1,25-(OH)D protects Schwann cells against advanced glycation end products-induced apoptosis through PKA-NF-κB pathway.

Aims: To explore the effect and mechanism of 1, 25-(OH)D on Schwann cell apoptosis induced by advanced glycation end products.

Main Methods: Schwann cells, isolated from rodent sciatic nerve were incubated with AGE-modified bovine serum albumin(AGE) to mimic diabetic conditions and 1,25-(OH)D was used as protector. Cell apoptosis was detected by PI/Annexin-V staining, caspase 3 activity assay and western blotting for caspase 3 and PARP.

Interleukin-10 Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis via NF-κB Suppression.

Demyelination resulting from Schwann cell injury is a main pathological feature of diabetic neuropathy, and a key contributor to this process may be inflammation due to advanced glycation end products (AGEs). Therefore, protection by anti-inflammation agents is anticipated. In this study, we showed that interleukin-10 (IL-10), an anti-inflammatory cytokine, inhibits apoptosis of Schwann cells induced by AGEs .

Protein kinase C and protein kinase A are involved in the protection of recombinant human glucagon-like peptide-1 on glomeruli and tubules in diabetic rats.

Aims/introduction: Blockade or reversal the progression of diabetic nephropathy is a clinical challenge. The aim of the present study was to examine whether recombinant human glucagon-like peptide-1 (rhGLP-1) has an effect on alleviating urinary protein and urinary albumin levels in diabetic rats.

Materials And Methods: Streptozotocin-induced diabetes rats were treated with rhGLP-1 insulin and saline.

Human Proislet Peptide Promotes Pancreatic Progenitor Cells to Ameliorate Diabetes Through FOXO1/Menin-Mediated Epigenetic Regulation.

We investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs) and explored the potential link between HIP signaling and the menin pathway, which is key to regulating pancreatic islet differentiation. The data show that HIP promoted expression of proislet transcription factors (TFs), including PDX-1, MAFA, and NKX6.1, as well as other maturation markers of β-cells, such as insulin, GLUT2, KIR6.

Pseudo-hemorrhagic region formation in pancreatic neuroendocrine tumors is a result of blood vessel dilation followed by endothelial cell detachment.

Aberrant blood vessel formation and hemorrhage may contribute to tumor progression and are potential targets in the treatment of several types of cancer. Pancreatic neuroendocrine tumors (PNETs) are highly vascularized, particularly when they are well-differentiated. However, the process of vascularization and endothelial cell detachment in PNETs is poorly understood.

Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet.

Transplantation of human fetal pancreatic progenitor cells ameliorates renal injury in streptozotocin-induced diabetic nephropathy.

Background: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem.

TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway.

Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis.

Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells.

Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation.

Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model.

Objective: Recent evidence has suggested that circulating endothelial progenitor cells (EPCs) can repair the arterial endothelium during vascular injury. However, a reliable source of human EPCs is needed for therapeutic applications. In this study, we isolated human fetal aorta (HFA)-derived EPCs and analyzed the capacity of EPCs to differentiate into endothelial cells.

Tumor endothelial cells promote metastasis and cancer stem cell-like phenotype through elevated Epiregulin in esophageal cancer.

Tumor endothelial cells have been found to be associated with metastasis and cancer progression. In this study, we reported that human esophageal cancer endothelial cells (HECEC), unlike corresponding human esophageal normal endothelial cells (HENEC) displayed several distinct feature couple with unique gene expression profile. Further studies showed that HECEC can enhance migration, invasion and self-renewal properties of esophageal carcinoma cell in vitro by a direct cell-cell interaction.

Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation.

Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation.

Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels.

Leukocyte transendothelial migration and sequestration are two distinct outcomes following leukocyte adhesion to endothelium during ischemia-reperfusion injury, in which platelets may play a pivotal role. In the present study, we established an in vitro hypoxia-reoxygenation model to mimic ischemia-reperfusion injury and found platelet pre-incubation significantly increased leukocyte adhesion to endothelial cells after hyoxia-reoxygenation (over 67%). Blockade of endothelial-cell-expressed adhesion molecules inhibited leukocyte direct adhesion to endothelial cells, while platelet-mediated leukocyte adhesion was suppressed by blockade of platelet-expressed adhesion molecules.

A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia.

Background: Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells (EPCs) derived from human early fetal aortas in rat injured arteries.

GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.

Aims: Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic β-cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes.

Colocalization of insulin and glucagon in insulinoma cells and developing pancreatic endocrine cells.

A significant portion of human and rat insulinomas coexpress multiple hormones. This character termed as multihormonality is also observed in some early pancreatic endocrine cells which coexpress insulin and glucagon, suggesting an incomplete differentiation status of both cells. Here we demonstrate that insulinoma cells INS-1 and INS-1-derived single cell clone INS-1-15 coexpressed insulin and glucagon in a portion of cells.

C-peptide ameliorates renal injury in type 2 diabetic rats through protein kinase A-mediated inhibition of fibronectin synthesis.

Type 1 diabetes mellitus (T1DM) is characterized by the deficiencies of insulin and C-peptide. Mounting evidences have proved the beneficial effects of C-peptide on the renal function in T1DM. However, it is still controversial about the roles of C-peptide in T2DM nephropathy since the level of C-peptide fluctuates greatly at different stages of T2DM.

Enhanced blood-brain barrier penetration and glioma therapy mediated by a new peptide modified gene delivery system.

Successful glioma gene therapy lays on two important factors, the therapeutic genes and efficient delivery vehicles to cross the blood-brain barrier (BBB) and reach gliomas. In this work, a new gene vector was constructed based on dendrigraft poly-l-lysines (DGL) and polyethyleneglycol (PEG), conjugated with a cell-penetrating peptide, the nucleolar translocation signal (NoLS) sequence of the LIM Kinase 2 (LIMK2) protein (LIMK2 NoLS peptide, LNP), yielding DGL-PEG-LNP. Plasmid DNA encoding inhibitor of growth 4 (ING4) was applied as the therapeutic gene.

Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells.

The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic β cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines.

Multifunctional targeting daunorubicin plus quinacrine liposomes, modified by wheat germ agglutinin and tamoxifen, for treating brain glioma and glioma stem cells.

Most anticancer drugs are not able to cross the blood-brain barrier (BBB) effectively while surgery and radiation therapy cannot eradicate brain glioma cells and glioma stem cells (GSCs), hence resulting in poor prognosis with high recurrence rates. In the present study, a kind of multifunctional targeting daunorubicin plus quinacrine liposomes was developed for treating brain glioma and GSCs. Evaluations were performed on in-vitro BBB model, murine glioma cells, GSCs, and GSCs bearing mice.

Functionalized nanoscale micelles with brain targeting ability and intercellular microenvironment biosensitivity for anti-intracranial infection applications.

Due to complication factors such as blood-brain barrier (BBB), integrating high efficiency of brain target ability with specific cargo releasing into one nanocarrier seems more important. A brain targeting nanoscale system is developed using dehydroascorbic acid (DHA) as targeting moiety. DHA has high affinity with GLUT1 on BBB.

A bacteria deriving peptide modified dendrigraft poly-l-lysines (DGL) self-assembling nanoplatform for targeted gene delivery.

Achieving effective gene therapy for glioma depends on gene delivery systems. The gene delivery system should be able to cross the blood-brain barrier (BBB) and further target glioma at its early stage. Active brain tumor targeted delivery can be achieved using the "Trojan horse" technology, which involves either endogenous ligands or extraneous substances that can recognize and bind to specific receptors in target sites.

In vitro and in vivo evidence for amphotericin B as a P-glycoprotein substrate on the blood-brain barrier.

Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in vitro was significantly enhanced after inhibition of P-gp by verapamil.

TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway.

Chronic exposure to free fatty acids (FFAs) may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3) is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues.