1.Three-dimensional scaffold materials for cell culture and their application in tumor tissue engineering
Xiaodong HAN ; Lei WANG ; Jun ZHENG ; Xiaolong HE ; Jinshan JI ; Zhaoying FU
Chinese Journal of Tissue Engineering Research 2016;20(42):6371-6377
BACKGROUND:The use of three-dimensional cel culture techniques can better simulate the cel ular microenvironment, providing new tools for tissue engineering research.
OBJECTIVE:To analyze the biomaterial selection and application characteristics in three-dimensional cel culture as wel as applications in tumor tissue engineering.
METHODS:We searched Wanfang database and PubMed database 1998-2015 years for relevant literature using keywords of“three-dimensional cultures;scaffold;cel growth;cel differentiation;tumor tissue engineering”in Chinese and English, respectively.
RESULTS AND CONCLUSION:The selection and application of three-dimensional scaffold materials is one of the keys. So far, scaffold materials, such as col agen gels, gelatin sponge, agarose, chitosan, demineralized bone matrix, cannot provide the extracel ular matrix similar to the micro-environment in which seed cel growth and proliferation are not affected, and the ability to secrete type II col agen and glycosaminoglycan is decreased, although they can provide three-dimensional space for seed cel s. Biomimetic scaffold characterized as little trauma and strong plasticity gradual y shows its unique advantages. Three-dimensional culture conditions raise pro-angiogenic growth factor secretion from tumor cel s, and this feature is positively correlated with the occurrence of in vivo tumor angiogenesis.
2.Tsallis entropy-based prior for PET reconstruction.
Yuanyuan GAO ; Lijun LU ; Jianhua MA ; Zhaoying BIAN ; Qingwen LU ; Lei CAO ; Shaoying GAO
Journal of Biomedical Engineering 2013;30(3):455-459
Maximum a Posteriori (MAP) method has been widely applied to the ill-posed problem of image reconstruction. The choice of prior is the crucial point on MAP methods. However, the most conventional priors will lead to a blurring of the whole image or cause ladder-like artifacts. We therefore proposed a Tsallis entropy-based prior for positron emission tomography (PET) iterative reconstruction in MAP framework. The method uses a Tsallis entropy-based prior to eliminate the uncertainty between prior information and the estimated images. We tested this method in the phantom image, compared it with the traditional prior methods. the results showed that the proposed algorithm could suppress noise and obtain better reconstructed image quality.
Algorithms
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Artifacts
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Entropy
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Image Processing, Computer-Assisted
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methods
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Phantoms, Imaging
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Positron-Emission Tomography
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methods
3.Research advances on brain computer interface technology in rehabilitation of post-stroke cognitive impairment
Haiyin DENG ; Zhenming HUANG ; Zhaoying LI ; Youze HE ; Jingnan TU ; Lei CAO ; Yize RUAN ; Jia HUANG ; Jingsong WU
Chinese Journal of Geriatrics 2024;43(9):1203-1209
Brain computer interface(BCI)is a rapidly developing rehabilitation technology in recent years, which has been gradually used for cognitive rehabilitation of stroke patients.BCI can activate brain regions related to cognition to a greater extent through motor imagery and neural feedback technology, promote functional connectivity between brain regions, and ameliorate cognitive impairment after stroke.This paper summarized the mechanisms involved in BCI promoting cognitive rehabilitation and current applications of BCI in post-stroke cognitive impairment, and identifies the shortcomings of BCI in the treatment of post-stroke cognitive impairment, in order to provide insight for the research and clinical practice of BCI in post-stroke cognitive rehabilitation.
4.AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization
QIU YUE ; WANG HONGYANG ; PAN HUAYE ; GUAN JING ; YAN LEI ; FAN MINGJIE ; ZHOU HUI ; ZHOU XUANHAO ; WU KAIWEN ; JIA ZEXIAO ; ZHUANG QIANQIAN ; LEI ZHAOYING ; LI MENGYAO ; DING XUE ; LIN AIFU ; FU YONG ; ZHANG DONG ; WANG QIUJU ; YAN QINGFENG
Journal of Zhejiang University. Science. B 2023;24(2):172-184,中插22-中插31
Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%?49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%?17.9%, which was significantly higher than that (6.9%?7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
5.A prospective birth cohort study on the association between gestational blood pressure and neurodevelopment in 2-year-old children
Xianhe XIAO ; Lei CHEN ; Yanlong LI ; Zhaoying XIONG ; Yuanzhong ZHOU ; Wei XIA ; Yuanyuan LI ; Shunqing XU ; Huaicai ZENG ; Hongxiu LIU
Chinese Journal of Preventive Medicine 2024;58(9):1302-1310
Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.
6.A prospective birth cohort study on the association between gestational blood pressure and neurodevelopment in 2-year-old children
Xianhe XIAO ; Lei CHEN ; Yanlong LI ; Zhaoying XIONG ; Yuanzhong ZHOU ; Wei XIA ; Yuanyuan LI ; Shunqing XU ; Huaicai ZENG ; Hongxiu LIU
Chinese Journal of Preventive Medicine 2024;58(9):1302-1310
Objective:To investigate the association between gestational blood pressure and neurodevelopment in 2-year-old children.Methods:Based on the"Wuhan Healthy Baby Birth Cohort", 3 754 mother-infant pairs were enrolled in this study. Based on multiple blood pressure measurements during pregnancy, the mean, cumulative, and variability of blood pressure throughout the entire pregnancy and each trimester were calculated. Blood pressure variability was evaluated using standard deviation (SD), coefficient of variability (CV), and variability independent of mean (VIM). Follow-up testing of neurodevelopment in infants and young children at the age of two was conducted to obtain the Mental Development Index (MDI) and the Psychomotor Development Index (PDI). The multivariate linear regression and generalized estimation equation were used to analyze the association between gestational blood pressure data and neurodevelopmental index.Results:The age of 3 754 pregnant women was (29.1±3.6) years, with a pre-pregnancy BMI of (20.9±2.7) kg/m2 and a gestational age of (39.3±1.2) weeks. The birth weight of 3 754 children was (3 330.9±397.7) grams, and the birth length was (50.3±1.6) centimeters. The results of the multivariate linear regression analysis showed that after adjusting for relevant confounding factors, the mean blood pressure, cumulative blood pressure, standard deviation of blood pressure, coefficient of variation of blood pressure, independent blood pressure variability of systolic blood pressure, diastolic blood pressure, and pulse pressure throughout pregnancy were negatively associated with the MDI and PDI scores of 2-year-old children. The analysis results of the generalized estimation equation showed that after adjusting for relevant confounding factors, the average systolic blood pressure in the first, second, and third trimesters was negatively associated with MDI/PDI. The negative association between cumulative blood pressure and MDI/PDI was only found in the first trimester. The negative association between blood pressure variation during pregnancy and MDI/PDI was mainly concentrated in the second and third trimesters.Conclusion:There is a negative association between gestational blood pressure and the neurodevelopmental index of 2-year-old children.
7.Chinese herbal medicine Euphorbia esula extract induces apoptosis and inhibits the proliferation, migration and invasion of multidrug resistant gastric carcinoma cells.
Xianli GUO ; Zhaoying FU ; Yun BI ; Jun ZHENG ; Lei WANG ; Xiaolong HE ; Fei LI ; Xing LEI ; Qingquan REN
Journal of Biomedical Engineering 2018;35(2):244-251
This paper aims to study the effects of traditional Chinese medicine on multidrug resistant human gastric cancer cells in the cell proliferation, migration, invasion and apoptosis, and to study the apoptosis-inducing pathway. Different dilutions of extract were used to process human multidrug resistant gastric cancer SGC7901/ADR cells. Cell proliferation inhibition phenomenon was determined by MTT experiment. Nuclear morphological changes of apoptotic cells and apoptotic indexes were observed and determined by Hochest33528 staining followed with fluorescence microscope observing. Flow cytometry was used to detect cell apoptosis rate. Cell migration and invasion ability were observed and determined by Transwell method. Spectrophotometry was used to detect caspase-3 and caspase-9 enzyme activity. Western blotting was used to detect subcellular distribution of cytochrome c. The results showed that extract had obvious inhibition effect on proliferation of gastric cancer multidrug resistant SGC7901/ADR cells, which was time- and concentration-dependent. After processing multidrug resistant gastric cancer SGC7901/ADR cells with extract, the apoptotic index and apoptosis rate were significantly increased than those in the control group, which showed a time- and dose-dependent mode; but if a caspase inhibitor was added, apoptosis index was not obviously increased. Transwell method showed that migration and invasion ability of the extract-processed SGC7901/ADR cells dropped significantly. Spectrophotometry showed that in extract-processed SGC7901/ADR cells, caspase-3 and caspase-9 expression were increased, which had significant differences with the control group. Western blotting test showed that the distribution of cytochrome c decreased in mitochondria, while increased in the cytoplasm (i.e., cytochrome c escaped from mitochondria to the cytoplasm). In conclusion, extract could inhibit the proliferation, migration and invasion, and induce apoptosis in human gastric cancer multidrug resistant SGC7901/ADR cells; and cytochrome c, caspase-9 and caspase-3 might be involved in cell apoptosis induced by extract, suggesting endogenous or mitochondrial apoptotic pathway.
8.AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization.
Yue QIU ; Hongyang WANG ; Huaye PAN ; Jing GUAN ; Lei YAN ; Mingjie FAN ; Hui ZHOU ; Xuanhao ZHOU ; Kaiwen WU ; Zexiao JIA ; Qianqian ZHUANG ; Zhaoying LEI ; Mengyao LI ; Xue DING ; Aifu LIN ; Yong FU ; Dong ZHANG ; Qiuju WANG ; Qingfeng YAN
Journal of Zhejiang University. Science. B 2023;24(2):172-184
Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‒49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‒17.9%, which was significantly higher than that (6.9%‒7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans
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Apoptosis Inducing Factor/metabolism*
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NAD/metabolism*
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Dimerization
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Apoptosis