RESUMO
Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which is one of the major factors leading to disability and severe economic burden. Necroptosis is an important form of programmed cell death (PCD), a highly regulated caspase-independent type of cell death that is regulated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL)-mediated, play a key role in the pathophysiology of various inflammatory, infectious and degenerative diseases. Recent studies have shown that necroptosis plays an important role in the occurrence and development of IDD. In this review, we provide an overview of the initiation and execution of necroptosis and explore in depth its potential mechanisms of action in IDD. The analysis focuses on the connection between NP cell necroptosis and mitochondrial dysfunction-oxidative stress pathway, inflammation, endoplasmic reticulum stress, apoptosis, and autophagy. Finally, we evaluated the possibility of treating IDD by inhibiting necroptosis, and believed that targeting necroptosis may be a new strategy to alleviate the symptoms of IDD.
Assuntos
Degeneração do Disco Intervertebral , Necroptose , Humanos , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/patologia , Animais , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Apoptose , Autofagia , Estresse Oxidativo , Proteínas Quinases/metabolismoRESUMO
Intervertebral disc degeneration (IDD), the key pathological process in low back pain, is characterized by chronic inflammation and progressive cell death. Pyroptosis is a type of pro-inflammatory programmed necrosis mediated by inflammasomes that is dependent on the gasdermin family of proteins. An in-depth study of the pathological mechanisms of IDD has revealed that pyroptosis plays an important role in its occurrence and development. The molecular characteristics and activation signaling mechanisms of pyroptosis are reviewed in this paper. Moreover, the specific roles of pyroptosis in IDD pathology are outlined and various targeted drugs for its treatment are highlighted.
Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Piroptose , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Apoptose , Transdução de SinaisRESUMO
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.
RESUMO
Increasing evidence has shown that long non-coding RNAs (lncRNAs), which are non-coding endogenous single-stranded RNAs, play an essential role in various physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Moreover, lncRNAs, as oncogenes or tumor suppressor genes, play an important role in the occurrence and development of human cancers. Prostate androgen-regulated transcript 1 (PART1) was initially identified as a carcinogenic lncRNA in prostate adenomas. The upregulated expression of PART1 plays a tumor-promoting role in liver, prostate, lung cancers, and other tumors. In contrast, the expression of PART1 is downregulated in esophageal squamous cell carcinoma, glioma, and other tumors, which may inhibit the tumor. PART1 plays a dual role in cancer and regulates cell proliferation, apoptosis, invasion, and metastasis through a variety of potential mechanisms. These findings suggest that PART1 is a promising tumor biomarker and therapeutic target. This article reviews the biological functions, related mechanisms, and potential clinical significance of PART1 in a variety of human cancers.