Preparation of Anatase Titanium Dioxide Nanoparticle Powders Submitting Reactive Oxygen Species (ROS) under Dark Conditions

Recently, under the circumstances of pandemic of COVID-19 much attention has been paid to titanium dioxide TiO2 as bactericidal agent;however, conventional TiO2 requires ultraviolet radiation or visible light to exercise its photocatalytic properties and its induced antimicrobial activity. In order to expand its applications directed at wide civil life, antibacterial TiO2 being usable under dark conditions has been demanded. The present paper describes the powder characterization of newly developed potassium K and phosphorous P co-doped nanometer-size anatase TiO2 powders using X-ray diffraction (XRD), scanning and transmission electron microscopies (SEM & TEM), Brunauer-Emmett-Teller method (BET), fourier-transform infrared spectroscopy (FT-IR), X-ray absorption fine structure (XAFS), electron spin resonance (ESR) and chemiluminescence (CL). It was found for the first time that thus prepared anatase TiO2 could submit much reactive oxygen species (ROS) even in the dark, which has close relation with bactericidal activity in light interception.

Fabrication of ZrC/ZrB2/C Composites Having High Mechanical Properties at Elevated Temperatures

Ultra-high temperature ceramics (UHTCs) are most recently getting much attention for structural parts of hypersonic missiles with their cruising speed of more than Mach 5. Most of the UHTCs are poor sinterability carbides, nitrides, and borides. Therefore, they have been studied and developed for a long time. However, there are still many problems to solve. In this paper, based on the solid-state reaction presented as an equation of (x + y)·ZrC + 2·y·B → x·ZrC + y·ZrB2 + y·C, three-phase ZrC/ZrB2/C composites have been fabricated from ZrC and amorphous B powders using pulsed electric-current pressure sintering at 1373 to 2173 K for 6.0 × 102 s under 50 MPa in a vacuum. ZrC/ZrB2/C = 30/70/C~70/30/C vol% composites with the relative densities Dr of 96.6 to 98.7% were obtained at 2073 K. The 60/40/C vol% composite revealed high bending strength σb (554 MPa), Vickers hardness Hv (19.2 GPa) and moderate fracture toughness KIC (5.25 MPa·m1/2) at room temperature. Furthermore, all composites showed elastic deformation up to 1873 K and revealed σb more than 600 MPa at this temperature, in addition, some composites showed higher σb than 900 MPa at the same temperature. These high mechanical behaviors are discussed with those of the simple binary ZrC/ZrB2 composites which were fabricated under the same conditions except for their starting materials. The best mechanical properties of binary composites were σb (474 MPa), Hv (18.5 GPa), and KIC (4.45 MPa·m1/2) at room temperature, and σb of 400 - 700 MPa at 1873 K. Overall, three-phase composites, nevertheless including soft carbon, have higher mechanical properties than the binary composites.

A new treatment strategy for acute liver failure

Acute liver failure (ALF) is a syndrome def ined by coa g ulopathy and encephalopathy and no effective treat ments have been established, except for liver transplantation. However, considering the limited supply of donors, we should endeavor to prevent the progre ssion of this syndrome in its early stage to improve the prognosis of patients with ALF. Recently, several authors have reported that over-activation of intrahepatic macrophages plays an important role in the progression of ALF and we have developed a new treatment method, transcatheter arterial steroid injection therapy (TASIT), to suppress macrophage activation. We have now used TASIT for 5 years and have found that TASIT is effective for patients with over-activation of macrophages in the liver but not for those with les ser activation of macrophages. Therefore, to identify the most appropriate patients for TASIT, we tried to categorize patients with ALF or acute liver injury according to markers for the degree of intrahepatic macrophage activation. This approach was helpful to select the appro-priate treatment including liver transplantation. We believe that it is essential to analyze disease progression in each patient before selecting the most appropriate treatment.

Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats

AIM:To investigate the metabolic changes in skeletal muscle and/or adipose tissue in glucagon-like peptide-1-induced improvement of nonalcoholic fatty liver disease(NAFLD).METHODS:Male Wistar rats were fed either a control diet(control group)or a high-fat diet(HFD).After 4wk,the HFD-fed rats were subdivided into two groups;one group was injected with exenatide[HFD-Ex(+)group]and the other with saline[HFD-Ex(-)group]every day for 12 wk.The control group received saline and were fed a control diet.Changes in weight gain,energy intake,and oxygen consumption were analyzed.Glucose tolerance tests were performed after 8 wk of treatment.Histological assessments were performed in liver and adipose tissue.RNA expression levels of lipid metabolism related genes were evaluated in liver,skeletal muscle,and adipose tissue.RESULTS:Exenatide attenuated weight gain[HFDEx(-)vs HFD-Ex(+)]and reduced energy intake,which was accompanied by an increase in oxygen consumption and a decrease in the respiratory exchange ratio[HFD-Ex(-)vs HFD-Ex(+)].However,exenatide did not affect glucose tolerance.Exenatide reduced lipid content in the liver and adipose tissue.Exenatide did not affect the expression of lipid metabolism-related genes in the liver or skeletal muscle.In adipose tissue,exenatide significantly upregulated lipolytic genes,including hormone-sensitive lipase,carnitine palmitoyltransferase-1,long-chain acyl-CoA dehydrogenase,and acyl-CoA oxidase 1[HFD-Ex(-)vs HFD-Ex(+)].Exenatide also upregulated catalase and superoxide dismutase 2[HFD-Ex(-)vs HFD-Ex(+)].CONCLUSION:In addition to reducing appetite,enhanced lipid use by exenatide in adipose tissue may reduce hepatic lipid content in NAFLD,most likely by decreasing lipid influx into the liver.

Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.

Thrombomodulin in the management of acute cholangitisinduced disseminated intravascular coagulation

AIM: To evaluate the need for thrombomodulin(r TM) therapy for disseminated intravascular coagulation(DIC) in patients with acute cholangitis(AC)-induced DIC. METHODS: Sixty-six patients who were diagnosedwith AC-induced DIC and who were treated at our hospital were enrolled in this study. The diagnoses of AC and DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria as defined by the Japanese Association for Acute Medicine, respectively. Thirty consecutive patients who were treated with r TM between April 2010 and September 2013(r TM group) were compared to 36 patients who were treated without r TM(before the introduction of r TM therapy at our hospital) between January 2005 and January 2010(control group). The two groups were compared in terms of patient characteristics at the time of DIC diagnosis(including age, sex, primary disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC drugs), the DIC resolution rate, DIC score, the systemic inflammatory response syndrome(SIRS) score, hematological values, and outcomes. Using logistic regression analysis based on multivariate analyses, we also examined factors that contributed to persistent DIC. RESULTS: There were no differences between the r TM group and the control group in terms of the patients' backgrounds other than administration. DIC resolution rates on day 9 were higher in the r TM group than in the control group(83.3% vs 52.8%, P < 0.01). The mean DIC scores on day 7 were lower in the r TM group than in the control group(2.1 ± 2.1 vs 3.5 ± 2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the r TM group than in the control group(1.1 ± 1.1 vs 1.8 ± 1.1, P = 0.03). Mortality on day 28 was 13.3% in the r TM group and 27.8% in the control group; these rates were not significantly different(P = 0.26). Multivariate analysis identified only the absence of biliary drainage as significantly associated with persistent DIC(P < 0.01, OR = 12, 95%CI: 2.3-60). Although the difference did not reach statistical significance, primary diseases(malignancies)(P = 0.055, OR = 3.9, 95%CI: 0.97-16) and the non-use of r TM had a tendency to be associated with persistent DIC(P = 0.08, OR = 4.3, 95%CI: 0.84-22).CONCLUSION: The add-on effects of r TM are anticipated in the treatment of AC-induced DIC, although biliary drainage for AC remains crucial.

Antithrombin Ⅲ injection via the portal vein suppresses liver damage

AIM:To investigate the effects of antithrombin Ⅲ(AT Ⅲ) injection via the portal vein in acute liver failure.METHODS:Thirty rats were intraperitoneally challenged with lipopolysaccharide(LPS) and D-galactosamine(GalN) and divided into three groups:a control group;a group injected with AT Ⅲ via the tail vein;and a group injected with AT Ⅲ via the portal vein.AT Ⅲ(50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN.Serum levels of inflammatory cytokines and fibrin degradation products,hepatic fibrin deposition,and hepatic mRNA expression of hypoxiarelated genes were analyzed.RESULTS:Serum levels of alanine aminotransferase,tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT Ⅲ injection compared with tail vein injection,and control rats.Portal vein AT Ⅲ injection reduced liver cell destruction and decreased hepatic fibrin deposition.This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1.CONCLUSION:A clinically acceptable dose of AT Ⅲ injection into the portal vein suppressed liver damage,probably through its enhanced anticoagulant and antiinflammatory activities.

Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

Drug-induced hypersensitivity syndrome(DIHS) is a severe reaction usually characterized by fever,rash,and multiorgan failure,occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release.A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth.About 10 d later,she had a high fever,skin rash and liver dysfunction.She was admitted to hospital and diagnosed with a drug eruption.She was treated with oral prednisolone 30 mg/d;however,she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia.She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS.She was transferred to the Department of Medicine and Bioregulatory Science,Kyushu University,where she was treated with arterial steroid injection therapy.Following this treatment,her liver function improved and serum ferritin immediately decreased.We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes,followed by a cytokine storm that affected various organs.The measurement of serum ferritin might be a useful marker of the severity of DIHS.

Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) treatment.METHODS:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based treatments.Variation in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA genotype.RESULTS:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype.However,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not significant.CONCLUSION:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose.However,CC genotype was not inferior to CA/AA genotype for SVR rates.When full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.

Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma

AIM To investigate the factors influenced the efficacy of tolvaptan(TLV) in liver cirrhosis.METHODS We retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated with furosemide and spironolactone before admission, and treated with TLV for 7 d in our hospital. The effect of TLV was defined by the rate of body weight loss, and the factors that influenced TLV efficacy were analyzed using multiple regression.RESULTS Coexistent hepatocellular carcinoma(HCC) was the only significant predictive variable that attenuated the efficacy of TLV. In stratified analysis, high doses of furosemide decreased the efficacy of TLV in patients with HCC, and increased efficacy in those without HCC. In the latter, a high Child-Pugh-Turcotte score had a positive influence and a high concentration of lactate dehydrogenase had a negative influence on the effectiveness of TLV.CONCLUSION Development of ascites may differ between patients with liver failure and those with HCC progression. A sufficient preceding dose of furosemide decreases diuretic effect of TLV.

Change in microstructural characteristics of laser powder bed fused Al–Fe binary alloy at elevated temperature

The present study addressed the change in the microstructure of Al-2.5 wt%Fe binary alloy produced using laser powder bed fusion(L-PBF)technique by thermal exposure at 300℃,and the associated mechanical and thermal properties were systematically examined as well.Multi-semi-cylindrical patterns corresponding to melt pools in the microstructure were macroscopically observed for the asmanufactured sample.No change in the melt-pool morphology was observed after thermal exposure for1000 h.Inside the melt pools,a large number of the nanoscale metastable Al6 Fe phase particles were uniformly distributed inside columnar grains of theα-Al matrix containing concentrated solute Fe in supersaturation.The sequential formation and coarsening of stableθ-Al13 Fe4 phases were observed upon exposure to a 300℃ environment,but a considerable amount of nano-sized metastable Al6 Fe phases remained even after 1000 h.Furthermore,the thermal exposure continuously reduced the concentration of solute Fe atoms in theα-Al matrix.No significant grain growth was found inα-Al matrix after 1000 h owing to the pinning effect of the dispersed fine particles on grain boundary migration.These results demonstrate a sluggish change in microstructural morphologies of the Al-2.5 wt%Fe alloy.The quantified microstructural parameters addressed dominant strengthening contributions by the solid solution of Fe element and Orowan strengthening mechanism by fine Al-Fe intermetallics in the L-PBF-produced alloy.The high strength level was sustained even after being exposed to 300℃ for long periods.The superior balance of mechanical properties and thermal conductivity can be achieved in the experimental alloys by taking advantage of the various microstructural parameters related to the Al-Fe intermetallic phases andα-Al matrix.