Article
Ophthalmology
Emma M. Lessieur, Haitao Liu, Aicha Saadane, Yunpeng Du, Jie Tang, Jianying Kiser, Timothy S. Kern
Summary: Previous studies indicate that neutrophils, especially neutrophil elastase (NE), play a causal role in the capillary degeneration observed in diabetic retinopathy (DR). In this study, it was found that blocking NE activity could be a novel therapy to inhibit DR development.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell & Tissue Engineering
Cathelijn E. M. Aarts, Eszter Varga, Steven Webbers, Judy Geissler, Marieke von Lindern, Taco W. Kuijpers, Emile van den Akker
Summary: Induced pluripotent stem cell line generated from erythroblasts of a patient with severe congenital neutropenia can be used to study the disease and the role of neutrophil elastase protein.
STEM CELL RESEARCH
(2021)
Article
Cell Biology
Kanokwan Sriwattanapong, Noppadol Sa-Ard-Iam, Lawan Boonprakong, Keskanya Subbalekha, Vorapat Trachoo, Narissara Suratannon, Thantrira Porntaveetus, Vorasuk Shotelersuk
Summary: This study suggests that in addition to neutropenia, the aberrant levels and functions of ELANE and SLPI in pulp cells play an important role in oral complications in SCN patients. ELANE cells exhibited impaired proliferation, colony forming, migration, attachment and spreading, and were highly responsive to inflammation.
CELL PROLIFERATION
(2021)
Article
Pharmacology & Pharmacy
Chun-lin Zhang, Hai-ling Wang, Peng-cheng Li, Can-dong Hong, An-qi Chen, Yan-mei Qiu, Ai-ping Zeng, Yi-fan Zhou, Bo Hu, Ya-nan Li
Summary: Research suggests that the failure of DHA therapy in some patients with diabetic retinopathy (DR) is associated with low expression of Mfsd2a, and the combination of Mfsd2a overexpression with DHA therapy may be an effective treatment.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cell & Tissue Engineering
Shuquan Rao, Yao Yao, Josias Soares de Brito, Qiuming Yao, Anne H. Shen, Ruth E. Watkinson, Alyssa L. Kennedy, Steven Coyne, Chunyan Ren, Jing Zeng, Anna Victoria Serbin, Sabine Studer, Kaitlyn Ballotti, Chad E. Harris, Kevin Luk, Christian S. Stevens, Myriam Armant, Luca Pinello, Scot A. Wolfe, Roberto Chiarle, Akiko Shimamura, Benhur Lee, Peter E. Newburger, Daniel E. Bauer
Summary: A study used a pooled CRISPR screen to uncover the correlation between ELANE mutations and neutrophil maturation potential, successfully overcoming maturation blockage in patients with congenital neutropenia through gene editing and establishing relevant animal models. Different types of chromosomal variations impact neutrophil maturation, which is crucial for elucidating disease mechanisms and developing universal treatment approaches.
Article
Multidisciplinary Sciences
Dion Kaiserman, Peishen Zhao, Caitlin Lorraine Rowe, Andrea Leong, Nicholas Barlow, Lars Thomas Joeckel, Corinne Hitchen, Sarah Elizabeth Stewart, Morley D. Hollenberg, Nigel Bunnett, Andreas Suhrbier, Phillip Ian Bird
Summary: GzmK and GzmA can activate PAR1 and PAR2, influencing cell signaling cascades and leading to the release of inflammatory cytokines. This suggests that GzmK acts as a pro-inflammatory regulator during immune responses.
Article
Multidisciplinary Sciences
Dion Kaiserman, Peishen Zhao, Caitlin Lorraine Rowe, Andrea Leong, Nicholas Barlow, Lars Thomas Joeckel, Corinne Hitchen, Sarah Elizabeth Stewart, Morley D. Hollenberg, Nigel Bunnett, Andreas Suhrbier, Phillip Ian Bird
Summary: Granzyme K (GzmK) and GzmA can activate PAR1 and PAR2, and are involved in inflammatory response and cell signaling cascade. Despite cleaving PAR2 at the same point as trypsin, GzmK activates a distinct signaling pathway instead of the classical Ca2+ flux. In epithelial cells, GzmK induces the release of inflammatory cytokines through the activation of PAR2.
Article
Ophthalmology
Hideaki Someya, Masataka Ito, Yoshiaki Nishio, Tomohito Sato, Kozo Harimoto, Masaru Takeuchi
Summary: Diabetic retinopathy, a major cause of blindness in developed countries, can be caused by elevated levels of osteopontin (OPN), leading to vascular hyperpermeability and retinal edema. This study found that anti-OPN treatment can mitigate vascular hyperpermeability and restore the expression of key proteins in the retina.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Chemistry, Medicinal
Yingjun Cui, Mengyi Zhang, Honglei Xu, Tingrong Zhang, Songming Zhang, Xiuhe Zhao, Peng Jiang, Jing Li, Baijun Ye, Yuanjun Sun, Mukuo Wang, Yangping Deng, Qing Meng, Yang Liu, Qiang Fu, Jianping Lin, Liang Wang, Yue Chen
Summary: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common complication in COVID-19. The natural macrocyclic peptide CTL-A has been identified as a potential elastase inhibitor for preventing ALI/ARDS. The first total synthesis of CTL-A was achieved in 24 steps, and preliminary structure-activity relationships were elucidated. In vivo studies using an ALI mouse model demonstrated that CTL-A effectively alleviated acute lung injury, outperforming the approved elastase inhibitor sivelestat. The findings highlight the potential of CTL-A as a candidate for COVID-19 pathogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Hematology
Patricia A. Olofsen, Dennis A. Bosch, Onno Roovers, Paulina M. H. van Strien, Hans W. J. de Looper, Remco M. Hoogenboezem, Sander Barnhoorn, Pier G. Mastroberardino, Mehrnaz Ghazvini, Vincent H. J. van der Velden, Eric M. J. Bindels, Emma M. de Pater, Ivo P. Touw
Summary: Mutations in ELANE gene lead to severe congenital neutropenia (SCN) and increase the risk of leukemia. Research shows that hematopoietic progenitor cells (HPCs) from SCN patients with ELANE mutations have elevated levels of reactive oxygen species (ROS), indicating acute oxidative stress.
Article
Chemistry, Multidisciplinary
Angelique Rivot, Natacha Jugniot, Samuel Jacoutot, Nicolas Vanthuyne, Philippe Massot, Philippe Mellet, Sylvain R. A. Marque, Gerard Audran, Pierre Voisin, Marie Delles, Gilles Devouassoux, Eric Thiaudiere, Abderrazzak Bentaher, Elodie Parzy
Summary: The study suggests using OMRI in mice to evaluate protease activity in the lungs, finding an increase in proteolysis in LPS-induced inflammation. This preclinical detection method may open new avenues for diagnosis and in vivo antiprotease testing.
Article
Cell Biology
Chinchu Jagadan Ushakumari, Qiong L. Zhou, Yu-Hua Wang, Sijia Na, Michael C. Rigor, Cindy Y. Zhou, Max K. Kroll, Benjamin D. Lin, Zhen Y. Jiang
Summary: In this study, it was found that neutrophil elastase (NE) activates protease-activated receptor-2 (PAR2) signaling pathway and promotes changes in actomyosin and VE-cadherin, leading to increased vascular permeability and leukocyte infiltration in obesity-related inflammation. Inhibition of NE may be a potential approach to mitigate vascular injury and leukocyte infiltration in obesity-related systemic inflammation.
Article
Biochemistry & Molecular Biology
Dongjoon Kim, Marcela Votruba, Sayon Roy
Summary: Reduced level of Opa1 promotes apoptosis and retinal vascular lesions associated with diabetic retinopathy. Downregulation of Opa1 expression contributes to the development of retinal cell death and capillary damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Shengshuai Shan, Fang Liu, Edith Ford, Ruth B. Caldwell, S. Priya Narayanan, Payaningal R. Somanath
Summary: Triciribine (TCBN), a tricyclic nucleoside analog and a weak Akt inhibitor, significantly reduces pathological neovascularization, vaso-obliteration, and inflammation in a mouse model of oxygen-induced retinopathy (OIR). TCBN also restores blood-retinal barrier homeostasis without affecting retinal structure and neuronal function. These findings suggest that TCBN may provide a novel therapeutic option for proliferative retinopathy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Lorenza Marinaccio, Azzurra Stefanucci, Giuseppe Scioli, Alice Della Valle, Gokhan Zengin, Angelo Cichelli, Adriano Mollica
Summary: This review provides an overview of the latest advancements in peptide human neutrophil elastase inhibitors isolated from natural sources, including their identification, structures, and mechanisms of action. These inhibitors play a significant role in the development of potent bioactive compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Ophthalmology
Meysam Yazdankhah, Peng Shang, Sayan Ghosh, Stacey Hose, Haitao Liu, Joseph Weiss, Christopher S. Fitting, Imran A. Bhutto, J. Samuel Zigler Jr, Jiang Qian, Jose-Alain Sahel, Debasish Sinha, Nadezda A. Stepicheva
Summary: The optic nerve, with its unique characteristics, plays a crucial role in maintaining neuronal activity in the central nervous system. Glial cells in the optic nerve provide essential support for retinal ganglion cells and are sensitive to pathological conditions, as seen in vision problems in multiple sclerosis. Current research focuses on understanding the organization and function of glial cells in the optic nerve for potential therapeutic advances.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Cell Biology
Meysam Yazdankhah, Sayan Ghosh, Peng Shang, Nadezda Stepicheva, Stacey Hose, Haitao Liu, Xitiz Chamling, Shenghe Tian, Mara L. G. Sullivan, Michael Joseph Calderon, Christopher S. Fitting, Joseph Weiss, Ashwath Jayagopal, James T. Handa, Jose-Alain Sahel, J. Samuel Zigler, Paul R. Kinchington, Donald J. Zack, Debasish Sinha
Summary: The differentiation of oligodendrocyte lineage cells involves autophagy and mitochondrial dynamics, with BNIP3L playing a crucial role in the regulation of mitochondrial function and cell viability. Targeting BNIP3L-mediated mitophagy could be a novel therapeutic approach for promoting myelin repair in optic nerve demyelinating diseases.
Article
Biology
Sayan Ghosh, Haitao Liu, Meysam Yazdankhah, Nadezda Stepicheva, Peng Shang, Tanuja Vaidya, Stacey Hose, Urvi Gupta, Michael Joseph Calderon, Ming-Wen Hu, Archana Padmanabhan Nair, Joseph Weiss, Christopher S. Fitting, Imran A. Bhutto, Santosh Gopi Krishna Gadde, Naveen Kumar Naik, Chaitra Jaydev, Gerard A. Lutty, James T. Handa, Ashwath Jayagopal, Jiang Qian, Jose-Alain Sahel, Dhivyaa Rajasundaram, Yuri Sergeev, J. Samuel Zigler, Swaminathan Sethu, Simon Watkins, Arkasubhra Ghosh, Debasish Sinha
Summary: Ghosh et al. discovered that the lens protein beta A1-crystallin interacts with PTP1B, regulating the metabolism of retinal astrocytes. Knockdown of beta A1-crystallin exacerbates the streptozotocin-induced diabetic retinopathy-like phenotype in mice, indicating a potential target for treating diabetic retinopathy.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Urvi Gupta, Sayan Ghosh, Callen T. Wallace, Peng Shang, Ying Xin, Archana Padmanabhan Nair, Meysam Yazdankhah, Anastasia Strizhakova, Mark A. Ross, Haitao Liu, Stacey Hose, Nadezda A. Stepicheva, Olivia Chowdhury, Mihir Nemani, Vishnu Maddipatla, Rhonda Grebe, Manjula Das, Kira L. Lathrop, Jose-Alain Sahel, J. Samuel Zigler, Jiang Qian, Arkasubhra Ghosh, Yuri Sergeev, James T. Handa, Claudette M. St Croix, Debasish Sinha
Summary: In dry age-related macular degeneration, increased LCN2 levels lead to pathological changes in retinal pigmented epithelial cells, which are known to drive dry AMD pathology. By regulating autophagy and ferroptosis activities, LCN2 is involved in the development of AMD and provides a potential therapeutic strategy.
Article
Endocrinology & Metabolism
Emma M. Lessieur, Haitao Liu, Aicha Saadane, Yunpeng Du, Jianying Kiser, Timothy S. Kern
Summary: This study found that the diabetes-induced upregulation of ICAM-1 on the luminal surface of vascular endothelium varies considerably among tissues and is highest in the retina. The induction of ICAM-1 on retinal vascular endothelial cells in diabetes is influenced by vision-related processes in photoreceptor cells. The unique presence of photoreceptors in the retina might contribute to the greater susceptibility of this tissue to vascular disease in diabetes.
Article
Nanoscience & Nanotechnology
Michelle A. Cruz, Dillon Bohinc, Elizabeth A. Andraska, Jurgis Alvikas, Shruti Raghunathan, Nicole A. Masters, Nadine D. van Kleef, Kara L. Bane, Kathryn Hart, Kathryn Medrow, Michael Sun, Haitao Liu, Shannon Haldeman, Ankush Banerjee, Emma M. Lessieur, Kara Hageman, Agharnan Gandhi, Maria de la Fuente, Marvin T. Nieman, Timothy S. Kern, Coen Maas, Steven de Maat, Keith B. Neeves, Matthew D. Neal, Anirban Sen Gupta, Evi X. Stavrou
Summary: "Neutrophils play a crucial role in defense against infections and inflammation, but their uncontrolled recruitment and activation can lead to prolonged inflammation and worsen specific pathological conditions. This study presents a targeted drug delivery strategy to specifically target activated, pro-inflammatory neutrophils and neutrophil-platelet complexes, offering a novel therapeutic approach for neutrophil-driven pathologies."
NATURE NANOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Haitao Liu, Nadezda A. Stepicheva, Sayan Ghosh, Peng Shang, Olivia Chowdhury, Rachel A. Daley, Meysam Yazdankhah, Urvi Gupta, Stacey L. Hose, Mallika Valapala, Christopher Scott Fitting, Anastasia Strizhakova, Yang Shan, Derrick Feenstra, Jose-Alain Sahel, Ashwath Jayagopal, James T. Handa, J. Samuel Zigler, Patrice E. Fort, Akrit Sodhi, Debasish Sinha
Summary: This study finds that Akt1 and Akt2 activities are reciprocally regulated in the RPE of diabetic retinopathy (DR) donor tissue and diabetic mice. Reduction of Akt2 in RPE leads to compensatory increase of Akt1, resulting in attenuating DR-induced retinal abnormalities.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Olivia Chowdhury, Sayan Ghosh, Ankur Das, Haitao Liu, Peng Shang, Nadezda A. Stepicheva, Stacey Hose, Debasish Sinha, Sreya Chattopadhyay
Summary: The study demonstrates the link between inflammation and autophagy in the progression of liver fibrosis. A mouse model with low-grade lipopolysaccharide (LPS) exposure showed hepatic damage and a pro-inflammatory condition in the liver. Inhibiting the inflammatory pathways and promoting autophagy could be a potential strategy for delaying liver fibrosis.
CELLULAR SIGNALLING
(2023)
Article
Endocrinology & Metabolism
Aicha Saadane, Alexander A. Veenstra, Martin S. Minns, Jie Tang, Yunpeng Du, Fatima Abubakr Elghazali, Emma M. Lessieur, Eric Pearlman, Timothy S. Kern
Summary: Inflammatory monocytes play a critical role in the early development of diabetic retinopathy.
Article
Cell Biology
Maeve Boyce, Ying Xin, Olivia Chowdhury, Peng Shang, Haitao Liu, Victoria Koontz, Anastasia Strizhakova, Mihir Nemani, Stacey Hose, J. Samuel Zigler, Matthew Campbell, Debasish Sinha, James T. Handa, Kai Kaarniranta, Jiang Qian, Sayan Ghosh
Summary: This study reveals the interaction between microglia and neutrophils in the pathogenesis of AMD, demonstrating that microglia trigger early RPE changes by regulating neutrophil function and inducing their activation. The study also identifies the Akt2 pathway in microglia as a potential therapeutic target for early AMD.
Article
Medicine, Research & Experimental
Haitao Liu, Sayan Ghosh, Tanuja Vaidya, Sridhar Bammidi, Chao Huang, Peng Shang, Archana Padmanabhan Nair, Olivia Chowdhury, Nadezda A. Stepicheva, Anastasia Strizhakova, Stacey Hose, Nikolaos Mitrousis, Santosh Gopikrishna Gadde, M. B. Thirumalesh, Pamela Strassburger, Gabriella Widmer, Eleonora M. Lad, Patrice E. Fort, Jose-Alain Sahel, J. Samuel Zigler Jr, Swaminathan Sethu, Peter D. Westenskow, Alan D. Proia, Akrit Sodhi, Arkasubhra Ghosh, Derrick Feenstra, Debasish Sinha
Summary: Diabetic retinopathy (DR) is a major cause of blindness in working-age adults and remains a significant public health issue worldwide. Increased expression of stimulator of interferon genes (STING) has been observed in DR patients and animal models of diabetic eye disease. This study investigated the role of STING in the pathogenesis of DR and found that its absence inhibited retinal endothelial cell senescence, inflammation, and capillary degeneration in diabetic mice. These protective effects were associated with reduced phosphorylation of TBK1, IRF3, and NF-KB. Targeting STING may be a potential therapy for the prevention and treatment of DR.
Article
Cell Biology
Rachel Daley, Vishnu Maddipatla, Sayan Ghosh, Olivia Chowdhury, Stacey Hose, J. Samuel Zigler, Debasish Sinha, Haitao Liu
Summary: Diabetic Retinopathy (DR) is a complication of diabetes that leads to blindness in adults. Retinal fibrosis is closely associated with the development of proliferative diabetic retinopathy (PDR). However, retinal fibrosis has received minimal attention as a potential target for therapeutic intervention.
CELL DEATH DISCOVERY
(2023)
Article
Ophthalmology
Emma M. Lessieur, Haitao Liu, Aicha Saadane, Yunpeng Du, Jie Tang, Jianying Kiser, Timothy S. Kern
Summary: Previous studies indicate that neutrophils, especially neutrophil elastase (NE), play a causal role in the capillary degeneration observed in diabetic retinopathy (DR). In this study, it was found that blocking NE activity could be a novel therapy to inhibit DR development.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)