Pancreatology, Год журнала: 2022, Номер 22(7), С. 838 - 845
Опубликована: Авг. 3, 2022
Язык: Английский
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Фев. 15, 2024
Low selectivity and tumor drug resistance are the main hinderances to conventional radiotherapy chemotherapy against tumor. Ion interference therapy is an innovative anti-tumor strategy that has been recently reported induce metabolic disorders inhibit proliferation of cells by reordering bioactive ions within cells. Calcium cation (Ca2+) indispensable for all physiological activities In particular, calcium overload, characterized abnormal intracellular Ca2+ accumulation, causes irreversible cell death. Consequently, overload-based ion potential overcome traditional treatment strategies holds promise clinical application. this review, we 1) Summed up current employed in therapy; 2) Described outcome death resulting from 3) Discussed its application synergistic with immunotherapy.
Язык: Английский
Процитировано
8
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116690 - 116690
Опубликована: Май 7, 2024
Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific supportive due to severity clinical course AP, which can fluctuate rapidly unpredictably. Mitochondria, cellular power plant produce energy, are involved in a variety physiological or pathological activities human body. There growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role pathogenesis progression AP. With pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding receptors, activating downstream molecules releasing inflammatory factors. This review focuses on possible interaction between AP mtDAMPs, include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) succinate, focus experimental research potential therapeutic targets practice. Preventing diminishing release targeting receptors might have progression.
Язык: Английский
Процитировано
8
Diagnostics, Год журнала: 2025, Номер 15(3), С. 258 - 258
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1
Cells, Год журнала: 2022, Номер 11(19), С. 3068 - 3068
Опубликована: Сен. 29, 2022
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis due to the lack of methods or biomarkers for early diagnosis and its resistance conventional treatment modalities, targeted therapies, immunotherapies. PDACs are a heterogenous group malignant epithelial neoplasms with various histomorphological patterns complex, genetic/molecular landscapes. The newly proposed molecular classifications PDAC based on extensive genomic, transcriptomic, proteomic epigenetic data have provided significant insights into heterogeneity aggressive biology this deadly disease. Recent studies characterizing tumor microenvironment (TME) shed light dynamic interplays between cells immunosuppressive TME PDAC, which is essential disease progression, as well chemotherapy, developed therapy immunotherapy. There critical need development predictive markers that can be clinically utilized select effective personalized therapies patients. In review, we provide overview histological subtypes precursor lesions, TME, currently available
Язык: Английский
Процитировано
29
Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12
Опубликована: Авг. 12, 2022
Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than century. With additional studies into the pathogenesis AP, new mechanisms been explored. Among them, role immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach importance to defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, modulate In this review, we discuss latest advances understanding pathological DAMPs NETs AP shed light on flexible crosstalk between these vital inflammatory mediators. We, then highlight potentially promising treatment targeting NETs, with focus novel insights mechanism, diagnosis, management AP.
Язык: Английский
Процитировано
26
Journal of Clinical Investigation, Год журнала: 2024, Номер 134(7)
Опубликована: Март 31, 2024
Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which effectively prevented when the cell at rest. Here we showed that of zymogen granules acinar cells was driven directly released from acidic stores including through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded Tmem63a) as an organellar regulator protein integral membrane controlled release via inhibition TPC1 and TPC2 currents. Deletion led extensive NAADP-responsive under basal conditions well upon stimulation GPCR receptors. Moreover, deletion exacerbated disease phenotype murine models severe chronic pancreatitis. Our findings a gatekeeper endows NAADP-sensitive with autoregulatory mechanism preventing uncontrolled pancreatic tissue damage.
Язык: Английский
Процитировано
6
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Авг. 12, 2024
As a chemotherapy agent, doxorubicin is used to combat cancer. However, cardiotoxicity has limited its use. The existing strategies fail eliminate doxorubicin-induced cardiotoxicity, and an in-depth exploration of pathogenesis in urgent need address the issue. Endoplasmic reticulum stress (ERS) occurs when Reticulum (ER) dysfunction results accumulation unfolded or misfolded proteins. Adaptive ERS helps regulate protein synthesis maintain cellular homeostasis, while prolonged stimulation may induce cell apoptosis, leading damage tissue organs. Numerous studies on strongly link excessive activation mechanisms including oxidative stress, calcium imbalance, autophagy, ubiquitination, apoptosis. researchers also found several clinical drugs, chemical compounds, phytochemicals, miRNAs inhibited by targeting ERS. present review aims outline interactions between other summarize ERS’s role this type cardiotoxicity. Additionally, enumerates for considering therapeutic regimens that
Язык: Английский
Процитировано
6
The Journal of Physiology, Год журнала: 2022, Номер 600(11), С. 2579 - 2612
Опубликована: Апрель 17, 2022
Abstract Disorders such as pancreatic or hepatic fibrosis are a cruel reminder that disruption of the delicate physiological balance could result in severe pathological consequences. Fibrosis is usually associated with chronic diseases and manifests itself excessive deposition extracellular matrix, which gradually leads to replacement cellular components by fibrotic lesions, significantly compromising normal tissue functions. The main mediators different populations fibroblasts, predominantly stellate cells liver pancreas, respectively. These undergo phenotypic switch response (bio)chemical physical stimuli acquire myofibroblast‐like phenotype characterised increased contractile adhesive properties, elevated expression certain cytoskeletal membrane proteins, prominent production matrix components. In past few decades, substantial scientific effort has been undertaken investigate pathogenesis fibrosis. Here, mechanisms fibrosis, their aetiological factors, prospective therapies discussed. New against likely be focused on regulation hepatic/pancreatic cell physiology well normalisation organ mechanostasis. image
Язык: Английский
Процитировано
23
Cells, Год журнала: 2022, Номер 11(16), С. 2514 - 2514
Опубликована: Авг. 12, 2022
Recent studies have highlighted the importance of autophagy and particularly non-canonical in development progression acute pancreatitis (a frequent disease with considerable morbidity significant mortality). An important early event is intrapancreatic activation trypsinogen, (i.e., formation trypsin) leading to autodigestion organ. Another prominent phenomenon associated initiation this vacuolisation specifically giant endocytic vacuoles pancreatic acinar cells. These organelles develop cells exposed several inducers (including taurolithocholic acid high concentrations secretagogues cholecystokinin acetylcholine). Notably, trypsinogen occurs vacuoles. trypsinogen-activating undergo activation, long-distance trafficking, autophagy. In review, we will discuss role focus on recently discovered LAP-like (LNCA)
Язык: Английский
Процитировано
22
Scientific Reports, Год журнала: 2022, Номер 12(1)
Опубликована: Май 12, 2022
Abstract Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently use are either too complicated or require data that unavailable on admission lack sufficient predictive value. We therefore aimed to develop tool aid prediction. The XGBoost machine learning algorithm processed from 2387 patients with AP. confidence of model was estimated by bootstrapping method and interpreted via 10th 90th percentiles prediction scores. Shapley Additive exPlanations (SHAP) values were calculated quantify contribution each variable provided. Finally, implemented as an online application using Streamlit Python-based framework. classifier provided AUC value 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender total white blood cell count have most impact based SHAP values. relationship between size training dataset performance shows can be improved. This study combines artificial intelligence. potential this comparable current scoring systems has several advantages over them.
Язык: Английский
Процитировано
21