Different iron deposition patterns in Parkinson's disease subtypes: a quantitative susceptibility mapping study.

BACKGROUND: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with various subtypes and uncertain pathogenesis. Iron deposition is considered to be involved in the pathological mechanisms of PD. The present study aimed to investigate the iron deposition in deep gray matter in patients with different PD subtypes using quantitative susceptibility mapping (QSM). METHODS: Forty-six PD patients and 22 healthy controls (HCs) were recruited for the study. PD patients were allocated to the tremor-dominant (TD) group (n=22), postural instability and gait disorder-dominant (PIGD) group (n=19), and intermediate group (n=5). Susceptibility values in deep gray matter nuclei measured by QSM among the PD-TD and PD-PIGD groups and the HCs, as well as the relationship between iron accumulation and clinical motor features, were investigated. RESULTS: Susceptibility values in the dentate nucleus (DN) were greater in the PD-TD (118.73±70.45) group than in the PD-PIGD (72.14±39.85, P=0.02) group and HCs (78.26±41.38, P=0.042). Further, a significant positive correlation was observed between the DN susceptibility values and tremor scores (r=0.324, P=0.028). Compared with the HCs (182.60±85.35), both the PD-TD (282.00±102.49, P=0.006) and PD-PIGD groups (284.91±118.54, P=0.007) exhibited greater susceptibility values in the substantia nigra (SN) pars reticulata. The susceptibility values in the SN pars compacta were also greater in the PD-PIGD group (164.51±89.44) than in the HCs (107.78±63.11, P=0.048). CONCLUSIONS: The present study demonstrated various iron deposition patterns in different PD phenotypes. These findings give insight into the pathophysiology underlying different PD phenotypes, and potentially illustrate the involvement of iron deposition in the PD-TD and PD-PIGD subtypes.

Prognostic Value of Albumin/Globulin Ratio in Survival and Lymph Node Metastasis in Patients with Cancer: A Systematic Review and Meta-analysis.

The impact of albumin to globulin ratio (AGR) on the prognosis of various human cancers has not been well established. Here, a systemic review and meta-analysis has been performed to comprehensively assess the relationships between AGR and lymph node metastasis (LNM) or overall survival (OS). Systematical search through six electronic databases has been carried out to identify reports involving the role of AGR on OS and LNM in human cancers. Hazard ratio (HR), odd ratio (OR) and their 95% confidence intervals (95% CI) were evaluated through meta-analysis according to standard steps. Of 403 studies retrieved, 14 eligible studies with 4136 patients were included in this study. The analysis based on random-effect model demonstrated that low AGR was significantly associated with poor OS in various cancers (HR=1.87, 95% CI 1.50-2.34; P < 0.001). Subsequent results showed a significant increase in the risk of LNM in the low AGR group when compared with high AGR group (HR=2.24; 95% CI=1.49-3.36; P<0.001). To conclusion, this study suggested that AGR was associated with OS and LNM in cancer patients and AGR may be a potential marker to assess prognosis of cancer patients. However, a large scale of samples and prospective studies are needed in the future to validate the role of AGR in practice.

Using microRNAs as Novel Predictors of Urologic Cancer Survival: An Integrated Analysis.

BACKGROUND: MicroRNAs(miRNAs) are involved in the formation, maintenance, and metastasis of urologic cancer. Here, we aim to gather and evaluate all of the evidence regarding the potential role of miRNAs as novel predictors of urologic cancer survival. METHODS: A systematic review was performed to identify and score all of the published studies that evaluated the prognostic effects of miRNAs in kidney (KCa), bladder (BCa) or prostate cancer (PCa). Where appropriate, the summary effects of miRNAs on urologic cancer were meta-analysed. The reliability of those results was then further validated by an integrated analysis of the TCGA cohort and miRNA panel. RESULTS: Of 151 datasets, 80 miRNAs were enrolled in this systematic review. A meta-analysis of the prognostic qualities of each miRNA identified an objective association between miRNA and prognosis. miR-21 was identified as an unfavourable miRNA with the overall survival (HR:2.699, 1.76-4.14, P < 0.001) across various prognostic events. Our further meta-analyses, integrating a parallel TCGA analysis, confirmed these partial previous results and further revealed different summary effects, such as the moderate effect of miR-21 in BCa. The refined miRNA panel (KCa-6: miR-27b, -942, -497, -144, -141 and -27a) was more capable of predicting the overall survival than was any single miRNAs included in it (HR: 3.214, 1.971-5.240, P < 0.01). CONCLUSIONS: A miRNA panel may be able to determine the prognosis of urologic tumour more effectively and compensate for the unreliability of individual miRNA in estimating prognosis. More large-scale studies are therefore required to evaluate the unbiased prognostic value of miRNAs in urologic cancer effectively.

Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells.

CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvß3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2@PAA-LXW7, a new compound that couples CeO2@PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2O2-induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO2@PAA, and CeO2@PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H2O2-induced injury. We used H2O2-induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO2@PAA-LXW7. In this study, LXW7, CeO2@PAA, and CeO2@PAA-LXW7 inhibit H2O2-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H2O2-induced NGF-differentiated PC12 cells, whereas LXW7, CeO2@PAA, and CeO2@PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO2@PAA-LXW7 on H2O2-induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO2@PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H2O2-induced NGF-differentiated PC12 cells. LXW7, CeO2@PAA, and CeO2@PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H2O2 in NGF-differentiated PC12 cells. CeO2@PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO2@PAA.

Long non-coding RNA ANRIL in gene regulation and its duality in atherosclerosis.

The antisense transcript long non-coding RNA (lncRNA) (antisense non-coding RNA in the INK4 locus, ANRIL) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on chromosome 9p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame (ARF). In the context of gene regulation, ANRIL is responsible for directly recruiting polycomb group (PcG) proteins, including polycomb repressive complex-1 (PRC-1) and polycomb repressive complex-2 (PRC-2), to modify the epigenetic chromatin state and subsequently inhibit gene expression in cis-regulation. On the other hand, previous reports have indicated that ANRIL is capable of binding to a specific site or sequence, including the Alu element, E2F transcription factor 1 (E2F1), and CCCTC-binding factor (CTCF), to achieve trans-regulation functions. In addition to its function in cell proliferation, adhesion and apoptosis, ANRIL is very closely associated with atherosclerosis- related diseases. The different transcripts and the SNPs that are related to atherosclerotic vascular diseases (ASVD-SNPs) are inextricably linked to the development and progression of atherosclerosis. Linear transcripts have been shown to be a risk factor for atherosclerosis, whereas circular transcripts are protective against atherosclerosis. Furthermore, ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation, which is considered to be one of the causes of atherosclerosis. Collectively, ANRIL plays an important role in the formation of atherosclerosis, and the artificial modification of ANRIL transcripts should be considered following the development of this disease.