The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post ...COVID-19 condition. Based on the results of our earlier study showing that “general fatigue” mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients’ backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = −0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.
The expression of podoplanin is reportedly involved in collective cell invasion, which is independent from the epithelial–mesenchymal transition (EMT). We focused on the expression of podoplanin in ...esophageal squamous cell carcinomas (ESCC) and investigated the correlation of podoplanin and EMT‐related markers, and evaluated its prognostic significance. Five ESCC cell lines were subjected to western blot analysis for podoplanin and EMT markers. The effects of podoplanin on EMT and carcinoma invasion were evaluated with wound healing assays, invasion assays and 3‐D culture. Transfection of ectopic podoplanin into a podoplanin‐negative ESCC cell line (TE‐15) induced cell migration and invasive activity (P < 0.001 and P < 0.05, respectively) without downregulation of E‐cadherin. In contrast, transfection of si‐podoplanin RNA into a podoplanin‐positive ESCC cell line (TE‐13) reduced cell migration and invasive activity (P < 0.05). We reviewed 101 patients who had undergone esophagectomy for ESCC. Podoplanin expression was observed in 58 patients (57.4%), and positive expression was positively correlated with expression of E‐cadherin (P < 0.01), deeper wall invasion (P < 0.01), venous invasion (P < 0.05) and poorer prognosis (P < 0.01). Multivariate Cox analysis revealed that expression of podoplanin was a significant and independent unfavorable predictor of survival (P < 0.05). These data suggest that podoplanin is significantly associated with and likely contributes to ESCC invasion in the absence of EMT.
We focused on the expression of podoplanin in esophageal squamous cell carcinoma and inestigated the correlation of podoplanin and epithelial‐mesenchymal transition. Podoplanin was significantly associated with and likely contibutes to the invasion of esophageal squamous cell caricinoma in absence of epithelial mesenchymal transition.
Hepatitis B virus (HBV) X (HBx) protein is associated with hepatocellular carcinogenesis via the induction of malignant transformation and mitochondrial dysfunction. However, the association between ...HBx and histone methyltransferase in carcinogenesis has not been fully clarified. In the current study, we analyzed the association between HBx and the histone methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39h1) using HBV replication models.
We constructed several HBx and SUV39h1 expression plasmids and analyzed the association between HBx and SUV39h1 with respect to HBV replication and hepatocarcinogenesis.
SUV39h1 up-regulation was observed in HBV-infected humanized mouse livers and clinical HBV-related hepatocellular carcinoma tissues, indicating that SUV39h1 expression might be regulated by HBV infection. Through in vitro analysis, we determined that the coactivator domain of HBx interacts with the PSET (PostSET) and SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domains of SUV39h1. The expression levels of 4 genes, activating transcription factor 6, α-fetoprotein, growth arrest and DNA damage-inducible 45a, and dual-specificity phosphatase 1, known to induce carcinogenesis via HBx expression, were up-regulated by HBx and further up-regulated in the presence of both HBx and SUV39h1. Furthermore, histone methyltransferase activity, the main function of SUV39h1, was enhanced in the presence of HBx.
We demonstrated that SUV39h1 and HBx enhance each other's activity, leading to HBx-mediated hepatocarcinogenesis. We propose that regulation of this interaction could help suppress development of hepatocellular carcinoma.
In this study, we investigate what kinds of feelings consumers have while watching TV commercials in the presence of words (lines, a jingle, a sound logo, and on-screen words) that were later ...remembered, by using an electroencephalogram (EEG) and questionnaires. Every day, a great number of TV commercials are broadcasting. Since TV commercials have become indispensable advertising media, it is essential for advertising agencies to create attractive and memorable TV commercials for consumers. This leads to many evaluations of TV commercials. Yet, few studies focused on consumers’ feelings during TV commercials along with words that remained in their minds afterward. In order to reveal this point, we carry out an experiment with Japanese award-winning and non-award-winning TV commercials. We also examine effects of words on consumers’ memories with time: soon after watching, a day later, a week later, and a month later. As the results of our EEG analysis, different consumers’ feelings were obtained in different cases. There was a strong correlation between concentration and stress while watching the award-winning TV commercials along with words, which consumers remembered not only soon after watching but also a month later. However, this tendency was not applicable to the non-award-winning TV commercials. Thus, we consider that the effects of memorable TV commercials along with words on consumers’ feelings could vary depending on winning an award or not.
Alcohol dehydrogenase (Adh) is the key enzyme in alcohol fermentation. We analyzed Adh expression in order to clarify the role of Adh of soybeans (
Glycine max
) to flooding stress. Proteome analysis ...confirmed that expression of Adh is significantly upregulated in 4-day-old soybean seedlings subjected to 2 days of flooding. Southern hybridization analysis and soybean genome database search revealed that soybean has at least 6
Adh
genes. The
GmAdh2
gene that responded to flooding was isolated from soybean cultivar Enrei.
Adh2
expression was markedly increased 6 h after flooding and decreased 24 h after floodwater drainage. In situ hybridization and Western blot indicated that flooding strongly induces Adh2 expression in RNA and protein levels in the root apical meristem. Osmotic, cold, or drought stress did not induce expression of
Adh2
. These results indicate that
Adh2
is a flooding-response specific soybean gene expressed in root tissue.
Image segmentation of medical images is a challenging problem with several still not totally solved issues, such as noise interference and image artifacts. Region-based and histogram-based ...segmentation methods have been widely used in image segmentation. Problems arise when we use these methods, such as the selection of a suitable threshold value for the histogram-based method and the over-segmentation followed by the time-consuming merge processing in the region-based algorithm. To provide an efficient approach that not only produce better results, but also maintain low computational complexity, a new region dividing based technique is developed for image segmentation, which combines the advantages of both regions-based and histogram-based methods. The proposed method is applied to the challenging applications: Gray matter (GM), White matter (WM) and cerebro-spinal fluid (CSF) segmentation in brain MR Images. The method is evaluated on both simulated and real data, and compared with other segmentation techniques. The obtained results have demonstrated its improved performance and robustness.
To compare postoperative changes in visual acuity between the transnasal endoscopic approach and the transcaruncular approach when comparison of preoperative values used for medial orbital wall ...decompression in patients with dysthyroid optic neuropathy.
We included 14 patients (23 sides) and divided them into a transnasal group (11 sides, 8 patients) and a transcaruncular group (12 sides, 6 patients). Visual acuity was examined preoperatively, on postoperative days 1, 3, and 7, and at a final follow-up visit. The differences in postoperative improvement of the logarithm of the minimum angle of resolution (logMAR) visual acuity and critical flicker frequency (CFF) between the two surgical groups at each time point were analyzed using the Mann–Whitney U test.
Postoperative improvement in logMAR visual acuity on postoperative days 1 and 3 and that in CFF on postoperative day 1 were greater in the endonasal group than in the transcaruncular group (P < 0.050). Vision was improved or maintained in all patients in the transnasal group at the final follow-up. One patient in the transcaruncular group had loss of vision on one side and decreased vision on the other side after surgery.
Medial orbital decompression appears to provide better postoperative vision when performed by the transnasal approach than by the transcaruncular approach in patients with dysthyroid optic neuropathy.
Moyamoya disease (MIM 252350) is characterized by stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries and by abnormal vascular networks at the base of the brain. ...There is a high incidence of moyamoya disease in Asia, especially in Japan. Multifactorial inheritance is estimated with lambda(s)>40. Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 maximum LOD score (MLS) of 3.6 and suggestive evidence for linkage to 12p12 (MLS=2.3). The present study revealed a novel locus for moyamoya disease.
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disorder characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor gain-of-function ...mutations in ACVR1 (FOP-ACVR1), a type I receptor for bone morphogenetic proteins. Despite numerous studies, no drugs have been approved for FOP. Here, we developed a high-throughput screening (HTS) system focused on the constitutive activation of FOP-ACVR1 by utilizing a chondrogenic ATDC5 cell line that stably expresses FOP-ACVR1. After HTS of 5,000 small-molecule compounds, we identified two hit compounds that are effective at suppressing the enhanced chondrogenesis of FOP patient-derived induced pluripotent stem cells (FOP-iPSCs) and suppressed the heterotopic ossification (HO) of multiple model mice, including FOP-ACVR1 transgenic mice and HO model mice utilizing FOP-iPSCs. Furthermore, we revealed that one of the hit compounds is an mTOR signaling modulator that indirectly inhibits mTOR signaling. Our results demonstrate that these hit compounds could contribute to future drug repositioning and the mechanistic analysis of mTOR signaling.
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•Established a screening system for fibrodysplasia ossificans progressiva (FOP)•Identified two hit compounds that are effective in multiple FOP model mice•An mTOR signaling modulator opens the door to a therapeutic strategy
Focusing on the ligand-independent constitutive activation of mutated ACVR1 in fibrodysplasia ossificans progressiva (FOP) patients, Ikeya and colleagues have identified two hit compounds that were effective in multiple FOP model mice. One of the hit compounds, TAK 165, was an mTOR signaling modulator that indirectly regulated enhanced mTOR signaling. These findings shed light on a therapeutic strategy for FOP.
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