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| 1 | Interleukin 17-Producing γδ T Cells Increased in Patients with Active Pulmonary Tuberculosis显示文摘Although it has been known that γδ T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the γδ T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of γδ T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in γδ T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-γ-producing γδ T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing γδ T cells were generated from HD and TB patients, whereas IFN-γ-producing γδ T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing γδ T cells were main source of IL-17 in mouse model of BCG infection, suggesting that γδ T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification. | Meiyu Peng Zhaohua Wang Chunyan Yao Lina Jiang Qili Jin Jing Wang Baiqing Li | 2008 | Cellular & Molecular Immunology2008，5，3： | 28 |
| 2 | Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure–activity relationship, crystal structural characterization and in vivo study显示文摘Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors(FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure–activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound(35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development. | Peng Wei Bo Liu Ruifeng Wang Yinglei Gao Lanlan Li Yuchi Ma Zhiwei Qian Yuelei Chen Maosheng Cheng Meiyu Geng Jingkang Shen Dongmei Zhao Jing Ai Bing Xiong | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 2 |
| 3 | HSP70 alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial dysfunction-initiated NLRP3 inflammasome-mediated pyroptosis in cardiomyocytes显示文摘Background:Sepsis-induced cardiomyopathy(SIC)is an identified serious complication of sepsis that is associated with adverse outcomes and high mortality.Heat shock proteins(HSPs)have been implicated in suppressing septic inflammation.The aim of this study was to investigate whether HSP70 can attenuate cellular mitochondrial dysfunction,exuberated inflammation and inflammasome-mediated pyroptosis for SIC intervention.Methods:Mice with cecal ligation plus perforation(CLP)and lipopolysaccharide(LPS)-treated H9C2 cardiomyocytes were used as models of SIC.The mouse survival rate,gross profile,cardiac function,pathological changes and mitochondrial function were observed by photography,echocardiography,hematoxylin-eosin staining and transmission electron microscopy.In addition,cell proliferation and the levels of cardiac troponin I(cTnI),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were determined by Cell Counting Kit-8,crystal violet staining and enzyme-linked immunosorbent assay.Moreover,mitochondrial membrane potential was assessed by immunofluorescence staining,and dynamin-related protein 1 and pyroptosis-related molecules[nucleotide-binding domain,leucine-rich-repeat containing family pyrin domain-containing 3(NLRP3),caspase-1,gasdermin-D(GSDMD),gasdermin-D N-terminal(GSDMD-N)]were measured by western blotting,immunoprecipitation and immunoblotting.Finally,hsp70.1 knockout mice with CLP were used to verify the effects of HSP70 on SIC and the underlying mechanism.Results:Models of SIC were successfully established,as reduced consciousness and activity with liparotrichia in CLP mice were observed,and the survival rate and cardiac ejection fraction(EF)were decreased;conversely,the levels of cTnI,TNF-αand IL-1βand myocardial tissue damage were increased in CLP mice.In addition,LPS stimulation resulted in a reduction in cell viability,mitochondrial destabilization and activation of NLRP3-mediated pyroptosis molecules in vitro.HSP70 treatment improved myocardial tissue damage,survival rate and cardiac dysfunction caused by CLP.Additionally,HSP70 intervention reversed LPS-induced mitochondrial destabiliza-tion,inhibited activation of the NLRP3 inflammasome,caspase-1,GSDMD and GSDMD-N,and decreased pyroptosis.Finally,knockout of hsp70.1 mice with CLP aggravated cardiac dysfunction and upregulated NLRP3 inflammasome activity,and exogenous HSP70 significantly rescued these changes.It was further confirmed that HSP70 plays a protective role in SIC by attenuating mitochondrial dysfunction and inactivating pyroptotic molecules.Conclusions:Our study demonstrated that mitochondrial destabilization and NLRP3 inflammasome activation-mediated pyroptosis are attributed to SIC.Interestingly,HSP70 ameliorates sepsis-induced myocardial dysfunction by improving mitochondrial dysfunction and inhibiting the acti-vation of NLRP3 inflammasome-mediated pyroptosis,and such a result may provide approaches for novel therapies for SIC. | Chenlu Song Yiqiu Zhang Qing Pei Li Zheng Meiyu Wang Youzhen Shi Shan Wu Wei Ni Xiujun Fu Yinbo Peng Wen Zhang Min Yao | 2022 | Burns & Trauma2022，10，1： | 2 |
| 4 | Lack of Corneal Toxicity of Interferon Alpha-2b Administered Subconjunctivally after Sclerectomy显示文摘Purpose: To evaluate the corneal toxicity of subconjunctival injection interferon α-2bat filtering bleb after sclerectomy in white rabbits.Methods: Eight rabbits which had been performed sclerectomy were randomlydivided into two groups. Each group consisted of four rabbits. Eight eyes in group 1were subconjunctivally received interferon α-2b 5 × 105IU/0. 2ml into filtering blebfrom the edge of the filtering site immediately after operation and every postoperativeday. The other eight eyes in group 2 were injected with 0. 2ml normal saline. All ofthe eyes underwent daily examination by slip-lamp microscopy and directophthalmoloscopy. Sodium fluorescein was used to assess corneal epithelial integrity.On day 3,4,7 and 14, every two rabbits (group 1 and 2 each, respectively) werekilled and removed cornea immediately to take examination of the viability of cornealendothelium by dual staining with typan blue and alizanin red S.Results: No sign of toxicity in corneal epithelium and endothelium were | Xiulan Zhang, Dawei Peng, Hulin Zheng, Meiyu LiangZhongshan Ophthalmic Center, Sun Yat-sen University of Medical Sciences , Guangzhou 510060 , China | 1997 | 眼科学报1997，13，1： | 1 |
| 5 | SYK-mediated epithelial cell state is associated with response to c-Met inhibitors in c-Met-overexpressing lung cancer显示文摘Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer(NSCLC)patients according to the predicted response to c-Met inhibitors(c-Metis),yet the overall clinical benefit of this strategy is quite limited.Notably,c-Met protein overexpression,which occurs in approximately 20–25%of NSCLC patients,has not yet been clearly defined as a clinically useful biomarker.An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking.Herein,we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status.Furthermore,TGF-β1 treatment resulted in SYK transcriptional downregulation,increased Sp1-mediated transcription of FRA1,and restored the mesenchymal state,which conferred resistance to c-Metis.Clinically,a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3%and longer progression-free survival with c-Meti treatment than other patients.SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance.In summary,SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state.Furthermore,our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy. | Ji Zhou Xu-Chao Zhang Shan Xue Mengdi Dai Yueliang Wang Xia Peng Jianjiao Chen Xinyi Wang Yanyan Shen Hui Qin Bi Chen Yu Zheng Xiwen Gao Zuoquan Xie Jian Ding Handong Jiang Yi-Long Wu Meiyu Geng Jing Ai | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 0 |
| 6 | Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyridazinone derivatives as covalent FGFR inhibitors显示文摘Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy.In this study,we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-d]pyridazinone derivatives.Kinase inhibition,cell proliferation,and whole blood stability assays were used to evaluate their activity on FGFR,allowing us to explore structureàactivity relationships and thus to gain understanding of the structural requirements to modulate covalent inhibitors’selectivity and reactivity.Among them,compound 10h exhibited potent enzymatic activity against FGFR and remarkably inhibited proliferation of various cancer cells associated with FGFR dysregulation,and suppressed FGFR signaling pathway in cancer cells by the immunoblot analysis.Moreover,10h displayed highly potent antitumor efficacy (TGI Z 91.6%,at a dose of 50 mg/kg) in the FGFR1-amplified NCI-H1581 xenograft model. | Xiaowei Wu Mengdi Dai Rongrong Cui Yulan Wang Chunpu Li Xia Peng Jihui Zhao Bao Wang Yang Dai Dan Feng Tianbiao Yang Hualiang Jiang Meiyu Geng Jing Ai Mingyue Zheng Hong Liu | 2021 | Acta Pharmaceutica Sinica B2021，11，3： | 0 |
| 7 | Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients显示文摘Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment.Whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)triggered ADCC responses contributes to COVID-19 disease development is currently not well understood.To understand the potential correlation between ADCC responses and COVID-19 disease development,we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease.ADCC was elicited by 10 days post-infection,peaked by 11-20 days,and remained detectable until 400 days post-infection.In general,patients with severe disease had higher ADCC activities.Notably,patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased.Importantly,ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern(VOCs)(B.1.1.7,B.1.351,and P.1)as that against the D614G mutant in human patients and vaccinated mice.Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions,which can be applied to estimate the extra-neutralization level against COVID-19,especially lethal COVID-19. | Yuanling Yu Meiyu Wang Xiaoai Zhang Shufen Li Qingbin Lu Haolong Zeng Hongyan Hou Hao Li Mengyi Zhang Fei Jiang Jiajing Wu Ruxia Ding Zehua Zhou Min Liu Weixue Si Tao Zhu Hangwen Li Jie Ma Yuanyuan Gu Guangbiao She Xiaokun Li Yulan Zhang Ke Peng Weijin Huang Wei Liu Youchun Wang | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 0 |
| 8 | From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H_(2)O_(2) and targeting nanotherapeutics显示文摘Liver fibrosis and hepatocellular carcinoma(HCC)have been worldwide threats nowadays.Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage.In pathological liver,excessive H_(2)O_(2) is generated and accumulated,which impacts the functionality of hepatocytes,Kupffer cells(KCs)and hepatic stellate cells(HSCs),leading to genesis of fibrosis and HCC.H_(2)O_(2) accumulation is associated with overproduction of superoxide anion(O_(2)^(·-))and abolished antioxidant enzyme systems.Plenty of therapeutics focused on H_(2)O_(2) have shown satisfactory effects against liver fibrosis or HCC in different ways.This review summarized the reasons of liver H_(2)O_(2) accumulation,and the role of H_(2)O_(2) in genesis of liver fibrosis and HCC.Additionally,nanotherapeutics targeting H_(2)O_(2) were summarized for further consideration of antifibrotic or antitumor therapy. | Meiyu Shao Yifan Wang Hongyan Dong Lu Wang Xiaoqing Zhang Xin Han Xianan Sang Yini Bao Mengyun Peng Gang Cao | 2023 | Bioactive Materials2023，，5： | 0 |
| 9 | Structure-based drug discovery of novel fusedpyrazolone carboxamide derivatives as potent and selective AXL inhibitors显示文摘a novel and promising antitumor target,AXL plays an important role in tumor growth,metastasis,immunosuppression and drug resistance of various malignancies,which has attracted extensive research interest in recent years.In this study,by employing the structure-based drug design and bioisosterism strategies,we designed and synthesized in total 54 novel AXL inhibitors featuring a fusedpyrazolone carboxamide scaffold,of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions.Notably,compound 59 showed a desirable AXL kinase inhibitory activity(IC_(50):3.5 nmol/L)as well as good kinase selectivity,and it effectively blocked the cellular AXL signaling.In turn,compound 59 could potently inhibit BaF3/TEL-AXL cell viability(IC_(50):1.5 nmol/L)and significantly suppress GAS6/AXL-mediated cancer cell invasion,migration and wound healing at the nanomolar level.More importantly,compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency,in which we observed significant AXL phosphorylation suppression,and its antitumor efficacy at 20 mg/kg(qd)was comparable to that of BGB324 at 50 mg/kg(bid),the most advanced AXL inhibitor.Taken together,this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. | Feifei Fang Yang Dai Hao Wang Yinchun Ji Xuewu Liang Xia Peng Jiyuan Li Yangrong Zhao Chunpu Li Danyi Wangh Yazhou Li Dong Zhang Dan Zhang Meiyu Geng Hong Liu Jing Ai Yu Zhou | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
| 10 | Role of Thermolysin in Catalytic-Controlled Self-Assembly of Fmoc-Dipeptides显示文摘In recent years,short peptide self-assembled materials,prepared under the control of the thermolysin catalyst,have been investigated extensively and shown to acquire various morphologies and functions as building blocks for a wide range of biomaterials and device applications.However,the role played by thermolysin in this enzymatically triggered peptide self-assembly is still ambiguous.Herein,we designed a series of Fmoc-dipeptide amphiphiles to explore the catalytic role of thermolysin. | Meiyue Wang Qiansen Zhang Honglei Jian Shijie Liu Jieling Li Anhe Wang Qianqian Dong Peng Ren Xin Li Shuo Bai | 2020 | CCS Chemistry2020，2，4： | 0 |
| 11 | Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma显示文摘miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/ miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs. | Dafu Chen Chengyue Lei Weifeng Liu Meiyu Shao Meizhou Sun Jianxun Guo Jingjing Cao Jing-Jun Nie Peng Luo Yuwen Luo Bingran Yu Renxian Wang Shun Duan Fu-Jian Xu | 2023 | Bioactive Materials2023，，10： | 0 |
| 12 | Redox-responsive phenyl-functionalized polylactide micelles for enhancing Ru complexes delivery and phototherapy显示文摘Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,endowing PEG-PLA micelles with high drug loading,self-assembly stability and fast intracellular drug release is still challenging.Redox-responsive diblock copolymers(MPEG-SS-PMLA)of poly(ethylene glycol)and phenyl-functionalized poly(lactic acid)with disulfide bond as the linker are synthesized to prepare PLA-based micelles that demonstrate excellent colloidal stability and high Ru loading.Notably,MPEGSS-PMLA achieved a remarkably high Ru loading efficiency of 84.3%due to the existence of strongπ-πstacking between phenyl and Ru complex.MPEG-SS-PMLA exhibited good colloidal stability in physiological condition but quickly destabilized by reductive tumor microenvironment.Interestingly,about 74%of Ru complex was released under 10 mmol/L GSH concentration.Ru-loaded MEPG-SS-PMLA showed efficient delivery and release of Ru complex into MCF-7 cancer cells,achieving enhanced in vitro and in vivo antitumor activity of photodynamic therapy.This feasible functionalization method of MPEG-PLA has appeared to be a clinically viable platform for controlled delivery therapeutic agents and enhanced phototherapy. | Maomao He Zongwei Zhang Ziyue Jiao Meiyu Yan Pengcheng Miao Zhiyong Wei Xuefei Leng Yang Li Jiangli Fan Wen Sun Xiaojun Peng | 2023 | Chinese Chemical Letters2023，34，3： | 0 |
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