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Trypsin and chymotrypsin were purified from the Kamori goat pancreas by affinity and ion exchange chromatography, and their activity was checked. The activity and stability of extracted enzymes under various conditions, including temperature, pH, and substrates, were studied. Extracted enzyme's activity and stability studies demonstrated that both enzymes possessed excellent activity at pH 8 and reached maximum activity after 8 hours. Purity was increased to 22.1-and 12.8-fold, with 29.2% and 25.3% yields for trypsin and chymotrypsin, respectively. According to SDS-PAGE, their molecular weights were approximately 24 and 25.5 kDa, respectively. Trypsin and chymotrypsin displayed maximum activity at 50°C, pH 8, using BAPNA (Na-benzoyl-DL-arginine 4-nitroanilide hydrochloride) and BTEE (N benzoyl-L-tyrosine ethyl ester) as substrates. Both enzymes were stabilized in the presence of Ca++ ions. The enzymes activity declined continuously as the concentration of NaCl increased. Enzymes were effectively inhibited by SBTI and PMSF but not by pepstatin A. Kcat of trypsin and chymotrypsin was 16.8 and 36.7 S−1, and Km was 0.91 and 0.17 mm, respectively. Results suggest that Kamori goat pancreas is a promising source of trypsin and chymotrypsin due to their excellent activity and stability. [ABSTRACT FROM AUTHOR]

Introduction: Current point-of-care testing for canine-specific pancreatic lipase (CPL) provides semi-quantitative measurements with binary results. Recently, a commercial point-of-care testing method (Vcheck CPL) that offers quantitative measurement of CPL has emerged. However, clinical studies on its value (or utility) are limited. Therefore, this study aimed to evaluate the clinical utility of this commercial point-of-care CPL in diagnosing dogs with suspected acute pancreatitis and to assess its correlation with a commercial semi-quantitative test and other clinicopathological variables. Methods: A prospective observational study included 33 dogs with suspected acute pancreatitis and 20 clinically healthy dogs. Serum Vcheck CPL and SNAP ® cPL were tested, and clinical consensus scores were determined by 5 internists. Eleven dogs with suspected acute pancreatitis underwent follow-up testing during hospitalization. The intra-class correlation coefficient (ICC) was used for statistical analysis to assess the agreement between assays and the internists' consensus score. Results: Dogs with suspected acute pancreatitis had significantly higher serum Vcheck CPL (median: 843 μg/L, range: 77–2001, p < 0.0001) than healthy control dogs (median: 94 μg/L, range: 49–294). By day 3 of hospitalization, serum Vcheck CPL had significantly decreased in dogs with suspected acute pancreatitis compared to day 1. The ICC score between the clinical consensus score, Vcheck CPL, and SNAP ® cPL was 0.75, indicating good agreement. Serum Vcheck CPL concentration was significantly correlated with serum concentrations of amylase, lipase, creatinine, ALP, and CRP. Discussion: This study found good agreement between Vcheck CPL and SNAP ® cPL. This quantitative Vcheck CPL testing could serve as an adjunctive tool in diagnosing dogs with acute pancreatitis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the 2nd most fatal cancer in the United States, but when detected early it is highly curable. Stool-derived extracellular vesicles (EVs) are a novel biomarker source that could augment the sensitivity for detection of CRC precursors. However, standardization of isolation methods for stool-derived EVs remains underexplored. We previously reported that size-exclusion chromatography (SEC) followed by ultrafiltration (UF-100kDa) was suitable for human stool supernatant EV isolation. In this study, we first assess alternative EV concentration methods (ultrafiltration [UF]; 10 kDa, 30 kDa, 50 kDa, 100 kDa and speed vacuum [SV]). Second, we investigate the host/bacterial EV proteomes by mass spectrometry. We report no difference in recovery, RNA and soluble protein contamination among concentration methods. Proteomic analysis reveals a diverse bacterial proteome, while human-derived proteins are more abundant. Specifically, pancreatic enzymes are among the most abundant proteins, further exploration revealed that zymogen granules are likely co-isolated in stool EV preparations. To enable discovery of EV-based molecular signatures of CRC precursors with high sensitivity, immunocapture strategies will likely be needed. Notably, we identified 10 surface proteins that may serve as candidates for the purification of colon-derived EVs. This work serves as framework for the future discovery and validation of EV-based biomarkers for CRC. This work uncovers the complex proteomic landscape of stool-derived extracellular vesicles (EVs). These findings serve as the framework for future stool EV biomarker discovery in gastrointestinal tract malignancies. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic exocrine insufficiency (PEI) is a condition defined by a reduction in pancreatic exocrine activity that impairs normal digestion. Despite established guidelines recommendations, precise diagnosis of PEI after pancreatic resection are infrequently achieved. This review aims to provide a comprehensive overview of the methodology and accuracy of diagnostic tools available for evaluating PEI after pancreatic resection. Methods: A review of PEI diagnostic tests was conducted using a combined text and MeSH search strategy to identify relevant articles focused on post-pancreatectomy PEI diagnosis. Results: The literature search yielded 4,874 records, and 30 studies were included in the analysis, with a total of 2,305 patients. The reported frequency of PEI across the included studies varied widely, though more than two-thirds of included papers reported an incidence of PEI above 65% in patients who underwent pancreatoduodenectomy or distal pancreatectomy. The faecal elastase-1 (FE-1) test was the most frequently used test for diagnosing post-pancreatectomy PEI. Six studies compared the diagnostic accuracy of FE-1 with faecal fat tests or 13 C breath tests, finding no significant differences. Five studies reported on micronutrient deficiencies. Conclusion: The FE-1 test is the most commonly used diagnostic tool for post-pancreatectomy PEI; however, well-designed studies comparing the diagnostic accuracy of various tests for PEI are lacking. Additionally, few studies report on micronutrient deficiencies, variations in anthropometric data or PEI-related patient-reported outcomes. Future studies should aim to establish a gold standard for diagnosis and severity assessment of post-pancreatectomy PEI and provide guidance for tailored pancreatic enzyme replacement therapy. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is a potentially life-threatening inflammatory disorder of the exocrine pancreas characterized by early activation of pancreatic enzymes followed by macrophage-driven inflammation, and pancreatic acinar cell death. The most common causes are gallstones and excessive alcohol consumption. Inflammation and oxidative stress play critical roles in its pathogenesis. Despite increasing incidence, currently, no specific drug therapy is available to treat or prevent acute pancreatitis, in particular severe acute pancreatitis. New therapeutic agents are very much needed. Plant polyphenols have attracted extensive attention in the field of acute pancreatitis due to their diverse pharmacological properties. In this review, we discuss the potential of plant polyphenols in inhibiting the occurrence and development of acute pancreatitis via modulation of inflammation, oxidative stress, calcium overload, autophagy, and apoptosis, based on the currently available in vitro, in vivo animal and very few clinical human studies. We also outline the opportunities and challenges in the clinical translation of plant polyphenols for the treatment of the disease. We concluded that plant polyphenols have a potential therapeutic effect in the management and treatment of acute pancreatitis. Knowledge gained from this review will hopefully inspire new research ideas and directions for the development and application of plant polyphenols for treating this disease. [ABSTRACT FROM AUTHOR]

Exocrine pancreatic insufficiency has been demonstrated in type 1 diabetes (T1D); lower concentrations of pancreatic enzymes have been associated with metabolic risk (MR). Influence of puberty and MR factors on serum concentrations of amylase and lipase remain unexplored in Indian youth with T1D. 1) To characterize and predict determinants of serum amylase and lipase concentrations in adolescents/youth with T1D. 2) To assess relationship between amylase, lipase, and prevalence of MR. Cross sectional, observational study on 291 (155 girls) adolescents/youth (10–24 years) with T1D. History, examination, body composition, biochemistry (glycated hemoglobin [HbA1c], thyroid stimulating hormone [TSH], lipids). Mean age, diabetes duration and HbA1c were 15.3, 7.0 years and 10.0 ± 2.1, respectively. Relative risk of lower amylase/higher lipase concentrations (9.5 %) was 1.42 and 1.34, respectively, though these did not reach statistical significance. In pubertal participants, amylase was lower and lipase higher; association was not found with MR. Higher TSH and lower serum calcium were significantly associated with higher lipase (p<0.001). We have characterized amylase and lipase concentrations across puberty; poor glycemic control tended to be associated with lower amylase and higher lipase, though these findings did not reach statistical significance. Amylase and lipase concentrations should be monitored in Indian adolescents with T1D, particularly in those with poor metabolic control, puberty, uncontrolled hypothyroidism, or reduced calcium intake, while further longitudinal and larger studies are needed to generalize these findings. [ABSTRACT FROM AUTHOR]

Background and Objectives: During acute pancreatitis, leakage of pancreatic enzymes into the gland results in autolysis of the pancreas. The lungs are also involved in this process. This study aimed to investigate the therapeutic effects of esomeprazole on damaged pancreatic tissue and affected lung tissue in rats with acute pancreatitis. Materials and Methods: The 24 Wistar-Albino male rats were divided into three groups: Control group (2 mL 0.9% saline solution was given intraperitoneally, n = 8); PCT group (acute pancreatitis was induced and then 2 mL 0.9% saline solution was administered intraperitoneally, n = 8); ESM group (acute pancreatitis was induced and then 10 mg/kg esomeprazole was administered intraperitoneally, n = 8). Then, the lungs and pancreas were completely removed, and blood samples were taken from all rats for histopathological and biochemical examination. Results: Pancreatic edema, vacuolization, necrosis, and inflammation in the PCT group were higher than in the control and ESM groups. Alveolar edema, alveolar distension, alveolar PMNL infiltration, and alveolar wall thickness in the PCT group were higher than in the control and ESM groups. Furthermore, IL-β (F = 40.137, p < 0.001), TNF-α (F = 40.132, p < 0.001), MIP-2 (X2 = 19.245, p < 0.001), ICAM-1 (F = 14.312, p < 0.001), NO (F = 25.873, p < 0. 001), amylase (F = 30.333, p < 0.001), and lipase (X2 = 16.141, p < 0.001) values measured in serum were different among groups. Pairwise group comparisons revealed that IL-β, TNF-α, MIP-2, and amylase levels in the ESM group were lower than in the PCT group (p < 0.05). Conclusions: Esomeprazole could be recommended in clinical practice during acute pancreatitis treatment due to its therapeutic effects on damaged pancreatic and lung tissues secondary to pancreatitis in rats. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory response in the pancreas. This is caused by the abnormal activation of pancreatic enzymes by a variety of etiologic factors, which results in a localized inflammatory response. The symptoms of this disease include abdominal pain, nausea and vomiting and fever. These symptoms are induced by a hyperinflammatory response and oxidative stress. In recent years, research has focused on developing anti-inflammatory and antioxidative therapies for the treatment of acute pancreatitis (AP). However, there are still limitations to this approach, including poor drug stability, low bioavailability and a short half-life. The advent of nanotechnology has opened up a novel avenue for the management of acute pancreatitis (AP). Nanomaterials can serve as an efficacious vehicle for conventional pharmaceuticals, enhancing their targeting ability, improving bioavailability and prolonging their half-life. Moreover, they can also exert a direct therapeutic effect. This review begins by introducing the general situation of acute pancreatitis (AP). It then discusses the pathogenesis of acute pancreatitis (AP) and the current status of treatment. Finally, it considers the literature related to the treatment of acute pancreatitis (AP) by nanomaterials. The objective of this study is to provide a comprehensive review of the existing literature on the use of nanomaterials in the treatment of acute pancreatitis (AP). In particular, the changes in inflammatory markers and therapeutic outcomes following the administration of nanomaterials are examined. This is done with the intention of offering insights that can inform subsequent research and facilitate the clinical application of nanomaterials in the management of acute pancreatitis (AP). [ABSTRACT FROM AUTHOR]

Introduction: Paraneoplastic syndromes are common in cancers such as lung, breast, and ovarian cancers. Still, the dual paraneoplastic syndromes of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) and raised pancreatic enzymes at the same time are rare. EAS is due to the production of ACTH by tumors other than the pituitary gland, which stimulates the hyperplasia of the adrenal cortex to secrete excessive corticosteroids, most commonly in lung cancer. Elevated pancreatic enzymes are associated with ectopic secretion from lung cancer. Clinically, some patients with small cell lung cancer (SCLC) have atypical early clinical manifestations and may present with paraneoplastic syndrome as the first symptom. Case Report: This article describes a case of a 45-year-old male patient who was admitted to the hospital with “intermittent mild edema of both lower extremities for more than 1 month” and showed persistent low potassium without diuretic drugs and with abnormally high blood amylase and blood lipase in the exclusion of pancreatitis. The persistent low potassium was caused by unusually high cortisol levels in patients with EAS that result from large amounts of cortisol secretion. Pancreatitis was excluded, and he was finally diagnosed with extensive-stage SCLC after bronchoscopic biopsy and histopathological confirmation. The patient presented with dual paraneoplastic syndromes of SCLC combined with EAS, high pancreatic enzymes, dual metastases, high malignancy, loss of surgical opportunities, and poor prognosis. The patient died at the end of the first cycle of chemotherapy due to the combination of IV degree of myelosuppression, metabolic alkalosis, severe infection, respiratory failure, and the rapid deterioration of his condition. Conclusion: Most of the clinical manifestations of lung cancer with paraneoplastic syndrome as the first symptom lack specificity. The paraneoplastic syndrome of lung cancer can appear in all stages of the disease, and if it appears before the diagnosis of lung cancer, it is of some significance in guiding the diagnosis of lung cancer. Meanwhile, when pancreatic lesions are excluded, we should consider malignancy-related hyperpancreatinemia. Introduction: Paraneoplastic syndromes are common in cancers such as lung, breast, and ovarian cancers. Still, the dual paraneoplastic syndromes of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) and raised pancreatic enzymes at the same time are rare. EAS is due to the production of ACTH by tumors other than the pituitary gland, which stimulates the hyperplasia of the adrenal cortex to secrete excessive corticosteroids, most commonly in lung cancer. Elevated pancreatic enzymes are associated with ectopic secretion from lung cancer. Clinically, some patients with small cell lung cancer (SCLC) have atypical early clinical manifestations and may present with paraneoplastic syndrome as the first symptom. Case Report: This article describes a case of a 45-year-old male patient who was admitted to the hospital with “intermittent mild edema of both lower extremities for more than 1 month” and showed persistent low potassium without diuretic drugs and with abnormally high blood amylase and blood lipase in the exclusion of pancreatitis. The persistent low potassium was caused by unusually high cortisol levels in patients with EAS that result from large amounts of cortisol secretion. Pancreatitis was excluded, and he was finally diagnosed with extensive-stage SCLC after bronchoscopic biopsy and histopathological confirmation. The patient presented with dual paraneoplastic syndromes of SCLC combined with EAS, high pancreatic enzymes, dual metastases, high malignancy, loss of surgical opportunities, and poor prognosis. The patient died at the end of the first cycle of chemotherapy due to the combination of IV degree of myelosuppression, metabolic alkalosis, severe infection, respiratory failure, and the rapid deterioration of his condition. Conclusion: Most of the clinical manifestations of lung cancer with paraneoplastic syndrome as the first symptom lack specificity. The paraneoplastic syndrome of lung cancer can appear in all stages of the disease, and if it appears before the diagnosis of lung cancer, it is of some significance in guiding the diagnosis of lung cancer. Meanwhile, when pancreatic lesions are excluded, we should consider malignancy-related hyperpancreatinemia. Introduction: Paraneoplastic syndromes are common in cancers such as lung, breast, and ovarian cancers. Still, the dual paraneoplastic syndromes of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) and raised pancreatic enzymes at the same time are rare. EAS is due to the production of ACTH by tumors other than the pituitary gland, which stimulates the hyperplasia of the adrenal cortex to secrete excessive corticosteroids, most commonly in lung cancer. Elevated pancreatic enzymes are associated with ectopic secretion from lung cancer. Clinically, some patients with small cell lung cancer (SCLC) have atypical early clinical manifestations and may present with paraneoplastic syndrome as the first symptom. Case Report: This article describes a case of a 45-year-old male patient who was admitted to the hospital with “intermittent mild edema of both lower extremities for more than 1 month” and showed persistent low potassium without diuretic drugs and with abnormally high blood amylase and blood lipase in the exclusion of pancreatitis. The persistent low potassium was caused by unusually high cortisol levels in patients with EAS that result from large amounts of cortisol secretion. Pancreatitis was excluded, and he was finally diagnosed with extensive-stage SCLC after bronchoscopic biopsy and histopathological confirmation. The patient presented with dual paraneoplastic syndromes of SCLC combined with EAS, high pancreatic enzymes, dual metastases, high malignancy, loss of surgical opportunities, and poor prognosis. The patient died at the end of the first cycle of chemotherapy due to the combination of IV degree of myelosuppression, metabolic alkalosis, severe infection, respiratory failure, and the rapid deterioration of his condition. Conclusion: Most of the clinical manifestations of lung cancer with paraneoplastic syndrome as the first symptom lack specificity. The paraneoplastic syndrome of lung cancer can appear in all stages of the disease, and if it appears before the diagnosis of lung cancer, it is of some significance in guiding the diagnosis of lung cancer. Meanwhile, when pancreatic lesions are excluded, we should consider malignancy-related hyperpancreatinemia. [ABSTRACT FROM AUTHOR]

Introduction: Acute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated. Methods: The present study employed network pharmacology combined with experimental verification to explore the protective effect of stigmasterol on AP and its molecular mechanism in a sodium taurocholate (STC)-induced AP mouse model. Results: Protein-protein interaction (PPI) analysis pinpointed out MAPK3, also named as ERK1, as a promising stigmasterol target in AP therapy. Molecular docking analysis further revealed a strong binding capacity of stigmasterol to ERK1 (−6.57 kL/mol). Furthermore, both in vivo and in vitro studies demonstrated that stigmasterol treatment notably attenuated STC-induced pancreatic injury, as evidented by decreased serum levels of lipase and amylase, improved systemic inflammation, and reduced acinar cell necrosis. At the molecular level, stigmasterol treatment exhibited a significant inhibition on STC-induced activation of ERK signaling pathway in pancreatic acinar cells, leading to the transition of acinar cell death from necrosis to apoptosis, thereby preventing acinar cell necrosis-induced systemic inflammation. Conclusion: This study demonstrated that stigmasterol exhibits a significant protective effect aganist AP, at least in part through enhancing acinar cell apoptosis via modulating the ERK signaling pathways. [ABSTRACT FROM AUTHOR]

Background/Objectives: In metabolic bariatric surgery, structured follow-up protocols may play an essential role in achieving optimal patient outcomes. This study aims to report postoperative biochemical outcomes in a cohort of post-bariatric patients who underwent a structured follow-up protocol. Methods: This retrospective study included patients who underwent metabolic bariatric surgery and completed a one-year follow-up at Cannizaro Hospital from October 2022 to May 2024. Anthropometric, clinical, and laboratory data were collected for each patient at five different timepoints: baseline, 1, 3, 6, and 12 months post-surgery. All data were organized into a database and analyzed through descriptive statistics. Results: The study cohort (n = 80) showed a follow-up adherence equal to 97.5%. The mean value of BMI decreased from 42 to 27 one year after surgery. Lipid profiles improved, with significant reduction in total cholesterol and triglycerides and increase in HDL levels; LDL levels decreased initially but at one year returned to baseline. Thyroid hormones TSH and fT3 decreased significantly, while fT4 remained stable. A reduction in hepatic inflammation was observed, as evidenced by the decrease in GGT and transaminase levels. Pancreatic enzymes showed an initial increase but stabilized at the subsequent timepoints. Glycemic control improved, with statistically significant reductions in insulin, HbA1c, and glucose levels, and complete remission of type 2 diabetes mellitus in affected patients. Conclusions: This study shows significant weight loss and improved health outcomes in post-bariatric patients who underwent a structured follow-up protocol, suggesting the potential benefits of metabolic bariatric surgery. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the impact of porcine pancreatic enzymes (Creon® pancrelipase) in comparison to microbial-derived alpha amylase (MD amylase) on the small intestine wall structure, mucosal glycogen accumulation, and enterocyte turnover. The impact of enzyme supplementation on the small intestine was explored in 18 pigs with surgically induced exocrine pancreatic insufficiency (EPI). Four healthy pigs served as the control group. EPI led to reduced villus length, crypt depth, and thickness of the mucosa and muscularis layers compared to those of healthy pigs. All these changes appeared to be reversible after enzyme supplementation. Brush border thickness was decreased in EPI and increased with both enzyme preparations, with MD amylase treatment leading to the highest values in the proximal jejunum. No EPI-induced changes were observed in the goblet cell (GC) population, but significant increases in GC number and area were observed following MD amylase treatment. Glycogen accumulation within the duodenal mucosa was significantly increased in EPI pigs. EPI was also shown to significantly increase apoptotic activity and decrease proliferative activity in comparison to healthy animals, while both enzyme preparations resulted in the complete recovery of both proliferative and apoptotic activity in all investigated intestinal segments. Creon® influenced the morphology of the small intestine. However, supplementation of exogenous microbial amylase alone also affected gut morphology in a similar way to that of the complex host pancreatic enzymes offered orally. These data indicate that in addition to their role in digestion of nutrients in EPI, intraluminal pancreatic enzymes, especially amylase, contribute to gut health through maintenance of the intestinal wall architecture and physiological enterocyte turnover. [ABSTRACT FROM AUTHOR]

Objective: Despite varying presentations of acute pancreatitis (AP) in children, the diagnosis has been increasing in recent years due to increased awareness. We aimed to identify the relationship among etiology, presentation symptoms, treatment response and complications of the children with acute pancreatitis. Material and Methods: Thirty children diagnosed with AP were evaluated for clinical and laboratory findings, treatment approaches, complications in the tertiary children hospital retrospectively. Results: The mean age of the patients was 12.4 ± 4.3 years and 60% were male. The drugs (30%), biliary tract diseases (26.7%), infections (16.7%), hyperlipidemia (10%) were the main causes of AP, in 10% of patients no etiological factor was detected. Abdominal pain (83.3%), nausea (70%), loss of appetite (63.3%), vomiting (56.7%), and fever (20%) were the most common symptoms. Ultrasonography, abdominal tomography and magnetic resonance cholangiopancreatography revealed pancreatitis related changes 63.3%, 85%, 70% of patients, respectively. Oral feeding was started on median 4 days (1-30), with polymeric diet (30%), and medium chain triglyceride rich enteral diet (70%). The median length of hospitalization (LOH) was 16.5 days (4-66). The patients fed with polymeric diet had a shorter hospitalization duration (p<0.036). The delayed initiation of oral feeding caused longer LOH (p<0.001). Conclusion: Consequently, this study underlines the children with acute abdominal pain, especially who use drugs like asparaginase and valproic acid, or that are known to have gallstone/biliary sludge, need to be examined for acute pancreatitis through pancreatic enzymes and ultrasonography. Moreover, the study also highlights that early feeding in acute pancreatitis is related with shorter hospitalization duration. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT). Methods: We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated. Results: Multivariate analyses identified osteosarcopenia (P = 0.049) and lymph node metastasis (P = 0.01) as independent recurrence predictors, and osteosarcopenia (P = 0.002), maximum tumor diameter ≥40 mm (P = 0.006), and no adjuvant therapy (P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher (P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007). Conclusions: Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

• Limited evidence exists regarding the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on the utilization of other routine treatments in cystic fibrosis. • Real-world evidence on drug utilization patterns is needed to inform health care providers as the treatment landscape of cystic fibrosis changes. • Two years post-ETI initiation, there was a marked reduction in the prevalence of several treatments, particularly airway medications and antibiotics. • These results underscore ETI's impact beyond traditional measures of effectiveness. Elexacaftor/tezacaftor/ivacaftor (ETI) has been effective in improving several outcomes in people living with cystic fibrosis (pwCF). Although clinical guidance regarding maintenance therapies has not changed, staff reports indicate that individuals reduce some therapies. This study aimed to evaluate ETI's effect on utilization of routine therapies among pwCF in Denmark. We included all pwCF initiating ETI between 1 September 2020 and 31 October 2022. Utilization of routine therapies was analysed by drug class (e.g., gastrointestinal medications) and individual treatments (e.g., pancreatic enzymes) before and after ETI initiation using national registry data. Odds ratios (ORs) for prescription redemptions pre- and post-ETI were calculated to assess ETIs impact on the use of routine therapies. The study population consisted of 351 individuals. Median age was 23 years (IQR 14–32) and mean ppFEV 1 was 76 (SD 22) at index. Two-year follow-up was available for 205 individuals. Two years post ETI initiation, the one-year prevalence was reduced for airway medications, (89.5 % to 75.1 %) and inhaled antibiotics (59.5 % to 42.9 %.). OR for redeeming a prescription two years post-ETI initiation (95 % CI) was reduced for four out of five drug classes: airway medications (OR: 0.24 [0.19; 0.29]), inhaled antibiotics (OR: 0.28 [0.2; 0.39]), oral antibiotics (OR: 0.49 [0.41; 0.58]), gastrointestinal medications (OR: 0.66 [0.57; 0.77]). Two years after ETI initiation, reductions in the use of several routine therapies were observed in a national cohort of pwCF, with the largest declines in airway medications and antibiotics. These findings highlight ETI's real-world impact beyond conventional clinical metrics. [ABSTRACT FROM AUTHOR]

Background and Aims: Although a relevant animal model is essential for studying human diseases, one has yet to be established for mouse pancreatitis. Early non-invasive models of mouse pancreatitis have serious limitations. Methods: In this study, we compared the efficiency, consistency, and reproducibility of inducing pancreatitis in 3 non-invasive mouse models of pancreatitis in Wistar albino mice: (1) L-arginine-induced model (2 intraperitoneal injections of 4 g/kg body weight of L-arginine spaced 1 h apart), (2) caerulein-induced model (6 intraperitoneal injections of 50 µg/kg body weight of caerulein at hourly intervals), and (3) caerulein + LPS (lipopolysaccharide)-induced model (6 intraperitoneal doses of 50 µg/kg body weight of caerulein at hourly intervals, along with an LPS [10 mg/kg body weight] injection immediately after the last caerulein injection). Results: Our findings showed that the L-arginine–induced model was inconsistent. The levels of the pancreatic enzymes, amylase and lipase, were higher in the caerulein and caerulein + LPS groups. Histological examination showed tissue destruction in the induced groups, with varying degrees of fibrosis in the caerulein + LPS group. Conclusions: The caerulein + LPS model was the most reliable model in Wistar albino mice. Our findings may be useful in helping investigators choose the most appropriate animal model for pancreatitis research. [ABSTRACT FROM AUTHOR]

Background and Aims: Pancreaticobiliary maljunction (PBMJ) has a long common channel (CC) that causes pancreaticobiliary reflux (PBR), which has been implicated in gallstones, cholangiocarcinoma, and pancreatitis. By contrast, PBR has occurred in cases with normal and longer CCs than normal but shorter than PBMJ. This pathophysiology has been primarily reported in adults and rarely in children. We sometimes observe this pathophysiology in children with pancreatitis and cholelithiasis. Herein, we report the clinical figures on the diagnosis of children with PBR in normal and relatively long CCs. Patients and Methods: This study included seven children who complained of refractory pancreatitis and cholelithiasis diagnosed with PBR in normal and relatively long CCs at our institution from August 2018 to September 2024. We measured the lengths of their CCs and sphincter of Oddi muscles via endoscopic retrograde cholangiopancreatography (ERCP) and cholangiography. In addition, amylase and lipase levels in bile juice were measured. Results: All seven children demonstrated elevated amylase and lipase levels in bile juice obtained from gallbladder drainage and/or the common bile duct. ERCP and cholangiography indicated 2.2–5.5-mm lengths of CCs in their cases, which are normal lengths in two cases and relatively longer (0.3–1.1 mm: mean 0.6 mm) than the normal upper limit of CC in children in five cases, with their CCs shorter than the sphincters of Oddi. All children underwent extrahepatic bile duct resection and bilio–jejunal anastomosis, demonstrating no clinical symptom recurrence postoperatively. Conclusions: Some children with cholelithiasis and pancreatitis exhibit normal and relatively long CCs, causing PBR and inducing gastrointestinal diseases. Careful investigation by ERCP and cholangiography focused on the CC length, and pancreatic enzyme level assessments in bile juice are useful for diagnosing PBR in children with cholelithiasis and refractory pancreatitis. [ABSTRACT FROM AUTHOR]

Introduction: The immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed. No study has yet evaluated whether serum exocrine pancreatic enzymes could delineate immunotherapy responders and non-responders. Methods: In this novel study, we sought to identify longitudinal trends in the most commonly measured circulating exocrine enzymes before and after treatment with anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) in individuals with new-onset type 1 diabetes (n=34). We defined response to immunotherapy as participants with at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. In the overall study (n=89), 42% of treated and 17% of placebo participants met this definition. Due to constraints of sample availability, we compared longitudinal serum amylase, lipase, and trypsin levels in a subset of responders to therapy (n=4-6), placebo "responders" (n=2), treated non-responders (n=16), and placebo non-responders (n=10). Results: There were no differences in amylase levels between groups at baseline or six months post-treatment. Baseline levels of lipase and trypsin tended to be lower in responders; however, these variations were not significant in this small study sample. Lipase and trypsin improved to 115% of baseline in responders to immunotherapy six months after treatment and declined to 80-90% of baseline in non-responders and placebo participants (p=0.03). This difference was not present before the six-month time point. Discussion: Our findings provide preliminary evidence that the exocrine pancreatic enzymes lipase and trypsin may be useful biomarkers of response to immunotherapy in type 1 diabetes. Further studies with larger numbers of participants are warranted. [ABSTRACT FROM AUTHOR]

Hemosuccus pancreaticus is a rare but potentially fatal cause of upper gastrointestinal (GI) bleeding. It is defined as bleeding from the pancreatic duct with blood draining into the duodenum through the ampulla of Vater. In patients with pancreatitis, peri-pancreatic blood vessels may be inflamed by pancreatic enzymes and form a pseudoaneurysm which can rupture and bleed into the pancreatic duct. We report a case of a 43-year-old man who presented with episodic upper GI bleeding of unclear etiology over 9 months without a clear documented history of pancreatitis. The etiology remained elusive even after multiple upper and lower endoscopies. Computed tomography angiography of the abdomen and pelvis during an acute episode detected a pseudoaneurysm of the gastroduodenal artery (GDA) with contrast extravasation into the dilated pancreatic duct. The pseudoaneurysm was treated with coil embolization, resulting in a persisting resolution of the patient's symptoms. Clinicians should consider abdominal angiography when diagnosing obscure GI bleeding. [ABSTRACT FROM AUTHOR]

Background: The duration of time a person with cystic fibrosis (pwCF) spends on the lung transplant waitlist is dependent on waitlist and post-transplant survival probabilities and can extend up to 2 years. Understanding the characteristics involved with lung transplant and survival prognoses may help guide decision making by the patient, the referring CF Center and the transplant team. Methods: This study seeks to identify clinical predictors of lung transplant and survival of individuals with CF using 29,847 subjects from 2003–2014 entered in the Cystic Fibrosis Foundation Patient Registry (CFFPR). Results: Predictors significant (p ≤ 0.05) in the final logistic regression model predicting probability of lung transplant/death were: FEV1 (% predicted), BMI, age of diagnosis, age, number of pulmonary exacerbations, race, sex, CF-related diabetes (CFRD), corticosteroid use, infections with B. cepacia, P. aeruginosa, S. aureus, MRSA, pancreatic enzyme use, insurance status, and consecutive ibuprofen use for at least 4 years. The final Cox regression model predicting time to lung transplant identified these predictors as significant FEV1 (% predicted), BMI, age of diagnosis, age, number of pulmonary exacerbations, race, sex, CF-related diabetes (CFRD), corticosteroid use, infections with B. cepacia, P. aeruginosa, S. aureus, MRSA, pancreatic enzyme use, and consecutive ibuprofen use for at least 4 years. The concordance indices were 0.89 and 0.92, respectively. Conclusions: The models are translated into nomograms to simplify investigation of how various characteristics relate to lung transplant and survival prognosis individuals with CF not receiving highly effective CFTR modulator therapy. [ABSTRACT FROM AUTHOR]

Acute pancreatitis, which sometimes results in mortality, is a significant complication of endoscopic retrograde cholangiopancreatography (ERCP). Many studies have been conducted to predict and prevent post‐ERCP pancreatitis (PEP), and meta‐analyses have been reported that summarized these studies. However, many issues remain unresolved. Many risk factors for PEP have been reported, and it is rare for patients undergoing ERCP to have only one risk factor. The use of artificial intelligence may be important for analyzing complex and diverse risk factors. It is desirable to develop an alternative test for pancreatic enzymes that can predict the onset of PEP within 1 h after ERCP. The effectiveness of low‐dose nonsteroidal anti‐inflammatory drugs (NSAIDs) are controversial. Nitrate and tacrolimus are considered medications that have additional effects on NSAIDs and may be used for the prevention of PEP. Pancreatic stent placement with deliberate placement of the guidewire into the pancreatic duct may be more effective in preventing PEP. A comparison between transpancreatic sphincterotomy with deliberate guidewire placement into the pancreatic duct and needle‐knife precut sphincterotomy is necessary. Early precutting is thought to be effective for the prevention of PEP, and the effectiveness of primary precut has been reported. However, the optimal timing of precut for the prevention of PEP has not been sufficiently discussed. Further research on prediction and prevention must be conducted to eliminate the mortality caused by PEP. [ABSTRACT FROM AUTHOR]

Pancreatic leaks occur when a disruption in the pancreatic ductal system results in the leakage of pancreatic enzymes such as amylase, lipase, and proteases into the abdominal cavity. While often associated with pancreatic surgical procedures, trauma and necrotizing pancreatitis are also common culprits. Cross-sectional imaging, particularly computed tomography, plays a crucial role in assessing postoperative conditions and identifying both early and late complications, including pancreatic leaks. The presence of fluid accumulation or hemorrhage near an anastomotic site strongly indicates a pancreatic fistula, particularly if the fluid is connected to the pancreatic duct or anastomotic suture line. Pancreatic fistulas are a type of pancreatic leak that carries a high morbidity rate. Early diagnosis and assessment of pancreatic leaks require vigilance and an understanding of its imaging hallmarks to facilitate prompt treatment and improve patient outcomes. Radiologists must maintain vigilance and understand the imaging patterns of pancreatic leaks to enhance diagnostic accuracy. Ongoing improvements in surgical techniques and diagnostic approaches are promising for minimizing the prevalence and adverse effects of pancreatic fistulas. In this pictorial review, our aim is to facilitate for radiologists the comprehension of pancreatic leaks and their essential imaging patterns. [ABSTRACT FROM AUTHOR]

Along with the development of technology and the increasing consumption of polymeric materials, which have become an integral part of man's everyday life, problems related to their disposal are arising. The presented research concentrates on the studies on the enzymatic degradation of selected epoxy-polyurethane materials filled with 2 or 5 wt.% of waste unmodified or chemically modified through mercerization wood flour. Composites, subjected to the degradation process, contained up to 60% of raw materials of natural origin. The enzymatic degradation was carried out for 28 days, in three environmental conditions, differing in the type of applied buffer, pH, process temperature, the amount, and the type of applied enzyme. In this study, the influence of two lipases was tested (specifically: lipase of microbiological origin—Rhizopus Oryzae Lipase, and one of animal origin—Porcine Pancreas Lipase). There were seven compositions tested, based on the polyaddition product of epoxidized soybean oil with bisphenol A, differing in the amount of filler and the type of modification to which wood flour was subjected before the application in the polymer composite. After enzymatic degradation, the greatest progress of biodegradation was observed at T = 30 °C, in a complex phosphate buffer with pH = 6.8, in the presence of the Porcine Pancreas enzyme. Under these conditions, a slightly smaller effect was also observed in the presence of the Rhizopus Oryzae enzyme. At the same time, the compositions containing mercerized wood flour turned out to be the most susceptible to biodegradation with the above-mentioned enzymes. After conducting the process in the full 4-week cycle numerous changes were noticed within the tested sample, such as (1) 7.0 %wt. of the overall weight loss of samples, (2) reducing the value of the static contact angle (e.g., from 116.7° before degradation to 27.2° at the end of the study), and (3) morphological appearance of the sample (sample's surface had suffered erosion noticed as smoothest roughnesses and numerous empty holes throughout its entire volume), concerning sample's condition before enzymatic degradation. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a severe, potentially life threatening inflammation of the pancreas with no clinically approved therapeutic intervention. Oxidative stress and inflammation are key drivers of the disease, contributing to pancreatic damage and worsening its progression. This study was designed to evaluate both the in vitro and in vivo effects of the methanolic extract of the rhizome of Smilax perfoliata (MESPR), a plant known for its traditional medicinal properties, on LPS-induced oxidative stress and inflammation in RAW 264.7 macrophages and L-arginine-induced AP mice model. In the in vitro model, MESPR exhibited significant antioxidant activity in RAW 264.7 macrophages by suppressing LPS-induced nitrosative-oxidative stress. MESPR treatment in mice reduced L-arginineinduced pancreatic enzyme changes, oxidative stress, and inflammation. It suppressed NF-κB p65, nitrotyrosine, and iNOS expression while increasing Nrf-2 and SOD1, thus mitigating oxidative stress and inflammation in acute pancreatitis. These results indicate that MESPR alleviated Larginine-induced acute pancreatitis by reducing oxidative-nitrosative stress and inflammation. [ABSTRACT FROM AUTHOR]

This experiment is to investigate whether interspecies differences exist in the effects of leucine (Leu) on digestive enzyme secretion in pancreatic tissues through in vitro. Five healthy Simmental cattle and Duroc × Landrace × Yorkshire growing-finishing pigs were selected, and pancreatic tissues were taken for culture after slaughter. Leu levels of 0, 2.62, 5.24, 10.48 mg/mL. Leu levels of 0, 5.24 mg/mL were selected to determine the expression of mRNA and proteins in the signaling pathways. The results showed that Leu increased the activity of digestive enzyme in cattle and pig, and there was an interaction was found on trypsin and chymotrypsin (P < 0.05). Leu had a significant effect on the mRNA (PKB, S6K1, 4E-BP1 and ATF4) and protein expression (PKB and 4E-BP1) and the phosphorylation (PKB, S6K1 and ATF4) levels (P < 0.05). Animal species had significant effects on the mRNA (PKB, S6K1 and ATF4) and protein (S6K1 and 4E-BP1) expression, and the phosphorylation (4E-BP1) levels (P < 0.05). There was an interaction between animal species and Leu on the expression of protein (PKB and S6K1) (P < 0.05). In summary, interspecies differences exist in the regulation of Leu on digestive enzyme secretion in pancreatic tissues in vitro of different animals. [ABSTRACT FROM AUTHOR]

Aims: Acute heart failure (AHF) is associated with end‐organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. Methods and results: In data from the Pragmatic Urinary Sodium‐based treatment algoritHm in Acute Heart Failure (PUSH‐AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33–63] U/L and 30 [21–44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P‐value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT‐proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). Conclusion: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT‐proBNP. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate how systemic antimony treatment in cutaneous leishmaniasis (CL) patients affects biochemical, hematological, and inflammatory parameters in child and adult patient groups. Methods: A total of 50 patients (29 adults, 21 children) who received systemic meglumine antimonate (MA) treatment in the skin and venereal diseases clinic between September 2022 and January 2024 and were diagnosed with CL by microscopic examination were included in the study. The medical records of the patients were examined retrospectively. Before and after treatment, neutrophil count, leukocyte count, lymphocyte count, hemoglobin concentration, platelet count, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen and serum creatinine levels were recorded. Results: In the children group, lymphocyte and platelet values decreased statistically significantly; and lipase value increased statistically significantly after treatment. In the adult group; hemoglobin, neutrophil, lymphocyte and leukocyte values decreased statistically significantly; ALT, AST, amylase, lipase, NLR and PLR values increased statistically significantly after treatment. Conclusion: Based on the data in our study, it was stated that systemic meglumine antimonate treatment may lead to an increase in pancreatic enzymes and transaminases and bone marrow suppression. We also think that patients in the adult age group should be followed more closely regarding pancreatic enzymes and kidney function tests than the pediatric age group. [ABSTRACT FROM AUTHOR]

AbstractFor the current aging population, protein is an important macronutrient to counteract the development of sarcopenia. Protein digestion is influenced by the capacity of the digestive system. The current evidence is reviewed about the impact of aging on the human digestive system and related to protein digestion in vivo. Aging changes the digestive organs which impacts protein digestion. Dentition decreases and mastication changes, potentially affecting particle size reduction. Stomach gastric acidity is unchanged, gastric emptying is delayed, while total transit time remains unchanged. Production of enzymes by the pancreas is decreased, but any changes in the small intestine remain unresolved. Animal studies showed decreased fecal protein digestion in older compared to young animals. Human studies showed decreased postprandial peripheral plasma appearance of ingested amino acids and increased splanchnic extraction. The findings suggest that the deteriorating digestive system with aging results in decreased protein digestion. Interpretation of the results should be taken with caution because of interindividual differences in the aging process, and because studies on protein digestion in aging humans are scarce. More information is needed on healthy aging and its relation to the digestive tract and protein digestion, several methods including in vitro experiments are valuable in this perspective. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Immune checkpoint inhibitors (ICI) are considered standard‐of‐care in the systemic treatment of melanoma. However, management of certain ICI‐associated adverse events (AE) can be challenging. Incidence, course and management of immune checkpoint inhibitor‐induced pancreatic injury (ICIPI) are not well‐documented and specific diagnostic and therapeutic algorithms are lacking. Current management includes serological monitoring of pancreatic enzymes, radiographic imaging and corticosteroid or further immunosuppressive treatment. Objectives: Based on previous data regarding adjuvant ICI treatment, we suspected that elevation of pancreatic enzymes may occur more frequently than reported while the clinical relevance of—particularly asymptomatic—ICIPI is still unclear.A collaboration of eight Austrian and Swiss dermato‐oncology centres was established to retrospectively analyse a large cohort of ICI‐treated patients regarding incidence and management of ICIPI. Additionally, a questionnaire‐based survey concerning ICIPI‐management was conducted.Among 1516 melanoma patients receiving ICI therapy, 204 patients exhibited ≥CTCAE II° lipase elevation. Of these patients, 41 (20.1%) had symptoms suggestive of pancreatitis. Immunotherapy was interrupted or discontinued due to pancreatic AE in almost half of the patients. Systemic corticosteroids were administered in 103 patients (50.5%), with higher doses reported in symptomatic cases. Six per cent of asymptomatic patients had radiographically proven pancreatitis. Maximum lipase elevation was >5xULN in all of these patients.Routine lipase monitoring was conducted in all participating centres, although not recommended in respective guidelines. Elevation of serum lipase was observed more frequently than recently reported. Although radiographic findings indicating pancreatitis were rare in asymptomatic patients, ICI treatment was frequently paused or discontinued and systemic steroids were administered. To reduce the existing uncertainty in routine clinical practice reflected by our findings, we provide an algorithm to guide the monitoring and management of potential pancreatic adverse events. Lipase measurement should be limited to symptomatic patients and/or those with radiographic findings indicative of pancreatic injury. [ABSTRACT FROM AUTHOR]

Obesity is a global health concern, steadily rising and posing risks to various health conditions. Despite available antiobesity drugs, their withdrawal due to severe side effects highlights the need for safer alternatives. Natural products, particularly mixed herbal formulations, present a promising avenue in obesity research. This study aimed to investigate the potential antiobesity effects of the NL herbal formula, a traditional remedy in Nakhon Si Thammarat, Thailand, composed of nine herbs. The specific focus was on the inhibitory effects on α‐glucosidase and pancreatic lipase enzyme activities, adipogenesis inhibition and lipolysis promotion. NL extract was phytochemically analyzed and assessed for its inhibitory effects on α‐glucosidase and pancreatic lipase. Its impact on lipid accumulation and glycerol release was also evaluated. Phytochemical analysis using liquid chromatography–tandem mass spectrometry (LC/MS‐MS) identified piperine as the major compound in the NL extract. NL extract exhibited significant inhibition of α‐glucosidase, moderate pancreatic lipase inhibition, and dose‐dependent reduction in fat accumulation and triglyceride content. Glycerol release increased compared to the control, indicating potential benefits in weight management. This research underscores the potential of the NL formula in combating obesity through its effects on adipogenesis, lipolysis, and enzyme activities. Further investigations into the molecular mechanisms are warranted to fully elucidate its therapeutic potential. [ABSTRACT FROM AUTHOR]

The growing interest in commercial Inland saline aquaculture has taken momentum across the globe due to the available technologies for aquaculture and the abundant resources of saline groundwater. However, the critical problems in inland saline ponds are degraded soil and imbalanced or deficient nutrients. To address these issues, a 75-day experiment was conducted to explore the effects of Paddy Straw Biochar (PSB) as a sediment amendment on sediment quality, water characteristics, growth parameters, and the well-being of Penaeus vannamei reared in inland saline environments. PSB was applied to the nursery ponds at 1 ton/hectare (Treatment, T1) and 2 ton/hectare (Treatment, T2). The findings of water quality parameters showed a significant increase in K+ and Mg++ with a decrease in ammonia-N levels in biochar-applied ponds. Similarly, the addition of biochar to ponds (T2) resulted in improved sediment characteristics with enhanced water holding capacity (24.75%), increased soil organic carbon content (77.94%), pH levels (0.37 units), cation exchange capacity (43.15%), available potassium (16.3%), and lower bulk density (12.61%) compared to ponds subjected to control conditions at the end of the experiment. Over the experiment, improvements in sediment and water quality parameters followed the T2 > T1 > control trend. Growth characteristics showed a significant rise in the percentage of weight gain (12.398 ± 0.12), SGR (11.80 ± 0.01% day−1) and PER (2.39 ± 0.01) with reduced FCR (1.19 ± 0.00) in biochar-treated ponds (T2), followed by T1 and control. The digestive enzyme activity (amylase) and metabolic enzymes like hepatopancreatic alanine aminotransferase (ALT) and muscle ALT activities were significantly higher in shrimps raised in the biochar-applied ponds. On the other hand, the oxidative stress enzyme superoxide dismutase (SOD) in gills, muscles, and hepatopancreas (HP) exhibited lower values, suggesting reduced oxidative stress due to the biochar amendment of the pond sediment. Overall, the study recommends incorporating PSB at a rate of 2 t/ha into nursery pond sediment to enhance water quality, physiological status, and the growth of P. vannamei juveniles. Moreover, this approach improves soil and water characteristics in saline soils, making it an effective culture practice in degraded environments. [ABSTRACT FROM AUTHOR]

In the present research work a sequence of substituted quinoline based thiazolidinedione moieties (12a–h) were designed and synthesized as potential antidiabetic agents. Pancreatic α‐amylase (PAA) and intestinal α‐glucosidase (IAG) enzymes were considered as potential targets for effective treatment of diabetes. The potential of all compounds (12a–h) was assessed in vitro against PAA and IAG using acarbose as standard. The results suggested that compound 12h has shown superior PAA and IAG inhibitory activity with respective to standard (IC50 = 4.683 ± 0.06 µM and 2.456 ± 0.07 µM). Furthermore, using computational (in silico) studies like AutoDock and Desmond, predicted the significant binding interactions responsible for the activity of all compounds (12a–h) at the active site of enzymes, while SwissADME and Osiris property explorer tools computed in silico drug likeliness and toxicity properties. The RMSD, RMSF, Rg and protein ligand contacts, confirmed the stable binding of compound 12h and 12g with the both PAA and IAG proteins. The in silico results confirmed the 12h molecule as a superior drug with high binding affinity and good drug likeness against PAA and IAG, confirming in vitro results. We also studied antioxidant activity (AOA) of all synthesized compounds and results confined that the compound 12h has good antioxidant potential (IC50 = 5.04 ± 0.054 µM) among all other compounds. In conclusion, in vitro, in silico and antioxidant studies revealed 12h compound was found to be potential compound. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the effects of commercial probiotic Bacillus sp. supplementation on seabream Sparus aurata larviculture under culture conditions. In this context, Bacillus was supplemented via rotifer feeding and water and its effects on pancreatic and intestinal enzyme activities as well as aquaculture parameters were evaluated during early life development. In the experimental group, as probiotic three Bacillus sp. spores were introduced via rotifer and larval culture tanks, while the larvae in control group did not feed any probiotic supplementation. At the end of the experiment on 40 days after hatching, the probiotic-supplemented group exhibited better growth performance and there were statistically differences in between groups of probiotic-treated and control regarding growth parameters (P  < 0.01), despite insignificant survival rate (P  > 0.05). In terms of enzymatic expressions, S. aurata larvae receiving probiotic supplementation through rotifers demonstrated noteworthy (P  < 0.05) enhancements in specific activities of pancreatic and intestinal enzymes, except for amylase (P  > 0.05), when compared to the control group. It is concluded that the administration of Bacillus sp. as probiotic bacteria through rotifer supplementation and water intake demonstrates significant positive impacts on both growth parameters and specific activities of main pancreatic and intestinal enzymes of seabream larvae. [ABSTRACT FROM AUTHOR]

Superior mesenteric artery aneurysms are a rare pathology, and rupture due to a pancreatic cyst in the context of alcohol-induced pancreatitis is an even rarer condition. The first line of treatment is usually an endovascular approach. We present the case of a 51-year-old male with alcohol-induced pancreatitis, diagnosed with a superior mesenteric artery aneurysm with active bleeding in close contact with a large pancreatic cyst. A covered stent was used to treat this condition. The patient developed hemorrhagic shock 12 h after the procedure and an urgent laparotomy was performed. A second rupture of the arterial wall at the distal end of the stent was observed and in order to obtain distal perfusion, first, an infrarenal aorta to superior mesenteric artery bypass distal to the rupture was performed in order to exclude the aneurysm. Secondly, a bypass originating from the distal end of the first bypass to the distal end of the superior mesenteric artery was performed. The patient had an uneventful recovery and was discharged after 10 days. We reviewed the literature regarding the incidence and the therapeutic management of superior mesenteric artery aneurysm complicated by pancreatic cyst. An advanced search on PubMed from 2004 to 2024 returned 194 results and after applying the inclusion–exclusion criteria, 11 publications were selected. Although the endovascular approach is usually the first line of treatment with obvious advantages for the patient, a patient-tailored approach should be made in such cases and surgery could be the first option, when considering that the mechanism of aneurysm rupture is due to erosion of the arterial wall by the pancreatic enzymes. Surgery has the advantage of cyst drainage and aneurysm exclusion and in our case proved lifesaving. [ABSTRACT FROM AUTHOR]

In this study, four groups of diet were prepared, with eel commercial diet without hydrolyzable tannin (HT) as the control group (H0), and the other three groups were fed with diet containing 0.05% (H1), 0.1% (H2), and 0.2% (H3) doses of HT to juvenile Mastacembelus armatus with an initial body weight of (0.40 ± 0.005) g. Juvenile fish in all groups were fed continuously for 60 days. Growth indices, hepatopancreatic antioxidant enzymes, biochemical indices (including total superoxide dismutase [T‐SOD], catalase [CAT], malondialdehyde [MDA], total antioxidant capacity [T‐AOC], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [AKP], and triglyceride [TG]), the content of muscle amino acids and fatty acids, stomach and intestine enzyme activities (pepsin, amylase, lipase), and genes expressions were evaluated. The results showed that 0.1% HT significantly improved the growth performance, hepatopancreatic antioxidant capacity, as well as muscle quality and lipase activity of juvenile M. armatus. In summary, the optimal addition level of HT in the diet of juvenile M. armatus is 0.1%, which helps to improve aquaculture efficiency and improve the muscle quality of M. armatus. However, the long‐term effects of feeding HT on M. armatus and its physiological reaction mechanism need to be further explored. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effectiveness of micropancreatic enzymes on biochemical profiles in patients who have undergone cholecystectomy. Method: A total of 122 patients with pancreatic exocrine insufficiency who visited the outpatient clinic of Sorgun State Hospital, Yozgat, Turkey and had undergone cholecystectomy in the last three months were assigned to study and control groups. Study group (n = 72) received micro pancreatic enzyme mixture for at least 4 weeks within 3 months of cholecystectomy. Control group (n = 50) with a history of cholecystectomy did not use any digestive aids or micro pancreatic enzyme mixture during the same period. Pancreatic insufficiency, water consumption, Vit D, B12, calcium, and lipid profiles were compared in both groups. Results: Severity of pancreatic exocrine insufficiency was significantly mild in study group compared to control group (p < 0.05). In patients who had undergone cholecystectomy, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein levels after at least 6 weeks were significantly lower in study group compared to control group (p < 0.05). Conclusion: Micropancreatic enzyme improves pancreatic function, and lowers lipid levels in patients who have undergone cholecystectomy. A prospective, randomized controlled study will be useful in determining the appropriate dosage and duration of use which provides symptomatic relief and biochemical improvement in patients who have undergone cholecystectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: The study focused on the effects of dietary arginine (Arg) supplementation on yellow catfish (Pelteobagrus fulvidraco) under low-temperature stress (18 °C). Over eight weeks, 720 fish were divided into six groups and fed diets with varying Arg levels. The results showed that Arg supplementation improved growth, feed efficiency, digestive enzyme activity, and antioxidant responses in the fish. It also enhanced the expression of antioxidant-related genes. Based on the findings, the optimal Arg intake for yellow catfish under these conditions is 26.8 g per kg of diet, equivalent to 37.0 g of dietary protein. The yellow catfish is an economically significant freshwater fish with increasing importance in aquaculture. However, the low temperature environments prevalent in certain regions pose challenges to its growth, development, and overall health. This study aimed to explore the impact of dietary arginine (Arg) addition on the growth, digestive capacity, and intestinal antioxidant response in fish under low temperature acclimation (18 °C). Total 720 fish were randomly distributed into six groups, each containing 120 fish. Over the course of eight weeks, each group was fed with diets about varying Arg concentrations (1.79–3.26 g/kg). The results indicated that Arg supplementation resulted in an increase in specific growth rate (SGR), feed intake (FI), feed efficiency (FE), as well as pancreatic enzyme activities in both pancreas and intestine. Conversely, malondialdehyde (MDA) and protein carbonyl (PC) contents initially decreased but increased with higher Arg concentrations. Glutathione peroxidase 1a (GPX1a) showed a positive correlation with nuclear factor-erythroid 2-related factor-2 (Nrf2), showing its role in antioxidative capacity. Furthermore, this study revealed that Arg significantly enhanced the activities of anti-superoxide anion, anti-hydroxyl radical, and anti-oxidative enzymes, along with the relative mRNA abundance of Copper-Zinc superoxide dismutase (CuZnSOD), catalase, GPX1a, glutamate-cysteine ligase catalytic subunit (GCLC), and Nrf2 in the intestine. It was determined that yellow catfish weighing between 61.0 g and 89.0 g require an intake of 26.8 g of Arg per kilogram of diet based on polynomial regression analysis of specific growth rate (SGR), which is equivalent to 37.0 g of dietary protein, under sub-low temperature conditions of 18 °C. [ABSTRACT FROM AUTHOR]

Pharmacological agents regarding the most optimal treatments of acute pancreatitis remain. One‐carbon metabolism nutrients as therapeutic agents in many diseases might be involved in acute pancreatitis. The roles are acquired exploration in acute pancreatitis. We utilized Mendelian randomization to assess the causal impact of folate, homocysteine, and vitamin B12 (VB12) on acute pancreatitis. Wild‐type and corresponding genetically modified mouse models were used to verify the genetic correlating findings. A negative association between genetically predicted serum VB12 levels and risks of acute pancreatitis was identified in human population. The transcobalamin receptor (TCblR)/CD320 gene ablation that decreased cellular VB12 uptake and ATP production in pancreatic tissues promoted necrosis, resulting in much severe pathological changes of induced acute pancreatitis in mice. VB12 pretreatment and posttreatment dramatically increased ATP levels in pancreatic tissues and reduced the necrosis, then the elevated levels of amylase in serum, the levels of CK‐19, the activity of trypsin, and T lymphocyte infiltration in pancreatic tissues, prevented the pancreatic gross loss and ameliorated histopathological changes of mouse pancreases with induced acute pancreatitis. The results reveal that VB12 is potential as a therapeutic agent to inhibit tissue injuries and adaptive inflammatory responses in the pancreas in patients with acute pancreatitis. [ABSTRACT FROM AUTHOR]

In this study, Lycium barbarum leaves polysaccharide (LBLP) was extracted by alkali extraction and ethanol precipitation. The monosaccharide composition and molecular weight distribution of LBLP were detected by ion chromatography and high performance gel permeation chromatography. The structure of LBLP was characterized by UV spectrum, infrared spectrum and X-ray diffraction. Its antioxidant and lipid metabolism regulation activities were evaluated by free radical scavenging test and enzyme activity inhibition test in vitro. The results showed that the total sugar content of LBLP was (65.78±0.85)%, the protein content was (12.25±0.25)%, and the uronic acid content was (19.26±0.14)%, indicating a protein complex acidic polysaccharide. LBLP was composed of 8 monosaccharides, the molar ratio of which was: narabinose:ngalactose:nrhamnose:nglucose:nxylose:nglucuronic acid:ngalacturonic acid:nglucosamine hydrochloride=427:293:86:73:42:40:31:8 of which arabinose had the highest content. LBLP mainly contained two polysaccharide components with different molecular weight distributions, among which the component with the highest content had a weight average molecular weight (Mw) of (67 380± 288) ku. The UV spectrum showed that the Lycium barbarum leaves extract contains protein absorption peaks, indicating that it was a protein complex polysaccharide, consistent with the protein content determination results. It could be seen from the infrared spectrum that LBLP has the characteristic absorption peak of polysaccharide and contains pyranoside. In antioxidant experiments, LBLP showed good scavenging effects on 2,2-diazo-bis-3-ethylbenzothiazole-6-sulfonic acid cations (ABTS+), 1,1-diphenyl-2-trinitrophenylhydrazine cations (DPPH+), superoxide anions, and hydroxyl radicals. When the LBLP mass concentration was 5 mg/mL, the scavenging rates of DPPH+ and superoxide anions reached 90%. In the enzyme activity inhibition experiment, LBLP had good inhibitory ability on the activities of α-amylase, α-glucosidase, trypsin, and pancreatic lipase, and had a dose effect relationship. The IC50 was (23.80±0.17), (9.53±0.39), (23.36±0.81) mg/mL and (16.03±0.59) mg/mL, respectively. This study could provide theoretical basis for the development of functional foods related to antioxidant, hypoglycemic, and lipid-lowering effects of Lycium barbarum leaves polysaccharides. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic and bariatric surgery (MBS) is often considered to be associated with macro- and micronutrient deficiency. A possible treatment option can be the implementation of pancreatic enzyme replacement (PERT) and may lead to better outcomes. We designed a prospective trial investigating the possible impact of PERT in patients undergoing MBS at a high-volume center. Materials and Methods: A prospective two-arm randomized controlled trial was conducted on patients who underwent either sleeve gastrectomy or gastric bypass procedures at a high-volume center. Patients underwent bariatric surgery and follow-up examinations at 3, 6, and 12 months after surgery. Patients were stratified either to the treatment group with PERT or to the control group. The primary endpoint of the study was a change in BMI. Lab testing was carried out to measure secondary endpoints, including albumin and vitamin D levels. Results: Overall, 204 patients were enrolled. Due to missing follow-ups, surgical complications, and side effects due to Kreon medication, 65 were excluded. Analysis of primary endpoints indicates that PERT does not lead to slower weight loss or BMI reduction. Analysis of secondary endpoints showed significantly better vitamin D levels in patients undergoing MBS and PERT. No statistical difference was seen regarding albumin. In both arms, fatty liver disease improved. Quality of life is positively judged as comparable by patients in both groups. Conclusion: Herein, we show an association between PERT and higher vitamin D levels in patients undergoing MBS. An optimized enzymatic environment due to PERT may therefore result in higher vitamin D levels and may improve clinical outcomes in patients undergoing MBS. [ABSTRACT FROM AUTHOR]

This document contains three research reports. The first report examines the relationship between El Niño events and rainfall patterns in the eastern Bay of Bengal. The second report focuses on resolving the Mahadayi water dispute by analyzing rainfall data and estimating water discharge in the river basin. The third report explores the use of nanoparticle-based drug delivery systems to improve the treatment of malaria. The first article discusses the dysregulation of calcium ion signaling in pancreatic acinar cells and its implications for medical conditions. The second article investigates the metabolic reprogramming in immune cells during Mycobacterium tuberculosis infection. The third article explores the use of electric fields to repel mosquitoes and prevent mosquito-borne diseases. [Extracted from the article]

Acute pancreatitis (AP) is one of the most severe mortal inflammatory diseases worldwide, which is characterized by the over‐activation of reactive oxygen species (ROS)‐induced inflammation and pancreatic enzymes (PEs). As the PEs induced by ROS exacerbate the progression of AP, therefore, scavenging ROS within PEs is a prerequisite for AP treatment. To address the daunting issue, the engineered bio‐heterojunctions (bio‐HJs) consisting of Mo2C‐Au (MA), phospholipid, and protease inhibitors are devised. First, the decorated phospholipid and protease inhibitors facilitate the delivery of MA to the inflammatory pancreas as well as neutralization of PEs. Next, the MA exhibits outstanding antioxidant and ROS scavenging abilities, primarily benefiting from the increased empty orbitals on Mo attributed to electron transfer between the Mo2C and Au confirmed by theoretical calculation. The in vitro experiments demonstrate that the bio‐HJs exhibit splendid biocompatibility, excellent trypsin neutralization, and efficient ROS elimination properties. More encouragingly, the in vivo studies further reveal that the bio‐HJs prevent the infiltration of inflammatory cells and alleviate the severity of AP by suppressing the ROS‐induced activation of the TLR4‐ERK1/2 MAPK‐MLCK inflammatory signaling pathway. As envisioned, the engineered bio‐HJs represent a promising approach to the treatment and prevention of AP. [ABSTRACT FROM AUTHOR]

Objective To establish the association of the SEPP1 gene's (rs7579) polymorphism with enzymatic, metabolic and hormonal activity in patients with chronic pancreatitis (CP) and primary hypothyroidism. Materials and methods Eighty CP patients (40 with comorbid hypothyroidism) and 30 healthy controls participated in the case-control study. Pancreatic enzymes, Selenoprotein P, NO metabolites (NO2-+NO3-), glucose, total cholesterol (TC), triglycerides (TG) and low/high density lipoprotein cholesterol (LDL-, HDL-C), Atherogenicity Index (AI), thyroid-stimulating hormone (TSH), Thyroxine (T4), glomerular filtration rate (GFR) were studied. SEPP1 (rs7579) genotyping performed by PCR (FlexCycler BU). Results and discussion SEPP1 (rs7579) gene's A-allele increases the risk of hypothyroidism twice in CP [OR=2.0; OR 95%CI:1.09-3.66; p=0.023]. Pancreatic patients with hypothyroidism and SEPP1 gene's (rs7579) AA-genotype had 60.0% (pAA=0.013) lower elastase and 13.78% (p=0.003) higher α-amylase as well as TSH by 10.81% (pAA=0.009) and 15.64% (pAA=0.009), especially in women 14.55-45.18% (p<0.001) at a lower value of Selenoprotein P - by 28.65-48.08% (p≤0.048) regardless of the SEPP1 gene (rs7579) variants. Women have 17.43-18.14% (pW≤0.032) higher NO metabolites than men; A-allele women have free T4 value 2.62 times lower (pGG=0.01) than GG-women and 2.97 times lower (pW=0.011) than men. Comorbid patients with A-allele had elevated TC and LDL-C, by 11.77-26.45% (pAA≤0.01) and 18.06-26.21% (pAA≤0.019), respectively. Women have 54.50% (pW=0.002) higher AI with 39.30% lower (pW=0.034) Selenoprotein P and 21.96-24.56% (pW≤0.033) GFR than men. Conclusion SEPP1 (rs7579) gene polymorphism influences the risk of hypothyroidism in CP patients, changes of pancreatic enzymes, dyslipidaemia particular in AA-genotype carriers, mainly women. There was no dependence of SEPP1 and total NO metabolites values on the SEPP1 gene (rs7579) polymorphism. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a complex malignancy associated with poor prognosis and high symptom burden. Optimal patient care relies on the integration of various sectors in the healthcare field as well as innovation through research. The Canadian National Pancreas Conference (NPC) was co-organized and hosted by Craig's Cause Pancreatic Cancer Society and The Royal College of Physicians and Surgeons in November 2023 in Montreal, Canada. The conference sought to bridge the gap between Canadian healthcare providers and researchers who share the common goal of improving the prognosis, quality of life, and survival for patients with pancreatic cancer. The accredited event featured discussion topics including diagnosis and screening, value-based and palliative care, pancreatic enzyme replacement therapy, cancer-reducing treatment, and an overview of the current management landscape. The present article reviews the NPC sessions and discusses the presented content with respect to the current literature. [ABSTRACT FROM AUTHOR]

Obesity and hyperlipidemia have become major disorders predominantly causing prevailing cardiovascular diseases and ultimately death. The prolonged use of anti‐obesity drugs and statins for reducing obesity and blood lipid levels is leading toward adverse effects of kidneys and muscles, specifically rhabdomyolysis. The objective of this study is to evaluate potential of seeds of Ficus carica against hyperlipidemia. Various extracts and isolated compounds from fig seeds were analyzed and evaluated for their anti‐hyperlipidemic potential. Methanol extract and its ethyl acetate fraction showed maximum pancreatic lipase inhibition of 61.93% and 86.45% in comparison to reference drug Orlistat. Four compounds isolated by HPLC‐PDA technique were determined as Gallic acid, Catechin, Epicatechin, and Quercetin also showed strong potential to inhibit enzyme pancreatic lipase comparable to Orlistat. These isolated compounds were further analyzed for molecular docking and MM‐GBSA studies. Three ligands, namely Quercetin, Epicatechin, and Catechin were found more effective against pancreatic lipase as these possessed docking scores (−9.881, −9.741, −9.410) higher to that of the reference ligand Orlistat (−5.273). The binding free energies of these compounds were −55.03, −56.54, and 60.35 kcal/mol, respectively. The results have shown that Quercetin has the highest binding affinity correlating with the highest inhibition of pancreatic lipase enzyme 1LPB. Hence, it is suggested that seeds of F. carica have promising anti‐hyperlipidemic potential and foremost in reducing obesity. Summary: Various extracts, fractions of methanol extract, and isolated compounds of seeds of Ficus carica, in combating hyperlipidemia, were evaluated utilizing in vitro anti‐lipase activity and computational analysis.All extracts, methanol fractions and compounds isolated through high‐performance liquid chromatographic technique (HPLC) exhibited anti‐hyperlipidemic potential comparable to reference Orlistat.Molecular docking and MM‐GBSA studies illustrated that isolated ligand Quercetin along with Epicatechin and Catechin strongly inhibit enzyme pancreatic lipase (1LPB) and displayed a high docking score in comparison to reference ligand.Quercetin amongst four isolated compounds could be more effective in treating hyperlipidemia and obesity as compared to reference Orlistat. Significance Statement: Ficus carica possess potential constituents with profound therapeutic and traditional uses due to which the whole plant is considered medicinally important. This study focuses on the anti‐hyperlipidemic potential of seeds of F. carica against pancreatic lipase by using computational and in vitro studies. The results of this study provides the evidence that Quercetin exhibits a potent anti‐hyperlipidemic effect by inhibiting pancreatic lipase and also possess a greater binding affinity for pancreatic protein 1LPB as compared to reference Orlistat. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of followup. Children with a SPINK1 mutation (P50.005) and those with ARP (compared with CP, P50.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 (P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP. [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European cohorts with chronic pancreatitis. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases. Proteolysis of the PNLIP variants yielded an intact Cterminal domain, while the N-terminal domain was degraded. The protease-sensitive PNLIP phenotype was strongly correlated with chronic pancreatitis, suggesting a novel pathological pathway underlying the disease. To facilitate preclinical mouse modeling, here we investigated how the human mutations affected the secretion and proteolytic stability of mouse PNLIP. We found that variants I265R, F300L, S304F, and F314L were secreted at high levels, while P245A had a secretion defect and accumulated inside the cells. Proteolysis experiments indicated that wild-type mouse PNLIP was resistant to cleavage, while variant I265R was readily degraded by mouse trypsin and chymotrypsin C. Variants F300L, S304F, and F314L were unaffected by trypsin but were slowly proteolyzed by chymotrypsin C. The proteases degraded the N-terminal domain of variant I265R, leaving the C-terminal domain intact. Structural analyses suggested that changes in stabilizing interactions around the I265R mutation site contribute to the increased proteolytic susceptibility of this variant. The results demonstrate that variant I265R is the best candidate for modeling the protease-sensitive PNLIP phenotype in mice. [ABSTRACT FROM AUTHOR]

This single‐center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post‐transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24–24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection. [ABSTRACT FROM AUTHOR]

Under the conditions of chronic obstructive pulmonary disease (COPD), chronic pancreatitis (CP) progresses with the development of exocrine pancreatic insufficiency (EPI), which occurs when the active area of the acinar epithelium decreases as a result of the inflammatory process and fibrosis of the organ. The objective of the study was to study the peculiarities of the processes of the pancreas tissue fibrosis in patients with chronic pancreatitis in case of comorbidity with chronic obstructive pulmonary disease. A prospective cohort study was conducted with the analysis of inpatients’ medical records of 305 patients. The first group of patients consisted of 96 people with an isolated course of CP, the second group consisted of 116 patients with CP with comorbid COPD, the third group consisted of 93 patients with isolated COPD. The comparison group consisted of 30 practically healthy persons. The study also used data from a clinical blood analysis, a biochemical study of the content of markers of the syndrome of deviation of the pancreas enzymes in the blood, the content of elastase-1 in feces, ultrasonographic examination of abdominal organs, changes in the carbohydrate-protein components of the extracellular matrix, the state of collagenolytic activity of the blood plasma. In patients with CP in the exacerbation phase without comorbid pathology, as well as with comorbid COPD and isolated COPD, a significant activation of fibrosing reactions was established: activation of collagen synthesis was registered as an indicator of an increase in the content of protein-bound oxyproline (PBOP) in the blood: in patients of the 1st group – 1.7 times, patients of the 2nd group – 2.1 times and 3rd group – 2.3 times (p<0.05). The specified direction of changes is confirmed by the indicator of the content of type IV collagen in the blood, which increased in comparison with the indicator in practically healthy persons, respectively, in patients of groups 1, 2, 3 – by 1.4 times, 2.4 and 2.5 times (ɪ<0.05), i.e. maximally in patients with COPD and with comorbidity of CP with COPD. In patients with a comorbid course of CP and COPD, a correlational interdependence was established between the indicators of the state of the protein components of the connective tissue of the extracellular matrix of the pancreas (PBOP) and hyperamylasemia (r=0.32, ɪ<0.05), the intensity of endotoxicosis (r=0, 37, p<0.05), the level of glycemia (r=0.45, p<0.05), and the inverse relationship between the content of elastase-1 in feces (r=-0.33, p<0.05 ), insulinemia (r=-0.46, p<0.05), which indicates the interdependence of these changes and their role in the pathogenesis of the progression of chronic pancreatitis. Correlation relationship between the parameter of ultrasonographic histography of the pancreas – L, which indicates the degree of the pancreas fibrosis, and the content of type IV collagen in the blood (r=0.54, p<0.05), the content of PBOP in the blood (r=0.46, p<0.05), hexosamines (r=0.38, p<0.05) points to the biochemical mechanisms of the pancreas fibrosis and opens up prospects for developing the ways of pathogenetic correction and prevention of CP progression in comorbidity with COPD. [ABSTRACT FROM AUTHOR]