摘要:
<jats:sec><jats:title>Background</jats:title><jats:p>With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation <jats:italic>in vitro</jats:italic>. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2′-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the <jats:italic>in vivo</jats:italic> effect of MIR22HG on the radiosensitivity of hepatoma.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity <jats:italic>via</jats:italic> miR-22-5p in HCC.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.</jats:p></jats:sec>
摘要:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions. In this study, we investigated the effects of OMT on diabetes‐associated aortic endothelial dysfunction in a rat model of diabetes and its mechanisms.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Male Sprague‐Dawley rats were randomly divided into five groups: control, diabetic rats, diabetic rats treated with OMT (60, 120 mg/kg per day, by gavage), and diabetic rats treated with metformin (20 mg/kg per day, by gavage). The serum fasting blood glucose, insulin, total cholesterol, triglyceride, and nitric oxide (NO) levels were determined with commercial kits. Biochemical indices reflecting oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) were analyzed with commercial kits. Mitochondrial reactive oxygen species 2′,7′‐dichlorofluorescein diacetate (DCFH‐DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes. Western blot analysis was applied to detect the expression levels of eNOS and NOX4. Reverse transcription polymerase chain reaction was used to detect the expressions of eNOS and NOX4 messenger RNA (mRNA).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The diabetic rats exhibited markedly reduced body weight and increased plasma glucose levels. Moreover, the diabetic rats showed oxidative stress (significantly increased MDA and decreased SOD, CAT, GSH‐Px, and serum NO levels). Hyperglycemia caused significant endothelial injury and dysfunction, including vasodilative and histologic changes in the diabetic rats. The expressions of phospho‐eNOS protein and mRNA were significantly decreased, while the NOX4 protein expression was increased in the aortas of the diabetic rats. All of these diabetes‐induced effects were reversed by OMT in the diabetic rats.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The OMT treatment ameliorates diabetic endothelial dysfunction through enhanced NO bioavailability by upregulating eNOS expression and downregulating expression of NOX4.</jats:p></jats:sec>
期刊:
CURRENT DRUG DELIVERY,2019年16(2):164-170 ISSN:1567-2018
通讯作者:
Huang, YY
作者机构:
[Wu, Yuting; Li, Jinhui; Li, Zhihong; Huang, Dong; Du, Lili; Zhao, Deyao] Peking Univ, Natl Key Lab Sci & Technol Micro Nano Fabricat, Inst Microelect, Inst Mol Med, Beijing 100871, Peoples R China.;[Li, Xiaoqiong; Huang, YY; Deng, Yulin; Huang, Yuanyu] Beijing Inst Technol, Minist Ind & Informat Technol, Key Lab Mol Med & Biotheranot, Adv Res Inst Multidisciplinary Sci,Sch Life Sci, Beijing 100081, Peoples R China.;[Xia, Xin-Hua] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Huang, YY ] B;Beijing Inst Technol, Minist Ind & Informat Technol, Key Lab Mol Med & Biotheranot, Adv Res Inst Multidisciplinary Sci,Sch Life Sci, Beijing 100081, Peoples R China.
关键词:
Drug delivery;gene therapy;chaotic microfluidics;nanoneedle array;staggered herringbone channel;microfluidic chip
摘要:
<jats:sec>
<jats:title>Background: </jats:title>
<jats:p>Delivery of foreign cargoes into cells is of great value for bioengineering research
and therapeutic applications.
</jats:p></jats:sec>
<jats:sec>
<jats:title>Objective:</jats:title>
<jats:p> In this study, we proposed and established a carrier-free gene delivery platform utilizing
staggered herringbone channel and silicon nanoneedle array, to achieve high-throughput in vitro gene
transfection.
</P><P>
Methods: With this microchip, fluidic micro vortices could be induced by the staggered-herringboneshaped
grooves within the channel, which increased the contact frequency of the cells with the channel
substrate. Transient disruptions on the cell membrane were well established by the nanoneedle array on
the substrate.
</P><P>
Result: Compared to the conventional nanoneedle-based delivery system, proposed microfluidic chip
achieved flow-through treatment with high gene transfection efficiency (higher than 20%) and ideal cell
viability (higher than 95%).
</jats:p></jats:sec>
<jats:sec>
<jats:title />
<jats:p> It provides a continuous processing environment that can satisfy the transfection requirement
of large amounts of biological molecules, showing high potential and promising prospect for both
basic research and clinical application.</jats:p>
</jats:sec>
作者机构:
[Ying‐Jiao Liu; Xun Li; Yao‐Mei Hu; Ye Peng; Nai‐Hong Chen] Hunan Univ Chinese Med, Coll Pharm, Changsha, Hunan, Peoples R China;[Ying‐Jiao Liu; Jiao Chen; Xin Zhou; Shi‐Feng Chu; Nai‐Hong Chen] Chinese Acad Med Sci, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med, Beijing, Peoples R China;[Ying‐Jiao Liu; Jiao Chen; Xin Zhou; Shi‐Feng Chu; Nai‐Hong Chen] Chinese Acad Med Sci, Neurosci Ctr, Beijing, Peoples R China;[Ying‐Jiao Liu; Jiao Chen; Xin Zhou; Shi‐Feng Chu; Nai‐Hong Chen] Peking Union Med Coll, 1 Xiannongtan St, Beijing 100050, Peoples R China;[Ying‐Jiao Liu; Xun Li; Yao‐Mei Hu; Ye Peng; Nai‐Hong Chen] Hunan Engn Technol Ctr Standardizat & Funct Chine, Changsha, Hunan, Peoples R China
通讯机构:
[Chen, NH ] P;Peking Union Med Coll, 1 Xiannongtan St, Beijing 100050, Peoples R China. Chinese Acad Med Sci, Dept Pharmacol, Inst Mat Med, 1 Xiannongtan St, Beijing 100050, Peoples R China.
摘要:
As an endogenous neuroprotectant agent, adenosine is extensively distributed and is particularly abundant in the central nervous system (CNS). Under physiological conditions, the concentration of adenosine is low intra- and extracellularly, but increases significantly in response to stress. The majority of adenosine functions are receptor-mediated, and primarily include the A1, A2A, A2B, and A3 receptors (A1R, A2AR, A2BR, and A3R). Adenosine is currently widely used in the treatment of diseases of the CNS and the cardiovascular systems, and the mechanisms are related to the disease types, disease locations, and the adenosine receptors distribution in the CNS. For example, the main infarction sites of cerebral ischemia are cortex and striatum, which have high levels of A1 and A2A receptors. Cerebral ischemia is manifested with A1R decrease and A2AR increase, as well as reduction in the A1R-mediated inhibitory processes and enhancement of the A2AR-mediated excitatory process. Adenosine receptor dysfunction is also involved in the pathology of Alzheimer's disease (AD), depression, and epilepsy. Thus, the adenosine receptor balance theory is important for brain disease treatment. The concentration of adenosine can be increased by endogenous or exogenous pathways due to its short half-life and high inactivation properties. Therefore, we will discuss the function of adenosine and its receptors, adenosine formation, and metabolism, and its role for the treatment of CNS diseases (such as cerebral ischemia, AD, depression, Parkinson's disease, epilepsy, and sleep disorders). This article will provide a scientific basis for the development of novel adenosine derivatives through adenosine structure modification, which will lead to experimental applications.
期刊:
Evidence-Based Complementary and Alternative Medicine,2019年2019:1-12 ISSN:1741-427X
通讯作者:
Chen, NH
作者机构:
[Li, Xun; Liu, Yinjiao; Chen, Naihong; Chen, NH] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.;[Chen, Naihong; Chu, Shifeng; Chen, NH] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China.;[Chen, Naihong; Chu, Shifeng; Chen, NH] Peking Union Med Coll, Beijing 100050, Peoples R China.
通讯机构:
[Chen, NH ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.;Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China.;Peking Union Med Coll, Beijing 100050, Peoples R China.
作者:
Zou, Yingjie;Sun, James;Zhou, Yangying;Bai, Harrison Xiao;Huang, Xiangyan;...
期刊:
SPINE,2018年43(10):E565-E573 ISSN:0362-2436
通讯作者:
Yang, L
作者机构:
[Zou, Yingjie; Tang, Xiangqi; Huang, Xiangyan; Yang, Li] Cent South Univ, Xiangya Hosp 2, Dept Neurol, Changsha, Hunan, Peoples R China.;[Zou, Yingjie] Hunan Univ Chinese Med, Coll Acupuncture & Moxibust, Changsha, Hunan, Peoples R China.;[Sun, James; Woo, John H.; Bai, Harrison Xiao] Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA.;[Zhou, Yangying] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Hunan, Peoples R China.;[Babu, Ranjith] Duke Univ Hosp, Dept Neurosurg, Durham, NC USA.
通讯机构:
[Yang, L ] C;Cent South Dept Pathol & Lab Med Univ, Xiangya Hosp 2, Dept Neurol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China.
关键词:
astrocytoma;extent of resection;glioma;radiotherapy;spinal cord
摘要:
<jats:sec>
<jats:title>Study Design.</jats:title>
<jats:p>Retrospective cohort analysis of patients with spinal astrocytoma from multi-institutional data and the literature.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objective.</jats:title>
<jats:p>To determine the prognostic factors, treatment, and survival of patients.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Summary of Background Data.</jats:title>
<jats:p>Our current understanding of the epidemiology, prognosis, and optimal treatment of spinal astrocytoma is limited. The literature is confined to case reports or small institutional case series.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Method.</jats:title>
<jats:p>Patient demographics, tumor characteristics, treatments, and outcomes were extracted. Univariate Kaplan-Meier survival analysis was performed to identify prognostic factors followed by multivariate Cox proportional hazard analysis. Wilcoxon signed-rank test was performed on pre- and postoperational functional status as measured by McCormick score.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results.</jats:title>
<jats:p>Ninety-four patients from four institutions and 339 patients from the literature were included. For the multi-institutional cohort, WHO grade IV tumors had shorter progression-free survival (PFS) than those of lower grades, whereas gross total resection (GTR) (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.14–1.27, <jats:italic toggle="yes">P</jats:italic> = 0.124) trended toward longer PFS when compared to subtotal resection (STR). Age 18 years or older, paresthesia as a presenting symptom, and higher WHO grade were associated with shorter overall survival (OS), whereas thoracic tumor location when compared to cervical tumor location, biopsy when compared to STR, and radiotherapy (HR: 0.42, 95% CI: 0.20–0.88, <jats:italic toggle="yes">P</jats:italic> = 0.022) were associated with longer OS. For the literature cohort, GTR (HR 0.43, 95% CI: 0.24–0.77, <jats:italic toggle="yes">P</jats:italic> = 0.005) was associated with longer PFS when compared to STR, whereas higher WHO grade was associated with shorter PFS. Higher WHO grade and recurrence/progression were associated with shorter OS. Postoperative McCormick score was significantly higher than preoperative score (<jats:italic toggle="yes">P</jats:italic> < 0.001), but subgroup analysis of the change in McCormick score by extent of resection revealed no differences among groups (<jats:italic toggle="yes">P</jats:italic> = 0.551).</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion.</jats:title>
<jats:p>In patients with spinal astrocytomas, GTR likely resulted in longer PFS when compared to STR. Adjuvant radiotherapy appears to be effective in improving survival outcomes for high-grade tumors.</jats:p>
<jats:p>
<jats:bold>Level of Evidence:</jats:bold> 4</jats:p>
</jats:sec>
摘要:
BACKGROUND: Nano bamboo charcoal is being widely used as sustained release carrier for chemicals for its high specific surface area, sound biocompatibility, and nontoxicity; however, there have been no reports on nano bamboo charcoal as sustained release carrier for traditional Chinese medicine (TCM). OBJECTIVE: To study the effect of nano bamboo charcoal in absorbing and sustained releasing Eucommia ulmoides extract (EUE) and to verify the in vitro anticancer effect of the sustained release liquid, so as to provide a theoretical basis for the development and utilization of nano bamboo charcoal as TCM sustained-release preparation. MATERIALS AND METHODS: The adsorption capacity for the nano bamboo charcoal on EUE was measured by Langmuir model, and the release experiment was carried out under intestinal fluid condition. Characteristic changes for the nano bamboo charcoal nano-drug delivery system with and without adsorption of E. ulmoides were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and specific surface area. In addition, the anticancer effect from this novel bamboo charcoal E. ulmoides delivery system was evaluated against a human colon cancer cell line (HCT116). RESULTS: It was found that nano bamboo charcoal exhibits good adsorption capacity (up to 462.96 mg/g at 37 degrees C). The cumulative release rate for EUE from this nano bamboo charcoal delivery system was 70.67%, and specific surface area for the nano bamboo charcoal decreased from 820.32 m(2)/g to 443.80 m(2)/g after EUE was loaded. An in vitro anticancer study showed that the inhibition rate for E. ulmoides against HCT116 cancer cells was 23.07%, for this novel bamboo charcoal nano-drug delivery system. CONCLUSION: This study provides a novel strategy for the delivery of traditional Chinese medicine using bamboo charcoal nano-drug delivery system. SUMMARY: The adsorption equilibrium was reached after 30 min of ultrasonic treatmentThe saturated adsorption capacity of Eucommia ulmoides extract by nano bamboo charcoal under ultrosonic condition was 462. 96 mg/gThe cumulative release rate of E. ulmoides extract from the nano bamboo charcoal delivery system in artificial intestinal juice was 70.67%The inhibition ratio of HCT116 cancer cells by sustained release liquid was 23.07%. Abbreviation used: EUE: Eucommia ulmoides extract.