An outbreak of coronavirus disease 2019 (COVID-19) that began in Wuhan, China, has spread rapidly to many countries. We herein report four cases of COVID-19 confirmed in Japan among passengers of the ...cruise ship Diamond Princess and describe the clinical features, clinical course, and progression of chest computed tomographic images, chest radiographs, and treatment. Although these four patients had symptoms that included a fever, malaise, runny nose, and cough, one patient had no symptoms on admission. Two of the four patients needed mechanical ventilation due to respiratory deterioration. One of the patients who required mechanical ventilation was transferred to a higher-level medical institution. Except for that patient, the other three patients were able to return home under their own power. Every patient took lopinavir/ritonavir, which was considered the most effective treatment at the time. We used it after receiving approval from the ethics committee in our hospital. In this case report, we emphasize that some patients need to be carefully monitored, even if their respiratory condition is stable at the initial presentation, as their respiratory status may deteriorate rapidly within a few days after oxygen administration begins.
TRPM3 is a non-selective cation channel that is activated by neural steroids such as pregnenolone sulfate, nifedipine, and clotrimazole. Despite the number of TRPM3 variants, few reports have ...described functional analyses of these different TRPM3 types. Here we identified a new TRPM variant from mouse dorsal root ganglion, termed TRPM3γ3. We classified TRPM3γ3 and another known variant (variant 6) into the γ subtype, and analyzed the TRPM3γ variants. mRNA expression of TRPM3γ was higher than that of TRPM3α variants in the mouse dorsal root ganglion. In Ca
-imaging of HEK293 cells expressing either the TRPM3γ variants or TRPM3α2, increases in cytosolic Ca
concentrations (Ca
) induced by pregnenolone sulfate or nifedipine were smaller in cells expressing the TRPM3γ variants compared to those expressing TRPM3α2. On the other hand, co-expression of TRPM3γ variants had no effect on Ca
increases induced by pregnenolone sulfate or nifedipine treatment of HEK293 cells expressing TRPM3α2. In Xenopus oocytes, small responses of TRPM3γ variants to chemical agonists compared to TRPM3α2 were also observed. Interestingly, Xenopus oocytes expressing TRPM3α2 displayed heat-evoked currents with clear thresholds of about 40 °C that were larger than those evoked in oocytes expressing TRPM3γ variants. Overall, these findings indicate that TRPM3γ variants have low channel activity compared to TRPM3α.
Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota–derived compounds remain to be understood. Therefore, in this study, we ...investigated the effects of KetoA 10‐oxo‐12(Z)‐octadecenoic acid—a linoleic acid metabolite produced by gut lactic acid bacteria—on whole‐body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet‐induced obesity. By using Ca2+ imaging and whole‐cell patch‐clamp methods, KetoA was noted to potently activate transient receptor potential vanilloid 1 (TRPV1) and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up‐regulated genes that are related to brown adipocyte functions, including uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later diminished in the presence of a β‐adrenoreceptor blocker. By using obese and diabetic model KK‐Ay mice, we further show that KetoA intake ameliorated obesity‐associated metabolic disorders. In the absence of any observed KetoA‐induced antiobesity effect or UCP1 up‐regulation in TRPV1‐deficient mice, we prove that the antiobesity effect of KetoA was caused by TRPV1 activation‐mediated browning in WAT. KetoA produced in the gut could therefore be involved in the regulation of host energy metabolism.—Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.‐I., Takahashi, H., Ohue‐Kitano, R., Jheng, H.‐F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. 10‐oxo‐12(Z)‐octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1. FASEB J. 31, 5036–5048 (2017). www.fasebj.org
Epigenetic modifications play important roles in the regulation of gene expression determining cellular phenotype as well as various pathologies such as cancer. Although the loss of keratin 13 ...(KRT13) is reportedly linked to malignant transformation of oral epithelial cells, the molecular mechanisms through which KRT13 is repressed in oral squamous cell carcinoma (OSCC) remain unclear. The aim of this study is to identify the epigenetic alterations of the KRT13 gene in OSCCs.
We investigated KRT13 expression levels and chromatin modifications of the KRT13 promoter in the three OSCC cell lines (HSC4, HSC3, and SAS). The expression levels of KRT13 protein and mRNA were analyzed by western blotting and quantitative reverse-transcription polymerase chain reaction, respectively, and the localization of KRT13 protein was detected by immunofluorescence. DNA methylation and histone modifications in the KRT13 promoter were determined by bisulfite sequencing and chromatin immunoprecipitation (ChIP), respectively. For the pharmacological depletion of Polycomb repressive complex 2 (PRC2), cells were treated with 3-deazaneplanocin A (DZNep).
KRT13 expression was transcriptionally silenced in the HSC3 and SAS cells and post-transcriptionally repressed in the HSC4 cells, while the KRT13 promoter was hypermethylated in all of the three OSCC cell lines. ChIP analysis revealed that PRC2-mediated trimethylation of Lys 27 on histone H3 (H3K27me3) was increased in the KRT13 promoter in the HSC3 and SAS cells. Finally, we demonstrated that the treatment of SAS cells with DZNep reactivated the transcription of KRT13 gene.
Our data provide mechanistic insights into the epigenetic silencing of KRT13 genes in OSCC cells and might be useful for the development of diagnostic markers and novel therapeutic approaches against OSCCs.
ABSTRACT Introduction: Fractal analysis can be used to quantify data from medical images by calculating the fractal dimensions of structures. The method is based on the self-similarity of biological ...structures. We hypothesized that the fractal dimensions calculated from ultrasonographic images would fluctuate in heart disease. We investigated the application of fractal analysis for quantitative evaluation of ultrasonographic images of the myocardium. Methods: A total of 1000 individuals who underwent echocardiography between January 2003 and December 2020 were enrolled in this retrospective study. Participants were categorized as "diseased," with reduced left ventricular ejection fraction (LVEF), and normal. Causes of reduced LVEF included ischemic heart disease, cardiomyopathy, valvular heart diseases, arrhythmia, or unknown etiologies. Fractal dimensions were calculated from echocardiographic images acquired in motion mode. The region of interest was set as the ventricular septum or posterior wall in systole or diastole, respectively. Fractal analysis was performed using the box-counting method. Results: The fractal dimension of the ventricular septum and posterior wall were significantly larger in systole than in diastole among normal participants. The fractal dimension of the ventricular septum was larger in diastolic outline mode among diseased participants. However, the fractal dimension of the ventricular septum and posterior wall was decreased in systolic outline for the diseased group. Conclusions: Fractal analysis of echocardiographic images may be useful for performing quantitative evaluations of myocardium impairment. This noninvasive method using still images is easily applicable in clinical settings.
FK506 (tacrolimus) is an immunosuppressant widely used as an ointment in the treatment of atopic dermatitis. However, local application of FK506 can evoke burning sensations in atopic dermatitis ...patients, and its mechanisms are unknown. In this study, we found that FK506 activates transient receptor potential ankyrin 1 (TRPA1) channels. In Ca
-imaging experiments, increases in intracellular Ca
concentrations (Ca
) by FK506 were observed in HEK293T cells expressing hTRPA1 or hTRPM8. FK506-induced currents were observed in HEK293T cells expressing hTRPA1 or mTRPA1, but less or not at all in cells expressing hTRPV1 or hTRPM8 using a patch-clamp technique. FK506 also evoked single-channel opening of hTRPA1 in an inside-out configuration. FK506-induced Ca
increases were also observed in TRPA1-expressing mouse primary sensory neurons. Furthermore, injection of FK506 evoked licking or biting behaviors and these behaviors were almost abolished in TRPA1 knockout mice. These results indicate that FK506 might cause pain sensations through TRPA1 activation.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare condition of systemic vasculitis of small to medium-sized blood vessels. We herein report the case of a 75-year-old man who presented ...with hemiplegia on his right side due to cerebral infarction following myalgia and a high fever. He had no history of asthma or allergic rhinitis. He was diagnosed with EGPA based on the presence of eosinophilia, sinusitis suggested by magnetic resonance imaging, and muscle pathology. His hemiplegia improved rapidly after corticosteroid therapy. This case suggests that EGPA should be a differential diagnosis of cerebral infarction with myalgia and eosinophilia.
Neuronal imaging using SPECT Yamashina, Shohei; Yamazaki, Jun-ichi
European journal of nuclear medicine and molecular imaging
34, Številka:
6
Journal Article
Recenzirano
123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is one of only a few methods available for objective evaluation of cardiac sympathetic function at a clinical level. Disorders in cardiac ...sympathetic function play an important role in various heart diseases, and MIBG provides an abundance of useful information for evaluation of disease severity, prognosis, and therapeutic effects; this information is of particular value in patients with heart failure, ischemic heart diseases, or arrhythmic disorders. On the other hand, the quantitative indices for MIBG differ between institutions, and evidence has not been sufficiently well established for MIBG, compared with myocardial perfusion imaging, in ischemic heart diseases.
In view of these difficulties, this review provides fundamental information regarding MIBG, its usefulness for various diseases and future difficulties.
The pro-inflammatory cytokine interleukin 1
(IL-1
) induces the synthesis of prostaglandin E
by upregulating cyclooxygenase-2 (COX-2) in the synovial tissue of individuals with autoimmune diseases, ...such as rheumatoid arthritis (RA). IL-1
-mediated stimulation of NF-
B and MAPK signaling is important for the pathogenesis of RA; however, crosstalk(s) between NF-
B and MAPK signaling remains to be understood. In this study, we established a model for IL-1
-induced synovitis and investigated the role of NF-
B and MAPK signaling in synovitis. We observed an increase in the mRNA and protein levels of COX-2 and prostaglandin E
release in cells treated with IL-1
. NF-
B and ERK1/2 inhibitors significantly reduced IL-1
-induced COX-2 expression. IL-1
induced the phosphorylation of canonical NF-
B complex (p65 and p105) and degradation of I
B
. IL-1
also induced ERK1/2 phosphorylation but did not affect the phosphorylation levels of p38 MAPK and JNK. IL-1
failed to induce COX-2 expression in cells transfected with siRNA for p65, p105, ERK1, or ERK2. Notably, NF-
B inhibitors reduced IL-1
-induced ERK1/2 phosphorylation; however, the ERK1/2 inhibitor had no effect on the phosphorylation of the canonical NF-
B complex. Although transcription and translation inhibitors had no effect on IL-1
-induced ERK1/2 phosphorylation, the silencing of canonical NF-
B complex in siRNA-transfected fibroblasts prevented IL-1
-induced phosphorylation of ERK1/2. Taken together, our data indicate the importance of the non-transcriptional/translational activity of canonical NF-
B in the activation of ERK1/2 signaling involved in the IL-1
-induced development of autoimmune diseases affecting the synovial tissue, such as RA.
Transforming growth factor-β1 (TGF-β1) reportedly causes the differentiation of fibroblasts to myofibroblasts during wound healing. We investigated the mechanism underlying the activation of latent ...TGF-β1 released by keratinocytes in efforts to identify promising pharmacological approaches for the prevention of hypertrophic scar formation. A three-dimensional collagen gel matrix culture was prepared using rat keratinocytes and dermal fibroblasts. Stratified keratinocytes promoted the TGF receptor–dependent increase in α-smooth muscle actin (α-SMA) immunostaining and mRNA levels in fibroblasts. Latent TGF-β1 was found to be localized suprabasally and secreted. α-SMA expression was inhibited by an anti-αv-integrin antibody and a matrix metalloproteinase (MMP) inhibitor, GM6001. In a two-dimensional fibroblast culture, α-SMA expression depended on the production of endogenous TGF-β1 and required αv-integrin or MMP for the response to recombinant latent TGF-β1. In keratinocyte-conditioned medium, MMP-dependent latent TGF-β1 secretion was detected. Applying this medium to the fibroblast culture enhanced α-SMA production. This effect was decreased by GM6001, the anti-αv-integrin antibody, or the preabsorption of latent TGF-β1. These results indicate that keratinocytes secrete latent TGF-β1, which is liberated to fibroblasts over distance and is activated to produce α-SMA with the aid of a positive-feedback loop. MMP inhibition was effective for targeting both keratinocytes and fibroblasts in this model. Supplementary Figure: available only at http://dx.doi.org/10.1254/jphs.13209FP
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