Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.197
Filtrar
1.
J Ethnopharmacol ; 246: 112231, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31520671

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liangxue Tongyu Prescription (LTP) is a traditional Chinese medicine formula composed of 8 crude drugs that is widely used to treat acute intracerebral hemorrhage (AICH). AIM OF THE STUDY: To verify the efficacy of LTP on the survival time in the treatment of acute intracerebral hemorrhagic rats (AICHs), and to elucidate its network pharmacodynamic mechanism of multi-component, multi-target, and multi-signaling pathways. MATERIALS AND METHODS: Survival analysis was used to evaluate the survival time of AICH rats induced by different doses of collagenase and the efficacy of three doses of LTP in the treatment of AICH rats. The Kaplan-Meier curves for survival time were produced and compared with the Log-rank test and Wilcoxon (Gehan) χ2. Differential mRNA-seq combined with network pharmacology was used to disclose the network effect mechanism of LTP on AICH, and the obtained differential genes were mapped into the predictive empirical compound-target network model (ECT network model) and the empirical compound-target-pathogenesis (disease) network model (ECTP network model). RESULTS: The median survival time of four different doses of LTP-treated groups (0.00 g/kg, 5.78 g/kg, 11.55 g/kg, 23.10 g/kg) for adult AICH rats by 0.18 U collagenase was 14 h, 37 h, 150 h, and 51 h respectively, and the 7-day survival rates were 33.3%, 41.7%, 50.0%, and 38.5%, of which the medium-dose group (MD) had a longer survival time and higher survival rate. Through further validation experiments, the MD group had a better efficacy trend with a median survival time of 168 h vs 23 h in the model control group (MC) (Wilcoxon Gehan Test, χ2 = 3.478, P = 0.062). The transcriptomic analysis of mRNA showed that 583 significant differential genes were found between the MC and MD group and 7 key therapeutic targets regulated by 29 compounds in LTP on AICH were screened out by VCT and VCTP network model. These targets were involved in 5 regulatory models or pathways. CONCLUSION: Our study confirmed the exact efficacy of the LTP in the treatment of AICH and revealed the potential pharmacodynamic components and mode of action of the LTP on AICH. Using differential transcriptome of mRNA combined with network pharmacology, we screened out 29 chemical compounds as the potential effective ingredients of LTP which acted on 7 targets of AICH involving 5 pathological pathways, mainly including repairing the brain function defect, improving neural function, protecting blood-brain barrier from damage, reducing inflammatory factors, and inhibiting apoptosis. The present study not only provides a new explanation for the 'multi-component, multi-target, multi-pathway' effects of the LTP on AICH but also screened out some major compounds of LTP and their potential targets which will facilitate the development of new drugs for AICH.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117389, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31377683

RESUMO

Rational design chelating fluorescent sensors probing metal ions in biological system are continuously hot essays nowadays, especially for zinc detection. Herein, a naphthylideneimine based zinc fluorescence probe (3) was prepared and characterized in this work. Structural features and optical properties of 3 and its metallic complexes were characterized. Fluorescent experiment indicates 3 is extremely sensitive and selective for Zn2+ with a strong fluorescence enhancement (∼34 folds) in aqueous buffer solution with a limit of detection (LOD) of 3.78 × 10-7 mol L-1. Formation constant (logKa) of the chelating complex of 3 and Zn2+ ion was determined to be 4.45. Theoretical studies were carried out to get deep insight into the response mechanism in the sensing process. Density functional theory (DFT) methods calculated formation Gibbs free energy (ΔrGmÓ©) of the deprotonated complexes model (32- ⊃ Zn) is -2.9 kcal/mol, which is in good agreement with the experimental result. The calculation results show that the low excitation states can be ascribe to S0 → T2 and S0 → S1 at 390-430 nm and 310-330 nm, respectively, due to the π → π∗ transition. Finally, yeast cell imaging experiments indicate that 3 can monitor intracellular Zn2+ as well. These findings would enable this fluorescent probe to be used as a Zinc sensor.

3.
J Affect Disord ; 260: 334-341, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521871

RESUMO

BACKGROUND: To investigate mental and physical health comorbidity with chronic back or neck pain in the Chinese population, and assess the level of disability associated with chronic back or neck pain. METHODS: Data were derived from a large-scale and nationally representative community survey of adult respondents on mental health disorders in China (n = 28,140). Chronic back or neck pain, other chronic pain conditions and chronic physical conditions were assessed by self-report. Mental disorders were assessed by the Composite International Diagnostic Interview (CIDI). Role disability during the past 30 days was assessed with the World Health Organization Disability Assessment Schedule (WHO-DAS-II). RESULTS: The 12-month prevalence of chronic back or neck pain was 10.8%. Most of respondents with chronic back or neck pain (71.2%) reported at least one other comorbid condition, including other chronic pain conditions (53.4%), chronic physical conditions (37.9%), and mental disorders (23.9%). It was found by logistic regression that mood disorders (OR = 3.7, 95%CI:2.8-4.8) showed stronger association with chronic back or neck pain than anxiety disorders and substance disorders. Most common chronic pains and physical conditions were significantly associated with chronic back or neck pain. Chronic back or neck pain was associated with role disability after controlling for demographics and for comorbidities. Physical and mental comorbidities explained 0.7% of the association between chronic back or neck pain and role disability. CONCLUSIONS: Chronic back or neck pain and physical-mental comorbidity is very common in China and chronic back or neck pain may increase the likelihood of other physical and mental diseases. This presents a great challenge for both clinical treatment and public health education. We believe that further study needs to be conducted to improve the diagnostic and management skills for comorbidity conditions.

4.
Toxicol In Vitro ; 62: 104671, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31698020

RESUMO

Under strictly Framework Convention on Tobacco Control, novel tobacco products are going to be promising alterations to consumers and manufactures. Even though the novel tobacco products have been considered less harmful than traditional tobaccos, there is a few knowledges about the subsequent substances during consume and their impacts to the consumers due to short introduction into the market. Thus, the present study aims to investigate the adverse effects of novel tobacco products on Caenorhabditis elegans(C. elegans) and to provide relevant references for novel tobacco products toxicity research and assessment. C. elegans individuals at L4 stage were exposed to different kinds of novel tobacco products, including electronic cigarettes liquid (e-liquid), the extract of e-cig aerosol (e-aerosol), mint and black tea flavor snus. After specific exposure time, the multiple toxic endpoints of C. elegans were measured, including acute toxicity, locomotion behavior, body length, and life-span. The oxidative stress was tested too. According to acute toxicity assays, the half lethal dose of four novel tobacco products calculated from theoretical nicotine concentration, ranked as follows e-liquid (0.29 mg/ml) > the extract of e-cig aerosol (0.43 mg/ml) > mint flavor snus (1.20 mg/ml) > black tea flavor snus (1.50 mg/ml). The equivalent lethal rate 5%~20% of four novel tobacco products were applied to following experiments. These novel tobacco products damaged nematode's locomotion including head thrashing and body bending, the damage was most evident in two flavors of snus. The similar trends were found in reproductive performance investigation. At tested concentrations, the retardation development of C. elegans was found throughout all stages with peak blockage at adulthood. Life-span tests showed that novel tobacco products at 5% lethal rate seemed no significant effect on affected the life-span of nematodes, with snus shortened the lifespan of C. elegans at 20% lethal rate. Imaging stress response indicted four types of tobacco productions causing stress response in C. elegans. Exposed to either 5% or 20% lethal levels (5% and 20%), the percentages of worms with DAF-16 redistribution among all groups varied, with higher frequencies in both snus. Summary, novel tobacco products caused multiple adverse impacts to C. elegans, including acute toxicity, locomotion behavior disruption, brood size reduction, development retardation, and life-span reduction. The toxicity was associated with both the feature and concentration of tobacco products, and oxidative stress was the main mechanism.

5.
Mater Sci Eng C Mater Biol Appl ; 107: 110224, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761194

RESUMO

Multi-drug resistance (MDR) remains the main culprit for the low survival rate of advanced colorectal cancer (CRC). Photothermal-therapy (PPT) is effective to kill MDR tumor cells, but fails to completely eradicate tumors. In this study, we prepared a nanocomposite based on gold nanorod core with triple layer coating (GNRs/mSiO2/PHIS/TPGS/DOX) to combat multidrug resistant (MDR) colorectal cancer via multi-strategies. We first synthesized the mesoporous silica-coated gold nanorods (GNRs/mSiO2), and loaded with antitumor drug doxorubicin (DOX) to realize a combination of chemo- and photothermal-therapy. To reverse DOX resistance, pH responsive poly-histidine (PHIS) was conjugated on GNRs/mSiO2 to increase drug intracellular accumulation via efficient endo/lysosome escape; d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was then assembled on the surface of the particles to realize drug intracellular retention by inhibition P-glycoprotein. The results showed that the nanocomposite exhibited a highly efficient photothermal conversion in the NIR region, a pH and NIR triggered drug release profile and an increment of DOX intracellular accumulation and cytotoxicity on MDR SW620/Ad300 cells. Most importantly, the nanocomposite showed the most potent antitumor efficacy without obvious systemic toxicity comparing to other control groups with either chemo- or photothermal therapy alone on SW620/Ad300 tumor bearing mice. Altogether, the successful preparation of the nanocomposite and its potent efficacy might provide evidence for the future design and develop of nano-therapeutic system in the treatment of MDR colorectal cancer.

6.
J Dent ; : 103220, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678476

RESUMO

OBJECTIVES: (1) develop a CPC-metformin scaffold with hPDLSC seeding for bone tissue engineering; and (2) investigate the effects of CPC-metformin scaffold on hPDLSC proliferation, osteogenic differentiation and bone matrix mineralization for the first time. METHODS: hPDLSCs were harvested from extracted teeth. CPC scaffolds (with or without metformin) were prepared. Three groups were tested: (1) control group (growth medium); (2) osteogenic group (osteogenic medium); (3) metformin + osteogenic group (CPC-metformin scaffold, cultured in osteogenic medium). hPDLSC viability, osteogenic differentiation and mineralization were measured. SEM was used to examine cell morphology. RESULTS: After culturing for 14 days, all three groups demonstrated excellent hPDLSC attachment and viability, as shown in live-dead staining, CCK-8 assay, and SEM examinations. The osteogenic group had 3-8 folds, 5 folds and 6 folds of increases in osteogenic gene expressions, ALP activity and mineral synthesis, compared to control group. Furthermore, the metformin + osteogenic group had 3-fold to 4-fold increases over those of the osteogenic group in osteogenic gene expressions, ALP activity and mineral synthesis. CONCLUSIONS: hPDLSCs were demonstrated to be a potent cell source for bone engineering. The novel CPC-metformin-hPDLSC construct is highly promising to enhance bone repair and regeneration efficacy in dental, craniofacial and orthopedic applications.

7.
Inorg Chem ; 58(22): 15039-15044, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31682430

RESUMO

The syntheses of 4'-substituted chiral 2,2':6',2″-terpyridine (tpy) ligands with predetermined configurations and directionalities are rather limited in the supramolecular chemistry field. In this study, a carbazole-linked ditopic chiral ligand L was synthesized using 4'-bromo-substituted pineno-fused tpy 5 as the precursor. Upon complexation with Cd(NO3)2·4H2O and Zn(NO3)2·6H2O, two enantiomerically pure metallosupramolecules, [Cd3L3] and [Zn4L4], have been self-assembled and characterized by NMR, electrospray ionization-mass spectrometry, traveling wave ion mobility-mass spectrometry, and DOSY analysis. In addition, their optical properties are characterized by UV-vis, fluorescence, circular dichroism, and circularly polarized luminescence, suggesting an efficiency transmission and amplification of chirality from the ligand to metal center via self-assembly.

8.
Pathol Res Pract ; 215(12): 152722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31718857

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) could differentiate into osteoblasts and have a great prospect in treating bone diseases. microRNAs (miRs) and nuclear factor kappa-B (NF-κB) signaling pathway have proved pivotal in regulating osteogenic differentiation. This study intended to discuss the mechanism of miR-132 and NF-κB in PDLSC osteogenesis. METHODS: PDLSCs were firstly cultured, induced, and identified by detecting the surface markers and observing cell morphology. Levels of osteogenic markers alkaline phosphatase (ALP), bone morphogenetic proteins 2 (BMP2), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN), along with miR-132 expression were measured. The osteoblast activity and mineral deposition were detected by ALP and alizarin red S (ARS) stainings. The targeting relationship between miR-132 and growth differentiation factor 5 (GDF5) was verified. The gain-and loss-of-function was performed to discuss roles of miR-132 and GDF5 in osteogenic differentiation of PDLSCs. Besides, levels of NF-κB signaling pathway-related proteins were measured. RESULTS: In osteogenic differentiation of PDLSCs, levels of ALP, BMP2, Runx2 and OCN were upregulated while miR-132 was downregulated. Overexpressing miR-132 reduced levels of osteogenic markers, osteoblast activity, ALP and ARS intensity and the activation of NF-κB axis. GDF5 is a target of miR-132 and GDF5 overexpression reversed the inhibitory effects of overexpressed miR-132 on PDLSC osteogenesis. CONCLUSION: Together, miR-132 could inhibit PDLSC osteogenesis via targeting GDF5 and activating NF-κB axis. These data provide useful information for PDLSC application in periodontal therapy.

9.
Biochem Pharmacol ; 171: 113696, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726045

RESUMO

Retinoic acid (RA) is a well-known differentiation inducer that exerts its effects by binding to nuclear RA receptors. Retinoic acid receptor α (RARα), as an important nuclear RA receptor, is activated upon RA binding and facilitates the transcription of target genes related to differentiation, which ultimately initiates cell differentiation. Previous studies have found that the transcriptional activity of RARα is regulated by various post-translational modifications, which influence its DNA binding efficiency, transactivation ability and even lead to degradation. Post-translational modifications of RARα, as a consequence, play an important role in the RA-induced differentiation process. Therefore, in this review, we focus on recent advances in the understanding of how these modifications affect the activity of RARα as well as strategies to increase the differentiation effect of RA treatment in cancer cells based on RARα modifications, which may promote the development of novel effective differentiation therapies for cancer treatment.

10.
Nutr Res ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31708186

RESUMO

The Geriatric Nutritional Risk Index (GNRI) is a valuable simplified tool to predict mortality. However, the results of previous studies are inconsistent and controversial. To summarize the evidence regarding the association of GNRI levels with the risk of all-cause and cardiovascular (CV) mortality, we conducted this meta-analysis. Relevant studies were identified through a systematic electronic literature search. We estimated combined hazard ratios (HRs) to assess the association between GNRI and the risk of mortality by using a meta-analysis method. The Cochrane Q test and the inconsistency statistic were used to assess the between-study heterogeneity. Subgroup analysis and sensitivity analysis were performed. Twenty-six observational studies involving 17 097 participants were identified in this meta-analysis. With the highest category used as the reference group, the lowest-category GNRI was significantly associated with an increased risk of all-cause (HR: 1.32, 95% confidence interval: 1.22-1.43) and CV (HR = 2.10, 95% confidence interval: 1.72-2.57) mortality. Subgroup analyses based on the participant ethnicity, age, and the duration of the follow-up period did not substantially change the main results. In summary, a lower GNRI is associated with an elevated risk of both all-cause and CV mortality. Given the significant heterogeneity among the included studies, further investigations with larger sample sizes are required to confirm the value of the GNRI in predicting mortality and to explore the combined effects of malnutrition and mortality.

11.
BMC Infect Dis ; 19(1): 993, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752713

RESUMO

BACKGROUND: The goal of this study was to further investigate the clinical effectiveness of the T-SPOT.TB test in diagnosing tuberculosis (TB), including the effects of T-SPOT.TB test on evaluating diverse TB types and locations. METHODS: We collected 20,332 specimens from patients suspected to have TB. Afterwards, we performed an integrative analysis of T-SPOT.TB results and clinical diagnoses, and evaluated the composition ratio and positive detection rate of the T-SPOT.TB test in various age groups, sample types, and hospital departments. In addition, we compared the spot number and composition rate between latent TB infection (LTBI), active TB infection, and old TB infection groups. The active TB group was then further divided into pulmonary TB (PTB), pulmonary and extrapulmonary TB (PETB), and extrapulmonary TB (EPTB) subgroups, and we evaluated whether there were statistical differences in spot number and composition rate between subgroups. RESULTS: Positive results from the T-SPOT.TB test were found across different age groups, specimen types, and hospital departments. Elderly patient groups, pleural effusion samples, and thoracic surgery departments showed the highest rates of positivity. There were no statistically significant differences in spot number of CFP-10 and ESAT-6 wells between disease groups or active TB subgroups. The composition rate, however, was significantly different when ESAT-6 and CFP-10 wells were double-positive. The spot number and composition rate were statistically different between the three disease groups, but showed no significant differences between the three subgroups of active TB. CONCLUSIONS: The results of T-SPOT. TB test showed differences in LTBI, active TB and old TB. Additionally, a higher spot number level was observed in the active TB group.

12.
Ren Fail ; 41(1): 995-1000, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31698978

RESUMO

Purpose: This study aimed to investigate the occurrence and risk factors of acute kidney injury (AKI) in ventilated newborns.Methods: In total, 139 newborns receiving mechanical ventilation (MV) were reviewed in this retrospective study. The demographic and clinical data were collected. Then, the independent risk factors for AKI were evaluated using univariate and multivariate logistic regression analyses.Results: The incidence rate of AKI was 15.11% (21/139) in ventilated newborns. Univariate analysis showed significant differences in gestational age, birth weight, Apagar scores, the highest oxygen concentration, serum creatinine levels at admission and 48 h after MV, history of asphyxia, urine output at 48 h after MV, invasive MV, noninvasive MV, and outcomes between AKI and non-AKI groups (all p < .05). The lower gestational age (odd ratio (OR): 1.194, 95% confidence interval (CI): 1.013-1.407, p = .035), the increased use of invasive mechanical ventilation (IMV) (OR: 4.790, 95% CI: 1.115-20.575, p = .035), and lower birth weight (OR: 0.377, 95% CI: 0.178-0.801, p = .011) were independent risk factors for the occurrence of AKI. Additionally, higher stage of AKI was significantly associated with poor prognosis of AKI (p = .018).Conclusion: In this retrospective study, it was found that lower gestational age, birth weight, and increased use of IMV were independent risk factors for AKI in ventilated newborns. The poor prognosis might be indicated by the higher AKI stage.

13.
JAMA Netw Open ; 2(11): e1915828, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747036

RESUMO

Importance: Positron emission tomography-computed tomography (PET-CT) has been increasingly used in the management of lung cancer, but its association with survival has not been convincingly documented. Objective: To examine the association of the use of PET-CT with non-small cell lung cancer (NSCLC) mortality in the US Department of Veterans Affairs (VA) health care system from 2000 to 2013. Design, Setting, and Participants: This cohort study included 64 103 veterans receiving care in the VA health care system who were diagnosed with incident NSCLC between September 2000 and December 2013. Data analysis took place in October 2018. Exposure: Use of PET-CT before and/or after diagnosis. Main Outcomes and Measures: All-cause and NSCLC-specific 5-year mortality; secondary outcome was receipt of stage-appropriate treatment. Results: A total of 64 103 veterans with the diagnosis of NSCLC were evaluated; 62 838 (98.0%) were men, and 50 584 (78.9%) were white individuals. Among these, 51 844 (80.9%) had a PET-CT performed: 25 735 (40.1%) in the 12 months before diagnosis and 41 242 (64.3%) in the 5 years after diagnosis. Increased PET-CT use (597 of 978 veterans [59.2%] in 2000 vs 3649 of 3915 [93.2%] in 2013) and decreased NSCLC-specific 5-year mortality (879 of 978 veterans [89.9%] in 2000 vs 3226 of 3915 veterans [82.4%] in 2013) were found over time. Increased use of stage-appropriate therapy was also seen over time, from 346 of 978 veterans (35.4%) in 2000 to 2062 of 3915 (52.7%) in 2013 (P < .001). Increased PET-CT use was associated with higher-complexity level VA facilities (26 127 veterans [82.3%] at level 1a vs 1289 [75.2%] at level 3 facilities; P < .001) and facilities with on-site PET-CT compared with facilities without on-site PET-CT (33 081 [82.2%] vs 17 443 [80.3%]; P < .001). Use of PET-CT before diagnosis was associated with increased likelihood of stage-appropriate treatment for all stages of NSCLC (eg, veterans with stage 1 disease: 4837 of 7870 veterans [61.5%] who received PET-CT underwent surgical resection vs 4042 of 7938 veterans [50.9%] who did not receive PET-CT; P < .001) and decreased mortality in a risk-adjusted model among all participants and among veterans undergoing stage-appropriate treatment (all-cause mortality: hazard ratio [HR], 0.78; 95% CI, 0.77-0.79; NSCLC-specific mortality: HR, 0.78; 95% CI, 0.76-0.80). Facilities with on-site PET-CT and higher-complexity level facilities were associated with a mortality benefit, with 16% decreased mortality at level 1a vs level 3 facilities (HR, 0.84; 95% CI, 0.80-0.89) and a 3% decrease in all-cause mortality in facilities with on-site PET-CT (HR, 0.97; 95% CI, 0.96-0.99). Conclusions: In this study, the use of PET-CT among veterans with NSCLC significantly increased from 2000 to 2013, coinciding with decreased 5-year mortality and an increase in stage-appropriate treatment. Variation in use of PET-CT was found, with the highest use at higher-complexity level facilities and those with PET-CT on-site. These facilities were associated with reduced all-cause and NSCLC-specific mortality.

14.
ChemSusChem ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680476

RESUMO

Morphology and composition tuning of layered materials have been greatly evaluated in influencing the electrochemical performance for energy storage and conversion applications. Herein, layered Co1-xNix hydroxides (x=0, 1/2, 1/3, 1/4, 1) of three different morphologies, i.e. nanocones, two-dimensional (2D) nanosheets obtained by the rapid exfoliation of nanoconical counterparts via a time-saving approach with a period of only 1 h and the 2D superlattice-like nanostructures alternately restacked by the oppositely charged hydroxide and graphene oxide (GO) nanosheets due to electrostatic interaction, were first systematically investigated for electrocatalytic oxygen oxidation. 2D Co2/3Ni1/3 hydroxide/graphene oxide superlattice (Co2/3Ni1/3NS-GO) was characterized with a high activity of achieving an current density of 10 mA cm-2 at a low overpotential of 259 mV accompanied by a small Tafel slope of 35.7 mV dec-1, surpassing nanocones and 2D nanosheets as well as the congeneric heterostructured Co1-xNix hydroxide-GO nanoarchitectures (Co1-xNixNS-GO, x=0, 1/2, 1/4, 1) and commercial RuO2 electroctalyst. The outstanding activity of Co2/3Ni1/3NS-GO superlattice uncovers the combined merits of 2D superlattice-like structure and composition optimization for electrocatalysis, providing a strategy for developing high-performance electrochemical materials by rational morphology and composition design.

15.
Mass Spectrom Rev ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682024

RESUMO

Metabolism is the collection of biochemical reactions enabled by chemically diverse metabolites, which facilitate different physiological processes to exchange substances and synthesize energy in diverse living organisms. Metabolomics has emerged as a cutting-edge method to qualify and quantify the metabolites in different biological matrixes, and it has the extraordinary capacity to interrogate the biological significance that underlies metabolic modification and modulation. Liquid chromatography combined with mass spectrometry (LC/MS), as a robust platform for metabolomics analysis, has increased in popularity over the past 10 years due to its excellent sensitivity, throughput, and versatility. However, metabolomics investigation currently provides us with only phenotype data without revealing the biochemical functions and associated mechanisms. This limitation indeed weakens the core value of metabolomics data in a broad spectrum of the life sciences. In recent years, the scientific community has actively explored the functional features of metabolomics and translated this cutting-edge approach to be used to solve key multifaceted questions, such as disease pathogenesis, the therapeutic discovery of drugs, nutritional issues, agricultural problems, environmental toxicology, and microbial evolution. Here, we are the first to briefly review the history and applicable progression of LC/MS-based metabolomics, with an emphasis on the applications of metabolic phenotyping. Furthermore, we specifically highlight the next era of LC/MS-based metabolomics to target functional metabolomes, through which we can answer phenotype-related questions to elucidate biochemical functions and associated mechanisms implicated in dysregulated metabolism. Finally, we propose many strategies to enhance the research capacity of functional metabolomics by enabling the combination of contemporary omics technologies and cutting-edge biochemical techniques. The main purpose of this review is to improve the understanding of LC/MS-based metabolomics, extending beyond the conventional metabolic phenotype toward biochemical functions and associated mechanisms, to enhance research capability and to enlarge the applicable scope of functional metabolomics in small-molecule metabolism in different living organisms.

16.
Parasit Vectors ; 12(1): 542, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727141

RESUMO

BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced by E. granulosus (s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear. METHODS: The activation status of peritoneal macrophages (PMs) derived from mice infected with E. granulosus (sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treated in vivo and in vitro with recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected. RESULTS: The expression of AAM-related genes in PMs was preferentially induced after E. granulosus (s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated from E. granulosus (s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained after E. granulosus (s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotype in vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor. CONCLUSIONS: This study demonstrates that E. granulosus (s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part, via the PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31728768

RESUMO

The effects of liquid hot water combined with 1, 4-butanediol (LHW-BDO) on the chemical composition and structure of moso bamboo were investigated. The structure changes of moso bamboo fibers were characterized by infrared spectroscopy, X-ray diffraction, and electronic scanning electron microscopy. The results showed that the delignification rates of 1, 4-butanediol (BDO) and LHW-BDO pretreatment methods were at the same level (91.42-93.08%). However, compared with BDO pretreatment, the cellulose content in solid residue after LHW-BDO pretreatment was increased by 17.06% with a recovery rate of 75.68%, while the hemicellulose removal rate increased by 115.33% and reached 50.34%. After LHW-BDO pretreatment, the intramolecular hydrogen bonds, intermolecular hydrogen bonds, methylene bonds, and aromatic ether bonds of the fibers were broken, which contributed to the depolymerization and separation of cellulose, hemicellulose, and lignin molecules. However, LHW-BDO pretreatment does not destroy the ß-glycoside bond which links the glucose molecule inside the fiber molecule, which was also beneficial to the separation of cellulose. In addition, the amorphous zone of bamboo fibers was destroyed by the above treatments, and the fiber structure of bamboo samples mostly exists in crystalline form. The crystallinity of bamboo pretreated with LHW-BDO was increased by 32.15%. It can be found by scanning electron microscopy that the surface of the pretreated bamboo samples showed uniformly distributed bubbly protuberance.

18.
BMC Urol ; 19(1): 115, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718622

RESUMO

BACKGROUND: Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms. METHODS: Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed. RESULTS: The expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found. CONCLUSION: The present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).

19.
Orthop Surg ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31762194

RESUMO

OBJECTIVE: To evaluate the long-term efficacy of Bryan cervical disc arthroplasty in the treatment of myelopathy patients compared with radiculopathy patients. METHODS: This study is a prospective study. Sixty-six patients (38 patients in myelopathy group and 28 patients in radiculopathy group) who were treated with Bryan cervical disc arthroplasty between 2004 and 2007 and followed for 10 years were included in this study. The Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and Odom's criteria were used to evaluate the clinical outcomes. X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) were used to evaluate the radiographic outcomes including the global range of motion (ROM), segmental ROM, and segment alignment before the surgery and at last follow-up. The incidence of segmental kyphosis, segmental mobility lost, and the grade of paravertebral ossification (PO) were also evaluated at last follow-up. RESULTS: The JOA score and NDI improved in both groups. Thirty-three of 38 patients in myelopathy group and all patients in radiculopathy group reported good or excellent outcomes according to Odom's criteria. The segmental ROM was (9.5° ± 4.4°) before surgery and maintained at (9.0° ± 5.5°) at last follow-up in myelopathy group. The segmental ROM was (9.5° ± 4.6°) and (9.0° ± 5.3°) before surgery and at last follow-up in radiculopathy group, respectively. The Bryan prosthesis remained mobile at last follow-up for 30 patients (78.9%) in the myelopathy group and 22 patients (78.6%) in the radiculopathy group. Of the patients in the myelopathy group, 21.1% developed segmental kyphosis, as did 21.4% of patients in the radiculopathy group. The incidence of PO and high-grade PO was 92.1 and 28.9% in the myelopathy group, and was 92.9 and 32.1% in the radiculopathy group. There was no significant difference between both groups. CONCLUSIONS: Bryan cervical disc arthroplasty was an effective and safe technique in treating patients with myelopathy. The clinical and radiographic outcomes in the myelopathy group were similar to those in the radiculopathy group at the 10-year follow-up.

20.
Pharm Biol ; 57(1): 787-791, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31747844

RESUMO

Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA