Diabetic Pancreas Research Articles

Arjunolic acid modulate pancreatic dysfunction by ameliorating pattern recognition receptor and canonical Wnt pathway activation in type 2 diabetic rats

BackgroundArjunolic acid (AA) is a potent phytochemical with multiple therapeutics effects. In this study, AA is evaluated on type 2 diabetic (T2DM) rats to understand the mechanism of β-cell linkage with Toll-like receptor 4 (TLR-4) and canonical Wnt signaling. However, its role in modulating TLR-4 and canonical Wnt/β-catenin crosstalk on insulin signaling remains unclear during T2DM.AimThe current study is aimed to examine the potential role of AA on insulin signaling and TLR-4-Wnt crosstalk in the pancreas of type 2 diabetic rats. MethodMultiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR. ResultsHistopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM. ConclusionOverall results, indicate that AA has potential to develop as an effective therapeutic in the treatment of T2DM associated meta-inflammation. However, future preclinical research at multiple dose level in a long-term chronic T2DM disease model is warranted to understand its clinical relevance in cardiometabolic disease.

The possible regenerative capability of Harmine on diabetic pancreas experimentally induced by streptozotocin in adult male rats.

The possible regenerative capability of Harmine on diabetic pancreas experimentally induced by streptozotocin in adult male rats.

Bone morphogenetic protein-7 attenuates pancreatic damage under diabetic conditions and prevents progression to diabetic nephropathy via inhibition of ferroptosis.

Approximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-β (TGF-β) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-β. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-β inhibiting TGF-β-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models. We used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion. mPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-β but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-β-stimulated rat kidney tubular cells. BMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-β pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas.

The effects of hydroxytyrosol on Prdx6 and insulin expression in diabetic rat pancreases.

Diabetes mellitus is a widespread endocrine disease worldwide, accompanying chronic hyperglycemia. In this study, we investigated the effect of hydroxytyrosol, which exerts an antioxidant effect, on the expressions of insulin and peroxiredoxin-6 (Prdx6), which protect cells against oxidative injury in diabetic rat pancreas. This experimental study had four groups with ten animals in each group: control (nondiabetic) group, hydroxytyrosol group [10mg/kg/day intraperitoneal injection (ip) hydroxytyrosol for 30days], streptozotocin group (single ip injection of 55mg/kg streptozotocin), and streptozotocin + hydroxytyrosol group (single ip injection of streptozotocin and ip injection of 10mg/kg/day hydroxytyrosol for 30days). During the experiment, blood glucose levels were measured at regular intervals. Insulin expression was determined by immunohistochemistry and Prdx6 expression was determined by immunohistochemistry and western blot. Immunohistochemistry and western blot results were analyzed by one-way ANOVA with applied Holm-Sidak multiple comparison test, and blood glucose results were analyzed by two-way repeated measures ANOVA with applied Tukey's multiple comparison test. Blood glucose levels on days 21 and 28 were significantly lower in the streptozotocin + hydroxytyrosol group compared with the streptozotocin group (day 21, p = 0.049 and day 28, p = 0.003). Expression of both insulin and Prdx6 were lower in the streptozotocin and the streptozotocin + hydroxytyrosol groups compared with the control and hydroxytyrosol groups (p < 0.001). Insulin and Prdx6 expression in the streptozotocin + hydroxytyrosol group were higher compared with the streptozotocin group (p < 0.001). The immunohistochemical findings of Prdx6 and western blot were the same. In conclusion, hydroxytyrosol, which is an antioxidant compound, increased Prdx6 and insulin expression in diabetic rats. Insulin increased by hydroxytyrosol may have been effective in reducing blood glucose levels. Furthermore, hydroxytyrosol may exert its effect on insulin by increasing Prdx6 expression. Thus, hydroxytyrosol may decrease or prevent several hyperglycemia-dependent complications by increasing the expression of these proteins.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

EVALUATION OF PROTECTIVE EFFECT OF AEGLE MARMELOS FRUITS EXTRACTS AGAINST STREPTOZOTOCIN-INDUCED TYPE 1 DIABETES MELLITUS IN RAT’S MODEL

Objective: The present study aims to investigate the activity of methanolic extract of Aegle marmelos on Type I anti-diabetic in STZ induced in rat’s model. Methods: Extracted A. marmelos fruits were evaluated for anti-diabetic activity. Type I Diabetes has been induced in Wistar rats through STZ 65 mg/ kg/b.w.I.P. During the experiment, the rat’s body weight and fasting blood sugar levels were monitored. At the end of the study, animals in all groups have been sacrificed and biochemical parameters such as lipid profile, C-Peptide, HbA1c, serum insulin, pancreatic insulin, and histology of the pancreas have been observed. Furthermore, levels of antioxidant enzymes superoxide dismutase, catalase, and lipid peroxidation were measured. Results: The observed extract A. marmelos was proven to be safe in the toxicity findings. It has been shown an in vivo significant effect to manage diabetic markers such as weight gain, blood glucose, lipid profile, C-Peptide, HbA1c, the release of insulin secretion, and pancreatic insulin. The diabetic pancreas of rats has been observed to fall over beta cell density and disruption of normal architecture, but treated groups have been determined to restore the mass over beta cells. Elevated oxidative enzymes also have been viewed to control the treatment with A. marmelos. Conclusion: All its findings and phytoconstituents existing inside the extract must stay the viable chemical materials involved in the prevention of diabetes

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy.

Type 1 diabetes (T1D) is an autoimmune disease with immune cells' islet infiltration (called "insulitis"), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels' dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

Proteomic identification of MHC class I-associated peptidome derived from non-obese diabetic mouse thymus and pancreas

The peptides repertoire presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC I-associated peptidome (MIP), which regulates thymus development, peripheral survival and function during lifetime of CD8+ T cells. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cells destruction mediated primarily by autoreactive CD8+ T cells. Non-obese diabetic (NOD) mouse is an important animal model of T1D. Here, we deeply analyzed the MIP derived from NOD mice thymus and pancreas, and demonstrated that the thymus MIP source proteins partially shared with the MIP source proteins derived from NOD mice pancreas and β cell line. One H-2Kd restricted peptide SLC35B126–34 which was shared by MIP derived from both NOD mice pancreatic tissues and islet β-cell line, but absent in MIP from NOD thymus tissues, showed ability to stimulate IFN-γ secretion and proliferation of NOD mice splenic CD8+ T cells. The global view of the MHC I-associated self-peptides repertoire in the thymus and pancreas of NOD mice may serve as a biological reference to identify potential autoantigens targeted by autoreactive CD8+ T cells in T1D. Data are available via ProteomeXchange with identifier PXD031966. SignificanceThe peptides repertoire presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC I-associated peptidome (MIP). The MIP presented by thymic antigen presenting cells (APCs) is crucial for shaping CD8+ T cell repertoire and self-tolerance, while the MIP presented by peripheral tissues and organs is not only involved in maintaining periphery CD8+ T cell survival and homeostasis, but also mediates immune surveillance and autoimmune responses of CD8+ T cells under pathological conditions. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the destruction of pancreatic β cells, mediated primarily by autoreactive CD8+ T cells. Non-obese diabetic (NOD) mouse is one of important animal models of spontaneous autoimmune diabetes that shares several key features with human T1D. The global view of the MHC I-associated self-peptides repertoire in the thymus and pancreas of NOD mice may serve as a good biological reference to identify potential autoantigens targeted by autoreactive CD8+ T cells in T1D. It has great significance for further clarifying the immune recognition and effect mechanism of autoreactive CD8+ T cells in the pathogenesis of T1D, and then developing antigen-specific immune intervention strategies.

Effect of hydroalcoholic seed extract of Nigella sativa on hepatic and pancreatic factors of Nrf2 and FGF21 in the regulation of insulin transcription factors of MafA and PDX-1 in streptozotocin-treated diabetic rats

IntroductionNigella sativa (N. sativa), one of the most commonly used medicinal herbs with antioxidant properties, increases blood insulin levels and lowers fasting blood sugar. Nuclear Erythroid Factor-Related Factor 2 (Nrf2) and Fibroblast Growth Factor 21 (FGF21) are two antioxidant factors that are increased by oxidative stress and hyperglycemia. The present study investigated how hydroalcoholic extract of N. sativa seed (HENS) increases blood insulin levels, taking into account changes in antioxidant factors and expression of insulin transcription factors.Materials and methodsTwo groups of male diabetic wistar rats were treated orally with HESN at doses of 200 and 400 mg/kg-body weight for one month. Fasting blood sugar (FBS) and insulin were measured using standard kits by photometric and ELISA methods, respectively. The expression levels of the Nrf2, FGF21 and β-Klotho genes as well as the insulin gene-stimulating transcription factors of MafA and PDX-1 were evaluated using real-time PCR. Oxidative stress was assessed by assessing serum total oxidation status (TOS), malondialdehyde (MDA), and total antioxidant capacity (TAC).ResultsHSEN showed a significant reducing effect on FBS and oxidative biomarkers and an increasing effect on serum insulin levels in treated diabetic rats compared to untreated diabetics (P < 0.05). The elevated levels of NRF2 and FGF21 in the liver and pancreas of the diabetic control group were significantly reduced after treatment with both HESN doses (P < 0.05). Following the ameliorative effects of HENS on pancreatic tissue and the reduction of oxidative stress, the expression level of MafA and PDX1 genes approached the level of these factors in healthy rats (P < 0.05).ConclusionThis study showed the therapeutic effects of HENS on diabetic pancreas by reducing oxidative stress and tissue damage, modifying the expression levels of PDX-1 and MafA genes, and regulating insulin secretion and blood glucose levels.

Activation of Neutrophils by Mucin–Vaterite Microparticles

Nano- and microparticles enter the body through the respiratory airways and the digestive system, or form as biominerals in the gall bladder, salivary glands, urinary bladder, kidney, or diabetic pancreas. Calcium, magnesium, and phosphate ions can precipitate from biological fluids in the presence of mucin as hybrid nanoparticles. Calcium carbonate nanocrystallites also trap mucin and are assembled into hybrid microparticles. Both mucin and calcium carbonate polymorphs (calcite, aragonite, and vaterite) are known to be components of such biominerals as gallstones which provoke inflammatory reactions. Our study was aimed at evaluation of neutrophil activation by hybrid vaterite–mucin microparticles (CCM). Vaterite microparticles (CC) and CCM were prepared under standard conditions. The diameter of CC and CCM was 3.3 ± 0.8 µm and 5.8 ± 0.7 µm, with ƺ-potentials of −1 ± 1 mV and −7 ± 1 mV, respectively. CC microparticles injured less than 2% of erythrocytes in 2 h at 1.5 mg mL−1, and no hemolysis was detected with CCM; this let us exclude direct damage of cellular membranes by microparticles. Activation of neutrophils was analyzed by luminol- and lucigenin-dependent chemiluminescence (Lum-CL and Luc-CL), by cytokine gene expression (IL-6, IL-8, IL-10) and release (IL-1β, IL-6, IL-8, IL-10, TNF-α), and by light microscopy of stained smears. There was a 10-fold and higher increase in the amplitude of Lum-CL and Luc-CL after stimulation of neutrophils with CCM relative to CC. Adsorption of mucin onto prefabricated CC microparticles also contributed to activation of neutrophil CL, unlike mucin adsorption onto yeast cell walls (zymosan); adsorbed mucin partially suppressed zymosan-stimulated production of oxidants by neutrophils. Preliminary treatment of CCM with 0.1–10 mM NaOCl decreased subsequent activation of Lum-CL and Luc-CL of neutrophils depending on the used NaOCl concentration, presumably because of the surface mucin oxidation. Based on the results of ELISA, incubation of neutrophils with CCM downregulated IL-6 production but upregulated that of IL-8. IL-6 and IL-8 gene expression in neutrophils was not affected by CC or CCM according to RT2-PCR data, which means that post-translational regulation was involved. Light microscopy revealed adhesion of CC and CCM microparticles onto the neutrophils; CCM increased neutrophil aggregation with a tendency to form neutrophil extracellular traps (NETs). We came to the conclusion that the main features of neutrophil reaction to mucin–vaterite hybrid microparticles are increased oxidant production, cell aggregation, and NET-like structure formation, but without significant cytokine release (except for IL-8). This effect of mucin is not anion-specific since particles of powdered kidney stone (mainly calcium oxalate) in the present study or calcium phosphate nanowires in our previous report also activated Lum-CL and Luc-CL response of neutrophils after mucin sorption.

ScGENA: A Single-Cell Gene Coexpression Network Analysis Framework for Clustering Cell Types and Revealing Biological Mechanisms.

Single-cell RNA-sequencing (scRNA-seq) is a recent high-throughput technique that can measure gene expression, reveal cell heterogeneity, rare and complex cell populations, and discover cell types and their relationships. The analysis of scRNA-seq data is challenging because of transcripts sparsity, replication noise, and outlier cell populations. A gene coexpression network (GCN) analysis effectively deciphers phenotypic differences in specific states by describing gene–gene pairwise relationships. The underlying gene modules with different coexpression patterns partially bridge the gap between genotype and phenotype. This study presents a new framework called scGENA (single-cell gene coexpression network analysis) for GCN analysis based on scRNA-seq data. Although there are several methods for scRNA-seq data analysis, we aim to build an integrative pipeline for several purposes that cover primary data preprocessing, including data exploration, quality control, normalization, imputation, and dimensionality reduction of clustering as downstream of GCN analysis. To demonstrate this integrated workflow, an scRNA-seq dataset of the human diabetic pancreas with 1600 cells and 39,851 genes was implemented to perform all these processes in practice. As a result, scGENA is demonstrated to uncover interesting gene modules behind complex diseases, which reveal biological mechanisms. scGENA provides a state-of-the-art method for gene coexpression analysis for scRNA-seq data.

Evaluation of Hypoglycemic and Hypolipidemic Activities of Methanolic Leaf Extract of Garcinia gummi-gutta Linn by HFD with Low Dose STZ Induced Type II Diabetes Mellitus on Rats

Objective: The present study aimed to evaluate the hypoglycemic and hypolipidemic activities of methanolic leaf extract of Garcinia gummi-gutta Linn. by HFD with low dose STZ induced T2DM on rats.&#x0D; Materials and Methods: The animals were divided into five groups of six animals, and HFD was induced for 8 weeks. After 4th week of HFD treatment, type-II diabetes was induced by a single dose of 35mg/kg (i.p) STZ, hyperglycemia was confirmed by the elevated levels of blood glucose determined at 72h and the animals with blood glucose concentration (&lt; 250mg/dl) were used for the study. The In vitro anti-diabetic activity was done by the DNS method.&#x0D; Results: The In vitro anti-diabetic activity by α-amylase inhibition activity by DNS method was very mild as compared to Acarbose and the IC50 value of Acarbose was very low (170.84µg/ml) than MEGG (1989.59µg/ml). However, potent In vivo anti-diabetic activity (P&lt;0.001) was observed after induction HFD with low dose STZ induced T2DM rats at the end of the 8th week, blood sugar level for MEGG high dose (173.40 ± 14.9mg/dl) was found to be almost same as that of standard drug Glibenclamide (164.60 ± 3.21mg/dl) as compared to control (287.90 ± 1.52). The lipid profile of the study showed a marked increase in TC, LDL, TG, and reduction in HDL in HFD with low dose STZ diabetic rats, whereas in MEGG and standard drugs treated by Glibenclamide were found to be substantially decreased and a fair amount of improvement in HDL level (P&lt;0.001). Histologically, focal necrosis was observed in the diabetic rat pancreas whereas on standard and test mild and no evidence of necrosis were observed respectively, similar positive results were found in liver and adipocyte histology for standard and test groups against the HFD with STZ-induced group&#x0D; Conclusion: Therefore MEGG possesses potent In vivo anti-diabetic effect as well as hypolipidemic effect and therefore MEGG might be a potent phytochemical alternative to prevent and treat T2DM and atherosclerosis and also to reduce its associated complications.

Identification of the DPP-IV Inhibitory Peptides from Donkey Blood and Regulatory Effect on the Gut Microbiota of Type 2 Diabetic Mice.

After being treated with protease K, peptides extracted from donkey blood were separated, identified, and characterized. The results showed that Sephadex G-25 medium purified with MW < 3 kDa had the highest dipeptidyl peptidase IV (DPP-IV) inhibition capacity. Three-hundred-and-thirty-four peptides were identified with UPLC–MS/MS. Peptide Ranker and molecular docking analysis were used to screen active peptides, and 16 peptides were finalized out of the 334. The results showed that the lowest binding energy between P7(YPWTQ) and DPP-IV was −9.1, and the second-lowest binding energy between P1(VDPENFRLL) and DPP-IV was −8.7. The active peptides(MW < 3 kDa) could cause a reduction in the fasting blood glucose levels of type 2 diabetic mice, improve glucose tolerance, and facilitate healing of the damaged structure of diabetic murine liver and pancreas. Meanwhile, the peptides were found to ameliorate the diabetic murine intestinal micro-ecological environment to a certain extent.

Ferula assa-foetida oleo gum resin ethanolic extract alleviated the pancreatic changes and antioxidant status in streptozotocin-induced diabetic rats: A biochemical, histopathological, and ultrastructural study.

The current research examines the effects of administration of 150 and 250 mg/kg body weight/day of ethanolic Ferula assa-foetida L. oleo gum resin extract (FAE) for 42 days in streptozotocin-induced diabetes in rats. On day 42, all rats were euthanized; HOMA-β, HOMA-IR, and QUICKI levels in pancreas were examined histopathologically and ultrastructurally . Low-dose FAE (150 mg/kg) treatment resulted in significant improvement in serum glucose, insulin and superoxide dismutase, glutathione, and catalase levels (p< .05). It also improved β-cell function, restored pancreatic β-cells, and reduced insulin resistance compared to the diabetic control rats. Necrotic and degenerative alterations in the islets, pyknotic β-cell nuclei, β-cell degranulation, reduced islet cellular density, and significant vacuolation were found in the islets of STZ-diabetic control group ratsby the histomorphological and ultrastructural examination. The pancreatic histomorphology of low dose of FAE-treated diabetic rats showed remarkable improvements in the islets, such as the β-cell number and the area of the pancreatic islets. PRACTICAL APPLICATIONS: The experiment revealed that Ferula assa-foetida L. may exert antihyperglycemic activity in STZ diabetes via β-cell regeneration and its high antioxidant capacity. This work elucidates the role of Ferula assa-foetida L. in diabetes management. Ferula assa-foetida L. gum extract improved the morphological changes of the diabetic pancreas and stimulated the regeneration of the β cells. The findings demonstrated positive results for the long-term cure of diabetes. Additionally, this study showed the potential of isolating nutraceuticals for the development of medications.

Imaging of the Pancreas in New-Onset Diabetes: A Prospective Pilot Study.

INTRODUCTION:The aim of this study was to assess the feasibility of cross-sectional imaging for detection of pancreatic cancer (PDAC) in patients with new-onset hyperglycemia and diabetes (NOD).METHODS:We conducted a prospective pilot study from November 2018 to March 2020 within an integrated health system. Patients aged 50–85 years with newly elevated glycemic parameters without a history of diabetes were invited to complete a 3-phase contrast-enhanced computed tomography pancreas protocol scan while participating in the Prospective Study to Establish a NOD Cohort. Abnormal pancreatic findings, incidental extrapancreatic findings, and subsequent clinical evaluation were identified. Variability in clinical reporting between medical centers based on descriptors of pancreatic duct and parenchyma was assessed.RESULTS:A total of 130 of 147 participants (88.4%) consented to imaging; 93 scans were completed (before COVID-19 stay-at-home order). The median age was 62.4 years (interquartile range 56.3–68.8), 37.6% women; Hispanic (39.8%), White (29.0%), Black (14.0%), and Asian (13.3%). One (1.1%) case of PDAC (stage IV) was diagnosed, 12 of 93 participants (12.9%) had additional pancreatic findings: 5 fatty infiltration, 3 cysts, 2 atrophy, 1 divisum, and 1 calcification. There were 57 extrapancreatic findings among 52 of 93 (56%) unique patients; 12 of 57 (21.1%) prompted clinical evaluation with 2 additional malignancies diagnosed (nonsmall cell lung and renal oncocytoma). Reports from 1 participating medical center more frequently provided description of pancreatic parenchyma and ducts (92.9% vs 18.4%), P < 0.0001.DISCUSSION:High proportion of incidental findings and variability in clinical reports are challenges to be addressed for a successful NOD-based early detection strategy for PDAC.

Anti-Type I Diabetic Activity of the Methanolic Extract of Aegle marmelos on Streptozotocin Induced Rat Model

Aegle marmelos, generally acknowledged as Bael, is being ancient in Ayurveda for the therapy of a number of disorders. All the components on it tree along with stem, bark, root, leaves, fruit and seeds at all stages of maturity have medicinal virtues and have been recorded in Ethno-medicine.&#x0D; Aims: The present investigation study the Anti-Type I diabetic activity of the methanolic extract of Aegle marmelos on STZ induced rat model.&#x0D; Study Design: In-vivo study in rat model&#x0D; Place and Duration of Study: Department of Pharmacology, Karnataka college of Pharmacy, Bangalore, India, between Jan 2021 to Dec 2021.&#x0D; Methodology: Extracted Aegle marmelos was to be evaluated the toxicity as per the OECD guidelines and biochemical, hematological and gross pathological analysis has been assessed. Type I Diabetes has been induced in Wistar rats through STZ 65mg/kg/b.w. I.P. During the experiment, Rat’s BW and FBS level were monitored. At the end of study, animals among all groups namely Group I: Normal control, Group II: STZ 65mg/kg, Group III: STZ + Insulin 4Ukg/b.w., Group IV: Aegle marmelos 250mg/kg and Group V: Aegle marmelos 500mg/kg were sacrificed and biochemical parameters like Lipid profile, C-Peptide, HbA1c, Serum insulin, pancreatic insulin, and histology of pancreas had been observed. Aegle marmelos was also screened for pro-inflammatory cytokines viz., IL-1β, IL-6 and TNF-α were assessed by ELISA test. Furthermore, Antioxidant Enzyme like SOD, CAT, LPO and GSH were performed.&#x0D; Results: The observed extract Aegle marmelos was shown safe in the toxicity data; B.W, Lipid Profile, RFT, LFT, hematological parameters were shown in the limit range and the vital organ tissue histology were not shown any anatomical and structural abnormalities. The findings of the other parameters have been shown significant impact in vivo to manage the diabetic markers like weight gain, blood glucose, lipid profile, C-Peptide, HbA1c, secretion of insulin, and pancreatic insulin. Diabetic pancreas of rats confirmed fall of beta cell density and disruption of normal architecture. But treated group were found to restore the mass of beta cells. Mediator of inflammatory cytokines like increased in STZ group and was inhibited by test chemicals. Elevated oxidative enzymes also have been seen to control upon the treatment with Aegle marmelos.&#x0D; Conclusion: All this findings and phytoconstituents present within the extract should be the possible chemical substances concerned in the prevention of diabetes.

Immune Infiltration of CD8+ T Cells in Patients With Diabetic Pancreatic Cancer Reduces the Malignancy of Cancer Tissues: An In Silico Study.

BackgroundAlthough the functional damage of the diabetic pancreas can affect the postoperative recovery of pancreatic cancer patients, there is no significant difference in the prognosis of pancreatic cancer patients with a history of diabetes and ordinary pancreatic cancer patients. There is still no practical theory to explain this phenomenon.Materials and MethodThe mRNA expression profile data of 141 cases and 51 cases with clinical data of diabetes status were obtained from the TCGA database and the GEO database, respectively. The CRA001160 data set was obtained in the TISCH database. The Seurat was used to process single-cell expression profile sequencing data. The Cibersortx was used to construct a feature matrix of single-cell sequencing data and to deconvolve Bulk-RNAseq data to obtain each pancreatic cancer patients’ tumour invasion score. TIDE was used to assess the immune escape potential of the tumour. MiRNet was used to construct the miRNA-mRNA regulatory network.ResultCompared with regular pancreatic cancer patients, the immune-related signal transduction pathways in diabetic pancreatic cancer patients are in an activated state. In patients with diabetic pancreatic cancer, the infiltration score of CD8+ T cells is high, and the infiltration score of corresponding malignant tumour cells is low. The Bayesian classifier can distinguish diabetic pancreatic cancer patients from non-diabetic pancreatic cancer patients based on 10 signature genes. The miRNA-mRNA regulatory network suggests that regulation by miRNA can influence mRNA expression and thus prognostic survival of pancreatic cancer patients.ConclusionThe activation of inflammatory-related signalling pathways in diabetic pancreatic cancer patients increases the immune infiltration of CD8+ T cells in cancer patients and reduces the development of malignant tumour tissues. The expression of 10 signature genes allowed the diagnosis of diabetic and non-diabetic pancreatic cancer patients. The miRNA-mRNA regulatory network may be the main cause of the differences in the tumour inflammatory microenvironment between the two groups of patients. These findings help us further understand the immune microenvironment of patients with diabetic pancreatic cancer.

Critical Illness Cholangiopathy in COVID-19 Long-haulers

Critical Illness Cholangiopathy in COVID-19 Long-haulers

Effect of Cymbopogon citratus (Lemon grass) on the Expression of Insulin sensitive and Proinflammatory Genes in the Pancreas of Diabetic Rats

Inflammation may result from chronic hyperglycemia, a disease of macromolecule metabolism disorder caused by diabetes mellitus due to insulin malfunction. Although Cymbopogon citratus (Lemon grass) has long been used as an anti-diabetic, not much is known about the mechanisms involved. The goal of this study was to see how C. citratus leaf extract modulates genes related to insulin sensitivity and inflammation in alloxan-induced diabetic rats' pancreas. Control, diabetic control, metformin (100 mg/kg), and C. citratus (100, 200, and 400 mg/kg) were the six groups of experimental rats. Alloxan (150 mg/kg) was administered intraperitoneally to five groups. ACCU-CHEK glucometer and glucose test strips were used to measure fasting blood glucose at three-day intervals. Treatments were given for fourteen (14) days after which the animals were sacrificed and the pancreas removed for RT-PCR analysis. Image J software and graph pad prism software were respectively used to quantify and present the results. Diabetes induction by alloxan significantly (p&gt;0.05) increased fasting blood glucose level compared to non-induced control after 3 days. Administration of C. citratus aqueous extract (14 days) reduced the blood glucose of diabetic rats significantly (p&lt;0.05). C. citratus up-regulated the expression of TGR5, PPAR-γ, GLUT2, and Glucokinase genes relative to diabetic control respectively. It also down-regulated IL-6 and TNF-α genes expression relative to diabetic control rats. The antidiabetic effect of C. citratus could be via its ability to up-regulate the expression of genes associated with insulin sensitivity and down-regulate the expression of pro-inflammatory genes.

Non-Alcoholic Fatty Pancreas Disease (NAFPD) Is a Risk Factor for Developing Diabetes Mellitus after Pancreatic Resection

Introduction: Pancreatic diabetes caused by deficiency of insulin after a pancreatectomy is a serious late complication, but the risk factors relating to it have yet to be clarified. In particular, the relationship between new-onset diabetes and non-alcoholic fatty pancreas disease (NAFPD), which has been attracting attention in recent years due to the obesity epidemic, has not been explained. The purpose of this study is to identify risk factors for the development of diabetes after pancreatectomy, including NAFPD.