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IGF-1 Accelerates Cell Aging by Inhibiting POLD1 Expression

Biomedical and Environmental Sciences 2022年第11期35卷 981-991页

作者： HOU Yu Li wang Yi Fei SONG Qiao ZHANG Xiao Min LIU Jing wang Ya Qi CUI Yu Ting FU Jing Xuan FENG Zi Yi ZHANG Chi wang pei chang Department of Clinical Laboratory Xuanwu HospitalNational Clinical Research Center for Geriatric DiseasesCapital Medical UniversityBeijing 100053China Clinical Laboratory Diagnostics Capital Medical UniversityBeijing 100053China

Objective The individual cascades of the insulin-like growth factor-1(IGF-1)signaling pathway and the molecular mechanism of aging have not been fully clarified.In the current study,we explored the effect of DNA polymerase delta 1(POLD1)on the IGF-1 signaling pathway in cell aging.Methods First,we analyzed the relationship between IGF-1 and POLD1 expression in aging.To investigate the effect of IGF-1 on POLD1 expression and aging,the 2BS cells were incubated with youngage or old-age human serum,IGF-1 protein,or linsitinib.Next,the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism.Results In this study,we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice,and a negative relationship between IGF-1 and POLD1 expression was observed.Furthermore,the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics,and the effect could be reversed by treatment with linsitinib or overexpression of POLD1,while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1.Conclusion Taken collectively,our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1.These findings offer a new target for anti-aging strategies.

关键词： Insulin-like growth factor-1 DNA polymerase delta 1 Aging Linsitinib

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Aminoguanidine delays the replicative senescence of human diploid fibroblasts

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Chinese Medical Journal 2007年第22期120卷 2028-2035页

作者： wang pei-chang ZHANG Jian ZHANG Zong-yu TONG Tan-jun Department of Medical Laboratory Xuanwu Hospital of Capital Medical University Beijing 100053 China Aging Research Center Medical and Health Center of Peking University Beiiing 100083 China

Background The accumulation of free radicals and advanced glycation end products （AGEs） in cell plays a very important role in replicative senescence. Aminoguanidine （AG） has potential antioxidant effects and decreases AGE levels. This study aimed to investigate its effect on replicative senescence in vitro. Methods The effects of aminoguanidine on morphology, replicative lifespan, cell growth and proliferation, AGEs, DNA damage, DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts （2BS）. Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling （PD） and increased cumulative population doublings by at least 17-21 PDs. Aminoguanidine also improved the potentials of growth and proliferation of 2BS cells as detected by the MTT assay. The AGE levels of late PD cells grown from early PD in DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similar to those of young control cells. In addition, the cells pretreated with aminoguanidine had a significant reduction in DNA strand breaks when they were exposed to 200 μmol/L H2O2 for 5 minutes which indicated that the compound had a strong potential to protect genomic DNA against oxidative stress. And most of the cells exposed to 100 μmol/L H2O2 had much shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM, which indicated that the compound strongly improved the DNA repair abilities of 2BS cells. Moreover, PD55 cells grown from PD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb, which was 0.83 kb or 1.11 kb longer than that of the control cells. Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect of aminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement, its inhibitory effect of AGE formation, antioxidant effect, improvement of

关键词： aminoguanidine replicative senescence human diploid fibroblast advanced glycation end products comet assay

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Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells

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Chinese Medical Journal 2008年第3期121卷 231-235页

作者： wang pei-chang ZHANG Zong-yu ZHANG Jian TONG Tan-jun Department of Medical Laboratory Xuanwu Hospital of CapitalMedical University Beijing 100053 China Ageing Researching Center Medical and Health Center of PekingUniversity Beijing 100083 China

Background Astragafi Radix, the root of Astragalus membranceus （Fish） Bunge Var. mongholicus （Bge）, is a crude drug considered as one of the effective traditional Chinese anti-ageing material. The two isomers of 4-hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6＇-spirane-5＇,6＇,7＇,8＇-tetrahydro-indolizine-3＇-carbaldehyde （HDTIC）, HDTIC-1 and HDTIC-2, were first extracted from the herb in 2002. We demonstrated previously that 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2 strongly delay replicaUve senescence of human fetal lung diploid fibroblasts （2BS）. In this study, we chose them to investigate their effects on the expression of senescence-associated genes to explore the mechanism of how HDTIC delays replicative senescence. Methods The effects of HDTIC-1 and HDTIC-2 on the expression of p16 and p21 were observed in vitro by RT-PCR and Western blot. The anti-oxidative activities of the compounds were also observed by phenotype alteration after treatment with antioxidants. Results There was an obvious expression of p16 in the control senescent cells. However, in the 2BS cells, after 56 population doublings （PDs） grown from PD28 in 0.1 μmol/L HDTIC-1 or 1.0 μmol/L HDTIC-2, there was a weak mRNA expression of p16 and no protein expression of pl 6 was observed. The expression level of p21 increased with cell ageing Moreover, there was no difference between the expression level of p21 in the control cells and that in the same PD cells cultured with HDTIC compounds. The results also showed that 2BS cells exposed to 100 μmol/L H202 for 5 minutes retum to their non-senescent phenotype and continue to be confluent after incubating the damaged cells with HDTIC-1 （1.0 μmol/L ） or HDTIC-2 （10 μmol/L ） for I hour. Conclusions Expression of p16 by 2BS cells was strongly inhibited by HDTIC compounds, which could contribute to their delayed replicative senescence by the way of p16^INK4a/Rb/MAPK. The anti-oxidative activities of HDTIC-1 and HDTIC-2, described in this study for the first time, might be indirectly related to their inhibit

关键词： HDTIC Astragali Radix replicative senescence fibroblast gene expression

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MicroRNA-135a in ABCA1-labeled Exosome is a Serum Biomarker Candidate for Alzheimer’s Disease

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Biomedical and Environmental Sciences 2021年第1期34卷 19-28页

作者： LIU Chen Geng MENG Shuang LI Ying LU Yao ZHAO Yue wang pei chang Clinical Laboratory of Xuanwu Hospital Captit al Medcial UniversityBeijing 100053China State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and PreventionBeijing 102206China Clinical Laboratory of Air Force General Hospital Chinese People's Liberation ArmyBeijing 100142China

Objective In the present study,the ABCA1 was used as a label to capture specific exosomes,the level of ABCA1-labeled exosomal microRNA-135 a(miR-135 a)was evaluated for the diagnosis of Alzheimer’s disease(AD),especially in patients with early stages of AD.Methods This is a preliminary research focused on the levels of ABCA1 in WBCs,RBCs,HT-22 cells,and neuron cells.The diagnostic value of ABCA1-labeled exosomal miR-135 a was examined using the CSF and serum of APP/PS1 double transgenic mice,and 152 patients with SCD,131 patients with MCI,198 patients with DAT,and 30 control subjects.Results The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs(P0.05)in the serum of SCD patient group,and significantly increased in MCI and DAT patient groups compared to those of the control group(P<0.05).Conclusion This study outlines a method to capture specific exosomes and detect them using immunological methods,which is more efficient for early diagnosis of AD.

关键词： Alzheimer’s disease Exosome MicroRNA Biomarker

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The Serum Exosome Derived MicroRNA-135a,-193b, and-384 Were Potential Alzheimer's Disease Biomarkers

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Biomedical and Environmental Sciences 2018年第2期31卷 87-96页

作者： YANG Ting Ting LIU Chen Geng GAO Shi Chao ZHANG Yi wang pei chang Department of Clinical Laboratory Xuanwu Hospital Capital Medical University

Objective MicroRNAs （miRs） are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer＇s disease （AD）. The goal of this study was to explore their potential value as biomarkers for the diagnosis of AD.Methods The expression levels of exosomal miR-135a, -193b, and -384 in the serum from mild cognitive impairment （MCI）, dementia of Alzheimer-type （DAT）, Parkinson＇s disease with dementia （PDD）, and vascular dementia （VaD） patients were measured with a real-time quantitative reverse transcriptase PCR （qRT-PCR） method.Results Both serum exosome miR-135a and miR-384 were up-regulated while miR-193b was down-regulated in serum of AD patients compared with that of normal controls. Exosome miR-384 was the best among the three miRs to discriminate AD, VaD, and PDD. Using the cut-off value could better interpret these laboratory test results than reference intervals in the AD diagnosis. ROC curve showed that the combination of miR-135a, -193b, and -384 was proved to be better than a particular one for early AD diagnosis.Conclusion Our results indicated that the exosomal miRs in the serum were not only potential biomarker of AD early diagnosis, but might also provide novel insights into the screen and prevention of the disease.

关键词： Alzheimer＇s disease Exosome MicroRNA Biomarker

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TREM2:A Novel Potential Biomarker of Alzheimer's Disease

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Biomedical and Environmental Sciences 2021年第9期34卷 719-724页

作者： ZHANG Xiao Min LIU Jing CAO Min YANG Ting Ting wang Ya Qi HOU Yu Li SONG Qiao CUI Yu Ting wang pei chang Department of Clinical Laboratory Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Clinical Laboratory the Hospital of Shunyi District BeijingBeijing 101300China

Alzheimer’s disease(AD)is the most common type of neurodegenerative dementia worldwide[1].Deposition of extracellular amyloid proteinβ(Aβ)-producing amyloid plaques and intracellular tau aggregation-comprising neur... 详细信息

关键词： Alzheimer Aβ tau

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Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong chang Li-Bo Liu pei-Gang wang Jing An Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

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Implementation of integrated nonlocal sensing for object shape and rotational speed

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 6-12页

作者： Zhenyu Guo Yunlong wang Zehong chang Jiawei wang Junliang Jia pei Zhang Ministry of Education Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter Shaanxi Province Key Laboratory of Quantum Information and Quantum Optoelectronic DevicesSchool of PhysicsXi’an Jiaotong UniversityXi’an 710049China

The expeditious acquisition of information pertaining to objects through the utilization of quantum technology has been a perennial issue of concern.So far,the efficient utilization of information from dynamic objects with limited resources remains a significant challenge.Here,we realize a nonlocal integrated sensing of the object's amplitude and phase information by combining digital spiral imaging with the correlated orbital angular momentum states.The amplitude information is utilized for object identification,while the phase information enables us to determine the rotational speed.We demonstrate the nonlocal identification of a rotating object's shape,irrespective of its rotational symmetry,and introduce the concept of the correlated rotational Doppler effect,establishing a fundamental connection between this effect and the classical rotational Doppler effect,i.e.,that both rely on extracting crucial information from the spiral spectrum of objects.The present study highlights a promising pathway towards the realization of quantum remote sensing and imaging.

关键词： digital spiral imaging orbital angular momentum correlated rotational Doppler effect

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Temporal assembly patterns of microbial communities in three parallel bioreactors treating low-concentration coking wastewater with differing carbon source concentrations

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Journal of Environmental Sciences 2024年第3期137卷 455-468页

作者： Weijia Li Yu Xia Na Li Jie chang Jing Liu pei wang Xuwen He School of Chemical and Environmental Engineering China University of Mining and Technology-BeijingBeijing 100083China

Carbon source is an important factor of biological treatment systems, the effects of which on their temporal community assembly patterns are not sufficiently understood currently.In this study, the temporal dynamics and driving mechanisms of the communities in three parallel bioreactors for low-concentration coking wastewater(CWW) treatment with differing carbon source concentrations(S0 with no glucose addition, S1 with 200 mg/L glucose addition and S2 with 400 mg/L glucose addition) were comprehensively studied. Highthroughput sequencing and bioinformatics analyses including network analysis and Infer Community Assembly Mechanisms by Phylogenetic bin-based null model(iCAMP) were used. The communities of three systems showed turnover rates of 0.0029~0.0034 every 15days. Network analysis results showed that the S0 network showed higher positive correlation proportion(71.43%) and clustering coefficient(0.33), suggesting that carbon source shortage in S0 promoted interactions and cooperation of microbes. The neutral community model analysis showed that the immigration rate increased from 0.5247 in S0 to 0.6478in S2. The iCAMP analysis results showed that drift(45.89%) and homogeneous selection(31.68%) dominated in driving the assembly of all the investigated microbial communities.The contribution of homogeneous selection increased with the increase of carbon source concentrations, from 27.92% in S0 to 36.08% in S2. The OTUs participating in aerobic respiration and tricarboxylic acid(TCA) cycle were abundant among the bins mainly affected by deterministic processes, while those related to the metabolism of refractory organic pollutants in CWW such as alkanes, benzenes and phenols were abundant in the bins dominated by stochastic processes.

关键词： Coking wastewater treatment Temporal dynamics Network analysis Deterministic processes Stochastic processes

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A new tetracyclic triterpenoid from endophytic fungus Fusarium sporotrichioides

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Chinese Herbal Medicines 2024年第2期16卷 231-234页

作者： Yajing wang Chunyue Liu Yihui Yang chang Li Yuehu pei Department of Medicinal Chemistry and Natural Medicine Chemistry College of PharmacyHarbin Medical UniversityHarbin 150081China

Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities.Methods: The chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR(1H-NMR and13C-NMR) and 2D NMR(1H–1H COSY,HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data.Results: One previously undescribed tetracyclic triterpenoid derivative, named as integracide L(1), 12aacetoxy-4,4-dimethyl-24-methylene-5a-cholesta-8,14-diene-2a,3β,11β-triol(2), 12a-acetoxy-4,4-dime thyl-24-methylene-5a-cholesta-8-momoene-2a,3β,11β-triol(3), 12a-acetoxy-4,4-dimethyl-24-methy lene-5a-cholesta-8,14-diene-3β,11β-triol(4), and 12a-acetoxy-4,4-dimethyl-24-methylene-5acholesta-8-momoene-3β,11β-triol(5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position.Conclusion: Compound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F.sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on Hep G-2 cells than the other compounds, with IC50values of(2.8 ± 0.1) and(6.3 ± 0.3) μmol/L respectively.

关键词： antitumor Fusarium sporotrichioides integracide L tetracyclic triterpenoid 12a-acetoxy-4,4-dimethyl-24-methylene5a-cholesta-814-diene-2a,3b,11b-triol 12a-acetoxy-4,4-dimethyl-24-methylene5a-cholesta-8-momoene-2a,3b,11b-triol 12a-acetoxy-4,4-dimethyl-24-methylene5a-cholesta-8-momoene-3b,11b-triol

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