Abstract
Background
Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and it can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut ...microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear.
Results
We found that the consumption of the prebiotic inulin markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice. Inulin consumption resulted in global changes in the gut microbiome, including concomitant enrichment of the genera
Bacteroides
and
Blautia
, and increased concentrations of short-chain fatty acids, particularly acetate, in the gut lumen and portal blood. The consumption of acetate-releasing resistant starch protected against NAFLD development. Colonisation by
Bacteroides acidifaciens
and
Blautia producta
in germ-free mice resulted in synergetic effects on acetate production from inulin. Furthermore, the absence of free fatty acid receptor 2 (FFAR2), an acetate receptor, abolished the protective effect of inulin, as indicated by the more severe liver hypertrophy, hypercholesterolaemia and inflammation. These effects can be attributed to an exacerbation of insulin resistance in the liver, but not in muscle or adipose tissue.
Conclusion
These findings demonstrated that the commensal microbiome–acetate–FFAR2 molecular circuit improves insulin sensitivity in the liver and prevents the development of NAFLD/NASH.
A direct diode pumped continuous-wave Ti:sapphire laser (DDPTS) is presented. A bow-tie geometry with optical diode is chosen for unidirectional single-mode operation. Frequency selection is ...performed with a standard combination of birefringent filter and etalon. To accomplish mode-hop free frequency tuning the piezo-driven etalon is stabilized to one of the cavity modes via dither-locking method. To suppress environmental fluctuations the cavity-mode is additionally locked to an external optical cavity with low frequency drift. Feasibility of the setup for high-resolution spectroscopy is demonstrated by saturated absorption spectroscopy of the D
2
line of Rubidium.
A direct approach to the P-matrix or P0-matrix problem is to evaluate all the principal minors of matrix A using standard numerical linear algebra techniques with O(2nn3) computational time ...complexity. The computational time complexity of the P-matrix problem has been reduced from O(2nn3) to O(2n) by applying recursively a criterion for P-matrices based on Schur complementation. But this algorithm can be not directly applied to test the P0-matrices because the Schur complementation can be not computed when some zero diagonal elements appear.
This paper proposes an asymptotic approach for testing P0-matrices with O(2n) computational time complexity. Some numerical examples show that the proposed algorithm is effective for testing P0-matrices.
Purpose
To investigate the usefulness of the positron emission tomography response criteria in solid tumors 1.0 (PERCIST1.0) for predicting tumor response to neoadjuvant chemotherapy and prognosis ...and determine whether PERCIST improvements are necessary for esophageal squamous cell carcinoma (ESCC) patients.
Patients and methods
We analyzed the cases of 177 ESCC patients and examined the association between PERCIST and their pathological responses. Associations of whole-PERCIST with progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and Cox proportional hazards model. To investigate potential PERCIST improvements, we used the survival tree technique to understand patients’ prognoses.
Results
There were significant correlations between the pathologic response and PERCIST of primary tumor (
p
< 0.001). The optimal cutoff value of the primary tumors’ SULpeak response to classify pathologic responses was −50.0%. The diagnostic accuracy of SULpeak response was 87.3% sensitivity, 54.1% specificity, 68.9% accuracy, positive predictive value 60.5%, and negative predictive value 84.1%. Whole-PERCIST was significantly associated with PFS and OS. The survival tree results indicated that a high reduction of the whole SULpeak response was significantly correlated with the patients’ prognoses. The cutoff values for the separation of prognoses were − 52.5 for PFS and − 47.1% for OS.
Conclusion
PERCIST1.0 can help predict tumor responses and prognoses. However,
18
F-FDG-PET/CT tends to underestimate residual tumors in histopathological response evaluations. Modified PERCIST, in which the partial metabolic response is further classified by the SULpeak response (−50%), might be more appropriate than PERCIST1.0 for evaluating tumor responses and stratifying high-risk patients for recurrence and poor prognosis.
Refractory peritoneal carcinomatosis is a common terminal feature of epithelial ovarian cancer (EOC). Previous reports have suggested that immunotherapy is a promising therapeutic strategy for EOC. ...Interleukin (IL)‑33 is a member of the IL‑1 superfamily of cytokines. The role of IL‑33 in tissue inflammation and promoting type 2 immune responses has been established, and recently, there is accumulating evidence to suggest the involvement of IL‑33 in carcinogenesis. In this study, we focused on the association between the tumor expression of IL‑33 and ovarian peritoneal carcinomatosis. We used an immunosufficient murine model of peritoneal carcinomatosis and human EOC samples. The overexpression of IL‑33 in the ID8 mouse EOC cell line tumors significantly prolonged the survival of immunocompetent mice in the peritoneal carcinomatosis setting, but not in the subcutaneous model. In addition, the silencing of IL‑33 in ID8‑T6 cells (subclone with high dissemination potential) significantly shortened the survival of the tumor‑bearing mice. This was likely due to the intratumoral accumulation of CD8+ and CD4+ T cells, and a decrease in CD11b+Gr1+ cells. Furthermore, IL‑33 induced the intraperitoneal microenvironment favoring tumor elimination through the inhibition of differentiation into CD11b+Gr1+ cells. On the whole, the findings of this study suggest IL‑33 to be a cytokine that reflects antitumor peritoneal conditions. Further investigation of the antitumorigenic role of IL‑33 may aid in the development of more effective therapeutic approaches for the treatment of EOC with peritoneal carcinomatosis.
Key message
IgG4‐related lung disease (IgG4‐RLD) can present with various types of radiological findings such as nodule, ground‐glass opacity, alveolar interstitial, and bronchovascular involvement. ...IgG4‐RLD generally manifests as mild clinical symptoms, despite evidence from the image findings. Herein we report an asymptomatic patient with IgG4‐RLD mimicking multiple pleural disseminated lung cancer.
Herein we report an asymptomatic patient with IgG4‐related lung disease mimicking multiple pleural disseminated lung cancer.
Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical ...settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search.
Congenital antithrombin (AT) deficiency, which arises from various SERPINC1 defects, is an autosomal-dominant thrombophilic disorder associated with a high risk of recurrent venous thromboembolism.
...We investigated SERPINC1 defects in Japanese patients with congenital AT deficiency who developed venous thromboembolism or had a family history of deep vein thrombosis. We analyzed the full DNA sequences of SERPINC1 exons and exon-intron junctions by PCR-mediated direct sequencing. If no mutation was found, multiplex ligation-dependent probe amplification (MLPA) was conducted for the relative quantification of the copy number of all exons in SERPINC1. If splice-site mutations were detected, mRNA splicing abnormalities were further investigated using an in vitro cell-based exontrap assay.
We identified 19 different SERPINC1 abnormalities, including 8 novel mutations, in 21 Japanese patients with AT deficiency. These abnormalities were distributed as follows: 9 missense mutations (42.9%), 3 nonsense mutations (14.3%), 1 splice-site mutation (4.8%), 2 small insertions (9.5%), 2 deletion mutations (9.5%) and 4 large deletions (19.0%). Cases with large deletions of SERPINC1 included Alu-mediated gene rearrangements and non-Alu-mediated complex gene rearrangements; the latter could conceivably be explained using the fork stalling and template switching (FoSTeS) model.
We identified a variety of SERPINC1 defects in Japanese patients with AT deficiency. The SERPINC1 mutations detected in patients with type I AT deficiency included single nucleotide missense or nonsense mutations, small intragenic insertions or deletions, and large genomic structural deletions. Large deletions of SERPINC1 were caused by various recurrent or non-recurrent complex genomic rearrangement mutations.
•Congenital antithrombin deficiency is caused by various SERPINC1 abnormalities.•We identified 8 novel SERPINC1 mutations in 21 Japanese antithrombin deficiencies.•A unique genomic structural mutation in type I antithrombin deficiency was found.•Deletions of SERPINC1 were due to recurrent or non-recurrent gene rearrangements.
Abstract
We present kinematics of six local extremely metal-poor galaxies (EMPGs) with low metallicities (0.016–0.098
Z
⊙
) and low stellar masses (10
4.7
–10
7.6
M
⊙
). Taking deep ...medium/high-resolution (
R
∼ 7500) integral-field spectra with 8.2 m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with H
α
emission. Carefully masking out substructures originating by inflow and/or outflow, we fit three-dimensional disk models to the observed H
α
flux, velocity, and velocity dispersion maps. All the EMPGs show rotational velocities (
v
rot
) of 5–23 km s
−1
smaller than the velocity dispersions (
σ
0
) of 17–31 km s
−1
, indicating dispersion-dominated (
v
rot
/
σ
0
= 0.29–0.80 < 1) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of
f
gas
≃ 0.9–1.0. Comparing our results with other H
α
kinematics studies, we find that
v
rot
/
σ
0
decreases and
f
gas
increases with decreasing metallicity, decreasing stellar mass, and increasing specific star formation rate. We also find that simulated high-
z
(
z
∼ 7) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope observations at
z
∼ 7.
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