7 results on '"Jiang, Jingwei"'
Search Results
2. M351‐0056 is a novel low MW compound modulating the actions of the immune‐checkpoint protein VISTA.
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Hu, Xinlei, Qie, Chenxin, Jiang, Jingwei, Xie, Xiaoxue, Chen, Wenting, Liu, Wanmei, and Liu, Jun
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T cells ,THERAPEUTICS ,AUTOIMMUNE diseases ,PROTEIN expression ,PROTEINS ,MONOCYTES ,IMMUNE checkpoint proteins - Abstract
Background and Purpose: The protein V‐domain immunoglobulin suppressor of T‐cell activation (VISTA) is a novel immune‐checkpoint molecule that belongs to the B7 family and regulates a broad spectrum of immune responses. So far, low MW compounds targeting VISTA for the treatment of autoimmune diseases or inflammation, have not been identified. Experimental Approach We developed a homology modelling for VISTA 3D structure and subsequent virtual screening for low MW ligands binding to VISTA. Visualization of the binding postures of docked ligands with protein VISTA indicated that compound M351‐0056 targeted VISTA. The biological activities of compound M351‐0056 targeting VISTA were investigated in vitro using monocytes and T cells and in vivo, using mice with imiquimod‐induced dermatitis. Key Results: The KD value of M351‐0056 for human VISTA‐extracellular domain was 12.60 ± 3.84 μM as assessed by microscale thermophoresis. M351‐0056 decreased cytokine secretion from PBMCs or human CD4+ T cells, suppressed proliferation of PBMCs and enhanced expression of Foxp3+ T cells. These effects of M351‐0056 modulating VISTA involved the JAK2–STAT2 pathway. Daily administration of M351‐0056 ameliorated imiquimod‐induced psoriasis‐like dermatitis. Expression of mRNA and protein of inflammatory cytokines in psoriatic lesions was decreased after M351‐0056 treatment. Conclusion and Implications: The compound M351‐0056 showed high affinity for VISTA and may modulate its immune function in vitro and in vivo. Our finding provides a lead compound for therapeutically enhancing VISTA‐mediated pathways to benefit the treatment of autoimmune diseases or inflammation. [ABSTRACT FROM AUTHOR]
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- 2021
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3. A meta-analysis of platinum plus gemcitabine or vinorelbine in the treatment of advanced non-small-cell lung cancer
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Gao, Guanghui, Jiang, Jingwei, Liang, Xiaohua, Zhou, Xinli, Huang, Ruofan, Chu, Zhaohui, and Zhan, Qiong
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NUCLEOSIDES , *VINORELBINE , *META-analysis , *PLATINUM , *METALS in medicine , *LUNG cancer treatment , *MEDICAL literature , *THERAPEUTICS - Abstract
Abstract: Objective: Whether platinum plus gemcitabine or vinorelbine are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) is still controversial, a meta-analysis was performed to compare the gemcitabine plus platinum with vinorelbine plus platinum regimens in first-line treatment of advanced NSCLC. Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database, EMBASE and the American Society of Clinical Oncology (ASCO) annual meeting abstracts. The following keywords were used: “non small cell lung cancer,” or “Carcinoma, Non-Small-Cell Lung”. Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Endpoints were overall survival, overall response, and toxicity. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided. Results: Nine randomized controlled trials involving 2186 patients were identified from 453 reports. They were all published as full-text articles. The intention-to-treatment (ITT) analysis demonstrated that the patients with gemcitabine plus platinum regimens had an equal overall response rate in comparison with vinorelbine plus platinum regimens (RR, 0.91; 95%CI, 0.81–1.03; P =0.15). Furthermore, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.06; 95%CI, 0.96–1.18; P =0.27). Subgroup analysis comparing the cisplatin plus gemcitabine or vinorelbine had achieved the same results. Vinorelbine plus platinum regimens led to more frequent grade 3 or 4 of neutropenia, nephrotoxicity, constipation and phlebitis (OR, 0.37; 95%CI, 0.26–0.52; P <0.00001; OR, 0.38; 95%CI, 0.25–0.57; P <0.00001; OR, 0.50; 95%CI, 0.27–0.92; P =0.03 and OR, 0.13; 95%CI, 0.05–0.32; P <0.00001, respectively), while gemcitabine plus platinum chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia (OR, 11.37; 95%CI, 4.56–28.38; P <0.00001). The incidence of grade 3 or 4 anemia, nausea and vomiting were almost comparable between the two arms (OR, 1.12; 95%CI, 0.62–2.02; P =0.71 and OR, 0.72; 95%CI, 0.41–1.28; P =0.27, respectively). Similar results were also achieved in subgroup analyses between the gemcitabine and vinorelbine in combination with the cisplatin. Conclusion: It could be concluded that the efficacy were similar between the platinum plus gemcitabine or vinorelbine regimens. The choice of platinum plus gemcitabine or vinorelbine depends on the toxicity of the drugs and patients’ tolerance. [Copyright &y& Elsevier]
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- 2009
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4. A meta-analysis of randomized controlled trials comparing carboplatin-based to cisplatin-based chemotherapy in advanced non-small cell lung cancer
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Jiang, Jingwei, Liang, Xiaohua, Zhou, Xinli, Huang, Ruofan, and Chu, Zhaohui
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DRUG therapy , *LUNG cancer , *META-analysis , *THERAPEUTICS - Abstract
Summary: Objective: Since the debate still exists whether cisplatin-based and carboplatin-based chemotherapy are equally effective for advanced non-small-cell lung cancer (NSCLC), a meta-analysis of trials was performed to compare the cisplatin-based with carboplatin-based regimens in first line chemotherapy of advanced NSCLC. Methods: A literature search was performed in PubMed database, the Cochrane Central Register of Controlled Trials (CENTRAL) database, the Physician Data Query (PDQ) database and the American Society of Clinical Oncology (ASCO) annual meeting abstracts in January 2007. The following keywords were used: “non small cell lung cancer,” or “Carcinoma, Non-Small-Cell Lung”. Reference lists of original articles and review articles were also examined. The published languages and years were not limited. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Results: Eighteen randomized controlled trials (6906 patients) were identified from 4240 reports. The intention to treatment (ITT) analysis demonstrated that the cisplatin-based regimens had a higher overall response rate in comparison with carboplatin-based regimens (RR, 0.91; 95%CI, 0.84–0.99; P =0.02). However, the 1-year survival rate for the two platinum-based regimens were comparable (RR, 1.00, 95%CI, 0.94–1.07; P =0.93), Both subgroup analysis comparing the doublet or triplet regimens of cisplatin or carboplatin in combination with new agents and the same agents had achieved the same results. Cisplatin-based chemotherapy led to more frequent grade 3 or 4 of nausea and vomiting, and nephrotoxicity (OR, 0.39; 95%CI, 0.30–0.52; P <0.00001 and OR, 0.31; 95%CI, 0.17–0.56; P =0.0001), while carboplatin-based chemotherapy inclined to developing more grade 3 or 4 thrombocytopenia, however, there were no statistical significance (OR, 1.63; 95%CI, 0.94–2.82; P =0.08). The risk of grade 3 or 4 anemia, neutropenia and neurotoxicity was almost comparable between the two arms (OR, 0.78; 95%CI, 0.59–1.02; P =0.07; OR, 1.08; 95%CI, 0.80–1.45; P =0.61 and OR, 1.59; 95%CI, 0.81–3.14; P =0.18, respectively). The subgroup analyses of the comparison between the doublet or triplet regimens of cisplatin and carboplatin in combination with the same agents, respectively, also achieved similar results, with the exception of thrombocytopenia between the two groups (OR, 1.94; 95%CI, 1.47–2.68; P <0.00001), which showed statistically significant. Cisplatin arm inclined to causing more treatment-related deaths compared as carboplatin arm, but there was no statistical significance (OR, 0.70; 95%CI, 0.48–1.02; P =0.06). Conclusion: Given cisplatin-based regimens had a higher overall response rate as compared with carboplatin-based regimens, there was not a survival advantage in the cisplatin group. Therefore, the toxicity profile might play an important role in decision to choose cisplatin-based or carboplatin-based regimens. [Copyright &y& Elsevier]
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- 2007
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5. Inhibition of endocytosis activates alternative degradation pathway of βAPP in cultured cells.
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Fukumori, Akio, Jiang, Jingwei, Tanii, Hisashi, Morihara, Takashi, Kamino, Kojin, Tanaka, Toshihisa, Kudo, Takashi, Ito, Naohiro, Tagami, Shinji, Okochi, Masayasu, and Takeda, Masatoshi
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ALZHEIMER'S disease , *AMYLOID , *ENDOCYTOSIS , *PRESENILINS , *ALCOHOLIC psychoses , *THERAPEUTICS - Abstract
Background: Alzheimer’s disease associated βAPP is sequentially endoproteolyzed by α/β-secretase and γ-cleavage. In the process, extracellular shedding by α-secretase (ADAM 9/10/17) or β-secretase (BACE 1/2) at position L17 or D1 (Aβ numbering) are prerequisites for the generation of P3 or Aβ, respectively. In addition, several alternative extracellular cleavage sites in βAPP have been reported at position I−6, V−3, R5, E11, F20, and A21. Among these sites, position R5 is considered to be cleaved by α-secretase-like activity, whereas position E11, F20 and A21 are cleaved by β-secretase. Therefore, extracellular shedding of βAPP is thought to be mediated exclusively by α/β-secretase activities. However, so far the characteristics of cleavages at position V−3 and I−6 are not well understood. The aim of this study is to characterize these two cleavages of βAPP. Methods: We analyzed the conditioned media of βAPP wt or sw expressing cells with or without pharmacological agents. Results: Here, we show that the cleavage at position I−6 of βAPP has characteristics distinct from that of α/β-secretase, while the cleavage at V−3 seems to be mediated by β-secretase. Although inhibition of endocytosis enhances the cleavages at both V−3 and I−6, PMA, an α-secretase stimulator, treatment enhances neither of these cleavages. Interestingly, a β-secretase inhibitor, z-VLL-CHO, suppressed V−3 but not I−6 cleavage. The pathological βAPP Swedish mutant adjacent to the cleavage sites shows similar effects. Conclusions: Our data demonstrate that neither α nor β-secretase undergoes extracellular shedding at I−6 of βAPP. Therefore, our data may indicate a novel alternative βAPP degradation pathway which is up-regulated upon low level of endocytosis. [ABSTRACT FROM AUTHOR]
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- 2006
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6. Two novel camptothecin derivatives inhibit colorectal cancer proliferation via induction of cell cycle arrest and apoptosis in vitro and in vivo.
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Du, Hongzhi, Huang, Yue, Hou, Xiaoying, Quan, Xingping, Jiang, Jingwei, Wei, Xiaohui, Liu, Yang, Li, Hongyang, Wang, Puhai, Zhan, Meixiao, Ai, Xun, Lu, Ligong, Yuan, Shengtao, and Sun, Li
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CAMPTOTHECIN , *COLON cancer treatment , *CELL cycle , *IRINOTECAN , *FLOW cytometry , *APOPTOSIS , *THERAPEUTICS - Abstract
Abstract At present, chemotherapy is still to be the preferred and most significant therapeutic strategy for cancer patients in clinical practice. Although Camptothecin (CPT) has been discovered for over half century, a series of CPT derivatives such as Topotecan (TPT) and irinotecan (CPT-11) have been approved and are still to be the first-line medicines for clinical application. Up to now, the topoisomerase 1 inhibitor continues to be a significant drug development research field. Based on previous study of the structure-activity relationship, we consider that the introduction of lipophilic group at C7 position can prolong the retention time and the hydroxyl esterification at C20 can eliminate the hydrogen bond interaction, stabilize the E-lactone form and promote the anti-cancer effect. In this study, we carried out an optimization at C7 and C20 positions to afford two CPT derivatives 3g and 3j. Firstly, we predicted the possibly binding sites of two compounds with topoisomerase 1 by molecular docking. Then we evaluated the anti-proliferation effect of the two novel derivatives and compared the IC50 with CPT-11. Furthermore, the induction of cell cycle arrest and apoptosis was explored through karyomorphology, flow cytometry (FCM) and Western blot analysis. At last, we evaluated the anti-cancer effect and detected the mechanism in colorectal cancer xenograft model. In brief, all the data showed that the novel CPT derivatives (3g and 3j) could inhibit colorectal cancer proliferation via induction of cell cycle arrest and apoptosis in vitro and in vivo. It suggested that the two agents may be a new potential therapeutic strategy in the future. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]
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- 2018
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7. In-depth profiling of miRNA regulation in the body wall of sea cucumber Apostichopus japonicus during skin ulceration syndrome progression.
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Sun, Hongjuan, Zhou, Zunchun, Dong, Ying, Yang, Aifu, Pan, Yongjia, Jiang, Jingwei, Chen, Zhong, Guan, Xiaoyan, Wang, Bai, Gao, Shan, and Jiang, Bei
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MICRORNA , *SKIN cancer prevention , *APOSTICHOPUS japonicus , *SEA cucumbers , *CELLULAR signal transduction , *PHYSIOLOGY , *THERAPEUTICS - Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that mediate mRNA degradation or translation repression. Previous study showed that the expression of miRNAs was significantly changed in the body wall of sea cucumber Apostichopus japonicus after skin ulceration syndrome (SUS) infection, which is a dynamic process. However, the critical miRNAs from body wall that involved in different infection stages of SUS remain unknown. In this study, four cDNA libraries were constructed with the body wall from healthy and three SUS-infected stages of A. japonicus . A total of 248 conserved miRNAs and five novel miRNAs were identified through Illumina HiSeq 2000 platform. Compared to the control, 238 miRNAs showed significant differential expression at three stages of SUS progression. Totally, 3149 miRNA-mRNA pairs were identified by target prediction and 314 miRNA-mRNA pairs showed negative correlation. It is noteworthy that 15 miRNAs and four mRNAs were located at the crucial positions of the network built with the anti-correlated miRNA-mRNA pairs. GO and KEGG enrichment analysis indicated that the predicted targets were involved in many immune-related processes. Deep analysis of miR-31c-5p, miR-29b-3p, NF-kB, mucin 2 and titin showed that they may play important roles in the pathogens attachment and recognition, signaling transduction and lesions repair of A. japonicus after SUS infection. These results would be useful for further investigating the potential roles of critical miRNAs and mRNAs in A. japonicus immune regulation. [ABSTRACT FROM AUTHOR]
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- 2018
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