Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF's effect on depression is unknown. We aimed to investigate Fast green FCF's effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms.

Patients undergoing major surgeries may experience certain cognitive decline, which is known as postoperative delirium (POD) or postoperative cognitive dysfunction (POCD). We employed integrated behavioral Z-scoring introduced by Guilloux et al. (2011) to investigate the effects of fracture fixation under anesthesia on hippocampus-dependent memory in mice.

Fast Green FCF (FGF), a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund's adjuvant (CFA) and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], but did not alter the spinal level of nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

Characterized as a mitotic inhibitor, paclitaxel has gained importance as a promising agent for the treatment of advanced non-small cell lung cancer (NSCLC). However, whether paclitaxel has immune modulatory effects remains unclear. In this study, we analyzed 55 peripheral blood samples from NSCLC patients who underwent paclitaxel-based chemotherapy. We found that among the lymphocyte subsets, paclitaxel selectively decreased the size of the regulatory T cell (Treg) population rather than other subsets including effector T cells (Teff). Apoptosis by upregulating the expression of the cell death receptor Fas (CD95) contributed to the reduced cell number of Treg. Importantly, the inhibitory function of Treg was significantly impaired, while the production of Th1 cytokines IFN-gamma and IL-2 and the expression of the activation marker CD44 among CD4(+) and CD8(+) T cells were augmented after paclitaxel treatment. These results strongly demonstrated that paclitaxel-based chemotherapy played important roles in modulating immune responses.

Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases.

Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12-14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1β, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.

The present study aimed to explore the molecular mechanisms underlying the development of thoracic spinal cord injury (SCI). The gene expression profile of GSE20907, which included 12 thoracic non‑injured spinal cord control samples and 12 thoracic transected spinal cord samples at different stages of SCI, was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package in R/Bioconductor. DEG‑associated pathways were analyzed using the Kyoto encyclopedia of genes and genomes database. A protein‑protein interaction (PPI) network was constructed and transcription factors (TFs) were predicted using cytoscape. Compared with the control samples, there were 1,942, 396, 188 and 396 DEGs identified at day 3 (d3), week 1 (wk1), wk2 and month 1 (m1), respectively. Cluster analysis indicated that the DEGs at m1 were similar to those in the control group. Downregulated DEGs were enriched in nervous system disease pathways, such as Parkinson's disease. Upregulated DEGs were enriched in immune response‑associated pathways, such as Fc γ R‑mediated phagocytosis at early stages (d3 and wk1). Upregulated DEGs were enriched in pathways associated with cancer and pyrimidine metabolism at wk2 and m1, respectively. In the PPI network, nodes including RAC2, CD4, STAT3 and JUN were identified. Furthermore, ATF3, JUN and EGR1 were identified as TFs associated with SCI. In conclusion, the results of the present study showed that the number of DEGs decreased in a time‑dependent manner following SCI. OLIG1, ATF3 and JUN may represent SCI regeneration‑associated genes. Immune-associated inflammation was shown to be important in SCI, and SCI exhibits causal associations with other diseases, including cardiovascular disease and cancers. The present study provided novel insight into the molecular mechanisms of SCI regeneration, which may aid in the development of strategies to enhance recovery following SCI.