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      The double‐edged role of neutrophil heterogeneity in inflammatory diseases and cancers

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          Abstract

          Neutrophils are important immune cells act as the body's first line of defense against infection and respond to diverse inflammatory cues. Many studies have demonstrated that neutrophils display plasticity in inflammatory diseases and cancers. Clarifying the role of neutrophil heterogeneity in inflammatory diseases and cancers will contribute to the development of novel treatment strategies. In this review, we have presented a review on the development of the understanding on neutrophil heterogeneity from the traditional perspective and a high‐resolution viewpoint. A growing body of evidence has confirmed the double‐edged role of neutrophils in inflammatory diseases and tumors. This may be due to a lack of precise understanding of the role of specific neutrophil subsets in the disease. Thus, elucidating specific neutrophil subsets involved in diseases would benefit the development of precision medicine. Thusly, we have summarized the relevance and actions of neutrophil heterogeneity in inflammatory diseases and cancers comprehensively. Meanwhile, we also discussed the potential intervention strategy for neutrophils. This review is intended to deepen our understanding of neutrophil heterogeneity in inflammatory diseases and cancers, while hold promise for precise treatment of neutrophil‐related diseases.

          Abstract

          Schematic representation of the neutrophil heterogeneity in inflammatory diseases and cancer (in blue). This figure is created with BioRender.com.

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          Most cited references366

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          Gastric cancer

          Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).
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            Colorectal cancer

            Several decades ago, colorectal cancer was infrequently diagnosed. Nowadays, it is the world's fourth most deadly cancer with almost 900 000 deaths annually. Besides an ageing population and dietary habits of high-income countries, unfavourable risk factors such as obesity, lack of physical exercise, and smoking increase the risk of colorectal cancer. Advancements in pathophysiological understanding have increased the array of treatment options for local and advanced disease leading to individual treatment plans. Treatments include endoscopic and surgical local excision, downstaging preoperative radiotherapy and systemic therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative chemotherapy, targeted therapy, and immunotherapy. Although these new treatment options have doubled overall survival for advanced disease to 3 years, survival is still best for those with non-metastasised disease. As the disease only becomes symptomatic at an advanced stage, worldwide organised screening programmes are being implemented, which aim to increase early detection and reduce morbidity and mortality from colorectal cancer.
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              RNA velocity of single cells

              RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena, such as embryogenesis or tissue regeneration. Here we show that RNA velocity—the time derivative of the gene expression state—can be directly estimated by distinguishing unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.
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                Author and article information

                Contributors
                qujiao19920819@163.com
                yangsun@nju.edu.cn
                Journal
                MedComm (2020)
                MedComm (2020)
                10.1002/(ISSN)2688-2663
                MCO2
                MedComm
                John Wiley and Sons Inc. (Hoboken )
                2688-2663
                23 July 2023
                August 2023
                : 4
                : 4 ( doiID: 10.1002/mco2.v4.4 )
                : e325
                Affiliations
                [ 1 ] Department of Pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Hangzhou China
                [ 2 ] State Key Laboratory of Pharmaceutical Biotechnology Department of Biotechnology and Pharmaceutical Sciences School of Life Science Nanjing University Nanjing China
                Author notes
                [*] [* ] Correspondence

                Yang Sun, State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China.

                Email: yangsun@ 123456nju.edu.cn

                Jiao Qu, State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China

                Email: qujiao19920819@ 123456163.com

                [#]

                These authors contributed equally to this work.

                Article
                MCO2325
                10.1002/mco2.325
                10363828
                37492784
                a988d877-f93a-4014-8a72-afec332c1a20
                © 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 May 2023
                : 01 February 2023
                : 09 June 2023
                Page count
                Figures: 7, Tables: 2, Pages: 30, Words: 18056
                Funding
                Funded by: National Key Research and Development Plan
                Award ID: 2022YFC3500202
                Funded by: the program A for Outstanding PhD candidate of Nanjing University
                Award ID: 202202A004
                Funded by: Fundamental Research Funds for the Central Universities , doi 10.13039/501100012226;
                Award ID: 020814380179
                Award ID: 020814380174
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                August 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.2 mode:remove_FC converted:24.07.2023

                cancers,inflammatory diseases,neutrophil extracellular traps,neutrophil heterogeneity,single‐cell sequencing

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