Integrated pharmacokinetic properties and tissue distribution of multiple active constituents in Qing-Yi Recipe: A comparison between granules and decoction DOI Creative Commons
Shurong Ma,

Tianfu Wei,

Biao Zhang

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155645 - 155645

Published: April 15, 2024

Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, efficacy which has been demonstrated in more than thirty clinical trials. However, in-vivo pharmacodynamic material basis this formula remains unclear. A sensitive and accurate method quantifying twenty-two potential bioactive constituents Recipe biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), fully validated. Then, integrated pharmacokinetic properties its major metabolites rats were investigated post-listed granules at both dosages. Subsequently, tissue distributions those nine organs (especially pancreas) determined, overall parameters between two formulations compared. Though chemical profiles formulas varied across formulations, exposure level very similar, baicalin, wogonoside, geniposide, rhein, costunolide, paeoniflorin top six compounds circulation. All natural products reached their first peak within 2 h, several them exhibited bimodal or multimodal patterns under complicated transformation metabolic enzymes, these markedly changed compared with monomers. Diverse emodin baicalin/baicalein detected circulation tissues, augmenting vivo forms compounds. Finally, enrichment tetrahydropalmatine corydaline pancreas observed most remained gastrointestinal system, providing foundation regulatory effects on gut microbiota as well intestinal functions. Herein, distribution multiple active dosages, time. This investigation expected to provide new perspective reference future studies physiological disposition treat abdomen diseases.

Language: Английский

Current trends in acute pancreatitis: Diagnostic and therapeutic challenges DOI Creative Commons
Enver Zerem, Admir Kurtčehajić, Suad Kunosić

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(18), P. 2747 - 2763

Published: May 10, 2023

Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which can progress to severe AP, with a high risk death. It one most complicated and clinically challenging all disorders affecting abdomen. The main causes AP are gallstone migration alcohol abuse. Other uncommon, controversial insufficiently explained. primarily characterized by inappropriate activation trypsinogen, infiltration cells, destruction secretory cells. According revised Atlanta classification, severity categorized into three levels: Mild, moderately severe, depending upon organ failure local as well systemic complications. Various methods have been used for predicting its outcome, such clinical evaluation, imaging evaluation testing various biochemical markers. However, very complex despite fact that there several clinical, criteria assessment it not easy task predict subsequent course. Therefore, existing controversies regarding diagnostic therapeutic modalities, their effectiveness complications in treatment AP. reason being fact, pathophysiologic mechanisms fully elucidated need be studied further. In this editorial article, we discuss efficacy management

Language: Английский

Citations

67

Polyamines: their significance for maintaining health and contributing to diseases DOI Creative Commons

Mengjuan Xuan,

Xinyu Gu, Juan Li

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 4, 2023

Abstract Polyamines are essential for the growth and proliferation of mammalian cells intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, post-translational modification. These regulate cellular proliferation, differentiation, programmed cell death, formation tumors. Several studies have confirmed positive effect polyamines on maintenance health, while others demonstrated that their activity may promote occurrence progression diseases. This review examines a variety topics, polyamine source metabolism, including transport, potential impact health disease. In addition, brief summary effects oncogenes signaling pathways tumor metabolism is provided.

Language: Английский

Citations

60

Overview of the vital roles of macro minerals in the human body DOI Creative Commons
Ali Adeeb Hussein Ali

Journal of Trace Elements and Minerals, Journal Year: 2023, Volume and Issue: 4, P. 100076 - 100076

Published: June 1, 2023

Macro minerals, also known as macro elements, are minerals that required in large amounts the human body. part of biological structure body, play an important role metabolic processes, and participate almost all processes occur can be toxic if consumed quantities for extended period. There is some evidence to suggest calcium intake may associated with a lower risk obesity. However, relationship between obesity not well understood, more research needed fully understand link. Calcium has been studied its potential development certain types cancer, specifically colorectal breast prostate cancer. higher A deficiency macroelement refers lack one or essential by humans. Macroelement deficiencies lead various health problems, such anemia, osteoporosis, muscle weakness, corrected. The macroelements blood cause many chronic diseases. Hormonal changes resulting from have consequences weight gain, obesity, increased cancer future. It maintain balanced diet ensure adequate elements.

Language: Английский

Citations

51

The Importance of Microbiota and Fecal Microbiota Transplantation in Pancreatic Disorders DOI Creative Commons
Adrian Boicean, Cristian Ichim, Samuel Bogdan Todor

et al.

Diagnostics, Journal Year: 2024, Volume and Issue: 14(9), P. 861 - 861

Published: April 23, 2024

The role of the intestinal microbiota in diagnosis and treatment pancreatic diseases is increasingly significant. Consequently, fecal transplantation (FMT) emerging as a promising therapeutic avenue for various disorders, including cancer, pancreatitis, type 1 diabetes (T1D). This innovative procedure entails transferring gut from healthy donors to individuals affected by ailments with potential restore balance alleviate associated symptoms. FMT represents pioneering approach improve patient outcomes diseases, offering tailored treatments customized individual microbiomes specific conditions. Recent research highlights benefits targeting personalized interventions disorders. However, comprehensive understanding intricate interplay between physiology warrants further investigation. necessity additional studies endeavors remains crucial, especially elucidating both adult pediatric cases pathological

Language: Английский

Citations

26

Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis DOI Creative Commons
Sanjay Pandanaboyana, Cecilie Siggaard Knoph, Søren Schou Olesen

et al.

United European Gastroenterology Journal, Journal Year: 2024, Volume and Issue: 12(3), P. 326 - 338

Published: March 4, 2024

Abstract Background The effect of analgesic modalities on short‐term outcomes in acute pancreatitis remains unknown. However, preclinical models have raised safety concerns regarding opioid use patients with pancreatitis. Objective This study aimed to assess the association between analgesics, particularly opioids, and severity mortality hospitalised Methods prospective multicentre cohort recruited consecutive admitted a first episode April 1 30 June 2022, 1‐month follow‐up. Data aetiology, clinical course, treatment were collected. primary outcome was analgesia severity, which analysed using univariate multivariate analyses. Results Among total 1768 patients, included from 118 centres across 27 countries, 1036 (59%) had opioids administered admission day, 167 (9%) received after day. On analysis, moderately severe or associated male sex, Asian ethnicity, alcohol comorbidity, predicted pancreatitis, higher pain scores, longer duration (all p < 0.001). scores increased risk Furthermore, day (but not day) doubled disease (OR 2.07 (95% CI, 1.29–3.33); = 0.003). Opioid for 6 days more an independent factor 3.21 2.16–4.79; mortality. Conclusion only when more. Future randomised studies should re‐evaluate whether might be safe

Language: Английский

Citations

18

Acute pancreatitis: A review of diagnosis, severity prediction and prognosis assessment from imaging technology, scoring system and artificial intelligence DOI Creative Commons

Jian-Xiong Hu,

Chengfei Zhao, Shuling Wang

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(37), P. 5268 - 5291

Published: Sept. 25, 2023

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by severity disease. Diagnosis, prediction, and prognosis assessment AP typically involve use imaging technologies, such as computed tomography, magnetic resonance imaging, ultrasound, scoring systems, including Ranson, Physiology Chronic Health Evaluation II, Bedside Index for Severity in scores. Computed tomography considered gold standard modality due to its high sensitivity specificity, while ultrasound can provide additional information on biliary obstruction vascular complications. Scoring systems utilize laboratory parameters classify patients into mild, moderate, or severe categories, guiding treatment decisions, intensive care unit admission, early enteral feeding, antibiotic use. Despite central role technologies management, these methods have limitations terms accuracy, reproducibility, practicality economics. Recent advancements artificial intelligence (AI) new opportunities enhance their performance analyzing vast amounts data. AI algorithms analyze large data, identify system patterns, predict course AI-based models shown promising results predicting mortality AP, but further validation standardization are required before widespread application. In addition, understanding correlation between three will aid developing that accurately, sensitively, specifically be used diagnosis, through complementary advantages.

Language: Английский

Citations

29

MSCs Deliver Hypoxia‐Treated Mitochondria Reprogramming Acinar Metabolism to Alleviate Severe Acute Pancreatitis Injury DOI Creative Commons
Zhengyu Hu, Dongyan Wang, Jian Gong

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(25)

Published: July 6, 2023

Abstract Mitochondrial function impairment due to abnormal opening of the mitochondrial permeability transition pore (MPTP) is considered central event in acute pancreatitis; however, therapeutic choices for this condition remain controversial. Mesenchymal stem cells (MSCs) are a family member with immunomodulatory and anti‐inflammatory capabilities that can mitigate damage experimental pancreatitis. Here, it shown MSCs deliver hypoxia‐treated functional mitochondria damaged pancreatic acinar (PACs) via extracellular vesicles (EVs), which reverse metabolic PACs, maintain ATP supply, exhibit an excellent injury‐inhibiting effect. Mechanistically, hypoxia inhibits superoxide accumulation upregulates membrane potential, internalized into PACs EVs, thus, remodeling state. In addition, cargocytes constructed cell denucleation as vectors exert similar effects MSCs. These findings reveal important mechanism underlying role MSC therapy offer possibility applying patients severe

Language: Английский

Citations

28

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition DOI
Yanan Wang, Xinyuan Wang, Xue Zhang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(18), P. 11778 - 11803

Published: April 23, 2024

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with high mortality rate (∼40%). Existing pharmaceutical therapies in development or clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped neutrophil membranes and surface modified the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) trypsin activity inhibitor gabexate mesylate (Ga). In AP mouse model, formulation exhibited efficient recruitment at endothelium, trans-endothelial migration, precise acinar cell targeting, resulting rapid localization higher accumulation. A low dose of (BA: 200 μg kg–1, Ga: 0.75 mg kg–1) significantly reduced pancreas function indicators close normal levels 24 h, effectively restored redox status, apoptotic proportion, blocked systemic amplified cascade, dramatic increase survival from 58.3 even 100%. Mechanistically, inhibited endoplasmic reticulum stress (IRE1/XBP1 ATF4/CHOP axis) impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying cells restoring cellular "health status". This provides an upstream strategy translation prospects management through synergistic ion homeostasis regulation autodigestion inhibition.

Language: Английский

Citations

16

Mitochondrial (mt)DNA–cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis DOI Creative Commons

Yiqiu Peng,

Yuxi Yang,

Yingying Li

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: April 27, 2024

Abstract Background Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate cellular immune suppression during process SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) plays an important role. However, function mechanism cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods Lipopolysaccharide (LPS) was combined with caerulein-induced SAP wild type, cGAS −/− sting mice . Primary macrophages were extracted via bronchoalveolar lavage peritoneal lavage. Ana-1 cells pretreated LPS stimulated nigericin sodium salt induce pyroptosis vitro. Results triggered NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated alveolar mouse model. Knockout / STING could ameliorate NLRP3 pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria induced a cGAS- dose-dependent manner. Upregulated signal promote inflammasome-mediated increase serum interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α levels thus, SAP-associated LI (SAP-ALI). Downstream molecules STING, IRF7, IRF3 connect mtDNA–cGAS–STING axis NLRP3–pyroptosis axis. Conclusions Negative regulation any molecule mtDNA–cGAS–STING–IRF7/IRF3 pathway affect inflammasomes, thereby reducing improving SAP-ALI

Language: Английский

Citations

16

Targeting mitochondrial quality control: new therapeutic strategies for major diseases DOI Creative Commons
Weilong Hong, He Huang, Xue Zeng

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Aug. 21, 2024

Abstract Mitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for prevention and treatment numerous diseases. Previous reviews on this topic have however been inconsistencies lack systematic organization. Therefore, review aims to provide comprehensive overview explore possibility targeting same major This systematically summarizes three fundamental characteristics control, including morphology dynamics, function metabolism, protein expression regulation. It also extensively examines how imbalances are linked diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, tumors. Additionally, explores innovative approaches target using small molecule drugs that regulate critical steps quality, nanomolecular materials designed precise mitochondria, novel cellular therapies, vesicle therapy transplantation. offers perspective comprehending shared mechanisms underlying occurrence progression diseases provides theoretical support practical guidance clinical implementation therapeutic strategies treating

Language: Английский

Citations

15