stacking interactions with residue TYR139 and undergoes hydrogen bonding with residue ASP217 of PDHE1. Additionally, the nonpolar residues PHE111, MET174, ILE 187, VAL188, and MET250 form strong hydrophobic interactions with IBC. The above results reveal that PDHE1 is a potential target for antifungal agents, which will be of great significance for guiding the design of new fungicides. This research clarified the mechanism of IBC against M. oryzae at the molecular level, which will underpin further studies of the inhibitory mechanism of flavonoids and the discovery of new targets. It also provides theoretical guidance for the field application of IBC.


Assuntos
Chalconas/farmacologia , Proteínas Fúngicas/metabolismo , Magnaporthe/efeitos dos fármacos , Oryza/enzimologia , Doenças das Plantas/imunologia , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Transcriptoma/efeitos dos fármacos , Proteínas Fúngicas/genética , Fungicidas Industriais/farmacologia , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Magnaporthe/fisiologia , Simulação de Acoplamento Molecular , Oryza/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Conformação Proteica , Piruvato Desidrogenase (Lipoamida)/genética , Piruvato Desidrogenase (Lipoamida)/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2276-2286, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047131

RESUMO

The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.


Assuntos
Tecnologia , Animais , Benzofuranos , Ácidos Cafeicos , Cromatografia Líquida de Alta Pressão , Lactatos , Espectrometria de Massas , Ratos
18.
Appl Opt ; 60(13): 3724-3731, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33983304

RESUMO

We demonstrate a novel, to the best of our knowledge, micro-opto-electro-mechanical system (MOEMS) gyroscope based on the Talbot effect of a single-layer near-field diffraction grating. The Talbot effect of an optical grating is studied both theoretically and experimentally. A structure of grating-mirror combination, fabricated by the micro-nano processing method, is used for out-of-plane structure detection. The detection of a weak Coriolis force is realized by using the highly sensitive displacement characteristic of Talbot imaging of near-field diffraction with a mirror mass block and single-layer grating. The experimental results show that, the micro-displacement detection sensitivity can reach up to 0.09%/nm, and the MOEMS gyroscope can be moved in the driven direction, with a resonant frequency of 7048 Hz and a quality factor of 700, which indicates great potential of the Talbot effect in developing novel high-performance micro-gyroscopes.

19.
J Biomed Mater Res A ; 109(10): 1979-1989, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33822474

RESUMO

Native decellularized extracellular matrix provides an adequate platform for tissues and organs and promotes the development of organogenesis and tissue remodeling. However, thrombosis poses a great challenge that hinders the transplantation for a substantial organ in vivo. Therefore, anticoagulation and re-reendothelialization of organ biological scaffolds are the primary concerns to be addressed before orthotopic transplantation. Herein, a heparinized decellularized kidney scaffold (HEP-DKSs) was prepared using end-point attachment technology, followed by binding the vascular endothelial growth factor (VEGF) to greatly improve the hemocompatibility and angiogenesis of DKSs. Based on the anticoagulant, co-culture of human umbilical vein endothelial cells, and subcapsular transplantation of kidney experiments, HEP-VEGF-DKSs are shown to reduce platelet adhesion, which is crucial for subsequent vascularization and slow release of heparin and VEGF, suggesting its ability of improve neovascularization. Taken together, these data indicated an optimal anticoagulation function of HEP-VEGF-DKSs and the potential of vascularization for regeneration of whole decellularized kidney.

20.
Food Chem Toxicol ; 151: 112154, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33774093

RESUMO

Smoking is an independent risk factor for atherosclerosis. The smoke produced by tobacco burning contains more than 7000 chemicals, among which nicotine is closely related to the occurrence and development of atherosclerosis. Nicotine, a selective cholinergic agonist, accelerates the formation of atherosclerosis by stimulating nicotinic acetylcholine receptors (nAChRs) located in neuronal and non-neuronal tissues. This review introduces the pathogenesis of atherosclerosis and the mechanisms involving nicotine and its receptors. Herein, we focus on the various roles of nicotine in atherosclerosis, such as upregulation of growth factors, inflammation, and the dysfunction of endothelial cells, vascular smooth muscle cells (VSMC) as well as macrophages. In addition, nicotine can stimulate the generation of reactive oxygen species, cause abnormal lipid metabolism, and activate immune cells leading to the onset and progression of atherosclerosis. Exosomes, are currently a research hotspot, due to their important connections with macrophages and the VSMC, and may represent a novel application into future preventive treatment to promote the prevention of smoking-related atherosclerosis. In this review, we will elaborate on the regulatory mechanism of nicotine on atherosclerosis, as well as the effects of interference with nicotine receptors and the use of exosomes to prevent atherosclerosis development.


Assuntos
Aterosclerose/patologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Aterosclerose/metabolismo , Fumar Cigarros/efeitos adversos , Angiopatias Diabéticas/patologia , Progressão da Doença , Endotélio Vascular/patologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores Nicotínicos/metabolismo
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