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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118888, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32947159

RESUMO

In this study, the feasibility of estimation and forecast of different vitality Quercus variabilis seeds by a hyperspectral imaging technique were investigated. Artificially accelerated aging was conducive to achieve the division of four vitality levels. Hyperspectral data in the first 10 h of germination were continuously collected at one-hour intervals. The optimal band was selected for the original and pre-processed spectra which were treated by multiple scatter correction (MSC) and the Savitzky-Golay first derivative (SG 1st). Five characteristic wavelength methods were compared: successive projections algorithm (SPA), competitive adaptive reweighted sampling (CARS), genetic algorithm (GA), variable important in projection (VIP), and random frog (RF). Partial least square-discriminant analysis (PLS-DA) and K-nearest neighbor (KNN) built the vitality estimation model based on different data sets, and GA + PLS-DA constructed the optimal model with the highest accuracy. According to the weight coefficient and reflectance of the characteristic band extracted by the GA, the reflectance curves of different levels over time were plotted. The data of 0 h was employed to establish the vitality forecast model. The forecast model had a high recognition rate, with PLS-DA exceeding 99% and KNN exceeding 85%. This indicated that hyperspectral imaging of seed germination processes could achieve non-destructive estimation of Q. variabilis seed vitality, and accurate prediction in a shorter time is feasible.

2.
Saudi J Biol Sci ; 27(12): 3307-3312, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304136

RESUMO

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.

3.
Cell Tissue Bank ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33106965

RESUMO

Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the posterior tibial nerve or its terminal branches compressed by its fibro-osseous tunnel beneath the flexor retinaculum on the medial side of the ankle. The current study was a retrospective study of 107 cases of patients with TTS, in which the onset characteristics were summarized, the factors that might affect the surgical treatment effects of TTS were discussed and analyzed. The syndrome diagnoses and treatment experiences of TTS were extracted and analyzed. In our cohort, TTS was more often found in middle-aged and older women. And the medial plantar nerve bundle was the most frequently affected nerve structure. The efficacy of surgical treatment were correlated to the causes of the disease, involved nerve bundles, methods of operation, and whether neurolysis of the epineurium was performed. Neurolysis of the epineurium is was recommended for patients with an enlarged tibial nerve due to impingement. The Singh method was recommended to release the tibial nerve and its branches. Patients with negative preoperative EMG results should carefully be cautious when considering their decision to undergo surgical treatment.

4.
Int J Immunopathol Pharmacol ; 34: 2058738420954598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33100093

RESUMO

INTRODUCTION: This work was to explore the connection of KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and microRNA-4319 (miR-4319), and to investigate the associated underlying mechanisms in gastric cancer (GC) progression. METHODS: Quantitative real-time PCR was performed to measure KCNQ1OT1, miR-4319 and DNA-damage regulated autophagy modulator 2 (DRAM2) expression levels in GC cells. Moreover, expression level of KCNQ1OT1 and DRAM2 in GC tissues was analyzed at ENCORI website (http://starbase.sysu.edu.cn/index.php). Cell proliferation, colony formation assay and flow cytometry assays were performed to analyze effects of KCNQ1OT1, miR-4319 and DRAM2 on cell growth and death. Dual-luciferase activity reporter assay and RNA immunoprecipitation assay was conducted to verify the interactions of KCNQ1OT1 or DRAM2 and miR-4319. RESULTS AND CONCLUSION: We found KCNQ1OT1 level was increased in tumor tissues and cells. Force the expression of KCNQ1OT1 promotes, while knockdown KCNQ1OT1 inhibits GC cell growth. Further studies indicated miR-4319 functioned as a bridge between KCNQ1OT1 and DRAM2. Finally, we showed KCNQ1OT1/miR-4319/DRAM2 axis regulates GC cell growth in vitro and in vivo. lncRNA KCNQ1OT1 promotes GC progression by sponging miR-4319 to upregulate DRAM2, indicating KCNQ1OT1 might be a promising target for GC treatment.

5.
Front Pharmacol ; 11: 1321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982739

RESUMO

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by uncontrolled proliferation and accumulation of myeloblasts in the bone marrow (BM), blood, and other organs. The nuclear receptors Nur77 is a common feature in leukemic blasts and has emerged as a key therapeutic target for AML. Cantharidin (CTD), a main medicinal component of Mylabris (blister beetle), exerts an anticancer effect in multiple types of cancer cells. Purpose: This study aims to characterize the anti-AML activity of CTD in vitro and in vivo and explore the potential role of Nur77 signaling pathway. Study Design/Methods: The inhibition of CTD on cell viability was performed in different AML cells, and then the inhibition of CTD on proliferation and colony formation was detected in HL-60 cells. Induction of apoptosis and promotion of differentiation by CTD were further determined. Then, the potential role of Nur77 signaling pathway was assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice. Results: In our study, CTD exhibited potent inhibition on cell viability and colony formation ability of AML cells. Moreover, CTD significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. Meanwhile, CTD promoted the cleavage of caspases 8, 3 and PARP in HL-60 cells. Furthermore, CTD obviously suppressed the proliferation and induced the cell cycle arrest of HL-60 cells at G2/M phase. Meanwhile, CTD effectively promoted the differentiation of HL-60 cells. Notably, CTD transiently induced the expression of Nur77 protein. Interestingly, CTD promoted Nur77 translocation from the nucleus to the mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2, which is critical for the conversion of Bcl-2 from an antiapoptotic to a proapoptotic protein. Importantly, silencing of Nur77 attenuated CTD-induced apoptosis, reversed CTD-mediated cell cycle arrest and differentiation of HL-60 cells. Additionally, CTD also exhibited an antileukemic effect in NOD/SCID mice with the injection of HL-60 cells into the tail vein. Conclusions: Our studies suggest that Nur77-mediated signaling pathway may play a critical role in the induction of apoptosis and promotion of differentiation by CTD on AML cells.

6.
Dose Response ; 18(3): 1559325820916345, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973415

RESUMO

Due to long-term coevolution, secondary metabolites present in plants apparently function as chemical defense against insect feeding, while various detoxification enzymes in insects are adaptively induced as a prosurvival mechanism. Coptis chinensis, a medicinal plant used in traditional Chinese medicine for a thousand years, was found to be less prey to insects in our earlier field observations. Herein, 4 crude extracts obtained from sequential partition of aqueous extract of Rhizoma coptidis with petroleum ether, ethyl acetate, and n-butanol exhibited antifeedant activity against Spodoptera litura (Fabricius) larvae at high doses and inducing activity at low doses. Furthermore, a similar biphasic dose-response of the antifeedant activity against S litura larvae was also observed for jateorhizine, palmatine, and obakunone in Coptis chinensis. Notably, the enzyme activities of glutathione-S-transferase and carboxyl esterase in S litura larvae affected by the different components (jateorhizine, palmatine, obakunone, berberine, and coptisine) of C chinensis also showed a biphasic dose-response with an increasing trend at low doses and a decreasing trend at high doses. Together, our study suggests that the components of C chinensis may play a chemical defensive role against S litura larvae in a hormetic manner.

7.
Oxid Med Cell Longev ; 2020: 9524635, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32832011

RESUMO

Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the somatosensory nervous system. The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.

8.
Sensors (Basel) ; 20(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731447

RESUMO

In this study, we investigate Pd3-cluster-modified 555-777 graphene (Pd3-graphene) as a novel resistor-type gas sensor to detect SF6 decomposition products based on density functional theory calculations. We obtained and minutely analyzed the relevant parameters of each most stable adsorption configuration to explore the microscopic mechanism during gas adsorption. Theoretical results reveal that Pd3-graphene shows great adsorption capacity and sensitivity toward those decompositions. High adsorption energies and abundant charge transfer amounts could guarantee a stable adsorption structure of decomposition gases on Pd3-graphene surface. The complex change of density of states verifies a strong chemical reaction between the gases and the surface. Moreover, the conductivity of Pd3-graphene would improve due to the decrease of energy gap, and the sensitivity was calculated as SOF2 > H2S > SO2 > SO2 F2. This work provides an effective method to evaluate the operation status of SF6 gas-insulated equipment.

9.
Open Forum Infect Dis ; 7(7): ofaa172, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32665955

RESUMO

Background: In phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZVIN) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZVIN immunogenicity from these studies. Methods: Patients were randomized to ZVIN or placebo (4 doses). Immunogenicity was assessed by glycoprotein enzyme-linked immunosorbent assay (gpELISA) and VZV interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in patients receiving all 4 doses without developing HZ at the time of blood sampling. Results: Estimated geometric mean fold rise ratios (ZVIN/placebo) by gpELISA and IFN-y ELISPOT ~28 days post-dose 4 were 2.02 (95% confidence interval [CI], 1.53-2.67) and 5.41 (95% CI, 3.60-8.12) in auto-HSCT recipients; 1.88 (95% CI, 1.79-1.98) and 2.10 (95% CI, 1.69-2.62) in patients with STMc; and not assessed and 2.35 (95% CI, 1.81-3.05) in patients with HM. Conclusions: ZVIN immunogenicity was directionally consistent with clinical efficacy in auto-HSCT recipients and patients with STMc even though HZ protection and VZV immunity were not statistically correlated. Despite a lack of clinical efficacy in patients with HM, ZVIN immunogenicity was observed in this population. Immunological results did not predict vaccine efficacy in these 3 populations. Clinical trial registration: NCT01229267, NCT01254630.

10.
Acta Pharm Sin B ; 10(4): 628-645, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32322467

RESUMO

Lappaconitine (LA), a natural compound with a novel C18-diterpenoid alkaloid skeleton, displayed extensive biological profile. Recent research on LA is focused mainly on its anti-tumor and analgesic effects, and therefore we aimed to investigate its anti-inflammatory potential. A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized. In the initial screening of LA derivatives against NO production, all the target compounds, except compound E2, exhibited excellent inhibitory ability relative to that of LA. Particularly, compound A4 exhibited the most potent inhibition with IC50 of 12.91 µmol/L. The elementary structure-activity relationships (SARs) of NO inhibitory activity indicated that replacement of the benzene ring with an electron donating group could improve the anti-inflammatory efficacy. Furthermore, compound A4 shows an anti-inflammatory mechanism by inhibiting NO, PGE2, and TNF-α generation via the suppression of NF-κB and MAPK signaling pathways. Notably, compound A4 could exert a significant therapeutic effect on LPS-induced acute lung injury (ALI) in vivo. Based on the above research, we further investigated the preliminary pharmacokinetic property of A4 in rats. Therefore, compound A4 could be a promising candidate for the development of anti-inflammatory agents in the future.

11.
Sensors (Basel) ; 20(6)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32192222

RESUMO

The detection of objects concealed under people's clothing is a very challenging task, which has crucial applications for security. When testing the human body for metal contraband, the concealed targets are usually small in size and are required to be detected within a few seconds. Focusing on weapon detection, this paper proposes using a real-time detection method for detecting concealed metallic weapons on the human body applied to passive millimeter wave (PMMW) imagery based on the You Only Look Once (YOLO) algorithm, YOLOv3, and a small sample dataset. The experimental results from YOLOv3-13, YOLOv3-53, and Single Shot MultiBox Detector (SSD) algorithm, SSD-VGG16, are compared ultimately, using the same PMMW dataset. For the perspective of detection accuracy, detection speed, and computation resource, it shows that the YOLOv3-53 model had a detection speed of 36 frames per second (FPS) and a mean average precision (mAP) of 95% on a GPU-1080Ti computer, more effective and feasible for the real-time detection of weapon contraband on human body for PMMW images, even with small sample data.

12.
Phytomedicine ; 68: 153142, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32045840

RESUMO

BACKGROUND: The dried heartwood of Caesalpinia sappan L. is traditionally prescribed in the formula of traditional Chinese medicine (TCM) for the treatment of acute myeloid leukemia (AML), while nothing is yet known of the active fractions and the underlying mechanisms. PURPOSE: This study aims to investigate the effect of the ethyl acetate extract of the dried heartwood of Caesalpinia sappan L. (C-A-E) on induction of apoptosis and promotion of differentiation in vitro and anti-AML activity in vivo. STUDY DESIGN/METHODS: The aqueous extract was sequentially separated with solvents of increasing polarity and the active fraction was determined through the inhibition potency. The inhibition of the active fraction on cell viability, proliferation and colony formation was performed in different AML cells. Induction of apoptosis and the promotion of differentiation were further determined. Then, the level of the reactive oxygen species (ROS) and its potential role were assessed. Finally, anti-AML activity was evaluated in NOD/SCID mice. RESULTS: C-A-E exhibited the highest inhibition on the cell viability of HL-60 cells. Meanwhile, C-A-E significantly suppressed the proliferation and the colony formation ability of HL-60 and Kasumi-1 cells. Moreover, C-A-E significantly induced the apoptosis, which was partially reversed by Z-VAD-FMK. C-A-E also reduced the level of mitochondrial membrane potential, promoted the release of cytochrome C, decreased the Bcl-2/Bax ratio, and promoted the cleavage of caspase-9 and -3. In addition, Mdivi-1 (mitochondrial fission blocker) remarkably reduced the apoptosis caused by C-A-E. Meanwhile, C-A-E also induced the expression of Mff and Fis1 and increased the location of Drp1 in mitochondria. Furthermore, C-A-E obviously promoted the differentiation of AML cells characterized by the typic morphological changes, the increased NBT positive cells, as well as the increased CD11b and CD14 levels. Notably, C-A-E significantly enhanced the intracellular ROS level. Moreimportantly, C-A-E-mediated apoptosis and differentiation of HL-60 cells was significantly mitigated by NAC. Additionally, C-A-E also exhibited an obvious anti-AML effect in NOD/SCID mice with the injection of HL-60 cells. CONCLUSIONS: C-A-E exhibited an inhibitory effect on AML cells by inducing mitochondrial apoptosis and promoting differentiation, both of which were highly correlated to the activation of ROS.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Caesalpinia/química , Leucemia Mieloide Aguda/tratamento farmacológico , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetatos/química , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Antígeno CD11b/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Receptores de Lipopolissacarídeos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos NOD , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Sensors (Basel) ; 19(24)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817536

RESUMO

Tomographic synthetic aperture radar (TomoSAR) produces 3-D point clouds with unavoidable noise or false targets that seriously deteriorate the quality of 3-D images and the building reconstruction over urban areas. In this paper, a Hough transform was adopted to detect the outline of a building; however, on one hand, the obtained outline of a building with Hough transform is broken, and on the other hand, some of these broken lines belong to the same segment of a building outline, but the parameters of these lines are slightly different. These problems will lead to that segment of a building outline being represented by multiple different parameters in the Hough transform. Therefore, an unsupervised clustering method was employed for clustering these line parameters. The lines gathered in the same cluster were considered to correspond to a same segment of a building outline. In this way, different line parameters corresponding to a segment of a building outline were integrated into one and then the continuous outline of the building in cloud points was obtained. Steps of the proposed data processing method were as follows. First, the Hough transform was made use of to detect the lines on the tomography plane in TomoSAR point clouds. These detected lines lay on the outline of the building, but they were broken due to the density variation of point clouds. Second, the lines detected using the Hough transform were grouped as a date set for training the building outline. Unsupervised clustering was utilized to classify the lines in several clusters. The cluster number was automatically determined via the unsupervised clustering algorithm, which meant the number of straight segments of the building edge was obtained. The lines in each cluster were considered to belong to the same straight segment of the building outline. Then, within each cluster, which represents a part or a segment of the building edge, a repaired straight line was constructed. Third, between each two clusters or each two segments of the building outline, the joint point was estimated by extending the two segments. Therefore, the building outline was obtained as completely as possible. Finally, taking the estimated building outline as the clustering center, supervised learning algorithm was used to classify the building cloud point and the noise (or false targets), then the building cloud point was refined. Then, our refined and unrefined data were fed into the neural network for building the 3-D construction. The comparison results show the correctness and the effectiveness of our improved method.

15.
Oxid Med Cell Longev ; 2019: 1957920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178952

RESUMO

Background: Activation of cell apoptosis is a major form of cell death during myocardial ischemia/reperfusion injury (I/RI). Therefore, examining ways to control cell apoptosis has important clinical significance for improving postischemic recovery. Clinical evidence demonstrated that miR-181c-5p was significantly upregulated in the early phase of myocardial infarction. However, whether or not miR-181c-5p mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study is aimed at investigating the role and the possible mechanism of miR-181c-5p in apoptosis during I/R injury by using H9C2 cardiomyocytes. Methods and Results: The rat origin H9C2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by 6 hours reoxygenation) to induce cell injury. The results showed that H/R significantly increased the expression of miR-181c-5p but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model, miR-181c-5p expression was also significantly increased. The overexpression of miR-181c-5p by its agomir transfection significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase level and reduced cell viability) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases 3 expression, Bax/Bcl-2 and more TUNEL-positive cells). In contrast, inhibition of miR-181c-5p in vitro had the opposite effect. By using computational prediction algorithms, protein tyrosine phosphatase nonreceptor type 4 (PTPN4) was predicted as a potential target gene of miR-181c-5p and was verified by the luciferase reporter assay. The overexpression of miR-181c-5p significantly attenuated the mRNA and protein expression of PTPN4 in H9C2 cardiomyocytes. Moreover, knockdown of PTPN4 significantly aggravated H/R-induced enhancement of LDH level, cleaved caspase 3 expression, and apoptotic cell death, which mimicked the proapoptotic effects of miR-181c-5p in H9C2 cardiomyocytes. Conclusions: These findings suggested that miR-181c-5p exacerbates H/R-induced cardiomyocyte injury and apoptosis via targeting PTPN4 and that miR-181c-5p/PTPN4 signaling may yield novel strategies to combat myocardial I/R injury.


Assuntos
Hipóxia Celular/fisiologia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 4/metabolismo , Animais , Apoptose/fisiologia , Masculino , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 4/genética , Ratos , Ratos Sprague-Dawley , Transfecção
16.
J Virol ; 93(15)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31092579

RESUMO

Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of the live attenuated zoster vaccine (ZVL) have a very-well-described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunological factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot assays and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak T helper 1 (VZV-Th1) responses to ZVL were independently predicted by prevaccination VZV-Th1 responses, regulatory T cells (Treg), and PD1-expressing immune checkpoint T cells (Tcheck) but not by the age of the vaccinee. Persistence of VZV-Th1 1 year after vaccination was independently predicted by the factors mentioned above, by peak VZV-Th1 responses to ZVL, and by the age of the vaccinee. We further demonstrated by ex vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of prevaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults.IMPORTANCE Vaccination is the most effective method to protect older adults against viral infections. However, the immunogenicity of viral vaccines in older adults is notoriously poor. The live attenuated zoster vaccine (ZVL) provides the best example of a gradual decrease of vaccine immunogenicity with every 10-year age increase above 50 years. Here we show that the abundance of regulatory T cells before vaccine administration to older adults has a significant inhibitory effect on immune responses to ZVL and, together with baseline immunity to varicella-zoster virus, explains the effect of age on the immunogenicity of ZVL. Moreover, in vitro blockade of regulatory T cell mechanisms of action with biologic modulators restores immune responses to varicella-zoster virus in vaccinees. Collectively, these observations suggest that immune modulators that block regulatory T cell activity may increase responses to viral attenuated vaccines in older adults.


Assuntos
Vacina contra Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/imunologia , Imunidade Celular , Subpopulações de Linfócitos T/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Vacina contra Herpes Zoster/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
17.
Oxid Med Cell Longev ; 2019: 8936856, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911353

RESUMO

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fenofibrato/farmacologia , Transplante de Rim/efeitos adversos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibrose , Peróxido de Hidrogênio/toxicidade , Rim/efeitos dos fármacos , Túbulos Renais/patologia , Modelos Biológicos , Fenótipo , Ratos , Transplante Homólogo
18.
J Infect Dis ; 219(2): 335-338, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30165651

RESUMO

Protection against zoster conferred by zoster vaccine live (ZVL; Zostavax) wanes over time. We compared varicella-zoster virus cell-mediated immunity (VZV-CMI) of adults ≥70 years who received a second dose of ZVL ≥10 years after the initial dose with de novo-immunized age-matched controls. Before and during the first year after vaccination, VZV-CMI was significantly higher in reimmunized compared with de novo vaccinees. At 3 years, VZV-CMI differences between groups decreased and only memory responses remained marginally higher in reimmunized participants. In conclusion, the increase in VZV-CMI generated by reimmunization with ZVL is at least equally persistent compared with de novo immunization.


Assuntos
Vacina contra Herpes Zoster/administração & dosagem , Vacina contra Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Imunidade Celular/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Feminino , Humanos , Memória Imunológica , Interferon gama/imunologia , Interleucina-2/imunologia , Masculino , Vacinação , Vacinas Atenuadas/imunologia
19.
Oxid Med Cell Longev ; 2018: 8364848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510628

RESUMO

Nitric oxide synthases (NOSs) are a family of enzymes that are responsible for the synthesis of nitric oxide (NO) from the amino acid L-arginine in the body. Among the three key NOSs, the expression of inducible NOS (iNOS) can only be induced by inflammatory stimuli and contribute to the large amount of NO production. iNOS-derived NO plays an important role in various physiological and pathophysiological conditions, including the ischemic heart disease. Nowadays, the development of specific iNOS inhibitors and the availability of iNOS knockout mice have provided substantial evidence to support the role of iNOS/NO signaling in the myocardium. Nevertheless, the role of iNOS/NO signaling in the myocardial ischemic reperfusion injury is very complex and highly perplexing; both detrimental and beneficial effects of iNOS have been described. Thus, this review will aim at providing basic insights into the current progress of the role of iNOS in myocardial ischemia reperfusion injury. A better understanding of the dual role of iNOS in details may help facilitate the development of more effective therapies for the management of ischemic heart diseases.


Assuntos
Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Gerenciamento Clínico , Humanos , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia
20.
Am J Transl Res ; 10(9): 2822-2833, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323869

RESUMO

BACKGROUND: Transcribed ultraconserved regions (T-UCRs) are a subset of long noncoding RNAs. It has been reported that T-UCRs are dysregulated in cancers and play an important role in the development and progression of malignancies. uc.160 was found to be a suppressive factor of cancer development, but its role has not been fully elucidated. METHODS: The uc.160 expression was examined in gastric cancer tissues and established cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological function of gastric cancer cells with uc.160 over-expression were investigated, and the interaction between uc.160 and microRNA miR-155 was examined by dual-luciferase reporter assay. PTEN levels were detected by Western blotting. Anti-tumor effects of uc.160 were further explored in tumor transplantation models. RESULTS: uc.160 expression was significantly down-regulated in gastric cancer tissues and gastric cell lines as compared to adjacent normal tissues and immortalized gastric epithelial cell line (GES-1), respectively. Over-expression of uc.160 in SGC-7901 and AGS gastric cancer cells significantly suppressed their proliferation in vitro and in vivo. Moreover, uc.160 positively regulated the tumor suppressor protein PTEN. Interestingly, uc.160 was inhibited by microRNA miR-155 that is also a negative regulator of gastric cancer. CONCLUSION: uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies.

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