To date, there are no definitive biomarkers for Parkinson's disease (PD) diagnosis. The detection of cerebrospinal fluid (CSF) alpha (α)-synuclein in PD patients has yielded promising but inconclusive results. To determine the performance of CSF α-synuclein as a diagnostic biomarker of PD and whether CSF α-synuclein can discriminate PD from other neurodegenerative diseases, a systematic search of all relevant studies investigating reproducible CSF α-synuclein quantification methods was conducted in electronic databases. A total of 17 studies that included 3311 patients were included in this systemic review and meta-analysis. The mean CSF α-synuclein concentration was significantly lower in PD patients compared to normal/neurological controls [weighted mean difference (WMD) -0.31; 95% CI, -0.45, -0.16; p < 0.0001] and patients with Alzheimer's disease (AD) [WMD -0.15; 95% CI, -0.26, -0.04; p < 0.0001]. There was no significant difference between PD patients and dementia with Lewy bodies (DLB) patients [WMD -0.03; 95% CI, -0.16, 0.09; p = 0.58] or patients with multiple system atrophy (MSA) [WMD 0.05; 95% CI, -0.04, 0.13; p = 0.25]. Sensitivity and specificity of CSF α-synuclein in the diagnosis of PD was 0.88 (95% CI, 0.84-0.91) and 0.40 (95% CI, 0.35-0.45), respectively. The positive and negative likelihood ratios of CSF α-synuclein in the diagnosis of PD were 1.41 (95% CI, 1.24-1.60), and 0.29 (95% CI, 0.15-0.56), respectively. The corresponding summary receiver operating characteristic (SROC) curve showed an area under the curve (AUC) of 0.73. The concentration of CSF α-synuclein may be a biomarker for the diagnosis of PD. The use of α-synuclein alone however is not sufficient as a single biomarker and it must therefore be used in conjunction with other documented and reliable biomarkers.

No abstract

No abstract

Ovarian cancer (OC) is a major cancer-related mortality among women. Recent studies suggest that many microRNAs (miRNAs) were dysregulated and involved in tumorigenesis of OC. The present study investigated the role of miR-25 in the development and progression of OC. The expression of miR-25 was increased in OC tissues and cell lines. Inhibition of miR-25 remarkably suppressed proliferation, migration, and invasion of OC cells. Large tumor suppressor 2 (LATS2), a tumor suppressor, was confirmed to be a direct target of miR-25 in OC cells. Moreover, restoration of LATS2 significantly attenuated the oncogenic effects of miR-25. Together, our data suggest an oncogenic role of miR-25 in OC and a potentially novel diagnostic and therapeutic target for OC treatment.

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal–organic framework (MOF)‐Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS‐mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF‐Fe2+, but also generate an acidic microenvironment to activate a MOF‐Fe2+‐based Fenton reaction. Importantly, MD@Lip promotes DCA‐mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2O2), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF‐Fe2+, leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome‐based combination therapy of DCA and MOF‐Fe2+ provides a promising oxidative stress–associated antitumor strategy for the management of malignant tumors.

BackgroundS2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells.Material/MethodsCell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p-mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression.ResultsOur results show that the proportion of early apoptotic and late apoptotic cells increased significantly for cells treated with S2101 at a concentration of 100 μM for 48 h. Treatment of S2101 in SKOV3 cells resulted in upregulation of Bax and downregulation of Bcl-2 in a time-dependent manner, indicating that S2101 can induce apoptosis in SKOV3. There was a downward trend in the expression of p62 when the SKOV3cells were treated with 100 μm S2101 for 12 h, 24 h and 48 h. The conversion of LC3-I to LC3-II was increased significantly at 24 h and 48 h. Autophagy was induced by S2101 in SKOV3 cells, evidenced by an increase in punctuate localization of GFP-LC3 and a change in expression of autophagy-related proteins.ConclusionsS2101 treatment decreased the levels of phosphorylated AKT and mTOR. S2101 inhibits SKOV3 cells viability and induces apoptosis and autophagy. The AKT/mTOR signaling pathway was found to be affected by S2101.

No abstract

Aims The aim of this research was to investigate the alterations in functional brain networks and to assess the relationship between depressive impairment and topological network changes in Parkinson's disease (PD) patients with depression (DPD). Methods Twenty‐two DPD patients, 23 PD patients without depression (NDPD), and 25 matched healthy controls (HCs) were enrolled. All participants were examined by resting‐state functional magnetic resonance imaging scans. Graph theoretical analysis and network‐based statistic methods were used to analyze brain network topological properties and abnormal subnetworks, respectively. Results The DPD group showed significantly decreased local efficiency compared with the HC group (P = .008, FDR corrected). In nodal metrics analyses, the degree of the right inferior occipital gyrus (P = .0001, FDR corrected) was positively correlated with the Hamilton Depression Rating Scale scores in the DPD group. Meanwhile, the temporal visual cortex, including the bilateral middle temporal gyri and right inferior temporal gyrus in the HC and NDPD groups and the left posterior cingulate gyrus in the NDPD group, was defined as hub region, but not in the DPD group. Compared with the HC group, the DPD group had extensive weakening of connections between the temporal‐occipital visual cortex and the prefrontal‐limbic network. Conclusions These results suggest that PD depression is associated with disruptions in the topological organization of functional brain networks, mainly involved the temporal‐occipital visual cortex and the posterior cingulate gyrus and may advance our current understanding of the pathophysiological mechanisms underlying DPD.