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1.
Mov Disord ; 38(12): 2258-2268, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37990409

RESUMO

BACKGROUND: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood. OBJECTIVE: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci. METHODS: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed. RESULTS: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Estudo de Associação Genômica Ampla , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Predisposição Genética para Doença/genética , Fenótipo , Encéfalo/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único/genética , Loci Gênicos
2.
J Headache Pain ; 24(1): 111, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592229

RESUMO

BACKGROUND: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. METHODS: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. RESULTS: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. CONCLUSIONS: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.


Assuntos
Transtornos de Enxaqueca , Proteoma , Humanos , Proteoma/genética , Estudo de Associação Genômica Ampla , Proteômica , Transcriptoma , Transtornos de Enxaqueca/genética
3.
Inorg Chem ; 61(1): 302-316, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34908402

RESUMO

The electron-rich squarate ion (C4O42-, SA2-) possesses electronic delocalization over the entire molecule and good redox activity, and the functionalization of metal-organic complexes with the SA2- group is desirable. In this work, a mixed-ligand method is used to construct novel uranyl squarate coordination polymers utilizing 4,4'-bipyridine (bpy), 4,4'-bipyridine-N,N'-dioxide (bpydo), 1,10-phenanthroline (phen), 4,4'-vinylenedipyridine (vidpy), and in situ formed oxalate (OA2-) as ancillary ligands. Seven mixed-ligand uranyl compounds, [(UO2)(OH)(SA)](Hbpy) (1), [(UO2)(H2O)(SA)2](H2bpy) (2), (UO2)(H2O)(SA)(bpydo)·2H2O (3), (UO2)(H2O)(SA)(phen)·H2O (4), (UO2)(OH)(SA)0.5(phen)·H2O (5), [(UO2)(SA)(OA)0.5](Hphen) (6), and [(UO2)(SA)(OA)0.5](Hvidpy) (7), with varying crystal structures were synthesized under hydrothermal conditions. Compound 1, together with bpy molecules filling in the interlayer space as template agents, has a two-dimensional (2D) network structure, while 2 gives a one-dimensional (1D) chain based on mononuclear uranium units. Compound 3 shows a neutral 2D network through the combined linkage of SA2- and bpydo. Both 4 and 5 have a similar chain-like structure due to the capping effect of phen motifs, while phen molecules in 6 act as templating agents after protonation. Similar to 6, compound 7 has a "sandwich-like" structure in which the Hvidpy motifs locate in the voids of layers of 2D uranyl-squarate networks. The redox properties of typical mixed-ligand uranyl-squarate compounds, 1, 4, and 5 with high phase purity, are characterized using cyclic voltammetry. All three of these uranyl coordination compounds show anode peaks (Ea) at 0.777, 0.804, and 0.760 V, respectively, which correspond to the oxidation process of SA2- → SA. Meanwhile, cathodic peaks (Ec) at -0.328, -0.315, and -0.323 V corresponding to the reduction process of U(VI) → U(V) are also observed. The results reveal that all three of these uranyl coordination compounds show good redox activity and, most importantly, the interplay between two different redox-active motifs of SA2- organic linker and uranyl node. This work enriches the library of redox-active uranyl compounds and provides a feasible mixed-ligand method for regulating the synthesis of functional actinide compounds.

4.
Inorg Chem ; 60(12): 8519-8529, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34096273

RESUMO

Monitoring and quantification of the photoresponsive behavior of metal-organic frameworks that respond to a light stimulus are crucial to establish a clear structure-activity relationship related to light regulation. Herein, we report the first azobenzene-modified photoresponsive thorium-organic framework (Th-Azo-MOF) with the formula [Th6O4(OH)4(H2O)6L6] (H2L = (E)-2'-p-tolyldiazenyl-1,1':4',4'-terphenyl-4,4″-dicarboxylic acid), in which the utilization of a thorium cluster as a metal node leads to one of the largest pore sizes among all the azobenzene-containing metal-organic frameworks (MOFs). The phototriggered transformation of the trans isomer to the cis isomer is monitored and characterized quantitatively by comprehensive analyses of NMR and UV spectroscopy, which reveals that the maximum isomerization ratio of cisTh-Azo-MOF in the solid state is 19.7% after irradiation for 120 min, and this isomerization is reversible and can be repeated several times without apparent performance changes. Moreover, the isomerization-related difference in the adsorption of the Rhodamine B guest is also illustrated and a possible photoregulated mechanism is proposed. This work will shed light on new explorations for constructing functionalized actinide porous materials by the elegant combination of actinide nodes with tailored organic ligands and furthermore will provide a comprehensive understanding of photoisomerization processes in MOF solids and insight into the mechanism on photoregulated cargo adsorption and release by photoactive MOFs.

5.
Inorg Chem ; 60(4): 2133-2137, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33496591

RESUMO

Because H2O2 is thermally unstable, it seems to be difficult to synthesize peroxides at elevated temperatures. We describe here the in situ generation of peroxide that is incorporated in a new uranyl peroxo complex, HT-UPO1, through the hydrothermal treatment of uranyl nitrate at 150 °C in the presence of organic ligands. In this novel process, a highly conjugated aromatic carboxylate linker, (E)-4-[2-(pyridin-4-yl)vinyl]benzoic acid (HPyVB), plays a crucial role by inducing the reduction of oxygen in air to form peroxide in situ and coordinating with uranyl to promote the preferred formation of thermally stable HT-UPO1. This work expands our knowledge on the speciation and chemistry of uranyl peroxide compounds and also sheds light on the possibility of their synthesis under more harsh conditions.

6.
BMC Cardiovasc Disord ; 21(1): 40, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468068

RESUMO

BACKGROUND: A simple and accurate scoring system to guide perioperative blood transfusion in patients with coronary artery disease (CAD) undergoing cardiac surgery is lacking. The trigger point for blood transfusions for these patients may be different from existing transfusion guidelines. This study aimed to evaluate the safety and efficacy of a new scoring strategy for use in guiding transfusion decisions in patients with CAD. METHODS: A multicenter randomized controlled trial was conducted at three third-level grade-A hospitals from January 2015 to May 2018. Data of 254 patients in a Cardiac Peri-Operative Transfusion Trigger Score (cPOTTS) group and 246 patients in a group receiving conventional evaluation of the need for transfusion (conventional group) were analysed. The requirements for transfusion and the per capita consumption of red blood cells (RBCs) were compared between groups. RESULTS: Baseline characteristics of the two groups were comparable. Logistic regression analyses revealed no significant differences between the two groups in primary outcomes (1-year mortality and perioperative ischemic cardiac events), secondary outcomes (shock, infections, and renal impairment), ICU admission, and ICU stay duration. However, patients in the cPOTTS group had significantly shorter hospital stays, lower hospital costs, lower utilization rate and lower per capita consumption of transfused RBCs than controls. Stratified analyses revealed no significant differences between groups in associations between baseline characteristics and perioperative ischemic cardiac events, except for hemofiltration or dialysis and NYHA class in I. CONCLUSIONS: This novel scoring system offered a practical and straightforward guideline of perioperative blood transfusion in patients with CAD. Trial registration chiCTR1800016561(2017/7/19).


Assuntos
Anemia/terapia , Perda Sanguínea Cirúrgica/prevenção & controle , Regras de Decisão Clínica , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Transfusão de Eritrócitos , Hemorragia Pós-Operatória/terapia , Adolescente , Adulto , Idoso , Anemia/etiologia , Anemia/mortalidade , Perda Sanguínea Cirúrgica/mortalidade , China , Tomada de Decisão Clínica , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
J Gen Intern Med ; 35(12): 3449-3457, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33021715

RESUMO

BACKGROUND: Strict medication guidance and lifestyle interventions to manage blood pressure (BP) in hypertensive patients are typically difficult to follow. OBJECTIVE: To evaluate the 1-year effectiveness of lifestyle and drug intervention in the management of rural hypertensive patients. DESIGN: Randomized community intervention trial. PARTICIPANTS: The control group comprised 967 patients who received standard antihypertensive drug intervention therapy from two communities, whereas the intervention group comprised 1945 patients who received antihypertensive drug and lifestyle intervention therapies from four communities in rural China. MAIN MEASURES: Data on lifestyle behaviors and BP measurements at baseline and 1-year follow-up were collected. A difference-in-difference logistic regression model was used to assess the effect of the intervention. KEY RESULTS: BP control after the 1-year intervention was better than that at baseline in both groups. The within-group change in BP control of 59.3% in the intervention group was much higher than the 25.2% change in the control group (P < 0.001). Along with the duration of the follow-up period, systolic and diastolic BP decreased rapidly in the early stages and then gradually after 6 months in the intervention group (P < 0.001). In the intervention group, drug therapy adherence was increased by 39.5% (from 48.1% at 1 month to 87.6% at 1 year) (P < 0.001), more in women (45.6%) than in men (31.2%; P < 0.001). The net effect of the lifestyle intervention improved the rate of BP control by 56.1% (70.8% for men and 44.7% for women). For all physiological and biochemical factors, such as body mass index, waist circumference, lipid metabolism, and glucose control, improvements were more significant in the behavioral intervention group than those in the control group (all P < 0.001). CONCLUSION: The addition of lifestyle intervention by physicians or nurses helps control BP effectively and lowers BP better than usual care with antihypertensive drug therapy alone.


Assuntos
Anti-Hipertensivos , Hipertensão , Estilo de Vida , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Preparações Farmacêuticas
8.
Org Biomol Chem ; 15(48): 10221-10229, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29177319

RESUMO

Three polyether-tethered berberine dimers (1a-c) were studied for their binding affinity, selectivity and thermal stabilization towards human telomeric dimeric quadruplex DNA (G2T1). Compound 1a with the shortest polyether linker showed the highest affinity (Ka > 108 M-1) and 76-508-fold higher selectivity for mixed-type G2T1 over antiparallel G2T1 and three monomeric G-quadruplexes, which are human telomeric monomeric quadruplex G1, c-kit 1 and c-kit 2. Compound 1a induced the formation of quadruplex structures and showed higher thermal stabilization for mixed-type G2T1 than for anti-parallel G2T1, G1 and ds DNA. Spectroscopic studies suggest that compound 1a could bind to mixed-type G2T1 via end-stacking and external binding modes. These results suggest that the polyether linkers in these compounds play an important role in regulating the binding affinity and selectivity towards mixed-type G2T1 and that compound 1a could target mixed-type G2T1 at other genome regions with antiparallel G2T1 and monomeric G-quadruplexes. These results may provide useful guidance for the rational design of selective multimeric G-quadruplex binders and potential anticancer agents.


Assuntos
Berberina/farmacologia , Quadruplex G/efeitos dos fármacos , Berberina/síntese química , Berberina/química , Dimerização , Humanos , Estrutura Molecular , Temperatura
9.
Front Aging Neurosci ; 16: 1403077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903900

RESUMO

Introduction: Alzheimer's disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods: Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes. Results: Based on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E-02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E-02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E-03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E-02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E-02) was related to dendritic cells (DCs). Conclusion: These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

10.
Aging (Albany NY) ; 16(2): 1555-1580, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38240717

RESUMO

Genome-wide association studies (GWAS) have identified multiple risk variants for Parkinson's disease (PD). Nevertheless, how the risk variants confer the risk of PD remains largely unknown. We conducted a proteome-wide association study (PWAS) and summary-data-based mendelian randomization (SMR) analysis by integrating PD GWAS with proteome and protein quantitative trait loci (pQTL) data from human brain, plasma and CSF. We also performed a large transcriptome-wide association study (TWAS) and Fine-mapping of causal gene sets (FOCUS), leveraging joint-tissue imputation (JTI) prediction models of 22 tissues to identify and prioritize putatively causal genes. We further conducted PWAS, SMR, TWAS, and FOCUS using a multi-trait analysis of GWAS (MTAG) to identify additional PD risk genes to boost statistical power. In this large-scale study, we identified 16 genes whose genetically regulated protein abundance levels were associated with Parkinson's disease risk. We undertook a large-scale analysis of PD and correlated traits, through TWAS and FOCUS studies, and discovered 26 casual genes related to PD that had not been reported in previous TWAS. 5 genes (CD38, GPNMB, RAB29, TMEM175, TTC19) showed significant associations with PD at both the proteome-wide and transcriptome-wide levels. Our study provides new insights into the etiology and underlying genetic architecture of PD.


Assuntos
Doença de Parkinson , Transcriptoma , Humanos , Estudo de Associação Genômica Ampla , Proteoma/genética , Predisposição Genética para Doença , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Glicoproteínas de Membrana/genética
11.
NPJ Parkinsons Dis ; 10(1): 70, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548756

RESUMO

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(10): 827-30, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24131832

RESUMO

OBJECTIVE: To study the perioperative change in serum neutrophil gelatinase-associated lipocalin (NGAL) level among children with congenital heart disease (CHD) and pulmonary hypertension (PH) and its significance. METHODS: Eighty children with CHD were divided into four groups according to pulmonary artery systolic pressure: non-PH, mild PH, moderate PH and severe PH groups. Serum NGAL levels were measured before operation, immediately after operation and 24 hours after operation. The relationship of serum NGAL level with PH and early prognosis was analyzed. RESULTS: The mild, moderate and severe PH groups had significantly higher serum NGAL levels than the non-PH group, and the severer the PH, the higher the serum NGAL level (P<0.01). All groups showed significant decreases in serum NGAL levels after operation (P<0.01). Serum NGAL level was positively correlated with the degree of PH and length of stay in the intensive care unit (P<0.01). CONCLUSIONS: Serum NGAL level increases in children with CHD and PH, and it gradually decreases after operation for closing the abnormal shunt. Serum NGAL level may be used as a serological indicator for evaluating the degree of PH and surgical outcome.


Assuntos
Cardiopatias Congênitas/sangue , Hipertensão Pulmonar/sangue , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Proteínas de Fase Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Lipocalina-2 , Masculino , Período Perioperatório
13.
Chem Sci ; 14(23): 6330-6340, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37325134

RESUMO

It is an ongoing goal to achieve the effective regulation of the thermal expansion properties of materials. In this work, we propose a method for incorporating host-guest complexation into a framework structure and construct a flexible cucurbit[8]uril uranyl-organic polythreading framework, U3(bcbpy)3(CB8). U3(bcbpy)3(CB8) can undergo huge negative thermal expansion (NTE) and has a large volumetric coefficient of -962.9 × 10-6 K-1 within the temperature range of 260 K to 300 K. Crystallographic snapshots of the polythreading framework at various temperatures reveal that, different from the intrinsic transverse vibrations of the subunits of metal-organic frameworks (MOFs) that experience NTE via a well-known hinging model, the remarkable NTE effect observed here is the result of a newly-proposed thermally induced relaxation process. During this process, an extreme spring-like contraction of the flexible CB8-based pseudorotaxane units, with an onset temperature of ∼260 K, follows a period of cumulative expansion. More interestingly, compared with MOFs that commonly have relatively strong coordination bonds, due to the difference in the structural flexibility and adaptivity of the weakly bonded U3(bcbpy)3(CB8) polythreading framework, U3(bcbpy)3(CB8) shows unique time-dependent structural dynamics related to the relaxation process, the first time this has been reported in NTE materials. This work provides a feasible pathway for exploring new NTE mechanisms by using tailored supramolecular host-guest complexes with high structural flexibility and has promise for the design of new kinds of functional metal-organic materials with controllable thermal responsive behaviour.

14.
Int J Stroke ; 18(1): 109-116, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367219

RESUMO

BACKGROUND: Lacunar stroke accounts for a quarter of all strokes, but little is known about the underlying pathological mechanisms. Analysis of serum metabolites may allow better understanding of the underlying biological processes. Mendelian randomization (MR) can provide information on the causality of associations. AIMS: To identify causal relationships between serum metabolites and lacunar stroke. METHODS: We applied a two-sample MR analysis to evaluate relationships between 486 serum metabolites and lacunar stroke. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of the exposure on the outcome, while sensitivity analyses were performed using MR-Egger, weighted median, and MR-PRESSO to eliminate the pleiotropy. We also performed a metabolic pathway analysis to identify potential metabolic pathways. RESULTS: We identified 15 known (8 risk and 7 protective) and 14 unknown serum metabolites associated with lacunar stroke. Among the known risk metabolites, two were lipids (1-linoleoylglycerophosphoethanolamine and dihomo-linolenate (20:3n3 or n6)), five amino acids (kynurenine, isobutyrylcarnitine, aspartate, trans-4-hydroxyproline, and 3-methyl-2-oxovalerate), and one peptide (ADSGEGDFXAEGGGVR). The known protective metabolites included four lipids (4-androsten-3beta,17beta-diol disulfate 1, 1-palmitoleoylglycerophosphocholine, adrenate (22:4n6), and glycodeoxycholate), one amino acid (methionine), and two exogenous metabolites (homostachydrine and 2-methoxyacetaminophen sulfate). Metabolic pathway analysis identified several pathways that might be involved in the disease. CONCLUSION: We identified eight risk and seven protective human serum metabolites associated with lacunar stroke. Isobutyrylcarnitine was positively associated with an increased risk of lacunar stroke. In addition, 3-methyl-2-oxovalerate and aspartate may be involved in the disease pathogenesis through metabolic pathways.


Assuntos
Acidente Vascular Cerebral Lacunar , Acidente Vascular Cerebral , Humanos , Ácido Aspártico , Análise da Randomização Mendeliana , Acidente Vascular Cerebral Lacunar/genética , Acidente Vascular Cerebral/genética , Lipídeos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único
15.
Cryobiology ; 65(2): 151-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22568927

RESUMO

In vitro matured (IVM) buffalo oocytes at the metaphase of the second meiotic division (MII) were vitrified in 20% Me(2)SO: 20% EG (v/v) and 0.5M sucrose (VA), or 35% EG (v/v), 50mg/mL polyvinylpyrrolidone (PVP), and 0.4M trehalose (VB), either on cryotops or as 2µL microdrops. The viability was assessed after warming by fluorescein diacetate (FDA) staining and all surviving oocytes were subjected to ICSI and ethanol activation. All vitrified groups had similar recovery rates but both VA groups had significantly higher survival and pronuclear formation rates than either of the VB groups. Non treated control oocytes and non cryopreserved oocytes exposed to FDA had significantly higher survival, 2nd polar body extrusion, PN and blastocyst formation rates than any of the four vitrified groups (P<0.05). In conclusion The cryotop and microdrop methods are equally effective for buffalo oocyte vitrification, and although vitrification in VA solution yielded higher rates of survival and formation of 2 pronuclei than VB, the rate of blastocyst formation was comparable for both solutions. A detailed analysis of oocytes that extruded the second polar body after ICSI and activation revealed that only a minority (7-20% of the vitrified and 46-48% of the control oocytes) also had two pronuclei, indicating that normal activation is compromised by vitrification.


Assuntos
Búfalos/fisiologia , Criopreservação/veterinária , Crioprotetores/farmacologia , Fertilização in vitro/veterinária , Oócitos/citologia , Injeções de Esperma Intracitoplásmicas/veterinária , Animais , Búfalos/embriologia , Sobrevivência Celular/efeitos dos fármacos , Criopreservação/métodos , Técnicas de Cultura Embrionária/veterinária , Feminino , Masculino , Oócitos/efeitos dos fármacos , Vitrificação
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(7): 975-9, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23019960

RESUMO

OBJECTIVE: To explore the action mechanism of ginsenoside Rb1 (GRb1) on protecting herpes simplex virus-1 (HSV-1) infected nerves by studying its inhibitory effects on abnormal changes of apoptosis and nerve growth factor (NGF) mRNA expression in HSV-1 infected human glioma cells U251. METHODS: The inhibitory effects of GRb1 on HSV-1 induced abnormal apoptosis of U251 cells were detected using MTT colorimetry and flow cytometry. The NGF mRNA expressions in different treatment groups were detected using semiquantitative RT-PCR. RESULTS: (1) In 400 microg/mL GRb1 + HSV-1 group, MTT value was higher than HSV-1 group at 24, 36, and 48 h after infection (P < 0.05). (2) Cytopathic effects (CPE) were observed in HSV-1 group at 36 h after infection. In 400 microg/mL GRb1 + HSV-1 group merges increased at 36 h after infection, but most cells were in normal shapes. (3) Results of flow cytometry showed that the cell apoptosis rate was lower in 400 microg/mL GRb1 + HSV-1 group than in the HSV-1 group at24 and 36 h after infection (P < 0.05). (4) Results of RT-PCR showed that in 400 microg/mL GRb1 + HSV-1 group, NGF mRNA expressions decreased at 6-12 h after infection (P < 0.05), but it increased at 24, 36, and 48 h after infection, and was obviously higher than that in the HSV-1 group (P < 0.05). CONCLUSIONS: GRb1 at an appropriate concentration could inhibit abnormal cell apoptosis and changes of NGF mRNA expressions in HSV-1 infection. Therefore, we inferred that GRb1 could protect nerves possibly through up-regulating NGF mRNA expressions and inhibiting apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Herpes Simples/metabolismo , Fator de Crescimento Neural/metabolismo , Linhagem Celular Tumoral , Herpesvirus Humano 1 , Humanos
17.
Zhonghua Wai Ke Za Zhi ; 50(11): 1021-6, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23302489

RESUMO

OBJECTIVE: To assess the effect of perioperative glucose-insulin-potassium (GIK) infusions on the prognosis in patients undergoing coronary artery bypass grafting. METHODS: Electronic databases including Cochrane library (Issue 3, 2011), Pubmed, EMbase, Highwire, CBM and CNKI were searched. A meta-analysis of all randomized controlled trials (RCTs) comparing GIK with control in coronary artery bypass grafting was performed. Study selection and meta-analysis were conducted which according to the Cochrane Handbook for systematic reviews. Date were extracted from these trials by 3 reviewers independently and analyzed by RevMan5.0 software. RESULTS: A total of 9 RCTs including 1029 patients were assessed in this study. GIK infusion was associated with significantly fewer perioperative myocardial infarctions (RR = 0.59, 95%CI: 0.38 - 0.91, P = 0.02), less inotropic support requirement (RR = 0.44, 95%CI: 0.35 - 0.56, P < 0.01), and increase the incidence of postoperative atrial fibrillation (RR = 1.23, 95%CI: 1.05 - 1.43, P = 0.009). CONCLUSIONS: GIK significantly reduces myocardial injury and improves cardiac function in patients undergoing coronary artery bypass grafting, but also increases the incidence of postoperative atrial fibrillation.


Assuntos
Ponte de Artéria Coronária , Glucose/administração & dosagem , Insulina/administração & dosagem , Potássio/administração & dosagem , Humanos , Infarto do Miocárdio/prevenção & controle , Período Pós-Operatório , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Nurs Open ; 9(5): 2335-2341, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661439

RESUMO

AIM: Parents of children with nocturnal enuresis (NE) may have uncertainty and anxiety. This study aimed to investigate the level of uncertainty and anxiety in the parents of children with NE and analyse its influencing factors. DESIGN: We conducted a descriptive cross-sectional study among the parents of children with NE in China. METHODS: A general information questionnaire, the Parent Perception of Uncertainty Scale (PPUS), and the Self-Rating Anxiety Scale (SAS) were used. Multiple linear regression analysis was used to identify factors influencing the parental uncertainty level independently. RESULTS: A total of 247 valid questionnaires were collected. The PPUS score of children with NE was 81.18 ± 10.82, and the anxiety self-rating scale score was 41.86 ± 9.20. Parents' working status, the family's per capita monthly income, and the children's treatment time were the main influencing factors of parental illness uncertainty.


Assuntos
Enurese Noturna , Criança , Estudos Transversais , Humanos , Enurese Noturna/terapia , Pais , Inquéritos e Questionários , Incerteza
19.
Nat Commun ; 13(1): 2030, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440111

RESUMO

Molecular machines based on mechanically-interlocked molecules (MIMs) such as (pseudo) rotaxanes or catenates are known for their molecular-level dynamics, but promoting macro-mechanical response of these molecular machines or related materials is still challenging. Herein, by employing macrocyclic cucurbit[8]uril (CB[8])-based pseudorotaxane with a pair of styrene-derived photoactive guest molecules as linking structs of uranyl node, we describe a metal-organic rotaxane compound, U-CB[8]-MPyVB, that is capable of delivering controllable macroscopic mechanical responses. Under light irradiation, the ladder-shape structural unit of metal-organic rotaxane chain in U-CB[8]-MPyVB undergoes a regioselective solid-state [2 + 2] photodimerization, and facilitates a photo-triggered single-crystal-to-single-crystal (SCSC) transformation, which even induces macroscopic photomechanical bending of individual rod-like bulk crystals. The fabrication of rotaxane-based crystalline materials with both photoresponsive microscopic and macroscopic dynamic behaviors in solid state can be promising photoactuator devices, and will have implications in emerging fields such as optomechanical microdevices and smart microrobotics.

20.
Anim Sci J ; 89(8): 1201-1206, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29888546

RESUMO

Nowadays, the efficiency of buffalo oocytes cryopreservation is still low. The purpose of this study was to evaluate effects of two combinations of cryoprotectant agents (CPAs) and two vitrification devices for vitrification of swamp buffalo oocytes on their survival after vitrification warming, and subsequent developmental ability after in vitro fertilization. In vitro matured (IVM) oocytes were vitrified by either Cryotop (CT) or solid surface vitrification (SSV) interacting with vitrification solution A (VA) or B (VB). In the VA or VB solution exposed test, the oocytes showed similar survival rates, but decreased blastocyst rates after in vitro fertilization compared with that of untreated oocytes. After vitrification, the CT method combined with VA solution yielded a higher survival rate (91.3 ± 5.84%) of vitrified oocytes than that combined with VB solution (69.8 ± 4.19%-75.8 ± 4.55%); however, all the vitrification treatments showed lower blastocyst rates (1.1 ± 0.07%-5.2 ± 0.24%) compared with that of untreated oocytes (18.0 ± 1.09%). Our results indicated that combined vitrification treatments in this study did not improve the decreased ability of vitrified oocytes developing to the blastocyst stage.


Assuntos
Búfalos , Criopreservação/métodos , Criopreservação/veterinária , Fertilização in vitro/veterinária , Oócitos/crescimento & desenvolvimento , Vitrificação , Animais , Blastocisto , Sobrevivência Celular , Crioprotetores/farmacologia , Feminino , Hemissuccinato de Metilprednisolona
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