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Pancreatic sympathetic innervation can directly affect the function of islet. The disorder of sympathetic innervation in islets during the occurrence of type 1 diabetes (T1D) has been reported to be controversial with the inducing factor unclarified. Several studies have uncovered the critical role that sympathetic signals play in controlling the local immune system. The survival and function of endocrine cells can be regulated by immune cell infiltration in islets. In the current review, we focused on the impact of sympathetic signals working on islets cell regulation, and discussed the potential factors that can induce the sympathetic innervation disorder in the islets. We also summarized the effect of interference with the islet sympathetic signals on the T1D occurrence. Overall, a comprehensive understanding of the regulatory effect of sympathetic signals on islet cells and local immune system could facilitate better strategies design to control inflammation and protect β cells in T1D therapy. Pancreatic sympathetic innervation and its disturbance during the occurrence of type 1 diabetes. The sympathetic nerve directly affects islet endocrine cells and immune cells via secreting transmitters, like NE, NPY and Galanin, acting on the corresponding receptors. The increase of infiltrating T cells and pro-inflammatory macrophages accelerates islet sympathetic disturbance. [Display omitted] • Pancreatic sympathetic innervation is disordered during the occurrence of T1D. • Inflammatory infiltration, especially macrophage, contributes to the loss of sympathetic neurons in islet. • The systemic crosstalk between sympathetic signals and immune system could be a potential therapeutic target for T1D. [ABSTRACT FROM AUTHOR]

Heat stress due to global warming exerts deleterious effects on both humans and animals. However, nutritional strategies to reduce heat stress-induced intestinal mucosal barrier dysfunction and the underlying mechanisms remain largely unknown. In the present study, 240 tilapia were distributed into four treatment groups that were fed a basal diet supplemented with or without 0.1% Yucca schidigera extract under normal (28 °C) temperature or heat stress (36 °C) conditions for 2 weeks. Our results showed that tilapia exposed to heat stress resulted in growth arrest, intestinal dysfunction, oxidative damage, endoplasmic reticulum stress, and pro-inflammatory response, which were significantly relieved by yucca supplementation. The alleviative effect of Yucca schidigera extract was related to the down-regulation of mRNA expression of ubiquitin-proteasome system (Polyubiquitin, Proteasome 26S, Proteasome α5, Proteasome β3, and Ubiquitin-like 3) and inflammatory factors (tumor necrosis factor α, interleukin 1β, and interleukin 8), as well as the improved histological structure and activation of Hsp70 , nuclear factor erythroid 2-related factor 2 signaling, interleukin 10, lysozyme, complement 3, and acid phosphatase in the intestine of tilapia. Collectively, these results indicated that heat stress-induced growth arrest, intestinal dysfunction, and oxidative damage were alleviated by dietary supplementation with Yucca schidigera extract. This offers a nutritional way of improving the growth and intestinal health of tilapia exposed to a hot environment. • Yucca alleviated the retarded growth and intestinal damage of tilapia induced by heat stress. • Yucca attenuated the endoplasmic reticulum stress in the intestine of heat-stressed tilapia. • Yucca enhanced the antioxidation and innate immunity of tilapia under heat stress conditions. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) play important roles in various biological activities as vital regulators. However, no study has focused on the lncRNA regulation of Outer membrane protein (OMP) immunization against aquatic bacterial infection. In this study, we examined the genome-wide expression of lncRNAs in the liver of European eel (Anguilla anguilla, Aa) administrated by a recombinant OmpA (rOmpA) from Edwardsiella anguillarum (Ea) to elucidate the functions of lncRNAs in the process of Ea infection and Aa anti- Ea infection using strand specific RNA-seq. Eels were challenged by Ea at 28 d post the immunization (dpi) of OmpA, and the result showed, compared to uninfected livers in the PBS group (Con group), the infected livers in the PBS group (Con_inf group) showed severe bleeding, hepatocyte atrophy and thrombi formed in the hepatic vessels; livers in the OmpA group (OmpA_inf) also formed slight thrombi in the hepatic vessels. The relative percent survival of eels in OmpA_inf vs Con_inf was 78.6%. Using high-throughput transcriptomics, we found 13405 lncRNAs in 3 compares of Con_inf vs Con, OmpA_inf vs Con and OmpA_inf vs Con_inf, of which 111, 129 and 158 DE-lncRNAs were ascertained. GO analysis of the DE-lncRNAs revealed the targeting DEGs were mainly involved in single-organism process, signaling, biological process and response to stimulus in BP, component of membrane in CC and binding in MF; KEGG pathways showed that the targeting DEGs in co-expression and co-location enriched in cell adhesion molecules. Finally, 54 DE-lncRNAs targeting 1675 DEGs were involved in an interaction network of 21692 co-expression and 483 co-location related links, of which 18 DE-lncRNAs appear to play crucial roles in anti- Ea infection. Thus, the interaction networks revealed crucial DE-lncRNAs underlying the process of Ea infection and Aa anti- Ea infection pre and post the immunization of OmpA. • LncRNAs activated by the infection of E. anguillarum after immunization was first reported. • The pathological changes of liver were greatly relieved after the OmpA immunization. • The relative percent survival of European eels was 78.6% after the OmpA immunization. • Eighteen DE-lncRNAs appear to play crucial roles in anti- E. anguillarum infection. [ABSTRACT FROM AUTHOR]

Cold tumor immune microenvironment (TIME) of pancreatic cancer (PC) with minimal dendritic cell (DC) and T cell infiltration can result in insufficient immunotherapy and chemotherapy. While gemcitabine (GEM) is a first-line chemotherapeutic drug for PC, its efficacy is reduced by immunosuppression and drug resistance. Ginsenoside Rh2 (Rh2) is known to have anti-cancer and immunomodulatory properties. Combining GEM with Rh2 may thus overcome immunosuppression and induce lasting anti-tumor immunity in PC. Here, we showed that after GEM−Rh2 therapy, there was significantly greater tumor infiltration by DCs. Caspase recruitment domain-containing protein 9 (CARD9), a central adaptor protein, was strongly up-regulated DCs with GEM−Rh2 therapy and promoted anti-tumor immune responses by DCs. CARD9 was found to be a critical target for Rh2 to enhance DC function. However, GEM−Rh2 treatment did not achieve the substantial anti-PC efficacy in CARD9−/− mice as in WT mice. The adoptive transfer of WT DCs to DC-depleted PC mice treated with GEM−Rh2 elicited strong anti-tumor immune responses, although CARD9−/− DCs were less effective than WT DCs. Our results showed that GEM−Rh2 may reverse cold TIME by enhancing tumor immunogenicity and decreasing the levels of immunosuppressive factors, reactivating DCs via the CARD9-BCL10-MALT1/ NF-κB pathway. Our findings suggest a potentially feasible and safe treatment strategy for PC, with a unique mechanism of action. Thus, Rh2 activation of DCs may remodel the cold TIME and optimize GEM chemotherapy for future therapeutic use. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to the pivotal role of microfilament in cancer cells, targeting microfilaments with cytochalasins is considered a promising anticancer strategy. Here, we obtained cytochalasin Q (CQ) from Xylaria sp. DO1801, the endophytic fungi from the root of plant Damnacanthus officinarum , and discovered its anti-melanoma activity in vivo and in vitro attributing to microfilament depolymerization. Mechanistically, CQ directly bound to and inactivated creatine kinase B (CKB), an enzyme phosphorylating creatine to phosphocreatine (PCr) and regenerating ATP to cope with high energy demand, and then inhibited the creatine metabolism as well as cytosolic glycolysis in melanoma cells. Preloading PCr recovered ATP generation, reversed microfilament depolymerization and blunted anti-melanoma efficacy of CQ. Knockdown of CKB resulted in reduced ATP level, perturbed microfilament, inhibited proliferation and induced apoptosis, and manifested lower sensitivity to CQ. Further, we found that either CQ or CKB depletion suppressed the PI3K/AKT/FoxO1 pathway, whereas 740Y-P, a PI3K agonist, elevated protein expression of CKB suppressed by CQ. Taken together, our study highlights the significant anti-melanoma effect and proposes a PI3K/AKT/FoxO1/ CKB feedback circuit for the activity of CQ, opening new opportunities for current chemotherapy. [Display omitted] • CQ suppresses melanoma cells with microfilament depolymerization. • CQ directly binds to CKB and inhibits CKB activity. • CQ interferes with CKB-related creatine metabolism and PI3K/AKT/FoxO1 axis in a feedback-regulated manner. [ABSTRACT FROM AUTHOR]