Phenochalasin A, a unique phenol-containing cytochalasin produced by the marine-derived fungus Phomopsis sp. FT-0211, was originally discovered in a cell morphological assay of observing the inhibition of lipid droplet formation in mouse peritoneal macrophages. To investigate the mode of action and binding proteins, phenochalasin A was radio-labeled by 125I. Iodinated phenochalasin A exhibited the same biological activity as phenochalasin A. [125I]Phenochalasin A was found to be associated with an approximately 40 kDa protein, which was identified as G-actin. Furthermore, detail analyses of F-actin formation in Chinese hamster ovary cells (CHO-K1 cells) indicated that phenochalasin A (2 µM) caused elimination of F-actin formation on the apical site of the cells, suggesting that actin-oriented specific function(s) in cytoskeletal processes are affected by phenochalasin A.
Parkinson's disease (PD) is the world's second most common neurological disorder. Oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. Eugenol is a phytochemical with potent antioxidant and anti-inflammatory activity. The present investigation is aimed to study the effect of eugenol in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of PD and its relationship to antioxidant effect. The effects of seven days of oral pre-treatment and post-treatment with three doses of eugenol (25, 50 and 100 mg/kg/day) were investigated against the MPTP-induced PD mouse model. In addition to the assessment of behavioural parameters using various tests (actophotometer, beam walking test, catalepsy, rearing, rotarod), biochemical parameters including lipid peroxidation and reduced glutathione levels in brain tissues, were also estimated in this study. The binding mode of eugenol in the human myeloid differentiation factor-2 (hMD-2) was also studied. Results showed that MPTP administration in mice resulted in the development of motor dysfunction (impaired motor coordination and hypo locomotion) similar to that of PD in different behavioural studies. Pre-treatment with eugenol reversed motor dysfunction caused by MPTP administration while post-treatment with eugenol at a high dose aggravated the symptoms of akinesia associated with MPTP administration. MPTP resulted in increased lipid peroxidation while decreased reduced glutathione levels in the brains of mice. MPTP-induced increased lipid peroxidation and attenuated levels of reduced glutathione were found to be alleviated with eugenol pre-treatment while augmented with eugenol post-treatment. Eugenol showed a binding affinity of -6.897 kcal/mol against the MD2 coreceptor of toll-like receptor-4 (TLR4). Biochemical, as well as neurobehavioral studies, showed that eugenol is having a protective effect, but does not have a curative effect on PD.
This study aims to clarify the clinical significance of dupilumab-induced elevation of blood eosinophil in Japanese patients with atopic dermatitis (AD). Eosinophil elevation was defined as ≥ 5% increase of eosinophil percentage within one year after dupilumab initiation. Seven patients (15.7%) were shown to have eosinophil elevation, six of whom developed dupilumab-associated conjunctivitis (DAC) and were accompanied with DAC more frequently than those without eosinophil elevation, with statistically significant difference. Eosinophil percentage resolved spontaneously in all seven patients, including the one without DAC, despite the continuation of dupilumab treatment. None of the patients with eosinophil elevation had cardiac or pulmonary complications attributable to the hypereosinophilia. The patients with eosinophil elevation were all male. Furthermore, none of four patients in whom efficacy of dupilumab was < 25% showed eosinophil elevation. Childhood onset tended to be more common in patients with the elevation of eosinophil. This study suggests that most eosinophil elevation is associated with DAC, and that the eosinophil ratio is a biomarker for DAC.
Thermography is a well-known risk-assessment tool for diabetic foot ulcers but is not widely used in the home setting due to the influence of the complicated home environment on thermographic images. This study investigated changes in thermographic images in complicated home environments to determine the feasibility of smartphone-based thermography in home settings. Healthy volunteers (age > 20 years) were recruited and required to take plantar thermal images using smartphone-based thermography attached to a selfie stick at different times of the day for 4 days. The thermal images and associated activities and environmental factors were then analyzed using content analysis. Areas with the highest temperature on the plantar thermal images were described and categorized. Device usability was evaluated using 10-point Likert scales, with 10 representing the highest satisfaction. A total of 140 plantar thermal images from 10 participants were analyzed. In 12 classifications, the three commonest patterns based on the highest temperature location were medial arch (42.1%), whole plantar (10.7%), and forefoot and medial arch (7.9%). The medial arch pattern is most frequently seen after awakening (67.5%) compared to other time points. Device usability was rated 7.5 out of 10 on average. This study was the first to investigate the plantar thermal patterns in the home settings, and the medial arch pattern was the most common hot area, which matches previous findings in well-controlled clinical settings. Therefore, smartphone-based thermography may be feasible as a self-assessment tool in the home setting.
Heart failure with reduced ejection fraction (HFrEF) due to ischemic heart disease (IHD) showed a progressive decline in left ventricular contractile function. However, no previous study has examined the left ventricular global longitudinal strain (LV GLS) parameter that represents LV contractile function. We investigated whether trimetazidine could improve the LV GLS value in patients with HFrEF due to IHD. We performed a double-blind, randomized controlled trial (RCT) including 26 patients with HFrEF due to stable IHD who were given modified-release trimetazidine 35 mg twice per day (n = 13) or placebo (n = 13) for 3 months in addition to standard medication. Left ventricular systolic function including GLS values was assessed at baseline and after 3 months using echocardiography. A total of 25 participants (13 control and 12 trimetazidine groups) were recruited with a baseline average age of 57.1 ± 10 years, and LV ejection fraction (LVEF) value of 34.6% ± 4.4%, and a GLS value of 7.4% ± 2.1%. Baseline clinical characteristics and echocardiogram were similar between the two groups. There was significant GLS improvement in the trimetazidine group (−6.9% ± 2.4% to −8.4% ± 2.6%, p = 0.000), but no significant differences were noted in the control group. The GLS improvement was significantly higher in the trimetazidine group than the control (1.5% + 0.9% vs. −0.7% + 1.7%, p = 0.001). No adverse drug reactions from the administration of trimetazidine in this study. Trimetazidine may improve GLS values in patients with HFrEF due to IHD.
School-based coronavirus disease 2019 (COVID-19) testing is an important part of a comprehensive prevention strategy in public health. To assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in a university athletic club community with repeated occurrences of SARS-CoV-2 infections, we conducted a cross-sectional survey for asymptomatic antibody prevalence using a SARS-CoV-2 rapid antibody test kit. On January 26, 2021 we administered questionnaires to determine their history of contact with infected individuals and took blood samples from 129 undergraduates. The prevalence of SARS-CoV-2 antibodies among the subjects was 3.9%. Only 6.2% of the participants reported close contact with infected individuals. In this study, we clarified the prevalence of asymptomatic SARS-CoV-2 antibodies in university athletic clubs where SARS-CoV-2 infections had repeatedly occurred, which will be helpful in discussing how to identify and prevent the transmission of infections within university athletic club communities.
We previously developed electrolyzed water (EW) using carbon electrodes and estimated its ability to inhibit the proliferation of human cervical carcinoma HeLa cells. In this study, we found that EW-containing media could not only inhibit HeLa cell proliferation, but were also capable of promoting the proliferation of normal human dermal fibroblasts (NHDF). In addition, the developed EW could reduce cytochrome c, as demonstrated by the cytochrome c reduction assay. Interestingly, EW with a greater pH, which was unable to inhibit HeLa cell proliferation, completely lost the ability to reduce cytochrome c. Our results indicate that EW has opposite effects on cancer and normal cell proliferation and has the ability to reduce cytochrome c. Based on our findings, we suggest the possibility that the reducing capacity of our developed EW may be involved in the significant inhibition of HeLa cell proliferation.
The coronavirus disease 2019 (COVID-19) pandemic continues to ravage the world, and the virus' constant evolution has made it increasingly difficult to contain. The combination of the neutralizing antibodies amubarvimab and romlusevimab has recently been introduced as a treatment for COVID-19 in China. Based on its potential to effectively combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron variant at a modest cost and under medical insurance, this controversial biotherapy is anticipated to be widely available in China. Hopefully, whether and how the proposed medication will alter the treatment of COVID-19 in China will be apparent soon, as well as if it will help to reduce hospitalizations, reduce the incidence of severe illness, or even act as pre-exposure prophylaxis.
This study was aimed at assessing the adherence and incorrect drug intake associated with changes in the dosing schedule of raltegravir, the first integrase strand transfer inhibitor, from 400 mg twice a day (BID) to 600 mg × 2 tablets once a day (QD) in human immunodeficiency virus (HIV)-infected patients. Medication adherence over 1 month was evaluated in 25 male patients using the 100-mm visual analog scale (VAS) at the 3-day recall pill count and during pharmacist counseling after the first post-change visit. VAS scores before and after the raltegravir formulation change were compared. Medication adherence increased from 96 ± 4.3 mm (BID) to 100 ± 0.3 mm (QD) (P < 0.05). The patients exhibited improved medication adherence; however, three patients incorrectly took the drug when the formulation changed. This discovery can be used to facilitate the treatment of HIV-infected patients to increase treatment suitability and safety.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematopoietic stem cell disorder, characterized by hemolytic anemia, bone marrow failure and thrombosis. Portal vein thrombosis (PVT) is relatively rare in patients with PNH. In this paper, we reported PVT as the first clinical presentation of PNH in a female patient. PVT related symptoms resolved after anticoagulation therapy.