MicroRNAs (miRNAs) are a non-coding family of genes involved in post-transcriptional gene regulation. These transcripts are associated with cell proliferation, cell differentiation, cell death and ...carcinogenesis. We analysed the miRNA expression profiles in 25 pairs of hepatocellular carcinoma (HCC) and adjacent non-tumorous tissue (NT) and nine additional chronic hepatitis (CH) specimens using a human miRNA microarray. Targets and references samples were co-hybridized to a microarray containing whole human mature and precursor miRNA sequences. Whereas three miRNAs exhibited higher expression in the HCC samples than that in the NT samples, five miRNAs demonstrated lower expression in the HCC samples than in the NT samples (P<0.0001). Classification of samples as HCC or NT by using support vector machine algorithms based on these data provided an overall prediction accuracy of 97.8% (45/46). In addition, the expression levels of four miRNAs were inversely correlated with the degree of HCC differentiation (P<0.01). A comparison of CH and liver cirrhosis samples revealed significantly different pattern of miRNA expression (P<0.01). There were no differences, however, between hepatitis B-positive and hepatitis C-positive samples. This information may help clarify the molecular mechanisms involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.
Microplastics are ubiquitous pollutants in the marine environment and a health concern. They are generated directly for commercial purposes or indirectly from the breakdown of larger plastics. ...Examining a toxicological profile for microplastics is a challenge due to their large variety of physico-chemical properties and toxicological behavior. In addition to their concentration, other parameters such as polymer type, size, shape and color are important to consider in their potential toxicity. Microplastics can adsorb pollutants such as polycyclic aromatic hydrocarbons (PAHs) or metals on their surface and are likely to contain plastic additives that add to their toxicity. The observations of microplastics in seafood increased concern for potential human exposure. Since literature considering microplastics in humans is scarce, using a One Environmental Health approach can help better inform about potential human exposures. Marine mammals and sea turtles are long-lived sentinel species regularly used for biomonitoring the health status of the ocean and share trophic chain and habitat with humans. This review considers the available research regarding microplastic and plastic fiber exposures in humans, marine mammals and turtles. Overall, across the literature, the concentration of microplastics, size, color, shape and polymer types found in GI tract and feces from sea turtles, marine mammals and humans are similar, showing that they might be exposed to the same microplastics profile. Additionally, even if ingestion is a major route of exposure due to contaminated food and water, dermal and inhalation studies in humans have provided data showing that these exposures are also health concerns and more effort on these routes of exposures is needed.
In vitro
studies looked at a variety of endpoints showing that microplastics can induce immune response, oxidative stress, cytotoxicity, alter membrane integrity and cause differential expression of genes. However, these studies only considered three polymer types and short-term exposures, whereas, due to physiological relevance, prolonged exposures might be more informative.
Summary
This study revealed the change in the paravertebral muscles in patients with osteoporotic vertebral fracture. Increased pain is likely to be the driver for reduced activity, reduced ...activities of daily living, and consequent increase in fat infiltration of the paravertebral muscles, assumed to be secondary to reduced activity level or, conversely, partial immobilization.
Introduction
To reveal the time courses and impact of the paravertebral muscles (PVMs) on the healing process of osteoporotic vertebral fractures and risk factors for PVM decrease.
Methods
Consecutive patients with symptomatic osteoporotic vertebral fractures were enrolled in 11 hospitals. At enrollment and 3- and 6-month follow-up, PVMs, including the multifidus and erector spinae, were examined using magnetic resonance imaging (MRI). The PVM cross-sectional area (CSA) and fat signal fraction (FSF) were measured at L3. Low back pain (LBP), activities of daily living (ADLs), and risk factors for PVM decrease at the 6-month follow-up were investigated. PVM decrease was defined as > 1 standard deviation decrease of the CSA or > 1 standard deviation increase of the FSF.
Results
Among 153 patients who completed the 6-month follow-up, 117 (92 women, 79%) had MRI of L3 at enrollment and 3- and 6-month follow-up (mean age at enrollment, 78.5 years). The CSA did not change 6 months from onset (
p
for trend = 0.634), whereas the FSF significantly increased (
p
for trend = 0.033). PVM decrease was observed in 30 patients (26%). LBP was more severe, and delayed union was more frequent in patients with PVM decrease (
p
= 0.021 mixed-effect model and
p
= 0.029 chi-square test, respectively). The risk factors for PVM decrease were ADL decline at the 3-month follow-up (adjusted odds ratio = 5.35,
p
= 0.026).
Conclusion
PVM decrease was significantly related to LBP and delayed union after osteoporotic vertebral fracture onset. ADL decline at the 3-month follow-up was a risk factor for PVM decrease. Therefore, restoring ADLs within 3 months after onset is important.
Genotypes are associated with the natural course of hepatitis C virus (HCV) infection and response to antiviral therapy for HCV. HCV genotype 1b has been the dominant genotype in Japan, where the ...prevention of HCV transmission through blood transfusion or nosocomial infection has been established since 1990. The distribution of HCV genotype was investigated based on patient's birth year in 5515 HCV-infected Japanese individuals at three institutions from different areas of Japan. At all three institutions, the proportion of HCV genotype 1b decreased and was <50% in individuals born after 1970. By contrast, the percentage of HCV genotype 2b increased in subsequent birth cohorts after 1920–1929. Significant changes in HCV genotype distribution were observed across Japan regardless of area.
Summary
This study revealed the time course of osteoporotic vertebral fracture by magnetic resonance imaging using a simple classification. Signal changes were associated with the compression degree ...and mobility of the fractured vertebral body. This classification showed sufficient reliability in categorizing magnetic resonance imaging findings of osteoporotic vertebral fractures.
Introduction
Magnetic resonance imaging (MRI) is useful in diagnosing osteoporotic vertebral fractures (OVFs). This study investigated the time course of OVFs by MRI using a simple classification.
Methods
This multicenter cohort study was performed from 2012 to 2015. Consecutive patients with ≤2-week-old OVFs were enrolled in 11 institutions. MRI was performed at enrollment and at 1-, 3-, 6-, and 12-month follow-up. Signal changes on T1-weighted imaging (T1WI), T2WI, and short τ inversion recovery (STIR) were classified according to signal intensity. Height and angular motion of vertebral bodies were also measured.
Results
The 6-month follow-up was completed by 153 patients. At enrollment, fractured vertebrae signal changes were 43 % diffuse and 57 % confined low on T1WI; on T2WI, 56, 24, and 5 % were confined low, high, and diffuse low, respectively; on STIR, 100 % were high. On T1WI, diffuse low remained most common (90 % at 1 month and 60 % at 3 months) until 6 and 12 months, when most were confined low (54 and 52 %, respectively). On T2WI, confined low remained most common (decreasing to 41 % at 12 months). On STIR, high signal change was shown in 98, 87, and 64 % at 3, 6, and 12 months, respectively. At 3, 6, and 12 months, diffuse low signal change was associated with significantly lower vertebral height, and high signal change was associated with significantly greater angular motion.
Conclusions
MRI signal changes were associated with the compression degree and angular motion of fractured vertebrae. This classification showed sufficient reliability in categorizing MRI findings of OVFs.
Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is ...thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.
To validate the utility of hepatic resection combined with complementary radiofrequency ablation (RFA) compared with resection alone for patients with multiple hepatocellular carcinoma (HCC), and to ...compare these results with those of a previous report.
A total of 78 HCC patients with multiple (≤5) tumours who were initially treated with hepatic resection only (Resection group) or with combined hepatic resection and RFA (Combination group) were included. Overall and disease-free survival were analysed.
There were 21 women and 57 men with a median age of 72.5 (64.3–76.8) years. Fifty-three patients were treated with resection alone and 25 received combination therapy. The 3-, 5-, and 7-year cumulative overall survival rates were 81.2%, 68.2%, and 57.1%, respectively, in the Resection group, and 81.3%, 59.6%, and 42.4%%, respectively, in the Combination group (hazard ratio HR, 1.462; 95% confidence interval CI, 0.682–3.136; p=0.329). The 1-, 3-, and 5-year cumulative disease-free survival rates were 61.4%, 45.7%, and 39.8%, respectively, in the Resection group, and 53.1%, 18.6%, and 0%, respectively, in the Combination group (HR, 2.080; 95% CI, 1.157–3.737; p=0.014). The overall survival rate was not significantly different between the Resection and Combination groups in patients within the up-to-seven HCC criteria (n=56; HR, 2.101; 95% CI, 0.805–5.486; p=0.130) or those beyond these criteria (n=22; HR, 0.804; 95% CI, 0.197–3.286; p=0.761).
The combination of hepatic resection and RFA therapy may be an effective strategy for HCC patients with multiple tumours.
•To validate the utility of hepatic resection combined with RFA for multiple HCC.•The overall survival was not different between the resection and combination therapy.•The combination of resection and RFA may be an effective strategy for multiple HCC.
Summary
Background
Whether direct‐acting anti‐viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear.
Aims
To evaluate changes in ...liver stiffness and steatosis in patients with HCV who received direct‐acting anti‐viral therapy and achieved sustained virological response (SVR).
Methods
A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct‐acting anti‐viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging‐determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24).
Results
Alanine aminotransferase and homeostatic model assessment‐insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70‐4.18) kPa and 2.80 (2.40‐3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7‐3.4)% and 1.9 (1.3‐2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24.
Conclusion
Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct‐acting anti‐viral therapy (UMIN000017020).
Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral ...blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled “optimization of the h-CLAT protocol” within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24
h and 48
h exposure to six known allergens (e.g., DNCB,
pPD, NiSO
4) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1×, 0.5×, 1×, and 2× of the 50% inhibitory concentration (IC
50)) were evaluated. IC
50 was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24
h and a 48
h exposure. We also found that the 24
h treatment time tended to have a better accuracy than the 48
h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24
h and the 48
h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen/non-allergen, especially using THP-1 cells. These results suggest that our method, human Cell Line Activation Test (h-CLAT), using human cell lines THP-1 and U-937, but especially THP-1 cells at 24
h treatment, may be a useful in vitro skin sensitization model to predict various contact allergens.
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