Xinjun Lu

Sun Yat-sen Memorial Hospital

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Shihong Fu

National Institute for Viral Disease Control and Prevention

Guodong Liang

National Institute for Viral Disease Control and Prevention

Xin Chen

Nanjing Drum Tower Hospital

Diego F. Calvisi

University of Sassari

Matthias Evert

University of Regensburg

Zhicheng Xue

Sun Yat-sen University

Xuzhi Zhang

Sun Yat-sen University

Yi Ma

Electric Power Research Institute

Huanqin Wang

University of Science and Technology of China

Ronghai Deng

The First Affiliated Hospital, Sun Yat-sen University

Cooperative Institutions

Sun Yat-sen University

The First Affiliated Hospital, Sun Yat-sen University

Sun Yat-sen Memorial Hospital

Chinese Academy of Sciences

National Institute for Viral Disease Control and Prevention

Huazhong University of Science and Technology

University of California, San Francisco

Chinese Center For Disease Control and Prevention

Chinese Academy of Medical Sciences & Peking Union Medical College

Sichuan University

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Arboviruses and their related infections in China: A comprehensive field and laboratory investigation over the last 3 decades

Reviews in Medical Virology (2017)

Guodong Liang Xiaolong Li Xiaoyan Gao Shihong Fu Huanyu Wang

Summary Since the 1980s, a comprehensive field and laboratory investigation has been conducted throughout China, and a total of 29 virus species belonging to 7 families and 13 genera were identified through virological, morphological, and immunological methods, as well as whole‐genome sequencing and molecular genetic analyses. Most of the virus isolates belong to 9 genera in the families Flaviviridae , Bunyaviridae , Togaviridae , and Reoviridae . Among them, 4 genera ( Orthobunyavirus , Bunyavirus , Phlebovirus , and Nairovirus ) belong to the family Bunyaviridae and 3 genera ( Seadonavirus , Orbivirus , and Cypovirus ) belong to the family Reoviridae . Analyses of the relationships between viruses and human/animal diseases indicated that Japanese encephalitis virus, dengue virus, severe fever with thrombocytopenia syndrome virus, tick‐borne encephalitis virus, Crimean‐Congo hemorrhagic fever virus, West Nile virus, and Tahyna virus can cause human and animal infections and disease epidemics in China. This review systematically introduces the current status of the diversity and geographical distribution of arboviruses and vectors in China. In addition, our results provide strong technical support for the prevention and control of arboviral diseases, the treatment of epidemics, and the early warning and prediction of diseases, and so they are significant for the control and prevention of arboviral diseases in Asia and around the world.

Phlebovirus

Orthobunyavirus

Orbivirus

Reassortment

10.1002/rmv.1959

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Citations (35)

[A new member of Brevidensovirus, 0507JS11 virus isolated from Culex mosquitoes collected in Xinjiang].

PubMed (2009)

Xinjun Lu You-gang Zhai Xiaohong Sun Shihong Fu Huanqin Wang

To probe the primary characteristic of 0507JS11 virus isolated from Culex sp. and determine the classification of 0507JS11 virus in taxonomy.0507JS11 virus was cultured in Aedes albopictus C6/36 cells and cytopathic effects (CPEs) were recorded. Electro-microscopic morphology of 0507JS11 virus was observed. Total DNA extract of 0507JS11 virus was detected by 1% Agarose Gel Electrophoresis. Complete genomic sequence of 0507JS11 virus was sequenced and then made phylogenetic analysis.0507JS11 virus could cause CPEs in Aedes albopictus C6/36 cells. Viral particles have no envelope and appear icosahedron symmetry with diameter of 20 nm. The genome of 0507JS11 virus was positive single strand DNA (ssDNA) with full length of 3977 nt. However, a DNA band about 4 kbp was observed in the electrophoresis of total DNA extract of 0507JS11 virus. The coding region of the genome included three ORFs, ORF1 and ORF2 code NSP1 and NSP2, ORF3 codes VP. Phylogenetic analysis of the complete genomic sequence of 0507JS11 virus indicated an independent linear in Brevidensovirus.0507JS11 virus is a new member in Brevidensovirus.

Aedes albopictus

ORFS

Agarose gel electrophoresis

DNA virus

genomic DNA

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Citations (1)

First isolation of Banna virus in northwestern part of Yunnan province

Xiaohong Sun Shihong Fu Jinglin Wang Xinjun Lu Huanqin Wang

Objective To identify the Banna viruses isolated in northwestern part of Yunnan prov-ince in order to make the difference clear between the isolates and other Banna viruses isolated in other parts of Yunnan. Methods Three isolates of Banna vires isolated in 2005 and 2006 were identified by morpholo-gy, RNA-PAGE profile and molecular biologic method. Nueleotide and amino acid sequences of segment 12 of the 3 isolates were sequenced and analyzed. Results Three Banna viruses were isolated from mosquitoes collected in northwestern part of Yunnan during 2005 and 2006. Electron microscopy study showed that they are spherical with a diameter of 70 nm, no envelope but two layers of eapsid. It was found that the genome of the 3 isolates composes of 12 segments presenting band profile of 6-6 in RNA-PAGE. Nueleotide acid se-quence analysis about segment 12 showed that the identity was 99% between the 3 new isolates, 98% and 90% between the 3 isolates and the strains isolated in other parts of Yunnan, China and Indonesia, respec-tively. Phylogenetie analysis based on segment 12 gene showed that 3 new isolates clnstered in the same branch with the viruses isolated in other parts of Yunnan. The same difference of amino acids was found between Banna viruses isolated in China and Indonesia strains in the analysis of segment 12. Conclusion Banna virus strains were firstly isolated from mosquitoes collected in northwestern part of Yunnan province. Nueleotide acid sequence analysis of the 3 new isolates showed higher identity with strains isolated in other parts of Yunnan. Key words: Banna virus; Phylogenetie analysis

10.3760/cma.j.issn.0254-5101.2009.06.003

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Preclinical and clinical studies of immunotherapy for the treatment of cholangiocarcinoma

JHEP Reports (2023)

Xinjun Lu Benjamin L. Green Changqing Xie Chao Liu Xin Chen

Cholangiocarcinoma (CCA) is a rare primary liver cancer associated with high mortality and few systemic treatment options. The behaviour of the immune system has come into focus as a potential treatment modality for many cancer types, but immunotherapy has yet to dramatically alter the treatment paradigm for CCA as it has for other diseases. Herein, we review recent studies describing the relevance of the tumour immune microenvironment (TIME) in CCA. Various non-parenchymal cell types are critically important in controlling CCA progression, prognosis, and response to systemic therapy. Knowledge of the behaviour of these leukocytes could help generate hypotheses to guide the development of potential immune-directed therapies. Recently, an immunotherapy-containing combination was approved for the treatment of advanced-stage CCA. However, despite level 1 evidence demonstrating the improved efficacy of this therapy, survival remained suboptimal. In the current manuscript, we provide a comprehensive review of the TIME in CCA, preclinical studies of immunotherapies against CCA, as well as ongoing clinical trials applying immunotherapies for the treatment of CCA. Particular emphasis is placed on microsatellite unstable tumours, a rare CCA subtype that demonstrates heightened sensitivity to approved immune checkpoint inhibitors. We also discuss the challenges involved in applying immunotherapies to the treatment of CCA and the importance of understanding the TIME.

Cancer Immunotherapy

Microsatellite Instability

10.1016/j.jhepr.2023.100723

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MAD2L1 supports MYC-driven liver carcinogenesis in mice and predicts poor prognosis in human hepatocarcinoma

Toxicological Sciences (2024)

Xinjun Lu Ya Zhang Jiahao Xue Matthias Evert Diego F. Calvisi

Abstract Mitotic arrest deficient 2 like 1 (MAD2L1) is a component of the mitotic spindle assembly checkpoint implicated in cancer cell proliferation and tumorigenesis. The functional role of MAD2L1 in hepatocellular carcinoma (HCC) has not been adequately investigated, especially in vivo. In the current manuscript, we sought to address the function of MAD2L1 in hepatocarcinogenesis. We found that MAD2L1 expression is upregulated in human HCCs, where its expression is associated with higher aggressive tumor grade, elevated proliferative activity, and poor prognosis. In human HCC cell lines, MAD2L1 knockdown led to decreased cell growth. Moreover, RNA-seq results demonstrated that MAD2L1 silencing induces the expression of genes associated with cell cycle, DNA replication, and various cancer-related pathways, supporting the critical role of MAD2L1 during HCC growth and differentiation. In a c-MYC-induced mouse HCC model, we revealed an increased expression of Mad2l1. Furthermore, Mad2l1 CRIPSR-mediated silencing prevented c-MYC-driven mouse liver development. Altogether, our study suggests that MAD2L1 plays a crucial role in hepatocarcinogenesis, and that its suppression could be a promising therapeutic strategy for treating human HCC.

HCCS

Liver Cancer

CHEK1

10.1093/toxsci/kfae126

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Cabozantinib-based combination therapy for the treatment of hepatocellular carcinoma

Gut (2020)

Runze Shang Xinhua Song Pan Wang Yi Zhou Xinjun Lu

Objective Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with limited treatment options. Cabozantinib, an orally bioavailable multikinase inhibitor is now approved by Food and Drug Administration (FDA) for HCC patients. We evaluated the therapeutic efficacy of cabozantinib, either alone or in combination, in vitro and in vivo. Design Human HCC cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody. Results Cabozantinib treatment led to stable disease in c-Met/β-catenin and Akt/c-Met mouse HCC while possessing limited efficacy on Akt/Ras and c-Myc liver tumours. Importantly, cabozantinib effectively inhibited c-MET and ERK activity, leading to decreased PKM2 and increased p21 expression in HCC cells and in c-Met/β-catenin and Akt/c-Met HCC. However, cabozantinib was ineffective in inhibiting the Akt/mTOR cascade. Intriguingly, a strong inhibition of angiogenesis by cabozantinib occurred regardless of the oncogenic drivers. However, cabozantinib had limited impact on other tumour microenvironment parameters, including tumour infiltrating T cells, and did not induce programmed death-ligand 1 (PD-L1) expression. Combining cabozantinib with MLN0128 led to tumour regression in c-Met/β-catenin mice. In contrast, combined treatment with cabozantinib and the checkpoint inhibitor anti-PD-L1 antibody did not provide any additional therapeutic benefit in the four mouse HCC models tested. Conclusion c-MET/ERK/p21/PKM2 cascade and VEGFR2-induced angiogenesis are the primary targets of cabozantinib in HCC treatment. Combination therapies with cabozantinib and mTOR inhibitors may be effective against human HCC.

Cabozantinib

Axitinib

10.1136/gutjnl-2020-320716

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Citations (86)

Short-Term Prognosis of Recipients with Pretransplant Exposure to Immune Checkpoint Inhibitors after Liver Transplantation for Hepatocellular Carcinoma： a Comparative Retrospective Cohort Study

Li Mei Pang Lei-Bo Xu Zhijun Chen Liu Yang Tao Ding

10.2139/ssrn.4915294

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Combined Treatment with MEK and mTOR Inhibitors is Effective in In Vitro and In Vivo Models of Hepatocellular Carcinoma

Cancers (2019)

Xianqiong Liu Junjie Hu Xinhua Song Kirsten Utpatel Yi Zhang

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer histotype, characterized by high biological aggressiveness and scarce treatment options. Recently, we have established a clinically relevant murine HCC model by co-expressing activated forms of v-akt murine thymoma viral oncogene homolog (AKT) and oncogene c-mesenchymal-epithelial transition (c-Met) proto-oncogenes in the mouse liver via hydrodynamic tail vein injection (AKT/c-MET mice). Tumor cells from these mice demonstrated high activity of the AKT/ mammalian target of rapamycin (mTOR) and Ras/ Mitogen-activated protein kinase (MAPK) signaling cascades, two pathways frequently co-induced in human HCC. Methods: Here, we investigated the therapeutic efficacy of sorafenib, regorafenib, the MEK inhibitor PD901 as well as the pan-mTOR inhibitor MLN0128 in the AKT/c-Met preclinical HCC model. Results: In these mice, neither sorafenib nor regorafenib demonstrated any efficacy. In contrast, administration of PD901 inhibited cell cycle progression of HCC cells in vitro. Combined PD901 and MLN0128 administration resulted in a pronounced growth constraint of HCC cell lines. In vivo, treatment with PD901 or MLN0128 alone moderately slowed HCC growth in AKT/c-MET mice. Importantly, the simultaneous administration of the two drugs led to a stable disease with limited tumor progression in mice. Mechanistically, combined mitogen-activated extracellular signal-regulated kinase (MEK) and mTOR inhibition resulted in a stronger cell cycle inhibition and growth arrest both in vitro and in vivo. Conclusions: Our study indicates that combination of MEK and mTOR inhibitors might represent an effective therapeutic approach against human HCC.

Regorafenib

10.3390/cancers11070930

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Citations (11)

Two diversities meet in the rhizosphere: root specialized metabolites and microbiome

Journal of genetics and genomics/Journal of Genetics and Genomics (2023)

Xiaochen Wang Jingying Zhang Xinjun Lu Yang Bai Guodong Wang

Plants serve as rich repositories of diverse chemical compounds collectively referred to as specialized metabolites (SMs). These compounds are of importance for adaptive processes, including interactions with various microbes both beneficial and harmful. Considering microbes as bioreactors, the chemical diversity undergoes dynamic changes when root-derived specialized metabolites (RSMs) and microbes encounter each other in the rhizosphere. Recent advancements in sequencing techniques and molecular biology tools have not only accelerated the elucidation of biosynthetic pathways of RSMs but also unveiled the significance of RSMs in plant-microbe interactions. In this review, we provide a comprehensive description of the effects of RSMs on microbe assembly in the rhizosphere and the influence of corresponding microbial changes on plant health, incorporating the most up-to-date information available. Additionally, we highlight open questions that remain for a deeper understanding of and harnessing the potential of RSM-microbe interactions to enhance plant adaptation to the environment. Finally, we propose a pipeline for investigating the intricate associations between root exometabolites and the rhizomicrobiome.

10.1016/j.jgg.2023.10.004

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Citations (15)

Review of: "A Harmless Avian Vaccine Virus Could Be Developed into an Off-the-Shelf “Antibiotic” for Viruses"

Xinjun Lu

Off the shelf

10.32388/yuire6

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