Modulatory role of neuropeptide FF system in macrophages.

Neuropeptide FF (NPFF) is an octapeptide that regulates various cellular processes, especially pain perception. Recently, there has been a growing interest in understanding the modulation of NPFF in neuroendocrine inflammation. This review aims to provide a thorough overview of the regulation of NPFF in macrophage-mediated biological processes. We delve into the impact of NPFF on macrophage polarization, self-renewal modulation, and the promotion of mitophagy, facilitating the transition from thermogenic fat to fat-storing adipose tissue. Additionally, we explore the NPFF-dependent regulation of the inflammatory response mediated by macrophages, its impact on the differentiation of macrophages, and its capacity to induce alterations in the transcriptome of macrophages. We also address the potential of NPFF as a therapeutic molecule in the field of neuroendocrine inflammation. Overall, our work offers an understanding of the influence of NPFF on macrophage, facilitating the exploration of its pharmacological significance in future studies.

A combination of umbilical cord mesenchymal stem cells and monosialotetrahexosy 1 ganglioside alleviates neuroinflammation in traumatic brain injury.

Neuro-inflammation and activated microglia play important roles in neuron damage in the traumatic brain injury (TBI). In this study, we determined the effect of neural network reconstruction after human umbilical cord mesenchymal stem cells (UMSCs) combined with monosialotetrahexosy 1 ganglioside (GM1) transplantation and the effect on the neuro-inflammation and polarization of microglia in a rat model of TBI, which was established in male rats using a fluid percussion brain injury device. Rats survived until day 7 after TBI were randomly treated with normal control (NC), saline (NS), GM1, UMSCs, and GM1 plus UMSCs. Modified neurological severity score (mNSS) was assessed on days 7 and 14, and the brain tissue of the injured region was collected. Immunofluorescence, RT-PCR, and western blot analysis found that inhibitory neuro-inflammatory cytokines TGF-ß and CD163 protein expression levels in injured brain tissues were significantly increased in rats treated with GM1 + UMSCs, GM1, or UMSCs and were up-regulated compared to saline-treated rats. Neuro-inflammatory cytokines IL-6, COX-2 and iNOS protein expressions were down-regulated compared to rats treated with saline. The protein expression levels of NE, NF-200, MAP-2 and ß-tubulin III were increased in the injured brain tissues from rats treated with GM1 + UMSCs, or GM1 and UMSCs alone compared to those in the rats treated with NS. The protein expression levels in rats treated with GM1 plus UMSCs were most significant on day 7 following UMSC transplantation. The rats treated with GM1 plus UMSCs had the lowest mNSS compared with that in the other groups. These data suggest that UMSCs and GM1 promote neural network reconstruction and reduce the neuro-inflammation and neurodegeneration through coordinating injury local immune inflammatory microenvironment to promote the recovery of neurological functions in the TBI.

Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3ß pathway in rats.

BACKGROUND: Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism. METHODS: Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov's scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3ß pathway-related proteins, as well as NOX2 and NLRP3 proteins. RESULTS: The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3ß expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment. CONCLUSION: Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3ß pathway.

miR-152-5p suppresses glioma progression and tumorigenesis and potentiates temozolomide sensitivity by targeting FBXL7.

A generally used chemotherapeutic drug for glioma, a frequently diagnosed brain tumour, is temozolomide (TMZ). Our study investigated the activity of FBXL7 and miR-152-5p in glioma. Levels of microRNA-152-5p (miR-152-5p) and the transcript and protein of FBXL7 were assessed by real-time PCR and Western blotting, respectively. The migratory and invasive properties of cells were measured by Transwell migration and invasion assay and their viability were examined using CCK-8 assay. Further, the putative interaction between FBXL7 and miR-152-5p were analysed bioinformatically and by luciferase assay. The activities of FBXL7, TMZ and miR-152-5p were analysed in vivo singly or in combination, on mouse xenografts, in glioma tumorigenesis. The expression of FBXL7 in glioma tissue is significantly up-regulated, which is related to the poor prognosis and the grade of glioma. TMZ-induced cytotoxicity, proliferation, migration and invasion in glioma cells were impeded by the knock-down of FBXL7 or overexpressed miR-152-5p. Furthermore, the expression of miR-152-5p reduced remarkably in glioma cells and it exerted its activity through targeted FBXL7. Overexpression of miR-152-5p and knock-down of FBXL7 in glioma xenograft models enhanced TMZ-mediated anti-tumour effect and impeded tumour growth. Thus, the miR-152-5p suppressed the progression of glioma and associated tumorigenesis, targeted FBXL7 and increased the effect of TMZ-induced cytotoxicity in glioma cells, further enhancing our knowledge of FBXL7 activity in glioma.

Neuroprotective Effects of Luteolin Against Spinal Cord Ischemia-Reperfusion Injury by Attenuation of Oxidative Stress, Inflammation, and Apoptosis.

Luteolin (LU) is a widely distributed flavonoid with multitarget effects. The objective of this study was to determine whether LU could reduce the ischemia-reperfusion injury of the spinal cord (SCII) in a rat model. Forty-eight rats were divided into four groups: sham, SCII, SCII+L-LU (50 mg/kg), and SCII+H-LU (100 mg/kg). Abdominal aortic occlusion was carried out for 40 min in all groups. Hindlimb motor functions were evaluated using the Tarlov scoring system. Nissl and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining were used to detect cell survival and apoptosis in the spinal cord. Spinal cord samples were taken for determination of malondialdehyde, xanthine oxidase, superoxide dismutase, and glutathione peroxidase activities. The levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-18 were assessed using ELISA kits to examine the inflammatory responses in the spinal cord. Western blot analysis was used to examine the expression of nuclear factor erythroid 2-related factor (Nrf2) and nod-like receptor pyrin domain-containing 3 protein (NLRP3) levels. We found that LU pretreatment significantly improved the locomotor function of rats after SCII, increased neuron survival, and inhibited apoptosis in the spinal cord. Furthermore, the oxidative stress and inflammatory response were significantly suppressed upon treatment with LU. Finally, LU upregulated Nrf2 levels and downregulated NLRP3 protein expression in SCII tissues. Thus, LU exhibited a neuroprotective effect following SCII by alleviating oxidative stress and inhibiting inflammatory responses and cell apoptosis. The possible mechanism may be related to the activation of Nrf2 and inhibition of NLRP3 inflammasome pathway.

Slit2 and Robo1 expression as biomarkers for assessing prognosis in brain glioma patients.

OBJECTIVES: This study was conducted to investigate the clinical significance of Slit2 and Robo1 expression in prognosis of patients with brain gliomas. METHODS: Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. Slit2 and Robo1 expression levels in cells were assessed by an immunohistochemistry (IHC), and population of the Slit2- and Robo1-presenting patients was examined. The Slit2 and Robo1 mRNA expression levels in three types of the brain cells was determined by RT-PCR. RESULTS: Slit2+ cell counts were decreased with increased Robo1+ cells in the low-grade and high-grade glioma tissues as compared to the control. The percentage of cells expressing Slit2 decreased from the control to the high-grade glioma and the percentage of cells expressing Robo1 in low- and high-grade gliomas was increased as compared to the control (P < 0.01). The decrease in the Slit2 mRNA expression was associated with the increase in the Robo1 mRNA expression in the low- and high-grade gliomas (P < 0.01 or 0.05). Survival time for patients with Slit2-/Robo1+ gliomas was shorter than patients with Slit2+/Robo1+ gliomas in the investigated cohorts (P < 0.01). CONCLUSION: Slit2 and Robo1 expression levels serve as a biomarker with utility in grading gliomas as well as predicting patient survival. The change in Slit2 expression is more reliable and effective than Robo1 expression in predicting a poor prognosis of brain glioma patients.