Integrated analysis reveals Atf3 promotes neuropathic pain via orchestrating JunB mediated release of inflammatory cytokines in DRG macrophage.

The dorsal root ganglion (DRG) is actively involved in the development of neuropathic pain (NP), serving as an intermediate station for pain signals from the peripheral nervous system to the central nervous system. The mechanism by which DRG is involved in NP regulation is not fully understood. The immune system plays a pivotal role in the physiological and pathological states of the human body. In recent years, the immune system has been thought to play an increasingly important role in the pathogenesis of NP. The immune system plays a key role in pain through specific immune cells and their immune-related genes (IRGs). However, the mechanism by which IRGs of DRG regulate NP action has not been fully elucidated. Here, we performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of IRGs in DRG bulk-RNA sequencing data from spared nerve injury (SNI) model mice and found that their IRGs were enriched in many pathways, especially in the immune response pathway. Subsequently, we analyzed single-cell RNA sequencing (scRNA-seq) data from DRGs extracted from the SNI model and identified eight cell populations. Among them, the highest IRG activity was presented in macrophages. Next, we analyzed the scRNA and bulk-sequencing data and deduced five common transcription factors (TFs) from differentially expressed genes (DEGs). The protein-protein interaction (PPI) network suggested that Atf3 and JunB are closely related. In vitro experiments, we verified that the protein and mRNA expressions of Atf3 and JunB were up-regulated in macrophages after lipopolysaccharide (LPS) stimulation. Moreover, the down-regulation of Atf3 reduced the release of inflammatory cytokines and decreased the protein and mRNA expression levels of JunB. The down-regulation of JunB also reduced the release of inflammatory cytokines. Furthermore, overexpression of JunB attenuated the effect of Atf3 down-regulation in reducing the release of inflammatory cytokines. Therefore, we speculated that Atf3 might promote NP through JunB-mediated release of inflammatory factors in DRG macrophages.

Identification and validation of biomarkers related to Th1 cell infiltration in neuropathic pain.

Neuropathic pain (NP) is a widespread chronic pain with a prevalence of 6.9-10% in the general population, severely affecting patients' physical and mental health. Accumulating evidence indicated that the immune environment is an essential factor causing NP. However, the mechanism is unclear. This study attempted to analyze NP-related immune infiltration patterns. We downloaded the expression profiles from the Gene Expression Omnibus (GEO) database. The novel method of single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) was applied to identify immune-related genes and verified in vitro and in vivo experiments. The spared nerve injury (SNI) group was closely related to type1 T helper cells (Th1 cells), and two key genes (Abca1 and Fyb) positively correlated with Th1 cell infiltration. At the single-cell level, Abca1 and Fyb were significantly expressed in macrophages. In addition, we verified that Abca1 could affect the function of macrophages. Finally, we hypothesized that Abca1 is involved in the infiltration of Th1 cells into dorsal root ganglion (DRG) tissues and induces NP via immunoinflammatory response. Hence, the present study aimed to elucidate the correlation between NP and neuroinflammation and identify a new therapeutic target for treating NP.

Compensatory movement detection by using near-infrared spectroscopy technology based on signal improvement method.

Introduction: Compensatory movements usually occur in stroke survivors with hemiplegia, which is detrimental to recovery. This paper proposes a compensatory movement detection method based on near-infrared spectroscopy (NIRS) technology and verifies its feasibility using a machine learning algorithm. We present a differential-based signal improvement (DBSI) method to enhance NIRS signal quality and discuss its effect on improving detection performance. Method: Ten healthy subjects and six stroke survivors performed three common rehabilitation training tasks while the activation of six trunk muscles was recorded using NIRS sensors. After data preprocessing, DBSI was applied to the NIRS signals, and two time-domain features (mean and variance) were extracted. An SVM algorithm was used to test the effect of the NIRS signal on compensatory behavior detection. Results: Classification results show that NIRS signals have good performance in compensatory detection, with accuracy rates of 97.76% in healthy subjects and 97.95% in stroke survivors. After using the DBSI method, the accuracy improved to 98.52% and 99.47%, respectively. Discussion: Compared with other compensatory motion detection methods, our proposed method based on NIRS technology has better classification performance. The study highlights the potential of NIRS technology for improving stroke rehabilitation and warrants further investigation.

Predicting the risk of acute kidney injury after cardiopulmonary bypass: development and assessment of a new predictive nomogram.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to establish a model to predict the probability of postoperative AKI in patients undergoing cardiac surgery with CPB. METHODS: We conducted a retrospective, multicenter study to analyze 1082 patients undergoing cardiac surgery under CPB. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the AKI model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the previously mentioned model. Finally, we used multiple methods to evaluate the accuracy and clinical applicability of the model. RESULTS: Age, gender, hypertension, CPB duration, intraoperative 5% bicarbonate solution and red blood cell transfusion, urine volume were identified as important factors. Then, these risk factors were created into nomogram to predict the incidence of AKI after cardiac surgery under CPB. CONCLUSION: We developed a nomogram to predict the incidence of AKI after cardiac surgery. This model can be used as a reference tool for evaluating early medical intervention to prevent postoperative AKI.

A Novel Marine Pyran-Isoindolone Compound Enhances Fibrin Lysis Mediated by Single-Chain Urokinase-Type Plasminogen Activator.

Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 µM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.

Non-Coding RNAs in Sepsis-Associated Acute Kidney Injury.

Sepsis is a systemic inflammatory response caused by a severe infection that leads to multiple organ damage, including acute kidney injury (AKI). In intensive care units (ICU), the morbidity and mortality associated with sepsis-associated AKI (SA-AKI) are gradually increasing due to lack of effective and early detection, as well as proper treatment. Non-coding RNAs (ncRNAs) exert a regulatory function in gene transcription, RNA processing, post-transcriptional translation, and epigenetic regulation of gene expression. Evidence indicated that miRNAs are involved in inflammation and programmed cell death during the development of sepsis-associated AKI (SA-AKI). Moreover, lncRNAs and circRNAs appear to be an essential regulatory mechanism in SA-AKI. In this review, we summarized the molecular mechanism of ncRNAs in SA-AKI and discussed their potential in clinical diagnosis and treatment.

Epigenetic modifications in neuropathic pain.

Neuropathic pain (NP) is a common symptom in many diseases of the somatosensory nervous system, which severely affects the patient's quality of life. Epigenetics are heritable alterations in gene expression that do not cause permanent changes in the DNA sequence. Epigenetic modifications can affect gene expression and function and can also mediate crosstalk between genes and the environment. Increasing evidence shows that epigenetic modifications, including DNA methylation, histone modification, non-coding RNA, and RNA modification, are involved in the development and maintenance of NP. In this review, we focus on the current knowledge of epigenetic modifications in the development and maintenance of NP. Then, we illustrate different facets of epigenetic modifications that regulate gene expression and their crosstalk. Finally, we discuss the burgeoning evidence supporting the potential of emerging epigenetic therapies, which has been valuable in understanding mechanisms and offers novel and potent targets for NP therapy.

TRESK Regulates Gm11874 to Induce Apoptosis of Spinal Cord Neurons via ATP5i Mediated Oxidative Stress and DNA Damage.

Reportedly, TWIK-related spinal cord K+ (TRESK) deficiency in spinal cord neurons positively correlates with the mechanism underlying neuropathic pain (NP). However, the precise effects of TRESK on neurons of the spinal cord remain elusive. In the present study, we investigated the impact of TRESK silencing on spinal cord neurons to further elucidate the downstream mechanisms of TRESK. Herein, neurons of the dorsal spinal cord were cultured as a cell model for investigations. Apoptosis, oxidative stress, and DNA damage-related proteins were evaluated. Additionally, flow cytometry, microarray profiling, real-time polymerase chain reaction (PCR), western blotting, fluorescence in situ hybridization (FISH), immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed. In cultured neurons, the downregulation of TRESK mRNA expression induced apoptosis of dorsal spinal cord neurons. Using real-time PCR and western blotting, the upregulation of LncRNA Gm11874 (Gm11874) and ATP5i, screened from the gene chip, was confirmed. On silencing TRESK, expression levels of γ-H2AX, poly [ADP-ribose] polymerase 1 (PARP-1), FoxO1, FoxO3, MitoSOX, malondialdehyde (MDA), and 8-hydroxy-2' -deoxyguanosine (8-OHdG), which are known indices of oxidative stress and DNA damage, were significantly elevated. Moreover, ATP induced oxidative stress, DNA damage, and apoptosis were reduced by ATP5i siRNA. Finally, Gm11874 and ATP5i were co-expressed in spinal cord neurons in a FISH experiment, and the expression of ATP5i was positively regulated by Gm11874. These results implied that ATP5i induced oxidative stress and DNA damage, resulting in neuronal apoptosis, and Gm11874 was confirmed to act upstream of ATP5i. Our study revealed that TRESK silencing upregulated Gm11874 to induce apoptosis of spinal cord neurons, which resulted in ATP5i promoting oxidative stress and DNA damage. These findings could highlight the TRESK-mediated NP mechanism.

MicroRNAs in the Spinal Microglia Serve Critical Roles in Neuropathic Pain.

Neuropathic pain (NP) can occur after peripheral nerve injury (PNI), and it can be converted into a maladaptive, detrimental phenotype that causes a long-term state of pain hypersensitivity. In the last decade, the discovery that dysfunctional microglia evoke pain, called "microgliopathic pain," has challenged traditional neuronal views of "pain" and has been extensively explored. Recent studies have shown that microRNAs (miRNAs) can act as activators or inhibitors of spinal microglia in NP conditions. We first briefly review spinal microglial activation in NP. We then comprehensively describe miRNA expression changes and their potential mechanisms in the response of microglia to nerve injury. We summarize the roles of the following two representative miRNAs: miR-124, which reverses NP by keeping microglia quiescent, and miR-155, which promotes NP following microglial activation. Finally, we focused on the therapeutic potential of microglial miRNAs in NP. The findings we summarized may be essential tools for basic research and clinical treatment of NP.

Changes in testicular gene expression following reduced estradiol synthesis: A complex pathway to increased porcine Sertoli cell proliferation.

Porcine Sertoli cell number including number present at puberty is increased if testicular estradiol synthesis is reduced during the neonatal interval. Evaluating the changes in gene expression during the crucial interval of suppressed estradiol that leads to the increased Sertoli cell population will increase our understanding of Sertoli cell biology but this evaluation first required a more precise determination of the critical interval for treatment and timing of a detectable response. Previously, reduced testicular estrogens from 1 week of age were accompanied by increased Sertoli cell number at 6.5 weeks of age but the age at which Sertoli cell numbers were initially increased was unknown, one of the current objectives. Additional experiments were designed to further delineate the essential timing of treatment for the Sertoli cell response. Finally, changes in gene expression induced by the reduced estradiol synthesis were evaluated to elucidate molecular mechanisms. Experimental design typically consisted of one member of littermate pairs of boars treated with the aromatase inhibitor, letrozole, beginning at 1 week of age and the remaining member treated with canola oil vehicle. Weekly treatments continued through 5 weeks of age or tissue collection, whichever came first. Increases in Sertoli cell numbers were not detectable prior to 6.5 weeks of age and persistent treatment through 5 weeks of age was required to induce the increase in Sertoli cell numbers. This increase resulted from prolonging the first interval of Sertoli cell proliferation in the treated animals. Few genes exhibited dramatically altered transcription and similarities in pathway analysis or principal modified genes were quite limited in 2, 3, and 5-week-old boars. The critical timing and prolonged treatment required and the sequential changes in gene expression suggest a complex mechanism is involved in this model of increased proliferation of Sertoli cells.

LncRNA Gm12840 mediates WISP1 to regulate ischemia-reperfusion-induced renal fibrosis by sponging miR-677-5p.

Aim: We aimed to identify that long noncoding RNAs (lncRNAs) are involved in ischemia-reperfusion (IR)-induced late fibrosis of kidney and may constitute novel therapeutic strategies for acute kidney injury-induced chronic kidney disease. Materials & methods: We performed the mouse model of IR later induced renal fibrosis and analyzed lncRNA profiles using second-generation sequencing during the pathogenesis. Results: The expression levels of 43 lncRNAs and 141 lncRNAs were respectively changed significantly 7 days and 2 weeks after IR treatment. Based on the correlation analysis of the differentially expressed genes, the interaction networks of lncRNAs, miRNAs and mRNA were structured. Conclusion: LncRNA (Gm12840) could act as a sponge for miR-677-5p to mediate fibroblast activation induced by TGF-ß1 via the WISP1/PKB (Akt) signaling pathway.

Regulation of Ptch1 by miR-342-5p and FoxO3 Induced Autophagy Involved in Renal Fibrosis.

The pathogenesis of renal fibrosis (RF) is not well understood. Here, we performed an integrative database analysis of miRNAs and mRNAs to discover the major regulatory pathway in RF. Putative miRNAs and mRNAs involved in RF in unilateral ureteral obstruction (UUO) model mice were extracted and analyzed using the Gene Expression Omnibus (GEO) database. The bioinformatics analysis suggested that Ptch1 expression is regulated by miR-342-5p and FoxO3. Then real-time PCR, Western blot, Fluorescence in situ hybridization were done to confirm the hypothesis. Sixty-three differentially expressed miRNAs (DE-miRNAs) in GSE118340, 141 DE-miRNAs in GSE42716, and 183 DE-mRNAs in GSE69101 were identified. Various bioinformatic analyses revealed miR-342-5p as a strong candidate regulator in RF. We also predicted that miR-342-5p targets Ptch1 and that FoxO3 is the transcription factor of Ptch1. We also observed that TGF-ß1 upregulated the expression of miR-342-5p and inhibited the expression of FoxO3 and Ptch1 in TCMK-1 cells. Furthermore, downregulation of miR-342-5p reversed the inhibitory effect of TGF-ß1 on the expression of Ptch1 in TCMK-1 cells, while downregulation of FoxO3 promoted the inhibitory effect of TGF-ß1 on the expression of Ptch1. Additionally, downregulation of Ptch1 increased TGF-ß1-induced autophagy, as evidenced by an increase in the number of GFP-LC3 puncta and the increased protein expression of SOSTM1/p62 and LC3II/LC3I. Our findings showed that Ptch1 expression is negatively regulated by miR-342-5p and positively regulated by FoxO3, and downregulation of Ptch1 induced autophagy in TGF-ß1-stimulated TCMK-1 cells. These findings will further our understanding of the molecular mechanisms of RF and provide useful novel therapeutic targets for RF.

Emerging role of lncRNAs in renal fibrosis.

Fibrosis is the final common pathological feature of a wide variety of chronic kidney disease (CKD). However, an understanding of the mechanisms underlying the development of renal fibrosis remains challenging and controversial. As the current focus of molecular research, noncoding RNAs (ncRNAs), mainly microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular noncoding RNAs (circRNAs), have powerful and abundant biological functions, which essentially makes them mediators of the physiological and pathological processes of various system diseases. The role of ncRNAs in renal fibrosis has also received great attention in recent years, but most research has mainly focused on miRNAs. In fact, although a large number of studies of lncRNAs have emerged recently, the role these molecules play in renal fibrosis haven't been fully understood till now. Thus, this review discusses the discovery of lncRNAs and their biological functions in different types of renal fibrosis, as well as the imminent applications of these findings in clinical use. Undoubtedly, in the future, further understanding of the function of all types of lncRNAs will reveal large breakthroughs in the treatment of renal fibrosis.

Performance, kinetics characteristics and enhancement mechanisms in anammox process under Fe(II) enhanced conditions.

In order to explore the performance, kinetics characteristics and enhancement mechanisms in anammox process under ferrous iron enhanced conditions, a laboratory-scale UASB anammox reactor has been built up and operated for 534 days. Experimental results showed that the Anammox process was successfully started up in a short operation period and the TNRE reached 83.34 ± 2.96% with a maximum total nitrogen removal rate of 14.4 kg m-3 d-1 after long-term operated under influent Fe(II) concentration of 5.3 mg L-1. Simulation results using different kinetic models showed that the Stover-Kincannon model and the Grau second-order model were useful for describing the anammox performance under Fe(II) enhanced conditions. Extracellular polymeric substance (EPS) act a pivotal part in the granulation of Anammox sludge and the improvement of anammox activity. Iron improved the hydrophobicity of the sludge by reducing the PN/PS ratios, and also increased the Anammox granular diameter. The granular diameter of higher than 2.00 accounted for 58.3% of the total sludge. At the same time, the presence of iron decreased EPS levels, and also decreased the iron adsorption ability to sludge. More iron was transported into Anammox, which improved the nitrogen removal ability in the Anammox reactor.

Adiponectin in renal fibrosis.

Renal fibrosis is an inevitable consequence of parenchymal scarring and is the common final pathway that mediates almost all progressive renal diseases. Adiponectin, a hormone produced by adipose tissue, possesses potent anti-insulin, anti-inflammatory, and anti-fibrotic properties. Reportedly, adiponectin serves as an important messenger that facilitates complex interactions between adipose tissue and other metabolically related organs. In recent years, a growing body of evidence supports adiponectin involvement in renal fibrosis. These studies provide a deeper understanding of the molecular mechanism of action of adiponectin in renal fibrosis and also offer a potential preventive and therapeutic target for renal fibrosis. In this review, the physiological role of adiponectin is briefly introduced, and then the mechanism of adiponectin-mediated renal fibrosis and the related signaling pathways are described. Finally, we summarize the findings regarding the clinical value of adiponectin in renal fibrotic diseases and prospected its application potential.

Identification of key candidate genes in neuropathic pain by integrated bioinformatic analysis.

This study aimed to disclose differentially expressed genes (DEGs) in dorsal root ganglia (DRGs) of neuropathic pain (NP) from spared nerve injury (SNI) model, thereby identifying specific and meaningful genetic targets for the diagnosis and treatment of NP. The GSE89224 was downloaded from the GEO database. DEGs were screened using the GEO2R online tool. Functional enrichment analysis of DEGs was then performed using the DAVID and constructed using the R ggplot2 package. Protein-protein interaction (PPI) network was constructed from the STRING database and visualized in Cytoscape software. MicroRNA targeting these DEGs was obtained from the TarBase and miRTarBase database, while transcription factor (TF)-targeting DEGs were predicted from the ENCODE database, both of which utilized the visual analytics platform NetworkAnayst. Finally, a merged microRNA-TF network was constructed based on the above two networks and was then analyzed with Cytoscape. Eighty DEGs were screened, only Vstm2b and Htr3a were downregulated and 78 genes were upregulated. The real-time polymerase chain reaction was applied to validate the gene expression of the top five DEGs (Npy, Atf3, Gpr151, Sprr1a, and Cckbr) in the DRG tissue 5 days after SNI surgery. It was found that Npy, Atf3, and Sprr1a have a significant increase after SNI stimulation, while Gpr151 and Cckbr showed a slight upward trend. Functional analysis was performed on all DEGs, of which 58 biological processes were enriched by gene ontology analysis, and 11 signaling pathways were enriched by KEGG analysis. In the PPI network, Atf3, Jun, Timp, and Npy had a higher degree. Thus, combined with various bioinformatic analyses, Npy and Atf3 may serve as the prognostic and therapeutic targets of NP. Key microRNA (mmu-mir-16-5p) and TF (MEF2A) were predicted to be associated with the pathogenetic process of NP with microRNA-TF regulatory network analysis, which were also identified as key regulators in the progression of NP.

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

Aldehyde dehydrogenase-2 acts as a potential genetic target for renal fibrosis.

Obstructive renal injury and drug-induced nephrotoxicity are the two most common causes of renal fibrosis diseases. However, whether these two different pathogeny induced same pathological outcomes contain common genetic targets or signaling pathway, the current research has not paid great attention. GSE121190 and GSE35257 were downloaded from the Gene Expression Omnibus (GEO) database. While GSE121190 represents a differential expression profile in kidney of mice with unilateral ureteral obstruction (UUO) model, GSE35257 represents cisplatin nephrotoxicity model. By using GEO2R, 965 differential expression genes (DEGs) in GSE121190 and 930 DEGs in GSE35257 were identified. 43 co-DEGs were shared and were extracted for protein-protein interaction (PPI) analysis. Subsequently, three shared pathways including glycolysis/gluconeogenesis, fatty acid degradation and pathways in cancer were involved in two models with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We reconfirmed that these three pathways have relatively high scores by using Gene Set Enrichment Analysis (GSEA) software. Additionally, further bioinformatic analysis showed that Aldehyde dehydrogenase-2 (Aldh2) involved in the progression of renal fibrosis by mediating glycolysis pathway. Then real-time PCR and western blotting were performed to validate the expression of Aldh2 in kidney tissue after three different etiologies that caused renal fibrosis. Basically consistent with our bioinformatics results, our experiment showed that the expression of Aldh2 is the most significantly decreased in the UUO model, followed by ischemia-reperfusion injury (IRI) model and finally the cisplatin-induced model. Thus, Aldh2 can act as a common potential genetic target for different renal fibrosis diseases.

Are testicular cortisol and WISP2 involved in estrogen-regulated Sertoli cell proliferation?

The number of Sertoli cells has a major effect on adult testis size and sperm production capacity. Mechanisms that regulate the number of Sertoli cells in livestock are at best nebulously understood; however, with lesser testicular estrogen production, proliferation of Sertoli cells is prolonged compared with vehicle-treated littermates. Decreased WISP2 gene expression in testes as a result of less endogenous estrogen is similar to altered WISP2 gene expression following corticosteroid treatment of some cultured cells. Taken together, these findings indicate decreased testicular cortisol might be in the signaling pathway between reduced endogenous estrogens and the prolonged interval of Sertoli cell proliferation. Hence, in these studies, potential actions of testicular corticosteroid on Sertoli cell numbers were evaluated. Testicular cortisol concentrations were reduced at 6.5 weeks of age (P < 0.05) in littermates treated with the aromatase inhibitor, letrozole, compared with littermates treated with vehicle. Letrozole treatment leads to reduced testicular estradiol and greater Sertoli cell numbers during the early juvenile interval in pigs. The inverse relationship between testicular glucocorticoid and Sertoli cell proliferation was also tested by increasing local testicular glucocorticoids using the synthetic compound, dexamethasone. Local administration beginning at 1.5 weeks of age (osmotic pump and catheter (n = 3) or a silastic implant (n = 5)) reduced Sertoli cell numbers at 6.5 weeks of age compared with littermates that received the vehicle treatment (P< 0.05). In summary, testicular glucocorticoid concentration was inversely correlated with Sertoli cell numbers during the first wave of Sertoli cell proliferation.

Functional roles of lncRNAs and its potential mechanisms in neuropathic pain.

Neuropathic pain (NP) is ranked as one of the major forms of chronic pain and emerges as a direct consequence of a lesion or disease affecting the somatosensory nervous system. Despite great advances into the mechanisms of NP, clinical practice is still not satisfactory. Fortunately, progress in elucidating unique features and multiple molecular mechanisms of long non-coding RNAs (lncRNAs) in NP has emerged in the past 10 years, suggesting that novel therapeutic strategies for pain treatment may be proposed. In this review, we will concentrate on recent studies associated with lncRNAs in NP. First, we will describe the alterations of lncRNA expression after spinal cord injury (SCI) and peripheral nerve injury (PNI), and then we illustrate the role of some specific lncRNAs in detail, which may offer new insights into our understanding of the etiology and pathophysiology of NP. Finally, we put special emphasis on the altered expression of lncRNAs in the diverse biological process of NP. Recent advances we summarized above in the development of NP may facilitate translation of these findings from bench to bedside in the future.