Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway.

Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed significantly increased proliferation and differentiation. We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products, i.e., IL-1 family members such as IL-1ß and IL-18 were upregulated in the PVAT of obese mini pigs; PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid. Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.

Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma.

BACKGROUND The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers. MATERIAL AND METHODS An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG. RESULTS A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein-protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway. CONCLUSIONS Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.

[Pharmacokinetics studies on tetramethylpyrazine by intravenous administration in rats].

OBJECTIVE: To investigate the pharmacokinetics behaviour of tetramethylpyrazine (TMP) by intravenous administration in rats. METHODS: Methanol-0.05 mol/L acetate buffer solution (50:50,V/V) was used as mobile phase with a flow rate of 1.0 mL/min. The UV detection wavelength was 280 nm. RESULTS: The profile of TMP in blood fitted a two-compartment model. The half time of drug distribution and elimination was short. The mean residence time MRT 0-infinity was 141.61 min, and the AUC0-infinity was 7521.70 microg x min/ mL. CONCLUSION: After intravenous injection, the pharmacokinetics behaviour of TMP fit a two-compartment model in rats. Both the distribution and the elimination are fast.

Cigarette smoking and risk of hip fracture in women: a meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVES: Whether cigarette smoking can increase the risk of hip fracture in women is unclear. This meta-analysis, which pooled results from 10 prospective cohort studies, was performed to derive a more precise estimation between cigarette smoking and the risk of hip fracture in women. MATERIALS AND METHODS: Pubmed, Cochrane Central Register of Controlled Trials and ISI Web of Science were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association among 10 studies. The pooled risk estimates were calculated by using both random- and fixed-effects model. Heterogeneity among articles and their publications bias were also tested. All of the statistical analyses were performed using the software programs STATA (version 12.0). RESULTS: Relative risk was significantly increased in current female smokers (pooled RR, 1.30; 95%CI, 1.16-1.45). The association was significant among the high-dose smokers (more than 15 cigarettes per day) while not among the low-does smokers (less than 15 cigarettes per day). Omission of any single study had little effect on the pooled risk estimate. Former smokers had a similar RR of hip fracture (RR, 1.02; 95%CI, 0.93-1.11) to published papers. Smoking cessation for ≥10 years leads to a significant decline in risk. CONCLUSIONS: Smoking is associated with an increased hip fracture risk in women. Cessation of smoking for ≥10 years had a decreased impact on risk of hip fracture. Given the inconsistency among the studies in the choice of adjustments, the associations between cigarette smoking and risk of hip fracture in women await further investigation.

Assessment of tibial rotation and meniscal movement using kinematic magnetic resonance imaging.

OBJECTIVE: This work aimed to assess tibial rotations, meniscal movements, and morphological changes during knee flexion and extension using kinematic magnetic resonance imaging (MRI). METHODS: Thirty volunteers with healthy knees were examined using kinematic MRI. The knees were imaged in the transverse plane with flexion and extension angles from 0° to 40° and 40° to 0°, respectively. The tibial interior and exterior rotation angles were measured, and the meniscal movement range, height change, and side movements were detected. RESULTS: The tibia rotated internally (11.55° ± 3.20°) during knee flexion and rotated externally (11.40° ± 3.0°) during knee extension. No significant differences were observed between the internal and external tibial rotation angles (P > 0.05), between males and females (P > 0.05), or between the left and right knee joints (P > 0.05). The tibial rotation angle with a flexion angle of 0° to 24° differed significantly from that with a flexion angle of 24° to 40° (P < 0.01). With knee flexion, the medial and lateral menisci moved backward and the height of the meniscus increased. The movement range was greater in the anterior horn than in the posterior horn and greater in the lateral meniscus than in the medial meniscus (P < 0.01). During backward movements of the menisci, the distance between the anterior and posterior horns decreased, with the decrease more apparent in the lateral meniscus (P < 0.01). The side movements of the medial and lateral menisci were not obvious, and a smaller movement range was found than that of the forward and backward movements. CONCLUSION: Knee flexion and extension facilitated internal and external tibial rotations, which may be related to the ligament and joint capsule structure and femoral condyle geometry.