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1.
Chemosphere ; 256: 127021, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32438128

RESUMO

The effect of gamma-irradiation doses of 0, 10, 100, and 500 kGy at the dose rates of 1 or 0.1 kGy/h on the molecular and chemical properties of humic substances (HS) were investigated using total organic carbon measurements, UV-Vis spectrometry, 13C nuclear magnetic resonance, and acid-base titration. A possible mechanism of the radiolysis on HS was also speculated. The complexation ability of irradiated HS with Ca2+ ions was studied using a Ca ion-selective electrode. The apparent formation constants of the Ca-HS complexes increased as the irradiation dose increased, and this was attributed to the relative increase in the ratio of phenolic -OH to carboxylic groups of HS. The contribution of the phenolic -OH groups to Ca-HS complexes was suppressed at pH 5 owing to its high acid dissociation constants. In addition, the radiation dose rates of 1 and 0.1 kGy/h did not significantly affect the properties of HS and the apparent formation constants of the Ca-HS complexes.

2.
Virus Genes ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430568

RESUMO

The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.

3.
J Artif Organs ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32232678

RESUMO

Two dialysis patients developed recurrent restless legs syndrome. The clinical courses and the association between the α1-microglobulin removal rate and the therapeutic effects of hemodiafiltration were analyzed. Case 1: a middle-aged woman was switched from predilution online hemodiafiltration to hemodialysis, following which the α1-microglobulin removal rate decreased from 39.1 to 29.9%. A month later, the severe restless legs syndrome occurred. The treatment was then switched to high-efficiency hemodiafiltration and 2 weeks later, these symptoms were resolved. The α1-microglobulin removal rate increased to 41.9%. Her symptoms recurred 5 years later with severity; thus, the hemodiafiltration treatment conditions were changed. Under revised conditions, the α1-microglobulin removal rate was 42.6%, and her symptoms were alleviated. Continuation of high-efficiency hemodiafiltration led to the resolution of the syndrome at 1 month after recurrence. Case 2: a middle-aged man on hemodialysis developed the restless legs syndrome in the second year of treatment. The α1-microglobulin removal rate was 23.8%. After switching to a month-long high-efficiency hemodiafiltration with a removal rate of ≥ 40%, his symptoms were resolved. However, the syndrome recurred after a year with severity. The symptoms were alleviated using various measures. The hemodiafilters were changed, and hemodiafiltration with an α1-microglobulin removal rate of ≥ 40% was continued; 2 months later, his symptoms resolved. High-efficiency online hemodiafiltration is an effective therapeutic strategy for restless legs syndrome in dialysis patients. We found, for the first time, that target removal efficiency is an α1-microglobulin removal rate of 40% or higher.

4.
J Artif Organs ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32266500

RESUMO

To assess the removal performance of low-volume post-hemodiafiltration (HDF) with Japanese hemodiafilters and the removal performance with 20 % reduction in the total dialysate flow rate (Qdtotal). Subjects were 8 patients undergoing pre-HDF. Study 1: Post-HDF was performed at a blood flow rate (Qb) of 250 mL/min and a total volume of substitution fluid (Vs) of 12 L/session(s) for 4 hrs using Fineflux-210Seco (FIX), ABH-21PA (ABH), and NVF-21H (NVF). We assessed removal efficiency of small molecular solutes, low-molecular-weight-proteins and the amount of albumin loss. Study 2: Post-HDF was performed at Vs of 12 L/s under G-1, Qdtotal of 500 and Qb of 250 mL/min; G-2, Qdtotal of 400 and Qb of 250 mL/min; and G-3, Qdtotal of 400 and Qb of 300 mL/min. Removal efficiency was compared and analyzed between these conditions. Subjects were 8 patients undergoing pre-HDF. Study 1: Post-HDF was performed at a blood flow rate (Qb) of 250 mL/min and a total volume of substitution fluid (Vs) of 12 L/session(s) for 4 hrs using Fineflux-210Seco (FIX), ABH-21PA (ABH), and NVF-21H (NVF). We assessed removal efficiency of small molecular solutes, low-molecular-weight-proteins and the amount of albumin loss. Study 2: Post-HDF was performed at Vs of 12 L/s under G-1, Qdtotal of 500 and Qb of 250 mL/min; G-2, Qdtotal of 400 and Qb of 250 mL/min; and G-3, Qdtotal of 400 and Qb of 300 mL/min. Removal efficiency was compared and analyzed between these conditions. Study 1: The results using FIX, ABH and NVF are shown in order. The Kt/V were 1.8, 1.9 and 1.8. The ß2-Microglobulin (MG) removal rate (RR) (%) were 81.2, 83.1 and 82.8, and the α1-MG RR were 37.4, 40.2 and 38.5, respectively. Study 2: The results in G-1, 2 and 3 are shown in order. The Kt/V and the RR of small solutes, were significantly higher in G-3. The ß2-MG RR (%) were 81.2, 80.1 and 81.0, and the α1-MG RR were 37.4, 37.5 and 38.0, respectively. ow-volume post-HDF performed at Qb of 250 mL/min with Japanese high-performance hemodiafilters exhibited favorable removal efficiency for all solutes. Even with 20 % reduction in Qdtotal, the removal performance was also favorable.

5.
J Virol ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269119

RESUMO

IgA antibodies on mucosal surfaces are known to play an important role in protection from influenza A virus (IAV) infection and are believed to be more potent than IgG for cross-protective immunity against IAVs of multiple hemagglutinin (HA) subtypes. However, in general, neutralizing antibodies specific to HA are principally HA subtype-specific. Here we focus on non-neutralizing but broadly cross-reactive HA-specific IgA antibodies. Recombinant IgG, monomeric IgA (mIgA), and polymeric secretory IgA (pSIgA) antibodies were generated based on the sequence of a mouse anti-HA monoclonal antibody (MAb) 5A5 that had no neutralizing activity but showed broad binding capacity to multiple HA subtypes. While confirming that there was no neutralizing activity of the recombinant MAbs against IAV strains A/Puerto Rico/8/1934 (H1N1), A/Adachi/2/1957 (H2N2), A/Hong Kong/483/1997 (H5N1), A/shearwater/South Australia/1/1972 (H6N5), A/duck/England/1/1956 (H11N6), and A/duck/Alberta/60/1976 (H12N5), we found that pSIgA, but not mIgA and IgG, significantly reduced budding and release of most of the viruses from infected cells. Electron microscopy demonstrated that pSIgA deposited newly produced virus particles on the surfaces of infected cells, most likely due to tethering of virus particles. Furthermore, we found that pSIgA showed significantly higher activity to reduce plaque sizes of the viruses than IgG and mIgA. These results suggest that non-neutralizing pSIgA reactive to multiple HA subtypes may play a role in inter-subtype cross-protective immunity against IAVs.Importance Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities in vitro These recombinant antibodies did not show "classical" neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with IAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from IAVs of multiple HA subtypes, including viruses with pandemic potential.

6.
Nat Neurosci ; 23(4): 510-519, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32203495

RESUMO

Specific cell populations may have unique contributions to schizophrenia but may be missed in studies of homogenate tissue. Here laser capture microdissection followed by RNA sequencing (LCM-seq) was used to transcriptomically profile the granule cell layer of the dentate gyrus (DG-GCL) in human hippocampus and contrast these data to those obtained from bulk hippocampal homogenate. We identified widespread cell-type-enriched aging and genetic effects in the DG-GCL that were either absent or directionally discordant in bulk hippocampus data. Of the ~9 million expression quantitative trait loci identified in the DG-GCL, 15% were not detected in bulk hippocampus, including 15 schizophrenia risk variants. We created transcriptome-wide association study genetic weights from the DG-GCL, which identified many schizophrenia-associated genetic signals not found in transcriptome-wide association studies from bulk hippocampus, including GRM3 and CACNA1C. These results highlight the improved biological resolution provided by targeted sampling strategies like LCM and complement homogenate and single-nucleus approaches in human brain.

7.
J Orthop Sci ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32139267

RESUMO

BACKGROUD: Exercises and vitamin D interventions have shown to improve muscle function and balance, and prevent falls in postmenopausal healthy women and in patients with osteoporosis. However, the effects of eldecalcitol on these factors remain undetermined. The present open-label, randomized, controlled study aimed to investigate the effects of eldecalcitol treatment in reducing falls in postmenopausal women, and improving muscle function and balance. METHODS: The study population included 226 Japanese postmenopausal women with osteoporosis. Patients were randomly divided into two groups on the basis of treatment with or without eldecalcitol (0.75 µg/day). Treatment continued for 6 months. Participants in both groups were instructed to perform back extensor muscle exercise. Isometric back extensor and leg extensor strength, grip power, ten-meter walking speed, timed up and go test and time of single leg standing were measured at baseline and 24 weeks. Patients were asked to record the number of falls during the 24-week period. RESULTS: The percentage increase in average bilateral quadriceps muscle strength was significantly higher in the eldecalcitol group compared with the non-eldecalcitol group (right, p = 0.041; left, p = 0.042). In contrast, there were no significant differences in the strength of back muscles and grip power and the parameters of balance and walking abilities between the groups. There was no significant difference in the number of falls between the groups. CONCLUSIONS: A 24-week intervention of eldecalcitol improves the strength of the quadriceps muscles in postmenopausal women with osteoporosis. However, eldecalcitol neither improve balance and walking abilities nor reduce the number of falls.

8.
J UOEH ; 42(1): 27-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32213740

RESUMO

5-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a photosensitizer itself, 5-ALA is a prodrug that accumulates protoporphyrin IX (PpIX) in the mitochondria of glioma cells; PpIX acts as a photosensitizer. Fluorescence-guided resection for malignant gliomas has some pitfalls. Moreover, 5-ALA is not merely a fluorescence marker but has potential as a mitochondria-targeting drug for malignant glioma therapy. In this article, we review the literature related to 5-ALA, discuss the pitfalls of fluorescence-guided resection using 5-ALA for malignant gliomas, and describe the application of 5-ALA for malignant glioma therapy with personal opinions.

9.
Sci Total Environ ; 722: 137783, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32208245

RESUMO

Groundwater is essential for the Earth biosphere but is often contaminated by harmful chemical compounds due to both anthropogenic and natural causes. A key factor controlling the fate of harmful chemicals in groundwater is the reduction/oxidation (redox) conditions. The formation factors for the groundwater redox conditions are insufficiently understood. In this study, long-term groundwater quality beneath one of the world megacities was monitored and evaluated. We measured and compared hydrogeochemical conditions including groundwater quality (35 chemical parameters) and redox conditions of five aquifers in the Arakawa Lowland and Musashino Upland, southern Kanto Plain of the Tokyo Metropolitan area, Japan. Monitoring results suggested the following: The main origin of groundwater is precipitation in both the Lowland and Upland areas. The three aquifers in the Arakawa Lowland are likely fully separated, with one unconfined and two confined aquifers under iron reducing and methanogenic conditions, respectively. Oppositely, in the Musashino Upland, the water masses in the two aquifers are likely partly connected, under aerobic conditions, and undergoing the same groundwater recharge and flow processes under similar hydrogeological conditions. The different groundwater redox conditions observed are likely caused by the very different groundwater residence times for the Arakawa Lowland and Musashino Upland.

10.
Ecotoxicol Environ Saf ; 192: 110238, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32036095

RESUMO

Mercury (Hg) is an extremely dangerous environmental contaminant, responsible for human diseases including neurological disorders. However, the mechanisms of inorganic Hg (iHg)-induced cell death and toxicity are little known. Dihydrolipoic acid (DHLA) is the reduced form of a naturally occurring compound lipoic acid, which act as a potent antioxidant through multiple mechanisms. So we hypothesized that DHLA has an inhibitory role on iHg-cytotoxicity. The purposes of this research were to investigate mechanism/s of cytotoxicity of iHg, as well as, the cyto-protection of DHLA against iHg induced toxicity using PC12 cells. Treatment of PC12 cells with HgCl2 (Hg2+) (0-2.5 µM) for 48 h resulted in significant toxic effects, such as, cell viability loss, high level of lactate dehydrogenase (LDH) release, DNA damage, cellular glutathione (GSH) level decrease and increased Hg accumulation. In addition, protein level expressions of akt, p-akt, mTOR, GR, NFkB, ERK1, Nrf2 and HO-1 in cells were downregulated; and cleaved caspase 3 and cytochrome c release were upregulated after Hg2+ (2.5 µM) exposure and thus inducing apoptosis. Hg2+induced apoptosis was also confirmed by flow cytometry. However, pretreatment with DHLA (50 µM) for 3 h before Hg2+ (2.5 µM) exposure showed inhibition against iHg2+-induced cytotoxicity by reversing cell viability loss, LDH release, DNA damage, GSH decrease and inhibiting Hg accumulation. Moreover, DHLA pretreatment reversed the protein level expressions of akt, p-akt, mTOR, GR, NFkB, ERK1, Nrf2, HO-1, cleaved caspase 3 and cytochrome c. In conclusion, results showed that DHLA could attenuate Hg2+-induced cytotoxicity via limiting Hg accumulation, boosting up of antioxidant defense, and inhibition of apoptosis in cells.


Assuntos
Apoptose/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Mercúrio/toxicidade , Ácido Tióctico/análogos & derivados , Animais , Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Poluentes Ambientais/metabolismo , Glutationa/metabolismo , Mercúrio/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos , Ácido Tióctico/farmacologia
11.
Semin Liver Dis ; 40(2): 189-212, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32074631

RESUMO

Advancement in both bioengineering and cell biology of the liver led to the establishment of the first-generation humanized liver chimeric mouse (HLCM) model in 2001. The HLCM system was initially developed to satisfy the necessity for a convenient and physiologically representative small animal model for studies of hepatitis B virus and hepatitis C virus infection. Over the last two decades, the HLCM system has substantially evolved in quality, production capacity, and utility, thereby growing its versatility beyond the study of viral hepatitis. Hence, it has been increasingly employed for a variety of applications including, but not limited to, the investigation of drug metabolism and pharmacokinetics and stem cell biology. To date, more than a dozen distinctive HLCM systems have been established, and each model system has similarities as well as unique characteristics, which are often perplexing for end-users. Thus, this review aims to summarize the history, evolution, advantages, and pitfalls of each model system with the goal of providing comprehensive information that is necessary for researchers to implement the ideal HLCM system for their purposes. Furthermore, this review article summarizes the contribution of HLCM and its derivatives to our mechanistic understanding of various human liver diseases, its potential for novel applications, and its current limitations.

12.
Biol Blood Marrow Transplant ; 26(5): 998-1004, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31962165

RESUMO

A multicenter retrospective study was performed to evaluate the prognostic factors in 104 patients with relapsed or refractory acute lymphoblastic leukemia (ALL), who underwent allogeneic hematopoietic cell transplantation (HCT) between 2005 and 2015. The median age was 38 (range, 17 to 68), and the median blast fraction in peripheral blood and bone marrow was 1% (range, 0 to 99%) and 52% (range, 0 to 100%), respectively. With a median follow-up of 47 months (range, 8.3 to 105 months), overall survival (OS), nonrelapse mortality, and relapse mortality at 1 year were 25%, 44%, and 31%, respectively. Multivariate analysis demonstrated independent predictors for poor OS, including nuclear cell count in the bone marrow ≥10 × 104/µL (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.33 to 3.43; P = .002), elevated lactate dehydrogenase level (HR, 1.66; 95% CI, 1.05 to 2.62; P = .031), and no primary induction failure (HR, 2.05; 95% CI, 1.11 to 3.78; P = .022). A prognostic scoring index was designed based on these survival predictors. At 2 years, OS was 28%, 14%, and 0% for good (score 0 or 1; n = 47), intermediate (score 2; n = 40), and poor (score 3; n = 17), respectively (P < .001). This scoring system may be useful in identifying the patient population for which allogeneic HCT is least beneficial in advanced stages of ALL.

13.
Sci Rep ; 10(1): 1156, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980687

RESUMO

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.

14.
Int J Hematol ; 111(1): 93-102, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31612307

RESUMO

Autologous hematopoietic cell transplantation (HCT) has not gained universal popularity in the treatment of acute myeloid leukemia (AML), and its status remains unclear. To determine the implementation status and outcomes of autologous HCT for adults with AML in Japan, we analyzed data from 1,174 patients (including 446 with acute promyelocytic leukemia [APL]) who underwent autologous HCT between 1992 and 2016 consecutively reported to the Japanese nationwide transplantation registry. The annual number of transplantations peaked at 82 cases in 1997, and has recently remained at around 40 cases. The percentage of APL has increased sharply since 2004, and currently exceeds 70%. While most non-APL patients underwent autologous HCT during first complete remission (CR), transplantation during second CR has become mainstream for APL patients since the early 2000s. The 5-year survival, relapse, and non-relapse mortality rates were 55.3%, 42.1%, and 8.6% for non-APL patients, and 87.6%, 12.9%, and 3.4% for APL patients, respectively. Patients transplanted in the later period showed better survival than those transplanted in the earlier period, both for non-APL (P < 0.001) and APL (P = 0.036). These results clearly show the various changes in transplantation practice and post-transplant outcomes in Japan over the past 25 years.

15.
Int J Food Sci Nutr ; 71(2): 226-234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31290360

RESUMO

Resveratrol (RSV) can protect against non-communicable diseases by improving cholesterol metabolism. However, it is unclear that effects of maternal RSV intake on health of adult offspring. In this study, we examined effects of maternal RSV intake during lactation on cholesterol metabolism in adult male rat offspring. Female Wistar rats were fed a control diet (CON) supplemented with or without RSV (20 mg/kg body weight/day) during their lactation period. Male offspring were weaned onto a standard diet and maintained on this diet for 36 weeks. As a result, plasma cholesterol level significantly decreased in RSV offspring compared to CON offspring. Furthermore, a decrease in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase level and an increase in hepatic LDL-receptor level were observed in the RSV offspring. These results indicate that maternal RSV intake causes long-term decrease in plasma cholesterol level in the offspring through suppression of hepatic cholesterol biosynthesis and promotion of hepatic cholesterol uptake.

16.
Hepatology ; 71(1): 291-305, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206736

RESUMO

Glisson's capsule is the connective tissue present in the portal triad as well as beneath the liver surface. Little is known about how Glisson's capsule changes its structure in capsular fibrosis (CF), which is characterized by fibrogenesis beneath the liver surface. In this study, we found that the human liver surface exhibits multilayered capsular fibroblasts and that the bile duct is present beneath the mesothelium, whereas capsular fibroblasts are scarce and no bile ducts are present beneath the mouse liver surface. Patients with cirrhosis caused by alcohol abuse or hepatitis C virus infection show development of massive CF. To examine the effect of alcohol on CF in mice, we first injected chlorhexidine gluconate (CG) intraperitoneally and then fed alcohol for 1 month. The CG injection induces CF consisting of myofibroblasts beneath the mesothelium. One month after CG injection, the fibrotic area returns to the normal structure. In contrast, additional alcohol feeding sustains the presence of myofibroblasts in CF. Cell lineage tracing revealed that mesothelial cells give rise to myofibroblasts in CF, but these myofibroblasts disappear 1 month after recovery with or without alcohol feeding. Capsular fibroblasts isolated from the mouse liver spontaneously differentiated into myofibroblasts and their differentiation was induced by transforming growth factor beta 1 (TGF-ß1) or acetaldehyde in culture. In alcohol-fed mice, infiltrating CD11b+ Ly-6CLow/- monocytes had reduced mRNA expression of matrix metalloproteinase 13 and matrix metalloproteinase 9 and increased expression of tissue inhibitor of matrix metalloproteinase 1, Tgfb1, and interleukin-10 during resolution of CF. Conclusion: The present study revealed that the structure of Glisson's capsule is different between human and mouse livers and that alcohol impairs the resolution of CF by changing the phenotype of Ly-6CLow/- monocytes.

17.
Environ Toxicol Pharmacol ; 74: 103302, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786496

RESUMO

Arsenic is awfully toxic metalloid responsible for many human diseases all over the world. Contrastingly, D-pinitol is a naturally occurring bioactive dietary compound has antioxidant properties. The objective of this study is to elucidate the protective actions of D-pinitol on arsenic-induced cytotoxicity and explore its controlling role in biomolecular mechanisms in PC12 cells. Obtained results demonstrated that co-exposure of D-pinitol with arsenic increases cell viability, decreases DNA damage and protects PC12 cells from arsenic-induced cytotoxicity by increasing glutathione (GSH) level and glutathione reductase (GR). Protein expression of western blot analysis showed that co-exposure of D-pinitol and arsenic significantly inhibited arsenic-induced autophagy which further suppressed apoptosis through up-regulation of survival factors; mTOR, p-mTOR, Akt, p-Akt, NF-кB, Nrf2, ERK1, GR, Bcl-x and down-regulation of death factors; p53, Bax, cytochrome c, LC3, although arsenic regulated those factors negatively. These results of this study suggested that D-pinitol protects PC12 cells from arsenic-induced cytotoxicity.

18.
Biol Blood Marrow Transplant ; 26(1): 162-170, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31536824

RESUMO

To prospectively validate the incidence, manifestations, and outcomes of graft-versus-host disease (GVHD) by National Institutes of Health criteria, we recruited 406 hematopoietic stem cell transplantation recipients at 16 transplant centers in Japan from May 2012 to June 2014. The 2-year cumulative incidence of late acute and chronic GVHD was 3.2% (n = 13) and 35.4% (n = 145), with a median onset of 3.6 and 4.7 months after transplant, respectively. The global severity at onset was mild in 30.3%, moderate in 43.5%, and severe in 26.2%. Eighty-two patients were followed up for 2 years, with 79.3% still manifesting GVHD symptoms, and 80.6% (n = 117) of the patients received systemic immunosuppressive treatment (IST), with a 2-year cumulative incidence of IST termination of 33.1%. Severe patients showed a significantly lower rate of IST termination than those with mild and moderate severities (mild, 38.5%; moderate, 40.9%; and severe, 17.2%). The 2-year incidence of nonrelapse mortality (NRM) and relapse was not significantly different according to the severity at onset (NRM: mild [16.6%] versus moderate [8.7%] versus severe [16.1%]; relapse: mild [14.9%] versus moderate [14.7%] versus severe [5.3%]). As a result, 2-year overall survival (OS) and GVHD-specific survival (GSS) were equivalent according to the severity at onset (mild: OS = 81.0%, GSS = 85.7%; moderate: OS = 84.2%, GSS = 92.5%; severe: OS = 83.9%, GSS = 89.2%). Our study helped identify the characteristics of late acute and chronic GVHD in Japanese patients. Further investigation is needed to identify an optimal endpoint for survival prediction.

19.
Biochem Biophys Res Commun ; 521(2): 457-462, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31676069

RESUMO

Polymethoxylated flavones (PMFs) are naturally occurring compounds that have biological effects on many cell types. We previously demonstrated that PMFs such as nobiletin potentiate the cytolytic activity of the human leukemic natural killer cell line KHYG-1 and increased level of the cytotoxic protein granzyme B (GrB) and the cytokine interferon-γ (IFN-γ). However, the precise mechanisms by which this occurs remain to be elucidated. In this study, we sought to identify and investigate the function of intracellular primary targets of the PMFs in KHYG-1 cells. Using affinity purification and mass spectrometry, we identified that 3'-hydroxy-4',5,6,7-tetramethoxyflavone (TMF) binds to the nuclear export factors Exportin-1 and -2 (XPO1 and XPO2) as TMF-binding proteins and demonstrated that nobiletin competes with TMF for XPO1 binding, suggesting that nobiletin also binds to XPO1. Treatment of KHYG-1 cells with leptomycin B, a specific XPO1 inhibitor, increased the expression of GrB and IFN-γ but did not potentiate lysis of specific target cells, suggesting that the cargo of XPO1 contributes to the expression of cytolytic genes but that this alone is insufficient to enhance cytolysis. Consistent with this, nobiletin and related PMFs induced the nuclear retention of NF-κB, a transcription factor that promotes GrB and IFN-γ expression. PMFs also induced the nuclear retention of the tumor suppressor protein p53, a known XPO1 cargo protein, resulting in KHYG-1 cell cycle arrest. Collectively, these results suggest that PMFs modulate KHYG-1 function, at least in part, by inhibiting XPO1.

20.
Nanotechnology ; 31(12): 125202, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31791028

RESUMO

We demonstrate that a planar single-walled carbon nanotube (SWCNT) film bolometer can exhibit enhanced thermal and optical properties. The SWCNT film were ink-printed on an oxidized silicon substrate between two pointed-tip Au electrodes across a gap of approximately 10 µm. We obtained a bolometer figure-of-merit temperature coefficient of resistance of greater than -3.0% at room temperature. An optical response of 1000 V W-1 was obtained from a 786 nm laser with an output power of 5 mW. The corresponding thermal time constant of 1.8 ms was estimated through the optical response by modulating the laser over a frequency range of 1 Hz-1 kHz. The optical noise equivalent power and optical detectivity of [Formula: see text] and [Formula: see text] respectively, were estimated from the responsivity, the spectral density, and area of the cell of the absorber, 4.9 × 10-4 cm2. We attribute the exceptional performance of the SWCNT microbolometer to the film nature of the absorber and to the high concentration of the incident electromagnetic radiation and localized heating between the tips of the electrode.

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