Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

PSD95 as a New Potential Therapeutic Target of Osteoarthritis: A Study of the Identification of Hub Genes through Self-Contrast Model.

Osteoarthritis (OA) is a worldwide joint disease. However, the precise mechanism causing OA remains unclear. Our primary aim was to identify vital biomarkers associated with the mechano-inflammatory aspect of OA, providing potential diagnostic and therapeutic targets for OA. Thirty OA patients who underwent total knee arthroplasty were recruited, and cartilage samples were obtained from both the lateral tibial plateau (LTP) and medial tibial plateau (MTP). GO and KEGG enrichment analyses were performed, and the protein-protein interaction (PPI) assessment was conducted for hub genes. The effect of PSD95 inhibition on cartilage degeneration was also conducted and analyzed. A total of 1247 upregulated and 244 downregulated DEGs were identified. Significant differences were observed between MTP and LTP in mechanical stress-related genes and activated sensory neurons based on a self-contrast model of human knee OA. Cluster analysis identified DLG4 as the hub gene. Cyclic loading stress increased PSD95 (encoded by DLG4) expression in LTP cartilage, and PSD95 inhibitors could alleviate OA progression. This study suggests that inhibiting PSD95 could be a potential therapeutic strategy for preventing articular cartilage degradation.

[Dose-response relationship between smoking status and carotid atherosclerosis].

OBJECTIVE: To examine the dose-response relationship of smoking status with carotid atherosclerosis in 959 relatively healthy Chinese men. METHODS: 959 older Chinese men were selected from Guangzhou Biobank Cohort Study (GBCS) on cardiovascular disease. Personal histories were collected and fasting plasma glucose and lipids, blood pressure, and common carotid artery intima-median thickness (CCA-IMT) were measured. RESULTS: (1) Composition of the cases: 39.1% were non-smokers, 25.7% were former smokers and 35.2% were current smokers. The mean (95% confidence interval) carotid IMT was 0.78 (0.77 - 0.79) mm. 18.4% of the subjects had carotid IMT equal to or thicker than 1.0 mm while 34.1% had carotid plaque. (2) After adjusting for age, sex, physical activity, body mass index, fasting glucose, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, compared to never smokers, current smokers had significantly increased risk for thicker IMT and carotid plaque [odds ratio (OR) = 1.82, 95%CI: 1.30 - 2.55 and OR = 1.95, 95%CI: 1.38 - 2.75, respectively, all P < 0.001]. The risk for thicker IMT and carotid plaque increased with the increasing amount (cigarettes/day) and duration of smoking (years) as well with cigarette pack-years (P for trend all ≤ 0.01). CONCLUSION: An elevated risk with a clear dose-response relationship was found between cigarette smoking and carotid atherosclerosis. Quitting smoking or reducing the amount of smoking may lower the risk of atherosclerosis, preventing and controlling the occurrence of cardiovascular diseases, and reducing the related cardiovascular mortalities.

[Electrocardiogram change of workers after disengaging occupational noise exposure].

OBJECTIVE: To examine electrocardiogram (ECG) change of workers after leaving occupational noise exposure. METHODS: In the first phase of the Guangzhou Biobank Cohort Study, 10413 Guangzhou residents aged 50 years or more received a face-to face interview including noise exposure history, a full medical check-up and laboratory tests in 2003 - 4. ECG examination was carried out using 12-lead MAC-CS ECG machine made in HP Ltd, Shanghai, China. ECG of every subject was independently diagnosed by two doctors who had obtained ECG diagnosis qualification. RESULTS: (1) Among 10413 subjects, 70% were female, and more than half were aged 60-69 years. The mean age and education level in males were higher than those in females. (2) 2119 subjects (21.0%) were previously exposed to noise and were retired now. (3) The prevalence of ECG abnormality was respectively 82.4% and 79.1% in females and males. Rate of ECG abnormality increased with age in both females and males (P = 0.000), and was lower in females with higher education level (P = 0.000). There was not significant difference in ECG abnormality between workers previously exposed or unexposed to noise in both females and males (P > 0.05). 4 Comparing workers previously exposed to those unexposed to noise in both females and males, after adjusting for age, educational level and smoking status, the rates of arrhythmia, axes deviation, atria and ventricle hypertrophy, ST-T change and coronary artery syndrome were not significantly different (P > 0.05). CONCLUSION: Our study showed that the prevalence of ECG abnormality was not significantly increased in workers previously exposed to noise and had left exposure now compared to those never exposed to noise. Because our study was cross section and occupational history was obtained from a questionnaire but was not confirmed by the companies, further study is needed.