A seed expansion-based method to identify essential proteins by integrating protein-protein interaction sub-networks and multiple biological characteristics.

BACKGROUND: The identification of essential proteins is of great significance in biology and pathology. However, protein-protein interaction (PPI) data obtained through high-throughput technology include a high number of false positives. To overcome this limitation, numerous computational algorithms based on biological characteristics and topological features have been proposed to identify essential proteins. RESULTS: In this paper, we propose a novel method named SESN for identifying essential proteins. It is a seed expansion method based on PPI sub-networks and multiple biological characteristics. Firstly, SESN utilizes gene expression data to construct PPI sub-networks. Secondly, seed expansion is performed simultaneously in each sub-network, and the expansion process is based on the topological features of predicted essential proteins. Thirdly, the error correction mechanism is based on multiple biological characteristics and the entire PPI network. Finally, SESN analyzes the impact of each biological characteristic, including protein complex, gene expression data, GO annotations, and subcellular localization, and adopts the biological data with the best experimental results. The output of SESN is a set of predicted essential proteins. CONCLUSIONS: The analysis of each component of SESN indicates the effectiveness of all components. We conduct comparison experiments using three datasets from two species, and the experimental results demonstrate that SESN achieves superior performance compared to other methods.

The Construction of ITP Diagnostic Modeling Based on the Expressions of Hub Genes Associated with M1 Polarization of Macrophages.

Purpose: Primary immune thrombocytopenia (ITP) is an immune disease with a diagnosis of exclusion, since no validated biomarkers have been identified. In this study, we explored biomarkers associated with the development of ITP from an immune perspective to inform the clinical diagnosis. Patients and Methods: Differentially expressed genes (DEGs) between normal and ITP samples were analyzed using limma package. Random forest algorithm and LASSO regression were further used to screen for DEGs associated with ITP. The expression of these hub genes was validated by PCR. The relationship between DEGs and immunity was explored by enrichment analysis. Immune cell infiltration in ITP was analyzed by CIBERSORT and ssGSEA, and the relationship between DEGs and infiltrating immune cells was analyzed by Spearman's rank correlation analysis. Finally, a diagnostic model related to DEGs was constructed by the neural network, and its efficiency was detected by the ROC curve. Results: After screening the GEO database and validation by PCR analysis, The expression of CTH and TAF8 were higher and while OSBP2 expression was lower in ITP patients compared to normal subjects (P<0.05). GO enrichment analysis showed that these DEGs were associated with inflammatory immune-related diseases, and KEGG analysis showed that they mainly regulated signaling pathways such as JAK-STAT. CIBERSORT and ssGSEA analyses showed that these DEGs were mainly associated with macrophage M1 polarization. The expression of CTH and TAF8 were positively correlated with M1 expression, while OSBP2 was negatively correlated with M1 expression. The ROC curve showed high accuracy of the neural network model [AUC= 0.939, 95% CI (0.8-1)]. Conclusion: Our results suggest that CTH, TAF8, and OSBP2 can be used as effective diagnostic biomarkers of ITP.

[Expression of MicroRNAs in Peripheral Blood of Patients with Primary Immune Thrombocytopenia and Its Correlation with the Imbalance of Th1/Th2 Cell].

OBJECTIVE: To investigate the expressions of microRNAs in peripheral blood of patients with primary immune thrombocytopenia(ITP) and its correlation with the imbalance of Th1/Th2 cells. METHODS: Thirty patients with ITP (ITP group) and 15 healthy people (control group) were enrolled．Real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of six miRNAs (miR-107,miR-205-5p,miR-138-5p,miR-326,miR-1827,miR-185-5p) and Th1-specific transcription factor T-bet mRNA and Th2-specific transcription factor GATA-3 mRNA in the peripheral blood of the two groups. Th1 and Th2 cells were detected by flow cytometry. The expressions of Th1-cytokines TNF-α and IFN-γ and Th2-cytokines IL-4 and IL-10 were detected by AimPlex multiple immunoassays for Flow. The expression difference of miRNAs, mRNA, Th1, Th2 cells and cytokines of the two groups were compared, and the correlations of miRNAs to mRNA, Th1, Th2 cells and cytokines were analyzed in ITP group. RESULTS: The expressions of miRNAs（miR-107, miR-205-5p, miR-138-5p, miR-326, miR-1827, miR-185-5p）and Th2-specific transcription factor GATA-3 mRNA of the patients in ITP group were significantly decreased (P<0.05) as compared with those in control, while the expressions of Th1 cells and Th1-specific transcription factor T-bet mRNA and Th1-cytokines TNF-α were significantly increased (P<0.05), also for the ratios of T-bet mRNA/GATA-3 mRNA and Th1/Th2 cells were significantly increased (P<0.05). The relative expressions of miR-107, miR-205-5p, miR-138-5p in ITP patients were negatively correlated with Th2 cells (r=-0.411, r=-0.593, r=-0.403,P<0.05) and the relative expression of miR-1827 was negatively correlated with TNF-α (r=-0.390). CONCLUSION: The relative expressions of the six miRNAs in peripheral blood of patients with ITP are significantly decreased, which result in the increasing ratio of T-bet mRNA/GATA-3 mRNA, then lead to the imbalance of Th1/Th2.

Bidirectional alterations in ALFF across slow-5 and slow-4 frequencies in the brains of postherpetic neuralgia patients.

PURPOSE: Postherpetic neuralgia (PHN) detrimentally affects brain function. Recent studies have suggested that frequency-dependent changes in electroencephalography in chronic pain patients and blood oxygenation level dependent (BOLD) fluctuations can reflect neuronal activity in different frequencies. The current study aimed to investigate PHN-related brain oscillatory activity in a specific frequency band by using the amplitude of low-frequency fluctuation (ALFF) method. MATERIALS AND METHODS: ALFF changes were analyzed across different frequencies (slow-4 band: 0.027-0.073 Hz; slow-5 band: 0.01-0.027 Hz; and typical band: 0.01-0.08 Hz) in the brains of PHN patients and compared with those in the brains of healthy controls (HCs) during resting-state fMRI. Eighteen HCs and PHN patients underwent fMRI scanning. RESULTS: In the typical band, compared with HCs, PHN patients showed prominently decreased ALFF in the right prefrontal cortex (Brodmann area 10/46) and increased ALFF in the bilateral brain stem/cerebellum anterior lobe (BS/CAL). In the slow-4 band, PHN patients exhibited significantly decreased ALFF in the bilateral cuneus/lingual gyrus and the right prefrontal cortex. In the slow-5 band, PHN patients presented significantly increased ALFF in the bilateral BS/CAL and left parieto-occipital cortex. Moreover, the increased ALFF in the left parieto-occipital cortex in the slow-5 band was positively correlated with VAS scores (P=0.022), and the increased ALFF in the bilateral BS/CAL in the slow-5 band was positively correlated with disease duration (P=0.020). CONCLUSION: Our results suggested that the intrinsic brain activity of PHN patients was abnormal and frequency dependent, especially the bidirectional alteration in ALFF across the slow-4 and slow-5 frequencies in the brains of PHN patients.

CT-guided selective percutaneous radiofrequency thermocoagulation via the foramen rotundum for isolated maxillary nerve idiopathic trigeminal neuralgia.

OBJECTIVE Although CT-guided selective percutaneous radiofrequency thermocoagulation (PRFT) via the foramen rotundum (FR) has been used in the clinic as a novel successful treatment for isolated, second division (maxillary nerve [V2]), idiopathic trigeminal neuralgia (ITN), there is only very limited related literature published to date. This report aims to provide more detail for physicians about this technique. METHODS Between March 2013 and April 2014, 20 patients with isolated V2 ITN refractory to or intolerant of drug treatment were treated by CT-guided selective PRFT via the FR at the First Affiliated Hospital of Nanchang University. The outcome of pain relief was assessed using the Barrow Neurological Institute (BNI) pain score, and grouped as good (BNI Class I or II, no medication required) and bad (BNI Class III-V, medication required or failed). Recurrence was defined as a relapse to a previous lower level after attainment of any higher level of pain relief. Adverse effects and complications were also monitored and recorded. RESULTS All patients (100%) obtained good pain relief including BNI Class I in 17 patients (85%) and BNI Class II in 3 patients (15%) immediately postoperatively. None of the patients were lost to follow-up. During the mean follow-up period of 24.3 months (range 18-30 months), 2 patients (10%) experienced recurring pain and the mean time until recurrence was 10.5 months (range 8-13 months). No adverse effects or complications occurred except for transient numbness restricted to the V2 dermatome in all patients (100%) and facial hematoma in 3 patients (15%). CONCLUSIONS In the current study, CT-guided selective PRFT via the FR not only achieved absolute selective lesioning to V2, but also helped patients attain successful pain relief with few adverse effects. These limited data suggest that CT-guided selective PRFT via the FR appears to be a feasible, safe, effective, and even relatively ideal treatment for isolated V2 ITN, but these findings need confirmation from further studies.

Efficacy of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis.

Spinal cord injury (SCI)­induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI­induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10­12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI­induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI­induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post­SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast­specific genes receptor activator of nuclear factor kappa­B ligand and cathepsin K were significantly upregulated and the osteoblast­specific gene core­binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI­induced osteoporosis.