Effect of econazole on membrane calcium transport in rat thymocytes

Econazole, one of azole antifungals, is proven to exhibit an inhibitory action on Mycobaterium tuberculosis and its multidrug-resistant strains under in vitro and ex vivo conditions. However, econazole has been used as a pharmacological tool for inhibiting capacitative Ca2+ influx and exerts multiple effects on cellular Ca2+ circumstance. Therefore, to suggest the toxic effect of econazole at therapeutic concentrations, we have tested on the effect on membrane Ca2+ transport in rat thymocytes by using a flow cytometer with Fluo-3, an indicator of intracellular Ca2+. Econazole at concentrations of 1-3 μM increased membrane Ca2+ permeability and inhibited capacitative Ca2+ influx without affecting passive Ca2+ influx, Ca2+ release from intracellular Ca2+ store sites, and membrane Ca2+ pump. Econazole at 0.3 μM, a therapeutic concentration against tuberculosis caused by multidrug-resistant and latent M. tuberculosis, did not affect membrane Ca2+ transport. It may be suggested that econazole at therapeutic concentrations exerts no side effect related to Ca2+

Spatio-temporal distribution of environmental DNA derived from Japanese sea nettle jellyfish Chrysaora pacifica in Omura Bay, Kyushu, Japan

We surveyed the spatial and temporal distribution of Japanese sea nettle jellyfish Chrysaora pacifica in Omura Bay, Japan, using an environmental DNA (eDNA) method. In 2018, the C. pacifica eDNA concentration increased from March?May at all depths. The seasonal pattern of C. pacifica eDNA was consistent with previous reports based on visual observations along the Japanese coast. Thus, the eDNA method might have advantages to follow the seasonal pattern of C. pacifica while being less time-consuming and less laborious compared with traditional methods. The eDNA concentrations tended to reach a maximum near and/or below the pycnocline throughout this study. Therefore, the vertical distribution of C. pacifica medusae may have been restricted by strong pycnocline formation in July and August 2018. However, even with a weak pycnocline, which C. pacifica should be able to swim across, the apparent distribution of C. pacifica eDNA seems to be restricted by the pycnocline. Therefore, the eDNA method cannot, currently, accurately assess the absolute vertical distribution pattern of C. pacifica, especially when a pycnocline is formed

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Prevalence of asthma symptoms based on the European Community Respiratory Health Survey questionnaire and FENO in university students: gender differences in symptoms and FENO

<p>Abstract</p> <p>Background</p> <p>The fractional concentration of nitric oxide in exhaled air (F<smcaps>E</smcaps>NO) is used as a biomarker of eosinophilic airway inflammation. F<smcaps>E</smcaps>NO is increased in patients with asthma. The relationship between subjective asthma symptoms and airway inflammation is an important issue. We expected that the subjective asthma symptoms in women might be different from those in men. Therefore, we investigated the gender differences of asthma symptoms and F<smcaps>E</smcaps>NO in a survey of asthma prevalence in university students.</p> <p>Methods</p> <p>The information about asthma symptoms was obtained from answers to the European Community Respiratory Health Survey (ECRHS) questionnaire, and F<smcaps>E</smcaps>NO was measured by an offline method in 640 students who were informed of this study and consented to participate.</p> <p>Results</p> <p>The prevalence of asthma symptoms on the basis of data obtained from 584 students (266 men and 318 women), ranging in age from 18 to 24 years, was analyzed. Wheeze, chest tightness, an attack of shortness of breath, or an attack of cough within the last year was observed in 13.2% of 584 students. When 38.0 ppb was used as the cut-off value of F<smcaps>E</smcaps>NO to make the diagnosis of asthma, the sensitivity was 86.8% and the specificity was 74.0%. F<smcaps>E</smcaps>NO was ≥ 38.0 ppb in 32.7% of students. F<smcaps>E</smcaps>NO was higher in men than in women. The prevalence of asthma symptoms estimated by considering F<smcaps>E</smcaps>NO was 7.2%; the prevalence was greater in men (9.4%) than women (5.3%). A F<smcaps>E</smcaps>NO ≥ 38.0 ppb was common in students who reported wheeze, but not in students, especially women, who reported cough attacks.</p> <p>Conclusions</p> <p>The prevalence of asthma symptoms in university students age 18 to 24 years in Japan was estimated to be 7.2% on the basis of F<smcaps>E</smcaps>NO levels as well as subjective symptoms. Gender differences were observed in both F<smcaps>E</smcaps>NO levels and asthma symptoms reflecting the presence of eosinophilic airway inflammation.</p> <p>Trial registration number</p> <p>UMIN000003244</p

Prevalence of Possible Dementia in Patients with Maxillofacial Defects and Difficulty of Inserting Obturator in Maxillectomy Patients: Toward Better Provision of Supportive Care

As society ages, it is important to understand the prevalence of dementia and the difficulties of inserting prostheses in patients with maxillofacial defects in order to clarify issues in supportive care. We screened 183 patients for dementia using the revised Hasegawa’s dementia scale (HDS-R) at the Clinic for Maxillofacial prosthetics, Tokyo Medical and Dental University, and investigated age and sex differences in HDS-R score. We asked 47 of the 183 participants about the difficulty of inserting a maxillofacial obturator prosthesis and collected subjective comments, information about the prosthesis, and data from five assessments. Multiple regression analysis was used to reveal factors associated with insertion difficulty. Overall, 8.7% of the participants were judged to have possible dementia. Men were more likely than women to have possible dementia, and the risk increased with age. Of the 47 participants, 26 reported difficulty inserting their prosthesis, 12 of whom attributed it to their oral defect. Fourteen patients advised following doctor’s instructions to practice insertion in order to become accustomed to it. A lower HDS-R score had a significant impact on insertion difficulty. Cognitive function and difficulty inserting maxillary obturator prostheses should be considered in the provision of continuous supportive care to patients with maxillary defects