Knowledge and Demand for Information about Islet Transplantation in Patients with Type 1 Diabetes

This cross-sectional study based on self-administrated questionnaire was conducted to investigate knowledge, related factors, and sources of information regarding islet transplantation in patients with type 1 diabetes in Japan. Among 137 patients who provided valid responses, 67 (48.9%) knew about islet transplantation. Their main source of information was newspapers or magazines (56.7%) and television or radio (46.3%). However, 85.8% of patients preferred the attending physician as their source of information. Although more than half of the patients were correctly aware of issues related to islet transplantation, the following specific issues for islet transplantation were not understood or considered, and there was little knowledge of them: need for immunosuppressants, lifestyle and dietary adaptations, fewer bodily burdens, and complications. The experience of hypoglycaemia, a high level of academic background, frequent self-monitoring of blood glucose, and the use of continuous subcutaneous insulin infusion were related to higher knowledge about islet transplantation

PBF-LB fabrication of microgrooves for induction of osteogenic differentiation of human mesenchymal stem cells

Matsugaki Aira, Matsuzaka Tadaaki, Mori Toko, et al. PBF-LB fabrication of microgrooves for induction of osteogenic differentiation of human mesenchymal stem cells. International Journal of Bioprinting 10, 1425 (2024); https://doi.org/10.36922/ijb.1425.Stem cell differentiation has important implications for biomedical device design and tissue engineering. Recently, inherent material properties, including surface chemistry, stiffness, and topography, have been found to influence stem cell fate. Among these, surface topography is a key regulator of stem cells in contact with materials. The most important aspect of ideal bone tissue engineering is to control the organization of the bone extracellular matrix with fully differentiated osteoblasts. Here, we found that laser powder bed fusion (PBF-LB)-fabricated grooved surface inspired by the microstructure of bone, which induced human mesenchymal stem cell (hMSC) differentiation into the osteogenic lineage without any differentiation supplements. The periodic grooved structure was fabricated by PBF-LB which induced cell elongation facilitated by cytoskeletal tension along the grooves. This resulted in the upregulation of osteogenesis via Runx2 expression. The aligned hMSCs successfully differentiated into osteoblasts and further organized the bone mimetic-oriented extracellular matrix microstructure. Our results indicate that metal additive manufacturing technology has a great advantage in controlling stem cell fate into the osteogenic lineage, and in the construction of bone-mimetic microstructural organization. Our findings on material-induced stem cell differentiation under standard cell culture conditions open new avenues for the development of medical devices that realize the desired tissue regeneration mediated by regulated stem cell functions

E22Δ Mutation in Amyloid β-Protein Promotes β-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity

Oligomers of 40- or 42-mer amyloid β-protein (Aβ40, Aβ42) cause cognitive decline and synaptic dysfunction in Alzheimer's disease. We proposed the importance of a turn at Glu22 and Asp23 of Aβ42 to induce its neurotoxicity through the formation of radicals. Recently, a novel deletion mutant at Glu22 (E22Δ) of Aβ42 was reported to accelerate oligomerization and synaptotoxicity. To investigate this mechanism, the effects of the E22Δ mutation in Aβ42 and Aβ40 on the transformation of β-sheets, radical production, and neurotoxicity were examined. Both mutants promoted β-sheet transformation and the formation of radicals, while their neurotoxicity was negative. In contrast, E22P-Aβ42 with a turn at Glu22 and Asp23 exhibited potent neurotoxicity along with the ability to form radicals and potent synaptotoxicity. These data suggest that conformational change in E22Δ-Aβ is similar to that in E22P-Aβ42 but not the same, since E22Δ-Aβ42 exhibited no cytotoxicity, unlike E22P-Aβ42 and wild-type Aβ42

C9orf72由来のプロリン : アルギニンポリペプチドは細胞骨格とメカニカルストレス応答を制御する

Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in C9orf72 have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR poly-dipeptides affect cytoskeletal organization and focal adhesion (FA) formation. Here, we show that changes to the cytoskeleton and FA by PR poly-dipeptides result in the alteration of cell stiffness and mechanical stress response. PR poly-dipeptides increased the junctions and branches of the IF network and increased cell stiffness. They also changed the distribution of actin filaments and increased the size of FA and intracellular calcium concentration. PR poly-dipeptides or an inhibitor of IF organization prevented cell detachment. Furthermore, PR poly-dipeptides induced upregulation of mechanical stress response factors and led to a maladaptive response to cyclic stretch. These results suggest that the effects of PR poly-dipeptides on mechanical properties and mechanical stress response may serve as a pathogenesis of C9orf72-related neurodegeneration.博士（医学）・甲第846号・令和4年9月28日Copyright © 2022 Shiota, Nagata, Kikuchi, Nanaura, Matsubayashi, Nakanishi,Kobashigawa, Isozumi, Kiriyama, Nagayama, Sugie, Yamashiro and Mori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy

金沢大学医薬保健研究域薬学系It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)-pIV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for tumor imaging and therapy. (+)-[125/131I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[125I]pIV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[125I]pIV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[131I]pIV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[125I]pIV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[125I]pIV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[131I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy. (Cancer Sci 2009). © 2009 Japanese Cancer Association

Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an agent for treatment of painful bone metastases

金沢大学学際科学実験センターアイソトープ総合研究施設Purpose: We have developed a 186Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate (186Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of 186Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of 99mTc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution. Methods: The displacement effects of several protein-binding inhibitors on the protein binding of 186Re-MAG3-HBP were investigated. Biodistribution experiments were performed by intravenously administering 186Re-MAG3-HBP into rats with ceftriaxone as a competitive protein-binding inhibitor or saline. Results: The protein binding of 186Re-MAG3-HBP in rat serum, human serum, and a human serum albumin solution was significantly decreased by the addition of ceftriaxone, which has high affinity for binding site I on serum albumin. In the biodistribution experiments, pretreatment with ceftriaxone enhanced the clearance of the radioactivity of 186Re-MAG3-HBP in blood and nontarget tissues but had no effect on accumulation in bone. Conclusions: The findings suggested that the use of protein-binding competitive inhibitors would be effective in improving the pharmacokinetics of radiopharmaceuticals with high affinity for serum protein. © 2008 Springer-Verlag