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Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease:a meta-analysis and systematic review

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Neural Regeneration Research 2022年第11期17卷 2381-2390页

作者： Wei-lin Liu Hua-Wei lin Miao-Ran lin Yan Yu Huan-Huan Liu Ya-ling Dai Le-Wen Chen Wei-Wei Jia xiao-Jun He xiao-ling Li Jing-Fang Zhu Xie-Hua Xue Jing Tao Li-Dian Chen Academy of Rehabilitation Industry Fujian University of Traditional Chinese MedicineFuzhouFujian ProvinceChina Department of Biochemistry and Molecular Biology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese MedicineFuzhouFujian ProvinceChina Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine FuzhouFujian ProvinceChina

Blood exosomes,which are extracellular vesicles secreted by living cells into the circulating blood,are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states.An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease.Therefo re,we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease.We performed a literature search in PubMed,Web of Science,Embase,and Cochrane Library from their inception to August 15,2020.The research subjects mainly included Alzheimer's disease,mild cognitive impairment,and preclinical Alzheimer's disease.We identified 34 observational studies,of which 15 were included in the quantitative analysis(Newcastle-Ottawa Scale score 5.87 points)and 19 were used in the qualitative analysis.The meta-analysis results showed that core biomarkers including Aβ_(1-42),P-T181-tau,P-S396-tau,and T-tau were increased in blood neuro nderived exosomes of preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease patients.M olecules related to additional risk facto rs that are involved in neuroinflammation(C1q),metabolism disorder(P-S312-IRS-1),neurotrophic deficiency(HGF),vascular injury(VEGF-D),and autophagy-lysosomal system dysfunction(cathepsin D)were also increased.At the gene level,the differential expression of transc ription-related factors(REST)and microRNAs(miR-132)also affects RNA splicing,transport,and translation.These pathological changes contribute to neural loss and synaptic dysfunction.The data confirm that the above-mentioned core molecules and additional ris k-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease.These findings support further development of exosome biomarkers for a clinical blood test for

关键词： Alzheimer's disease amyloid-β biomarkers blood exosomes extracellular vesicles meta-analysis mild cognitive impairment systematic review tau protein

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Single-cell RNA sequencing reveals a hierarchical transcriptional regulatory network of terpenoid biosynthesis in cotton secretory glandular cells

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Molecular Plant 2023年第12期16卷 1990-2003页

作者： Jia-ling lin Longxian Chen Wen-Kai Wu xiao-Xiang Guo Cheng-Hui Yu Min Xu Gui-Bin Nie Jun-ling Dun Yan Li Baofu Xu ling-Jian Wang xiao-Ya Chen Wei Gao Jin-Quan Huang State Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyUniversity of CASChinese Academy of SciencesShanghai 200032China School of Life Science and Technology ShanghaiTech UniversityShanghai 200031China Chongqing Key Laboratory of Micro-Nano Systems and Intlligent Transduction Collaborative InnovationNational Research Base of Inteligent Manufacturing ServiceChongqing Technology and Business UniversityChongqing 400067China Analytical Applications Center Shimadzu(China)Co.Ltd.Shanghai 200233China Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Insttute for Drug DiscoveryYantai 264117ShandongChina State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Shanghai Key Laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai 201602China National Key Laboratory of Cotton Bio-breeding and Integrated Utilization(Henan University) Henan 475004China

Plants can synthesize a wide range of terpenoids in response to various environmental cues.However,the specific regulatory mechanisms governing terpenoid biosynthesis at the cellular level remain largely elusive.In this study,we employed single-cell RNA sequencing to comprehensively characterize the transcriptome profile of cotton leaves and established a hierarchical transcriptional network regulating cellspecific terpenoid production.We observed substantial expression levels of genes associated with the biosynthesis of both volatile terpenes(such asβ-caryophyllene andβ-myrcene)and non-volatile gossypol-type terpenoids in secretory glandular cells.Moreover,two novel transcription factors,namely GoHSFA4a and GoNAC42,are identified to function downstream of the Gossypium PIGMENT GLAND FORMATION genes.Both transcription factors could directly regulate the expression of terpenoid biosynthetic genes in secretory glandular cells in response to developmental and environmental stimuli.For convenient retrieval of the single-cell RNA sequencing data generated in this study,we developed a user-friendly web server.Our findings not only offer valuable insights into the precise regulation of terpenoid biosynthesis genes in cotton leaves but also provide potential targets for cotton breeding endeavors.

关键词： hierarchical network cotton

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Historical trends in maize morphology from the 1950s to the 2010s in China

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Journal of Integrative Agriculture 2022年第8期21卷 2159-2167页

作者： MA Da-ling XIE Rui-zhi YU xiao-fang LI Shao-kun GAO Ju-lin Agricultural College Inner Mongolia Agricultural UniversityHohhot 010019P.R.China Institute of Crop Sciences Chinese Academy of Agricultural Sciences/Key Laboratory of Crop Physiology and EcologyMinistry of Agriculture and Rural AffairsBeijing 100081P.R.China

The morphology of the plant and ear is a preliminary selection characteristic in breeding new varieties of maize.As new maize cultivars were developed from the 1950s through the 2010s in China,most had changes in both plant and ear morphological characteristics that contributed substantially to maize yield gains.Over the seven decades,plant and ear height fluctuated with a small increase from the 1950s to 2000s,and then a decrease in the 2010s,while the ear ratio and internodes length below the ear decreased significantly.Leaf angles became significantly more upright,especially for the leaves above the ear,and the leaf area per plant improved markedly.Leaf orientation increased from the 1950s to the 2000s then decreased in the 2010s.Tassel size and the anthesis-silking interval were both reduced substantially.Ear diameter,kernel number,and kernel weight increased from the 1950 to the 2000s,then decreased in the 2010s under the same cultivation conditions.We found that modern maize hybrids have a lower plant height,ear height and ear ratio which increased lodging resistance,a more erect leaf which increased high-density planting tolerance,and smaller ears and kernels which facilitated rapid dehydration during late grain filling.These morphological selection criteria,which are suitable for mechanized operations,are proposed as the focus for future maize breeding.

关键词： maize yield morphological characteristics breeding direction artificial selection improved maize cultivars mechanized farming

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Human Sulfatase-1 Improves the Effectiveness of Cytosine Deaminase Suicide Gene Therapy with 5-Fluorocytosine Treatment on Hepatocellular Carcinoma Cell line HepG2 In Vitro and In Vivo

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Chinese Medical Journal 2015年第10期128卷 1384-1390页

作者： xiao-Ping Yang ling Liu Ping Wang Sheng-lin Ma Department of General Surgery Hangzhou First People's Hospital Hangzhou Hospital Affiliated to Nanjing Medical University Hangzhou Zhejiang 310006 China

Background：Human sulfatase-1 （Hsulf-l） is an endosulfatase that selectively removes sulfate groups from heparan sulfate proteoglycans （HSPGs）,altering the binding of several growth factors and cytokines to HSPG to regulate cell proliferation,cell motility,and apoptosis.We investigated the role of combined cancer gene therapy with Hsulf-l and cytosine deaminase/5-fluorocytosine （CD/5-FC） suicide gene on a hepatocellular carcinoma （HCC） cell line,HepG2,in vitro and in vivo.Methods：Reverse transcription polymerase chain reaction and immunohistochemistry were used to determine the expression of Hsulf-1 in HCC.Cell apoptosis was observed through flow cytometry instrument and mechanism of Hsulf-1 to enhance the cytotoxicity of 5-FC against HCC was analyzed in HCC by confocal microscopy.We also establish a nude mice model of HCC to address the effect of Hsulf-1 expression on the CD/5-FC suicide gene therapy in vivo.Results：A significant decrease in HepG2 cell proliferation and an increase in HepG2 cell apoptosis were observed when Hsulf-1 expression was combined with the CD/5-FC gene suicide system.A noticeable bystander effect was observed when the Hsulf-1 and CD genes were co-expressed.Intracellular calcium was also increased after HepG2 cells were infected with the Hsulf-1 gene.In vivo studies showed that the suppression of tumor growth was more pronounced in animals treated with the Hsulf-1 plus CD than those treated with either gene therapy alone,and the combined treatment resulted in a significant increase in survival.Conclusions：Hsulf-1 expression combined with the CD/5-FC gene suicide system could be an effective treatment approach for HCC.

关键词： Cytosine Deaminase/5-Fluorocytosine Suicide System Hepatocellular Carcinoma Human Sulfatase-1

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SnO_2 hollow nanospheres assembled by single layer nanocrystals as anode material for high performance Li ion batteries

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Chinese Chemical Letters 2015年第1期26卷 124-128页

作者： Wei Wei ling-xiao Song lin Guo School of Chemistry and Chemical Engineering Shangqiu Normal University School of Chemistry and Environment Beijing University of Aeronautics & Astronautics College of Chemistry and Molecular Engineering Zhengzhou University

SnO2 hollow nanospheres were successfully synthesized via a facile one-step solvothermal method.Characterizations show that the as-prepared SnO2 spheres are of hollow structure with a diameter at around 50 nm,and especially,the shell of the spheres is assembled by single layer SnO2 nanocrystals.The surface area of the material reaches up to 202.5 m^2/g.As an anode material for Li ion batteries,the sample exhibited improved electrochemical performance compared with commercial SnO2 particles.After cycled at high current rate of 0.5 C,1 C and 0.5 C for 20 cycles,respectively,the electrode can maintain a capacity of 509 mAh/g.The suitable shell thickness/diameter ratio endows the good structural stability of the material during cycling,which promises the excellent cycling performance of the electrode.The large surface area and the ultra thin shell ensure the high rate performance of the material.

关键词： SnO2 Hollow nanospheres Single layer Li ion batteries

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Modified Liujunzi Decoction (六君子汤) Alleviates Chemotherapy-Induced Anorexia in Advanced Non-Small Cell Lung Cancer: A Propensity Score Matched Case-Control Study

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Chinese Journal of Integrative Medicine 2020年第4期26卷 256-262页

作者： SUN ling-ling LAI He-zheng CHEN Zhuang-zhong ZHU xiao-shu lin Li-zhu Integrative Cancer Centre Guangzhou University of Chinese Medicine First Affiliated HospitalGuangzhou(510405)China Guangzhou University of Chinese Medicine GuangzhouChina Chinese Medicine Center Western Sydney UniversityCampbelltown(2751)NSWAustralia NICM Health Research Institute Western Sydney University CampbelltownNSW(2751)Australia

Objective:To evaluate the effect of Chinese herbal medicine formula,modified Liujunzi Decoction(六君子汤,MLJZT),for anorexia,utilized as adjunct therapy during chemotherapy treatment for patients with advaneed non-small cell lung cancer(NSCLC).Methods:The study adopted a propensity score-matched design based on a prospective database.From February 2016 to September 2017,patients with advanced NSCLC that received both cisplatin-based chemotherapy and MLJZT(IM group)were 1:1 propensity score-matched to patients that received the cisplatin-based chemotherapy alone(control group).Changes in anorexia and weight,as well as side effects were evaluated per week within 4-cycle chemotherapy.Results:Overall,156 patients with advaneed NSCLC that had received chemotherapy from our database were ide ntified and 53 pairs were matched successfully.In total,48.6%(50/53)of patients in the IM group had anorexia-improvement compared to 28.3%(15/53)of patients in the control group,and a total of 39.6%(21/53)of patients in the control group had a worsening of anorexia compared to only 7.8%(8/53)of patients in the IM group(P<0.01).The weight reduced significantly over time in the control group(-2.36±2.53 kg)as compared to the IM group(-0.62±3.89 kg,P<0.01).CHM didn't reduce the efficacy of chemotherapy in shrinking tumor size,and didn't increase the incidence of side effects such as hematological and hepatorenal toxicity.Conclusion:MLJZT is effective and safe for alleviating anorexia in patients with NSCLC.These fin dings warrant the con duct of a randomized con trolled trial.

关键词： anorexia food intake Chinese medicine chemotherapy lung cancer

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linC01268 promotes epithelial-mesenchymal transition,invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1366-1383页

作者： ling-Han Tang Peng-Cheng Ye lin Yao Ya-Jun Luo Wang Tan Wan-Ping Xiang Zi-lin Liu ling Tan Jiang-Wei xiao Department of Gastrointestinal Surgery Clinical Medical College and the First Affiliated Hospital of Chengdu Medical CollegeChengdu 610000Sichuan ProvinceChina Department of Gastrointestinal Surgery The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina Department of Gastrointestinal Surgery Sichuan Cancer HospitalChengdu 610000Sichuan ProvinceChina Department of Gastrointestinal Surgery Yaan People’s HospitalYaan 625000Sichuan ProvinceChina Department of Thoracic Surgery The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina Department of Surgery People’s Hospital Affiliated to Chongqing Three Gorges Medical CollegeChongqing 404041China

BACKGROUND Long non-coding RNAs(lncRNAs)with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer(GC),but their specific mechanisms and roles still need to be further elucidated.AIM To investigate the expression of linC01268 in GC and its mechanism of affecting GC progression.METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of linC01268 in GC tissues,cell lines and plasma.The Kaplan-Meier method was used to evaluate the value of linC01268 in the prognostication of GC patients.An receiver operating characteristic curve was constructed to evaluate the value of linC01268 in the diagnosis of GC.Transwell migration and invasion assays and wound healing assays were used to confirm the effect of linC01268 on the invasion and migration of GC cells.The regulatory relationship between linC01268 and myristoylated alanine rich protein kinase C substrate(MARCKS),the PI3K/Akt signaling pathway,and the epithelial-mesenchymal transition(EMT)process in GC was demonstrated by western blot analysis.RESULTS The expression of linC01268 was increased in GC tissues and cell lines.The expression level of linC01268 was significantly correlated with lymph node metastasis,TNM stage,and tumor differentiation in patients with GC.Over-expression of linC01268 indicated a poor prognosis for patients with GC,and it had a certain auxiliary diagnostic value for GC.In vitro functional experiments proved that the abnormal expression of linC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.CONCLUSION This study elucidates that linC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS,and ultimately promotes the invasion and metastasis of GC.linC01268 may be a potential effective target for the treatment of GC.

关键词： Gastric cancer Long non-coding RNA linC01268 Myristoylated alanine rich protein kinase C substrate Invasion Metastasis

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CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice

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Neuroscience Bulletin 2021年第3期37卷 339-352页

作者： Yan-Fang Kong Wei-lin Sha xiao-Bo Wu lin-Xia Zhao ling-Jie Ma Yong-Jing Gao Institute of Pain Medicine Institute of Nautical MedicineNantong UniversityNantong 226019China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

Chemokines and receptors have been implicated in the pathogenesis of chronic pain.Here,we report that spinal nerve ligation(SNL)increased CXCR3 expression in dorsal root ganglion(DRG)neurons,and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia.SNL also increased the m RNA levels of CXCL9,CXCL10,and CXCL11,whereas only CXCL10 increased the number of action potentials(APs)in DRG neurons.Furthermore,in Cxcr3^(-/-)mice,CXCL10 did not increase the number of APs,and the SNL-induced increase of the numbers of APs in DRG neurons was reduced.Finally,CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons.Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10.Our data indicate that CXCR3,activated by CXCL10,mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability,which contributes to the maintenance of neuropathic pain.

关键词： CXCR3 CXCL10 DRG Neuropathic pain Mice

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Qualitative detection of ginsenosides in brain tissues after oral administration of high-purity ginseng total saponins by using polyclonal antibody against ginsenosides

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Chinese Journal of Natural Medicines 2018年第3期16卷 175-183页

作者： ZHAO Yu-Nan SHAO xiao OUYANG Liu-Feng CHEN lin GU ling Laboratory of Pathological Sciences College of Medicine and Life Nanjing University of Chinese Medicine Laboratory of Pathological Sciences College of Medicine Yan'an University Research Center Basic Medical College Nanjing University of Chinese Medicine

Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood–brain barrier(BBB) remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rg1 was detectable and no other ginsenosides or their metabolites were found. No ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed the localization of ginsenosides in brain tissues. Furthermore, immunofluorescence double staining revealed that ginsenosides widely existed in vascular endotheliocytes and astrocytes, and in few neurons. These results indicated that Rg1 was the main component that entered the brain after oral administration of ginseng total saponins and that ginsenosides could cross the BBB, although the transport capability of ginsenosides through the BBB may be poor.

关键词：人参人参皂甙 Immunostaining 集体 spectrometry 血大脑障碍

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High mobility group box-1 release from H2O2-injured hepatocytes due to sirt1 functional inhibition

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World Journal of Gastroenterology 2019年第36期25卷 5434-5450页

作者： Ting-Jie Ye Yan-lin Lu xiao-Feng Yan Xu-Dong Hu xiao-ling Wang Department of Biology School of Basic Medical Sciences Shanghai University of Traditional Chinese Medicine Shanghai 201203 China Department of Oncology and Institute of Traditional Chinese Medicine in Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai 200032 China

BACKGROUND High mobility group box-1 (HMGB1), recognized as a representative of damageassociated molecular patterns, is released during cell injury/death, triggering the inflammatory response and ultimately resulting in tissue damage. Dozens of studies have shown that HMGB1 is involved in certain diseases, but the details on how injured hepatocytes release HMGB1 need to be elicited. AIM To reveal HMGB1 release mechanism in hepatocytes undergoing oxidative stress. METHODS C57BL6/J male mice were fed a high-fat diet for 12 wk plus a single binge of ethanol to induce severe steatohepatitis. Hepatocytes treated with H2O2 were used to establish an in vitro model. Serum alanine aminotransferase, liver H2O2 content and catalase activity, lactate dehydrogenase and 8-hydroxy-2- deoxyguanosine content, nicotinamide adenine dinucleotide (NAD+) levels, and Sirtuin 1 (Sirt1) activity were detected by spectrophotometry. HMGB1 release was measured by enzyme linked immunosorbent assay. HMGB1 translocation was observed by immunohistochemistry/immunofluorescence or Western blot. Relative mRNA levels were assayed by qPCR and protein expression was detected by Western blot. Acetylated HMGB1 and poly(ADP-ribose)polymerase 1 (Parp1) were analyzed by Immunoprecipitation. RESULTS When hepatocytes were damaged, HMGB1 translocated from the nucleus to the cytoplasm because of its hyperacetylation and was passively released outside both in vivo and in vitro. After treatment with Sirt1-siRNA or Sirt1 inhibitor (EX527), the hyperacetylated HMGB1 in hepatocytes increased, and Sirt1 activity inhibited by H2O2 could be reversed by Parp1 inhibitor (DIQ). Parp1 and Sirt1 are two NAD+-dependent enzymes which play major roles in the decision of a cell to live or die in the context of stress . We showed that NAD+ depletion attributed to Parp1 activation after DNA damage was caused by oxidative stress in hepatocytes and resulted in Sirt1 activity inhibition. On the contrary, Sirt1 suppressed Parp1 by negatively regulating its gene expression and deace

关键词： Sirtuin1 Poly ADP-ribose polymerase 1 High mobility group box-1 Hepatocytes Hydrogen peroxide

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