The authors selected some interesting current topics among many in the field of functional MRI (fMRI) of the brain. The selection was based on authours’ immediate interests in exploring these aspects further; the topics are presented and discussed along with their perspectives. If progress can be made in these areas, it would be very advantageous to the field of brain research. The topics are (I) Detectable MRI signals in response to functional activity of the brain, including the current status of neurocurrent MRI; (II) Vascular-dependent and vascular-independent MRI signals, leading to the distinction of functional and structural MRI; (III) Functional specificity and functional connectivity of local sites, including differences between task-fMRI and resting state fMRI; (IV) Functional networks: an example of application to assessing the vocational aptitude test by fMRI; (V) Neural oscillation relevant to the formation of fMRI signals and of networks; (VI) Upgrading fMRI to “information-content-reflecting” fMRI, discussed as one of the prospects of near-future fMRI.

Some patients with hypertrophic cardiomyopathy (HCM) develop systolic dysfunction, called the dilated phase of HCM (d-HCM), which is associated with increased morbidity and mortality. We conducted a retrospective study using an HCM database to clarify the incidence, clinical characteristics, and long-term outcomes of d-HCM. We analyzed an HCM cohort consisting of 434 patients (273 with apical HCM and 161 with non-apical HCM; 18 had obstructive HCM, 16 had dilated HCM, and 127 had other HCM) diagnosed by echocardiography in our hospital between 1991 and 2010. The follow-up period was 8.4 ± 6.7 years. The mean age at final follow-up was 67 ± 14 years, and 304 patients (70%) were men. The mean age of the 16 d-HCM patients at the initial visit was 45 ± 17 years, the age at final follow-up was 59 ± 18 years, and 13 were men. Thirteen d-HCM patients developed atrial fibrillation and six patients developed ischemic stroke. Twelve d-HCM patients were implanted with cardiac devices: one pacemaker, nine implantable cardioverter-defibrillators, and two cardiac resynchronization therapy with defibrillator. Five patients died of progressive heart failure at the age of 61 ± 23 years. The age at the initial visit and final follow-up were lower and the NYHA class, brain natriuretic peptide levels, and left ventricular function at initial evaluation were worse in the d-HCM group. Univariate analysis demonstrated that a lower age at the initial visit was associated with d-HCM (hazard ratio 0.955/1 year increase; 95% CI 0.920–0.991, P = 0.015). In our HCM cohort, the incidence of d-HCM was 4%. A high prevalence of atrial fibrillation and cerebral infarction and poor prognosis were noted in this group, despite patients undergoing medication and device implantation.

Stem cells are the foundation of all mammalian life. Stem cells build and maintain our bodies throughout life. Two types of stem cells are discerned.

1) Embryonic stem cells (ES cells) are briefly present in the early human or mouse embryo, a few days after fertilization. These ES cells can be grown indefinitely in the lab and have the potential to build each and every tissue in our body. Because of this ‘pluripotency’, ES cells hold great promise for therapeutic application in the field of regenerative medicine. It is also possible to take skin cells (or other cells) from adults and convert these in the lab into cells with ES properties, so called iPS cells. Many of the hurdles that ES cell technology have faced, do not exist for iPS cells.

2) Adult stem cells. Every organ in our body is believed to harbor its own dedicated stem cells. These adult stem cells replace tissue that is lost due to wear and tear, trauma and disease. Adult stem cells are highly specialized and can only produce the tissue in which they reside; they are ‘multipotent’. Examples are bone marrow stem cells that make all blood cells, skin stem cells and gut stem cells. Even the brain is now known to harbor its specialized stem cells. The adult stem cells allow us to live 80-90 years, but this comes at a cost: they are the cells that most easily transform into cancer cells.

Both types of stem cells can be used to establish ‘organoids’, 3D structures established in a dish, that recapitulate many aspects of the organ they represent. Pluripotent stem cells can be taken through the developmental steps that establish organs during embryogenesis. This has worked particularly well for parts of the the central nervous system, the kidney and GI organs. We have shown that adult epithelial stem cells carrying the generic Lgr5 marker can be cultured under tissue-repair conditions and generate epithelial organoids directly from healthy and diseased organs such as the gut, the liver, the lung and the pancreas. Organoid technology opens a range of avenues for the study of development, physiology and disease, for drug development and for personalized medicine. In the long run, cultured mini-organs may replace transplant organs from donors and hold promise in gene therapy.

A series of our studies on IL-6 have revealed that it has a pleiotropic activity in various tissues and cells and its deregulated expression is responsible for several chronic inflammations and hemopoietic malignancies.

Humanized antibody against 80kd IL-6R (Tocilizumab) has shown significant therapeutic effect in RA, JIA, Castleman’s diseases and several other autoimmune inflammatory diseases, such as, giant cell arteritis, reactive arthritis, polymyalgia rheumatica and adult still’s disease. Cytokine storm induced by CAR-T cell therapy has been shown to be controlled by Tocilizumab.

Therapeutic effect of Tocilizumab confirmed that over and constitutive-production of IL-6 is responsible for the pathogenesis of autoimmune diseases.

Then, the question to be asked is how is IL-6 production regulated. We identified a novel molecule called Arid5a which binds with the 3’-UTR of IL-6 mRNA and protects its degradation by competing with Regnase-1. Interestingly, this molecule is present in nuclei and inflammatory stimulation induced translocation of Arid5a from nuclei into cytoplasm and it competes with Regnase-1 for the protection of mRNA of IL-6.

Our study indicates that Arid5a is one of the key molecules for inflammation as well as the development of septic shock.

The results also suggest the therapeutic potential of anti-agonistic agents for Arid5a in the prevention of various inflammatory diseases and septic shock.