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1.
Infect Dis Poverty ; 9(1): 14, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019611

RESUMO

BACKGROUND: Despite the availability of free tuberculosis (TB) diagnosis and treatment, TB care still generates substantial costs that push people into poverty. We investigated out-of-pocket (OOP) payments for TB care and assessed the resulting economic burden and economic consequences for those with varying levels of household income in eastern China. METHODS: A cross-sectional study was conducted among TB patients in the national TB programme networks in eastern China. TB-related direct OOP costs, time loss, and coping strategies were investigated across households in different economic strata. Analysis of Variance was used to examine the differences in various costs, and Kruskal-Wallis tests were used to compare the difference in total costs as a percentage of annual household income. RESULTS: Among 435 patients, the mean OOP total costs of TB care were USD 2389.5. In the lower-income quartile, OOP payments were lower, but costs as a percentage of reported annual household income were higher. Medical costs and costs prior to treatment accounted for 66.4 and 48.9% of the total costs, respectively. The lower the household income was, the higher the proportion of medical costs to total costs before TB treatment, but the lower the proportion of medical costs patients spent in the intensive phase. TB care caused 25.8% of TB-affected households to fall below the poverty line and caused the poverty gap (PG) to increase by United States Dollar (USD) 145.6. Patients in the poorest households had the highest poverty headcount ratio (70.2%) and PG (USD 236.1), but those in moderately poor households had the largest increase in the poverty headcount ratio (36.2%) and PG (USD 177.8) due to TB care. Patients from poor households were more likely to borrow money to cope with the costs of TB care; however, there were fewer social consequences, except for food insecurity, in poor households. CONCLUSIONS: Medical and pretreatment costs lead to high costs of TB care, especially among patients from the poorest households. It is necessary to train health system staff in general hospitals to promptly identify and refer TB patients. Pro-poor programmes are also needed to protect TB patients from the medical poverty trap.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31995526

RESUMO

The emerging two-dimensional (2D) materials such as graphene have opened the door to industrial applications. Here, we consider the oxide perovskite monolayer of SrTiO3(STO), LaAlO3(LAO) and their heterostructures as the two-dimensional transitional metal system. Results show that a band-gap transition from indirect to direct occurs when the separated monolayer STO (indirect band gap of 3.210 eV), and LAO (indirect band gap of 4.024 eV), form the heterostructures (direct band gap of 2.976 eV). The obtained bandgap for the stable bilayers may effectively be modulated by biaxial strains from -12% to 8%. With 12% compressive biaxial strain, the band gap reduces to be 0.23 eV. The optical properties for the stable bilayers are also tuned by the biaxial strain. When the strain increases from compressive strain to tensile strain, the strongest peak of the imaginary part of dielectric function red shifts to lower energy. In comparing with the monolayer STO and LAO, the elastic property enhances obviously for the stable heterostructure, suggesting the heterostructure can be more stable freestanding or may be applied in device fabrications.

3.
Medicine (Baltimore) ; 99(2): e18757, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914099

RESUMO

RATIONALE: Rosai-Dorfman disease (RDD) is a rare nonmalignant cell histiocytosis. Here, we report a rare, unusual clinical presentation of epibulbar and orbital tumor as a manifestation of RDD. We also review the literatures on clinical cases of orbital RDD. PATIENT CONCERNS: A 44-year-old Chinese male was admitted with a 3-month history of eye redness, subconjunctival mass, and diplopia. DIAGNOSIS: An initial diagnosis of epibulbar and orbital tumor was made according to the clinical symptoms, signs, and pre-operative contrast-enhanced computerized tomography results. INTERVENTIONS: The mass was completely resected and pathology confirmed the RDD diagnosis. The patient received steroids after surgery. OUTCOMES: The patient recovered well on 18-month follow-up. CONCLUSION: This appears to be the first report of RDD manifesting as epibulbar and orbital tumor. Pre-operative diagnosis of RDD remains challenging. When the lesion causes diplopia, surgical resection is the most effective treatment.


Assuntos
Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Adulto , Diagnóstico Diferencial , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/patologia , Histiocitose Sinusal/cirurgia , Humanos , Masculino , Tomografia Computadorizada por Raios X
4.
Nat Prod Res ; : 1-6, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951483

RESUMO

During the course of searching for structurally interesting and bioactive compounds, a further chemical investigation of the leaves of Heynea trijuga Roxburgh was performed, which led to the isolation of a new ergostane derivative, named 3ß, 4ß, 20S-trihydroxyergosta-5, 24(28)-dien-16-one (1), together with five known sterides (3ß, 23S)-ergosta-5, 24(28)-diene-3, 23-diol (2), ergosta-5, 24(28)-diene-3ß-diol (3), stigmast-5-ene-3ß, 7α-diol (4), sitoindoside I (5) and stigmast-3ß, 5α, 6ß-triol (6). The structure of the new compound was elucidated using a combination of 1 D, 2 D NMR techniques and HR-EI-MS analyses. All the compounds were evaluated for cytotoxic activity against tumor cell line BEL-7402 by MTT method.

5.
Nat Prod Res ; : 1-7, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31983227

RESUMO

Three new dimeric 2-(2-phenylethyl)chromones crassin I ∼ K (1-3), together with one known analogue (4), were isolated from the artificial holing agarwood originating from Aquilaria sinensis. Their structures including the absolute configuration were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR, ECD), and HRESIMS analysis, as well as by comparison with the literature data. Compounds 1 and 2 exhibited weak acetylcholinesterase inhibitory activity.

6.
J Am Chem Soc ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31986016

RESUMO

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.

7.
Bioorg Chem ; 95: 103551, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31911301

RESUMO

Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and DP4 calculations. The inhibitory effects of 1-12 against human gastric adenocarcinoma (AGS) cells were investigated in vitro, among which 1-3 and 8 showed remarkable cytotoxic activity with IC50 values in the range of 6.69-10.25 µM. The results suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on C-8. In order to rationalize the binding interactions of active compounds with the active site of NF-кB, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.

8.
J Pharm Biomed Anal ; 179: 112938, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31816471

RESUMO

Sennoside B is a specific dianthrone compound extracted from senna, which is widely used as a stimulant laxative but has potential side effects. This study aimed to obtain the metabolic and pharmacokinetic data of sennoside B. The metabolic profiles of sennoside B were obtained from rat plasma, urine, bile and feces by an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). As a result, 14 metabolites were structurally identified and the proposed metabolic pathways of sennoside B included hydrolysis to aglycones, release of rhein-type anthrone, and extensive conjugation. As the only compound detected in the plasma samples after intravenous and intragastric administrations, the prototype was selected as the plasma marker in the pharmacokinetic study. A simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitation of sennoside B in rat plasma. The linear range of sennoside B was 5-1000 ng/mL (R2 ≥ 0.991) and the lowest limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter- precisions of the assay were less than 10%, whereas accuracy ranged from 85.80% to 103.80%. The extraction recovery, matrix effect and stability of sennoside B were within acceptable limits. The established method was well validated and successfully applied to the pharmacokinetic study of sennoside B. The oral absolute bioavailability of sennoside B was calculated as 3.60% and the value apparent volume of distribution of intravenous and intragastric administrations were 32.47 ±â€¯10.49 L/kg and 7646 ±â€¯1784 L/kg, respectively. The maximum plasma concentrations were 212.6 ±â€¯50.9 µg/L and 14.06 ±â€¯2.73 µg/L for intravenous and intragastric dosing groups, respectively. According to the current results of pharmacokinetic and metabolic profiling studies, metabolites with high abundance in tissues would be the next object in the pharmacokinetic study of sennoside B.

9.
Int Immunopharmacol ; 78: 105947, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31796384

RESUMO

Our previous study has found that zileuton, a selective 5-lipoxygenase (5LO) inhibitor, abrogated lipopolysaccharide-induced depressive-like behaviors and hippocampal neuroinflammation. Herein, we further extended our curiosity to investigate effects of zileuton on stress-induced depressive-like behaviors. Our data indicated that zileuton significantly ameliorated depressive-like behaviors in mice subjected to chronic mild stress (CMS), as shown in the tail suspension test, forced swimming test and novelty-suppressed feeding test. The further studies indicated that zileuton suppressed hippocampal neuroinflammation, evidenced by lower levels of TNF-α, IL-1ß and nuclear NF-κB p65 as well as decreased number of Iba1-positive cells. It also significantly ameliorated hippocampal apoptosis, indicated by deceased number of TUNEL-positive cells, deceased ratio of cleaved caspase-3/procaspase-3 and increased ratio of Bcl-2/Bax. More importantly, zileuton increased the level of synaptic proteins PSD-95 and SYN and the number of NeuN+/BrdU+ cells in the hippocampus. Over all, zileuton alleviated CMS-induced depressive-like behaviors, neuroinflammatory and apoptotic responses, abnormalities of synapse and neurogenesis in the hippocampus, suggesting that it might has beneficial effects on depression.

10.
Endocrine ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786774

RESUMO

PURPOSE: Serum complement C3 has been shown to contribute to the incidence of type 2 diabetes (T2D), but how serum complement C3 affects islet ß-cell function throughout the course of T2D is unclear. This study explored whether serum complement C3 is independently associated with changes in islet ß-cell function over time in patients with T2D. METHODS: Serum complement C3 was measured, and endogenous ß-cell function was evaluated by area under the C-peptide curve (AUCcp) during an oral glucose tolerance test (OGTT) in 411 patients with T2D at baseline from 2011 to 2015. Next, 347 of those patients with available data were pooled for a final follow-up analysis from 2014 to 2018. Changes in islet ß-cell function at follow-up were evaluated by AUCcp percentage changes (ΔAUCcp%). In addition, other possible clinical risks for diabetes were also examined. RESULTS: The 347 patients included in the analysis had a diabetes duration of 4.84 ± 3.63 years at baseline. Baseline serum complement C3 (baseline C3) levels were positively correlated with baseline natural logarithm of AUCcp (lnAUCcp) (n = 347, r = 0.288, p < 0.001), and baseline C3 was independently associated with baseline lnAUCcp (ß = 0.17, t = 3.52, p < 0.001) after adjustment for baseline glycemic status and other clinical confounders by multivariate liner regression analysis. Compared with the baseline values, complement C3 changes (ΔC3) and ΔAUCcp% was -0.15 ± 0.28 mg/ml and -17.2 ± 18.4%, respectively, at a follow-up visit 4.57 ± 0.78 years later. Moreover, ΔC3 was positively correlated with ΔAUCcp% (n = 347, r = 0.302, p < 0.001). Furthermore, each 0.1 mg/ml increase in ΔC3 was associated with a higher ΔAUCcp% (1.41% [95% CI, 0.82-2.00%]) after adjusting for changes in glycemic status and other clinical confounders at follow-up. CONCLUSIONS: In addition to serum complement C3 being independently associated with islet ß-cell function at baseline, its changes were also independently associated with changes in islet ß-cell function over time in patients with T2D.

11.
Int J Nanomedicine ; 14: 9453-9467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819443

RESUMO

Background: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. Methods: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. Results: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. Conclusion: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

12.
J Asian Nat Prod Res ; : 1-7, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31885279

RESUMO

A couple of new cycloheximide epimers, 13(α)-acetoxy-anhydroisoheximide (1) and 13(ß)-acetoxy-anhydroisoheximide (2), together with six known compounds (3-8), were obtained from the cultures of Streptomyces sp. YG7. The structures were elucidated based on a comprehensive spectroscopic data analysis including 1D and 2D NMR, as well as HRESIMS, and by comparison with the literature. The X-ray crystal analysis of 1 further confirmed the structure. All the compounds were tested for antifungal activity. Compounds 1, 2 and 5-8 showed moderate Canidia albicans inhibitory activity, while 5 and 6 presented moderate Pyricularia oryzae inhibitory activity.

13.
Biomater Sci ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31867583

RESUMO

Three-dimensional (3D)-printed porous Ti6Al4V implants are commonly used for reconstructing bone defects in the treatment of orthopaedic diseases owing to their excellent osteoconduction. However, to achieve improved therapeutic outcomes, the osteoinduction of these implants requires further improvement. The aim of this study was to investigate the combined use of recombinant human BMP-2 (rhBMP-2) with a 3D-printed artificial vertebral implant (3D-AVI) to improve the osteoinduction. Eight male Small Tail Han sheep underwent cervical corpectomy, and 3D-AVIs with or without loaded rhBMP-2 in cavities designed at the center were implanted to treat the cervical defect. Radiographic, micro-computed tomography, fluorescence labelling, and histological examination revealed that the osseointegration efficiency of the rhBMP-2 group was significantly higher than that of the blank control group. The biomechanical test results suggested that rhBMP-2 reduced the range of motion of the cervical spine and provided a more stable implant. Fluorescence observations revealed that the bone tissue grew from the periphery to the center of the 3D-AVIs, first growing into the pore space and then interlocking with the Ti6Al4V implant surface. Therefore, we successfully improved osseointegration of the 3D-AVI by loading rhBMP-2 into the cavity designed at the center of the Ti6Al4V implant, realizing earlier and more stable fixation of implants postoperatively in a simple manner. These benefits of rhBMP-2 are expected to expand the application range and reliability of 3D-printed porous Ti6Al4V implants and improve their therapeutic efficacy.

14.
Med Sci Monit ; 25: 10105-10113, 2019 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-31884508

RESUMO

BACKGROUND The objective of the present study was to identify prognostication biomarkers in patients with cervical cancer. MATERIAL AND METHODS Survival related genes were identified in The Cancer Genome Atlas (TCGA) cervical cancer study, and they were included into an elastic net regularized Cox proportional hazards regression model (CoxPH). The genes that their coefficients that were not zero were combined to build a prognostication combination. The prognostication performance of the multigene combination was evaluated and validated using Kaplan-Meier curve and univariate and multivariable CoxPH model. Meanwhile, a nomogram was built to translate the multigene combination into clinical application. RESULTS There were 37 survival related genes identified, 9 of which were integrated to build a multigene combination. The area under the curve (AUC) of receiver operating characteristic (ROC) curve at 1-year, 3-year, 5-year, and 7-year in the training set were 0.757, 0.744, 0.799, and 0.854, respectively, and the multigene combination could stratify patients into significantly different prognostic groups (hazard ratio [HR]=0.2223, log-rank P<0.0001). Meanwhile, the corresponding AUCs in the test set was 0.767, 0.721, 0.735, and 0.703, respectively, and the multigene combination could classify patients into different risk groups (HR=0.3793, log-rank P=0.0021). The multigene combination could stratify patients with early stage and advanced stage into significantly different survival groups in the training set and test set. The prognostication performance of the multigene combination was better compared with 3 existing prognostic signatures. Finally, a multigene containing nomogram was developed. CONCLUSIONS We developed a multigene combination which could be treated as an independent prognostic factor in cervical cancer and be translated into clinical application.

15.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4670-4676, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872663

RESUMO

This research was performed to establish the HPLC fingerprint of Sabia parviflora. HPLC method was carried out on a Thermo Accucore-C18(4. 6 mm×150 mm,2. 6 µm) column by 30% tetrahydrofuran in methyl alcohol-acetonitrile-0. 1% phosphate solution as mobile phase at a flow rate of 1. 0 m L·min-1,the column temperature was 30 ℃ and the detection wavelength was 360 nm. The fingerprints were further evaluated by chemometrics methods including similarity analysis,hierarchical clustering analysis,and principal component analysis. In HPLC fingerprint,15 common peaks were selected as the common peaks,and 6 contents of them were identified. The similarity degrees of 38 batches of the samples was more than 0. 710,and the samples were divided into 6 clusters by their quality difference. The method was precision,repeatable,stable,simple and reliable,which could be used for quality control and evaluation of S. parviflora.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Análise de Componente Principal , Controle de Qualidade
16.
Huan Jing Ke Xue ; 40(7): 3339-3346, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854736

RESUMO

The effects of heavy metal contamination on farmland continues to worsen progressively with an increase in anthropogenic activities such as industrial pollution and mining. Excess Cd and Pb in agricultural soils enter the food chain and adversely affect all organisms. Therefore, it is important to find an eco-friendly way to reduce heavy metal accumulation in crops. Based on their heavy metal resistance and growth-promoting characteristics, functional bacterial strains were screened and their effects on growth and heavy metal accumulation in wheat were verified via shaking flask adsorption and sand culture tests. Eighteen functional strains were isolated from the rhizospheric soil of Salvia setaria. Among them, Bacillus megaterium N3 and Serratia liquefaciens H12 were most effective at resisting high Cd (650 mg·L-1) and Pb (2700 mg·L-1) concentrations, and at producing indole-3-acetic acid (IAA) (56.6 mg·L-1and 69.1 mg·L-1, respectively), siderophores, and 1-Amino-1-cyclopropanecarboxylic acid (ACC) deaminase. Static incubation experiments showed that strains N3 and H12 significantly increased the NH4+ concentration and pH, and decreased the Cd (63.1%-73.8%) and Pb (69.1%-81.8%) concentration in solution. In sand cultures, strains N3 and H12 not only increased the dry weight of wheat roots (47.2%-97.4%) and shoots (65.3%-153%) significantly, but also significantly reduced the Cd (49.2%-68.3%) and Pb (27.4%-84.5%) content in wheat roots and shoots. Thus, the results provide strain resources and a theoretical basis for the remediation of Cd- and Pb-contaminated farmlands for the safer production of crops.


Assuntos
Bactérias/isolamento & purificação , Metais Pesados/análise , Microbiologia do Solo , Poluentes do Solo/análise , Triticum/química , Triticum/microbiologia
17.
J Immunol Res ; 2019: 7684352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781682

RESUMO

Background: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. Methods: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4+T subsets were compared before and after the treatment. Results: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p > 0.05). Conclusions: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).

18.
J Immunol Res ; 2019: 1058738, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772947

RESUMO

Objective: Accumulating evidence indicates that regulatory T cells (Tregs) may be involved in the pathogenesis of ankylosing spondylitis (AS). As different markers have been used to identify Tregs, some studies on the proportions of Tregs in AS patients have generated considerable controversy. To clarify the status of Tregs in such patients, we determine the proportion changes of peripheral Tregs during development of the disease, with different cellular markers. Methods: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in AS patients. Using the PRISMA guidelines, we performed a random-effects meta-analysis of the frequencies of peripheral Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I 2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. Results: A total 29 studies involving 1732 participants were included in the meta-analysis. Their conclusions of using the diversity of Tregs surface markers were inconsistent with each other. No significant difference in the proportions of Tregs was evident regardless of the definitions used [-0.709, (-1.455, 0.037, p = 0.063), I 2 = 97.3%]. Six studies used "single CD25-positive" cells as Tregs, which revealed a significant increase in AS patients compared with healthy blood donors [0.736, (0.138, 1.334), p = 0.016, I 2 = 80.7%]. Notably, the proportions of "CD4+CD25+FOXP3+," "CD4+CD25highCD127low/-," or "CD4+CD25+CD127low" T cells were lower in AS patients [-2.856, (-4.645, -1.066), p = 0.002; -1.812, (-2.648, -0.977), p < 0.001; -1.12, (-1.605, -0.635), p < 0.001]. Tregs defined as "CD25high," "CD25bright," "CD25bright/highCD127low/-," "CD4+FOXP3+," "CD4+CD25highFOXP3+," and "CD4+CD25+CD127-" did not differ in proportion between AS patients and healthy blood donors. Conclusions: The levels of Tregs varied based on the cellular identification markers used. The proportions of CD4+CD25+FOXP3+Tregs, CD4+CD25highCD127low/-, or CD4+CD25+CD127low in blood of AS patients were significantly decreased as compared with those in healthy blood donors, and our findings lend support to the idea that the Treg status of AS patients is important. And we recommend the above as the best definition of Tregs when evaluating the status of such patients.

19.
Horm Behav ; 118: 104640, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31765661

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the health and lifespan of the elderly worldwide. Recently, the correlation between AD and type 2 diabetes mellitus (T2DM) has received intensive attention, and a promising new anti-AD strategy is the use of anti-diabetic drugs. Oxyntomodulin (Oxm) is a peptide hormone and growth factor that acts on neurons in the hypothalamus. OXM activates glucagon-like peptide 1 (GLP-1) and glucagon (Gcg) receptors, facilitates insulin signaling and has neuroprotective effects against Aß1-42-induced cytotoxicity in primary hippocampal neurons. Here, we tested the effects of the protease-resistant analogue (D-Ser2)Oxm on spatial memory and synaptic plasticity and the underlying molecular mechanisms in the APP/PS1 transgenic mouse model of AD. The results showed that (D-Ser2)Oxm not only alleviated the impairments of working memory and long-term spatial memory, but also reduced the number of Aß plaques in the hippocampus, and reversed the suppression of hippocampal synaptic long-term potentiation (LTP). Moreover, (D-Ser2)Oxm administration significantly increased p-PI3K/p-AKT1 expression and decreased p-GSK3ß levels in the hippocampus. These results are the first to show an in vivo neuroprotective role of (D-Ser2)Oxm in APP/PS1 mice, and this role involves the improvement of synaptic plasticity, clearance of Aß and normalization of PI3K/AKT/GSK3ß cell signaling in the hippocampus. This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD.

20.
Cancer Biol Ther ; : 1-10, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31747856

RESUMO

Objective: To investigate and define the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in regulating the tumor growth of gastric cancer (GC).Methods: TRIM58 expression in GC tissues and cells was detected by real-time PCR and Western blot, followed by lentiviral-induced overexpression or knockdown of TRIM58. Subsequently, CCK8, BrdU-ELISA, flow cytometry, immunoprecipitation, in vitro animal experiments and immunochemistry were performed to explore the function of TRIM58. Western blotting was used to detect ß-catenin, C-myc, Cyclin D1, and survivin expression.Results: TRIM58 expression was significantly reduced in tumor tissues of GC patients and GC cell lines, whereas ß-catenin, C-myc, Cyclin D1, and survivin were highly expressed. Overexpression of TRIM58 in GC cells resulted in decreases in ß-catenin, C-myc, Cyclin D1, and survivin protein expression and significantly suppressed proliferation by preventing cell-cycle progression and promoting cell apoptosis. Conversely, TRIM58 knockdown resulted in the opposite effects. Furthermore, the effect of TRIM58 knockdown on GC cells was potently reversed by a ß-catenin inhibitor, XAV939. Immunoprecipitations showed the interaction between TRIM58 and ß-catenin, and TRIM58 overexpression significantly enhanced ß-catenin degradation. In addition, we found a significant decrease in the growth and weight of tumors and an increase in tumor cell apoptosis in TRIM58-overexpression nude mice, which were also accompanied by reduced ß-catenin expression.Conclusions: These data suggest that TRIM58 may function as a tumor suppressor in GC and potentially suppress the tumor growth of gastric cancer by inactivation of ß-catenin signaling via ubiquitination.

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