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1.
ACS Nano ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682416

RESUMO

We developed a biodegradable photothermal therapeutic (PTT) agent, π-conjugated oligomer nanoparticles (F8-PEG NPs), for highly efficient cancer theranostics. By exploiting an oligomer with excellent near-infrared (NIR) absorption, the nanoparticles show a high photothermal conversion efficiency (PCE) up to 82% surpassing those of reported inorganic and organic PTT agents. In addition, the oligomer nanoparticles show excellent photostability on one hand but also good biodegradability. The F8-PEG NPs are also demonstrated to have excellent biosafety and PTT efficacy both in vitro and in vivo. This contribution not only proposes a promising oligomer-based PTT agent, but also provides insight into developing highly efficient nanomaterials for cancer theranostics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31685622

RESUMO

Increasing maize grain yield has been a major focus of both plant breeding and genetic engineering to meet the global demand for food, feed, and industrial uses. We report that increasing and extending expression of a maize MADS-box transcription factor gene, zmm28, under the control of a moderate-constitutive maize promoter, results in maize plants with increased plant growth, photosynthesis capacity, and nitrogen utilization. Molecular and biochemical characterization of zmm28 transgenic plants demonstrated that their enhanced agronomic traits are associated with elevated plant carbon assimilation, nitrogen utilization, and plant growth. Overall, these positive attributes are associated with a significant increase in grain yield relative to wild-type controls that is consistent across years, environments, and elite germplasm backgrounds.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31677814

RESUMO

The three-dimensional Bi2MoO6 mesoporous architectures constructed by nanosheets were synthesized through solvothermal method. The photocatalytic efficiency for tetracycline (TC) by the pristine Bi2MO6 and the BMO-450 (pristine Bi2MO6 was calcined at 450 °C) reached 73% and 90% after 150 min light irradiation, respectively. Compared to the photocatalytic efficiency of pristine Bi2MoO6, the BMO-450 exhibited much higher photocatalytic performance owing to the presence of oxygen vacancies obvious change the band structure of BMO-450. The X-ray photoelectron spectroscopy (XPS) revealed that the presence of oxygen vacancy in the BMO-450 crystal, which endowed it outstanding photocatalytic performance. Moreover, the BMO-450 possess high crystallization degree, mesoporous structure and the decreasing band gap. The excellent photocatalytic performance for the degradation of TC aqueous solutions, which demonstrate that the calcined Bi2MoO6 mesoporous spheres would have potential applications in the fields of treating wastewater.

4.
Ann Hum Genet ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691269

RESUMO

Single-nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome-wide association study (GWAS) data of SLE (1,047 cases and 1,205 controls from a mainland Han Chinese population) to explore the association between the UHRF1BP1 gene and SLE. We conducted a large-scale replication study in an additional independent sample of 3,509 cases and 8,246 controls from a mainland Han Chinese population. Real-time PCR was used to determine gene expression differences in peripheral blood mononuclear cells (PBMCs) from cases and controls. As a result, we replicated the association between the UHRF1BP1 gene and SLE (rs13205210, missense, Pmeta   = 2.26E-17, odds ratio = 1.41) by a meta-analysis of our previous GWAS and this replication study involving a total of 4,556 cases and 9,451 controls. The UHRF1BP1 mRNA expression level in PBMCs was significantly decreased in patients with SLE compared with that in healthy controls. SNP rs13205210 exhibited an expression quantitative trait loci effect on the UHRF1BP1 gene in PBMCs from patients. In conclusion, this study not only suggests that the UHRF1BP1 gene was associated with SLE in a mainland Han Chinese population, but also implied that it might be a common genetic factor contributing to SLE susceptibility in multiple populations.

5.
Target Oncol ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691892

RESUMO

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

6.
Clin Nutr ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31694759

RESUMO

BACKGROUND: Previous clinical and animal studies suggested that medium-chain triglycerides (MCT) might be an alternative energy substrate for the brain and might benefit patients with Alzheimer's disease (AD), but the clinical evidence is not substantial or totally convincing. OBJECTIVE: To investigate the effects of MCT on cognitive ability in patients with mild to moderate AD and explore the changes in peripheral blood metabolomics. METHODS: A double-blind, randomized, placebo-controlled crossover study was undertaken in 53 mild to moderate AD patients. Participants were randomized between two sequences (placebo followed by MCT or MCT followed by placebo) and took MCT jelly or placebo jelly (canola oil) by mouth three times daily (total daily fat dose: 17.3 g MCT, or 19.7 g canola oil) for 30 days per phase. The primary outcome was cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version (ADAS-Cog-C). The secondary outcome was self-care as measured by the activities of daily living scale (ADL) and changes in plasma metabolites. RESULTS: This study showed a significant (p < 0.01) reduction in ADAS-Cog-C scores between the MCT (2.62 points below baseline) and placebo interventions (2.57 points above baseline). Data from 46 (86.8%) APOE4-/- subjects who completed the entire study were analyzed. Changes in ADL scores were not significantly different between the MCT and placebo interventions (p > 0.05). The concentrations of TC, HDL-C, ß-hydroxybutyrate and acetoacetate were significantly higher in the MCT group than in the placebo group (p < 0.05). Lysophosphatidylcholine 16:0 (LysoPC (16:0)), LysoPC (P-18:0), LysoPC (P-18:1(9Z)), LysoPC (20:2(11Z,14Z)), and LysoPC (22:5(4Z,7Z,10Z,13Z,16Z)) were significantly increased after MCT intervention, and the concentrations of LysoPC (18:0), palmitic acid, linoleic acid, oleic acid, and 7,12-dimethylbenz[a]anthracene were significantly decreased (p < 0.05), whereas no significant changes appeared after the placebo intervention. Androstenedione concentration increased after placebo intervention. Furthermore, a significant negative correlation was observed between changes in LysoPC (P-18:1(9Z)) and ADAS-Cog-C scores after MCT intervention (r = -0.1472, p < 0.05). CONCLUSIONS: MCT had positive effects on cognitive ability in mild to moderate AD patients with APOE4-/-. These effects of MCT might be related to the metabolism of LysoPC, oleic acid, linoleic acid and palmitic acid, in addition to the ketogenic effect. STUDY ID NUMBER: ChiCTR-IOR-16009737. REGISTRY WEBSITE: WHO ICTRP Search Portal - http://apps.who.int/trialsearch/Default.aspx.

7.
Clin Immunol ; 210: 108272, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683055

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiple system involvement and positive serum autoantibodies. Lupus nephritis (LN) is the most common and serious complication of SLE, and it is the main cause of death in patients with SLE. Abnormalities in the immune system lead to LN and involve a variety of cells (T cells, B cells, macrophages, NK cells, etc.), cytokines (interleukin, tumor necrosis factor α, etc.) and their related pathways. Previous studies have shown that the interactions of genetic, epigenetic and environmental factors contribute to the pathogenesis and development of LN. In recent years, one genome-wide association study (GWAS) and a number of gene association studies have explored the susceptibility genes of LN, including immunization-, inflammation-, adhesion- and other pathway-related genes. These genes participate in or suggest the pathogenesis and progression of LN. In this review, we summarize the genetic susceptibility of LN and discuss the possible mechanism underlying the susceptibility genes of LN.

8.
Mol Med Rep ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31702028

RESUMO

The present study aimed to explore the role of the PTEN/Akt/mTOR signaling pathway in the neurite outgrowth and apoptosis of cortical neurons. Cortical neurons were seeded on or adjacent to chondroitin sulfate proteoglycans. The length, number and crossing behavior of the neurites were calculated. Immunohistochemical staining and TUNEL data were analyzed. Neurites treated with PTEN inhibitor exhibited significant enhancements in elongation, initiation and crossing abilities when they encountered chondroitin sulfate proteoglycans in vitro. These effects disappeared when the PTEN/Akt/mTOR signaling pathway was blocked. Neurons exhibited significant enhancements in survival ability following PTEN inhibition. The present study demonstrated that PTEN inhibition can promote axonal elongation and initiation in cerebral cortical neurons, as well as the ability to cross the chondroitin sulfate proteoglycan border. In addition, PTEN inhibition is useful for protecting the neuron from apoptosis. The PTEN/Akt/mTOR signaling pathway is an important signaling pathway.

9.
Appl Opt ; 58(27): 7359-7366, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674381

RESUMO

The phase-coding method has been widely used for 3D shape measurement, which uses sinusoidal phase-shifting patterns to recover the wrapped phase and the stair phase-coding patterns to determine the fringe order. However, due to random noises and image blurring, the fringe order is always misaligned with the wrapped phase, which will lead to fringe order errors. This paper presents an enhanced phase-coding method to address this misalignment problem by using half-period codewords, in which each codeword is aligned to the half-period of the sinusoidal patterns. Then, two complementary fringe orders with half-period dislocation can be calculated, which can effectively eliminate the fringe order errors. To extend the coding range of stair phase, this paper further develops a computational scheme based on the geometric constraint method. Simulations and experiments have been carried out, and their results confirm that the enhanced method can reliably recover the 3D shape of the measured objects.

10.
J Med Virol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674680

RESUMO

Poliovirus (PV) is a member of the species Enterovirus C (EV-C), which may cause irreversible paralysis and death. So, for the purpose of analyzing the evolution of PV2 to help in eradicating polioviruses globally, a recombination analysiswas performed to verify all viral genomes of Enterovirus C, and we found 13 putative recombination events that produced PV1, 14 recombination events that can give rise to PV2, and 9 events that can lead to PV3. By analyzing our findings, we found that PV2 was involved in 25 of 36 PV recombination events, whereas coxsackievirus A strains (CVAs) were involved in 12 of 36 PV recombination events, indicating that PV2 and CVAs play major roles in the natural recombination of PV. In addition, we found 11 of 36 breakpoint positions located in 2A region, which is the most active region of the recombination events. This article is protected by copyright. All rights reserved.

11.
Sci Total Environ ; 699: 134395, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31678886

RESUMO

Catalytic ozonation is an efficient process that can be utilized to degrade recalcitrant organics. Char-clay composite derived from refinery spent bleaching earth (SBE) is an economical and readily available catalyst that can be used during the ozonation treatment of recalcitrants in wastewater. Four catalysts of SBE-N2-650, SBE-N2-850, SBE-O2-650, and SBE-O2-850 were prepared by heating the SBE at 650 and 850 °C under N2 or O2 conditions. High surface OH sites in the SBE-N2-650 and SBE-O2-650 relative to the SBE-N2-850 and SBE-O2-850 resulted in an increase in catalytic activity. Additional carbon (C), that existed in the SBE-N2-650 and SBE-N2-850, had a positive effect on catalytic activity. The SBE-N2-650 exhibited the highest activity among those prepared catalysts. During catalytic ozonation, the SBE-N2-650 increased the mineralization rate of benzoic acid by 36% when compared with single ozonation. Molecular ozone was decomposed at the surface active sites on SBE-N2-650, generating active •OH, •O2-, or 1O2 species. Gas and liquid products having calorific values that are generated during SBE-N2-650 preparation can be further utilized. This study introduces a potential use of SBE for the ozonation treatment of recalcitrant wastewaters.

12.
Int J Food Sci Nutr ; : 1-9, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31583921

RESUMO

This study was a prospective, randomised, double-blind, placebo-controlled clinical trial and aimed to compare the effect of placebo, soy isoflavone, calcium and soy isoflavone combined with calcium on bone mineral density (BMD). One hundred and sixty perimenopausal women with osteoporosis or osteopenia were enrolled and randomised into four groups: control, soy isoflavone, calcium and soy isoflavone combined with calcium groups. After intervention, compared with control, isoflavone and calcium groups, mean changes from their corresponding baseline values of BMD, calcium/phosphorus, vitamin D and glutathione peroxidase (GSH-pX) activity were significantly increased, however, those of phosphorus, osteocalcin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly decreased in isoflavone combined with calcium group. The results showed that soy isoflavone, calcium and isoflavone combined with calcium therapy were effective and safe on attenuating BMD loss in perimenopausal women and isoflavone combined with calcium therapy was better than soy isoflavone and calcium alone.

13.
Opt Lett ; 44(19): 4674-4677, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568414

RESUMO

Yb3+/Er3+ co-doped nano-glass ceramics (GCs) containing isotropic KY3F10 nanocrystals (NCs) are obtained from a simple ternary oxyfluoride glass by controlled crystallization. The nano-GCs thus obtained, albeit having very large crystallinity of ∼35%, are ultratransparent in the whole visible-light wavelength region of 300-700 nm. Remarkably enhanced green upconversion luminescence (UCL) of Er3+ (by 55 times) is observed in the nano-GCs as compared to the precursor glass. Absolute quantum efficiency of the green UCL reaches as high as 0.41±0.02% in the GCs under 10 W/cm2 power density. The UCL efficiency is comparable to that of the famous ZBLAN: Yb3+/Er3+ glass and GCs containing ß-NaYF4:Yb3+/Er3+ NCs, and nearly twice as large as that of GCs containing KYF4:Yb3+/Er3+ NCs under the same excitation conditions.

14.
Cell Cycle ; : 1-13, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31594449

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide. However, tumor suppressor genes remain to be systemically determined for lung cancer. Here we report interferon regulatory factor 8 (IRF8), a member of the IRF family of transcription factors, as a potent lung tumor suppressor gene. Expression of IRF8 is frequently diminished in lung tumoral tissues and is associated with prognosis of non-small cell lung cancer (NSCLC) patients. Ectopic expression of IRF8 suppresses the NSCLC cells proliferation in vitro and tumorigenic potential in vivo. More importantly, forced expression of IRF8 through infection of recombinant virus inhibits lung tumorigenesis in genetically engineered mouse model (GEMM). Mechanistically, IRF8 inhibits AKT signaling and promotes accumulation of P27 protein, which results in senescence of lung cancer cells. Ectopic expression of IRF8 in tumor cells leads to regression of lung cancer tumor nodules in a xenograft tumor model. Our data, therefore, solidly shows IRF8 to be a lung cancer suppressor gene and may denote an opportunity for therapeutic intervention of NSCLC.

15.
ISME J ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595050

RESUMO

Global-scale N-oxide contamination of groundwater within aquifers occurs due to the widespread use of N-bearing fertilizers and chemicals, threatening both human and environmental health. However, the conversion of these pollutants in active nitrogen (N) cycling processes in the subsurface biosphere still remains unclear. This study investigates the global occurrence of anaerobic ammonium oxidation (anammox) in aquifers, where anammox was found to be turned on and off between saturated and unsaturated soil horizons, and contributed 36.8-79.5% to N loss in saturated soil horizons, the remainder being due to denitrification which has traditionally been considered the main pathway for removal of N-pollutants from aquifers. Although anammox activity was undetectable in the unsaturated soil horizons, it could potentially be activated by contact with ascending groundwater. High-throughput pyrosequencing analysis identified Candidatus Brocadia anammoxidans as being the most abundant anammox bacterium in the saturated soils investigated. However, the anammox bacterial abundance was determined by the relative richness of Candidatus Jettenia asiatica. Isotopic pairing experiments revealed that coupling anammox with ammonium oxidation and respiratory ammonification enabled the formation of a revised N cycle in aquifer systems, in which respiratory ammonification acted as an important coordinator. Anammox can therefore contribute substantially to aquifer N cycling and its role in remediation of aquifers contaminated with N-oxides may be of global importance.

16.
Chin Med J (Engl) ; 132(21): 2565-2571, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31592906

RESUMO

BACKGROUND: The predominant method for Manske type IIIB and IV thumb hypoplasia is pollicization. However, for those who are not willing to sacrifice the index finger, a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable. This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative. METHODS: From May 2014 to January 2017, 15 patients with Manske type IIIB or IV thumb hypoplasia who were admitted to the Department of Hand Surgery, Beijing Jishuitan Hospital were included in this study. An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint. The donor site was reconstructed by a split half of the third metatarsal. Various functional reconstructions were commenced at second stage. The reconstructed thumbs were evaluated using the Kapandji score, pinch force, and the capacities of performing daily activities through a detailed questionnaire. RESULTS: Among these 15 patients (seven type IIIB and eight type IV), there were ten boys and five girls with median age of 4.2 years (range: 2.0-7.0 years). There were seven right, three left, and five bilateral thumbs for whom only the right thumb received surgery. There were 14 metatarsal flaps survived (14/15). With an average follow-up of 19.2 months, the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function. All 15 children have improved the Kapandji score (from 0 to an average of 6.7), pinch force (from 0 to an average of 1.5 kg), with ability of grip and pen holding. X-ray indicated continuous bone growth. Patients and parents had good acceptance of the new thumb. CONCLUSIONS: Reconstruction of an unstable hypoplastic thumb (Manske type IIIB and IV) with use of a vascularized metatarsal is an effective strategy. It offers an alternative solution for parents insisting on saving the thumb.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31634961

RESUMO

OBJECTIVE: MicroRNAs serve important roles in the regulation of endoplasmic reticulum stress (ERs). This study aimed to investigate the role of microRNA-320 (miR-320) in the development of ERs and the inflammatory response in 3T3-L1 adipocytes. MATERIALS AND METHODS: The adipose tissue expression levels of miR-320 and ERs markers (GRP78, GRP94, Derlin-1 and CHOP) and the serum concentration of inflammatory cytokines (TNF-α, NF-κB and IL-6) in obese patients were evaluated using quantitative real-time RT-PCR. The correlation of miR-320 with genes involved in ERs and inflammation was analyzed. The effects of miR-320 on ERs and inflammation were explored using mature 3T3-L1 adipocytes, which were pretreated with palmitic acid (PA). RESULTS: ERs markers and inflammatory cytokines were all upregulated in obese patients. Adipose tissue miR-320 expression was also increased in obese patients, and had positive correlations with the levels of ERs markers and inflammatory cytokines. After PA treatment, the levels of ERs markers and inflammatory cytokines were elevated significantly in 3T3-L1 adipocytes. Moreover, miR-320 expression was increased in the cells under ERs status. The upregulation of miR-320 could enhance the expression of ERs markers and inflammatory cytokines, but the downregulation of miR-320 resulted in the opposite results. CONCLUSION: The data of this study indicate that miR-320 expression is upregulated in ERs status, and the downregulation of miR-320 ameliorates ERs and the inflammatory response in 3T3-L1 adipocytes. We consider that the approaches to decrease miR-320 expression may be novel therapeutic strategies for the treatment of obesity and obesity-related diseases.

18.
Biosci Trends ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611486

RESUMO

Transcatheter arterial chemoembolization (TACE) plays an important role in the treatment of unresectable liver cancer. We conducted this meta-analysis to compare the clinical safety and efficacy of conventional TACE (C-TACE) and drug-eluting beads (DEB)-TACE. A search for those procedures was performed using the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis of patients who underwent C-TACE or DEB-TACE was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of 334 studies, 30 were analyzed. The complete response rate, disease control rate, objective response rate, 3-year survival rate, and non-response rate were significantly higher in patients who underwent DEB-TACE than those in patients who underwent C-TACE. The 1-year survival rate, 2-year survival rate, 30-day mortality rate, complete response rate, disease control rate, complete necrosis rate, non-response rate, objective response rate, progressive disease rate, and recurrence did not differ significantly between patients who underwent C-TACE and patients who underwent DEB-TACE. Patients who undergo DEB-TACE might have a higher complete response rate, disease control rate, and 3-year survival rate than patients who undergo C-TACE. Safety did not differ significantly between C-TACE and DEB-TACE.

19.
Opt Lett ; 44(20): 5093-5096, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613272

RESUMO

We propose and demonstrate a novel and compact optical fiber surface plasmon resonance (SPR) sensor for the simultaneous measurement of the refractive index (RI) and temperature. The sensor is fabricated by employing the eccentric-core fiber (ECF), which is polished to a V-shaped micro-structure optical fiber (MOF). One side of the MOF is used as the RI sensing channel, and the other side is used as the temperature sensing channel. Two sensing channels are independent without crosstalk. The sensor has high RI sensitivity up to the maximum of 3376 nm/RIU from 1.333 to 1.385 RIU, and high-temperature sensitivity up to -2.65 nm/°C from 20°C to 60°C. In addition, owing to the few-mode light in the ECF, the full width at half-maximum is smaller than other SPR sensors based on multimode fiber. This sensor will be extremely helpful to improve the RI measurement uncertainty caused by temperature disturbance.

20.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31652890

RESUMO

The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b/NMDAR2b, TrpV3, IL-6, Cacna1b/Cav2.2, Itgam/Cd11b, Scn9a/Nav1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE2 at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.

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