|
1
|
Wang Y, Ni Q, Xu S, Cui M, Wang R, Liu R. MiR-486-5p predicts the progression of severe acute pancreatitis by mediating the inflammatory response and ATG7/p38 MAPK pathway. Am J Med Sci 2025:S0002-9629(25)00982-6. [PMID: 40169118 DOI: 10.1016/j.amjms.2025.01.011] [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: 07/04/2024] [Revised: 12/30/2024] [Accepted: 01/30/2025] [Indexed: 04/03/2025]
Abstract
BACKGROUND Acute pancreatitis (AP) is a serious disorder, and is frequently accompanied by shock or organ failure. The study aimed to investigate the predictive value of serum miR-486-5p for the prognosis of SAP patients and the underlying mechanism. METHODS The concentration of mRNAs was detected by Real-Time PCR reaction. The correlation between miRNA and each scoring system was analyzed via Pearson's correlation analysis. ROC curve was performed for diagnostic value evaluation. The predictive value of miRNA expression in the severity of AP was estimated by logistic regression analysis. HPDE6-C7 cells were treated with cerulein (Cer) to mimic AP in vitro. The cell apoptosis, viability, and inflammatory response were detected by flow cytometry, CCK-8, and ELISA, respectively. The targeting relationship was verified by DLR assay and RIP assay. RESULTS The expression of miR-486-5p was elevated in the serum of non-SAP and SAP groups (P < 0.001), which was interconnected with APACHE II, SOFA, and Ranson scores. MiR-486-5p can differentiate SAP patients from non-SAP with the AUC of 0.916, and it was an independent risk for the severity of AP patients. The miR-486-5p/ATG7 axis affected the apoptosis, viability, and inflammatory response of HPDE6-C7 cell models by the p38 MAPK pathway, thus involving the progression of AP. CONCLUSIONS Serum miR-486-5p may have a certain predictive value for the severity of AP and influence AP development through mediating cell inflammatory response via targeting ATG7.
Collapse
Affiliation(s)
- Yang Wang
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China
| | - Qi Ni
- Department of Endocrinology, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China
| | - Shuying Xu
- Department of Emergency, Binzhou Medical University Hospital, Binzhou, Shandong 256600, PR China
| | - Mingli Cui
- Department of Cardiovascular Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256600, PR China
| | - Ruixia Wang
- Department of Emergency, Binzhou Medical University Hospital, Binzhou, Shandong 256600, PR China.
| | - Rong Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China.
| |
Collapse
|
|
2
|
Burzyński J, Fichna J, Tarasiuk A. Putative molecular targets for vitamin A in neutralizing oxidative stress in acute and chronic pancreatitis - a systematic review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023:10.1007/s00210-023-02442-4. [PMID: 36843131 DOI: 10.1007/s00210-023-02442-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 02/21/2023] [Indexed: 02/28/2023]
Abstract
Acute pancreatitis (AP) and chronic pancreatitis (CP) are debilitating diseases of gastrointestinal tract and constitute great threat for human health in high-income countries. Recent studies emphasize the impact of oxidative stress on development of these pathologies, and numerous authors evaluate the effect of the antioxidant therapy on the course of AP and CP. Though several antioxidative agents were discovered in the past decades, vitamins remain canonical antioxidants. Despite the fact that vitamin A is known for its antioxidative effect, there is little data about the impact of vitamin A on oxidative stress in the pathogenesis of AP and CP. The scope of the review is to evaluate molecular targets for vitamin A, which may be involved in oxidative stress occurring in the course of AP and CP. Our research of available literature revealed that several mechanisms are responsible for attenuation of oxidative stress in AP and CP, including Nrf2, MAPK, AMPK, TLR3, and TLR4. Furthermore, these factors are at least partially expressed in vitamin A-dependent manner, though further investigations are required for elucidating in detail the role of vitamin A in defense against reactive oxygen species. Our review revealed that vitamin A might influence the expression of several molecular pathways involved in antioxidative defense and cytoprotection; thus, its administration during AP and CP may change the course of the disease.
Collapse
Affiliation(s)
- Jacek Burzyński
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
| | - Aleksandra Tarasiuk
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland.
| |
Collapse
|
|
3
|
Fu X, Zhang Y. Research progress of p38 as a new therapeutic target against morphine tolerance and the current status of therapy of morphine tolerance. J Drug Target 2023; 31:152-165. [PMID: 36264036 DOI: 10.1080/1061186x.2022.2138895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
With the development of the medical industry, new painkillers continue to appear in people's field of vision, but so far no painkiller can replace morphine. While morphine has a strong analgesic effect, it is also easy to produce pain sensitivity and tolerance. Due to the great inter-individual differences in patient responses, there are few clear instructions on how to optimise morphine administration regimens, which complicates clinicians' treatment strategies and limits the effectiveness of morphine in long-term pain therapy. P38MAPK is a key member of the MAPK family. Across recent years, it has been discovered that p38MAPK rises dramatically in a wide range of morphine tolerance animal models. Morphine tolerance can be reduced or reversed by inhibiting p38MAPK. However, the role and specific mechanism of p38MAPK are not clear. In this review, we synthesise the relevant findings, highlight the function and potential mechanism of p38MAPK in morphine tolerance, as well as the present status and efficacy of morphine tolerance therapy, and underline the future promise of p38MAPK targeted morphine tolerance treatment.
Collapse
Affiliation(s)
- Xiao Fu
- Inner Mongolia Medical University, Hohhot, China
| | - Yanhong Zhang
- Department of Anesthesiology, People's Hospital Affiliated to Inner Mongolia Medical University, Hohhot, China
| |
Collapse
|
|
4
|
Huang H, Wang M, Guo Z, Wu D, Wang H, Jia Y, Liu H, Ding J, Peng J. Rutaecarpine alleviates acute pancreatitis in mice and AR42J cells by suppressing the MAPK and NF-κB signaling pathways via calcitonin gene-related peptide. Phytother Res 2021; 35:6472-6485. [PMID: 34661951 DOI: 10.1002/ptr.7301] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 09/02/2021] [Accepted: 09/11/2021] [Indexed: 11/09/2022]
Abstract
Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. Previous studies have shown that rutaecarpine (RUT), an important alkaloid component of Evodia rutaecarpa, exhibits certain protective effects against AP in rats by upregulating calcitonin gene-related peptide (CGRP). However, the molecular mechanism of RUT in AP remains unknown. This study aimed to investigate the effects of RUT on cerulein-induced AP in vivo and in vitro, and to explore the underlying molecular mechanisms. In cerulein/LPS-treated wild-type mice, but not CGRP gene knock-out mice, RUT significantly ameliorated pancreatic inflammation by alleviating histopathological changes, reducing IL-6 and TNF-α levels, and increasing in IL-10 levels. Moreover, RUT improved AP by suppressing the MAPK and NF-κB signaling pathways. These effects were mostly mediated through CGRP. Cell-based studies revealed that RUT significantly improved cell viability while suppressing the apoptosis of AR42J cells with cerulein-induced AP, downregulating IL-6 and TNF-α, stimulating IL-10 release, and inhibiting MAPK, NF-κB, and STAT3 signaling activation, all in a CGRP-dependent manner. RUT ameliorated cerulein/LPS-induced AP inflammatory responses in mice and AR42J cells in a CGRP-dependent manner and thus may represent a potential therapeutic option for AP patients. Our study provides valuable insights for AP drug development.
Collapse
Affiliation(s)
- Haosu Huang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Meng Wang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Zimeng Guo
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Di Wu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Hanyue Wang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Jia
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Honghui Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Junjie Ding
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Jie Peng
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
5
|
Xue J, Liu Y, Zhang S, Ding L, Shen B, Shao Y, Wei Z. CGRP protects bladder smooth muscle cells stimulated by high glucose through inhibiting p38 MAPK pathway in vitro. Sci Rep 2021; 11:7643. [PMID: 33828162 PMCID: PMC8027675 DOI: 10.1038/s41598-021-87140-y] [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: 07/18/2020] [Accepted: 03/24/2021] [Indexed: 11/09/2022] Open
Abstract
This study aimed to explore the effect of calcitonin gene-related peptide (CGRP) on bladder smooth muscle cells (BSMCs) under high glucose (HG) treatment in vitro. BSMCs from Sprague-Dawley rat bladders were cultured and passaged in vitro. The third-generation cells were cultured and divided into control group, HG group, HG + CGRP group, HG + CGRP + asiatic acid (AA, p-p38 activator) group, CGRP group, AA group, HG + CGRP + CGRP-8-37 (CGRP receptor antagonist) group and HG + LY2228820 (p38 MAPK inhibitor) group. The cell viability, apoptosis, malondialdehyde (MDA) and superoxide dismutase (SOD) levels of BSMCs were observed by the relevant detection kits. The expressions of α-SM-actin, p38 and p-p38 were detected by qRT-PCR or Western blot analysis. Compared with the control group, the cell viability, SOD and α-SM-actin levels of BSMCs were decreased and apoptotic cells, MDA and p-p38 levels were increased after HG treatment, while these changes could be partly reversed when BSMCs were treated with HG and CGRP or LY2228820 together. Moreover, AA or CGRP-8-37 could suppress the effect of CGRP on BSMCs under HG condition. Our data indicate that CGRP protects BSMCs from oxidative stress induced by HG in vitro, and inhibit the α-SM-actin expression decrease through inhibiting the intracellular p38 MAPK signaling pathway.
Collapse
Affiliation(s)
- Jun Xue
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China
| | - Yadong Liu
- Department of Urology, The Third People's Hospital of Yancheng, Yancheng, 224001, Jiangsu, China
| | - Sichong Zhang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China
| | - Liucheng Ding
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China
| | - Baixin Shen
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China
| | - Yunpeng Shao
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China
| | - Zhongqing Wei
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, China.
| |
Collapse
|
|
6
|
CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis. Biosci Rep 2021; 40:222486. [PMID: 32219332 PMCID: PMC7560515 DOI: 10.1042/bsr20200092] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/22/2020] [Accepted: 03/26/2020] [Indexed: 12/14/2022] Open
Abstract
Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. The present study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 overexpression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 overexpression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.
Collapse
|
|
7
|
Sah SK, Samuel VP, Dahiya S, Singh Y, Gilhotra RM, Gupta G, Mishra A, Sharma RK, Kumar GS, SreeHarsha N, Chellappan DK, Dua K. A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia. Chem Biol Interact 2019; 306:117-122. [PMID: 31004596 DOI: 10.1016/j.cbi.2019.04.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/11/2019] [Accepted: 04/17/2019] [Indexed: 01/07/2023]
Abstract
Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.
Collapse
Affiliation(s)
| | - Vijaya Paul Samuel
- Department of Anatomy, RAK College of Medicine, RAK Medical and Health Sciences, University, Ras Al Khaimah, United Arab Emirates
| | - Sunita Dahiya
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USA
| | - Yogendar Singh
- Department of Pharmaceutical Sciences, Mahatma Gandhi College of Pharmaceutical Sciences, Sitapura, Jaipur, India
| | - Ritu M Gilhotra
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India.
| | - Anurag Mishra
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India
| | - Rakesh Kumar Sharma
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India
| | | | - Nagaraja SreeHarsha
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney (UTS), Ultimo, NSW 2007, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, NSW 2308, Australia.
| |
Collapse
|