104 research outputs found
Abstract 4795: Nrf2 protects against chemotherapy-induced steatohepatitis and peripheral neurotoxicity
No full textAbstract
The indiscriminating protection of either normal or cancerous cells against electrophilic stresses by nuclear factor E2-related factor 2 (Nrf2) has evoked continuous controversy over its Janus face in cancer. However, both normal and cancerous cells co-exist in cancer patients, and the outcome of therapy is determined by responses of both. Here we systemically analyzed the correlation between Nrf2 expression in normal cells and chemotherapy-associated myelosuppression, steatohepatitis and peripheral neurotoxicity, and explored the possibility to predict and prevent these adverse effects by targeting Nrf2 signaling. Firstly, the toxicities of 22 clinically-used chemotherapeutic drugs were tested in bone marrow cells, liver cells and embryonic fibroblasts derived from either Nrf2 (-/-) or wild type mice, and the toxicities of drugs with IC50 in wild type cells > 2 folds higher than their Nrf2(-/-) counterparts are considered as significantly dependent on Nrf2. The dependency of taxol-induced myelosuppression on Nrf2 was confirmed in vivo, and the mRNA level of Nrf2 in peripheral blood mononuclear cells from cancer patients was reversely correlated to taxol-associated myelosuppression. Then steatohepatitis induced by irinotecan (CPT-11) and peripheral neurotoxicity induced by oxaliplatin were further investigated. CPT-11 induced intestinal toxicity in wild type mice but no significant steatohepatitis/liver toxicity was observed; however, CPT-11 treatment in Nrf2 (-/-) mice caused severer intestinal toxicity and pronounced steatohepatitis, associated with dramatically elevated serum biomarkers, accumulation of fat in liver cells, and altered liver histology. Similar results were observed for oxaliplatin-induced hepatotoxicity. Furthermore, Nrf2 deficiency significantly exaggerated oxaliplatin-induced peripheral neurotoxicity, as indicated by Von Frey test and cold plate assay. Interestingly, CDDO-Me was found to activate Nrf2 signaling in both normal tissues and xenograft tumors, while sulforaphane selectively activated Nrf2 in liver, bone marrow and peripheral nerves but not in tumors. As expected, sulforaphane significantly alleviated CPT-11-induced intestinal toxicity and oxaliplatin-induced peripheral neurotoxicity, while did not impact the therapeutic efficacy of drugs. Taken together, our results demonstrate that the toxicities of some of chemotherapeutic drugs currently in clinic usage are significantly affected by Nrf2, therefore it is possible to personalize therapeutic regimens according to Nrf2 expression in tumors and normal tissues. Specifically, CPT-11-induced steatohepatitis and intestinal toxicity and oxaliplatin-induced peripheral neurotoxicity are significantly determined by Nrf2, and Nrf2 could be selectively targeted to prevent or treat chemotherapy-induced toxicities. The present works were supported by the NSFC (No. 81272468, 91429305 and 81372266).
Note: This abstract was not presented at the meeting.
Citation Format: Liu He, Linling Que, Wenchen Yin, Baoshan Cao, Siwang Yu. Nrf2 protects against chemotherapy-induced steatohepatitis and peripheral neurotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4795. doi:10.1158/1538-7445.AM2017-4795</jats:p
Ji yu zhi jue de tu xiang xiang si xing du liang zhun ze
No full text圖像相似性度量準則是一個傳統的研究領域。大量經典的圖像處理技術被用來為各種類型的圖像設計相似性度量準則，這些圖像包括了線條圖，灰度圖，彩圖以及高動態範圍圖像。儘管已有的度量準則在指定的條件下可以實現優良的圖像相似度比較，這些度量準則極少系統地考慮或檢驗自身與人類視覺感知之間的一致性。而與人類知覺的一致性是由大量實際應用提出的共同需求。隨著三維立體設備的廣泛應用，圖像的相似性已經不只是傳統的可視差別，更包括了人眼利用三維立體設備同時觀看兩張不同的圖片時的視覺可接受度。非嚴謹對準形狀相似性度量準則（AISS）可以比較兩幅具有固定尺寸的線條圖的形狀相似度。對於該度量準則，兩幅待比較圖像的形狀不要求完全對齊，同時，又會考慮到圖像的形變，例如位置，方向和縮放上的變化。雙目觀看舒適度預測器（BVCP）是另一個度量準則。當人的雙眼同時觀看兩幅不同的圖像時，該準則可用以預測視覺的舒適度。根據著名的双眼單视理論，人的視覺可以將兩幅具有細節、對比度以及亮度差別的圖像合成一幅圖像，只要這些差別在限定的程度之內。在計算機圖形學領域，BVCP 首次嘗試去預測雙目的圖像差別會否引起觀看的不舒適。在本論文中，實用的應用程序也被提出用以衡量AISS 和BVCP。AISS 被用在了一個名為“基於結構的ASCII 藝術的應用程序中，該應用程序可以利用ASCII 字符的形狀近似地表現參考圖像的線條結構信息。而BVCP 則被用在一個創新地應用框架中，該框架可以從單幅高動態範圍圖像中生成一組（兩幅）低動態範圍圖像。當這一組低動態範圍圖像組被人的雙眼同時觀看時，可以比傳統的單幅低動態範圍圖像保留更多的人類可感知視覺信息。可信的結果和使用者研究也用來證明SSIM 和BVCP 的有效性以及與人類知覺的一致性。Image similarity metric is a traditional research field. Classical image processing techniques are used to design similarity metrics for all kinds of images, such as line drawings, gray or color image and even high-dynamic range (HDR) images. While existing metrics perform well for the tasks of comparing images in specified situations, few of them have systematically considered or examined the consistency with human perception required by practical applications. With the blooming of stereo devices, the similarity to be measured is not only the traditional visual difference between two images, but also the visual acceptance of two images when they are viewed simultaneously with 3D devices. This thesis presents two image similarity metrics motivated by perceptual principles, also with applications to demonstrate their novelty and practical values.Alignment-Insensitive Shape Similarity Metric (AISS) measures shape similarity of line drawings. This metric can tolerate misalignment between two shapes and, simultaneously, accounts for the differences in transformation such as, position, orientation and scaling.Binocular Viewing Comfort Predictor (BVCP) is another metric proposed to measure visual discomfort when human's two eyes view two different images simultaneously. According to a human vision phenomenon - binocular single vision, human vision is able tofuse two images with differences in detail, contrast and luminance, up to a certain limit. BVCP makes a first attempt in computer graphics to predict such visual comfort limit.Applications are also proposed to evaluate AISS and BVCP. AISS is utilized in an application of Structure-based ASCII Art, which approximates line structure of the reference image content with the shapes of ASCII characters. BVCP is utilized in a novel framework - Binocular Tone Mapping which generates a binocular low-dynamic range (LDR) image pair from one HDR image. Such binocular LDR pair can be viewed with stereo devices and can preserve more human-perceivable visual content than traditional one single LDR image. Convincing results and user studies are also shown to demonstrate that both AISS and BVCP are consistent with human perception and effective in practical usage.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Zhang, Linling.Thesis (Ph.D.)--Chinese University of Hong Kong, 2012.Includes bibliographical references (leaves 122-132).Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Abstract also in Chinese.Abstract --- p.iAcknowledgement --- p.vChapter 1 --- Introduction --- p.1Chapter 2 --- Alignment-Insensitive Shape Similarity Metric --- p.8Chapter 2.1 --- Related Work --- p.10Chapter 2.2 --- Design of AISS --- p.13Chapter 2.2.1 --- Misalignment Tolerance --- p.14Chapter 2.2.2 --- Transformation Awareness --- p.16Chapter 2.2.3 --- Parameter Setting --- p.17Chapter 2.3 --- Results and Discussion --- p.18Chapter 2.4 --- Discussion --- p.20Chapter 3 --- Application for AISS: Structure-based ASCII Art --- p.21Chapter 3.1 --- Overview --- p.24Chapter 3.2 --- Optimization --- p.28Chapter 3.3 --- User Study and Discussion --- p.35Chapter 3.3.1 --- Metrics Comparison --- p.35Chapter 3.3.2 --- Comparison to Existing Work --- p.38Chapter 3.3.3 --- User Study --- p.40Chapter 3.4 --- Summary --- p.44Chapter 4 --- Binocular Viewing Comfort Predictor --- p.48Chapter 4.1 --- Background --- p.51Chapter 4.2 --- Design of BVCP --- p.54Chapter 4.2.1 --- Fusional Area --- p.55Chapter 4.2.2 --- Contour Fusion --- p.58Chapter 4.2.3 --- Contour and Regional Contrasts --- p.68Chapter 4.2.4 --- Failure of Rivalry --- p.70Chapter 4.2.5 --- The Overall Fusion Predictor --- p.74Chapter 4.3 --- User Study --- p.77Chapter 4.4 --- Discussion and Limitations --- p.84Chapter 5 --- Application for BVCP: Binocular Tone Mapping --- p.86Chapter 5.1 --- Framework --- p.90Chapter 5.1.1 --- Overview --- p.90Chapter 5.1.2 --- Optimization --- p.93Chapter 5.2 --- Results and Discussion --- p.96Chapter 5.2.1 --- Results --- p.96Chapter 5.2.2 --- User Study --- p.103Chapter 5.2.3 --- Incorporating Stereopsis --- p.106Chapter 5.2.4 --- Limitations --- p.109Chapter 5.3 --- Summary --- p.112Chapter 6 --- Conclusion --- p.113Chapter A --- User Study for ASCII art --- p.117Bibliography --- p.12
Activation of Nrf2-ARE signaling mitigates cyclophosphamide-induced myelosuppression
No full textMyelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2(-/-) mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2(-/-) mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice. Single dosage of cyclophosphamide induced significantly severer acute myelosuppression in Nrf2(-/-) mice than in wild type mice. Furthermore, Nrf2(-/-) mice exhibited greater loss of peripheral blood nucleated cells and recovered slower from myelosuppression nadir upon multiple consecutive dosages of cyclophosphamide than wild type mice did. This was accompanied with decreased antioxidant and detoxifying gene expressions and impaired colony formation ability of Nrf2(-/-) bone marrow cells. More importantly, activation of Nrf2 signaling by CDDO-Me significantly alleviated cyclophosphamide-induced myelosuppression, while this alleviation was diminished in Nrf2(-/-) mice. In conclusion, the present study shows that Nrf2 plays a protective role in cyclophosphamide-induced myelosuppression and activation of Nrf2 is a promising strategy to prevent or treat chemotherapy-induced myelosuppression. (C) 2016 Elsevier Ireland Ltd. All rights reserved.National Natural Science Foundation of China [81272468, 21001011]; WU JIEPING Medical foundation [320.6750.12196]SCI(E)[email protected]; [email protected]
Time-series analysis on relationship between short-term exposure to atmospheric ozone and the risk of non-accidental deaths in Hefei during 2017−2020
No full textBackgroundIn recent years, Hefei has experienced rapid industrial development, and the concentration of ozone (O3) in the environment has increased year by year. Ambient O3 pollution has become one of the big issues in Hefei.ObjectiveTo explore the health risks of non-accidental deaths (NAD) in local residents associated with ambient O3 in Hefei City, and propose effective measures.MethodsThe data of daily NAD, mortality due to circulatory system diseases, mortality due to respiratory system diseases, atmospheric pollution, and meteorological factors were collected in Hefei from 2017 to 2020. By fitting daily average temperature, relative humidity, time trend, and seasonal trend, a generalized additive model was applied to evaluate the single-day effects (lag0-lag5) and cumulative lag effects (lag01-lag05) of NAD, circulatory system mortality, and respiratory system mortality among residents of Hefei City for every 10 μg·m−3 increase in the daily maximum 8-hour average ozone (O3-8 h) concentration. The effects of O3-8 h concentration on total NAD were also examined by stratification of age and sex.ResultsDuring the period of 2017 to 2020, the average concentration of O3-8 h in Hefei City was 99.12 μg·m−3, and the total number of non-accidental deaths was 45787. For the O3-8 h concentration per 10 μg·m−3 increase, the single-day effect and cumulative lag effect on NAD among residents reached their maximum values at lag0 and lag02, respectively, with the NAD increasing by 0.46% (95%CI: 0.06%, 0.87%) and 0.76% (95%CI: 0.27%, 1.26%); the maximum estimates for deaths from circulatory diseases appeared on lag03 increasing by 0.78% (95%CI: 0.08%, 1.48%). The stratified analyses results showed that the single-day effects on the NAD in males and females reached the maximum values on lag1 and lag0, increasing by 0.64% (95%CI: 0.21%, 1.08%) and 0.61% (95%CI: 0.03%, 1.20%), respectively; on lag02, the NAD among males was the highest, reaching 0.98% (95% CI: 0.39%, 1.57%); significant estimates for NAD among residents aged 65 years and above were observed on lag1 and lag02 rising by 0.41% (95%CI: 0.02%, 0.81%) and 0.67% (95%CI: 0.13%, 1.21%), respectively. After adjusting the degrees of freedom of time trend and other atmospheric pollutants, there was no statistically significant change in the risk of NAD death among residents associated with O3-8h concentration.ConclusionThe increase O3 concentration in Hefei is correlated with an increased NAD risk among residents, with males and people over 65 years old having a higher risk of death due to O3 exposure. It is necessary for the government to play an important role in developing prevention and control measures to reduce the excess risk of death associated with O3 exposure
Magnetically Driven Muco-Inert Janus Nanovehicles for Enhanced Mucus Penetration and Cellular Uptake
No full textOne of the main challenges of transmucosal drug delivery is that of enabling particles and molecules to move across the mucosal barrier of the mucosal epithelial surface. Inspired by nanovehicles and mucus-penetrating nanoparticles, a magnetically driven, mucus-inert Janus-type nanovehicle (Janus-MMSN-pCB) was fabricated by coating the zwitterionic polymer poly(carboxybetaine methacrylate) (pCB) on the mesoporous silica nanorod, which was grown on one side of superparamagnetic Fe3O4 nanoparticle using the sol–gel method. X-ray diffraction, transmission electron microscopy, vibrating sample magnetometry, and Fourier infrared spectroscopy were used to characterize the structure and morphology of the nanovehicles, proving the success of each synthesis step. The in vitro cell viability assessment of these composites using Calu-3 cell lines indicates that the nanovehicles are biocompatible in nature. Furthermore, the multiparticle tracking, Transwell® system, and cell imaging experimental results demonstrate that both the modification of pCB and the application of a magnetic field effectively accelerated the diffusion of the nanovehicles in the mucus and improved the endocytosis through Calu-3. The favorable cell uptake performance of Janus-MMSN-pCB in mucus systems with/without magnetic driving proves its potential role in the diagnosis, treatment, and imaging of mucosal-related diseases
Implications from protein uptake kinetics onto dextran-grafted Sepharose FF coupled with ion exchange and affinity ligands
No full text
An Enhanced Random Access Scheme: Multi-Power Contention Resolution Diversity Slotted Aloha
No full textThe influence of training surface on the effectiveness of plyometric training on physical fitness attributes of volleyball players
No full textAbstract The objective of the present study was to examine the impact of different plyometric training (PT) surfaces on the adaptive changes of jumping ability, sprinting speed, change of direction ability and strength performance in volleyball players. Forty male players participated in the study and were divided into four equal groups performing PT in aquatic (APT), sand (SPT), and land (LPT) surfaces, or an active control group (CON). All training groups indicated small to large significant (p = 0.001) improvements in countermovement vertical jump (CMVJ), standing long jump (SLJ), spike jump, block jump, 10-m sprint, T-test, and maximal strength after the 6 weeks of progressive volume-based overload PT and in comparison to CON group (p < 0.05). Both the APT (standardized mean difference [SMD] = 0.97, p = 0.01) and SPT (SMD = 1.10, p = 0.04) exhibited superior training advancements compared to LPT in the CMVJ performance. Notably, the APT displayed significantly greater improvements than the LPT in SLJ (SMD = 0.31, p = 0.043), sprint (SMD = -0.63, p = 0.028), T-test, (SMD = -0.46, p = 0.022) and strength (SMD = 0.61, p = 0.03) performance. Based on these results, it is recommended that incorporating APT and SPT induced greater training benefits than LPT in the CMVJ, while the application of APT is suggested for greater enhancing in linear sprint, change of direction ability, and maximal strength compared to land training method
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