Browsing by Author "Zhou, Hao"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies
    (Elsevier, 2023) Dhama, Kuldeep; Nainu, Firzan; Frediansyah, Andri; Yatoo, Mohd Iqbal; Mohapatra, Ranjan K.; Chakraborty, Sandip; Zhou, Hao; Islam, Md Rabiul; Mamada, Sukamto S.; Kusuma, Hendrix Indra; Rabaan, Ali A.; Alhumaid, Saad; Al Mutair, Abbas; Iqhrammullah, Muhammad; Al-Tawfiq, Jaffar A.; Al Mohaini, Mohammed; Alsalman, Abdulkhaliq J.; Tuli, Hardeep Singh; Chakraborty, Chiranjib; Harapan, Harapan; Medicine, School of Medicine
    Newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves of coronavirus disease 2019 (COVID-19) pandemic. Depending on the extent of genomic variations, mutations and adaptation, few of the variants gain the ability to spread quickly across many countries, acquire higher virulency and ability to cause severe disease, morbidity and mortality. These variants have been implicated in lessening the efficacy of the current COVID-19 vaccines and immunotherapies resulting in break-through viral infections in vaccinated individuals and recovered patients. Altogether, these could hinder the protective herd immunity to be achieved through the ongoing progressive COVID-19 vaccination. Currently, the only variant of interest of SARS-CoV-2 is Omicron that was first identified in South Africa. In this review, we present the overview on the emerging SARS-CoV-2 variants with a special focus on the Omicron variant, its lineages and hybrid variants. We discuss the hypotheses of the origin, genetic change and underlying molecular mechanism behind higher transmissibility and immune escape of Omicron variant. Major concerns related to Omicron including the efficacy of the current available immunotherapeutics and vaccines, transmissibility, disease severity, and mortality are discussed. In the last part, challenges and strategies to counter Omicron variant, its lineages and hybrid variants amid the ongoing COVID-19 pandemic are presented.
  • Thumbnail Image
    Item
    β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers
    (Taylor & Francis, 2024-06-04) Tumbath, Soumya; Jiang, Lingxiang; Li, Xiaoguang; Zhang, Taolan; Zahid, Kashif Rafiq; Zhao, Ye; Zhou, Hao; Yin, Zhijun; Lu, Tao; Jiang, Shu; Chen, Yaomin; Chen, Xiang; Fu, Yang-Xin; Huang, Xiumei; Radiation Oncology, School of Medicine
    NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. β-Lapachone (β-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between β-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that β-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with β-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug's therapeutic efficacy. Further, the presence of β-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8+ T cell proliferation. β-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-β expression and reduced TGF-β cytokine expression, along with increased CD95 and CD54 surface markers. β-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into β-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by β-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the β-Lap-induced antitumor activity against NQO1-positive murine tumors.
  • Thumbnail Image
    Item
    β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation
    (Frontiers, 2021) Zhao, Wenxiu; Jiang, Lingxiang; Fang, Ting; Fang, Fei; Liu, Yingchun; Zhao, Ye; You, Yuting; Zhou, Hao; Su, Xiaolin; Wang, Jiangwei; Liu, Sheng; Chen, Yaomin; Wan, Jun; Huang, Xiumei; Radiation Oncology, School of Medicine
    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of β-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. β-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of β-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients.