Identification of procyanidins as α-glucosidase inhibitors, pancreatic lipase inhibitors, and antioxidants from the bark of Cinnamomum cassia by multi-bioactivity-labeled molecular networking.

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods.

Prevalence of Pancreatic Steatosis and Its Associated Factors in Turkey: A Nation-Wide Multicenter Study.

BACKGROUND/AIMS:  Pancreatic steatosis (PS) is a pathology associated with metabolic syndrome (MS), endocrin and exocrine disfunctions of the pancreas, and fatty liver. The data on the frequency of PS are very limited. We aimed to evaluate the frequency of PS detected by transabdominal ultrasonography (TAU) in gastroenterology clinics located in different geographical regions of Turkey and the factors associated with it. MATERIALS AND METHODS:  Volunteers were evaluated by TAU for PS and hepatosteatosis (HS), and its degree. Pancreatic stiffness was evaluated by ultrasonographic shear wave elastography (SWE). All demographic, physical, and biochemical parametres were measured. RESULTS:  A total of 1700 volunteers from 14 centers throughout Turkey were included in the study. Mean age was 48.03 ± 20.86 years (56.9% female). Prevalance of PS was detected in 68.9%. In the PS group, age, body mass index (BMI), waist circumference, systolic blood pressure, fasting blood glucose (FBG), lipid levels, insulin resistance, diabetes mellitus, hypertension, MS frequency, and pancreatic SWE score were increasing, and fecal elastase level was decreasing in correlation with the degree of PS. The frequency of HS was 55.5%. Hepatosteatosis [odds ratio (OR): 9.472], increased age (OR: 1.02), and BMI (OR: 1.089) were independent risk factors for the occurrence of PS. Lean-PS rate was 11.8%. The lean-PS group was predominantly female and younger than non-lean PS. Also it has lower blood pressure, FBG, liver enzymes, lipid levels, and HS rates. CONCLUSION:  The frequency of PS was found 68.9% in Turkey. Its relationship was determined with age, BMI, HS, MS (and its components), pancreatic stiffness, and fecal elastase level.

Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function.

The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology. Therefore, it is necessary to investigate how exocrine-endocrine "crosstalk" may impact pancreatic function. In this article, we discuss common exocrine diseases, including cystic fibrosis, acute, hereditary, and chronic pancreatitis, and the impact of these exocrine diseases on endocrine function. Additionally, we review how obesity and fatty pancreas influence exocrine function and the impact on cellular communication between the exocrine and endocrine compartments. Interestingly, in all pathologies, there is evidence that signals from the exocrine disease contribute to endocrine dysfunction and the progression to diabetes. Continued research efforts to identify the mechanisms that underlie the crosstalk between various cell types in the pancreas are critical to understanding normal pancreatic physiology as well as disease states. © 2024 American Physiological Society. Compr Physiol 14:5371-5387, 2024.

Minimally invasive removal of a foreign body in the pancreas using digital intelligent technology: a case report.

Pancreatitis caused by a fish bone penetrating the posterior wall of the stomach and entering the pancreas is rare. We herein report a case involving a woman in her late 30s with an approximately 1-month history of recurrent upper abdominal pain. Initial evaluation at another hospital failed to identify the cause but raised suspicion of pancreatic cancer. Computed tomography, magnetic resonance imaging, and a detailed consultation led us to suspect that the patient's pain had been caused by inadvertent ingestion of a fish bone. We used three-dimensional visualization technology to determine the location of the fish bone and informed the patient of the lesion and surgical plan through a simulated surgical demonstration. During surgery, we applied augmented reality navigation technology to remove the fish bone by a minimally invasive approach. The patient was discharged on postoperative day 3. She was followed up by telephone 24 hours after discharge. Outpatient follow-up was performed 1 week after discharge and on day 30. The patient recovered well and developed no complications. This case shows that digital medical technology can be applied in patients undergoing surgical removal of a pancreatic foreign body. Such technology assists with preoperative evaluation, patient education, and intraoperative trauma reduction.

[Robotic enucleation of pancreatic insulinoma]. / Robot-assistirovannaya enukleatsiya insulinomy podzheludochnoi zhelezy.

We demonstrate robot-assisted treatment of a patient with benign pancreatic insulinoma. A 31-year-old patient suffered from attacks of weakness, numbness of the fingertips and «turbidity of consciousness¼ for 2 years. These symptoms occurred on an empty stomach and regressed after eating. We found pancreatic insulinoma. The patient underwent robotic enucleation of pancreatic tumor. Surgery time was 145 min. Postoperative period proceeded without complications. Hyperglycemia up to 10.5 mmol/l on the first postoperative day was followed by normalization after 4 days. The patient was discharged in 6 days after surgery. Minimally invasive robotic enucleation of insulinoma minimizes surgical trauma and provides precise resection of tumor. The key aspect of safe enucleation is localization of tumor at a distance of at least 2 mm from the pancreatic duct.

Spindle Cell Neoplasms of Pancreas.

Null.

Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in ß-cell regeneration.

Regeneration of insulin-producing ß-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of ß-cells. Here, we aimed to characterize how hepatocytes can contribute to ß-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of ß-cell loss. Using lineage tracing, we show that hepatocytes do not directly convert into ß-cells even under extreme ß-cell ablation conditions. A transcriptomic analysis of isolated hepatocytes after ß-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role of the molybdenum cofactor (Moco) biosynthetic pathway in ß-cell regeneration and glucose metabolism in zebrafish. Consistently, molybdenum cofactor synthesis 2 (Mocs2) haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.

Non-human primate model of long-COVID identifies immune associates of hyperglycemia.

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

Pancreatic head carcinoma derived from the dorsal pancreas is more likely to metastasize early than from the ventral pancreas through microvascular invasion.

The development of the pancreatic head originates from the fusion of the ventral and dorsal pancreatic primordia during embryonic development. Theoretically, the origin of pancreatic head cancer also exists from the ventral pancreas and the dorsal pancreas. Among 49 patients with pancreatic head cancer, pancreatic head cancer was divided into pancreatic head cancer originating from the ventral (PHCv) or dorsal pancreas (PHCd) through imaging and pathological classification. The clinical data was collected and compared between the PHCv group and the PHCd group. The results showed that the patients from the PHCd group had worse long-term survival than those from the PHCv group (10 months vs 14.5 months). Similarly, the progression-free survival (PFS) results also indicate that patients from the PHCd group had a shorter time than those from the PHCv group (5 months vs 9.5 months). Further stratified analysis of potentially related factors showed that microvascular invasion is related to poor prognosis, and patients with pancreatic head cancer derived from the dorsal pancreas are more likely to develop microvascular invasion.

Diagnostic Efficacy of Cell Block and Liquid-Based Cytology for Endoscopic Ultrasound-Guided Fine Needle Aspiration in Pancreatic Tumors.

This study aimed to evaluate the diagnostic efficacy of cell block (CB) and liquid-based cytology (LBC) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic tumors. The study included patients who underwent EUS-FNA for pancreatic tumors between January 2015 and February 2021 and whose cytology samples were both processed for LBC and CB. Data of 390 patients (220 men, mean age: 64.2 ± 11.4 years) were retrospectively analyzed. Of the detected lesions (size: 17-120 mm; mean: 39.9 ± 13.9 mm), 220 (56.4%) were located in the head and uncinate process of the pancreas. Lesions in 339 (86.9%) patients were diagnosed as malignant using CB and/or LBC and suspicious for malignancy in 44 (11.3%) patients. In 7 patients with non-diagnostic (6 cases) or negative for malignancy (1 case) EUS-FNA results using both methods, the diagnosis of malignancy was established via ultrasound-guided percutaneous biopsy. Malignancy was detected in 324 (92.4%), 313 (87.9%), and 298 (87.9%) patients using CB, LBC, and both CB and LBC, respectively. Final diagnosis was obtained in 339 (98%) patients by using CB and/or LBC. The combined use of the both methods exhibited significantly superior diagnostic accuracy compared with CB and LBC alone (P < .001). Liquid-based cytology and CB exhibit high diagnostic accuracy for the detection of pancreatic tumors in patients undergoing EUS-FNA. The combined use of both methods showed a significantly higher diagnostic accuracy than LBC and CB alone.

Accessibility of Percutaneous Biopsy in Retrocolic-Placed Pancreatic Grafts With a Duodeno-Duodenostomy.

Duodeno-duodenostomy (DD) has been proposed as a more physiological alternative to conventional duodeno-jejunostomy (DJ) for pancreas transplantation. Accessibility of percutaneous biopsies in these grafts has not yet been assessed. We conducted a retrospective study including all pancreatic percutaneous graft biopsies requested between November 2009 and July 2021. Whenever possible, biopsies were performed under ultrasound (US) guidance or computed tomography (CT) guidance when the US approach failed. Patients were classified into two groups according to surgical technique (DJ and DD). Accessibility, success for histological diagnosis and complications were compared. Biopsy was performed in 93/136 (68.4%) patients in the DJ group and 116/132 (87.9%) of the DD group (p = 0.0001). The graft was not accessible for biopsy mainly due to intestinal loop interposition (n = 29 DJ, n = 10 DD). Adequate sample for histological diagnosis was obtained in 86/93 (92.5%) of the DJ group and 102/116 (87.9%) of the DD group (p = 0.2777). One minor complication was noted in the DD group. The retrocolic position of the DD pancreatic graft does not limit access to percutaneous biopsy. This is a safe technique with a high histological diagnostic success rate.

Pancreas Fine Needle Aspiration: Current and Future Impact on Patient Care.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

[Isolated pancreatic injury after blunt abdominal trauma: severe pathology in initially asymptomatic patient]. / Pancreasletsel na een stomp buiktrauma.

BACKGROUND: Isolated pancreatic injury after blunt abdominal trauma is rare but unreliably excludable based on clinical symptoms. A CT-abdomen is the golden standard in diagnosing. Undiagnosed pancreatic injury can result in severe complications as abscesses and fistulas. CASE DESCRIPTION: A sixteen-year old patient was brought to the Emergency Department (ED) with epigastric pain, two days after a low-energy scooter accident. No (abdominal) alarming symptoms were objectified during direct assessment by the general practitioner. However, a complete pancreatic transection was diagnosed after assessment at the ED, eventually resulting in a distal pancreatectomy with postoperative associated complications. CONCLUSION: In all traumas, the mechanism of injury should be judged critically for the possibility of abdominal injury (as pancreatic damage) and thus the need for imaging. An initially harmless clinical condition can mask extensive injury. This case illustrates the importance of thoughtful expectant policies with return instructions or demarcated follow-up when no CT-scan is performed.

Robotic surgery reduces the consumption of medical consumables: cost analysis of robotic pancreatic surgery from a tertiary hospital in China.

Robotic surgery has been increasingly adopted in various surgical fields, but the cost-effectiveness of this technology remains controversial due to its high cost and limited improvements in clinical outcomes. This study aims to explore the health economic implications of robotic pancreatic surgery, to investigate its impact on hospitalization costs and consumption of various medical resources. Data of patients who underwent pancreatic surgery at our institution were collected and divided into robotic and traditional groups. Statistical analyses of hospitalization costs, length of stay, costs across different service categories, and subgroup cost analyses based on age, BMI class, and procedure received were performed using t tests and linear regression. Although the total hospitalization cost for the robotic group was significantly higher than that for the traditional group, there was a notable reduction in the cost of medical consumables. The reduction was more prominent among elderly patients, obese patients, and those undergoing pancreaticoduodenectomy, which could be attributed to the technological advantages of the robotic surgery platform that largely facilitate blood control, tissue protection, and suturing. The study concluded that despite higher overall costs, robotic pancreatic surgery offers significant savings in medical consumables, particularly benefiting certain patient subgroups. The findings provide valuable insights into the economic viability of robotic surgery, supporting its adoption from a health economics perspective.

Coupling Microdroplet-Based Sample Preparation, Multiplexed Isobaric Labeling, and Nanoflow Peptide Fractionation for Deep Proteome Profiling of the Tissue Microenvironment.

There is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity in a cell-type-specific manner to better understand and predict the function of complex biological systems such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverage due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (microdroplet processing in one pot for trace samples), multiplexed isobaric labeling, and a nanoflow peptide fractionation approach. The integrated workflow allowed us to maximize proteome coverage of laser-isolated tissue samples containing nanogram levels of proteins. We demonstrated that the deep spatial proteomics platform can quantify more than 5000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 µm2) and differentiate unique protein abundance patterns in pancreas. Furthermore, the use of the microPOTS chip eliminated the requirement for advanced microfabrication capabilities and specialized nanoliter liquid handling equipment, making it more accessible to proteomic laboratories.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology.

Ras-related Rap1A GTPase is implicated in pancreas ß-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein ß (Ero1lß), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lß and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.

Diagnostic Challenge in Heterotopic Pancreas in the Ampulla of Vater with Obstructive Jaundice - A Case Report and Literature Review.

Heterotopic pancreas is a rare congenital abnormality. The most common location is the stomach, duodenum and proximal jejunum. Rare locations are represented by the ampulla of Vater, esophagus, ileum, Meckel diverticulum, biliary tract, mesentery and spleen. We present the case of a 49 year old patient investigated for obstructive jaundice and diagnosed with an ampullar heterotopy of pancreas parenchyma, initially considered to be a malignant tumor. A Whipple pancreatoduodenectomy was performed with good postoperative evolution, the serum levels of bilirubin being normal after the first postoperative week.

Autophagy-mediated ferroptosis is involved in development of severe acute pancreatitis.

BACKGROUND: Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. METHODS: We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. RESULTS: Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. CONCLUSIONS: Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP.