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Development of hybrid-type modified chitosan derivative nanoparticles for the intracellular delivery of midkine-siR NA in hepatocellular carcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2015年第1期14卷 82-89页

作者： Jing Zhong Hui-Lian Huang Jing Li Fu-Chu Qian Li-Qin Li Ping-Ping Niu Li-Cheng Dai Huzhou key laboratory of molecular medicine Huzhou Central Hospital

BACKGROUND： Hepatocellular carcinoma（HCC） is one of the most common cancers worldwide. Most of the patients with HCC lose the surgical opportunity at the time of diagno sis. Some novel therapeutic modalities, like gene therapy, are promising for the treatment of HCC. However, the success of gene therapy depends on two aspects： efficient gene materials and gene delivery vectors. The present study was to develop new chitosan-based nanoparticles for a midkine-si RNA（anti HCC gene drug） ***： The novel gene delivery vector（MixN CH） was syn thesized by hybrid-type modification of chitosan with 2-chloro ethylamine hydrochloride and N, N-dimethyl-2-chloroethylamine hydrochloride. The chemical structure of Mix NCH was char acterized by FT-IR and 1HNMR. The cytotoxicity of Mix NCH was determined by MTS assay. The gene condensation ability and size, zeta potential and morphology of Mix NCH/MK si RNA nanoparticles were measured. The in vitro transfection and gene knockdown efficiency of midkine by Mix NCH/MK si RNA nanoparticles was detected by q RT-PCR and Western blotting. Gene knockdown effect at the molecule level on the proliferation of Hep G2 in vitro was determined by MTS ***： Mix NCH was successfully acquired by aminoalkyl ation modification of chitosan. The Mix NCH could condense MK-siR NA well above the weight ratio of 3. The average size of Mix NCH/MK-si RNA nanoparticles was 100-200 nm, and thesurface charge was about ＋5 m V. Morphologically, Mix NCH/MK-si RNA nanoparticles were in regular spherical shape-with no aggregation. Regarding to the in vitro transfection of nanoparticles, the MixN CH/MK-siR NA nanoparticles reduced MK m RNA level to 14.03%±4.03%, which were comparable to Biotrans（8.94%±3.77%）. Mix NCH/MK-si RNA effectively inhibited the proliferation of Hep G2 in vitro.-CONCLUSION： Mix NCH/MK-si RNA nanoparticles could be effective for the treatment of hepatocellular carcinoma.

关键词： chitosan gene vector nanoparticles midkine siRNA hepatocellular carcinoma

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Superstable homogeneous lipiodol-ICG formulation:initial feasibility and first-in-human clinical application for ruptured hepatocellular carcinoma

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Regenerative Biomaterials 2023年第1期10卷 326-332页

作者： Yongfu Xiong Pan He Yang Zhang Hu Chen Yisheng Peng Peng He Jie Tian Hongwei Cheng Gang Liu Jingdong Li Department of Hepatobiliary Surgery Academician(Expert)WorkstationAffiliated Hospital of North Sichuan Medical CollegeNanchong 637600China State key laboratory of molecular Vaccinology and molecular Diagnostics Center for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China nuclear medicine and molecular Imaging key laboratory of Sichuan Province Luzhou 646000China key laboratory of molecular Imaging Institute of AutomationChinese Academy of SciencesBeijing 100190China

The most common treatment of spontaneous tumor rupture hemorrhage(STRH)is transcatheter arterial embolization(TAE)followed by liver resection,and surgical navigation using near-infrared fluorescence is effective method for detecting hidden lesions and ill-defined tumor ***,due to the blockage of the tumor-supplying artery after effective TAE treatment,it is difficult to deliver sufficient fluorescent probes to the tumor *** this study,we report on the successful application of superstable homogeneous intermixed formulation technology(SHIFT)in precise conversion hepatectomy for ruptured hepatocellular carcinoma(HCC).A homogeneous lipiodol-ICG formulation obtained by SHIFT(SHIFT-ICG)was developed for clinical practice for STRH.A ruptured HCC patient received the combined protocol for embolization and fluorescence surgical navigation and exhibited excellent hemostatic *** and ICG were both effectively deposited in the primary lesion,including a small metastatic *** follow-up laparoscopic hepatectomy,SHIFT-ICG could clearly and precisely image the full tumor regions and boundaries in real time,and even indistinguishable satellite lesions still expressed a remarkable fluorescence *** conclusion,the simple and green SHIFT-ICG formulation can be effectively used in emergency embolization hemostasis and later precise fluorescence navigation hepatectomy in patients with ruptured HCC bleeding and has high clinical application value.

关键词： conversion therapy fluorescent navigation hepatectomy spontaneous tumor rupture

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and nuclear medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing key laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina key laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 594-604页

作者： Yanjin WANG Yifei CHEN Fuji YANG Xiaolong YU Ying CHU Jing ZHOU Yongmin YAN Jianbo XI Department of laboratory medicine Wujin Hospital Affiliated with Jiangsu UniversityJiangsu UniversityChangzhou 213017China Department of laboratory medicine School of MedicineJiangsu UniversityZhenjiang 212013China Changzhou key laboratory of molecular Diagnostics and Precision Cancer medicine Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213017China

Liver fibrosis is a significant health burden,marked by the consistent deposition of ***,the currently available treatment approaches for this condition are far from *** oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver *** stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver *** studies have found that MSC-sEV can be used for microRNA delivery into target cells or *** is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC ***,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver *** study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis *** results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in ***,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in ***-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse ***-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 *** conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

关键词： Mesenchymal stem cell(MSC) Small extracellular vesicle(sEV) MicroRNA-4465(miR-4465) Hepatic stellate cell(HSC) Liver fibrosis

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Assessment of tumor response to chemotherapy in patients with breast cancer using ^(18)F-FLT: a meta-analysis

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Chinese Journal of Cancer Research 2014年第5期26卷 517-524页

作者： Sheng-Ming Deng Wei Zhang Bin Zhang Yi-Wei Wu Department of nuclear medicine The First Affiliated Hospital of Soochow University School of Radiation medicine and Protection Medical College of Soochow University key laboratory of nuclear medicine Ministry of HealthJiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear Medicine

Purpose： To determine the diagnostic performance of 3＇-deoxy-3＇-18F-fluorothymidine positron emission tomography/computed tomography（FLT PET/CT） and FLT PET for evaluating response to chemotherapy in patients with breast cancer.Methods： Databases such as Pub Med（MEDLINE included） and excerpta medica database（EMBASE）, were searched for relevant original articles. The included studies were assessed for methodological quality with quality assessment of diagnosis accuracy studies（QUADAS） score tool. Histopathological analysis and/or clinical and/or radiological follow-up for at least 6 months were used as the reference standard. The data were extracted by two reviewers independently to analyze the sensitivity, specificity, summary receiver operating characteristic（SROC） curve, area under the curve（AUC）, and heterogeneity.Results： The present study analyzed a total of 4 selected articles. The pool sensitivity was 0.773 [95% confidence interval（CI）： 0.594-0.900]. The pooled specificity was 0.685（95% CI： 0.479-0.849） on basis of FEM. The pooled LR^＋, LR^-, and DOR were 2.874（1.492-5.538）, 0.293（0.146-0.589）, and 14.891（3.238-68.475）, respectively. The AUC was 0.8636（±0.0655）, and the Q＊ index was 0.7942（±0.0636）.Conclusions： Our results indicate that 18^F-FLT PET/CT or PET is useful to predict chemotherapy response in breast cancer with reasonable sensitivity, specificity and DOR. However, future larger scale clinical trials will be needed to assess the regimen of 18^F-FLT PET/CT or PET in monitoring the response to chemotherapy in breast cancer patients.

关键词： Breast cancer 18 ^F-FLT PET chemotherapy meta-analysis

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Endothelial mechanosensors: the gatekeepers of vascular homeostasis and adaptation under mechanical stress

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Science China(Life Sciences) 2014年第8期57卷 755-762页

作者： DENG QiuPing HUO YingQing LUO JinCai laboratory of Vascular Biology Institute of Molecular MedicineBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking University

Endothelial cells(ECs)not only serve as a barrier between blood and extravascular space to modulate the exchange of fluid,macromolecules and cells,but also play a critical role in regulation of vascular homeostasis and adaptation under mechanical stimulus via intrinsic ***,with the dissection of microdomains responsible for cellular responsiveness to mechanical stimulus,a lot of mechanosensing molecules(mechanosensors)and pathways have been identified in *** addition,there is growing evidence that endothelial mechanosensors not only serve as key vascular gatekeepers,but also contribute to the pathogenesis of various vascular *** review focuses on recent findings in endothelial mechanosensors in subcellular microdomains and their roles in regulation of physiological and pathological functions under mechanical stress.

关键词： endothelial cells mechanotransduction mechanosensors vascular adaptation vascular pathogenesis

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Construction and Characterization of Novel Staphylokinase Variants with Antiplatelet Aggregation Activity and Reduced Immunogenecity

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Acta Biochimica et Biophysica Sinica 2004年第5期36卷 336-342页

作者： Hua-Bo SU, Yu-Gao ZHANG, Jin-Tian HE, Wei MO, Yan-Ling ZHANG, Xian-Mei TAO, and Hou-Yan SONG* Department of molecular Genetics, Shanghai Medical School, Fudan University, key laboratory of molecular medicine, Ministry of Education, Shanghai 200032, China Department of molecular Genetics Shanghai Medical School Fudan University Key Laboratory of Molecular Medicine Ministry of Education

To develop target thrombolytic agents with fibrinolytic activity, antiplatelet aggregation activity and reduced immunogenicity, two staphylokinase variants containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced in E. coli JF1125 and the variants, designated DGR and RL1, were purified with gel filtration and ion-exchange chromatography and the purity was over 95%. The fibrinolytic activity and kinetic constants of the two variants were comparable to those of recombinant wild-type staphylokinase. Both the variants can inhibit the platelet aggregation at a final concentration of 2 μM. The titers of antibodies against variants were much lower than those against recombinant staphylokinase in guinea pigs, which indicated that the immunogenicity of the variants was greatly reduced. These results confirm that it is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggrega- tion activities.

关键词： staphylokinase RGD antiplatelet aggregation immunogenicity

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Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

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Neural Regeneration Research 2020年第6期15卷 1094-1101页

作者： Fang Xing Xin Fang Xiang-Dan Gong Xin Zhao Ying Du Zheng-Liang Ma Xiao-Ping Gu Tian-Jiao Xia Department of Anesthesiology Affiliated Drum Tower Hospital of Medical Department of Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu key laboratory of molecular medicine Nanjing UniversityNanjingJiangsu ProvinceChina

Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive *** treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern *** this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance *** established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest *** used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive *** results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep ***,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory ***,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian ***,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake *** animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on N

关键词： circadian rhythm cognitive impairment fear conditioning light intervention photoacoustic treatment rhythm disturbance rhythm shift sleep deprivation sleep-wake rhythm sound intervention

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention

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Neural Regeneration Research 2020年第1期15卷 96-102页

作者： Ying Du Xiang-Dan Gong Xin Fang Fang Xing Tian-Jiao Xia Xiao-Ping Gu Department of Anesthesiology Affiliated Drum Tower Hospital of Medical Department of Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu key laboratory of molecular medicine Nanjing UniversityNanjingJiangsu ProvinceChina

Isoflurane and sevoflurane are both inhalation anesthetics,but in clinical application,sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential ***,recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity,cost,and long-term anesthetic ***,sevoflurane possibly has less cognitive impact on young *** this study,C57BL/6 mice aged 8–10 weeks were exposed to 1.2%isoflurane or 2.4%sevoflurane for 6 *** function and memory were examined in young mice using the novel object recognition,contextual fear conditioning,and cued-fear extinction *** blot assay was performed to detect expression levels of D1 dopamine receptor,catechol-O-methyltransferase,phospho-glycogen synthase kinase-3β,and total glycogen synthase kinase-3βin the *** results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition *** memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane ***-term sevoflurane exposure did not affect memory consolidation,while isoflurane led to memory consolidation and reduced *** of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3βand upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or *** results confirm that sevoflurane has less effect on cognitive impairment than isoflurane,which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3βin the *** study was approved by the Institutional Animal Care and Use Committee,Nanjing University,China on November 20,2017(approval No.20171102).

关键词： catechol-O-methyltransferase cognitive impairment D1 dopamine receptors fear memory glycogen synthase kinase-3β isoflurane neurotoxicology sevoflurane

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