我々は蛋白質構造解析に特化したアニーリング方式の量子コンピューターを検討している. この手法では, 蛋白質の折り畳みに寄与する生物化学的な作用を数理モデルに取り入れ, 量子ビット回路に直接実装する. 共に最小エネルギー状態に帰着するという観点で, 蛋白質の折り畳みと量子アニーリングのメカニズムは親和性が高いと考えている. 疾病の原因究明に踏み込むことができるような量子コンピューターの実現を目指している.

Three artificial intelligence (AI) booms have occurred since Alan Turing, the creator of the world's first computer, dreamed of reproducing human brain in electric circuits. In the first AI Boom Rosenblatt devised Perceptron (Neural Network: NN) that electrically represented nervous networks. The second AI boom started when Fukushima proposed Neocognitron in 1979, which imitated the visual nervous system of cats in the electronic circuit board. LeCun embedded it in computer program as a convolutional NN, LeNet in 1989. In 2006, Hinton proposed Autoencoder, a nonlinearization of Principal Component Analysis, and in 2012, AKrizhevsky multilayered it as AlexNet, the dramatic improvement of which in classification accuracy led to the third AI boom. Although there are not many applications in the organ transplantation yet, iBox which uses Cox regression has been proposed by Loupy to predict the prognosis of renal transplant patients. We proposed a model for predicting the difficulty of laparoscopic donor nephrectomy in living donor kidney transplantation, and a model for optimizing the trough concentration of immunosuppressive drug in renal transplant patients. AI in the field of organ transplantation would enhance the safety of surgery and improve the long-term prognosis of transplanted kidneys.

In this 21st century, when science has advanced and democracy has permeated, there are untrustful natural and man-made disasters for us human beings. One of them is the pandemic of COVID-19, and the other is the invasion of Ukraine by force that does not have justice of Russia. What is common as a solution to these two events is that the International Organizations that control them have become ruins and their functions cannot be fully demonstrated.

The period background is similar to the period before the outbreak of World War I and II. If the worst happens, it will be World War III, and if it becomes a nuclear war, humanity will be ruined. It is the wisdom of humanity that can solve these problems.

This time, I would like to consider COVID-19, which affects about 500 million people worldwide as of April 2022, of which about 6 million people die.

About two years have passed since the COVID-19 pandemic began. Exposed to the ideological conflict between democracy and tyranny, the globalization of large corporations beyond national frameworks, economic disparities, the structural complex problems of society and the wave of commercialization, COVID-19 pandemics that began with natural disasters are replacing man-made disasters.

During this time, there has been little progress other than the development of vaccines. And its basic policy is no different from the extension of Albert Camus’s “La Peste” lockdown policy in 1947. Under such a passive policy, Japan’s economy will stall and be removed from the framework of the seven developed countries. In order to solve this problem, it is necessary to quickly switch to a simple active policy.

血液透析は個人所得1005ドル以下の人の98%が受けられません. 世界の総人口78億人のうち9億人が慢性腎臓病(CKD)で, その大部分が血液透析(HD)を受けられず尿毒症による死を迎えます. 私は51年前にすべての人がHDの恩恵を受けられない現状を直そうと, CTC(conservative treatment for CKD)の路に入りました. Stage3では44%, Stage4では25%の人がCKD進行が停止します. しかしStage5では9%しか停止しません. つまりStage3, 4の早期からCTCを始める必要があります. これが51年間CTCを行った結論です.

Viral RNA produced by upper respiratory tract influenza infection induces cytokines and interferon by innate immunity and develops influenza-specific symptoms. Varicella is systemically infected by the virus, and on the skin, cytokines from Langerhans cells, which play the main role in the innate immunity, cause prodromal symptoms such as fever and itching, and cell mediated immunity as adaptive immunity causes varicella symptoms such as papules and vesicles. As described above, influenza symptoms are caused by innate immunity, and varicella is caused by cell-mediated immunity. Photodistribution shows the importance of innate immunity because UV light damages Langerhans cells in the skin, which are important for innate immunity, and varicella and herpes simplex virus infections produce dense and severe lesions in the irradiate regions. This review details the relationship between innate immunity, adaptive immunity, and clinical symptoms in viral infections and the optimal timing of antiviral administration.

Amniotic epithelial cells (AECs) have garnered significant interest for use in regenerative medicine due to promising features, such as multipotency, low immunogenicity, non-tumorigenicity, and anti-inflammatory capacity. AEC transplantation has been attempted as an alternative to hepatocyte transplantation for the treatment of certain liver diseases. Although intra-portal infusion has been considered as one of the leading candidates of transplantation methods in clinical practice, the protocol of intra-portal AEC administration has not been fully investigated. Thus, in order to clinically introduce new cell transplantation treatment using AECs, an optimal cell administration protocol needs to be established.

Ferroptosis is known to be implicated in various liver diseases; however, the liver-specific regulatory mechanism of ferroptosis is not fully understood. We identified 7-dehydrocholesterol reductase (DHCR7) as a novel regulator of ferroptosis in hepatocytes. DHCR7 inhibition suppressed ferroptosis in Huh-7 cells. The DHCR7 inhibition increased the accumulation of intracellular 7-dehydrocholesterol (7-DHC), a substrate for DHCR7, and extrinsic 7-DHC supplementation suppressed ferroptosis. We assessed that oxidation of 7-DHC compensatory prevents cellular membrane lipid peroxidation related to ferroptosis. DHCR7 inhibitor also suppressed ferroptosis in murine primary hepatocytes and hepatic ischemia-reperfusion injury in mice. These findings suggest that targeting DHCR7 is a potential therapeutic strategy for ferroptosis-related liver disease.

iPS細胞を用いた移植医療では, 臨床グレードの細胞を迅速かつ低コストで使用するために, 既製品化された他家iPS細胞をoff-the-shelf製剤として使用することが予定されている. off-the-shelf製剤として使用するiPS細胞には, 拒絶反応のリスクを低減する目的で, Human leukocyte antigen(HLA；ヒト白血球型抗原)型をホモ接合体で持つ, HLA型ホモ接合体iPS細胞を使用することが計画されており, 将来のHLA型適合移植に向けて複数株が樹立されている. 本稿では, 他家HLA型ホモ接合体iPS細胞由来組織移植における拒絶反応制御に向け筆者らが行なった, 免疫抑制剤併用プロトコールの構築を中心に紹介する.

Pulmonary fibrosis is known as a progressive disease in which the interstitium is damaged by some factor, resulting in fibrosis of the lungs and a gradual decline in respiratory function. There are very few treatments, various problems and it is not a fundamental treatment. On the other hand, regenerative medicine has attracted attention in recent years as a fundamental treatment for pulmonary fibrosis. In particular, stem cell transplantation using mesenchymal stem cells have already begun to be applied clinically as a regenerative medicine method for many diseases, as they are relatively easy to harvest from living organisms and have a low risk of tumorigenesis and high safety. However, to establish stem cell transplantation, it is important to clarify the in vivo behavior and accumulation sites of transplanted stem cells. In this study, therefore, to ensure the safety and high therapeutic efficacy of stem cell transplantation for pulmonary fibrosis, adipose tissue-derived mesenchymal stem cells labelled with quantum dots, the most advanced fluorescent nanomaterial, were administered to bleomycin pulmonary fibrosis model mice, and the in vivo behavior and therapeutic efficacy of the transplanted stem cells were investigated.

欧米における心停止ドナーなどのマージナルドナーの増加に伴い心臓, 肺, 肝臓, 腎臓の機械灌流保存は多数の臨床試験の報告がなされ, 腎臓では急速に普及した. 我々は2016年より企業と灌流保存システムの研究開発に取り組んできた. ブタを用いて実験を繰り返し, その有効性を報告してきた. 2019年11月, マージナルドナーからの腎移植に対する多施設共同臨床試験を計画し旭川医大ならびに参加施設の倫理委員会で承認された. 現在まで11例において灌流保存後の腎移植が行われた. 良好な経過をたどった腎グラフトは灌流圧の低下と, 流量の上昇が観察された. 一方, 灌流保存に直結する有害事象はなく, 全例安透析を離脱した. 一方, 肝臓灌流保存については臨床応用を意識した基礎実験, たとえば, 分割肝移植をイメージした過少肝グラフトの灌流保存実験においては単純冷却保存よりも移植前短時間酸素化灌流保存の有効性を確認した. 今後, 我が国でも各臓器での臨床試験が期待される.