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  • 1
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 7 ( 2021-03-27), p. 1370-
    Abstract: As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and 〈 55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 2
    In: Vaccines, MDPI AG, Vol. 10, No. 11 ( 2022-10-28), p. 1815-
    Abstract: To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2703319-3
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  • 3
    In: Cells, MDPI AG, Vol. 11, No. 1 ( 2021-12-27), p. 66-
    Abstract: Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 4
    In: Biomedicines, MDPI AG, Vol. 10, No. 10 ( 2022-10-12), p. 2549-
    Abstract: Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients’ disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 5
    In: Life, MDPI AG, Vol. 13, No. 5 ( 2023-04-28), p. 1103-
    Abstract: Life most likely started during the Hadean Eon; however, the environmental conditions which contributed to the complexity of its chemistry are poorly known. A better understanding of various environmental conditions, including global (heliospheric) and local (atmospheric, surface, and oceanic), along with the internal dynamic conditions of the early Earth, are required to understand the onset of abiogenesis. Herein, we examine the contributions of galactic cosmic rays (GCRs) and solar energetic particles (SEPs) associated with superflares from the young Sun to the formation of amino acids and carboxylic acids in weakly reduced gas mixtures representing the early Earth’s atmosphere. We also compare the products with those introduced by lightning events and solar ultraviolet light (UV). In a series of laboratory experiments, we detected and characterized the formation of amino acids and carboxylic acids via proton irradiation of a mixture of carbon dioxide, methane, nitrogen, and water in various mixing ratios. These experiments show the detection of amino acids after acid hydrolysis when 0.5% (v/v) of initial methane was introduced to the gas mixture. In the set of experiments with spark discharges (simulation of lightning flashes) performed for the same gas mixture, we found that at least 15% methane was required to detect the formation of amino acids, and no amino acids were detected in experiments via UV irradiation, even when 50% methane was used. Carboxylic acids were formed in non-reducing gas mixtures (0% methane) by proton irradiation and spark discharges. Hence, we suggest that GCRs and SEP events from the young Sun represent the most effective energy sources for the prebiotic formation of biologically important organic compounds from weakly reducing atmospheres. Since the energy flux of space weather, which generated frequent SEPs from the young Sun in the first 600 million years after the birth of the solar system, was expected to be much greater than that of GCRs, we conclude that SEP-driven energetic protons are the most promising energy sources for the prebiotic production of bioorganic compounds in the atmosphere of the Hadean Earth.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662250-6
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