Embryological development of pancreas is a complex phenomenon and therefore, it can have multiple developmental aberrations. Fortunately, majority of these pancreatic ductal anomalies are asymptomatic with no clinical relevance and are incidentally detected during diagnostic cross sectional imaging or endoscopic retrograde cholangiopancreatography (ERCP) or autopsy. Occasionally, pancreatic duct anomalies can result in symptoms like abdominal pain or recurrent pancreatitis. Also, accurate pre-operative diagnosis of ductal anomalies can prevent inadvertent duct injury during surgery. Conventionally, ERCP had been used for accurate diagnosis of pancreatic duct anomalies. However, because of being invasive and associated with risk of pancreatitis, it has been replaced with magnetic resonance cholangiopancreatography (MRCP). MRCP has demonstrated high sensitivity and specificity for diagnosis of ductal anomalies which can be further improved with use of secretin enhanced MRCP. Endoscopic ultrasound (EUS) is a new diagnostic and interventional tool in the armamentarium of endoscopists and has demonstrated promising results in detection of pancreatic duct variations and anomalies. In this article, we will focus on the role of EUS in diagnosis of various pancreatic duct anomalies.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignant tumor of the pancreas, carrying a poor prognosis, in most cases patients being diagnosed in a nonresectable stage. Image-based artificial intelligence (AI) models implemented in tumor detection, segmentation and classification could improve diagnosis with better treatment options and increased survival. This review included papers published in the last 5 years and describes the current trends in AI algorithms used in PDAC. We analyzed the applications of AI in detection of PDAC, segmentation of the lesion and classification algorithms used in differential diagnosis, prognosis, and histopathological and genomic prediction. The results show lack of multi-institutional collaboration and stresses the need for bigger datasets in order for AI models to be implemented in a clinically relevant manner.

Background: We aimed to study the frequency, management, and outcomes of patients with blunt pancreatic trauma. Methods: We reviewed the medical records for all patients admitted with pancreatic injuries between 2011 and 2017 at the only level 1 trauma center in the country. Results: There were 71 patients admitted with pancreatic trauma (0.6% of trauma admissions and 3.4% of abdominal injury admissions) with a mean age of 31 years. Sixty-two patients had pancreatic injury grade I-II and 9 had grade III-IV. Thirty-eight percent had GCS <9 and 73% had ISS >16. The level of pancreatic enzymes was significantly proportional to the grade of injury. Over half of patients required a laparotomy, of them 12 patients had an intervention on the pancreas. Eight patients developed complications related to pancreatic injuries ranging from pancreatitis to pancreatico-cutaneous fistula while 35% developed hemorrhagic shock. Mortality was 31% and regardless of the grade of injury, the mortality was associated with high ISS, low GCS and presence of hemorrhagic shock. Conclusion: Pancreatic injuries following blunt trauma are rare and the injured subjects are usually young male. However, most injuries are of low-grade severity. This study shows that shock, higher ISS and lower GCS are associated with worse in-hospital out-comes. Non-operative management may suffice in patients with lower grade injuries, which may not be the case in patients with higher grade injuries unless carefully selected

Diabetes is a life-long illness, it requires life-long solution. Today’s treatment is trading one type of pain with another, never truly ride off the illness. When Artificial Pancreas (AP) offered a possibility of cure, it stirred up a great deal of interest in the diabetic community (1). The system was based on artificial intelligence. It can automate the dosing of insulin to reduce high blood sugar levels overnight. The most dangerous time for diabetes. Artificial Pancreas may be able to allow diabetic patients to sleep through the night without waking up to check and manage their blood glucose levels. It was a significant advancement. However, the achievement was limited: 76.4% in range with the system vs. 67.8% without the system. This accomplishment was creditable, but not optimal. If Artificial Pancreas was to be offered as a viable treatment for diabetes, it must be a life-long solution and must be a total solution. Artificial Pancreas has failed in this challenge. We decided to pursue an alternative approach, a self-regulated system: bioartificial pancreas. It has the potential became a complete cure.

Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND). ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease egg productions, mortality, and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading to overall decreased growth rate. In this study, we report the damage caused by the NDV infection in the pancreatic tissues of vaccinated as well as specific pathogen free chickens. The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aimed to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. Median age was 56 (range 16- 80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (> 1.5cm; p = 0.001) and nodal metastasis (p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (p = 0.008) and high Ki-67 index (≥3%; p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decision about small NF-pNETs.

Pancreas transplantation is a high-risk operation that requires significant skill and expertise from the surgeons and the postoperative care team. Prior to candidate qualification, all contraindications to this procedure must be excluded. The use of screening tools and nutritional assessment aims to emphasize the importance of accurately diagnosing nutritional status in order to implement early nutritional interventions and reduce complications associated with malnutrition. This plays a crucial role in improving postoperative outcomes for patients undergoing pancreas and/or kidney transplantation. Objective: The aim of this study was to analyze the parameters of nutritional status in patients eligible for kidney transplantation and kidney with pancreas transplantation. Methods: The study analyzed the database of hospitalized patients in our Center from 2020 to 2023 to identify preoperative parameters of nutritional status in patients eligible for kidney transplantation (Ktx) and kidney with pancreas transplantation (SPKTx). Participants: A total of 59 patients participated in the study, who were candidates for kidney transplantation (23, including 11 females and 12 males) or kidney with pancreas transplantation (36, including 24 females and 12 males). Parameters examined included: Onoder's Prognostic Nutritional Index (PNIO), Nutrition Risk Index (NRI), ideal body weight (IBW) calculated using the Lorenz formula, and the neutrophil-to-lymphocyte ratio (NLR). All patients admitted to the clinic underwent the NRS-2002 clinical assessment scale for nutritional status. Results: Upon analyzing the obtained results, it was found that BMI was not a good differentiating parameter for the studied groups. The PNIO index also insufficiently differentiated the studied groups, and similarly, the NRI index was a weak differentiating parameter. The NRS-2002 index and albumin level were the best indicators of differences between the groups. In the group of transplantation candidates, several parameters indicated that patients in the Ktx group (kidney transplantation candidates) had better nutritional status than SPKtx candidates (kidney with pancreas transplantation candidates), despite the former group being older patients. Conclusion: It seems that more effort should be made to start a proper nutrition plan for SPKTx (and especially peritoneal dialysis) patients. Regular assessment of nutrition status should be performed. SPKtx patients in the perioperative period should receive parenteral nutrition and, as soon as their general condition allows it, enteral nutrition, taking into account the caloric and protein needs

Cholinergic innervation in pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The pharmacological ACh concentration further increases the oscillation frequency on the level of individual beta cells, inhibits the synchronization between these cells, and abolishes oscillatory activity in acinar cells. We discuss possible mechanisms leading to the observed phenomena.

Aim: Ectopic lipid accumulation, including pancreatic steatosis, exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified to correlate with clinical measures of pancreatitis, pancreatic cancer, and type 1 diabetes. The aim of the current study was, therefore, to examine the association between circulating abundances of candidate miRNAs and pancreatic and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Methods: Asian Chinese (n=34; BMI=26.7±4.2 kg/m2) and European Caucasian (n=34; BMI=28.0±4.5 kg/m2) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%pancreas) and liver (MR-%liver fat) respectively to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with pancreatic and liver steatosis were quantified by qRT-PCR. Results: miR-21-3p and miR-320a-5p correlated with MR-%pancreas fat, plasma insulin and HOMA2-IR but not MR-%liver fat. MR-%pancreas fat remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. Conclusions: miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%pancreas fat, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for wider application as a specific circulatory correlate of pancreatic steatosis.

Cancer is considered nowadays one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds with anti-tumor attributes have been described, many of them from plant origin. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin content (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the variety Alegría riojana, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with pepper fruit crude extracts were determined including, among others, protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX). Besides, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced the catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H2O2 and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating whole body iron metabolism. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β-cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important role of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months postoperatively. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. To our knowledge, this is the first report in English on mucin-positive signet-ring cells of CC arising in an intestinal-type IPMNHGD evaluated by SPACE cytology.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Multi-step evolution characterizes the carcinogenesis of GI malignancies, where the disease progresses through the accrual of genetic mutations, co-option of multiple host cellular factors and the acquisition of increasingly aggressive pathological features. Ensuing cancer complexity and plasticity are challenges for therapeutic approaches. On the other hand, disease inception is often triggered by a defined oncogenic event, which leads to escalating effects on gene expression, cellular metabolism, chromatin organization and ultimately cell identity. Decoding this molecular cascade of events is crucial to design strategies for early diagnosis as well as to tackle tumor onset. To this aim, the in vitro culture of non-transformed epithelial cells represents a major technical challenge. Genetic studies, combined with lineage-tracing experiments demonstrated that pancreatic cancerous lesions originate from acinar cells, a specialized cell type in the pancreatic epithelium, following mutations of the KRAS oncogene. Ex vivo culture of pancreatic acinar cells has allowed the identification of early mutant KRAS-driven alterations. Primary acinar cells survive in vitro in organoid-like 3D spheroids, which can recapitulate histological and molecular features of disease initiation. Here, we will discuss the isolation and culture of primary mouse pancreatic acinar cells, providing and historical and technical perspective. Impact for pancreatic cancer research will also be debated; in particular we will dissect the role of KRAS signaling in driving oncogenic transformation and highlight differences with canonical 2D culture of established cancer cell lines.

1) Background: Ultrasound-based strain imaging is now available in several ultrasound (US) scanners. Strain ratio (SR) can be used to quantify strain recorded simultaneously in two different user-selected areas, ideally exposed to the same amount of stress. The aim of this study was to evaluate SR variability when assessed in an in-vitro setup with a tissue-mimicking phantom, on resected tissue samples and in live tissue scanning with endoscopic applications. 2) Material and methods: Retrospective analysis of SR for quantification of elastic contrasts in a tissue-mimicking phantom containing four homogenous inclusions, in 38 resected bowel wall lesions and in 48 focal pancreatic lesions examined in vivo. Median SR and the inter-quartile range (IQR) was calculated on all external and endoscopic US-applications. The IQR/median provides a measure of the SR variability focusing on the two percentiles of the data closest to the median value. 3) Results: The overall variability of SR was lowest in a tissue-mimicking phantom (mean QR/median SR: 0.07). In resected bowel wall lesions representing adenomas, adenocarcinomas or Crohn lesions, the variability increased (mean IQR/Median: 0.62). During an endoscopic examination of focal pancreatic lesions in vivo, the variability increased further (mean IQR/Median: 2.04). 4) Conclusion: SR variability increased when assessed on different targets with growing heterogeneity and biological variability as one moved from homogeneous media to live tissues and endoscopic application. This may indicate a limitation for the accuracy SR evaluation in clinical applications.

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in the current study. In situ hybridization detected SAV3 in the heart, pseudobranch, gills, pyloric caeca, and pancreas after virus infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus at different adipose tissues associated with the internal organs of the salmon, suggests a specific affinity of SAV3 to adipocyte’s components. The innate immune response to SAV3 in the pseudobranch after infection dominated over the adaptive responses, yet it did not mitigate the infection in that tissue. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.