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Understanding microglia development could improve our understanding of the central nervous system (CNS) and neurological diseases. To explore the immune phenotypic changes that occur in microglia during development, we studied the morphology, inflammatory response, and expression of several important immune-related proteins in normal microglia from the embryonic, neonatal (postnatal day 3), and adult stages. Results showed that implantation of microglia into the CNS until adulthood resulted in dynamic changes in the expression levels of CD11b (α chain of complement receptor 3) and CX3CR1 (a chemokine receptor), which were consistent and correlated. Expression of proinflammatory cytokines in microglia during development is dynamic and highest in perinatal period. The inflammatory response of microglia was more vigorous and intense in the neonatal microglia than in the adult microglia. Furthermore, the morphology and function of neonatal and adult microglia differed, and thus neonatal microglia cannot be used in lieu of adult microglia for functional studies. Taken together, our results suggest that microglial integrin, chemokine receptors, and inflammatory responses vary with developmental age, which is an important finding for studying the role of microglia in different age-related neurological diseases. • CD11b show dynamic expression changes from embryonic to adult microglia. • CX3CR1 show dynamic expression changes from embryonic to adult microglia. • CD11b expression correlated with CX3CR1expression in microglia. • IL-1β and TNF-α expression levels change during microglial development. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which can lead to poor outcome and increased risk of mortality. Dabrafenib (DAB) is an approved cancer treatment. Little is known about the effect of DAB in prevention or treatment of renal IRI. For in vivo experiments, C57BL/6 mice were divided into four groups: sham (no IRI, no DAB), IRI, DAB, and DAB + IRI. IRI was induced by clamping of bilateral renal pedicles for 30 min. For in vitro experiments, HK-2 cells were used to establish the hypoxia/reoxygenation (H/R) injury model, with four groups: control (no H/R, no DAB), H/R, DAB, and DAB + H/R. Renal function and renal histological changes were recorded. Expression of NGAL and KIM-1 proteins and mRNAs were determined by western blotting and qRT-PCR; secretion of inflammatory cytokines (IL-6 and TNF- α) was determined by qRT-PCR; Cell death was determined using the TUNEL assay, measurement of cleaved caspase-3, and flow cytometry. Necroptosis-related proteins were determined by western blotting. In mice, DAB pretreatment improved renal function and also reduced histological injury, inflammation, cell death, and expression of necroptosis-associated proteins. In HK-2 cells, DAB significantly decreased the levels of NGAL and KIM-1, inflammatory cytokines, cell death, and necroptosis-related proteins. Our in vitro and in vivo experiments indicated that DAB appears to alleviate renal IRI by suppressing cell death and inhibiting inflammatory responses. DAB has potential use for the clinical prevention and treatment of AKI-induced IRI. • We clarified dabrafenib could attenuate renal IRI in vivo and in vitro , which may by inhibiting RIP3 mediated necroptosis. • First, we found that dabrafenib could alleviate mouse renal IRI and supress the expression of necroptotic related proteins. • Then, we established the model of renal ischemia reperfusion injury by using HK-2 cells in vitro. • Our data showed that dabrafenib could decrease cell death and downregulate the level of necroptotic related proteins. • Our study suggests that DAB should be examined as a potential therapeutic option for the prevention or treatment of AKI. [ABSTRACT FROM AUTHOR]

Background Oxidative stress and inflammation play important roles in the development of diabetes. Metformin (MET) is considered as the first-line therapy for patients with type 2 diabetes (T2D). Hypothalamic paraventricular nucleus (PVN) and hypothalamic arcuate nucleus (ARC) are vital in obesity and diabetes. However, there have been few studies on the effects of MET on inflammatory reaction and oxidative stress in the PVN and ARC of T2D diabetic rats. Methods Male Sprague-Dawley (SD) rats were fed with high-fat diet (HFD), and intraperitoneally injected with low-dose streptozotocin (STZ, 30 mg/kg) at 6th week to induce T2D diabetes. After injection of STZ, they were fed with HFD continually. Starting from the 8th week of HFD feeding, T2D rats received intragastrical administration of MET (150 mg/kg/day) in addition to the HFD for another 8 weeks. At the end of the 15th week, the rats were anaesthetized to record the sympathetic nerve activity and collect blood and tissue samples. Results In comparison with control rats, T2D diabetic rats had higher levels of pro-inflammatory cytokines (PICs) and excessive oxidative stress in the PVN and ARC, accompanied with more activated astrocytes. The renal sympathetic nerve activity (RSNA) and the plasma norepinephrine (NE) increased in T2D diabetic rats. The expression of tyrosine hydroxylase (TH) increased and the expression of 67-kDa isoform of glutamate decarboxylase (GAD67) decreased in T2D diabetic rats. Supplementation of MET decreased blood glucose, suppressed RSNA, decreased PICs (TNF-α, IL-1β and IL-6) in PVN and ARC, attenuated oxidative stress and activation of astrocytes in ARC and PVN of T2D diabetic rats, as well as restored the balance of neurotransmitter synthetase. The number of Fra-LI (chronic neuronal excitation marker) positive neurons in the ARC and PVN of T2D diabetic rats increased. Chronic supplementation of MET also decreased the number of Fra-LI positive neurons in the ARC and PVN of T2D diabetic rats. Conclusion These findings suggest that the PVN and ARC participate in the beneficial effects of MET in T2D diabetic rats, which is possibly mediated via down-regulating of inflammatory molecules, attenuating oxidative stress and restoring the balance of neurotransmitter synthetase by MET in the PVN and ARC. • Beneficial effects of metformin mediated by hypothalamic mechanisms in diabetic rats. • PVN and ARC involve in brain mechanisms of diabetes and metformin supplementation. • Metformin inhibits sympathoexcitation and astrocytes in PVN and ARC in diabetes. • Metformin attenuates inflammation and oxidative stress in PVN and ARC in diabetes. • Metformin restores the balance of neurotransmitters in PVN and ARC in diabetes. [ABSTRACT FROM AUTHOR]

Edwardsiellosis, an extremely harmful disease can be caused by Edwardsiella tarda , severely restricts the development of turbot (Scophthalmus maximus) farming worldwide, especially in China. This study aimed to establish an effective and feasible prophylaxis by feeding chitosan-alginate coated egg yolk immunoglobulin (IgY) against E. tarda 2CDM001 infections in the process of turbot farming. Enzyme-linked immunosorbent assays proved that the obtained specific IgY could specifically target E. tarda 2CDM001 and five other E. tarda isolates (1a5p, Hz-s, 1a1s, fs-a1 and 58p8). In-vitro, the bacteriostatic effects of specific IgY showed dose dependencies at concentrations ranging from 1 to 10 mg/mL. Moreover, E. tarda 2CDM001 incubated with 10 mg/mL specific IgY could induce the destruction of cell wall structures and significantly decrease the bacterial surface hydrophobicity (p < 0.05). In this study, turbots were challenged with 107 CFU E. tarda 2CDM001 after seven days of continuous feeding with basal diets containing microencapsulated IgYs. Survival rates of the 5%, 3% and 1% microencapsulated specific IgY groups were 63.3%, 56.7% and 20% on the tenth day post infection, respectively, while the turbots in the positive control and non-specific IgY groups all died within ten days. Oral administration of basal diets containing 5% microencapsulated specific IgY significantly reduced IL-1β, IL-8, TNF-α and C3 transcript levels in the head kidney and spleen of turbots compared with the positive and non-specific IgY groups at 24 h after E. tarda 2CDM001 challenging (p < 0.05). Pathological increase of leukocytes in the specific IgY group was significantly lower than that in the positive control and non-specific IgY groups (p < 0.05), decreasing slowly after 24 h of infection and showing a recovery trend. Erythrocyte counts and hemoglobin concentrations of turbots in positive and non-specific IgY groups showed a marked decrease compared with the negative and specific groups at 96 h after E. tarda 2CDM001 infection (p < 0.05). These results suggest that passive immunity via feeding microencapsulated specific IgY could be used as a valuable preventative in turbot against E. tarda 2CDM001 infections. • Specific IgY could effectively inhibit the growth of E. tarda 2CDM001 in vitro. • Pre-feeding chitosan-alginate coated specific IgY could improve the survival rate of E. tarda 2CDM001-infected turbots. • Specific IgY could significantly reduce the inflammatory responses of turbots after E. tarda 2CDM001 infection. • CRediT authorship contribution statement. [ABSTRACT FROM AUTHOR]

Currently, there is a growing interest in understanding the cellular and molecular events of immune–cell trafficking and recruitment of hepatic stellate cells (HSCs) in liver diseases. Aberrant activation of HSCs is the key event leading to chronic liver fibrosis. However, the underlying mechanisms of the recruitment of HSCs in a locally injured liver are not clearly understood. Here, we report a new experimental approach for the study of inflammatory responses as well as the recruitment of HSCs into the localized cryolesion. We observed a significant liver damage accompanied by the up-regulation of plasma ALT and AST. In addition, we also found increased levels of MCP-1, IL-6 and IL-10 cytokines. The peak cytokine levels were detected at 8 h after injury, followed by intrahepatic infiltration of neutrophils and monocytes into the injury site (from 8 h to day 3), while the kupffer cells (KCs) and HSCs were mainly detected on day 3 after injury. Interestingly, the depletion of KCs, but not neutrophils, reduced the directional recruitment and accumulation of HSCs at the injury site. Moreover, the combinatorial recruitment of KCs and HSCs resulted in the gradual restoration of fibrotic area to almost typical histological appearance on day 14 post-injury. In conclusion, our data demonstrated a localized infiltration and accumulation of neutrophils and monocytes at a "predefined loci", and further revealed that KCs are critical for the recruitment of HSCs during injury, and thus, may play an important role in tissue repair. • Cryoinjury can induce a predefined localized liver damage. • Neutrophils represent the initial immune cell population recruited at the cryoinjured site. • KCs and HSCs are predominantly accumulated and co-localized at the injured site. • KCs are critical for the recruitment of HSCs at the injury site. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that artemisinin (ART) can modulate pathogen-induced immune responses and metabolic dysregulation. However, whether this modulation is associated with metabolic pathways related to oxidative stress and inflammation remains unclear. The aim of this study was to investigate the antioxidant and anti-inflammatory effects on the ART-fed juvenile fat greenling Hexagrammos otakii and the associated metabolic pathways in response to ART administration using an integrated biochemical and metabolomic approach. Biochemical analysis and histological examination showed that ART significantly increased body weight gain and improved tissue structure. ART effectively attenuated reactive oxygen species (ROS), malondialdehyde (MDA) and inflammatory responses (NFκB, TNF-α, IL-6, and MCP-1) in the Edwardsiella tarda -induced H. otakii model. Liver metabolomics analysis revealed that twenty-nine metabolites were up-regulated and twenty-one metabolites were down-regulated after ART administration compared to those in pathogen-induced fish. Pathway analysis indicated that ART alleviated the E. tarda -induced inflammation and oxidative stress through two major pathways, namely lipid metabolism and amino acid metabolism. Taken together, ART showed great potential as a natural feed additive against pathogen-induced oxidative stress and inflammation. [Display omitted] • Dietary artemisinin could enhance the antioxidant capacity of the liver in H. otakii. • Dietary artemisinin could promote the growth in H.otakii. • Dietary artemisinin may have a beneficial effect on liver structure after Edwardsiella tarda infection. • Dietary artemisinin can treat liver immune diseases in H.otakii. • Metabolic analysis combined with experimental verification will play an important role in analyzing aquatic feeds work. [ABSTRACT FROM AUTHOR]

• IL-33 induced airways hyperresponsiveness, inflammation, and goblet cell hyperplasia are attenuated in IL-9 deficient mice. • IL-9 is required for IL-33 induced remodelling in asthma. • IL-9 is one downstream cytokine of IL-33 in asthmatic airways. Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33. In line with previous report, per-nasal challenge of WT mice with IL-33 significantly increased the responsiveness of the airways along with infiltration of inflammatory cells, goblet cell hyperplasia, collagen deposition and smooth muscle hypertrophy, and the expression of cytokines compared with control group. Surprisingly, all of these pathological changes were significantly attenuated in IL-9 deficient mice following identical IL-33 challenge. These data suggest that IL-9 is one downstream cytokine relevant to the effects of IL-33 in asthmatic airways and consequently a potential therapeutic target for the treatment of asthma. [ABSTRACT FROM AUTHOR]