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1.
Artigo em Inglês | MEDLINE | ID: mdl-32049638

RESUMO

OBJECTIVE: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) may convey disparate risks of metabolic consequences. Fasting plasma glucose (FPG), while an expedient screening procedure, may not adequately assess metabolic risk, particularly among youths. In order to inform a strategy for screening Chinese youth for pre-diabetes, we examined the relative value of IFG versus IGT to define metabolic risk by assessing their association with insulin resistance, beta-cell dysfunction, adverse adipokine profiles and other cardiometabolic risk factors. RESEARCH DESIGN AND METHODS: We recruited 542 subjects (age 14-28 years) from the Beijing Child and Adolescent Metabolic Syndrome study for an in-depth assessment of cardiometabolic risk factors, including a 2-hour oral glucose tolerance test, liver ultrasound and serum levels of four adipokines. RESULTS: FPG failed to identify nearly all (32/33) youths with IGT, whereas 2-hour plasma glucose (2 h PG) missed 80.8% (21/26) of subjects with IFG. Impaired beta-cell function was evident from decreased oral disposition indices in those with isolated impaired fasting glucose (iIFG) or isolated impaired glucose tolerance (iIGT) versus normal glucose tolerance (NGT) (all p<0.001), whereas reduced insulin sensitivity (Matsuda) index was most pronounced in the iIGT group (p<0.01). Moreover, alterations in adipokine levels (fibroblast growth factor 21, adiponectin and leptin/adiponectin ratio) were associated with iIGT (p<0.05) but not iIFG. Youths with iIGT had a 2-fold to 32-fold increased incidence of hypertriglyceridemia, hypertension and metabolic syndrome (MetS) compared with those with NGT. In addition, subgroup analyses of participants with normal FPG revealed that the odds of having IGT increased 3-fold to 18-fold among those with elevated TGs, hypertension, moderate-to-severe non-alcoholic fatty liver disease or MetS. CONCLUSIONS: Chinese youth with iIGT exhibit a higher cardiometabolic risk profile than those with iIFG. Thus, 2 h PG is preferred over FPG to identify the pre-diabetes phenotype at greatest risk of subsequent development of cardiovascular disease. TRIAL REGISTRATION NUMBER: NCT03421444.

2.
Int Angiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052947

RESUMO

BACKGROUND: Insomnia may affect vascular factors and promote arteriosclerosis. Microparticles (MPs) are a heterogeneous group of bioactive small vesicles that can be found in blood and body fluids following activation, necrosis or apoptosis of virtually any eukaryotic cells. MPs are believed to participate in the pathogenesis of atherosclerosis. Few studies have been concerned with the microparticle level in patients with sleep disorder. The purpose of the present study is to measure the levels of endothelial microparticles (EMPs), platelet microparticles (PMPs) and leukocyte-derived microparticles (LMPs) in middle-aged and elderly patients with or without insomnia. METHODS: Patients with insomnia (n=30) and without insomnia (n=18) were enrolled. The insomnia group covered patients with chronic insomnia (n=16) and acute insomnia (n=14). Levels of EMPs (CD31 +, CD62E +) and PMPs (CD41a +, CD42a +) and granulocyte-derived (CD11a +) MPs were measured. Flow cytometry was performed on the Beckman Coulter analyzer. Reference gate was defined for the level of MPs using 0.22-0.45-0.88µm microspheres, and the size gate for MPs was 0.5-1.0µm. RESULTS: Of all types of MPs detected, the levels of CD31 +MPs, CD62E +MPs and CD11a +MPs were significantly higher in the insomnia group than in the non-insomnia group (P<0.05). Besides, compared with acute insomnia, the levels of CD31 + MPs and CD11a +MPs were significantly higher in chronic insomnia (P<0.001). CONCLUSIONS: In insomnia patients, atherosclerosis progression may be increased by the CD31+ EMPs-mediated apoptosis and endothelial injury. The level of CD11a+ LMPs kept increasing as insomnia persisted, which may indicate atherosclerosis progression.

3.
Inorg Chem ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31994877

RESUMO

One-pot reaction of an asymmetrical acylhydrazone ligand H3L with Ln(ClO4)3 and CuCl2 in MeOH and MeCN solvents resulted in two novel octanuclear complexes, [Cu4Dy4L4Cl6(CH3OH)8(H2O)4]·Cl2(CH3OH)9(H2O)3 (1) and [Cu4Tb4L4Cl6(CH3OH)2(H2O)10]·Cl2(H2O)x (2). Single-crystal X-ray diffraction studies revealed that these two complexes are isostructural and can be viewed as being built from two {Cu2Ln2L2} (Ln = Dy or Tb) butterfly-shaped units. Direct current magnetic susceptibilities and field-dependent magnetization measurements demonstrated the presence of strong ferromagnetic interaction between CuII and LnIII and magnetic anisotropy. Furthermore, alternating current (ac) magnetic measurements illustrated that these two complexes showed temperature- and frequency-dependent signals in the out-of-phase ac susceptibility under zero applied field, which are typical features of the slow relaxation of the magnetization for 1 and 2. The effective energy barrier (Ueff) for 1 was 54 K, which is one of the highest Ueff values yet reported for CuII/LnIII single-molecule magnets.

4.
Eur J Endocrinol ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999622

RESUMO

OBJECTIVE: A subset of normal-weight individuals appears predisposed to obesity-related cardiometabolic abnormalities. Studies of this metabolically obese, normal weight (MONW) phenotype in youth are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. METHODS: Overall, 1,475 normal-weight Chinese children aged 6-18 were recruited from the Beijing Children and Adolescents Metabolic Syndrome study cohort. Birthweight, childhood lifestyle, socio-economic factors, and 20 genetic variants previously shown to be associated with BMI or glucose metabolism in East Asian adults were examined for their association with the MONW phenotype. MONW was defined by exhibiting any metabolic syndrome component. RESULTS: After adjusting for covariates including BMI, low birthweight and low levels of physical activity, fruit consumption, parental education and household income, as well as CDKAL1 rs2206734 genotype, were independent predictors of the MONW phenotype (all P<0.05). Moreover, rs2206734 interacted with birthweight to predict the MONW phenotype (Pinteraction=0.0008). Among high (>75th percentile) birthweight individuals, each C allele at this locus was associated with a 62% reduced risk of MONW (OR=0.38; 95% CI=0.26-0.58; P=5.71×10-6), while no such genetic associations were found in intermediate or low birthweight individuals (P >0.1). This CDKAL1-MONW relationship in high birthweight individuals was especially strong in the presence of favorable childhood environmental factors (high levels of physical activity, fruit consumption, parental education and household income) (Pinteraction=0.013). CONCLUSIONS: Our findings provided the novel evidence that early environment (especially birthweight) and genetics, along with their interaction with one another, play important roles in predicting the MONW phenotype among children.

5.
Cell Death Dis ; 11(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907353

RESUMO

Ubiquitin-conjugating enzyme E2O (UBE2O) is a large E2 ubiquitin-conjugating enzyme that possesses both E2 and E3 ligase activities. Ectopic UBE2O overexpression is associated with a variety of human diseases, especially cancers. However, the expression profile and functional biology of UBE2O in human breast cancer (BC) remain unclear. In this study, we found that UBE2O was significantly overexpressed in human BC tissues and cells. Patients with high UBE2O expression tended to have a high risk of metastasis and poor prognosis. In vitro assays revealed that UBE2O promoted BC cell proliferation and epithelial-mesenchymal transformation (EMT) and endowed BC cells with cancer stemness properties (CSPs). UBE2O knockdown in MDA-MB-231 cells suppressed tumour growth and lung metastasis in MDA-MB-231 xenograft mouse models. Mechanistically, UBE2O functioned as a ubiquitin enzyme of AMPKα2, promoting its ubiquitination and degradation and thus activating the mTORC1 signal pathway and contributing to BC oncogenesis and metastasis. Furthermore, as a downstream factor of the UBE2O/AMPKα2/mTORC1 axis, the oncoprotein MYC transcriptionally promoted UBE2O and formed a positive feedback loop in human BC. Collectively, our study demonstrated that UBE2O/AMPKα2/mTORC1-MYC forms a positive feedback loop in human BC cells that regulates BC cell proliferation and EMT and endows BC cells with CSPs.

6.
PLoS One ; 15(1): e0227532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940324

RESUMO

OBJECTIVES: To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration. RESULTS: The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60-23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17-26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71-197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24-15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity. CONCLUSION: Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.

7.
Neurosci Lett ; 717: 134654, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31785308

RESUMO

BACKGROUND: SS31 has been shown to have neuroprotective effects in a number of neurological degenerative diseases. However, the mechanisms and its role of neuroprotection after subarachnoid hemorrhage (SAH) remain unexplored. The aim of the present study is to evaluate the neuroprotective effects of SS31 on early brain injury (EBI) induced by SAH in rats and the potential mechanisms of the protective effects of SS31. METHODS: Sprague-Dawley rats were randomly divided into four groups: Sham, SAH, SAH + vehicle, and SAH + SS31 groups. The SAH-induced prechiasmatic cistern rat model was established in this study. Neurological scores were evaluated at 24 h and 72 h after SAH. The brain edema, blood-brain barrier (BBB) permeability, neuronal apoptosis, malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, as well as the expression of mitochondrial and cytosolic cytochrome C (Cyt C), and Bax were analyzed at 24 h after SAH. RESULTS: When compared with the vehicle-treated group, treatment with SS31 significantly reduced MDA levels and restored the activities of GPx and SOD in the temporal cortex following SAH when compared with the vehicle-treated group. In addition, the levels of mitochondrial Cyt C and Bax respectively increased and decreased by SS31 treatment. Moreover, SS31 treatment ameliorated brain edema and Evans blue dye extravasation, improved neurological deficits, and decreased neuronal apoptosis at 24 h after SAH. CONCLUSION: Our data provides initial evidence that SS31 could alleviate EBI after SAH through its antioxidant property and ability in inhibiting neuronal apoptosis, likely by modulating the mitochondrial apoptotic pathway.

8.
Neurosci Lett ; 715: 134611, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31698026

RESUMO

Continuous theta burst stimulation (cTBS) has been widely recognized as a therapeutic treatment for ischemic stroke, but the underlying mechanism is still elusive. Here, we investigated the protective effects of cTBS in the posterior parietal cortex during the chronic phase of stroke in the photothrombotic ischemic model. Infarction volume and neuron excitability in the peri-infarct area were assessed using immunohistochemistry and whole-cell patch-clamp. Spatial cognitive function was measured using the Morris water maze. Gamma-Amino butyric acid (GABA) interneurons were responsive to cTBS, and cTBS induced elevated phasic inhibition rather than tonic inhibition. Given that GABA-A-mediated phasic inhibition was elevated during the chronic phase of ischemic stroke for 30 days and was beneficial for stroke recovery, we investigated the therapeutic potential of cTBS in promoting functional recovery and found that the elevated phasic inhibition by cTBS improved spatial cognitive function in the photothrombotic stroke mouse model with induction in the posterior parietal cortex. Our study indicates the mechanism by which cTBS may modify the excitability of the brain cortex and provides novel insight into the potential of cTBS to protect against neuronal dysfunction in ischemic stroke.

9.
Stem Cells ; 38(2): 218-230, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31648394

RESUMO

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD.

10.
J Atheroscler Thromb ; 27(1): 71-99, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31142690

RESUMO

AIM: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS. METHODS: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with early-onset ICAS and 21 age- and gender-matched controls. RESULTS: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P=0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586-0.866; P=0.002). CONCLUSIONS: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.

11.
J Environ Sci (China) ; 88: 145-154, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862056

RESUMO

A series of vanadium based catalysts (VxMn(4-x)Mo3Ce3/Ti) with different vanadium (x wt.%) and manganese ((4-x) wt.%) contents have been prepared by the wet impregnation method and investigated for selective catalytic reduction (SCR) of NOx by NH3 in the presence of 8 vol.% H2O and 500 ppmV SO2. The physicochemical characteristics of the catalysts were thoroughly characterized. The SCR of NOx by NH3 (NH3-SCR) activity, especially the low-temperature activity, significantly increased with increasing V2O5 content in the catalyst until the V2O5 content reached 1.5 wt.%, which corresponds well with the redox properties of the catalyst. All of the metal oxides were well dispersed and strongly interacted with each other on the catalyst surface. V mainly exists in the V5+ state in the catalysts. The strong synergistic effect between the vanadium and cerium species led to formation of more Ce3+ species, and that between the vanadium and manganese species contributed to formation of more manganese species with low valences. All of the catalysts exhibited strong acidity, while the redox properties determined the NH3-SCR activity, especially the low-temperature activity. H2O and SO2 had severe inhibiting effects on the activity of V1.5Mn2.5Mo3Ce3/Ti. However, good H2O and SO2 resistance and high NOx conversion by V1.5Mn2.5Mo3Ce3/Ti could be achieved in the presence of SO2 and almost no decline was observed in a long-term test at 275°C for 168 hr in the presence of SO2 and H2O, which can be attributed to the sulfate species formed on the catalyst surface.

12.
Physiol Biochem Zool ; 93(1): 13-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31657971

RESUMO

The surface area (SA) theory proposes that resting metabolic rate (RMR) scales with body mass, which parallels the exchange SA of organisms, and that a species with a larger scaling exponent of exchange SA has a larger scaling exponent of RMR. However, the effects of exchange SA on metabolic scaling may be eclipsed because oxygen transfer across the respiratory surface is determined not only by the exchange SA but also by ventilation. We hypothesize that the scaling of both gill surface area (GSA) and ventilation frequency (VF) positively affects the scaling of metabolic rate. In six closely related species of carp maintained under the same experimental conditions, the scaling exponents of RMR and GSA were analyzed. In the goldfish, RMR scaled with body mass by an exponent significantly lower than that of GSA but not different from the exponents of GSA in the remaining five species. The scaling exponent of RMR was positively related to those of both GSA and VF among the species. In addition, the VF-corrected metabolic scaling exponent was positively related to the scaling exponent of GSA among the species. These results suggest that variations in GSA scaling and in VF scaling among species mutually affect metabolic scaling.

13.
J Hazard Mater ; 381: 120998, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31422345

RESUMO

The type of chalcopyrite plays a key role in determining its physicochemical properties. In this study, we present a systematic comparative study on the use of p- and n-type chalcopyrite (Cpy A and Cpy B, respectively) as Fenton catalysts for wastewater treatment. Experimental results showed that 60% of AO7 removal could be achieved in 30 min at a natural pH when H2O2 was activated by Cpy A. The removal rate could be further enhanced by up to 100% within 5 min using Cpy B as the catalyst. This is because Cpy B released far more Cu+ and Fe2+ ions, and less Cu2+ after being washed, and then activated H2O2 to produce more ·OH radicals (main active species). On the other hand, the excess copper ions released from Cpy A could react with AO7 to generate an intermediate product that would negatively affect the degradation process. Finally, the relative contribution of the homogeneous vs. heterogeneous process was calculated. Although only about 20% of the contribution for AO7 degradation was provided by heterogeneous processes in both systems, the time for full removal could be obviously reduced to 5 min from 20 min (homogeneous process) in the Cpy B/H2O2 system.

14.
Brain Res ; 1726: 146488, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586625

RESUMO

Acute ischemic stroke is a leading cause of disability with limited therapeutic options. Continuous theta burst stimulation (cTBS) has recently been shown to be a promising noninvasive therapeutic strategy for neuroprotection in ischemic stroke patients. Here, we investigated the protective effects of cTBS following acute infarction using a photothrombotic stroke (PTS) model in the right posterior parietal cortex (PPC) of C57BL/6 mice. Treatment with cTBS resulted in a reduction in the volume of the infarct region and significantly increased vascular diameter and blood flow velocity in peri-infarct region, as well as decreased the numbers of calcium binding adapter molecule 1 (Iba-1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes. Moreover, the number of CD16/32 positive microglia was decreased, whereas the number of CD206 positive microglia was increased. In addition, performance in a water maze task was significantly improved. These results indicated that cTBS protected against PPC infarct region, leading to an improvement in spatial cognitive function, possibly as a result of changes to cerebral microvascular function and inflammatory responses.

15.
Int J Nanomedicine ; 14: 8819-8834, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819410

RESUMO

Purpose: Age-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases. Methods: We prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications. Results: The eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model. Conclusion: The eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31849167

RESUMO

Commercial ultrafiltration membranes have proliferated globally for water treatment. However, their pore sizes are too large to sieve gases. Conjugated microporous polymers (CMPs) feature well-developed microporosity yet are difficult to be fabricated into membranes. Herein, we report a strategy to prepare molecular-sieving membranes by partitioning the mesoscopic channels in water ultrafiltration membrane (PSU) into ultra-micropores by space-confined polymerization of multi-functionalized rigid building units. Nine CMP@PSU membranes were obtained, and their separation performance for H2 /CO2 , H2 /N2 , and H2 /CH4 pairs surpass the Robeson upper bound and rival against the best of those reported membranes. Furthermore, highly crosslinked skeletons inside the channels result in the structural robustness and transfer into the excellent aging resistance of the CMP@PSU. This strategy may shed light on the design and fabrication of high-performance polymeric gas separation membranes.

17.
Adv Sci (Weinh) ; 6(22): 1901240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763143

RESUMO

Tissue engineering produces constructs with defined functions for the targeted treatment of damaged tissue. A complete spinal cord injury (SCI) model is generated in canines to test whether in vitro constructed neural network (NN) tissues can relay the excitatory signal across the lesion gap to the caudal spinal cord. Established protocols are used to construct neural stem cell (NSC)-derived NN tissue characterized by a predominantly neuronal population with robust trans-synaptic activities and myelination. The NN tissue is implanted into the gap immediately following complete transection SCI of canines at the T10 spinal cord segment. The data show significant motor recovery of paralyzed pelvic limbs, as evaluated by Olby scoring and cortical motor evoked potential (CMEP) detection. The NN tissue survives in the lesion area with neuronal phenotype maintenance, improves descending and ascending nerve fiber regeneration, and synaptic integration with host neural circuits that allow it to serve as a neuronal relay to transmit excitatory electrical signal across the injured area to the caudal spinal cord. These results suggest that tissue-engineered NN grafts can relay the excitatory signal in the completely transected canine spinal cord, providing a promising strategy for SCI treatment in large animals, including humans.

18.
Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756487

RESUMO

OBJECTIVE: Fas is a positive regulator of Th17 cells differentiation in experimental autoimmune encephalomyelitis (EAE). However, its upstream regulators are still not fully determined. This study was designed to explore the upstream regulators of Fas in regulating Th17 cells differentiation in EAE. METHODS: The mouse model of EAE was established by myelin oligodendrocyte glycoprotein injection. Th17 cells differentiation was induced by IL-23, IL-6 and TGF-ß. RESULTS: Down-regulated Hsp70 and miR-374c and up-regulated Fas were observed in the spleen and brain of EAE mice. Hsp70 overexpression evidently reduced Fas protein level, but not mRNA level. The luciferase reporter assay indicated that miR-374c targets Fas. Overexpression of miR-374c down-regulated the mRNA and protein level of Fas. The concentration of IL-17A in CD4+ T-cells was reduced by miR-374c or Hsp70 overexpression, and Fas overexpression altered this trend. Hsp70 did not regulate the expression of miR-374c, and likewise, miR-374c did not regulate the expression of Hsp70. Further results suggested that Hsp70 and miR-374c regulated Fas expression through different ways to affect Th17 cells differentiation in EAE. CONCLUSIONS: This study suggested that down-regulated miR-374c and Hsp70 promote Th17 cell differentiation by inducing Fas expression in EAE.

19.
BMC Health Serv Res ; 19(1): 873, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752845

RESUMO

BACKGROUND: The statement format of the Decisional Conflict Scale (sf-DCS) is designed and widely used to assess patients' state of uncertainty during health related decision making. As yet no Mandarin version of the sf-DCS has been produced. This study aims to produce the first Mandarin version of the sf-DCS and test its validity and reliability in mainland China. METHODS: The translation and cross-cultural adaptation of the original English version of the sf-DCS into Mandarin was carried out in accordance with previously published guidelines. The psychometric properties of sf-DCS were assessed in two hypothesized decision-making contexts through online surveys. RESULTS: In the online survey designed to test scale validity and reliability, 437 people responded to the influenza immunization survey and 238 responded to the breast cancer screening survey. The results confirm that the Mandarin version of sf-DCS has good criteria validity and the exploratory factor analysis suggested a fitted revised five factors model by removing three items. Respondents who were "unsure" about their decisions/intentions, had read less information, and reported lower self-perceived prior knowledge level scored higher on sf-DCS. The Cronbach's alpha for the sf-DCS total score was 0.963 and that for each subscale ranged from 0.784 to 0.937 in both decision making contexts, and the test-retest correlation coefficient was 0.528. CONCLUSIONS: The Mandarin version of sf-DCS has good criteria validity and its internal consistency is satisfactory. Our analysis suggests a refinement of the original sf-DCS's factor structure is needed.

20.
Nat Med ; 25(11): 1739-1747, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700183

RESUMO

Type 2 diabetes is characterized by insulin resistance and a gradual loss of pancreatic beta cell mass and function1,2. Currently, there are no therapies proven to prevent beta cell loss and some, namely insulin secretagogues, have been linked to accelerated beta cell failure, thereby limiting their use in type 2 diabetes3,4. The adipokine adipsin/complement factor D controls the alternative complement pathway and generation of complement component C3a, which acts to augment beta cell insulin secretion5. In contrast to other insulin secretagogues, we show that chronic replenishment of adipsin in diabetic db/db mice ameliorates hyperglycemia and increases insulin levels while preserving beta cells by blocking dedifferentiation and death. Mechanistically, we find that adipsin/C3a decreases the phosphatase Dusp26; forced expression of Dusp26 in beta cells decreases expression of core beta cell identity genes and sensitizes to cell death. In contrast, pharmacological inhibition of DUSP26 improves hyperglycemia in diabetic mice and protects human islet cells from cell death. Pertaining to human health, we show that higher concentrations of circulating adipsin are associated with a significantly lower risk of developing future diabetes among middle-aged adults after adjusting for body mass index (BMI). Collectively, these data suggest that adipsin/C3a and DUSP26-directed therapies may represent a novel approach to achieve beta cell health to treat and prevent type 2 diabetes.


Assuntos
Complemento C3a/genética , Fator D do Complemento/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fosfatases de Especificidade Dupla/genética , Células Secretoras de Insulina/efeitos dos fármacos , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Animais , Índice de Massa Corporal , Desdiferenciação Celular/efeitos dos fármacos , Fator D do Complemento/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Hiperglicemia/patologia , Insulina/genética , Resistência à Insulina/genética , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Endogâmicos NOD
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