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Abstract. Melanoma inoculation induced marked mechanical allodynia and hyperalgesia in the periphery of the melanoma mass in mice from about day 10 post-inoculation. In the middle of the tumor, there were slight hyperalgesia and response disappearance in the early and late phases, respectively. PGP9.5-like immunoreactivities increased in the epidermis of the periphery of the tumor and disappeared from the dermis of the middle on day 18 post-inoculation, without apparent alterations on day 10. When using this pain model, one should consider the tumor site-dependent responses.Keywords: skin cancer pain, primary afferent fiber, allodynia and hyperalgesia Although pain at the end stage of cancer is a severe problem for patients, the mechanisms of cancer pain remain unclear. Recently, several kinds of animal models of cancer pain have been developed. These include bone cancer pain (1, 2), skin cancer pain (3) and neuropathic cancer pain (4). These models have demonstrated the distinct pharmacological and neurochemical aspects of cancer pain, suggesting that cancer pain is not simply a form of pain due to inflammation and / or neuropathy.When given orthotopic inoculation of melanoma cells into the hind paw, mice show moderate and marked thermal hyperalgesia on days 7 -10

Background Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. Methods Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. Results Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1β) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1β expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. Conclusions These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS.

The capabilities of four white-rot fungi to improve the digestibility of sugarcane bagasse for ruminants were determined. Bagasse was cultured with Lentinula edodes, Pleurotus eryngii, Pleurotus salmoneostramineus, Ceriporiopsis subvermispora (ATCC 90467) or C. subvermispora (CZ-3) at 26°C for 8, 12 or 16 weeks. The in vitro organic matter digestibility (IVOMD) and in vitro neutral detergent fiber digestibility (IVNDFD) in untreated bagasse were 45.6 and 40.3%, respectively. Meanwhile, the bagasse cultured with L. edodes and two strains of C. subvermispora, respectively, for 12 weeks, were elevated to 68.6 and 59.1%, 60.6 and 49.9% and 59.9 and 49.0%, respectively. In contrast, the IVOMD and the IVNDFD in bagasse cultured with P. eryngii and P. salmoneostramineus were the same or lower than those in untreated bagasse. In vitro gas production (IVGP) in bagasse cultured with L. edodes and two strains of C. subvermispora for 12 weeks was also higher than that of untreated bagasse. These changes in IVOMD, IVNDFD and IVGP demonstrate that L. edodes has a higher capability of improving the digestibility for ruminants than C. subvermispora, P. eryngii or P. salmoneostramineus.Values without untreated bagasse and rice straw represent the means of three media, and those within columns with different superscript letters (a-h) denote significant difference at a 5% level.

Small-cell lung cancer (SCLC) is a highly aggressive cancer with poor prognosis, due to a lack of therapeutic targets. Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables and has shown anticancer effects against numerous types of cancer. However, its anticancer effect against SCLC remains unclear. The present study aimed to demonstrate the anticancer effects of SFN in SCLC cells by investigating cell death (ferroptosis, necroptosis and caspase inhibition). The human SCLC cell lines NCI-H69, NCI-H69AR (H69AR) and NCI-H82 and the normal bronchial epithelial cell line, 16HBE14o-were used to determine cell growth and cytotoxicity, evaluate the levels of iron and glutathione, and quantify lipid peroxidation following treatment with SFN. mRNA expression levels of cystine/glutamate antiporter xCT (SLC7A11), a key component of the cysteine/glutamate antiporter, were measured using reverse transcription-quantitative PCR, while the levels of SLC7A11 protein were measured using western blot analysis. Following the addition of SFN to the cell culture, cell growth was significantly inhibited, and cell death was shown in SCLC and multidrug-resistant H69AR cells. The ferroptotic effects of SFN were confirmed following culture with the ferroptosis inhibitor, ferrostatin-1, and deferoxamine; iron levels were elevated, which resulted in the accumulation of lipid reactive oxygen species. The mRNA and protein expression levels of SLC7A11 were significantly lower in SFN-treated cells compared with that in the control cells (P<0.0001 and P=0.0006, respectively). These results indicated that the anticancer effects of SFN may be caused by ferroptosis in the SCLC cells, which was hypothesized to be triggered from the inhibition of mRNA and protein expression levels of SLC7A11. In conclusion, the present study demonstrated that SFN-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in SCLC cells. The anticancer effects of SFN may provide novel options for SCLC treatment.