Review
Immunology
Jingjing Ji, Jie Fan
Summary: This article provides an overview of the current understanding of the mechanism and roles of PMN reverse migration (rM) in inflammation and sepsis. Evidence suggests that PMN rM can be both a protective response and a tissue-damaging event, highlighting its importance in the development of novel prophylactic and therapeutic strategies for sepsis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sladjana Skopelja-Gardner, Joyce Tai, Xizhang Sun, Lena Tanaka, James A. Kuchenbecker, Jessica M. Snyder, Paul Kubes, Tomas Mustelin, Keith B. Elkon
Summary: Exposure to UV light triggers a neutrophil-dependent injury response in the kidney, leading to subclinical renal inflammation and injury. Neutrophils not only migrate to the skin but also to the kidney post UV light exposure, contributing to the renal induction of inflammation and injury genes. Patients with lupus have blood neutrophils similar to those observed in mice post-UV exposure, suggesting a potential role of these cells in mediating inflammation and injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Xiaoping Li, Wenwen Wang, Yu Shao, Ji Zhou, Jiaqi Huang, Fei Xu, Xiu Gao, Mengyun Wu, Yongli Dong, Wenyan Wu, Jiamin Cai, Junyao Wang, Yunfei Ye, Zhengrong Chen, Chuangli Hao, Yi Yang, Jinping Zhang
Summary: The study demonstrates that lncRNA lncTRPM2-AS is involved in promoting macrophage inflammation in asthma by regulating apoptotic pathways and cytokine production. Interaction between TRPM2, lncTRPM2-AS, and TRIM21 affects ubiquitination levels, calcium ion levels, and subsequently autophagy in macrophages. Downregulation of lncTRPM2-AS inhibits ubiquitination of TRPM2 and enhances autophagy-induced apoptosis, contributing to the inhibition of macrophage inflammation.
CELL DEATH & DISEASE
(2021)
Article
Immunology
Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina Madruga Carvalho, Essia de Almeida Lima, Sandra Rodrigues-Mascarenhas
Summary: The study showed that ouabain may interfere with neutrophil migration by inhibiting p38 MAPK, thus reducing neutrophil chemotaxis induced by the chemotactic peptide fMLP.
INFLAMMOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hanze Chen, Xinxin Xu, Qiwen Tang, Linhui Ni, Shuxia Cao, Yonggang Hao, Li Wang, Xingyue Hu
Summary: (+)-Borneol reduces ROS levels in activated neutrophils and inhibits NETosis induced by PMA stimulation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Szilvia Baron, Tami Rashal, Dmitry Vaisman, Ronit Elhasid, Rachel Shukrun
Summary: In this study, we demonstrate that selinexor can effectively inhibit the formation of neutrophil extracellular traps (NETs), which are involved in various disease conditions. This finding suggests the potential use of selinexor in reducing disease burden by targeting NETs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Engineering, Biomedical
Jin Gao, Yujie Su, Zhenjia Wang
Summary: Lung bacterial infections can lead to acute lung inflammation/injury and progress to acute respiratory distress syndrome (ARDS), resulting in death. This study proposes a new strategy to specifically target bacteria and inflammatory pathways using neutrophil nanovesicles co-loaded with antibiotics and anti-inflammatory agents. The results show that cholesterol infilling in the nanovesicle membrane enables remote loading of both drugs, achieving high delivery efficiency and effectively preventing lung damage caused by infections. This research reveals the potential of neutrophil nanovesicles for the translational treatment of ARDS.
Article
Cell Biology
Ruth A. Houseright, Veronika Miskolci, Oscar Mulvaney, Valeriu Bortnov, Deane F. Mosher, Julie Rindy, David A. Bennin, Anna Huttenlocher
Summary: MYDGF, induced by tissue damage, regulates neutrophil motility to damaged tissues through the HIF-1α pathway. Depletion of MYDGF impairs wound healing and inflammation resolution, while persistent neutrophil inflammation in MYDGF mutants is dependent on HIF-1α pathway.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Critical Care Medicine
Gabriel Jakobsson, Praveen Papareddy, Henrik Andersson, Megan Mulholland, Ravi Bhongir, Irena Ljungcrantz, Daniel Engelbertsen, Harry Bjorkbacka, Jan Nilsson, Adrian Manea, Heiko Herwald, Marisol Ruiz-Meana, Antonio Rodriguez-Sinovas, Michelle Chew, Alexandru Schiopu
Summary: This study revealed the association between elevated plasma S100A8/A9 levels and left ventricle dysfunction in severe sepsis patients, and demonstrated the potential therapeutic effects of pharmacological blockade of S100A8/A9 in mitigating myocardial dysfunction.
Article
Oncology
Yanze Yin, Huijuan Dai, Xicheng Sun, Zhifeng Xi, Jiang Zhang, Yixiao Pan, Yongxin Huang, Xueyun Ma, Qiang Xia, Kang He
Summary: This study reveals that liver cancer promotes tumor lung metastasis by regulating neutrophil recruitment and NETs formation in the metastatic microenvironment through reducing HRG secretion. The findings of this study will contribute to the development of possible strategies for treating metastases.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Yan Deng, Maodi Xie, Qian Li, Xuewen Xu, Wei Ou, Yabing Zhang, Haitao Xiao, Hai Yu, Yanyi Zheng, Yu Liang, Chunling Jiang, Guo Chen, Dan Du, Wen Zheng, Shisheng Wang, Meng Gong, Yaohui Chen, Rong Tian, Tao Li
Summary: This study identified the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, and showed that increasing beta-hydroxybutyrate levels can ameliorate the disease by reducing inflammation and mitochondrial dysfunction.
CIRCULATION RESEARCH
(2021)
Article
Nanoscience & Nanotechnology
Adityanarayan Mohapatra, Santhosh Kalash Rajendrakumar, Gopalakrishnan Chandrasekaran, Vishnu Revuri, Padmanaban Sathiyamoorthy, Yong-Kyu Lee, Jae Hyuk Lee, Seok-Yong Choi, In-Kyu Park
Summary: A peroxidase-mimicking nanoscavenger was developed to block the secretion of reactive oxygen species (ROS) and proinflammatory cytokines in gouty arthritis induced by monosodium urate (MSU) crystals. The nanoparticles alleviated joint swelling by abrogating ROS and inflammatory cytokine secretions from proinflammatory macrophages, preventing neutrophil infiltration and fluid buildup at the inflammation site. The treatment also reduced macrophage and neutrophil influx in the injured region in zebrafish and mouse models. Overall, the strategy of using biomineralized nanoscavengers shows clinical significance in dual blocking of peroxides and COX2 to prevent inflammation cell influx.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Oncology
Li Xu, Xiao-Min Wu, Yu-Kun Zhang, Ming-Jie Huang, Jun Chen
Summary: This study demonstrates that simvastatin partially reverses the decreased cell viability of neutrophils in human sepsis, while also reducing the production of inflammatory mediators and reactive oxygen species. Furthermore, simvastatin enhances autophagy induction in neutrophils. Hence, enhancing neutrophil autophagy may serve as a potential therapeutic target for sepsis.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Endocrinology & Metabolism
Yener Akyuva, Mustafa Naziroglu, Kenan Yildizhan
Summary: The study indicates that interferon-gamma activates TRPM2 channels in microglia cells, leading to cell apoptosis and increased cytokine production, while selenium treatment can mitigate these effects.
METABOLIC BRAIN DISEASE
(2021)
Article
Multidisciplinary Sciences
Hassan O. J. Morad, Suaib Luqman, Larissa Garcia Pinto, Kevin P. Cunningham, Bruno Vilar, Georgia Clayton, Manu Shankar-Hari, Peter A. McNaughton
Summary: The antimalarial compound artemisinin has been identified as a potent inhibitor of neutrophil and macrophage chemotaxis induced by various chemotactic agents. It releases calcium from intracellular stores and selectively blocks the SERCA3 isoform. In mouse infection models, artemisinin suppresses neutrophil invasion and inhibits the release of cytokines/chemokines and NETs.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Yoshikazu Tsukasaki, Peter T. Toth, Esmaeil Davoodi-Bojd, Jalees Rehman, Asrar B. Malik
Summary: This study describes a novel intravital imaging approach based on a computer-vision stabilization algorithm, which corrects lung movements and deformations in respiring mouse lungs with submicron precision. This method allows for high-throughput quantitative analysis of intravital pulmonary polymorphonuclear neutrophil (PMN) dynamics and provides valuable insights into PMN physiology and role in inflammatory lung injury.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joseph Farahany, Yoshikazu Tsukasaki, Amitabha Mukhopadhyay, Manish Mittal, Saroj Nepal, Chinnaswamy Tiruppathi, Asrar B. Malik
Summary: CD38 inhibits NLRP3 activation and can prevent endotoxemic ALI, suggesting it as a potential therapeutic target.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
PamelaSara E. Head, Sangho Myung, Yong Chen, Jessica L. Schneller, Cindy Wang, Nicholas Duncan, Pauline Hoffman, David Chang, Abigael Gebremariam, Marjan Gucek, Irini Manoli, Charles P. Venditti
Summary: Organic acidemias like methylmalonic acidemia (MMA) are genetic metabolic disorders caused by defects in the breakdown of amino and fatty acids. This study discovered a widespread posttranslational modification called methylmalonylation that inhibits enzymes in the urea cycle and glycine cleavage pathway in MMA. The researchers found that SIRT5 controls the metabolism of these posttranslational modifications. Gene therapy using modified SIRT5 improved symptoms of MMA in mice.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Hiroyuki Hirai, Xiubin Liang, Yifei Sun, Yihan Zhang, Jifeng Zhang, Y. Eugene Chen, Hongmei Mou, You-Yang Zhao, Jie Xu
Summary: This study derived human proximal lung organoids (HLOs) from patient-derived pluripotent stem cells (PSCs) carrying CFTR mutations, and found that HLOs responded to CFTR modulators in a mutation-dependent manner. The study also discovered that SGLT1 expression was upregulated in CF HLOs and airway epithelial cells, suggesting SGLT1 as a potential therapeutic target for CF lung diseases.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Oncology
Yinghan Su, Jiang Li, Weidan Ji, Gang Wang, Lin Fang, Qin Zhang, Lin Ang, Min Zhao, Yuan Sen, Lei Chen, Junnian Zheng, Changqing Su, Lunxiu Qin
Summary: This study investigated the efficacy and mechanisms of a novel oncolytic adenovirus, OncoViron, in the treatment of multiple solid tumors. Results showed that OncoViron selectively targeted various solid tumors and significantly inhibited cancer cell proliferation. Combination therapy with PD-1 antibody and CAR T cells further enhanced the anticancer effects. Moreover, OncoViron remodels the tumor microenvironment to promote immune cell activation, thereby enhancing the efficacy of immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Jie Li, Peiyu Cao, Yuxin Chen, Junqi Wang, Xiaolei Sun, Renfu Chen, Gang Wang, Jianquan Hou
Summary: Anlotinib has shown therapeutic effects on RCC, but drug resistance is a problem. This study explored the resistance mechanisms and found that Anlotinib induced PD-L1-mediated immunosuppression. However, combining Anlotinib with PD-L1 blockade resulted in a synergistic therapeutic effect by promoting the induction and activation of immune killer cells.
EXPERIMENTAL CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Jiage Ding, Yanyan Zheng, Gang Wang, Junnian Zheng, Dafei Chai
Summary: Therapeutic dendritic cell (DC) vaccines have potential in anti-tumor immune responses, but the suppression of DC function by immune checkpoints limits their clinical response rate. The use of immune checkpoint inhibitors and immune checkpoint activators expands the range of immunotherapy with DC vaccines. Various strategies such as chemotherapy and genetic therapies can maximize the efficacy of DC vaccines. Further research and application of immune checkpoints can aid in the development of improved DC vaccines.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Biochemistry & Molecular Biology
Yi Peng, Jingbo Dai, You-Yang Zhao
Summary: Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by increased pulmonary vascular resistance and vascular remodeling. Egln1(Tie2Cre) mice model exhibits severe PAH and responds similarly to FDA-approved drugs as PAH patients in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Xiaoqing Shi, Jiage Ding, Yanyan Zheng, Jiawe Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Junnian Zheng, Dafei Chai
Summary: PLGA/PEI-HMGB1/GPC3 vaccine induced a strong and long-lasting CTL effect, inhibiting the progression and re-attack of hepatocellular carcinoma.
Article
Biology
Long Shuang Huang, Mohammad Anas, Jingsong Xu, Bisheng Zhou, Peter T. Toth, Yamuna Krishnan, Anke Di, Asrar B. Malik, Sivapriya Vanaja
Summary: The study shows that during homeostasis, the potassium channel TWIK2 is localized in endosomal compartments. Stimulation with extracellular ATP leads to the fusion of endosomes with the plasma membrane, resulting in potassium efflux and activation of the NLRP3 inflammasome. This process is regulated by Rab11a and purinergic receptor P2X7. Targeting the endosomal trafficking of TWIK2 to the plasma membrane may have therapeutic potential in acute or chronic inflammatory conditions.
Article
Immunology
Sreeparna Chakraborty, Abhalaxmi Singh, Li Wang, Xinge Wang, Mark A. Sanborn, Zijing Ye, Mark Maienschein-Cline, Amitabha Mukhopadhyay, Balaji B. Ganesh, Asrar B. Malik, Jalees Rehman
Summary: Recent studies have found that training of tissue-resident macrophages through repeated noxious stimuli can enhance host defense responses. This study focused on lung-resident alveolar macrophages (AMs) and found that trained AMs displayed greater resilience to pathogen-induced cell death and had increased capacity for efferocytosis and injury resolution. Transcriptomic analysis and functional assays revealed that training induced expansion of a specific subset of AMs with a proresolving phenotype. Adoptive transfer of these trained AMs restricted inflammatory lung injury in mice exposed to lethal pathogens, highlighting the importance of trained immunity in preventing hyperinflammation and maintaining tissue homeostasis.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Xiaojia Huang, Xianming Zhang, Narsa Machireddy, Colin E. Evans, Shawn D. Trewartha, Guochang Hu, Yun Fang, Goekhan M. Mutlu, David Wu, You-Yang Zhao
Summary: Aging impairs endothelial regeneration and vascular repair, leading to increased mortality in acute respiratory distress syndrome (ARDS) after sepsis challenge. Reactivation of the FoxM1 gene or treatment with the DNA demethylating agent decitabine promotes endothelial regeneration, normalizes vascular repair and resolution of inflammation, and improves survival in aged mice. FOXM1 induction is impaired in elderly patients with ARDS, suggesting that targeting FoxM1-mediated endothelial regeneration may be a potential therapy for this population.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Chinnaswamy Tiruppathi, Dong-Mei Wang, Mohammad Owais Ansari, Shabana Bano, Yoshikazu Tsukasaki, Amitabha Mukhopadhyay, Jagdish C. Joshi, Christian Loch, Hans W. M. Niessen, Asrar B. Malik
Summary: This study identifies the ubiquitin E3-ligase CHFR as a key mechanism for the degradation of VE-cadherin and demonstrates its importance in regulating the expression of VE-cadherin and maintaining endothelial junctional barrier integrity. The findings suggest that CHFR plays a role in inflammation-induced vascular injury and provides potential therapeutic targets for maintaining vascular integrity.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Nan Jiang, Yanyan Zheng, Jiage Ding, Jiawei Wang, Fei Zhu, Meng Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Hailong Li, Junnian Zheng, Dafei Chai
Summary: An adenovirus vaccine encoding tumor antigen CAIX combined with immune checkpoint PD-L1 was developed for renal carcinoma treatment. The combination vaccine significantly reduced subcutaneous tumor growth and promoted strong tumor-specific CD8+ T cell immune responses. Moreover, it effectively inhibited tumor growth and lung metastasis in metastatic or orthotopic models.
Article
Cardiac & Cardiovascular Systems
Bin Liu, Dan Yi, Jiakai Pan, Jingbo Dai, Maggie M. Zhu, You-Yang Zhao, S. Paul Oh, Michael B. Fallon, Zhiyu Dai
Summary: This study demonstrates that patients with pulmonary arterial hypertension have a deficiency in BMP signaling in the lungs. It also suggests a novel mechanism of dysregulated BMP signaling in the development of pulmonary arterial hypertension, as PHD2 deficiency suppresses BMP signaling in lung endothelial cells.
PULMONARY CIRCULATION
(2022)
