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1.
RNA Biol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32070191

RESUMO

RNA secondary structure elements in the mRNA 3'-untranslated regions (3'UTR) play important roles in post-transcriptional regulation. RNA structure elements in the viral RNA provide valuable model for studying diverse regulation mechanisms. Herpesvirus genomes are double-stranded DNA with GC-rich sequences, which can be transcribed into abundant GC-rich RNAs. It is valuable to explore the structures and function of those GC-rich RNAs. We identified a G2-quadruplex-forming sequence named PQS18-1 in the 3'UTR of the unique immediate early gene of Pseudorabies virus (PRV), an important member of alphaherpesvirus subfamily. The RNA PQS18-1 was folded into parallel G-quadruplex structure, enhancing gene expression. Both non-G-quadruplex mutant and G3-quadruplex mutant in the 3'UTR showed lower gene expression level than the wildtype G2-quadruplex. A chemical compound destroyed PQS18-1 G2-quadruplex and suppressed gene expression, accordingly reducing PRV replication by one titre in the PK15 cells at 24 hours post infection. Our findings indicated that the RNA G2-quadruplex in 3'UTR was essential for high expression of IE180 gene, and it could be a specific post-transcription regulation element in response to small molecules or other macromolecules. This study discovers a novel RNA G2-quadruplex in the 3'UTR of an immediate early gene of alphaherpesvirus, and provides a new nucleic acid target for anti-virus drug design.

2.
Org Lett ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013456

RESUMO

The Cu-catalyzed 1,4-protosilylation and protoborylation of trifluoromethyl-substituted conjugated enynes were developed to access functionalized homoallenylsilanes and homoallenylboronates. This protocol also provides a general method to synthesize optically active homoallenylsilanes and homoallenylboronates in moderate to excellent yields with high enantiomeric excess by using new designed chiral bisoxazoline ligands. Simultaneously, the transformations of homoallenylsilanes and homoallenylboronates were also explored to synthesize useful building blocks.

3.
BMC Public Health ; 20(1): 150, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005214

RESUMO

BACKGROUND: Food environments have rapidly changed over the past years in China and children have more access to unhealthy food in convenience stores near schools. Since the studies on the association between convenience stores near schools and obesity had inconsistent results and no similar study in China, we conducted a study on the association in Beijing of China, which will provide scientific evidence for the intervention of childhood obesity. METHODS: The study included 2201 students at grade 4 of 37 primary schools in Dongcheng or Miyun district of Beijing. The food environment data was acquired from AMAP, the free web-based geospatial service provider. The numbers of convenience stores were captured within the 800-m network buffer near schools using Geographic Information System. The weight and height of each student were measured by trained health professionals. Students' dietary and physical behaviors and other information associated with obesity were collected with questionnaires for students and their parents. The generalized linear mixed model (GLMM) was used to analyze the data. RESULTS: The average age of the students was 10.2 years (Standard Deviation (SD) = 0.33). The prevalence of obesity in students was 14.9%. The median number of convenience stores within the 800-m network buffer near schools was 24 in two districts. The number of convenience stores near each school varied from 5 to 67 (median: 25) in Dongcheng district and from 1 to 57 (median: 22) in Miyun district. After adjusting for the confounding factors at the family and individual levels, the association between convenience stores and childhood obesity was statistically significant. Additional ten convenience stores near schools were associated with an increased risk of obesity (Odds Ratio (OR) = 1.13, 95% confidence interval (CI): 1.03,1.24, P = 0.011). Compared with less than 24 convenience stores near schools, the students with more than or equal to 24 convenience stores near schools had an increased risk of obesity (OR = 1.49, 95% CI: 1.09, 2.03, P = 0.013). CONCLUSION: The students with more convenience stores near their schools had an increased risk of obesity. The findings provided evidence for developing public health policy to restrict the number of convenience stores near schools to prevent and control childhood obesity.

4.
Adv Mater ; : e1906536, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027430

RESUMO

Internal magnetic moments induced by magnetic dopants in MoS2 monolayers are shown to serve as a new means to engineer valley Zeeman splitting (VZS). Specifically, successful synthesis of monolayer MoS2 doped with the magnetic element Co is reported, and the magnitude of the valley splitting is engineered by manipulating the dopant concentration. Valley splittings of 3.9, 5.2, and 6.15 meV at 7 T in Co-doped MoS2 with Co concentrations of 0.8%, 1.7%, and 2.5%, respectively, are achieved as revealed by polarization-resolved photoluminescence (PL) spectroscopy. Atomic-resolution electron microscopy studies clearly identify the magnetic sites of Co substitution in the MoS2 lattice, forming two distinct types of configurations, namely isolated single dopants and tridopant clusters. Density functional theory (DFT) and model calculations reveal that the observed enhanced VZS arises from an internal magnetic field induced by the tridopant clusters, which couples to the spin, atomic orbital, and valley magnetic moment of carriers from the conduction and valence bands. The present study demonstrates a new method to control the valley pseudospin via magnetic dopants in layered semiconducting materials, paving the way toward magneto-optical and spintronic devices.

5.
BMC Plant Biol ; 20(1): 60, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024458

RESUMO

BACKGROUND: Shade stress, a universal abiotic stress, suppresses plant growth and production seriously. However, little is known regarding the protein regulatory networks under shade stress. To better characterize the proteomic changes of maize leaves under shade stress, 60% shade (S) and supplementary lighting (L) on cloudy daylight from tasseling stage to physiological maturity stage were designed, the ambient sunlight treatment was used as control (CK). Isobaric tag for relative and absolute quantification (iTRAQ) technology was used to determine the proteome profiles in leaves. RESULTS: Shading significantly decreased the SPAD value, net photosynthetic rate, and grain yield. During two experimental years, grain yields of S were reduced by 48 and 47%, and L increased by 6 and 11%, compared to CK. In total, 3958 proteins were identified by iTRAQ, and 2745 proteins were quantified including 349 proteins showed at least 1.2-fold changes in expression levels between treatments and CK. The differentially expressed proteins were classified into photosynthesis, stress defense, energy production, signal transduction, and protein and amino acid metabolism using the Web Gene Ontology Annotation Plot online tool. In addition, these proteins showed significant enrichment of the chloroplasts (58%) and cytosol (21%) for subcellular localization. CONCLUSIONS: 60% shade induced the expression of proteins involved in photosynthetic electron transport chain (especially light-harvesting complex) and stress/defense/detoxification. However, the proteins related to calvin cycle, starch and sucrose metabolisms, glycolysis, TCA cycle, and ribosome and protein synthesis were dramatically depressed. Together, our results might help to provide a valuable resource for protein function analysis and also clarify the proteomic and physiological mechanism of maize underlying shade stress.

6.
Nat Commun ; 11(1): 772, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034131

RESUMO

Lateral heterostructures of two-dimensional transition metal dichalcogenides (TMDs) have offered great opportunities in the engineering of monolayer electronics, catalysis and optoelectronics. To explore the full potential of these materials, developing methods to precisely control the spatial scale of the heterostructure region is crucial. Here, we report the synthesis of ultra-long MoS2 nano-channels with several micrometer length and 2-30 nanometer width within the MoSe2 monolayers, based on intrinsic grain boundaries (GBs). First-principles calculations disclose that the strain fields near the GBs not only lead to the preferred substitution of selenium by sulfur but also drive coherent extension of the MoS2 channel from the GBs. Such a strain-driven synthesis mechanism is further shown applicable to other topological defects. We also demonstrate that the spontaneous strain of MoS2 nano-channels can further improve the hydrogen production activity of GBs, paving the way for designing GB based high-efficient TMDs in the catalytic application.

7.
BMC Musculoskelet Disord ; 21(1): 86, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033563

RESUMO

BACKGROUND: To compare the clinical and radiological outcomes between posterior mono-segment and short-segment fixation combined with one-stage posterior debridement and bone grafting fusion in treating single-segment lumbar spinal tuberculosis (LSTB). METHODS: Sixty-two patients with single-segment LSTB treated by a posterior-only approach were divided into two groups: short-segment fixation (Group A, n = 32) and mono-segment fixation (Group B, n = 30). The clinical and radiographic outcomes were analyzed and compared between the two groups. RESULTS: The intraoperative bleeding volume, operation time, and hospitalization duration were lower in Group B than in Group A. All patients achieved the bony fusion criteria. The visual analog scale score, Japanese Orthopedic Association score, and Oswestry Disability Index were substantially improved 3 months postoperatively and at the last visit in both groups, with no significant difference between the two groups (P > 0.05). Kirkaldy-Willis functional evaluation at the final follow-up demonstrated that all patients in both groups achieved excellent or good results. The difference in the angle correction rate and correction loss between Groups A and B was not significant (P > 0.05). CONCLUSIONS: One-stage posterior debridement, bone grafting fusion, and mono-segment or short-segment fixation can provide satisfactory clinical and radiological outcomes. Mono-segment fixation is more suitable for the treatment of single-segment LSTB because the lumbar segments with normal motion can be preserved with less trauma, a shorter operation time, shorter hospitalization, and lower costs.

8.
Nanotechnology ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053795

RESUMO

In this work, a new hybrid optical Janus color architecture is introduced that can lead to impressive, highly directional optical properties. Based on a simple and straightforward annealing process, a thin metallic nanoparticles metasurface is produced, which forms the strong light absorption layer and creates optical Janus effects in the multilayer structure. The observed reflective colors are remarkably different on one side of the structurally colored material than that is obtained on the other side. The optical properties of the systems under different geometry and composition situations are performed. The asymmetric color materials could hold broad application prospects such as displays, color filters, architecture and anti-counterfeit labels.

9.
Ann Coloproctol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32054250

RESUMO

Background: : Current acceptance of a watch-and-wait (W&W) approach by surgeons in Asia-Pacific countries is unknown. An international survey was performed to determine the current status of W&W on behalf of Asia-Pacific Federation of Coloproctology (APFCP). Methods: Surgeons in APFCP completed an IRB-approved anonymous e-survey and printed letters from China containing 19 questions regarding non-surgical close observation in patients who achieved clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT). Results: Of the 417 responses, 80.8% (n=337) supported the W&W approach, and 65.5% (n=273) have treated patients who achieved cCR after nCRT. Importantly, 78% of participants (n=326) preferred a selective W&W approach in patients with old age and medical co-morbidities who achieved cCR. In regard to restaging methods after nCRT, the majority of respondents base their decision to use W&W based on a combination of MRI (94.5%, n=394). For interval between nCRT completion and tumor response assessment, most participants used 8 weeks (n=154, 36.9%), followed by 6 weeks (n=127, 30.5%) and 4 weeks (n=102, 24.5%). In response to the question of how often do responders follow-up after W&W, the predominant period was every three months (209 participants, 50.1%), followed by every two months (75 participants, 18.0%). If local regrowth was found during follow-up, most participants (79.9%, n=333) recommended radical surgery as an initial management. Conclusion: Watch-and-wait is supported by 80% of Asia-Pacific surgeons and is being practiced in 65%, although heterogeneous hospital or society protocols were observed. These results inform oncologists of future clinical study participation.

10.
J Cell Physiol ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037547

RESUMO

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

11.
Biomed Res Int ; 2020: 9871390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076625

RESUMO

Spinal tuberculosis (STB), which is the most frequent and serious form of skeletal TB, is seriously harmful to a patient's life. However, very little research has been conducted on clinical isolates of STB. The purpose of this study was to genotype clinical isolates of Mycobacterium tuberculosis (MTB) from patients with STB, investigate their drug resistance profiles, and determine whether the genotypes and drug resistance patterns share any relationships with the demographic and clinical features of the patients. Preliminary species identification of the MTB strains was performed using a TCH/PNB culture method and multilocus polymerase chain reactions. Of the specimens collected from 85 hospital in-patients with STB at Xiangya Hospital, China, the 56 culture-positive MTB strains we identified were genotyped by spoligotyping. The strains were tested for resistance to anti-tuberculosis drugs (ATDs), and the demographic and clinical features of the patients were analyzed in combination with the genotyping and drug resistance results. Of the 56, cases, 53 involved M. tuberculosis and 3 involved M. bovis. Spoligotyping revealed 27 Beijing-type cases and 29 nonBeijing cases. When patients with STB were relapsing or experiencing systemic toxicity signs/symptoms (STS), the Beijing MTB-type strains predominated (p < 0.05), but when the patients were receiving initial treatment or lacked STS, the nonBeijing type MTB strains dominated. The Beijing and nonBeijing types differed in their resistance patterns to 8 ATDs, and the resistance rate of the Beijing type was higher than that of the nonBeijing type (p < 0.05). The bacteriological features of STB, including genotype and drug resistance, shared close relationships with the clinical features of patients with STB. Our data provide a reference for the diagnosis and treatment of STB.

12.
Eur J Med Chem ; 190: 112074, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32045788

RESUMO

A series of thiochromeno[2,3-c]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8, 10, 12, 14, 19, and 26) of 23 compounds showed strong inhibitory activities against Topo-mediated DNA relaxation and proliferation of five human cell lines including breast (MDA-MB-231, MDA-MB-468 and MCF7), colorectal (HCT116) and non-small cell lung (H1299) cancers. Among these, compounds 14 and 26 exhibited full inhibitory activities against Topo I at 3 µM and Topo IIα at 1 µM. Cancer cells treated with 26 accumulated DNA damage and were arrested at the G2/M phase. With time, cells proceeded to apoptosis, as revealed by increased amounts of cells with fragmented DNA and cleavage of caspase-8 and -9. In contrast, normal breast epithelial cells showed low sensitivity to 26. Taken together, our study identifies 26 as a potent Topo dual-inhibitor with low toxicity to normal cells, and elucidates that the terminal amino group of N-2-aminoethylamino or N-3-aminopropylamino at the 6th position and 8,10-di-halogen substituents on thiochromeno[2,3-c]quinolin-12-one are critical for the Topo-inhibiting and cancer-killing activities.

13.
Cancer Res ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066565

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignant diseases. Multiple studies with large clinic-based cohorts have revealed that variations of phospholipase C epsilon 1 (PLCE1) correlate with esophageal cancer susceptibility. However, the causative role of PLCE1 in ESCC has remained elusive. Here, we observed that hypomethylation-mediated upregulation of PLCE1 expression was implicated in esophageal carcinogenesis and poor prognosis in ESCC cohorts. PLCE1 inhibited cell autophagy and suppressed the protein expression of p53 and various p53-targeted genes in ESCC. Moreover, PLCE1 decreased the half-life of p53 and promoted p53 ubiquitination, whereas it increased the half-life of mouse double minute 2 homolog (MDM2) and inhibited its ubiquitination, leading to MDM2 stabilization. Mechanistically, the function of PLCE1 correlated with its direct binding to both p53 and MDM2, which promoted MDM2-dependent ubiquitination of p53 and subsequent degradation in vitro. Consequently, knockdown of PLCE1 combined with transfection of a recombinant adenoviral vector encoding wild-type p53 resulted in significantly increased levels of autophagy and apoptosis of esophageal cancer in vivo. Clinically, the upregulation of PLCE1 and mutant p53 protein predicted poor overall survival of ESCC patients, and PLCE1 was positively correlated with p53 in ESCC cohorts. Collectively, this work identified an essential role for PLCE1- and MDM2-mediated ubiquitination and degradation of p53 in inhibiting ESCC autophagy and indicates that targeting the PLCE1-MDM2-p53 axis may provide a novel therapeutic approach for ESCC.

14.
Diabetes Res Clin Pract ; 161: 108033, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32006644

RESUMO

Previous studies have shown that FXR is involved in glycolipid metabolism, tissue inflammation and regeneration in organs such as the liver, intestines and kidneys. Although FXR has been reported in cardiac tissue, its function in diabetic cardiomyopathy has not been reported. Here, we successfully constructed a diabetic mouse model of FXR-/- and evaluated the effects of FXR knockout on cardiac function in mice by measuring various indicators. We demonstrated that blood glucose levels in diabetic mice are significantly elevated in the case of FXR knockout. Our findings from cardiac ultrasound and tissue HE staining supported that FXR knockout aggravates diabetic cardiomyopathy. Masson staining of myocardial tissue and quantitative detection of α-SMA by qPCR suggest that FXR knockout exacerbates cardiac fibrosis in diabetic cardiomyopathy. Combined with the results of Oil Red staining and quantitative detection of triglycerides in fresh tissue blocks, we hypothesized that FXR knockout aggravates diabetes-induced cardiac lipid accumulation. Altogether our results revealed a role of the FXR in the diabetic cardiomyopathy, suggesting a possible novel target for the treatment of diabetic cardiomyopathy.

15.
J Am Chem Soc ; 142(6): 2948-2955, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31961673

RESUMO

Transition metal dichalcogenides (TMDs) have become a playground for exploring rich physical phenomena like superconductivity and charge-density-waves (CDW). Here, we report the synthesis of the atom-thin TaSe2 with a rare 3R phase and enhanced superconductivity. The 3R phase is achieved by an ambient pressure chemical vapor deposition (CVD) strategy and confirmed by the high-resolution aberration-corrected STEM. Low-temperature transport data reveal an enhanced superconducting transition temperature (Tc) of 1.6 K in the 3R-TaSe2, which undoubtedly breaks the traditional perception of TaSe2 crystal as a material with Tc close to 0 K. This work demonstrates the strength of ambient pressure CVD in the exploration of crystal polymorphism, highlights a decisive role of layer stacking order in the superconducting transition, and provides fresh insights on manipulating crystal structures to gain access to enhanced Tc.

16.
Soft Matter ; 16(6): 1653-1667, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31965137

RESUMO

The stability of ion-conductive membranes, such as perfluorosulfonic-acid (PFSA) membranes, as a solid-electrolyte separator in energy devices is strongly linked to their mechanical properties, the characterization of which presents challenges, especially in the presence of ionic interactions. Ionomer membranes' elastic properties are affected by cations; however, their influence on deformation at small and large strains is relatively unexplored. In this paper, we report the stress-strain response and fracture behavior of Nafion membranes exchanged with various cations examined in three deformation regimes. In the small-strain regime, the Young's modulus is strongly dependent on cation size, due to the reduced mobility and local stiffening of polymer chains. The Young's modulus, yield limit and strain-hardening modulus all increase with monovalent cation size in the order H+ < Li+ < Na+ < K+ < Cs+, but with varying dependence. In the failure regime, however, the break strain and fracture energy of the membrane decrease in the presence of larger cations, which promote deformation instability while decreasing plastic dissipation energy during crack propagation, thereby leading to more brittle fracture. These results not only demonstrate the trade-off between strength and fracture toughness, but also reveal how it is altered by the ionic interactions, which also dictate the inverse relationship between stretchability and stiffness. Moreover, the measured stress-strain data are reproduced by the constitutive relations to extract parameters that are correlated to the fracture energy through craze instability. Such relationships provide insight into how parameters extracted from tensile testing can be used to assess membrane stability and the role of ionic interactions.

17.
ACS Nano ; 14(1): 595-602, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31891248

RESUMO

A carbon microtube aerogel (CMA) with hydrophobicity, strong adsorption capacity, and superb recyclability was obtained by a feasible approach with economical raw material, such as kapok fiber. The CMA possesses a great adsorption capacity of 78-348 times its weight. Attributed to its outstanding thermal stability and excellent mechanical properties, the CMA can be used for many cycles of distillation, squeezing, and combustion without degradation, which suggests a potential practical application in oil-water separation. In addition, the adsorption capacity still retained 98% by distillation, 97% by squeezing, and 90% by combustion after 10 cycles. Therefore, the obtained CMA has a broad prospect as an economical, efficient, and environmentally friendly adsorbent.

18.
ACS Chem Neurosci ; 11(3): 314-327, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31922720

RESUMO

We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced neurotoxicity in rat primary cultured cerebellar granule neurons (CGNs). Western blotting assays revealed that MN-12 might possess neuroprotective effects through the inhibition of ERK pathway and activation of PI3K/Akt pathway concurrently. Moreover, MN-12 concentration-dependently dilated precontracted rat middle cerebral artery through activation of NO-cGMP pathway ex vivo. In the 2-vessel occlusion (2VO) rat model, MN-12 alleviated the impairments of spatial memory and motor dysfunction possibly via neuroprotection and improvement of the cerebral blood flow. Furthermore, the results of preliminary pharmacokinetic studies showed that MN-12 might quickly distribute to the major organs including the brain, indicating that MN-12 could penetrate the blood-brain barrier. Taken together, MN-12 might provide multifunctional therapeutic benefits for dementia associated with Alzheimer's disease, vascular dementia, and ischemic stroke, via neuroprotection and vessel dilation to improve the cerebral blood flow.

19.
Theranostics ; 10(1): 231-246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903117

RESUMO

The blood-brain barrier (BBB) dysfunction is an initial event of various neuroinflammatory diseases. However, the absence of reliable markers and mechanisms for BBB damage greatly limits the diagnosis and treatment of neuroinflammatory diseases. Soluble CD146 (sCD146) is mainly derived from vascular endothelial cells (ECs) and highly elevated in inflammatory settings. Based on a small cohort, our previous study showed that sCD146 is elevated in the cerebrospinal fluid (CSF) of multiple sclerosis (MS), which is accompanied with BBB damage. Nevertheless, whether sCD146 monitors and regulates the BBB dysfunction remains unknown. Methods: Coupled serum and CSF samples from patients with or without neuroinflammatory diseases were collected via multicenter collaborations. sCD146 was measured by sandwich ELISA using anti-CD146 antibodies AA1 and AA98, both of which were generated in our laboratory. The correlations between sCD146 and other clinical parameters or inflammatory factors were analyzed by Spearman's correlation coefficient analysis. The role of sCD146 on BBB function was examined in an in vitro BBB model. Results: Between July 20, 2011, and February 31, 2017, we collected coupled serum and CSF samples from 823 patients, of which 562 (68.3%) had neuroinflammatory diseases, 44 (5.3%) had remitting MS, and 217 (26.4%) had non-inflammatory neurological diseases (NIND). We found that sCD146 in CSF, but not in serum, is abnormally elevated in neuroinflammatory diseases (37.3 ± 13.3 ng/mL) compared with NIND (4.7 ± 2.9 ng/mL) and remitting MS (4.6 ± 3.5 ng/mL). Abnormally elevated CSF sCD146 is significantly correlated with the hyperpermeability-related clinical parameters of BBB and neuroinflammation-related factors. Moreover, CSF sCD146 shows higher sensitivity and specificity for evaluating BBB damage. Using an in vitro BBB model, we found that sCD146 impairs BBB function by promoting BBB permeability via an association with integrin αvß1. Blocking integrin αvß1 significantly attenuates sCD146-induced hyperpermeability of the BBB. Conclusion: Our study provides convincing evidence that CSF sCD146 is a sensitive marker of BBB damage and neuroinflammation. Furthermore, sCD146 is actively involved in BBB dysfunction.

20.
Sci Rep ; 10(1): 978, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969646

RESUMO

Societal lifestyle changes, especially increased consumption of a high-fat diet lacking dietary fibers, lead to gut microbiota dysbiosis and enhance the incidence of adiposity and chronic inflammatory disease. We aimed to investigate the metabolic effects of inulin with different degrees of polymerization on high-fat diet-fed C57BL/6 J mice and to evaluate whether different health outcomes are related to regulation of the gut microbiota. Short-chain and long-chain inulins exert beneficial effects through alleviating endotoxemia and inflammation. Antiinflammation was associated with a proportional increase in short-chain fatty acid-producing bacteria and an increase in the concentration of short-chain fatty acids. Inulin might decrease endotoxemia by increasing the proportion of Bifidobacterium and Lactobacillus, and their inhibition of endotoxin secretion may also contribute to antiinflammation. Interestingly, the beneficial health effects of long-chain inulin were more pronounced than those of short-chain inulin. Long-chain inulin was more dependent than short-chain inulin on species capable of processing complex polysaccharides, such as Bacteroides. A good understanding of inulin-gut microbiota-host interactions helps to provide a dietary strategy that could target and prevent high-fat diet-induced endotoxemia and inflammation through a prebiotic effect.

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