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Oral cancer pain is debilitating and understanding mechanisms for it is critical to develop novel treatment strategies treatment strategies. Brain-derived neurotrophic factor (BDNF) signaling is elevated in oral tumor biopsies and is involved with tumor progression. Whether BDNF signaling in oral tumors contributes to cancer-induced pain is not known. The current study evaluates a novel peripheral role of BDNF-tropomyosin receptor kinase B (TrkB) signaling in oral cancer pain. Using human oral squamous cell carcinoma (OSCC) cells and an orthotopic mouse tongue cancer pain model, we found that BDNF levels were upregulated in superfusates and lysates of tumor tongues and that BDNF was expressed by OSCC cells themselves. Moreover, neutralization of BDNF or inhibition of TrkB activity by ANA12, within the tumor-bearing tongue reversed tumor-induced pain-like behaviors in a sex-dependent manner. Oral squamous cell carcinoma conditioned media also produced pain-like behaviors in naive male mice that was reversed by local injection of ANA12. On a physiological level, using single-fiber tongue-nerve electrophysiology, we found that acutely blocking TrkB receptors reversed tumor-induced mechanical sensitivity of A-slow high threshold mechanoreceptors. Furthermore, single-cell reverse transcription polymerase chain reaction data of retrogradely labeled lingual neurons demonstrated expression of full-form TrkB and truncated TrkB in distinct neuronal subtypes. Last but not the least, intra-TG siRNA for TrkB also reversed tumor-induced orofacial pain behaviors. Our data suggest that TrkB activities on lingual sensory afferents are partly controlled by local release of OSCC-derived BDNF, thereby contributing to oral cancer pain. This is a novel finding and the first demonstration of a peripheral role for BDNF signaling in oral cancer pain.

Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) treatment has demonstrated survival benefits but noticeable side effects in patients with pancreatic ductal adenocarcinoma (PDAC) that is refractory to gemcitabine-based therapy. This study aimed to explore whether combining albumin with the neutrophil-to-lymphocyte ratio (NLR), herein known as the albumin and neutrophil-to-lymphocyte ratio score (ANS), could be utilized as a simple tool to predict survival and safety profiles in such patient groups. We retrospectively enrolled 434 consecutive PDAC patients treated with nal-IRI + 5-FU/LV between 2018 and 2020 at nine medical centers in Taiwan. Patients were divided into three groups: ANS 0 (high albumin and low NLR), ANS 1 (low albumin or high NLR), and ANS 2 (low albumin and high NLR), for comparison. The median overall survival times for the ANS 0, 1, and 2 groups were 8.7 months (95% confidence interval (CI), 7.0-10.3 months), 5.2 months (95% CI, 4.3-6.0 months), and 2.6 months (95% CI, 1.9-3.3 months), respectively. The ANS was found to be an independent variable for overall survival and time-to-treatment failure in multivariate analyses. Patients in the ANS 2 group had significantly higher incidences of grade 3 or higher treatment-related adverse events than those in the other two groups. The present study showed that the ANS was an independent prognosticator in PDAC patients receiving nal-IRI + 5-FU/LV therapy. The ANS can be a simple predictor of survival outcome and safety profiles in PDAC patients treated with nal-IRI + 5-FU/LV.

In order to find a new preservation solution for avian coccidial oocysts that can replace potassium dichromate (K2Cr2O7) solution, Eimeria tenella oocysts were preserved in 0.1 to 10% potassium sorbate (C6H7KO2) solution in this study. The results showed that there was no significant difference between the sporulation rate of E. tenella oocysts preserved in 0.1 to 10% C6H7KO2 solution and in 2.5% K2Cr2O7 solution (p > 0.05). The 0.5 to 10% C6H7KO2 solution could also effectively inhibit the growth of bacterial microorganisms. E. tenella oocysts preserved in 1% C6H7KO2 solution at 4 °C for 3, 6, 9, and 12 months, with the oocyst production of E. tenella oocysts being 1.3-, 1.2-, 1.6-, and 1.3-fold higher than that of oocysts stored in 2.5% K2Cr2O7 solution (p

The path tracking control problem is investigated in this paper for autonomous vehicles (AVs) with time-varying input delay and actuator saturation. Based on the Lyapunov–Krasovskii function and th...

Secondary metabolites in marine organisms exhibit various pharmacological activities against diseases, such as cancer. In this study, the anti-proliferative effect of JBIR-100, a macrolide isolated from Streptomyces sp., was investigated in breast cancer cells. Cell growth was inhibited in response to JBIR-100 treatment concentration- and time-dependently in both MCF-7 and MDA-MB-231 breast cancer cells. JBIR-100 caused apoptosis, as verified by caspase activation and the cleavage of PARP. Western blotting revealed that JBIR-100 modulated the expression of Akt/NF-κB signaling components and Bcl-2 family members. Overexpression of Mcl-1 partially rescued MCF-7 cells from JBIR-100-induced cytotoxicity. In addition, transmission electron microscopy analyses, confocal analysis, and western blot assay indicated that JBIR-100 inhibited autophagy in MCF-7 cells. Exposure to the autophagy inhibitor did not synergize JBIR-100-induced apoptosis. In summary, our results suggested that JBIR-100 may be potentially used for breast cancer therapy.

PurposePrevious research has shown that consumers prefer a bonus pack to a price discount for virtue foods, whereas they prefer a price discount to a bonus pack for vice foods. Acting as a guilt-mitigating mechanism, a price discount justifies consumers' purchasing behavior, allowing them to save money and consume less vice foods. However, for virtue foods, neither the anticipated post-consumption guilt nor the resulting need for justification lead consumers to prefer a bonus pack to a price discount. This study investigates whether product promotions remain effective with other moderating variables.Design/methodology/approachThe authors use pricing tactic persuasion knowledge (PTPK), which refers to the consumer persuasion knowledge of marketers' pricing tactics, as a lens to understand whether the power of these promotions could be enhanced or mitigated. The authors inferred that increasing the frequency of exposure to these foods could positively influence consumers' purchasing choices. They conducted three studies to examine these effects. In Study 1, using pearl milk tea (vice food) and sugar-free tea (virtue food), the authors contended that consumers would prefer a price discount when purchasing pearl milk tea, but a bonus pack when purchasing sugar-free tea. In Studies 2 and 3, the authors varied the participants' frequency of exposure to photographs of people in everyday situations with vice (virtue) foods.FindingsIn Study 1, PTPK was shown to be more predictive of consumer choices regarding price discounts and bonus packs. In Studies 2 and 3, the authors contended that increased exposure to vice (virtue) foods increases the selection of vice (virtue) foods by participants who were unaware of having been exposed to vice (virtue) foods.Originality/valueThis research has not only made quite managerial and policy implications for marketing but also brought the theoretical contributions for marketing researches. This research demonstrates that either for vice foods or virtue foods, a price discount is preferred to a bonus pack.