PAI-1 inhibitor TM5614 leads osteosarcoma cells to G2 arrest

Osteosarcoma is a malignant tumor that histologically forms a tumor-like osteoid or bone. Plasminogen activator inhibitor 1 (PAI-1) is highly expressed in the blood of patients with various malignant tumors or in the tumors themselves, and its expression is positively correlated with tumor grade. Therefore, PAI-1 is a potential target for cancer therapy. In this study, a small-molecule PAI-1 inhibitor, TM5614, was tested on U2OS cells, which are osteosarcoma cell-like cells, to examine its effect on cell metabolism. The MTT assays and cell count analysis showed that TM5614 inhibited U2OS cell proliferation. We also tested the apoptotic activity of U2OS cells by multiple assays, and no induction of apoptosis by TM5614 was observed. In contrast, cell cycle analysis revealed that TM5614 induced U2OS cells in G2-M arrest. This study revealed that TM5614 treatment increased p53 and p21 Waf1/Cip1 expression in U2OS cells. In conclusion, we showed that the PAI-1 inhibitor TM5614 induced G2-M arrest in U2OS cells

Development, application, and evaluation of interactive simulation materials for learning the dental hygiene process of care

Dental hygiene students find it challenging to understand and perform the dental hygiene process of care (DHPC) after only a limited amount of clinical training; they generally improve their DHPC skills through clinical experience after graduation. In this study, we developed and evaluated interactive learning materials that simulate the DHPC. We divided the learning contents of the DHPC into six components and created five simulation materials. Using these materials, students could experience a typical DHPC virtually. In total, 30 third-year university dental hygiene students were divided into two groups (A and B), and then pre-quizzes were carried out for each group (group A: Quiz I, group B: Quiz II). Next, the students learned using the developed materials and took post-quizzes (group A: Quiz II, group B: Quiz I) to clarify their understanding of the DHPC. After the post-quizzes, a questionnaire survey was conducted. Both groups showed significantly higher scores on the post-quiz than on the pre-quiz (Group A: p = 0.0451 vs. Group B: p = 0.0090, paired Student’s t-test). In addition, more than 80% of the responses to the questionnaire were favorable. These results suggest that the simulation materials developed in this study are effective for learning the DHPC

Changes in Japanese Doctors’ Perspective after Battling Serious Illnesses and the Consequent Impact on their Medical Practice —The Wounded Healer

This study explored changes in the thinking and behavior of Japanese doctors who had personally battled serious illness. Doctors are often assumed to be physically and mentally healthy. When falling sick, they are prone to self-stigmatization. However, the positive outcomes of doctors battling illnesses have attracted scholarly attention. Psychiatrist Carl Jung advocated the concept of the “wounded healer,” a person who has endured an illness, gains wisdom from the experience, and uses it to heal others more effectively. We analyzed the aforementioned changes by narrowing down the “wounded healer” effect data group. We qualitatively analyzed verbatim transcripts of semi-structured interviews conducted with 14 doctors who had personally battled cancer, cerebrovascular disease, or heart disease using multilevel text condensation. After serious illness, doctors were more likely to believe that they had gained a lot from their experience. Changes in thinking related to medical practice included the acquisition of diverse knowledge. Such changes translated into behavioral changes; for example, understanding the patient’s perspective manifested in their improved communication with the patients. Most doctors diversified their activities outside of medical practice. Many also experienced significant changes in their views on life. The “wounded healer” effect was confirmed, bearing valuable implications for medical education

A cross-sectional survey on the status of oral health administration for students in Japanese universities

Purpose: A rapid deterioration of oral health after high school age is an issue to be addressed in Japan. Although this problem may relate to the weakness of oral health promotion for university students, the investigation of oral health-promoting activities, including annual dental checkups (DCs), undertaken by universities has never been conducted. Therefore, a questionnaire survey among health administration departments (HADs) was conducted to clarify the status of oral health-promoting activities for students. Methods: Self-administered questionnaire was voluntarily answered by HAD’s staff in 2015-2016. The major questions were on information concerning the university, HAD’s staff, implementation of DCs, and oral health-promoting activities for students. Results: Of 295 universities, 130 valid responses (response rate 44.1%) were analyzed. DCs were implemented in 10.9% of the universities. The main reasons for not implementing DCs were the large budgetary burden and low needs of students. The dental clinic introductory service was undertaken by 62.3%, whereas provision of oral health information was undertaken by only 23.8%. Conclusion: A low ratio of universities implemented DCs and provided oral health information. Further expansion of DC implementation is considered difficult because of the budgetary burden. Promoting the provision of oral health information from universities is required to improve students’ oral health

Cumulative Incidences of Lung Cancer in Various Interstitial Lung Diseases

Introduction: Interstitial lung disease (ILD) patients often develop lung cancer (LC). However, previous studies on the incidences of LC in ILDs focused on specific aetiologies, such as idiopathic pulmonary fibrosis (IPF). To investigate the incidences of LC in ILDs other than IPF, we conducted this study. Materials and Methods: ILD patients at our hospital were retrospectively reviewed. The cumulative incidences of LC in various ILD patients were estimated and compared among ILD groups for up to five years. The association between several variables at initial diagnosis and LC development was assessed to identify predictors. Results: In all, 587 ILD patients, including 161 IPF, 160 chronic HP, 133 non-IPF idiopathic interstitial pneumonias (IIPs), 87 connective tissue disease-related ILDs (CTD-ILDs), and 46 other ILDs, were included. Twenty-seven patients developed LC. The cumulative incidences of LC at 1, 3, and 5 years were 1.9%, 5.7%, and 12.3% in IPF, respectively; 2.0%, 4.6%, and 11.0% in chronic HP; 0.8%, 0.8%, and 4.0% in non-IPF IIPs; and 1.1%, 1.1%, and 2.9% in CTD-ILDs. Chronic HP patients had a high incidence of LC as IPF patients. Pack-years was associated with LC development in chronic HP patients. Conclusions: The incidences of LC are equally high in patients with chronic HP and IPF

Survey analysis on clinical problems of healthcare workers using blood collection devices in Japan

The purpose of this study was to investigate the clinical problems recognized and reported by healthcare workers (HCWs) who handle medical devices and analyze the factors associated with each problem, in order to investigate the development of blood collection support devices that are not widely used. An online survey was administered to 300 HCWs registered with a net research company to investigate how the intensity and frequency of 10 predetermined clinical problems would be reported. The relationship between the clinical problems and the attributes of the survey subjects was then analyzed using logistic regression analyses. As a result, the clinical problems frequently reported by the respondents were, to reduce labor, simplify data management, and obtain good medical materials. The need for imaging devices was reported to be low. The larger the scale of the medical institution, the more the problems reported by the HCWs. The fewer years of experience the HCWs had, the more likely they were to report a greater number of issues. In the development of blood collection support devices, it is necessary to listen to the opinions of HCWs with short clinical experience, working in large medical institutions and prioritize the development of devices that reduce labor

Optimal initial cell density that yields the highest number of primary synovial mesenchymal stem cells in a clinical setting

Synovial mesenchymal stem cell (MSC) transplantation improved clinical outcomes in knees. In clinical situations, nucleated cells were cultured with 10% autologous serum for 14 days. Nucleated cell number and serum volume practically varied by patient, and initial cell density and dish number affected yield/donor. Our purpose was to estimate the MSC yield/donor from the fold increase obtained in this experiment in several patterns. We obtained the data of the autologous serum volume, nucleated cell number, and initial plating cell density from 10 patients who participated in our previous clinical studies. We used these previous clinical data and the current experimental data. Experimentally, fold increase significantly decreased between 700 and 1,900 cells/cm². In cases where the nucleated cell number was low and the serum volume was high, the estimated MSC yield/donor decreased along with the initial plating density. In cases where the nucleated cell number was high and the serum volume was low, the estimated MSC yield/donor increased along with the initial plating density. In cases where some nucleated cells were discarded, the maximum MSC yield/donor were obtained when the initial cell density was the highest cell density where some nucleated cells were discarded

Doublecortin-like kinase 1 expression is induced by alternative NF-κB signaling in human lung cancer cells

Idiopathic pulmonary fibrosis (IPF), a devastating fibrotic lung disease of unknown etiology, is frequently associated with lung cancer. However, the molecular mechanism underlying this association remains unclear. We analyzed the gene expression profiles of IPF lungs using public datasets and extracted 94 genes that were upregulated in all of them. Among these, we identified DCLK1, a wellknown cancer stem cell-marker. A recent study revealed that DCLK1 enhances cancer stem cell-like features in lung cancer cells. Therefore, if DCLK1 expression is induced in IPF, it could be a molecular link between IPF and lung cancers. In this study, we confirmed that DCLK1 expression was enhanced in human IPF lungs and in lungs of mice with bleomycin- induced fibrosis. We also found that the human lung cancer H1299 cells expressed DCLK1 when exposed to the conditioned medium derived from the lipopolysaccharide-stimulated murine macrophage- like RAW264.7 cells. Further, this DCLK1-inducing activity was sensitive to heat inactivation and proteinase K treatment. We also revealed that IL17 and lymphotoxin-α induced DCLK1 expression in human lung cancer H1299 cells. Moreover, RELB silencing, but not RELA silencing, blocked the induction of DCLK1 expression by conditioned medium. Hence, the inhibition of alternative NF-κB signaling may be useful to prevent cancer development in IPF lungs