Yohan Park

Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells

Objectives and designChlorogenic acid, which belongs to the polyphenols, is an anti-oxidant and anti-obesity agent. In this study, we investigated the role of chlorogenic acid in inflammation.Materials and methodsAnti-inflammatory effects of chlorogenic acid were examined in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and BV2 microglial cells. We observed the level of various inflammation markers such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 1 (CXCL1) under LPS treatment with or without chlorogenic acid. To clarify the specific effect of chlorogenic acid, we evaluated the adhesion activity of macrophages and ninjurin1 (Ninj1) expression level in macrophages. Finally, we confirmed the activation of the nuclear factor-κB (NF-κB) signaling pathway, which is one of the most important transcription factors in the inflammatory process.ResultsChlorogenic acid significantly inhibited not only NO production but also the expression of COX-2 and iNOS, without any cytotoxicity. Chlorogenic acid also attenuated pro-inflammatory cytokines (including IL-1β and TNF-α) and other inflammation-related markers such as IL-6 in a dose-dependent manner. Additionally, endotoxin-induced adhesion of macrophages and the expression level of ninjurin1 (Ninj1) were decreased by chlorogenic acid. Finally, chlorogenic acid inhibited the nuclear translocation of NF-κB.ConclusionsChlorogenic acid may be beneficial for the prevention and treatment of anti-inflammatory diseases.

Lack of association between the -759C/T polymorphism of the 5-HT2c receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients

Background:  Weight gain can be an adverse effect of antipsychotics that significantly affects long‐term health and treatment compliance. Many reports have suggested that the 5‐HT2C receptor gene (HTR2C) is related to appetite and eating behaviours associated with body weight change. We hypothesized that there was a relationship between the HTR2C −759C/T polymorphism and olanzapine‐induced weight gain.

Green synthesis of gold nanoparticles using chlorogenic acid and their enhanced performance for inflammation.

UNLABELLED Here we developed a novel green synthesis method for gold nanoparticles (CGA-AuNPs) using chlorogenic acid (CGA) as reductants without the use of other chemicals and validated the anti-inflammatory efficacy of CGA-AuNPs in vitro and in vivo. The resulting CGA-AuNPs appeared predominantly spherical in shape with an average diameter of 22.25±4.78nm. The crystalline nature of the CGA-AuNPs was confirmed by high-resolution X-ray diffraction and by selected-area electron diffraction analyses. High-resolution liquid chromatography/electrospray ionization mass spectrometry revealed that the caffeic acid moiety of CGA forms quinone structure through a two-electron oxidation causing the reduction of Au(3+) to Au(0). When compared to CGA, CGA-AuNPs exhibited enhanced anti-inflammatory effects on NF-κB-mediated inflammatory network, as well as cell adhesion. Collectively, green synthesis of CGA-AuNPs using bioactive reductants and mechanistic studies based on mass spectrometry may open up new directions in nanomedicine and CGA-AuNPs can be an anti-inflammatory nanomedicine for future applications. FROM THE CLINICAL EDITOR Gold nanoparticles (Au NPs) have been shown to be very useful in many applications due to their easy functionalization capability. In this article, the authors demonstrated a novel method for the synthesis of gold nanoparticles using chlorogenic acid (CGA) as reductants. In-vitro experiments also confirmed biological activity of the resultant gold nanoparticles. Further in-vivo studies are awaited.

Antibacterial nanocarriers of resveratrol with gold and silver nanoparticles

This study focused on the preparation of resveratrol nanocarrier systems and the evaluation of their in vitro antibacterial activities. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) for resveratrol nanocarrier systems were synthesized using green synthetic routes. During the synthesis steps, resveratrol was utilized as a reducing agent to chemically reduce gold and silver ions to AuNPs and AgNPs. This system provides green and eco-friendly synthesis routes that do not involve additional chemical reducing agents. Resveratrol nanocarriers with AuNPs (Res-AuNPs) and AgNPs (Res-AgNPs) were observed to be spherical and to exhibit characteristic surface plasmon resonance at 547 nm and at 412-417 nm, respectively. The mean size of the nanoparticles ranged from 8.32 to 21.84 nm, as determined by high-resolution transmission electron microscopy. The face-centered cubic structure of the Res-AuNPs was confirmed by high-resolution X-ray diffraction. Fourier-transform infrared spectra indicated that the hydroxyl groups and C=C in the aromatic ring of resveratrol were involved in the reduction reaction. Res-AuNPs retained excellent colloidal stability during ultracentrifugation and re-dispersion, suggesting that resveratrol also played a role as a capping agent. Zeta potentials of Res-AuNPs and Res-AgNPs were in the range of -20.58 to -48.54 mV. Generally, against Gram-positive and Gram-negative bacteria, the Res-AuNPs and Res-AgNPs exhibited greater antibacterial activity compared to that of resveratrol alone. Among the tested strains, the highest antibacterial activity of the Res-AuNPs was observed against Streptococcus pneumoniae. The addition of sodium dodecyl sulfate during the synthesis of Res-AgNPs slightly increased their antibacterial activity. These results suggest that the newly developed resveratrol nanocarrier systems with metallic nanoparticles show potential for application as nano-antibacterial agents with enhanced activities.

Efficient enantioselective total synthesis of (-)-horsfiline.

A new efficient and concise enantioselective synthetic method for (-)-horsfiline is reported. (-)-Horsfiline could be obtained from diphenylmethyl tert-butyl malonate in 9 steps (32%,>99% ee) by using the enantioselective phase-transfer catalytic allylation (91% ee) as the key step. This approach can be applied as a practical route for the large-scale synthesis of spirooxindole natural products, which enables a systematic investigation of their biological activity to be performed.

Hemodynamics-compliant reconstruction of the right hepatic vein for adult living donor liver transplantation with a right liver graft.

Secure reconstruction of the right hepatic vein (RHV) is essential for the successful implantation of a right liver graft during living donor liver transplantation (LDLT). To develop reliable surgical techniques for RHV reconstruction, we performed 3 concurrent studies: a simulation study using a fluid dynamics experimental model and a computational simulation model; an observational study analyzing the hemodynamic changes during radiological interventions for RHV stenosis; and a prospective clinical study establishing hemodynamics‐compliant surgical techniques. The simplified fluid dynamics experimental model revealed that actually measured outflow volumes were very similar to theoretical values derived from a fluid dynamics formula. The computational simulation model showed that outflow decreases were nearly linearly correlated with the degree of stenosis when it exceeded 50%. The clinical observational study revealed that mild (≤50%), moderate (50%‐75%), and severe RHV stenoses (≥75%) had mean pressure gradients of 2.5 ± 1.0, 6.6 ± 2.3, and 9.6 ± 2.8 mm Hg, respectively. The prospective clinical study was performed for patients who underwent RHV reconstruction with RHV angle blunting and inferior vena cava enlargement (n = 274); a historical control group of patients who underwent reconstruction by other methods (n = 225) was also used. RHV stenting within 2 weeks and 1 year was necessary for 1 patient (0.4%) and 5 patients (1.8%) in the study group, respectively, and for 9 patients (4.0%) and 21 patients (9.1%) in the control group, respectively (P < 0.01). The mean cephalocaudal length of patulous RHV anastomoses was greater in the study group versus the control group (P < 0.001). In conclusion, our modified RHV reconstruction technique significantly reduces the risk of RHV stenosis. We thus suggest the routine or selective use of this technique as a part of graft standardization for LDLT using a right liver graft. Liver Transpl, 2012.

Highly enantioselective synthesis of 5-phenyl-2-alkylprolines using phase-transfer catalytic alkylation

An efficient enantioselective synthetic method for the synthesis of (2R)-5-phenyl-2-alkylproline tert-butyl esters was reported. The phase-transfer catalytic alkylation of tert-butyl-5-phenyl-3,4-dihydro-2H-pyrrole-2-carboxylate in the presence of chiral quaternary ammonium catalysts gave the corresponding alkylated products (up to 97% ee). The following diastereoselective reductions afforded chiral 5-phenyl-2-alkylprolines which can be applied to asymmetric synthesis as organocatalysts or synthesis of biologically active proline based compounds, such as chiral α-alkylated analogues of (+)-RP66803, as potential CCK antagonists.

Section 15. A desensitizing protocol without local graft infusion therapy and splenectomy is a safe and effective method in ABO-incompatible adult LDLT.

Background The use of rituximab (Rit) to prevent antibody-mediated rejection (AMR) of ABO-incompatible (ABOi) adult living donor liver transplants (ALDLTs) has raised questions about the role of local graft infusion therapy (LGIT) and splenectomy (SPN); however, they are still regarded as essential components of the desensitization (DSZ) protocol. Methods The DSZ protocol consisted of plasma exchange and Rit. None of the patients underwent SPN. The patients were divided into two groups. The patients in Group I (n=20) received LGIT via the hepatic artery or portal vein. The patients in Group II (n=100) did not receive LGIT. Results One hundred twenty ABOi ALDLTs were performed from November 2008 to June 2012, and there was only one case of operative mortality (0.8%). There was no significant difference in the 3-year patient survival rates between patients receiving ABO-compatible and ABOi ALDLT (88.8% vs. 94.8%; P=0.11). LGIT catheter-related complications occurred in six patients (30.0%). There was no statistically significant difference in the 3-year patient survival rates between the groups (90.0% vs. 95.0%; P=0.26). One patient in Group 1 (0.8%) experienced AMR. Diffuse intrahepatic biliary stricture occurred in two patients (10.0%) in Group I and in five patients (5.0%) in Group II, although the difference was not statistically significant (P=0.11). The incidence of biliary stricture was similar in both groups (P=0.06), but the incidence of infection was significantly higher in Group I (P=0.03). Conclusion The DSZ protocol without LGIT and splenectomy is a safe and effective method of attaining a successful outcome of ABOi ALDLT.

Section 6. Management of extensive nontumorous portal vein thrombosis in adult living donor liver transplantation.

Background Patent portal vein (PV) and adequate portal inflow is essential for successful living donor liver transplantation (LDLT). In extensive portal vein thrombosis (PVT) patients, however, complete PV thrombectomy is not feasible particularly at intrapancreatic portion, and subsequently portal flow steal through preexisting sizable collaterals or rethrombosis can occur. To overcome those problems, we introduced interruption of sizable collaterals and intraoperative cine-portogram (IOP), which is useful for diagnosis and treatment of residual PVT and sizable collaterals. Methods Fourteen percent of adult LDLT (188/1399) had PVT from February 2008 to December 2012 and were subdivided into Yerdel’s grades 1, 2, 3, and 4 based on preoperative imaging and operative findings. Considering the severity of PVT and presence of sizable collaterals, the managements were as follows: thrombectomy alone, additional PV plasty, PV stenting, interposition graft, or additional interruption of collaterals. Results The Yerdel’s grade of PVT patients were 1 (42%), 2 (54%), 3 (3%), and 4 (1%). One hundred one (77%) patients underwent interruption of sizable collaterals. The most common management for PVT was thrombectomy alone in grades 1 and 2, thrombectomy plus PV stenting and/or ballooning in grade 3, and interposition graft in grade 4. In LDLT for PVT patients, 1-year mortality was 9%, and PV-related complication occurred in 5%. The severity of PVT made no difference in the outcome. Conclusion Multi-disciplinary approaches including surgical correction of PVT, IOP, and interruption of sizable collaterals resulted in excellent outcome, and it was not affected by the severity of PVT.

Synthesis of gold nanoparticles with glycosides: synthetic trends based on the structures of glycones and aglycones.

A new, room temperature synthetic method for gold nanoparticles from auric acid with glycosides as reducing agents in aqueous NaOH is presented. As a mechanistic study of the oxidation sites on the glycosides, eight sugar-containing reductants (glycoside, glucose, glucuronic acid) have been tested in the synthesis of gold nanoparticles to determine their trends based on the structures of glycones and aglycones. As a result of the comparison among the eight sugar-containing reductants, it was determined that C-6 of glycosides is oxidized to a carboxylic acid during the reduction of auric acid. To detect the oxidized compounds of the glycosides, the reaction mixtures were monitored by (13)C NMR. Among the eight sugar-containing reductants, phenyl β-D-glucoside generated the highest synthetic yield of mono-dispersed, round gold nanoparticles (13.15±1.30 nm, 99.7% yield).