Microscopic Magnetic Properties of (V1−x_{1-x}Tix_{x})2_2O3_3 near the Phase Boundary of the Metal-Insulator Transition

Magnetic susceptibility (chi) and $^{51}$V NMR have been measured in (V$_{1-x}$Ti$_{x}$)$_2$O$_3$ near the phase boundary of the metal-insulator transition. It is established that the transition from antiferromagnetic insulating (AFI) to antiferromagnetic metallic phases near $x_{\rm c}\approx 0.05$ is not quantum critical but is discontinuous with a jump of the transition temperature. In the AFI phase at 4.2 K, we observed the satellite in the zero-field $^{51}$V NMR spectrum around 181 MHz in addition to the ``host'' resonance around 203 MHz. The satellite is also observable in the paramagnetic metallic phase of the x = 0.055 sample. We associated the satellite with the V sites near Ti which are in the V$^{3+}$-like oxidation state but has different temperature dependence of the NMR shift from that of the host V site. The host d-spin susceptibility for x = 0.055 decreases below $\sim$60 K but remains finite in the low-temperature limit.Comment: 9 pages, 4 eps figures; corrected the author lis

A new therapeutic strategy with istradefylline for postural deformities in Parkinson’s disease

Aim of the study. Postural deformities are common in Parkinson’s disease (PD) patients. Several treatment options have been reported, but responses to these treatments appear unpredictable. Istradefylline is a novel drug for PD. Cases of PD patients whose postural deformities were improved after withdrawal of dopamine agonists and initiation of istradefylline are presented. Materials and Methods. Four consecutive patients with postural deformities including antecollis, Pisa syndrome, and camptocormia were recruited and treated with istradefylline in combination with withdrawal of dopamine agonists, which are possible causes of postural deformities. Results. The dopamine agonists were discontinued an average of 26 months after the development of the postural deformities, and istradefylline was initiated an average of 1.3 months after dopamine agonist withdrawal. Three patients with preserved paraspinal muscle volume showed good responses to the treatment regimen at least two months after dopamine agonist withdrawal. Conclusions and clinical Implications. Postural deformities caused by dopamine agonists generally improve less than two weeks after dopamine agonist withdrawal. Given the response time in the present study, the response was unlikely to be caused solely by dopamine agonist withdrawal. Istradefylline can be a potential therapeutic option; however, appropriate selection of patients for treatment with istradefylline is warranted

FoxO1 Gain of Function in the Pancreas Causes Glucose Intolerance, Polycystic Pancreas, and Islet Hypervascularization

Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG). TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts

Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin

プロドラッグ型クルクミン注射製剤の抗腫瘍効果及び治療標的の包括的な解析 --安全性の高い抗がん薬としての開発に期待--. 京都大学プレスリリース. 2022-10-21.Curcumin (aglycone curcumin) has antitumor properties in a variety of malignancies via the alteration of multiple cancer-related biological pathways; however, its clinical application has been hampered due to its poor bioavailability. To overcome this limitation, we have developed a synthesized curcumin β-D-glucuronide sodium salt (TBP1901), a prodrug form of aglycone curcumin. In this study, we aimed to clarify the pharmacologic characteristics of TBP1901. In β-glucuronidase (GUSB)-proficient mice, both curcumin β-D-glucuronide and its active metabolite, aglycone curcumin, were detected in the blood after TBP1901 injection, whereas only curcumin β-D-glucuronide was detected in GUSB-impaired mice, suggesting that GUSB plays a pivotal role in the conversion of TBP1901 into aglycone curcumin in vivo. TBP1901 itself had minimal antitumor effects in vitro, whereas it demonstrated significant antitumor effects in vivo. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen disclosed the genes associated with NF-κB signaling pathway and mitochondria were among the highest hit. In vitro, aglycone curcumin inhibited NF-kappa B signaling pathways whereas it caused production of reactive oxygen species (ROS). ROS scavenger, N-acetyl-L-cysteine, partially reversed antitumor effects of aglycone curcumin. In summary, TBP1901 can exert antitumor effects as a prodrug of aglycone curcumin through GUSB-dependent activation

Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population

departmental bulletin pape

Serum Amyloid A Promotes E-Selectin Expression via Toll-Like Receptor 2 in Human Aortic Endothelial Cells

Periodontitis is a chronic inflammatory disease that affects the periodontium. Recent studies suggest an association between periodontal and cardiovascular diseases. However, the detailed molecular mechanism is unknown. A previous study has demonstrated that experimental periodontitis induces serum amyloid A (SAA) in the liver and peripheral blood of ApoE-deficient mice as an atherosclerosis model. SAA is an acute-phase protein that affects systemic inflammation. The aim of this study is to investigate the atherosclerosis-onset mechanism using human aortic endothelial cells (HAECs) stimulated by SAA in vitro. Atherosclerosis PCR array and qPCR analyses showed upregulation of adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in HAECs upon SAA stimulation. In addition, the results demonstrated that Toll-like receptor, TLR2, could serve as an important receptor of SAA in HAECs. Furthermore, small interfering RNA (siRNA) against TLR2 inhibited the upregulation of adhesion molecules in HAECs stimulated by SAA. Our results suggest that SAA stimulates the expression of adhesion molecules via TLR2. SAA could be an important molecule for atherosclerosis induced by periodontal disease

Pathway to psychiatric care in Japan: A multicenter observational study

<p>Abstract</p> <p>Background</p> <p>This study examines pathways to psychiatric care in Japan using the same method as the collaborative study carried out in 1991 under the auspices of the World Health Organization.</p> <p>Methods</p> <p>Thirteen psychiatric facilities in Japan were involved. Of the 228 patients who contacted psychiatric facilities with any psychiatric illness, eighty four visiting psychiatric facilities for the first time were enrolled. Pathways to psychiatric care, delays from the onset of illness to treatment prior to reaching psychiatrists were surveyed.</p> <p>Results</p> <p>Thirty three patients (39.4%) directly accessed mental health professionals, 32 patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via private practitioners. The patients who consulted mental health professionals as their first carers took a longer time before consulting psychiatrists than the patients who consulted non-mental health professionals as their first carers. The patients who presented somatic symptoms as their main problem experienced longer delay from the onset of illness to psychiatric care than the patients who complained about depressive or anxiety symptoms. Prior to the visit to mental health professionals, patients were rarely informed about their diagnosis and did not receive appropriate treatments from their physicians. Private practitioners were more likely to prescribe psychotropics than physicians in general hospitals, but were less likely to inform their patients of their diagnosis.</p> <p>Conclusion</p> <p>This first pathway to psychiatric care study in Japan demonstrated that referral pathway in Japan heavily relies on medical resources. The study indicates possible fields and gives indications, underlining the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders presenting with somatic and depressive symptoms in the general health care system and by private practitioners.</p