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1.
Artigo em Inglês | MEDLINE | ID: mdl-31703294

RESUMO

Sleep disturbance and non-medical prescription opioid use (NMPOU) are currently growing public health concerns, and sex differences may result in differential exposure to frequency of NMPOU or sleep disturbance. This study aimed to explore the association between the frequency of lifetime or past-year NMPOU and sleep disturbance and to evaluate whether there was any sex difference in this association among Chinese adolescents. A cross-sectional study was performed in seven randomly selected Chinese provinces through the 2015 School-Based Chinese Adolescents Health Survey. A total of 159,640 adolescents were invited to participate and among them, 148,687 adolescents' questionnaires were completed and qualified for this study (response rate: 93.14%). All analyses were performed for boys and girls separately. There were significant sex differences in the prevalence of lifetime or past-year opioid misuse and sleep disturbance (p < 0.05). Among girls, frequent lifetime NMPOU (adjusted odds ratio [aOR] = 2.09, 95% CI = 1.80-2.44) and past-year NMPOU (aOR = 2.16, 95% CI = 1.68-2.77) were positively associated with sleep disturbance. Among boys, these associations were also statistically significant, while the magnitudes of associations between frequent lifetime NMPOU or past-year NMPOU and sleep disturbance were greater in girls than those in boys. There is a significant sex difference in the prevalence of lifetime or past-year NMPOU and sleep disturbance. Furthermore, exposure to more frequent lifetime or past-year NMPOU is associated with a greater risk of sleep disturbance, especially among girls. Taking into account the sex difference for lifetime or past-year NMPOU may help to decrease the risk of sleep disturbance.

2.
Eur J Pediatr ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754776

RESUMO

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency disease that can be divided into two types: SAP deficiency (XLP1) and XIAP deficiency (XLP2), caused by mutations in the SH2D1A and XIAP genes, respectively. Few cases of XLP (particularly XIAP deficiency) have been reported in mainland China; hence, little is known about the characteristics of Chinese patients with XLP. We identified 13 and 7 patients with SAP and XIAP deficiency, respectively, in our center. Of our 20 patients, 19/20 (95%) presented with disease symptoms at a very early age: six in infancy and 13 in childhood. One XIAP- and three SAP-deficient patients died, while 3/7(42.9%) and 4/13(30.8%), respectively, developed hemophagocytic lymphohistiocytosis (HLH). Epstein-Barr virus (EBV) infection was significantly more common in SAP-deficient 10/13 (76.9%) than XIAP-deficient 2/7 (28.6%) patients, as was hypogammaglobulinemia (10/13 (76.9%) vs. 1/7 (14.3%)). None of the seven XIAP-deficient patients had colitis or lymphoma. Nine SAP-deficient patients and five XIAP-deficient patients showed markedly deficient SAP and XIAP expression, respectively, in lymphocytes. Significantly reduced levels of switched memory B cells were observed in six SAP-deficient patients with persistent hypogammaglobulinemia. One of 13 (7.7%) SAP-deficient patients and 1 of 7 (12.3%) XIAP-deficient patients have received HSCT treatment and are now alive and well; the other alive patients were waiting for HSCT. We also summarized clinical, genetic, and immunological characteristics of all 55 patients (including our 20 patients) reported in the literature in mainland China today.Conclusion: The overall characteristics of SAP deficiency in mainland China were consistent with those in previous reports, whereas manifestations of XIAP deficiency varied significantly. None of inflammatory bowel disease (IBD) has been reported among XIAP-deficient patients in our center; however, whether Chinese XIAP-deficient patients will develop colitis in the future warrants further investigation. HSCT is the only curative therapy for XLP and this therapy should be urgently considered.What is Known:• SAP and XIAP deficiencies share common clinical feature, HLH, whereas they also have their own specific manifestations.• IBD affects 25-30% of XIAP-deficient patients, which has been reported in other countries especially in European country and Japan.What is New:• This is the largest patient cohort study of XLP in China.• We firstly summarized the clinical features and outcomes of Chinese XIAP-deficient patients and found only 1 in 22 patients developed IBD and diet background may contribute to it; Asian SAP-deficient patients carrying SH2D1A R55X mutation were more prone to HLH.

3.
Bioorg Chem ; : 103363, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31669092

RESUMO

NVR3-778, one of the most advanced capsid assembly modulators (CAMs), is currently in phase II clinical trial for the treatment of HBV infection. In this study, we reported the first structure optimization of NVR3-778. Compound 2d was found to exhibit more potent anti-HBV activity (IC50: 0.25 µM), lower cytotoxicity (CC50: 10.68 µM) and higher selectivity index (SI: 40.72) than NVR3-778 (IC50: 0.33 µM; CC50: 5.14 µM; SI: 18.36) in vitro, and also display similar inhibitory effect on the assembly of HBV capsids as NVR3-778. Molecular docking further suggested that compound 2d might form a stronger interaction with core protein. Moreover, compound 2d also showed acceptable pharmacokinetic profiles. Currently compound 2d was selected as a new lead for further modifications, and studies to determine the in vivo anti-HBV studies of 2d will begin soon.

4.
ACS Nano ; 13(11): 13304-13316, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31689082

RESUMO

Despite the excellent photodynamic and photothermal properties of organic molecular photosensitizers (PSs) and photothermal agents (PTAs), such as porphyrin and naphthalocyanine, their poor water solubility severely impedes their biological applications. Covalent organic frameworks (COFs), as an emerging class of organic crystalline porous materials, possess free active end groups (bonding defects) and large inner pores, which make them an ideal type of nanocarriers for loading hydrophobic organic molecular PSs and PTAs by both bonding defect functionalization (BDF) and guest encapsulation approaches to obtain multifunctional nanomedicines for PDT/PTT combination therapy. In this work, we report a nanoscale COF (NCOF) prepared via a facile synthetic approach under ambient conditions. Furthermore, a dual-modal PDT/PTT therapeutic nanoagent, VONc@COF-Por (3), is successfully fabricated by stepwise BDF and guest encapsulation processes. The covalently grafted porphyrinic PS (Por) and the noncovalently loaded naphthalocyanine PTA (VONc) are independently responsible for the PDT and PTT functionalities of the nanoagent. Upon visible (red LED) and NIR (808 nm laser) irradiation, VONc@COF-Por (3) displayed high 1O2 generation and photothermal conversion ability (55.9%), consequently providing an excellent combined PDT/PTT therapeutic effect on inhibiting MCF-7 tumor cell proliferation and metastasis, which was well evidenced by in vitro and in vivo experiments. We believe that the results obtained herein can significantly promote the development of NCOF-based multifunctional nanomedicines for biomedical applications.

5.
Front Med ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31598881

RESUMO

Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells (HCs) and supporting cells during mouse inner ear development; however, the relationship between the two signaling pathways in the mouse cochlea remains largely unknown. Here, we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5+ progenitors during different cochlear development stages. We found that the downregulation of Notch1 in Lgr5+ cells from embryonic day (E) 14.5 to E18.5 can drive the quiescent Lgr5+ cells to re-enter the cell cycle and differentiate into extra HCs, whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells. No effect was observed on the upregulation or downregulation of Notch1 in Lgr5+ cells from E10.5 to E14.5. We concluded that the roles of Notch1 in Wnt-responsive Lgr5+ cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5+ progenitor activation during cochlear differentiation. Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.

6.
Planta Med ; 85(16): 1263-1274, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31604352

RESUMO

In an effort to identify agents from natural products that inhibit protein tyrosine phosphatase 1B (PTP1B), 5 new prenylated stilbenes, (±)-styrastilbene A (1: ), styrastilbene B (2: ), and (±)-styrastilbenes C - E (3, 4: , and 7: ), along with 4 known structurally related compounds (5, 6, 8: , and 9: ), were isolated from the roots of Artocarpus styracifolius. Their structures were elucidated by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), ultraviolet (UV), and infrared (IR). Based on these isolates, a new plausible biosynthetic pathway for the unusual stilbene derivatives 3: -8: with a tetracyclic ring system is proposed. Among these compounds, 1: -3, 8: , and 9: displayed significant PTP1B inhibitory effects with IC50 values ranging from 2.40 (95% confidence interval [CI]: 2.21 - 2.59) to 8.80 (95% CI: 8.28 - 9.32) µM. Moreover, kinetic analysis and molecular docking simulations were performed to provide insight into the inhibition type as well as the interaction and binding mode of these active isolates with PTP1B. Our results revealed mixed-type PTP1B inhibition for all compounds tested. Docking simulations of these stilbene derivatives showed negative binding energies and close proximity to residues at the allosteric and catalytic sites of PTP1B. These findings suggest that these compounds may have a potential to be further developed as agents for the management of type 2 diabetes mellitus.

7.
Stem Cells Dev ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31552804

RESUMO

Hematopoietic stem cell (HSC) transplantation therapy is one of the most effective treatments for life-threatening hematopoietic diseases. Bone marrow (BM) and mobilized peripheral blood are the major sources of HSCs, but these resources are limited by a paucity of human leukocyte antigen (HLA)-matched donors. Umbilical cord blood (UCB) is the most promising alternative to obtain HSCs for transplantation therapy. However, UCB transplantation therapy is limited by low numbers of HSCs per unit of UCB. In vitro HSC expansion is believed to be the most effective and applicable strategy to address this issue. Here we report that a moderate concentration of GSK3 inhibitor promotes HSC expansion by inducing moderate levels of ß-catenin activity in HSCs. However, such a concentration of GSK3 inhibitor also stimulates myeloid cells to produce inflammatory cytokines, which attenuate HSC expansion by inducing p38 activation. Thus, when unpurified HSCs were used in culture, inhibition of p38-induced inflammatory cytokine signaling was required to ensure HSC expansion induced by the low concentration of GSK3 inhibitor. Our study suggests that the combination of a moderate concentration of p38 inhibitor plus a GSK3 inhibitor synergistically promotes the expansion of both murine BM HSCs and human UCB HSCs.

8.
Dalton Trans ; 48(44): 16502-16508, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31528960

RESUMO

Although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformations. In this contribution, three new MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G', were prepared via the single-crystal-to-single-crystal post-synthetic modification approach. For bioimaging, nanosized UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G' were also prepared. Herein, nanosized UiO-68-R6G with a rhodamine-based fluorescence switch was found to be a highly sensitive and selective fluorescent probe for the detection of Hg2+ both in vitro and in vivo.

9.
Nat Commun ; 10(1): 3733, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427575

RESUMO

Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration.

10.
Mol Med Rep ; 20(4): 3043-3054, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432179

RESUMO

The present study was designed to investigate the role of microRNA­451 (miRNA­451) on cerebral ischemia­reperfusion and to explore its possible mechanism. The expression of miRNA­451 was downregulated in rats with cerebral ischemia­reperfusion. In an in vitro model of cerebral ischemia­reperfusion, the downregulation of miRNA­451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)­1b, IL­6 and IL­18. However, the upregulation of miRNA­451 expression decreased inflammation in the same in vitro model of cerebral ischemia­reperfusion. In addition, it was found that the downregulation of miRNA­451 induced the expression of Toll­like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor­κB (NF­κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF­κB/p65 in the in vitro model of cerebral ischemia­reperfusion, inhibiting the effects of miRNA­451 upregulation on inflammation. A TLR4 inhibitor, TAK­242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia­reperfusion. TAK­242 suppressed the effects of miRNA­451 downregulation on inflammation. The present study suggested that miRNA­451 regulated cerebral ischemia­reperfusion­induced inflammation, which is mediated through the TLR4/MyD88/NF­κB signaling pathway.

11.
Bioresour Technol ; 292: 121948, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31408776

RESUMO

To improve the adsorption efficiency, a H3PO4-modified biochar (CFCP) was prepared using chicken feather and applied to Cd2+ and Pb2+ adsorption. The pseudo-second-order model could explain the Cd2+ and Pb2+ adsorption behavior. CFCP had faster adsorption rate than non-modified biochar (CFC2). The Langmuir and Freundlich isotherm could better describe the Cd2+ and Pb2+ adsorption, respectively. The value of qm for Cd2+ adsorption and KF for Pb2+ adsorption by CFCP was 7.84 mg·g-1 and 24.41 mg1-(1/n)·L1/n·g-1, which was 1.38 and 5.41 times of the corresponding results of CFC2. Relative to Cd2+, Pb2+ was selectively adsorbed by biochars in the binary metal system. Phosphate precipitation explained in part the selective adsorption of Pb2+. Proline, glucose, and pH (4-6) had little influence on Cd2+ and Pb2+ adsorption. Electrostatic interaction, precipitation, and O-H bonds were the primary adsorption mechanisms. The increased N-containing heterocycles of CFCP accounted for the increased Cd2+ and Pb2+ adsorption.


Assuntos
Cádmio , Galinhas , Adsorção , Animais , Carvão Vegetal , Plumas , Íons , Chumbo , Ácidos Fosfóricos
12.
J Affect Disord ; 258: 25-32, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382101

RESUMO

BACKGROUND: There were differences in the characteristics and prevalence rates between individuals with a history of one suicide attempt and those with multiple suicide attempts. This large-scale study was conducted to test, among Chinese adolescents, the associations of emotional and behavioral problems with single and multiple suicide attempts and whether these associations vary with adolescents' academic performance. METHODS: Data were drawn from the 2019 School-based Chinese Adolescents Health Survey (n = 20,702). Information about emotional and behavioral problems, suicide attempts, suicidal ideation, academic performance, and sleep duration was gathered. Multinomial logistic regression models using Firth penalized likelihood approach and appropriate sampling weights were performed. RESULTS: Compared with no suicide attempt, peer problems, emotional problems, conduct problems, and hyperactivity were associated with an elevated risk of both a single suicide attempt and multiple suicide attempts, respectively (P < 0.05); the magnitudes of these associations in multiple suicide attempters were higher than those in single suicide attempters. Further stratification analyses by academic performance showed a greater association of the four difficulties with multiple suicide attempts in adolescents reporting poor academic performance than in those with good or average academic performance. LIMITATIONS: The school-based study sample only included students, and causal inference could not be delineated due to the cross-sectional design. CONCLUSIONS: Emotional and behavioral problems are associated with an elevated risk of single and multiple suicide attempts with differences between multiple suicide attempters and single suicide attempters. Adolescent academic performance plays a modulating role in these associations for multiple suicide attempts.

13.
J Affect Disord ; 258: 89-95, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400628

RESUMO

BACKGROUND: There is a lack of literature about the joint effects of PM2.5 exposure and sleep disturbance on suicide attempts. This study aimed to estimate the association of PM2.5 exposure or sleep disturbance with suicide attempts among Chinese adolescents and to test their interaction effects on both additive and multiplicative scales. METHODS: Data was drawn from a subsample of the School-based Chinese Adolescents Health Survey (SCAHS) during 2014-2015 in Guangdong province, including 21,780 eligible participants. The 3-year (2011-2013) annual average concentration of PM2.5 was estimated using satellite data. Multi-level logistic regression models with weights were fitted, and both multiplicative and additive interactions for PM2.5 and sleep disturbance were tested. RESULTS: A total of 608 students (2.8%) reported having suicide attempts. After adjusting for significant demographics and depressive symptoms, PM2.5 exposure (Adjusted odds ratio [AOR] = 1.25, 95% CI = 1.03-1.56) and sleep disturbance (AOR = 1.69, 95% CI = 1.41-2.02) were positively associated with suicide attempts, respectively. The adjusted additive interaction effect of PM2.5 and sleep disturbance was 2.42 (95% CI = 1.80-3.26) with a synergistic index of 1.31. The multivariable multi-level logistic regression models did not find any significant multiplicative interaction item (P > 0.05). LIMITATION: The school-based cross-sectional study design CONCLUSION: Long-term exposure to PM2.5 may elevate the risks of suicide attempts among Chinese adolescents. Moreover, the significant interaction effects of PM2.5 exposure and sleep disturbance on suicide attempts were found in the additive model, suggesting decreasing long-term exposure to a higher level of PM2.5 may be helpful to reduce the risk of suicide attempts among adolescents with sleep disturbance.

14.
Neurosci Lett ; 711: 134406, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377244

RESUMO

The cochlea is the essential organ for hearing and includes both auditory sensory hair cells and spiral ganglion neurons. The discovery of inner ear stem cell brings hope to the regeneration of hair cell and spiral ganglion neuron as well as the followed hearing re-establishment. Thus the investigation on characteristics of inner ear stem/progenitor cells and related regulating clue is important to make such regeneration a reality. In addition, attempts have also been made to transplant exogenous stem cells into the inner ear to restore hearing function. In this review, we describe recent advances in the characterization of mammalian inner ear progenitor/stem cells and the mechanisms of regulating their proliferation and differentiation, and summarize studies that have used exogenous stem cells to repair damaged hair cells and neurons in the inner ear.

15.
Org Lett ; 21(14): 5670-5674, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31268339

RESUMO

Salpratlactones A (1) and B (2), a pair of abietane cis-trans tautomers from Salvia prattii, were identified as the first naturally occurring agonists of T-type calcium channel (TTCC). Structurally, 1 and 2 were featured by unique 6/5 carbocyclic rings bearing a γ-lactone ring through an exocyclic double bond. Moreover, both compounds and their mixture at 10 µM potently and equally increased Cav3.1 TTCC peak currents, and 1 had an EC50 value of 12.48 µM.

16.
Sci Total Environ ; 690: 438-446, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299576

RESUMO

The application of iron oxide nanoparticles (IONs) is often limited by agglomeration and low loading. Here, we presented a facile phase change material (PCM) -based sol-gel strategy for the fabrication of α-Fe2O3 nanoparticles. Rosin was used as the PCM in the sol-gel process and the carbon-based substrate of α-Fe2O3 nanoparticles in the thermal process. The α-Fe2O3 nanoparticle embedded rosin-derived biochar(α-Fe2O3@HrBc)were highly dispersed. The dispersity of α-Fe2O3 nanoparticle could be regulated by the weight ratios of rosin to FeCl3·6H2O during the preparation, as evidenced by the scanning electron microscope (SEM) spectrum and the sorption capacity results. Among a series of α-Fe2O3@HrBc nanocomposites, the one with the weight ratios of 1/1.5 rosin/FeCl3·6H2O had the highest capacity for hexavalent chromium (Cr(VI)) sorption. This phenomenon can be ascribed to a remarkably enhanced interfacial reactivity due to an increase in the dispersity of α-Fe2O3 nanoparticle. In addition, SEM showed that the majority of α-Fe2O3 nanoparticles was dispersed on and inside the biochar substrate. Batch adsorption experiments revealed that the α-Fe2O3@HrBc adsorbed 90% Cr(VI) within one minute, and the maximum capacity was up to 166 mg·g-1 based on the Langmuir model. The FTIR and XPS spectra revealed that the adsorbed Cr(VI) species were partially reduced to less toxic Cr(III). Considering that α-Fe2O3 nanoparticles provided important sorption sites, the newly formed Cr(III) and the remaining Cr(VI) ions could be adsorbed on α-Fe2O3@HrBc via the formation of FeCr coprecipitation.

17.
Environ Health Prev Med ; 24(1): 50, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351468

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are widely found in the environment, and comparing to adults, children are more vulnerable to PAHs exposure. Urinary metabolites of PAHs are used as preferred biomarkers to estimate the PAHs exposure. Systematic review on the internal exposure level of children and adolescents is rare. We aimed to calculate the internal exposure levels of PAHs in children and adolescents and compare the levels of PAHs internal exposure in various children groups. We searched PubMed, OVID, Web of Science, EBSCO, ACS, and four Chinese databases, and all studies examining the urinary concentrations of PAHs in children and adolescent were identified. The total exposure level of 11 PAHs metabolites were pooled. Standard mean difference (SMD) and 95% confidence intervals (CIs) of PAHs urinary concentration were calculated and pooled by RevMan5.3 to compare the exposure levels of different children groups. We found that 1-OHPyr, 2-OHNap, 2-OHFlu, 3-OHPhe, and 4-OHPhe were five PAHs metabolites most commonly studied in existing studies in children, and their total exposure levels were 0.38 ± 0.98, 2.32 ± 4.83, 0.81 ± 1.54, 0.09 ± 0.14, 0.03 ± 0.10 µmol/mol creatinine, respectively. The meta-analysis showed that the levels of 1-OHPyr were higher in higher environmental exposure group (SMD = 0.21, 95% CI = 0.03~0.40), ETS exposure group (SMD = 0.31, 95% CI = 0.08~0.54), and 6~11 years group (SMD = 0.16, 95% CI = 0.09~0.24); the level of 2-OHNap (SMD = 0.27, 95% CI = 0.01~0.53) was higher in higher environmental exposure group; however, the levels of 3-OHPhe (SMD = - 0.34, 95% CI = - 0.57~- 0.12) and 4-OHPhe (SMD = - 0.48, 95% CI = - 0.69~- 0.28) were higher in lower environmental exposure group. The levels of 1-OHPyr (SMD = - 0.01, 95% CI = - 0.11~0.10) and 2-OHNap (SMD = 0.01, 95% CI = - 0.20~0.22) were not statistically different between boys and girls. In conclusions, we found that the internal diversity of PAHs existed in children and adolescents, and the level of 1-OHPyr in children and adolescents was in higher status compared with non-occupational people who do not smoke.

18.
Phytother Res ; 33(9): 2288-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359520

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease, and the role of neuroinflammation in the pathogenesis and progression of PD has been confirmed. The polysaccharides and triterpenoids of antrodia camphorata (a polyporous fungus) harbor diverse and powerful pharmacological effects. In this study, 6-hydroxydopamine was used to construct a PD mouse model. After antrodia camphorata polysaccharide (ACP) intervention, neurobehavioral changes were detected, neurotransmitter changes in striatum were determined by high-performance liquid chromatography, the alterations of striatal NOD-like receptor pyrin domain containing three (NLRP3) were examined by immunohistochemistry, and the expression of NLRP3, IL-1ß, Caspase-1, and proCaspase-1 were detected by western blot. To be specific, the items of neurobehavioral test included open field activity, rotary test, pole test, gait analysis, and swimming test. As a result, 6-hydroxydopamine could lead to PD-like lesions, including tremor, stiffness, attenuated spontaneous activity, and bradykinesia in mice, and the expression of tyrosine hydroxylase in the striatum was decreased. After ACP intervention, the neuroethology of mice was significantly improved, as demonstrated by the elevated levels of dopamine in the striatum and the decreased expression of dopamine in the striatum in NLRP3 inflammasome. NLRP3 inflammasome played an important role in neuroinflammation in PD mice. ACP could reduce the activation of NLRP3 and expression of related inflammatory factors.


Assuntos
Antrodia/metabolismo , Inflamassomos/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos NOD , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia , Polissacarídeos
19.
Digestion ; : 1-8, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31203287

RESUMO

INTRODUCTION: Asia-Pacific Colorectal Screening (APCS) score has been implemented for colorectal cancer screening in asymptomatic cohort in many regions. However, no study has validated its efficiency in Asian outpatients with mild-self-limited gastrointestinal symptoms yet. The purpose of this study was to validate its efficiency in asymptomatic subjects and outpatients in Ningxia. METHODS: The records of 329 asymptomatic participants and 300 outpatients were collected and analyzed from database in the General Hospital of Ningxia Medical University from September 2017 to April 2018. These 2 main groups were divided into 3 tiers based on the scores calculated by the category of APCS score. The detection rates of advanced colorectal neoplasia (ACRN) were further compared according to histopathological classifications of tissues acquired during colonoscopy. RESULTS: Among the 329 participants screened in the asymptomatic cohort, 78 subjects (23.7%) were in the low-risk (LR) tier, 187 subjects (56.8%) in the moderate-risk (MR) tier, and 64 subjects (19.5%) in the high-risk (HR) tier. The percentage of ACRN in the LR, MR, and HR groups was 1.3, 8.6, and 20.3%, respectively. In the 300 outpatient cohorts, 78 patients (26%) were in the LR tier, 140 patients (46.7%) in the MR tier, and 82 patients (27.3%) in the HR tier. The detection rates of ACRN in the LR, MR, and HR groups were 0, 10, and 39%, respectively. CONCLUSION: APCS score is an effective method for ACRN screening in asymptomatic and also the outpatient subjects. Individuals with HR scores should be given priority for colonoscopy.

20.
BMC Pediatr ; 19(1): 189, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176364

RESUMO

BACKGROUND: Neutrophils and eosinophils are multifunctional granulocytes derived from common myelocytic-committed progenitor cells. Severe congenital neutropenia 1 (SCN1) caused by ELANE mutations is a rare disease characterized by very low numbers of circulating neutrophils. Little is known about the functional characteristics of the SCN1 granulocytes, except that eosinophilia has been noticed in both bone marrow and peripheral blood. In this study, we profiled the number and function of granulocytes in patients suffering from SCN1. METHODS: Nine patients diagnosed with SCN1 were enrolled in this study and absolute counts of eosinophils and neutrophils from bone marrow aspirates and peripheral blood samples were analysed. In addition, Ficoll-Paque enriched granulocytes from patients and healthy controls were analysed for specific eosinophil and neutrophil markers using flow cytometry and for NADPH-oxidase activity-profile by chemiluminescence. RESULTS: Our data demonstrate a skewed granulocyte population in SCN1 patients dominated by eosinophils in both bone marrow and peripheral blood. The latter was detected only by blood smear examination, but not by automated blood analysers. Furthermore, we show that the SCN1 eosinophils exerted normal production of reactive oxygen species generated by the NADPH-oxidase, however the response was profoundly different from that of healthy control neutrophils. CONCLUSIONS: SCN1 patients with ELANE mutations suffer from neutropenia yet display eosinophilia in the bone marrow and blood, as revealed by smear examination but not by automatic blood analysers. The SCN1 eosinophils are functionally normal regarding production of reactive oxygen species (ROS). However, the ROS profile produced by eosinophils differs drastically from that of neutrophils isolated from the same blood donor, implying that the eosinophilia in SCN1 cannot compensate for the loss of neutrophils regarding ROS-mediated functions.

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