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1.
J Immunother Cancer ; 9(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33883257

RESUMO

BACKGROUND: In the tumor microenvironment, tumor cells are able to suppress antitumor immunity by competing for essential nutrients, including amino acids. However, whether amino acid depletion modulates the activity of CD8+ tumor-infiltrating lymphocytes (TILs) is unclear. METHOD: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8+ TILs. RESULTS: We discovered that the Rag complex, particularly RagD, was crucial for CD8+ T-cell antitumor immunity. RagD expression was positively correlated with the antitumor response of CD8+ TILs in both murine syngeneic tumor xenografts and clinical human colon cancer samples. On RagD deficiency, CD8+ T cells were rendered more dysfunctional, as demonstrated by attenuation of mTORC1 signaling and reductions in proliferation and cytokine secretion. Amino acids maintained RagD-mediated mTORC1 translocation to the lysosome, thereby achieving maximal mTORC1 activity in CD8+ T cells. Moreover, the limited T-cell access to leucine (LEU), overshadowed by tumor cell amino acid consumption, led to impaired RagD-dependent mTORC1 activity. Finally, combined with antiprogrammed cell death protein 1 antibody, LEU supplementation improved T-cell immunity in MC38 tumor-bearing mice in vivo. CONCLUSION: Our results revealed that robust signaling of amino acids by RagD and downstream mTORC1 signaling were crucial for T-cell receptor-initiated antitumor immunity. The characterization the role of RagD and LEU in nutrient mTORC1 signaling in TILs might suggest potential therapeutic strategies based on the manipulation of RagD and its upstream pathway.

2.
J Mol Med (Berl) ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822264

RESUMO

Angiogenesis is an integral process in many ischemic disorders, and vascular endothelial growth factor (VEGF) plays an important role in it. Protein arginine methyltransferase 4 (PRMT4), a member of the type I PRMT family, is involved in various biological activities, but its role in endothelial cell (EC) remains elusive. Here, we aimed to investigate the role of PRMT4 in ischemic angiogenesis and explore the possible underlying mechanism. We found that PRMT4 was upregulated in ischemic muscles, and VEGF treatment potentiated its expression in ECs. In vitro, adenovirus-mediated PRMT4 overexpression promoted, while its gene disruption inhibited, EC proliferation, migration, and tube formation. In an in vivo hindlimb ischemia model, forced expression of PRMT4 in ECs showed accelerated blood flow recovery and increased capillary density, whereas its knockdown exhibited the opposite effect. Mechanistically, PRMT4 activated the transcription of VEGF via the interaction with Y-box binding protein-1 (YB1), leading to accelerated angiogenesis. Interestingly, the loss of YB1 partially abolished PRMT4-mediated angiogenesis in vitro. Collectively, our data revealed that PRMT4 promoted angiogenesis through interacting with YB1 and the consequential VEGF upregulation, suggesting that PRMT4 may present as a potential therapeutic target in ischemic angiogenesis. KEY MESSAGES: •PRMT4 is induced by VEGF and upregulated in a hindlimb ischemia model. •PRMT4 promotes angiogenesis both in vitro and in vivo. •PRMT4 regulates VEGF expression through interacting with YB1. •YB1 knockdown retards PRMT4-mediated angiogenic effects in vitro.

3.
Int J Colorectal Dis ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864506

RESUMO

PURPOSE: The aim of this study was to develop and validate a nomogram to assist physicians making further decisions on the requirement of a radical surgery for T1 colorectal cancer (CRC) after local excision through preoperative prediction of lymph node metastasis (LNM). METHODS: A total of 141 T1 CRC patients were enrolled from January 2013 to August 2020. The independent predictive parameters were determined in multivariate analyses. The nomogram was constructed based on predictors of LNM and its performance was evaluated with respect to its calibration, discrimination, and decision curve analysis. Internal validation by bootstrapping was performed to verify the applicability of the nomogram. RESULTS: cN in CT/MRI (N+), histologic type (poorly differentiated, mucinous adenocarcinoma, and signet-ring cell carcinoma), tumor budding (G3), and lymphovascular invasion were identified in the multivariable analysis (p<0.05). The developed nomogram incorporated these four predictors and it yielded good discrimination and calibration, with an area under the curve (AUC) of 0.89 (95% confidence interval [CI]: 0.80-0.97). However, the Japanese guideline yielded an AUC of 0.75 (95% CI: 0.63-0.87). A decision curve analysis showed that the predictive scoring system had a high clinical application value, and the nomogram conferred a greater benefit than the Japanese guideline did (range of threshold within 10%-80%). CONCLUSIONS: This study proposed a novel predictive model to assist physicians in making treatment decisions regarding additional surgery after local excision.

4.
Thorac Cancer ; 12(9): 1336-1346, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33751832

RESUMO

BACKGROUND: Major pathologic response (MPR) is mainly focused on residual viable tumor in the tumor bed regardless of lymph node. Herein, we investigated the predictive value of MPR and node status on survival in nonsmall-cell lung cancer (NSCLC) patients receiving neoadjuvant chemotherapy (NAC) and surgery. METHODS: A total of 194 eligible cases were included. Tumor pathologic response and node status were assessed. Based on these evaluations, patients were divided into the MPR group and the non-MPR group, the nodal downstaging (ND) group and non-ND group. Furthermore, patients were assigned into four subgroups (MPR + ND, MPR + non-ND, non-MPR + ND, and non-MPR + non-ND). Overall survival (OS) and disease-free survival (DFS) were compared between groups. Multivariate analyses were performed to identify prognostic factors. RESULTS: MPR was identified in 32 patients and ND was present in 108 patients. OS and DFS were better in the MPR group than in the non-MPR group, but with no statistical significance (OS, p = 0.158; DFS, p = 0.126). The ND group had better OS than the non-ND group (p = 0.031). However, the DFS between these two groups was comparable (p = 0.103). Further analyses suggested that both OS and DFS were better in the MPR + ND group than in the non-MPR + non-ND group (OS, p = 0.017; DFS, p = 0.029). Multivariate analyses confirmed that MPR + ND was an independent favorable predictor. CONCLUSIONS: MPR combined with ND could improve the predictive value on survival in NSCLC patients receiving NAC.

5.
Cancer Res ; 81(5): 1413-1425, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33402387

RESUMO

Novel strategies to treat late-stage nasopharyngeal carcinoma that often develop resistance to chemotherapy remains an unmet clinical demand. In this study, we identify the multi-kinase inhibitor pacritinib as capable of resensitizing the response to paclitaxel in an acquired resistance model. Transcriptome analysis of paclitaxel-sensitive and -resistant cell lines, as well as chemorefractory clinical samples, identified S100A9 as the top candidate gene suppressed by pacritinib and whose overexpression was significantly associated with paclitaxel resistance and poor clinical outcome. Moreover, both paclitaxel-resistant nasopharyngeal carcinoma cells and relapsed/metastatic clinical samples exhibited increased IRAK1 phosphorylation and demonstrated that pacritinib could abolish the IRAK1 phosphorylation to suppress S100A9 expression. Functional studies in both in vitro and in vivo models showed that genetic or pharmacologic blockade of IRAK1 overcame the resistance to paclitaxel, and combined treatment of pacritinib with paclitaxel exhibited superior antitumor effect. Together, these findings demonstrate an important role for the IRAK1-S100A9 axis in mediating resistance to paclitaxel. Furthermore, targeting of IRAK1 by pacritinib may provide a novel therapeutic strategy to overcome chemoresistance in nasopharyngeal carcinoma. SIGNIFICANCE: Deregulation of the IRAK1-S100A9 axis correlates with poor prognosis, contributes to chemoresistance in nasopharyngeal carcinoma, and can be targeted by pacritinib to overcome chemoresistance in nasopharyngeal carcinoma.

6.
J Obstet Gynaecol Res ; 47(3): 1145-1152, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462940

RESUMO

AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of intervention, while only one of 10 fatty liver participants in control group disappeared. CONCLUSIONS: In addition to improving the menstrual cycle, KD had the additional benefits of reducing blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional pharmacological treatment in women with PCOS and liver dysfunction who were obese.

7.
Int Heart J ; 61(6): 1220-1228, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33191343

RESUMO

Transcatheter closure (TCC) has emerged as the first-line treatment for coronary artery fistulas. However, limited data exist regarding the long-term outcomes and technical aspects of this procedure. We aimed to report the long-term outcomes and technical aspects of TCC of large coronary-cameral fistulas (CCFs).All patients with large CCFs who underwent attempted TCC using the patent ductus arteriosus (PDA) occluder or Amplatzer vascular plug (AVP), from June 2002 to December 2017, were retrospectively reviewed. A total of 23 patients with large CCFs underwent attempted TCC using the PDA occluder or AVP. Most CCFs originated from the right coronary artery and drained predominantly into the right heart chamber. Procedural success was achieved in 21 (91.3%) patients. Devices were deployed using the arteriovenous loop in 15, transarterial approach in 4, and arterio-artery loop approach in 2 patients. Procedural complications included coronary spasm in one and side branch occlusion in one patient. Among these 21 patients with successful device implantation, follow-up angiograms or computed tomography angiograms were obtained in 14 (66.7%) patients at a median of 11.0 (range, 9.8-16.3) months. Late complications included thrombosis of residual fistula segment without myocardial infarction (MI) in one, coronary thrombosis resulting in MI in one, and recanalization necessitating re-intervention in one patient. No death and device embolization occurred.TCC of large CCFs using the PDA occluder or AVP is an effective therapy in anatomically suitable candidates, with favorable long-term outcomes. Given that potentially hazardous complications may occur late after the procedure, long-term periodic evaluation is mandatory.

8.
Food Chem ; 341(Pt 2): 128202, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33038806

RESUMO

Parboiled rice has high nutritional value but unpleasant palatability. In this study, rice stickiness was significantly reduced by steaming during the parboiling process; however, continuing steaming past certain durations no longer affected rice stickiness. It was also found: (i) the degree of starch gelatinization (DSG) increases and starch crystallinity decreases with increasing steaming time; (ii) the molecular size and chain length distribution (CLD) of leached starch for both white and parboiled rice are significantly different from those of native starch; (iii) the relation between leached amylopectin amount and rice stickiness explains the reduced stickiness by parboiling; and (iv) starch gelatinization in the surface layer of rice grains during parboiling might be critically important in blocking starch leaching, consequently leading to a less sticky texture. This study supplies a way to manage glutinous rice stickiness by parboiling for the production of non-sticky rice foods.

9.
Int J Biol Macromol ; 165(Pt A): 214-221, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32980409

RESUMO

This study investigated the effects of acid degradation of amylopectin on the structure, pasting, and rheological properties of waxy maize starch. It is found that: 1) the amount of amylopectin short-chains with degree of polymerization (DP) ~ 15-50 increased while that of amylopectin long-chains with DP ~ 50-200 decreased by acid hydrolysis; 2) acid hydrolysis produced smaller amylopectin molecules with a narrower size distribution; 3) acid hydrolysis had a minor effect on the crystalline and granular structures of native starch; 4) the pasting viscosity of acid hydrolyzed starch during heating and the consistency coefficient, K, of starch gels increased, whereas the flow behavior index, n, decreased. Correlation analysis was used to clarify the molecular causes for the variations of pasting and rheological properties of acid hydrolyzed starch.

10.
World J Stem Cells ; 12(8): 879-896, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32952864

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases. AIM: To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases. METHODS: Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language. The keywords, such as "MSCs," "EVs," "exosome," "autoimmunity," "tumor immunity," and "transplantation immunity," and Boolean operator "AND" and "NOT" coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded. RESULTS: A total of 96 articles were chosen for final reference lists. After analyzing those publications, we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease. CONCLUSION: MSC-EVs play an equally important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

11.
Vet Res ; 51(1): 111, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891183

RESUMO

In our previous studies, a novel T. spiralis peptidase (TsP) was identified among the excretory/secretory (ES) proteins of T. spiralis intestinal infective larvae (IIL) and T. spiralis at the adult worm (AW) stage using immunoproteomics, but the biological function of TsP in the life cycle of T. spiralis is not clear. The objective of this study was to investigate the biological properties and functions of TsP in larval intrusion and protective immunity induced by immunization with rTsP. The complete TsP cDNA sequence was cloned and expressed. The results of RT-PCR, indirect immunofluorescence assay (IIFA) and western blotting revealed that TsP is a surface and secretory protein expressed in T. spiralis at different stages (muscle larvae, IIL, AWs and newborn larvae) that is principally localized at the epicuticle of the nematode. rTsP facilitated the larval intrusion of intestinal epithelial cells (IECs) and intestinal mucosa, whereas anti-rTsP antibodies suppressed larval intrusion; these facilitative and suppressive roles were dose-dependently related to rTsP or anti-rTsP antibodies. Immunization of mice with rTsP triggered an obvious humoral immune response (high levels of IgG, IgG1/IgG2a, and sIgA) and also elicited systemic (spleen) and intestinal local mucosal (mesenteric lymph node) cellular immune responses, as demonstrated by an evident increase in the cytokines IFN-γ and IL-4. Immunization of mice with rTsP reduced the numbers of intestinal adult worms by 38.6% and muscle larvae by 41.93%. These results demonstrate that TsP plays a vital role in the intrusion, development and survival of T. spiralis in hosts and is a promising candidate target molecule for anti-Trichinella vaccines.

12.
Am J Physiol Renal Physiol ; 319(4): F697-F711, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865013

RESUMO

Praliciguat, a clinical-stage soluble guanylate cyclase (sGC) stimulator, increases cGMP via the nitric oxide-sGC pathway. Praliciguat has been shown to be renoprotective in rodent models of hypertensive nephropathy and renal fibrosis. In the present study, praliciguat alone and in combination with enalapril attenuated proteinuria in the obese ZSF1 rat model of diabetic nephropathy. Praliciguat monotherapy did not affect hemodynamics. In contrast, enalapril monotherapy lowered blood pressure but did not attenuate proteinuria. Renal expression of genes in pathways involved in inflammation, fibrosis, oxidative stress, and kidney injury was lower in praliciguat-treated obese ZSF1 rats than in obese control rats; fasting glucose and cholesterol were also lower with praliciguat treatment. To gain insight into how tubular mechanisms might contribute to its pharmacological effects on the kidneys, we studied the effects of praliciguat on pathological processes and signaling pathways in cultured human primary renal proximal tubular epithelial cells (RPTCs). Praliciguat inhibited the expression of proinflammatory cytokines and secretion of monocyte chemoattractant protein-1 in tumor necrosis factor-α-challenged RPTCs. Praliciguat treatment also attenuated transforming growth factor-ß-mediated apoptosis, changes to a mesenchyme-like cellular phenotype, and phosphorylation of SMAD3 in RPTCs. In conclusion, praliciguat improved proteinuria in the ZSF1 rat model of diabetic nephropathy, and its actions in human RPTCs suggest that tubular effects may contribute to its renal benefits, building upon strong evidence for the role of cGMP signaling in renal health.


Assuntos
Apoptose/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Agonistas da Guanilil Ciclase C/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Nefrite/tratamento farmacológico , Pirazóis/farmacologia , Pirimidinas/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Linhagem Celular , Citocinas/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Progressão da Doença , Enalapril/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Nefrite/metabolismo , Nefrite/patologia , Fosforilação , Ratos Zucker , Transdução de Sinais , Proteína Smad3/metabolismo
13.
J Mater Chem B ; 8(37): 8684-8694, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32856659

RESUMO

Commercially available drug-eluting embolization beads (100-500 µm) reduced the occurrence of adverse events related to an anticancer drug, but were unascertained to remarkably benefit the transcatheter arterial chemoembolization (TACE) treatment of intermediate-stage liver cancer. Dextran-coated arsenite nanoparticles with the size ranging from 400 to 600 nm were developed as a nanosized drug-eluting bead (NDEB) for chemoembolization therapy of the rabbit VX2 liver tumor. We fully characterized their relevant physicochemistry and drug release properties. Their hemolysis was investigated before vessel embolization. The introduction of the NDEB allowed continuous embolization of tumor feeding vessels and sustained release of arsenic trioxide, thereby causing severe tumor necrosis and reduced vascularity. Sonography including B mode ultrasound, color Doppler flow imaging (CDFI) and dynamic contrast-enhanced ultrasound (CEUS) were performed to evaluate the tumor vascularity and viability. Additionally, its hepatotoxicity was tolerable at a medium dose. NDEB-TACE might be an effective therapeutic strategy for interventional therapy.

14.
ACS Omega ; 5(30): 18975-18986, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32775899

RESUMO

Almost all existing methods for preparing reduced graphene oxide/Mn3O4 (RGO/Mn3O4) composites are based on the synthetized graphene or graphene oxides (GO), which make them complicated and high-cost processes. Here, we reported a new method, which is able to convert graphite directly to RGO/Mn3O4 composites. Thus, it is simpler, more economical, and productive. The structure of RGO/Mn3O4 inheriting intermediate product GO/MnO2 composites that are formed by the present method is a novel three-dimensional "multilayer steamed bread" nanostructure, which constitutes mutually beneficial "symbiosis". The nano-Mn3O4 supports the space between RGO layers and further to the combination of RGO to self-assemble into large-sized (>40 µm) nanocomposites. Meanwhile, the formed Mn3O4 particles were small (60 × 10 nm2) in diameter and distributed homogeneously without the use of any template and surfactant. Because the structure and nanosize of composite cause the excellent electrochemical properties, RGO/Mn3O4 electrodes deliver an enhanced specific capacitance of 438.7 F/g at 0.3 A/g and outstanding cyclic stability (77.5% of its initial capacitance is retained after 1000 cycles).

15.
Cancer Manag Res ; 12: 5729-5737, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765076

RESUMO

Background: The N6-methyladenosine (m6A) RNA modification of mRNA mediates various cellular functions and cancer progression. However, the roles of m6A RNA modification in the regulation of esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer in Asia, were unclear. Materials and Methods: Here, we analyzed the mRNA expression level of methyltransferase like 3 (METTL3) in the public available datasets of ESCC tissues and matched adjacent normal tissues. We also performed immunohistochemistry (IHC) assays to detect the protein expression of METTL3 in human ESCC tissue specimen. In our study, we also analyzed the association between METTL3 expression and prognosis using Cox proportional hazard regression in 207 ESCC patients. Results: The results of public available datasets and IHC assays showed that METTL3 was upregulated in tumor compared with adjacent nonmalignant esophageal mucosal tissues. The IHC results indicated that higher expression level of METTL3 was associated with worse survival. We also found that METTL3 expression level was an independent predictor for disease-free survival and overall survival of ESCC patients. Conclusion: Our results revealed that the METTL3 expression level could be used as an independent prognostic biomarker for ESCC prognosis.

16.
ACS Sens ; 5(7): 2061-2066, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32608223

RESUMO

Aerosol plays an important role in a broad range of scientific disciplines, such as atmospheric chemistry and physics, fuel combustion, and human health. Current particle sizing instruments are usually bulky, complicated, and expensive, while the portable ones cannot provide sufficient measurement channels to describe the particle size distribution accurately. To address this challenge, we propose an optical sensing method to analyze the particle size distribution of aerosols based on the light scattering intensity field (LSIF). The LSIF is a set of scattering lights in all directions around the particles, which contains the scattering light signals in different observing angles. Then, the particle size distribution of the aerosol samples is retrieved by the Tikhonov regularization algorithm. A portable and low-cost aerosol sizing prototype sensor is designed to image part of the LSIF signals, where the LSIF is collected by a parabolic reflector and projected on the image sensor as an image with telecentric lenses. According to the experimental result of di-ethyl-hexyl-sebacate aerosol test, the relative measurement error of LSIF can be controlled to ±10%. With an integrated and cost-effective design, this particle sizing sensor shows great potential for routine field measurements outside of the laboratory.

17.
BMC Cardiovasc Disord ; 20(1): 282, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522146

RESUMO

BACKGROUND: While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China. METHODS: Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th-24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC < 0.5 using Cox regression models in primary and secondary prevention subgroups. Sensitivity analyses were conducted in propensity score matched groups. RESULTS: 99,655 patients were finally included. The mean (SD) PDC was 0.19 (0.15) in primary prevention subgroup (N = 34,372), with 5.4% patients had PDC ≥ 0.5. The patients with PDC ≥ 0.5 had a 37% reduced risk of MACE compared with patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 1.1% vs. 1.4%; all-adjusted HR = 0.63; 95% CI, 0.41-0.98). While, no significant difference was observed in the secondary prevention subgroup (N = 65,283) between patients with PDC ≥ 0.5 and patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 4.6% vs. 2.8%; all-adjusted HR = 1.08, 95% CI, 0.92-1.28). These findings were confirmed by the sensitivity analyses in propensity score matched groups. CONCLUSIONS: Statin adherence was very poor in China, and statin adherence is associated with decreased risk of MACE in patients for primary prevention, while further exploration is needed for secondary prevention.

18.
Vet Parasitol ; : 109160, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522393

RESUMO

The aim of this study was to ascertain the characteristics of a Trichinella spiralis cathepsin X (TsCX) and its role on larval invasion of intestinal epithelial cells (IECs). The full-length of TsCX cDNA sequence was cloned and expressed in Escherichia coli BL21. The results of RT-PCR, IFA and Western blot revealed that TsCX was expressed at T. spiralis muscle larvae (ML), intestinal infective larvae, adult worm and newborn larvae, and it was located in whole worm section. The results of Far western and confocal microscopy demonstrated that there was a specific binding of rTsCX and IEC, and the binding site was located within the IEC cytoplasm. rTsCX promoted T. spiralis larval invasion of mouse IECs while anti-rTsCX antibody inhibited larval invasion into the IECs. Silencing TsCX by specific siRNA reduced the TsCX expression and larval invasive capacity. These results indicated that TsCX specifically binds to IECs and promotes larval invasion of intestinal epithelia, and it might be a potential target of vaccines against enteral stages of T. spiralis.

19.
Int J Biol Macromol ; 161: 72-77, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32522545

RESUMO

High-pressure homogenization (HPH) is a common physical method used for starch modification. In this study, starch molecular structure in terms of chain-length distribution (CLD) and molecular size is characterized to explore the structural variations during HPH and its internal relations. It is found that: 1) the molecular size is significantly reduced by HPH treatments and further gradually decreases with HPH pressure increasing; 2) HPH degrades the long amylose chains with degree of polymerization (DP) ~ 2000-20,000 into short- and intermediate-amylose chains with DP ~ 100-1000 and DP ~ 1000-2000; 3) by HPH treatment, the proportion of amylopectin chains with DP ~ 6-12 and DP ~ 12-24 decreases while that with DP ~ 24-36 and DP ~ 36-100 increases, whereas, the amylopectin CLDs between HPH treated starch samples are not significantly varied; and 4) by a subtraction analysis, the molecular size of HPH treated starches shows a strong correlation with the proportion of degraded long amylose chains, indicating these long amylose chains might play a critical role in maintaining the large molecular size of starch. This study provides a further understanding of molecular features from the individual chains assembling into a whole branched molecule.

20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 90-93, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476379

RESUMO

OBJECTIVE: To observe the regulatory effect of 6-Shogaol on Notch signal pathway in colonic epithelial cells of mice with ulcerative colitis. METHODS: Forty Kunming mice were randomly divided into normal group (n=10) and model group (n=30). The model of ulcerative colitis was induced by free drinking of 2% dextran sulfate sodium salt(DSS). After 15 days, the mice were divided into model group, 6-gingerenol group and positive control group with 10 mice in each group. Normal group and model group were treated with normal saline, 6-gingerenol group was treated with 6-Shogaol 100 mg/(kg·d), positive control group was treated with sulfasalazine 100 mg/(kg·d), for 20 days. The histopathological changes of colon were observed, and the expressions of Hes-1 and Math-1protein in colonic epithelial cells were detected by immunofluorescence double labeling method. The expressions of Notch-1, Hes-1 and Math-1 mRNA in colonic epithelial tissue were detected by RT-PCR. The expressions of Notch-1, Hes-1 and Math-1 protein in colonic epithelial tissue was detected by Western blot. RESULTS: Compared with the normal group, the expression of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of model group were significantly increased (P<0.01), while the relative expressions of Math-1 mRNA and protein were decreased significantly (P<0.01). Compared with the model group, the expressions of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of 6-Shogaol group and sulfasalazine group were decreased significantly(P<0.01), while the relative expressions of Math-1 mRNA and protein were increased significantly(P<0.01). CONCLUSION: 6-Shogaol can inhibit the over activation of Notch pathway and regulate the balance of differentiation between colonic epithelialabsorptive cell line and secretory cell line and repair damaged mucosal tissue.


Assuntos
Catecóis/farmacologia , Colite Ulcerativa , Células Epiteliais/efeitos dos fármacos , Transdução de Sinais , Animais , Colo/citologia , Modelos Animais de Doenças , Mucosa Intestinal/patologia , Camundongos , Receptores Notch/metabolismo
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