Comprehensive analysis of transcriptome-wide expression patterns and a circRNA/lncRNA-miRNA-mRNA network in the pathogenesis of cerebral ischemia in Rattus norvegicus.

BACKGROUND: Although ischemic stroke exhibits a high prevalence in the elderly population, the involved genes and pathways are poorly understood. In this study, we proposed to identify differentially expressed genes (DEGs) and constructed a circular RAN (circRNA)/long noncoding RNA (lncRNA)/microRNA (miRNA)-mRNA network associated with the pathogenesis of ischemic stroke by using bioinformatics analysis. METHODS: We constructed a rat model of middle cerebral artery occlusion (MCAO) and conducted total RNA and microRNA sequencing in brain specimens from MCAO and normal rats. Transcriptome-wide expression patterns were analyzed and DEGs were defined by applying Ballgown and a cut of log2-transformed fold-change (log2FC) ≥ 1 (or ≤ -1) with a P value < 0.05. We exploited Pearson correlation analysis to determine the association between the circRNA/lncRNA/mRNA network and miRNAs (P < 0.05 and corr ≤ -0.6), and the competing endogenous RNAs (ceRNA) interaction network was visualized with Cytoscape software and separated into subnetworks using the Molecular Complex Detection (MCODE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented for the pathway analysis of DEGs. RESULTS: Upregulated DEGs were significantly enhanced in positive regulation of cell migration, response to wounding, blood vessel morphogenesis, inflammatory response, and cell activation; Downregulated DEGs were associated with control of the modulation of chemical synaptic transmission, synapse organization, regulation of membrane potential, and regulation of ion transport. KEGG-pathway analysis showed that DEG-enhanced pathways were associated with the pathways of TNF signaling pathway, Fluid shear stress and atherosclerosis, NF-kappa B signaling pathway, Lipid and atherosclerosis, Human cytomegalovirus infection, Osteoclast differentiation, Chemokine signaling pathway, IL-17 signaling pathway, Viral protein interaction with cytokine and cytokine receptor, and Cytokine-cytokine receptor interaction. We uncovered several novel lncRNAs (lnc_00231, lnc_002239, lnc_004172; and a novel_circ0001704), five miRNAs (miR-200b-3p, miR-223-3p, miR-200c-3p, miR-3084a-3p, and miR-664-2-5p), and the top-10 mRNAs (upregulated mRNAs were Pdgfa, Il1b, Gdf15, Fosl1, and Cxcl2; downregulated mRNAs were Prkar2b, Olfm3, Lrrc73, Tmem38a, and Dlgap3) that were involved in ischemic stroke. CONCLUSIONS: Through bioinformatic network analysis, we identified the underlying molecular mechanisms and key central genes that may contribute to an inflammatory response after cerebral infarction.

Serum total oxidant/antioxidant status and trace element levels in breast cancer patients.

BACKGROUND: Oxidative stress and trace elements have been implicated in the development of breast cancer. However, how they contribute to the pathogenesis of the disease and the relationship between them remain unclear. In addition, most previous studies detecting one or a few oxidant/antioxidant markers failed to consider the overall oxidant/antioxidant status of the subjects. This study was designed to address this and to investigate the association between oxidative status and trace elements in the pathogenesis of breast cancer. METHODS: Fifty-six patients with breast carcinoma at different clinical stages, 32 patients with benign breast tumor, and 20 healthy subjects (controls) were recruited into this study. Their serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and levels of Cu, Zn, Fe, Se, Mg, and Mn were measured. RESULTS: Levels of TAS, TOS, OSI, and trace elements significantly differed between the study groups. Among subgroups of patients with different clinical stages of breast cancer, the levels of all the trace elements except Zn were similar, whereas TAS, TOS, and OSI levels were all significantly different. There were significant correlations between oxidative stress parameters and levels of trace elements in patients with breast carcinoma but not in patients with benign breast tumor or in the healthy controls. CONCLUSIONS: Disturbed oxidative stress status and trace element levels may contribute to the pathogenesis of breast tumors. TAS, TOS, and OSI may be useful biomarkers for monitoring the clinical status of breast cancer.

[Rule mining of acupoint and medication selection of acupoint application therapy for functional constipation].

OBJECTIVE: To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology. METHODS: The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed. RESULTS: A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel, yangming stomach meridian of foot and taiyang bladder meridian of foot. The core prescription of medication was rheum officinale, mirabilite, immature bitter orange, mangnolia officinalis, common aucklandia root and borneol. CONCLUSION: The use of local acupoint and regulating-qi and purgating medication is an important principle of acupoint application therapy for FC.

Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages.

BACKGROUND: Reactive oxygen species (ROS) are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress (OxS). It is known that OxS plays an important role in the occurrence, development, and metastasis of breast cancer. The present study aimed to assess serum total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI) in patients at different clinical stages of breast cancer and to evaluate their diagnostic accuracy. METHODS: Serum TOS, TAS, and OSI were determined in 91 patients with breast cancer at different stages, 51 patients with benign breast tumors, and 35 healthy adults. RESULTS: Significant differences in serum TOS (F=104.384, p=0.000), TAS (F=18.247, p=0.000), and OSI (F=62.598, p=0.000) were observed among the 3 groups (benign breast tumor patients, breast cancer patients, and healthy women). Of the enrolled breast cancer patients, significant differences were also observed among different tumor stages, with TOS and OSI gradually increasing as the disease progressed, while TAS diminished. Receiver operating characteristic curve analysis revealed that the area under the ROC curve for OSI (AUCOSI) was significantly higher than AUCTAS (z=2.344, p=0.019) in distinguishing breast cancer from control groups (including disease control and the healthy control). The AUCOSI (z=4.700, p=0.001) or AUCTOS (z=4.700, p=0.001) was significantly higher than AUCTAS in distinguishing breast cancer from the healthy control. The AUCOSI (z=5.907, p=0.000) or AUCTOS (z=5.667, p=0.000) was significantly higher than AUCTAS in distinguishing benign breast tumors from the healthy control. CONCLUSION: Oxidative stress parameters might serve as important indexes for monitoring breast cancer occurrence and progression. The combined evaluation of TOS, TAS, and OSI could be more beneficial for clinical assessment.

Total oxidant/antioxidant status in sera of patients with thyroid cancers.

Oxidative stress is considered to be involved in the pathophysiology of all cancers. In order to evaluate the total oxidant/antioxidant status in patients with thyroid cancer and to investigate the relationship between oxidative stress parameters and serum thyroid profiles among thyroid cancer patients and various controls, we determined oxidative status including total antioxidant status (TAS) and total oxidant status (TOS) and calculation of oxidative stress index (OSI) in sera in 82 thyroid cancer patients, 56 benign thyroid disease patients, and 50 healthy controls. It was found that serum TAS levels were significantly lower in patients with thyroid cancer than in controls (P<0.001), while serum TOS levels and OSI values were significantly higher (both P<0.001) in the cancer patients. No significant correlations were observed between various oxidative stress markers and thyroid profiles in either the thyroid cancer patients or the controls. Receiver operating characteristic curve analysis demonstrated that OSI was the best indicator for distinguishing cancer patients from benign thyroid diseased or healthy controls, followed by TOS and TAS. Risk estimate statistics also indicated that TOS and/or OSI were good risk factors to discriminate patients with thyroid cancer from two controls. These findings suggested that oxidants are increased and antioxidants are decreased in patients with thyroid cancer. OSI may be a more useful oxidative stress biomarker than TAS and TOS for monitoring the clinical status of thyroid cancer patients.