Pancreatic Secretion Research Articles

Unveiling the Impact of Rapeseed Meal on Feeding Behavior and Anorexigenic Endocrine in Litopenaeus vannamei.

Litopenaeus vannamei, with high plant protein acceptance and high global aquaculture production, is a potential species for rapeseed meal application. However, rapeseed meal has been associated with anorexia in fish, and whether the same occurs in L. vannamei remains unknown. This study demonstrated the effects of rapeseed meal on the feeding and anorexigenic endocrine of L. vannamei based on feeding behavior and transcriptomics. Soybean meal was replaced with fermented rapeseed meal (50%), and a significant increase in remaining diet and dietary discard was observed with a significant reduction in dietary visits. Transcriptome analysis revealed that the pathways involved in rapeseed meal-induced anorexia mainly included signal transduction, the digestive system, the sensory system, the endocrine system, phototransduction-fly, the thyroid hormone signaling pathway and pancreatic secretion. Moreover, this study further analyzed and identified seven neuropeptides involved in rapeseed meal-induced anorexia, and it explored the complex expression regulation strategies of these neuropeptides. In summary, this study confirmed through feeding behavior that rapeseed meal causes anorexia in L. vannamei, and it identified seven neuropeptides that were closely related to the anorexia process.

Investigating the Impact of Varied Dietary Protein Levels on Litopenaeus vannamei: An Exploration of the Intestinal Microbiota and Transcriptome Responses

This study explored the effects of dietary protein levels on Litopenaeus vannamei with its intestinal microbiota and transcriptome responses. Previous studies on the effects of dietary protein levels on L. vannamei have focused on growth performance, antioxidant indices, and digestive enzyme activity, but few studies have been conducted at the microbiological and molecular levels. In this study, five isolipid experimental diets with protein levels of 32% (P32), 36% (P36), 40% (P40), 44% (P44), and 48% (P48) were used in an L. vannamei (0.63 ± 0.02 g) feeding trial for 56 days. At the end of the feeding trial, the growth performance, immunity, intestinal health, and transcriptional responses of L. vannamei were determined. This study demonstrated that higher protein levels (P44) led to superior weight gain and growth rates for L. vannamei, with lower feed conversion ratios (FCR) observed in the P48 and P44 groups compared to the P32 and P36 groups (p ≤ 0.05). The P44 and P48 groups also showed a notably higher protein efficiency ratio (PER) compared to others (p ≤ 0.05), and there was no significant difference between them. Upon Vibrio parahaemolyticus infection, the P48 group exhibited a significantly lower survival rate (SR) within 48 h, while during 72 h of white spot syndrome virus (WSSV) infection, the P44 group had a notably higher survival rate than the P32 group (p ≤ 0.05). Digestive enzyme activity and antioxidant levels in L. vannamei initially increased and then decreased as protein levels increased, usually peaking in the P40 or P44 groups. Lower dietary protein levels significantly reduced the relative abundance of beneficial bacteria and increased the relative abundance of pathogenic bacteria in the intestines of L. vannamei. Transcriptome sequencing analysis revealed that most differentially expressed genes (DEGs) were up-regulated and then down-regulated as dietary protein levels increased. Furthermore, KEGG pathway enrichment analysis indicated that several immune and metabolic pathways, including metabolic pathways, glutathione metabolism, cytochrome P450, and lysosome and pancreatic secretion, were significantly enriched. In summary, the optimal feed protein level for L. vannamei shrimp was 40–44%. Inappropriate feed protein levels reduced antioxidant levels and digestive enzyme activity and promoted pathogen settlement, deceasing factors in various metabolic pathways that respond to microorganisms through transcriptional regulation. This could lead to stunted growth in L. vannamei and compromise their immune function.

Exocrine pancreatic insufficiency as a possible predictor of pancreatic cancer development.

679 Background: Chronic and acute pancreatitis are established risk factors for pancreatic cancer. Chronic pancreatitis and pancreatic cancer are also common causes of exocrine pancreatic insufficiency (EPI), which is characterized by inadequate pancreatic secretion of exocrine digestive enzymes. Although the association between EPI and pancreatic cancer has been thought to be linked by preceding chronic pancreatitis, it is unclear if EPI, regardless of etiology, is a risk factor or early marker for pancreatic cancer or cancer in general. Methods: This is a retrospective observational study utilizing the electronic health records of Ochsner Health System, Louisiana, over a 3-year period from January 2017 to January 2020 to identify patients with a diagnosis of EPI by ICD-10 codes. Two cohorts were reviewed: patients with EPI (n=677) and patients with pancreatitis (n=1852). Both history of acute and/or chronic pancreatitis were included in the pancreatitis cohort. The cohorts were compared based on cancer prevalence at the start and end of the 3 year observation period. Results: In the EPI cohort, the cancer prevalence was 15.95% (108) at start, and 43.9% (297) at end, (p<0.05); and pancreatic cancer prevalence at start was 6.65% (123) and 29.8% (552) at end (p<0.05). In the pancreatitis cohort, the cancer prevalence was 5.4% (100) at start and 15.9% (294) at end (p<0.05); and pancreatic cancer 0.8% at start and 5% at end (p<0.05). Conclusions: Over a 3 year period, the rise in prevalence of general cancer and pancreatic cancer was higher in the EPI cohort compared to the pancreatitis cohort. Additionally, there was a statistically significant 2.8-fold increase in prevalence of cancer diagnosis and 4.5-fold increase in prevalence of pancreatic cancer diagnosis in the EPI cohort over the 3 year observation period. Though this is an observational study, it suggests the possibility that EPI, regardless of etiology, may be an independent predictor/risk factor for the development of future cancer in general and pancreatic cancer in particular. In addition it appears that this risk potential is substantively greater than that from a history of pancreatitis alone.

The impact of consumed coffee on the digestive system - review of the latest research

IntroductionCoffee stands as the second most widely consumed beverage globally, following water.[1] Recent research on the effects of coffee consumption underscores its positive outcomes when adhering to recommended doses—typically ranging from 2 to 5 cups a day, amounting to a maximum of 400 mg of caffeine daily. This newfound perspective highlights the potential benefits of moderate coffee intake on our overall health and well-being.
 Aim of the studyThe objective of this study was to comprehensively review the existing knowledge regarding the impact of coffee consumption on diverse aspects of the gastrointestinal tract.Materials and methodologyA literature review was conducted utilizing the PubMed, Google Scholar, and Google databases. Articles were systematically searched in both English and Polish, employing the keywords: coffee, caffeine, digestive system, digestion, and cancer.ResultsRecent research highlights coffee's diverse benefits, aiding digestion, hastening transit, and showing potential in cancer prevention. It stimulates gastric acid, enhances bile and pancreatic secretion, reduces gallstone risk, promotes large intestine movement, and modulates intestinal flora. Importantly, coffee isn't a primary factor in conditions like reflux, ulcers, inflammatory bowel diseases, or cancer.
 ConclusionsFurther research is essential to deepen our understanding of coffee's impact on the digestive system and its systemic effects on the body. Additionally, promoting awareness of safe daily caffeine doses that can contribute to health is worthwhile.

Surgical treament of chronic pancreatitis (literature review)

Target. To summarize the available literature data on the methods of surgical treatment of chronic pancreatitis, evaluate their results, identify shortcomings and possible solutions.Materials and Methods. We conducted a literature review of scientific papers over the past 20 years, using the resources of the search engines PubMed, Cyberleninka and eLIBRARY, on the available methods of surgical treatment of chronic pancreatitis. For this meta-analysis, we used articles containing an evidence-based experimental and clinical base on issues related to long-term and immediate results of surgical treatment.Results and discussion. We analyzed the immediate and long-term results of the methods of surgical treatment of chronic pancreatitis. In almost all studies, resection-drainage methods made it possible to effectively stop the pain syndrome for a long time. However, exoand endocrine insufficiency in most cases persisted or progressed, regardless of the method used. Another disadvantage of the existing methods was the inability to stop bleeding from the area of pancreatojejunostomy in the early postoperative period, so mortality after the development of these complications ranged from 5 to 60%.Conclusion. Based on the results studied, we identified the following disadvantages of the known methods of surgical treatment of chronic pancreatitis: 1. A long loop of the small intestine, at least 70 cm, turned off from digestion, leading to a significant decrease in the length of the intestinal tube, and, accordingly, the area of absorption of food nutrients. 2. The features of the reconstructive stage of the operation do not provide the physiological flow of pancreatic secretion into the duodenum and, accordingly, the activation of enzymes, thereby turning off the duodenal phase of digestion. 3. Roux-enabled loop of the small intestine creates favorable conditions for the development of excessive bacterial growth. 4. Lack of endoscopic evaluation of the pancreas to stop bleeding in the early postoperative period. After analyzing the literature data, we came to the conclusion that the elimination of these shortcomings will improve the results of chronic pancreatitis treatment.

Multi-omics analysis revealed the differences in lipid metabolism of the gut between adult and juvenile yellowfin tuna (Thunnus albacares).

Tuna has a cost-effective energy supply to support the regional endothermic and high-speed swimming performance. The gut symbiotic microbiotas and their metabolites play essential roles in tuna's diet digestion, absorption, and energy acquirement, which are often highly related to the ontogenetic development of tuna. We compared gut microbial compositions and metabolites, as well as mRNA expression of the intestine between juvenile and adult yellowfin tuna using 16S rRNA sequencing, metabolomic and transcriptomic, respectively. The results revealed that adults had a significantly higher microbial diversity and abundance of Acinetobacter than juveniles. Regarding the gut microbiota-derived metabolites, fatty acids, especially glycerophospholipid and sphingolipid, were significantly enriched in adults than in juveniles. Moreover, the short-chain fatty acid (butyrate and isobutyrate) contents were significantly higher in adults than in juveniles. To find the relationship between gut microbiotas and host physiology, intestinal transcriptome analysis demonstrated that the enriched pathways of differential expression genes (DEGs) in adult tuna were the lipid metabolism pathway, including "fat digestion and absorption," "cholesterol metabolism," "steroid hormone biosynthesis," "glycerolipid metabolism," and "glycerophospholipid metabolism." However, protein digestion and absorption and pancreatic secretion pathways were significantly enriched in the juveniles. The conjoint analysis indicated that the enriched pathways of both differential metabolites (DMs) and DEGs were remarkably related to the regulation of glycerophospholipids metabolism in adult tunas. This study highlights the role of gut microbiotas in fish nutrition metabolism. These findings provide new insights into the view of ontogenetic shifts of gut microbiotas and their metabolites on host health and gut function in endothermic and high-speed swimming marine fish species.

The Modulation of Euglycemic Endocrine and Exocrine Pancreatic Secretions in Iron Deficiency

Objectives: The contribution of pancreatic secretions in iron metabolism has been elucidated, but the clinical outcomes of iron deficiency on pancreatic function are debatable. This study aimed to investigate the modulation of euglycemic endocrine and exocrine pancreatic excretions in response to variations in iron availability. Subjects and Methods: Serum levels of insulin, glucagon, insulin-to-glucagon ratio (IGR), and amylase were determined in 170 adult subjects with variable levels of serum iron. Results: Control (n = 46) and iron-deficient (n = 124) subjects had significant differences (p < 0.001) in their average levels of insulin (68.7 ± 0.5 vs. 100.0 ± 2.0 pmol/dL), glucagon (17.9 ± 0.6 vs. 10.8 ± 0.8 pmol/dL), IGR (4.0 ± 0.1 vs. 19.5 ± 2.1), and amylase (29.7 ± 0.9 vs. 17.5 ± 0.2). The upregulation of serum insulin levels increases proportionally and gradually to the extent of iron deficiency as compared to an abrupt downregulation of serum levels of glucagon and amylase. A significant association was observed between serum iron and IGR (r = −0.645, p < 0.001) and amylase levels (r = 0.653, p < 0.001). The receiver operating characteristic curve analysis defines an excellent predictivity of the reduced serum iron level to discriminate subjects with upregulated IGR and amylase levels with area under curves of 0.938 and 0.905, respectively. Conclusion: Iron deficiency is associated with an adaptive modulation of euglycemic endocrine and exocrine secretions that is consistent with a status of insulin resistance.

Prognosis poor, immune infiltration of colon adenocarcinoma associated with low expression levels of calcium-activated chloride channel.

The calcium-activated chloride channel (CLCA4) in colon adenocarcinoma (COAD) and immunological infiltration have not been extensively studied. This work thoroughly employed several datasets to assess the expression, prognosis, and association between immune infiltration and clinicopathological characteristics of CLCA4 in cancer, as well as look into potential signalling pathways. The human protein atlas (HPA), TIMER, UALCAN, TISIDB, GSCA, SangerBox, GeneMANIA, and LinkedOmics were among the datasets that were used. The findings demonstrated that, in comparison to normal tissues, COAD tissues had lower levels of CLCA4 expression. The prognosis was worse for those whose levels of CLCA4 expression were lower. For validation, immunohistochemistry (HPA) was used. Positive correlations between CLCA4 mRNA expression and its copy number variation (CNV) were observed, and CLCA4 CNV was linked to immunological infiltration. Subsequent investigation demonstrated the association between immune cell markers, immune checkpoint genes, and immunological infiltration with CLCA4. The overall survival and disease-free survival of M0 patients were considerably better than those of M1 patients, and the groups with tumour stages M0 and M1 had notably different levels of CLCA4 expression. Its substantial enrichment in ion channel activity, transmembrane transporter activity, digestion, and other biological processes was revealed by gene ontology analysis. Oxidative phosphorylation, pancreatic secretion, Parkinson's and Alzheimer's diseases, renin secretion, and other signalling pathways were the primary associations found for CLCA4. It is evident that the immunological microenvironment and functions like ion transport, metabolism, and intestinal digestion are all impacted by CLCA4 expression.

Study on the signaling pathways involved in the anti-hyperglycemic effect of raspberry ketone on zebrafish using integrative transcriptome and metabolome analyses.

Hyperglycemia leads to increased oxidative stress in mitochondria, an abnormal activation of intracellular inflammatory signals, and mediate multiple dysfunctions. Raspberry ketone (RK) is an aromatic phenolic compound found in many plants and could contribute to weight loss, restore impaired glucose tolerance, and has antioxidant properties. In our investigation, RK could greatly prevent islet, brain and other tissue damage caused by hyperglycemia in a zebrafish model with streptozotocin (STZ)-induced hyperglycemia. Body weight, insulin level, and food intake indexes were also restored by RK. Using transcriptome profiling, we found that RK administration could significantly attenuate STZ-induced insulin synthesis and pancreatic secretion as well as alter protein and carbohydrate metabolism. Metabolomics analysis results showed that RK could also prevent STZ-induced metabolic disorders, such as adenosine and sphingolipid metabolism. Integrative analysis of metabolome and transcriptome data and qRT-PCR validation of key metabolic regulatory genes (glut1, glut2, ctrb1, ccka, gck, pklr) confirmed that the purine pathway was the most enriched metabolic pathway, in which both metabolite accumulation and gene expression levels showed consistent change patterns upon RK treatment. Our study provides a new perspective for understanding the hypoglycemic mechanism of RK and may be helpful for investigating the modes of action of hypoglycemic drugs using the zebrafish hyperglycemia model.

Recent Advances in the Nutrition and Metabolism of Dogs and Cats.

Domestic dogs (facultative carnivores) and cats (obligate carnivores) have been human companions for at least 12,000 and 9000 years, respectively. These animal species have a relatively short digestive tract but a large stomach volume and share many common features of physiological processes, intestinal microbes, and nutrient metabolism. The taste buds of the canine and feline tongues can distinguish sour, umami, bitter, and salty substances. Dogs, but not cats, possess sweet receptors. α-Amylase activity is either absent or very low in canine and feline saliva, and is present at low or substantial levels in the pancreatic secretions of cats or dogs, respectively. Thus, unlike cats, dogs have adapted to high-starch rations while also consuming animal-sourced foods. At metabolic levels, both dogs and cats synthesize de novo vitamin C and many amino acids (AAs, such as Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) but have a very limited ability to form vitamin D3. Compared with dogs, cats have higher requirements for AAs, some B-complex vitamins, and choline; greater rates of gluconeogenesis; a higher capacity to tolerate AA imbalances and antagonism; a more limited ability to synthesize arginine and taurine from glutamine/proline and cysteine, respectively; and a very limited ability to generate polyunsaturated fatty acids (PUFAs) from respective substrates. Unlike dogs, cats cannot convert either β-carotene into vitamin A or tryptophan into niacin. Dogs can thrive on one large meal daily and select high-fat over low-fat diets, whereas cats eat more frequently during light and dark periods and select high-protein over low-protein diets. There are increasing concerns over the health of skin, hair, bone, and joints (specialized connective tissues containing large amounts of collagen and/or keratin); sarcopenia (age-related losses of skeletal-muscle mass and function); and cognitive function in dogs and cats. Sufficient intakes of proteinogenic AAs and taurine along with vitamins, minerals, and PUFAs are crucial for the normal structures of the skin, hair, bone, and joints, while mitigating sarcopenia and cognitive dysfunction. Although pet owners may have different perceptions about the feeding and management practice of their dogs and cats, the health and well-being of the companion animals critically depend on safe, balanced, and nutritive foods. The new knowledge covered in this volume of Adv Exp Med Biol is essential to guide the formulation of pet foods to improve the growth, development, brain function, reproduction, lactation, and health of the companion animals.

Morphological study of the pancreatic duct system in chinchilla (Chinchilla laniger Molina).

The aim of our investigation was analysis of the morphology of the pancreatic duct system in chinchilla. Investigation was carried out on twenty adult individuals of either sex. Macromorphological studies of pancreatic duct system were performed using colored latex. The histological studies were performed paraffin slides with H&amp;E staining method. Photography documentations were prepared using a Nikon Digital Sight SD-L1 System. The pancreas in this species is formed of three irregular flattened parts or lobes. The main accessory duct was not observed. The accessory pancreatic duct was the only duct to drain pancreatic secretion into the duodenum on the minor duodenal papilla. The histological structure of these ducts does not differ from the general scheme. Our investigation demonstrated significant anatomical variability of the pancreatic duct system in chinchilla which is not always accurately described in literature.

Роль многокомпонентного комплекса нутриентов для мужчин в рамках преконцепционной подготовки супружеской пары к зачатию.

Introduction. The COVID-19 pandemic has also greatly impacted people's psychological well-being, increasing stress levels, as well as their lifestyle and well-being. Therefore, to maintain health, men should take multicomponent complexes that have a beneficial effect on various organs and systems (including reproductive), have an antioxidant effect and help normalize basic physiological processes in the body. In particular, such supplements can be used as a preconception preparation of a man for conception in a couple. Objective. To evaluate the action of the antioxidant complex «AndroDoz Light» in a group of men in the framework of preconceptional preparation (for conception of a child by a sexual partner). Materials and methods. The data of 30 men aged 23 to 48 years (the average age was 26.3 ± 5.4 years) preparing for conception with a sexual partner were analyzed in this paper. AndroDoz Light was used by men for 1 month: effervescent tablet dissolved in a glass of water (200 ml) once a day during or after meals. To everyone in addition to the spermogram, microbiological examination of the ejaculate, finger rectal examination of the prostate gland (pancreas), ultrasound examination (ultrasound) of the scrotum organs, microscopic examination of the pancreatic secretion (SPH), microscopic examination of the urethral smear and PCR diagnostics of sexually transmitted diseases (androflor) were performed. The concentration of testosterone in the blood, the level of zinc in the sperm plasma were determined. The assessment of the quality of life and sexual function of men was carried out on the IIEF-15 scale (International Index of Erectile Function) and on the NIH-CPSI scale. Results. The multicomponent complex AndroDoz Light helps not only to increase male fertility, improving the functional state of the male reproductive system (qualitative and quantitative spermogram indicators) and morphological indicators: reduces the percentage of sperm with DNA fragmentation, but also improves copulatory function, and is an additional source of necessary nutrients for the male body. Conclusion. The use of the multicomponent complex AndroDoz Light in men as part of the preconceptional preparation of a married couple for conception is accompanied by an improvement in both general well-being and the quality of men's sexual life in general, positively affects the qualitative and quantitative indicators of the spermogram and sperm DNA fragmentation. The results obtained allow us to recommend the use of the multicomponent complex AndroDoz Light in men in the absence of pronounced reproductive problems as part of the preconceptional preparation of a married couple for conception.

Zinc deficiency affects insulin secretion and alters insulin-regulated metabolic signaling in rats

BackgroundThe essential trace element zinc is important in stabilizing pancreatic insulin secretion. Zinc not only influences the synthesis of insulin but also affects its activity. Insulin not only exerts a hypoglycemic effect but also regulates glucose and lipid metabolisms in insulin target organs. In this study, we aimed to determine changes to pancreatic β cells and insulin secretion induced by different zinc concentrations and to evaluate the effect of zinc deficiency on glucose intolerance, insulin resistance, and insulin target organs via changing insulin levels. MethodsWe set up two experimental trials. In the first trial, male Sprague Dawley (SD) rats were divided into three groups. Group one (ZnC) received a standard diet, group two (ZnF) was given a zinc-free diet, and group three (ZnFC) was initially fed a zinc-free diet followed by a reversion to the standard diet. After sacrifice, we observed changes in blood parameters, including insulin, and examined alterations in pancreatic tissue using immunostaining, with focus on the localization of pancreatic β-cells. In the second trial, male SD rats were split into two groups, with one receiving a standard diet and the other a zinc-free diet. Oral glucose tolerance and insulin tolerance tests were then performed. After sacrifice, we evaluated changes in lipid and glucose metabolism within insulin target organs using quantitative polymerase chain reaction. ResultsIn the first trial, blood insulin levels and the area of insulin-positive staining in pancreatic β-cells decreased in the ZnF compared to the ZnC group. The ZnFC group did not show recovery in either blood insulin levels or the area of insulin-positive staining in pancreatic β-cells. In the second trial, no differences were observed in glucose tolerance or insulin resistance between the ZnC and ZnF groups. However, changes in the expression of insulin target genes were noted in the liver and adipose tissue in the ZnF group. ConclusionWe reveal that dietary zinc concentrations not only affect the concentration of insulin in the blood but also impact the localization of pancreatic β-cells involved in insulin production. Furthermore, our results suggest that changes in blood insulin levels, induced by different zinc concentrations, could cause metabolic alterations in insulin target organs such as the liver and adipose tissue. This study sheds more light on the role of zinc in insulin-regulated metabolic diseases.

GLP-1 metabolite GLP-1(9–36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion

Aims/hypothesisDiabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure. Following its release GLP-1 is rapidly degraded from GLP-1(7–36) to GLP-1(9–36). We hypothesised that the metabolite GLP-1(9–36) (previously believed to be biologically inactive) exerts a direct inhibitory effect on glucagon secretion and that this mechanism becomes impaired in diabetes.MethodsWe used a combination of glucagon secretion measurements in mouse and human islets (including islets from donors with type 2 diabetes), total internal reflection fluorescence microscopy imaging of secretory granule dynamics, recordings of cytoplasmic Ca2+ and measurements of protein kinase A activity, immunocytochemistry, in vivo physiology and GTP-binding protein dissociation studies to explore how GLP-1 exerts its inhibitory effect on glucagon secretion and the role of the metabolite GLP-1(9–36).ResultsGLP-1(7–36) inhibited glucagon secretion in isolated islets with an IC50 of 2.5 pmol/l. The effect was particularly strong at low glucose concentrations. The degradation product GLP-1(9–36) shared this capacity. GLP-1(9–36) retained its glucagonostatic effects after genetic/pharmacological inactivation of the GLP-1 receptor. GLP-1(9–36) also potently inhibited glucagon secretion evoked by β-adrenergic stimulation, amino acids and membrane depolarisation. In islet alpha cells, GLP-1(9–36) led to inhibition of Ca2+ entry via voltage-gated Ca2+ channels sensitive to ω-agatoxin, with consequential pertussis-toxin-sensitive depletion of the docked pool of secretory granules, effects that were prevented by the glucagon receptor antagonists REMD2.59 and L-168049. The capacity of GLP-1(9–36) to inhibit glucagon secretion and reduce the number of docked granules was lost in alpha cells from human donors with type 2 diabetes. In vivo, high exogenous concentrations of GLP-1(9–36) (>100 pmol/l) resulted in a small (30%) lowering of circulating glucagon during insulin-induced hypoglycaemia. This effect was abolished by REMD2.59, which promptly increased circulating glucagon by >225% (adjusted for the change in plasma glucose) without affecting pancreatic glucagon content.Conclusions/interpretationWe conclude that the GLP-1 metabolite GLP-1(9–36) is a systemic inhibitor of glucagon secretion. We propose that the increase in circulating glucagon observed following genetic/pharmacological inactivation of glucagon signalling in mice and in people with type 2 diabetes reflects the removal of GLP-1(9–36)’s glucagonostatic action.Graphical

Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs.

Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography-mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration (p = 0.035), but not in PES (p = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively (p's < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; p = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms.

Obesity, heart failure with preserved ejection fraction, and the role of glucagon-like peptide-1 receptor agonists.

Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss in diabetic and non-diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta-cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP-1 RA administration to obese patients with HFpEF.

"Transformation of pancreatic secretion with intraduodenal administration of trypsin and amylase with nonspecific substrates for them."

The results of the study on the effects of enter sorbents allowed us to draw a fundamental conclusion, in our view, that the inhibitory influence on the secretion of pancreatic enzymes is exerted by only the solubilized enzymes in the duodenum contents. Immobilized enzymes bound to enter sorbents lose or significantly reduce this ability to inhibit pancreatic secretion. The de-blocking effects are also induced by nutrients introduced intraduodenally. In our laboratory, it has been demonstrated (Korotko G.F., Baybekova G.D.) that starch as a substrate for amylase removes its selective inhibitory effect on the secretion of pancreatic amylase; the selective inhibition of pancreatic protein secretion is reduced by intraduodenal administration of protein, and emulsified fat eliminates inhibitory effects on pancreatic secretion of lipase. The fundamental similarity of effects between sorbents and nutrients, considering the latter as factors immobilizing enzymes, allows us to observe some external analogy between the comparable effects.

МИНИИНВАЗИВНЫЕ ТЕХНОЛОГИИ В ЛЕЧЕНИИ ОСЛОЖНЕНИЙ ОСТРОГО ПАНКРЕАТИТА

Abstract. Introduction. Hollow organ perforations accompanying pancreatic necrosis are a severe complication. In this case, surgical intervention is limited to a degree due to the extensive process in the upper abdomen and the patient’s functional condition. Aim. To share our experience in the minimally invasive repair of gastric perforation in a case series of severely infected pancreatic necroses and retroperitoneal phlegmons. Materials and Methods. We analyzed a case series in our clinic over 5 years, including the necrotizing forms of acute pancreatitis with complications, such as acute perforations of hollow organs. This paper describes the minimally invasive surgeries we performed to treat perforations in upper abdominal. Results and Discussion. In 3 of 4 cases in our clinic, acute perforations of the upper gastrointestinal tract developed along with necrotizing pancreatitis were successfully released using the minimally invasive approach. Conclusions. Hollow organ perforation is one of the most severe complications of infected pancreatic necrosis resulting from the aggressive effects of pancreatic secretion. In this case, the tactical approach depends on the nature and localization of perforation, the course of pancreatic necrosis, and the patient’s functional condition. For perforation of acute gastric ulcers, it is technically possible to use a minimally invasive approach using endoscopic clips, which has been successfully demonstrated in our clinic. We hope that our experience will allow avoiding extended operations in this category of patients.

Subtyping and prognostic model construction based on vesicle-mediated transport-related genes in colorectal cancer.

Colorectal cancer (CRC) is impacted by various environmental and genetic variables. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) has been observed in many malignancies, but their effect on prognosis in CRC remains unclear. CRC samples were clustered into varying subtypes per differential expression of VMTRGs. R package was utilized to explore differences in survival, immune, and drug sensitivity among different disease subtypes. According to differentially expressed genes (DEGs) between subtypes, regression analysis was employed to build a riskscore model and identify independent prognostic factors. The model was validated through a Gene Expression Omnibus (GEO) dataset. Immune landscape, immunophenoscore (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) scores for different risk groups were calculated. Two subtypes of CRC were identified based on VMTRGs, which showed significant differences in survival rates, immune cell infiltration abundance, immune functional activation levels, and immune checkpoint expression levels. Cluster2 exhibited higher sensitivity to anti-tumor drugs such as Nilotinib, Cisplatin, and Oxaliplatin compared to Cluster1. DEGs were mainly enriched in biological processes such as epidermis development, epidermal cell differentiation, and receptor-ligand activity, and signaling pathways like pancreatic secretion. The constructed 13-gene riskscore model demonstrated good predictive ability for CRC patients' prognosis. Furthermore, differences in immune landscape, IPS, and TIDE scores were observed among different risk groups. This study successfully obtained two CRC subtypes with distinct survival statuses and immune levels based on differential expression of VMTRGs. A 13-gene risk model was constructed. The findings had important implications for prognosis and treatment of CRC.

Transcriptome Sequencing of the Oral Mucosa Reveals Gene Expression Differences in Patients With Parry-Romberg Syndrome

Objective: Parry-Romberg syndrome (PRS) is an acquired disease characterized by progressive unilateral atrophy of the facial skin, subcutaneous tissue, muscle, and bone. There are various hypotheses to try to explain the occurrence of the disease, but the specific etiology and pathogenesis remain unclear. This study aimed to explore the potential molecular pathogenesis of the disease by using next-generation RNA-sequencing technology. Methods: The authors collected oral mucosal tissue from the affected side and the healthy side from 3 patients with PRS. Tissue samples were subjected to RNA extraction, whole transcriptome sequencing, and bioinformatics analysis. Differentially expressed genes were obtained from both groups of samples and then analyzed for functional enrichment. Results: A total of 186 differentially expressed genes were screened from the 2 groups of samples. Compared with the healthy side, several immune-related genes, including immunoglobulin kappa variable (IGKV)2D-28, IGKV1D-33, IGKV1-33, and NLRP10, were significantly upregulated in the affected tissue. In addition, the differential genes were significantly enriched in metabolic pathways including pancreatic secretion, protein and fat digestion, and absorption. Conclusions: The authors described the gene expression differences between the affected and healthy tissues of patients with PRS for the first time. Immune responses may play a role in the pathogenesis of PRS.