BRTO assisted endoscopic Histoacryl injection in treating gastric varices with gastrorenal shunt.

AIMS: We evaluated the feasibility, efficacy and safety of a novel technique of balloon-occluded retrograde transvenous obliteration (BRTO) assisted endoscopic Histoacryl (N-buthyl-2-cyanoacrylate) injection. MATERIAL AND METHODS: A total with 11 patients were enrolled and analyzed in this single center, open-label, prospective study. Patients with high-risk gastric varices (defined as fundal varices, large GV (>5 mm), presence of a red spot, and Child-Pugh score C) and concurrent gastrorenal shunt underwent endoscopic Histoacryl injection while the gastrorenal shunt was temporarily occluded with an occlusion balloon. Feasibility, hemostatic effect, intra- and postoperative complications, and varices recurrence were evaluated. RESULTS: All procedures were successfully done per protocol. Except for one patient who underwent rescue Histoacryl injection due to residual varices, single therapy was sufficient to eliminate gastric varices in ten patients. Intra-operative hemorrhage occurred in one case and was stopped after additional Histoacryl injection. One patient was confirmed to have treatment-related fungemia. No death or major complications occurred, including ectopic embolism, worsening of hepatic and renal function, etc. No recurrence of the varices was found during a median follow-up time (mean ± SD) of 228 ± 153 days. CONCLUSIONS: BRTO assisted endoscopic Histoacryl injection is effective and safe for patients with high-risk gastric varices and concurrent gastrorenal shunt.

A Tween-80 modified hypoxia/esterase dual stimulus-activated nanomicelle as a delivery platform for carmustine - Design, synthesis, and biological evaluation.

As a clinical anti-glioma agent, the therapeutic effect of carmustine (BCNU) was largely decreased because of the drug resistance mediated by O6-alkylguanine-DNA alkyltransferase (AGT) and the blood-brain barrier (BBB). To overcome these obstacles, we synthesized a BCNU-loaded hypoxia/esterase dual stimulus-activated nanomicelle, abbreviated as T80-HACB/BCNU NPs. In this nano-system, Tween 80 acts as the functional coating on the surface of the micelle to facilitate transport across the BBB. Hyaluronic acid (HA) with active tumor-targeting capability was linked with the hypoxia-sensitive AGT inhibitors (O6-azobenzyloxycarbonyl group) via an esterase-activated ester bond. The obtained T80-HACB/BCNU NPs had an average particle size of 232.10 ± 10.66 nm, the zeta potential of -18.13 ± 0.91 mV, and it showed high drug loading capacity, eximious biocompatibility and dual activation of hypoxia/esterase drug release behavior. The obtained T80-HACB/BCNU NPs showed enhanced cytotoxicity against hypoxic T98G and SF763 cells with IC50 at 132.2 µM and 133.1 µM, respectively. T80 modification improved the transportation of the micelle across an in vitro BBB model. The transport rate of the T80-HACB/Cou6 NPs group was 12.37 %, which was 7.6-fold (p<0.001) higher than the micelle without T80 modification. T80-HACB/BCNU NPs will contribute to the development of novel CENUs chemotherapies with high efficacy.

Phoenixin-20 suppresses lipopolysaccharide-induced inflammation in dental pulp cells.

Pulpal infection is one of the most common causes of dental emergency admission. Tooth pain due to infection caused by gram-negative bacteria is the main manifestation of this sort of dental problem. The GPR173 signaling pathway is a highly conserved G-protein-coupled receptor that mediates neurological and reproductive function. In this study, we found that GPR173 was fairly expressed in isolated human dental pulp cells, and its expression was reduced in response to pro-inflammatory lipopolysaccharide (LPS) treatment. The activation of GPR173 by its ligand Phoenixin-20 reduced LPS-induced cytotoxicity, as revealed by a reduction in the release of LDH. Additionally, Phoenixin-20 suppressed LPS-induced release of pro-inflammatory cytokines and inflammatory mediators, including IL-6, MCP-1, VCAM-1, and ICAM-1, as well as MMP-2 and MMP-9. Mechanistically, we showed the suppressive action of Phoenixin-20 on LPS-induced activation of TLR-4 and Myd88 as well as the activation of the NF-κB pathway. Collectively, our study demonstrates that the GPR173 signaling pathway is an important mediator of LPS-induced inflammation, and the activation of GPR173 by its natural ligand Phoenixin-20 exhibits robust anti-inflammatory effects in dental pulp cells, suggesting that GPR173 is an interesting target molecule in the development of pulp cell-based therapies.

Clinical characteristics and endoscopic treatment with cyanoacrylate injection in patients with duodenal varices.

OBJECTIVE: To summarize the clinical characteristics and evaluate the effectiveness of cyanoacrylate injection in patients with duodenal varices (DV). MATERIAL AND METHODS: Between June 2003 and June 2008 all patients with DV (n=14) were analyzed retrospectively. Their clinical characteristics, endoscopic diagnoses and values of endoscopic cyanoacrylate injection were summarized. RESULTS: Fourteen of 396 patients receiving endoscopic treatment for upper gastroesophageal varices were diagnosed with DV. Four of these patients underwent endoscopic cyanoacrylate injection, with satisfactory results. No episodes of rebleeding occurred after 7-30 months' follow-up. Viral hepatitis-associated cirrhosis is the most common cause of DV (8/14), and the second section of the duodenum is the most common location of DV (14/14). CONCLUSIONS: The second section of the duodenum should be routinely endoscopically examined to identify and evaluate DV in all patients with gastroesophageal varices, and endoscopic cyanoacrylate injection appears to be a simple and effective hemostatic measure for DV bleeding.

Construction of physical-crosslink chitosan/PVA double-network hydrogel with surface mineralization for bone repair.

Weak mechanical properties, lack biocompatibility and relatively bioinert are formidable obstruct in application of bone repair materials. Multifunctional composite materials have been considered as a viable solution to this problem. Here, a new double network (DN) hydrogel was constructed by physical cross-linking of medical grade poly (vinyl alcohol) (PVA) and chitosan in KOH/urea dissolution system. The obtained hydrogel demonstrated excellent tensile strength (0.24 MPa), elongation at break (286%), and high compressive strength (0.11 MPa on the strain of 60%). Our studies showed that the prepared hydrogel had excellent biocompatibility in vitro and the introduction of hydroxyapatite (HAp) by surface mineralization imparted hydrogel the ability to induce rat bone marrow stem cells (rBMSCs) differentiation. The in vivo experiments revealed that the surface mineralized double network hydrogel significantly accelerated simultaneous regeneration of bone defects in a rabbit bone defect model. All the results indicated that this hydrogel has the potential as a bone repair material.

Mussel-inspired antibacterial polydopamine/chitosan/temperature-responsive hydrogels for rapid hemostasis.

The aim of this study was to develop an effective wound dressing using a temperature-responsive hydroxybutyl chitosan (HBC) based hydrogel. The HBC - chitosan (CS) - dopamine (HCS-DOPA) composite hydrogels were prepared by the dopamine self-polymerization at different concentrations (0, 0.5, 1.0 and 2.0 mg/mL), termed as HCS, HCS-DOPA-0.5, HCS-DOPA-1 and HCS-DOPA-2, respectively. The gelling characteristic of HBC hydrogel was not influenced by composite CS and DOPA. The HCS-DOPA composite hydrogels were non-cytotoxic to mouse fibroblast cells (L929), and induced under 5.0% hemolysis rate. In vitro antibacterial studies, composite HCS-DOPA-2 hydrogels exhibited lasting inhibition to S. aureus >8 h. The whole blood test in vitro demonstrated that blood clotting time treated with HCS-DOPA-2 composite hydrogels was shortened to 95.6 s compared with that of HCS in vitro hemostasis. The results suggested that HCS-DOPA-2 composite hydrogels could be applied as a promising wound dressing for hemostasis in vitro.

Protective effects of SIRT6 against lipopolysaccharide (LPS) are mediated by deacetylation of Ku70.

Progression of pulpitis is facilitated by the immune system's response to bacteria, enhancing the production of inflammatory regulators. Bacterial lipopolysaccharide (LPS) is the major structural component of the outer wall of all Gram-negative bacteria and a potent activator of the immune system. Apoptosis is believed to play an important role in the inflammatory process of pulpitis. SIRT6 is a member of class III of histone deacetylases (HDACs), also called sirtuins (SIRTs). The role of SIRT6 in apoptosis in pulpitis is unknown. In this study, we found that the expression of SIRT6 in human dental pulp cells (hDPCs) was down-regulated by treatment with LPS. MTT and LDH assays revealed that overexpression of SIRT6 in hDPCs attenuated cell death induced by LPS. Consistently, our results demonstrated that SIRT6 was able to protect hDPCs from apoptosis. We found that SIRT6 could interact with Ku70, an important apoptosis regulator, by the immunoprecipitation (IP) experiment. SIRT6 physically binds to Ku70. Overexpression of SIRT6 reduced acetylation of Ku70 and promoted interaction of Ku70 with the proapoptotic protein Bax. These studies underscore an essential role of SIRT6 in the survival of hDPCs in stress situations.

Treatment of gastric varices by endoscopic sclerotherapy using butyl cyanoacrylate: 10 years' experience of 635 cases.

BACKGROUND: Gastric varices (GV) are life-threatening for patients with portal hypertension. Endoscopic injection with butyl cyanoacrylate (BC), the mainstay of the therapy for GV, has been reported to be effective for hemostasis of bleeding varices, but its efficacy in the obliteration of GV and impact on the survival of patients still needs clarification. Here we summarized our experience of 10 years' practice to evaluate the efficacy and safety of endoscopic therapy using BC for GV patients. METHODS: From January 1997 to April 2006, GV cases treated with endoscopic injection using BC were collected. The "sandwich method" and the "modified sandwich method" were used to inject BC intravascularly. Retrograde analysis was made on the data of treatment and follow-up. RESULTS: A total of 635 GV cases treated with endoscopic injection using BC were collected, most of them (90.2%) suffered from post-hepatitis cirrhosis. Emergency hemostasis was achieved in 139 out of 146 sessions (95.2%). Complications occurred in 32 cases (5.2%), including hemorrhage due to early expulsion of tissue glue (3.1%), septicemia (1%) and ectopic thrombosis (0.5%), such as spleen infarction. Endoscopic follow-up in 503 patients showed complete disappearance (76.9%), collapse (17.3%) or remnants (5.8%) of gastric varices. A total of 550 patients were followed up clinically for 3 to 115 months. Of these patients, 44 had recurrent bleeding (8.0%) and 44 died from hepatic failure, recurrent bleeding, hepatic carcinoma or other causes. The longest survival was 115 months, with a median survival of 25 months. Survival rates at 1, 2, 3, 4 and 5 year were 95%, 92%, 90%, 83% and 81%, respectively. CONCLUSIONS: Endoscopic sclerotherapy with BC is effective for the hemostasis of bleeding GV, as well as obliteration of GV which contributes to less rebleeding and better survival. The modified sandwich method may be useful to minimize ectopic embolism, which we speculated to result from excess iodized oil.