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Carrasco-Mantis A, Reina-Romo E, Sanz-Herrera JA. A multiphysics hybrid continuum - agent-based model of in vitro vascularized organoids. Comput Biol Med 2025; 185:109559. [PMID: 39709871 DOI: 10.1016/j.compbiomed.2024.109559] [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: 10/11/2024] [Revised: 12/02/2024] [Accepted: 12/08/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Organoids are 3D in vitro models that fulfill a hierarchical function, representing a small version of living tissues and, therefore, a good approximation of cellular mechanisms. However, one of the main disadvantages of these models is the appearance of a necrotic core due to poor vascularization. The aim of this work is the development of a numerical framework that incorporates the mechanical stimulation as a key factor in organoid vascularization. Parameters, such as fluid velocity and nutrient consumption, are analyzed along the organoid evolution. METHODS The mathematical model created for this purpose combines continuum and discrete approaches. In the continuum part, the fluid flow and the diffusion of oxygen and nutrients are modeled using a finite element method approach. Meanwhile, the growth of the organoid, blood vessel evolution, as well as their interaction with the surrounding environment, are modeled using agent-based methods. RESULTS Continuum model outcomes include the distribution of shear stress, pressure and fluid velocity around the organoid surface, in addition to the concentration of oxygen and nutrients in its interior. The agent models account for cell proliferation, differentiation, organoid growth and blood vessel morphology, for the different case studies considered. CONCLUSIONS Two main conclusions are achieved in this work: (i) the results of the study quantitatively predict in vitro data, with an enhanced blood vessel invasion under high fluid flow and (ii) the diffusion and consumption model parameters of the organoid cells determine the thickness of the proliferative, quiescent, hypoxic and necrotic layers.
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Affiliation(s)
| | - Esther Reina-Romo
- Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Spain
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Liu YY, Wu DK, Chen JB, Tang YM, Jiang F. Advances in the study of gastric organoids as disease models. World J Gastrointest Oncol 2024; 16:1725-1736. [PMID: 38764838 PMCID: PMC11099456 DOI: 10.4251/wjgo.v16.i5.1725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/23/2024] [Accepted: 03/25/2024] [Indexed: 05/09/2024] Open
Abstract
Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.
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Affiliation(s)
- Yi-Yang Liu
- Graduate School, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - De-Kun Wu
- Teaching Experiment and Training Center, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - Ji-Bing Chen
- Central Laboratory, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - You-Ming Tang
- Department of Digestive Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - Feng Jiang
- AIDS Research Center, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
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Lin YC, Ku CC, Wuputra K, Liu CJ, Wu DC, Satou M, Mitsui Y, Saito S, Yokoyama KK. Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells. Int J Mol Sci 2024; 25:5177. [PMID: 38791215 PMCID: PMC11120835 DOI: 10.3390/ijms25105177] [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: 03/16/2024] [Revised: 04/29/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.
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Affiliation(s)
- Ying-Chu Lin
- School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Cha-Chien Ku
- Graduate Institute of Medicine, Department of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-C.K.); (K.W.)
- Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
| | - Kenly Wuputra
- Graduate Institute of Medicine, Department of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-C.K.); (K.W.)
- Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
- Waseda Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan
| | - Chung-Jung Liu
- Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (D.-C.W.)
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
| | - Deng-Chyang Wu
- Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (D.-C.W.)
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
| | - Maki Satou
- Research Institute, Horus Co., Ltd., Iruma 358-0032, Saitama, Japan; (M.S.); (Y.M.)
| | - Yukio Mitsui
- Research Institute, Horus Co., Ltd., Iruma 358-0032, Saitama, Japan; (M.S.); (Y.M.)
| | - Shigeo Saito
- Graduate Institute of Medicine, Department of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-C.K.); (K.W.)
- Research Institute, Horus Co., Ltd., Iruma 358-0032, Saitama, Japan; (M.S.); (Y.M.)
- Saito Laboratory of Cell Technology, Yaita 329-1571, Tochigi, Japan
| | - Kazunari K. Yokoyama
- School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Department of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-C.K.); (K.W.)
- Regenerative Medicine and Cell Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-J.L.); (D.-C.W.)
- Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
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Cen C, Du Q, Luo B, Wang T, Su J, Qin X, Zhang W, Lu L, Liao Y, Huang Y, Liang Y. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients. Open Life Sci 2024; 19:20220839. [PMID: 38585629 PMCID: PMC10997148 DOI: 10.1515/biol-2022-0839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 01/25/2024] [Accepted: 02/06/2024] [Indexed: 04/09/2024] Open
Abstract
Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori (H. pylori) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group, Helicobacter, Bacteroides, Klebsiella, and Pseudomonas. In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori-positive (HP_Pos) and H. pylori-negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.
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Affiliation(s)
- Chao Cen
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Qiuying Du
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Bin Luo
- Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Tonghua Wang
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Jianwei Su
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Xiaoshan Qin
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Wenyan Zhang
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Lijing Lu
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Yang Liao
- Graduate School of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
| | - Yanqiang Huang
- Department of Pathogen Biology and Immunology, Youjiang Medical University for Nationalities School of Basic Medical Sciences, Baise, Guangxi 533000, China
| | - Yumei Liang
- Department of Neonatology, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18, Zhongshan Second Road, Youjiang District, Baise, Guangxi 533000, China
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Ma X, Wang Q, Li G, Li H, Xu S, Pang D. Cancer organoids: A platform in basic and translational research. Genes Dis 2024; 11:614-632. [PMID: 37692477 PMCID: PMC10491878 DOI: 10.1016/j.gendis.2023.02.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 02/16/2023] [Indexed: 09/12/2023] Open
Abstract
An accumulation of previous work has established organoids as good preclinical models of human tumors, facilitating translation from basic research to clinical practice. They are changing the paradigm of preclinical cancer research because they can recapitulate the heterogeneity and pathophysiology of human cancers and more closely approximate the complex tissue environment and structure found in clinical tumors than in vitro cell lines and animal models. However, the potential applications of cancer organoids remain to be comprehensively summarized. In the review, we firstly describe what is currently known about cancer organoid culture and then discuss in depth the basic mechanisms, including tumorigenesis and tumor metastasis, and describe recent advances in patient-derived tumor organoids (PDOs) for drug screening and immunological studies. Finally, the present challenges faced by organoid technology in clinical practice and its prospects are discussed. This review highlights that organoids may offer a novel therapeutic strategy for cancer research.
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Affiliation(s)
- Xin Ma
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
| | - Qin Wang
- Sino-Russian Medical Research Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
- Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150086, China
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, Heilongjiang 150086, China
| | - Guozheng Li
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
| | - Hui Li
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
| | - Shouping Xu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
- Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150086, China
| | - Da Pang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
- Sino-Russian Medical Research Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
- Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150086, China
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Chehelgerdi M, Behdarvand Dehkordi F, Chehelgerdi M, Kabiri H, Salehian-Dehkordi H, Abdolvand M, Salmanizadeh S, Rashidi M, Niazmand A, Ahmadi S, Feizbakhshan S, Kabiri S, Vatandoost N, Ranjbarnejad T. Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy. Mol Cancer 2023; 22:189. [PMID: 38017433 PMCID: PMC10683363 DOI: 10.1186/s12943-023-01873-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/27/2023] [Indexed: 11/30/2023] Open
Abstract
The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical and social implications, and the comparative analysis with other stem cell types for cancer treatment. The article will also discuss the applications of iPSCs in tumorigenesis, the future of iPSCs in tumorigenesis research, and highlight successful case studies utilizing iPSCs in tumorigenesis research. The conclusion will summarize the advancements made in iPSC-based tumorigenesis research and the importance of continued investment in iPSC research to unlock the full potential of these cells.
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Affiliation(s)
- Matin Chehelgerdi
- Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Fereshteh Behdarvand Dehkordi
- Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Mohammad Chehelgerdi
- Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran.
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
| | - Hamidreza Kabiri
- Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | | | - Mohammad Abdolvand
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Sharareh Salmanizadeh
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar-Jereeb Street, Isfahan, 81746-73441, Iran
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
- The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Anoosha Niazmand
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Saba Ahmadi
- Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia
| | - Sara Feizbakhshan
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Saber Kabiri
- Novin Genome (NG) Lab, Research and Development Center for Biotechnology, Shahrekord, Iran
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Nasimeh Vatandoost
- Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Tayebeh Ranjbarnejad
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
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Zhou B, Feng Z, Xu J, Xie J. Organoids: approaches and utility in cancer research. Chin Med J (Engl) 2023; 136:1783-1793. [PMID: 37365679 PMCID: PMC10406116 DOI: 10.1097/cm9.0000000000002477] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Indexed: 06/28/2023] Open
Abstract
ABSTRACT Organoids are three-dimensional cellular structures with self-organizing and self-differentiation capacities. They faithfully recapitulate structures and functions of in vivo organs as represented by functionality and microstructural definitions. Heterogeneity in in vitro disease modeling is one of the main reasons for anti-cancer therapy failures. Establishing a powerful model to represent tumor heterogeneity is crucial for elucidating tumor biology and developing effective therapeutic strategies. Tumor organoids can retain the original tumor heterogeneity and are commonly used to mimic the cancer microenvironment when co-cultured with fibroblasts and immune cells; therefore, considerable effort has been made recently to promote the use of this new technology from basic research to clinical studies in tumors. In combination with gene editing technology and microfluidic chip systems, engineered tumor organoids show promising abilities to recapitulate tumorigenesis and metastasis. In many studies, the responses of tumor organoids to various drugs have shown a positive correlation with patient responses. Owing to these consistent responses and personalized characteristics with patient data, tumor organoids show excellent potential for preclinical research. Here, we summarize the properties of different tumor models and review their current state and progress in tumor organoids. We further discuss the substantial challenges and prospects in the rapidly developing tumor organoid field.
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Affiliation(s)
- Bingrui Zhou
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Zhiwei Feng
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xu
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplant Center, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, Shanxi 030001, China
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Hu J, He T, Liu J, Jia S, Li B, Xu W, Liao M, Guo L. Pharmacological and molecular analysis of the effects of Huangqi Jianzhong decoction on proliferation and apoptosis in GES-1 cells infected with H. pylori. Front Pharmacol 2022; 13:1009705. [PMID: 36249768 PMCID: PMC9556892 DOI: 10.3389/fphar.2022.1009705] [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: 08/02/2022] [Accepted: 09/05/2022] [Indexed: 11/21/2022] Open
Abstract
Background: Infection with Helicobacter pylori (H. pylori) can cause chronic gastritis and other digestive tract diseases, and represents a public health concern. Current anti-H. pylori treatment can result in antibiotic resistance and other adverse reactions. Huangqi Jianzhong decoction (HQJZD) is a prescription form of traditional Chinese medicine for chronic gastritis that increases probiotics and inhibits H. pylori. In this study, its anti-bacterial activity against H. pylori receives a preliminary evaluation, and a pharmacology analysis is performed to predict its underlying mechanisms. Methods: Human GES-1 cells are divided into a blank control group, a model group, a HQJZD low-dose (2.08 mg·mL−1), a high-dose group (4.16 mg·mL−1), and a positive control group (amoxicillin, 5 μg·mL−1). After culture, the CCK-8 method is used to detect cell viability; flow cytometry is used to detect cell apoptosis rate; and RT-qPCR is used to detect the expression of mRNA virulence factors, including HpPrtC, OPiA, IceA1, and BabA2. Network pharmacology analysis and molecular docking were performed to explore the mechanisms of HQJZD in treating H. pylori gastritis, based on its anti-H. pylori infection effect. Results: We noted lower cell survival rates in the model group, but higher apoptosis rates and mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 than in the control group (p < 0.05). Compared to the model group, the cell survival rate of each dosage group of Huangqi Jianzhong decoction and the positive control group increased significantly, while the apoptosis rate and the mRNA expressions of HpPrtC, OPiA, IceA1, and BabA2 were decreased significantly. The effect in each HQJZD group was dose-dependent (p < 0.05). Network pharmacological analysis involving 159 signaling pathways was used to screen 6 key active components of HQJZD and 102 potential target proteins for the treatment of H. pylori-related gastritis. The molecular docking results revealed that the 6 active compounds had a strong binding ability with the target proteins of ALB, IL-6, AKT1, IL-1B, and JUN. Conclusion: HQJZD effectively increases the proliferation rate of human GES-1 cells after infection, while reducing the level of apoptosis. The mechanism may be related to multiple components, multiple targets and pathways, which provides a scientific basis for further elucidating the mechanism of action, the pharmacodynamic material basis, and the clinical application of HQJZD against H. pylori infection.
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Affiliation(s)
- Jingnan Hu
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
- Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation, Shijiazhuang, China
| | - Tao He
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
| | - Jianfang Liu
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
- Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation, Shijiazhuang, China
| | - Sujie Jia
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
| | - Bolin Li
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
| | - Weichao Xu
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
| | - Man Liao
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
- Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation, Shijiazhuang, China
| | - Lifang Guo
- Hebei Province Hospital of Chinese Medicine, Shijiazhuang, China
- *Correspondence: Lifang Guo,
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