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  1. Article: 2-Hydroxy-4-methoxybenzaldehyde, a more effective antifungal aroma than vanillin and its derivatives against

    Li, Qian / Wang, Chong / Xiao, Hongying / Zhang, Yiming / Xie, Yanli

    Frontiers in microbiology

    2024  Volume 15, Page(s) 1359947

    Abstract: ... Fusarium ... ...

    Abstract Fusarium graminearum
    Language English
    Publishing date 2024-02-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2024.1359947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effect of lower esophageal gastric tube implantation in postoperative enteral nutritional support in patients with laryngeal cancer: A study protocol for a randomized controlled trial.

    Xiao, Hongying / Liu, Jianmin / Liu, Sisi / Chen, Xiaofang

    Medicine

    2020  Volume 99, Issue 16, Page(s) e19771

    Abstract: Background: For a long time, postoperative nutritional support for laryngeal cancer patients has depended on the gastric tube for enteral nutrition. Silica gel gastric tube is often used in clinical practice; however, the gastric tube placed in the ... ...

    Abstract Background: For a long time, postoperative nutritional support for laryngeal cancer patients has depended on the gastric tube for enteral nutrition. Silica gel gastric tube is often used in clinical practice; however, the gastric tube placed in the conventional depth often leads to various complications in the stomach, thus damaging the nutritional status of patients and leading to the poor prognosis.
    Methods/design: A total of 80 patients with laryngeal cancer in otolaryngology, head and neck surgery department of Deyang people's hospital from May 2020 to April 2022 will be selected and randomly divided into control group and experimental group according to the numerical table. Patients in the control group will receive conventional gastric tube placement, with a depth of 45 to 55 cm, which can extract gastric juice. B-ultrasound accurately positioned the gastric tube in the stomach instead of the cardia, and postoperative nasal feeding nutrition will be provided. In the experimental group, the gastric tube will be pulled out 10 cm after conventional placement and no gastric juice will be extracted. B-ultrasonography verified that the gastric tube will be located below the esophagus or above the cardia, and routine nasal feeding will be performed postoperatively. Analysis for comfort and prognosis were performed by general comfort questionnaire and various index including height, body mass index, albumin value, electrolyte, wound healing, pharyngeal fistula.
    Discussion: In this study, visual simulation scale and general comfort questionnaire developed by Kolaba, an American comfort nursing specialist, were used to evaluate the comfort level of the 2 groups of patients, including pain, acid reflux, upper abdominal burning sensation, and hiccup. Objective indexes such as height, body mass index, albumin value, electrolyte, wound healing, and pharyngeal fistula were used to evaluate the prognosis of the 2 groups of patients. The visual simulation scale can preliminarily judge the subjective feelings of patients.
    Trial registration: It has been registered at http://www.chictr.org.cn/listbycreater.aspx (Identifier: ChiCTR2000030378), Registered February 29, 2020.
    MeSH term(s) Enteral Nutrition/instrumentation ; Humans ; Laryngeal Neoplasms/surgery ; Postoperative Period ; Randomized Controlled Trials as Topic
    Language English
    Publishing date 2020-04-19
    Publishing country United States
    Document type Clinical Trial Protocol ; Journal Article
    ZDB-ID 80184-7
    ISSN 1536-5964 ; 0025-7974
    ISSN (online) 1536-5964
    ISSN 0025-7974
    DOI 10.1097/MD.0000000000019771
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge.

    Mao, Zhongwei / Xiao, Hongying / Shen, Panpan / Yang, Yu / Xue, Jing / Yang, Yunyun / Shang, Yanguo / Zhang, Lilan / Li, Xin / Zhang, Yuying / Du, Yanan / Chen, Chun-Chi / Guo, Rey-Ting / Zhang, Yonghui

    Cell discovery

    2022  Volume 8, Issue 1, Page(s) 5

    Abstract: KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS's Asp12 residue. Our ITC results ... ...

    Abstract KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS's Asp12 residue. Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Among KRAS family proteins and mutants, both ITC and enzymatic assays demonstrate the selectivity of the inhibitors for KRAS(G12D); and the inhibitors disrupt the KRAS-CRAF interaction. We also observed the inhibition of cancer cell proliferation as well as MAPK signaling by a representative inhibitor (TH-Z835). However, since the inhibition was not fully dependent on KRAS mutation status, it is possible that our inhibitors may have off-target effects via targeting non-KRAS small GTPases. Experiments with mouse xenograft models of pancreatic cancer showed that TH-Z835 significantly reduced tumor volume and synergized with an anti-PD-1 antibody. Collectively, our study demonstrates proof-of-concept for a strategy based on salt-bridge and induced-fit pocket formation for KRAS(G12D) targeting, which warrants future medicinal chemistry efforts for optimal efficacy and minimized off-target effects.
    Language English
    Publishing date 2022-01-25
    Publishing country England
    Document type Journal Article
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-021-00368-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma.

    Wang, Pengyu / Zhang, Tao / Wang, Xinjing / Xiao, Hongying / Li, Huiti / Zhou, Lin-Lin / Yang, Teng / Wei, Bingyan / Zhu, Zeyun / Zhou, Lu / Yang, Song / Lu, Xiongxiong / Zhang, Yonghui / Huang, Yue / Gan, Jianhua / Yang, Cai-Guang

    Cell chemical biology

    2022  Volume 29, Issue 9, Page(s) 1396–1408.e8

    Abstract: The mitochondrial caseinolytic protease P (ClpP) is a target candidate for treating leukemia; however, the effects of ClpP modulation on solid tumors have not been adequately explored. Here, we report a potent activator of ClpP with the therapeutic ... ...

    Abstract The mitochondrial caseinolytic protease P (ClpP) is a target candidate for treating leukemia; however, the effects of ClpP modulation on solid tumors have not been adequately explored. Here, we report a potent activator of ClpP with the therapeutic potential for pancreatic ductal adenocarcinoma (PDAC). We first validated that aberrant ClpP activation leads to growth arrest of PDAC cells and tumors. We then performed high-throughput screening and synthetic optimization, from which we identified ZG111, a potent activator of ClpP. ZG111 binds to ClpP and promotes the ClpP-mediated degradation of respiratory chain complexes. This degradation activates the JNK/c-Jun pathway, induces the endoplasmic reticulum stress response, and consequently causes the growth arrest of PDAC cells. ZG111 also produces inhibitory effects on tumor growth in cell line-derived and patient-derived xenograft mouse models. Altogether, our data demonstrate a promising therapeutic strategy for PDAC suppression through the chemical activation of ClpP.
    MeSH term(s) Animals ; Carcinoma, Pancreatic Ductal/metabolism ; Endopeptidase Clp/metabolism ; Homeostasis ; Humans ; Mice ; Pancreatic Neoplasms/metabolism ; Peptide Hydrolases/metabolism ; Proteome/metabolism ; Pancreatic Neoplasms
    Chemical Substances Proteome ; Peptide Hydrolases (EC 3.4.-) ; ClpP protein, human (EC 3.4.21.92) ; Endopeptidase Clp (EC 3.4.21.92)
    Language English
    Publishing date 2022-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2451-9448
    ISSN (online) 2451-9448
    DOI 10.1016/j.chembiol.2022.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Combining Vγ9Vδ2 T Cells with a Lipophilic Bisphosphonate Efficiently Kills Activated Hepatic Stellate Cells.

    Zhou, Xiaoying / Gu, Yanzheng / Xiao, Hongying / Kang, Ning / Xie, Yonghua / Zhang, Guangbo / Shi, Yan / Hu, Xiaoyu / Oldfield, Eric / Zhang, Xueguang / Zhang, Yonghui

    Frontiers in immunology

    2017  Volume 8, Page(s) 1381

    Abstract: Activated hepatic stellate cells (aHSCs) are now established as a central driver of fibrosis in human liver injury. In the presence of chronic or repeated injury, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) can occur, so there is interest in ... ...

    Abstract Activated hepatic stellate cells (aHSCs) are now established as a central driver of fibrosis in human liver injury. In the presence of chronic or repeated injury, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) can occur, so there is interest in down-regulating aHSCs activity in order to treat these diseases. Here, we report that Vγ9Vδ2 T cells are reduced in patients with liver cirrhosis, stimulating us to investigate possible interactions between Vγ9Vδ2 T cells and aHSCs. We find that Vγ9Vδ2 T cells kill aHSCs and killing is enhanced when aHSCs are pretreated with BPH-1236, a lipophilic analog of the bone resorption drug zoledronate. Cytotoxicity is mediated by direct cell-to-cell contact as shown by Transwell experiments and atomic force microscopy, with BPH-1236 increasing the adhesion between aHSCs and Vγ9Vδ2 T cells. Mechanistically, BPH-1236 functions by inhibiting farnesyl diphosphate synthase, leading to accumulation of the phosphoantigen isopentenyl diphosphate and recognition by Vγ9Vδ2 T cells. The cytolytic process is largely dependent on the perforin/granzyme B pathway. In a Rag2
    Language English
    Publishing date 2017-10-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.01381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A Structural Change in Butyrophilin upon Phosphoantigen Binding Underlies Phosphoantigen-Mediated Vγ9Vδ2 T Cell Activation.

    Yang, Yunyun / Li, Liping / Yuan, Linjie / Zhou, Xiaoying / Duan, Jianxin / Xiao, Hongying / Cai, Ningning / Han, Shuai / Ma, Xianqiang / Liu, Weidong / Chen, Chun-Chi / Wang, Lingle / Li, Xin / Chen, Jiahuan / Kang, Ning / Chen, Jing / Shen, Zhixun / Malwal, Satish R / Liu, Wanli /
    Shi, Yan / Oldfield, Eric / Guo, Rey-Ting / Zhang, Yonghui

    Immunity

    2019  Volume 50, Issue 4, Page(s) 1043–1053.e5

    Abstract: Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T ... ...

    Abstract Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for γδ T cell activation. Analyses with chemical probes and molecular dynamic simulations demonstrated that dimerized intracellular proteins cooperate in sensing HMBPP to enhance the efficiency of γδ T cell activation. HMBPP binding to butyrophilin doubled the binding force between a γδ T cell and a target cell during "outside" signaling, as measured by single-cell force microscopy. Our findings provide insight into the "inside-out" triggering of Vγ9Vδ2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design.
    MeSH term(s) Antigens, CD/chemistry ; Antigens, CD/metabolism ; Binding Sites ; Butyrophilins/chemistry ; Butyrophilins/metabolism ; Crystallography, X-Ray ; Dimerization ; Drug Design ; Humans ; Hydrogen Bonding ; Immunotherapy ; Lymphocyte Activation ; Models, Molecular ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Organophosphates/metabolism ; Protein Conformation ; Protein Domains ; Protein Isoforms/chemistry ; Protein Processing, Post-Translational ; Receptors, Antigen, T-Cell, gamma-delta ; Single-Cell Analysis ; Structure-Activity Relationship ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
    Chemical Substances 4-hydroxy-3-methyl-2-butenyl diphosphate ; Antigens, CD ; BTN3A1 protein, human ; Butyrophilins ; Organophosphates ; Protein Isoforms ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2019-03-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2019.02.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery.

    Xia, Yun / Xie, Yonghua / Yu, Zhengsen / Xiao, Hongying / Jiang, Guimei / Zhou, Xiaoying / Yang, Yunyun / Li, Xin / Zhao, Meng / Li, Liping / Zheng, Mingke / Han, Shuai / Zong, Zhaoyun / Meng, Xianbin / Deng, Haiteng / Ye, Huahu / Fa, Yunzhi / Wu, Haitao / Oldfield, Eric /
    Hu, Xiaoyu / Liu, Wanli / Shi, Yan / Zhang, Yonghui

    Cell

    2018  Volume 175, Issue 4, Page(s) 1059–1073.e21

    Abstract: Motivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. We found that lipophilic statin drugs and ... ...

    Abstract Motivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. We found that lipophilic statin drugs and rationally designed bisphosphonates that target three distinct enzymes in the mevalonate pathway have potent adjuvant activities in mice and cynomolgus monkeys. These inhibitors function independently of conventional "danger sensing." Instead, they inhibit the geranylgeranylation of small GTPases, including Rab5 in antigen-presenting cells, resulting in arrested endosomal maturation, prolonged antigen retention, enhanced antigen presentation, and T cell activation. Additionally, inhibiting the mevalonate pathway enhances antigen-specific anti-tumor immunity, inducing both Th1 and cytolytic T cell responses. As demonstrated in multiple mouse cancer models, the mevalonate pathway inhibitors are robust for cancer vaccinations and synergize with anti-PD-1 antibodies. Our research thus defines the mevalonate pathway as a druggable target for vaccine adjuvants and cancer immunotherapies.
    MeSH term(s) Adjuvants, Immunologic/pharmacology ; Animals ; Antigen Presentation ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Diphosphonates/pharmacology ; Endosomes/drug effects ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Macaca fascicularis ; Male ; Mevalonic Acid/metabolism ; Mice ; Mice, Inbred C57BL ; Protein Prenylation ; rab5 GTP-Binding Proteins/antagonists & inhibitors ; rab5 GTP-Binding Proteins/metabolism
    Chemical Substances Adjuvants, Immunologic ; Cancer Vaccines ; Diphosphonates ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; rab5 GTP-Binding Proteins (EC 3.6.5.2) ; Mevalonic Acid (S5UOB36OCZ)
    Language English
    Publishing date 2018-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.08.070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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