APOBEC-1 deletion enhances cisplatin-induced acute kidney injury.

Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI.

Inhibition of renalase drives tumour rejection by promoting T cell activation.

Background: Although programmed cell death protein 1 (PD-1) inhibitors have revolutionised treatment for advanced melanoma, not all patients respond. We previously showed that inhibition of the flavoprotein renalase (RNLS) in preclinical melanoma models decreases tumour growth. We hypothesised that RNLS inhibition promotes tumour rejection by effects on the tumour microenvironment (TME).

Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation.

Background: Repeated administration of cisplatin causes CKD. In previous studies, we reported that the kidney-secreted survival protein renalase (RNLS) and an agonist peptide protected mice from cisplatin-induced AKI.

Methods: To investigate whether kidney-targeted delivery of RNLS might prevent cisplatin-induced CKD in a mouse model, we achieved specific delivery of a RNLS agonist peptide (RP81) to the renal proximal tubule by encapsulating the peptide in mesoscale nanoparticles (MNPs).

Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma.

Dysregulated expression of the secretory protein renalase can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized renalase expression in premalignant and malignant PDAC tissue and investigated whether plasma renalase levels corresponded to clinical PDAC characteristics. Renalase immunohistochemistry was used to determine the presence and distribution of renalase in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues.

Extracellular renalase protects cells and organs by outside-in signalling.

Renalase was discovered as a protein synthesized by the kidney and secreted in blood where it circulates at a concentration of approximately 3-5 μg/ml. Initial reports suggested that it functioned as an NAD(P)H oxidase and could oxidize catecholamines. Administration of renalase lowers blood pressure and heart rate and also protects cells and organs against ischaemic and toxic injury.

Small Endoscopic Sphincterotomy plus Large-Balloon Dilation for Removal of Large Common Bile Duct Stones during ERCP.

Objective: This study compared the therapeutic benefits and complication rates of small endoscopic sphincterotomy plus large-balloon dilation (ESLBD) with those of endoscopic sphincterotomy (EST) alone for large bile duct stones.

Methods: We compared prospectively ESLBD group (n=63) with conventional EST group (n=69) for the treatment of large bile duct stones (≥15mm). Mechanical lithotripsy was performed when the stone could not be removed using a normal basket.

The role of double-balloon enteroscopy following capsule endoscopy in diagnosis of obscure Small intestinal diseases.

Objective: The aim of this study was to evaluate the detection rate accuracy of Double-balloon Enteroscopy (DBE) after Capsule Endoscopy (CE) in patients with suspected small bowel diseases.

Methodology: From January 2009 to March 2012, sixty-two patients with obscure small bowel diseases who underwent CE followed by DBE were included in this study. Introduction of the endoscope by DBE was either orally or anally according to CE.

Development of modified siRNA molecules incorporating 5-fluoro-2'-deoxyuridine residues to enhance cytotoxicity.

Therapeutic small interfering RNAs (siRNAs) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson-Crick base pairing. However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown. Previously, we demonstrated that deoxythymidine release from degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS inhibitor compounds.

Laparoscopic treatment of choledocholithiasis with novel self-releasing biliary stent.

Objectives: The aim of this study was to evaluate the effect of a self-releasing biliary stent antegradely placed during laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis.

Materials And Methods: The soft biliary stent, made of polyurethane, was designed as a J-umbrella form with a pigtailed duodenal part and an umbrella-like biliary anchoring part shaped with the rapidly absorbable suture. After the clearance of stones during LCBDE, a guide wire was inserted into the duodenum through the choledochoscope.

Identification of a cis-acting element of human dihydrofolate reductase mRNA.

Human dihydrofolate reductase (DHFR) is a critical target in cancer chemotherapy. Previous studies showed that an 82-nt RNA fragment within the DHFR mRNA protein-coding region functions as a DHFR cis-acting response element. In this study, we further investigated the key elements contained within this sequence that are required for the DHFR mRNA-DHFR protein interaction.

Translational autoregulation of thymidylate synthase and dihydrofolate reductase.

The folate-dependent enzymes, thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are critical for providing the requisite nucleotide precursors for maintaining DNA synthesis and DNA repair. In addition to their essential roles in enzyme catalysis, these two enzymes have now been shown to function as RNA binding proteins. Using in vitro and in vivo experimental model systems, we have shown that the functional consequence of binding of TS protein to its own cognate mRNA, as well as binding of DHFR to its own DHFR mRNA, is translational repression.

Small interfering double-stranded RNAs as therapeutic molecules to restore chemosensitivity to thymidylate synthase inhibitor compounds.

RNA interference is a post-transcriptional mechanism by which double-stranded RNA specifically silence expression of a corresponding gene. Small interfering double-stranded RNA (siRNA) of 21-23 nucleotides can induce the process of RNA interference. Studies from our laboratory have shown that translation of thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in a negative autoregulatory manner.

Characterization of a cis-acting regulatory element in the protein-coding region of human dihydrofolate reductase mRNA.

Previous studies have shown that human DHFR (dihydrofolate reductase), in addition to its critical role in DNA biosynthesis, functions as an RNA-binding protein. The interaction between DHFR and its own mRNA results in translational repression. In this study, we characterized the cis-acting elements on human DHFR mRNA that are required for the DHFR mRNA-DHFR protein interaction.

Thymidylate synthase as a translational regulator of cellular gene expression.

Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein. There is evidence that TS, in addition to interacting with its own TS mRNA, forms a ribonucleoprotein complex with a number of other cellular mRNAs, including those corresponding to the p53 tumor suppressor gene and the myc family of transcription factors. Using both in vitro and in vivo model systems, we have demonstrated that the functional consequence of binding of TS protein to its own cognate mRNA, as well as binding of TS to the p53 mRNA, is translational repression.