Acute Pancreatitis: Diagnosis and Treatment

Drugs, Journal Year: 2022, Volume and Issue: 82(12), P. 1251 - 1276

Published: Aug. 1, 2022

Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including children, pregnancy and the elderly. Moderately severe acute with fluid and/or necrotic collections causes substantial morbidity, disease persistent organ failure significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit normal, cross-sectional imaging findings. Gallstones ethanol predominate while hypertriglyceridaemia drugs are notable among many causes. Serum triglycerides, full blood count, renal liver function tests, glucose, calcium, transabdominal ultrasound, chest indicated, if there diagnostic uncertainty. Subsequent undertaken to detect complications, example, C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, inflammatory responses critical pathogenesis, targeted current treatment trials, which crucially important as no internationally licenced drug treat prevent complications. Initial priorities intravenous resuscitation, analgesia, enteral nutrition, when necessary, care support, parenteral antibiotics, pancreatic exocrine endocrine replacement therapy; all may have adverse effects. Patients local complications should be referred specialist tertiary centres guide further management, include drainage necrosectomy. impact can devastating, so prevention reduction risk recurrence progression chronic an increased pancreas cancer proactive management that long term some patients.

Language: Английский

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Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy

Nano-Micro Letters, Journal Year: 2022, Volume and Issue: 14(1)

Published: July 18, 2022

As the indispensable second cellular messenger, calcium signaling is involved in regulation of almost all physiological processes by activating specific target proteins. The importance ions (Ca

Language: Английский

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Physiology of intracellular calcium buffering

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2767 - 2845

Published: June 16, 2023

Calcium signaling underlies much of physiology. Almost all the Ca

Language: Английский

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Self‐Reinforced Bimetallic Mito‐Jammer for Ca²⁺ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 11, 2024

Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature damage‐repair capabilities malignant tumors strongly limit efficacy treatments based on a single treatment mode. To address this challenge, self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) calcium peroxide (CaO 2 ) into hyaluronic (HA) ‐modified metal‐organic frameworks (MOF). After cellular, dissociates CaO Cu 2+ tumor microenvironment. The exposed further yields hydrogen (H O Ca weakly acidic environment to strengthen ‐based Fenton‐like reaction. Furthermore, combination chemodynamic therapy overload exacerbates ROS storms mitochondrial damage, resulting downregulation intracellular adenosine triphosphate (ATP) levels blocking Cu‐ATPase sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic death suppresses metastasis simultaneously. study presents multivariate model for revolutionizing mitochondria relying continuous retention ions boost cuproptosis/immunotherapy cancer.

Language: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca²⁺ Homeostasis Regulation and Pancreas Autodigestion Inhibition

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

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Targeting mitochondrial quality control: new therapeutic strategies for major diseases

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

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Association between serum creatinine to albumin ratio and short- and long-term all-cause mortality in patients with acute pancreatitis admitted to the intensive care unit: a retrospective analysis based on the MIMIC-IV database

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 15, 2024

Background Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels prognosis patients AP. To our knowledge, association short- long-term all-cause AP blood to ratio (CAR) has not been investigated. Therefore, this study aimed evaluate relationships CAR Methods We conducted a retrospective utilizing data from Medical Information Market for Intensive Care (MIMIC-IV) database. The involved analyzing variables obtaining values at time admission. X-tile software was used determine optimal threshold CAR. Kaplan-Meier (K-M) survival curves multivariate Cox proportional hazards regression models were assess both mortality. predictive power, sensitivity, specificity, area under curve (AUC) after hospital admission investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses conducted. Results A total 520 participants included study. ideal threshold, determined by software, 0.446. model revealed an independent CAR≥0.446 7-day (d), 14-d, 21-d, 28-d, 90-d, 1-year (y) before adjustment confounders. K-M showed that had lower rates 7-d, 1-y. demonstrated superior performance, higher AUC than Cr, Alb, serum calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, Sepsis-related Organ Failure Assessment score 1-y intervals. Subgroup did interact majority subgroups. Conclusion can serve as predictor This enhances understanding serum-based biomarkers

Language: Английский

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Unraveling the Connection Between Ion Channels and Pancreatic Stellate Cell Activation

Cellular Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: 59(S1), P. 25 - 40

Published: Jan. 18, 2025

Quiescent pancreatic stellate cells (PSCs) represent only a very low proportion of the tissue, but their activation leads to stroma remodeling and fibrosis associated with pathologies such as chronic pancreatitis ductal adenocarcinoma (PDAC). PSC can be induced by various stresses, including acidosis, growth factors (PDGF, TGFβ), hypoxia, high pressure, or intercellular communication cancer cells. Activated targeting represents promising therapeutic strategy, little is known regarding molecular mechanisms underlying PSCs. Identification new biomarkers desmoplasia in PDAC could lead targets for exocrine disease treatments. Ion channels transporters are transmembrane proteins involved numerous physiological pathological processes, PDAC. They well act biosensors tissue microenvironment, they easily accessible drugs. However, role not fully understood. In this review, we briefly discuss activated PSCs pancreas inflammation (associated PDAC), describe specific ion (Ca2+, K+, Na+ Cl-) these processes light recent literature.

Language: Английский

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Diagnosis and Management of Acute Pancreatitis

Diagnostics, Journal Year: 2025, Volume and Issue: 15(3), P. 258 - 258

Published: Jan. 23, 2025

Acute pancreatitis is an inflammatory condition of the exocrine pancreas that a common indication for hospital admission and has had increasing incidence in last few decades. The diagnosis acute requires satisfaction two out three criteria: (1) abdominal pain radiating to back, (2) serum lipase or amylase levels more times upper limit normal level, (3) findings indicating obtained via computed tomography (CT) scan magnetic resonance imaging (MRI). different etiologies include gallstones, autoimmune disorders, alcohol abuse, smoking, hypertriglyceridemia, obesity, drugs, post-endoscope retrograde cholangiopancreatography (ERCP). initial investigation includes analysis, lipid panel including triglycerides, analysis immunoglobulins, full blood count, electrolyte hemoglobin A1c test, complete metabolic panel, transabdominal ultrasound. therapy oxygen supplementation, provision intravenous fluids, control, nutrition regime. Early oral feeding encouraged if tolerated; not, liquid supplement enteral tube within 48 h shown better outcomes. Some complications are necrosis, infection, insulin resistance leading diabetes mellitus, pancreatic insufficiency requiring enzyme supplementation. Patients need attend regular follow-ups abstain from smoking (if warranted) prevent recurrence pancreatitis. mortality rate decreased past decades because management skills, but recent rise episodes concerning. Sustained endeavors through clinical trials required establish broad variety drugs can be used episodes.

Language: Английский

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