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Zhang J, Liu Z, Zhou Z, Huang Z, Yang Y, Wu J, Liu Y. HNP-1: From Structure to Application Thanks to Multifaceted Functions. Microorganisms 2025; 13:458. [PMID: 40005828 PMCID: PMC11858525 DOI: 10.3390/microorganisms13020458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 02/02/2025] [Accepted: 02/09/2025] [Indexed: 02/27/2025] Open
Abstract
Antimicrobial peptides (AMPs) are critical components of innate immunity in animals and plants, exhibiting thrilling prospectives as alternatives to traditional antibiotics due to their ability to combat pathogens without leading to resistance. Among these, Human Neutrophil Peptide-1 (HNP-1), primarily produced by human neutrophils, exhibits broad-spectrum antimicrobial activity against bacteria and viruses. However, the clinical application of HNP-1 has been hampered by challenges associated with mass production and inconsistent understanding of its bactericidal mechanisms. This review explores the structure and function of HNP-1, discussing its gene expression, distribution, immune functions and the regulatory elements controlling its production, alongside insights into its antimicrobial mechanisms and potential clinical applications as an antimicrobial agent. Furthermore, the review highlights the biosynthesis of HNP-1 using microbial systems as a cost-effective alternative to human extraction and recent studies revealing HNP-1's endogenous bactericidal mechanism. A comprehensive understanding of HNP-1's working mechanisms and production methods will pave the way for its effective clinical utilization in combating antibiotic-resistant infections.
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Affiliation(s)
- Jiaqi Zhang
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Zhaoke Liu
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Zhihao Zhou
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Zile Huang
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Yifan Yang
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Junzhu Wu
- Department of Biochemistry and Molecular Biology, Center for Experimental Teaching of Basic Medical Science, School of Basic Medical Science, Wuhan University, Wuhan 430072, China; (J.Z.)
| | - Yanhong Liu
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
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Chen X, Zhao Z, Laster KV, Liu K, Dong Z. Advancements in therapeutic peptides: Shaping the future of cancer treatment. Biochim Biophys Acta Rev Cancer 2024; 1879:189197. [PMID: 39413854 DOI: 10.1016/j.bbcan.2024.189197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 10/03/2024] [Accepted: 10/07/2024] [Indexed: 10/18/2024]
Abstract
In the evolving landscape of cancer treatment, therapeutic peptides are assuming to play an increasingly vital role. Although the number of peptide drugs available for clinical cancer treatment is currently limited, extensive preclinical research is underway, presenting a promising trajectory for the future. The collaborative efforts of natural anti-cancer peptides (ACPs) and synthetic ACPs, propelled by advancements in molecular biology and peptide chemistry, are steering remarkable progress in this domain. We explores the intricate mechanisms underlying the anti-cancer effects of these peptides. The exploration of innovative strategies, including cancer immunotherapy and advanced drug delivery systems, is likely to contribute to the increasing presenceuse of peptide drugs in clinical cancer care. Furthermore, we delve into the potential implications and challenges associated with this anticipated shift, emphasizing the need for continued research and development to unlock the full therapeutic potential of peptide drugs in cancer treatment.
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Affiliation(s)
- Xiaojie Chen
- School of Basic Medical Sciences, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450003, China
| | - Zhiwei Zhao
- School of Basic Medical Sciences, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China
| | | | - Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou 450003, China; Research Center of Basic Medicine Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou 450003, China; Research Center of Basic Medicine Sciences, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
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Six KR, Vertongen S, Seghers S, De Bleser D, Compernolle V, Feys HB. Differential composition and yield of leukocytes isolated from various blood component leukoreduction filters. J Immunol Methods 2024; 533:113733. [PMID: 39098592 DOI: 10.1016/j.jim.2024.113733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 07/22/2024] [Accepted: 07/31/2024] [Indexed: 08/06/2024]
Abstract
In Flanders, an estimated 300,000 leukoreduction filters are discarded as biological waste in the blood establishment each year. These filters are a possible source of fresh donor leukocytes for downstream purposes including research. We investigated leukocyte isolation from two types of filters either used for the preparation of platelet concentrates (PC-LRF) or erythrocyte concentrates (EC-LRF). Outcome parameters were leukocyte yield, differential count, turnaround time and effect of storage conditions. Leukocytes were harvested by reverse flow of a buffer solution. Control was the gold standard density gradient centrifugation of buffy coats. Total leukocyte number isolated from PC-LRF (1049 (± 40) x 106) was almost double that of control (632 (± 66) x 106) but the differential count was comparable. Total leukocyte number isolated from EC-LRF (78 (± 9) x 106) was significantly lower than control, but the sample was specifically enriched in granulocytes (81 ± 4%) compared to control (30 ± 1%). Isolation of leukocytes from either PC- or EC-LRF takes 20 min compared to 240 min for control density gradient centrifugation. Leukocyte viability is optimal when harvested on day 1 post donation (95 ± 0.9%) compared to day 3 (76.4 ± 2.4%). In conclusion, our study demonstrates that leukoreduction filters from specific blood component processing are easy to use and present a valuable source for viable leukocytes of all types.
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Affiliation(s)
- Katrijn R Six
- Transfusion Research Center, Belgian Red Cross Flanders, Ghent, Belgium.
| | - Sarah Vertongen
- Transfusion Research Center, Belgian Red Cross Flanders, Ghent, Belgium
| | - Sabrina Seghers
- Transfusion Innovation Center, Belgian Red Cross Flanders, Ghent, Belgium
| | | | - Veerle Compernolle
- Transfusion Research Center, Belgian Red Cross Flanders, Ghent, Belgium; Transfusion Innovation Center, Belgian Red Cross Flanders, Ghent, Belgium; Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Blood Services, Belgian Red Cross Flanders, Mechelen, Belgium
| | - Hendrik B Feys
- Transfusion Research Center, Belgian Red Cross Flanders, Ghent, Belgium; Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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Role of Defensins in Tumor Biology. Int J Mol Sci 2023; 24:ijms24065268. [PMID: 36982340 PMCID: PMC10049535 DOI: 10.3390/ijms24065268] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/12/2023] Open
Abstract
Defensins have long been considered as merely antimicrobial peptides. Throughout the years, more immune-related functions have been discovered for both the α-defensin and β-defensin subfamily. This review provides insights into the role of defensins in tumor immunity. Since defensins are present and differentially expressed in certain cancer types, researchers started to unravel their role in the tumor microenvironment. The human neutrophil peptides have been demonstrated to be directly oncolytic by permealizing the cell membrane. Further, defensins can inflict DNA damage and induce apoptosis of tumor cells. In the tumor microenvironment, defensins can act as chemoattractants for subsets of immune cells, such as T cells, immature dendritic cells, monocytes and mast cells. Additionally, by activating the targeted leukocytes, defensins generate pro-inflammatory signals. Moreover, immuno-adjuvant effects have been reported in a variety of models. Therefore, the action of defensins reaches beyond their direct antimicrobial effect, i.e., the lysis of microbes invading the mucosal surfaces. By causing an increase in pro-inflammatory signaling events, cell lysis (generating antigens) and attraction and activation of antigen presenting cells, defensins could have a relevant role in activating the adaptive immune system and generating anti-tumor immunity, and could thus contribute to the success of immune therapy.
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Tan ZX, Tao R, Li SC, Shen BZ, Meng LX, Zhu ZY. Role of defensins in diabetic wound healing. World J Diabetes 2022; 13:962-971. [PMID: 36437862 PMCID: PMC9693740 DOI: 10.4239/wjd.v13.i11.962] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/22/2022] [Accepted: 10/31/2022] [Indexed: 11/11/2022] Open
Abstract
The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.
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Affiliation(s)
- Zhi-Xiang Tan
- Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Rui Tao
- Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Si-Cheng Li
- Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Bing-Zheng Shen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Lan-Xia Meng
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Zhan-Yong Zhu
- Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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Zaman R, Islam RA, Chowdhury EH. Evolving therapeutic proteins to precisely kill cancer cells. J Control Release 2022; 351:779-804. [DOI: 10.1016/j.jconrel.2022.09.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 09/27/2022] [Accepted: 09/29/2022] [Indexed: 10/31/2022]
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Ting DSJ, Mohammed I, Lakshminarayanan R, Beuerman RW, Dua HS. Host Defense Peptides at the Ocular Surface: Roles in Health and Major Diseases, and Therapeutic Potentials. Front Med (Lausanne) 2022; 9:835843. [PMID: 35783647 PMCID: PMC9243558 DOI: 10.3389/fmed.2022.835843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 05/17/2022] [Indexed: 11/13/2022] Open
Abstract
Sight is arguably the most important sense in human. Being constantly exposed to the environmental stress, irritants and pathogens, the ocular surface – a specialized functional and anatomical unit composed of tear film, conjunctival and corneal epithelium, lacrimal glands, meibomian glands, and nasolacrimal drainage apparatus – serves as a crucial front-line defense of the eye. Host defense peptides (HDPs), also known as antimicrobial peptides, are evolutionarily conserved molecular components of innate immunity that are found in all classes of life. Since the first discovery of lysozyme in 1922, a wide range of HDPs have been identified at the ocular surface. In addition to their antimicrobial activity, HDPs are increasingly recognized for their wide array of biological functions, including anti-biofilm, immunomodulation, wound healing, and anti-cancer properties. In this review, we provide an updated review on: (1) spectrum and expression of HDPs at the ocular surface; (2) participation of HDPs in ocular surface diseases/conditions such as infectious keratitis, conjunctivitis, dry eye disease, keratoconus, allergic eye disease, rosacea keratitis, and post-ocular surgery; (3) HDPs that are currently in the development pipeline for treatment of ocular diseases and infections; and (4) future potential of HDP-based clinical pharmacotherapy for ocular diseases.
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Affiliation(s)
- Darren Shu Jeng Ting
- Academic Ophthalmology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- Department of Ophthalmology, Queen's Medical Centre, Nottingham, United Kingdom
- Anti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore
- *Correspondence: Darren Shu Jeng Ting
| | - Imran Mohammed
- Academic Ophthalmology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | | | - Roger W. Beuerman
- Anti-Infectives Research Group, Singapore Eye Research Institute, Singapore, Singapore
| | - Harminder S. Dua
- Academic Ophthalmology, School of Medicine, University of Nottingham, Nottingham, United Kingdom
- Department of Ophthalmology, Queen's Medical Centre, Nottingham, United Kingdom
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Ferdowsi S, Abbasi-Malati Z, Pourfathollah AA. Leukocyte reduction filters as an alternative source of peripheral blood leukocytes for research. Hematol Transfus Cell Ther 2021; 43:494-498. [PMID: 33422490 PMCID: PMC8573042 DOI: 10.1016/j.htct.2020.10.963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 09/11/2020] [Accepted: 10/01/2020] [Indexed: 11/28/2022] Open
Abstract
INTRODUCTION Peripheral blood leukocytes are a suitable cell model for science research. However, blood samples from healthy volunteers are limited in volume and difficult to obtain due to the complexity of volunteer recruitment. OBJECTIVE Therefore, it is urgent to find an alternative source of peripheral blood leukocytes. METHOD One of the possibilities is the use of leukocyte reduction filters (LRFs) in blood banks that is used for preparation of leukoreduced blood products. More than 90% of the leukocytes are trapped in the leukofilters allowing the desired blood product to pass through. RESULTS It has been reported that the biological function of leukocytes collected from the filters are no different from those isolated from buffy coats, leukapheresis products and whole blood (WB) cells. Moreover, LRFs are waste products that are discarded after leukoreduction. CONCLUSION Thus, leukofilters represent an economic source of human cell populations that can be used for a variety of investigative purposes, with no cost. In the present study, we reviewed the different usage of LRFs in the research, clinical and commercial applications.
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Affiliation(s)
- Shirin Ferdowsi
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Zahra Abbasi-Malati
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Ali Akbar Pourfathollah
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Tarbiat Modares University, Faculty of Medical Sciences, Tehran, Iran.
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Berghmans E, Jacobs J, Deben C, Hermans C, Broeckx G, Smits E, Maes E, Raskin J, Pauwels P, Baggerman G. Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients. Cancers (Basel) 2020; 12:E863. [PMID: 32252405 PMCID: PMC7225984 DOI: 10.3390/cancers12040863] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 03/30/2020] [Accepted: 04/01/2020] [Indexed: 12/17/2022] Open
Abstract
(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC. These results were verified and confirmed with immunohistochemical analyses. In addition, we provide in-vitro evidence of the immune stimulatory effect of neutrophil defensins towards cancer cells; and (4) Conclusions: With proteomic approaches, we have discovered neutrophil defensins as additional prospective biomarkers for an anti-PD-(L)1 immunotherapy response. Thereby, we also demonstrated that the neutrophil defensins contribute in the activation of the immune response towards cancer cells, which could provide a new lead towards an anticancer therapy.
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Affiliation(s)
- Eline Berghmans
- Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium;
- Health Unit, VITO, 2400 Mol, Belgium
| | - Julie Jacobs
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Christophe Deben
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Christophe Hermans
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Glenn Broeckx
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Evelien Smits
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Evelyne Maes
- Food & Bio-Based Products, AgResearch Ltd., Lincoln 7674, New Zealand;
| | - Jo Raskin
- Thoracic Oncology Department, Antwerp University Hospital, 2650 Edegem, Belgium;
| | - Patrick Pauwels
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Geert Baggerman
- Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium;
- Health Unit, VITO, 2400 Mol, Belgium
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