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Significant pancreatic islet dysfunction and loss shortly after transplantation to the liver limit the widespread implementation of this procedure in the clinic. Nonimmune factors such as reactive oxygen species and inflammation have been considered as the primary driving force for graft failure. The adipokine adiponectin plays potent roles against inflammation and oxidative stress. Previous studies have demonstrated that systemic administration of adiponectin significantly prevented islet loss and enhanced islet function at post-transplantation period. In vitro studies indicate that adiponectin protects islets from hypoxia/reoxygenation injury, oxidative stress as well as TNF-α-induced injury. By applying adenovirus mediated transfection, we now engineered islet cells to express exogenous adiponectin gene prior to islet transplantation. Adenovirus-mediated adiponectin transfer to a syngeneic suboptimal islet graft transplanted under kidney capsule markedly prevented inflammation, preserved islet graft mass and improved islet transplant outcomes. These results suggest that adenovirus-mediated adiponectin gene therapy would be a beneficial clinical engineering approach for islet preservation in islet transplantation.

Acute kidney injury (AKI) is a serious disease for which effective therapeutic agents are required. The capacity of curcumin (CUR) to resolve renal inflammation/oxidative stress and mitochondrial damage has been reported, but crosstalk between these effects and the consequence of this crosstalk remain elusive. In this study, a hypoxia/reoxygenation (H/R)‐induced renal tubular epithelial cell (TEC) injury model and an ischaemia/reperfusion (I/R)‐induced mouse AKI model were treated with CUR with or without mitochondrial inhibitors (rotenone and FCCP) or siRNA targeting mitochondrial transcription factor A (TFAM). Changes in mitochondrial function, inflammation, the antioxidant system and related pathways were analysed. In vitro, CUR suppressed NFκB activation and cytokine production and induced NRF2/HO‐1 signalling in TECs under H/R conditions. CUR treatment also reduced mitochondrial ROS (mtROS) and mitochondrial fragmentation and enhanced mitochondrial biogenesis, TCA cycle activity and ATP synthesis in damaged TECs. However, the anti‐inflammatory and antioxidant effects of CUR in damaged TECs were markedly abolished upon mitochondrial disruption. In vivo, CUR treatment improved renal function and antioxidant protein (NRF2 and SOD2) expression and reduced oxidative stress (8‐OHdG), tubular apoptosis/death, cytokine release/macrophage infiltration and mitochondrial damage in the kidneys of AKI mice. In vitro, the anti‐inflammatory and antioxidant effects of CUR in damaged kidneys were impaired when mitochondrial function was disrupted. These results suggest mitochondrial damage is a driving factor of renal inflammation and redox imbalance. The therapeutic capacity of CUR in kidneys with AKI is primarily dependent on mitochondrial mechanisms; thus, CUR is a potential therapy for various diseases characterized by mitochondrial damage.

Hydrocephalus is a cerebrospinal fluid physiological disorder that causes ventricular dilation with normal or high intracranial pressure. The current regular treatment for hydrocephalus is cerebrospinal fluid shunting, which is frequently related to failure and complications. Meanwhile, considering that the current nonsurgical treatments of hydrocephalus can only relieve the symptoms but cannot eliminate this complication caused by primary brain injuries, the exploration of more effective therapies has become the focus for many researchers. In this article, the current research status and progress of nonsurgical treatment in animal models of hydrocephalus are reviewed to provide new orientations for animal research and clinical practice., Inflammation, fibrosis, iron overload, etc., play an important role in the development of hydrocephalus. By targeting these mechanisms, researchers have discovered a series of drugs that have therapeutic effects on hydrocephalus.

Altered expression of circEPHB4, miR‐637 or SOX10 was independently associated with overall survival of glioma patients. By sponging miR‐637, circEPHB4 up‐regulated SOX10 and its target Nestin to promote stemness and self‐proliferation of glioma cells, stimulating the malignant progression of gliomas. Consistently, silencing circEPHB4 or overexpressing miR‐637 inhibited xenograft growth of glioma cells in vivo and has therapeutic prospects., Gliomas are the most common type of primary brain tumors. CircRNA ephrin type‐B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSC) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up‐regulated and microRNA (miR)‐637 was down‐regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10 but negatively correlated with miR‐637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up‐regulated SOX10 and Nestin by directly sponging miR‐637, thereby stimulating stemness, proliferation and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR‐637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR‐637/SOX10/Nestin axis plays a central role in controlling stem properties, self‐renewal and glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.

Diabetic kidney disease (DKD) is a severe DM complication. While complement C5 up‐regulation and gut dysbiosis are found in T2DM, their roles in DKD are unclear. Here, we investigated the effect of C5 on the gut microbiota during DKD development. Renal C5a/C5a receptor (C5aR) expression changes were measured in T2DM patients and db/db mice. Db/db mice were treated with a C5aR antagonist (C5aRA), and renal function, gut microbiota and renal genome changes were analysed. The effects of C5a and short‐chain fatty acids (SCFAs) on the signal transducer and activator of transcription 3 (STAT3) pathway were examined in vitro. C5a was up‐regulated in glomerular endothelial cells (GECs) of T2DM patients and db/db mice. Although glucose and lipid metabolism were unchanged, C5aR blockade alleviated renal dysfunction, ECM deposition, macrophage infiltration and proinflammatory factor expression in db/db mice. C5aRA partly reversed the declines in gut microbiota diversity and abundance and gut SCFA levels in db/db mice. C5aRA down‐regulated the expression of many immune response‐related genes, such as STAT3, in db/db mouse kidneys. C5aRA and SCFAs suppressed C5a‐induced STAT3 activation in human renal glomerular endothelial cells (HRGECs). Based on our results, C5 hyperactivation promotes DKD by activating STAT3 in GECs and impairing the gut‐kidney axis, suggesting that this hyperactivation is a potential target for the treatment of DKD.

Diabetic nephropathy (DN) as a kind of serious microvascular complication of Diabetes Mellitus (DM) usually causes the end‐stage of renal disease (ESRD). Studies have demonstrated that CD103+ dendritic cells (DCs) exhibited a renal pathogenic effect in murine chronic kidney disease (CKD). Mesenchymal stem cells (MSCs) can alleviate DN and suppress the DCs maturation. To explore the role of CD103+ DCs and the potential mechanisms underlying MSCs‐mediated protective effects in DN, we used bone marrow MSCs (BM‐MSCs) to treat DN rats. MSCs transplantation considerably recovered kidney function and diminished renal injury, fibrosis and the population of renal CD103+ DCs in DN rat. The MSCs‐treated DN rats had decreased mRNA expression levels of interleukin (IL)1β, IL6, tumour necrosis factor alpha (TNF‐α), monocyte chemotactic protein 1 (MCP‐1) and reduced CD8 T cell infiltration in the kidney. MSCs significantly down‐regulated the genes expression of transcription factors (Basic leucine zipper transcriptional factor ATF‐like 3, Batf3 and DNA‐binding protein inhibitor ID‐2, Id2) and FMS‐like tyrosine kinase‐3 (Flt3) which are necessary for CD103+ DCs development. The protective effect of MSCs may be partly related to their immunosuppression of CD8+ T cell proliferation and activation mediated by CD103+ DCs in the kidney of DN rats.

SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and neuron‐specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression‐free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P

Hyperuricemia is an important risk factor for cardiovascular and renal diseases. Phloretin had shown antioxidant and anti‐inflammatory properties, but its role in endothelial injury is rarely reported. In this study, we aimed to investigate the protective effect of phloretin on UA‐induced injury in human umbilical vein endothelial cells. The effects of UA and phloretin on cell viability, inflammation, THP‐1 monocyte adhesion, endothelial cell tube formation, GLUT9 expression and UA uptake in human umbilical vein endothelial cells were evaluated. The changes of nuclear factor‐kappa B/extracellular regulated protein kinases signalling were also analysed. Our results showed that UA reduced cell viability and tube formation, and increased inflammation and monocytes adhesion in human umbilical vein endothelial cells in a dose‐dependent manner. In contrast, phloretin significantly attenuated pro‐inflammatory factors expression and endothelial injury induced by UA. Phloretin inhibited the activation of extracellular regulated protein kinases/nuclear factor‐kappa B pathway, and reduced GLUT9 and it mediated UA uptake in human umbilical vein endothelial cells. These results indicated that phloretin attenuated UA‐induced endothelial injury via a synergic mechanism including direct anti‐inflammatory effect and lowering cellular UA uptake. Our study suggested that phloretin might be a promising therapy for hyperuricemia‐related cardiovascular diseases.

The promising potential of a RAD-16 self-assembly-peptide hydrogel as a scaffold for tissue-engineered cartilage was investigated. Within 3 weeks of in vitro culture, chondrocytes within the hydrogel produced a high amount of GAG and type-II collagen, which are the components of cartilage-specific extracellular matrix (ECM). With the culture time increased, toluidine-blue staining for GAG and immuno-histochemistry staining for type-II collagen of the chondrocytes-hydrogel composites became more intense. Analysis of the gene expression of the ECM molecules also confirmed the chondrocytes in the peptide hydrogel maintained their phenotype within 3 weeks of in vitro culture.

Tetraalkylphosphonium–Tetrafluoroborate–Tetrafluoroboric Acid was used as a catalyst in the curing of a liquid crystalline epoxy. Under some conditions the Tetraalkylphosphonium–Tetrafluoroborate–Tetrafluoroboric Acid actually retarded the reaction. An extensive experimental and kinetic analysis is presented anda mechanism for the reaction retardation is proposed. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1457–1471, 1998

The curing kinetics of a system containing 4,4′-diglycidyloxy-α-methylstilbene (DOMS) and different functionality amines, N-ethylaniline (NEA), aniline, benzenesulfonamide (BSA), and sulfanilamide (SAA), have been studied by differential scanning calorimetry (DSC) under isothermal conditions. The phase transformations during curing of the systems have been monitored by a crosspolarized optical microscope equipped with a hot-stage and photo detector. It has been found that the growth of a nematic liquid crystal structure does not cause a discrepancy from the autocatalytic model for the reactions between aniline and epoxy. There is no liquid crystalline structure formed for the systems containing NEA or BSA, which follow the autocatalytic kinetic models within the temperature range of 120–150°C. For the curing reactions between DOMS and SAA, there is a big deviation from the autocatalytic model when the liquid crystals transfer from a nematic structure to a smectic structure. Unlike the usual decrease of reaction rate resulting from diffusion in a heterogeneous reaction, the reaction rate is enhanced. A modified kinetic model has been constructed for this reaction system by introducing a pseudoconcentration term caused from the liquid crystalline structure formation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1105–1124, 1997

Five 1,3-disubstituted imidazolium salts were synthesized. Their Heck reaction activities were evaluated. A convenient, efficient and high yielding procedure based on these compounds for the arylation of olefins was developed. Heck reactions mediated by these palladium-N-heterocyclic carbene complexes were conducted under air and even in the presence of several common oxidants.

A highly effective, easy to handle and environmentally benign process for palladium mediated Suzuki cross-coupling was developed. By utilizing a solid support based NHC–palladium catalyst, cross couplings of aryl bromides with phenylboronic acid were achieved in neat water under air. A high ratio of substrate to catalyst was also realized.