Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 676
Filtrar
1.
J Ethnopharmacol ; 258: 112813, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32259665

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chemical hepatotoxicity, especially alcoholic liver injury (ALI), commonly occurs in young and middle-aged people who drink heavily. ALI is extremely harmful and can induce severe disease states, such as hepatitis, liver fibrosis, cirrhosis, or liver cancer, which are similar to CCl4-induced liver disease states in animals. In recent studies, the pathological changes of hepatocytes and the hepatic stellate cell have shown a significant connection between endoplasmic reticulum (ER) stress and the development of liver pathology in patients. However, the detailed pathological mechanism needs to be further studied. Schisandra chinensis, (S. chinensis), a fruit-bearing vine used in Traditional Chinese Medicine (TCM), has been used to treat chronic or acute diseases, including liver disease. S. chinensis-derived lignans (SCDLs) in particular have been shown to alleviate liver pathological changes. AIM OF THE STUDY: This study sought to elucidate the mechanisms underlying SCDL-mediated hepatoprotection. MATERIALS AND METHODS: We first used in silico target prediction and computational simulation methods to identify putative lignan-binding targets relative to the hepatoprotective effect. A gene microarray analysis was performed to identify differently expressed genes that might have significance in the disease pathological process. We then used histological analyses in a mice hepatotoxicity model to test the effectiveness of SCDLs in vivo, and a hepatocellular toxicity model to analyze the candidate-compound-mediated hepatoprotection and expression states of the key targets in vitro. RESULTS: The in silico analysis results indicated that endothelin receptor B (ETBR/EDNRB) is likely a significant node during the liver pathological change process and a promising key target for the SCDL compound schisantherin D on the hepatoprotective effect; experimental studies showed that schisantherin D alleviated the EtOH- and ET-1-induced HL-7702 cell (belongs to liver parenchymal cell lines) injury ratio, decreased the expression of ETBR, and inhibited ECMs and ET-1 secretion in LX-2 cells (one form of hepatic stellate cells). SCDLs ameliorated EtOH- and CCl4-induced fibrosis formation in mice liver tissue. Liver tissue western blots of SCDL-treated mice showed downregulated α-SMA, ETBR, PLCß, CHOP, Bax, and the apoptotic factors of cleaved-caspase 12, cleaved-caspase 9, and cleaved-caspase 3 hinted at an anti-apoptosis and hepatoprotective effect. The SCDL treatment also elevated serum glutathione (GSH) and reduced the serum-transforming growth factor-ß1 (TGF-ß1) level. CONCLUSION: The findings indicated that SCDLs prevent hepatotoxicity via their anti-fibrotic, anti-oxidant, and anti-apoptosis properties. ETBR may be the key factor in promoting chemical hepatotoxicity.

2.
iScience ; 23(4): 101034, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32315832

RESUMO

Three-dimensional chromatin structures undergo dynamic reorganization during mammalian spermatogenesis; however, their impacts on gene regulation remain unclear. Here, we focused on understanding the structure-function regulation of meiotic chromosomes by Hi-C and other omics techniques in mouse spermatogenesis across five stages. Beyond confirming recent reports regarding changes in compartmentalization and reorganization of topologically associating domains (TADs), we further demonstrated that chromatin loops are present prior to and after, but not at, the pachytene stage. By integrating Hi-C and RNA-seq data, we showed that the switching of A/B compartments between spermatogenic stages is tightly associated with meiosis-specific mRNAs and piRNAs expression. Moreover, our ATAC-seq data indicated that chromatin accessibility per se is not responsible for the TAD and loop diminishment at pachytene. Additionally, our ChIP-seq data demonstrated that CTCF and cohesin remain bound at TAD boundary regions throughout meiosis, suggesting that dynamic reorganization of TADs does not require CTCF and cohesin clearance.

3.
Mol Genet Genomic Med ; : e1218, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32337810

RESUMO

BACKGROUND: Age-related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis. METHODS: The study collected 191 sporadic cataracts and 208 healthy people from the eastern provinces of China, with an average age of about 60 years. All participants were subjected to a comprehensive ophthalmic clinical examination and peripheral blood samples were collected and their genomic DNA was extracted. Mutations were screened among 792 candidate genes to enhance understanding of the disease through targeted capture and high-throughput sequencing. RESULTS: We identified novel candidate susceptibility gene, which may serve as a potential susceptibility factor leading to an increase in the incidence of age-related cataracts. Three novel loci are associated with age-related cataracts significant significance: rs129882 in DBH (p = 5.27E-07, odds ratio = 3.9), rs1800280 in DMD (p = 2.85E-06, odds ratio = 1.4) and rs2871776 in ATP13A2 (p = 4.18E-05, odds ratio = 0.04). Gene-gene interaction analysis revealed that the most significant interactions between genes include the interaction between DBH and TUB (rs17847537 in TUB, rs129882 in DBH, p-value = 2.12E-14), and the interaction between DBH and DMD (rs1800280 in DMD, rs129882 in DBH, p-value = 2.12E-14). Pathway analysis shows that the most significant processes are concentrated in response to light stimulation (adjusted p-Value = 5.56E-03), response to radiation (adjusted P-Value = 5.56E-03), abiotic stimulus (adjusted p-Value = 5.56E-03). eQTL analysis shows that DBH rs129882 could regulate the expression of DBH mRNA in various tissues including retina. CONCLUSION: Our study indicates rs129882 and rs1800280 loci are associated with age-related cataracts, which enlarge the gene map of age-related cataracts.

4.
J Orthop Surg (Hong Kong) ; 28(2): 2309499020915797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301391

RESUMO

BACKGROUND: We consider dual-plate fixation to improve construct rigidity in cases with fracture complexity. The purpose of this study is to compare the rate of nonunion, prognosis, and complications at 6-12 months for surgically treated acute mid-shaft clavicle fractures when extra-periosteal dual-plate fixation is used in place of the conventional single-plate fixation. MATERIALS AND METHODS: The comparative study was conducted on 47 patients who received acute mid-shaft clavicular fracture treatment in our hospital from March 2015 to July 2018. All patients were divided into dual-plate fixation treatment (group A) and single-plate fixation (group B). Patients undergoing single-plate fixation were compared to dual-plate fixation. Patients were followed up for 6-12 months. Charts were reviewed to assess union rates, prognosis, and complications. RESULTS: Forty-seven clavicles (30 single plates and 17 dual plates) were evaluated. All patients (100%) in dual plating group and 128 (93.3%) in single plating group obtained bony union by 1 year. When comparing groups at 3 months, radiographic union was present in 50.0% of single plates and 64.7% in the dual plating group (p = 0.032). However, at 6 months, no significant difference existed (90.0% vs. 94.1%, p = 0.297). Comparing groups at 1.5 and 6 months, Constant-Murley outcome scores were present with no significant difference (p = 0.129, p = 0.054) between single plates and dual plating group. However, at 3 months, significance difference existed. DISCUSSION: Three months after the operation, patients with dual-plate fixation showed good functional recovery. Extra-periosteal dual plating for acute mid-shaft clavicle fractures can be safely considered for the treatment of complex acute mid-shaft clavicle fractures without increasing the risk of nonunion or revision. CONCLUSIONS: Open reduction and internal fixation with an extra-periosteal dual plating technique is a reliable option for treatment of acute mid-shaft clavicle fractures, especially in the setting of severely comminuted fractures and in situations where bone quality is questionable and additional fixation is desired.

5.
Chemosphere ; 251: 126442, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32169715

RESUMO

This study aimed to compare the effectiveness of MAER and L20 resin for the adsorption treatment of secondary effluent, and evaluate the applicability of ozone oxidation for the reuse of desorption eluate. Bench-scale adsorption experiments showed that the MAER resin exhibited higher efficiency than L20 resin in removal of COD within 600 treated bed volumes (BV), which declined from 32.5% to 14.1% in the first and sixth treatment loading of 100 BV. On the other hand, the L20 resin displayed obviously higher removal efficiency of total nitrogen (TN) than MAER resin within 600 BV, which dropped from 74.6% to 9.8% at the same condition. The ozone oxidation treatment could achieve desirable reuse of desorption eluate, although its chemical oxygen demand (COD) concentration increased gradually in line with the reuse numbers. The uptake of COD, TN and total phosphorus declined steadily by using ozone treated eluate as the regenerant in successive adsorption-desorption cycles, but increased obviously with a new batch of regenerant. Overall, the resin adsorption could efficiently remove organic and inorganic matters from secondary effluent, while the treatment loop including desorption eluate oxidation and eluate reuse could markedly enhance the concentration ratio of treated effluent.

6.
Int J Biol Macromol ; 154: 499-510, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32194114

RESUMO

To evaluate if mixed micelles of Dox@FA-BSP-SA/TPGS can allow for the superior antitumor efficiency than Dox@FA-BSP-SA micelles. The complex of doxorubicin (Dox) and sodium cholate was encapsulated into the mixed micelles composed of folate-mediated stearic acid-modified Bletilla striata polysaccharide (FA-BSP-SA) and D-α-tocopheryl polyethylene glycol succinate (TPGS). Its average particle size increased whereas load capacity (LC) and encapsulation efficiency (EE) decreased with the increase of TPGS mass ratio in the mixed micelles. The changes of morphology, particle size and doxorubicin release in vitro demonstrated the pH sensitivity of micelles. FA-BSP-SA/TPGS mixed micelle exhibited average particle size of 147.3 nm, LC of 14.4% and EE of 91.9% for doxorubicin at the weight ratio of 3: 1. The doxorubicin release rate of micelles was faster in pH 5.0 media compared with that in pH 6.0 and 7.4 media. The cytotoxicity in vitro and antitumor efficacy in vivo results of Dox@FA-BSP-SA/TPGS micelle were more superior to that of free doxorubicin and Dox@FA-BSP-SA single micelle. For Dox@FA-BSP-SA/TPGS micelle, the clathrin-mediated endocytosis was the dominant mechanism of intracellular uptake. The FA-BSP-SA/TPGS mixed micelle may be a promising drug delivery system for cancer chemotherapy.

7.
Sci Total Environ ; 723: 137991, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213407

RESUMO

Biochar has been received increasing concerns regarding its environmental effect, which is promising in wastewater treatment. In this study, the performance of ß-cyclodextrin functionalized biochar (ß-BC) on the removal of antibiotic resistance genes (ARGs) in wastewater treatment under the co-stresses of heavy metals and dye is evaluated. Results show that when 20 mg/L heavy metals (HMs) and 150 mg/L methyl orange (MO) are present in daily fed influent, only 0.05 mg/L HMs residual and 96.79%-98.84% MO removal efficiency achieved in ß-BC additive group, compare to 0.16 mg/L and 87.92%-94.11% of that in control, respectively, indicating that ß-BC can benefits the performance of contaminants removal. To evaluate the role of ß-BC plays on ARGs in multi-contaminants stressed system, tet W, tet M, sul-1, sul-2, blaTEM, oxa-1, qnr-S, erm-B and intI-1 are identified. The relative abundance of all identified ARGs are decreased when ß-BC presence compared to the corresponding groups without ß-BC additive. The diversity and composition of microbial community are explored and the reduction of potential antibiotic-resistant bacteria is speculated as a driver of ARGs removal. In conclusion, our study demonstrates that ß-BC possesses the ability to promote the removal of ARGs during continuous wastewater treatment under HMs-MO co-contaminant.

8.
Br J Ophthalmol ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188678

RESUMO

AIMS: To investigate the frequency of USH2A mutation and the clinical and genetic differences between Usher syndrome type II (USH2) and retinitis pigmentosa (RP) in a large cohort of Chinese patients. METHODS: A total of 1381 patients with inherited retinal disease (IRD) were recruited. The phenotypic and genotypic information of patients with USH2A mutations was evaluated. RESULTS: The prevalence of patients with USH2A mutations was 15.75%, which was the most frequently detected gene in this cohort of patients. Hotspot of USH2A mutations was c.8559-2A >G and c.2802T >G. Patients with USH2 had an earlier and more serious decline of visual function and damage to retina structure than did patients with RP in the first 10 years (p<0.05), but there was no difference in the visual prognosis between the two groups when the course of disease exceeded 10 years (p>0.05). Missense variants had less severe consequences and were found more commonly in RP, whereas more deleterious genotypes were associated with an earlier onset of disease and were found more commonly in USH2. CONCLUSIONS: This study provides detailed clinical-genetic assessment of patients with USH2A mutations of Chinese origin, enabling precise genetic diagnoses, better management of these patients and putative therapeutic approaches.

9.
J Oral Sci ; 62(2): 236-238, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32161232

RESUMO

Qualified diagrams of removable partial denture (RPD) designs created by dentists provide technicians with clear and dynamic information. Generating RPD design in the clinical decision support system (CDSS) can be achieved by producing the RPD design in a textual format and then transferring the design onto diagrams. The drawing of RPD diagrams automatically and efficiently for the given textual designs is still under investigation. A new workflow consisting of three major steps is developed to produce and visualize two-dimensional RPD design diagrams. Annotations and orientations of teeth are established from the base maps in the first step, and built-in rules are then incorporated to describe the variations caused by the interactions of the RPD components. Finally, the software draws each component using a series of curve functions. To validate the performance of the software, 112 RPD clinical design plans are randomly selected as inputs for the software, and the outputs are independently verified by experienced clinicians. The proposed methods are proven to be efficient and accurate and thus can be used to improve clinical quality.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Prótese Parcial Removível , Dente , Planejamento de Dentadura , Software
10.
Invest Ophthalmol Vis Sci ; 61(3): 10, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32176261

RESUMO

Purpose: To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. Methods: Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. Results: The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. Conclusions: To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.

11.
Blood ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32202636

RESUMO

SETD2, the histone H3 lysine 36 methyltransferase previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in MDS has been unclear. In this study, we show that low expression of SETD2 correlates with shortened survival in MDS patients and that the SETD2 levels in CD34+ bone marrow (BM) cells of MDS patients can be increased by decitabine. We knock out Setd2 in the NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and demonstrate that loss of Setd2 accelerates the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhances the ability of NHD13+ HSPCs to self-renew, with increased symmetric self-renewal division and decreased differentiation/cell death. The growth of MDS-associated leukemia cells can be inhibited though increasing H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulates hematopoietic stem cell (HSC) signaling and downregulates myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and ChIP-seq analysis indicate that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including IƙBα and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrate that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

12.
Cancer Cell ; 37(3): 371-386.e12, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32109374

RESUMO

Deficient DNA mismatch repair (dMMR) induces a hypermutator phenotype that can lead to tumorigenesis; however, the functional impact of the high mutation burden resulting from this phenotype remains poorly explored. Here, we demonstrate that dMMR-induced destabilizing mutations lead to proteome instability in dMMR tumors, resulting in an abundance of misfolded protein aggregates. To compensate, dMMR cells utilize a Nedd8-mediated degradation pathway to facilitate clearance of misfolded proteins. Blockade of this Nedd8 clearance pathway with MLN4924 causes accumulation of misfolded protein aggregates, ultimately inducing immunogenic cell death in dMMR cancer cells. To leverage this immunogenic cell death, we combined MLN4924 treatment with PD1 inhibition and found the combination was synergistic, significantly improving efficacy over either treatment alone.

13.
BMC Med Genet ; 21(1): 27, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039712

RESUMO

BACKGROUND: Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present. METHODS: By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1. RESULTS: There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found. CONCLUSIONS: Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.


Assuntos
Artrite/genética , Doenças do Tecido Conjuntivo/genética , Análise Mutacional de DNA , Perda Auditiva Neurossensorial/genética , Mutação/genética , Descolamento Retiniano/genética , Artrite/epidemiologia , Artrite/patologia , Doenças do Tecido Conjuntivo/epidemiologia , Doenças do Tecido Conjuntivo/patologia , Oftalmopatias Hereditárias , Estudos de Associação Genética , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/patologia , Humanos , Fenótipo , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/patologia
14.
Clin Chem Lab Med ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32069228

RESUMO

Background The complete blood count (CBC) is a basic test routinely ordered by physicians as a part of initial diagnostic work-up on their patients. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are needed to establish analytical performance specifications. Our aim was to define the BV of CBC parameters using a rigorous protocol that is compliant with the Biological Variation Data Critical Appraisal Checklist (BIVAC) provided by the European Federation of Clinical Chemistry and Laboratory Medicine. Methods Blood samples drawn from 41 healthy Chinese subjects (22 females and 19 males; 23-59 years of age) once monthly for 6 consecutive months were analyzed using an ABX Pentra 80 instrument. The instrument was precisely calibrated. All samples were analyzed in duplicate for 13 CBC parameters. The data were assessed for outliers, normality, and variance homogeneity prior to nested ANOVA. Gender-stratified within-subject (CVI) and between-subject (CVG) BV estimates were calculated. Results The number of remaining data for each subject was 442-484 after removing outliers. No significant differences existed between female/male CVI estimates. Except for leukocytes, neutrophils, and lymphocytes, the mean values of 10 parameters differed significantly between genders, rendering partitioning of CVG data between genders. No significant differences were detected between most BV estimates and recently published estimates representing a Europid population. Conclusions Most BV estimates in BIVAC-compliant studies are similar. The turnover time of blood cells and age distribution of participants should be considered in a CBC BV study. Our study will contribute to global BV estimates and future studies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32009386

RESUMO

MXenes are a new type of two-dimensional material, and they have attracted extensive attention because of their outstanding conductivity and rich surface functional groups that make surface engineering easy and possible for adapting to diverse applications. However, there are scarce studies on surface engineering of MXene. Herein, we demonstrate for the first time that octylphosphonic acid-modified Ti3C2Tx MXene can be used as an active layer for memory devices and exhibits stable ternary memory behavior. Low threshold voltage, steady retention time, clearly distinguishable resistance states, high ON/OFF rate, OFF/ON1/ON2 = 1:102.7:104.1, and considerable ternary yield (58%) were obtained. In the proof of the mechanism, in situ conductive atomic force microscopy was conducted and the electrode-area relationship was analyzed to demonstrate that charge trapping and filament conduction are more suitable in the nonvolatile information memory of Ti3C2Tx-OP MXene devices. In addition, a polyethylene-terephthalate-based flexible Ti3C2Tx-OP memory device can maintain its stable ternary memory performance after being bent 5000 times. This work provides an easy method for surface modification of MXene and broadens the field of MXene.

16.
Ann Palliat Med ; 9(1): 45-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32005062

RESUMO

BACKGROUND: It is high of the incidence of stroke and dementia with the advent of an aging society. Post-stroke cognitive impairment is one of the common complications of stroke, which not only seriously affects the life quality of patients, but also significantly reduces the survival time of stroke patients. Moreover, it also brings in heavy burden to the family and society. The development of vascular dementia could be reduced by early intervention after stroke. Management of vascular risk factors could be an effective way to prevent dementia. This study aimed to investigate the plasma biochemical parameters of post-stroke cognitive impairment (PSCI) and its potential risk factors. METHODS: Four hundred eighty-seven consecutive patients with ischaemic stroke were included and followed up for 3 years. Among these patients, 132 cases were diagnosed as PSCI. The cognitive impairment of patients with PSCI was assessed by the Mini Mental State Examination and Montreal cognitive assessment scale. The plasma biochemical parameters and blood coagulation, as well as computed tomography and magnetic resonance imaging of all the patients after admission, were measured. RESULTS: Multivariate analyses revealed that increased age, carotid plaque, cerebral atrophy, white matter lesions (WML), alcohol use, smoking and history of systolic blood pressure ≥170 mmHg was highly associated with PSCI (P<0.05). Elevated homocysteine, low-density lipoprotein (LDL), and uric acid were also highly associated with PSCI. Logistic regression analysis identified five risk factors correlated with PSCI including alcohol use [odds ratio (OR): 5.138, 95% confidence interval (CI): 1.014-26.04, P=0.048], history of high systolic blood pressure (OR: 12.171, 95% CI: 3.339-44.363, P=0.001), carotid plaque (OR: 1.692, 95% CI: 1.032-2.796, P=0.040), cerebral atrophy (OR: 2.280, 95% CI: 1.294-4.001, P=0.004), and WML (OR: 3.155, 95% CI: 1.868-5.324, P=0.001). Three plasma biochemical parameters were also associated with PSCI including homocysteine (OR: 1.018, 95% CI: 0.944-1.042, P=0.010), and LDL (OR: 0.83, 95% CI: 0.6-1.148, P=0.051), and uric acid (OR: 1.00, 95% CI: 0.998-1.002, P=0.007). The area under the receiver operating curve for the risk factors of PSCI was 0.821 with the sensitivity of 76.3% and specificity of 71.9%. CONCLUSIONS: Elevated homocysteine, LDL, and uric acid were highly related to PSCI, which may help predict PSCI. These plasma biochemical parameters together with vascular risk factors, may improve the sensitivity for early detection of PSCI.

17.
Int J Food Microbiol ; 319: 108494, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31918346

RESUMO

Nisin and grape seed extract (GSE) have been widely used as food preservatives; however, the mechanism against pathogens at molecular level has not been well elucidated. This work aimed to investigate their antimicrobial effect against Listeria monocytogenes and to elucidate the mechanism by NMR-based metabolomics. Nisin exhibited enhanced in vitro antilisterial effect when combined with GSE (4.49 log CFU/mL reduction). Marked change in cell membrane permeability was observed in the combination group using confocal laser scanning microscopy; this was verified by increased leakage of protein and nucleic acid. The underlying antimicrobial mechanism was revealed by NMR coupled with multivariate analysis. Significant decreases in threonine, cysteine, ATP, NADP, adenine were observed, whereas a few of metabolites such as lactic acid and γ-aminobutyric acid (GABA) increased after nisin-GSE treatment (P < 0.05). Pathway analysis further manifested that the nisin-GSE inhibited the survival of L. monocytogenes by blocking the TCA cycle, amino acid biosynthesis and energy-producing pathway. Lastly, nisin and GSE were applied to shrimp and binary combination showed remarkably antilisterial activity (1.79 log CFU/g reduction). GABA shunt and protein degradation from shrimp compensated the unbalanced glycolysis and amino acid metabolism by providing energy and carbon source for L. monocytogenes inoculated on shrimp. Thus, they were more tolerant to nisin and GSE stresses as compared to the broth-grown culture.

18.
J Hazard Mater ; 388: 122070, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954307

RESUMO

The emerging antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are increasingly appreciated to be as important as microbial contaminants. This paper focused on UV-activated persulfate (UV/PS), an advanced oxidation process, in removing ARB and ARGs from secondary wastewater effluent. Results showed that the inactivation efficiency of macrolides-resistant bacteria (MRB), sulfonamides-resistant bacteria (SRB), tetracyclines-resistant bacteria (TRB) and quinolones-resistant bacteria (QRB) by UV/PS reached 96.6 %, 94.7 %, 98.0 % and 99.9 % in 10 min, respectively. UV/PS also showed significant removal efficiency on ARGs. The reduction of total ARGs reached 3.84 orders of magnitude in UV/PS which is more than that in UV by 0.56 log. Particularly, the removal of mobile genetic elements (MGE) which might favor the horizontal gene transfer of ARGs among different microbial achieved 76.09 % by UV/PS. High-throughput sequencing revealed that UV/PS changed the microbial community. The proportions of Proteobacteria and Actinobacteria that pose human health risks were 4.25 % and 1.6 % less than UV, respectively. Co-occurrence analyzes indicated that ARGs were differentially contributed by bacterial taxa. In UV/PS system, hydroxyl radical and sulfate radical contributed to the removal of bacteria and ARGs. Our study provided a new method of UV/PS to remove ARGs and ARB for wastewater treatment.

19.
Int J Mol Sci ; 21(2)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968661

RESUMO

Melanotan II (MTII), a synthetic analogue of the alpha-melanocyte stimulating hormone (α-MSH), has been applied for skin tanning in humans. However, the carcinogenic consequence of topical MTII has been equivocal. This study aims to delineate the anti-neoplastic efficacy and mechanism of MTII using the B16-F10 melanoma model in vitro and in vivo. It was found that, despite a lack of influence on proliferation, MTII potently inhibited the migration, invasion, and colony-forming capability of melanoma cells. Moreover, topical MTII application significantly attenuated the tumor progression in mice bearing established melanoma. Histological analysis revealed that MTII therapy induced apoptosis while inhibiting the proliferation and neovaluarization in melanoma tissues. By immunoblot and immunohistochemical analysis, it was found that MTII dose-dependently increased the phosphatase and tensin homolog (PTEN) protein level while reducing PTEN phosphorylation, which resulted in the inhibition of AKT/nuclear factor kappa B (NFκB) signaling. Consistently, MTII treatment inhibited cyclooxygenase II (COX-2) expression and prostaglandin E2 (PGE2) production in melanoma cells. Finally, studies of antibody neutralization suggest that the melanocortin 1 receptor (MC1R) plays a critical role in MTII-induced PTEN upregulation and melanoma suppression. Together, these results indicate that MTII elicits PTEN upregulation via MC1R, thereby suppressing melanoma progression through downregulating COX-2/PGE2 signaling. Hence, topical MTII therapy may facilitate a novel therapeutic strategy against melanoma.

20.
Molecules ; 25(2)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963527

RESUMO

Aromatic heterocycles are ubiquitous building blocks in bioactive natural products, pharmaceutical and agrochemical industries. Accordingly, the carborane-fused heterocycles would be potential candidates in drug discovery, nanomaterials, metallacarboranes, as well as photoluminescent materials. In recent years, the transition metal catalyzed B-H activation has been proved to be an effective protocol for selective functionalization of B-H bond of o-carboranes, which has been further extended for the synthesis of polyhedral borane cluster-fused heterocycles via cascade B-H functionalization/annulation process. This article summarizes the recent progress in construction of polyhedral borane cluster-fused heterocycles via B-H activation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA