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Assessing individual external exposure doses from ambient dose equivalents is valuable for predictive and retrospective purposes when personal dosimeters are impractical. This study developed a model to assess individual external exposure doses from ambient dose equivalents, considering daily life patterns (location and time spent in various places), and evaluated parameters associated with individual external exposure doses, such as the reduction effects of radiation due to buildings and vehicles. The model parameters were evaluated using the robust datasets of environmental radiation measured in areas affected by the Fukushima Daiichi Nuclear Power Station (FDNPS) accident. The effective dose estimated by the model was compared to 106 daily personal dose equivalents measured using personal dosimeters in the residents' living environments near the FDNPS. The estimated effective dose well consists with the measured personal dose equivalents, particularly when considering natural radiation in indoor dose estimation. This model is adequate for radiation protection, enabling the predictive and retrospective estimation of individual external exposure doses using environmental radiation monitoring data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Alkylating reagent chemotherapy for human cancers is not curative, and relapse occurs due to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD cells after chemotherapy, a phenomenon referred to as intrinsic resistance, depends on reactive oxygen species. Well-differentiated regions of the tumor are intrinsically resistant to chemotherapy. Receptor tyrosine kinase erythropoietin-producing human hepatocellular receptor A4 (EphA4) protein is highly expressed in the well-differentiated tumor-derived cervical cancer cell line Caski, but not in poorly differentiated tumor-derived cervical cancer cell lines such as HeLa or SiHa. Here, we report that reactive oxygen species produced by cisplatin exposure induce tyrosine phosphorylation of EphA4. After observing that EphA4 is activated by cisplatin, we rationalized a combination chemotherapy that induces well-differentiated cervical cancer death. Pharmacological inhibition of EphA4 increased cisplatin-induced cell death in Caski cells. Moreover, we observed increased expression levels of the senescence marker cyclin-dependent kinase inhibitor 2A (p16) in the absence of EphA4 kinase function after stimulation of Caski cells with cisplatin exposure. Mechanistically, cisplatin induces chemotherapy resistance of Caski cells by upregulating Lyn, a Src family kinase (SFK) that interacts with EphA4, through a pathway involving reactive oxygen species. Thus, the reactive oxygen species-SFK-EphA4 axis presents new potential drug targets for chemotherapy resistance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, we examined the interaction between histamine H1 receptor and μ-opioid receptor in scratching behavior in ICR mice. Both histamine and morphine caused scratching and simultaneous injection of histamine and morphine had an additive effect. Chlorpheniramine and naloxone inhibited histamine-induced scratching behavior. These two drugs also inhibited morphine-induced scratching behavior. Simultaneous injection of chlorpheniramine and naloxone caused a significant inhibition of histamine-induced scratching compared with separate injections. The same findings were also noted for morphine-induced scratching. These results strongly indicate a close relationship between histamine H1 receptor and μ-opioid receptor in scratching behavior in ICR mice., (Copyright © 2016 Elsevier B.V. All rights reserved.)

For decades, platinum drugs have been the mainstay of cancer treatment. However, over time, drug resistance develops, leaving few treatment options. Here we show that platelet-derived growth factor α receptor (PDGF α receptor)-mediated signaling plays a key role in hepatocyte growth factor (HGF) receptor (c-Met) upregulation, which in turn is thought to play an important role in chemotherapy resistance. PDGF α receptor inhibition eliminates cisplatin-dependent Met expression in cervical cancer cell lines. PDGF α receptor inhibitors are widely used in clinical settings, suggesting that the clinical translation of our findings could reduce the suffering of people from drug resistance., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We examined the effect of antiallergic drugs, azelastine and epinastine, on the expression of FcepsilonRIalpha, beta, and gamma chains and phosphorylation of the gamma chains in rat basophilic leukemia (RBL-2H3) cells. The cells were cultured for 24 h with IgE treatment in the presence of azelastine or epinastine at the concentration of 10(-5) M. The FcepsilonRIalpha mRNA expression was determined by northern blot analysis. The protein level of FcepsilonRI expressed on the plasma membrane was examined following IgE treatment by immunoprecipitation with anti-IgE light chain, followed by western blot analysis with anti-gamma chain of FcR. Azelastine and epinastine had no effect on the FcepsilonRIalpha, beta and gamma mRNA levels. Although the amount of gamma chain assembled into IgE-bound FcepsilonRI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of gamma chains of IgE-bound FcepsilonRI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of FcepsilonRIgamma protein is not due to their inhibition of mRNA and protein expression, but due to abrogating phosphorylation of the gamma chains, which is important for initiation of FcepsilonRI signaling cascade elicited by IgE interaction.

We asked whether or not antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit IgE secretion from IgE-producing hybridoma FE-3 cells. FE-3 cells were cultured in the presence of azelastine or epinastine for 24 h, washed in phosphate-buffered saline , and then recultured in the medium in the absence of the antiallergic drugs. IgE levels in the cultured medium as well as those in the cytoplasm of FE-3 cells were measured by enzyme-linked immunosorbent assay. mRNA levels of Cepsilon, activation-induced cytidine deaminase (AID), XBP-1, and Bip were estimated by northern blot or reverse transcriptase polymerase chain reaction analysis. The activities of nuclear factor-kappa B (NF-kappaB) were analyzed by electrophoretic mobility shift assay (EMSA). Phosphorylation of I kappa B alpha (IkappaBalpha) was analyzed by immunoprecipitation followed by western blot analysis. IgE levels in the cultured medium and in the microsome fraction were lower on the treatment with 10(-5) M azelastine or epinastine than those on the treatment with vehicle. Cepsilon and AID mRNA levels were lower on the treatment with 10(-5) M azelastine than those on the treatment with vehicle, but were not decreased on the treatment with 10(-5) M epinastine. XBP-1 and Bip mRNA levels were not altered following treatment of the antiallergic drugs. Azelastine at 10(-5) M, but not epinastine, reduced DNA binding activity of NF-kappaB and also diminished IkappaBalpha phosphorylation, leading to sustaining IkappaBalpha protein levels. These findings suggest that azelastine exerts its inhibitory effect on the IgE secretion from FE-3 cells through the inhibition of Cepsilon mRNA expression, and that the inhibitory effect of epinastine is, at least in part, due to suppression of IgE synthesis at the post-transcriptional level.

The development of a successful recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vector-based vaccine for human immunodeficiency virus type 1 (HIV-1) requires the induction of high levels of HIV-1-specific immunity while at the same time maintaining immunity to tuberculosis. To examine a combined vaccination strategy for enhancement of immune responses specific for HIV-1, guinea pigs were inoculated with either a single or combination intradermal (i.d.), intrarectal (i.r.) and intranasal (i.n.) administration of rBCG-pSOV3J1 which secretes a chimeric protein of HIV-1 V3J1 peptide and alpha-antigen. Significant level of delayed-type hypersensitivity to both V3J1 peptide and tuberculin was induced in guinea pigs inoculated with human doses of rBCG-pSOV3J1 by a combination of intrarectal and intradermal routes. Guinea pigs inoculated by combined routes also had significantly higher titers of HIV-1-specific serum IgG and IgA compared with those animals immunized only intrarectally, which led to the enhanced neutralization activity against HIV-1(MN). In addition, the induction of high levels of IFNgamma and interleukin-2 (IL-2) mRNA in PBMC, splenocytes, and intraepithelial lymphocytes from the immunized animals was detected until at least 110 weeks post-inoculation. These results suggest that enhanced immune responses specific for HIV-1 are efficiently induced by combined intrarectal and intradermal immunization with rBCG-HIV, and antigen-specific Th1-type memory cells are maintained for more than 2 years in the immunized animals. Thus, inoculation with rBCG-HIV by combined routes represents an effective vaccination strategy to elicit high levels of HIV-1-specific immune responses.