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As one of the most popular woody species that blooms in summer, Lagerstroemia speciosa has been used abundantly in urban landscape for its excellent floral beauty. For the first time, we discovered a double-flower variant with all petaloid stamens. To understand the molecular basis of this variation, we contrasted the transcriptomes of single- and double-flower buds at three stamen development stages. In total, 73,536 unigenes were mapped and 30,714 differently expressed genes (DEGs) were identified in the tissues. We focused on the DEGs expressing in both phenotypes and investigated the association of their expression profiles with their functions in transcription pathways. Furthermore, we performed WGCNA and identified co-expressed genes with four floral homeotic genes as hubs (MADS16 , Unigene0026169; AP2 , Unigene0042732; SOC1 , Unigene0046314; AG , Unigene0056437). The expression of these hub genes has been conserved across the three developmental stages but significantly different between the two floral phenotypes. As a result, the robust transcriptional regulation of stamen petaloidy in double flowers was deduced. These findings will help to unravel the regulatory mechanisms of several specific genes, thereby providing a basis to study double-flower molecular breeding in L. speciosa. Image 1 • All stamens are converted into petals in our first discovered double-flower Lagerstroemia speciosa. • Phytohormone signals and transcription factors involve in the conversion of stamen petaloidy. • Floral homeotic genes are co-expressed and take a conservatively significant role in the regulatory network. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii can infect all warm-blooded animals including human beings. T. gondii dense granule protein 16 (TgGRA16) as a crucial virulence factor could modulate the host gene expression. Here, a DNA vaccine expressing TgGRA16 was constructed to explore the protective efficacy against T. gondii infection in Kunming mice. The immune responses induced by pVAX-GRA16 were also evaluated. Mice immunized with pVAX-GRA16 could elicit higher levels of specific IgG antibody and strong cellular response compared to those in controls. The DNA vaccination significantly increased the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) and the percentages of CD4+ and CD8+ T cells in mice. After lethal challenge, mice immunized with pVAX-GRA16 (8.4±0.78 days) did not show a significant longer survival time than that in controls (7.1±0.30 days) (p>0.05). However, in chronic toxoplasmosis model (administration of 10 brain cysts of PRU strain orally), numbers of tissue cysts in mice immunized with pVAX-GRA16 were significantly reduced compared to those in controls (p<0.05) and the rate of reduction could reach 43.89%. The results indicated that the TgGRA16 would be a promising vaccine candidate for further development of effective epitope-based vaccines against chronic T. gondii infection in mice. [ABSTRACT FROM AUTHOR]

Background: Disulfidptosis is a recently discovered form of programmed cell death that could impact cancer development. Nevertheless, the prognostic significance of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) requires further clarification. Methods: This study systematically explores the genetic and transcriptional variability, prognostic relevance, and expression profiles of DRGs. Clusters related to disulfidptosis were identified through consensus clustering. We used single-sample gene set enrichment analysis and ESTIMATE to assess the tumor microenvironment (TME) in different subgroups. We conducted a functional analysis of differentially expressed genes between subgroups, which involved gene ontology, the Kyoto encyclopedia of genes and genomes, and gene set variation analysis, in order to elucidate their functional status. Prognostic risk models were developed using univariate Cox regression and the least absolute shrinkage and selection operator regression. Additionally, single-cell clustering and cell communication analysis were conducted to enhance the understanding of the importance of signature genes. Lastly, qRT-PCR was employed to validate the prognostic model. Results: Two clearly defined DRG clusters were identified through a consensus-based, unsupervised clustering analysis. Observations were made concerning the correlation between changes in multilayer DRG and various clinical characteristics, prognosis, and the infiltration of TME cells. A well-executed risk assessment model, known as the DRG score, was developed to predict the prognosis of LUAD patients. A high DRG score indicates increased TME cell infiltration, a higher mutation burden, elevated TME scores, and a poorer prognosis. Additionally, the DRG score showed a significant correlation with the tumor mutation burden score and the tumor immune dysfunction and exclusion score. Subsequently, a nomogram was established for facilitating the clinical application of the DRG score, showing good predictive ability and calibration. Additionally, crucial DRGs were further validated by single-cell sequencing data. Finally, crucial DRGs were further validated by qRT-PCR and immunohistochemistry. Conclusion: Our new DRG signature risk score can predict the immune landscape and prognosis of LUAD. It also serves as a reference for LUAD's immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Accumulation of amyloid β-peptide (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. Therefore, we conduct a systematic identification of the promising role of miRNAs in Aβ deposition, and shed light on the molecular mechanism of target miRNAs underlying SH-SY5Y cells treated with Aβ-induced cytotoxicity. Results: Statistical analyses of microarray data revealed that 155 significantly upregulated and 50 significantly downregulated miRNAs were found on the basis of log2 | Fold Change | ≥ 0.585 and P < 0.05 filter condition through 2588 kinds of mature miRNA probe examined. PCR results show that the expression change trend of the selected six miRNAs (miR-6845-3p, miR-4487, miR-4534, miR-3622-3p, miR-1233-3p, miR-6760-5p) was consistent with the results of the gene chip. Notably, Aβ25–35 downregulated hsa-miR-4487 and upregulated hsa-miR-6845-3p in SH-SY5Y cell lines associated with Aβ-mediated pathophysiology. Increase of hsa-miR-4487 could inhibit cells apoptosis, and diminution of hsa-miR-6845-3p could attenuate axon damage mediated by Aβ25–35 in SH-SY5Y. Conclusions: Together, these findings suggest that dysregulation of hsa-miR-4487 and hsa-miR-6845-3p contributed to the pathogenesis of AD associated with Aβ25–35 mediated by triggering cell apoptosis and synaptic dysfunction. It might be beneficial to understand the pathogenesis and development of clinical diagnosis and treatment of AD. Further, our well-designed validation studies will test the miRNAs signature as a prognostication tool associated with clinical outcomes in AD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of miRNAs involving oxidative stress response in doxorubicin (DOX)-induced cardiotoxicity based on the data from Gene Expression Omnibus (GEO) database and experimental results via integrated bioinformatics analysis. MiRNA expression profiles of DOX-induced cardiotoxicity in rat myocardial tissues and adult rat cardiomyocytes (ARC) were extracted from GEO datasets (GSE36239). Differential expression miRNA (DEMs) were separately captured in rat myocardial tissues and in ARC, and intersected between rat myocardial tissues and ARC via Venny 2.1. Subsequently, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analyzed 46 target genes of miR-143, one of 6 DEMs, and HIF-1 and PI3K-Akt signaling pathway were significantly enriched. Further experimental results showed DOX-induced oxidative stress downregulated the expression of miR-143, and then promoted target gene Bbc3 expression and H9c2 apoptosis, the intervention of phosphocreatine (PCr) or N -acetyl-L-cystine (NAC) alleviated oxidative stress, apoptosis and Bbc3 expression, upregulated miR-143 in DOX-induced cardiotoxicity in vivo and in vitro. Our findings elucidated the regulatory network between miR-143 and oxidative stress in DOX-induced cardiotoxicity, and might unveiled a potential biomarker and molecular mechanisms, which could be helpful to the diagnosis and treatment of DOX-induced cardiotoxicity. • Analysis of miRNA expression profile of GSE36239 obtained from GEO database. • The expression of miR-143, One of DEMs, was verified in vivo and in vitro. • Enrichment analysis of GO and KEGG signal pathway on target genes of miR-143. • Potential role of miR-143 in PCr improvement of DOX-cardiotoxicity. [ABSTRACT FROM AUTHOR]

Aims. The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods. Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results. H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion. The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC. [ABSTRACT FROM AUTHOR]

H. pylori-related gastric diseases (HPGD) are a series of gastric mucosal benign and malignant lesions associated with H. pylori infection. Exploring the pathogenesis of HPGD will be of great significance to prevent and treat gastric malignancy. Traditional Chinese medicine (TCM) syndrome is the essence of TCM, reflecting the state of whole body. Potential similarities of TCM syndrome may provide a new perspective in understanding development and treatment of diseases. To seek an early warning signal for gastric malignant pathology and similarities of TCM syndrome from the viewpoint of molecular biology, we examined the relationships among H. pylori, gastric pathology, and TCM syndrome and effects of Interleukin-1β (IL-1β) gene polymorphisms and expression on gastric pathology and TCM syndrome in HPGD. The results indicated that detection of H. pylori with differentiation of TCM syndrome may have a predictive function to gastric pathology. H. pylori may lead to gastric atrophy via enhancing IL-1β mRNA expression, and IL-1β mRNA overexpression in gastric mucosa may be one of the generality characteristics for H. pylori-negative subjects with syndrome of dampness-heat in the spleen and stomach. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the clinicopathological significance and the role of Jun Activation Domain-Binding Protein 1 (JAB1), Ser10-phosphorylated p27 (p27S10), and total p27 in human hepatocellular carcinoma (HCC) prognosis. Methods: We evaluated the expression of JAB1 and p27S10 in tissues by immunohistochemical and immunoblot analyses. p27 Ser10 phosphorylation and Ser10 phosphorylation-dependent p27-JAB1 interaction were demonstrated in proliferating Huh7 cells following transfection of pEGFP-p27WT/p27S10A/p27S10D plasmids and pcDNA3.1-p27WT/p27S10A/p27S10D-Myc plasmids. Univariate and multivariate analysis were used to determine their role in HCC prognosis. Results: JAB1 and p27S10 are overexpressed in HCC samples compared with paired normal tissues. There was a strong correlation between JAB1 and p27S10 expression ( P < 0.001), and expression of both inversely correlated with total p27 levels ( P < 0.001). High JAB1 and p27S10 expression correlated with histological grade, vascular invasion, and serum α-fetoprotein (AFP) level (all P < 0.01). Total p27 expression also correlated with histological tumor grade ( P = 0.048) and AFP level ( P = 0.015). The p27S10(high)/JAB1(high)/p27(1ow) profile was the most reliable indication of poor prognostic. Ser10 phosphorylation increased and total p27 levels decreased in a time-dependent manner in serum-starved Huh7 cells following addition of serum. Immunoprecipitation analysis revealed that p27 Ser-to-Asp substitution at position 10 (S10D) markedly enhanced the interaction between JAB1 and p27, but replacement of S10A reduced binding. Conclusions: This study revealed that combined JAB1, p27S10, and total p27 expression may serve as a prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

Abstract: Rabbit (Oryctolagus cuniculus) is the only lagomorph animal of which the genome has been sequenced. Establishing a rabbit miRNA resource will benefit subsequent functional genomic studies in mammals. We have generated small RNA sequence reads with SOLiD and Solexa platforms to identify rabbit miRNAs, where we identified 464 pre-miRNAs and 886 mature miRNAs. The brain and heart miRNA libraries were used for further in-depth analysis of isomiR distributions. There are several intriguing findings. First, several rabbit pre-miRNAs form highly conserved clusters. Second, there is a preference in selecting one strand as mature miRNA, resulting in an arm selection preference. Third, we analyzed the isomiR expression and validated the expression of isomiR types in different rabbit tissues. Moreover, we further performed additional small RNA libraries and defined miRNAs differentially expressed between brain and heart. We conclude also that isomiR distribution profiles could vary between brain and heart tissues. [Copyright &y& Elsevier]

Abstract: In bacterial-induced peripheral nervous system (PNS) inflammation, Schwann cells (SCs) are activated, producing inducible nitric oxide synthase (iNOS), contributed to the pathogenesis of demyelinating disease, such as multiple sclerosis. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been shown to play a protective role in cellular inflammatory responses. Here we showed that LPS-induced iNOS biosynthesis was in a concentration and time-dependent manner. In LPS-treated primary SCs, retreatment with PPAR-γ agonist remitted the increase of iNOS, p38 phosphorylation and TLR4, MyD88, augmented the expression of PPAR-γ and localization in nuclear. Coadministration of GW 9662 reversed the effect of PPAR-γ agonists. These results suggest that PPAR-γ agonists, 15d-PGJ2 and pioglitazone, had the anti-inflammatory effects. [Copyright &y& Elsevier]