MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc ...activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRAS
(HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression. AKT/HRAS-induced tumorigenesis was almost completely abolished when MadMyc, a competitive Myc inhibitor, was expressed simultaneously. The Tet-On induction of MadMyc in preneoplastic cells significantly inhibited the progression of AKT/HRAS-induced tumours; its induction in transformed cells suppressed their proliferative activity with alterations in lipid metabolism and protein translation. Transposon-mediated Myc overexpression facilitated tumorigenesis by AKT or HRAS, and when it was co-introduced with AKT and HRAS, diffusely infiltrating tumours without lipid accumulation developed as early as 2 weeks. Examination of the dose-responses of Myc in the enhancement of AKT/HRAS-induced tumorigenesis revealed that a reduction to one-third retained enhancing effect but three-times greater introduction damped the process with increased apoptosis. Myc overexpression suppressed the mRNA expression of proteins involved in the synthesis of fatty acids, and when combined with HRAS introduction, it also suppressed the mRNA expression of proteins involved in their degradation. Finally, the MYC-positive human hepatocellular carcinoma was characterized by the cytoplasm devoid of lipid accumulation, prominent nucleoli and a higher proliferative activity. Our results demonstrate that in hepatocarcinogenesis induced by both activated AKT and HRAS, activation of endogenous Myc is an enhancing factor and adequate levels of Myc deregulation further facilitate the process with alterations in cellular metabolism.
Aims
This study aimed to investigate the effect of Bacillus subtilis var. natto on the susceptibility of the model host, Caenorhabditis elegans, to bacterial infection.
Methods and Results
...Caenorhabditis elegans worms were fed with a standard food consisting of Escherichia coli OP50 strain (control) or B. subtilis (natto) during their larval stage. The worms were then infected with pathogenic bacteria. We analyzed their survival time and RNA sequencing‐based transcriptome. Upon infection with Staphylococcus aureus and Enterococcus faecalis, the survival time of B. subtilis (natto)‐fed worms was longer than that of the control. Transcriptome analyses showed upregulation of genes associated with innate immunity and defense response to gram‐positive bacteria in B. subtilis (natto)‐fed worms.
Conclusions
Bacillus subtilis (natto) conferred an increased resistance of C. elegans to gram‐positive bacteria. Our findings provided insights into the molecular mechanisms underlying B. subtilis (natto)‐regulated host immunity and emphasized its probiotic properties for preventing and alleviating infections caused by gram‐positive bacteria.
Significance and Impact of the Study
To the best of our knowledge, this is the first study to show that B. subtilis (natto) confers specific resistance against gram‐positive bacteria.
In this study, an electromagnetic field approach is used to clarify the mechanism of on-body transmission. A homogeneous cylinder is used as an arm model, and the characteristic of electromagnetic ...field distribution around the cylinder is extracted based on surface wave approximation and numerical analysis, respectively. As a result, the surface wave approximation is found to be valid in the far-field region from the excitation source in the frequency range of 10-150 MHz. Moreover, in the near-field region of the excitation source, the attenuation along the cylinder surface is much smaller than that toward the outside. In addition, by using a numerical human body model, the path loss for on-body transmission is also formulated.
Disopyramide reduces the left ventricular outflow tract (LVOT) pressure gradient and improves symptoms in humans with hypertrophic obstructive cardiomyopathy (HOCM). However, the efficacy of ...disopyramide in cats has not been reported. We treated a cat with HOCM with carvedilol and disopyramide cotherapy and monitored the changes in LVOT flow velocity and N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration. A 10-month-old neutered male Norwegian Forest cat was referred with a moderate systolic cardiac murmur. Echocardiography revealed thickening of the left ventricular wall, systolic anterior motion of the mitral valve leaflets, and turbulent aortic flow in the LVOT at systole. The LVOT flow velocity was 5.6 m/s. The plasma NT-proBNP concentration exceeded 1,500 pmol/L. The cat was diagnosed with HOCM and the β-blocker carvedilol was started and gradually increased to 0.30 mg/kg, bid. After 57 days, the LVOT flow velocity (4.8 m/s) and plasma NT-proBNP concentration (870 pmol/L) had decreased but remained elevated. Therefore, disopyramide was added at 5.4 mg/kg po bid and increased to 10.9 mg/kg po bid after 22 days. After 141 days of carvedilol and disopyramide treatment, the systolic anterior motion of the mitral valve leaflets had disappeared and the LVOT flow velocity and plasma NT-proBNP concentration had decreased to 0.7 m/s and 499 pmol/L, respectively. No adverse effect has been observed during the follow-up. Disopyramide might relieve feline LVOT obstruction after only partial response to a beta-blocker. Further large-scale studies are required to investigate the efficacy and safety of disopyramide use in cats with moderate to severe HOCM.
The total direct count (TDC) microbial enumeration method is rapid and suitable for analysing environmental samples containing numerous un‐culturable micro‐organisms. Conventional TDC methods require ...the addition of a fluorescent stain and are thus unsuitable for automatic monitoring. We unexpectedly found that heated micro‐organisms emit strong autofluorescence. This study was conducted to determine how heating enhances the autofluorescence of bacteria and fungi and to evaluate whether the phenomenon could be exploited to develop a new TDC method. Bacterial autofluorescence was augmented by heating cells at 200°C. ELISA results indicated that levels of advanced glycation end products (AGEs) increased in heated microbes. Catechin, an inhibitor of the Maillard reaction, disrupted the intensification of autofluorescence. These results suggest that the enhanced autofluorescence is associated with the formation of AGEs and that the reaction could be utilized as alternative probe in TDC methods.
Significance and Impact of the Study
Autofluorescence of bacteria and fungi was prominently intensified by heat treatment at 200°C. This phenomenon was associated with advanced glycation end products formed in micro‐organisms via the Maillard reaction. The fluorescence signal was strong enough to be utilized as an alternative probe for fluorescent dye in the total direct count method. This phenomenon could be incorporated in an automatic apparatus for microbial enumeration, as it does not require staining.
Significance and Impact of the Study: Autofluorescence of bacteria and fungi was prominently intensified by heat treatment at 200°C. This phenomenon was associated with advanced glycation end products formed in micro‐organisms via the Maillard reaction. The fluorescence signal was strong enough to be utilized as an alternative probe for fluorescent dye in the total direct count method. This phenomenon could be incorporated in an automatic apparatus for microbial enumeration, as it does not require staining.
Purpose
Stable iodine prophylaxis helps prevent childhood thyroid cancer in nuclear emergencies; however, there is limited information on its effect on thyroid function. This study aimed to examine ...thyroid function and autoimmunity among children and adolescents that took stable iodine after the Fukushima Nuclear Disaster.
Methods
For this observational study, data were obtained from children and adolescents that underwent thyroid cancer screening at Hirata Central Hospital from April 2012 to March 2018. Participant characteristics, including possible hypothyroidism and hyperthyroidism, were compared between the prophylaxis and no-prophylaxis groups. Multivariable logistic regression models were used to assess for possible hypothyroidism, autoantibodies positive, and hyperthyroidism.
Results
A total of 1,225 participants with stable iodine prophylaxis and 3,946 without prophylaxis were enrolled. Of those participants, blood samples were available for 144 and 1,201 participants in the prophylaxis and no-prophylaxis groups, respectively. There were 17 (11.8%) and 146 cases (12.2%) of possible hypothyroidism or autoantibodies positive cases in the prophylaxis and no-prophylaxis groups, respectively, and there were no cases and 3 cases (0.2%) of possible hyperthyroidism in those two groups, respectively. Multivariable analysis for possible hypothyroidism revealed no association between stable iodine intake and possible hypothyroidism or autoantibodies positive odds ratio 0.716 (95% confidence interval 0.399–1.284) (
p
= 0.262). We did not perform multivariable analysis for hyperthyroidism due to the limited number of cases.
Conclusion
Significant adverse effects of stable iodine intake on thyroid function were not observed among children and adolescents 7 years after the Fukushima Nuclear Disaster.
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