Bioinformatic analysis identifies the immunological profile of turner syndrome with different X chromosome origins.

Introduction: Turner syndrome (TS) is a chromosomal disorder that affects phenotypic females who have one intact X chromosome and complete or partial absence of the second sex chromosome in association with one or more clinical manifestations. However, the immunological profile of TS with different X chromosome origins is incompletely understood. Methods: In this study, transcriptomic expression profiles of 26 TS (45,X) samples and 10 normal karyotype (46,XX) samples derived from GSE46687 cohort were employed. Differentially expressed immune-related genes (DEIRGs) between monosomy X TS patients with different X chromosome origins and normal females were investigated respectively. Subsequently, functional annotation, protein-protein interaction (PPI) network analysis, immunocyte infiltration evaluation, tissue-specific gene expression and Weighted gene co expression network analysis (WGCNA) were performed to explore the immunological characteristic in TS with different X chromosome origins. Results: 34 and 52 DEIRGs were respectively identified in 45,Xm and 45,Xp patients compared with normal individuals. The identified DEIRGs in Xm group were significantly enriched in pathways associated with cancer. In Xp TS patients, the most enriched signals were immune response-related. A majority of genes involved in the above pathways were downregulated. PPI analysis identified 4 (FLT3, IL3RA, CSF2RA, PIK3R3) and 6 (PDGFRB, CSF2, IL5, PRL, CCL17 and IL2)hub genes for Xm and Xp groups, respectively. CIBERSORT results showed that the proportion of Tregs in the Xm group and the naive B cells and resting NK cells in the Xp group significantly increased, respectively. Tissue-specific expression results indicated that BDCA4+_dentritic cells and CD19+ B cells were the prominent specific expressed tissues in Xp patients. Results of WGCNA support the above analysis. Conclusions: This study aims at studying the immunological characteristics of TS with different X chromosome origins. Pathways in cancer in Xm group and immune response in Xp group were suppressed. 4 and 6 hub IRGs were identified as biomarkers for Xm and Xp patients, respectively. B cells played important roles in Xp patients. Further studies are needed to draw more attention to the functional validation of these hub genes and the roles of B cells.

The protective effects of miR-128-3p on sevoflurane-induced progressive neurotoxicity in rats by targeting NOVA1.

MiR-128 is highly expressed in the central nervous system and may regulate the directional differentiation of bone marrow stromal stem cells into nerve cells. However, its role and mechanism in sevoflurane-induced progressive neurotoxicity in rats are rarely reported. Therefore, this study aims to explore the protection of miR-128-3p on sevoflurane-induced neurotoxicity. Hippocampal neurons were isolated and sevoflurane was used to treat the cells. Cell counting kit-8 (CCK-8) was used to detect cell viability. Immunofluorescence was used to detect enrichment of GFAP or ßIII tubulin to identify nerve cells. Dual luciferase assay was used to identify the targeted binding relationship between miR-128-3p and NOVA1. The effect of miR-128-3p and sevoflurane on cells regarding apoptosis was detected by flow cytometry. The expression of apoptosis-related protein and oxidative stress-related proteins were detected by western blot. Enzyme-linked immuno-sorbent assay (ELISA) was used to measure inflammatory cytokine levels. Hippocampal neurons' cell viability was significantly decreased by treatment with sevoflurane. MiR-128-3p was down-regulated after sevoflurane treatment in cells. Overexpressed miR-128-3p partially reversed the role of sevoflurane treatment in triggering cell apoptosis, enhancing the expression of Bax and cleaved caspase-3 and inhibiting Bcl-2 expression obviously. Overexpressed miR-128-3p partially reversed the role of sevoflurane treatment in promoting the expression of NOX1and NOX4, and inflammatory cytokine levels by targeting with NOVA1. MiR-128-3p might be a potential therapeutic target for the prevention or treatment of sevoflurane-induced neurotoxicity by targeting with NOVA1.

Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway.

Glioma is life-threatening tumor of the central nervous system. Although lidocaine is usually used as local anesthetic, it also has antitumor effects. However, its clinical application in glioma is hampered by limited distribution to the brain. The aim of the present study was to enhance the ability of lidocaine to penetrate the blood-brain barrier (BBB) to target glioma and investigate its antitumor mechanism. A folic acid (FA)-modified lidocaine-carrying liposome (Lid-FA-Lip) was prepared, and its particle size, ζ potential, encapsulation efficiency, release profile stability and hemolytic effect were characterized in vitro. The targeting capacity and antitumor activities of Lid-FA-Lip were also investigated in vitro and in vivo. The results indicated that the modification of liposomes with FA significantly improved the ability of lidocaine to cross the BBB in an in vitro model and increased its uptake by U87 cells. Additionally, Lid-FA-Lip significantly suppressed the motility of U87 glioma cells and stimulated apoptosis. Furthermore, the results confirmed that Lid-FA-Lip targeted the PI3K/AKT pathway and suppressed the growth of glioma xenografts in mice. In summary, the study demonstrated that Lid-FA-Lip is a promising liposomal formulation of lidocaine that may provide improved therapeutic effects on glioma, mediated via the PI3K/AKT pathway.

Exploration of Potential Molecular Targets of Dexmedetomidine in the Intestinal Repair of Burnt Rats.

BACKGROUND: More and more burn survivors were suffering from varying degrees of damage to the intestinal barrier. Dexmedetomidine (Dex) was frequently used as sedative in more cases, but it was found to have repair effect on intestinal barrier dysfunction recently. This study aimed to explore the potential specific targets of Dex in intestinal barrier repair in burn rats model. METHODS: Male adult SD rats were used to establish 40% TBSA III degree scald model in our study. The samples were divided into four groups: burn rats (Burn), burn rats with Dex medication (Burn-Dex), sham rats (Sham) and sham rats with Dex medication (Sham-Dex). And plasma FITC-dextran and diamine oxidase (DAO) were detected to determine the intestinal permeability. Differentially expressed proteins were further adopted to protein-protein interaction network analysis, Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: It showed that 40% TBSA III degree scald model was successfully constructed. And plasma FITC-dextran and DAO decreased significantly after Dex administration. Additionally, differentially expressed genes Psmb10, Psmb7 among the experimental groups were screened, which were significantly enriched in proteasome and other several pathways. CONCLUSION: The results above suggested that Q4KM35 and Q9JHW0, which are encoded by Psmb10 and Psmb7, respectively, are two possible protein targets of Dex in intestinal barrier repair.

cRGDyK-modified procaine liposome inhibits the proliferation and motility of glioma cells via the ERK/p38MAPK pathway.

Glioma is a common type of primary tumor in the central nervous system. Glioma has been increasing in incidence yearly and is a serious threat to human life and health. The aim of the present study was to prepare liposomes for enhanced penetration of the blood-brain barrier and targeting of glioma. A procaine-loaded liposome modified with the cyclic pentapeptide cRGDyK (Pro/cRGDyK-L) was designed and developed. The particle size, ζ potential, encapsulation efficiency, release profile, stability and hemolysis of Pro/cRGDyK-L were characterized in vitro. The targeting and antitumor effects of Pro/cRGDyK-L were also investigated in vitro and in vivo. The results suggested that the cRGDyK peptide significantly facilitated the ability of liposomes to transfer procaine across the BBB and improved the cellular uptake of procaine by C6 glioma cells. The results further demonstrated that Pro/cRGDyK-L strongly suppressed cell motility, stimulated apoptosis and induced cell cycle arrest. The findings further confirmed that Pro/cRGDyK-L exhibited superior antitumor effects by targeting the ERK/p38MAPK pathway and thereby suppressed tumor growth in mice. In conclusion, the present study indicated the potential of Pro/cRGDyK-L as a means to provide improved therapeutic effects on glioma through the ERK/p38MAPK pathway.

Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice.

Sepsis-associated encephalopathy (SAE) can cause acute and long-term cognitive impairment and increase the mortality rate in sepsis patients, and we previously reported that 2% hydrogen gas (H2) inhalation has a therapeutic effect on SAE, but the underlying mechanism remains unclear. Dynamic DNA methylation, which catalyzed by DNA methyltransferases (DNMTs), is involved in the formation of synaptic plasticity and cognitive memory in the central nervous system. And brain-derived neurotrophic factor (BDNF), to be a key signaling component in activity-dependent synaptic plasticity, can be induced by neuronal activity accompanied by hypomethylation of its promoter IV. This study was designed to illustrate whether H2 can mediate SAE by alter the BDNF promoter IV methylation mediated by DNMTs. We established an SAE model by cecal ligation and perforation (CLP) in C57BL/6 mice. The Morris water maze test from the 4th to the 10th day after sham or CLP operations were used to evaluate mouse cognitive function. Hippocampal tissues were isolated at the 24 after sham or CLP surgery. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and High Mobility Group Box 1 (HMGB1) were measured by enzyme-linked immunosorbent assay (ELISA). mRNA or protein levels of DNMTs (DNMT1, DNMT3a and DNMT3b), BDNF promoter IV and total BDNF were detected by RT-PCR and Western blot tests. Immunofluorescence staining were used to determine the expressions of DNMT1 and DNMT3a. The quantitative methylation analysis of the 11 CpG island of the promoter region of BDNF exon IV was determined using theAgena's MassARRAY EpiTYPER system. We found that 2% H2 inhalation can reduce pro-inflammatory factors, alleviate DNMT1, DNMT3a but not DNMT3b expression, make hypomethylation of BDNF promoter IV at 5 CpG sites, enhance the BDNF levels and then decrease escape latency but increase platform crossing times in septic mice. Our results suggest that 2% H2 inhalation may alleviate SAE through altering the regulation of BDNF promoter IV methylation which mediated by DNMT1 and DNMT3a in the hippocampus of septic mice.

Effectiveness of High Tibial Osteotomy with or without Other Procedures for Medial Compartment Osteoarthritis of Knee: An Update Meta-Analysis.

To improve the long-term outcomes of high tibial osteotomy (HTO) for gonarthritis, many cartilage repair procedures appeared, but their effects were controversial. To evaluate the efficacy of cartilage repair procedures during HTO for gonarthritis, we performed this update meta-analysis. We performed the system retrieval for clinical trials using various databases and then pooled the outcomes of the included studies. Fifteen studies were involved. The pooled results indicated that there were no significant differences in Kellgren and Lawrence (KL) scale (mean difference [MD] = 0.02, 95% confidence interval [CI] = -0.01 to 0.06, p = 0.24), the femorotibial angle (MD = 0.06, 95% CI = -0.04 to 0.16, p = 0.22), and magnetic resonance imaging (MRI) outcomes (MD = 12.53, 95% CI = -2.26 to 27.32, p = 0.10) of patients in experimental group than control. The subgroup analysis showed that the clinical outcomes of abrasion arthroplasty (AA) were worse than control group (standardized mean difference [SMD] -2.65, 95% CI = -3.67 to -1.63, p < 0.001), while mesenchymal stem cells (MSCs) injection improved the clinical outcomes (SMD = 2.37, 95% CI = 1.25-3.50, p < 0.001). There were significant differences between the two groups in arthroscopic (SMD = 1.38, 95% CI = 0.82-1.94, p < 0.001) and histologic results (relative risk [RR] = 1.77, 95% CI = 1.36-2.29, p < 0.001). The pain relief (MD = 0.17, 95% CI = -3.26 to 3.61, p = 0.92) and operative complications (RR = 1.42, 95% CI = 0.83-2.42; p = 0.19) of the two groups had no significant differences. Our analysis supports that concurrent cartilage repair procedures might improve arthroscopic and histologic outcomes, but they have no beneficial effect on clinical outcomes, radiograph, MRI, and pain relief. The concurrent procedures do not increase the risk of operative complication. Furthermore, MSC has some beneficial effects on clinical outcomes, while AA might play an opposite role.

Gardenoside suppresses the pain in rats model of chronic constriction injury by regulating the P2X3 and P2X7 receptors.

OBJECTIVES: Here, using rat model, we investigated the roles of gardenoside in the chronic constriction injury (CCI) of the ischiadic nerve. METHODS: Bennett and Xie's unilateral sciatic nerve CCI model was used in this study. A total of 60 rats were divided into control group (CN), sham group (Sham), CCI group, and gardenoside administrated CCI group. An aliquot of 5 mL gardenoside solution was administrated through gavage once per day for 14 d. Mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) were detected. The levels of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in spinal fluid were detected by ELISA. By using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, we analyzed the expression of P2X purinoceptor 3 and 7 (P2X3 and P2X7 receptors) in different groups. The expression of p-ERK/ERK and p-p38/p38 were also detected by western blot. RESULTS: We found out that gardenoside could significantly improve the sciatica by partially restore the decrease of MWT and TWL in CCI rats. The levels of iNOS, IL-1ß, and TNF-α were higher in CCI group (p < .05). The expressions of P2X3 and P2X7 were significantly increased in the CCI rats compared to control rats (p < .05). The levels of p-ERK/ERK and p-p38/p38 were also obviously increased in CCI group (p < .05). After treated with the gardenoside, these increases were decreased. CONCLUSIONS: These results indicated that gardenoside may be able to relief CCI-induced neuropathic pain by regulating the P2X3 and the P2X7 expression on the ischiadic nerve.

Gardenoside combined with ozone inhibits the expression of P2X3 and P2X7 purine receptors in rats with sciatic nerve injury.

Neuropathic pain is a severe health problem for which there is a lack of effective therapy. Ozone and Gardenia fruits have been used separately in pain relief for many years; however, their underlying mechanisms remain unclear. To investigate the pain­relieving effects of combined ozone and Gardenia, a chronic constriction sciatic nerve injury (CCI) rat model was constructed and treated with ozone and gardenoside (Ozo&Gar), which is a compound found in Gardenia fruits. A total of 70 rats were randomly divided into five groups: Control (Ctrl), Ctrl + Ozo&Gar, Sham, CCI, and CCI + Ozo&Gar. The rats in the Ctrl + Ozo&Gar and CCI + Ozo&Gar groups were administered an intravenous injection of 30 µg/ml ozone and 300 µmol/l gardenoside. The rats in the Ctrl, Sham and CCI groups were administered the same volume of saline. Pain behavior, mechanical hyperalgesia, thermal hyperalgesia, and the protein expression levels of P2X3 and P2X7 purine receptors in L4­L5 dorsal root ganglion (DRG) were determined 15 days post­surgery. The results demonstrated that treatment with a combination of ozone and gardenoside increased mechanical withdrawal threshold and thermal withdrawal latency, thus confirming their pain­relieving effects. In addition, a significant increase in the mRNA and protein expression levels of P2X3 and P2X7 was detected in the DRG of rats in the CCI group compared with in the control groups; however, following treatment with a combination of ozone and gardenoside, the mRNA and protein expression levels of P2X3 and P2X7 receptors were significantly reduced compared with in the CCI group. These results indicated that the mechanism underlying the pain­relieving effects of ozone and gardenoside may be mediated by inhibition of P2X3 and P2X7 purine receptors in the DRG. This finding suggested that ozone and gardenoside may be considered potential drug candidates that target P2X3 and P2X7 purine receptors.

Association of asthma with coronary heart disease: A meta analysis of 11 trials.

PURPOSE: While the relationship of asthma and coronary heart disease (CHD) (a specific manifestation of cardiovascular disease) has not been described consistently, we tried to defined this relation and explore the influence of gender and asthma status (child- and adult-onset asthma) on this issue. METHODS: We searched published reports that described the relationship of asthma and CHD. RESULTS: Eleven trials were identified, covering 666,355 subjects. Asthma overall was significantly associated with CHD both for prospective trials (HR 1.34 [1.09,1.64], P = 0.005) and for retrospective trials(OR 1.29 [1.13,1.46], P = 0.001), when compared to individuals without asthma. Subgroup analysis split by gender indicated that females with asthma were significantly associated with CHD (HR 1.40 [1.20,1.62], P<0.001), but males with asthma were not significantly related with CHD (HR 1.19 [0.98,1.44], P = 0.07). For the four subgroups (Females with adult-onset asthma,males with adult-onset asthma,females with child-onset asthma,and males with child-onset asthma), pooled analysis of two trials indicated that only females with adult-onset asthma were significantly associated with CHD (HR 2.06 [1.32,3.19], P<0.001). CONCLUSIONS: Our data indicated that asthma was associated with CHD, and the relationship between them seemed to derived mostly from females with adult-onset asthma. Considering the limits of our study, these findings should be taken with caution.

In situ synthesis of cobalt ferrites-embedded hollow N-doped carbon as an outstanding catalyst for elimination of organic pollutants.

Using polydopamine-metal ions complex as precursor, hollow mesoporous N-doped carbon microspheres encapsulating spinel ferrites nanocrystals (HM-NC/CoFe2O4) were facilely prepared with the aim of creating a novel heterogeneous catalyst for sulfate radical-based oxidation of organic contaminants. The surface morphology, structure and composition of HM-NC/CoFe2O4 catalyst were thoroughly investigated. The applicability of the catalyst was systematically assessed through numerous controlled trials, several operating parameters, as well as different model pollutants by means of peroxymonosulfate (PMS) activation. Outstanding efficiency and excellent reusability were achieved due to the unique structure and composition of HM-NC/CoFe2O4. The HM-NC scaffold with high porosity and surface area not only stabilizes the CoFe2O4 nanoparticles but also greatly facilitates the accessibility and adsorption of substrates to the active sites. In addition, both HM-NC and CoFe2O4 on the material surface can act as active sites. Sulfate radicals and hydroxyl radicals are identified as main active species and a possible enhancement mechanism of catalytic performance is also proposed. Due to the simple synthesis method, low-cost precursors, unique structure and excellent catalytic activity and stability, this novel composite have great potential as new strategic materials for remediation of water pollution.

Phylogenetic and antigenic characterization of reassortant H9N2 avian influenza viruses isolated from wild waterfowl in the East Dongting Lake wetland in 2011-2012.

BACKGROUND: Wild waterfowl are recognized as the natural reservoir for influenza A viruses. Two distinct lineages, the American and Eurasian lineages, have been identified in wild birds. Gene flow between the two lineages is limited. The H9N2 virus has become prevalent in poultry throughout Eurasia, and mainly circulates in wild ducks and shorebirds in North America. METHODS: In this study, 22 H9N2 avian influenza viruses were isolated from wild waterfowl feces in East Dongting Lake Nature Reserve in November 2011 and March 2012. The phylogenetic, molecular, and antigenic characteristics of these viruses were analyzed based on analyses of the whole genome sequence of each isolate. RESULTS: Phylogenetic analyses indicated that these H9N2 viruses were generated by reassortment events. The HA, NA, PA, and NS genes were derived from the American gene pool, and the other four genes were derived from the Eurasian gene pool. Antigenic analyses indicated that these viruses were significantly different from the Eurasian lineage viruses. CONCLUSIONS: This study presents the isolation of novel intercontinental recombinant H9N2 viruses from wild waterfowl in the East Dongting Lake wetland. The novel genotype H9N2 virus has not been detected in poultry in the region yet, and may be transmitted to naïve birds in poultry farms. Therefore, our results highlight the need for ongoing surveillance of wild birds and poultry in this region.

Investigation of avian influenza infections in wild birds, poultry and humans in Eastern Dongting Lake, China.

We investigated avian influenza infections in wild birds, poultry, and humans at Eastern Dongting Lake, China. We analyzed 6,621 environmental samples, including fresh fecal and water samples, from wild birds and domestic ducks that were collected from the Eastern Dongting Lake area from November 2011 to April 2012. We also conducted two cross-sectional serological studies in November 2011 and April 2012, with 1,050 serum samples collected from people exposed to wild birds and/or domestic ducks. Environmental samples were tested for the presence of avian influenza virus (AIV) using quantitative PCR assays and virus isolation techniques. Hemagglutination inhibition assays were used to detect antibodies against AIV H5N1, and microneutralization assays were used to confirm these results. Among the environmental samples from wild birds and domestic ducks, AIV prevalence was 5.19 and 5.32%, respectively. We isolated 39 and 5 AIVs from the fecal samples of wild birds and domestic ducks, respectively. Our analysis indicated 12 subtypes of AIV were present, suggesting that wild birds in the Eastern Dongting Lake area carried a diverse array of AIVs with low pathogenicity. We were unable to detect any antibodies against AIV H5N1 in humans, suggesting that human infection with H5N1 was rare in this region.

[Effect of dexmedetomidine pretreatment on hypoxia/reoxygenation-induced injury in human umbilical vein endothelial cells and the possible mechanism].

OBJECTIVE: To investigate the effect of dexmedetomidine pretreatment on hypoxia/reoxygenation-induced injury in human umbilical vein endothelial cells and the possible mechanism. METHODS: Cultured human umbilical vein endothelial cell-12 (HUVEC-12) were randomly divided into four groups(n = 24): group control (C), group dexmedetomidine (D), group hypoxia/reoxygenation (H/R), group hypoxia/reoxygenation plus dexmedetomidine (H/R+D). In groups D and H/R+D, Dexmedetomidine 50 µmol/L was added to the culture medium and the cells were incubated for 2 h. Then groups C and D were exposed to regular incubator and incubated for 12 h, groups H/R and H/R+D were incubated in an anaerobic chamber for 6 h and then returned to a regular incubator and incubated for 6 h. Cell growth conditions were observed under inverted microscope, the cell viability and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CHOP mRNA. Western blotting was used to detect the expression of CHOP and cleaved caspase-3 protein. RESULTS: Compared with group C, the cell survival rate was significantly decreased, the expression of CHOP mRNA and CHOP protein, cleaved caspase-3 protein were up-regulated, the apoptotic rate was significantly increased in group H/R and group H/R+D (P < 0.05),No significant difference was found in group D (P > 0.05);compared with group H/R, the cell survival rate was significantly increased, the expression of CHOP mRNA and CHOP protein, cleaved caspase-3 protein were down-regulated, the apoptotic rate was decreased significantly in the group H/R+D (P < 0.05). CONCLUSIONS: Dexmedetomidine pretreatment can effectively attenuate hypoxia/reoxygenation-induced apoptosis to human umbilical vein endothelial cell-12. The mechanism maybe related with down-regulating the expression of CHOP.