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Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-Hsi Wu program in Clinical Drug Development from Herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China program in Drug Discovery and Development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of Pharmacy Taipei Medical UniversityTaipei 11031China Graduate institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary *** traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut *** aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured *** indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of *** was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in ***,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured *** conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

Fluorine-doped carbon quantum dots with deep-red emission for hypochlorite determination and cancer cell imaging

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Chinese Chemical Letters 2024年第6期35卷 433-438页

作者： Boran Cheng Lei Cao Chen Li Fang-Yi Huo Qian-Fang Meng Ganglin Tong Xuan Wu Lin-Lin Bu Lang Rao Shubin Wang Department of Oncology Shenzhen Key Laboratory of Gastrointestinal Cancer Translational ResearchCancer InstitutePeking University Shenzhen HospitalShenzhen-Peking University-Hong Kong University of Science and Technology Medical CenterShenzhen 518036China institute of Biomedical health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518132China The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School&Hospital of StomatologyWuhan UniversityWuhan 430079China

As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent ***,the CDs with deep-red(DR)or near-infrared(NIR)emission have rarely been *** this work,we prepared deep-red emissive fluorine-doped carbon quantum dots(F-CDs)by introducing a precursor simultaneously containing fluorine and *** synergistic effect of nitrogen doping and D-π-A pattern production contributed to the maximum emission of F-CDs at 636 nm with an absolute quantum yield of 36.00%±0.68%.Moreover,we designed an F-CDs-based fluorescence assay to determine the content of hypochlorite(ClO^(-)),with a limit of detection(LOD)as low as 15.4 nmol/L,indicating the high sensitivity of F-CDs to ClO^(-).In real samples,the F-CDs-based fluorescent sensor exhibited excellent sensitivity and selectivity in the detection of ClO^(-),with an error below 2%,suggesting their great potential in daily *** cancer cell imaging,the F-CDs not only demonstrated high sensitivity to ClO^(-)but also exhibited excellent mitochondria targeting,as evidenced by the high Pearson's correlation coefficient(PCC)of 0.93 in colocalization *** work presented here suggests the great potential of replacing commercial dyes with F-CDs for highly specific mitochondria labeling and cell imaging.

关键词： Carbon dots Near-infrared Cell imaging Mitochondria labeling Hypochlorite determination

Genomic characterization of peritoneal lavage cytology-positive gastric cancer

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Chinese Journal of cancer research 2024年第1期36卷 66-77页

作者： Zhouqiao Wu Tingfei Gu Changxian Xiong Jinyao Shi Jingpu Wang Ting Guo Xiaofang Xing Fei Pang Ning He Rulin Miao Fei Shan Yuan Zhou Ziyu Li Jiafu Ji Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Biomedical Informatics Department of Physiology and PathophysiologyCenter for Noncoding RNA MedicineMOE Key Lab of Cardiovascular SciencesSchool of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric ***: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric ***: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

关键词： Cytology gastric carcinoma peritoneal metastasis whole exome sequencing

Clinical efficacy and identification of factors confer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3130-3140页

作者： Yanni Wang Chang Liu Huan Chen Xi Jiao Yujiao Wang Yanshuo Cao Jian Li Xiaotian Zhang Yu Sun Na Zhuo Fengxiao Dong Mengting Gao Fengyuan Wang Liyuan Dong Jifang Gong Tianqi Sun Wei Zhu Henghui Zhang Lin Shen Zhihao Lu Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Genecast Biotechnology Co. LtdWuxiPR China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Key Laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijingChina Precision Scientific(Beijing)Co. Ltd.BeijingChina Generulor Company Bio-X Lab ZhuhaiGuangdongChina Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory for Therapeutic cancer Vaccines Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival *** preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing *** proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity *** analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR ***,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib *** study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

关键词： esophageal squamous expressing

The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

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Biomedical and Environmental Sciences 2024年第1期37卷 31-41页

作者： HONG Tao SUN Wei DENG Yuan LYU Jian Da JIN Cui Hong BAI Ying Long NA Jun ZHANG Rui GAO Yuan PAN Guo Wei YANG Zuo Sen YAN Ling Jun research Center for Universal health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Pain Management Shengjing Hospital of China Medical UniversityShenyang 110004LiaoningChina Department of Toxicology School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Maternal and Child health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina institute of Preventive Medicine China Medical UniversityShenyang 110122LiaoningChina institute of Chronic Diseases Liaoning Provincial Center for Disease Control and PreventionShenyang 110000LiaoningChina

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in *** Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after *** was performed to corroborate these *** In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by *** peak time of nanoplastic absorption in blood was *** Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

关键词： Microplastics Nanoplastics IVIS Spectrum small-animal imaging system Tissue distribution Blood

Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition

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Chinese Chemical Letters 2024年第6期35卷 456-461页

作者： Chenlu Huang Xinyu Yang Qingyu Yu Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor *** overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that encapsulated Toll-like receptor(TLR)7/8 agonist imiquimod(IMQ)and photosensitizer indocyanine green(ICG)in the hydrophobic layer as well as bubble-generator NH_(4)HCO_(3) in the hydrophilic cavity to inhibit the growth of primary and distant tumors,and prevent tumor metastasis through synergistic *** AIRL polymersomes exhibited uniform and stable size,and high drug encapsulation efficiency,acid/reduction/laser responsiveness,excellent photothermal conversion efficiency,effective reactive oxygen species generation,high tumor *** could be effectively internalized by dendritic cells(DCs),achieve lysosome escape and enhance DCs *** synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells,elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant ***,the endurable immunological memory prevented tumor metastasis,which provided a promising nanoplatform for the combination therapy of cancer.

关键词： Polymersomes Phototherapy Immunotherapy TLR 7/8 agonist Gas-generating

Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong Wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive medical Center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China Center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast cancer

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Current medical Science 2024年第1期44卷 156-167页

作者： Zi-guo YANG Le-hao REN Feng WANG Pi-lin WANG Wen-yan WANG Shu-ye LIN Department of General Surgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Critical Care Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China cancer research Center Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at ***,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher ***-67 is associated with the prognosis and response to therapy,and it changes after *** A total of 105 BC patients who received anthracycline-containing NAC were ***,the optimal model of Ki-67 was selected,and its predictive efficacy was ***(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 *** in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 *** ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and *** area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),*** logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictor

关键词： breast cancer change in Ki-67 neoadjuvant chemotherapy anthracycline,response

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric research institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China institute for Brain Science and Disease of Chongqing medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation