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Lu C, Qiao H. Embryo-Fetal Developmental Toxicity and Toxicokinetics Studies of YWS1903, a Novel Potassium-Competitive Acid Blocker, in Pregnant Rats. Birth Defects Res 2025; 117:e2481. [PMID: 40329921 DOI: 10.1002/bdr2.2481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 04/23/2025] [Accepted: 04/25/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND In this study, we investigated the developmental and reproductive toxicity of YWS1903, a novel potassium-competitive acid blocker, in pregnant Sprague-Dawley rats. METHODS YWS1903 was administered orally at doses of 0 (control), 20, 60, and 200 mg kg-1 from gestation days 6 to 17 (n = 24 per group). Concurrent toxicokinetic analysis was conducted to characterize the toxicokinetic profile and placental transfer of YWS1903. RESULTS Aside from hair loss at the highest dose, no significant maternal toxicity was observed up to 200 mg kg-1. Fetal assessments revealed reductions in body weight and crown-rump length at 200 mg kg-1, alongside increased skeletal malformations, but no visceral abnormalities were detected. Toxicokinetic linearity studies revealed that within the 20-200 mg kg-1 dose range, both Cmax and AUC0-t of YWS1903 exhibited disproportionate increases following initial and final administrations. In the high-dose group, the escalation in AUC0-t substantially exceeded the corresponding dose changes, suggesting potential saturation of metabolic pathways at higher exposure levels. YWS1903 was shown to cross the placenta, although fetal plasma concentrations were consistently lower than maternal levels, suggesting reduced direct fetal exposure. CONCLUSION The no observed adverse effect level was established at 60 mg kg-1, supporting the compound's safety at moderate doses. These findings provide valuable insights into YWS1903's developmental and reproductive safety profile and offer reference for its clinical application as a therapeutic agent for gastroesophageal reflux disease.
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Affiliation(s)
- Chaoying Lu
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China
| | - Hongqun Qiao
- School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China
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Bai X, Huang Z, Tan H, Gu Y, Wang X, Jin L, Shang P, Long K, Li D, Li M. Insights into high-altitude adaptation and meat quality regulation by gastrointestinal metabolites in Tibetan and black pigs. Front Vet Sci 2025; 12:1569196. [PMID: 40206253 PMCID: PMC11979216 DOI: 10.3389/fvets.2025.1569196] [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: 01/31/2025] [Accepted: 03/05/2025] [Indexed: 04/11/2025] Open
Abstract
Introduction Tibetan pigs, native to the Qinghai-Tibet Plateau, have adapted over millennia to extreme conditions such as low oxygen, harsh cold, and high UV radiation, impacting their muscle characteristics and digestive tract microbiota. The quality of pork from Tibetan pigs (TP) and black pigs (BP) is influenced by various factors, including genetics, diet, and environmental adaptation. However, the specific influence of digestive tract microbiota metabolites on muscle traits remains poorly understood. Our goal was to correlate omic variations with meat quality traits and identify potential biomarkers predictive of superior meat quality, elucidate the regulatory effects of digestive tract microbial metabolites on Tibetan pig muscle characteristics, and reveal the genetic and nutritional mechanisms that promote adaptation to extreme environmental conditions. Methods This analysis encompassed metabolomic profiling of the entire digestive tract-including the stomach, jejunum, cecum, colon, and rectum-as well as histological, amino acid, fatty acid composition, and transcriptomic assessments of the longissimus dorsi muscle tissues to investigate how digestive tract microbial metabolites influence muscle adaptation to high altitudes. Results Analyses revealed that Tibetan pig muscles contain smaller, more oxidative fibers enriched with flavor-enhancing amino acids. This was accompanied by a more favorable n-6/n-3 fatty acid ratio. Distinct patterns of microbial metabolites were observed in the digestive tract, influencing protein digestion and purine metabolism, and correlating with muscle glycine levels. Transcriptomic data showed varied gene expression in metabolic pathways related to salivary and pancreatic secretion, as well as carbohydrate and fatty acid metabolism. Integrated multi-omics approaches linked stomach metabolism, particularly through bile secretion pathways influenced by acetylcholine, to muscle functionality, highlighting the important role played by the ATP1B4 gene in enabling muscle physiology in Tibetan pigs. Discussion This study highlights the importance of targeted dietary interventions in improving meat quality for specific pig breeds. It also provides a theoretical foundation for precision agriculture strategies aimed at enhancing the meat quality of both TP and BP pigs.
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Affiliation(s)
- Xue Bai
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Zhiying Huang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Helin Tan
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Yiren Gu
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Xun Wang
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Long Jin
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Peng Shang
- Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, China
| | - Keren Long
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Diyan Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Mingzhou Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
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Bai X, Gu Y, Li D, Li M. Gut Metagenome Reveals the Microbiome Signatures in Tibetan and Black Pigs. Animals (Basel) 2025; 15:753. [PMID: 40076036 PMCID: PMC11899681 DOI: 10.3390/ani15050753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
The harsh conditions of the Qinghai-Tibet Plateau pose significant physiological challenges to local fauna, often resulting in gastrointestinal disorders. However, Tibetan pigs have exhibited remarkable adaptability to the high-altitude stress of the Tibetan Plateau, a phenomenon that remains not fully understood in terms of their gastrointestinal microbiota. This study collected 57 gastrointestinal tract samples from Tibetan pigs (n = 6) and plain black pigs (n = 6) with comparable genetic backgrounds. Samples from the stomach, jejunum, cecum, colon, and rectum, underwent comprehensive metagenomic analysis to elucidate the gut microbiota-related adaptive mechanisms in Tibetan pigs to the extreme high-altitude environment. A predominance of Pseudomonadota was observed within gut microbiome of Tibetan pigs. Significant differences in the microbial composition were also identified across the tested gastrointestinal segments, with 18 genera and 141 species exhibiting differential abundance. Genera such as Bifidobacterium, Megasphaera, Fusobacterium, and Mitsuokella were significantly more abundant in Tibetan pigs than in their lowland counterparts, suggesting specialized adaptations. Network analysis found greater complexity and modularity in the microbiota of Tibetan pigs compared to black pigs, indicating enhanced ecological stability and adaptability. Functional analysis revealed that the Tibetan pig microbiota was particularly enriched with bacterial species involved in metabolic pathways for propionate and butyrate, key short-chain fatty acids that support energy provision under low-oxygen conditions. The enzymatic profiles of Tibetan pigs, characterized by elevated levels of 4-hydroxybutyrate dehydrogenase and glutaconyl-CoA decarboxylase, highlighted a robust fatty acid metabolism and enhanced tricarboxylic acid cycle activity. In contrast, the gut microbiome of plain black pigs showed a reliance on the succinate pathway, with a reduced butyrate metabolism and lower metabolic flexibility. Taken together, these results demonstrate the crucial role of the gastrointestinal microbiota in the adaptation of Tibetan pigs to high-altitude environments by optimizing carbohydrate metabolism and short-chain fatty acid production for efficient energy utilization. This study not only highlights the metabolic benefits conferred by the gut microbiota of Tibetan pigs in extreme environments, but also advances our understanding of the adaptive gastrointestinal mechanisms in plateau-dwelling animals. These insights lay the foundation for exploring metabolic interventions to support health and performance in high-altitude conditions.
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Affiliation(s)
- Xue Bai
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China;
| | - Yiren Gu
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu 610041, China;
| | - Diyan Li
- School of Pharmacy, Chengdu University, Chengdu 610106, China
| | - Mingzhou Li
- State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China;
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Liu A, Huang Z, Cui S, Xiao Y, Guo X, Pan G, Song L, Deng J, Xu T, Fan Y, Wang R. Ionically assembled hemostatic powders with rapid self-gelation, strong acid resistance, and on-demand removability for upper gastrointestinal bleeding. MATERIALS HORIZONS 2024; 11:5983-5996. [PMID: 39422136 DOI: 10.1039/d4mh00837e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Upper gastrointestinal bleeding (UGIB) is bleeding in the upper part of the gastrointestinal tract with an acidic and dynamic environment that limits the application of conventional hemostatic materials. This study focuses on the development of N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride/phytic acid (HTCC/PA, HP) powders with fast hemostatic capability and strong acid resistance, for potential applications in managing UGIB. Upon contact with liquids within 5 seconds, HP powders rapidly transform into hydrogels, forming ionic networks through electrostatic interactions. The ionic crosslinking process facilitates the HP powders with high blood absorption (3.4 times of self-weight), sufficient tissue adhesion (5.2 and 6.1 kPa on porcine skin and stomach, respectively), and hemostasis (within 15 seconds for in vitro clotting). Interestingly, the PA imparts the HP powders with strong acid resistance (69.8% mass remaining after 10 days of incubation at pH 1) and on-demand removable sealing while HTCC contributes to fast hemostasis and good wet adhesion. Moreover, the HP powders show good biocompatibility and promote wound healing. Therefore, these characteristics highlight the promising clinical potential of HP powders for effectively managing UGIB.
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Affiliation(s)
- Ashuang Liu
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
- Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 325035, P. R. China
| | - Zhimao Huang
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Shengyong Cui
- Department of Burn Surgery, Ningbo No. 2 Hospital, Ningbo, 315010, P. R. China
| | - Ying Xiao
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Xiangshu Guo
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Gaoke Pan
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Lei Song
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Junjie Deng
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
- Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, 325035, P. R. China
| | - Ting Xu
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
| | - Youfen Fan
- Department of Burn Surgery, Ningbo No. 2 Hospital, Ningbo, 315010, P. R. China
| | - Rong Wang
- Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.
- Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo, 315300, P. R. China
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Qiao K, Song Z, Liang L, Zhou X, Feng X, Xu Y, Yang R, Sun B, Zhang Y. Exploring the Underlying Mechanisms of Preventive Treatment Related to Dietary Factors for Gastric Diseases. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:17782-17801. [PMID: 39102359 DOI: 10.1021/acs.jafc.4c05361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
Gastric diseases have emerged as one of the main chronic diseases in humans, leading to considerable health, social, and economic burdens. As a result, using food or "food and medicinal homologous substances" has become an effective strategy to prevent gastric diseases. Diet may play a crucial role in the prevention and mitigation of gastric diseases, particularly long-term and regular intake of specific dietary components that have a protective effect on the stomach. These key components, extracted from food, include polysaccharides, alkaloids, terpenoids, polyphenols, peptides, probiotics, etc. The related mechanisms involve regulating gastric acid secretion, protecting gastric mucosa, increasing the release of gastric defense factors, decreasing the level of inflammatory factors, inhibiting Helicobacter pylori infection, producing antioxidant effects or reducing oxidative damage, preventing gastric oxidative stress by inhibiting lipid peroxides, activating Nrf2 signaling pathway, and inhibiting NF-κB, TLR4, and NOS/NO signaling pathways.
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Affiliation(s)
- Kaina Qiao
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Food Laboratory of Zhongyuan, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
| | - Zichong Song
- Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Li Liang
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Food Laboratory of Zhongyuan, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
| | - Xuewei Zhou
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Food Laboratory of Zhongyuan, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
| | - Xiaoyan Feng
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100048, China
| | - Youqiang Xu
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Food Laboratory of Zhongyuan, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
| | - Rui Yang
- Tianjin Key Laboratory of Food Quality and Health, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China
| | - Baoguo Sun
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
| | - Yuyu Zhang
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China
- Food Laboratory of Zhongyuan, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Flavor Science of China General Chamber of Commerce, Beijing Technology and Business University, Beijing 100048, China
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Ndoye NA, Welle IB, Lamega B, Diawara A, Zeng FTA, Ngom G. Ileal perforation peritonitis secondary to ingestion of magnetic beads in the older child: A case report. Int J Surg Case Rep 2024; 121:109915. [PMID: 38909390 PMCID: PMC11245974 DOI: 10.1016/j.ijscr.2024.109915] [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: 10/23/2023] [Revised: 06/10/2024] [Accepted: 06/15/2024] [Indexed: 06/25/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Foreign body ingestion is frequent in younger children, with generally good outcome on conservative management. However, magnetic beads ingestion is an exceptional cause of intestinal perforation in the older children. CASE PRESENTATION An 8-year-old boy presented with clinical signs of generalized acute peritonitis. Abdominal plain X-ray confirmed the foreign object in the digestive tract and oriented the etiology by highlighting several air-fluid levels, distended small bowel loops, pneumoperitoneum and the presence of a bilobed foreign body projected adjacent to the 5th lumbar vertebra. Open surgical exploration was performed and revealed a peritoneal fluid, 2 perforations in the small bowel and 2 adhered pieces of magnets. A 20 cm ileal resection, including the segment with the 2 perforations, was performed followed by a terminal ileostomy. The restoration of gastrointestinal continuity was performed 16 days later. After a follow-up of 2 years and 8 months, the patient was free of any symptom. CLINICAL DISCUSSION In cases of acute peritonitis due to perforation, the general condition deteriorates progressively. Fever may be absent, as was the case with our patient. Abdominal pain is the predominant symptom, it is often accompanied by vomiting that can be alimentary, bilious, or even fecaloid and/or by cessation of bowel movements and/or gas. Abdominal rigidity is a major physical sign, sometimes replaced by generalized guarding. CONCLUSION Ingestion of gastrointestinal foreign bodies is rare in older children, the presence of more than one magnet can lead to peritonitis due to intestinal perforation.
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Affiliation(s)
- Ndèye Aby Ndoye
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Université Cheikh Anta Diop, Dakar, Senegal.
| | - Ibrahima Bocar Welle
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Dakar, Senegal
| | - Bembo Lamega
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Dakar, Senegal
| | - Amadou Diawara
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Dakar, Senegal
| | - Florent Tshibwid A Zeng
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Dakar, Senegal
| | - Gabriel Ngom
- Department of Pediatric Surgery, Albert Royer National Children's Hospital Center, Université Cheikh Anta Diop, Dakar, Senegal
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Fan J, Zhu J, Xu H. Strategies of Helicobacter pylori in evading host innate and adaptive immunity: insights and prospects for therapeutic targeting. Front Cell Infect Microbiol 2024; 14:1342913. [PMID: 38469348 PMCID: PMC10925771 DOI: 10.3389/fcimb.2024.1342913] [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: 11/22/2023] [Accepted: 02/08/2024] [Indexed: 03/13/2024] Open
Abstract
Helicobacter pylori (H. pylori) is the predominant pathogen causing chronic gastric mucosal infections globally. During the period from 2011 to 2022, the global prevalence of H. pylori infection was estimated at 43.1%, while in China, it was slightly higher at approximately 44.2%. Persistent colonization by H. pylori can lead to gastritis, peptic ulcers, and malignancies such as mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas. Despite eliciting robust immune responses from the host, H. pylori thrives in the gastric mucosa by modulating host immunity, particularly by altering the functions of innate and adaptive immune cells, and dampening inflammatory responses adverse to its survival, posing challenges to clinical management. The interaction between H. pylori and host immune defenses is intricate, involving evasion of host recognition by modifying surface molecules, manipulating macrophage functionality, and modulating T cell responses to evade immune surveillance. This review analyzes the immunopathogenic and immune evasion mechanisms of H. pylori, underscoring the importance of identifying new therapeutic targets and developing effective treatment strategies, and discusses how the development of vaccines against H. pylori offers new hope for eradicating such infections.
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Affiliation(s)
- Jiawei Fan
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
| | - Jianshu Zhu
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Hong Xu
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China
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Zhang H, Liu X, Zheng Z, Xue Y, Yin J, Zhang J. Exploring the safety and efficacy of stomach-partitioning gastrojejunostomy with distal selective vagotomy versus conventional gastrojejunostomy with highly selective vagotomy for treating benign gastric outlet obstruction: study protocol for a randomised controlled trial. BMJ Open 2023; 13:e070735. [PMID: 37770279 PMCID: PMC10546111 DOI: 10.1136/bmjopen-2022-070735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 08/15/2023] [Indexed: 09/30/2023] Open
Abstract
INTRODUCTION Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO. METHODS AND ANALYSIS This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery). ETHICS AND DISSEMINATION This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER ChiCTR2100052197.
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Affiliation(s)
- Haiqiao Zhang
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaoye Liu
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhi Zheng
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yasheng Xue
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jie Yin
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jun Zhang
- Department of General Surgery, Affiliated Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Wu HY, Wei ZL, Shi DY, Li HB, Li XM, Yang D, Zhou SQ, Peng XX, Yang ZW, Yin J, Chen TJ, Li JW, Jin M. Simulated Gastric Acid Promotes the Horizontal Transfer of Multidrug Resistance Genes across Bacteria in the Gastrointestinal Tract at Elevated pH Levels. Microbiol Spectr 2023; 11:e0482022. [PMID: 37070984 PMCID: PMC10269839 DOI: 10.1128/spectrum.04820-22] [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: 11/23/2022] [Accepted: 03/31/2023] [Indexed: 04/19/2023] Open
Abstract
The assessment of factors that can promote the transmission of antibiotic resistance genes (ARGs) across bacteria in the gastrointestinal tract is in great demand to understand the occurrence of infections related to antibiotic-resistant bacteria (ARB) in humans. However, whether acid-resistant enteric bacteria can promote ARG transmission in gastric fluid under high-pH conditions remains unknown. This study assessed the effects of simulated gastric fluid (SGF) at different pH levels on the RP4 plasmid-mediated conjugative transfer of ARGs. Moreover, transcriptomic analysis, measurement of reactive oxygen species (ROS) levels, assessment of cell membrane permeability, and real-time quantitative assessment of the expression of key genes were performed to identify the underlying mechanisms. The frequency of conjugative transfer was the highest in SGF at pH 4.5. Antidepressant consumption and certain dietary factors further negatively impacted this situation, with 5.66-fold and 4.26-fold increases in the conjugative transfer frequency being noted upon the addition of sertraline and 10% glucose, respectively, compared with that in the control group without any additives. The induction of ROS generation, the activation of cellular antioxidant systems, increases in cell membrane permeability, and the promotion of adhesive pilus formation were factors potentially contributing to the increased transfer frequency. These findings indicate that conjugative transfer could be enhanced under certain circumstances in SGF at elevated pH levels, thereby facilitating ARG transmission in the gastrointestinal tract. IMPORTANCE The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited. In this study, we constructed a conjugative transfer model in the presence of simulated gastric fluid (SGF) and found that SGF could promote the dissemination of ARGs under high-pH conditions. Furthermore, antidepressant consumption and certain dietary factors could negatively impact this situation. Transcriptomic analysis and a reactive oxygen species assay revealed the overproduction of reactive oxygen species as a potential mechanism by which SGF could promote conjugative transfer. This finding can help provide a comprehensive understanding of the bloom of antibiotic-resistant bacteria in the body and create awareness regarding the risk of ARG transmission due to certain diseases or an improper diet and the subsequent decrease in gastric acid levels.
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Affiliation(s)
- Hai-yan Wu
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Zi-lin Wei
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Dan-yang Shi
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Hai-bei Li
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Xin-mei Li
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Dong Yang
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Shu-qing Zhou
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Xue-xia Peng
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Zhong-wei Yang
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Jing Yin
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Tian-jiao Chen
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Jun-wen Li
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
| | - Min Jin
- Department of Environment and Health, Tianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment and Food Safety, Tianjin, China
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Infantes-Garcia MR, Verkempinck SHE, Carriére F, Hendrickx ME, Grauwet T. Pre-duodenal lipid digestion of emulsions: Relevance, colloidal aspects and mechanistic insight. Food Res Int 2023; 168:112785. [PMID: 37120232 DOI: 10.1016/j.foodres.2023.112785] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/27/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023]
Abstract
The digestion of lipids in the human body has several health and nutritional implications. Lipid digestion is an interfacial phenomenon meaning that water-soluble lipases need to first adsorb to the oil-water interface before enzymatic conversions can start. The digestion of lipids mainly occurs on colloidal structures dispersed in water, such as oil-in-water (o/w) emulsions, which can be designed during food formulation/processing or structured during digestion. From a food design perspective, different in vitro studies have demonstrated that the kinetics of lipid digestion can be influenced by emulsion properties. However, most of these studies have been performed with pancreatic enzymes to simulate lipolysis in the small intestine. Only few studies have dealt with lipid digestion in the gastric phase and its subsequent impact on intestinal lipolysis. In this aspect, this review compiles information on the physiological aspects of gastric lipid digestion. In addition, it deals with colloidal and interfacial aspects starting from emulsion design factors and how they evolve during in vitro digestion. Finally, molecular mechanisms describing gastric lipolysis are discussed.
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Affiliation(s)
- Marcos R Infantes-Garcia
- Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre (LFoRCe), Department of Microbial and Molecular Systems (M2S), KU Leuven, Kasteelpark Arenberg, 22, PB 2457, 3001 Leuven, Belgium
| | - Sarah H E Verkempinck
- Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre (LFoRCe), Department of Microbial and Molecular Systems (M2S), KU Leuven, Kasteelpark Arenberg, 22, PB 2457, 3001 Leuven, Belgium
| | - Fréderic Carriére
- CNRS, Aix-Marseille Université, Bioénergétique et Ingénierie des Protéines, UMR 7281, 31, Chemin Joseph Aiguier, 13402 Marseille cedex 9, France
| | - Marc E Hendrickx
- Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre (LFoRCe), Department of Microbial and Molecular Systems (M2S), KU Leuven, Kasteelpark Arenberg, 22, PB 2457, 3001 Leuven, Belgium
| | - Tara Grauwet
- Laboratory of Food Technology and Leuven Food Science and Nutrition Research Centre (LFoRCe), Department of Microbial and Molecular Systems (M2S), KU Leuven, Kasteelpark Arenberg, 22, PB 2457, 3001 Leuven, Belgium
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Liu K, Salvati A, Sabirsh A. Physiology, pathology and the biomolecular corona: the confounding factors in nanomedicine design. NANOSCALE 2022; 14:2136-2154. [PMID: 35103268 DOI: 10.1039/d1nr08101b] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The biomolecular corona that forms on nanomedicines in different physiological and pathological environments confers a new biological identity. How the recipient biological system's state can potentially affect nanomedicine corona formation, and how this can be modulated, remains obscure. With this perspective, this review summarizes the current knowledge about the content of biological fluids in various compartments and how they can be affected by pathological states, thus impacting biomolecular corona formation. The content of representative biological fluids is explored, and the urgency of integrating corona formation, as an essential component of nanomedicine designs for effective cargo delivery, is highlighted.
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Affiliation(s)
- Kai Liu
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
| | - Anna Salvati
- Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Groningen 9713AV, The Netherlands
| | - Alan Sabirsh
- Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
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12
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Wollmer E, Ungell AL, Nicolas JM, Klein S. Review of paediatric gastrointestinal physiology relevant to the absorption of orally administered medicines. Adv Drug Deliv Rev 2022; 181:114084. [PMID: 34929252 DOI: 10.1016/j.addr.2021.114084] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 11/13/2021] [Accepted: 12/13/2021] [Indexed: 12/11/2022]
Abstract
Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adults is essential. Several review articles have been published addressing the ontogeny of GI characteristics, including luminal conditions in the GI tract of children. However, the data reported in most of these reviews are of limited quality because (1) information was cited from very old publications and sometimes low quality sources, (2) data gaps in the original data were filled with textbook knowledge, (3) data obtained on healthy and sick children were mixed, (4) average data obtained on groups of patients were mixed with data obtained on individual patients, and (5) results obtained using investigative techniques that may have altered the outcome of the respective studies were considered. Consequently, many of these reviews draw conclusions that may be incorrect. The aim of the present review was to provide a comprehensive and updated overview of the available original data on the ontogeny of GI luminal conditions relevant to oral drug absorption in the paediatric population. To this end, the PubMed and Web of Science metadatabases were searched for appropriate studies that examined age-related conditions in the oral cavity, esophagus, stomach, small intestine, and colon. Maturation was observed for several GI parameters, and corresponding data sets were identified for each paediatric age group. However, it also became clear that the ontogeny of several GI traits in the paediatric population is not yet known. The review article provides a robust and valuable data set for the development of paediatric in vitro and in silico biopharmaceutical tools to support the development of age-appropriate dosage forms. In addition, it provides important information on existing data gaps and should provide impetus for further systematic and well-designed in vivo studies on GI physiology in children of specific age groups in order to close existing knowledge gaps and to sustainably improve oral drug therapy in children.
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Wei Y, Ren S, Wang J, Wang Y, Cui Y, Tian M, Wang R, Liu H, Zhao Y. Dehydroevodiamine ameliorates indomethacin-induced gastric injury via inhibition of ERK and p38 signaling pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 93:153764. [PMID: 34628242 DOI: 10.1016/j.phymed.2021.153764] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 09/12/2021] [Accepted: 09/16/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Dehydroevodiamine (DHE), a pivotal quinazoline alkaloid isolated from Fructus Evodiae (Tetradium ruticarpum (A. Juss.) Hartley), has various pharmacological effects. However, the effect of DHE on gastric injury is still uncharted. PURPOSE To clarify the pharmacological effect and mechanism of DHE on gastric injury (GI) induced by indomethacin (IDO). STUDY DESIGN The gastric injury was induced in rat by oral administration of 5 mg/kg IDO for 7 days. Then the rats were treated with DHE (10, 20, 40 mg/kg, ig) for 7 days. METHODS The changes of food intake, body weight, gastric pH and general state observation were determined. And HE staining and AB-PAS staining was analyzed. Then, the inflammatory infiltration of gastric tissue was observed through MPO immunohistochemical approach, and the expression of TNF-α, IL-6 and IL-10 were measured. Furthermore, the levels of proteins ERK, p-ERK, P38, p-P38, JNK and p-JNK were determined to elucidate the molecular mechanism of DHE. RESULTS DHE alleviated food intake reduction, weight loss and gastric injury induced by IDO and made gastric pH and mucosal thickness return to normal. In addition, DHE could down regulate the expression of MPO, TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage induced by inflammatory, and create a healing environment. Furthermore, DHE could significantly inhibit the phosphorylation of ERK and p38 not JNK. CONCLUSION DHE ameliorated dyspepsia, inflammatory infiltration and tissue damage induced by IDO through ERK and p38 signaling pathways rather than JNK pathway.
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Affiliation(s)
- Ying Wei
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Pharmacy, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Sichen Ren
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Pharmacy, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jian Wang
- Department of Pharmacy, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yanling Wang
- China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yanfei Cui
- China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Miao Tian
- China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ruilin Wang
- China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Honghong Liu
- China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yanling Zhao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Pharmacy, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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14
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Feng ZY, Liu TT, Sang ZT, Lin ZS, Su X, Sun XT, Yang HZ, Wang T, Guo S. Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties. Front Bioeng Biotechnol 2021; 9:756758. [PMID: 34568306 PMCID: PMC8458873 DOI: 10.3389/fbioe.2021.756758] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.
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Affiliation(s)
- Zi-Yi Feng
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Tao-Tao Liu
- School of Intelligent Medicine, China Medical University, Shenyang, China
| | - Zhen-Tao Sang
- School of Intelligent Medicine, China Medical University, Shenyang, China
| | - Zhen-Sheng Lin
- School of Intelligent Medicine, China Medical University, Shenyang, China
| | - Xin Su
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiao-Ting Sun
- School of Forensic Medicine, China Medical University, Shenyang, China
| | - Hua-Zhe Yang
- School of Intelligent Medicine, China Medical University, Shenyang, China
| | - Ting Wang
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Shu Guo
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
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15
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do Nascimento RF, de Oliveira Formiga R, Machado FDF, de Sales IRP, de Lima GM, Alves Júnior EB, Vieira GC, Pereira RF, de Araújo AA, de Araújo Junior RF, Barbosa Filho JM, Batista LM. Rosmarinic acid prevents gastric ulcers via sulfhydryl groups reinforcement, antioxidant and immunomodulatory effects. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2020; 393:2265-2278. [PMID: 32642876 DOI: 10.1007/s00210-020-01894-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 05/01/2020] [Indexed: 02/08/2023]
Abstract
Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000 mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD50 set around 2500 mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200 mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H+]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1β) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms. Graphical abstract.
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Affiliation(s)
- Raphaela Francelino do Nascimento
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Rodrigo de Oliveira Formiga
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Flávia Danielle Frota Machado
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Igor Rafael Praxedes de Sales
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Gedson Moraes de Lima
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Edvaldo Balbino Alves Júnior
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Giciane Carvalho Vieira
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Raquel Fragoso Pereira
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Aurigena Antunes de Araújo
- Department of Biophysics and Pharmacology and Department of Morphology, Histology and Basic Pathology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Raimundo Fernandes de Araújo Junior
- Department of Biophysics and Pharmacology and Department of Morphology, Histology and Basic Pathology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - José Maria Barbosa Filho
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil
| | - Leônia Maria Batista
- Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil.
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa, PB, 58051-970, Brazil.
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Differentially Expressed mRNAs and Their Long Noncoding RNA Regulatory Network with Helicobacter pylori-Associated Diseases including Atrophic Gastritis and Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3012193. [PMID: 33282942 PMCID: PMC7686847 DOI: 10.1155/2020/3012193] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/28/2020] [Accepted: 10/31/2020] [Indexed: 02/08/2023]
Abstract
Background Helicobacter pylori (Hp) infection is the strongest risk factor for gastric cancer (GC). However, the mechanisms of Hp-associated GC remain to be explored. Methods The gene expression profiling (GSE111762) data were downloaded from the GEO database. Differentially expressed genes (DEGs) between normal samples (NO) and Hp-atrophic gastritis (GA) or Hp-GA and Hp-GC were identified by GEO2R. Gene Ontology and pathway enrichment analysis were performed using the DAVID database. lncRNA-TF-mRNA and ceRNA regulation networks were constructed using Cytoscape. The cross-networks were obtained by overlapping molecules of the above two networks. GSE27411 and GSE116312 datasets were employed for validation. Results DEGs between NO and Hp-GA are linked to the activity of inward rectifying potassium channels, digestion, etc. DEGs between Hp-GA and Hp-GC were associated with digestion, positive regulation of cell proliferation, etc. According to the lncRNA-TF-mRNA network, 63 lncRNAs, 12 TFs, and 209 mRNAs were involved in Hp-GA while 16 lncRNAs, 11 TFs, and 92 mRNAs were contained in the Hp-GC network. In terms of the ceRNA network, 120 mRNAs, 18 miRNAs, and 27 lncRNAs were shown in Hp-GA while 72 mRNAs, 8 miRNAs, and 1 lncRNA were included in the Hp-GC network. In the cross-network, we found that immune regulation and differentiation regulation were important in the process of NO-GA. Neuroendocrine regulation was mainly related to the process of GA-GC. In the end, we verified that CDX2 plays an important role in the pathological process of NO to Hp-GA. Comparing Hp-GA with Hp-GC, DEGs (FPR1, TFF2, GAST, SST, FUT9, and SHH), TF, and GATA5 were of great significance. Conclusions We identified the DEGs, and their lncRNA regulatory network of Hp-associated diseases might provide insights into the mechanism between Hp infection and GC. Furthermore, in-depth studies of the molecules might be useful to explore the multistep process of gastric diseases.
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Jabri MA, Marzouki L, Sebai H. Ethnobotanical, phytochemical and therapeutic effects of Myrtus communis L. berries seeds on gastrointestinal tract diseases: a review. Arch Physiol Biochem 2018; 124:390-396. [PMID: 29303617 DOI: 10.1080/13813455.2017.1423504] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Medicinal plants have always had an important place in the therapeutic arsenal of humanity and particularly in the treatment of gastrointestinal tract diseases. Myrtus communis L., known as common myrtle, is native to Southern Europe, North Africa, and Western Asia. The different parts of this plant are used as antiinflammatory, antiulcer, antidiabetic, urinary antiseptic, and to treat the respiratory and digestive systems diseases. For the first time, an exhaustive bibliographic research of the seeds of myrtle berries has been carried out. As a result, it has been found that this plant is very rich in biologically active compounds such as phospholipids, polyunsaturated fatty acids, and phenolic compounds. This has made it effective in the treatment of digestive diseases. In order to emphasize the importance of myrtle berries seeds, this review has been established by discussing its botanical, morphological, phytochemical, ethnomedicinal studies as well as its effect on digestive tract diseases.
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Affiliation(s)
- Mohamed-Amine Jabri
- a Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Ressources - Institut Supérieur de Biotechnologie de Béja , Université de Jendouba , Béja , Tunisia
| | - Lamjed Marzouki
- a Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Ressources - Institut Supérieur de Biotechnologie de Béja , Université de Jendouba , Béja , Tunisia
| | - Hichem Sebai
- a Laboratoire de Physiologie Fonctionnelle et Valorisation des Bio-Ressources - Institut Supérieur de Biotechnologie de Béja , Université de Jendouba , Béja , Tunisia
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Jing JJ, Wang ZY, Li H, Sun LP, Yuan Y. Key elements involved in Epstein-Barr virus-associated gastric cancer and their network regulation. Cancer Cell Int 2018; 18:146. [PMID: 30258285 PMCID: PMC6151003 DOI: 10.1186/s12935-018-0637-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 09/10/2018] [Indexed: 12/31/2022] Open
Abstract
Background The molecular mechanism of Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains elusive. A collection of molecular regulators including transcription factor and noncoding RNA (ncRNAs) may affect the carcinogenesis of EBVaGC by regulating the expression and function of key genes. In this study, integration of multi-level expression data and bioinformatics approach was used to identify key elements and their interactions involved in mechanism of EBVaGC and their network regulation. Methods Data of the gene expression profiling data sets (GSE51575) was downloaded from GEO database. Differentially expressed genes between EBVaGC and normal samples were identified by GEO2R. Gene ontology and pathway enrichment analyses were performed using R packages Cluster profiler. STRING database was used to find interacting proteins between different genes. Transcription factors in differentially expressed genes were obtained from TF Checkpoint database. Using Cytoscape, we built transcription factor regulation network. miRNAs involved in the gene-interacting proteins and the miRNA-targeted lncRNA were predicted through miRWalk. Using ViRBase, EBV related miRNA regulation network was built. Overlapping genes and regulators of the above three networks were further identified, and the cross network was constructed using Cytoscape software. Moreover, the differential expressions of the target genes and transcription factors in the cross network were explored in different molecular subtypes of GC using cBioPortal. By histological verification, the expression of two main target genes in the cross network were further analyzed. Results A total of 104 genes showed differential expressions between EBVaGC and normal tissues, which were associated with digestion, G-protein coupled receptor binding, gastric acid secretion, etc. Pathway analysis showed that the differentially expressed genes were mainly enriched in gastric acid secretion and protein digestion and absorption. Using STRING dataset, a total of 54 proteins interacted with each other. Based on the transcription factor network, the hub transcription factors IRX3, NKX6-2, PTGER3 and SMAD5 were identified to regulate their target genes SST and GDF5, etc. After screening and matching in miRwalk datasets, a ceRNA network was established, in which the top five miRNAs were hsa-miR-4446-3p, hsa-miR-5787, hsa-miR-1915-3p, hsa-miR-335-3p and hsa-miR-6877-3p, and the top two lncRNAs were RP5-1039K5.19 and TP73-AS1. According to the EBV related miRNA regulation network, CXCL10 and SMAD5 were found to be regulated by EBV-miR-BART1-3p and EBV-mir-BART22, respectively. By overlapping the three networks, CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22 were found to be key elements of regulation mechanism of EBVaGC. CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. Conclusion In the current study, our results revealed key elements and their interactions involved in EBVaGC. Some hub transcription factors, miRNAs, lncRNAs and EBV related miRNAs were observed to regulate their target genes. Overlapping genes and regulators were observed in diverse regulation networks, such as CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22. Moreover, CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. Therefore, the identified key elements and their network regulation may be specifically involved in EBVaGC mechanisms. Electronic supplementary material The online version of this article (10.1186/s12935-018-0637-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jing-Jing Jing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning China
| | - Ze-Yang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning China
| | - Hao Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning China
| | - Li-Ping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, Liaoning China
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Minalyan A, Gabrielyan L, Scott D, Jacobs J, Pisegna JR. The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors. Curr Gastroenterol Rep 2017; 19:42. [PMID: 28733944 PMCID: PMC5621514 DOI: 10.1007/s11894-017-0577-6] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2023]
Abstract
PURPOSE OF REVIEW The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract. RECENT FINDINGS Culture-independent techniques, such as 16S rRNA sequencing, have revolutionized our understanding of the microbial biodiversity in the gastrointestinal tract. Luminal and mucosa-associated microbial populations are not identical. Streptococcus is overrepresented in the biopsies of patients with antral gastritis and may also be responsible for the development of peptic ulcer disease. The use of PPIs favors relative streptococcal abundance irrespective of H. pylori status and may explain the persistence of dyspeptic symptoms in patients on PPI therapy. Increased risk of enteric infections has also been seen in patients taking PPIs. The overuse of PPIs leads to significant shift of the gastrointestinal microbiome towards a less healthy state. With the advent of PPIs, many studies have demonstrated the significant changes in the microbial composition of both gastric and intestinal microbiota. Although they are considered relatively safe over-the-counter medications, PPIs in many cases are over- and even inappropriately used. Future studies assessing the safety of PPIs and their role in the development of microbiome changes should be encouraged.
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Affiliation(s)
- Artem Minalyan
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Lilit Gabrielyan
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- USC School of Pharmacy, Los Angeles, CA, USA
| | - David Scott
- Division of Digestive Diseases, Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jonathan Jacobs
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Department of Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Joseph R Pisegna
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Veterans Affairs and VA Greater Los Angeles Healthcare System (691/111C), David Geffen School of Medicine at UCLA, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.
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20
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Trypsin and N-aminopeptidase (APN) activities in the hepatopancreas of an intertidal euryhaline crab: Biochemical characteristics and differential modulation by histamine and salinity. Comp Biochem Physiol A Mol Integr Physiol 2017; 204:228-235. [DOI: 10.1016/j.cbpa.2016.12.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 10/14/2016] [Accepted: 12/01/2016] [Indexed: 12/18/2022]
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Servetas SL, Carpenter BM, Haley KP, Gilbreath JJ, Gaddy JA, Merrell DS. Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation. J Bacteriol 2016; 198:2536-48. [PMID: 27432830 PMCID: PMC4999924 DOI: 10.1128/jb.00324-16] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 07/07/2016] [Indexed: 01/01/2023] Open
Abstract
UNLABELLED Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ΔnikR ΔarsS, and Δfur ΔnikR ΔarsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. IMPORTANCE Despite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual regulatory proteins, such as Fur, NikR, and ArsRS, few studies have examined the combined effect of these factors. Analysis of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS revealed a previously unrecognized role for the acid-responsive two-component system ArsRS in biofilm formation.
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Affiliation(s)
- Stephanie L Servetas
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Beth M Carpenter
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Kathryn P Haley
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Jeremy J Gilbreath
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Jennifer A Gaddy
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA Tennessee Valley Health Care Systems, U.S. Department of Veterans Affairs, Nashville, Tennessee, USA
| | - D Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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22
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Vijayakumar AR, Daniel EP, Ilavarasan R, Venkataraman S, Vijayakumar S. Ulcer Protective Activity of Jatropha gossypiifolia Linn. in Wistar Rats. Pharmacognosy Res 2016; 8:S61-6. [PMID: 27114695 PMCID: PMC4821110 DOI: 10.4103/0974-8490.178640] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Several synthetic drugs are useful in the treatment of peptic ulcer, but almost of these drugs are used in prolonging time, it may cause several adverse reactions. However, the herbal medicines are more potent to the treatment and minimize the side effects. OBJECTIVE To evaluate the methanol extract of Jatropha gossypiifolia Linn. (MEJG) for gastro protective activity against Wistar rats. MATERIALS AND METHODS Anti-ulcer potency of MEJG (100 and 200 mg/kg, b.w.) was assessed using aspirin (200 mg/kg, p.o.) plus pylorus ligation ulcer model and the parameters studied were ulcer index (UI), gastric juice volume, pH, total acidity, and total acid output. Same extract was studied by ethanol-induced (80%, 5 mL/kg, intragastrically) ulcer model, and the UI and biochemical parameters were studied. RESULTS The oral administration of MEJG (100 and 200 mg/kg) significantly (P < 0.001) attenuated the ulcer score and anti-secretary parameters (such as the volume of gastric content, free acidity, total acidity, and total acid output) in the aspirin plus pylorus ligation rats. The extract also significantly attenuated (P < 0.001) ulcer score in ethanol-induced ulcer model and lipid peroxidation level and significantly increased the level of glutathione peroxides, catalase, and superoxide dismutase activity. The MEJG may possess active constituents such as alkaloids, glycosides, flavonoids, and terpenes, which may play a major role in gastroprotective effect in Wistar rats. CONCLUSION The present study provides scientific support for the anti-ulcer activities of extracts of JG and also claimed that antioxidant potential of the extracts. However, substantiates the traditional claims for the usage of this drug in the treatment of gastric ulcer. SUMMARY The methanolic extract of jatropha gossypiifolia Linn. for gastro protective activity against aspirin plus pyloric ligation and ethanol induced ulcer models was studied in Wistar rats. JG shows significantly attenuated the ulcer score in both models. And also attenuated in anti-secretory parameters in aspirin induced ulcer model. MEJG may possess active constituents such as alkaloids, glycosides, flavonoids and terpenes, which may play a major role in gastroprotective effect in Wistar rats. Abbreviation Used: MEJG: Methanolic extract of jatropha gossypiifolia, mg: Milli gram, kg: Kilogram, b.w.: Body weight, p.o.: Per oral, UI: Ulcer index, pH: Concentration of H+ ion, mL: Milli litre, JG: Jatropha gossypiifolia,USD: United States Dollar, NSAIDs: Non steroidal anti-inflammatory drugs, v/v: Volume by volume, w/v: Weight by volume, SCMC: Sodium carboxy methyl cellulose, g: Gram, h: Hour, °C: Degree centigrade, n: Number, Rpm: Rotation per minute, Min: Minute, N: Normality, NaoH: Sodium hydroxide, mM - Millimole, TBA: Thiobarbituric acid, nmol: Nanomole, nm: Nanometer, GPx: Glutathione peroxidase, GSH: Reduced glutathione, H2O2: Hydrogen peroxide, SOD: Superoxide dismutase, ANOVA Analysis of Variance, μmol: Micromole.
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Affiliation(s)
| | - Epison Prabu Daniel
- Department of Pharmacology, CL Baid Metha College of Pharmacy, Thoraipakkam, Chennai, Tamil Nadu, India
| | - Raju Ilavarasan
- Department of Pharmacology, Captain Srinivasa Murti Drug Research Institute for Ayurveda and Siddha Drug Development, CCRAS, Ministry of AYUSH, Government of India, Arumbakkam, Chennai, Tamil Nadu, India
| | - S Venkataraman
- CL Baid Metha Foundation for Pharmaceutical Education and Research, Thoraipakkam, Chennai, Tamil Nadu, India
| | - S Vijayakumar
- Department of Pharmacy Practice, Vels School of Pharmaceutical Sciences, Vels University, Pallavaram, Chennai, Tamil Nadu, India
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Abstract
Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies.
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Al Asmari AK, Al Omani S, Elfaki I, Tariq M, Al Malki A, Al Asmary S. Gastric antisecretory and antiulcer activity of bovine hemoglobin. World J Gastroenterol 2013; 19:3291-3299. [PMID: 23745031 PMCID: PMC3671081 DOI: 10.3748/wjg.v19.i21.3291] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2012] [Revised: 03/09/2013] [Accepted: 04/16/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate gastric antisecretory and gastroprotective activity of bovine hemoglobin (B-Hb) in rats.
METHODS: Adult Albino-Wistar rats were divided into groups of 6 animals each. B-Hb in doses of 100, 300 and 900 mg/kg body weight was tested for gastric acid secretion and antiulcer activity. Gastric secretions were measured 6 h after pylorus ligation in rats pretreated with B-Hb. The acidity was measured by titrating gastric contents against 0.01 mol/L NaOH to pH 7. Indomethacin ulcers were produced by oral administration of 30 mg/kg bw in the rats pretreated with B-Hb one hour before indomethacin. Six hours after indomethacin stomach removed and ulcer index was recorded. Ethanol ulcer were produced by 1 mL of ethanol in the rats pretreated with B-Hb 30 min before the ethanol. One hour after ethanol stomach were cut open to score ulcers. Histological examination and analysis of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), and myeloperoxidase (MPO) were carried in gastric tissue following ethanol administration.
RESULTS: In control rats pylorus ligation for 6 h resulted in the accumulation of 8.1 ± 0.61 mL of gastric secretion. The treatment of the rats with 100, 300 and 900 mg/kg of B-Hb produced a significant decrease in the volume of gastric secretion 5.6 ± 0.63, 5.5 ± 0.75 and 4.7 ± 0.58 mL respectively as compared to the control group [analysis of variance (ANOVA) F = 4.77, P < 0.05]. The lesion area in the control group was found to be 22.4 ± 3.2 mm2 six hours after the administration of indomethacin. Treatment of rats with B-Hb at doses of 100 mg/kg (24.3 ± 3.29 mm2), 300 mg/kg (16.2 ± 1.45 mm2) and 900 mg/kg (12.6 ± 1.85 mm2) produced a dose dependent decreased the lesion scores (ANOVA F = 4.50, P < 0.05). The ulcer index following one hour after 1 mL ethanol was 7.1 ± 0.31. Pretreatment of rats with B-Hb at the doses of 100 mg/kg (2.5 ± 0.42), 300 mg/kg (2.1 ± 0.4) and 900 mg/kg (0.7 ± 0.21) significantly inhibited the formation of gastric lesions (ANOVA F = 63.26, P < 0.0001). Histological examination of gastric mucosa following ethanol showed significant lesions in the form of gastric pits with detachment of the surface epithelium; vacuolation of epithelial cells and elongation of microvessels. The changes were dose-dependently attenuated by B-Hb. The treatment of rats with ethanol significantly decreased the Alcian blue binding capacity of gastric wall mucus (480 ± 25.6 μg Alcian blue/g of tissue) as compared to control rats (667 ± 25.8 μg). Pretreatment of rats with B-Hb at the doses of 100 mg/kg (516 ± 31.6 μg/g), 300 mg/kg (558 ± 28.8 μg/g) and 900 mg/kg (654 ± 33.8 μg/g) significantly attenuated ethanol induced depletion of gastric wall mucus (ANOVA F = 8.05, P < 0.005). A significant and dose dependent increase of gastric mucosal NP-SH (ANOVA F = 19.62, P < 0.001) and decrease in MPO activity (ANOVA F = 3.1, P < 0.05) was observed in B-Hb treated rats.
CONCLUSION: B-Hb possesses significant gastric antisecretory and gastroprotective activity against experimentally induced gastric lesion. The gastroprotective effects of B-Hb are accompanied by inhibition of neutrophils activity, reduction of oxidative stress and maintenance of mucosal integrity.
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The gastric fluid proteome as a potential source of gastric cancer biomarkers. J Proteomics 2013; 90:3-13. [PMID: 23665003 DOI: 10.1016/j.jprot.2013.04.035] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2012] [Revised: 04/17/2013] [Accepted: 04/18/2013] [Indexed: 12/17/2022]
Abstract
Gastric cancer is a significant cause of death in many parts of the world. Although timely intervention is associated with better clinical outcome, early gastric cancer detection is frequently not possible given its asymptomatic nature. As such, sensitive and specific gastric cancer biomarkers are highly sought after as diagnostic surrogates that may replace invasive endoscopic and histological examinations. Unlike gastric cancer tissue and serum which are heterogeneous and overloaded with abundant proteins, the gastric fluid contains a concentrated molecular biopsy of the stomach that accurately reflects gastric oncology. This review attempts to (i) summarise the state of proteomics-based gastric cancer biomarker discovery from patient gastric fluids, (ii) outline key considerations in working with the body fluid, and (ii) discuss how the challenges in gastric cancer diagnosis may be overcome with new perspectives in gastric cancer screening.
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