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Nuclear factor-kappa B (NF-κB), which is reported to play an important role in the pathogenesis of depression, also has a central role in the genesis and progression of inflammation. Here, we have targeted the nuclear translocation of NF-κB using 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) to elucidate its role in depression. We investigated the antidepressant-like effects of JSH-23 in the chronic mild stress (CMS) mouse model, which is a valid, reasonably reliable, and useful model of depression. The antidepressant-like effects of JSH-23 were evaluated using the sucrose preference test (SPT) and the forced swimming test (FST). We also assessed inflammatory markers [interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)] and components of antioxidant defense [superoxide dismutase (SOD) and nuclear factor erythroid-2-related factor 2 (Nrf 2)] in the hippocampus. Fluoxetine, a classical antidepressant, was used in this study as a positive control. Administration of JSH-23 significantly prevented the decreased sucrose preference in the SPT and prevented the increased immobility time in the FST caused by CMS, but had no effect on locomotor activity. Expression of NF-κB p65 protein in the hippocampus was decreased, and elevated levels of IL-6 and TNF-α were reduced, after JSH-23 administration. In addition to its anti-inflammatory effect, JSH-23 treatment increased the expression of SOD and Nrf 2 in the hippocampus, suggesting that it strengthens antioxidant defense. The current study demonstrated that inhibiting the NF-κB signaling cascade using JSH-23 prevented depressive-like behaviors by decreasing inflammation and improving antioxidant defense in the hippocampus. We concluded that NF-κB activation plays an important role in the pathophysiology of depression and that targeting NF-κB signaling may provide a novel and effective therapy for depression. Additional preclinical studies and clinical trials are, however, needed to further elucidate the effects of this therapeutic strategy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes ( Per1 , Per2 , Per3 , Rev-erbα and Dbp ) expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation., Competing Interests: The authors declare no conflict of interest.

Src family kinases (SFKs) are non-receptor tyrosine kinases and play a key role in regulating signal transduction. The mechanism of SFKs in various tumors has been widely studied, and there are more and more studies on its role in the kidney. Acute kidney injury (AKI) is a disease with complex pathogenesis, including oxidative stress (OS), inflammation, endoplasmic reticulum (ER) stress, autophagy, and apoptosis. In addition, fibrosis has a significant impact on the progression of AKI to developing chronic kidney disease (CKD). The mortality rate of this disease is very high, and there is no effective treatment drug at present. In recent years, some studies have found that SFKs, especially Src, Fyn, and Lyn, are involved in the pathogenesis of AKI. In this paper, the structure, function, and role of SFKs in AKI are discussed. SFKs play a crucial role in the occurrence and development of AKI, making them promising molecular targets for the treatment of AKI. [ABSTRACT FROM AUTHOR]

Inflammatory and invasive fibroblast‐like synoviocytes (FLS) contribute to the pathology of rheumatoid arthritis (RA). Isoginkgetin (IGKG) has been identified as having anti‐inflammatory properties. This study investigated whether IGKG could be utilized to treat RA. Primary FLS were isolated from synovial tissues derived from six RA patients, which were over‐expressed with matrix metallopeptidase 9 and cultured with or without tumor necrosis factor (TNF)‐α and then further treated with IGKG. IGKG down‐regulated the content of various interleukins (ILs), namely, IL‐1β, IL‐6, and IL‐8, in RA‐FLS supernatant with or without TNF‐α stimulation, with diminished migration and invasion properties as assayed by the transwell system. Furthermore, down‐regulated inflammatory cytokine secretion and down‐regulated migration and invasion properties could be reversed through matrix metallopeptidase 9 overexpression. Dual‐luciferase reporter gene assay indicated that IGKG could inhibit nuclear factor kappa B transcription activity. Western blot analysis also demonstrated that IGKG down‐regulated the expression of p‐IκBα, p‐p65, and MMP9. IGKG displayed the ability to inhibit the inflammatory response of RA‐FLS through the NF‐κB/MMP9 pathway with diminished migration and invasion. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that there are significant changes in the gut microbiota (GM) of humans with depression and animal models of depression and chronic stress. In our present study, we determined whether an alteration in GM is a decisive factor in anxiety-like and depression-like behavior and its impact on brain neurochemistry. An antibiotic cocktail was used to deplete the GM of mice before they were colonized, via fecal microbiota transplantation (FMT), by the GM of control mice or mice that had been exposed to chronic unpredictable mild stress (CUMS donors). The CUMS-donor group of mice and the mice that were colonized by their microbiota (the CUMS-recipient group) both showed higher levels of anxiety- and depression-like behavior compared to the controls. The GM community of the CUMS-donor and CUMS-recipient was distinctively different from the controls, with the CUMS group characterized by a lower relative abundance of Lactobacillus and a higher relative abundance of Akkermansia. Interestingly, FMT affected both behavior and neuroinflammation. Mice given the CUMS microbiota had significant elevations of interferon-γ (IFN-γ) and the tumor necrosis factor-alpha (TNF-α) in the hippocampus, which were accompanied by upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in the hippocampus. These results suggest that GM modulates pro-inflammatory cytokines in the hippocampus through dysfunctional microbiota–gut–brain axis, exacerbating anxiety- and depression-like phenotypes. Chronic unpredictable mild stress increased anxiety- and depression-like behavior in mice. Mice colonized with gut microbiota (GM) from stressed mice showed similar behaviors. The GM composition of the donor and recipient mice was also comparable. Their relative pattern of two bacteria has been tied to neuroinflammatory activity. The results suggest a link between GM, brain function, and anxiety and depression. [ABSTRACT FROM AUTHOR]

In recent years, a burgeoning body of research has revealed links between depression and the gut microbiota, leading to the therapeutic use of probiotics for stress-related disorders. In this study, we explored the potential antidepressant efficacy of a multi-strain probiotics treatment (Lactobacillus helveticus R0052 , Lactobacillus plantarum R1012 , and Bifidobacterium longum R0175) in a chronic mild stress (CMS) mouse model of depression and determined its probable mechanism of action. Our findings revealed that mice subjected to CMS exhibited anxiety- and depressive-like behaviors in the sucrose preference test, elevated plus maze, and forced swim test, along with increased interferon-γ, tumor necrosis factor-α, and indoleamine 2,3-dioxygenase-1 levels in the hippocampus. Moreover, the microbiota distinctly changed from the non-stress group and was characterized by highly diverse bacterial communities associated with significant reductions in Lactobacillus species. Probiotics attenuated CMS-induced anxiety- and depressive-like behaviors, significantly increased Lactobacillus abundance, and reversed the CMS-induced immune changes in the hippocampus. Thus, the possible mechanism involved in the antidepressant-like activity of probiotics is correlated with Lactobacillus species via the gut microbiota-inflammation-brain axis. [ABSTRACT FROM AUTHOR]

[Display omitted] Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI. [ABSTRACT FROM AUTHOR]

There is little research on the effects of adolescent administration of antidepressants on behavioural function and inflammation in early-life stressed adult mice. Using maternal separation (MS), a paradigm of early adversity, we investigated the effects of adolescent (PND 33-54) escitalopram (ES; 10 mg/kg) exposure on depression- and anxiety-like behaviours and the levels of inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, and IL-10) in the ventral hippocampus (HPV), prefrontal cortex (PFC), and serum in adult (PND 61) male offspring mice. The results showed that MS has no effect on locomotor activity, but increased depression-like behaviours in the saccharin preference test and increased anxiety-like behaviours in the social preference and elevated plus maze tests. MS increased the levels of IL-1β in the HPV, PFC, and serum, while decreasing the level of IL-10 in the HPV. Furthermore, adolescent ES treatment inhibited these depression- and anxiety-like behaviours, decreased the levels of IL-1β, and increased the level of IL-10 in the HPV. The results also showed that there are no effects of chronic escitalopram administration on normal behaviour in control mice. Taken together, the current data provide experimental evidence that MS increases depression and anxiety levels in adult male offspring. Additionally, the findings support the idea that early pharmacological intervention with ES may be an effective treatment for reducing the behavioral abnormalities induced by early adversity and regulating the underlying inflammatory mechanisms involved. [ABSTRACT FROM AUTHOR]