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Luo Y, Li J, Fu Q, Zhang P, Song X, Liu M, Mo R, Fu J, Tang S, Wu J, Yang X, Liu X, Wang T, Ni G. Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells. Sci Rep 2025; 15:13377. [PMID: 40251208 PMCID: PMC12008296 DOI: 10.1038/s41598-025-96438-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 03/28/2025] [Indexed: 04/20/2025] Open
Abstract
Caerin peptides exhibit a dual role in cancer treatment by directly killing cancer cells and modulating the tumour microenvironment to enhance anti-tumour immunity. This study investigates the mechanisms underlying caerin 1.1/1.9-induced acute cell death in epithelial cancer cells and explores their therapeutic potential. HeLa, A549, and Huh-7 cancer cell lines were treated with caerin 1.1/1.9 peptides. Morphological observations, flow cytometry, lactate dehydrogenase (LDH) release, and IL-18 secretion assays revealed the occurrence of pyroptosis following treatment. Specifically, a 1-h treatment with caerin 1.1/1.9 induced pyroptosis in HeLa, A549, and Huh-7 cells, characterised by cell swelling, membrane bubbling, and the release of IL-18 and LDH. Western blotting confirmed the upregulation of pyroptosis markers, including caspase-3, cleaved caspase-3, and GSDME-N fragments. These findings highlight the significant role of caerin peptides in inducing acute pyroptosis, a form of programmed cell death that enhances the immunogenicity of dying cancer cells, thus potentially improving the effectiveness of immunotherapies. This research underscores the therapeutic potential of caerin 1.1/1.9 peptides in cancer treatment, providing a foundation for developing new anti-cancer strategies that leverage both direct cytotoxic effects and immune modulation to achieve more effective and sustained anti-tumour responses.
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Affiliation(s)
- Yuandong Luo
- Medical College of Guizhou University, Guiyang, 550025, Guizhou, China
| | - Junjie Li
- Zhongao Biomedical Technology (Guangdong) Co. Ltd, Zhongshan, 528400, Guangdong, China
| | - Quanlan Fu
- Medical College of Guizhou University, Guiyang, 550025, Guizhou, China
| | - Pingping Zhang
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China
| | - Xinyi Song
- The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Mengqi Liu
- Medical College of Guizhou University, Guiyang, 550025, Guizhou, China
| | - Rongmi Mo
- The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Jiawei Fu
- The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Shuxian Tang
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China
| | - Jialing Wu
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China
| | - Xiaodan Yang
- The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
| | - Xiaosong Liu
- Medical College of Guizhou University, Guiyang, 550025, Guizhou, China.
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China.
| | - Tianfang Wang
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.
| | - Guoying Ni
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China.
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Li J, Luo Y, Fu Q, Tang S, Zhang P, Frazer IH, Liu X, Wang T, Ni G. Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine IFNα and is enhanced by CD47 blockade. Sci Rep 2025; 15:3789. [PMID: 39885296 PMCID: PMC11782643 DOI: 10.1038/s41598-025-87687-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 01/21/2025] [Indexed: 02/01/2025] Open
Abstract
Previously, we demonstrated that natural host-defence peptide caerin 1.1/caerin 1.9 (F1/F3) increases the efficacy of anti-PD-1 and therapeutic vaccine, in a HPV16 + TC-1 tumour model, but the anti-tumor mechanism of F1/F3 is still unclear. In this study, we explored the impact of F1/F3 on the tumor microenvironment in a transplanted B16 melanoma model, and further investigated the mechanism of action of F1/F3 using monoclonal antibodies to deplete relevant cells, gene knockout mice and flow cytometry. We show that F1/F3 is able to inhibit the growth of melanoma B16 tumour cells both in vitro and in vivo. Depletion of macrophages, blockade of IFNα receptor, and Stat1 inhibition each abolishes F1/F3-mediated antitumor responses. Subsequent analysis reveals that F1/F3 increases the tumour infiltration of inflammatory macrophages, upregulates the level of IFNα receptor, and promotes the secretion of IFNα by macrophages. Interestingly, F1/F3 upregulates CD47 level on tumour cells; and blocking CD47 increases F1/F3-mediated antitumor responses. Furthermore, F1/F3 intratumor injection, CD47 blockade, and therapeutic vaccination significantly increases the survival time of B16 tumour-bearing mice. These results indicate that F1/F3 may be effective to improve the efficacy of ICB and therapeutic vaccine-based immunotherapy for human epithelial cancers and warrants consideration for clinical trials.
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Affiliation(s)
- Junjie Li
- Key Laboratory of Cancer Immunotherapy of Guangdong Tertiary Education, Guangdong CAR-T Treatment Related Adverse Reaction Key Laboratory, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
- Zhongao Biomedical Technology (Guangdong) Co., Ltd, Zhongshan, 528403, Guangdong, China
| | - Yuandong Luo
- Medical School of Guizhou University, Guiyang, 550000, Guizhou, China
| | - Quanlan Fu
- Medical School of Guizhou University, Guiyang, 550000, Guizhou, China
| | - Shuxian Tang
- Cancer Research Institute, Foshan First People's Hospital, Foshan, 528000, Guangdong, China
| | - Pingping Zhang
- Cancer Research Institute, Foshan First People's Hospital, Foshan, 528000, Guangdong, China
| | - Ian H Frazer
- Diamantia Institute, Translational Research Institute, University of Queensland, Woolloongabba, Brisbane, QLD, 4002, Australia
| | - Xiaosong Liu
- Key Laboratory of Cancer Immunotherapy of Guangdong Tertiary Education, Guangdong CAR-T Treatment Related Adverse Reaction Key Laboratory, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China
- Cancer Research Institute, Foshan First People's Hospital, Foshan, 528000, Guangdong, China
| | - Tianfang Wang
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.
| | - Guoying Ni
- Key Laboratory of Cancer Immunotherapy of Guangdong Tertiary Education, Guangdong CAR-T Treatment Related Adverse Reaction Key Laboratory, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China.
- Cancer Research Institute, Foshan First People's Hospital, Foshan, 528000, Guangdong, China.
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Long Y, Duan X, Fu Q, Liu M, Fu J, Song X, Mo R, You H, Qin L, Wang T, Li H, Ni G, Liu X, Yang W. Caerin 1.9-Titanium Plates Aid Implant Healing and Inhibit Bacterial Growth in New Zealand Rabbit Mandibles. Int Dent J 2024; 74:1287-1297. [PMID: 38866671 PMCID: PMC11551552 DOI: 10.1016/j.identj.2024.04.020] [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: 02/05/2024] [Revised: 03/31/2024] [Accepted: 04/22/2024] [Indexed: 06/14/2024] Open
Abstract
OBJECTIVES With rising rates of maxillofacial fracture, postoperative infection following rigid internal fixation is an important issue that requires immediate resolution. It is important to explore an alternative antibacterial method apart from conventional antibiotics. A controlled experiment was conducted to evaluate the effectiveness of a caerin 1.9 peptide-coated titanium plate in reducing mandibular infection in New Zealand (NZ) rabbits, aiming to minimise the risk of post-metallic implantation infection. METHODS Twenty-two NZ rabbits were randomly divided into 3 groups. The experiment group received caerin 1.9 peptide-coated titanium plates and mixed oral bacteria exposure. The control group received normal titanium plates with mixed oral bacteria exposure. The untreated group served as a control to prove that bacteria in the mouth can cause infection. Weight, temperature, hepatic function, and C-reactive protein levels were measured. Wound and bone conditions were evaluated. Further analysis included local infection, anatomic conditions, histology, and bacterial load. RESULTS No significant differences were found in temperature, weight, blood alanine aminotransferase, and C-reactive protein levels amongst the 3 groups. The experiment group showed the lowest amount of bacterial RNA in wounds. Additionally, the experiment group had higher peripheral lymphocyte counts compared to the control group and lower neutrophil counts on the third and seventh day postoperatively. Histologic analysis revealed lower levels of inflammatory cell infiltration, bleeding, and areas of necrosis in the experimental group compared with the controls. CONCLUSIONS A caerin 1.9-coated titanium plate is able to inhibit bacterial growth in a NZ rabbit mandibular mixed bacteria infection model and is worth further investigation.
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Affiliation(s)
- Yuqing Long
- School of Stomatology, Zunyi Medical University, Zunyi, Guizhou Province, China; Guiyang Dental Hospital, Guiyang, Guizhou Province, China
| | - Xubo Duan
- Medical School of Guizhou University, Guiyang, Guizhou Province, China
| | - Quanlan Fu
- Medical School of Guizhou University, Guiyang, Guizhou Province, China
| | - Mengqi Liu
- Medical School of Guizhou University, Guiyang, Guizhou Province, China
| | - Jiawei Fu
- Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
| | - Xinyi Song
- Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
| | - Rongmi Mo
- Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
| | - Hang You
- School of Stomatology, Zunyi Medical University, Zunyi, Guizhou Province, China; Guiyang Dental Hospital, Guiyang, Guizhou Province, China
| | - Li Qin
- School of Stomatology, Zunyi Medical University, Zunyi, Guizhou Province, China; Guiyang Dental Hospital, Guiyang, Guizhou Province, China
| | - Tianfang Wang
- Centre for Bio-innovation, University of the Sunshine Coast, Maroochydore BC, Queensland 4558, Australia
| | - Hejie Li
- Centre for Bio-innovation, University of the Sunshine Coast, Maroochydore BC, Queensland 4558, Australia
| | - Guoying Ni
- Centre for Bio-innovation, University of the Sunshine Coast, Maroochydore BC, Queensland 4558, Australia; Cancer Research Institute, First People's Hospital of Foshan, Guangzhou, Guangdong Province, China
| | - Xiaosong Liu
- Cancer Research Institute, First People's Hospital of Foshan, Guangzhou, Guangdong Province, China
| | - Wei Yang
- School of Stomatology, Zunyi Medical University, Zunyi, Guizhou Province, China; Medical School of Guizhou University, Guiyang, Guizhou Province, China.
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Hillberg AK, Smith MK, Lausen BS, Suwansa-ard S, Johnston R, Mitu SA, MacDonald LE, Zhao M, Motti CA, Wang T, Elizur A, Nakashima K, Satoh N, Cummins SF. Crown-of-thorns starfish spines secrete defence proteins. PeerJ 2023; 11:e15689. [PMID: 37637177 PMCID: PMC10448888 DOI: 10.7717/peerj.15689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 06/14/2023] [Indexed: 08/29/2023] Open
Abstract
Background The crown-of-thorns starfish (COTS; Acanthaster species) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity. Methods Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively. Results We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa (p > 0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (e.g., vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.
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Affiliation(s)
- Adam K. Hillberg
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Meaghan K. Smith
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Blake S. Lausen
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Saowaros Suwansa-ard
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Ryan Johnston
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Shahida A. Mitu
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Leah E. MacDonald
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Min Zhao
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Cherie A. Motti
- Australian Institute of Marine Science, Townsville, Australia
| | - Tianfang Wang
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Abigail Elizur
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Keisuke Nakashima
- Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan
| | - Noriyuki Satoh
- Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa, Japan
| | - Scott F. Cummins
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia
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He T, Du J, Zhu K, Zhou Y, Xiao Z, Liu W, Ren W, Liu X, Chen T, Liu W, Chen Z, Ni G, Liu X, Wang T, Quan J, Zhang P, Yuan J. Experimental study of 131I-caerin 1.1 and 131I-c(RGD) 2 for internal radiation therapy of esophageal cancer xenografts. Biomed Pharmacother 2023; 164:114891. [PMID: 37209630 DOI: 10.1016/j.biopha.2023.114891] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/09/2023] [Accepted: 05/13/2023] [Indexed: 05/22/2023] Open
Abstract
OBJECTIVE The aim of this study was to analyze and compare the therapeutic effects of 131I-caerin 1.1 and 131I-c(RGD)2 on TE-1 esophageal cancer cell xenografts. METHODS (1) The in vitro antitumor effects of the polypeptides caerin 1.1 and c(RGD)2 were verified by MTT and clonogenic assays. 131I-caerin 1.1 and 131I-c(RGD)2 were prepared by chloramine-T (Ch-T) direct labeling, and their basic properties were measured. The binding and elution of 131I-caerin 1.1, 131I-c(RGD)2, and Na131I (control group) in esophageal cancer TE-1 cells were studied through cell binding and elution assays. (2) The antiproliferative effect and cytotoxicity of 131I-caerin 1.1, 131I-c(RGD)2, Na131I, caerin 1.1 and c(RGD)2 on TE-1 cells were detected by Cell Counting Kit-8 (CCK-8) assay. (3) A nude mouse esophageal cancer (TE-1) xenograft model was established to study and compare the efficacy of 131I-caerin 1.1 and 131I-c(RGD)2 in internal radiation therapy for esophageal cancer. RESULTS (1) Caerin 1.1 inhibited the in vitro proliferation of TE-1 cells in a concentration-dependent manner, with an IC50 of 13.00 µg/mL. The polypeptide c(RGD)2 had no evident inhibitory effect on the in vitro proliferation of TE-1 cells. Therefore, the antiproliferative effects of caerin 1.1 and c(RGD)2 on esophageal cancer cells were significantly different (P < 0.05). The clonogenic assay showed that the clonal proliferation of TE-1 cells decreased as the concentration of caerin 1.1 increased. Compared with the control group (drug concentration of 0 µg/mL), the caerin 1.1 group showed significantly lower clonal proliferation of TE-1 cells (P < 0.05). (2) The CCK-8 assay showed that 131I-caerin 1.1 inhibited the in vitro proliferation of TE-1 cells, while 131I-c(RGD)2 had no evident inhibitory effect on proliferation. The two polypeptides showed significantly different antiproliferative effects on esophageal cancer cells at higher concentrations (P < 0.05). Cell binding and elution assays showed that 131I-caerin 1.1 stably bound to TE-1 cells. The cell binding rate of 131I-caerin 1.1 was 15.8 % ± 1.09 % at 24 h and 6.95 % ± 0.22 % after 24 h of incubation and elution. The cell binding rate of 131I-c(RGD)2 was 0.06 % ± 0.02 % at 24 h and 0.23 % ± 0.11 % after 24 h of incubation and elution. (3) In the in vivo experiment, 3 days after the last treatment, the tumor sizes of the phosphate-buffered saline (PBS) group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 68.29 ± 2.67 mm3, 61.78 ± 3.58 mm3, 56.67 ± 5.65 mm3, 58.88 ± 1.71 mm3, 14.40 ± 1.38 mm3, and 60.14 ± 0.47 mm3, respectively. Compared with the other treatment groups, the 131I-caerin 1.1 group had significantly smaller tumor sizes (P < 0.001). After treatment, the tumors were isolated and weighed. The tumor weights in the PBS group, caerin 1.1 group, c(RGD)2 group, 131I group, 131I-caerin 1.1 group, and 131I-c(RGD)2 group were 39.50 ± 9.54 mg, 38.25 ± 5.38 mg, 38.35 ± 9.53 mg, 28.25 ± 8.50 mg, 9.50 ± 4.43 mg, and 34.75 ± 8.06 mg, respectively. The tumor weights in the 131I-caerin 1.1 group were significantly lighter than those in the other groups (P < 0.01). CONCLUSION 131I-caerin 1.1 has tumor-targeting properties, is capable of targeted binding to TE-1 esophageal cancer cells, can be stably retained in tumor cells, and has an evident cytotoxic killing effect, while 131I-c(RGD)2 has no evident cytotoxic effect. 131I-caerin 1.1 better suppressed tumor cell proliferation and tumor growth than pure caerin 1.1, 131I-c(RGD)2, and pure c(RGD)2.
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Affiliation(s)
- Tiantian He
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Juan Du
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Keke Zhu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Yixuan Zhou
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Zewei Xiao
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Wenjie Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Weiwei Ren
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiongying Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Tongsheng Chen
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Wenjuan Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Zhuanming Chen
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Guoying Ni
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiaosong Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Tianfang Wang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China; Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD 4558, Australia; School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore BC, QLD 4558, Australia
| | - Jiangtao Quan
- Department of Radiology, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, China.
| | - Peipei Zhang
- Department of Radiology, The First People's Hospital of Foshan, Foshan, Guangdong, China.
| | - Jianwei Yuan
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
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Yang X, Liu X, Li J, Zhang P, Li H, Chen G, Zhang W, Wang T, Frazer I, Ni G. Caerin 1.1/1.9 Enhances Antitumour Immunity by Activating the IFN-α Response Signalling Pathway of Tumour Macrophages. Cancers (Basel) 2022; 14:cancers14235785. [PMID: 36497272 PMCID: PMC9738106 DOI: 10.3390/cancers14235785] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/09/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022] Open
Abstract
Macrophages are one of the essential components of the tumour microenvironment (TME) of many cancers and show complex heterogeneity and functions. More recent research has been focusing on the characterisation of tumour-associated macrophages (TAMs). Previously, our study demonstrated that caerin 1.1/1.9 peptides significantly improve the therapeutic efficacy of combined specific immunotherapy and immune checkpoint blockade in a murine transplantable tumour model (TC-1). In this study, the mice inoculated with TC-1 tumour were immunised differently. The TAMs were isolated using flow cytometry and characterised by cytokine ELISA. The survival rates of mice with different treatments containing caerin 1.1/19 were assessed comparatively, including those with/without macrophage depletion. The single-cell RNA sequencing (scRNA-seq) data of previous studies were integrated to further reveal the functions of TAMs with the treatments containing caerin 1.1/1.9. As a comparison, the TAMs of stage I and II cervical cancer patients were analysed using scRNA-seq analysis. We demonstrate that caerin induced tumour clearance is associated with infiltration of tumours by IL-12 secreting Ly6C+F4/80+ macrophages exhibiting enhanced IFN-α response signalling, renders animals resistant to further tumour challenge, which is lost after macrophage depletion. Our results indicate that caerin 1.1/1.9 treatment has great potential in improving current immunotherapy efficacy.
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Affiliation(s)
- Xiaodan Yang
- The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China
| | - Xiaosong Liu
- The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan 528000, China
| | - Junjie Li
- The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China
| | - Pingping Zhang
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan 528000, China
| | - Hejie Li
- School of Science, Engineering and Technology, University of the Sunshine Coast, Maroochydore BC, QLD 4558, Australia
| | - Guoqiang Chen
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan 528000, China
| | - Wei Zhang
- The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China
| | - Tianfang Wang
- School of Science, Engineering and Technology, University of the Sunshine Coast, Maroochydore BC, QLD 4558, Australia
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD 4558, Australia
| | - Ian Frazer
- Faculty of Medicine, University of Queensland Diamantina Institute, Translational Research Institute, the University of Queensland, Woolloongabba, QLD 4102, Australia
- Correspondence: (I.F.); (G.N.)
| | - Guoying Ni
- The First Affiliated Hospital, Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510080, China
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan 528000, China
- Correspondence: (I.F.); (G.N.)
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Souza NM, Wang T, Suwansa-Ard S, Nahrung HF, Cummins SF. Ovi-protective mothers: exploring the proteomic profile of weevil ( Gonipterus) egg capsules. Heliyon 2022; 8:e10516. [PMID: 36119877 PMCID: PMC9475328 DOI: 10.1016/j.heliyon.2022.e10516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/22/2022] [Accepted: 08/26/2022] [Indexed: 12/01/2022] Open
Abstract
Insects of different orders produce elaborate structures to protect their eggs from the many threats they may face from the environment and natural enemies. In the weevil genus Gonipterus, their dark, hardened egg capsule is possibly generated by a mixture of the insects' excrement and glandular substances. To test this hypothesis, this study focused on the elucidation of protein components present in the egg capsule cover and interrogated them through comparative analysis and gene expression to help infer potential functions. First, female Gonipterus sp. n. 2 reproductive and alimentary tissues were isolated to establish a reference transcriptome-derived protein database. Then, proteins from weevil frass (excrement) and egg capsule cover were identified through mass spectrometry proteomics. We found that certain egg capsule cover proteins were both exclusive and shared between frass and egg capsule cover, including those of plant origin (e.g. photosystem II protein) and others secreted by the weevil, primarily from reproductive tissue. Among them, a mucin/spidroin-like protein and novel proteins with repetitive units that likely play a structural role were identified. We have confirmed the dual origin of the egg capsule cover substance as a blend of the insects’ frass and secretions. Novel proteins secreted by the weevils are key candidates for holding the egg case cover together.
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Affiliation(s)
- Natalia M Souza
- Tropical Fruit and Market Access RD&E, Horticulture and Forestry Science, Department of Agriculture and Fisheries, Portsmith, QLD 4870, Australia
| | - Tianfang Wang
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore 4558, QLD, Australia.,School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore 4558, QLD, Australia
| | - Saowaros Suwansa-Ard
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore 4558, QLD, Australia
| | - Helen F Nahrung
- Forest Research Institute, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia
| | - Scott F Cummins
- Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore 4558, QLD, Australia.,School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore 4558, QLD, Australia
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8
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Liu N, He T, Xiao Z, Du J, Zhu K, Liu X, Chen T, Liu W, Ni G, Liu X, Wang T, Quan J, Zhang J, Zhang P, Yuan J. 131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer. Front Oncol 2022; 12:861206. [PMID: 36046040 PMCID: PMC9420947 DOI: 10.3389/fonc.2022.861206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 07/21/2022] [Indexed: 11/20/2022] Open
Abstract
Objective To investigate the effect of the 131I-labeled high-affinity peptides Caerin 1.1 and Caerin 1.9 for the treatment of A549 human NSCLC cells. Methods ① 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and plate clone formation assays were performed to confirm the in vitro anti-tumor activity of Caerin 1.1 and Caerin 1.9. ② Chloramine-T was used to label Caerin 1.1 and Caerin 1.9 with 131I, and the Cell Counting Kit 8 assay was performed to analyze the inhibitory effect of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9 on the proliferation of NSCLC cells. An A549 NSCLC nude mouse model was established to investigate the in vivo anti-tumor activity of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9. Results ① Caerin 1.1 and Caerin 1.9 inhibited the proliferation of NSCLC cells in vitro in a concentration-dependent manner. The half-maximal inhibitory concentration was 16.26 µg/ml and 17.46 µg/ml, respectively, with no significant intergroup difference (P>0.05). ② 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 were equally effective and were superior to their unlabeled versions in their ability to inhibit the proliferation and growth of NSCLC cells (P>0.05). Conclusions 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 inhibit the proliferation and growth of NSCLC cells and may become potential treatments for NSCLC.
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Affiliation(s)
- Na Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Tiantian He
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Zewei Xiao
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Juan Du
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Keke Zhu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiongying Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Tongsheng Chen
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Wenjuan Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Guoying Ni
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiaosong Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- Thoracic and Abdominal Radiotherapy Department, The First People’s Hospital of Foshan, Foshan, China
| | - Tianfang Wang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- Genecology Research Centre, University of the Sunshine Coast, Sunshine Coast, QLD, Australia
| | - Jiangtao Quan
- Department of Nuclear Medicine, General Hospital of the Southern Theatre Command, People’s Liberation Army of China, Guangzhou, China
| | - Jinhe Zhang
- Department of Nuclear Medicine, General Hospital of the Southern Theatre Command, People’s Liberation Army of China, Guangzhou, China
- *Correspondence: Jinhe Zhang, ; Peipei Zhang, ; Jianwei Yuan,
| | - Peipei Zhang
- Thoracic and Abdominal Radiotherapy Department, The First People’s Hospital of Foshan, Foshan, China
- *Correspondence: Jinhe Zhang, ; Peipei Zhang, ; Jianwei Yuan,
| | - Jianwei Yuan
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
- *Correspondence: Jinhe Zhang, ; Peipei Zhang, ; Jianwei Yuan,
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9
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de Amaral M, Ienes-Lima J. Anurans against SARS-CoV-2: A review of the potential antiviral action of anurans cutaneous peptides. Virus Res 2022; 315:198769. [PMID: 35430319 PMCID: PMC9008983 DOI: 10.1016/j.virusres.2022.198769] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/05/2022] [Accepted: 04/06/2022] [Indexed: 01/17/2023]
Abstract
At the end of 2019, in China, clinical signs and symptoms of unknown etiology have been reported in several patients whose sample sequencing revealed pneumonia caused by the SARS-CoV-2 virus. COVID-19 is a disease triggered by this virus, and in 2020, the World Health Organization declared it a pandemic. Since then, efforts have been made to find effective therapeutic agents against this disease. Identifying novel natural antiviral drugs can be an alternative to treatment. For this reason, antimicrobial peptides secreted by anurans' skin have gained attention for showing a promissory antiviral effect. Hence, this review aimed to elucidate how and which peptides secreted by anurans' skin can be considered therapeutic agents to treat or prevent human viral infectious diseases. Through a literature review, we attempted to identify potential antiviral frogs' peptides to combat COVID-19. As a result, the Magainin-1 and -2 peptides, from the Magainin family, the Dermaseptin-S9, from the Dermaseptin family, and Caerin 1.6 and 1.10, from the Caerin family, are molecules that already showed antiviral effects against SARS-CoV-2 in silico. In addition to these peptides, this review suggests that future studies should use other families that already have antiviral action against other viruses, such as Brevinins, Maculatins, Esculentins, Temporins, and Urumins. To apply these peptides as therapeutic agents, experimental studies with peptides already tested in silico and new studies with other families not tested yet should be considered.
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Affiliation(s)
- Marjoriane de Amaral
- Comparative Metabolism and Endocrinology Laboratory, Department of Physiology, Federal University of Rio Grande do Sul (UFRGS), Sarmento Leite, 500, Porto Alegre, Rio Grande do Sul 90050-170, Brazil.
| | - Julia Ienes-Lima
- Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, United States
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10
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Whaite A, Klein A, Mitu S, Wang T, Elizur A, Cummins S. The byssal-producing glands and proteins of the silverlip pearl oyster Pinctada maxima (Jameson, 1901). BIOFOULING 2022; 38:186-206. [PMID: 35282730 DOI: 10.1080/08927014.2022.2049256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 02/22/2022] [Accepted: 02/28/2022] [Indexed: 06/14/2023]
Abstract
Pinctada maxima are most well known for their production of high-quality natural pearls. They also generate another natural material, the byssus, an adhesive thread critical for steadfast attachment underwater. Herein, P. maxima byssal threads were analysed via proteotranscriptomics to reveal 49 proteins. Further characterisation was undertaken on five highly expressed genes: glycine-rich thread protein (GRT; also known as PUF3), apfp1/perlucin-like protein (Pmfp1); peroxidase; thrombospondin 1, and Balbiani ring 3 (BR3), which showed localised tissue expression. The spatial distribution of GRT and Pmfp1 via immunodetection combined with histology helped to identify glandular regions of the foot that contribute to byssal thread production: the byssal gland, the duct gland, and two thread-forming glands of basophilic and acidophilic serous-like cells. This work advanced primary knowledge on the glands involved in the creation of byssal threads and the protein composition of the byssus for P. maxima, providing a platform for the design of marine biopolymers.
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Affiliation(s)
- Alessandra Whaite
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
| | - Anne Klein
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
| | - Shahida Mitu
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
| | - Abigail Elizur
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
| | - Scott Cummins
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
- School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland, Australia
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11
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Ni G, Liu X, Li H, Fogarty CE, Chen S, Zhang P, Liu Y, Wu X, Wei MQ, Chen G, Zhang P, Wang T. Topical Application of Temperature-Sensitive Gel Containing Caerin 1.1 and 1.9 Peptides on TC-1 Tumour-Bearing Mice Induced High-Level Immune Response in the Tumour Microenvironment. Front Oncol 2021; 11:754770. [PMID: 34858827 PMCID: PMC8632150 DOI: 10.3389/fonc.2021.754770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 10/11/2021] [Indexed: 01/22/2023] Open
Abstract
The development of topical cream drugs that increase the immune activation of tumour-infiltrating lymphocytes against tumour and chronic viral infection-associated lesions is of great immunotherapeutic significance. This study demonstrates that the topical application of a temperature-sensitive gel containing caerin 1.1 and 1.9 peptides reduces nearly 50% of the tumour weight of HPV16 E6/E7-transformed TC-1 tumour-bearing mice via improving the tumour microenvironment. Confocal microscopy confirms the time-dependent penetration of caerin 1.9 through the epidermal layer of the ear skin structure of mice. Single-cell transcriptomic analysis shows that the caerin 1.1/1.9 gel expands the populations with high immune activation level and largely stimulates the pro-inflammatory activity of NK and dendritic cells. Closely associated with INFα response, Cebpb seems to play a key role in altering the function of all Arg1hi macrophages in the caerin group. In addition, the caerin gel treatment recruits almost two-fold more activated CD8+ T cells to the TME, relative to the untreated tumour, which shows a synergistic effect derived from the regulation of S1pr1, Ccr7, Ms4a4b and Gimap family expression. The TMT10plex-labelling proteomic quantification further demonstrates the activation of interferon-alpha/beta secretion and response to cytokine stimulus by the caerin gel, while the protein contents of several key regulators were elevated by more than 30%, such as Cd5l, Gzma, Ifit1, Irf9 and Stat1. Computational integration of the proteome with the single-cell transcriptome consistently suggested greater activation of NK and T cells with the topical application of caerin peptide gel.
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Affiliation(s)
- Guoying Ni
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China.,Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, QLD, Australia.,Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.,The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University , Guangzhou, China
| | - Xiaosong Liu
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China.,Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, QLD, Australia
| | - Hejie Li
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, QLD, Australia.,School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD, Australia
| | - Conor E Fogarty
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, QLD, Australia.,School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD, Australia
| | - Shu Chen
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China
| | - Pingping Zhang
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China
| | - Ying Liu
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China
| | - Xiaolian Wu
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China
| | - Ming Q Wei
- Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia
| | - Guoqiang Chen
- Cancer Research Institute, First People's Hospital of Foshan, Foshan, China
| | - Ping Zhang
- Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, QLD, Australia.,School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD, Australia
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12
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Chen S, Zhang P, Xiao L, Liu Y, Wu K, Ni G, Li H, Wang T, Wu X, Chen G, Liu X. Caerin 1.1 and 1.9 Peptides from Australian Tree Frog Inhibit Antibiotic-Resistant Bacteria Growth in a Murine Skin Infection Model. Microbiol Spectr 2021; 9:e0005121. [PMID: 34259550 PMCID: PMC8552723 DOI: 10.1128/spectrum.00051-21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/18/2021] [Indexed: 01/04/2023] Open
Abstract
The host defense peptide caerin 1.9 was originally isolated from skin secretions of an Australian tree frog and inhibits the growth of a wide range of bacteria in vitro. In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such as Staphylococcus aureus, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus haemolyticus in vitro. Importantly, unlike the antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds of in vitro culture. Moreover, caerin 1.1, another peptide of the caerin family, has an additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature-sensitive gel inhibit MRSA growth in a skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 peptides could be considered an alternative for conventional antibiotics. IMPORTANCE Antibiotic-resistant bacteria cause severe problems in the clinic. We show in our paper that two short peptides isolated from an Australian frog and prepared in the form of a gel are able to inhibit the growth of antibiotic-resistant bacteria in mice, and, unlike antibiotics, these peptides do not lead to the development of peptide-resistant bacteria strains.
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Affiliation(s)
- Shu Chen
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Pingping Zhang
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Liyin Xiao
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Ying Liu
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Kuihai Wu
- Clinical Microbiological Laboratory, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Guoying Ni
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
- Department of Rheumatology, Foshan Frist People’s Hospital, Foshan, Guangdong, China
| | - Hejie Li
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Xiaolian Wu
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
| | - Guoqiang Chen
- Department of Rheumatology, Foshan Frist People’s Hospital, Foshan, Guangdong, China
| | - Xiaosong Liu
- Cancer Research Institute, Foshan First People’s Hospital, Foshan, Guangdong, China
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
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13
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Ni G, Yang X, Li J, Wu X, Liu Y, Li H, Chen S, Fogarty CE, Frazer IH, Chen G, Liu X, Wang T. Intratumoral injection of caerin 1.1 and 1.9 peptides increases the efficacy of vaccinated TC-1 tumor-bearing mice with PD-1 blockade by modulating macrophage heterogeneity and the activation of CD8 + T cells in the tumor microenvironment. Clin Transl Immunology 2021; 10:e1335. [PMID: 34429969 PMCID: PMC8369845 DOI: 10.1002/cti2.1335] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 06/25/2021] [Accepted: 08/05/2021] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES Developing a vaccine formula that alters the tumor-infiltrating lymphocytes to be more immune active against a tumor is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen-specific immunotherapy, and IL-10 and PD-1 blockade, intratumoral administration of caerin 1.1/1.9 peptides improves TC-1 tumor microenvironment (TME) to be more immune active than injection of a control peptide. METHODS We compared the survival time of vaccinated TC-1 tumor-bearing mice with PD-1 and IL-10 blockade, in combination with a further injection of caerin 1.1/1.9 or control peptides. The tumor-infiltrating haematopoietic cells were examined by flow cytometry. Single-cell transcriptomics and proteomics were used to quantify changes in cellular activity across different cell types within the TME. RESULTS The injection of caerin 1.1/1.9 increased the efficacy of vaccinated TC-1 tumor-bearing mice with anti-PD-1 treatment and largely expanded the populations of macrophages and NK cells with higher immune activation level, while reducing immunosuppressive macrophages. More activated CD8+ T cells were induced with higher populations of memory and effector-memory CD8+ T subsets. Computational integration of the proteome with the single-cell transcriptome supported activation of Stat1-modulated apoptosis and significant reduction in immune-suppressive B-cell function following caerin 1.1 and 1.9 treatment. CONCLUSIONS Caerin 1.1/1.9-containing treatment results in improved antitumor responses. Harnessing the novel candidate genes preferentially enriched in the immune active cell populations may allow further exploration of distinct macrophages, T cells and their functions in TC-1 tumors.
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Affiliation(s)
- Guoying Ni
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
- Genecology Research CentreUniversity of the Sunshine CoastMaroochydore DCQLDAustralia
- The First Affiliated Hospital/Clinical Medical SchoolGuangdong Pharmaceutical UniversityGuangzhouChina
| | - Xiaodan Yang
- The First Affiliated Hospital/Clinical Medical SchoolGuangdong Pharmaceutical UniversityGuangzhouChina
| | - Junjie Li
- The First Affiliated Hospital/Clinical Medical SchoolGuangdong Pharmaceutical UniversityGuangzhouChina
| | - Xiaolian Wu
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
| | - Ying Liu
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
| | - Hejie Li
- Genecology Research CentreUniversity of the Sunshine CoastMaroochydore DCQLDAustralia
| | - Shu Chen
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
| | - Conor E Fogarty
- Genecology Research CentreUniversity of the Sunshine CoastMaroochydore DCQLDAustralia
| | - Ian H Frazer
- Faculty of MedicineUniversity of Queensland Diamantina InstituteTranslational Research InstituteThe University of QueenslandWoolloongabbaQLDAustralia
| | - Guoqiang Chen
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
| | - Xiaosong Liu
- Cancer Research InstituteFirst People’s Hospital of FoshanFoshanGuangdongChina
- Genecology Research CentreUniversity of the Sunshine CoastMaroochydore DCQLDAustralia
- The First Affiliated Hospital/Clinical Medical SchoolGuangdong Pharmaceutical UniversityGuangzhouChina
| | - Tianfang Wang
- Genecology Research CentreUniversity of the Sunshine CoastMaroochydore DCQLDAustralia
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14
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Lin R, Ma B, Liu N, Zhang L, He T, Liu X, Chen T, Liu W, Liang Y, Wang T, Ni G, Liu X, Yang N, Zhang J, Yuan J. Targeted radioimmunotherapy with the iodine-131-labeled caerin 1.1 peptide for human anaplastic thyroid cancer in nude mice. Ann Nucl Med 2021; 35:811-822. [PMID: 33948902 PMCID: PMC8197720 DOI: 10.1007/s12149-021-01618-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 04/20/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The combination of two or more drugs with different mechanisms is a promising strategy for cancer treatment, and radioimmunotherapy (RIT) is a trending antitumor strategy. Radiotherapy (RT) can promote and activate antitumor immune effects, and immunotherapy can strengthen the effects of selective internal radiotherapy (SIRT); the RIT combination is synergistic and can overcome the adverse side effects of monotherapy. In this study, we developed a radioimmunoconjugate (RIC)-the iodine-131 (131I)-labeled caerin 1.1 peptide-to treat human anaplastic thyroid cancer (ATC). METHODS Antitumor activity of caerin 1.1 peptide was determined by MTT assay, plate colony formation and cell wound scratch assays, and the mechanism of the inhibition of carein 1.1 peptide on the growth of CAL-62 cells was identified by cell cycle and western blot. Then, we investigated the efficacy of the caerin 1.1 peptide as a single drug and the 131I-labeled caerin 1.1 peptide for ATC. H&E and TUNEL staining was performed to detect dead cells in the tumor tissue sections. RESULTS We found that caerin 1.1 arrested cells in the S phase to induce apoptosis and inhibited tumor growth to inhibit phosphorylation of Akt. In vivo, the iodine-131 (131I)-labeled caerin 1.1 peptide achieved better antitumor efficacy than radiotherapy alone and showed a good biosafety profile. CONCLUSIONS Our study demonstrates for the first time that the iodine-131 (131I)-labeled caerin 1.1 peptide can inhibit CAL-62 tumor growth and migration. The iodine-131 (131I)-labeled caerin 1.1 peptide, which represents a radioimmunotherapy strategy based on the combination of SIRT with a peptide-drug conjugate, could provide a treatment means for the radical cure of ATC.
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Affiliation(s)
- Ruoting Lin
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Bowei Ma
- Department of TCM Resident Training, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, Guangdong, China
| | - Na Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Lu Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Tiantian He
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Xiongying Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Tongsheng Chen
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Wenjuan Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Yongnan Liang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Tianfang Wang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
- Genecology Research Centre, University of Sunshine Coast, Maroochydore DC, QLD, 4558, Australia
| | - Guoying Ni
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
- Genecology Research Centre, University of Sunshine Coast, Maroochydore DC, QLD, 4558, Australia
| | - Xiaosong Liu
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
- The First People's Hospital of Foshan, Foshan, 528000, Guangdong, China
- Genecology Research Centre, University of Sunshine Coast, Maroochydore DC, QLD, 4558, Australia
| | - Ning Yang
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China
| | - Jinhe Zhang
- Department of Nuclear Medicine, General Hospital of the Southern Theatre Command, People's Liberation Army of China, Guangzhou, 510010, Guangdong, China
| | - Jianwei Yuan
- Department of Nuclear Medicine, The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, Guangdong, China.
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15
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Ni G, Chen S, Chen M, Wu J, Yang B, Yuan J, Walton SF, Li H, Wei MQ, Wang Y, Chen G, Liu X, Wang T. Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells. Front Cell Dev Biol 2020; 8:676. [PMID: 32850805 PMCID: PMC7412766 DOI: 10.3389/fcell.2020.00676] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 07/03/2020] [Indexed: 01/07/2023] Open
Abstract
Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.
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Affiliation(s)
- Guoying Ni
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
- The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China
| | - Shu Chen
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
| | - Mo Chen
- Menzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, Australia
| | - Jialing Wu
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
| | - Binbin Yang
- Menzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, Australia
- Department of Laboratory Medicine, Institute of Nanomedicine Technology, Weifang Medical University, Weifang, China
| | - Jianwei Yuan
- The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China
| | - Shelley F. Walton
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
| | - Hejie Li
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
- Department of Mechanical and Biofunctional System, Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
| | - Ming Q. Wei
- Menzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, Australia
| | - Yuejian Wang
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
| | - Guoqiang Chen
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
| | - Xiaosong Liu
- Cancer Research Institute, First People’s Hospital of Foshan, Foshan, China
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
- The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, Australia
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16
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Ma B, Yuan J, Chen S, Huang K, Wang Q, Ma J, Lin R, Zhang L, Zhou Y, Wang T, Walton SF, Pan X, Chen G, Wang Y, Ni G, Liu X. Topical application of temperature-sensitive caerin 1.1 and 1.9 gel inhibits TC-1 tumor growth in mice. Am J Transl Res 2020; 12:191-202. [PMID: 32051748 PMCID: PMC7013226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 01/02/2020] [Indexed: 06/10/2023]
Abstract
Genital warts, which are one of the most common sexually transmitted diseases (STDs), result from persistent infection with human papillomavirus (HPV), especially subtypes 6 or 11. Topical application of 5% imiquimod cream is currently recommended as a first-line treatment choice for genital warts, but the clearance and patient compliance rates remain less than sufficient. In the current study, we developed a temperature-sensitive gel that contains the host-defense peptides caerin 1.1 and 1.9, which were originally isolated from Australian tree frogs of the genus Litoria. Growth of HPV16 E6/E7-transformed TC-1 cells was inhibited in vitro and in vivo following injection of the tumor with the caerin gel in a TC-1 tumor mouse model. Furthermore, when the caerin gel was topically applied, the inhibitory effect remained, and T, NK cells were attracted to the tumor site. In addition, the gel maintained a similar level of bioactivity after incubation at room temperature for 30 days. Our results suggest that this caerin gel, following further optimization, may provide an alternative method for the management of genital warts.
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Affiliation(s)
- Bowei Ma
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Jianwei Yuan
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Shu Chen
- Cancer Research Institute, Foshan First People’s HospitalFoshan 528000, Guangdong, China
| | - Kunsong Huang
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Qianbo Wang
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Jianchun Ma
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Ruoting Lin
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Lu Zhang
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Yingying Zhou
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Tianfang Wang
- Genecology Research Centre, University of Sunshine CoastMaroochydore DC, QLD 4558, Australia
| | - Shelley F Walton
- Inflammation and Healing Research Cluster, School of Health and Sport Sciences, University of Sunshine CoastMaroochydore DC, QLD 4558, Australia
| | - Xuan Pan
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
| | - Guoqiang Chen
- Cancer Research Institute, Foshan First People’s HospitalFoshan 528000, Guangdong, China
| | - Yuejian Wang
- Cancer Research Institute, Foshan First People’s HospitalFoshan 528000, Guangdong, China
| | - Guoying Ni
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
- Inflammation and Healing Research Cluster, School of Health and Sport Sciences, University of Sunshine CoastMaroochydore DC, QLD 4558, Australia
- Genecology Research Centre, University of Sunshine CoastMaroochydore DC, QLD 4558, Australia
| | - Xiaosong Liu
- The First Affiliated Hospital/Clinical Medical School, Department of Nuclear Medicine, Guangdong Pharmaceutical UniversityGuangzhou 510080, Guangdong, China
- Cancer Research Institute, Foshan First People’s HospitalFoshan 528000, Guangdong, China
- Inflammation and Healing Research Cluster, School of Health and Sport Sciences, University of Sunshine CoastMaroochydore DC, QLD 4558, Australia
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17
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Chieu HD, Suwansa-Ard S, Wang T, Elizur A, Cummins SF. Identification of neuropeptides in the sea cucumber Holothuria leucospilota. Gen Comp Endocrinol 2019; 283:113229. [PMID: 31348958 DOI: 10.1016/j.ygcen.2019.113229] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 07/17/2019] [Accepted: 07/22/2019] [Indexed: 12/17/2022]
Abstract
Neuropeptides play important roles in the regulation of physiological processes such as growth, metabolism and reproduction. In sea cucumbers (Phylum Echinodermata), numerous neuropeptides have been identified and some are attributed to reproductive processes. In this study, our goal was to gain a better understanding of the neuropeptide repertoire for the black sea cucumber Holothuria leucospilota, a species that has been severely overfished from the wild due to human consumption. We applied in silico transcriptome analysis of the adult H. leucospilota radial nerve cord, gonad and body wall to elucidate 35 neuropeptides that are conserved throughout the Bilateria. Then, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of radial nerve cord was employed and showed an additional 8 putative novel neuropeptide precursors, whose predicative cleaved peptides do not share sequence similarity with any reported neuropeptides. These data provide an important basis for experimental approaches to manipulate H. leucospilota broodstock reproduction and growth in culture, which will hopefully re-establish population numbers.
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Affiliation(s)
- Hoang Dinh Chieu
- Genecology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia; Research Institute for Marine Fisheries (RIMF), 224 LeLai Street, HaiPhong City, Viet Nam
| | - Saowaros Suwansa-Ard
- Genecology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Abigail Elizur
- Genecology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Scott F Cummins
- Genecology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia.
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18
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Smith MK, Chieu HD, Aizen J, Mos B, Motti CA, Elizur A, Cummins SF. A Crown-of-Thorns Seastar recombinant relaxin-like gonad-stimulating peptide triggers oocyte maturation and ovulation. Gen Comp Endocrinol 2019; 281:41-48. [PMID: 31102581 DOI: 10.1016/j.ygcen.2019.05.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 05/04/2019] [Accepted: 05/14/2019] [Indexed: 12/31/2022]
Abstract
The Acanthaster planci species-complex [Crown-of-Thorns Seastar (COTS)] are highly fecund echinoderms that exhibit population outbreaks on coral reef ecosystems worldwide, including the Australian Great Barrier Reef. A better understanding of the COTS molecular biology is critical towards efforts in controlling outbreaks and assisting reef recovery. In seastars, the heterodimeric relaxin-like gonad stimulating peptide (RGP) is responsible for triggering a neuroendocrine cascade that regulates resumption of oocyte meiosis prior to spawning. Our comparative RNA-seq analysis indicates a general increase in RGP gene expression in the female radial nerve cord during the reproductive season. Also, the sensory tentacles demonstrate a significantly higher expression level than radial nerve cord. A recombinant COTS RGP, generated in a yeast expression system, is highly effective in inducing oocyte germinal vesicle breakdown (GVBD), followed by ovulation from ovarian fragments. The findings of this study provide a foundation for more in-depth molecular analysis of the reproductive neuroendocrine physiology of the COTS and the RGP.
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Affiliation(s)
- Meaghan K Smith
- GeneCology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Hoang Dinh Chieu
- GeneCology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Joseph Aizen
- The School of Marine Science, Ruppin Academic Centre, 4029700 Michmoret, Israel; GeneCology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Benjamin Mos
- National Marine Science Centre, Southern Cross University, 2 Bay Drive, Coffs Harbour, NSW 2450, Australia
| | - Cherie A Motti
- Australian Institute of Marine Science (AIMS), Cape Ferguson, Townsville, Queensland 4810, Australia
| | - Abigail Elizur
- GeneCology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia
| | - Scott F Cummins
- GeneCology Research Centre, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland 4556, Australia.
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19
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Pan X, Ma B, You X, Chen S, Wu J, Wang T, Walton SF, Yuan J, Wu X, Chen G, Wang Y, Ni G, Liu X. Synthesized natural peptides from amphibian skin secretions increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 19:163. [PMID: 31277636 PMCID: PMC6612097 DOI: 10.1186/s12906-019-2571-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 06/19/2019] [Indexed: 02/01/2023]
Abstract
Background Therapeutic vaccines against cervical cancer remain ineffective. Previously, we demonstrated that blocking the signalling of a cytokine, interleukin 10, at the time of immunisation elicited significantly higher numbers of antigen specific T cells and inhibited tumour growth in mice. Results In the current paper, we demonstrate, in a HPV16 E6/E7 transformed TC-1 tumour mouse model, that despite increased antigen specific T cell numbers, blocking IL-10 signalling at the time of immunisation does not increase the survival time of the TC-1 tumour bearing mice compared to mice receiving the same immunisation with no IL-10 signalling blockade. Moreover, the function of tumour infiltrating T cells isolated 3 weeks post TC-1 transplantation is more suppressed than those isolated 2 weeks after tumour inoculation. We demonstrate that synthesized caerin peptides, derived from amphibian skin secretions, 1) were able to inhibit TC-1 tumour growth both in vitro and in vivo; 2) are environmentally stable; and 3) promote the secretion of pro-inflammatory interlukine-6 by TC-1 cells. Notably caerin peptides were able to increase the survival time of TC-1 tumour bearing mice after therapeutic vaccination with a HPV16E7 peptide-based vaccine containing IL-10 inhibitor, via recruiting increased levels of T cells to the tumour site. Conclusion Caerin peptides increase the efficacy of a therapeutic vaccine by recruiting more T cells to the tumour site.
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20
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Comparative proteomic study reveals the enhanced immune response with the blockade of interleukin 10 with anti-IL-10 and anti-IL-10 receptor antibodies in human U937 cells. PLoS One 2019; 14:e0213813. [PMID: 30897137 PMCID: PMC6428271 DOI: 10.1371/journal.pone.0213813] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 03/01/2019] [Indexed: 01/25/2023] Open
Abstract
Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes.
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21
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Chieu HD, Turner L, Smith MK, Wang T, Nocillado J, Palma P, Suwansa-Ard S, Elizur A, Cummins SF. Aquaculture Breeding Enhancement: Maturation and Spawning in Sea Cucumbers Using a Recombinant Relaxin-Like Gonad-Stimulating Peptide. Front Genet 2019; 10:77. [PMID: 30838021 PMCID: PMC6389678 DOI: 10.3389/fgene.2019.00077] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Accepted: 01/28/2019] [Indexed: 12/22/2022] Open
Abstract
Wild sea cucumber resources have been rapidly exhausted and therefore there is an urgent need to develop approaches that will help restocking. Currently, there is a lack of information regarding the genes involved in sea cucumber reproductive processes. The neurohormone relaxin-like gonad-stimulating peptide (RGP) has been identified as the active gonad-stimulating peptide in sea stars (Asteroidea), which could also be present in other echinoderm groups. In this study, a sea cucumber RGP was identified and confirmed by phylogenetic analysis. A recombinant Holothuria scabra RGP was produced in the yeast Pichia pastoris and confirmed by mass spectrometry. To assess bioactivity, four levels of purification were tested in an in vitro germinal vesicle breakdown (GVBD) bioassay. The most pure form induced 98.56 ± 1.19% GVBD in H. scabra and 89.57 ± 1.19% GVBD in Holothuria leucospilota. Cruder levels of purification still resulted in some GVBD. Upon single injection into female H. scabra, the recombinant RGP induced head waving behavior followed by spawning within 90–170 min. Spawned oocytes were fertilized successfully, larvae settled and developed into juveniles. Our results provide a key finding for the development of a break-through new artificial breeding approach in sea cucumber aquaculture.
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Affiliation(s)
- Hoang Dinh Chieu
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia.,Research Institute for Marine Fisheries, HaiPhong, Vietnam
| | - Luke Turner
- Tasmanian Seafoods Pty. Ltd., Smithton, TAS, Australia
| | - Meaghan K Smith
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Tianfang Wang
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Josephine Nocillado
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Peter Palma
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia.,Aquaculture Department, Southeast Asian Fisheries Development Center, Iloilo, Philippines
| | - Saowaros Suwansa-Ard
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Abigail Elizur
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Scott F Cummins
- Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD, Australia
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