Spinal interleukin-24 contributes to neuropathic pain after peripheral nerve injury through interleukin-20 receptor2 in mice.

Neuroinflammation is critically involved in nerve injury-induced neuropathic pain, characterized by local and systemic increased levels of proinflammatory cytokines. Interleukin-24 (IL-24), a key member of the IL-10 family, has been extensively studied for its therapeutic potential in various diseases, including cancer, autoimmune disorders, and bacterial infections, but whether it is involved in the regulation of neuropathic pain caused by peripheral nerve injury (PNI) has not been well established. In this study, we reported that spared nerve injury (SNI) induced a significant upregulation of IL-24 in fibroblasts, neurons, and oligodendrocyte precursor cells (OPCs, also called NG2-glia) in the affected spinal dorsal horns (SDHs), as well as dorsal root ganglions (DRGs). We also found that tumor necrosis factor α (TNF-α) induced the transcriptional expression of IL-24 in cultured fibroblasts, neurons, and NG2-glia; in addition, astrocytes, microglia, and NG2-glia treated with TNF-α exhibited a prominent increase in interleukin-20 receptor 2 (IL-20R2) expression. Furthermore, we evaluated the ability of IL-24 and IL-20R2 to attenuate pain in preclinical models of neuropathic pain. Intrathecal (i.t.) injection of IL-24 neutralizing antibody or IL-20R2 neutralizing antibody could effectively alleviate mechanical allodynia and thermal hyperalgesia after PNI. Similarly, intrathecal injection of IL-24 siRNA or IL-20R2 siRNA also alleviated mechanical allodynia after SNI. The inhibition of IL-24 reduced SNI-induced proinflammatory cytokine (IL-1ß and TNF-α) production and increased anti-inflammatory cytokine (IL-10) production. Meanwhile, the inhibition of IL-20R2 also decreased IL-1ß mRNA expression after SNI. Collectively, our findings revealed that IL-24/IL-20R might contribute to neuropathic pain through inflammatory response. Therefore, targeting IL-24 could be a promising strategy for treating neuropathic pain induced by PNI.

How Wealth Inequality Affects Happiness: The Perspective of Social Comparison.

Since Easterlin pointed out that economic growth in nations does not guarantee increasing happiness for the average citizen, the underlying reason has remained controversial. The present study focuses on income inequality to explain the "Easterlin Paradox," ignoring the permanent inequality that long-term wealth accumulation brings. Based on social comparison theory, the literature aims to determine how wealth inequality, which accompanies economic growth, diminishes one's happiness (inequality aversion). Specifically, we conduct this study in which we split the wealth inequality into the upward wealth inequality and the downward wealth inequality as measures of upward comparison and downward comparison, respectively. The upward wealth inequality measures the average gap between one and the better-off in wealth while the downward wealth inequality measures the average gap between one and the worse-off in wealth. Furthermore, the heterogeneity of the area of respondent is analyzed and the family life cycle is tested as a moderator. The main findings of the paper are as follows: (1) The empirical test results of hypothesis 1 indicate that the upward wealth inequality aversion (jealousy effect: people envy who is richer than themselves) is stronger than the downward wealth inequality inclination (proud effect: people enjoy having a superior position in the wealth hierarchy). It is due to the psychological preference: loss aversion. As an increase in upward distance implies a loss in relative status and an increase in downward distance implies a gain in relative status, people focus more on loss rather than gain. (2) The empirical test results of hypothesis 2 indicate that residents who live in rural areas do not have a proud effect as much as those who live in urban areas. There is a huge urban-rural wealth gap in China. With the expansion of the social network, people living in rural areas realize that even he is almost the rich in rural areas but still the lower classes in the whole society. It is hard for rural residents to have a proud effect. (3) The empirical test results of hypothesis 3 indicate that family members have the strongest upward inequality aversion in the middle-stage phase of the life cycle (when the family head is approximately 50). During the family life cycle, inequality aversion will be different in different life stages due to the changes in economic status expectations. At the beginning of the family life cycle, family members assume their life has limitless possibilities, and they have high expectations for the future. Logically, they can be easily satisfied by achieving a little more than their peers. In later periods, with increasing age, the members will pay more attention to health instead of wealth. The results shed light on how macroeconomics influence changes in individual psychology.

MicroRNA expression profiles of neural stem cells following valproate inducement.

Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p, and miR-210-3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.

Estrogen inhibits lipid peroxidation after hypoxic-ischemic brain damage in neonatal rats.

Sprague-Dawley neonatal rats within 7 days after birth were used in this study. The left common carotid artery was occluded and rats were housed in an 8% O2 environment for 2 hours to establish a hypoxic-ischemic brain damage model. 17ß-estradiol (1 × 10(-5) M) was injected into the rat abdominal cavity after the model was successfully established. The left hemisphere was obtained at 12, 24, 48, 72 hours after operation. Results showed that malondialdehyde content in the left brain of neonatal rats gradually increased as modeling time prolonged, while malondialdehyde content of 17ß-estrodial-treated rats significantly declined by 24 hours, reached lowest levels at 48 hours, and then peaked at 72 hours after injury. Nicotinamide-adenine dinucleotide phosphate histochemical staining showed the nitric oxide synthase-positive cells and fibers dyed blue/violet and were mainly distributed in the cortex, hippocampus and medial septal nuclei. The number of nitric oxide synthase-positive cells peaked at 48 hours and significantly decreased after 17ß-estrodial treatment. Our experimental findings indicate that estrogen plays a protective role following hypoxic-ischemic brain damage by alleviating lipid peroxidation through reducing the expression of nitric oxide synthase and the content of malondialdehyde.

Morphological differences in skeletal muscle atrophy of rats with motor nerve and/or sensory nerve injury.

Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional area and altered ultrastructure of muscle cells, as well as decreased cross-sectional area and increased gray scale of the gastrocnemius muscle motor end plate. Moreover, at the same time point, the pathological changes were most severe in mixed nerve injury, followed by simple motor nerve injury, and the changes in simple sensory nerve injury were the mildest. These findings indicate that normal skeletal muscle morphology is maintained by intact innervation. Motor nerve injury resulted in larger damage to skeletal muscle and more severe atrophy than sensory nerve injury. Thus, reconstruction of motor nerves should be considered first in the clinical treatment of skeletal muscle atrophy caused by denervation.

Biotinylated dextran amine anterograde tracing of the canine corticospinal tract.

In this study, biotinylated dextran amine (BDA) was microinjected into the left cortical motor area of the canine brain. Fluorescence microscopy results showed that a large amount of BDA-labeled pyramidal cells were visible in the left cortical motor area after injection. In the left medulla oblongata, the BDA-labeled corticospinal tract was evenly distributed, with green fluorescence that had a clear boundary with the surrounding tissue. The BDA-positive corticospinal tract entered into the right lateral funiculus of the spinal cord and descended into the posterior part of the right lateral funiculus, close to the posterior horn, from cervical to sacral segments. There was a small amount of green fluorescence in the sacral segment. The distribution of BDA labeling in the canine central nervous system was consistent with the course of the corticospinal tract. Fluorescence labeling for BDA gradually diminished with time after injection. Our findings indicate that the BDA anterograde tracing technique can be used to visualize the localization and trajectory of the corticospinal tract in the canine central nervous system.

Fluoro-ruby retrograde tracing and three- dimensional visualization of the corticospinal tract in the guinea pig.

Fluoro-ruby was injected into the posterior funiculus of the spinal cord in the cervical (C5-T2) and lumbar (L3-6) segments of adult guinea pigs. The spinal cord was cut into serial frozen sections. The Fluoro-ruby labeling was clearly delineated from the surrounding structure. The labeling traversed the cervical, thoracic and lumbar segments, and was located on the ventral portion of the posterior funiculus on the injected side, proximal to the intermediate zone of the dorsal gray matter. The fluorescence area narrowed rostro-caudally. The spinal cord, spinal cord gray matter and corticospinal tract were reconstructed using 3D-DOCTOR 4.0 software, resulting in a robust three-dimensional profile. Using functionality provided by the reconstruction software, free multi-angle observation and sectioning could be conducted on the spinal cord and corticospinal tract. Our experimental findings indicate that the Fluoro-ruby retrograde fluorescent tracing technique can accurately display the anatomical location of corticospinal tract in the guinea pig and that three-dimensional reconstruction software can be used to provide a three-dimensional image of the corticospinal tract.

[Experimental study of recording and analysing electrophysiological signals from corticospinal tract in rats].

OBJECTIVE: To explore the recording method of the electrophysiological signals in corticospinal tract (CST) of adult rats by plugging microelectrodes and analyze the characteristics of these signals. These could provide some valuable and basic neural electrophysiological information for further research of recovering and refunctioning after spinal cord injury. METHODS: The microelectrodes were plugged into the corticospinal tract at the T8 spinal section of Sprague-Dawley rats and the neuro-electrical signals were identified and recorded from CST by means of the Cerebus System. The characteristics of the recorded signals were described with the help of the Offline sorter and Neuroexplorer softwares, including the wavelength, amplitude, discharging frequency, the synchrony among the multi-discharging units from the same electrode and two different electrodes, analysis of interspike interval (ISI), etc. RESULTS: The continuous and steady spontaneous electrophysiological signals were recorded from CST. Three or four types of discharging signals originated from different discharging units were collected with each electrode. The waveform of the signals appeared bidirectional. The wavelengths were 0.6 - 1.3 ms with wave amplitudes at a grade of hundred microvoltage and high signal-noise ratios. The LFB staining proved that the electrodes were accurately plugged into the corticospinal tract. CONCLUSION: The neuro-electrical signals at a grade of hundred microvoltage could be recorded stably from the corticospinal tract of rats by the Cerebus System with the microelectrodes, which provided valuable and basic neural electrophysiological information for further research on recovering and refunctioning after spinal cord injury (SCI) by analyzing the characteristics of electrophysiological signals.

[Tbx3 upregulation may be one of the malignant biomarkers of breast cancer].

OBJECTIVE: To explore the role of abnormal Tbx3 expression in the pathogenesis of breast cancer. METHOD: The total RNA of 4 breast cancer cell lines and 5 normal breast samples was extracted by routine Trizol method. After reverse transcription of the total RNA into cDNA, Tbx3 mRNA expression was detected in these samples by real-time PCR. Immunohistochemistry was used to examine the differences in Tbx3 protein expression between 60 breast cancer samples and 34 normal breast tissue samples. RESULTS: Compared to normal breast tissue samples, the breast cancer cell lines showed markedly increased Tbx3 mRNA expression. The results of immunohistochemistry demonstrated a significant upregulation of Tbx3 protein expression in the 60 breast cancer tissues in comparison with the normal breast tissues, as was consistent with Tbx3 mRNA expressions in these tissue samples. CONCLUSIONS: The mRNA and protein expressions of Tbx3 are markedly upregulated in breast cancer cell lines and tissue samples, suggesting that Tbx3 may serve as one of the malignant biomarkers in the pathogenesis of breast cancer.