MAPK8 and CAPN1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and ceRNA.

Background: Intervertebral disc degeneration (IDD) is one of the most common health problems in the elderly and a major causative factor in low back pain (LBP). An increasing number of studies have shown that IDD is closely associated with autophagy and immune dysregulation. Therefore, the aim of this study was to identify autophagy-related biomarkers and gene regulatory networks in IDD and potential therapeutic targets. Methods: We obtained the gene expression profiles of IDD by downloading the datasets GSE176205 and GSE167931 from the Gene Expression Omnibus (GEO) public database. Subsequently, differentially expressed genes (DEGs) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology (GO), and gene set enrichment analysis (GSEA) were performed to explore the biological functions of DEGs. Differentially expressed autophagy-related genes (DE-ARGs) were then crossed with the autophagy gene database. The hub genes were screened using the DE-ARGs protein-protein interaction (PPI) network. The correlation between the hub genes and immune infiltration and the construction of the gene regulatory network of the hub genes were confirmed. Finally, quantitative PCR (qPCR) was used to validate the correlation of hub genes in a rat IDD model. Results: We obtained 636 DEGs enriched in the autophagy pathway. Our analysis revealed 30 DE-ARGs, of which six hub genes (MAPK8, CTSB, PRKCD, SNCA, CAPN1, and EGFR) were identified using the MCODE plugin. Immune cell infiltration analysis revealed that there was an increased proportion of CD8+ T cells and M0 macrophages in IDD, whereas CD4+ memory T cells, neutrophils, resting dendritic cells, follicular helper T cells, and monocytes were much less abundant. Subsequently, the competitive endogenous RNA (ceRNA) network was constructed using 15 long non-coding RNAs (lncRNAs) and 21 microRNAs (miRNAs). In quantitative PCR (qPCR) validation, two hub genes, MAPK8 and CAPN1, were shown to be consistent with the bioinformatic analysis results. Conclusion: Our study identified MAPK8 and CAPN1 as key biomarkers of IDD. These key hub genes may be potential therapeutic targets for IDD.

Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Effects of different "rigid-flexible" structures of carbon fibers surface on the interfacial microstructure and mechanical properties of carbon fiber/epoxy resin composites.

In order to comprehend the influence of different "rigid-flexible" structures on the interface strength of carbon fiber(CF)/epoxy composites, CNTs was firstly chemically grafted on CFs surface, and then polyamide (PA) was grafted onto CF-CNTs surface through varying anionic polymerization time of caprolactam [CF-CNTs-PAn (n = 6 h, 12 h, 24 h)]. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy indicated the successful establishment of CNTs and PA. TGA demonstrated the different grafting amounts of CF-CNTs-PAn (n = 6 h, 12 h and 24 h). SEM images revealed a compactness and uniform coverage of the CNTs/PA, with increasing polymerization time, the CF and CNTs surface was covered by a thick layer of PA. The surface energy increased and then decreased. The optimal interfacial shear strength (IFSS) and interlaminar shear strength (ILSS) of the CF/epoxy composites with a polymerization time of 12 h (CF-CNTs-PA12h) was 86.7 and 85.4 MPa, which was 77.6% and 45.7% higher than that of untreated CF/epoxy composite. As the polymerization time grew, the impact toughness and tensile strength of CF/epoxy composites enhanced and conductivity of CF/epoxy composite reduced. In addition, the mechanisms of reinforcement and toughening were also illuminated. This work would provide a certain theoretical basis for the preparation and applications of high-performance CF composites with different structures.

Hydroxyl-Terminated Triazine Derivatives Grafted Graphene Oxide for Epoxy Composites: Enhancement of Interfacial and Mechanical Properties.

An effective approach to the fabrication of progressive epoxy nanocomposites by the incorporation of hydroxyl-terminated dendrimers functionalized graphene oxide (GO-TCT-Tris) is reported. The relationship between surface grafting, chemical construction, morphology, dispersion, and interfacial interaction as well as the corresponding mechanical properties of the composites were studied in detail. It was shown that hydroxyl-terminated triazine derivatives have been resoundingly bonded onto the GO surface through covalent bonding, which effectively improved the dispersion and compatibility of GO sheets in epoxy resin. The tensile and flexural tests manifested that the GO-TCT-Tris/epoxy composites exhibited greater tensile/flexural strength and modulus than either the pure epoxy or the GO/epoxy composites. For GO-TCT-Tris (0.10 wt%)/epoxy composite, the tensile strength and elastic modulus increased from 63 ± 4 to 89 ± 6 MPa (41.27%) and from 2.8 ± 0.1 to 3.6 ± 0.2 GPa (28.57%), and the flexural strength and modulus increased from 106 ± 5 to 158 ± 6 MPa (49.06%) and from 3.0 ± 0.1 to 3.5 ± 0.2 GPa (16.67%), respectively, compared to the pure epoxy matrix. Moreover, the fractographic analysis also illustrated the ameliorative interfacial interaction between GO-TCT-Tris and epoxy matrix.

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention.

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

8-Meth-oxy-3-methyl-3,4-di-hydro-2H-1,3-benzoxazine.

The title compound, C10H13NO2, crystallizes with two crystallographically independent mol-ecules of similar geometry in the asymmetric unit; the six-membered oxazine rings adopts a half-chair conformation. Neither hydrogen bonds nor π-π inter-actions are observed in the crystal structure.