Search

The article explores the use of dopamine D2-like receptor agonists in treating dysglycemia in autoimmune diabetes. A case study showed that cabergoline, an agonist of DA D2-like receptors, improved glycemic control in a patient with autoimmune diabetes. The study suggests that D2-like receptor agonists may act on central nervous system and peripheral targets, such as the endocrine pancreas, adipose tissue, skeletal muscle, and T cells, to improve insulin sensitivity and glycemic control. The findings highlight the potential of D2-like receptor agonists as a novel treatment approach for autoimmune diabetes and type 2 diabetes mellitus. [Extracted from the article]

Objectives: To develop and validate imaging-based models for predicting the malignancy risk of intraductal papillary mucinous neoplasm (IPMN). Materials and methods: We retrospectively analyzed data from 241 IPMN patients who underwent preoperative CT and MRI for model development. Cyst size, presence and size of the enhancing mural nodule (EMN), main pancreatic duct (MPD) diameter, thickened/enhancing cyst wall, abrupt MPD caliber change with distal atrophy, and lymphadenopathy were assessed. Multiple logistic regression models predicting malignancy risk were created using either continuous (Model C) or dichotomized variables (Model D) using these imaging features. Validation included internal (n = 55) and external (n = 43) datasets. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and compared with that of the international guideline-based model (Model F). Results: Model C identified age, EMN size, MPD diameter, and lymphadenopathy as independent predictors on CT, and age and presence and size of EMN on MRI. Model D identified age ≥ 68, cyst size ≥ 31 mm, EMN ≥ 6 mm, MPD ≥ 7 mm, and lymphadenopathy as independent predictors on CT, and age ≥ 68, EMN ≥ 4.5 mm, and lymphadenopathy on MRI. Model C (AUC, 0.763–0.899) performed slightly better than Model D (AUC, 0.753–0.912) without statistical significance. No significant difference was observed between Models C and F (AUC, 0.729–0.952). Combining Model C with obstructive jaundice improved performance (AUC, 0.802–0.941) without statistical significance. Conclusion: Our imaging-based models effectively predicted the malignancy risk of IPMNs, comparable to international consensus guidelines. Clinical relevance statement: Imaging features are important for predicting the malignant potential of IPMNs. Our imaging-based model may help determine surgical candidacy for patients with IPMNs. Key Points: Non-invasively determining the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) allows for appropriate treatment decision-making We identified multiple imaging features that are associated with malignant transformation and developed models for this prediction. Our model performs comparably with international consensus guidelines in predicting the malignant potential of IPMNs. [ABSTRACT FROM AUTHOR]

The study aimed to assess the toxic effect of cadmium (Cd) on the exocrine and endocrine functions of pancreas, the changes in pancreatic tissue after Cd withdrawal, and the protective effects of vitamin C (VC) and Nigella sativa (NS) against Cd-induced damage. Rats were assigned to: control, Cd-treated (0.5 mg/kg/d intraperitoneal [IP] injection), VC and Cd-treated (receiving 100 mg/kg/d VC orally and Cd concomitantly), NS and Cd-treated (receiving 20 mg/kg/d NS and Cd, simultaneously), and Cd withdrawal (receiving Cd for 30 d then living free for recovery for other 30 d). Blood samples were collected and post-sacrifice pancreatic specimens were processed for light and electron microscope study. Quantitative analyses of pancreatic collagen area%, pancreatic islet parameters, β cell density, and insulin immunoexpression were done. Fasting blood glucose was significantly increased in Cd-treated and Cd-withdrawal groups, while co-treatment with VC and NS caused significant reductions (p < 0.05). Cd-induced extensive degenerative changes in pancreatic acini and islets at light and ultrastructure levels. Obvious fibrosis and congestion of blood vessels were noticed. Significant reductions in pancreatic islet number, volume, and surface area and diminished beta cell count and insulin immunoexpression were observed. After withdrawal of Cd, the whole pancreatic tissue still showed a serious impact. Concomitant treatment with VC or NS obviously reduced these degenerative changes and significantly improved pancreatic islet parameters and insulin immunoexpression. VC showed a better amendment than NS, but this difference was statistically insignificant. Therefore, VC and NS could be used as prophylactic agents that lessen Cd consequences on the pancreas. [ABSTRACT FROM AUTHOR]

We report the development of an immunotherapeutic molecule, a Humanized immunotoxin, for treating hCG-expressing advanced-stage cancers. PiPP, a high-affinity anti-hCG monoclonal antibody, is used in the immunotoxin for 'homing' hCG-positive cancer cells. The deimmunized (DI) form of α-Sarcin, a fungal-origin toxin that lacks functional T-cell epitopes, is used in the design to ensure minimal immunogenicity of the immunotoxin for repetitive use in humans. A single-chain variable fragment (scFv) of PiPP was constructed by linking the Humanized VH and VL regions of the antibody. The scFv part of the antibody was further linked to the toxin α-Sarcin (DI) at the gene level and expressed as a recombinant protein in E. coli. The immunotoxin was purified from the bacterial cell lysate and analysed for binding and cytotoxicity to hCG-secreting colorectal and pancreatic cancer cells. The results showed that the scFv(PiPP)-Sarcin immunotoxin was able to bind to colorectal and pancreatic cancer cells and killed approximately 85% of the cells. In vivo testing of the immunotoxin produced results similar to those of in vitro testing against colorectal adenocarcinoma-induced tumours. This immunotoxin could be a promising immunotherapeutic agent for treating colorectal, pancreatic and other terminal-stage hCG-expressing cancers. [ABSTRACT FROM AUTHOR]

Pancreatic development is a complex process vital for maintaining metabolic balance, requiring intricate interactions among different cell types and signaling pathways. Fibroblast growth factor receptors 2b (FGFR2b)-ligands signaling from adjacent mesenchymal cells is crucial in initiating pancreatic development and differentiating exocrine and endocrine cells through a paracrine mechanism. However, the precise critical time window that affects pancreatic development remains unclear. To explore the roles of FGFR2b-ligands and identify the narrow window of time during which FGFR2b-ligand signaling affects pancreatic development, we used an inducible mouse model to control the expression of soluble dominant-negative FGFR2b (sFGFR2b) at various stages of pancreatic development. Our findings revealed a significant effect of FGFR2b-ligand signaling on epithelial morphology, lumen formation, and pancreatic branching during primary and secondary transition stages. Additionally, sFGFR2b expression reduced the number of Pdx1+ progenitor cells and altered the pancreatic islet structure. Furthermore, we examined the effect of mutation in FGF10, an FGFR2b ligand, on embryonic pancreatic β-cell function. FGF10 null mutant embryos exhibited reduced pancreatic size and a decrease number of islet-like structure. Although neonatal mice with haploinsufficiency for FGF10 exhibited abnormal glucose tolerance test results, indicating a potential diabetes predisposition, these abnormalities normalized with age, aligning with observations in wild type mice. Our study underscores the critical role of FGFR2b-ligand signaling in pancreatic development and postnatal islet function, offering insights into potential therapeutic targets for pancreatic disorders. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential trace element for humans and animals. Development and application of new forms of Se sources with lower toxicity and higher bioavailability has been attracting more attention. However, the bioavailabilities of Se from several new Se sources for broilers remain unclear. Therefore, the aim of this study was to assess the relative bioavailabilities of Se from Se yeast (SY), selenomethionine (SM), hydroxyl-selenomethionine (SO) and nano-Se (NS) relative to sodium selenite (SS) for broilers fed a conventional corn-soybean meal diet. A total of 576 one-day-old Arbor Acres commercial male broilers were randomly assigned to 16 treatments with 6 replicate cages per treatment in a completely randomized design involving a 5 (Se sources: SY, SM, SO, NS and SS) × 3 (added Se levels: 0.15, 0.30 and 0.45 mg Se/kg) factorial design of treatments plus 1 (a Se-unsupplemented control) for 21 d. The relative bioavailabilities of Se sources were estimated based on plasma or tissue Se concentrations as well as selenoprotein mRNA expressions and activities in broilers. The results showed that the Se concentrations and glutathione peroxidase (GPX) activities in plasma, liver, breast muscle, pancreas and kidney as well as Se concentration in erythrocytes of broilers, and Gpx1 and Selenop mRNA expressions in pancreas increased linearly (p < 0.03) as added Se level increased. Furthermore, the differences (p < 0.05) among different Se sources were detected for the Se concentrations in liver, breast muscle, pancreas and erythrocytes, GPX activities in pancreas and kidney. Based on slope ratios from the multiple linear regressions of the above indices, the Se bioavailabilities of SY, SM, SO, NS relative to SS (100%) were 78 to 367%, 67.8 to 471%, 57 to 372%, and 45 to 92%, respectively. The results from this study indicated that the Se from SM, SY and SO are more available to broilers than the Se from SS in enhancing the Se concentrations in liver, breast muscle, pancreas and erythrocytes and GPX activity in pancreas, and the Se from SM had the highest while the Se from NS had the lowest relative bioavailability. [ABSTRACT FROM AUTHOR]

Insulinoma is the most common pancreatic tumor diagnosed in dogs. This study aimed to report incidence risk, breed predispositions and other demographic risk factors for insulinoma diagnosed in dogs under primary veterinary care in the UK. The VetCompass Program supports research on anonymized electronic health records (EHRs) from dogs under UK veterinary care. This study included all VetCompass EHRs from dogs under primary veterinary care during 2019. Multivariable logistic regression analysis was used to evaluate demographic risk factors for insulinoma diagnosis. Of 2,250,741 study dogs, 278 were confirmed as insulinoma cases at any date. The estimated 2019 incidence risk was 0.003% (95% CI 0.002–0.004%). Compared to crossbreeds, predisposed breeds included Dogue de Bordeaux, German Pointer, Flat Coated Retriever, Boxer and West Highland White Terrier. The Labrador Retriever showed decreased odds for insulinoma diagnosis. Additionally, being a terrier breed and being a breed predisposed to other endocrine cancers were associated with increased odds for insulinoma diagnosis. Other risk factors associated with increased odds for insulinoma diagnosis included being female neutered, being 9 - <15 years of age, having an adult median bodyweight of 20 - <30 kg and having a bodyweight above the median for the sex/breed. This is the first study to report the epidemiology of canine insulinoma in dogs under primary veterinary care, resulting in crucial leads for further research in the epidemiology and etiology of canine insulinoma and possible links of canine insulinoma with other canine endocrine cancers. Additionally, the results can aid veterinarians to identify dogs at greater risk of insulinoma. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) is a promising minimally invasive technique for the treatment of pancreatic lesions. This review first focuses on the technical aspects in EUS-RFA: the procedure typically employs EUS probes with integrated radiofrequency electrodes, enabling accurate targeting and ablation of pancreatic lesions. Different types of RFA devices, monopolar and bipolar energy delivery systems, are discussed, along with considerations for optimal ablation, including energy settings, procedure time, and pre- and post-procedural management. This paper presents a comprehensive literature review of EUS-RFA applied to both solid and cystic pancreatic lesions, including functioning and non-functioning pancreatic neuroendocrine tumors (pNETs), pancreatic cystic lesions (PCLs), pancreatic ductal adenocarcinoma (PDAC), and pancreatic metastases (PMs), discussing current evidence on safety, efficacy, clinical outcomes, and adverse events (AEs). EUS-RFA is an emerging technique with expanding potential for the treatment of both benign and malignant conditions; however, further studies are needed to better define patient selection criteria, assess long-term benefits, and establish definitive indications for its use. [ABSTRACT FROM AUTHOR]

Simple Summary: This Phase 2 trial investigated the combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in patients with advanced, refractory neuroendocrine carcinomas (NECs) of gastroenteropancreatic (GEP) or unknown origin. Eleven patients were enrolled, with nine evaluable for response. The treatment showed a partial response in one patient, stable disease in six, and progressive disease in two. The median overall survival was 9.4 months, and progression-free survival was 4.4 months. Common side effects included diarrhea, nausea, vomiting, and fatigue. Genetic analysis revealed that mutations in TP53, CHEK2, and APC were common, with CHEK2 and APC mutations linked to longer progression-free survival. The study found no significant association between the UGT1A1*28 polymorphism and treatment outcomes or toxicity. Overall, Nal-IRI with 5-FU/LV was found to be a safe and promising treatment option for refractory high-grade NECs, warranting further investigation in future trials. Background: Neuroendocrine carcinomas (NECs) are treated with a frontline platinum–etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity. Methods: We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy. Eligible patients received nal-IRI 70 mg/m2 and leucovorin 400 mg/m2, followed by 5-FU 2400 mg/m2 biweekly till disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Next-generation sequencing (NGS) was performed on blood/tissue samples at baseline and during treatment. Results: Eleven patients were enrolled, with nine evaluable for the primary endpoint. Seven were male, the median age was 66.7 years, and the median Ki-67 was 90%. We observed partial response in one patient, stable disease in six patients, and progressive disease in two patients. The median OS was 9.4 months (95% CI 2.9–29.3), and the median PFS was 4.4 months (95% CI 1.7–6.7). The most common adverse events were diarrhea (45%), nausea (45%), vomiting (45%), and fatigue (45%). The most common genetic mutations on NGS were TP53 (88.9%), CHEK2 (88.9%), and APC (33.3%). Patients with CHEK2 and APC mutation had longer PFS (p = 0.005 and p = 0.013, respectively). UGT1A1*28 polymorphism was not associated with OS, PFS, or toxicity. Conclusion: Nal-IRI with 5-FU/LV is a safe and effective treatment for refractory high-grade NECs of GEP or unknown origin. Future studies should explore novel combinations with Nal-IRI in high-grade NECs both in frontline and refractory settings. [ABSTRACT FROM AUTHOR]

Simple Summary: We have already demonstrated that an SBRT-escalated protocol allows for very high doses per fraction (11Gy/fraction), up to total dose up to 55Gy, which is safe and feasible in a standard LINAC-platform for patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). In this study, we demonstrated for the first time that after neoadjuvant Cht and escalated dose SBRT, resection was indicated in 84.6% of BRPC and 20% of LAPC. Furthermore, all evaluable patients after surgery had complete or minimal disease resection (R0/R1), with objective pathological responses of 81.8% (TRS0-2). The present follow-up (FUP) was closed on 1 November 2024. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. This study shows that neoadjuvant ChT-SBRT, particularly with BED > 100, is highly effective in converting BRPC/LAPC to resectable status, providing a pathway to potentially curative surgery in a subset of patients. Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses. Materials/Methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer). Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC (p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6–71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23–49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up. [ABSTRACT FROM AUTHOR]

Background: Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear. Methods: To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC–Q–Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia. Results: A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body. Conclusion: JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders. [ABSTRACT FROM AUTHOR]

Background: The pancreas is a multifunctional organ involving both endocrine and exocrine functions which plays a crucial role in metabolism and digestion. The pancreas extends horizontally from the C-loop of the duodenum to the splenic hilum, located retroperitoneally at the first and second lumbar vertebrae. The uncinate process, a small hook-like projection from the head of the pancreas, may be absent in about 10% of individuals. The pancreas produces both exocrine secretions (pancreatic juice from acinar cells) and endocrine hormones (insulin and glucagon). This review aims to provide a comprehensive overview of the morphological, physiological, and histological aspects of human pancreas development. Conclusions: All professionals who treat problems of the human pancreas must possess thorough knowledge of its development, anatomy, histology, and physiology. [ABSTRACT FROM AUTHOR]

Quantitative abdominal magnetic resonance imaging (MRI) offers non-invasive, objective assessment of diseases in the liver, pancreas, and other organs and is increasingly being used in the pediatric population. Certain quantitative MRI techniques, such as liver proton density fat fraction (PDFF), R2* mapping, and MR elastography, are already in wide clinical use. Other techniques, such as liver T1 mapping and pancreas quantitative imaging methods, are emerging and show promise for enhancing diagnostic sensitivity and treatment monitoring. Quantitative imaging techniques have historically required a breath-hold, making them more difficult to implement in the pediatric population. However, technological advances, including free-breathing techniques and compressed sensing imaging, are making these techniques easier to implement. The purpose of this article is to review current liver and pancreas quantitative techniques and to provide a practical guide for implementing these techniques in pediatric practice. Future directions of liver and pancreas quantitative imaging will be briefly discussed. [ABSTRACT FROM AUTHOR]