Integrating bioinformatics and experimental validation to Investigate IRF1 as a novel biomarker for nucleus pulposus cells necroptosis in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a prevalent spinal disorder and the principal cause of lower back pain (LBP). Diverse forms of programmed cell death (PCD) have been identified as the key phenotypes of the disease and have the potential to serve as new indicators for the diagnosis and prognosis of IDD. However, the mechanism underlying necroptosis in IDD remains unclear.

Role of mitophagy in intervertebral disc degeneration: A narrative review.

Objective: The pivotal role of mitophagy in the initiation and progression of intervertebral disc (IVD) degeneration (IDD) has become increasingly apparent due to a growing body of research on its pathogenesis. This review summarizes the role of mitophagy in IDD and the therapeutic potential of targeting this process.

Design: This narrative review is divided into three parts: the regulatory mechanisms of mitophagy, the role of mitophagy in IDD, and the applications and prospects of mitophagy for the treatment of IDD.

Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration.

Low back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve a definitive cure. The cartilage endplate (CEP), a crucial nutrient-supplying tissue of the intervertebral disc, plays a pivotal role in disc degeneration.

Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration.

Mitophagy plays a crucial role in maintaining the homeostasis of intervertebral disc (IVD). Early Growth Response 1 (EGR1), a conservative transcription factor, is commonly upregulated under oxidative stress conditions and participates in regulating cellular senescence, apoptosis, and inflammatory responses. However, the specific role of EGR1 in nucleus pulposus (NP) cell senescence and mitophagy remains unclear.

TGF-β1 Inhibits Osteoclast Differentiation and Abnormal Angiogenesis in Intervertebral Disc Degeneration: Evidence from RNA Sequencing and Animal Studies.

Objective: Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing-identified transforming growth factor (TGF-β), underlying the effects on bone homeostasis in IDD.

Methods: A mouse model for IDD was established.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases.

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

This study aimed to determine the effects of SKI on interleukin (IL)-1β-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.

Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism.

Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers.

An Immune-Related Long Non-Coding RNA Signature to Predict the Prognosis of Ewing's Sarcoma Based on a Machine Learning Iterative Lasso Regression.

The aim of this study was to construct a new immune-associated long non-coding RNA (lncRNA) signature to predict the prognosis of Ewing sarcoma (ES) and explore its molecular mechanisms. We downloaded transcriptome and clinical prognosis data from the Gene Expression Omnibus (GSE17679, which included 88 ES samples and 18 matched normal skeletal muscle samples), and used it as a training set to identify immune-related lncRNAs with different expression levels in ES. Univariable Cox regression was used to screen immune-related lncRNAs related to ES prognosis, and an immune-related lncRNA signature was constructed based on machine learning iterative lasso regression.

Development of a Machine Learning-Based Autophagy-Related lncRNA Signature to Improve Prognosis Prediction in Osteosarcoma Patients.

Background: Osteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients.

NF-κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series of factors, such as inflammation, oxidative stress and mechanical stress, promote degradation of the extracellular matrix (ECM) of the intervertebral discs (IVD), leading to dysfunction and structural destruction of the IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded as a pathogenic factor of IDD.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

Background: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS.

Role of the Wnt pathway in the formation, development, and degeneration of intervertebral discs.

Intervertebral disc degeneration (IVDD) is an age-related degenerative disease that is the main cause of low back pain. It seriously affects the quality of life of patients and places a heavy economic burden on families and society. The Wnt pathway plays an important role in the growth, development, and degeneration of intervertebral discs (IVDs).

Ski: Double roles in cancers.

The Ski (Sloan-Kettering Institute) is an evolutionarily conserved protein that plays a dual role as an oncoprotein and tumor suppressor gene in the development of human cancer. The Ski oncogene was first identified as a transforming protein of the avian Sloan-Kettering retrovirus in 1986. Since its discovery, Ski has been identified as a carcinogenic regulator in a variety of malignant tumors.

Development of a novel immune-related genes prognostic signature for osteosarcoma.

Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases.

A four-methylated LncRNA signature predicts survival of osteosarcoma patients based on machine learning.

Risk stratification using prognostic markers facilitates clinical decision-making in treatment of osteosarcoma (OS). In this study, we performed a comprehensive analysis of DNA methylation and transcriptome data from OS patients to establish an optimal methylated lncRNA signature for determining OS patient prognosis. The original OS datasets were downloaded from the the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database.

An immune-related gene signature for determining Ewing sarcoma prognosis based on machine learning.

Purpose: Ewing sarcoma (ES) is one of the most common malignant bone tumors in children and adolescents. The immune microenvironment plays an important role in the development of ES. Here, we developed an optimal signature for determining ES patient prognosis based on immune-related genes (IRGs).

The role of long non-coding RNA MIAT in cancers.

Long non-coding RNAs (lncRNAs), a kind of non-coding single-strand RNAs, play an important role as carcinogenic genes or tumor suppressors in the development of human cancer. Myocardial infarction-associated transcript (MIAT) was first identified as a lncRNA in 2006 and originally isolated as a candidate gene for myocardial infarction. Later, it was reported that MIAT exhibits regulatory effects on the human cell cycle.

Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis.

Neuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and differentially expressed genes were screened using the R software.

Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma.

Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES.