We have investigated superconducting quantum circuit based on the quantum annealing methodology, dedicated for a protein folding. In our original method, problem Hamiltonian composed of force fields with amino-acid interactions is directly implemented in the superconducting quantum circuit. Due to perspective of taking minimum energy in final state, mechanisms of the protein folding and the quantum annealing have high affinity. Our aim is to establish the quantum computer that will clarify the causes of disease.

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.

Hemodialysis, HD is not available to 98% of individuals with a personal income of $1005. 900 million people among the world’s total population of 7.8 billion suffer from CKDs, the majority of whom do not have access to hemodialysis and die from uremia. I started my CTC (conservative treatment for CKD) journey 51 years ago in an attempt to rectify the current situation in which not everyone can benefit from HD. The progression of CKD stops for 44% of individuals at Stage 3 and 25% at Stage 4. However, it only stops for 9% at Stage 5. In other words, we need to start CTC early at Stages 3, 4. This is the conclusion I have drawn from my 51 years of experience with CTC.

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.

In transplantation medicine using iPS cells, it is planned to use off-the-shelf iPS cells derived from allogeneic iPS cells for rapid and low-cost utilization of clinical-grade cells. To reduce the possibility of rejection, it is designed to use HLA-homozygous iPS cells for the off-the-shelf product, and several lines have been established for future HLA-matched transplants. This article describes our efforts to control rejection in HLA-matched allogeneic iPS cell-based transplantation, focusing on establishing immunosuppression protocols.

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.

The shortage of donors for transplantation is a universal problem. The use of marginal donors is one source to increase supply. However, recipients with marginal donor graft experience a higher incidence of primary nonfunction and delayed graft function (DGF). Recently, ex vivo machine perfusion (MP) is used to reduce the incidence of DGF by decreasing the ischemic damaged graft. In addition, MP provides for assessing graft viability that is essential for optimal organ allocation. The original MP for kidney and liver graft were developed in our institute. The, first multi-center clinical trial (UMIN000038181) for marginal kidney transplantation in Japan has been started since 2020. The study design is short time hypothermic oxygenated end-ischemic perfusion for brain death marginal and DCD kidney graft. As a results so far, no trouble related MP were seen. All case was HD free at the time of discharge. Current status of MP is reviewed this context.