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1.
Food Chem ; 366: 130643, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34330031

RESUMO

To protect walnut peptides from harsh external environments during their storage and digestion, proliposomes loaded with walnut peptides were fabricated using sucrose, trehalose, and mannitol as carriers and lyoprotectants. The physicochemical properties, environmental stability, antioxidant/antibacterial activities, and digestion in vitro of the proliposomes were evaluated. The freshly prepared liposomes were uniform in size, but the hydrated proliposomes showed a more uneven size distribution. The lyoprotectants helped maintain favorable liposome shape during lyophilization. Alongside the lyoprotectants, the walnut peptides further stabilized the lipid bilayer. Proliposomes encapsulation didn't impact the peptides' antioxidant activity. Furthermore, walnut peptides-loaded proliposomes exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. The proliposomes were stable during gastric-phase digestion. The lyoprotectants changed the free fatty acid release behaviors of the proliposomes. These characteristics suggest potential applications for proliposomes as effective delivery systems for biopeptides in food stuffs, thereby protecting bioactivities during storage and passage through the gastrointestinal tract.

2.
J Bone Miner Res ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490953

RESUMO

The nutritional level of vitamin D may affect musculoskeletal health. We have reported that vitamin D is a pivotal protector against tissue injuries by suppressing local renin-angiotensin system (RAS). This study aimed to explore the role of vitamin D receptor (VDR) in the protection against muscle atrophy and the underlying mechanism. A cross-sectional study on participants (n = 1034) in Shanghai (China) was performed to analyze the association between vitamin D level and the risk of low muscle strength as well as to detect the circulating level of angiotensin II (Ang II). In animal studies, dexamethasone (Dex) was applied to induce muscle atrophy in wild-type (WT) and VDR-null mice, and the mice with the induction of muscle atrophy were treated with calcitriol for 10 days. The skeletal muscle cell line C2C12 and the muscle satellite cells were applied in in vitro studies. The increased risk of low muscle strength was correlated to a lower level of vitamin D (adjusted OR, 0.58) accompanied by an elevation in serum Ang II level. Ang II impaired the myogenic differentiation of C2C12 myoblasts as illustrated by the decrease in the area of myotubes and the down-regulation of myogenic factors (MHC & MyoD). The phenotype of muscle atrophy induced by Dex and Ang II was aggravated by VDR ablation in mice and in muscle satellite cells, respectively, and mediated by RAS and its downstream PI3K/Akt/FOXO1 signaling. Calcitriol treatment exhibited beneficial effects on muscle function as demonstrated by the increased weight-loaded swimming time, grip strength and fiber area, and improved fiber type composition via regulating ubiquitin ligases and their substrates MHC and MyoD through suppressing renin/Ang II axis. Taken together, VDR protects against skeletal muscle atrophy by suppressing RAS. Vitamin D could be a potential agent for the prevention and treatment of skeletal muscle atrophy. This article is protected by copyright. All rights reserved.

3.
Colloids Surf B Biointerfaces ; 208: 112069, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34478957

RESUMO

Antimicrobial peptides/DNA complexes were designed based on AMPs chensinin-1b and its corresponding lipo-chensinin-1b conjugated with an aliphatic acid with different chain lengths and therapeutic genes. The main goal of such a complex includes two aspects: first, antimicrobial peptides deliver therapeutic genes to cancer cells and genes expressed in targeted tissue for cancer gene therapy, and, second, the antimicrobial peptide kills cancer cells when used alone as an anticancer agent. This study presents a model composed of chensinin-1b and its lipo-chensinin-1b and eGFP plasmids, which were used as reporter genes, and the final peptide/eGFP plasmid complexes were analyzed by TEM and DLS. The gene transfection efficiency of the complex was evaluated by a microplate reader, FACS and CLSM. Compared with Lipo2000, the antimicrobial peptide showed specific selectivity for transfection against cancer cells and mammalian cells. The peptides chensinin-1b and lipo-chensinin-1b binding with the eGFP plasmid displayed optimal transfection efficiencies at a mass ratio of 8. In addition, PA-C1b can deliver p53-eGFP plasmids into MCF-7 cancer cells, and the proliferation of cells was inhibited and even caused cell death. Overall, PA-C1b was screened and found to have the highest transfection efficiency for gene delivery and good cellular uptake capability. The in vivo transfection ability of PA-C1b was investigated using a tumor-bearing mouse model, and the transfection efficiency reflected by the fluorescence of expressed GFP was determined by in vivo imaging. Conclusively, the antimicrobial peptide PA-C1b could be used as the nonviral vector with high efficiency for cancer gene therapy.

4.
Anal Chim Acta ; 1178: 338800, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482860

RESUMO

Accurate quantification of multiple miRNAs biomarkers in body fluid is still a challenge for early screening of cancer. Herein, by catalytic hairpin assembly as a signal amplification strategy, we designed a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) strip for ultrasensitive detection of miR-21 and miR-196a-5p in non-small cell lung cancer (NSCLC) urine on a single test (T) line. 4-mercaptobenzoic acid or 5,5'-dithiobis-2-nitrobenzoic acid as Raman molecules was labeled and two hairpin DNA sequence was modified gold nanocages (GNCs) were designed as two SERS tags. Through target miRNA-triggered catalytic hairpin assembly (CHA), the double-stranded DNAs (H1-H2 complex) formed by SERS tags and the related hairpin-structured DNA sequence 2 (H2) were immobilized on a single T line of SERS-LFA strip. This generated abundant "hot spots" because of the formation of numerous H1-H2 complex thus facilitated the SERS measurement. Through this method, two kinds of miRNAs were analyzed, resulting in limits of detection of 2.08 pM and 3.31 pM for miR-21 in PBS buffer and human urine, 1.77 pM and 2.18 pM for miR-196a-5p in PBS buffer and human urine. Significantly, the SERS-LFA strip exhibited high specificity and good repeatability toward miRNAs. The whole detection time was only 30 min, which means that the high detection efficiency of the strip. The clinical feasibility of the proposed method was also evaluated by detecting the levels of miR-21 and miR-196a-5p in urine samples from NSCLC patients and healthy subjects. The developed SERS-LFA strip has wide application prospect in biomedical research, drug development and early clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas Metálicas , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/genética , Ouro , Humanos , Limite de Detecção , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Análise Espectral Raman
5.
Front Immunol ; 12: 702425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489952

RESUMO

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-ß2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.

6.
BMC Oral Health ; 21(1): 429, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482838

RESUMO

BACKGROUND: It has been widely accepted that oral health status is related to oral health literacy. The need to measure oral health literacy has led to the development of measurement instruments. This study aimed to develop a comprehensive instrument for adults and to examine its reliability and validity in China. METHODS: A three-step design process was used. First, a literature review and expert panel discussion were used to draw up a 37-item pool covering oral health knowledge, belief, practice, skill, and functional oral health literacy. The Delphi method was used to delete and modify questions in the item pool. The draft instrument was evaluated by nine experts and the consensus among them was calculated using the content validity index. The scale was then used to conduct a psychometric study among 370 participants from community health centers in Beijing. Construct validity, discriminant validity and concurrent validity were examined. The Cronbach's alpha coefficient, and test-retest methods were used to assess reliability. RESULTS: The final scale included 30 items across four dimensions. The item-level content validity index was 0.90. Exploratory factor analysis extracted four fixed factors, and the result of the Kaiser-Meyer-Olkin and Bartlett's tests was 0.752, with the model explaining 35.21% of the total variance. The four dimensions were associated with oral health knowledge, perceptions of oral health issues, oral health practice and skills, and functional oral health literacy. The mean score of the lowest 27% was significantly lower than the highest 27% (P < 0.01), suggesting adequate discriminant validity. The associations between comprehensive oral health literacy scores and educational level, income and self-reported literacy level were significant (P < 0.001), showing adequate overall concurrent validity. Internal consistency and test-retest reliability were acceptable, with a Cronbach's alpha of 0.72 and a total test-retest reliability coefficient of 0.979. CONCLUSIONS: Initial testing of the comprehensive oral health literacy instrument suggested that it is a valid and reliable instrument to evaluate individuals' oral health literacy, with four dimensions for evaluating knowledge, belief, skills, and functional oral health literacy.

7.
FEBS Lett ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510437

RESUMO

Programmed death ligand 1 (PD-L1) is critical for the ability of cancer cells to evade attacks by the host immune system. However, the molecular mechanisms controlling PD-L1 expression have not been fully understood. Here, we demonstrate that sorting nexin 6 (SNX6) is a novel regulator of PD-L1 expression. Knockdown of SNX6 in cancer cells significantly decreases PD-L1 protein levels. In contrast, loss of SNX6 does not reduce PD-L1 mRNA levels. Instead, SNX6 interacts with Cullin3, an E3 ubiquitin ligase responsible for PD-L1 ubiquitination and subsequent degradation. By binding with Cullin3, SNX6 decreases the interaction between the adaptor protein speckle-type POZ protein and Cullin3, which in turn downregulates Cullin3-mediated PD-L1 ubiquitination. This research reveals a novel molecular nexus in modulating PD-L1.

8.
Ann Palliat Med ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34498478

RESUMO

BACKGROUND: Shenqisherong pill (SQSRP) has been used clinically to treat cervical spondylotic myelopathy (CSM) with satisfactory results; however, its active ingredients and mechanisms are unclear. The present study aimed to explore the active ingredients and molecular mechanisms of SQSRP against CSM using network pharmacology and molecular docking. METHODS: The compounds in SQSRP were obtained from public databases and related literature, and oral bioavailability (≥30%) and drug-likeness (≥0.18) were screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Compounds-related and CSM-related target genes were identified using public databases, and the overlapping genes between compounds and CSM target genes were identified using a Venn diagram. Cytoscape and STRING were used to construct, visualize, and analyze the interaction network between these overlapping targets. Gene Ontology (GO) and KEGG pathway enrichment analysis of overlapping targets used Omicshare tools and constructed a compound-overlapping targets network, target-pathway network, and compound-target-pathway network using Cytoscape. Finally, molecular docking software was used to verify the targets. RESULTS: A total of 447 compounds in SQSRP were identified, and ADME screening identified 96 compounds as potentially active ingredients. A total of 249 compound-related genes and 280 CSMrelated genes were identified using public databases, and 53 overlapping genes were identified. The results of compound targets and protein-protein interaction network analysis showed that the pharmacological effects of SQSRP against CSM involved 56 compounds and 53 genes. The results of GO and KEGG pathway enrichment analysis suggested that the therapeutic effects of SQSRP against CSM were exerted by reducing inflammation, inhibiting apoptosis, and protecting neurons. The molecular mechanisms may be strongly associated with PI3K-Akt, MAPK, IL-17, and TNF, which might be pivotal signaling pathways. CONCLUSIONS: The active ingredients and mechanisms of SQSRP against CSM were investigated using network pharmacology. The findings proved that the pill could treat CSM through multi-component, multitarget, and multi-pathway synergy and provide a theoretical basis for the subsequent extraction of active ingredients from SQSRP.

9.
Rheumatol Int ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499196

RESUMO

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

10.
Small ; : e2101505, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499411

RESUMO

Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.

11.
Sci Total Environ ; 803: 150029, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34525714

RESUMO

The effect of microplastics (MPs) on the biological treatment of organic waste has been extensively studied, but little is known about the influence of different MPs on composting humification and the fungal community. In this study, PE, PVC, and PHA MPs were individually mixed with cow dung and sawdust and then composted. The results showed that different MPs had various influences on humification, and the humic acid to fulvic acid ratio of all MP-added treatments (0.44-0.83) was lower than that of the control (0.91). During the composting process, Ascomycota (26.32-89.14%) and Basidiomycota (0.47-4.78%) are the dominant phyla in all treatments and all microplastics decreased the diversity and richness of the fungal community at the thermophilic stage of composting. Exposure to MPs had an obvious effect on the fungal community at the genus level, and the addition of PHA and PE MPs increased the relative abundance of phytopathogenic fungi. LEfSe and network analysis indicated that MPs reduced the number of biomarkers and led to a simpler and more unstable fungal community structure compared to the control. This study has important implications for assessing microplastic pollution and organic waste disposal.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34508561

RESUMO

OBJECTIVES: To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody. METHODS: Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from Octobor 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. RESULTS: 88.9% (8/9) subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, Health Assessment Questionnaire (HAQ), manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy. CONCLUSION: PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents.

13.
Enzyme Microb Technol ; 150: 109886, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34489039

RESUMO

Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine. Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great significance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis. In this study, a de novo biosynthetic pathway for the production of tyrosol acetate and hydroxytyrosol acetate was constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3-hydroxylase HpaBC.


Assuntos
Escherichia coli , Álcool Feniletílico , Acetatos , Escherichia coli/genética , Glucose , Humanos , Azeite de Oliva , Álcool Feniletílico/análogos & derivados
14.
Artigo em Inglês | MEDLINE | ID: mdl-34496129

RESUMO

The pulsatile stress in the microcirculation may contribute to development or progression of chronic kidney disease. However, there is no prospective data confirming whether pulsatile stress in early life affect renal function in middle age. The authors performed a longitudinal analysis of 1738 participants aged 6-15 years at baseline, an ongoing Adolescent Prospective Cohort with a follow-up of 30 years. The authors evaluated the association between pulsatile stress in childhood and adult subclinical renal damage (SRD), adjusting for related covariates. Pulsatile stress was calculated as resting heart rate × pulse pressure. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR). The results showed that pulsatile stress in childhood was associated with adult SRD (Relative Risk, 1.43; p = .032), and the predictive value of combined pulse pressure and heart rate for SRD was higher than either of them alone. The high pulsatile stress in childhood increased the risk of adult SRD in males (RR, 1.92; p = .003), but this association was not found in females (RR, 0.91; p = .729). Further, the participants were categorized into four groups on the basis of pulsatile stress status in childhood and adulthood. Male patients with high pulsatile stress during childhood but normal pulsatile stress as adults still had an increased risk of SRD (RR, 2.04; 95% CI, 1.18-3.54), while female patients did not (RR, 0.96; 95% CI, 0.46-1.99). The study demonstrated that high pulsatile stress in childhood significantly increased the risk of adult SRD, especially in males. Adequate control of pulse pressure and heart rate from childhood, in the long-term, is very important for preventing kidney damage.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34363473

RESUMO

OBJECTIVE: To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits. METHODS: Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P < 5 × 10 -8) were selected from public GWAS, and SNPs of Outcomes were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the fasting glucose, insulin and HbA1c. The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis. RESULTS: The ß estimates per 1 SD increasement of arachidonic acid (AA) level was 0.16 (95% CI: 0.078, 0.242; P<0.001). Genetic predisposition to higher plasma AA levels were associated with higher FG levels (ß 0.10 [95%CI: 0.064, 0.134], P<0.001), higher HbA1c levels (ß 0.04 [95%CI: 0.027, 0.061]) and lower FI levels (ß -0.025 [95%CI: -0.047, -0.002], P=0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have positive causal effect on glycemic traits. CONCLUSIONS: Our findings suggest that AA and 2-HBA may have the causal associations on T2DM and glycemic traits. It is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34363725

RESUMO

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

17.
Biol Direct ; 16(1): 13, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362407

RESUMO

BACKGROUND: Growing evidence has demonstrated that long non-coding RNAs (lncRNAs) can function as modulators in the development of triple-negative breast cancer (TNBC). However, the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in TNBC remains unclear. Therefore, our study aimed at investigating the role of SNHG8 in the proliferation and migration of TNBC cells. METHODS: SNHG8 expression was evaluated using RT-qPCR assay. Cell proliferation and migration were assessed by EdU, colony formation and Transwell assays. The levels of proteins related to EMT process were examined by western blot assay. The interaction among SNHG8, miR-335-5p and pygopus family PHD finger 2 (PYGO2) was detected by RIP assay, RNA pull down assay and luciferase reporter assay. RESULTS: SNHG8 expression was significantly up-regulated in TNBC cells. SNHG8 silencing obviously inhibited TNBC cell proliferation, migration and EMT process. Moreover, SNHG8 acted as a sponge to sequester miR-335-5p in TNBC cells. Besides, PYGO2 was proven as a target gene of miR-335-5p, and SNHG8 promoted TNBC cell proliferation, migration and EMT process through regulating miR-335-5p and PYGO2. CONCLUSIONS: Totally, our study indicated that SNHG8 promoted TNBC cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34444588

RESUMO

The adjustment of administrative division is one of the powerful tools used to promote urbanization by the Chinese government in recent decades, and there is little literature to discuss whether the government-led expansion of urban space through city-county mergers can bring about a decline in urban energy intensity. With the multi-period difference-in-differences (DID) method and comprehensive urban datasets, this research investigates the urban energy intensity results of the city-county mergers policy experiment in China from 2000 to 2017. We present evidence that city-county mergers are indeed beneficial in reducing urban energy intensity, and that the energy-saving effect of the policy only starts to become significant in the third year after implementation. We also further adopt a series of robustness tests, such as the counterfactual test, placebo tests and PSM-DID tests to find if this effect still exists. The mechanism test with mediating effects indicates they are potential contributors to the positive effects of mergers with moderate fiscal centralization, population agglomeration and regional integration. We further explore positive effects of mergers, relying on the scientifically design official appraisal system and improve government efficiency.


Assuntos
Urbanização , China , Cidades
19.
Ecotoxicol Environ Saf ; 224: 112650, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34403946

RESUMO

Cadmium(Cd) is a toxic and carcinogenic heavy metal pollutant leading to serious damage in various organs. Ferroptosis and necrosis as inflammation-related cell death are involved in several diseases of nervous system. In the present study, 10 weaning piglets with similar weight for 6 weeks were randomly divided into two groups. The daily grain containing 0 mg and 20 mg/kg of Cd chloride was fed in 20-26 â„ƒ environment, animals were sacrificed to collect cerebrum and cerebellum tissues after 40 days. Morphology and ultrastructure results were observed using HE and TEM. Moreover, molecular biological technologies western blot and qRT-PCR were used to detect the expression abundance of genes. Cerebrum and cerebellum injury was observed in Cd-exposed group, antioxidant capacity decreased significantly and oxidative stress increased; immunofluorescence, real-time quantification, and western blot results showed decreased necrosis genes and increased ferroptosis pathway genes abundance in cerebrum, whereas the results were reversed in cerebellum. These results indicated that Cd exposure can activated necrosis and ferroptosis pathways by increased oxidative stress, further resulting in cerebrum and cerebellum damage in pigs. These findings may provide a theoretical basis for early monitoring of Cd exposure in environment.

20.
Curr Neuropharmacol ; 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34429056

RESUMO

BACKGROUND: Erenumab is a novel monoclonal calcitonin gene-related peptide receptor antibody that is used for the preventive treatment of migraine. OBJECTIVES: To evaluate overall safety and efficacy and dose-response relationship of erenumab in patients with episodic migraine and patients with prior migraine treatment failures. METHODS: We searched randomized clinical trials on PUBMED, EMBASE database, and Cochrane Library database. A pair-wise meta-analysis and Bayesian network analysis were performed. RESULTS: For efficacy outcomes, the network meta-analysis suggests that compared with erenumab 70 mg, participants received erenumab 140 mg reported significantly decreased monthly acute migraine-specific medication days(MSMD) and increased 50% response rate, and erenumab was most likely to be ranked first for monthly migraine days(MMD), MSMD and 50% response rate. For safety outcomes, the network meta-analysis has found no significant difference between the 70 mg group and the 140 mg group measured by adverse events and serious adverse events. For patients with ≥2 treatment failures, 140mg erenumab group, patients with ≥2 treatment failures reported significantly reduced MMD and MSMD, increased 50%, and 75% response rate, compared with placebo. For safety outcomes, no significant difference was found between 140 mg erenumab group and the placebo group. CONCLUSION: Erenumab was effective in patients with episodic migraine. 140 mg erenumab was associated with better efficacy outcomes without increased risk for developing adverse events compared with 70 mg erenumab, and 140 mg erenumab was effective in patients with prior migraine treatment failures.

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