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Tempeh, yam, and sunflower's flour have been known to have antidiabetic effects, but their combined effect on the histopathology of hyperglycemic rat pancreatic cells in an enteral formula has not been proven. This study aimed to analyze the effect of GLITEROS specific-diabetes enteral formula modification based on tempeh flour, yam flour, and sunflower seed flour on the score pancreatic damage, number and diameter of the islets of langerhans of hyperglycemic rats with streptozotocin induction. The intervention was administered via an oral probe for 28 days to 30 Wistar rats, with each group consisting of 6 rats. The formula was given at a dose of 3.97 g/200 g/day (P1) and 8.75 g/200gr/day (P2) compared to standard control (K), positive control (K +), and negative control (K-). Histopathological features of the pancreas were analyzed using the hematoxylin–eosin staining method. Data were analyzed using paied t-test/Wilcoxon and ANOVA/Kruskal Wallis. The results showed a significant repair of pancreatic cell damage in the treatment group (P1 and P2) after the intervention (p < 0.05), but there was no difference in the number and diameter of the islets of Langerhans (p > 0.05). Overall, our findings suggest that the modified GLITEROS specific-diabetes enteral formula made from tempeh, yam, and sunflower seeds flour on the histopathological picture of hyperglycemia-induced rat pancreas, especially in the repair of damage to pancreatic Langerhans cells. [ABSTRACT FROM AUTHOR]

Inflammation and redox imbalance are hallmarks of cancer, diabetes, and other degenerative disorders. Pathophysiological response to these disorders leads to oxidative stress and mitochondrial dysfunction by alterations and reprogramming in cellular signaling and metabolism. Pancreatic beta cells are very sensitive to the inflammatory and altered nutrient signals and hence play a crucial role in diabetes and cancer. In this study, we treated insulin-secreting pancreatic beta cells, Rin-5F, with the bacterial endotoxin, LPS (1 μg/ml) to induce an inflammatory response in vitro and then treated the cells with a known anti-inflammatory, anticancer and antioxidant phytochemical, azadirachtin (AZD, 25 µM for 24 h). Our results demonstrated lipid peroxidation and nitric oxide production causing increased nitro/oxidative stress and alterations in the activities of anti-oxidant enzymes, superoxide dismutase and catalase after LPS treatment. Pro-inflammatory responses caused by translocation of nuclear factor kappa B and release of inflammatory cytokines were also observed. These changes were accompanied by GSH-dependent redox imbalance and alterations in mitochondrial membrane potential and respiratory complexes enzyme activities leading to mitochondrial respiratory dysfunction, reduced ATP synthesis, and intrinsic caspase-9 mediated apoptosis. Caspase-9 was activated due to alterations in Bcl-2 and Bax proteins and release of cytochrome c into the cytosol. The activities of oxidative stress-sensitive mitochondrial matrix enzymes, aconitase, and glutamate dehydrogenase were also inhibited. Treatment with AZD showed beneficial effects on the recovery of antioxidant enzymes, inflammatory responses, and mitochondrial functions. GSH-dependent redox homeostasis also recovered after the treatment with AZD. This study may help in better understanding the etiology and pathogenesis of inflammation-induced disorders in pancreatic beta cells to better manage therapeutic strategies.

Due to insulin resistance and excessive blood sugar levels, type 1 diabetes mellitus (T1DM) is characterized by pancreatic cell loss. This condition affects young people at a higher rate than any other chronic autoimmune disease. Regardless of the method, exogenous insulin cannot substitute for insulin produced by a healthy pancreas. An emerging area of medicine is pancreatic and islet transplantation for type 1 diabetics to restore normal blood sugar regulation. However, there are still obstacles standing in the way of the widespread use of these therapies, including very low availability of pancreatic and islets supplied from human organ donors, challenging transplantation conditions, high expenses, and a lack of easily accessible methods. Efforts to improve Type 1 Diabetes treatment have been conducted in response to the disease's increasing prevalence. Type 1 diabetes may one day be treated with stem cell treatment. Stem cell therapy has proven to be an effective treatment for type 1 diabetes. Recent progress in stem cell-based diabetes treatment is summarised, and the authors show how to isolate insulin-producing cells (IPCs) from a variety of progenitor cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Di(2-ethylhexyl) phthalate (DEHP) is a common indoor pollutant in the world, which may cause lots of harmful effects in human including diabetes according to epidemiological studies. To explore the underlying role of DEHP in diabetes-like symptoms, Balb/c mice were chose to be the experimental animals in this paper. They were separated as eight groups as follows: (1) saline+normal diet (vehicle control), (2) 10 mg/kg.day DEHP+normal diet, (3) 50 mg/kg.day DEHP+normal diet, (4) 250 mg/kg.day DEHP+normal diet, (5) streptozotocin (STZ)+high fat diet (diabetes model), (6) 10 mg/kg.day DEHP+ STZ+high fat diet, (7) 50 mg/kg.day DEHP+STZ +high fat diet, (8) 250 mg/kg.day DEHP+STZ+high fat diet. The biomarkers of this experiment include four groups: (1) general indicates: body weight and drinking water, (2) blood biomarkers: serum insulin and fasting glucose, (3) pathological examination: pancreas section and kidney section, and (4) biomarkers of oxidative stress: reactive oxygen species (ROS) and malondialdehyde (MDA) in liver cells. Our study results demonstrate that: (1) at our treatment levels DEHP cannot directly induce diabetes, but reduce serum insulin level in DEHP-exposed non-STZ-treated animals, (2) pathological examination finds that these is a dose-dependent damage in the pancreas in DEHP- exposed STZ-treated groups, and (3) the oxidative mechanism may be involved in this pathological process. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a serious chronic metabolic disorder. To develop novel anti-diabetic drugs from nature sources has always been the focus of research. Red deer (Cervus elaphu Linnaeus) antler is one of the most famous Chinese traditional medicines. We found that the peptides of 5-10 kDa from red deer antlers (PRDA) promoted the growth of cultured rat islet cells. The purpose of this study was to investigate the anti-diabetic actions of PRDA in vivo and purify a pure active peptide. We therefore investigated the hypoglycemic, hypolipidemic and antioxidant effects of PRDA in streptozotocin-induced diabetic mice and isolated a pure anti-diabetic peptide. PRDA, given intraperitoneally (75, 150, or 300 µ g/kg), significantly decreased the blood glucose levels, significantly increased the insulin concentrations, and remarkably improved the lipid metabolism in the diabetic mice. PRDA significantly increased the superoxide dismutase activity, catalase activity and the total antioxidant capacity in the serum and liver, and simultaneously decreased the malondialdehyde levels. The activities of hexokinase and pyruvate kinase, two important enzymes involved in glucose utilization, were also significantly increased in the liver of the PRDA-treated diabetic mice. Moreover, a novel anti-diabetic peptide isolated from PRDA significantly promoted the viability of cultured rat insulinoma cells. The molecular mass of the purified peptide was 7064.8 Da under mass spectrometry, and its N-terminal amino acid sequence was identified as LSPFTTKTYFPHFDLSHGSA. Thus, PRDA may be useful in managing the hyperglycemia, hyperlipidemia, and oxidative stress in diabetes, and the anti-diabetic peptide is a promising drug for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

COVID-19 can cause multiple organ damages as well as metabolic abnormalities such as hyperglycemia, insulin resistance, and new onset of diabetes. The insulin/IGF signaling pathway plays an important role in regulating energy metabolism and cell survival, but little is known about the impact of SARS-CoV-2 infection. The aim of this work was to investigate whether SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the host cell/tissue, and if so, the potential mechanism and association with COVID-19 pathology. To determine the impact of SARS-CoV-2 on insulin/IGF signaling pathway, we utilized transcriptome datasets of SARS-CoV-2 infected cells and tissues from public repositories for a wide range of high-throughput gene expression data: autopsy lungs from COVID-19 patients compared to the control from non-COVID-19 patients; lungs from a human ACE2 transgenic mouse infected with SARS-CoV-2 compared to the control infected with mock; human pluripotent stem cell (hPSC)-derived liver organoids infected with SARS-CoV-2; adipose tissues from a mouse model of COVID-19 overexpressing human ACE2 via adeno-associated virus serotype 9 (AAV9) compared to the control GFP after SARS-CoV-2 infection; iPS-derived human pancreatic cells infected with SARS-CoV-2 compared to the mock control. Gain and loss of IRF1 function models were established in HEK293T and/or Calu3 cells to evaluate the impact on insulin signaling. To understand the mechanistic regulation and relevance with COVID-19 risk factors, such as older age, male sex, obesity, and diabetes, several transcriptomes of human respiratory, metabolic, and endocrine cells and tissue were analyzed. To estimate the association with COVID-19 severity, whole blood transcriptomes of critical patients with COVID-19 compared to those of hospitalized noncritical patients with COVID-19. We found that SARS-CoV-2 infection impaired insulin/IGF signaling pathway genes, such as IRS, PI3K, AKT, mTOR, and MAPK, in the host lung, liver, adipose tissue, and pancreatic cells. The impairments were attributed to interferon regulatory factor 1 (IRF1), and its gene expression was highly relevant to risk factors for severe COVID-19; increased with aging in the lung, specifically in men; augmented by obese and diabetic conditions in liver, adipose tissue, and pancreatic islets. IRF1 activation was significantly associated with the impaired insulin signaling in human cells. IRF1 intron variant rs17622656-A, which was previously reported to be associated with COVID-19 prevalence, increased the IRF1 gene expression in human tissue and was frequently found in American and European population. Critical patients with COVID-19 exhibited higher IRF1 and lower insulin/IGF signaling pathway genes in the whole blood compared to hospitalized noncritical patients. Hormonal interventions, such as dihydrotestosterone and dexamethasone, ameliorated the pathological traits in SARS-CoV-2 infectable cells and tissues. The present study provides the first scientific evidence that SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in respiratory, metabolic, and endocrine cells and tissues. This feature likely contributes to COVID-19 severity with cell/tissue damage and metabolic abnormalities, which may be exacerbated in older, male, obese, or diabetic patients. [Display omitted] • SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1 activation. • IRF1 expression is highly relevant to risk factors for severe COVID-19, such as older age, male sex, obesity, and diabetes. • Critical COVID-19 patients have higher IRF1 and lower insulin/IGF signaling pathway genes in whole blood. • DHT and DEX interventions may ameliorate the pathological traits in SARS-CoV-2 infectable cells and tissues. [ABSTRACT FROM AUTHOR]

Abstract: A polymeric crosslinker was developed to promote the formation of cellular spheroids. Our approach was based on the crosslinking of cell membrane using a polymeric crosslinker that worked via hydrophobic interaction. The crosslinker, a poly(ethylene glycol) derivative with oleyl groups as a hydrophobic group at both ends, was synthesized and characterized by gel permeation chromatography and Fourier-transform infrared spectroscopy. Cell culture experiments were then performed to confirm spheroid formation. The rat pancreatic islet β-cell line RIN, which possesses the ability to secrete insulin, was cultured with the crosslinker in a round-bottomed 96-well plate. The formation of a spheroid was achieved when the crosslinker was added to the cell suspension, especially in the absence of serum. The size of the spheroid decreased with time and with increasing crosslinker concentration, and depended on the number of cells plated in each well. The number of cells cultured with crosslinker was almost constant during 7days and hardly proliferated in crosslinker concentrations of 0–2.5mgml−1, while the number of cells showed a decrease in the 25mgml−1 crosslinker concentration. It was shown that the insulin protein secretion in the spheroid cultured with crosslinker for 1week was enhanced. The cell adhesion protein E-cadherin mRNA expression of the resulting spheroid was also enhanced. These results indicate that the promoted cell function was due to the cell–cell and cell–matrix interactions in the spheroid, suggesting that this polymeric crosslinker was useful for the formation of cell spheroids. [Copyright &y& Elsevier]

The diagnosis of pancreatic cancer is very important. The main method of diagnosis is based on pathological analysis of microscopic image of Pap smear slide. The accurate segmentation and classification of images are two important phases of the analysis. In this paper, we proposed a new automatic segmentation and classification method for microscopic images of pancreas. For the segmentation phase, firstly multi-features Mean-shift clustering algorithm (MFMS) was applied to localize regions of nuclei. Then, chain splitting model (CSM) containing flexible mathematical morphology and curvature scale space corner detection method was applied to split overlapped cells for better accuracy and robustness. For classification phase, 4 shape-based features and 138 textural features based on color spaces of cell nuclei were extracted. In order to achieve optimal feature set and classify different cells, chain-like agent genetic algorithm (CAGA) combined with support vector machine (SVM) was proposed. The proposed method was tested on 15 cytology images containing 461 cell nuclei. Experimental results showed that the proposed method could automatically segment and classify different types of microscopic images of pancreatic cell and had effective segmentation and classification results. The mean accuracy of segmentation is 93.46%±7.24%. The classification performance of normal and malignant cells can achieve 96.55%±0.99% for accuracy, 96.10%±3.08% for sensitivity and 96.80%±1.48% for specificity.

Human embryonic stem cells (hESCs) are genetically stable with unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of a large supply of disease-targeted human somatic cells that are restricted to the lineage in need of repair. There is a large healthcare need to develop hESC-based therapeutic solutions to provide optimal regeneration and reconstruction treatment options for the damaged or lost tissue or organ that have been lacking. In spite of controversy surrounding the ownership of hESCs, the number of patent applications related to hESCs is growing rapidly. This review gives an overview of different patent applications on technologies of derivation, maintenance, differentiation, and manipulation of hESCs for therapies. Many of the published patent applications have been based on previously established methods in the animal systems and multi-lineage inclination of pluripotent cells through spontaneous germ-layer differentiation. Innovative human stem cell technologies that are safe and effective for human tissue and organ regeneration in the clinical setting remain to be developed. Our overall view on the current patent situation of hESC technologies suggests a trend towards hESC patent filings on novel therapeutic strategies of direct control and modulation of hESC pluripotent fate, particularly in a 3-dimensional context, when deriving clinically-relevant lineages for regenerative therapies.