A prominent gene activation role for C-terminal binding protein in mediating PcG/trxG proteins through Hox gene regulation.

The evolutionarily conserved C-terminal binding protein (CtBP) has been well characterized as a transcriptional co-repressor. Herein, we report a previously unreported function for CtBP, showing that lowering CtBP dosage genetically suppresses Polycomb group (PcG) loss-of-function phenotypes while enhancing that of trithorax group (trxG) in Drosophila, suggesting that the role of CtBP in gene activation is more pronounced in fly development than previously thought. In fly cells, we show that CtBP is required for the derepression of the most direct PcG target genes, which are highly enriched by homeobox transcription factors, including Hox genes. Using ChIP and co-IP assays, we demonstrate that CtBP is directly required for the molecular switch between H3K27me3 and H3K27ac in the derepressed Hox loci. In addition, CtBP physically interacts with many proteins, such as UTX, CBP, Fs(1)h and RNA Pol II, that have activation roles, potentially assisting in their recruitment to promoters and Polycomb response elements that control Hox gene expression. Therefore, we reveal a prominent activation function for CtBP that confers a major role for the epigenetic program of fly segmentation and development.

Rational of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of endocervical canal low-grade squamous intraepithelial lesion with high-risk human papillomavirus infection.

BACKGROUND: The detection and continuous monitoring of low-grade squamous intraepithelial lesions (LSIL) within the endocervical canal pose considerable challenges, and the effectiveness of ablation treatment is also constrained. In this context, the potential efficacy of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) in targeting these concealed lesions merits exploration. The present study undertakes a comprehensive analysis of the clinical effectiveness and safety aspects associated with the utilization of 5-ALA PDT. METHODS: A retrospective analysis was conducted on a cohort of 13 patients who were diagnosed with LSIL within the endocervical canal, concomitant with high-risk human papillomavirus (hrHPV) infection. These patients were subjected to treatment with 5-ALA PDT and subsequently monitored over a period of 3-6 months following the intervention. RESULTS: The study cohort comprised 13 patients, among whom 4 presented with isolated lesions within the endocervical canal, 5 exhibited LSIL involving both the endocervical canal and the cervix vaginal portion, 3 displayed LSIL within the endocervical canal in conjunction with vaginal involvement, and 1 patient demonstrated lesions across all three of these anatomical sites. All identified lesions underwent therapeutic intervention via 5-ALA PDT. Before treatment initiation, 9 patients returned positive results in the liquid-based cytologic test (LBC), 4 displayed concurrent multiple hrHPV infections, and 5 manifested infections specifically with HPV 16/18. Subsequent to the application of 5-ALA PDT, regression was observed in the LBC results of all patients, with only 3 individuals retaining a singular type of hrHPV infection. Adverse reactions following treatment encompassed mild aberrant vaginal secretions and mild to moderately pronounced distending abdominal discomfort, all of which were remitted within a span of 7 days. CONCLUSIONS: Within the context of LSIL within the endocervical canal in association with hrHPV infection, the findings affirm the efficacy and safety of 5-ALA PDT as a viable therapeutic modality.

[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/ß-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 µg/ml) treatment group,a DDP (1.40 µg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/ß-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t=8.062,P=0.001;t=7.090,P=0.002),colony formation (t=8.062,P=0.001;t=6.144,P=0.004),and migration (t=7.424,P=0.002;t=4.317,P=0.013),and promoted the apoptosis (t=5.530,P=0.031;t=6.036,P=0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t=24.450,P<0.001;t=14.750,P<0.001),Snail (t=29.640,P<0.001;t=70.700,P<0.001),Slug (t=89.230,P<0.001;t=87.360,P<0.001),matrix metalloproteinase (MMP) 2 (t=84.540,P<0.001;t=67.120,P<0.001),and MMP9 (t=19.010,P<0.001;t=10.890,P<0.001),as well as those of Wnt/ß-catenin signaling pathway related proteins including Wnt (t=35.480,P<0.001;t=14.670,P<0.001),ß-catenin (t=155.800,P<0.001;t=118.100,P<0.001),C-myc (t=20.870,P<0.001;t=3.334,P=0.029),and cyclin D1 (t=5.007,P=0.008;t=8.347,P=0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin (t=36.450,P<0.001;t=33.810,P<0.001) and ZO-1 (t=37.060,P<0.001;t=37.030,P<0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/ß-catenin signaling pathway.

Characterization of the Sperm Proteome and Reproductive Outcomes with in Vitro, Fertilization after a Reduction in Male Ejaculatory Abstinence Period.

Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 h) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (p, < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and p, < 0.05), with 224 upregulated and 98 downregulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus, long abstinence (p, < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro, fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.

Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-naïve schizophrenia.

BACKGROUND: Schizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia. METHODS: 93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions. RESULTS: Our results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score. CONCLUSIONS: These findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.

[Mechanism of astragaloside â £ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments].

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

[Research progress on chemical constituents, pharmacological action and quality control of Scutellaria barbata].

Scutellaria barbata is a recognized anti-cancer traditional Chinese medicine, with the effects of clearing heat and detoxi-fication, dispelling blood stasis and stopping bleeding, diuresis and detumescence. At present, terpenoids, flavonoids, polysaccharides and volatile oils have been isolated from S. barbata, which have many pharmacological effects, such as resisting tumor, virus, bacteria and oxidation, and immunomodulation. This paper reviews the studies on the chemical constituents, pharmacological action and quality control of S. barbata, in the expectation of providing ideas and references for the further development and studies of S. barbata.

Polycomb inhibits histone acetylation by CBP by binding directly to its catalytic domain.

Drosophila Polycomb (PC), a subunit of Polycomb repressive complex 1 (PRC1), is well known for its role in maintaining repression of the homeotic genes and many others and for its binding to trimethylated histone H3 on Lys 27 (H3K27me3) via its chromodomain. Here, we identify a novel activity of PC: inhibition of the histone acetylation activity of CREB-binding protein (CBP). We show that PC and its mammalian CBX orthologs interact directly with the histone acetyltransferase (HAT) domain of CBP, binding to the previously identified autoregulatory loop, whose autoacetylation greatly enhances HAT activity. We identify a conserved PC motif adjacent to the chromodomain required for CBP binding and show that PC binding inhibits acetylation of histone H3. CBP autoacetylation impairs PC binding in vitro, and PC is preferentially associated with unacetylated CBP in vivo. PC knockdown elevates the acetylated H3K27 (H3K27ac) level globally and at promoter regions of some genes that are bound by both PC and CBP. Conversely, PC overexpression decreases the H3K27ac level in vivo and also suppresses CBP-dependent Polycomb phenotypes caused by overexpression of Trithorax, an antagonist of Polycomb silencing. We find that PC is physically associated with the initiating form of RNA polymerase II (Pol II) and that many promoters co-occupied by PC and CBP are associated with paused Pol II, suggesting that PC may play a role in Pol II pausing. These results suggest that PC/PRC1 inhibition of CBP HAT activity plays a role in regulating transcription of both repressed and active PC-regulated genes.

Repair of osteonecrosis of the femoral head : 3D printed Cervi cornus Colla deproteinized bone scaffolds.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common joint disease and a major cause of morbidity. OBJECTIVE: In this study Cervi cornus Colla (CCC) deproteinized bone scaffolds were designed and three dimensional (3D)-printed for the repair of ONFH in rats. MATERIAL AND METHODS: The CCC-deproteinized bone scaffolds were 3D-printed using polycaprolactone mixed with the CCC-deproteinized bone powder. The scaffolds were viewed under a scanning electron microscope and subjected to compression analysis. Osteoblasts were isolated from rats and coated onto the scaffolds. Cell proliferation assays were performed with the MTT (3­[4,5-dimethylthiazole­2]-2,5-diphenyltetrazolium bromide) kit from Promega. An ONFH was induced in rats and a CCC-deproteinized bone scaffold was implanted into the necrotic femoral head. General observations, X­ray imaging, and pathological examination of the femoral head were performed to evaluate the treatment of ONFH in the rats. RESULTS: The scaffolds were porous with a mean pore diameter of 315.70 ± 41.52 nm and a porosity of 72.86 ± 5.45% and exhibited favorable mechanical properties and degradation. In vitro assays showed that osteoblasts accumulated in the pores and adhered to the scaffolds. The CCC-deproteinized bone scaffolds enhanced the proliferation of osteoblasts. The in vivo experiments revealed that the general observation score of rats in the CCC-scaffold implanted group was significantly higher than that in the control group. The X­ray images showed significant alleviation of ONFH in the CCC-deproteinized bone scaffold implanted rats. The femoral heads of rats in the treatment group showed less destruction or ossification of cartilage cells, few bone cement lines, very little necrosis or irregularities on the cartilage surface and only a small amount of inflammatory cell infiltration in the medullary cavity. CONCLUSION: These results suggest that CCC-deproteinized bone scaffold implants facilitated the repair of ONFH in rats. This research provides a new therapeutic approach for the repair of early and mid-term ONFH.

Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing.

Trithorax (TRX) antagonizes epigenetic silencing by Polycomb group (PcG) proteins, stimulates enhancer-dependent transcription, and establishes a 'cellular memory' of active transcription of PcG-regulated genes. The mechanisms underlying these TRX functions remain largely unknown, but are presumed to involve its histone H3K4 methyltransferase activity. We report that the SET domains of TRX and TRX-related (TRR) have robust histone H3K4 monomethyltransferase activity in vitro and that Tyr3701 of TRX and Tyr2404 of TRR prevent them from being trimethyltransferases. The trx(Z11) missense mutation (G3601S), which abolishes H3K4 methyltransferase activity in vitro, reduces the H3K4me1 but not the H3K4me3 level in vivo. trx(Z11) also suppresses the impaired silencing phenotypes of the Pc(3) mutant, suggesting that H3K4me1 is involved in antagonizing Polycomb silencing. Polycomb silencing is also antagonized by TRX-dependent H3K27 acetylation by CREB-binding protein (CBP). We show that perturbation of Polycomb silencing by TRX overexpression requires CBP. We also show that TRX and TRR are each physically associated with CBP in vivo, that TRX binds directly to the CBP KIX domain, and that the chromatin binding patterns of TRX and TRR are highly correlated with CBP and H3K4me1 genome-wide. In vitro acetylation of H3K27 by CBP is enhanced on K4me1-containing H3 substrates, and independently altering the H3K4me1 level in vivo, via the H3K4 demethylase LSD1, produces concordant changes in H3K27ac. These data indicate that the catalytic activities of TRX and CBP are physically coupled and suggest that both activities play roles in antagonizing Polycomb silencing, stimulating enhancer activity and cellular memory.

Knockdown of DNMT1 and DNMT3a Promotes the Angiogenesis of Human Mesenchymal Stem Cells Leading to Arterial Specific Differentiation.

Human mesenchymal stem cells (hMSCs) possess the potential to differentiate into endothelial cells (EC). DNA methylation plays an important role in cell differentiation during development. However, the role of the DNA methyltransferases Dnmt1 and Dnmt3a in specific arterial differentiation of hMSCs is not clear. Here, we show that the CpG islands in the promoter regions of the EC specification and arterial marker genes were highly methylated in hMSCs based on bisulfite genomic sequencing. Treatment with the DNMT inhibitor 5-aza-dc induced the reactivation of EC specification and arterial marker genes by promoting demethylation of these genes as well as stimulating tube-like structure formation. The hMSCs with stable knockdown of Dnmt1/Dnmt3a were highly angiogenic and expressed several arterial specific transcription factors and marker genes. A Matrigel plug assay confirmed that Dnmt1/Dnmt3a stable knockdown hMSCs enhanced blood vessel formation compared with WT MSCs. We also identified that the transcription factor E2F1 could upregulate the transcription of arterial marker genes by binding to the promoters of arterial genes, suggesting its critical role for arterial specification. Moreover, miRNA gain/loss-of-function analyses revealed that miR152 and miR30a were involved in endothelial differentiation of hMSCs by targeting Dnmt1 and Dnmt3a, respectively. Taken together, these data suggest that Dnmt1 and Dnmt3a are critical regulators for epigenetic silencing of EC marker genes and that E2F1 plays an important role in promoting arterial cell determination. Stem Cells 2016;34:1273-1283.

The variation and clinical significance of hormone receptors and Her-2 status from primary to metastatic lesions in breast cancer patients.

The objective of this study is to investigate how the change of hormone receptor (HR) and human epidermal growth factor receptor-2 (Her-2) status is related to patients' clinical features. One hundred ninety-three cases of patients treated at general hospital of PLA from 2000 to 2015 with advanced breast cancer were included. All patients developed recurrence that were re-biopsied and had complete pathological profile both at initial diagnosis and at relapse. HR status before and after relapse were available for all patients, while only 143 cases had Her-2 status at the two stages. The changes of ER, PR, and Her-2 status and their association with clincopathological factors and DFS were analyzed. The discordant rates of ER, PR, and Her-2 status between primary breast cancer and recurrent tumor were 34.2, 38.3, and 16.8 %, respectively. At relapse, the rates of gain of ER and PR positivity were 10.9 and 13.5 %, respectively; the rates of loss of ER and PR positivity were 23.3 and 24.9 %. Loss of positivity was more frequent than gain of positivity (p ER < 0.000, p PR = 0.001). Among patients with Her-2 negative primary tumors, 15.4 % acquired Her-2 positivity at relapse; and among Her-2 positive patients at initial diagnosis, 1.4 % turned to Her-2 negative at relapse; gain of positivity was more frequent than loss of positivity (p < 0.000). Patients with tumor larger than 2 cm in diameter were more likely to experience change of Her-2 status (25.0 vs 5.8 %, p = 0.005). Yet, the change of ER/PR was not significantly associated with the size of primary tumor. Patients with ER positive recurrent disease and PR positive primary tumor had a DFS of more than 40 months. Compared to patients who maintained PR negative, patients who gained PR positivity at relapse had significantly longer DFS by 8.5 % (35.2 vs 26.7 months, p = 0.024). Patients losing ER positivity at relapse had shorter DFS by 7.8 months compared to those with stable ER positive tumors; patients gaining ER positivity experienced longer DFS by 8.3 months; but both differences were not statistically significant. Loss of Her-2 positivity was associated with longer DFS by 13.8 months as opposed to stable Her-2 status, without statistical significance. For patients with Her-2 negative primary tumor, the changes of Her-2 status were not associated with DFS. 34.2, 38.3, and 16.8 % of breast cancer patients had their ER, PR, and Her-2 status changed after recurrence, and these changes of receptor status were associated with DFS to some degree. Gain of PR positivity at relapse was significantly correlated with longer DFS.

EFFECT OF COLLA CORNUS CERVI COMBINED WITH LV-MEDIATED BMP7 TRANSFECTED BMSCs ON ANFH IN RATS.

In the present study, we investigated the combined effect of Colla Comus Cervi (CCC) and BMP7-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs) on osteogenic induction and the treatment of avascular necrosis of the femoral head (ANFH). BMSCs were isolated from rats. BMP7-overexpressing BMSCs were generated by lentiviral-mediated gene transduction. Cell proliferation, alkaline phosphatase (ALP) activity, osteogenesis related gene expression, osteocalcin levels, and calcified nodules were quantified and compared between four groups: untreated controls, BMSCs cultured with CCC complex medium, BMP7-overexpressing BMSCs, and BMP7-overexpressing BMSCs cultured with CCC complex medium (CCC+BMP7). CCC+BMP7 BMSCs showed higher proliferation rate. ALP activity and osteaocalcin content were significantly increased in CCC+BMP7 BMSCs. The osteogenesis related genes, COLI, and integrin-α2, -α5, and -ß1, were expressed significantly higher in CCC+BMP7 BMSCs. The number of calcified nodules in the CCC+BMP7 group was significantly higher than that in other groups. For in vivo assays, ANFH was induced in rats, and BMSCs were injected into the femoral head of the lower left extremity. In rats with induced ANFH, general observation scores of the CCC+BMP7 injected group were significantly higher than the model group. X-ray and microscopic observations revealed that ANFH was significantly improved and femoral head cells gradually recovered in rats treated with CCC+BMP7 BMSCs. Our results suggest that CCC+BMP7 significantly promote the proliferation and osteogenic differentiation of BMSCs in vitm. CCC+BMP7 BMSCs promote the ability of repairing ANFH in rats, providing a new therapeutic paradigm for the treatment of ANFH.

Investigation on Spectral Characteristic and Threshold Behavior of Network Structure of Ge-Sb-S Chalcogenide Glasses.

Two series of chalcogenide glasses in Ge-Sb-S ternary system were synthesized with melt-quenching method. The phycochemical properties and spectral characteristic of glasses with different content of Ge and Sb were obtained with a series of measurements, and the systematic analysis on the change of optical properties was conducted in terms of microstructure of glasses combined with the Raman spectra. With constraint theory based on mean coordination number (Z), we described the variation trend of network structure directly. It was found that as long as the value of Z reaches 2.6, new vibration peaks would be formed in the Raman spectra indicating the presence of threshold behavior as well as the change of the network structure of the Ge-Sb-S glasses which could be expressed in a specific varition in the number of metal bonds and the nonmetal bonds. The appearance of new functional groups in the network have changed the total bond energy of glasses, and then affected the energy band structure of glasses representing the corresponding threshold behavior of the value of optical band gap (Eopg).

Serum IL-17 & eotaxin levels in asthmatic patients with allergic rhinitis.

OBJECTIVE: To investigate the serum levels of Interleukin (IL)-17 and eotaxin levels and the relationship between serum IL-17, eotaxin and pulmonary function in asthmatic patients with allergic rhinitis. METHODS: Serum IL-17 and eotaxin levels in asthmatic patients with allergic rhinitis during attacking and remission and in healthy control subjects were measured using enzyme-linked immunosorbent assay (ELISA) kits. Then we studied the correlation between the serum IL-17, eotaxin levels and pulmonary function in patients. RESULTS: Serum IL-17 and eotaxin levels were significantly elevated in patients during asthma attack and remission compared with healthy control subjects. These levels in patients during asthma attack were much higher than those during remission. Furthermore, serum IL-17 and eotaxin levels were negatively correlated with pulmonary function in asthmatic patients with allergic rhinitis, respectively. CONCLUSION: Our findings suggest that IL-17 and eotaxin are important factors in asthma with allergic rhinitis, and the correlation between serum IL-17, eotaxin and lung function possibly lead to improvements in the diagnosis and treatment of asthma with allergic rhinitis and related diseases.

Polycomb silencing of the Drosophila 4E-BP gene regulates imaginal disc cell growth.

Polycomb group (PcG) proteins are best known for their role in maintaining stable, mitotically heritable silencing of the homeotic (HOX) genes during development. In addition to loss of homeotic gene silencing, some PcG mutants also have small imaginal discs. These include mutations in E(z), Su(z)12, esc and escl, which encode Polycomb repressive complex 2 (PRC2) subunits. The cause of this phenotype is not known, but the human homologs of PRC2 subunits have been shown to play a role in cell proliferation, are over-expressed in many tumors, and appear to be required for tumor proliferation. Here we show that the small imaginal disc phenotype arises, at least in part, from a cell growth defect. In homozygous E(z) mutants, imaginal disc cells are smaller than cells in normally proliferating discs. We show that the Thor gene, which encodes eIF4E-binding protein (4E-BP), the evolutionarily conserved inhibitor of cap-dependent translation and potent inhibitor of cell growth, is involved in the development of this phenotype. The Thor promoter region contains DNA binding motifs for transcription factors found in well-characterized Polycomb response elements (PREs), including PHO/PHOL, GAGA factor, and others, suggesting that Thor may be a direct target of Polycomb silencing. We present chromatin immunoprecipitation evidence that PcG proteins are bound to the Thor 5' region in vivo. The Thor gene is normally repressed in imaginal discs, but Thor mRNA and 4E-BP protein levels are elevated in imaginal discs of PRC2 subunit mutant larvae. Deletion of the Thor gene in E(z) mutants partially restores imaginal disc size toward wild-type and results in an increase in the fraction of larvae that pupariate. These results thus suggest that PcG proteins can directly modulate cell growth in Drosophila, in part by regulating Thor expression.

Role and interrelationship of Gα protein, hydrogen peroxide, and nitric oxide in ultraviolet B-induced stomatal closure in Arabidopsis leaves.

Heterotrimeric G proteins have been shown to transmit ultraviolet B (UV-B) signals in mammalian cells, but whether they also transmit UV-B signals in plant cells is not clear. In this paper, we report that 0.5 W m(-2) UV-B induces stomatal closure in Arabidopsis (Arabidopsis thaliana) by eliciting a cascade of intracellular signaling events including Gα protein, hydrogen peroxide (H2O2), and nitric oxide (NO). UV-B triggered a significant increase in H2O2 or NO levels associated with stomatal closure in the wild type, but these effects were abolished in the single and double mutants of AtrbohD and AtrbohF or in the Nia1 mutants, respectively. Furthermore, we found that UV-B-mediated H2O2 and NO generation are regulated by GPA1, the Gα-subunit of heterotrimeric G proteins. UV-B-dependent H2O2 and NO accumulation were nullified in gpa1 knockout mutants but enhanced by overexpression of a constitutively active form of GPA1 (cGα). In addition, exogenously applied H2O2 or NO rescued the defect in UV-B-mediated stomatal closure in gpa1 mutants, whereas cGα AtrbohD/AtrbohF and cGα nia1 constructs exhibited a similar response to AtrbohD/AtrbohF and Nia1, respectively. Finally, we demonstrated that Gα activation of NO production depends on H2O2. The mutants of AtrbohD and AtrbohF had impaired NO generation in response to UV-B, but UV-B-induced H2O2 accumulation was not impaired in Nia1. Moreover, exogenously applied NO rescued the defect in UV-B-mediated stomatal closure in the mutants of AtrbohD and AtrbohF. These findings establish a signaling pathway leading to UV-B-induced stomatal closure that involves GPA1-dependent activation of H2O2 production and subsequent Nia1-dependent NO accumulation.

[Down-regulatory effects of budesonide on expression of STAT6 and ORMDL3 in lung tissues of asthmatic mice].

OBJECTIVE: To investigate the roles of signal transduction and activator of transcription 6 (STAT6) and orosomucoid 1-like 3 (ORMDL3) in airway remodeling among asthmatic mice and to observe the effects of budesonide (BUD) on their expression. METHODS: Thirty BALB/c mice were randomly divided into control, asthma, and BUD intervention group. The mice were sensitized and challenged with ovalbumin (OVA) to establish a mouse model of asthma. The BUD intervention group received aerosol inhalation of BUD dissolved in normal saline 30 minutes before each OVA challenge, while normal saline was used instead of OVA solution in the control group. The pathological changes in the airway were observed by hematoxylin-eosin staining and Masson staining. The interleukin-13 (IL-13) level in lung homogenate was measured by enzyme-linked immunosorbent assay. The mRNA expression of STAT6 and ORMDL3 was measured by RT-PCR. RESULTS: The asthma group showed more pathological changes in the airway than the control and BUD intervention groups, and the BUD intervention group had reduced pathological changes in the airway compared with the asthma group. The asthma and BUD intervention groups had significantly higher IL-13 levels and mRNA expression of STAT6 and ORMDL3 than the control group (P<0.05), and these indices were significantly higher in the asthma group than in the BUD intervention group (P<0.05). The Pearson correlation analysis showed that STAT6 mRNA expression was positively correlated with ORMDL3 mRNA expression (r=0.676, P=0.032). CONCLUSIONS: STAT6 and ORMDL3 may be involved in the airway remodeling of mice, and BUD can reduce airway remodeling in asthmatic mice, possibly by down-regulating mRNA expression of STAT6 and ORMDL3.

Rupture of a giant jejunal mesenteric cystic lymphangioma misdiagnosed as ovarian torsion: A case report.

BACKGROUND: Cystic lymphangioma is a rare benign tumor that affects the lymphatic system. Mesenteric lymphangiomas in the small bowel are extremely uncommon. CASE SUMMARY: We present a 21-year-old female patient who complained of abdominal pain. The diagnosis of ovarian torsion was suspected after abdominopelvic unenhanced computed tomography and ultrasound revealed a large cyst in contact with the bladder, ovary, and uterus. The patient underwent emergency laparotomy performed by gynecologists, but it was discovered that the cystic tumor originated from the jejunum. Gastrointestinal surgeons were then called in to perform a cystectomy. Pathological examination confirmed the diagnosis of cystic lymphangioma of the mesentery. The patient had an uneventful postoperative recovery. CONCLUSION: Mesenteric lymphangiomas can cause abdominal pain, and imaging techniques can help determine their characteristics, location, and size. Complete surgical excision and pathological examination are considered the standard treatment and diagnostic method.

Research progress on the role of lncRNA, circular RNA, and microRNA networks in regulating ferroptosis in osteosarcoma.

Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid peroxidation. Recent studies have shown that ncRNAs such as microRNAs, long noncoding RNAs, circular RNAs, and ferroptosis are involved in the occurrence and development of osteosarcoma (OS). Studies have confirmed that ncRNAs participate in the development of OS by regulating the ferroptosis. However, systematic summary on this topic are still lacking. This review summarises the potential role of ncRNAs in the diagnosis, treatment, drug resistance, and prognosis of OS and the basis for diagnosing, preventing, and treating clinical OS and developing effective drugs. This review summarises the latest research progress on ncRNAs that regulate ferroptosis in OS, attempts to clarify the molecular mechanisms by which ncRNAs regulate ferroptosis in the pathogenesis of OS, and elaborates on the involvement of ferroptosis in OS from the perspective of ncRNAs.