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Inhibition of Src ameliorates the progression of pulmonary arterial hypertension in experimental mouse model
Get PDFBackgrounds: Pulmonary arterial hypertension （PAH） is characterized by progressive remodeling of pulmonary arterioles, resulting in right heart failure. Although currently available therapeutic agents have improved clinical outcomes of PAH patients, the efficacy remains unsatisfactory. Src, originally identified as oncogene, participates in numerous signaling pathways regulating cell survival and proliferation. However, its role in the pathogenesis of PAH is largely unknown.
Methods and Results: We treated wild-type mice with monocrotaline （MCT, 600 mg/kg） or vehicle （control） once a week for eight weeks to induce PAH, and Src-specific inhibitor PP1 （4 mg/kg） was injected three times per week concurrently with MCT. Right ventricular systolic pressure was significantly higher in MCT-treated mice than in control （60.1±8.1 vs. 20.6±1.1 mmHg, p<0.0001）, and PP1 attenuated the increase to 32.8±12.7 mmHg （p=0.0005）. The fibrotic area in the lung was greater in MCT-treated mice than in control （14.7±0.6 vs. 5.6±2.0%, p<0.0001）, and PP1 attenuated the increase to 8.9%±2.6%（ p=0.02）. In human pulmonary artery smooth muscle cells, endothelin
increased mRNA expression of interleukin-6, and pretreatment with PP1 inhibited its increase.
Conclusions: Src inhibition may attenuate the progression of PAH induced by MCT through inhibiting inflammatory cytokine production. Our results may provide a novel clinical implication for PAH treatment.弘前大学博士（医学）Author: Naotake Miura, Kenji Hanada, Shun Hirosawa, Hitoshi Umezaki, Yuki Konno, Kazufumi Kato, Toshihiro Iwasaki, and Hirofumi TomitaCitation: The Hirosaki Medical Journal Vol75, No.1, 31-38, 202
Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome
Get PDFMyeloid leukemia associated with Down syndrome (ML-DS) responds well to chemotherapy and has a favorable prognosis, but the clinical outcome of patients with refractory or relapsed ML-DS is dismal. We recently reported a case of relapsed ML-DS with an effective response to a DNA methyltransferase inhibitor, azacitidine (AZA). However, the efficacy of AZA for refractory or relapsed ML-DS remains uncertain. Here, we investigated the effects and mechanism of action of AZA on three ML-DS cell lines derived from relapsed cases. AZA inhibited the proliferation of all examined ML-DS cell lines to the same extent as that of AZA-sensitive acute myeloid leukemia non-Down syndrome cell lines. Transient low-dose AZA treatment exerted durable antileukemic effects on ML-DS cells. The inhibitory effect included cell cycle arrest, apoptosis, and reduction of aldehyde dehydrogenase activity. Comprehensive differential gene expression analysis showed that AZA induced megakaryocytic differentiation in all ML-DS cell lines examined. Furthermore, AZA induced activation of type I interferon-stimulated genes, primarily involved in antiproliferation signaling, without stimulation of the interferon receptor-mediated autocrine system. Activation of the type I interferon pathway by stimulation with interferon-α exerted antiproliferative effects on ML-DS cells, suggesting that AZA exerts its antileukemic effects on ML-DS cells at least partially through the type I interferon pathway. Moreover, the effect of AZA on normal hematopoiesis did not differ significantly between individuals with non-Down syndrome and Down syndrome. In summary, this study suggests that AZA is a potentially effective treatment option for ML-DS disease control, including relapsed cases, and has reduced side effects.弘前大学博士（医学）Author: Tatsuhiko Tanaka, Ko Kudo, Rika Kanezaki, Kentaro Yuzawa, Tsutomu Toki, Ryo Okuse, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Kiminori Terui, Etsuro ItoCitation: Experimental Hematology :132 :104179, Apr 202
Experimental study of contact stress measurement acting on frequent sites of pressure injury when backrest of nursing care bed is operated
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Biochar-Assisted Steam Co-Gasification: A Pathway to Enhance Hydrogen-Rich Syngas Generation using Various Biomass Feedstocks
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Boosting production of formic acid from carbon dioxide electroreduction via high-entropy material
Get PDF弘前大学修士（地域共創工学）Excessive carbon dioxide emissions have brought about serious resource, environmental, and climate issues. Therefore, converting CO2 into valuable chemical fuels has attracted increasing research attention. As one of the most attractive CO2 reduction products, formic acid (HCOOH) is widely considered an ideal hydrogen carrier. Due to intense competitive hydrogen evolution reaction (HER) in aqueous media, high applied potential as well as current density often leads to low Faradaic efficiency (FE). Therefore, achieving a low-cost, environmentally friendly, and highly active catalyst to promote the generation of HCOOH by reducing CO2 in aqueous solutions with high current density and FE is of great interest but remains a challenge. Additionally, the carbon dioxide reduction reaction is always combined with the oxygen evolution reaction (OER), therefore, the development of efficient OER electrocatalysts is also impotent and sometimes it becomes the main obstacle to affect the efficiency of overall electrochemical process.
This study focuses on the applications of high-entropy materials (HEMs) as either cathode or anode electrocatalysts in electrochemical CO2 reduction reaction (CO2RR). Here, HEMs always consist of five or more primary elements with close atomic ratios ranged from 5~35 at% for each. These usually offer adjustable composition, optimal grain size, stable crystalline structure, modified bond length and good electron cloud distribution, endowing HEMs long-term stability and unexcepted catalytic performance. Moreover, the complex components and structure of HEMs could result in discrepant atomic distribution and special binding sites, which can modulate the binding energy of reactants in a continuous form by varying elemental ratio. Unfortunately, as of now, there have been no reports of high-entropy catalysts that can be used to produce formic acid effectively from CO2.
Herein, we chose Bi, In, Sn, Pb, and Cu five elements with carbon paper (CP) as the substrate and synthesized a catalyst by a simple hydrothermal method. XRD and elemental analysis confirmed the formation of a high-entropy structure of BiInSnPbCu on the CP. The obtainedelectrocatalyst exhibited high selectivity (over 80% Faradaic efficiency) and stability in electrochemical CO2RR to formic acid. Meanwhile, a kind of high-entropy precursor with a fusiform microstructure was used to prepare high entropy oxide (HEO) of (FeCoNiMnCu)Ox for OER. It is observed that, with thermal oxidization, the morphology of obtained high-entropy (FeCoNiMnCu)Ox was conversed to layered sphere-shape microstructure built by nanodots. This HEO also showed excellent stability with running continuously for 160 hours at current densities even exceeding 100 mA cm-2, which surpassed the performances of precious metal based electrocatalysts. Due to the excellent performances of the above obtained CO2RR and OER high entropy electrocatalysts, it is expected to combine them to achieve efficient CO2RR-OER electrolysis
Serial longitudinal changes of coronary calcified plaques with clear outer borders under intensive lipid management: insights from optical coherence tomography
Get PDF弘前大学博士（医学）掲載誌：Heart and Vessels 2024 May;39(5):373-38
Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019
Get PDF弘前大学博士（医学）掲載誌：Auris Nasus Larynx 2024 Jun;51(3):443-44