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Copyright of Advances in Biochemistry / Postepy Biochemii is the property of Polish Biochemical Society / Acta Biochimica Polonica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Biomedical engineering, especially tissue engineering, is trying to provide an alternative solution to generate functional organs/tissues for use in various applications. These include beyond the final goal of transplantation, disease modeling and drug discovery as well. The aim of this study is to comprehensively review the existing literature on hydrogel-based vascularized organ (i.e., liver, pancreas, kidneys, intestine, stomach and spleen) tissue engineering of the abdominal organs. Methods: A comprehensive literature search was conducted on the Scopus database (latest search 1 September 2024). The research studies including hydrogel-based vascularized organ tissue engineering in the organs examined here were eligible for the review. Results: Herein, 18 studies were included. Specifically, 10 studies included the liver or hepatic tissue, 5 studies included the pancreas or pancreatic islet tissue, 3 studies included the kidney or renal tissue, 1 study included the intestine or intestinal or bowel tissue, 1 study included the stomach or gastric tissue, and 0 studies included spleen tissue. Conclusion: Hydrogels are biocompatible materials with ideal characteristics for use as scaffolds. Even though organ tissue engineering is a rapidly growing field, there are still many obstacles to overcome to create a fully functional and long-lasting organ. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background The effects of postoperative pancreatic fistula on survival rates remain controversial. The aim of the present study was to evaluate the influence of postoperative pancreatic fistula on overall survival and recurrence-free survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Methods Patients operated on between January 2007 and December 2017 at seven tertiary pancreatic centres for pancreatic ductal adenocarcinoma were included in the study. Postoperative pancreatic fistula was defined using the 2016 International Study Group on Pancreatic Surgery grading system. The impact of postoperative pancreatic fistula on overall survival, recurrence-free survival (excluding 90-day postoperative deaths) and corresponding risk factors were investigated by univariable and multivariable analyses. Comparisons between groups were made using the chi-squared or Fisher's exact test for categorical variables and the Mann–Whitney U test for continuous variables. Odds ratios were estimated with their 95% confidence intervals. Survival rates were calculated using the Kaplan–Meier method with their 95% confidence intervals. Results A total of 819 patients were included between 2007 and 2017. Postoperative pancreatic fistula occurred in 14.4% (n = 118) of patients; of those, 7.8% (n = 64) and 6.6% (n = 54) accounted for grade B and grade C postoperative pancreatic fistula respectively. The 5-year overall survival was 37.0% in the non-postoperative pancreatic fistula group and 45.3% in the postoperative pancreatic fistula cohort (P = 0.127). Grade C postoperative pancreatic fistula (excluding 90-day postoperative deaths) was not a prognostic factor for overall survival. The 5-year recurrence-free survival was 26.0% for patients without postoperative pancreatic fistula and 43.7% for patients with postoperative pancreatic fistula (P = 0.003). Eight independent prognostic factors for recurrence-free survival were identified: age over 70 years, diabetes, moderate or poor tumour differentiation, T3/T4 tumour stage, lymph node positive status, resection margins R1, vascular emboli and perineural invasion. Conclusion This high-volume cohort showed that grade C postoperative pancreatic fistula, based on the 2016 International Study Group on Pancreatic Surgery grading system, does not impact overall or recurrence-free survival (excluding 90-day postoperative deaths). [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low‐risk/grade(PaN‐Low) and pancreaticobiliary neoplasm, high‐risk/grade(PaN‐High). Low‐grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category. Methods: An institutional pathology database search identified patients who underwent endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow‐up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems. Results: In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN‐Low, 46.7% for PaN‐High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival. Conclusions: The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN‐Low and PaN‐High categories and reassigning low‐grade malignancies to the malignant category. Analyzing EUS‐FNA samples with the WHO system provides critical insights for guiding clinical management. The World Health Organization reporting system significantly improves the stratification of risk of malignancy and overall survival across diagnostic categories by introducing the pancreaticobiliary neoplasm, low‐risk/grade and pancreaticobiliary neoplasm, high‐risk/grade categories and redistributing low‐grade malignancies to the malignant category. By incorporating clinical data, radiologic findings, and ancillary studies, the analysis of endoscopic ultrasound‐guided fine‐needle aspiration samples using the World Health Organization system will yield critical insights to guide clinical management. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the potential of ethanolic extract of propolis on the secondary lesions of the liver, renal, and pancreatic that were derived by primary colorectal cancer, and comparison of the ethanolic extract of propolis with the vitamin E. The groups included the control, ethanolic extract of propolis, vitamin E, dimethylhydrazine, dimethylhydrazine + ethanolic extract of propolis, and dimethylhydrazine + vitamin E. After 13 weeks of treatment, the blood and tissue samples were taken from all the rats, and alanine transaminase, aspartate transaminase, alkaline phosphatase, uric acid, creatinine, blood urea nitrogen, insulin, amylase, and lipase indices along with the tissue pathological examination of the kidney, liver, and pancreas were evaluated. Ethanolic extract of propolis effectively alleviated the colorectal cancer‐induced secondary lesions in the liver by significantly lowering the alanine transaminase significantly. Ethanolic extract of propolis significantly decreased uric acid in rats; and also significantly elevated the pancreatic insulin. In addition, inflammation and cell necrosis indices in all these tissues were significantly reduced when ethanolic extract of propolis was consumed compared to the dimethylhydrazine group. It seemed ethanolic extract of propolis showed high antioxidant, anticancer, and anti‐inflammatory potentials, and can be used practically to reduce the side lesions of colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical utility of ultrasound parameters in diagnosing neonatal annular pancreas. Methods A total of 56 neonates with descending duodenal obstruction underwent saline-contrast ultrasound examination. Ultrasonic parameters, including dilated duodenum diameter (DDD), dilated duodenum thickness (DDT), and stenosis duodenum diameter (SDD), were measured. The cases were categorized into three groups: annular pancreas (group A, n = 28), descending duodenal atresia (group B, n = 3), and descending duodenal septum (group C, n = 25). One-way ANOVA was employed to compare statistical differences among the three ultrasonic parameters across the groups, followed by LSD-t test for pairwise comparisons between two groups showing significant differences. Receiver operating characteristics analysis was conducted to calculate the area under the curve and determine the cut-off value if there were statistically significant differences observed. Results In group A, group B, group C, the diameters of DDD were measured as(23.2 ± 2.4)mm, (25 ± 1.0)mm, (19.4 ± 2.6) mm, respectively. When comparing these three groups, there was a statistically significant difference between group A or group B and group C in terms of DDD diameter measurements (t = 5.7, P < 0.05; t = 3.793, P < 0.05). However, no statistically significant difference was observed between group A and group B for DDD diameter measurements (t = 1.232, P > 0.05). The corresponding values for DDT were measured as (3.0 ± 0.6)mm, (3.2 ± 0.4) mm, and (2.4 ± 0.3) mm, respectively. When comparing these three groups, the results showed a statistically significant difference between either Group A or Group B compared to Group C in terms of DDT measurement (t = 4.695, P < 0.05; t = 2.778, P < 0.05). However, no statistically significant difference was found between Group A and Group B regard- ing the measurement of DDT (t = 0.666, P > 0.05). The SDD measurements in the three groups were (1.9 ± 0.3) mm, (3.6 ± 0.8)mm, (5.5 ± 0.7)mm, respectively. Statistical analysis using LSD-t test revealed significant differences between the three groups (t = 5.521, P < 0.05; t = 6.142, P < 0.05; t = 25.828, P < 0.05).The sensitivity, specificity, positive predictive value, and negative predictive value for detecting annular pancreas at a cutoff of 2.3 mm were determined to be 96.4%, 100%, 100%, and 96.6%, respectively, with an area under the receiver operating characteristic curve of 0.999. Conclusion SDD could be employed for the diagnosis of neonatal annular pancreas. [ABSTRACT FROM AUTHOR]

The biological system has attracted many researchers with a lot of smart advances in the control system field. The control approaches have been effectively utilized in biological application to regulate the biological parameter functions based on the set point and threshold value. However, the controller's high disturbance has resulted in low gain and tuning performance. So, the current work has expected to plan a new African Buffalo based Recurrent Fractional-Order Sliding Mode (ABR-FOSM) for the biological system to tune the specific parameters like protein, pancreas, and Genetic Regulatory Network (GRN). Here, the incorporation of the buffalo algorithm has provided better tuning results. Moreover, the robustness of the designed controller has been validated by gaining the finest tuning performance and reduced Error and settling time. [ABSTRACT FROM AUTHOR]

Introduction: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of nonfunctional ACH with glucagon-producing NET is herein presented. Case report: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and 68Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative 68Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis. Discussion and conclusion: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome. [ABSTRACT FROM AUTHOR]

Oleuropein (OLP) is a naturally occurring phenolic compound in olive plant with antioxidant and anti-inflammatory potential and can possibly be used in treating pancreatic injuries. This investigation aimed to follow the molecular mechanism behind the potential therapeutic effect of OLP against pancreatic injury persuaded by ischemia–reperfusion (I/R). Pancreatic I/R injury was induced by splenic artery occlusion for 60 min followed by reperfusion. Oral administration of OLP (10 and 20 mg/kg) for 2 days significantly alleviated I/R-persuaded oxidative damage and inflammatory responses in pancreatic tissue as indicated by the decreased malondialdehyde (MDA) content and increased glutathione peroxidase (GPx) activity, accompanied by the suppression of myeloperoxidase (MPO) activity and reduced levels of interleukin-1beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) in pancreatic tissues. Furthermore, OLP treatment markedly restored the serum levels of amylase, trypsinogen-activated peptide (TAP), and lipase, with concurrent improvement in pancreatic histopathological alterations. Moreover, treatment with OLP regulated the pancreatic expression of inducible nitric oxide synthase (iNOS) and high-mobility group box 1 (HMGB1) relative to rats of the pancreatic IR group. Thus, OLP treatment significantly alleviates the I/R-induced pancreatic injury by inhibiting oxidative stress and inflammation in rats through downregulation of HMGB1 and its downstream NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex® χMAP (Magpix®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10−6, 10−9, and 10−12 M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Grade 3 neuroendocrine tumor (G3 PanNET) and poorly differentiated neuroendocrine carcinoma (PanNEC) of the pancreas are considered distinct entities from a biological and prognostic perspective but may have overlapping features complicating a definitive diagnosis. Case Presentation: A 52-year-old female presented with a pancreatic body mass and liver lesions. Initial biopsies showed variable lower- and higher-grade morphologies and modestly elevated Ki67 proliferation index up to 30%, leading to a diagnosis of G3 PanNET. The patient underwent everolimus treatment followed by surgical resection, revealing a complex tumor with features of both G3 PanNET and PanNEC, including admixed well- and poorly differentiated morphologies, modestly elevated hotspot Ki67 of 28%, retained ATRX/DAXX expression, and loss of RB expression. The final diagnosis rendered was "high-grade neuroendocrine neoplasm" with discussion of both entities in the differential. Post-operatively, the patient remains alive with stable metastases. Conclusions: This case highlights the diagnostic complexities of distinguishing G3 PanNET and PanNEC even with the support of ancillary immunohistochemical and molecular studies. In addition, such cases raise the possibility that G3 PanNET and PanNEC may lie on a spectrum of disease with potential biological overlap. [ABSTRACT FROM AUTHOR]

Glucokinase (GCK), a key enzyme in glucose metabolism, plays a central role in glucose sensing and insulin secretion in pancreatic β-cells, as well as glycogen synthesis in the liver. Mutations in the GCK gene have been associated with various monogenic diabetes (MD) disorders, including permanent neonatal diabetes mellitus (PNDM) and maturity-onset diabetes of the young (MODY), highlighting its importance in maintaining glucose homeostasis. Additionally, GCK gain-of-function mutations lead to a rare congenital form of hyperinsulinism known as hyperinsulinemic hypoglycemia (HH), characterized by increased enzymatic activity and increased glucose sensitivity in pancreatic β-cells. This review offers a comprehensive exploration of the critical role played by the GCK gene in diabetes development, shedding light on its expression patterns, regulatory mechanisms, and diverse forms of associated monogenic disorders. Structural and mechanistic insights into GCK's involvement in glucose metabolism are discussed, emphasizing its significance in insulin secretion and glycogen synthesis. Animal models have provided valuable insights into the physiological consequences of GCK mutations, although challenges remain in accurately recapitulating human disease phenotypes. In addition, the potential of human pluripotent stem cell (hPSC) technology in overcoming current model limitations is discussed, offering a promising avenue for studying GCK-related diseases at the molecular level. Ultimately, a deeper understanding of GCK's multifaceted role in glucose metabolism and its dysregulation in disease states holds implications for developing targeted therapeutic interventions for diabetes and related disorders. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a multifaceted inflammatory disorder stemming from the aberrant activation of trypsin within the pancreas. Despite the contribution of various factors to the pathogenesis of AP, such as trypsin activation, dysregulated increases in cytosolic Ca2+ levels, inflammatory cascade activation, and mitochondrial dysfunction, the precise molecular mechanisms underlying the disease are still not fully understood. Mitophagy, a cellular process that preserves mitochondrial homeostasis under stress, has emerged as a pivotal player in the context of AP. Research suggests that augmenting mitophagy can mitigate pancreatic injury by clearing away malfunctioning mitochondria. Elucidating the role of mitophagy in AP may pave the way for novel therapeutic strategies. This review article aims to synthesize the current research findings on mitophagy in AP and underscore its significance in the clinical management of the disorder. [ABSTRACT FROM AUTHOR]

Stem cell-derived β-cells (SC-BCs) represent a potential source for curing diabetes. To date, in vitro generated SC-BCs display an immature phenotype and lack important features in comparison to their bona-fide counterparts. Transplantation into a living animal promotes SC-BCs maturation, indicating that components of the in vivo microenvironment trigger final SC-BCs development. Here, we investigated whether cues of the pancreas specific extracellular matrix (ECM) can improve the differentiation of human induced pluripotent stem cells (hiPSCs) towards β-cells in vitro. To this aim, a pancreas specific ECM (PanMa) hydrogel was generated from decellularized porcine pancreas and its effect on the differentiation of hiPSC-derived pancreatic hormone expressing cells (HECs) was tested. The hydrogel solidified upon neutralization at 37 °C with gelation kinetics similar to Matrigel. Cytocompatibility of the PanMa hydrogel was demonstrated for a culture duration of 21 days. Encapsulation and culture of HECs in the PanMa hydrogel over 7 days resulted in a stable gene and protein expression of most β-cell markers, but did not improve β-cell identity. In conclusion, the study describes the production of a PanMa hydrogel, which provides the basis for the development of ECM hydrogels that are more adapted to the demands of SC-BCs. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) treatment is known to potentially cause adverse effects, notably as the most common cause of drug-induced acute pancreatitis. It is crucial to balance the therapeutic benefits and potential major side effects of VPA administration. Complications associated with VPA may arise from toxic VPA metabolites and alterations in antioxidant levels. While chard is well-known for its anti-hyperglycemic and antioxidant properties, there is a lack of research on its impact on the pancreas during VPA treatment. This study aimed to explore the possible protective effects of chard against VPA-induced complications in the pancreas using histological and biochemical approaches. Animals were separated into four groups: i) Control, ii) received chard (100 mg/kg), iii) received VPA (500 mg/kg), and iv) received VPA+Chard (in the same dosages and time). On the eighth day, the rats' pancreatic tissue and blood specimens were collected. In the Chard and VPA+Chard groups, chard decreased blood glucose levels compared to the control and VPA groups. In comparison to the VPA group, the VPA+Chard group pancreatic glutathione level and catalase activity increased whereas malondialdehyde levels decreased. Furthermore, administration of chard to the control and VPA groups increased tissue factor activity and sialic acid level as compared to the VPA group. The histological findings confirmed the biochemical results. It is therefore concluded that chard has the potential to protect pancreatic tissue from VPA-induced complications by reducing lipid peroxidation and blood glucose while enhancing antioxidants and sialic acid levels. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Superoxide dismutase (SOD) is an enzyme that plays a crucial role in protecting cells from oxidative damage. Our study aims to address the lack of papers simultaneously analyzing the immunoreactivity of all three distinct isoforms of SOD in human exocrine pancreas cells. BACKGROUND: Superoxide dismutases (SODs) facilitate the conversion of superoxide radicals into less harmful substances. By neutralizing superoxide radicals, SODs help prevent the formation of highly reactive and destructive species that can adversely affect manifold cellular components. METHODS: The study analyzed immunoreactivity of SODs in samples of six healthy adult human pancreases, while using the indirect immunohistochemical method under a light microscope. RESULTS: SOD1 was predominantly found in centroacinar cells and epithelial cells of the duct system while SOD2 was mainly detected in the epithelial cells of interlobular ducts. Both enzymes were prominently present in the basal region of acinar cells near the cell nucleus. The expression of SOD3 was observed to be rare. CONCLUSION: Understanding the intracellular metabolism of SODs in healthy exocrine pancreas cells serves as a basis for determining the precise role of oxidative damage and SOD signaling in the pathogenesis of various pancreatic diseases, including chronic pancreatitis and pancreatic cancer [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: Defensins play a crucial role in the innate immune system's first defense against microbial threats. However, little is known about the defensin system in the pancreas, especially in relation to Type 1 diabetes. We explore the expression of defensins in different disease stages of Type 1 diabetes and correlated obtained findings to the degree of inflammation, providing new insights into the disease and the innate immune system. Material and methods: Pancreases from non-diabetic human organ donors of different age groups and donors with Type 1 diabetes with different disease duration were examined. Sections from head, body and tail of the pancreas were stained for eight different defensins and for immune cells; CD3+, CD45+, CD68+ and NES+ (granulocytes). Results: In non-diabetic adult controls the level of expression for defensins Beta-1,Alpha-1, Cathelicidin and REG3A correlated with the level of inflammation. In contrast, individuals with Type 1 diabetes exhibit a reduction or absence of several central defensins regardless of the level of inflammation in their pancreas. The expression of Cathelicidin is present in neutrophils and macrophages but not in T-cells in subjects with Type 1 diabetes. Conclusions: Obtained findings suggest a pancreatic dysfunction in the innate immune system and the bridging to the adaptive system in Type 1 diabetes. Further studies on the role of the local innate immune system in Type 1 diabetes is needed. [ABSTRACT FROM AUTHOR]

The serine protease chymotrypsin protects the pancreas against pancreatitis by degrading trypsinogen, the precursor to the digestive protease trypsin. Taking advantage of previously generated mouse models with either the Ctrb1 gene (encoding chymotrypsin B1) or the Ctrl gene (encoding chymotrypsin-like protease) disrupted, here we generated the novel Ctrb1-del × Ctrl-KO strain in the C57BL/6N genetic background, which harbors a naturally inactivated Ctrc gene (encoding chymotrypsin C). The newly created mice are devoid of chymotrypsin, yet the animals develop normally, breed well, and show no spontaneous phenotype, indicating that chymotrypsin is dispensable under laboratory conditions. When given cerulein, the Ctrb1-del × Ctrl-KO strain exhibited markedly increased intrapancreatic trypsin activation and more severe acute pancreatitis, relative to wild-type C57BL/6N mice. After the acute episode, Ctrb1-del × Ctrl-KO mice spontaneously progressed to chronic pancreatitis, whereas C57BL/6N mice recovered rapidly. The cerulein-induced pancreas pathology in Ctrb1-del × Ctrl-KO mice was highly similar to that previously observed in Ctrb1-del mice; however, trypsin activation was more robust and pancreatitis severity was increased. Taken together, the results confirm and extend prior observations demonstrating that chymotrypsin safeguards the pancreas against pancreatitis by limiting pathologic trypsin activity. In mice, the CTRB1 isoform, which constitutes about 90% of the total chymotrypsin content, is responsible primarily for the anti-trypsin defenses and protection against pancreatitis; however, the minor isoform CTRL also contributes to an appreciable extent. NEW & NOTEWORTHY: Chymotrypsins defend the pancreas against the inflammatory disorder pancreatitis by degrading harmful trypsinogen. This study demonstrates that mice devoid of pancreatic chymotrypsins are phenotypically normal but become sensitized to secretagogue hyperstimulation and exhibit increased intrapancreatic trypsin activation, more severe acute pancreatitis, and rapid progression to chronic pancreatitis. The observations confirm and extend the essential role of chymotrypsins in pancreas health. [ABSTRACT FROM AUTHOR]

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. [ABSTRACT FROM AUTHOR]

Sepsis remains a significant challenge in the intensive care unit (ICU), with prompt diagnosis and management being critical to improving patient outcomes. Biomarkers have emerged as valuable tools for identifying and predicting sepsis outcomes, with pancreatic stone protein (PSP), procalcitonin (PCT) and C-reactive protein (CRP) as three promising candidates. This systematic review aimed to analyse and compare the diagnostic accuracy of PSP, PCT and CRP regarding sepsis in the ICU. A review of the literature on the diagnostic performance of the three biomarkers was performed using PubMed Central, PubMed, ScienceDirect, Oxford Academic, SpringerLink and Cochrane Library. Data regarding the diagnostic accuracy of the three biomarkers were extracted, compared, and represented as the area under the curve (AUC) receiver operating characteristics (ROC). Three studies examining PSP, PCT and CRP biomarkers in 858 adult patients admitted to the ICU were included in this review. Compared with PCT and CRP, the PSP biomarker, with its unique applications and properties that may potentially benefit patients, doctors and hospitals, performed well and proved reliable in diagnosing sepsis in adult patients. PSP demonstrated reliability in sepsis diagnosis. Further analysis should be conducted to establish a formal, appropriate indication, as well as to determine a suspected sepsis patient's condition when testing each biomarker. [ABSTRACT FROM AUTHOR]

Cisplatin, which is used as a chemotherapy drug in some types of cancer, can cause DNA damage in cells and some organ damage after certain limits. Damage studies with cisplatin are mostly on organs such as the liver and lungs and some types of cancer. Damage studies on pancreatic tissue are relatively few, and they are especially related to insulin. In this study, the protective effects of epigallocatechin-3-gallate (EGCG), which has antioxidant and antitumor properties, were investigated against the general damage caused by cisplatin on the pancreatic tissue. A total of 28 male rats were used, divided into 4 groups, in the 4-week study. Cisplatin and EGCG were given intraperitoneally. Malondialdehyde, catalase and glutathione levels were measured spectrophotometrically. Caspase-3, IL-1α, IL-6, p53, and HO-1 protein expressions were determined by the Western Blotting method. In addition, histopathological examination of the pancreatic tissue was performed and the findings were evaluated statistically. In our findings, a decrease in malondialdehyde levels and an increase in catalase activity and glutathione levels were observed in the pancreatic tissue in rat groups to which EGCG was administered. It was observed that the expression levels of IL-1α, IL-6 proteins, which are markers of inflammation, were significantly decreased in the EGCG-treated group (EGCG+Cis) compared to the cisplatin group. In the histopathological examination, it was observed that pancreatic damage occurred significantly in the cisplatin-administered group and decreased in the treatment group. According to these data, it has been shown that treatment with EGCG can prevent toxicity in cisplatin-induced pancreotoxicity by providing an anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Objective Certain types of bacteria contain lipopolysaccharide (LPS), which can cause widespread inflammation in the body, including the pancreas. Fluvoxamine (FLV), a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for psychiatric disorders, has been shown to possess anti-inflammatory properties and may be beneficial in conditions involving tissue damage and inflammation. This study aims to evaluate the potential protective effects of FLV against experimentally induced pancreatic disease in rats using LPS. Material and Method In this experiment, a total of 32 Wistar albino male rats were randomly divided into four groups: control, LPS (5 mg/kg, intraperitoneally (i.p.)), LPS + FLV (50 mg/kg FLV, i.p.) and FLV. The rats were euthanatized 6 hours after the administration of LPS, and serum and pancreas tissue samples were collected during the necropsy for biochemical, histopathological, and immunohistochemical evaluations. Results According to the study findings, LPS lowered blood glucose levels. Histological examination showed that LPS caused edema, mild infiltration of inflammatory cells, increased vacuolization in the cells of the Langerhans islet, and severe hyperemia. Immunohistochemical investigations revealed a reduction in the expression of insulin and amylin. The biochemical, histopathological, and immunohistochemical outcomes were improved by FLV. Conclusion The results of this experimental rat model study indicated that LPS causes damage to the endocrine pancreas. However, FLV demonstrated significant ameliorative effects on the pancreas in rats with LPS- induced pancreatitis. [ABSTRACT FROM AUTHOR]

To understand the information processing mechanism of the brain, it is important to decode the bidirectional communication between the brain and organs. For this purpose, computational models were proposed to simulate brain–organ interfaces at different levels of abstraction. Conventional computational models can be modified to understand the bidirectional interactions for further clarification and treatment of morbidity. In this work, a unified model of excitable cells (brain, heart, and pancreatic cells) is proposed that can predict the electrical response with adrenergic features. This enables us to activate the sparsely coupled cardio-neural network to estimate the heart rate variability, one of the key features to identify a healthy heart. The recent advancements in nano- and bioelectronics will make it possible to build and deploy the brain–heart interface as a nanochip in the body to monitor and control the electrophysiological abnormality of the brain and heart by integrating nano-regulators with ion channels for stimulation. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a gram-negative bacterium that is quite common among the world's population. To date, the pathogenetic mechanisms of the bacterium's influence on gastroduodenal ulcers and gastric cancer have been most deeply studied. However, there is a growing number of sources devoted to the association of Helicobacter pylori with the occurrence of many extra-gastric diseases. These data are quite contradictory and controversial. Given the close anatomical and functional relationship of the digestive system (digestive tract and digestive glands), it is quite natural that the bacterium Helicobacter pylori, which persists in the antrum of the stomach, has a pathological effect on this system, causing the development of a number of diseases and their complications. The purpose of this study is to analyze the current state of the problem of the role of Helicobacter pylori in the pathogenesis of diseases of the digestive system. This review presents the latest data on the pathogenetic mechanisms of gastroduodenal ulcer and gastric cancer. The persistence of the bacterium in the pancreatic-biliary system causes cholecystitis, and gallstone disease, including cholelithiasis, acute and chronic pancreatic inflammation, non-alcoholic fatty liver disease, and liver cirrhosis. Various mechanisms of carcinogenesis of tumors of the liver, gallbladder and bile ducts, and pancreas, in which Helicobacter pylori is directly involved, are highlighted. Further study of the role of the bacterium as a predictor of the development of diseases of the digestive system and their complications is promising and relevant. [ABSTRACT FROM AUTHOR]

Background: Leiomyomas are benign neoplasms that originate from smooth muscle cells and most commonly occur in soft tis- sues, the gastrointestinal tract, and the uterus. Leiomyomas of the pancreas are exceptionally rare, with, to our knowledge, only 6 documented cases prior to this report. This case was also challenging because of the young age of the patient and an atypical initial presentation. Case Report: A 21-year-old male presented with progressive jaundice and severe anemia. Contrast-enhanced computed tomography revealed a heterogeneously hyper enhancing mass in the arterial phase in the head of the pancreas with a double-duct sign. Endoscopic biliary drainage was performed, followed by endoscopic biopsy that revealed amesenchymal tumor; leiomyoma was confirmed with an immunohistochemical evaluation. The patient underwent pancreatic oduodenectomy, and the histopathologic and immunohistochemical examinations of the resected specimen conirmed the diagnosis of a low-grade leiomyoma arising from the ampulla of Vater. Conclusion: This case not only highlights the rarity of pancreatic leiomyomas and the potential for atypical presentation but also emphasizes the importance of considering leiomyoma in the differential diagnosis, even in young patients, and supports surgical resection as the preferred treatment approach. [ABSTRACT FROM AUTHOR]

Primary pancreatic hydatid cyst is a rare form of echinococcosis, even in endemic areas. The present study reports the case of a 67-year-old male patient with a primary pancreatic hydatid cyst who presented with severe epigastric pain, vomiting and fever for a period >2 weeks. An endoscopic ultrasound revealed a cystic lesion in the pancreatic head with a solid component. A computed tomography scan and magnetic resonance imaging confirmed the ultrasound finding. Under general anesthesia, the patient underwent total pancreatectomy and splenectomy. A histopathological examination confirmed a primary pancreatic hydatid cyst. Hydatid cysts rarely occur primarily in the pancreas. They may spread to the pancreas through the hematogenous route. Various procedures can be performed for cyst removal, depending on the size and location of the cysts. Open surgery, laparoscopy and hybrid options are available; however, to date, the gold standard is open surgery to prevent spillage and reduce the chance of recurrence. Although rare, primary pancreatic hydatid cysts can occur, with surgery being the main treatment modality due to the vague preoperative diagnosis based on imaging. [ABSTRACT FROM AUTHOR]

This study aims to elucidate the surgical anatomy of the superior mesenteric vessels (SMV) and their relevance in colon and pancreatic surgeries. The superior mesenteric artery (SMA) and vein (SMV) play critical roles in the vascular supply and drainage of the intestines. Accurate knowledge of their anatomy is crucial for minimizing complications during surgical interventions. We conducted a detailed anatomical study using cadaveric dissections and imaging techniques to provide a comprehensive overview of the SMV's relationships with the colon and pancreas. The results are tabulated and analyzed to guide surgical practice. [ABSTRACT FROM AUTHOR]

Insulinomas are rare insulin-secreting tumors that most commonly affect adults. A 26-month-old child presented to her local emergency department with severe hypoglycemia. Initial workup was consistent with hyperinsulinemic hypoglycemia. Over the course of 10 months, multiple therapies for hyperinsulinism (HI) were trialed without significant benefit. Genetic testing for genes associated with HI was negative. At age 35 months, the patient was transferred to our center for further treatment. She underwent several imaging tests that revealed a lesion on her pancreas concerning for an insulinoma. The patient underwent surgical intervention to enucleate the lesion. Histopathological review of the specimen confirmed a benign, well-circumscribed insulinoma. A postoperative fasting test proved the patient was cured and she was discharged without the need for further glucose monitoring. [ABSTRACT FROM AUTHOR]

Distal pancreatectomy (DP) is performed for lesions in the body and tail of the pancreas. The morbidity profile is considerable, mainly due to clinically relevant postoperative pancreatic fistula (CR-POPF). This study aims to investigate potential differences in CR-POPF related to transection site. An observational cohort study from a prospectively maintained database was performed. Subtotal distal pancreatectomy (SDP) was defined as transection over the superior mesenteric vein, and DP was defined as transection lateral to this point. Propensity score matching (PSM) in 1:1 fashion was applied based on demographical and perioperative variables. Six hundred and six patients were included in the analysis (1997–2020). Four hundred twenty (69.3%) underwent DP, while 186 (30.7%) underwent SDP. The rate of CR-POPF was 19.3% after DP and 20.4% after SDP (p = 0.74). SDP was associated with older age (63.1 vs 60.1 years, p = 0.016), higher occurrence of ductal adenocarcinoma (37.1 vs 17.6%, p = 0.001) and more frequent use of neoadjuvant chemotherapy (3.8 vs 0.7%, p = 0.012). After PSM, 155 patients were left in each group. The difference in CR-POPF between DP and SDP remained statistically non-significant (20.6 vs 18.7%, p = 0.67). This study found no difference in CR-POPF related to transection site during distal pancreatectomy. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation, express α-smooth muscle actin (α-SMA), and play a crucial role in injury and inflammation sites. This study aims to evaluate the relationship between α-SMA expression and histopathological parameters of pancreatic ductal adenocarcinoma (PDAC), and investigate their association with prognosis. Material and Methods: Eighty-one consecutive pancreatectomies diagnosed as usual pancreatic ductal adenocarcinoma were included. The stromal density was scored as loose, moderate, or dense, and α-SMA expression was evaluated immunohistochemically. Results and Conclusion: Mean survival was 19.6 months. Male gender, larger tumor diameter (>3.7 cm), and older age (>64 years) were identified as independent poor prognostic factors. Perineural invasion significantly effected survival. A statistically significant correlation was found between high α-SMA expression and the presence of angioinvasion (p=0.01). Stromal α-SMA expression in PDAC may help determine the risk of angioinvasion. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a common resident in the stomach of at least half of the world's population and recent evidence suggest its emergence in other organs such as the pancreas. In this organ, the presence of H. pylori DNA has been reported in cats, although the functional implications remain unknown. In this work, we determined distinct features related to the H. pylori manifestation in pancreas in a rodent model, in order to analyse its functional and structural effect. Gerbils inoculated with H. pylori exhibited the presence of this bacterium, as revealed by the expression of some virulence factors, as CagA and OMPs in stomach and pancreas, and confirmed by urease activity, bacterial culture, PCR and immunofluorescence assays. Non-apparent morphological changes were observed in pancreatic tissue of infected animals; however, delocalization of intercellular junction proteins (claudin-1, claudin-4, occludin, ZO-1, E-cadherin, β-catenin, desmoglein-2 and desmoplakin I/II) and rearrangement of the actin-cytoskeleton were exhibited. This structural damage was consistent with alterations in the distribution of insulin and glucagon, and a systemic inflammation, event demonstrated by elevated IL-8 levels. Overall, these findings indicate that H. pylori can reach the pancreas, possibly affecting its function and contributing to the development of pancreatic diseases. [ABSTRACT FROM AUTHOR]

Obesity has become a global epidemic, contributing to various metabolic diseases. Despite existing therapies, the need to investigate new molecular targets to combat obesity-associated pathologies persists. Glycogen Synthase Kinase-3 (GSK-3), a serine/threonine kinase with two paralogs (GSK-3α and GSK-3β), has emerged as a critical player in obesity-associated metabolic pathologies such as type 2 diabetes (T2D), and cardiovascular diseases (CVDs). However, its ubiquitous dynamic expression and complex context-dependent signaling pathways present challenges in understanding its precise role in metabolic perturbations. In the present review, we will highlight the specific role and the proposed mechanisms via which the two GSK-3 paralogs impact obesity-associated pathologies such as T2D, diabetic cardiomyopathy (DCM), and cognitive impairment, a hallmark of Alzheimer's disease (AD). We will also highlight studies delineating the role of GSK-3s using either GSK-3 inhibitors or non-pharmacological compounds to inhibit/taper GSK-3 activity in metabolic diseases. Thus, the primary goal of this review is to highlight recent findings delineating the regulation/dysregulation of GSK-3α/β in tissues such as heart, liver, skeletal muscle, pancreas, brain, and adipose tissue that undergo morphological and metabolic changes with diet-induced obesity which predisposes obese individuals to numerous devastating chronic conditions by GSK-3 overactivity. [ABSTRACT FROM AUTHOR]

Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and peptides involved in these processes are targeted against almost all organs. In brain they are associated with neurodegenerative disease, and the Translocator Protein (TSPO), overexpressed in these inflammatory conditions, is one of the target for the diagnostic. Moreover, TSPO ligands have been described as promising therapeutic drugs for neurodegenerative diseases. Type 2 diabetes, another amyloidosis, is due to a beta cell mass decrease that has been linked to hIAPP (human islet amyloid polypeptide) fibril formation, leading to the reduction of insulin production. In the present study, in a first approach, we link overexpression of TSPO and inflammation in potentially prediabetic patients. In a second approach, we observed that TSPO deficient rats have higher level of insulin secretion in basal conditions and more IAPP fibrils formation compared with wild type animals. In a third approach, we show that diabetogenic conditions also increase TSPO overexpression and IAPP fibril formation in rat beta pancreatic cell line (INS-1E). These data open the way for further studies in the field of type 2 diabetes treatment or prevention. [Display omitted] • TSPO is overexpressed in overweight patients. • TSPO knockout in rat increases basal insulin secretion and fibril formation. • TSPO knockout in rat down regulates insulin secretion in diabetogenic conditions. • TSPO is overexpressed in cells upon diabetogenic conditions. [ABSTRACT FROM AUTHOR]

Late diagnosis of pancreatic cancer leads to an unfavourable prognosis and therefore a high mortality. Imaging methods are used for diagnosis, but they are also a significant burden for the patient. Currently, studies are being conducted in the Czech Republic to screen at-risk individuals for pancreatic cancer using imaging methods. Research efforts aimed at introducing biomarkers for early cancer detection are primarily focused on genetic and immunochemical approaches. Another option is a lipidomic test based on a patented method developed by prof. Holčapek's group, which is based on the concentration differences of lipids in the blood plasma of healthy individuals and patients with pancreatic cancer. In order to evaluate clinical performance, a study will be conducted in the coming years by Lipidica, a.s. in cooperation with 14 clinical sites across the Czech Republic. [ABSTRACT FROM AUTHOR]

As the incidence of neuroendocrine tumors increases, so does the diagnosis. In the 21st century, diagnosis relies mainly on imaging tests supplemented with serum biomarkers, which can reveal a specific tumor subtype already in its early stages. Many times, however, neuroendocrine tumors are an incidental finding due to the asymptomatic nature of imaging examinations. In the article, we deal with general serum biomarkers and subsequently basic imaging examinations used in asymptomatic neuroendocrine tumors and functional imaging methods used in symptomatic neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-associated mortality, with a rising global incidence. A paucity of strong predictive risk factors mean screening programmes are difficult to implement. Historically, a lack of identifiable and actionable driver mutations, coupled with a relatively immunosuppressed tumour microenvironment, has led to a reliance on cytotoxic chemotherapy. The NAPOLI-3 trial has reported data supporting consideration of NALIRIFOX as a new first-line standard of care. Kirsten Rat Sarcoma Virus (KRAS) G12D mutations are present in >90% of all PDAC's; exciting breakthroughs in small molecule inhibitors targeting KRAS G12D may open new modalities of treatment, and therapies targeting multiple KRAS mutations are also in early clinical trials. Although immunotherapy strategies to date have been disappointing, combination with chemotherapy and/or small molecule inhibitors hold promise and warrant further exploration. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have recently been used as nanocarriers in drug delivery systems for nucleic acid drugs. Their practical applications are currently primarily limited to the liver and specific organs. However, altering the type and composition ratio of phospholipids improves their distribution in organs other than the liver, such as the spleen and lungs. This study aimed to elucidate the effects of LNP components and particle size on in vivo distribution through systemic circulation to pancreatic islets to achieve better targeting of islets, which are a fundamental therapeutic target for diabetes. Fluorescence-labeled LNPs were prepared using three phospholipids: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), with particle sizes of 30–160 nm (diameter) using a microfluidic device. Baffled-structured iLiNP devices with adjusted flow-rate ratios and total flow rates were used. After the intravenous administration of LNPs to C57BL/6 J mice, the distribution of each LNP type to the major organs, including the pancreas and pancreatic islets, was compared using ex vivo fluorescence imaging and observation of pancreatic tissue sections. DSPC-LNPs- and DOPE-LNPs showed the highest distribution in the spleen and liver, respectively. In contrast, the DOPC-LNPs showed the highest distribution in the pancreas and the lowest distribution in the liver and spleen. In addition, smaller particles showed better distribution throughout the pancreas. The most significant LNP distribution in the islets was observed for DOPC-LNPs with a particle size of 160 nm. Furthermore, larger LNPs tended to be distributed in the islets, whereas smaller LNPs tended to be distributed in the exocrine glands. DOPC-LNPs were distributed in the islets at all cholesterol concentrations, with a high distribution observed at >40% cholesterol and > 3% PEG and the distribution was higher at 24 h than at 4 h. Thus, LNP composition and particle size significantly affected islet distribution characteristics, indicating that DOPC-LNPs may be a drug delivery system for effectively targeting the pancreas and islets. [Display omitted] • DOPC-LNP showed higher distribution in the pancreas. • Larger particle size showed higher distribution in islets. • Higher cholesterol content showed higher distribution in islets. • Higher DSG-PEG content showed higher distribution in islets. • Larger PEG-modified DOPC-LNPs are suitable drug delivery carriers to islets. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis. [ABSTRACT FROM AUTHOR]

We aimed to evaluate clinical characteristics and quantitative CT imaging features for the prediction of liver metastases (LMs) in patients with pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with pathologically confirmed PNETs were included, 133 patients were in the training group, 22 patients in the prospective internal validation group, and 28 patients in the external validation group. Clinical information and quantitative features were collected. The independent variables for predicting LMs were confirmed through the implementation of univariate and multivariate logistic analyses. The diagnostic performance was evaluated by conducting receiver operating characteristic curves for predicting LMs in the training and validation groups. PNETs with LMs demonstrated significantly larger diameter and lower arterial/portal tumor-parenchymal enhancement ratio, arterial/portal absolute enhancement value (AAE/PAE value) (p < 0.05). After multivariate analyses, A high level of tumor marker (odds ratio (OR): 5.32; 95% CI, 1.54–18.35), maximum diameter larger than 24.6 mm (OR: 7.46; 95% CI, 1.70–32.72), and AAE value ≤ 51 HU (OR: 4.99; 95% CI, 0.93–26.95) were independent positive predictors of LMs in patients with PNETs, with area under curve (AUC) of 0.852 (95%CI, 0.781–0.907). The AUCs for prospective internal and external validation groups were 0.883 (95% CI, 0.686–0.977) and 0.789 (95% CI, 0.602–0.916), respectively. Tumor marker, maximum diameter and absolute enhancement value in arterial phase were independent predictors with good predictive performance for the prediction of LMs in patients with PNETs. Combining clinical and quantitative features may facilitate the attainment of good predictive precision in predicting LMs. [ABSTRACT FROM AUTHOR]

To analyze the diagnostic performance of three short magnetic resonance imaging (MRI) protocols for the follow-up of pancratic intraductal papillary mucinous neoplasms (IPMN). Follow-up MRI examinations of 287 patients with IPMN performed in two centers were retrospectively retrieved. Four MRI protocols were identified as follows: T1-weighted (T1w), T2-weighted (T2w), and MRCP sequences (protocol 1); T1w, T2w, MRCP, and diffusion-weighted (DWI) sequences (protocol 2); T1w, T2w, MRCP, and post-contrast T1w-sequences (protocol 3); and a comprehensive protocol including all previous sequences (protocol 4). Three radiologists with different experience in abdominal imaging expressed their opinion upon the optimal patient's management upon the evaluation of each protocol. Intra-and inter-observer agreement and concordance with the clinical decision expressed by a pancreatic surgeon were calculated with Cohen's kappa test. 223 patients were included (66±10 years; 92 men, 131 women). 143 patients had branch-duct-IPMNs, 25 main-duct-IPMNs and 55 mixed-type-IPMNs. 79 patients underwent surgery, resulting in 52 high-grade dysplasia (HGD) and 27 low-grade dysplasia (LGD). Concordance for the expert reader between protocols 1, 2 and 3 and the actual clinical decision were 0.63, 0.72, and 0.74 respectively (95% CI, 0.53–0.73, 0.63–0.81, and 0.65–0.83). Inter-observer agreement between reader 1 and reader 2, reader 1 and reader 3, and reader 2 and reader 3 were: 0.71, 0.50, and 0.75 for protocol 1 (95% CI, 0.63–0.81, 0.40–0.60, and 0.66–0.84);0.68, 0.54, and 0.84 for protocol 2 (95% CI, 0.59–0.77, 0.44–0.64, and 0.76–0.91); and 0.77, 0.65, and 0.86 for protocol 3 (95% CI, 0.69–0.86, 0.55–0.74, and 0.80–0.93). Short MRI protocol is suitable for IPMN surveillance. [ABSTRACT FROM AUTHOR]

The presence of abundant tumor stroma is a prominent characteristic of pancreatic ductal adenocarcinomas (PDAC) that potentially influences disease progression and therapy response. This study aims to investigate immune cell infiltration and epigenetic profiles in tumor cell enriched ("Tumor") and stroma cell enriched ("Stroma") regions within human PDAC tissue samples. By comparing those regions, we identified 25,410 differentially methylated positions (DMPs) distributed across 6,963 unique genes. Pathway enrichment analysis using the top 2,000 DMPs that were either hyper- or hypomethylated indicated that immune response pathways and the estrogen receptor pathway are epigenetically dysregulated in Tumor and Stroma regions, respectively. In terms of immune cell infiltration, we observed overall low levels of T cells in both regions. In Tumor regions however, occurrence of tumor-associated macrophages (TAMs) was higher than in Stroma regions (p = 0.02) concomitant with a dualistic distribution that stratifies PDAC patients into those with high and low TAM infiltration. By categorizing TAM levels into quartiles, our analysis revealed that PDAC patients with more than 1,515 TAMs per mm² exhibited significantly shorter overall survival (p = 0.036). Our data suggest that variations in inflammatory characteristics between the Tumor and Stroma defined compartments of PDAC may primarily stem from the presence of macrophages rather than lymphocytes. The abundance of TAMs within regions enriched with tumor cells correlates with patient survival, underscoring the potential significance of exploring therapeutic interventions targeting TAMs. Furthermore, directing attention towards the estrogen receptor pathway may represent a promising strategy to address the stroma cell component within the PDAC tumor microenvironment. [ABSTRACT FROM AUTHOR]

The pancreas is neither part of the five Zang organs (五脏) nor the six Fu organs (六腑). Thus, it has received little attention in Chinese medical literature. In the late 19th century, medical missionaries in China started translating and introducing anatomical and physiological knowledge about the pancreas. As for the word pancreas, an early and influential translation was "sweet meat" (甜肉), proposed by Benjamin Hobson (合信). The translation "sweet meat" is not faithful to the original meaning of "pancreas", but is a term coined by Hobson based on his personal habits, and the word "sweet" appeared by chance. However, in the decades since the term "sweet meat" became popular, Chinese medicine practitioners, such as Tang Zonghai (唐宗海), reinterpreted it by drawing new medical illustrations for "sweet meat" and giving new connotations to the word "sweet". This discussion and interpretation of "sweet meat" in modern China, particularly among Chinese medicine professionals, is not only a dissemination and interpretation of the knowledge of "pancreas", but also a construction of knowledge around the term "sweet meat". [ABSTRACT FROM AUTHOR]

Over the past decade, medical researchers in China have debated whether the Pi (脾) corresponds to the biomedical spleen or pancreas. This debate exemplifies a broader phenomenon of "anatomical retrofitting", or the anachronistic imposition of contemporary categories onto living historical objects. "Anatomical retrofitting" as a means of rectifying cases of mistranslation further positions the biomedical spleen and pancreas as representing ahistorical, universal truths. This framework gives rise to a conceptual binary: while the biomedical spleen is universalized as what philosophers may describe as "logical" ontology, the Pi connects to a different nature of reality, or "metaphysical" ontology. Far from being an object of imprecision, the Pi was a dynamic vessel that also shared characteristics with the humoral spleen. Given that scholars in China have already subjected Pi to historical scrutiny, this paper urges scholars to do the same with biomedical anatomy. For instance, historically situating the humoral spleen demonstrates that it became less known and less articulated as it transformed into the biomedical spleen. Meanwhile, the pancreas remained an unstable epistemic object that took on the dynamic functions of the humoral spleen in nineteenth-century organotherapy. Through primary source analysis and literature review, this paper contends that the apparent ontological incommensurability between Pi and spleen is neither mutually exclusive nor irreconcilable. Instead, the dynamic nature of internal viscera, their many functions, and their participation in epistemic practices contribute to an ongoing ontological ambivalence that persists despite the forced certainty of anatomical retrofitting. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a common global health disorder characterized by chronic hyperglycaemia owing to decreased insulin secretion or sensitivity. Medicinal plants have continued to gain more relevance in diabetes treatment owing to their reliance as alternative therapy. This study examined the histological effects of Myrianthus arboreus leaf extracts on the pancreas of alloxan-induced diabetic albino Wister rats. Two extracts of Myrianthus arboreus leaves were formulated; aqueous extract (AEME) and ethanol extract (EEMA). Qualitative and quantitative phytochemical assays were investigated on both extracts. Induction of diabetes was made after overnight fasting of rats by a single intraperitoneal injection of 150 mg/kg (body weight) solution of alloxan. AEMA and EEMA were administered at 100, 200, and 400 mg/kg body weight daily for 28 days. Also, glibenclamide was administered at 5 mg/kg body weight to the positive control group. The rats were monitored every week for body weight and blood glucose levels. They were fasted 12 hours after the last treatment before sacrifice by cervical decapitation under ether anesthesia. A histological study was carried out on pancreas tissues. All treated groups, except the untreated group, had significant (p < 0.05) weight gain. Administration of AEMA and EEMA led to a significant (p < 0.05) decrease in blood glucose level, restoration of islets of Langerhans, and increased pancreatic beta cells compared to the diabetic group. Therefore, Myrianthus arboreus leaves showed potent antidiabetic properties, as evidenced by the increase in several beta cells and a decrease in blood glucose levels. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

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Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted. [ABSTRACT FROM AUTHOR]

Introduction: Patients with intraductal papillary mucinous neoplasms (IPMNs) exhibit a high incidence of pancreatic cancer. An IPMN presents as a pancreatic cystic lesion (PCL). Artificial intelligence (AI) can be used to enhance ultrasonographic images. We retrospectively evaluated the utility of AI‐assisted ultrasonography in terms of PCL detection. Methods: In total, 969 patients who underwent artificial narrow intelligence‐assisted transabdominal ultrasound examinations (AI group) were compared with 943 patients who underwent non‐AI‐assisted examinations (control group). The morphological changes and the frequencies of newly detected PCLs were compared between the groups. Results: The PCL detection rate was significantly higher in the AI group than in the control group (1.25 ± 0.36 and 0.21 ± 0.15%, respectively; p =.008). AI‐assisted ultrasound evaluation was independently associated with enhanced PCL detection (odds ratio: 5.83, 95% confidence interval: 1.29–26.29, p =.02). PCLs smaller than 8 mm and all PCLs in the pancreatic tail were detected in the AI group. PCL morphological changes were more common in the AI group than in the control group (63.6 ± 14.5 and 16.7 ± 15.2%, respectively; p =.04). Conclusion: AI‐assisted transabdominal ultrasonography enhances the PCL detection rate. The use of AI is likely to increase the IPMN detection rate. [ABSTRACT FROM AUTHOR]