Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

al., 1985;Young et al., 1986a). PFP released from killer cells forms pores on the target cell membrane and induces cell lysis (Henkart, 1985;Zalman et al., 1986;Young et al., 1986b). Recent success in the cloning of PFP cDNA (Shinkai et al., 1988a;Lichtenheld et al., 1988;Lichtenheld & Podack, 1989;Lowrey et al., 1989) has allowed the examination of mRNA expression of PFP in killer cells. In the T cell lines, PFP gene expression was ascertained in the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but not in helper T (Th) cells (Shinkai et al., 1988a;Lichtenheld et al., 1988).The role of tumour infiltrating lymphocytes (TIL) in the defense mechanism of a tumour-bearing host has been thoroughly reported (Werkmeister et al., 1979). It is known that CTL and NK cells directly kill tumour cells (Reinherz et al., 1979;Lanier et al., 1983;Lanier et al., 1986 (v/v) hydrogen peroxidase, freshly prepared ABC complex (Vectastain R ABC Kit, Vector) was applied and followed by incubation for 30 min. After the excess complex was washed out, the localisation of PFP was visualised by incubating the sections for 5 min in freshly prepared Tris-HCI containing both 0.02% (w/v) 3.3'-diaminobenzidine tetrahydrochloride (Sigma, St Louis, MO) and 0.03% (v/v) hydrogen peroxide. The nuclei were counterstained with haematoxylin.

Bromoxynil, 3,5-dibromo-4-hydroxybenzonitrile, is a commonly used herbicide and is also used as a tool to trigger rapid cell death in basic botany. However, the primary effect inducing cell death is not known. Bromoxynil inhibited the cytoplasmic streaming and killed cells in Chara corallina when it was applied in the acidic external medium. At higher pH, bromoxynil was inert even at high concentrations. It was speculated that bromoxynil in the protonated form enters the cell and acidifies the cytosol by releasing H(+). Experiments using analogues of bromoxynil supported this possibility. Acidification of the cytosol by bromoxynil was confirmed by experiments using pollen tubes. Based on the acidity of the apoplast, the herbicide action of bromoxynil in higher plants was discussed.

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Mamushi bites cause swelling and pain that extend from the bitten site. The coagulopathic, anti‐coagulopathic, and vasculopathic actions of mamushi venom result in various laboratory abnormalities, occasionally with muscular, renal, and other organ damage. We investigated the serum biomarkers that were associated with the pathogenesis of mamushi bites, focusing on markers related to tissue‐damage and neutrophil activation. Twenty patients (one case of grade 2, 13 cases of grade 3, and six cases of grade 4 of severity) seen by us in one summer season were enrolled. Peripheral blood samples were taken from the patients on day 0, day 2, and day 7 after mamushi bites. In addition to routine blood examination, serum samples were subjected to enzyme‐linked immunosorbent assay for citrullinated histone H3 (CitH3), interleukin (IL)‐8, IL‐17A, IL‐22, vascular endothelial growth factor (VEGF), high mobility group box protein 1 (HMGB1), tumor necrosis factor (TNF)‐α, and IL‐33. Creatinine kinase (CK) values significantly correlated with prothrombin time (PT) levels, suggesting that muscular damage is associated with exaggerated coagulation and fibrinolysis. In the vast majority of patients, HMGB1, TNF‐α, and IL‐33 were under detection levels. Neutrophil counts did not correlate with PT or CK, indicating that the coagulation disorder and muscular damage were virtually independent of the neutrophil activation. The neutrophil number significantly correlated with CitH3, a representative marker of neutrophil extracellular traps. Moreover, there were significant correlations between neutrophil number, CitH3, IL‐8, IL‐22, and VEGF. Our study suggests that there are two major cascades in mamushi bites. One is an already characterized venom effect on coagulation, vessels, and muscles. In the other novel cascade, we propose that neutrophil activation with IL‐8 leads to the production of IL‐22 and VEGF. This sequential event may contribute to both vascular damage and repair.

To protect against COVID-19, SARS-CoV-2 vaccines have been widely used. Besides anaphylaxis, some less severe adverse effects may occur at higher frequencies. It remains unclear whether present or past histories of allergic diseases exert effects on local and systemic reactions. We conducted a questionnaire survey among workers in our hospital. We analyzed the adverse effects occurring after the first and second doses of the Pfizer–BioNTech vaccine in 955 subjects. The presence or absence of local injection reactions and systemic reactions (headache, fatigability, fever, muscle pain, and joint pain) was questioned. The intensities of these reactions were graded on a scale of 0–4 (except fever) or 0–2 (fever). The allergic diseases that we focused on were bronchial asthma, atopic dermatitis, food allergy, pollinosis, and hand eczema. For the systemic reactions, fatigability after the first dose tended to be more severe in the bronchial asthma than in the non-allergic group. Headache, joint pain, and fever tended to be more severe in the food allergy than in the non-allergic group after the second dose. For the local skin reactions, atopic dermatitis subjects tended to show rather less severe local skin reactions after the second dose. The results contribute to the guidelines for the care of individuals with different allergy histories, so that they may safely receive their vaccine.

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