Objective Insulin-like growth factor 1 (IGF-1) protects neuronal-cell damage by ischemia. Although neuronal cells have been reported to produce IGF-1, the molecular mechanisms remains obscure. Dexmedetomidine (DEX) protects neuronal cells from ischemic damage. We investigated the involvement of IGF-1 in the effect of DEX pretreatment on neuronal ischemic damage using an in vitro mouse hippocampal neuron model.

Materials We used Dexmedetomidine and cryopreserved passaged mouse hippocampal neuronal HT22. Other reagents in this study were analytical grade.

Methods Ischemia-reperfusion was modeled using the in vitro oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of DEX was examined by incubating cells in DEX-containing medium for 1 hour prior to OGD/R. The cell damages were evaluated by lactate dehydrogenase (LDH) release. The amount of released IGF-1 were evaluated quantitatively by ELISA. The degree of Akt phosphorylation was evaluated by western blotting.

Results OGD/R loading promoted LDH release from neuronal cells, while DEX pretreatment suppressed the LDH release. IGF-1 release from them was primed by DEX pretreatment under OGD/R condition, but not under normal conditions. Akt was activated in DEX-pretreated cells following OGD/R loading. IGF-1 neutralizing antibody (αIGF-1) eliminated the above effects of DEX pretreatment. However, IGF-1 receptor expression in neuronal cells was not affected by DEX pretreatment prior to OGD/R loading.

Conclusions Our results demonstrate that neuronal cells primed with DEX under OGD/R conditions could release IGF-1 and potentially protect themselves via the IGF-1/Akt pathway. Consequently, it appears that neuronal cells activated by DEX have the capacity to self-protect from ischemic damage.

Background/Objective Patients with polymyalgia rheumatica experience flares and require a lengthy course of glucocorticoid treatment. Ultrasound application is often used for diagnosing polymyalgia rheumatica. This study aimed to determine whether polymyalgia rheumatica diagnosed with ultrasound complementation has a more favorable clinical course compared with that of only clinically diagnosed patients.

Methods In this cohort study, we retrospectively identified 152 patients with polymyalgia rheumatica from January 2008 to December 2018. We extracted patients' clinical and ultrasound information, and hazard ratio and propensity-score matched analyses were performed.

Results Among 152 patients with polymyalgia rheumatica, the flare, methotrexate add-on, and C-reactive protein normalization rates were 15.9 (95% confidence interval, 8.8-23.1)/100 person-years, 9.3 (3.6-15.0) /100 person-years, and 70.3 (61.3-79.2) /100 person-months, respectively. Age (p=0.01), C-reactive protein levels (p=0.03), and absence of peripheral joint pain (p=0.03) were significantly different between 81 and 71 patients with and without ultrasound complementation, respectively. The hazard ratio showed that ultrasound complementation did not contribute to the clinical course; flare, methotrexate add-on, and C-reactive protein level normalization yielded values of 0.88 (p=0.64), 1.93 (p=0.056), and 0.94 (p=0.72), respectively. Propensity-score-matched analysis showed a similar clinical course between 51 pairs: flare (p=0.45), methotrexate add-on (p=0.15), and C-reactive protein normalization (p=0.94).

Conclusions Age, C-reactive protein, and involved joint distribution were factors leading to ultrasound complementation at the time of polymyalgia rheumatica diagnosis. Ultrasound complementation at PMR diagnosis is useful for differential diagnosis but may not affect the clinical course after GC introduction.

　In 1985, when I entered the Graduate School of Science at Kyoto University, I began my research on cellular slime molds, a group of soil microorganisms. The cellular slime mold Dictyostelium discoideum is studied globally as a model organism for cell and developmental biology. I was conducting basic biological research into cell differentiation and migration using D. discoideum, and during this process, our research group made a discovery with potential implications for drug development. Specifically, we found that a chlorinated polyketide named differentiation-inducing factor 1 (DIF-1), derived from D. discoideum, exhibits antitumor activity. Based on this discovery, I began elucidating the mechanism of the antitumor action of DIF-1 and developing anticancer drugs using DIF-1 as a lead compound. During this period, in 1991, I obtained my Ph.D. in research related to D. discoideum cell differentiation, and subsequently served as a Japan Society for the Promotion of Science (JSPS) Special Research Fellow before joining the Institute for Molecular and Cellular Regulation (IMCR) at Gunma University in 1993. I then joined the Graduate School of Health and Sports Sciences at Juntendo University in 2015, where I have been until 2024. Throughout this period, I continued my research on DIF-1 and discovered that DIF-1 and its derivatives possess various biological activities ─ such as anti-diabetic, immunoregulatory, anti-bacterial, and anti-malarial activities ─ that could be applicable in drug development. In this review, I aim to present a segment of both our fundamental and applied research on D. discoideum and DIF-1.