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PM_(2.5) obtained from urban areas in beijing induces apoptosis by activating nuclear factor-kappa B

Military Medical Research 2017年第4期4卷 200-209页

作者： Hui Peng Xiao-Hong Zhao Ting-Ting Bi Xiao-Yan Yuan Jia-Bin Guo Shuang-Qing Peng Evaluation and Research Center for Toxicology Institute of Disease Control and Prevention Academy of Military Medical Sciences beijing key laboratory of bioactive substances and functional foods Beijing Union University

Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well ***: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent ***: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling path

关键词： Particulate matter NF-κB pathway Apoptosis BAD protein

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Fermented soy whey induced changes on intestinal microbiota and metabolic inﬂuence in mice

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Food Science and Human Wellness 2022年第1期11卷 41-48页

作者： Wei Han Xuhui Zhuang Qian Liu Bo Sun Haijiang Miao Xiaolin Zhang Academy of State Administration of Grain Beijing 100037China beijing key laboratory of bioactive substances and functional foods Beijing Union UniversityBeijing 100191China COFCO Nutrition and Health Institute Beijing 102209China

Soy whey(SW)is generated as process waste while preparing soy protein isolates(SPI),and causing severe environmental ***,its value-added utilization is of prime importance for transforming and upgrading traditional *** study aims to utilize SW as a substrate for the growth of probiotics and produce a SW based *** a series of trials,the effect of the dietary supplementation with this fermented SW(FSW)was analyzed on ICR mice's body weight,metabolites,and intestinal microbiota in 4 *** results showed that,when SW was concentrated 15 times,the count of viable Lactobacillus casei reached 3.4×10^(9) CFU/mL by liquid fermentation method,which was the highest viable cell count among all test *** this FSW,the protein,amino acid,total dietary fibre,soluble dietary fibre,and oligosaccharide were 2.10%,1.63%,0.52%,0.51% and 0.79%,*** to two control group,the total yields of the short chain fatty acids(SCFAs)were significantly improved(75%-125% at average),while the SCFAs structure was also significantly changed(especially acetic acid and butyrate)in the faeces of mice fed ***,FSW dietary addition was associated with the diversity and richness of the intestinal ***,with mice's body weight loss,Firmicutes/Bacteroides ratio reduced accordingly(<1.21),and the abundance of Akkermansia muciniphila was significantly increased(the maximum amount was about 0.013%).In summary,our results indicated that the dietary supplementation of FSW affected mice's intestinal microbiota and metabolism and improved their health profile.

关键词： Soy whey Microbiota Short chain fatty acids Lactobacillus casei Akkermansia muciniphila

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Taraxastane-type triterpenoids from the medicinal and edible plant Cirsium setosum

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Chinese Journal of Natural Medicines 2019年第1期17卷 22-26页

作者： LIN Peng-Cheng JI Lin-Lin ZHONG Xiang-Jian LI Jin-Jie WANG Xin SHANG Xiao-Ya LIN Sheng College of Pharmaceutical Sciences Qinghai University for Nationalities Beiijing key laboratory of bioactive substances and functional foods Beijing Union University State key laboratory of bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

Guided by TNF-α secretion inhibitory activity assay, four taraxastane-type triterpenoids, including two new ones, 22-oxo-20-taraxasten-3β, 30-diol(1) and 22α-hydroxy-20-taraxasten-30β, 30-triol(2), have been obtained from an active fraction of the petroleum ether-soluble extract of the the medicinal and edible plant Cirsium setosum. Their structures were elucidated by spectroscopic data and CD data analysis. In the TNF-α secretion inhibitory activity assay, compounds 1 and 2 were active with the IC50 of 2.6 and 3.8 μmol·L-1, respectively. In addition, compounds 1 and 2 showed moderately selective cytotoxicity against the human ovarian cancer(A2780) and colon cancer(HCT-8) cell lines.

关键词： Cirsium setosum Taraxastane-type triterpenoid TNF-α secretion inhibitory activity Cytotoxicity

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Three new ursane-type triterpenoids from Rosmarinus officinalis and their biological activities

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Chinese Journal of Natural Medicines 2022年第2期20卷 155-160页

作者： ZHONG Xiang-Jian ZHOU Na WANG Xin LI Jin-Jie MA Hui JIAO Yue XU Jia-Hui LIN Peng-Cheng SHANG Xiao-Ya beijing key laboratory of bioactive substances and functional foods Beijing Union UniversityBeijing 100191China Shandong Institute for Product Quality Inspection Jinan 250100China key laboratory for Qinghai-Tibet Plateau Phytochemistry of Qinghai Province Qinghai Nationalities UniversityXining 810000China

Three new ursane-type triterpenoids,3-oxours-12-en-20,28-olide(1),3β-hydroxyurs-12-en-20,28-olide(2)and 3β-hydroxyurs-11,13(18)-dien-20,28-olide(3),were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus *** structures were elucidated by a combination of extensive 1D-and 2D-NMR experiments,MS data and comparisons with literature *** 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages,but no antibacterial activity was found at a concentration of 128μg·mL^(-1).

关键词： Rosmarinus officinalis Isolation and purification Triterpenoid Biological activity

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Silkworm pupa peptide ameliorates dextrose sodium sulfate-induced colitis by enhancing gut barriers and modifying gut flora

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Food Science and Human Wellness 2024年

作者： Yaxi Zhou Diandian Wang Hao Duan Shiqi Zhou Jinhong Guo Yu Guo Jian Zhao Wenjie Yan beijing key laboratory of bioactive substances and functional Food， College of Biochemical Engineering， beijing Union University

The anti-inflammatory properties of silkworm pupa peptide (SPP) have been recognized for their potential benefits in colitis treatment. However， the underlying mechanism of SPP in colitis animal models remains unclear. The objective of our work was to investigate the improving effect and the mechanism of action of SPP on a mouse model of dextrose sodium sulfate (DSS)-induced colitis. The findings suggested that SPP effectively eased ulcerative colitis (UC) symptoms in mice by decreasing disease activity index， ameliorating histopathological injury， and decreasing serum and colonic markers of inflammation. In addition， our research findings demonstrated that SPP restored intestinal barrier function by increasing the production of tight junction proteins such as zonula occludens-1 (ZO-1)， claudin-1， claudin-3， occludin， and adherens junction protein E-cadherin1. Further， SPP supplementation enhanced the concentration of short-chain fatty acids and positively altered the makeup of the gut bacteria in the mice’s gut. These findings underscore SPP’s ability to slow the progression of colitis and point to its possible use as a functional component in dietary supplements for the prevention of early-stage colitis.

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A general strategy for in situ assembly of light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling

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Chinese Chemical Letters 2022年第9期33卷 4223-4228页

作者： Xiang Li Hong Yang Yu Teng Yongcheng Wang Dali Yin Yulin Tian key laboratory of bioactive substances and Function of Natural Medicine Beijing Key Laboratory of Active Substances Discovery and Drugability EvaluationInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Herein we presented a general strategy for in situ assembly of intramolecular charge-transfer(ICT)-based light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling *** introducing iodo group at the appropriate position,five fluorophores with different scaffolds including naphthalimide,coumarin,naphthalene sulfonate,nitrobenzoxadiazole,and acetonaphthone,were designed as bioorthogonal multicolor fluorogenic probes,which could produce significant fluorescence enhancement and high fluorescence quantum yield after Suzuki-Miyaura reaction with aryl boronic acid or *** the substituents andπscaffold in the fluorophores allows fine-tuning of their photophysical *** this strategy,we succeeded in peptide conjugation,no-wash fluorogenic protein labeling,and mitochondria-selective bioorthogonal imaging in live cells.

关键词： Bioorthogonal reaction Suzuki-Miyaura cross-coupling Fluorogenic probes Naphthalimide Live-cell imaging

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Magnetic Resonance Imaging of Alzheimer's Disease:from Diagnosis to Therapeutic Evaluation

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Chinese Journal of Integrative Medicine 2010年第3期16卷 276-282页

作者：顾雪梅姜招峰黄汉昌 beijing Military General Hospital beijing key laboratory of bioactive substances and functional foods Beijing Union University College of Arts and Science Beijing Union University

Alzheimer＇s disease（AD）is a devastating late-life dementia that produces progressive loss of memory and mental faculties in elderly *** is important to identify the earliest evidence of AD and to monitor the development of this disease for us to make positive response to its *** resonance imaging（MRI）is powerful to image the tissue or organ without *** can be employed to diagnose the early AD development and monitor the key biomarker development in *** may be helpful not only in diagnosing early AD,but also in evaluating its *** article reviews the progress of MRI on the diagnosis and detection of AD,and makes comments on its therapeutic application.

关键词： Alzheimer's disease diagnosis magnetic resonance imaging

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A targeted covalent inhibitor of p97 with proteome-wide selectivity

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Acta Pharmaceutica Sinica B 2022年第2期12卷 982-989页

作者： Zi Ye Ke Wang Lianguo Chen Xiaofeng Jin Hao Chen Guanghui Tang Shao Q.Yao Zhiqiang Feng Chong-Jing Zhang State key laboratory of bioactive substances and Functions of Natural Medicines and beijing key laboratory of Active substances Discovery and Drugability Evaluation Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Department of Chemistry National University of Singapore

A resurging interest in targeted covalent inhibitors(TCIs)focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target.p97 is an emerging protein target for cancer therapy,viral infections and neurodegenerative *** efforts were devoted to the development of p97 *** most promising inhibitor of p97 was in phase 1 clinical trials,but failed due to the off-target-induced toxicity,suggesting the selective inhibitors of p97 are highly *** report herein a new type of TCIs(i.e.,FL-18)that showed proteome-wide selectivity towards *** with a Michael acceptor and a basic imidazole,FL-18 showed potent inhibition towards U87 MG tumor cells,and in proteome-wide profiling,selectively modified endogenous p97 as confirmed by in situ fluorescence scanning,label-free quantitative proteomics and functional ***-18 selectively modified cysteine residues located within the D2 ATP site of *** covalent labeling of cysteine residue in p97 was verified by LC-MS/MS-based site-mapping and site-directed *** structure-activity relationship(SAR)studies with FL-18 analogs were ***,FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity,thus providing a promising scaffold for cancer therapy.

关键词： p97 Activity-based protein profiling Targeted covalent inhibitor Chemical proteomics

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Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1903-1913页

作者： Ziru Yu Dewen Kong Yu Liang Xiaoyue Zhao Guanhua Du State key laboratory of bioactive substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Target and Screening ResearchInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Nicotinicα4β2 receptor antagonists have drawn increasing attention in the development of new *** this study,we aimed to investigate the protective effect of VMY-2-95,the new selective antagonist ofα4β2 nicotinic acetylcholine receptor(nAChR)on corticosterone(CORT)injured mice and cellular *** was applied as a positive control,and the effects of VMY-2-95 were investigated with three different doses or concentrations(1,3,10 mg/kg in mice,and 0.003,0.03,0.1μmol/L in cells).As a result,VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function,promoting hippocampal nerve proliferation,and regulating the contents of monoamine ***,VMY-2-95 exhibited protective effects on cell viability,cell oxidant,cell apoptosis,and mitochondrial energy metabolism on corticosterone-impaired SH-SY5 Y ***,the PKA-CREB-BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo,and pathway blockers were also combined with VMY-2-95 to verify the effects ***,we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5 Y cells against injuries induced by *** work indicated that the application of VMY-2-95 is a potential pharmacological solution for *** study also supported the development ofα4β2 nAChR antagonists towards neuropsychiatric dysfunctions.

关键词： α4β2 nAChR antagonist VMY-2-95 Cholinergiceadrenergic theory Depression Corticosterone SH-SY5Y cells PKA-CREB-BDNF signaling pathway

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A Bioorthogonal-Activated Fluorescence Turn-On Probe Based on Nitrone-Modified 1,8-Naphthalimide for Live-Cell Imaging

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Chinese Journal of Chemistry 2022年第2期40卷 209-214页

作者： Yu Teng Hong Yang Xiang Li Yongcheng Wang Dali Yin Yulin Tian State key laboratory of bioactive substances and Function of Natural Medicine Beijing Key Laboratory of Active Substances Discovery and Drugability EvaluationInstitute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical Sciences1st Xian Nong Tan StreetBeijing 100050China

A nitrone-modified 1,8-naphthalimide was desig ned as a novel bioorthog on alactivated turn-on probe based on strain-promoted alkyne-nitrone cycloadditio n(SPANC).The bioorthog onal cycloadducts were subseque ntly tran sformed into fluoresce nt rearra nge-ment products by photo-accelerati on,which exhibited sign ificant fluoresce nee enhan ceme nt,large stokes shift,and high fluores-cence qua ntum *** calculati ons were performed to elucidate the fluoresce nee OFF-ON mecha *** fluoroge nic strategy was successfully applied to labeling of proteins and visualizing mitochondria in live cells in real time.

关键词： Bioorthogonal reaction Fluorescence Naphthalimide Imaging agents Cycloaddition

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