Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity

老化神経幹細胞の若返りによるニューロン産生の復活と認知機能の改善. 京都大学プレスリリース. 2021-12-17.The regenerative potential of neural stem cells (NSCs) declines during aging, leading to cognitive dysfunctions. This decline involves up-regulation of senescence-associated genes, but inactivation of such genes failed to reverse aging of hippocampal NSCs. Because many genes are up-regulated or down-regulated during aging, manipulation of single genes would be insufficient to reverse aging. Here we searched for a gene combination that can rejuvenate NSCs in the aged mouse brain from nuclear factors differentially expressed between embryonic and adult NSCs and their modulators. We found that a combination of inducing the zinc finger transcription factor gene Plagl2 and inhibiting Dyrk1a, a gene associated with Down syndrome (a genetic disorder known to accelerate aging), rejuvenated aged hippocampal NSCs, which already lost proliferative and neurogenic potential. Such rejuvenated NSCs proliferated and produced new neurons continuously at the level observed in juvenile hippocampi, leading to improved cognition. Epigenome, transcriptome, and live-imaging analyses indicated that this gene combination induces up-regulation of embryo-associated genes and down-regulation of age-associated genes by changing their chromatin accessibility, thereby rejuvenating aged dormant NSCs to function like juvenile active NSCs. Thus, aging of NSCs can be reversed to induce functional neurogenesis continuously, offering a way to treat age-related neurological disorders

Transient Regional Wall Motion Abnormality and Increased Wall Thickness of the Left Ventricle in Acute Myopericarditis Occurring in the Puerperium

An unusual sequence of echocardiographic abnormalities of a 25-year-old female with acute myopericarditis was described. She presented with shortness of breath and a high body temperature after the birth of her first child. Regional asynergy and increased thickness of the left ventricle were transiently observed by echocardiography. It is considered that these abnormalities resulted from inflammatory changes in heart muscle such as edema, which was ascribable to acute myopericarditis in the puerperium

非侵襲的新指標である E' max/V 100 を用いた高血圧性肥大心の左室機能評価 : 非肥心， ST-T 変化を伴わない肥大心および ST-T 変化を伴う肥大心における比較検討

In forty-one essential hypertensive (EHT) patients with and without left ventricular hypertrophy (LVH), the left ventricular (LV) contractile performance was determined noninvasively using echocardiography. Classification was made with respect to the LVH, as measured by the sum of end-diatolic posterior wall thickness and interventricular septal thickness, and the presence of ST-T changes on electrocardiogram. Patients who had neither LVH nor ST-T changes formed Hl-subgroup (H1; n=22), those who had LVH without ST-T changes served as HZ-subgroup (H2; n =8), and those with LVH accompanied by ST-T changes constituted HS-subgroup (H3; n = 11), Sixteen normal volunteers served as normal control (N). LV systolic phase indices such as ejection fraction (EF), mean velocity of circumferential fiber shortening (mVcf) and end-systolic wall stress (ESWS), and diastolic indices such as isovolumic relaxation time (IVRT) and PR-AC interval were compared among each subgroup and normal subjects. All systolic and diastolic indices showed a depressed LV function in H3. Of these variables, the only IVRT could separate H2 from H1, suggesting deteriorated diastolic function at an early stage of hypertrophy. By altering LV systolic loading, peak systolic pressure-end-systolic volume relation, E’ max, and E' max-volume intercept at 100 mmHg peak systolic pressure ratio, E' max/V 100, were designated and these indices were used for the expression of the myocardial contractile state. E' max and E’ max/V 100 were significantly lower in H2 and H3 than in the control group, indicating depressed myocardial contractility. The value of these variables in Hl did not differ from N, indicating a normal level of inotropic state. E’ max/V 100 in H3, 0.13±0.04 mmHg/ml2, was significantly less than in H2, 0.23±0.05 (p<0.01), and the value in H2 was significantly lower than that in H1, 0.36 ±0.07 (p< 0.01), indicating a validity of E' max/V 100 to differentiate each EHT subgroup. It is concluded that in patients with LVH induced by pressure overload the LV function is declined, furthermore, LV contractile performance is more impaired when LVH is accompanied by ST-T changes. E’ max/V 100 is highly sensitive in identifying the presence of LV contractile impairment and may be a useful approach to the quantitation of LV. performance

Addition to Electron Deficient Olefins of α-Oxy Carbon- Centered Radicals, Generated from Cyclic Ethers and Acetals by the Reaction with Alkylperoxy- λ3-iodane

Thermal decomposition of 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in cyclic ethers and acetals at 50 °C generates α-oxy carbon-centered radicals, which undergo an addition reaction with vinyl sulfones and unsaturated esters

The Protective Effect of Low Power He-Ne Laser Against Erythrocytic Damage Caused by Artificial Heart-Lung Machines

We studied the protective effects of low power He-Ne laser irradiation on erythrocytes against the damage caused by experimental artificial heart-lung machines.　　 The erythrocyte suspension in a closed circuit was perfused with a roller pump. One of two circuits was used for laser treatment and the other for control. The laser group demonstrated significantly higher erythrocyte deformability and erythrocyte ATP levels, and lower free hemoglobin and lipid peroxide levels. A laser output power of 8.5 mW was most effective in protecting the erythrocytes. A further morphological finding using a scanning electron microscope showed fewer echinocytes and more discocytes in the laser group. This finding was consistent with the results of physiological and biochemical tests.　　 Low power He-Ne laser irradiation was shown to protect human erythrocytes from the damage caused by an experimental artificial heart-lung machine, raising the possibility of the clinical application of low power He-Ne laser treatment during extracorporeal circulation in cardiovascular surgery.This study was presented at the 6th Japan Laser Therapy Association, held on June 25-26, 1994 in Kobe, at the 32d Japanese Society for Artificial Organs, held on October 12-13, 1994 in Tokyo, at the 47th Japanese Association for Thoracic Surgery, held on October 25-27, 1994 in Chiba, at the 95th Japan Surgical Society, held on April 10-12, 1995 in Nagoya, and at the 33d Japanese Society for Artificial Organs, held on November 7-9, 1995 in Osaka

Difference between Proximal and Distal Right Coronary Flow Velocity Pattern in Humans

The purpose of this study is to clarify the difference between proximal and distal right coronary artery flow velocity pattern in humans. Each portion of the coronary artery in thirteen patients with chest pain syndrome was measured by means of Doppler guide wire. The systolic I diastolic peak velocity ratio and velocity integral ratio at the proximal portion of the right coronary artery were significantly higher than those at distal portion of the right coronary artery (0.97 ± 0.27, 0.61 ± 0.20, 0.66 ± 0.19, 0.44 ± 0.13, respectively). In the right ventricular branch, coronary flow velocity pattern showed systolic dominancy. Systolic I diastolic peak velocity ratio and integral ratio showed 1.69 ± 0.62 and 1.00 ± 0.62 in the right ventricular branch, respectively. It is speculated that the less marked diastolic predominant pattern in the proximal right coronary artery flow velocity may be due to the fact that the proximal right coronary artery supplies both the right and left ventricle but that the distal right coronary artery supplies only the left ventricular inferior wall