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Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive spatial disorientation, learning and memory deficits, responsible for 60%–80% of all dementias. However, the pathological mechanism of AD remains unknown. Numerous studies revealed that kinin/kinin receptors system (KKS) may be involved in the pathophysiology of AD. In this review article, we summarized the roles of KKS in neuroinflammation, cerebrovascular impairment, tau phosphorylation, and amyloid β (Aβ) generation in AD. Moreover, we provide new insights into the mechanistic link between KKS and AD, and highlight the KKS as a potential therapeutic target for AD treatment. [ABSTRACT FROM AUTHOR]

Growth hormone secretagogue receptor 1α (GHSR1a) and Orexin 1 receptor (OX1R) are involved in various important physiological processes, and have many similar characteristics in function and distribution in peripheral tissues and the central nervous system. We explored the possibility of heterodimerization between GHSR1a and OX1R and revealed a signal transduction pathway mechanism. In this study, bioluminescence and fluorescence resonance energy transfer and co-immunoprecipitation (Co-IP) analyses were performed to demonstrate the formation of functional GHSR1a/OX1R heterodimers. This showed that a peptide corresponding to the 5-transmembrane domain of OX1R impaired heterodimer construction. We found that ghrelin stimulated GHSR1a/OX1R heterodimer cells to increase the activation of Gαs protein, compared to the cells that express GHSR1a. Stimulation of GHSR1a/OX1R heterodimers with orexin-A did not alter GPCR interactions with Gα protein subunits. GHSR1a/OX1R heterodimers induced Gαs and downstream signaling pathway activity, including increase of cAMP-response element luciferase reporter activity and cAMP levels. In addition, ghrelin induced a higher proliferation rate in SH-SY5Y cells than in controls. This suggests that ghrelin GHSR1a/OX1R heterodimers promotes an upregulation of a Gαs-cAMP-cAMP-responsive element signaling pathway in vitro and an increase in neuroblastoma cell proliferation. [ABSTRACT FROM AUTHOR]

In recent years, there have been many studies on the function of nitric oxide synthase (NOS) in experimental animals and humans. This review analyzes and explores the relationship between inducible nitric oxide synthase (iNOS) and T cells, macrophages, and dendritic cell et al. differentiation using data based on laboratory research, highlighting recent NOS laboratory research. Our insights into research prospects and directions are also presented. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests granulocyte macrophage-colony stimulating factor (GM-CSF) can function as an inflammatory mediator, but whether GM-CSF-producing CD4+ T cells (T H -GM-CSF) are a distinct T helper cell subset is lacking. Herein we demonstrate that interleukin (IL)-1β exclusively drives differentiation of naïve CD4+ T cells into T H -GM-CSF cells via inducing ubiquitination of IL-1 receptor-associated kinase 1 (IRAK1) and subsequent activation of the transcription factor NF-kappaB (NF-κB), independent of RAR-related orphan receptor gamma (RORγt) required for T H 17 differentiation. In vivo, T H -GM-CSF cells are present in murine Citrobacter Rodentium infections and mediate colitis following adoptive transfer of CD4+ T cells into Rag1 −/− mice via GM-CSF-induced macrophage activation. The T H -GM-CSF cell phenotype is stable and distinct from the T H 17 genetic program, but IL-1β can convert pre-formed T H 17 cells into T H -GM-CSF cells, thereby accounting for previously reported associations between IL-17 and GM-CSF. Together, our results newly identify IL-1β/NF-κB-dependent T H -GM-CSF cells as a unique T helper cell subset and highlight the importance of CD4+ T cell-derived GM-CSF induced macrophage activation as a previously undescribed T cell effector mechanism. • Our study newly identifies GM-‐CSF-‐single producing T helper cells (TH-‐GM-‐CSF) as a unique T helper subset. • Our study reveals that IL-‐1® directly programs TH-‐GM-‐CSF differentiation via IRAK1/NF-‐κB axis and that IL-‐1® induces conversion of TH17 into TH-‐GM-‐CSF. • Our study shows that TH-‐GM-‐CSF cells are critically involved in the development of T cell transfer induced colitis. These novel findings will lead to more exciting investigations concerning the contributions of TH-‐GM-‐CSF in various T cell-‐ mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract The follicular helper T cell (T FH) are established regulators of germinal center (GC) B cells, whether T FH have pathogenic potential independent of B cells is unknown. Based on in vitro T FH cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, T FH and its functions in colitis development were analyzed by FACS, ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal tissues of patients and colon tissues obtained from Rag1 −/− recipients of naïve CD4+ T cells with colitis, each over-express T FH -associated gene products. Adoptive transfer of naïve Bcl6 −/− CD4+ T cells into Rag1 −/− recipient mice abrogated development of colitis and limited T FH differentiation in vivo , demonstrating a mechanistic link. In contrast, T cell deficiency of interferon regulatory factor 8 (IRF8) resulted in augmentation of T FH induction in vitro and in vivo. Functional studies showed that adoptive transfer of IRF8 deficient CD4+ T cells into Rag1 −/− recipients exacerbated colitis development associated with increased gut T FH -related gene expression, while Irf8 −/− /Bcl6 −/− CD4+ T cells abrogated colitis, together indicating that IRF8-regulated T FH can directly cause colon inflammation. Molecular analyses revealed that IRF8 suppresses T FH differentiation by inhibiting transcription and transactivation of the TF IRF4, which is also known to be essential for T FH induction. Our documentation showed that IRF8-regulated T FH can function as B-cell-independent, pathogenic, mediators of colitis suggests that targeting T FH could be effective for treatment of IBD. Highlights • Our study reveals that T FH cells are critically involved in the development of T cell-mediated inflammatory diseases. • The study defines IRF8 as an important intrinsic suppressor of T FH differentiation. • Our studies are really novel and will lead to more exciting investigations concerning the contributions of T FH cells in the development of various T cell-mediated inflammatory diseases in future. [ABSTRACT FROM AUTHOR]

A Gram-stain-negative and rod-shaped bacterium, designated strain CY04 T , was isolated from a sediment sample collected from the Yellow Sea. CY04 T exhibited the highest 16S rRNA gene sequence similarity of 98.7 % to Zongyanglinia huanghaiensis CY05 T , followed by the similarities of 98.6 %, 98.0 and 98.0 % to Zongyanglinia marina DSW4-44 T , Parasedimentitalea marina W43 T and Parasedimentitalea psychrophila QS115 T respectively. Phylogenetic analysis based on 16S rRNA gene and phylogenomic analysis based on genome sequences revealed that CY04 T formed a robust cluster with Z. huanghaiensis CY05 T , Z. marina DSW4-44 T , P. marina W43 T and P. psychrophila QS115 T . Calculated digital DNA-DNA hybridisation and average nucleotide identity values between CY04 T and its closely related species were 22.2-23.7 % and 79.0-81.2 % respectively. Cells of CY04 T were strictly aerobic, non-motile and positive for catalase, oxidase and denitrification. CY04 T harboured a set of genes encoding the enzymes involved in denitrification. Growth occurred at 10-30 °C (optimum, 20 °C), at pH 6.5-9.5 (optimum, pH 8.0) and with 1-6 % (w/v) (optimum, 2.5 %,) NaCl. The major component of the fatty acids was summed feature 8 (C 18 : 1 ω7 c and/or C 18 : 1 ω6 c ). The isoprenoid quinone was Q-10. Results of the phenotypic, chemotaxonomic and molecular study indicate that strain CY04 T represents a novel species of the genus Parasedimentitalea , for which the name Parasedimentitalea denitrificans sp. nov. is proposed. The type strain is CY04 T (=MCCC 1K08635 T =KCTC 62199 T ). It is also proposed that Zongyanglinia huanghaiensis and Zongyanglinia marina should be reclassified as Parasedimentitalea huanghaiensis comb. nov. and Parasedimentitalea maritima nom. nov. An emended description of the genus Parasedimentitalea is also proposed.

Immune-mediated liver injury plays a crucial role in the pathogenesis of liver diseases, which can result from viral infections, autoimmunity, alcohol intake, and drug use. Concanavalin A (Con A)-induced hepatitis is a well-characterized murine model with similar pathophysiology to that of human viral and autoimmune hepatitis. Capsaicin, a selective agonist of the transient potential vanilloid subfamily member 1 (TRPV1) receptor, exhibits anti-inflammatory effects on various causes of inflammation. In the present study, we investigated the effect of capsaicin on Con A-induced hepatitis. Capsaicin (1 mg/kg body weight) was administered by intraperitoneal injection, after which (30 minutes), the mice were challenged intravenously with Con A (20 μg/g body weight). We collected serum for plasma transaminase analysis. Pro-inflammatory cytokine levels and hepatocyte apoptosis were assayed by ELISA and TUNEL, respectively. Liver samples were collected for real-time PCR, hematoxylin and eosin staining, and measuring oxidative stress and myeloperoxidase levels. Activation of splenocytes and hepatic mononuclear cells was analyzed by flow cytometry. Compared with control, the capsaicin-treated group showed significantly decreased aminotransferase levels and markedly prolonged mouse survival. Capsaicin pretreatment also attenuated hepatocyte apoptosis and oxidative stress. Furthermore, tumor necrosis factor-α and interferon-γ levels in serum and liver were significantly suppressed, while the percentage of myeloid-derived suppressor cells increased after capsaicin pretreatment. Our findings indicate that capsaicin pretreatment protects mice from Con A-induced hepatic damage and is partially involved in inhibiting hepatocyte apoptosis, oxidative stress, and inflammatory mediators as well as regulating activation and recruitment of intrahepatic leukocytes., Competing Interests: None.

Growth hormone secretagogue receptor 1α (GHSR1a) and Orexin 1 receptor (OX1R) are involved in various important physiological processes, and have many similar characteristics in function and distribution in peripheral tissues and the central nervous system. We explored the possibility of heterodimerization between GHSR1a and OX1R and revealed a signal transduction pathway mechanism. In this study, bioluminescence and fluorescence resonance energy transfer and co-immunoprecipitation (Co-IP) analyses were performed to demonstrate the formation of functional GHSR1a/OX1R heterodimers. This showed that a peptide corresponding to the 5-transmembrane domain of OX1R impaired heterodimer construction. We found that ghrelin stimulated GHSR1a/OX1R heterodimer cells to increase the activation of Gαs protein, compared to the cells that express GHSR1a. Stimulation of GHSR1a/OX1R heterodimers with orexin-A did not alter GPCR interactions with Gα protein subunits. GHSR1a/OX1R heterodimers induced Gαs and downstream signaling pathway activity, including increase of cAMP-response element luciferase reporter activity and cAMP levels. In addition, ghrelin induced a higher proliferation rate in SH-SY5Y cells than in controls. This suggests that ghrelin GHSR1a/OX1R heterodimers promotes an upregulation of a Gαs-cAMP-cAMP-responsive element signaling pathway in vitro and an increase in neuroblastoma cell proliferation.