Pathogenomics model for personalized medicine in cervical cancer: Cross-talk of gene expressions and pathological images related to oxidative stress.

An increasing number of studies have shown that oxidative stress plays an important role in the development and progression of cancer. Cervical cancer (CC) is a disease of unique complexity that tends to exhibit high heterogeneity in molecular phenotypes. We aim here to characterize molecular features of cervical cancer by developing a classification system based on oxidative stress-related gene expression profiles. In this study, we obtained gene expression profiling data for cervical cancer from the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) (GSE44001) databases. Oxidative stress-related genes used for clustering were obtained from GeneCards. Patients with cervical cancer were divided into two subtypes (C1 and C2) by non-negative matrix factorization (NMF) classification. By performing Kaplan-Meier survival analysis, differential expression analysis, and gene set enrichment analysis (GSEA) between the two subtypes, we found that subtype C2 had a worse prognosis and was highly enriched for immune-related pathways as well as epithelial-mesenchymal transition (EMT) pathways. Subsequently, we performed metabolic pathway analysis, gene mutation landscape analysis, immune microenvironment analysis, immunotherapy response analysis, and drug sensitivity analysis of the two isoforms. The results showed that the isoforms were significantly different between metabolic pathway enrichment and the immune microenvironment, and the chromosomes of subtype C1 were more unstable. In addition, we found that subtype C2 tends to respond to treatment with anti-CTLA4 agents, a conclusion that coincides with high chromosomal variation in C1, as well as C2 enrichment of immune-related pathways. Then, we screened 10 agents that were significantly susceptible to C2 subtype. Finally, we constructed pathogenomics models based on pathological features and linked them to molecular subtypes. This study establishes a novel CC classification based on gene expression profiles of oxidative stress-related genes and elucidates differences between immune microenvironments between CC subtypes, contributing to subtype-specific immunotherapy and drug therapy.

Fibroblast growth factor-21 alleviates proteasome injury via activation of autophagy flux in Parkinson's disease.

Parkinson's disease (PD) is one of the most common and complex Neurodegeneration, with an inherited metabolic disorder. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in metabolic regulation. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here, we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vitro, proteasome impairment models of PD were utilized. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 µmol/L) for 12 h, then with 50 ng/ml FGF-21 with or without 5 mmol/L of 3-methyladenine.The cells were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against proteasome impairment induced PD syndrome, indicating it might be a potent candidate for developing novel drugs to deal with PD.

Effectiveness and influencing factors of online education for caregivers of patients with eating disorders during COVID-19 pandemic in China.

OBJECTIVE: The goals were twofold: To estimate the depression and anxiety levels among caregivers of patients with eating disorders (ED) in China during the COVID-19 pandemic when compared with a control group, and to assess whether an online education program was effective in decreasing the anxiety and depression of the caregivers of patients with ED, and associated factors. METHOD: Caregivers of patients with ED (n = 254) and a comparison group of non-ED caregivers (N = 254) were recruited at baseline. Additionally, caregivers of patients with ED were invited into a free 4-week online education program, with an additional online group as support. Depression and anxiety levels were assessed at baseline and after the intervention. RESULTS: Caregivers of patients with ED showed significantly higher levels of depression and anxiety than the comparison group of non-ED caregivers. The online education program showed no significant effect on decreasing depression and anxiety levels of caregivers of patients with ED overall. Caregivers who had older loved ones and not living with them were more likely to decrease their depression levels. Caregivers of patients with longer illness duration were less likely to decrease their anxiety levels. DISCUSSION: These results showed that caregivers of ED patients suffered more serious psychological distress during the pandemic. A more structured and intensive online intervention with a limited number of participants might be required to address caregivers' distress in post-COVID-19 China.

miR-30b protects nigrostriatal dopaminergic neurons from MPP(+)-induced neurotoxicity via SNCA.

OBJECTIVE: To explore the function of miR-30b in pathogenesis of Parkinson's disease (PD) and its underlying molecular mechanism. MATERIALS AND METHODS: We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP(+)) as a tool for constructing the PD cell model, using miR-30b mimics or inhibitors to manipulate miR-30b level for an experimental model of acquisition. The cell viability of SH-SY5Y was detected by CCK, and luciferase was used to screen the binding of target genes. The protein levels of SNCA were measured by Western blot. Then, we investigate the changes in pro- and anti-apoptotic markers with or without miR-30b treatment. RESULTS: There was a significant low expression of MiR-30b in MPP(+)-induced cells. SH-SY5Y cell viability was rescued by MiR-30b overexpression. Luciferase experiments showed that MiR-30b may bind to the 3'-UTR side of SNCA and inhibited its expression. By Western blot, the SNCA level was markedly decreased by miR-30b. miR-30b attenuated the upregulation of Bax and the depletion of Bcl-2 induced by MPP(+).

High serum levels of malondialdehyde and antioxidant enzymes are associated with post-stroke anxiety.

Post-stroke anxiety (PSA) is a common neuropsychiatric affective disorder occurring after stroke. The purpose of this study was to investigate the association between anxiety and the serum levels of oxidative stress markers at admission. First-ever or recurrent ischemic stroke patients were consecutively recruited into the study and followed up 1 month. Patients were divided into PSA and non-PSA group according DSM-IV criteria for anxiety due to stroke. Overall, 49 patients (24.1%) were diagnosed anxiety. Serum GPX (glutathione peroxidase), CAT (catalase), SOD (superoxide dismutase), and MDA (malondialdehyde) were significantly higher in patients with anxiety than patients without anxiety. The HAM-A scores had a significant positive association with MDA levels. In multivariate logistic regression analysis, serum antioxidant enzymes and MDA were independent predictors of PSA. An increased risk of PSA was associated with serum MDA levels ≥ 3.0 nmol/ml (adjusted OR 8.68, 95% CI 3.02-24.95; P < 0.001) after adjusting for relevant confounders such as social support and treatments at admission. Elevated serum levels of lipid oxidation products and antioxidant enzymes at admission were associated with anxiety 1 month after stroke, suggesting that these alterations might participate in the pathophysiology of anxiety symptoms in stroke patients.

Relationship between serum vitamin D levels and inflammatory markers in acute stroke patients.

Introduction: Low serum vitamin D levels are associated with the development of poststroke depression (PSD). Inflammatory markers play an important role in pathophysiology of PSD. The relationship between vitamin D levels and inflammatory markers has been discussed in nonstroke individuals. The purposes of this study were to explore the relationship between vitamin D levels and inflammatory markers in acute stroke patients and examine the effect of vitamin D and inflammatory markers on PSD. Methods: A total of 152 acute stroke patients were recruited. Serum levels of 25-hydroxyvitamin D and inflammatory markers were measured by standardized laboratory methods. Depression symptoms were assessed with the 17-item Hamilton Depression Scale (HAMD-17). Patients with the HAMD-17 scores ≥7 were identified to have depression symptoms. Results: Serum vitamin D levels were negatively correlated with serum levels of interleukin-6 and high-sensitivity C-reactive protein (hsCRP) (r = -.244, p = .002; r = -.231, p = .004). Multiple regression analysis showed that interleukin-6 and hsCRP levels were associated with vitamin D levels (B = -0.355, p = .003; B = -2.085, p = .006), whereas age, height, weight, leukocyte count, neutrophil ratio, and lymphocyte rate could be omitted without changing the results. In multivariate analyses, the serum levels of vitamin D and interleukin-6 were associated with the development of PSD after adjusted possible variables (OR = 0.976, 95% CI: 0.958-0.994, p = .009; OR = 1.029, 95% CI: 1.003-1.055, p = .027). Conclusions: Serum vitamin D levels are inversely associated with the levels of interleukin-6 and hsCRP, suggesting a potential anti-inflammatory role for vitamin D in stroke individuals.

Antioxidant and antibacterial activity of six edible wild plants (Sonchus spp.) in China.

The total phenolic and flavonoid, antioxidant and antibacterial activities of six Sonchus wild vegetables (Sonchus oleraceus L., Sonchus arvensis L., Sonchus asper (L.) Hill., Sonchus uliginosus M.B., Sonchus brachyotus DC. and Sonchus lingianus Shih) in China were investigated. The results revealed that S. arvensis extract and S. oleraceus extract contained the highest amount of phenolic and flavonoid, respectively. Among the methanol extracts of six Sonchus species, S. arvensis extract exhibited the highest radical (DPPH and ABTS+ scavenging power and lipid peroxidation inhibitory power. It also exhibited the highest reducing power at 500 µg mL⁻¹ by A (700) = 0.80. The results of antibacterial test indicated that the S. oleraceus extract showed higher activity than the other five Sonchus wild vegetables extracts, both in Gram-negative bacteria (Escherichia coli, Salmonella enterica and Vibrio parahaemolyticus) and in a Gram-positive bacterium (Staphylococcus aureus). These results indicate that Sonchus wild food plants might be applicable in natural medicine and healthy food.