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1.
Artigo em Inglês | MEDLINE | ID: mdl-32163642

RESUMO

BACKGROUND: Ocular involvement can occur at any stage of syphilis. Prompt diagnosis and proper treatment of ocular syphilis are vital to avoid long-term consequences. OBJECTIVES: To describe the risk factors for ocular syphilis and clinical features of blindness caused by syphilis. METHODS: We report risk factors for ocular syphilis amongst patients seen at the Shanghai Skin Disease Hospital between October 2009 to October 2017. We identify patients with ocular syphilis resulting in blindness and report the clinical characteristics, laboratory findings and treatment outcomes of these patients. RESULTS: A total of 8310 new cases of syphilis were seen, of which 213 patients had ocular disease and 50 patients had blindness due to syphilis. Increasing age and higher RPR titers were associated with ocular involvement but there was no association with HIV status. Blindness in syphilis was restricted predominantly to patients with optic nerve involvement and not patients with isolated uveitis. Fifty patients (and a total of 67 eyes) met the WHO definition of blindness prior to treatment for syphilis. At the end of follow-up vision had improved in 24 of 67 eyes (35.8%) after treatment. Successful treatment of uveitis was associated with the best improvement in visual acuity, whilst patient with underlying optic atrophy prior to treatment had the worst visual outcome. CONCLUSIONS: Ocular involvement is an important manifestation of syphilis which may result in blindness. Our data demonstrates outcomes for ocular syphilis are poor if detected late; early recognition and diagnosis is therefore vital to avoid permanent visual loss.

2.
J Mol Histol ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193744

RESUMO

As a crucial virulence factor of Porphyromonas gingivalis, gingipains play an important role in periodontal destruction. This study aimed to investigate the effect of gingipains on osteoclastogenesis. We used RAW264.7 cells as osteoclast precursors in our study. In experimental groups, cells were treated with gingipains and/or receptor activator of nuclear factor-κB ligand (RANKL). Tartrate-resistant acid phosphatase (TRAP) activity staining assay showed osteoclast precursors and RANKL-induced mature osteoclasts were increased in a gingipains dose-dependent manner. Real-time reverse transcription polymerase chain reaction analysis demonstrated that gingipains upregulated osteoclastic genes including the protease cathepsin K (Ctsk), matrix metalloprotein 9 (Mmp9), nuclear factor of activated T cells 1 (Nfatc1) and acid phosphatase 5, tartrate resistant (Acp5) in a time-dependent manner. Western blotting assays presented upregulated expressions of TNF receptor-activating factor 6 (TRAF6) and integrin ß3 induced by gingipains and RANKL compared to RANKL alone. Enhanced integrin-related signaling was also demonstrated by elevated phosphorylations of FAK and paxillin compared to control. Moreover, the pit resorption assays showed that gingipains augmented bone resorptive function of osteoclasts induced by RANKL. When we used Cilengitide to block integrin αvß3, gingipains reversed the reduction of formation and resorptive function in RANKL-induced osteoclasts, as they enhanced integrin αvß3 levels more than RANKL treatment alone. In conclusion, our data suggest that gingipains augmented the differentiation and function of mature osteoclasts induced by RANKL through the increase in integrin αvß3.

3.
J Biomater Sci Polym Ed ; : 1-14, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175824

RESUMO

Cancer is one of the biggest killers threat to human life and health and is still difficult to treat mainly due to the lack of targeted drug delivery stages and limitations associated with delivering drugs to targeted cancer tissues. The goal of this work was to develop a magnetic, pH-sensitive formulation for targeted delivery of chemotherapeutic agents to cancer cells. Then the functional drug delivery system (Fe3O4@CS/PEG-DOX) was synthesized by the layer-by-layer (LbL) self-assembly technique. And the drug loading content is calculated to be 19.1%. In addition, the Fe3O4@CS/PEG-DOX exhibited excellent pH-sensitivity, 73.1% DOX was released within 48 h at pH 4.0. Furthermore, all the release behaviors fit the Higuchi model very well and the dissolution of CS/PEG layers played a key role on DOX release from Fe3O4@CS/PEG-DOX. The results of toxicity analysis in human liver hepatocellular carcinoma cells (HepG2) revealed that Fe3O4@CS/PEG-DOX exhibited high anti-tumor activity, while the Fe3O4@CS/PEG nanocomposites were practically non-toxic. Therefore, all the results demonstrated that the Fe3O4@CS/PEG-DOX could have an important impact on the development of targeted intracellular delivery nanodevices for cancer therapy.

4.
Sci Total Environ ; 721: 137689, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32169643

RESUMO

Step-feeding (SF) strategies have been adopted in several types of constructed wetlands (CWs) to enhance nitrogen (N) removal. However, it is unclear how SF affects the N-transforming bacterial communities in CWs. Herein, four multi-stage vertical flow constructed wetlands (MS-VFCWs), each including three vertical flow stages (stage 1-3), were operated under different SF ratios (0%, 10%, 20% and 30%) in the stage 2. The physicochemical influent and effluent parameters, i.e., redox potential (ORP), pH value, chemical oxygen demand (COD), total nitrogen (TN), ammonia (NH4+-N), nitrate (NO3--N), and nitrite (NO2--N), free-ammonia (FA) concentration, COD/TN ratio, as well as the abundance, structure, and activity of N-transforming bacteria were investigated. Results showed that N removal in a multi-stage vertical flow constructed wetland in the absence of SF was 45.0 ± 7.74%. Alternatively, a combined SF ratio of 20% increased N removal to 61.7% ± 4.50%, accounting for a 37.1% increase compared to the SF ratio of 0%. In the microbial community, FA was determined to be the primary physicochemical parameter governing nitrification processes in MS-VFCWs. Further, partial nitrification processes played an important role in ammonium removal during stage 1, while ammonia-oxidizing archaea were major contributors to ammonium removal in stage 3. Furthermore, abundance of nitrite reductase genes (nirS, nirK) and relative abundance of denitrifying bacteria increased with increasing SF ratio; while the nirS/nirK ratio and the alpha diversity of nirK denitrifiers were significantly affected by SF ratios, and the influent NO3--N concentration was related to a shift in denitrifier composition toward strains containing the nirS gene. Autotrophic (e.g., Thiobacillus, Sulfurimonas, Arenimonas, Gallionella and Methyloparacoccus) and facultative chemolithoautotrophic (e.g., Pseudomonas and Denitratisoma) denitrifying bacteria were enriched in stage 2. Hence, the synergy between heterotrophic and autotrophic denitrifying bacteria promoted excellent N removal efficiency with a low COD/TN ratio.

5.
J Zhejiang Univ Sci B ; 21(3): 256-262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133802

RESUMO

Primary age-related tauopathy (PART) is characterized by the presence of tau neurofibrillary tangles (NFTs) which are typically observed in Alzheimer's disease (AD) brains, with few or without ß-amyloid (Aß) plaques. The diagnosis of PART can be categorized into "definite" or "possible" depending on the amount of Aß plaques. Definite PART is diagnosed when NFTs are observed and the Braak stage is ≤IV, with Thal Aß Phase 0 (Crary et al., 2014). According to the neuropathological diagnostic criteria, we reported that PART was frequently observed in the Chinese population according to our findings from specimens in our brain bank, with 47% of brain bank subjects meeting the criteria for PART. There is no consensus on the nature of PART. It remains to be elucidated whether PART is an early form of AD or a novel tauopathy (Duyckaerts et al., 2015; Jellinger et al., 2015).

6.
Noncoding RNA ; 6(1)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110879

RESUMO

AtR8 lncRNA was previously identified in the flowering plant Arabidopsis thaliana as an abundant Pol III-transcribed long non-coding RNA (lncRNA) of approximately 260 nt. AtR8 lncRNA accumulation is responsive to hypoxic stress and salicylic acid (SA) treatment in roots, but its function has not yet been identified. In this study, microarray analysis of an atr8 mutant and wild-type Arabidopsis indicated a strong association of AtR8 lncRNA with the defense response. AtR8 accumulation exhibited an inverse correlation with an accumulation of two WRKY genes (WRKY53/WRKY70) when plants were exposed to exogenous low SA concentrations (20 µM), infected with Pseudomonas syringae, or in the early stage of development. The highest AtR8 accumulation was observed 5 days after germination, at which time no WRKY53 or WRKY70 mRNA was detectable. The presence of low levels of SA resulted in a significant reduction of root length in atr8 seedlings, whereas wrky53 and wrky70 mutants exhibited the opposite phenotype. Taken together, AtR8 lncRNA participates in Pathogenesis-Related Proteins 1 (PR-1)-independent defense and root elongation, which are related to the SA response. The mutual regulation of AtR8 lncRNA and WRKY53/WRKY70 is mediated by Nonexpressor of Pathogenesis-Related Gene 1 (NPR1).

7.
Perit Dial Int ; 40(1): 26-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32063144

RESUMO

BACKGROUND: This study was to analyze the incidence, risk factors, and clinical outcomes of peritonitis in elderly continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Incident patients undergone CAPD from 1 January 2006 to 30 June 2015 in our center were enrolled and divided into aged < 65 years and ≥ 65 years groups. Risk factors were evaluated using a logistic regression model, and outcome comparison was evaluated using a Cox proportional model. RESULTS: Among 1953 patients, 111(33.2%) in elderly (n = 334) and 470 (29.0%) in younger (n = 1619) developed at least one episode of peritonitis. Comparing with younger patients, elderly ones had a higher peritonitis rate (0.203 vs. 0.145 episodes/patient-year, p < 0.05). The multivariate Cox regression showed that advanced age (hazard ratio (HR) = 1.06, 95% confidence interval (CI) = 1.01-1.11, p = 0.015), assistant-assisted peritoneal dialysis (PD; HR = 2.64, 95% CI = 1.23-5.64, p = 0.012), higher body mass index (BMI; HR = 1.11, 95% CI = 1.02-1.20, p = 0.010), and low serum albumin level (HR = 0.94, 95% CI = 0.90-0.98, p = 0.004) were associated with increased peritonitis risk in elderly patients. Compared with younger ones with peritonitis, elderly patients had an approximately fourfold increased risk of peritonitis-related mortality (odd ratio (OR) = 3.57, 95% CI = 1.38-9.28, p = 0.009). During the cohort, peritonitis was the risk factor associated with technique failure (HR = 3.19, 95% CI = 2.33-4.39, p < 0.001) in younger patient but not in the elderly population (HR = 1.82, 95% CI = 0.84-3.94, p = 0.132). CONCLUSIONS: Elderly PD patients had higher prevalence for peritonitis and peritonitis-related mortality. Advanced age, assistant-assisted PD, a higher BMI, and lower serum albumin level were independently associated with the first episode of peritonitis in elderly patients. However, peritonitis was not the predictor of death-censored technique failure in elderly ones.

8.
Environ Pollut ; 261: 114117, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32062092

RESUMO

Whether toxicity of silver nanoparticles (AgNPs) to organisms originates from the nanoparticles themselves or from the dissolved Ag-ions is still debated, with the majority of studies claiming that extracellular release of Ag-ions is the main cause of toxicity. The objective of this study was to determine the contributions of both particles and dissolved ions to toxic responses, and to better understand the underlying mechanisms of toxicity. In addition, the pathways of AgNPs exposure to plants might play an important role and therefore are explicitly studied as well. We systematically assessed the phytotoxicity, internalization, biodistribution, and antioxidant responses in lettuce (Lactuca sativa) following root or foliar exposure to AgNPs and ionic Ag at various concentrations. For each endpoint the relative contribution of the particle-specific versus the ionic form was quantified. The results reveal particle-specific toxicity and uptake of AgNPs in lettuce as the relative contribution of particulate Ag accounted for more than 65% to the overall toxicity and the Ag accumulation in whole plant tissues. In addition, particle toxicity is shown to originate from the accumulation of Ag in plants by blocking nutrient transport, while ion toxicity is likely due to the induction of excess ROS production. Root exposure induced higher toxicity than foliar exposure at comparable exposure levels. Ag was found to be taken up and subsequently translocated from the exposed parts of plants to other portions regardless of the exposure pathway. These findings suggest particle related toxicity, and demonstrate that the accumulation and translocation of silver nanoparticles need to be considered in assessment of environmental risks and of food safety following consumption of plants exposed to AgNPs by humans.

9.
Nanoscale ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009133

RESUMO

As an anode electrode material for lithium-ion batteries, SnS has high specific capacity and has received widespread attention, but its practical application is still hindered by the low reversibility of the conversion reaction and the large irreversible capacity caused by the solid electrolyte interphase (SEI). In this paper, SnS nanoparticles are encapsulated into a sulfur-doped graphene bubble film (SnS@G) by a scalable electrostatic self-assembly of SnS2/graphene oxide and hexadecyl trimethyl ammonium bromide, followed by the thermal decomposition of SnS2 and sulfur doping in graphene. Due to electrostatic attraction, the SnS nanoparticles are tightly wrapped in multilayer graphene sheets to form a flake-graphite-like structure. Compared with the disordered stacked SnS/graphene sheet composite, the closely packed SnS@G shows a much lower specific surface area and smaller irreversible Li+ consumption and surface film resistance after lithiation. The SnS@G composite anode exhibits great initial coulombic efficiency (83.2%), which is the highest value among the chemically synthesized SnS anodes. It also presents unprecedented cycling stability (1462 mA h g-1 after 200 cycles at 0.1 A g-1 and 1020 mA h g-1 after 500 cycles at 1 A g-1) and superior rate capabilities (750 mA h g-1 at 5 A g-1) upon Li storage, which demonstrates its excellent electrochemical performance and great potential as a negative electrode material for lithium-ion batteries.

10.
Curr Mol Med ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32072910

RESUMO

PURPOSE: A small molecular compound, aminooxy-acetic acid (AOA), has been shown to modulate experimental autoimmune encephalomyelitis (EAE). The current study was designed to investigate whether AOA has a similar effect on the development of experimental autoimmune uveitis (EAU) and to further explore underlying mechanisms of this drug. METHODS: EAU was induced in C57BL/6J mice by immunization with interphotoreceptor retinoid binding protein peptide 651-670 (IRBP 651-670). AOA (500µg or 750µg) or vehicle was administered by intraperitoneal injection from day 10 to 14 after EAU induction. The severity was assessed by clinical and histological scores. The integrity of the blood retinal barrier was detected with Evans Blue. Frequencies of splenic Th1, Th17 and Foxp3+ Treg cells were examined by flow cytometry. The production of cytokines was tested by ELISA. The mRNA expression of IL-17, IFN-γ and IL-10 was detected by RT-PCR. The expression of p-Stat1 and NF-κB was detected by Western Blotting. RESULTS: AOA was found to markedly inhibit the severity of EAU, as determined by clinical and histopathological examinations. AOA can relieve the leakage of blood retinal barrier (BRB). Functional studies found a decreased frequency of Th1 and Th17 cells and an increased frequency of Treg cells in EAU mice as compared with controls. Further studies showed that AOA not only downregulated the production of the pro-inflammatory cytokines including IFN-γand IL-17 but also upregulated the expression of anti-inflammatory cytokine such as IL-10, which might be caused by inhibiting the expressions of p-Stat1 and NF-κB. CONCLUSION: This study shows that AOA inhibits the severity and development of EAU by modulating the balance between regulatory and pathogenic lymphocyte subsets.

11.
Int J Biol Macromol ; 149: 81-92, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945436

RESUMO

Three algae polysaccharides (APs) extracted from Ascophyllum nodosum (ANP), Fucus vesiculosus (FVP) and Undaria Pinnatifida (USP) significantly differed in the zeta potential, water and oil holding capacity, monosaccharide composition, organic element composition, molecular weight distribution, microstructure and rheological properties. Antidiabetic effects of APs were compared by oral intervention at the dose of 400 mg/kg·body weight/day in high sugar and fat diets and streptozotocin injection induced type 2 diabetic rats. The analysis of body weight, water intake, fasting blood glucose, insulin, oral glucose tolerance, blood lipid indicators (including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA)), liver function indexes (involving alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and renal function profiles (comprising uric acid (UA) and urea nitrogen (BUN)) showed that APs possessed obvious antidiabetic activities, and FVP showed better effects in controlling the levels of FFA, AST, ALT, UA and BUN. Intervention of FVP reduced the total bile acid (TBA) level and elevated high density lipoprotein cholesterol (HDL-C) level of diabetic rats. Histomorphological observation further demonstrated that APs, especially FVP, could attenuate liver and kidney damage caused by diabetes. This study concluded that the antidiabetic effects of ANP, FVP and USP were distinctly different, which might be attributed to their different chemical structures. Therefore, the structure-activity relationship and antidiabetic mechanism of APs will be our future research direction.

12.
Mol Med Rep ; 21(2): 549-556, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974605

RESUMO

The purpose of the present study was to explore aging­associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4­month­old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress­related protein PKR­like ER kinase, glucose­regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP­specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age­induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age­induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP­protein kinase G signaling.

14.
Carbohydr Polym ; 230: 115578, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887880

RESUMO

The present work deals with a new type of hybrid polysaccharide-silica hydrogel fabricated by the sol-gel process in which a completely water-soluble precursor of tetrakis-(2-hydroxyethyl) orthosilicates (THEOS) and a biocompatible polysaccharide of carboxymethylated curdlan (CMCD) have been used. The kinetic gelation process, mechanical properties and morphological structures of hybrid silica hydrogels at different concentrations of CMCD and THEOS were investigated by dynamic rheology, compression testing and scanning electron microscopy. CMCD was found to be served as a catalyst and template in the sol-gel process of THEOS in water. The mechanical strength of the resulting silica gels was tunable by the modulation of either the concentration of CMCD or THEOS. Higher content of THEOS and CMCD resulted in stiffer gels. Due to the tunable mechanical property and good biocompatibility, these hybrid hydrogels are promising for the applications as drug release systems in biomedical fields.

15.
Int J Rheum Dis ; 23(3): 435-442, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31957331

RESUMO

OBJECTIVE: The aim of this study was to investigate cross-sectional associations between serum levels of citrate and knee structural changes and cartilage enzymes in patients with knee osteoarthritis (OA). METHOD: A total of 137 subjects with symptomatic knee OA (mean age 55.0 years, range 34-74, 84% female) were included. Knee radiography was used to assess knee osteophytes, joint space narrowing (JSN) and radiographic OA assessed by Kellgren-Lawrence (K-L) grading system. T2-weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI) was used to determine knee cartilage defects, bone marrow lesions (BMLs) and infrapatellar fat pad (IPFP) signal intensity alternations. Colorimetric fluorescence was used to measure the serum levels of citrate. Enzyme-linked immunosorbent assay was used to measure the serum cartilage enzymes including matrix metalloproteinase (MMP)-3 and MMP-13. RESULTS: After adjustment for potential confounders (age, sex, body mass index), serum citrate was negatively associated with knee osteophytes at the femoral site, cartilage defects at medial femoral site, total cartilage defects, and total BMLs (odds ratio [OR] 0.17-0.30, all P < .05). Meanwhile, serum citrate was negatively associated with IPFP signal intensity alteration (OR 0.30, P = .05) in multivariable analyses. Serum citrate was significantly and negatively associated with MMP-13 (ß -3106.37, P < .05) after adjustment for potential confounders. However, citrate was not significantly associated with MMP-3 in patients with knee OA. CONCLUSION: Serum citrate was negatively associated with knee structural changes including femoral osteophytes, cartilage defects, and BMLs and also serum MMP-13 in patients with knee OA, suggesting that low serum citrate may be a potential indicator for advanced knee OA.

16.
Int J Biol Macromol ; 147: 428-438, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31899245

RESUMO

Two polysaccharide fractions (SFPs, designated as respectively SFP-1 and SFP-2) were acquired from Sargassum fusiforme by ultrasound-assisted enzymatic extraction, and their physicochemical properties and hypoglycemic and hypolipidemic effects were investigated. Structural analysis indicated that SFPs were obvious different in the zeta potential, molecular weight distribution, characteristic organic group, microstructure and the contents of total sugar, uronic acid, sulfate and moisture. SFPs consisted of fucose, mannose, rhamnose, glucose, galactose and glucuronic acid with different molar ratios. Congo red test explained that SFPs had no triple-helix structure. SFP-1 exhibited lower viscosity due to its lower molecular weight. Regarding to hypoglycemic and hypolipidemic effects, oral administration of SFPs prominently restrained loss of body weight and increase of water intake, and also significantly controlled the increase of levels of fasting blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), uric acid (UA), urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of diabetic rats, and SFP-2 showed better effects in controlling fasting blood glucose, ALT, UA and BUN levels. Intervention of SFP-2 reduced the levels of insulin, FFA and TBA of diabetic rats. Histomorphological observation further demonstrated that SFPs could attenuate liver and kidney damage caused by hyperglycemia and hyperlipidemia. Data indicated that SFPs, especially SFP-2, significantly improved hyperglycemia, hyperlipidemia and liver and kidney function of diabetic rats.

17.
Toxicology ; 432: 152381, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31981724

RESUMO

Chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative disorders. A small but significant loss of membrane cholesterol has been reported following a short stimulation of ionotropic glutamate receptors (iGluRs). We investigated the alteration of brain cholesterol following chronic glutamate treatment. The alteration of cholesterol levels was evaluated in the hippocampus from the adult rats that received the subcutaneous injection with monosodium l-glutamate at 1, 3, 5, and 7 days of age. The regulation of CYP46A1, LXRα, and ApoE levels were assayed following subtoxic glutamate treatment in SH-SY5Y cells as well as HT-22 cells lacking iGluRs. The ratio of 24S-hydroxycholesterol to cholesterol was elevated in the adult rats exposed to monosodium l-glutamate before the weaning age, compared to the control. The blockers of NMDA receptor (MK801) and mGluR5 (MPEP) attenuated the glutamate-induced loss of cholesterol and elevation of 24S-hydroxycholesterol level in SH-SY5Y cells. The induction of the mRNA levels of CYP46A1, LXRα, and ApoE by glutamate was observed in both SH-SY5Y cells and HT-22 cells; additionally, MK801 and MPEP attenuated the increases in these genes in SH-SY5Y cells. The increase in the binding of LXRα proteins with ApoE promoter following glutamate treatment was attenuated by MK801. The luciferase assay indicated the binding of CREB protein with CYP46A1 promoter, and the glutamate-induced CREB expression was inhibited by MK801. The results suggest that glutamate, the major excitatory neurotransmitter, may affect the metabolism and redistribution of cholesterol in the neuronal cells via its specific receptors during chronic exposure.

18.
Biol Blood Marrow Transplant ; 26(3): 606-611, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31715306

RESUMO

Damage-associated angiogenic factors (AFs), including follistatin (FS) and soluble endoglin (sEng), are elevated in circulation at the onset of acute graft-versus-host disease (GVHD). We hypothesized that regimen-related tissue injury also might be associated with aberrant AF levels and sought to determine the relevance of these AF on nonrelapse mortality (NRM) in patients with acute GVHD and those without acute GVHD. To test our hypothesis, we analyzed circulating levels of FS, sEng, angiopoietin-2 (Ang2), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) A and B, placental growth factor (PlGF), and soluble VEGF receptor (sVEGFR)-1 and -2, in plasma samples from patients enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402 (n = 221), which tested GVHD prophylaxis after myeloablative hematopoietic stem cell transplantation (HCT). We found that the interaction between FS and sEng had an additive effect in their association with 1-year NRM. In multivariate analysis, patients with the highest levels of day +28 FS and sEng had a 14.9-fold greater hazard ratio (HR) of NRM (95% confidence interval, 3.2 to 69.4; P < .01) when compared with low levels of FS and sEng. We validated these findings using an external cohort of patients (n = 106). Pre-HCT measurements of FS and sEng were not associated with NRM, suggesting that elevations in these factors early post-HCT may be consequences of early regimen-related toxicity. Determining the mechanisms responsible for patient-specific vulnerability to treatment toxicities and endothelial damage associated with specific AF elevation may guide interventions to reduce NRM post-HCT.

19.
Dalton Trans ; 49(3): 651-658, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31844872

RESUMO

A novel 3D coordination polymer {[Cu4.5 (BTZE)1.5 (µ3-OH)3(µ-OH)(SO4)(H2O)1.5·4H2O]}n (1) was synthesized by a solvothermal reaction of 1,2-bis(tetrazol-5-yl) ethane (BTZE) with copper sulfate. Compound (1) contained triangular [Cu3(µ3-OH)] cluster based magnetic Δ-chains linked with in situ generated µ2-BTZE ligands to form a 2D cyclic annular layer. This 2D layer structure was further modified with sulfate and symmetry-related µ3-OH groups, extending to a 3D coordination framework structure. The magnetic performance of (1) was characterized in the temperature range of 2-300 K in terms of direct-current and alternating-current magnetic susceptibilities, revealing that (1) was a canted ferromagnet with a critical temperature (Tc) of 9.5 K. Notably, (1) behaved as a hard magnet with a coercive field of 2.3 kOe at 2 K, showing significant unique characteristics compared to those of the reported spin canting systems based on pure Cu(ii) ions.

20.
J Ethnopharmacol ; 248: 112304, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31626908

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Trillium tschonoskii Maxim, a perennial herb of the Trilliaceae, has been widely used to treat inflammation, hypertension and cancer. We investigated Paris saponin VII's (PS VII), isolated from Trillium tschonoskii Maxim, function in mediating autophagy and apoptosis in NSCLC cells. MATERIALS AND METHODS: We treated various NSCLC cells with different concentrations of PS Ⅶ and then measure the cell apoptosis by using flow cytometry assays and western blot. Autophagy were investigated by using western blot, transmission electron microscopy and immunofluorescence analysis. We also use a xenograft model of nude mice to measure the effect of PS Ⅶ in vivo. RESULTS: Treatment with PS Ⅶ significantly inhibit NSCLC cell growth, especially for A549 (IC50 = 1.53 µM). Moreover, PS VII induces caspase-dependent apoptosis and autophagy through AMPK-ULK1 pathway. After blocking autophagy by 3-methyladenine (3-MA), PS VII induced cell death was significantly increased. In vivo, the co-treatment with PS VII and 3-MA dramatically inhibited A549 tumor growth in immune deficient mice and has similar inhibition rates as cisplatin group. CONCLUSION: Our results suggest that a combination of PS VII and autophagy inhibitor may be a potential anticancer strategy in the NSCLC therapy.

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