Bibliometric and visual analysis of microglia-related neuropathic pain from 2000 to 2021.

Background: Microglia has gradually gained researchers' attention in the past few decades and has shown its promising prospect in treating neuropathic pain. Our study was performed to comprehensively evaluate microglia-related neuropathic pain via a bibliometric approach. Methods: We retrospectively reviewed publications focusing on microglia-related neuropathic pain from 2000 to 2021 in WoSCC. VOS viewer software and CiteSpace software were used for statistical analyses. Results: A total of 2,609 articles were finally included. A steady increase in the number of relevant publications was observed in the past two decades. China is the most productive country, while the United States shares the most-cited and highest H-index country. The University of London, Kyushu University, and the University of California are the top 3 institutions with the highest number of publications. Molecular pain and Pain are the most productive and co-cited journals, respectively. Inoue K (Kyushu University) is the most-contributed researcher and Ji RR (Duke University) ranks 1st in both average citations per article and H-index. Keywords analyses revealed that pro-inflammatory cytokines shared the highest burst strength. Sex differences, neuroinflammation, and oxidative stress are the emerging keywords in recent years. Conclusion: In the field of microglia-related neuropathic pain, China is the largest producer and the United States is the most influential country. The signaling communication between microglia and neurons has continued to be vital in this field. Sexual dimorphism, neuroinflammation, and stem-cell therapies might be emerging trends that should be closely monitored.

SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/ß-catenin pathway and ameliorates disc degeneration.

This study aimed to determine the effects of SKI on interleukin (IL)-1ß-induced apoptosis of nucleus pulposus (NP) cells, intervertebral disc degeneration (IDD), and the Wnt signaling pathway. NP tissue specimens of different Pfirrmann grades (II-V) were collected from patients with different grades of IDD. Real-time polymerase chain reaction and western blotting were used to compare SKI mRNA and protein expression in NP tissues from patients. Using the IL-1ß-induced IDD model, NP cells were infected with lentivirus-coated si-SKI to downregulate the expression of SKI and treated with LiCl to evaluate the involvement of the Wnt/ß-catenin signaling pathway. Western blotting, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect NP cell apoptosis, extracellular matrix (ECM) metabolism, and related protein expression changes in the Wnt/ß-catenin signaling pathway. To investigate the role of SKI in vivo, a rat IDD model was established by needle puncture of the intervertebral disc. Rats were injected with lentivirus-coated si-SKI and evaluated by magnetic resonance imaging (MRI), and hematoxylin and eosin (HE) and safranin O staining. SKI expression positively correlated with the severity of human IDD. In the IL-1ß-induced NP cell degeneration model, SKI expression increased significantly and reached a peak at 24 h. SKI knockdown protected against IL-1ß-induced NP cell apoptosis and ECM degradation. LiCl treatment reversed the protective effects of si-SKI on NP cells. Furthermore, lentivirus-coated si-SKI injection partially reversed the NP tissue damage in the IDD model in vivo. SKI knockdown reduced NP cell apoptosis and ECM degradation by inhibiting the Wnt/ß-catenin signaling pathway, ultimately protecting against IDD. Therefore, SKI may be an effective target for IDD treatment.

Transcription Factor SP2 Regulates Ski-mediated Astrocyte Proliferation In Vitro.

Transcription factors bind specific sequences upstream of the 5' end of their target genes to ensure proper spatiotemporal expression of the target gene. This study aims to demonstrate that the transcription factor SP2 regulates expression of the Ski gene, which has specific binding sites for SP2, and thus enables Ski to regulate astrocyte proliferation. The upstream regulation mechanism of astrocyte proliferation was explored to further regulate the formation of glial scar in specific time and space after spinal cord injury. JASPAR and UCSC databases were used to predict transcription factor binding and the threshold was gradually reduced to screen transcription factors upstream of Ski, leading to the identification of SP2. Next, we analyzed the correlation between the expression of SP2 and Ski in normal astrocytes and reactive astrocytes, as well as the changes in astrocyte proliferation. To confirm that SP2 regulates Ski during astrocyte proliferation, astrocytes were transfected siRNA targeting SP2 and then astrocyte proliferation were analyzed. Finally, a dual luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay confirmed that the promoter region of Ski contained a specific SP2 binding site. This is the first that SP2 has been identified and confirmed to play an important role in astrocyte proliferation by regulating Ski expression. These results may help identify novel targets for the treatment of spinal cord injury.

Role of HAND2-AS1 in human tumors.

Long noncoding RNAs (lncRNAs) are molecules more than 200 nucleotides in length. They play roles in various cells, mainly regulating cell growth, differentiation, and apoptosis. They also participate in the pathogenesis of many diseases. In fact, several studies have shown that lncRNAs function as cancer or tumor suppressor genes and play important roles in the occurrence and development of cancer in humans. New evidence has shown that lncRNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) hinders the occurrence and development of various tumors. Overexpression of HAND2-AS1 was found to be significantly related to the clinical and pathological characteristics of cancer patients, as well as the regulation of cell proliferation, apoptosis, invasion, metastasis, and energy metabolism through several possible mechanisms. Therefore, HAND2-AS1 may be a promising tumor biomarker and therapeutic target. Here, we review the biological functions, mechanisms, and potential clinical significance of HAND2-AS1 in numerous human tumors.

Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model.

The activation of opioid and neuropeptide FF (NPFF) receptors plays important roles to modulate nociceptive signal in inflammatory pain states. Recently, BN-9 (Tyr-D. Ala-Gly-Phe-Gln-Pro-Gln-Arg-Phe-NH2) was pharmacologically characterized as a novel bifunctional agonist at both opioid and NPFF receptors. In the present study, the anti-allodynic activity and site(s) of action of BN-9 were assessed in a mouse model of carrageenan-induced inflammatory pain. In mice, BN-9 induced a dose-dependent anti-allodinic effect through opioid receptor at supraspinal or spinal level, and this effect was augmented by pretreatment with the NPFF receptor antagonist at the same level. In contrast, peripheral administration of BN-9 produced opioid receptor-mediated anti-allodynia, which was insensitive of the NPFF receptor antagonist. In addition, systemic BN-9 produced anti-allodynic effect via opioid receptors, independent of NPFF system. Therefore, these data indicate that central, peripheral or systemic administrations of BN-9 exert potent analgesic activities in inflammatory pain model via opioid receptor, and central effects of BN-9 are associated with NPFF system. Interestingly, systemic anti-allodynia of BN-9 was blocked by intraperitoneal administration of the opioid receptor antagonists, naloxone and naloxone methiodide, but not by intracerebroventricular injection of the peripherally acting opioid antagonist naloxone methiodide. Furthermore, BN-9-induced systemic anti-allodynia was reversed by intraplantar administration of naloxone, but not by peripheral administration of the NPFF receptor antagonist. Taken together, our data further suggest that systemic BN-9-induced anti-allodynic effect is mainly mediated by peripheral opioid receptors, independent of NPFF receptors.