Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis.

PURPOSE: To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. METHODS: Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. RESULTS: The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. CONCLUSIONS: FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

Lipopolysaccharide-induced depression is associated with estrogen receptor-α/SIRT1/NF-κB signaling pathway in old female mice.

The present study aims to investigate the influence of sex/age on depressive-like behaviors in lipopolysaccharide (LPS)-challenged mice model, and explore the underlying mechanisms. Tail suspension test and forced swimming test were used to evaluate the depressive-like behaviors. SIRT1 mRNA expression was assessed by PCR. Levels of 17ß-estradiol (E2), SIRT1, NF-κB, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA). In the behavior tests, under the same LPS stimulation, significant depressive-like behavior was observed in young male mice but not in young female mice, however, female mice were more likely to be depressed than male mice in the old age. Moreover, we found age-related depression difference existed only in female mice. In the experiments of mechanism exploration in old female mice, E2 improved LPS-induced depressive-like behavior, and simultaneously elevated SIRT1 levels and downregulated expressions of NF-κB and inflammatory cytokines in the hippocampus and frontal cortex. Interestingly, ERα inhibition, not ERß inhibition, abolished E2's function. Additionally, SIRT1 antagonist also reversed E2's effects on depressive-like behavior and the expressions of NF-κB and inflammatory cytokines. These results suggested that E2 could protect the old female mice from depression via E2/ERα/SIRT1/NF-κB signaling pathway. In other words, LPS-induced depression was associated with ER-α/SIRT1/NF-κB signaling pathway in old female mice. By comparing the results of mechanism exploration in old male mice and old female mice and the different expression levels of E2, SIRT1, NF-κB and inflammatory cytokines in young female mice and old female mice, we speculate that the age or gender-related depression difference may be associated with the different activation levels of the ERα/SIRT1/NF-κB signaling pathway.

Irisin protects female mice with LPS-induced endometritis through the AMPK/NF-κB pathway.

OBJECTIVES: This research was designed to determine the role of irisin in lipopolysaccharide (LPS)-induced endometritis in female mice. MATERIALS AND METHODS: Animals were randomly assigned into sham, sham + irisin, LPS, LPS + irisin (0.1, 1, 10 µg/kg), and LPS + irisin + compound C groups. Histological features and expression of AMPK, NF-κB, inflammatory mediators, and oxidative stress markers were compared among different groups. RESULTS: The results showed that LPS resulted in obvious uterus damage, meanwhile, the inflammatory mediators (COX-2, iNOS, IL-1ß, IL-6, and TNF-α), as well as NF-κB in the uterine tissue, were significantly increased and the level of adenosine monophosphate-activated protein kinase (AMPK) was reduced. Nevertheless, pretreatment with irisin reversed the phenomena caused by LPS. Interestingly, compound C (AMPK inhibitor) abolished irisin's effects on the uterus, which suggested that irisin's beneficial function was achieved through regulating the AMPK-NF-κB pathway. Moreover, LPS-induced alterations of oxidative factors (MnSOD, GSH, and MDA) were reversed significantly by pretreatment with irisin. This data indicated irisin's beneficial function was also related to antioxidation besides anti-inflammation. CONCLUSION: Our study implies that irisin is a potential therapeutic agent for endometritis.

Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis

ABSTRACT Purpose To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. Methods Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. Results The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. Conclusions FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

A Robust Noise Mitigation Method for the Mobile RFID Location in Built Environment.

The exact location of objects, such as infrastructure, is crucial to the systematic understanding of the built environment. The emergence and development of the Internet of Things (IoT) have attracted growing attention to the low-cost location scheme, which can respond to a dramatic increasing amount of public infrastructure in smart cities. Various Radio Frequency IDentification (RFID)-based locating systems and noise mitigation methods have been developed. However, most of them are impractical for built environments in large areas due to their high cost, computational complexity, and low noise detection capability. In this paper, we proposed a novel noise mitigation solution integrating the low-cost localization scheme with one mobile RFID reader. We designed a filter algorithm to remove the influence of abnormal data. Inspired the sampling concept, a more carefully parameters calibration was carried out for noise data sampling to improve the accuracy and reduce the computational complexity. To achieve robust noise detection results, we employed the powerful noise detection capability of the random sample consensus (RANSAC) algorithm. Our experiments demonstrate the effectiveness and advantages of the proposed method for the localization and noise mitigation in a large area. The proposed scheme has potential applications for location-based services in smart cities.

Chronic trans-astaxanthin treatment exerts antihyperalgesic effect and corrects co-morbid depressive like behaviors in mice with chronic pain.

Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. Trans-astaxanthin has been shown in our previous studies to exert antidepressant-like effect. This work aimed to investigate the effects of trans-astaxanthin on pain-related depressive-like behaviors in mice and explored the mechanism(s). Chronic constriction injury (CCI) model was used in this research. Chronic pain was evaluated by thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test, depressive-like behaviors were evaluated by immobility time in forced swim test and tail suspension test. Chronic trans-astaxanthin treatment ameliorated mechanical allodynia and thermal hyperalgesia, as well as decreasing immobility time in forced swim test and tail suspension test in CCI mice, and these actions were abolished by co-treatment with P-Chlorophenylalanine (PCPA). Subsequent study indicated that indoleamine 2,3-dioxygenase (IDO) expression increased after CCI surgery in hippocampus and spinal cord, accompanied by increase of kynurenine (KYN)/tryptophan (TRY) ratio, decrease of serotonin (5-HT)/TRY ratio and decrease of 5-HT/5-HIAA ratio. The above results affected by CCI surgery were reversed by trans-astaxanthin treatment. Moreover, trans-astaxanthin at 80mg/kg was demonstrated to effectively antagonize IL-1ß, IL-6 and TNF-α expression in hippocampus and spinal cord of CCI mice. Taken together, chronic trans-astaxanthin administration exerts therapeutic effects on thermal hyperalgesia and co-morbid depressive-like behaviors in CCI mice. These effects of trans-astaxanthin involves the serotonergic system, and also may be owing to its potent anti-inflammatory property.

Proanthocyanidin prevents lipopolysaccharide-induced depressive-like behavior in mice via neuroinflammatory pathway.

Recent studies have demonstrated neuroinflammation and increased cytokine levels are associated with depression. Aware of the efficacy the potential anti-inflammatory and antioxidative activity of proanthocyanidin, the present study was designed to investigate the effects of proanthocyanidin on lipopolysaccharide (LPS)-induced depressive-like behavior in mice. In depressive behavior tests, the immobility time of forced swimming test (FST) and tail suspension test (TST) was increased when mice were administrated a single dose of LPS (0.83mg/kg, i.p.), whereas these alterations were reversed by proanthocyanidin treatment (80mg/kg, p.o.). In anxiety behavior tests, all the anxiety-related parameters, such as number of buried marble, time spent in the open arm and close arm did not show statistical differences between LPS and control groups. However, anxiolytic effects were observed in marble-burying test and elevated plus maze test in single proanthocyanidin treatment and proanthocyanidin treatment together with LPS group. Further assays indicated that LPS-induced overexpression of pro-inflammatory cytokines in the hippocampus, prefrontal cortex (PFC) and amygdala were reversed by proanthocyanidin treatment. Furthermore, proanthocyanidin inhibited the LPS-induced iNOS and COX-2 overexpression, via the modulation of NF-κB in the hippocampus, PFC and amygdala. Taken together, proanthocyanidin may be an effective therapeutic agent for LPS-induced depressive-like behaviors via its potent anti-inflammatory property.

Predicting functional cortical ROIs via DTI-derived fiber shape models.

Studying structural and functional connectivities of human cerebral cortex has drawn significant interest and effort recently. A fundamental and challenging problem arises when attempting to measure the structural and/or functional connectivities of specific cortical networks: how to identify and localize the best possible regions of interests (ROIs) on the cortex? In our view, the major challenges come from uncertainties in ROI boundary definition, the remarkable structural and functional variability across individuals and high nonlinearities within and around ROIs. In this paper, we present a novel ROI prediction framework that localizes ROIs in individual brains based on their learned fiber shape models from multimodal task-based functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data. In the training stage, shape models of white matter fibers are learnt from those emanating from the functional ROIs, which are activated brain regions detected from task-based fMRI data. In the prediction stage, functional ROIs are predicted in individual brains based only on DTI data. Our experiment results show that the average ROI prediction error is around 3.94 mm, in comparison with benchmark data provided by working memory and visual task-based fMRI. Our work demonstrated that fiber bundle shape models derived from DTI data are good predictors of functional cortical ROIs.