Pancreatic acinar cells

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in 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 with neutrophil membranes and surface modified with the N , N -dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga)...

Since the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+ ;Trp53flox/flox ;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell datasets revealed that the ECM shapes an alternate route of acinar-ductal transdifferentiation of acinar cells into a central hub of elegantly restrained TOP2A-overexpressing cancer cells that spread out as unique cancer clusters with copy number amplifications in MYC-PTK2 locus and PIK3CA...

BACKGROUND: The advances of minimally invasive endoscopy-guided procedures that usually yield limited diagnostic material changed pancreaticobiliary cytopathology into one of the most challenging areas of Cytopathology given the abundance of differential diagnoses to be considered when dealing with limited specimens. SUMMARY: We describes a few challenging, examples of potential pitfalls in pancreatobiliary cytopathology evaluation collected from a busy academic hospital (tertiary) center...

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis...

CASE PRESENTATION: A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the duodenum. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion in the descending part of the duodenum. Endoscopic ultrasound revealed a well-defined hypoechoic tumor. Biopsy and immunohistochemical findings including negative Synaptophysin and Chromogranin A staining and positive Trypsin and BCL10 staining suggested a carcinoma with acinar cell differentiation...

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (m6 A) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the m6 A modification of ZKSCAN3 in the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors...

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine...

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study...

Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance...

BACKGROUND: Postoperative pancreatic fistula (POPF) contributes significantly to morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms remain unclear. This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD. CASE SUMMARY: Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD...

Pancreatic inflammation is a risk factor for the development of pancreatic cancer. Increased presence of inflammatory macrophages can be found in response to a KRAS mutation in acinar cells or in response to experimentally-induced pancreatitis. Inflammatory macrophages induce pancreatic acinar cells to undergo dedifferentiation to a duct-like progenitor stage, a process called acinar-to-ductal metaplasia (ADM). Occurrence of ADM lesions are believed to be the initiating event in tumorigenesis. Here we will discuss how macrophage-induced oxidative stress contributes to ADM and how ADM cells shape the fibrotic stroma needed for further progression...

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UBE2F, a neddylation E2, neddylates CUL5 to activate cullin-RING ligase-5, upon coupling with neddylation E3 RBX2/SAG. Whether and how UBE2F controls pancreatic tumorigenesis is previously unknown. Here, we showed that UBE2F is essential for the growth of human pancreatic cancer cells with KRAS mutation. In the mouse KrasG12D pancreatic ductal adenocarcinoma (PDAC) model, Ube2f deletion suppresses cerulein-induced pancreatitis, and progression of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia...

Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination...

The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs...

Pancreatic acinar cell carcinoma (PACC) is a rare form of pancreatic cancer that commonly harbors targetable alterations, including activating fusions in the MAPK pathway and loss-of-function (LOF) alterations in DNA damage response/homologous recombination DNA repair-related genes. Here, we describe a patient with PACC harboring both somatic biallelic LOF of NBN and an activating NTRK1 fusion. Upon disease progression following 13 months of treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), genomic analysis of a metastatic liver biopsy revealed the emergence of a novel reversion mutation restoring the reading frame of NBN...

Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents...

The immunoregulatory role of mesenchymal stem cells (MSCs) in inflammation is heterogeneous and can exhibit anti-inflammatory or proinflammatory properties depending on the microenvironment. We herein observed that the activation of Toll-like receptor 3 (TLR3) by polyinosinic : polycytidylic acid (poly(I : C)) stimulation facilitated the transformation of adipose-derived stem cells (ADSCs) into an anti-inflammatory phenotype. The enhanced anti-inflammatory properties were assessed in a taurocholate-induced pancreatitis model...

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane...

Acute pancreatitis (AP) continues to pose a major challenge as targeted therapeutic interventions are absent. Mitochondrial dysfunction and inflammasome-dependent pyroptosis are involved in the pathogenic mechanisms of AP. CIRP is a stress-response protein and a damage-associated molecular pattern (DAMP) molecule. In our previous studies, we discovered that excessive CIRP can directly damage pancreatic acinar cells. Nonetheless, the precise involvement of CIRP in AP is still unexplored. The primary aim of this study was to examine the potential involvement of CIRP in the development of pyroptosis and mitochondrial dysfunction in AP...