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| 1 | Adoptive cell transfer therapy for hepatocellular carcinoma显示文摘Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma? Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research. | Renyu Zhang Zhao Zhang Zekun Liu Ding Wei Xiaodong Wu Huijie Bian Zhinan Chen | 2019 | Frontiers of Medicine2019，13，1： | 17 |
| 2 | Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy显示文摘Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvlll) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvlll in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery. | Zhao Zhang Jun Jiang Xiaodong Wu Mengyao Zhang Dan Luo Renyu Zhang Shiyou Li Youwen He Huijie Bian Zhinan Chen | 2019 | Frontiers of Medicine2019，13，1： | 11 |
| 3 | CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells显示文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19. | Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping Zhu Zhi-Nan Chen | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 9 |
| 4 | A natural variation in Ribonuclease H-like gene underlies Rht8 to confer“Green Revolution”trait in wheat显示文摘Dear Editor,Introduction of gibberellin(GA)-insensitive Reduced height(Rht)genes,Rht-B1b and Rht-D1b,has resulted in the“Green Revolution”in modern wheat cultivars(Triticum aestivum)that has skyrocketed wheat grain yields worldwide since the 1960s(Peng et al.,1999;Velde et al.,2021).However,Rht-B1b/D1b also reduce coleoptiles,which is undesired in dryland regions where deep planting is essential for seedling establishment(Rebetzke et al.,1999,Rebetzke et al.,2001;Ellis et al.,2004). | Lingling Chai Mingming Xin Chaoqun Dong Zhaoyan Chen Huijie Zhai Junhong Zhuang Xuejiao Cheng Naijiao Wang Jia Geng Xiaobo Wang Ruolin Bian Yingyin Yao Weilong Guo Zhaorong Hu Huiru Peng Guihua Bai Qixin Sun Zhenqi Su Jie Liu Zhongfu Ni | 2022 | Molecular Plant2022，15，3： | 8 |
| 5 | CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta,alpha,beta,and gamma显示文摘SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a'spike protein-CD147-CyPA signaling axis':Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment. | Jiejie Geng Liang Chen Yufeng Yuan Ke Wang Youchun Wang Chuan Qin Guizhen Wu Ruo Chen Zheng Zhang Ding Wei Peng Du Jun Zhang Peng Lin Kui Zhang Yongqiang Deng Ke Xu Jiangning Liu Xiuxuan Sun Ting Guo Xu Yang Jiao Wu Jianli Jiang Ling Li Kun Zhang Zhe Wang Jing Zhang Qingguo Yan Hua Zhu Zhaohui Zheng Jinlin Miao Xianghui Fu Fengfan Yang Xiaochun Chen Hao Tang Yang Zhang Ying Shi Yumeng Zhu Zhuo Pei Fei Huo Xue Liang Yatao Wang Qingyi Wang Wen Xie Yirong Li Mingyan Shi Huijie Bian Ping Zhu Zhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 6 |
| 6 | CD147 regulates antitumor CD8^(+)T-cell responses to facilitate tumor-immune escape显示文摘Negative regulation of antitumor T-cell-immune responses facilitates tumor-immune escape.Here,we show that deletion of CD147,a type I transmembrane molecule,in T cells,strongly limits in vivo tumor growth of mouse melanoma and lung cancer in a CD8^(+)T-cell-dependent manner.In mouse tumor models,CD147 expression was upregulated on CD8^(+)tumor-infiltrating lymphocytes(TILs),and CD147 was coexpressed with two immune-checkpoint molecules,Tim-3 and PD-1.Mining publicly available gene-profiling data for CD8^(+)TILs in tumor biopsies from metastatic melanoma patients showed a higher level of CD147 expression in exhausted CD8^(+)TILs than in other subsets of CD8^(+)TILs,along with expression of PD-1 and TIM-3.Additionally,CD147 deletion increased the abundance of TILs,cytotoxic effector function of CD8^(+)T cells,and frequency of PD-1^(+)CD8^(+)TILs,and partly reversed the dysfunctional status of PD-1^(+)Tim-3^(+)CD8^(+)TILs.The cytotoxic transcription factors Runx3 and T-bet mediation enhanced antitumor responses by CD147^(-/-)CD8^(+)T cells.Moreover,CD147 deletion in T cells increased the frequency of TRM-like cells and the expression of the T-cell chemokines CXCL9 and CXCL10 in the tumor microenvironment.Analysis of tumor tissue samples from patients with non-small-cell lung cancer showed negative correlations between CD147 expression on CD8^(+)TILs and the abundance of CD8^(+)TILs,histological grade of the tumor tissue samples,and survival of patients with advanced tumors.Altogether,we found a novel function of CD147 as a negative regulator of antitumor responses mediated by CD8^(+)TILs and identified CD147 as a potential target for cancer immunotherapy. | Yatong Chen Jing Xu Xiaodong Wu Hui Yao Zhou Yan Ting Guo Wenjing Wang Peixiao Wang Yu Li Xiangmin Yang Hao Li Huijie Bian Zhi-Nan Chen | 2021 | Cellular & Molecular Immunology2021，18，8： | 4 |
| 7 | UBE2S interacting with TRIM28 in the nucleus accelerates cell cycle by ubiquitination of p27 to promote hepatocellular carcinoma development显示文摘Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine.However,identifying a key driver gene or mutation that can be used for hepatocellular carcinoma(HCC)treatment remains difficult.Here,we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S(p.Gly57Ala and p.Lys63Asn).Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious.Further,we observed that wild-type UBE2S,especially in the nucleus,was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC.Functional assays revealed that overexpression of UBE2S promoted the proliferation,invasion,metastasis,and G1/S phase transition of HCC cells in vitro,and promoted the tumor growth significantly in vivo.Mechanistically,UBE2S interacted with TR1M28 in the nucleus,both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression.Most importantly,the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen(HTS)to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo,which may represent a promising strategy for HCC therapy. | Ren-Yu Zhang Ze-Kun Liu Ding Wei Yu-Le Yong Peng Lin Hao Li Man Liu Nai-Shan Zheng Ke Liu Cai-Xia Hu Xiao-Zhen Yang Zhi-Nan Chen Huijie Bian | 2021 | Signal Transduction and Targeted Therapy2021，6，3： | 3 |
| 8 | Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial显示文摘Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication.Meplazumab is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)patients.Here,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients.In phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was observed.The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics.No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort.The biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32.In the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent control.The meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control group.These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile. | Huijie Bian Zhao-Hui Zheng Ding Wei Aidong Wen Zheng Zhang Jian-Qi Lian Wen-Zhen Kang Chun-Qiu Hao Jing Wang Rong-Hua Xie Ke Dong Jie-Lai Xia Jin-Lin Miao Wen Kang Guoquan Li Di Zhang Mingru Zhang Xiu-Xuan Sun Likun Ding Kui Zhang Junfeng Jia Jin Ding Zhiqin Li Yanyan Jia Lin-Na Liu Zhe Zhang Zhao-Wei Gao Hong Du Na Yao Qing Wang Ke Wang Jie-Jie Geng Bin Wang Ting Guo Ruo Chen Yu-Meng Zhu Li-Juan Wang Qian He Rui-Rui Yao Ying Shi Xiang-Min Yang Jian-Sheng Zhou Yi-Nan Ma Ya-Tao Wang Xue Liang Fei Huo Zhe Wang Yang Zhang Xu Yang Ye Zhang Lu-Hua Gao Ling Wang Xiao-Chun Chen Hao Tang Shuang-Shuang Liu Qing-Yi Wang Zhi-Nan Chen Ping Zhu | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 2 |
| 9 | Tumor-targeted gene transfer in vivo via recombinant Newcastle diseasevirus modified by a bispecific fusion protein显示文摘 | Huijie Bian Philippe Fournier Ben Peeters Volker Schirrmacher | 2005 | International Journal of Oncology2005，，2： | 1 |
| 10 | Alteration of protein glycosylation in human hepatic stellate cells activated with transforming growth factor-β1显示文摘 | Yannan Qin Yaogang Zhong Liuyi Dang Minzhi Zhu Hanjie Yu Wentian Chen Jihong Cui Huijie Bian Zheng Li | 2012 | Journal of Proteomics2012，，13： | 1 |
| 11 | Meplazumab in hospitalized adults with severe COVID-19(DEFLECT):a multicenter,seamless phase 2/3,randomized,third-party double-blind clinical trial显示文摘Meplazumab,a humanized CD147 antibody,has shown favourable safety and efficacy in our previous clinical studies.In DEFLECT(NCT04586153),167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo.Meplazumab at 0.12 mg/kg,compared to the placebo group,showed clinical benefits in significantly reducing mortality by 83.6%(2.4%vs.14.6%,p=0.0150),increasing the proportion of patients alive and discharged without supplemental oxygen(82.9%vs.70.7%,p=0.0337)and increasing the proportion of patients who achieved sustained clinical improvement(41.5%vs.31.7%).The response rate in the 0.2 mg/kg group was relatively increased by 16.0%compared with the placebo group(53.7%vs.46.3%).Meplazumab also reduced the viral loads and multiple cytokine levels.Compare with the placebo group,the 0.3 mg/kg significantly increased the virus negative rate by 40.6%(p=0.0363)and reduced IL-8 level(p=0.0460);the 0.2 mg/kg increased the negative conversion rate by 36.9%,and reduced IL-4(p=0.0365)and IL-8 levels(p=0.0484).In this study,the adverse events occurred at a comparable rate across the four groups,with no unexpected safety findings observed.In conclusion,meplazumab promoted COVID-19 convalescence and reduced mortality,viral load,and cytokine levels in severe COVID-19 population with good safety profile. | Huijie Bian Liang Chen Zhao-Hui Zheng Xiu-Xuan Sun Jie-Jie Geng Ruo Chen Ke Wang Xu Yang Shi-Rui Chen Si-Yu Chen Rong-Hua Xie Kui Zhang Jin-Lin Miao Jun-Feng Jia Hao Tang Shuang-Shuang Liu Hong-Wei Shi Yong Yang Xiao-Chun Chen Vinay Malhotra Nosheen Nasir Iffat Khanum Faisal Mahmood Saeed Hamid Claudio Marcel Berdun Stadnik Kengi Itinose Caroline Cândida Carvalho de Oliveira Cesar Dusilek Lucas Rivabem Adilson Joaquim Westheimer Cavalcante Suzara Souto Lopes Wladmir Faustino Saporito Fábio JoséConcilio Fucci Jesus Abraham Simon-Campos Ling Wang Lin-Na Liu Qing-Yi Wang Ding Wei Zheng Zhang Zhi-Nan Chen Ping Zhu | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 1 |
| 12 | Immunological and metabolic characteristics of the Omicron variants infection显示文摘The Omicron variants of SARS-CoV-2,primarily authenticated in November 2021 in South Africa,has initiated the 5th wave of global pandemics.Here,we systemically examined immunological and metabolic characteristics of Omicron variants infection.We found Omicron resisted to neutralizing antibody targeting receptor binding domain(RBD)of wildtype SARS-CoV-2.Omicron could hardly be neutralized by sera of Corona Virus Disease 2019(COVID-19)convalescents infected with the Delta variant.Through mass spectrometry on MHC-bound peptidomes,we found that the spike protein of the Omicron variants could generate additional CD8+T cell epitopes,compared with Delta.These epitopes could induce robust CD8+T cell responses.Moreover,we found booster vaccination increased the cross-memory CD8+T cell responses against Omicron.Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells.Consistently,a greater fraction of memory CD8+T cells existed in Omicron stimulated peripheral blood mononuclear cells(PBMCs).In addition,CD147 was also a receptor for the Omicron variants,and CD147 antibody inhibited infection of Omicron.CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia.Taken together,our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron. | Jiejie Geng Xu Yang Kun Wang Ke Wang Ruo Chen Zhi-Nan Chen Chuan Qin Guizhen Wu Youchun Wang Ke Xu Peng Du Jiangning Liu Shirui Chen Tao Zhang Xiuxuan Sun Ting Guo Ying Shi Zheng Zhang Ding Wei Peng Lin Qingyi Wang Jing Yuan Jiuxin Qu Jin Zou Yingxia Liu Hongzhou Lu Ping Zhu Huijie Bian Liang Chen | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 0 |
| 13 | CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells显示文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19. | Ke Wang Wei Chen Zheng Zhang Yongqiang Deng Jian-Qi Lian Peng Du Ding Wei Yang Zhang Xiu-Xuan Sun Li Gong Xu Yang Lei He Lei Zhang Zhiwei Yang Jie-Jie Geng Ruo Chen Hai Zhang Bin Wang Yu-Meng Zhu Gang Nan Jian-Li Jiang Ling Li Jiao Wu Peng Lin Wan Huang Liangzhi Xie Zhao-Hui Zheng Kui Zhang Jin-Lin Miao Hong-Yong Cui Min Huang Jun Zhang Ling Fu Xiang-Min Yang Zhongpeng Zhao Shihui Sun Hongjing Gu Zhe Wang Chun-Fu Wang Yacheng Lu Ying-Ying Liu Qing-Yi Wang Huijie Bian Ping ZhuZhi-Nan Chen | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
| 14 | HMMR alleviates endoplasmic reticulum stress by promoting autophagolysosomal activity during endoplasmic reticulum stress-driven hepatocellular carcinoma progression显示文摘Background The mechanism of hepatitis B virus(HBV)-induced carcinogenesis remains an area of interest.The accumulation of hepatitis B surface antigen in the endoplasmic reticulum(ER)of hepatocytes stimulates persistent ER stress.Activity of the unfolded protein response(UPR)pathway of ER stress may play an important role in inflammatory cancer transformation.How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma(HCC)is still unclear.Here,we aimed to define the key molecule hyaluronan-mediated motility receptor(HMMR)in this process and explore its role under ER stress in HCC development.Methods An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression.Proteomics and transcriptomics analyses were performed to identify the potential key molecule,screen the E3 ligase,and define the activation pathway.Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines.Luciferase reporter assay,chromatin immunoprecipitation,coimmunoprecipitation,immunoprecipitation,and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress.Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues.Results We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC.HMMR was transcribed by c/EBP homologous protein(CHOP)and degraded by tripartite motif containing 29(TRIM29)after ubiquitination under ER stress,which caused the inconsistent expression of mRNA and protein.Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR.HMMR could alleviate ER stress by increasing autophagic lysosome activity.The negative correlation between HMMR and ER stress,positive correlation between HMMR and autophagy,and negative correlation between ER stress and autophagy were verified in human tissues.Conclusions This study identified the complicated role of HMMR in autophagy and ER stress,that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression,which could be a novel explanation for HBV-related carcinogenesis. | Lin He Hao Li Can Li Ze-Kun Liu Meng Lu Ren-Yu Zhang Dong Wu Ding Wei Jie Shao Man Liu Hao-Lin Wei Cong Zhang Zhe Wang Ling-Min Kong Zhi-Nan Chen Huijie Bian | 2023 | Cancer Communications2023，43，9： | 0 |
| 15 | CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis显示文摘COVID‐19 patients can develop clinical and histopathological features associated with fibrosis,but the pathogenesis of fibrosis remains poorly understood.CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants,which could initiate COVID-19-related cytokine storm.Here,we systemically analyzed lung pathogenesis in SARS-CoV-2-and its delta variant-infected humanized CD147 transgenic mice.Histopathology and Transmission Electron Microscopy revealed inflammation,fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs.Consistently,RNA-sequencing identified a set of fibrosis signature genes.Furthermore,we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2.We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts,decreasing susceptibility to bleomycin-induced pulmonary fibrosis.Meplazumab,a CD147 antibody,was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins,thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2.In conclusion,we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis. | Jiao Wu Liang Chen Chuan Qin Fei Huo Xue Liang Xu Yang Kui Zhang Peng Lin Jiangning Liu Zhuan Feng Jiansheng Zhou Zhuo Pei Yatao Wang Xiu-Xuan Sun Ke Wang Jiejie Geng Zhaohui Zheng Xianghui Fu Man Liu Qingyi Wang Zheng Zhang Huijie Bian Ping Zhu Zhi-Nan Chen | 2022 | Signal Transduction and Targeted Therapy2022，7，12： | 0 |
| 16 | The application of Melissa officinalis L.essential oil nanoemulsions protects sea bass(Lateolabrax japonicus)against myofibrillar protein and lipid oxidation during refrigeration显示文摘Objectives:The nutrient rich sea bass is prone to oxidation of lipid and protein during refrigeration.Materials and Methods:The research was to investigate the effect of different concentrations of Melissa officinalis L.essential oil(MOEO)nanoemulsions on myofibrillar protein(MP)and lipid oxidation in sea bass(Lateolabrax japonicus)during refrigeration at 4°C.Results:The results of thiobarbituric acid reactive substances and mitochondrial membrane potential showed that carboxymethyl chitosan/locust bean gum active coating solutions incorporating 2%MOEO nanoemulsions(C/L-2M)was the most effective in inhibiting lipid oxidation that occurred in sea bass under attack by reactive oxygen species.Low-field nuclear magnetic resonance results showed that C/L-2M maximally slowed the conversion of bound water to free water during storage.The oxidation of lipids and MP disrupted the secondary and tertiary conformations of MP and accelerated protein aggregation and degradation.Conclusions:C/L-2M slowed the oxidation of lipids and proteins by inhibiting the oxidation of reactive oxygen species.C/L-2M is a very promising preservative emulsion for the preservation of sea bass. | Yao Xie Huijie Yu Xin Zhao Chuhan Bian Hao Cheng Jun Mei Jing Xie | 2023 | Food Quality and Safety2023，7，3： | 0 |
| 17 | Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C显示文摘Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted. | Ping Zhu Shi-You Li Jin Ding Zhou Fei Sheng-Nan Sun Zhao-Hui Zheng Ding Wei Jun Jiang Jin-Lin Miao San-Zhong Li Xing Luo Kui Zhang Bin Wang Kun Zhang Su Pu Qian-Ting Wang Xin-Yue Zhang Gao-Liu Wen Jun OLiu John Thomas August Huijie Bian Zhi-Nan Chen You-Wen He | 2023 | Journal of Pharmaceutical Analysis2023，13，6： | 0 |
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