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Pyropia haitanensis polysaccharide extends lifespan by inhibiting protein aggregation in Caenorhabditis elegans

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Journal of Oceanology and Limnology 2021年第2期39卷 705-713页

作者： Zhongshan ZHANG Xiaomei WANG Yongliang PAN Zhanqi WANG Zhengshun WEN Feng LIU genxiang mao Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province Huzhou UniversityHuzhou Central HospitalHuzhou 313000China Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products School of Food Science and PharmaceuticsZhejiang Ocean UniversityZhoushan 316022China CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Zhejiang Provincial Key Lab of Geriatrics Department of GeriatricsZhejiang HospitalHangzhou 310013China

Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as *** Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,reproduction,pharyngeal pumping,stress response,quantitative fluorescence of polyglutamic acid,and nuclear localization of DAF-16 of *** results reveal that LP could extend the adult lifespan of wild-type and polyQ nematodes,indicating a connection of its anti-aging benefit with the toxicity-suppressing *** number of polyglutamic acid aggregates in high concentration groups decreased by 24.39%(P<0.05)to the *** high-dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared with the control(P<0.001).Therefore,we believe that LP could extend the lifespan and reduce the protein aggregation in *** through nuclear DAF-16∷GFP expression.

关键词： Pyropia haitanensis polysaccharide protein aggregation Caenorhabditis elegans

BSA stabilized photothermal-fenton reactor with cisplatin for chemo/chemodynamic cascade oncotherapy

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Nano Research 2022年第3期15卷 2235-2243页

作者： Nan Yang Tian Zhang Changyu Cao genxiang mao Jinjun Shao Xuejiao Song Wenjun Wang Xiaozhou Mou Xiaochen Dong Key Laboratory of Flexible Electronics(KLOFE)and Institute of Advanced Materials(IAM) School of Physical and Mathematical SciencesNanjing Tech University(NanjingTech)Nanjing 211816China School of Physical Science and Information Technology Liaocheng UniversityLiaocheng 252059China Zhejiang Provincial Key Lab of Geriatrics&Geriatrics Institute of Zhejiang Province Department of GeriatricsZhejiang HospitalHangzhou 310013China Clinical Research Institute Zhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou 310014China

Cisplatin(CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence *** therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment ***,chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin(BSA)stabilized gallic acid-functionalized iron nanoparticles(GA-Fe NPs)to achieve chemo/chemodynamic synergistic cascade *** Pt-GA-Fe NPs can be utilized to generate H_(2)O_(2) via the activation of nicotinamide adenine dinucleotide phosphate(NADPH)oxidases(NOXs)in the tumor microenvironment(TME),which would then greatly boost H2O2-depending chemodynamic therapy(CDT).The generated cytotoxic reactive oxygen species(hydroxyl radicals,·OH)and the depletion of glutathione(GSH)would further promote CDDP-induced DNA ***,benefiting from the absorption in the near-infrared(NIR)region,Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency(η=45.5%)and allow photoacoustic imaging(PAI)guided photothermal therapy(PTT).In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic *** work highlights a new type of therapeutic agent based on CDDP with the ability of H_(2)O_(2) self-generation,thermal responsiveness,and enhanced CDT effects for applications in cancer therapy.

关键词： chemotherapy chemodynamic therapy cascade therapy CDDP Fenton reaction

Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3134-3149页

作者： Xiaojia Liu Mingxiao Yin Jingwen Dong genxiang mao Wenjian Min Zean Kuang Peng Yang Lu Liu Na Zhang Hongbin Deng Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Zhejiang Provincial Key Lab of Geriatrics Department of GeriatricsZhejiang HospitalHangzhou 310013China State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization China Pharmaceutical UniversityNanjing 210009China Qingdao Women and Children’s Hospital Qingdao UniversityQingdao 266034China

Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)*** PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor *** flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 ***-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of ***,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell ***,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent ***-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome ***,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)*** findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.

关键词： PD-L1 Immune checkpoint blockade Transcription factor EB Lysosome mTOR

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2299-2312页

作者： Yang Liu Xiaojia Liu Na Zhang Mingxiao Yin Jingwen Dong Qingxuan Zeng genxiang mao Danqing Song Lu Liu Hongbin Deng Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Zhejiang Provincial Key Lab of Geriatrics Department of GeriatricsZhejiang HospitalHangzhou 310013China Qingdao Women and Children’s Hospital Qingdao UniversityQingdao 266034China

Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer *** with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently *** we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical *** enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer *** addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent ***,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of *** data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

关键词： PD-L1 Immune checkpoint blockade COP9 signalosome 5 Berberine PD-1/PD-L1 axis T-cell immunity

Fucoidan sulfate from Sargassum fusiforme regulates the SARS-CoV-2 receptor AXL expression in human embryonic lung diploid fibroblast cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第11期24卷 1047-1052页

作者： Xuqiang ZHOU Weihua JIN Di JIANG Yipeng XU Sanying WANG Xinna WU Yunchuang CHANG Huili SU Tianjun ZHU Xiaogang XU genxiang mao College of Life Science Zhejiang Chinese Medical UniversityHangzhou310053China Zhejiang Provincial Key Lab of Geriatrics&Geriatrics Institute of Zhejiang Province Department of GeriatricsZhejiang HospitalHangzhou310030China College of Biotechnology and Bioengineering Zhejiang University of TechnologyHangzhou310014China Zhejiang Cancer Hospital the Key Laboratory of Zhejiang Province for Aptamers and TheranosticsInstitute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou310022China School of Medicine Zhejiang UniversityHangzhou310058China School of Biological and Chemical Engineering Zhejiang University of Science and TechnologyHangzhou310023China

Coronavirus disease 2019(COVID-19)is a global infectious disease that seriously endangers human life and health and affects normal social *** the pandemic outbreak from December 2019 to February 2023,the total number of confirmed cases has exceeded 753 million,and the deaths caused by COVID-19 have reached 6.6 million(https://***;accessed on Feb.16,2023).

关键词： Sargassum lung cases

Sirtinol suppresses human cytomegalovirus(hCMV) infection and protects against hCMV-induced cellular senescence in human fibroblasts

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Sirtinol suppresses human cytomegalovirus(hCMV) infection an...

No association of rs35767 polymorphism of IGF-1 with bone mineral density in Chinese postmenopausal population

2015年老年医学学术年会

作者： genxiang mao Huifen Li Guofu Wang Sean X.Leng Zhejiang Provincial Key Laboratory of Geriatrics & Geriatrics Institute of Zhejiang Province Zhejiang Hospital Division of Geriatric Medicine and Gerontology Department of Medicine Johns Hopkins University School of Medicine

Human cytomegalovirus (h CMV) causes birth defects in newborns and severe infections in immunocompromised patients. Chronic CMV infection may also contribute to immunosenescence during aging. Anti-h CMV treatments currently available are limited and have significant drawback. This study aimed to investigate sirtinol, a sirtuin inhibitor, as a novel anti-h CMV agent and its effects on h CMV infection and h CMV-induced cellular senescence and production of reactive oxygen species (ROS). Human diploid fibroblast WI-38 cells were infected by h CMV Towne strain in the absence or presence of sirtinol and resveratrol. h CMV replication was measured using q PCR. Senescent phenotype was determined by senescence-associated β galactosidase (SA-b-Gal) activity. Expression of h CMV immediate early (IE) and early (E) proteins and senescence proteins (p Rb and Rb, p16INK4, and p53) and ROS production were assessed using standard laboratory *** suppressed h CMV infection in a dose dependent fashion with over 95% reduction of h CMV replication and expression of IE and E proteins at sirtinol concentration of 20μM. Sirtinol and resveratrol both suppressed h CMV-induced cellular senescence and ROS production. Our findings indicate sirtinol as a potent anti-CMV agent and provide a basis for potential development of sirtinol or its derivatives as effective anti-h CMV therapies. They also provide insights into molecular pathways of h CMV control, cellular senescence, and aging.

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No association of rs35767 polymorphism of IGF-1 with bone mi...

Insulin-like growth factor-1 gene polymorphism was associated with bone mineral density in Chinese postmenopausal women

第三届江浙沪三地老年医学高峰论坛暨2012年浙江省老年医学学术年会

作者： Weihong Xu mao genxiang Xilian Hu Guofu Wang Liping Wang Zhejiang Provincial Key Lab of Geriatrics Zhejiang Hospital The Affiliated Hospital of Hangzhou Normal University

It has been showed that Insulin-like growth factor-1(IGF-1) may be related with bone mineral density(BMD) or *** little is known about genetic variation in IGF-1 was associated with BMD or osteoporosis. In this study,we observed the association of polymorphisms in IGF-1(rs35767) and BMD in a Chinese postmenopausal female *** of 168 women were recruited in this *** participants completed a questionnaire and BMD was measured by dual energy x-ray absorptiometry(DEXA) at the lumbar spine L1-L4/ L2-L4,femoral neck and femoral *** polymorphism was determined by direct sequence analysis of PCR of genomic ***,there was no obvious association between polymorphisms in IGF-1(rs35767) and BMD(P > 0.05)/osteoporosis(P = 0.78),the BMD of women with TT alleles were lower than those with CC alleles by 4.5%,7.2%,6.6%and 6.2%for L1-L4,femoral neck,femoral trochanter and proximal *** study suggested that polymorphisms in IGF-1(rs35767) may be susceptibility loci for reduced BMD in postmenopausal women.

关键词： Insulin-like growth factor-1 IGF-1 bone mineral density osteoporosis

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Insulin-like growth factor-1 gene polymorphism was associate...

7,8-二羟基黄酮纳米粒子通过保护卵巢储备缓解代谢综合征

2013年浙江省医学会老年医学学术年会暨国家级继教项目老年人优化健康管理研讨班

作者： Weihong Xu Bingbing Jia genxiang mao Xilian Hu Guofu Wang Jing Yan Zhejiang Provincial Key Lab of Geriatrics Zhejiang Hospital

It has been showed that Insulin-like growth factor-1 (IGF-1) may be related with bone mineral density (BMD) or osteoporosis. But little is known about genetic variation in IGF-1 was associated with BMD or osteoporosis. Here, we observed the association of polymorphisms in IGF-1 (rs35767) and BMD in Chinese postmenopausal female population. A total of 168 women completed a questionnaire and BMD was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine L2-L4, femoral neck and femoral trochanter. The polymorphism was determined by direct sequence analysis of PCR of genomic DNA. All 168 subjects fall within three genotypes (CC, CT and TT) at rs35767 site. The prevalence of each genotype was 48.2% CT, 40.5% CC, and 11.3% TT. The genotype frequencies satisfied the Hardy-Weinberg equilibrium (χ2 = 0.59, P> 0.05). Although, there was no significant association between polymorphisms in IGF-1(rs35767) and BMD/osteoporosis, the BMD of women with TT alleles were lower than those with CC alleles by 4.5%, 7.2%, 6.6% and 6.2% for L2-L4, femoral neck, femoral trochanter and proximal femur, respectively (all the P values <0.05). Our results suggested that polymorphisms in IGF-1(rs35767) may be a susceptible loci for reduced BMD in Chinese postmenopausal women.

关键词： Insulin-like growth factor-1 IGF-1 bone mineral density osteoporosis

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精细化工 2022年第2期39卷 358-366页

作者：赵镇雷薛凡徐小刚毛根祥张英浙江医院浙江省老年医学研究所&浙江省老年医学重点实验室浙江杭州310013 浙江大学生物系统工程与食品科学学院浙江杭州310058

以芜菁多糖构建的7,8-二羟基黄酮(7,8-DHF)纳米粒子对两种不同膳食模式(高脂和低脂)饲养的C57BL/6J雌性小鼠进行24周的干预,采用分子生物学方法对代谢综合征(MetS)各项指标、炎症因子及卵巢储备功能进行了测定,探究了其对小鼠MetS的改... 详细信息

以芜菁多糖构建的7,8-二羟基黄酮(7,8-DHF)纳米粒子对两种不同膳食模式(高脂和低脂)饲养的C57BL/6J雌性小鼠进行24周的干预,采用分子生物学方法对代谢综合征(MetS)各项指标、炎症因子及卵巢储备功能进行了测定,探究了其对小鼠MetS的改善作用和机制。结果表明,7,8-DHF及其纳米粒子均可有效缓解小鼠MetS的症状,可显著降低高脂膳食(HFD)诱导的小鼠体重过度增长,与HFD对照组相比,7,8-DHF及7,8-DHF纳米粒子组体重分别下降了8.5%和16.4%;可显著改善血脂、血糖及血胰岛素水平、小鼠的葡萄糖耐受性和胰岛素敏感性;能够显著降低血清中循环脂多糖、肿瘤坏死因子(TNF-α)和白细胞介素-6(IL-6)等炎症相关指标;可以有效保护小鼠卵巢储备功能,维持其正常的动情周期和血清雌二醇、卵泡刺激素的水平稳态。7,8-DHF纳米粒子对MetS各项指标的干预效果显著优于单独的7,8-DHF。7,8-DHF及其纳米粒子对雌性小鼠MetS的干预作用可能是通过缓解肠道菌群介导的全身炎症并作用于对卵巢储备功能的保护而实现的。

关键词： 7 8-二羟基黄酮芜菁多糖纳米粒子代谢综合征卵巢储备中药活性成分医药原料