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Search results for: Human Pancreatic Microvascular Endothelial Cells

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#31963760   2020/01/18 To Up

Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection.

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal-regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.
Selma B Souto, Joana R Campos, Joana F Fangueiro, Amélia M Silva, Nicola Cicero, Massimo Lucarini, Alessandra Durazzo, Antonello Santini, Eliana B Souto

1161 related Products with: Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection.

96 assays1.00 flask1 mg10 ug20 16 Arrays/Slide96 tests100ug Lyophilized100ug Lyophilized

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#31781326   2019/11/06 To Up

Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway.

Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP). Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation. Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear. This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4. First, we confirmed that LXA4 strongly inhibited AP-ALI in mice. Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro. In addition, TNF- treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression. This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2. Moreover, when Nrf2-knockout (Nrf2) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI. Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway. These findings have laid a foundation for the treatment of AP-ALI.
Wen Ye, Chenlei Zheng, Dinglai Yu, Fan Zhang, Reguang Pan, Xiaofeng Ni, Zhehao Shi, Zhongjing Zhang, Yukai Xiang, Hongwei Sun, Keqing Shi, Bicheng Chen, Qiyu Zhang, Mengtao Zhou

2971 related Products with: Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway.

100.00 ul100.00 ul100 1 ml100.00 ul100.00 ul1 ml0.1 mg

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#31739987   2019/09/05 To Up

Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.

In the setting of type-2 diabetes, there are declines of structural stability and functionality of blood capillaries and red blood cells (RBCs), increasing the risk for microcirculatory disturbances. Correcting hyperglycemia is not entirely effective at reestablishing normal cellular metabolism and function. Therefore, identification of pathological changes occurring before the development of overt hyperglycemia may lead to novel therapeutic targets for reducing the risk of microvascular dysfunction. Here we determine whether RBC-capillary interactions are altered by prediabetic hypersecretion of amylin, an amyloid forming hormone co-synthesized with insulin, and is reversed by endothelial cell-secreted epoxyeicosatrienoic acids. In patients, we found amylin deposition in RBCs in association with type-2 diabetes, heart failure, cancer and stroke. Amylin-coated RBCs have altered shape and reduced functional (non-glycated) hemoglobin. Amylin-coated RBCs administered intravenously in control rats upregulated erythropoietin and renal arginase expression and activity. We also found that diabetic rats expressing amyloid-forming human amylin in the pancreas (the HIP rat model) have increased tissue levels of hypoxia-inducible transcription factors, compared to diabetic rats that express non-amyloid forming rat amylin (the UCD rat model). Upregulation of erythropoietin correlated with lower hematocrit in the HIP model indicating pathologic erythropoiesis. In the HIP model, pharmacological upregulation of endogenous epoxyeicosatrienoic acids protected the renal microvasculature against amylin deposition and also reduced renal accumulation of HIFs. Thus, prediabetes induces dysregulation of amylin homeostasis and promotes amylin deposition in RBCs and the microvasculature altering RBC-capillary interaction leading to activation of hypoxia signaling pathways and pathologic erythropoiesis. Hence, dysregulation of amylin homeostasis could be a therapeutic target for ameliorating diabetic vascular complications.
Nirmal Verma, Miao Liu, Han Ly, Analia Loria, Kenneth S Campbell, Heather Bush, Philip A Kern, Pedro A Jose, Heinrich Taegtmeyer, Donald M Bers, Sanda Despa, Larry B Goldstein, Andrew J Murray, Florin Despa

1635 related Products with: Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.

25 mg1 ml100ug96T100ml1x10e7 cells96 tests15ml50 mg50 ug 15ml100.00 ul

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#31724494   2020/01/20 To Up

Microvessel Network Formation and Interactions with Pancreatic Islets in Three-Dimensional Chip Cultures.

The pancreatic islet is a highly vascularized micro-organ, and rapid revascularization postislet transplantation is important for islet survival and function. However, the various mechanisms involved in islet revascularization are not fully understood, and we currently lack good platforms to explore this. Our aim for this study was to generate perfusable microvascular networks in a microfluidic chip device, in which islets could be easily integrated, to establish an platform for investigations on islet-microvasculature interactions. We compared the ability of mesenchymal stem cells (MSCs) and fibroblasts to support microvascular network formation by human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived endothelial colony-forming cell in two-dimensional and three-dimensional models of angiogenesis, and tested the effect of different culture media on microvessel formation. HUVECs that were supported by MSCs formed patent and perfusable networks in a fibrin gel, whereas networks supported by fibroblasts rapidly regressed. Network morphology could be controlled by adjusting relative cell numbers and densities. Incorporation of isolated rat islets demonstrated that islets recruit local microvasculature , but that the microvessels did not invade islets, at least during the course of these studies. This microvascularization platform can provide a useful tool to study how various parameters affect islet integration with microvascular networks and could also be utilized for studies of vascularization of other organ systems. Impact statement To improve pancreatic islet graft survival and function posttransplantation, rapid and adequate revascularization is critical. Efforts to improve islet revascularization are demanding due to an insufficient understanding of the mechanisms involved in the process. We have applied a microfluidics platform to generate microvascular networks, and by incorporating pancreatic islets, we were able to study microvasculature-islet interactions in real time. This platform can provide a useful tool to study islet integration with microvascular networks, and could be utilized for studies of vascularization of other organ systems. Moreover, this work may be adapted toward developing a prevascularized islet construct for transplantation.
Mia H Rambøl, Edward Han, Laura E Niklason

2846 related Products with: Microvessel Network Formation and Interactions with Pancreatic Islets in Three-Dimensional Chip Cultures.

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#31724333   2019/11/13 To Up

Pancreatic cancer cell-derived exosomal microRNA-27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2.

Pancreatic cancer (PC) remains a primary cause of cancer-related deaths worldwide. Existing literature has highlighted the oncogenic role of microRNA-27a (miR-27a) in multiple cancers. Hence, the current study aimed to clarify the potential therapeutic role of PC cell-derived exosomal miR-27a in human microvascular endothelial cell (HMVEC) angiogenesis in PC. Initially, differentially expressed genes (DEGs) and miRs related to PC were identified by microarray analysis. Microarray analysis provided data predicting the interaction between miR-27a and BTG2 in PC, which was further verified by the elevation or depletion of miR-27a. Next, the expression of miR-27a and BTG2 in the PC tissues was quantified. HMVECs were exposed to exosomes derived from PC cell line PANC-1 to investigate the effects associated with PC cell-derived exosomes carrying miR-27a on HMVEC proliferation, invasion and angiogenesis. Finally, the effect of miR-27a on tumorigenesis and microvessel density (MVD) was analysed after xenograft tumour inoculation in nude mice. Our results revealed that miR-27a was highly expressed, while BTG2 was poorly expressed in both PC tissues and cell lines. miR-27a targeted BTG2. Moreover, miR-27a silencing inhibited PC cell proliferation and invasion, and promoted apoptosis through the elevation of BTG2. The in vitro assays revealed that PC cell-derived exosomes carrying miR-27a stimulated HMVEC proliferation, invasion and angiogenesis, while this effect was reversed in the HMVECs cultured with medium containing GW4869-treated PANC-1 cells. Furthermore, in vivo experiment revealed that miR-27a knockdown suppressed tumorigenesis and MVD. Taken together, cell-derived exosomes carrying miR-27a promotes HMVEC angiogenesis via BTG2 in PC.
Dan Shang, Chao Xie, Jin Hu, Jinru Tan, Yufeng Yuan, Zhisu Liu, Zhiyong Yang

2151 related Products with: Pancreatic cancer cell-derived exosomal microRNA-27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2.

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#31622202   // To Up

Protective Effects of Incretin Against Age-Related Diseases.

Incretin contains two peptides named glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Drug therapy using incretin has become a new strategy for diabetic treatments due to its significant effects on improving insulin receptors and promoting insulinotropic secretion. Considering the fact that diabetes millitus is a key risk factor for almost all age-related diseases, the extensive protective roles of incretin in chronic diseases have received great attention. Based on the evidence from animal experiments, where incretin can protect against the pathophysiological processes of neurodegenerative diseases, clinical trials for the treatments of Alzheimer's disease (AD) and Parkinson's disease (PD) patients are currently ongoing. Moreover, the protective effect of incretin on heart has been observed in cardiac myocytes, smooth muscle cells and endothelial cells of vessels. Meanwhile, incretin can also inhibit the proliferation of aortic vascular smooth muscle cells, which can induce atherosclerogenesis. Incretin is also beneficial for diabetic microvascular complications, including nephropathy, retinopathy and gastric ulcer, as well as the hepatic-related diseases such as NAFLD and NASH. Besides, the anti-tumor properties of incretin have been proven in diverse cancers including ovarian cancer, pancreas cancer, prostate cancer and breast cancer.
Di Zhang, Mingzhu Ma, Yueze Liu

1810 related Products with: Protective Effects of Incretin Against Age-Related Diseases.

1 mg96 tests 6 ml Ready-to-use 96T500 tests100ug10ml12ml200ul540 tests0.05 mg Aff Pur

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#31343130   // To Up

The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by a destruction of pancreatic  cells, which leads to absolute insulin deficiency. Persistently high glycaemia causes vascular damage throughout the body. Microvascular complications com-prise the following: nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease (leading to strokes), and peripheral vascular disease. The pathogene-sis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products. Precise understanding of these mechanisms could help clinicians to identify diabetic complications earlier and subsequently implement indispensable therapy on time. It is vital to determine biomarkers of microvascular and macrovascular complications in children affected with T1DM. Advanced glycation end-products and their receptors, adhesive molecules, pro- and anti-inflammatory cytokines, enzymes such as N-acetyl-β-D-glucosaminidase, and growth factors are the subject of ongoing studies. Numerous biomarkers of diabetic microangiopathy are already known and may constitute therapeutic targets in the future. Unfortunately, despite substantial progress in the understanding of the processes by which microvascular and macrovascu-lar complications develop, much effort still needs to be devoted to the matter, and further investigations are required.
Anna Wołoszyn-Durkiewicz, Małgorzata Myśliwiec

2552 related Products with: The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes.

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#30839006   // To Up

Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

The development of drugs to treat cancer is hampered by the inefficiency of translating pre-clinical in vitro monoculture and mouse studies into clinical benefit. There is a critical need to improve the accuracy of evaluating pre-clinical drug efficacy through the development of more physiologically relevant models. In this study, a human triculture 3D in vitro tumor microenvironment system (TMES) was engineered to accurately mimic the tumor microenvironment. The TMES recapitulates tumor hemodynamics and biological transport with co-cultured human microvascular endothelial cells, pancreatic ductal adenocarcinoma, and pancreatic stellate cells. We demonstrate that significant tumor cell transcriptomic changes occur in the TMES that correlate with the in vivo xenograft and patient transcriptome. Treatment with therapeutically relevant doses of chemotherapeutics yields responses paralleling the patients' clinical responses. Thus, this model provides a unique platform to rigorously evaluate novel therapies and is amenable to using patient tumor material directly, with applicability for patient avatars.
Daniel Gioeli, Chelsi J Snow, Michael B Simmers, Stephen A Hoang, Robert A Figler, J Ashe Allende, Devin G Roller, J Thomas Parsons, Julia D Wulfkuhle, Emanuel F Petricoin, Todd W Bauer, Brian R Wamhoff

1748 related Products with: Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells.

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