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1.
Cell Death Dis ; 11(1): 78, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001671

RESUMO

Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality. Numerous studies have shown that women with PE develop autoantibody, termed angiotensin II type 1 receptor autoantibody (AT1-AA), and key features of the disease result from it. Emerging evidence has indicated that inflammatory cell necrosis, such as pyroptosis, could lead to autoantigen exposure and stimulate autoantibody production. Caspase-1, the central enzyme of inflammasome and key target of pyroptosis, may play roles in AT1R exposure and AT1-AA production. Exploring endogenous regulator that could inhibit AT1-AA production by targeting pyroptosis will be essential for treating PE. Lipoxin A4 (LXA4), endogenous dual anti-inflammatory and proresolving lipid mediator, may inhibit AT1-AA production via modulating caspase-1. Thus, we explore whether caspase-1 is essential for AT1-AA production and LXA4 inhibits AT1-AA via modulating caspase-1. PE patients and mice developed AT1-AA associated with caspase-1 activation. Caspase-1 deletion leaded to AT1-AA decrease in PE mice. Consistent with these findings, we confirmed caspase-1 activation, trophoblast pyroptosis and AT1R exposure in PE mice and trophoblast model, while caspase-1 deficiency showed decreased trophoblast pyroptosis and AT1R exposure in vitro and in vivo. Interestingly, LXA4 could suppress AT1-AA production via regulating caspase-1 as well as enhancing phagocytosis of dead trophoblasts by macrophages. These results suggest that caspase-1 promotes AT1-AA production via inducing trophoblast pyroptosis and AT1R exposure, while LXA4 suppresses AT1-AA production via modulating caspase-1, supporting caspase-1 serving as a therapeutic target for attenuating AT1-AA and LXA4 protecting patients from AT1-AA and PE.

2.
World Neurosurg ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001411

RESUMO

BACKGROUND: A pressure wire offers a dynamic tool to assist in the measurement of the pressure gradient and assessment of the functional significance of stenosis. The author presents a patient with idiopathic intracranial hypertension(IIH) who was diagnosed with cerebral venous sinus stenosis (CVSS). Venography accompanied by pressure measurement was utilized to guide the stent placement for CVSS. CASE DESCRIPTION: A 27-year-old woman was referred to our hospital with a chief complaint of headache and neckache lasting for seven weeks, with an 8-day history of binocular diplopia and blurred vision. Magnetic resonance venography (MRV) and digital subtraction angiography (DSA) showed a filling defect in the right transverse sinus. A pressure wire was used before endovascular treatment and showed that the pressure gradient was 10mmHg, which meets the surgical indication. After a stent was placed, no pressure gradient was recorded by the pressure wire. CONCLUSIONS: This is the first report of use of a pressure wire for CVSS. The finding suggests that use of a pressure wire can be a new approach in the diagnosis and treatment of CVSS.

3.
J Proteome Res ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053377

RESUMO

We reported and evaluated a microflow, single-shot, short gradient SWATH MS method intended to accelerate the discovery and verification of protein biomarkers in preclassified clinical specimens. The method uses a 15 min gradient microflow-LC peptide separation, an optimized SWATH MS window configuration, and OpenSWATH software for data analysis. We applied the method to a cohort containing 204 FFPE tissue samples from 58 prostate cancer patients and 10 benign prostatic hyperplasia patients. Altogether we identified 27,975 proteotypic peptides and 4037 SwissProt proteins from these 204 samples. Compared to a reference SWATH method with a 2 h gradient, we found 3800 proteins were quantified by the two methods on two different instruments with relatively high consistency (r = 0.77). The accelerated method consumed only 17% instrument time, while quantifying 80% of proteins compared to the 2 h gradient SWATH. Although the missing value rate increased by 20%, batch effects reduced by 21%. 75 deregulated proteins measured by the accelerated method were selected for further validation. A shortlist of 134 selected peptide precursors from the 75 proteins were analyzed using MRM-HR, and the results exhibited high quantitative consistency with the 15 min SWATH method (r = 0.89) in the same sample set. We further verified the applicability of these 75 proteins in separating benign and malignant tissues (AUC = 0.99) in an independent prostate cancer cohort (n = 154). Altogether, the results showed that the 15 min gradient microflow SWATH accelerated large-scale data acquisition by 6 times, reduced batch effect by 21%, introduced 20% more missing values, and exhibited comparable ability to separate disease groups.

4.
Proteomics Clin Appl ; : e1900080, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32067389

RESUMO

PURPOSE: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with hepatocellular carcinoma. EXPERIMENTAL DESIGN: In this study, we performed proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid-assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent. Then the expression level and function of differentially expressed plasma membrane proteins are verifed. RESULTS: In total, 25 plasma membrane proteins showed differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 were up-regulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 was closely related to the chemoresistance of Bel/5Fu to 5Fu. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with hepatocellular carcinoma. CLINICAL RELEVANCE: Hepatocellular carcinoma is one of the malignant tumors with high malignancy, poor prognosis and serious threat to human life and health. The 5-year survival rate of patients with hepatocellular carcinoma is only about 5%. Systemic chemotherapy is still the main treatment method. However, the occurrence of chemoresistance to tumor cells is the most important cause of chemotherapy failure. In order to understand the specific molecular mechanism of tumor cell chemoresistance more comprehensively, we utilized an ionic liquid-assisted protein extraction method to perform proteomics on 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line. The advantage of the protein extraction method is that plasma membrane proteins can be extracted to a wider range. Via this method, new plasma membrane proteins related to chemoresistance of hepatocellular carcinoma cells can be found. These proteins also can be used as potential targets for drug therapy to suppress chemoresistance of tumor cells. Ultimately, it may improve the clinical prognosis of patients. This method can also be widely applied in drug resistance related research of other tumors. This article is protected by copyright. All rights reserved.

5.
BMC Med Imaging ; 20(1): 13, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028907

RESUMO

BACKGROUND: Uterine angioleiomyoma is a rare variant of leiomyoma, and the main therapy is complete surgery. This study introduces the benefit of three-dimensional computed tomography reconstruction for preoperative preparation. CASE PRESENTATION: A 50-year-old woman presented because of chest distress after activity, with worsening symptoms. After examination, the final diagnosis was uterine angioleiomyoma. The tumour originated in the uterus; grew into the right iliac vein; coursed along the iliac vein, inferior vena cava, and right atrium; and finally invaded the right ventricle. To best complete the surgery, a multidisciplinary surgery was selected. Before the surgery, a three-dimensional computed tomography reconstruction model was created to assess the tumour status, and this model enabled the surgery to be completed successfully. CONCLUSION: Three-dimensional computed tomography reconstruction is of great significance for the preoperative diagnosis of uterine angioleiomyoma and the formulation of surgical treatment plans. Based on its vivid images, surgeons can perform operations more effectively and safely.

6.
Soft Matter ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039413

RESUMO

The encapsulation of small hydrophilic molecules and response to specific biological triggers in a controlled manner have become two of the significant challenges in biomedical research, in particular in the field of localized drug delivery and biosensing. This work reports the fabrication of free-standing microchamber array films made of biodegradable polymers for the encapsulation and enzymatically triggered release of small hydrophilic molecules. Polycaprolactone (PCL) microchamber arrays were demonstrated to fully biodegrade within 5 hours of exposure to lipase from Pseudomonas cepacia (lipase PS) at a concentration of 0.5 mg ml-1, with lower concentrations producing correspondingly longer degradation times. The gradual process of deterioration was real-time monitored utilising laser Fraunhofer diffraction patterns. Additionally, a small hydrophilic molecule, 5(6)-carboxyfluorescein (CF), was loaded into the PCL microchamber arrays in a dry state; however, the substantial permeability of the PCL film led to leakage of the dye molecules. Consequently, polylactic acid (PLA) was blended with PCL to reduce its permeability, enabling blended PCL-PLA (1 : 2 ratio correspondingly) microchamber arrays to trap the small hydrophilic molecule CF. PCL-PLA (1 : 2) microchamber arrays hold potential for controlled release under the catalysis of lipase within 26 hours. Additionally, it is calculated that approximately 11 pg of CF dye crystals was loaded into individual microchambers of 10 µm size, indicating that the microchamber array films could yield a highly efficient encapsulation.

7.
BMJ Open ; 10(1): e034290, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31911525

RESUMO

INTRODUCTION: Migraine is the second-leading cause of years lived with disability worldwide. The high prevalence of migraine-related emotional disorders is often overlooked. Acupuncture is often used to treat both migraine and emotional disorders. This systematic review protocol aims to analyse whether acupuncture is effective for treating emotional disorders in patients with migraine. METHODS AND ANALYSIS: Nine databases will be searched from inception to may 2019: cochrane central register of controlled trials, medline, embase, allied and complementary medicine database, cinahl, china national knowledge infrastructure, chinese biomedical literature database, vip database and wanfang database. Randomised controlled trials (rcts) of acupuncture therapy for migraine with emotional functioning outcomes, which were reported in chinese or english, will be included. The primary outcome is the change in emotional functioning. Study selection, data extraction and assessment of the risk of bias will be performed independently by two or more reviewers. Revman software (v.5.3) will be used to perform the assessment of the risk of bias and data synthesis. ETHICS AND DISSEMINATION: Ethics approval is not be needed because the data will not contain individual patient data, and there are no concerns about privacy. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal or relevant conference. TRIAL REGISTRATION NUMBER: CRD42019139433.

8.
Trials ; 21(1): 12, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907056

RESUMO

BACKGROUND: Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. METHODS/DESIGN: In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle-brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. DISCUSSION: This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.

9.
Drug Deliv ; 27(1): 170-179, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31913724

RESUMO

Targeted nanocarriers have shown great promise in drug delivery because of optimized drug behavior and improved therapeutic efficacy. How to improve the targeting efficiency of nanocarriers for the maximum possible drug delivery is a critical issue. Here we developed L-carnitine-conjugated nanoparticles targeting the carnitine transporter OCTN2 on enterocytes for improved oral absorption. As a variable, we introduced various lengths of the polyethylene glycol linker (0, 500, 1000, and 2000) between the nanoparticle surface and the ligand (CNP, C5NP, C10NP and C20NP) to improve the ligand flexibility, and consequently for more efficient interaction with the transporter, to enhance the oral delivery of the cargo load into cells. An increased absorption was observed in cellular uptake in vitro and in intestinal perfusion assay in situ when the polyethylene glycol was introduced to link L-carnitine to the nanoparticles; the highest absorption was achieved with C10NP. In contrast, the linker decreased the absorption efficiency in vivo. As the presence or absence of the mucus layer was the primary difference between in vitro/in situ versus in vivo, the presence of this layer was the likely reason for this differential effect. In summary, the size of the polyethylene glycol linker improved the absorption in vitro and in situ, but interfered with the absorption in vivo. Even though this strategy of increasing the ligand flexibility with the variable size of the polyethylene glycol failed to increase oral absorption in vivo, this approach is likely to be useful for enhanced cellular uptake following intravenous administration of the nanocarriers.

10.
Biomater Sci ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995039

RESUMO

Disulfiram (DSF) exerts potent anticancer activity via the formation of chelates with copper or zinc ions in tumor tissues, but the low abundance of these ions in the tumor cannot sustain its antitumor activity. Herein, we show that a zwitterionic water-soluble N-oxide polymer, poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate] (OPDMA), can complex cupric ions and form nanogels (OPDMA/Cu), which efficiently deliver copper ions to tumor tissue to potentiate DSF significantly for effective antitumor therapy.

11.
Pediatr Surg Int ; 36(3): 279-287, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31919580

RESUMO

PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is considered to benefit the patients with vesico-prostatic fistula. The aim of this study is to present the details of our LAARP technique for improving the short- and long-term outcomes in the patients with high and intermediate types of anorectal malformations (ARMs). METHODS: 330 patients with high-type (174 cases) and intermediate-type (156 cases) anorectal malformation (aged 8 days to 15 years) underwent LAARP from 2001 to 2019. LAARP was performed for full mobilization and resection of the dilated rectum, intra-rectal closure of the fistula, visualization, and enlargement of the center of the longitudinal muscle tube (LMT) from pelvic and perineal aspects. RESULTS: LAARP was performed in all patients and no patient was converted to open procedure. The urethral diverticulum was found in three patients (1.02%, 3/294) according to postoperative protocol voiding cystourethrogram but was not associated with any symptoms such as urinary tract infection and dysuria. Rectal prolapse requiring surgical intervention developed in 25 (7.6%) of 330 patients. Anal stricture occurred in three patients and re-do anoplasty was performed 5 months after LAARP. Anal retraction occurred in two patients and re-pull-through was conducted at 5 and 6 days, respectively, after LAARP. 228 patients who were older than 3 years were followed up. The median follow-up period was 5.8 years (range 3-15 years). 217 patients (95.2%) had voluntary bowel movements; 202 patients (88.6%) were free from soiling or with grade 1 soiling; 30 patients (13.6%) and 25 patients (11.3%) suffered from grade 1 and grade 2 constipation, respectively, while no patient had grade 3 constipation. CONCLUSION: Our experience demonstrates that the LAARP has advantages on rectal mobilization and resection, intra-rectal fistula closure and accurate tunnel formation in the LMT with minimal trauma. The improvement of the short-term and long-term outcomes after LAARP has been shown not only for high-type ARM but also for intermediate-type ARM.

12.
Org Biomol Chem ; 18(5): 964-974, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31930265

RESUMO

A facile one-step reaction of [60]fullerene with cinnamaldehydes and amines promoted by magnesium perchlorate/ferric perchlorate under air conditions afforded a series of rare amino-substituted cyclopentafullerenes in moderate to good yields. Stereoselectivity was readily achieved. Secondary amines exclusively produced N,N-disubstituted cyclopentafullerenes as cis isomers, while arylamines gave N-monosubstituted cyclopentafullerenes with a preference of cis isomers as major products. N-Monosubstituted cyclopentafullerenes could be further converted into other scarce cyclopentafullerenes in the presence of acid chloride or paraformaldehyde. A possible reaction pathway was proposed to elucidate the formation of amino-substituted cyclopentafullerenes.

13.
Anal Chim Acta ; 1099: 136-144, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-31986270

RESUMO

A novel label-free fluorescence "turn-on" strategy was developed for the sensitive detection of Hg2+ based on the thymine-Hg2+-thymine (T-Hg2+-T) coordination and the fact that single-stranded DNA (ssDNA) greatly enhances the fluorescence of terbium (III) (Tb3+), but double-stranded DNA (dsDNA) does not. In the absence of Hg2+, the mercury-specific DNA (MSD) hybridized with the corresponding complementary strand (cDNA) to form a double helix structure in solution based on Watson-Crick base pairings, which cannot enhance the fluorescence of Tb3+. In the presence of Hg2+, MSD preferentially bound with Hg2+ to form the T-Hg2+-T complex due to the strong affinity of Hg(II) for the T bases of DNA, thus avoiding the hybridization of the cDNA to MSD. The free cDNA can greatly enhance the emission of Tb3+, leading to a sharp increase in fluorescence intensity. Under the optimized conditions, the increased fluorescence intensity was proportional to the concentration of Hg2+ in the range from 10 to 600 nM, and this method can detect concentrations of Hg2+ as low as 0.24 nM. Moreover, satisfactory results were obtained for the detection of Hg2+ in river water and fish samples, and the results were consistent with those from the atomic fluorescence spectroscopy (AFS). Thus, the fluorescence characteristics of Tb3+ were here used in a "turn on" approach to detect Hg2+, which represents a new opportunity for Hg2+ analysis in the field of environmental monitoring and food safety.

14.
Thorac Cancer ; 11(1): 103-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31692283

RESUMO

BACKGROUND: Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive. METHODS: We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes. RESULTS: Of the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR-mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes. CONCLUSION: These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions.

15.
Int J Biol Macromol ; 142: 484-491, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593721

RESUMO

P2X3 is a ligand-gated nonselective cation channel and permeable to Na+, K+ and Ca2+. Adenosine triphosphate (ATP) activation of the P2X3 on primary sensory ganglion neurons is involved in nociceptive transmission. Puerarin is a major active ingredient extracted from the traditional Chinese medicine Ge-gen. Puerarin inhibits nociceptive signal transmission by inhibiting the P2X3 in the dorsal root ganglia (DRG) and sympathetic ganglia, but its molecular mechanism is unclear. The aim of this study was to explore the molecular mechanism of puerarin on the P2X3. Here, molecular docking results revealed that puerarin binds well to the human P2X3 protein in the vicinity of the ATP binding pocket. Protein-ligand docking showed that the V64A mutation reduced the effect of puerarin but had little effect on ATP. V64A site-directed mutagenesis of P2X3 was performed using an overlap extension PCR technique. The wild-type and V64A mutant pEGFP-C1-P2X3 recombinant plasmids were transfected into HEK 293 cells. The electrophysiology results demonstrated that puerarin exerted an obvious inhibitory effect on ATP-activated currents in HEK 293 cells transfected with the wild-type P2X3, while little inhibition was observed in HEK 293 cells transfected with the mutant P2X3. These studies suggest that puerarin inhibits the P2X3 by binding to V64A.

16.
J Chromatogr A ; 1609: 460496, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31519406

RESUMO

Velvet antlers (VA) have been used as medicines and nutraceuticals for over 2000 years. Meanwhile, deer antlers are the only mammalian organs that can fully regenerate after annual shedding. The antler formation and regeneration rely on the stem cells resident in antlerogenic periosteum (AP), transplantation of which can induce ectopic antler formation. Here, a comprehensive quantitative proteomic analysis of antlerogenic periosteal cells (AP cells), compared with the adjacent facial periosteal cells (FP cells), was carried out, from both extracellular and intracellular perspectives. In this study, the stable isotope labeling by amino acids in cell culture (SILAC) was applied to ensure the precision of quantification. Then, the protein equalization strategy and reverse-phase liquid chromatography (RPLC) separation in high pH were utilized to improve the depth of proteome profiling. Proteomics analysis of the conditioned media (CM) from AP and FP cells showed that significantly over-expressed extracellular proteins in AP cells were involved in cell proliferation, angiogenesis and neurogenesis. Combining the extracellular and intracellular proteomes, we found several potential secreted proteins might regulate antler formation and regeneration, such as SFRP4 and LUM. These results provide new insight into the underlying mechanism of antler formation and regeneration.

17.
Gut ; 69(2): 264-273, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31097538

RESUMO

OBJECTIVE: The interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation. DESIGN: We analysed protein and RNA expression, signalling and localisation in human monocyte-derived macrophages (MDMs) through western blot, ELISA, real-time PCR, flow cytometry, immunoprecipitation and microscopy. RESULTS: IL23R was critical for optimal levels of pattern-recognition receptor (PRR)-induced signalling and cytokines in human MDMs. In contrast to the coreceptor IL12Rß1, IL23 induced dynamic IL23R cell surface regulation and this required clathrin and dynamin-mediated endocytosis and endocytic recycling-dependent pathways; these pathways were essential for IL23R-mediated outcomes. The IBD-protective IL23R R381Q variant showed distinct outcomes. Relative to IL23R R381, HeLa cells expressing IL23R Q381 showed decreased IL23R recycling and reduced assembly of IL23R Q381 with Janus kinase/signal transducer and activator of transcription pathway members. In MDMs from IL23R Q381 carriers, IL23R accumulated in late endosomes and lysosomes on IL23 treatment and cells demonstrated decreased IL23R- and PRR-induced signalling and cytokines relative to IL23R R381 MDMs. CONCLUSION: Macrophage-mediated inflammatory pathways are key contributors to IBD pathogenesis, and we identify an autocrine/paracrine IL23 requirement in PRR-initiated human macrophage outcomes and in human intestinal myeloid cells, establish that IL23R undergoes ligand-induced recycling, define mechanisms regulating IL23R-induced signalling and determine how the IBD-protective IL23R R381Q variant modulates these processes.


Assuntos
Citocinas/imunologia , Doenças Inflamatórias Intestinais/imunologia , Macrófagos/imunologia , Receptores de Interleucina/imunologia , Comunicação Autócrina/imunologia , Endocitose/imunologia , Endossomos/imunologia , Variação Genética , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/prevenção & controle , Interleucina-23/imunologia , Janus Quinase 2/metabolismo , Comunicação Parácrina/imunologia , Receptores de Interleucina/genética , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais/imunologia
18.
J Nanosci Nanotechnol ; 20(4): 2114-2121, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492219

RESUMO

Organophosphorus pesticides (OPs) are an important class of common pesticides. However, due to the abuse of organophosphorus pesticides, pesticide residue problems have been highlighted. In this study, the colorimetric detection method for OPs residues was established based on the broadspectrum aptamer. Through optimization, isocarbophos and omethoate were analyzed to verify the performance of the colorimetric assay. Under optimal conditions, the method proved effective for detecting an isocarbophos range of 50-1000 ng/mL and an omethoate range of 100-500 ng/mL. The protective effects of broad-spectrum aptamers and the split (28-mer P1+26-mer P2) aptamers on gold nanoparticles (AuNPs) were also comparatively studied. The present results suggested that the colorimetric assay based on broad-spectrum aptamer could be applied for a preliminary screening of different kinds of OPs.

19.
Biomed Pharmacother ; 121: 109599, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707345

RESUMO

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

20.
Nanomaterials (Basel) ; 9(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795272

RESUMO

A comprehensive insight into the electronic and optical properties of small-lattice-mismatched InSe-GeTe heterobilayer (HBL) is performed based on the density functional theory (DFT) with van der Waals corrections from first-principles perspective. The optimization of most stable geometric stacking mode for the InSe-GeTe HBL is demonstrated. In addition, it is found that the InSe-GeTe HBL forms a type-II heterostructure of staggered-gap band alignment, resulting in an indirect band gap of 0.78 eV, which could be employed as a separator for electron-hole pairs. Moreover, the influence of biaxial strain on the electronic and optical properties of the InSe-GeTe HBL are systematically explored by calculating the band structures, density of states (PDOS), electron density differences, and optical absorption spectra of InSe-GeTe HBL under compressive and tensile biaxial strains. The results indicate that the electronic structures and optical performance of InSe-GeTe HBL could be modulated by changing the biaxial strain conveniently. Our findings provide new opportunities for the novel InSe-GeTe HBL to be applied in the electronic and optoelectronic fields.

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