CARMA3 Drives NF-κB Activation and Promotes Intervertebral Disc Degeneration: Involvement of CARMA3-BCL10-MALT1 Signalosome.

Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBαSer32/36 and p-p65Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.

The impact of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fractures.

PURPOSE: This study aims to investigate the impact of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fractures. MATERIALS AND METHODS: Patients diagnosed with definitive thoracolumbar spine fractures and underwent surgical treatment at our hospital between February 2022 and August 2023 were selected. Patients were divided into a treatment group (specialized nursing care at fracture sites coordinated with disease progression monitoring) and a control group (conventional care) based on different nursing methods. RESULTS: A comparative assessment was conducted to evaluate the role and significance of specialized nursing care at fracture sites coordinated with disease progression monitoring in thoracolumbar spine fracture rehabilitation. The results showed that compared to conventional care, specialized nursing care at fracture sites coordinated with disease progression monitoring could better promote the recovery of patients' neurological functions, alleviate pain, and effectively improve symptoms and functional recovery, thus enhancing patients' quality of life and satisfaction. CONCLUSION: The study confirms the effectiveness of specialized nursing care at fracture sites coordinated with disease progression monitoring in clinical practice post thoracolumbar spine fractures.

Clinical Features of Central Retinal Vein Occlusion in Young Patients.

Retinal vein occlusion (RVO) is the second most common retinal vascular disease. Central RVO (CRVO), in which obstruction occurs posterior to the lamina cribrosa due to various causes, manifests with extensive venous tortuosity, dilatation of blood vessels in the four quadrants, and retinal hemorrhage. The presence of macular edema decreases visual acuity in patients with CRVO, especially in elderly patients with hypertension, hyperlipidemia, and diabetes. In the last decade, treatment modalities for CRVO have improved, with anti-vascular endothelial growth factor agents being widely used as treatment. However, there are cases of refractory or recurrent macular edema. Moreover, CRVO also occurs in young patients. This article reviews previous studies and case reports and summarizes the differences in etiological factors, clinical manifestations, treatment, and prognosis between young and elderly patients. Due to the low incidence of CRVO in young patients, clinical data from these age groups are limited. Hence, further studies are warranted to explore the differences between age groups to improve individualization of treatment of young patients.

Human Bone Marrow Mesenchymal Stromal Cell-Derived Extracellular Vesicles Promote Proliferation of Degenerated Nucleus Pulposus Cells and the Synthesis of Extracellular Matrix Through the SOX4/Wnt/ß-Catenin Axis.

Objective: Intervertebral disk degeneration (IDD) is a major cause of pain in the back, neck, and radiculus. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are therapeutic in musculoskeletal degenerative diseases such as IDD. This study explored the effect and functional mechanism of human bone MSCs (hBMSCs)-derived EVs in proliferation and apoptosis of degenerated nucleus pulposus cells (DNPCs) and extracellular matrix (ECM) synthesis. Methods: Extracellular vesicles were isolated from hBMSCs and identified. DNPCs were induced by TNF-α. EVs were incubated with DNPCs for 24h. Internalization of EVs by DNPCs, DNPCs proliferation, apoptosis, and expressions of ECM synthetic genes, degrading genes and miR-129-5p were assessed. Downstream target genes of miR-129-5p were predicted. Target relation between miR-129-5p and SRY-box transcription factor 4 (SOX4) was verified. DNPCs proliferation, apoptosis, and ECM synthesis were measured after treatment with EVs and miR-129-5p inhibitor or SOX4 overexpression. Expressions of SOX4 and Wnt/ß-catenin pathway-related proteins were determined. Results: hBMSC-EVs promoted DNPCs proliferation, inhibited apoptosis, increased expressions of ECM synthetic genes, and reduced expressions of ECM degrading genes. hBMSC-EVs carried miR-129-5p into DNPCs. Silencing miR-129-5p in EVs partially inverted the effect of EVs on DNPCs proliferation and ECM synthesis. miR-129-5p targeted SOX4. SOX4 overexpression annulled the effect of EVs on DNPCs proliferation and ECM synthesis. Expressions of Wnt1 and ß-catenin were decreased in EVs-treated DNPCs, while silencing miR-129-5p in EVs promoted expressions of Wnt1 and ß-catenin. Conclusion: hBMSC-EVs promoted DNPCs proliferation and ECM synthesis by carrying miR-129-5p into DNPCs to target SOX4 and deactivating the Wnt/ß-catenin axis.

Resveratrol alleviates lipopolysaccharide-induced inflammation in PC-12 cells and in rat model.

BACKGROUND: Spinal cord injury (SCI) remains a huge medical problem nowadays as there is no hospital providing the versatile strategies for repairing central nervous system and restoring function. Herein, we focused on PC-12 cells as an important research tool and studied the potential role of resveratrol (RSV) in inflammation induced by LPS. RESULTS: RSV improved inflammatory injury and functional recovery in rat model of SCI. RSV inhibited LPS-induced inflammatory injury in PC-12 cells via increasing viability, decreasing apoptosis, and suppressing IL-1ß, IL-6, and TNF-α expression. miR-132 was down-regulated after LPS treatment but up-regulated after RSV administration. miR-132 silence curbed the protective effect of RSV. The results including increase of cell growth, suppression of inflammatory response, and blocking of NF-κB and p38MAPK pathways produced by RSV were all reversed by miR-132 silence. CONCLUSION: RSV could up-regulate miR-132 and further ameliorate inflammatory response in PC-12 cells by inhibiting NF-κB and p38MAPK pathways.

A synergic effect of sodium on the phase transition of tungsten-doped vanadium dioxide.

A synergic effect of sodium on the metal-insulator transition temperature reduction of tungsten-doped vanadium dioxide is noted. With the assistance of sodium, doping with tungsten yields an extra depression in phase temperature of 6-12 °C over that of 20-26 °C per at% of tungsten.