The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies

<p>Abstract</p> <p>Background</p> <p><it>CYP2E1 </it>encodes a member of the cytochrome P450 superfamily of enzymes which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. The PstI/RsaI and DraI polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of head and neck cancer, but the results are conflicting.</p> <p>Methods</p> <p>We performed a meta-analysis using 21 eligible case-control studies with a total of 4,951 patients and 6,071 controls to summarize the data on the association between the <it>CYP2E1 </it>PstI/RsaI and DraI polymorphism and head and neck cancer risk, especially by interacting with smoking or alcohol.</p> <p>Results</p> <p>Compared with the wild genotype, the OR was 1.96 (95% CI: 1.33-2.90) for PstI/RsaI and 1.56 (95% CI: 1.06-2.27) for DraI polymorphism respectively. When stratified according to ethnicity, the OR increased in the Asians for both polymorphisms (OR = 2.04, 95% CI: 1.32-3.15 for PstI/RsaI; OR = 2.04, 95% CI: 1.27-3.29 for DraI), suggesting that the risk is more pronounced in Asians.</p> <p>Conclusion</p> <p>Our meta-analysis suggests that individuals with the homozygote genotypes of PstI/RsaI or DraI polymorphism might be associated with an increased risk of head and neck cancer, especially in Asians.</p

Genetic Polymorphisms in CYP2E1: Association with Schizophrenia Susceptibility and Risperidone Response in the Chinese Han Population

CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.10) are reported to be related to the development of several mental diseases and to be involved in the clinical efficacy of some psychiatric medications. We investigated the possible association of CYP2E1 polymorphisms with susceptibility to schizophrenia in the Chinese Han Population as well as the relationship with response to risperidone in schizophrenia patients.In a case-control study, we identified 11 polymorphisms in the 5' flanking region of CYP2E1 in 228 schizophrenia patients and 384 healthy controls of Chinese Han origin. From among the cases, we chose 130 patients who had undergone 8 weeks of risperidone monotherapy to examine the relationship between their response to risperidone and CYP2E1 polymorphisms. Clinical efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS).Statistically significant differences in allele or genotype frequencies were found between cases and controls at rs8192766 (genotype p = 0.0048, permutation p = 0.0483) and rs2070673 (allele: p = 0.0018, permutation p = 0.0199, OR = 1.4528 95%CI = 1.1487-1.8374; genotype: p = 0.0020, permutation p = 0.0225). In addition, a GTCAC haplotype containing 5 SNPs (rs3813867, rs2031920, rs2031921, rs3813870 and rs2031922) was observed to be significantly associated with schizophrenia (p = 7.47E-12, permutation p<0.0001). However, no association was found between CYP2E1 polymorphisms/haplotypes and risperidone response.Our results suggest that CYP2E1 may be a potential risk gene for schizophrenia in the Chinese Han population. However, polymorphisms of the CYP2E1 gene may not contribute significantly to individual differences in the therapeutic efficacy of risperidone. Further studies in larger groups are warranted to confirm our results

Characterization of the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana (Myrtaceae)

Plants in the genus Melaleuca have been widely used as traditional medicine mainly because of their broad spectrum antimicrobial activity. In this study, we reported the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana. The chloroplast genome of this species is 158,855 bp in length, including a pair of inverted repeat regions (IRs) (26,727 bp) that is divided by a large single-copy (LSC) area (87,338 bp) and a small single-copy (SSC) area (18,063 bp). The circular chloroplast genome of M. cajuputi subsp. cumingiana contains 135 unique genes, composing of 87 protein-coding genes, 40 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicates that M. cajuputi subsp. cumingiana was clustered with species in the tribe Melaleuceae. This complete chloroplast genome of M. cajuputi subsp. cumingiana will provide a powerful tool to accelerate breeding, biotechnological and phylogenetic study

Calcitonin gene‐related peptide and persistent corneal pain: A trigeminal nerve sensitization perspective

Abstract Persistent corneal pain (PCP) has excellent research prospects, especially the central sensitization mechanism of the trigeminal nerve, which is involved in migraine, corneal pain, and trigeminal neuralgia. The cornea has dense sensory innervation, and repeated corneal neuropathic pain has been associated with trigeminal nerve central sensitization, which is induced in PCP. The calcitonin gene‐related peptide (CGRP) is involved in corneal pain conduction, injury protection, and immune homeostasis. A high CGRP level maintains corneal pain perception and protects corneal epithelial cells. However, a persistently high CGRP level causes hypersensitivity of the corneal and trigeminal nerves, resulting in PCP. CGRP‐related drugs can effectively improve trigeminal nerve sensitization and relieve central sensitization‐related pain (PCP, migraine, and trigeminal neuralgia). Exploring the role of CGRP in PCP's pain sensitization mechanism is vital in the pain perception field, with the potential to improve the quality of life of patients with PCP and strengthen the understanding of CGRP's dual role in corneal pain

Comparative study of transcriptome profiles in the eyes and brain of the tiger puffer Takifugu rubripes brooder under red light filtered LED

Light spectrum is an important environmental factor affecting fish activities. However, the existing studies on spectrum are usually conducted under monochromatic light, which are multiple variables compared to the natural light conditions and increase uncertainty. The results may be caused by the absence of all other chromatic lights. The tiger puffer Takifugu rubripes is an important commercial marine fish in China, Japan, and Korea. In this study, the effects of red light on the eyes and brain of T. rubripes brooder, including histological changes in retina and optic tectum, the levels of oxidative stress indicators in serum, and changes in gene expression at transcriptome level were examined, after the treatment of full spectrum LED (Fs) and red light filtered LED (Rf) for 52 days. The results showed that the growth and histological structure of retina and optic tectum were not significantly altered. While, Rf significantly decreased the activity of superoxide dismutase and catalase, and increased the content of cortisol (P < 0.05), but had no effect on the levels of glutathione peroxidase and malondialdehyde. Transcriptome data revealed that there were 147 differentially expressed genes (DEGs) in the eyes of Rf vs Fs. Many DEGs related to vision changed significantly. KEGG enrichment and GSEA analyses showed that the significantly enriched arachidonic acid pathway down-regulated in the Rf group, in which genes related to sexual maturation and ovulation presented significant changes, suggesting that Rf may affect the ovulation process through this pathway. In the brain, the number of DEGs was only 20, which are most correlated with circadian rhythm. The present study displayed for the first time the role of red light in promoting ovulation in mature fish by filtering it, which may provide more supports to highlight the function of red light in fish culture

Dynamic network of transcription and pathway crosstalk to reveal molecular mechanism of MGd-treated human lung cancer cells.

Recent research has revealed various molecular markers in lung cancer. However, the organizational principles underlying their genetic regulatory networks still await investigation. Here we performed Network Component Analysis (NCA) and Pathway Crosstalk Analysis (PCA) to construct a regulatory network in human lung cancer (A549) cells which were treated with 50 uM motexafin gadolinium (MGd), a metal cation-containing chemotherapeutic drug for 4, 12, and 24 hours. We identified a set of key TFs, known target genes for these TFs, and signaling pathways involved in regulatory networks. Our work showed that putative interactions between these TFs (such as ESR1/Sp1, E2F1/Sp1, c-MYC-ESR, Smad3/c-Myc, and NFKB1/RELA), between TFs and their target genes (such as BMP41/Est1, TSC2/Myc, APE1/Sp1/p53, RARA/HOXA1, and SP1/USF2), and between signaling pathways (such as PPAR signaling pathway and Adipocytokines signaling pathway). These results will provide insights into the regulatory mechanism of MGd-treated human lung cancer cells

p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation

Abstract Background Brachydactyly type A1 (BDA1, OMIM 112500) is a rare inherited malformation characterized primarily by shortness or absence of middle bones of fingers and toes. It is the first recorded disorder of the autosomal dominant Mendelian trait. Indian hedgehog (IHH) gene is closely associated with BDA1, which was firstly mapped and identified in Chinese families in 2000. Previous studies have demonstrated that BDA1-related mutant IHH proteins affected interactions with its receptors and impaired IHH signaling. However, how the altered signaling pathway affects downstream transcriptional regulation remains unclear. Results Based on the mouse C3H10T1/2 cell model for IHH signaling activation, two recombinant human IHH-N proteins, including a wild type protein (WT, amino acid residues 28–202) and a mutant protein (MT, p.E95k), were analyzed. We identified 347, 47 and 4 Gli1 binding sites in the corresponding WT, MT and control group by chromatin immunoprecipitation and the overlapping of these three sets was poor. The putative cis regulated genes in WT group were enriched in sensory perception and G-protein coupled receptor-signaling pathway. On the other hand, putative cis regulated genes were enriched in Runx2-related pathways in MT group. Differentially expressed genes in WT and MT groups indicated that the alteration of mutant IHH signaling involved cell-cell signaling and cellular migration. Cellular assay of migration and proliferation validated that the mutant IHH signaling impaired these two cellular functions. Conclusions In this study, we performed integrated genome-wide analyses to characterize differences of IHH/Gli1 downstream regulation between wild type IHH signaling and the E95K mutant signaling. Based on the cell model, our results demonstrated that the E95K mutant signaling altered Gli1-DNA binding pattern, impaired downstream gene expressions, and leaded to weakened cellular proliferation and migration. This study may help to deepen the understanding of pathogenesis of BDA1 and the role of IHH signaling in chondrogenesis

MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation

AbstractMiR-140 is a microRNA specially involved in chondrogenesis and osteoarthritis pathogenesis. However, its transcriptional regulation and target genes in cartilage development are not fully understood. Here we detected that miR-140 was uniquely expressed in chondrocyte and suppressed by Wnt/β-catenin signalling. The miR-140 primary transcript was an intron-retained RNA co-expressed with Wwp2-C isoform, which was directly induced by Sox9 through binding to the intron 10 of Wwp2 gene. Knockdown of miR-140 in limb bud micromass cultures resulted in arrest of chondrogenic proliferation. Sp1, the activator of the cell cycle regulator p15INK4b, was identified as a target of miR-140 in maintaining the chondrocyte proliferation. Collectively, our findings expand our understanding of the transcriptional regulation and the chondrogenic role of miR-140 in chondrogenesis

Open Access Identification of aberrant microRNA expression pattern in pediatric gliomas by microarray

Background: Brain tumor remains the leading cause of disease-related death in children. Many studies have focused on the complex biological process involved in pediatric brain tumors but little is know about the possible role of microRNAs in the genesis of these tumors. Methods: In this study, we used a microRNA microarray assay to study the expression pattern of microRNAs in pediatric gliomas and matched normal tissues. Results: We found 40 differentially expressed microRNAs, among which miR-1321, miR-513b, miR-769-3p were found be related to cancer genesis for the first time. The expression of selected microRNAs were then confirmed by qRT-PCR. Furthermore, GO and pathway analysis showed that the target genes of the 40 differentially expressed microRNAs were significantly enriched in nervous system-related and tumor-related biological processes and signaling pathways. Additionally, an apoptosis-related network of microRNA–mRNA interaction, representing the critical microRNAs and their targets, was constructed based on microRNA status. Conclusions: In the present study we identified the changed expression pattern of microRNAs in pediatric gliamas. Our study also provides a better understanding of pediatric brain tumor biology and may assist in the development of less toxic therapies and in the search for better markers for disease stratification. Virtual slides: The virtual slide(s) for this article can be found here

Hierarchical clustering in the context of a defined regulatory network.

<p>(A) The adjusted strength matrix was used for clustering, with the gene expression matrix appended. Four major clusters, which have more than three associated genes, were highlighted. In the adjusted strength matrix heatmap, white indicated a weak regulatory influence. (B) Clustering with gene expression.</p