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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: 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

The leaves of Annona squamosa (AS) are known for their anti-diabetic properties, although the specific active principles and mechanisms of action remain unidentified. To explore these properties further, various extracts of AS leaves were prepared, including hexane, chloroform, butanol, hexane-washed methanol, total methanol extract, and water decoction. These extracts were characterized and tested for their inhibitory effects on pancreatic á-amylase activity under both in vitro and in vivo conditions. Among the extracts, the hexane extract demonstrated the lowest IC50 value of 0.925 mg/mL, prompting further investigation in a streptozotocin-induced diabetic model. The hypoglycemic response of this extract was correlated with its inhibitory activity against a-amylase in pancreatic homogenates. Different doses of the hexane extract were administered and compared with standard drugs such as acarbose and glimepiride. The results indicated that the hexane extract significantly reduced elevated glucose levels by 41.18±2.46% at a dosage of 100 mg/kg body weight (BW) and by 78.10±1.57% at 400 mg/kg BW. Additionally, it increased serum insulin levels from 8.56±1.42 µU/mL (in the experimental control group) to 16.26±1.20 µU/mL at the higher dosage of 400 mg/kg BW. The extract also inhibited á-amylase activity by 76.69±2.52% at 100 mg/kg BW and by 86.67±2.30% at 400 mg/kg BW. In comparison, glimepiride-treated rats exhibited a significant increase in serum insulin levels without a corresponding inhibition of a-amylase activity. Conversely, acarbose-treated rats showed significant inhibition of a-amylase but did not experience a notable rise in serum insulin levels. These findings suggest that the hexane extract of Annona squamosa leaves acts as both an insulin secretagogue--enhancing insulin secretion--and an inhibitor of pancreatic a-amylase in the small intestine. Consequently, this extract could be beneficial for managing postprandial hyperglycemia in diabetic patients. [ABSTRACT FROM AUTHOR]

Introduction: Disconnected pancreatic duct syndrome (DPDS) is a pathological condition that causes various symptoms due to the continuous secretion of pancreatic enzymes from the pancreas upstream, which has been separated due to disconnection of the pancreatic duct (DPD) for various reasons. Acute necrotizing pancreatitis includes a certain probability of DPDS appearance, which makes it necessary to provide various treatments for DPDS. Furthermore, DPDS can impact long-term results, such as recurrence and impaired pancreatic function. Although the development of various modalities has contributed to diagnosis and treatment, especially less invasive endoscopic therapy, DPDS is often overlooked, and the diagnosis can be delayed due to the lack of consensus on its definition and classification. This review summarizes the current knowledge and challenges of DPDS and discusses the optimal strategy for its diagnosis and treatment, as well as future perspectives. Areas covered: Given the lack of established definition, diagnosis, and treatment of DPDS, we conducted a thorough review of the existing literature. Expert opinion: It is emphasized that a standardized definition and classification of DPDS is essential for designing and conducting clinical studies to address current unmet needs in managing patients with DPDS. [ABSTRACT FROM AUTHOR]

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro. [ABSTRACT FROM AUTHOR]

Introduction: Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI. Methods: A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. Results: We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. Conclusions: This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes. [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]

Background: A pancreatic duct rupture can lead to various complications such as a fistula, pseudocyst, ascites, or walled-off necrosis. Due to pleural effusion, pancreaticopleural fistula typically causes dyspnea and chest pain. Leaks of enzyme-rich pancreatic fluid forming a pleural effusion can be verified in a thoracocentesis following radiological imaging such as computed tomography or magnetic resonance tomography. While management strategies range from a conservative to endoscopic and surgical approach, we report a case with successful minimally invasive treatment of pancreaticopleural fistula and effusion. Case presentation: We present a case of a patient with pancreaticopleural fistula and successful minimally invasive surgical treatment. A 62-year old Caucasian man presented with acute chest pain and dyspnea. A computed tomography scan identified a left-sided cystoid formation, extending from the abdominal cavity into the left hemithorax with concomitant pleural effusion. Pleural effusion analysis indicated significantly elevated pancreatic enzymes. Magnetic resonance cholangiopancreatography revealed a rupture of the pancreatic duct and nearby fluid accumulation. Endosonography later confirmed proximity to the tail of the pancreas, suggesting a pancreatic pseudocyst with visible tract into the pancreas. We assumed a pancreatic duct rupture with a fistula from the tail of the pancreas transdiaphragmatically into the left hemithorax with a commencing pleural empyema. A visceral and parietal decortication on the left hemithorax and a laparoscopic distal pancreatectomy with splenectomy was performed. The suspected diagnosis of a fistula arising from the pancreatic duct was confirmed histologically. Conclusion: Pancreaticopleural fistulas often have a long course and may remain undiagnosed for a long time. At this point diagnostic management and therapy demand a high level of expertise. In instances of unclear symptomatic pleural effusion, considering an abdominal focus is crucial. If endoscopic treatment is not feasible, minimally invasive surgery should strongly be considered, especially when located in the distal pancreas. [ABSTRACT FROM AUTHOR]

Pancreatic ribonuclease (RNase1), a digestive enzyme produced by the pancreas, is associated with the functional adaptation of dietary habits and is regarded as an attractive model system for studies of molecular evolution. In this study, we identified 218 functional genes and 48 pseudogenes from 114 species that span all four Cetartiodactyla lineages: two herbivorous lineages (Ruminantia and Tylopoda) and two non‐herbivorous lineages (Cetancodonta and Suoidea). Multiple RNase1 genes were detected in all species of the two herbivorous lineages, and phylogenetic and genomic location analyses demonstrated that independent gene duplication events occurred in Ruminantia and Tylopoda. In Ruminantia, the gene duplication events occurred in the ancestral branches of the lineage in the Middle Eocene, a time of increasing climatic seasonality during which Ruminantia rapidly radiated. In contrast, only a single RNase1 gene was observed in the species of the two non‐herbivorous lineages (Cetancodonta and Suoidea), suggesting that the previous Cetacea‐specific loss hypothesis should be rejected. Moreover, the duplicated genes of RNase1 in the two herbivorous lineages (Ruminantia and Tylopoda) may have undergone functional divergence. In combination with the temporal coincidence between gene replication and the enhanced climatic seasonality during the Middle Eocene, this functional divergence suggests that RNase1 gene duplication was beneficial for Ruminantia to use the limited quantities of sparse fibrous vegetation and adapt to seasonal changes in climate. In summary, the findings indicate a complex and intriguing evolutionary pattern of RNase1 in Cetartiodactyla and demonstrate the molecular mechanisms by which organisms adapt to the environment. [ABSTRACT FROM AUTHOR]

A study on the phytochemical composition of the roots of Polygonum multiflorum collecting in Vietnam and an evaluation of its capacity to inhibit pancreatic lipase enzyme was conducted. In total, 12 metabolites (1 – 12) were isolated from anti-lipase activity-guided fractionation of P. multiflorum. The isolated compounds (1 – 12) were identified as trans -resveratrol (1), methyl protocatechuate (2), methyl gallate (3), catechin (4), epicatechin (5), myrciaphenone A (6), quercetin (7), kaempferol (8), apigenin (9), luteolin (10), tricin (11), and afzelin (12). This is the first time Compound 12 has been reported from P. multiflorum. However, 12 second metabolites (1 – 12) were tested in vitro to assess the anti-lipase potential. The results revealed Compound 7 exhibited the most significant lipase inhibition, with an IC50 value of 0.30 ± 0.04 μM. Following closely, Compounds 6, 8, 10, and 12 displayed IC50 values of 5.38 ± 0.65, 0.72 ± 0.10, 0.79 ± 0.19, and 1.22 ± 0.18 μM, respectively. For comparison, orlistat (positive control), the most common anti-obesity drug available on the market, has an IC50 value of 0.91 ± 0.10 μM. Molecular docking was applied to explore the affinity and interactions between active compounds 6 – 8, 10, and 12 and proteins associated with obesity, namely pancreatic lipase–colipase complex (PLCC) and pancreatic lipase-related protein 1 (PLRP1). In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) were used in predictions. The results indicate that the active compounds isolated from P. multiflorum could be further in-depth research on lipase inhibition. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis is an inflammation of the parenchyma of the pancreas. Acute pancreatitis is described as an acute condition characterised by abdominal discomfort, a threefold or more increase in serum levels of the pancreatic enzymes amylase or lipase, and/or typical signs of pancreatic inflammation on contrast-enhanced CT. Objective: To compare and assess the accuracy of PANC3 and BISAP scoring systems with Glasgow IMRIE scoring system in predicting the severity of acute pancreatitis. Methods: After obtaining informed written consent. (Annexure 1) Details of cases were recorded, including history and clinical examination. Routine blood investigations were performed. Radiological investigations, such as chest x-ray and ultrasonography, were also done. Follow-up was conducted until the patient was discharged from the hospital Results: The BISAP score has good discriminatory power in identifying severe acute pancreatitis (AP) with sensitivity and specificity values are 80.00% and 90.62%, respectively. The GLASGOWIMRIE score also has good discriminatory power in detecting severe AP, with sensitivity and specificity values are 77.78% and 91.46%, respectively. PANC3 also has good discriminatory power in identifying severe AP with specificity and sensitivity values are 91.03% and 72.73%, respectively.. Conclusions: In general, these scores have good performance in identifying severe AP, with the GLASGOW IMRIE score having the highest AUC value among the three scores. However, each score has its own strengths and weaknesses, and the choice of which score to use may depend on various factors, such as the availability of resources and the specific characteristics of the patient population. [ABSTRACT FROM AUTHOR]

Pistacia species (P. spp) have been used as a treatment for various diseases, including diabetes and inflammation. This study aimed to identify the main components of flavonoids in Pistacia species and evaluate the effect of aqueous extracts of P. spp on pancreatic enzymes and on cancer cells associated with obesity in colon and rectum. HPLC was used to identify the major components of flavonoids. The potent inhibitory effect of Pistacia species against pancreatic α-amylase, α-glucosidase and lipase was examined. The antiproliferative efficacy of the plant extract against several colorectal cancer cell lines were then measured. The main flavonoids component found in Pistacia species are quercetin-3-β-D-glucoside, rutin, kaempferol and vitexin. The starch blockade IC50 (µg/mL) of Pistacia species in a descending order were: P. lentiscus leaves: 1.09±0.01; P. atlantica leaves: 0.96±0.09 and P. atlantica fruits: 0.48±0.02. Pistacia species exerted promising inhibition effect for pancreatic lipase (PL). Besides the aglycones of P. atlantica leaves, all the tested aqueous extracts exerted appreciably novel antiproliferative activity against the tested colorectal cancer cell lines. This study provides useful indication for the Pistacia species as a potential novel therapeutic agent against diabesity and cancer. [ABSTRACT FROM AUTHOR]

World Health Organization grade II/III meningiomas frequently recur despite maximal safe surgical resection and adjuvant radiation. Notoriously resistant to medical therapy, no well-established guidelines for pharmacologic treatment currently exist. In recent years, a small number of clinical trials have investigated immune checkpoint inhibitors (ICIs) for patients with recurrent grade II/III meningiomas. We reviewed the existing literature to 1) summarize the clinical responses that have been observed and 2) identify tumor genomic characteristics that may predict a better response to ICI therapy. PubMed was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to include studies reporting clinical data for recurrent grade II or grade III meningiomas treated with ICIs. Clinical features, available tumor genomics, and outcomes were analyzed. Four studies were included comprising 59 patients; 74.6% had World Health Organization grade II meningiomas and 25.4% had grade III meningiomas. Thirt-two patients (54%) received nivolumab, 26 (44%) received pembrolizumab, and 1 (2%) received an ICI not named. While tumor genomic data was not consistently reported across studies, favorable response was most associated with mismatch repair deficiency and high tumor mutational burden. Common adverse effects included liver/pancreas enzyme elevations (11.5%), fatigue (11.5%), and leukopenia/infection (9%). Checkpoint inhibitors represent a promising investigational therapy for patients with recurrent grade II/III meningiomas. These drugs may be more efficacious for tumors with mismatch repair deficiency or high tumor mutational burden. Future investigations would benefit from research consortia with prospective enrollments of patients, descriptive characterization of tumor genomics, and standardized assessment of radiographic response [ABSTRACT FROM AUTHOR]

Context In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). Objective To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS). Methods We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset. Results Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11 , INS , ABCC8 , 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6 , PDX1 , GATA6 , HNF1B , FOXP3 , IL2RA , LRBA , BSCL2) during 2013-2022 (8/42 or 19%, P =.034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3 , IL2RA , LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6 , PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin. Conclusion NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy. [ABSTRACT FROM AUTHOR]

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

Objectives: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled‐off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. Methods: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure‐related adverse events, and clinical outcomes were investigated. Results: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure‐related adverse events, and seven (6.9%) died during the treatment period. During a median follow‐up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new‐onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure‐related adverse event rate, and long‐term follow‐up outcomes were not significantly different among the three groups. High APACHE‐II scores (≥15) and organ failure were identified as factors related to treatment failure. Conclusions: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short‐term and long‐term outcomes. [ABSTRACT FROM AUTHOR]

Acute Pancreatitis (AP) is a common condition with an overall mortality rate of 6-15%. Internationally, gall stones and alcohol are the most common causes of pancreatitis. Amylase estimation is technically simple, inexpensive, and sensitive but it has low specificity. Lipase has a greater sensitivity in acute alcoholic pancreatitis and in patients who present late to the emergency room and remains elevated longer than amylase. The presence of elevated liver enzymes usually indicates liver damage. Alanine Transaminase (ALT) is more specific to the liver than Aspartate Transaminase (AST). The present study was conducted to see whether changes in specific biochemical markers are significant enough to act as a diagnostic tool to differentiate between alcoholic pancreatitis and gallstone pancreatitis. Thorough history (especially of alcohol abuse, >4-5 drinks/day) and clinical examination were recorded. Severity grading of all patients was done based on BISAP scoring. Abdominal ultrasound was used for screening for gall stones, common bile duct stones and pancreatitis. Patients diagnosed with gall stone on abdominal ultrasound were tested for liver and pancreatic enzyme levels. A total of 140 cases (70 of each group) was analyzed in this study. There was no statistically significant co-relation of serum amylase, lipase, AST, ALT, ALKP with the severity of pancreatitis. However, a direct co-relation was seen between raised TLC, BUN and severity of pancreatitis. The average serum amylase level was significantly higher for gallstone pancreatitis as compared to alcoholic pancreatitis at presentation. The serum AST, serum ALT, serum bilirubin and serum ALKP levels in gallstone pancreatitis were higher as compared to alcoholic pancreatitis. However, a direct co-relation was seen between raised TLC, BUN, and severity of pancreatitis. Raised biochemical markers like AST, ALT, amylase, lipase, ALP and serum bilirubin can be used as good markers for diagnosis of gallstone pancreatitis. However, a normal or low serum level of these markers does not rule out possibility of gallstones in the aetiology of pancreatitis and may require further evaluation. [ABSTRACT FROM AUTHOR]

Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp. Association analysis of 10,084 genetic variants within 28 genes involved in sphingolipid pathways identified a missense variant (rs267738, A>C, E115A) in exon 4 of CERS2 that was associated with higher sleeping EE (116 kcal/day) and increased rates of endogenous glucose production during basal (5%) and insulin-stimulated (43%) conditions, both indicators of hepatic insulin resistance. The rs267738 variant did not affect ceramide synthesis in HepG2 cells but resulted in a 30% decrease in basal mitochondrial respiration. In conclusion, we provide evidence that the CERS2 rs267738 missense variant may influence hepatic glucose production and postabsorptive sleeping metabolic rate. Article Highlights: The genetic determinants of interindividual differences in energy expenditure (EE) are not well established. Sphingolipids have been proposed to influence EE by altering mitochondrial function. Association analysis of genetic variants in genes involved in sphingolipid pathways identified a missense variant (rs267738, A>C, E115A) in CERS2 associated with higher sleeping EE assessed by whole-room indirect calorimetry. The rs267738 variant was associated with increased glucose production under basal and insulin-stimulated conditions and with decreased basal mitochondrial respiration. The rs267738 missense variant may affect the expression of key gluconeogenic genes G6PC1 and PCK1. [ABSTRACT FROM AUTHOR]