Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(4)

Published: June 20, 2023

The pivotal roles of gut microbiota in severe acute pancreatitis-associated lung injury (SAP-ALI) are increasingly revealed, and recent discoveries the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used clinical to treat However, underlying mechanisms remain be fully elucidated. Herein, by using caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model antibiotics (Abx) cocktail-induced pseudogermfree model, we tried uncover administration QYD explored its possible mechanisms. Immunohistochemical results showed that severity intestinal barrier functions could affected relative depletion bacteria. composition was partially recovered after treatment with decreased Firmicutes/Bacteroidetes ratio increased abundance short-chain fatty acids (SCFAs)-producing Correspondingly levels SCFAs (especially propionate butyrate) feces, gut, serum, lungs were observed, generally consistent changes microbes. Western-blot analysis RT-qPCR indicated AMPK/NF-κB/NLRP3 signaling pathway activated oral QYD, which found possibly related regulatory effects on intestine lungs. In conclusion, our study provides new insights into through modulating has prospective practical value use future. IMPORTANCE Gut affects function. During SAP, significant increase pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) observed. At same time, pathogenic bacteria SCFAs-producing (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). addition, mediated along may play an essential role preventing pathogenesis SAP-ALI, allows reduced systemic inflammation restoration barrier.

Language: Английский

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Understanding Hypertriglyceridemia: Integrating Genetic Insights

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 190 - 190

Published: Jan. 30, 2024

Hypertriglyceridemia is an exceptionally complex metabolic disorder characterized by elevated plasma triglycerides associated with increased risk of acute pancreatitis and cardiovascular diseases such as coronary artery disease. Its phenotype expression widely heterogeneous heavily influenced conditions obesity, alcohol consumption, or syndromes. Looking into the genetic underpinnings hypertriglyceridemia, this review focuses on variants in LPL, APOA5, APOC2, GPIHBP1 LMF1 triglyceride-regulating genes reportedly abnormal transcription translation proteins participating triglyceride-rich lipoprotein metabolism. resulting from abnormalities can be categorized monogenic polygenic. Monogenic also known familial chylomicronemia syndrome, caused homozygous compound heterozygous pathogenic five canonical genes. Polygenic multifactorial syndrome extreme cases variable penetrance affecting genes, a set common non-pathogenic (polymorphisms, using former nomenclature) well-established association triglyceride levels. We further address recent progress triglyceride-lowering treatments. Understanding basis hypertriglyceridemia opens new translational opportunities scope screening development novel therapies.

Language: Английский

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Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 147 - 147

Published: Jan. 23, 2025

Hypertriglyceridemia (HTG) is associated with a residual risk of atherosclerotic cardiovascular disease. Extremely elevated triglyceride (TG) concentrations, particularly due to familial chylomicronemia syndrome (FCS), pose for acute pancreatitis. Standard therapies statins, fibrates, omega-3 fatty acids, and niacin may be insufficient reduce TG levels improve clinical outcomes in patients HTG. Novel antisense oligonucleotides small interfering ribonucleic acids target the key modulators TG-rich lipoprotein catabolism. Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen plozasiran appear safer alternatives volanesorsen regarding drug-induced thrombocytopenia FCS or severe After failure vupanorsen, new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated potential decrease moderate Meanwhile, fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate treatment This comprehensive review outlines pharmacological targets metabolism, discusses international guidelines, summarizes latest evidence from trials provide insight into current emerging options primary

Language: Английский

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Association between serum triglyceride level and severity of acute biliary pancreatitis

Pancreatology, Journal Year: 2024, Volume and Issue: 24(3), P. 343 - 349

Published: Feb. 6, 2024

Acute biliary pancreatitis (ABP) is the most common type of acute pancreatitis. However, effect serum triglyceride (TG) levels on severity ABP remains unclear. The aim this study was to assess correlation between TG and ABP. Data from 526 patients analyzed in study. were divided into normal elevated groups according level measured within 24 hours after admission, group further mild, moderate, severe groups. demographic data clinical outcomes each compared. Of patients, 394 132 (36 57 39 severe). younger (51.5 ± 12.9 vs. 58.9 13.9), predominantly male (66.7% 45.2%), had more history diabetes (22.7% 12.4%) hyperlipidemia (19.7% 0.8%), developed systemic inflammatory response syndrome (SIRS) (25.8% 15.5%), persistent organ failure (POF) (11.4% 2.8%), local complications (62.9% 42.1%) frequently compared (P < 0.05). incidence SIRS, POF, peripancreatic fluid collection (APFC), necrotic (ANC) increased with increasing (Ptrend In multivariate analysis, independently associated APFC, ANC increments 100 mg/dl 0.05), there a linear relationship (non-linear P > 0.05, overall <0.05). addition, nonalcoholic fatty liver disease not risk factor for ANC, APFC patients. Elevated increase levels, relationship.

Language: Английский

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Research progress on the mechanism of acute hypertriglyceridemic pancreatitis

Pancreas, Journal Year: 2024, Volume and Issue: 53(8), P. e700 - e709

Published: May 1, 2024

The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause acute (AP). HTGP is often associated more severe local and systemic complications. Recognized metabolic disorder (HTG), it holds significant relevance pathogenesis HTGP, yet its mechanisms are not fully understood. Both primary (genetic) secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence progression HTGP. This article presents comprehensive review evolving research on pathogenesis, encompassing lipid synthesis metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, gene mutations. By unraveling intricate underlying this aims enhance physicians' understanding disease facilitate development potential targeted pharmacological interventions for patients.

Language: Английский

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Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 2036 - 2057

Published: Jan. 1, 2024

Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity triglyceride-rich lipoproteins (TRLs).Although the role in extrahepatic triglyceride (TG) metabolism circulation has been well documented, relationship between nonalcoholic fatty disease (NAFLD) remains incompletely understood underlying molecular mechanism still needs to be elucidated.Methods: We used CRISPR/Cas9 gene editing delete Apoa5 from Syrian golden hamster, small rodent model replicating human metabolic features.Then, ApoA5-deficient (ApoA5 -/-) hamsters were investigate NAFLD with or without challenging high fat diet (HFD).Results: -/-hamsters exhibited hypertriglyceridemia (HTG) markedly elevated TG levels at 2300 mg/dL hepatic steatosis on regular chow diet, accompanied an increase expression genes regulating lipolysis adipocytes adipose tissue.An HFD challenge predisposed -/- severe HTG (sHTG) steatohepatitis (NASH).Mechanistic studies vitro vivo revealed that targeting disrupted NR1D1 mRNA stability HepG2 cells reduce both protein NR1D1, respectively.Overexpression adeno-associated virus 8 (AAV8) livers significantly ameliorated affecting plasma lipid levels.Moreover, restoration activation UCP1 brown tissue (BAT) cold exposure CL316243 administration could correct sHTG hamsters.Conclusions: Our data demonstrate caused deficiency sufficient elicit aggravates reducing levels, which provides mechanistic link suggests new insights into potential therapeutic approaches for treatment related disorders due clinical trials future.

Language: Английский

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Ultra-early indicators of acute hypertriglyceridemic pancreatitis may influence treatment decision-making

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 10, 2025

This study aimed to explore whether ultra-early indicators can predict the severity of acute hypertriglyceridemic pancreatitis (HTGP) and guide clinical decisions. retrospective analyzed data from HTGP patients who were categorized into mild (MAP) moderately severe/severe (MSAP/SAP) groups based on their final outcomes. Ultra-early (serum calcium, triglyceride [TG], interleukin-6 [IL-6], D-dimer, hemoglobin A1c [HbA1c], arterial lactate) measured within 6 h admission. Among 110 patients, 56 had MAP 54 MSAP/SAP. Within admission, TG, IL-6, HbA1c, lactate levels significantly higher in MSAP/SAP group, while serum calcium was lower. Multivariable logistic regression receiver operator characteristic curve identified as independent risk factors predictors severity. Patients with received blood purification 24 a shorter hospital stay compared those treated later. are promising biomarkers for early prediction Early reduces complications traditional treatments remain effective potentially reducing medical costs.

Language: Английский

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Association Between Serum Triglyceride Levels and the Severity of Acute Pancreatitis: A Retrospective Study

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Background Acute pancreatitis (AP) is a potentially fatal condition with poor prognosis if it escalates to its severe form. The pathophysiology of AP has been associated serum triglyceride (TG) levels. However, the relationship between levels and severity remains poorly understood. Therefore, this study aimed investigate correlation TG AP. Methods This retrospective was conducted at Benazir Bhutto Hospital (BBH) in Rawalpindi, Pakistan, from January 2023 2024, among 210 patients Data gathered on self-devised proforma medical records. Ranson criteria score utilized assess Patients were divided into two groups: non-severe basis their score. analysis done Statistical Package for Social Sciences (SPSS) version 25 (IBM Corp., Armonk, NY) through chi-squared test, independent t-test, Pearson's correlation, simple linear regression analysis. p-value less than 0.05 set as significant. Results Of patients, 135 (64.28%) had AP, while 75 (35.72%) Values variables including gender, age, white blood cell (WBC) count, aspartate transaminase (AST) levels, glucose lactate dehydrogenase (LDH) score, amylase lipase body mass index, length hospital stay significantly (p < 0.05) higher indicated that positively scores (coefficient {r} = 0.80; p 0.003). Moreover, confirmed level significant predictor severity, beta coefficient (β) 3.21 95% confidence interval (CI) 1.82-4.72 0.002). frequency clinical outcomes such pancreatic necrosis, intensive care unit (ICU) admission, mortality elevated Conclusions In current study, found be an increased suggested by adverse raised supports use reliable tool prompt identification high-risk facilitating timely interventions improved outcomes.

Language: Английский

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Association between the triglyceride–glucose index and the risk of acute kidney injury in critically ill patients with acute pancreatitis: a retrospective study

Journal of Intensive Care, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 5, 2025

Abstract Background The triglyceride–glucose (TyG) index is increasingly recognized for its ability to predict cardiovascular and metabolic risks. This study investigated the correlation between TyG risk of acute kidney injury(AKI) in critical ill patients with pancreatitis(AP). Methods Medical Information Mart Intensive Care IV database was retrospectively searched identify AP hospitalized intensive care unit. primary outcome measure incidence AKI. secondary endpoint in-hospital mortality rate renal replacement therapy(RRT) use. Cox regression analysis restricted cubic spline were used analyze association AKI risk. Kaplan–Meier survival performed assess endpoints different groups. Results A total 848 enrolled. 61.56%.The 11.69%. showed that ≥ 8.78 group has a high requiring RRT ( P < 0.001). Multivariable whether continuous variable (HR, 1.65 [95% CI 1.10–2.48], = 0.015) or categorical 1.72 1.09–2.79], 0.028), independently associated patients. splines model illustrated linear relationship higher increased this specific patient population. Conclusions High an independent factor AP. Assessing may be beneficial early stratification interventions improve prognosis.

Language: Английский

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Association between the development of sepsis and the triglyceride-glucose index in acute pancreatitis patients: a retrospective investigation utilizing the MIMIC-IV database

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 12, 2025

Sepsis is a serious consequence of acute pancreatitis (AP) that requires immediate detection and treatment. Triglyceride-glucose (TyG) index demonstrated predictive ability for number diseases. In an effort to enhance clinical care early warning systems, this study examined the association between TyG sepsis risk with aim improving systems. Patients who were first admitted satisfied diagnostic criteria (ICD-9: 5770; ICD-10: K85) chosen from MIMIC-IV database, excluding those lacking essential demographic or laboratory data. Using Sepsis-3.0 criteria. Depending on whether they had not, patients divided into group non-sepsis group. Utilizing formula ln[(triglycerides mg/dl) × (glucose mg/dl)/2], was calculated. The Boruta algorithm Xgboost model used feature selection in order pinpoint important variables affecting results. Logistic regression univariate multivariate factors assess start after admission. Twenty-eight thousand AP screened all, among which 661 ultimately included study. Of these, 228 (34.5%) developed sepsis. shown have significant correlation (OR = 1.891, 95% CI: 1.408–2.555) sepsis, increased observed increase (all P values trend < 0.001). Subgroup analysis showed various ages, sexes, hypertension diabetes, there positive probability 0.05). combination indicators area under curve (AUC) 0.828 (0.794–0.862), significantly greater than alone (0.657 [0.613–0.701]), statistically difference (Z= -7.362, AP, substantially linked higher when combined markers, its power enhanced. findings imply might be helpful determining are at developing

Language: Английский

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