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1.
Sci Rep ; 10(1): 443, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949259

RESUMO

Herein, we describe the synthesis of highly water-dispersible and biocompatible 3D adsorbents via a rapid two-step strategy employing a mesoporous magnetic nanomulberry-shaped Fe3O4 (MNM) on diatomaceous earth (DE) and cucurbituril (CB; MNM-DE-CB). Coating of CB on the surface of MNM-DE via hydrogen bonds not only enhanced the dispersibility of CB, but also improved the stability of MNM-DE. The ability of the adsorbent to remove dyes from water was investigated as a function of metal ions, solution pH, temperature, and concentration to determine optimum reaction conditions. Unlike MNM-DE, MNM-DE-CB exhibited highly efficient, rapid dye removal and recyclability in aqueous solution, and low cytotoxicity toward cancer cells in drug delivery tests. MNM-DE-CB is a promising green adsorbent with potential for diverse applications including water remediation, interface catalysis, bio-sample preparation, and drug delivery.

2.
Sensors (Basel) ; 20(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936790

RESUMO

The basic phenomena of a cantilever energy harvesting device based on iron-gallium alloy magnetostrictive material for low frequency were systematically studied. The results highlighted how the physical parameters, geometric structure and bias conditions affected the vibration harvesting capacity through a thorough experimental aimed at enhancing the vibration energy harvesting capacity through an optimal design. How the performance is affected by the configuration of the multi-layers composite beam, material and dimensions of the elastic layer, arrangement position and number of bias magnets, the matching load resistance and other important design parameters was studied in depth. For the first time, it was clearly confirmed that the magnetic field of bias magnets and electromagnetic vibration shaker have almost no effect on the measurement of the voltage induced from the harvester. A harvesting power RMS up to 13.3 mW and power density RMS up to 3.7 mW/cm3/g was observed from the optimized prototype. Correspondingly, the DC output power and power density after the two-stage signal processing circuit were up to 5.2 mW and 1.45 mW/cm3/g, respectively. The prototype successfully powered multiple red light emitting diode lamps connected in a sinusoidal shape and multiple red digital display tubes, which verified the vibration harvesting capability or electricity-generating capability of the harvester prototype and the effectiveness of the signal converter.

3.
Antiviral Res ; 174: 104704, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917237

RESUMO

AIMS: Deguelin, a natural compound derived from Mundulea sericea (Leguminosae) and some other plants exhibits an activity to inhibit autophagy, a cellular machinery required for hepatitis C virus (HCV) replication. This study aimed to illuminate the impact of deguelin on HCV replication and mechanism(s) involved. METHODS: HCV JFH-1-Huh7 infectious system was used for the investigation. Real time RT-PCR, Western blot, fluorescent microscopy assay were used to measure the expression levels of viral or cellular factors. Overexpression and silencing expression techniques were used to determine the role of key cellular factors. RESULTS: Deguelin treatment of Huh7 cells significantly inhibited HCV JFH-1 replication in a dose- and time-dependent manner. Deguelin treatment suppressed autophagy in Huh7 cells, evidenced by the decrease of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the increase of p62 level in deguelin-treated cells compared with control cells. HCV infection could induce autophagy which was also suppressed by deguelin treatment. Mechanism research reveals that deguelin inhibited expression of Beclin1, which is a key cellular factor for the initiation of the autophagosome formation in autophagy. Overexpression or silencing expression of Beclin1 in deguelin-treated Huh7 cells could weaken or enhance the inhibitory effect on autophagy by deguelin, respectively, and thus partially recover or further inhibit HCV replication correspondingly. CONCLUSIONS: Deguelin may serve as a novel anti-HCV compound via its inhibitory effect on autophagy, which warrants further investigation as a potential therapeutic agent for HCV infection.

4.
Emerg Microbes Infect ; 8(1): 367-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851879

RESUMO

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/µL, 50-99 cells/µL, 100-199 cells/µL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/µL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

5.
Molecules ; 24(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703405

RESUMO

A simple, sensitive and effective magnetic solid-phase extraction (MSPE) technique was developed for the extraction of pyrethroid pesticides from environmental water samples, followed by gas chromatography tandem triple quadrupole mass spectrometry determination. An adsorbent of magnetic zeolitic imidazolate framework-8@deep eutectic solvent (M-ZIF-8@DES) was prepared using deep eutectic solvent coated on the surface of M-ZIF-8. The features of M-ZIF-8@DES were confirmed by material characterizations, and the results indicated that M-ZIF-8@DES has a good magnetism (61.3 emu g-1), a decent surface area (96.83 m2 g-1) and pore volume (0.292 mL g-1). Single factor experiments were carried out to investigate the effect of different conditions on the performance of MSPE. Under the optimal conditions, the developed method performs good linearity (R2 ≥ 0.9916) in the concentration range of 1-500 µg L-1. The limits of detection were in the range of 0.05-0.21 µg L-1 (signal/noise = 3/1). The intraday relative standard deviation (RSD) and interday RSD were less than 9.40%. Finally, the proposed technique was applied for the determination of pyrethroid pesticides in environmental water samples. This work shows the potential of DES-modified metal-organic frameworks for different sample pretreatment techniques.

6.
Sci Rep ; 9(1): 16374, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705044

RESUMO

Here, we describe a simple, universal protocol for use in nucleic acid testing-based pathogen diagnostics, which requires only hand-powered sample preparation, including the processes of pathogen enrichment and nucleic acid isolation. The protocol uses low-cost amine-functionalized diatomaceous earth with a 1-µm Teflon filter as a reaction matrix in both stages of the process, using homobifunctional imidoesters. Using a simple syringe as a pump, the capture efficiency for a large sample volume (<50 mL) was enhanced by up to 98.3%, and the detection limit was 1 CFU/mL, 100-fold better than that of common commercial nucleic acid isolation kit. This protocol can also be combined with commercialized 96-well filter plates for robust sample preparation. Our proposed system is robust, simple, low-cost, universal, and rapid (taking <20 min), and it works regardless of the ambient environment and sample pretreatment, requiring no electricity or instruments. Its benefits include the simplicity of producing its components and its ease of operation, and it can be readily integrated with other assays for point-of-care diagnostics.

7.
J Cell Physiol ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680239

RESUMO

Diabetic nephropathy (DN) is a severe end-stage kidney disease developed from diabetes mellitus. The involvement of circular RNAs (circRNAs) in modulating DN pathogenesis has been implied, but underlying mechanism is still lacking. In this study, we demonstrated that the expression of circ_0080425 correlated with the DN progression, and exerted positive effect on cell proliferation and fibrosis in mesangial cells. Further assessment suggested that circ_0080425 function as sponge harboring miR-24-3p. Moreover, miR-24-3p negatively correlated with the DN progression, and showed an antagonistic effect to circ_0080425on regulating MCs cell proliferation and fibrosis. Bioinformatics analysis predicted fibroblast growth factor 11 (FGF11) acting as direct downstream target of miR-24-3p. Indeed, the expression of FGF11 was significantly activated by circ_0080425 while suppressed by miR-24-3p. Knockdown of FGF11 resulted in a significant reduced cell proliferation rate and fibrosis. In addition, miR-24-3p inhibitor rescued the suppression of si-circ_0080425 on FGF11, suggesting that circ_0080425 competitive binding to miR-24-3p could release FGF11 from miR-24-3p suppression, which subsequently promoted DN progression.In conclusion, we have reported a novel circ_0080425-miR-24-3p-FGF11 axis, and explored the underlying mechanism in regulating DN pathogenesis.

8.
Am J Cancer Res ; 9(10): 2064-2078, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31720075

RESUMO

The activating receptor natural killer group 2, member D (NKG2D) is involved in both innate and adaptive immunities, and functions as a "master switch" in determining the activation status of natural killer (NK) cells. NKG2D binds to a diverse family of ligand molecules, which are only expressed at low levels in normal cells but can be upregulated by a cellular stress response. The NKG2D-NKG2D ligand (NKG2DL) pathway has been considered to be promising target for immunotherapy because of the selective expression of "stress-induced ligands" on tumor cells and the strong NK cell activating potency of NKG2D. Diverse strategies that are aimed at targeting the NKG2D pathway for cancer therapy are based on a thorough understanding of this mechanism, as well as that of NKG2D-mediated cancer immunity. In this review, we summarize the major findings regarding the antitumor immune response mediated by the NKG2D receptor and its ligands, and discuss the potential clinical applications of targeting the NKG2D/NKG2DL pathway for immunotherapy in cancer patients.

9.
ACS Appl Mater Interfaces ; 11(45): 41829-41841, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31617343

RESUMO

Photodynamic therapy (PDT) is an encouraging alternative therapy for melanoma treatment and Ce6-mediated PDT has shown some exciting results in clinical trials. However, PDT in melanoma treatment is still hampered by some melanoma's protective mechanisms like antiapoptosis mechanisms and treatment escape pathways. Combined therapy and enhancing immune stimulation were proposed as effective strategies to overcome this resistance. In this paper, a Chlorin-based photoactivable Galectin-3-inhibitor nanoliposome (PGIL) was designed for enhanced Melanoma PDT and immune activation of Natural Killer (NK) cells. PGIL were synthesized by encapsulating the photosensitizer chlorin e6 and low molecular citrus pectin in the nanoliposome to realize NIR-triggered PDT and low molecular citrus pectin (LCP) release into the cytoplasm. The intracellular release of LCP inhibits the activity of galectin-3, which increases the apoptosis, inhibits the invade ability, and enhances the recognition ability of Natural Killer (NK) cells to tumor cells in melanoma cells after PDT. These effects of PGIL were tested in cells and nude mice, and the mechanisms during the in vivo treatment were preliminarily studied. The results showed that PGIL can be an effective prodrug for melanoma therapy.

10.
Int Immunopharmacol ; 77: 105948, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629216

RESUMO

OBJECTIVE: The role of iNKT cells was investigated in chronic adipose tissue inflammation in obese mice after administration of α-GalCer in different pathways. METHODS: C57BL/6J mice were fed high-fat diet (HFD) for 12 weeks to establish the obese mouse model. The pathology of adipose tissue was observed by H&E staining. The rates of iNKT cells, macrophages and cell subsets in adipose tissue were detected by FCM. Cytokine levels in serum and adipose tissue lymphocyte-stimulated supernatants were assessed with the CBA kit. The expression levels of related transcription factor in adipose tissue were detected by Western blot. RESULTS: The proportions of iNKT cells, iNKT10 cells and M2 macrophages were decreased, while those of iNKT1 and M1 macrophages were increased in adipose tissue of HFD-fed mice. The expression levels of the related transcriptional proteins E4BP4 and Arg-1 were decreased while iNOS expression was increased in adipose tissue. Administration of α-GalCer by subcutaneous injection resulted in increased rates of iNKT10 cells and M2 macrophages, and decreased amounts of M1 macrophages in adipose tissue of HFD-fed mice. The expression of E4BP4 and Arg-1 were up-regulated, but iNOS was down-regulated. Meanwhile, infiltration of inflammatory cells into adipose tissue was further reduced. CONCLUSION: The imbalance between the proportions of iNKT1 and iNKT10 cells may be involved in the development of chronic inflammation in obese adipose tissue. Administration of α-GalCer by subcutaneous injection in HFD-fed mice activates adipose tissue iNKT10 cells, which promote M2 macrophage polarization and improve chronic inflammation in obese adipose tissue.

11.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500111

RESUMO

Purple turnip Brassica rapa ssp. rapa is highly appreciated by consumers but the metabolites and molecular mechanisms underlying the root skin pigmentation remain open to study. Herein, we analyzed the anthocyanin composition in purple turnip (PT) and green turnip (GT) at five developmental stages. A total of 21 anthocyanins were detected and classified into the six major anthocynanin aglycones. Distinctly, PT contains 20 times higher levels of anthocyanins than GT, which explain the difference in the root skin pigmentation. We further sequenced the transcriptomes and analyzed the differentially expressed genes between the two turnips. We found that PT essentially diverts dihydroflavonols to the biosynthesis of anthocyanins over flavonols biosynthesis by strongly down-regulating one flavonol synthase gene, while strikingly up-regulating dihydroflavonol 4-reductase (DFR), anthocyanidin synthase and UDP-glucose: flavonoid-3-O-glucosyltransferase genes as compared to GT. Moreover, a nonsense mutation identified in the coding sequence of the DFR gene may lead to a nonfunctional protein, adding another hurdle to the accumulation of anthocyanin in GT. We also uncovered several key members of MYB, bHLH and WRKY families as the putative main drivers of transcriptional changes between the two turnips. Overall, this study provides new tools for modifying anthocyanin content and improving turnip nutritional quality.

12.
Sensors (Basel) ; 19(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382645

RESUMO

Vibration energy harvesting attempts to generate electricity through recycling the discarded vibration energy that is usually lost or dissipated, and represents an alternative to traditional batteries and may even lead to reliable self-powered autonomous electronic devices. Energy harvesting based on magnetostrictive materials, which takes advantage of the coupling characteristics of the Villari effect and the Faraday electromagnetic induction effect, is a recent research field of great interest. Aiming to develop a new type of magnetostrictive energy harvester using Fe-Ga alloy, which is suitable for harvesting the vibration energy from base excitations and free excitations, a Fe-Ga based cantilever harvester was proposed. The energy harvesting performance of the harvester prototype, including its resonance characteristics, open-circuit output voltage-frequency response and amplitude characteristic under base excitation, influence of external resistance, energy harvesting performance under free excitation, the function of pre-magnetization and so on was studied systematically and carefully by experiments. In terms of the volume power density, the harvester prototype without pre-magnetized magnet when in series with the optimal resistor load displays a value of 2.653 mW/cm3. The average conversion efficiency without a pre-magnetic field is about 17.7% when it is in series with a 200 resistance. The energy harvesting and converting capability can therefore be improved greatly once the Fe-Ga beam is highly pre-magnetized. The prototype successfully lit up multi-LEDs and digital display tubes, which validates the sustainable power generation capacity of the fabricated prototype.

13.
Transl Neurodegener ; 8: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428316

RESUMO

Background: Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors. Main body: The prevalence of PD rises exponentially with age, and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death. However, the majority of those over the age of 80 do not have PD, thus other factors in addition to aging are needed to cause disease. Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk. Nevertheless, the causality of most environmental factors is not conclusively established, and alternative explanations such as reverse causality and recall bias cannot be excluded. The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD. Rare mutations as well as common variants in genes such as SNCA, LRRK2 and GBA are associated with risk of PD, but Mendelian causes collectively only account for 5% of PD and common polymorphisms are associated with small increase in PD risk. Heritability of PD has been estimated to be around 30%. Thus, aging, genetics and environmental factors each alone is rarely sufficient to cause PD for most patients. Conclusion: PD is a multifactorial disorder involving interplay of aging, genetics and environmental factors. This has implications on the development of appropriate animal models of PD which take all these factors into account. Common converging pathways likely include mitochondrial dysfunction, impaired autophagy, oxidative stress and neuroinflammation, which are associated with the accumulation and spread of misfolded α-synuclein and neurodegeneration. Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.

14.
Molecules ; 24(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362458

RESUMO

As persistent organic pollutants, dichlorodiphenyltrichloroethanes (DDTs) and their metabolites pose considerable risks to human health and the environment. Therefore, monitoring DDTs in the environment is essential. Here, we developed a green, simple, and effective magnetic solid-phase extraction (MSPE) method coupled with gas chromatography tandem triple-quadrupole mass spectrometry to determine the DDT content of environmental water samples. A magnetic ionic liquid (IL) adsorbent was developed based on a modified magnetic multiwalled carbon nanotube/zeolitic imidazolate framework-8 (MM/ZIF-8/IL), synthesized by immobilizing the IL on the surface of MM/ZIF-8. We confirmed successful synthesis of MM/ZIF-8/IL by material characterization, and our results suggested that the MM/ZIF-8/IL had a high Brunauer-Emmett-Teller surface area (159.9 m2 g-1), good thermostability (<800 °C), and a high degree of superparamagnetism (52.9 emu g-1). Several experimental conditions affecting the MSPE efficiency were optimized. Under the best conditions, good detection linearity was achieved (0.5-500 µg L-1) with determination coefficients ranging from 0.9927 to 0.9971. The lower limits of detection (0.0016-0.0072 µg L-1) also had good precision, having an intraday relative standard deviation (RSD) ≤ 6.5% and an interday RSD ≤ 8.9%. Finally, we used the as-developed method to determine DDT levels in environmental water samples.

15.
ACS Nano ; 13(7): 7556-7567, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31259530

RESUMO

Bone metastasis, a clinical complication of patients with advanced breast cancer, seriously reduces the quality of life. To avoid destruction of the bone matrix, current treatments focus on inhibiting the cancer cell growth and the osteoclast activity through combination therapy. Therefore, it could be beneficial to develop a bone-targeted drug delivery system to treat bone metastasis. Here, a bone-targeted nanoplatform was developed using gold nanorods enclosed inside mesoporous silica nanoparticles (Au@MSNs) which were then conjugated with zoledronic acid (ZOL). The nanoparticles (Au@MSNs-ZOL) not only showed bone-targeting ability in vivo but also inhibited the formation of osteoclast-like cells and promoted osteoblast differentiation in vitro. The combination of Au@MSNs-ZOL and photothermal therapy (PTT), triggered by near-infrared irradiation, inhibited tumor growth both in vitro and in vivo and relieved pain and bone resorption in vivo by inducing apoptosis in cancer cells and improving the bone microenvironment. This single nanoplatform combines ZOL and PTT to provide an exciting strategy for treating breast cancer bone metastasis.

16.
Int Immunopharmacol ; 74: 105727, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284229

RESUMO

The existence of association between the subpopulation of iNKT cells with different functions and nonalcoholic fatty liver disease has not been confirmed. To investigative the role of iNKT cells in the pathogenesis of nonalcoholic fatty liver disease, we established a non-alcoholic fatty liver model by feeding C57BL/6J mice for 12 weeks with a high-fat diet and injecting α-GalCer through different routes to activate hepatic iNKT cells. The liver of the mice fed a high-fat diet (HFD) had severe hepatic steatosis appearance, elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines in the liver, and high serum levels of TC, LDL, HDL, and ALT. Our results showed that the percentage of iNKT cells in the liver of the HFD-fed mice was lower than that of the control mice. The expression levels of the related transcription factor of T-bet increased but that of GATA-3 decreased in the HFD-fed mice. The administration of α-GalCer by intraperitoneal injection resulted in increasing of hepatic iNKT and iNKT2 cells but decreasing of hepatic iNKT1 cells, and the expression of GATA-3 and anti-inflammatory cytokine (IL-4) was increased in the liver, and hepatic steatosis was ameliorated in the HFD-fed mice. The administration of α-GalCer by subcutaneous injection resulted in a decrease in hepatic iNKT and iNKT2 and an augmentation of hepatic iNKT1 cells. However, hepatic steatosis was not significantly improved. We concluded that the intraperitoneal injection with α-GalCer effectively improved hepatic steatosis, according to increasing the number of hepatic iNKT2 cells. The precise mechanism requires further exploration.

17.
Immunogenetics ; 71(7): 489-499, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31297569

RESUMO

Epigenetic modifications have been shown to be important for immune cell differentiation by regulating gene transcription. However, the role and mechanism of histone methylation in the development and differentiation of iNKT cells in rheumatoid arthritis (RA) mice have yet to be deciphered. The DBA/1 mouse RA model was established by using a modified GPI mixed peptide. We demonstrated that total peripheral blood, thymus, and spleen iNKT cells in RA mice decreased significantly, while iNKT1 in the thymus and spleen was increased significantly. PLZF protein and PLZF mRNA levels were significantly decreased in thymus DP T cells, while T-bet protein and mRNA were significantly increased in thymus iNKT cells. We found a marked accumulation in H3K27me3 around the promoter regions of the signature gene Zbtb16 in RA mice thymus DP T cells, and an accumulation of H3K4me3 around the promoters of the Tbx21 gene in iNKT cells. The expression levels of UTX in the thymus of RA mice were significantly reduced. The changes in the above indicators were particularly significant in the progressive phase of inflammation (11 days after modeling) and the peak phase of inflammation (14 days after modeling) in RA mice. Developmental and differentiation defects of iNKT cells in RA mice were associated with abnormal methylation levels (H3K27me3 and H3K4me3) in the promoters of key genes Zbtb16 (encoding PLZF) and Tbx21 (encoding T-bet). Decreased UTX of thymus histone demethylase levels resulted in the accumulation of H3K27me3 modification.


Assuntos
Artrite Reumatoide/patologia , Lisina/metabolismo , Células T Matadoras Naturais/patologia , Regiões Promotoras Genéticas , Timo/fisiologia , Animais , Artrite Experimental/patologia , Diferenciação Celular , Epigênese Genética , Regulação da Expressão Gênica , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Metilação , Camundongos Endogâmicos DBA , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Baço/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo
18.
Mediators Inflamm ; 2019: 3140183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320835

RESUMO

To investigate the effect of ILC2s on Th2-type adaptive immunity during the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the study enrolled healthy people, stable COPD patients, and AECOPD patients. Flow cytometry was used to detect Th1, Th2, and ILC2 in the peripheral blood and CD80 and MHC II levels on ILC2. The mRNA levels of GATA3, RORα, and CRTH2 of ILC2s were detected by RT-PCR. In addition, ILC2s from the peripheral blood of AECOPD patients were cocultured with CD4+ T cells from the peripheral blood of healthy controls. Cytokine levels in serum of the three groups and the in vitro coculture supernatants were measured by ELISA. Compared with the stable COPD group or the healthy control group, Th2 in the peripheral blood of AECOPD group increased dramatically, inducing an increase of Th2/Th1 ratio in AECOPD patients. Meanwhile, the level of IL-4 in the serum of this group was also increased. However, we also detected ILC2s in the peripheral blood of the AECOPD group and found that it was also increased, alone with the increased GATA3, RORα, and CRTH2 mRNA levels. We also found that the CD80 and MHC II on ILC2 were significantly upregulated and the proportion of MHC II+ ILC2 cells was significantly positively correlated with the proportion of Th2 cells in AECOPD patients. To further demonstrate the effect of ILC2 on Th2 cells, we cocultured ILC2 with CD4+ T cells in vitro, which also showed a significant increase of Th2 ratio as well as Th2-associated cytokines IL-4, IL-5, and IL-13. However, we found that this effect of ILC2s on Th2 cells could be inhibited by the addition of anti-MHC II. The Th2/Th1 balance shifts to Th2 in AECOPD. ILC2s may function as APC by the upregulation of MHC II and regulate adaptive immunity shift to Th2-type response in AECOPD.

19.
Chin J Cancer Res ; 31(3): 453-462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31354214

RESUMO

Objective: Multidetector-row computed tomography (MDCT) and serum tumor biomarkers are commonly used to evaluate the preoperative lymph node metastasis and the clinical staging of gastric cancer (GC). This study intends to evaluate the clinical predictive value of MDCT and serum tumor biomarkers in lymph node metastasis of GC. Methods: The clinicopathologic data of 445 GC patients who underwent radical gastrectomy were retrospectively analyzed to evaluate the diagnostic value of MDCT and serum tumor biomarkers in lymph node metastatic staging of GC before surgery. Results: With the multinomial logistic regression analysis, the independent relative factors of lymph node metastasis of GC were identified as tumor size, depth of tumor invasion, vessel invasion, vascular embolus, and soft tissue invasion. The optimal critical value of the short diameter of lymph nodes detected by MDCT scanning for evaluation of preoperative lymph node metastasis was 6.0 mm, with 75.7% as predictive accuracy of lymph node metastasis compared to the postoperative pathological results of GC patients. In addition, the critical value of the short diameter of lymph nodes combined with serum tumor biomarkers [including carbohydrate antigen (CA)-724 and CA-199] could show an enhancement of predictive sensitivity of lymph node metastasis (up to 89.3%) before surgery. Conclusions: MDCT combined with serum tumor biomarkers should be adopted to improve preoperative sensitivity and accuracy of lymph node metastasis for GC patients.

20.
Gastroenterol Rep (Oxf) ; 7(3): 193-198, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31217983

RESUMO

Background: In addition to the stepwise manner of lymph-node metastasis from the primary tumour, the skip lymph-node metastasis (SLNM) was identified as a low-incidence metastasis of gastric cancer (GC). So far, both the mechanism and outcome of SLNM have not been elucidated completely. The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis. Methods: Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome. According to the pathological results, all GC patients who had lymph-node metastasis were categorized into three groups: patients with the perigastric lymph-node metastasis, patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results: Among the 505 GC patients who had lymph-node metastasis, 24 (4.8%) had pathologically identified SLNM. The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival (OS) (P = 0.194). The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC (P = 0.001). The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis (P < 0.001). The case-control matched logistic regression analysis results showed that tumour size (P = 0.002) was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery. Among the 19 pN1 GC patients with SLNM, 17 (89.5%) had metastatic lymph nodes along the common hepatic artery, around the celiac artery or in the hepatoduodenal ligament. Conclusions: SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.

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