Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains ...unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male ...C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
Interferon (IFN)-based therapy for chronic hepatitis C (CHC) is cost-effective and is associated with reduced risk of disease progression. We aimed to assess the incidence of cirrhosis and ...hepatocellular carcinoma (HCC) and to identify risk factors associated with disease progression.
We retrospectively reviewed 280 CHC patients who were registered at our hospital between 2001 and 2010.
About 80% of patients received antiviral treatment. The 10-year cumulative incidence of cirrhosis was significantly lower among patients who received antiviral therapy than among those who did not (8.3 vs. 44.0%; p = 0.001). Among them, patients with sustained virological response (SVR) had a significantly lower incidence of cirrhosis than those without SVR (0.6 vs. 33.9%; p < 0.001). Cox proportional hazards regression showed that SVR was the significant independent factor for reducing the risk of cirrhosis (hazard ratio, HR = 0.03; p = 0.034). The 10-year cumulative incidence of HCC was higher among patients who did not receive antiviral therapy than among those who did (43.9 vs. 6.1%; p < 0.001). Multivariate analysis showed that underlying cirrhosis was the only independent risk factor associated with HCC development (HR = 7.70; p = 0.010).
SVR secondary to IFN-based therapy could reduce cirrhosis development in CHC patients. Underlying cirrhosis was the strongest predictor of HCC development.
Key message
The ectopic expression of
AtDFR
results in increased accumulation of anthocyanins leading to enhanced salinity and drought stress tolerance in
B
.
napus
plants.
Flavonoids with ...antioxidant effects confer many additional benefits to plants. Evidence indicates that flavonoids, including anthocyanins, protect tissues against oxidative stress from various abiotic stressors. We determined whether increases in anthocyanins increased abiotic stress tolerance in
Brassica napus
, because the values of
B
.
napus
L. and its cultivation area are increasing worldwide. We overexpressed
Arabidopsis
dihydroflavonol-4-reductase (
DFR
) in
B
.
napus
. Increased DFR transcript levels for
AtDFR
-
OX B
. shoots correlated with higher anthocyanin accumulation.
AtDFR
-
OX
Brassica shoots exhibited lower reactive oxygen species (ROS) accumulation than wild-type (WT) shoots under high NaCl and mannitol concentrations. This was corroborated by 3,3-diaminobenzidine staining for ROS scavenging activity in 1,1-diphenyl-2-picryl-hydrazyl assays. Shoots of the
AtDFR
-
OX B
.
napus
lines grown in a high salt medium exhibited enhanced salt tolerance and higher chlorophyll content than similarly grown WT plants. Our observations suggested that the
AtDFR
gene can be effectively manipulated to modulate salinity and drought stress tolerance by directing to high accumulation of anthocyanins in oilseed plants.
Receptor-interacting protein kinase 3 (RIPK3) functions as a key regulator of necroptosis. Here, we report that the RIPK3 expression level is negatively regulated by CHIP (carboxyl terminus of ...Hsp70-interacting protein; also known as STUB1) E3 ligase-mediated ubiquitylation. Chip(-/-) mouse embryonic fibroblasts and CHIP-depleted L929 and HT-29 cells exhibited higher levels of RIPK3 expression, resulting in increased sensitivity to necroptosis induced by TNF (also known as TNFα). These phenomena are due to the CHIP-mediated ubiquitylation of RIPK3, which leads to its lysosomal degradation. Interestingly, RIPK1 expression is also negatively regulated by CHIP-mediated ubiquitylation, validating the major role of CHIP in necrosome formation and sensitivity to TNF-mediated necroptosis. Chip(-/-) mice (C57BL/6) exhibit inflammation in the thymus and massive cell death and disintegration in the small intestinal tract, and die within a few weeks after birth. These phenotypes are rescued by crossing with Ripk3(-/-) mice. These results imply that CHIP is a bona fide negative regulator of the RIPK1-RIPK3 necrosome formation leading to desensitization of TNF-mediated necroptosis.
A logging sonde was designed for neutron-induced gamma-ray spectroscopy in a geophysics project by re-evaluating the previous design method and modifying it for an improvement. This study further ...considered radiation interaction with materials and detector responses. The detector responses were calculated with pulse height (f8) tallies with a Monte Carlo transport simulation code and they were compared with the flux (f4) tally results which were mainly used for the previous sonde design. Analyses were focused on gamma rays produced from neutron capture reactions with silicon, sodium, and potassium and neutron inelastic scattering reactions with oxygen in Korean geostandard formations. Simulated responses from sodium iodine (NaI), bismuth germanate (BGO), gadolinium oxyorthosilicate (GSO), and lanthanum bromide (LaBr3) detectors were studied to compare the anticipated performances of the logging sonde depending on detector materials. We attempted to determine optimal detector locations from the simulated energy spectra, in which one can observe differences in capture and inelastic scattering gamma-ray peaks depending on the given formation configurations in a clearer manner. A comprehensive evaluation on the physical properties of detectors and the simulation result tentatively concluded that GSO detectors placed at 30, 70, and 90 cm positions can efficiently collect the data of interest from the Korean geostandard formations.
Abstract
Bacteria emit volatile compounds that modulate plant growth. Previous studies reported the impacts of bacterial volatile compounds on plant growth; however, the results varied depending on ...bacterial nutrient availability. We investigated whether the effects of plant growth–inhibiting volatiles (PGIVs) and plant growth–promoting volatiles (PGPVs) depended on the perceived dose by evaluating the growth of Arabidopsis thaliana seedlings placed at 7, 14, and 21 cm away from Bacillus amyloliquefaciens GB03 colonies growing in rich medium. A large bacterial colony (500 μl inoculum) inhibited plant growth at 7 cm and promoted growth at 21 cm, whereas a small bacterial colony (100 μl inoculum) induced the opposite pattern of response. We identified pyrazine and 2,5-dimethylpyrazine as candidate PGIVs that significantly reduced plant growth at a distance of 7 cm. PGIV effects were validated by exposing plants to synthetic 2,5-dimethylpyrazine and bacteria emitting PGPVs, which showed that PGIVs overwhelm PGPVs to rapidly increase salicylic acid content and related gene expression. This is referred to as the defence-growth trade-off. Our results indicate that high PGIV concentrations suppress plant growth and promote immunity, whereas low PGPV concentrations promote growth. This study provides novel insights into the complex effects of bacterial volatile mixtures and fine-tuning of bacteria-plant interactions.
Bacillus amyloliquefaciens GB03 emits volatile pyrazines, which exhibit plant growth inhibitory activity at shorter distances between plants and the volatile source.
The vertebral heart scale (VHS) is the most common method used for the objective evaluation of heart size, however, VHS cannot evaluate the entire heart area. This retrospective study aimed to ...evaluate the development and feasibility of vertebral heart area ratio (VHAR=heart area/the fourth thoracic vertebra T4 body area) as a new cardiac measurement method. A total of 125 dogs considered without clinical heart abnormalities in the pre-anesthetic examination, measurements of the VHS and VHAR using thoracic radiography were compared with computed tomography measurements of the vertebral cardiac volume ratio (VCVR=cardiac volume/T4 body volume) and investigate whether the VHAR values differed between observers. The mean cardiac and T4 body volumes were 116.99 ± 108.07 cm3 and 0.92 ± 0.91 cm3, respectively. The mean values of observers 1 and 2 were 9.9 ± 0.7 v (VHS), 42.64 ± 27.94 cm2 (heart area), and 1.37 ± 0.96 cm2 (T4 body area). Intraclass coefficients were the highest for the heart area, followed by the T4 body area and VHS. The VHAR showed a moderate correlation with VHS in observers 1 (r=0.671) and 2 (r=0.633). The VCVR showed a more positive correlation with VHAR (r=0.573) than with VHS (r=0.426). These results indicated that VHAR could be used as a complement to VHS for heart size measurement, and the high degree of observer agreement for the measurements indicated the measurement reproducibility of VHAR.
Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often ...become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70–80% of patients. To address some of the challenges faced by the current cancer treatments, here T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T‐cell‐membrane‐originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas‐ligand‐mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor‐β1 (TGF‐β1)) and programmed death‐ligand 1 (PD‐L1) of cancer cells by scavenging TGF‐β1 and PD‐L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti‐tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen‐nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.
T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. The TCMNPs can be targeted at tumors and kill cancer cells while being resistant to the pro‐tumoral factors in the tumor microenvironment. Indeed, the TCMNPs exhibit a higher therapeutic efficacy than current cancer treatments based on immune checkpoint blockade, and they are effective for the treatment of various tumors.
Hyperbaric oxygen therapy (HBO
) is recommended for symptomatic patients within 24 h of carbon monoxide (CO) poisoning. Currently, there is no consensus on the number of HBO
sessions within 24 h ...after arrival at the hospital. Therefore, we evaluated differences in the therapeutic effects according to the number of HBO
sessions in acute CO poisoning.
This cohort study included data collected from our CO poisoning registry and prospective cohorts between January 2006 and August 2021 in a single academic medical center in South Korea. Based on the number of HBO
sessions performed within 24 h, we classified patients into one- and multiple- (two or three) session groups. We also compared mild (non-invasive mechanical ventilation) and severe (invasive mechanical ventilation) groups. CO-related neurocognitive outcomes were measured using the Global Deterioration Scale (GDS; stages: 1-7) combined with neurological impairment at 1 month after poisoning. We classified GDS stages as favorable (1-3 stages) and poor (4-7 stages) neurocognitive outcomes. Patients belonging to a favorable group based on GDS assessment, but with observable neurological impairment, were assigned to the poor outcome group. Propensity score matching (PSM) was performed to adjust for age, sex, and related variables to identify statistical differences between groups.
We analyzed the data of 537 patients between ages 16 and 70 years treated with HBO
. After PSM, there was no significant difference in neurocognitive outcomes at 1 month among the two groups of patients (
= 0.869). Furthermore, there were no significant differences in neurocognitive outcomes between invasive mechanical ventilation and non-invasive mechanical ventilation patients in the three groups (
= 0.389 and
= 0.295).
There were no significant differences in the reduction of poor neurocognitive outcomes according to the number of HBO
sessions implemented within 24 h of CO exposure.
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