MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes

GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-expression of miR-133 reduced the protein level of KLF15, which reduced the level of the downstream target GLUT4. Cardiac myocytes infected with lenti-decoy, in which the 3′UTR with tandem sequences complementary to miR-133 was linked to the luciferase reporter gene, had decreased miR-133 levels and increased levels of GLUT4. The expression levels of KLF15 and GLUT4 were decreased at the left ventricular hypertrophy and congestive heart failure stage in a rat model. The present results indicated that miR-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiomyocytes

Fluid Mode Spectroscopy for measuring dynamic viscosity of fluids in open cylindrical containers

On a daily basis we stir tee or coffee with a spoon and leave it to rest. We know empirically the larger the stickiness, viscosity, of the fluid, more rapidly its velocity slows down. It is surprising, therefore, that the variation has not been utilized for measuring (dynamic) viscosity of fluids. This study shows that a spectroscopy decomposing a velocity field into fluid modes (Stokes eigenmodes) allows us to measure accurately the dynamic viscosity. The method, Fluid Mode Spectroscopy (FMS), is based on the fact that each Stokes eigenmode has its inherent decay rate of eigenvalue and that the dimensionless rate of the slowest decaying mode (SDM) is constant, dependent only on the normalized shape of a fluid container, obtained analytically for some shapes including cylindrical containers. The FMS supplements major conventional measuring methods with each other, particularly useful for measuring low dynamic viscosity.Comment: 18 pagese, 6 figure

Detection of Disease-specific Fusion Genes of Soft Tissue Tumors Using Formalin-fixed Paraffin-embedded Tissues; Its Diagnostic Usefulness and Factors Affecting the Detection Rates

[Background] Recent rapid advances in molecular biology have led the discovery of disease-specific novel fusion genes in a variety of soft tissue tumors. In this study, we attempted to detect these fusion genes using formalin-fixed paraffin-embedded (FFPE) tumor tissues and investigated their clinical utility and factors that affect the results of examination. [Methods] Reverse transcription polymerase chain reaction for the detection of tumor-specific fusion genes was performed using 41 FFPE tumor samples obtained from 37 patients representing nine histological types of soft tissue tumors that were diagnosed from 2006 to 2017 in our laboratory. [Results] Fusion genes in 19 (51.3%) out of 37 cases were detected successfully. Relatively high detection rates were observed in synovial sarcomas (100%, 4/4) and alveolar rhabdomyosarcomas (75%, 3/4). The detection rates of fusion genes were inversely correlated with the storage period of FFPE blocks. Decalcification by Plank-Rychlo solution significantly affected detection rates of the internal control gene (P = 0.0038). In contrast, there was no significant difference in detection rates between primary and metastatic lesion, or biopsy and resection material, or presence and absence of treatment history. [Conclusion] In certain histological types, detection of disease-specific fusion genes of soft tissue tumors using FFPE tissues showed high sensitivity and thus had diagnostic utility. However, due to the diversity of fusion patterns and the low-quality of nucleic acid, the detection rate as a whole was sluggish and required further improvement. For factors affecting the detection results, our results suggested that it was impossible to detect fusion genes by decalcified FFPE tissues, but it may be not necessary to consider factors such as the type of specimen (biopsy or resection) and treatment history of the patients when selecting the FFPE tissues

Activation of Antioxidative Functions by Radon Inhalation Enhances the Mitigation Effects of Pregabalin on Chronic Constriction Injury-Induced Neuropathic Pain in Mice

Radon inhalation brings pain relief for chronic constriction injury- (CCI-) induced neuropathic pain in mice due to the activation of antioxidative functions, which is different from the mechanism of the pregabalin effect. In this study, we assessed whether a combination of radon inhalation and pregabalin administration is more effective against neuropathic pain than radon or pregabalin only. Mice were treated with inhaled radon at a concentration of 1,000 Bq/m3 for 24 hours and pregabalin administration after CCI surgery. In mice treated with pregabalin at a dose of 3 mg/kg weight, the 50% paw withdrawal threshold of mice treated with pregabalin or radon and pregabalin was significantly increased, suggesting pain relief. The therapeutic effects of radon inhalation or the combined effects of radon and pregabalin (3 mg/kg weight) were almost equivalent to treatment with pregabalin at a dose of 1.4 mg/kg weight or 4.1 mg/kg weight, respectively. Radon inhalation and the combination of radon and pregabalin increased antioxidant associated substances in the paw. The antioxidant substances increased much more in radon inhalation than in pregabalin administration. These findings suggested that the activation of antioxidative functions by radon inhalation enhances the pain relief of pregabalin and that this combined effect is probably an additive effect

シンエコー ドップラーホウ ニヨル ソウボウベンリン セッカイカ ニ トモナウ ベンリン キョウサク ノ ジュウショウド ヒョウカ

Recently, mitral annular calcification (MAC) is a common finding with increasing of elderly orrenal failure patients. Mitral stenosis secondary to MAC is not rarely observed. Pressure halftime method by continuous wave Doppler echocardiography is often used to evaluate the severityof the stenotic mitral valve due to MAC. But, the method for calculating correct mitral orifice areais not established. We performed transthoracic Doppler echocardiography and cardiac catheterizationin 15 patients with rheumatic mital stenosis and 10 with mitral stenosis due to MAC, and calculatedthe severity of the mitral stenosis by pressure half time (PHT), continuity equation methods andGorlin formula. Pulsed tissue Doppler imaging methods were used for evaluating left ventricular(LV) early diastolic wall motion velocities. Results were as follows. 1) The mitral orifice areas determinedby PHT method were lower than those by continuity equation methods or Gorlin formulain patients with mitral stenosis due to MAC, and significant correlation was observed in rheumaticmital stenosis between the mitral orifice areas obtained by PHT and continuity equation methods,but not in mitral stenosis due to MAC. 2) The peak early diastolic LV myocardial velocities alonglong and short axes decreased significantly in mitral stenosis due to MAC than those in rheumaticmital stenosis. In conclusion, as mitral orfice area determined from PHT method is strongly influencedby early diastolic LV dysfunction in mitral stenosis due to MAC, continuity equation methodshould be recommended

Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine

AIM : Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa. METHODS : We compared the PGE2 and LTB4 levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group ; n=5), and the group treated for 8 weeks with an H2 blocker, ranitidine (H2 blocker group ; n=6), as well as in nonulcer subjects (control group ; n=5). RESULTS : The mucosal levels of PGE2 and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB4 level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE2 and decreased LTB4 levels in comparison to the H2 blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H2 blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H2 blocker group during the ulcer-healing stage. CONCLUSION : These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE2 production and reducing the LTB4 production

An incident involving blood sucking by a tick in a suburb in Japan

We encountered a patient whose blood was sucked by Haemaphysalis longicornis in the suburb of a business city in Tokushima prefecture in Japan. The tick, which had been attached to the lower limb of the patient for one week, measured 10 mm in length. There were no notable objective or subjective findings after the complete extirpation of the tick. The area had not been known in recent history to be a habitat of ticks, and, thus, this case is of importance in terms of predicting future trends of tick-borne diseases in Japan

A patient with adult extrahepatic portal obstruction, of which distinction from intrahepatic cholangiocarcinoma was difficult

A 51-year-old Japanese male with chief complaints of slightly high fever and epigastralgia was hospitalized at our facility. The inflammatory response was enhanced, and liver dysfunction was observed. Abdominal ultrasonography demonstrated a hyperechoic lesion occupying the left portal vein, and abdominal plain CT indicated a low density of the lesion with a clear boundary, measuring about 3 cm× 2 cm, between the porta hepatis and segment IV of the liver. Contrast CT showed no enhancement in the arterial and portal phases, but a reduction in the density inside the tumor in the equilibration phase was noted. MRI showed hypointensity by T1-weighted imaging and hyperintensity by T2-weighted imaging. Angiography demonstrated an obstruction of the left portal vein and superior mesenteric vein, and endoscopic retrograde cholangiography revealed a constriction in the left intrahepatic bile duct. Since the possibility of intrahepatic cholangiocarcinoma could not be excluded, extended left hepatectomy combined with caudate lobectomy was performed. The tumor, measuring 31 mm× 21 mm×20 mm, was pathohistologically diagnosed as an extrahepatic portal obstruction. Extrahepatic portal obstruction is an important disease that is sometimes difficult to rule out oncologic origin

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis

マイクロRNA-33bの阻害は非アルコール性脂肪肝炎を改善する --核酸医薬による治療応用へ--. 京都大学プレスリリース. 2023-06-13.Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element–binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element–binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism–related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH