Oxidative stress has been suggested to play a key role in Parkinson's disease, but inconsistent results were found in clinical studies. This study sought to quantitatively summarize the blood and cerebrospinal fluid (CSF) oxidative stress marker data in PD patients. We performed a systematic search of PubMed and Web of Science, and studies were included if they provided data on peripheral blood and CSF oxidative stress marker concentrations in PD patients and healthy control (HC) subjects. Data were extracted by three independent investigators from 80 included studies encompassing 7,212 PD patients and 6,037 HC subjects. Of the 22 oxidative stress markers analyzed, random effects meta-analysis showed that blood concentrations of 8-OhdG, MDA, nitrite, and ferritin were increased in patients with PD compared with HC subjects. In contrast, we showed that blood levels of catalase, uric acid, glutathione, and total-cholesterol were significantly down-regulated in patients with PD when compared with controls. There were no significant differences between PD patients and HC subjects for blood, Mn, Cu, Zn, Fe, SOD, albumin, glutathione peroxidase, vitamin E, ceruloplasmin, triglycerides, lactoferrin, transferrin, LDL-cholesterol, and HDL-cholesterol. Due to the limited number of CSF studies with small sample size, this meta-analysis only showed non-significant association between CSF 8-OhdG and PD. The findings of our meta-analysis demonstrated higher blood concentrations of 8-OhdG, MDA, nitrite and ferritin, and lower blood concentrations of catalase, uric acid, glutathione and total-cholesterol in PD patients, strengthening the clinical evidence that PD is accompanied by increased oxidative stress.
Background: Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis. Methods: Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias. Results: Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581-0.779; P < 0.001] and PD (OR: 0.470; 95% CI: 0.368-0.600; P < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis. Conclusion: We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.
Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.
Background MicroRNAs (miRs) have been suggested to be biomarkers to inform the diagnosis of major depressive disorder (MDD). We have previously shown that exosome-derived miR-139-5p had potential in differentiating between patients with MDD and healthy control (HC) subjects. Materials and Methods To validate the potential of exosome-derived miR-139-5p as a biomarker for MDD, here we recruited 30 patients with MDD and 30 HC subjects, and used TaqMan probes to detect serum exosomal miR-139-5p levels. Results The data showed that patients with MDD had significantly increased exosomal miR-139-5p levels when compared with controls. Correlation analysis suggested that sex, age, and body mass index did not significantly affect blood exosomal miR-139-5p levels in the tested subjects. The ROC curve showed that serum-derived miR-139-5p had reasonable performance in discriminating patients with MDD and HC subjects, with a sensitivity of 0.867 and specificity of 0.767, and the AUC was 0.807. Discussion Taken together, these results demonstrated that patients with MDD were accompanied by significantly increased blood exosomal miR-139-5p levels, and exosomal miR-139-5p is a promising biomarker for the diagnosis of MDD.
Aims To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs). Design Systematic review and meta‐analysis. Setting Clinical studies that evaluated peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls Participants SUD patients and healthy controls. Measurements PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta‐analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random‐effects model by the Comprehensive Meta‐Analysis version 2 software. Findings Concentrations of interleukin (IL)‐6) in 32 studies, tumor necrosis factor (TNF)‐α in 28 studies, IL‐10 in 20 studies, IL‐8 in 17 studies, C‐reactive protein in 14 studies, IL‐4 in 10 studies, IL‐12 in seven studies, monocyte chemoattractant protein (MCP)‐1 in 6 studies, TNF‐receptor 2 (TNF‐R2) in four studies and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon‐γ, IL‐1β, IL‐2, IL‐1 receptor antagonist (IL‐1RA), transforming growth factor (TGF)‐β1, G‐CSF, C‐C motif chemokine 11, TGF‐α and SUDs. Conclusions People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, TNF‐α, C‐reactive protein, MCP‐1, TNF‐R2 and GM‐CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.
To evaluate the effects of robot‐assisted rehabilitation training on knee function and the daily activity ability of older adults following total knee arthroplasty (TKA). Eighty‐eight patients who underwent TKA were randomly assigned to a robot‐assisted rehabilitation or traditional therapy group. The patients in the control group were treated with traditional manual rehabilitation therapy, while the patients in the experimental group were subjected to the robot‐assisted rehabilitation program. Range of motion of the knee joint, Hospital for Special Surgery Knee Rating Score, and the modified Barthel Index were assessed on the first or second day after TKA (preintervention) and the discharge day (postintervention). Additionally, the length of hospital stay and related hospitalization expenses of the two groups were collected on the discharge day. Improvements in the active range of motion (p < 0.001), passive range of motion (p = 0.001), Hospital for Special Surgery Knee Rating Score (p < 0.001), and modified Barthel Index score (p = 0.004) were significantly better in the robot‐assisted rehabilitation group than in the traditional therapy group. Interestingly, the length of hospital stay in the experimental group (9 days) was shorter than that in the control group (13 days), and the total cost of hospitalization was lower (p = 0.002). The robot‐assisted rehabilitation training program is an effective intervention that significantly improves the daily activity ability and knee function of older adults following TKA.
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