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Journal of Ethnopharmacology Jan 2024Acute pancreatitis (AP) is an acute inflammatory condition of pancreas with high morbidity and mortality, which has no effective medical treatment. Chaiqin chengqi...
ETHNOPHARMACOLOGICAL RELEVANCE
Acute pancreatitis (AP) is an acute inflammatory condition of pancreas with high morbidity and mortality, which has no effective medical treatment. Chaiqin chengqi decoction (CQCQD) has been clinically used for AP for many years in China. However, the underlying mechanisms are still unknown.
AIM OF THE STUDY
To investigate the mechanism of CQCQD on gasdermin D (GSDMD) -mediated pyroptosis in AP.
MATERIALS AND METHODS
In this study, network pharmacology was used to screen the potential mechanism of CQCQD protecting against AP and then we focused to investigate the mechanism of CQCQD on GSDMD mediated pyroptosis. Mouse models of AP were conducted by caerulein and L-arginine. In order to clarify the mechanism of CQCQD, two kinds of GSDMD gene knockout mice (Gsdmd and Pdx1Gsdmd) were applied. And the potential interaction between the main components of CQCQD and GSDMD was explored by molecular docking.
RESULTS
In the caerulein-induced AP model, CQCQD ameliorated pancreatic pathological injury, attenuated systemic inflammation and serum enzymatic levers. Moreover, network pharmacology analysis showed GSDMD mediated pyroptosis was one of the core targets of CQCQD protecting against AP. Additionally, CQCQD appreciably decreased the levels of pyroptosis-related proteins N-terminal GSDMD, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3, and cleaved Caspase-1. Furthermore, the protective effect of CQCQD was neutralized in Gsdmd and Pdx1Gsdmd mice in caerulein-induced AP. In addition, we found that CQCQD protects pancreatic tissue from damage and pancreatitis-associated lung injury in the L-arginine-induced mouse model. Moreover, all of the main components of CQCQD possessed binding activity with GSDMD by molecular docking. Seventeen components bound with the human GSDMD Cys191 successfully, which is important for GSDMD pore formation. Among the components, rhein possessed the highest binding activity.
CONCLUSION
CQCQD could reduce pancreatic necrosis and inflammatory response via inhibiting GSDMD-mediated pyroptosis in acinar cells of AP. Rhein may be the key active ingredient of CQCQD in suppressing pyroptosis.
Topics: Mice; Humans; Animals; Pancreatitis; Gasdermins; Pyroptosis; Acute Disease; Ceruletide; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 37480969
DOI: 10.1016/j.jep.2023.116920 -
World Journal of Gastroenterology Mar 2024Approximately 20%-30% of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis (IPN), a highly morbid and potentially lethal complication....
Approximately 20%-30% of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis (IPN), a highly morbid and potentially lethal complication. Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes. In the past two decades, several markers and predictive tools have been proposed and evaluated for this purpose. Conventional biomarkers like C-reactive protein, procalcitonin, lymphocyte count, interleukin-6, and interleukin-8, and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN. On the other hand, scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested, and the results showed that they may provide better accuracy. For early prevention of IPN, several new therapies were tested, including early enteral nutrition, antibiotics, probiotics, immune enhancement, , but the results varied. Taken together, several evidence-supported predictive markers and scoring systems are readily available for predicting IPN. However, effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition. In this editorial, we summarize evidence concerning early prediction and prevention of IPN, providing insights into future practice and study design. A more homogeneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN, thereby achieving individualized treatment.
Topics: Humans; Pancreatitis, Acute Necrotizing; Biomarkers; C-Reactive Protein; Treatment Outcome; Acute Disease; Necrosis
PubMed: 38577189
DOI: 10.3748/wjg.v30.i9.1005 -
Pancreatology : Official Journal of the... Dec 2023Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and... (Observational Study)
Observational Study
Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and risk factors. We evaluated data from a prospective, multicenter observational cohort study that enrolled adults hospitalized with AP between 2017 and 2021 and followed them for one year. Ninety-eight participants who completed 12-month follow-up were included in this analysis. Diabetes status was assessed using a combination of measured glycated hemoglobin (HbA1c) at predetermined time intervals or physician diagnosis. In 68 participants without diabetes at enrollment, the cumulative incidence of new-onset diabetes was 4.4 % (n = 3) at 3 months and 10.3 % (n = 7) at 12 months. No differences were observed in demographic or pancreatitis-related characteristics between those who did versus did not develop diabetes, in part due to small sample size. In summary, new-onset diabetes was identified in approximately 10 % within one year after an episode of AP. Larger prospective studies are needed to further define the incidence, risk factors, and mechanisms of diabetes and pre-diabetes following AP. NCT03063398.
Topics: Adult; Humans; Pancreatitis; Acute Disease; Prospective Studies; Diabetes Mellitus; Risk Factors
PubMed: 37839923
DOI: 10.1016/j.pan.2023.10.009 -
Frontiers in Immunology 2024Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors... (Review)
Review
Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors ranging from genetics, alcohol use, gall stones, and ductal obstruction caused by calcification or neutrophil extracellular traps. Acute pancreatitis is also characterized by immune cell infiltration of neutrophils and M1 macrophages. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. This receptor can be found on a variety of cell types from endothelial cells to resident and infiltrating immune cells leading to production of pro-inflammatory cytokines as well as immune cell activation and maturation resulting in the furthering of pancreatic damage during acute pancreatitis. In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition.
Topics: Humans; Acute Disease; Endothelial Cells; Pancreas; Pancreatitis; Toll-Like Receptor 4
PubMed: 38585277
DOI: 10.3389/fimmu.2024.1362727 -
Indian Heart Journal Mar 2024Non-statin drugs find utility in the management of dyslipidaemia in mixed dyslipidaemia, patients with statin intolerance, and when guidelines directed low-density... (Review)
Review
Non-statin drugs find utility in the management of dyslipidaemia in mixed dyslipidaemia, patients with statin intolerance, and when guidelines directed low-density lipoprotein cholesterol (LDL-C) target cannot be achieved despite maximally tolerated statin. The most definite indication of fenofibrate monotherapy is fasting serum triglyceride >500 mg/dl to reduce the risk of acute pancreatitis It offers a modest reduction in cardiovascular events. The statin-ezetimibe combination is commonly used for lipid lowering particularly after ACS. Fish oils reduce serum triglycerides by about 25 %. EPA (and not DHA) seems to have cardioprotective effects. Despite cardiovascular outcome benefits, bile-exchange resins have limited use due to poor tolerance. Bempedoic acid added to maximally tolerated statin therapy is approved to lower LDL-C in adults with primary hypercholesterolemia or mixed dyslipidaemias, HeFH, in patients with ASCVD who require additional lowering of LDL-C, and in patients who are statin-intolerant. Inclisiran is a long-acting double-stranded small interfering RNA (siRNA) that inhibits the transcription of PCSK-9 leading to a decrease in PCSK9 generation in hepatocytes and an increase in LDL receptor expression in the liver cell membrane leading to about 50 % reduction in serum LDL-C levels. Lomitapide lowers plasma levels of all ApoB-containing lipoproteins, including VLDL, LDL, and chylomicrons by inhibiting the enzyme microsomal triglyceride transfer protein (MTP) and approved for the treatment of adult patients with homozygous familial hypercholesterolemia (HoFH). Close monitoring for hepatotoxicity is required. Mipomersen is a single-stranded synthetic antisense oligonucleotide (ASO) that affects the production and secretion of apoB-containing lipoproteins with demonstrated efficacy in both homozygous and heterozygous FH patients. It is approved for restricted use due to risk of hepatotoxicity. Pelacarsen is an antisense oligonucleotide that reduces the production of apo(a) in the liver.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Cholesterol, LDL; Anticholesteremic Agents; Acute Disease; Pancreatitis; Hypolipidemic Agents; Oligonucleotides, Antisense; Dyslipidemias; Chemical and Drug Induced Liver Injury
PubMed: 37979722
DOI: 10.1016/j.ihj.2023.11.003 -
International Immunopharmacology Aug 2023Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology....
BACKGROUND
Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid with antioxidant activity. This article seeks to assess the impact of AKBA on AP and investigate its underlying mechanisms.
METHODS
AP was induced in wild-type, Lyz2 Nrf2 mice and Pdx1 Nrf2 mice by caerulein. Serum amylase and lipase levels, along with histological grading, were utilized to evaluate the severity of AP. Murine bone marrow-derived macrophages (BMDMs) were isolated, cultured, and polarized to the M1 subtype. Flow cytometry and ELISA were utilized to identify the macrophage phenotype. Alterations in oxidative stress damage and intracellular ROS were observed. Nrf2/HO-1 signaling pathways were also evaluated.
RESULTS
In a caerulein-induced mouse model of AP, treatment with AKBA reduced blood amylase and lipase activity and ameliorated pancreatic tissue histological and pathological features. Furthermore, AKBA significantly mitigated oxidative stress-induced damage and induced the expression of Nrf2 and HO-1 protein. Additionally, by using conditional knockout mice (Lyz2 Nrf2 and Pdx1 Nrf2 mice), we verified that Nrf2 primarily functions in macrophages rather than acinar cells. In vitro, AKBA inhibits pro-inflammatory M1-subtype macrophage polarization and reduces ROS generation through Nrf2/HO-1 oxidative stress pathway. Moreover, the protective effects of AKBA against AP were abolished in myeloid-specific Nrf2-deficient mice and BMDMs. Molecular docking results revealed interactions between AKBA and Nrf2.
CONCLUSION
Our results confirm that AKBA exerts protective effects against AP in mice by inhibiting oxidative stress in macrophages through the Nrf2/HO-1 Pathway.
Topics: Animals; Mice; Pancreatitis; NF-E2-Related Factor 2; Reactive Oxygen Species; Ceruletide; Acute Disease; Molecular Docking Simulation; Oxidative Stress; Macrophages; Lipase; Amylases
PubMed: 37364326
DOI: 10.1016/j.intimp.2023.110501 -
International Journal of Molecular... Jul 2023Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and... (Review)
Review
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).
Topics: Humans; Glucocorticoids; Acute Disease; Pancreatitis; Respiratory Insufficiency; Respiratory Distress Syndrome; Acute Lung Injury; Sepsis
PubMed: 37569514
DOI: 10.3390/ijms241512138 -
European Review For Medical and... Oct 2023Hyperlipidemic acute pancreatitis (HLAP) remains one of the major digestive emergencies with increasing health risks. Oral refeeding tolerant (ORT) and enteral tube...
OBJECTIVE
Hyperlipidemic acute pancreatitis (HLAP) remains one of the major digestive emergencies with increasing health risks. Oral refeeding tolerant (ORT) and enteral tube feeding tolerant (ETFT) are commonly used for nutritional management in HLAP. However, the differences between ORT and ETFT are yet to be characterized.
PATIENTS AND METHODS
This study included consecutive patients admitted to the Ordos Central Hospital between January 2019 and April 2023, with predefined inclusion criteria.
RESULTS
A total of 335 HLAP patients were recruited according to the inclusion criteria. 268 patients were diagnosed with moderately severe acute pancreatitis (MSAP), of which 193 were in the OFT group and 75 in the ETFT group. In the ETFT group, abdominal pain and abdominal distension were significantly higher than that in the OFT group. No significant result was identified in the laboratory data. However, the OFT group showed a higher hospitalization and cost, as well as exocrine insufficiency and newly onset diabetes, than the ETFT group.
CONCLUSIONS
Based on the incidence of HLAP retrieved in this study, MSAP is the major type with increasing clinical value. From the nutritional management sense, patients who received OFT showed higher hospitalization and cost, as well as lower exocrine insufficiency and newly onset diabetes.
Topics: Humans; Pancreatitis; Acute Disease; Hyperlipidemias; Retrospective Studies; Diabetes Mellitus
PubMed: 37843344
DOI: 10.26355/eurrev_202310_33958 -
Microenvironment of pancreatic inflammation: calling for nanotechnology for diagnosis and treatment.Journal of Nanobiotechnology Nov 2023Acute pancreatitis (AP) is a common and life-threatening digestive disorder. However, its diagnosis and treatment are still impeded by our limited understanding of its... (Review)
Review
Acute pancreatitis (AP) is a common and life-threatening digestive disorder. However, its diagnosis and treatment are still impeded by our limited understanding of its etiology, pathogenesis, and clinical manifestations, as well as by the available detection methods. Fortunately, the progress of microenvironment-targeted nanoplatforms has shown their remarkable potential to change the status quo. The pancreatic inflammatory microenvironment is typically characterized by low pH, abundant reactive oxygen species (ROS) and enzymes, overproduction of inflammatory cells, and hypoxia, which exacerbate the pathological development of AP but also provide potential targeting sites for nanoagents to achieve early diagnosis and treatment. This review elaborates the various potential targets of the inflammatory microenvironment of AP and summarizes in detail the prospects for the development and application of functional nanomaterials for specific targets. Additionally, it presents the challenges and future trends to develop multifunctional targeted nanomaterials for the early diagnosis and effective treatment of AP, providing a valuable reference for future research.
Topics: Humans; Pancreatitis; Acute Disease; Nanotechnology; Reactive Oxygen Species; Inflammation
PubMed: 37996911
DOI: 10.1186/s12951-023-02200-x -
BMJ Open May 2024Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate...
INTRODUCTION
Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment goals for acute pancreatitis. Though opioids are commonly used for analgesia in these patients, there have been concerns about short-term and long-term side effects of using opioids. Recently, non-opioid medications have been studied to treat pain in patients with acute pancreatitis. This systematic review and network meta-analysis aims to assess the comparative efficacy of analgesic medication for non-severe, acute pancreatitis.
METHODS AND ANALYSIS
We will search multiple electronic databases for randomised controlled trials that study pain management in patients with non-severe, acute pancreatitis. The intervention will be any analgesic for acute pancreatitis in the hospital setting. The comparison group will be patients who received a placebo or other active interventions for pain management. The primary outcomes of interest include pain scores and the need for supplementary analgesia. The secondary outcomes will be serious adverse events, local complications, progression to severe pancreatitis, transfer to the intensive care unit, length of hospitalisation, time to start enteral feeds, 30-day all-cause mortality and Quality of Life Scale scores. If sufficient homogeneity exists among included studies, the findings will be pooled using a traditional pairwise and network meta-analysis. The risk of bias in randomised control trials will be evaluated using the Cochrane Risk of Bias Tool 2.0. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to report the certainty of evidence.
ETHICS AND DISSEMINATION
This systematic review will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal. They will give healthcare providers a better awareness of the optimal analgesic medication for pain treatment in non-severe, acute pancreatitis.
Topics: Humans; Systematic Reviews as Topic; Pancreatitis; Network Meta-Analysis; Pain Management; Analgesics; Research Design; Acute Disease; Analgesia; Randomized Controlled Trials as Topic; Analgesics, Opioid
PubMed: 38740508
DOI: 10.1136/bmjopen-2023-081971