Species Differences of Bakuchiol-induced Liver Injury in Mice Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

Transcriptome Analysis of Xianlian Jiedu Prescription in Intervention of Colorectal Carcinoma Due to Dampness， Heat， Stasis， and Toxin in Mice / 中国实验方剂学杂志

ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription （XLJDP） in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing （RNA-seq）. MethodNinety male C57BL/6 mice were randomly divided into the control group， colorectal carcinoma due to dampness， heat， stasis， and toxin model group， and XLJDP group， with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate （AOM/DSS） for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin （HE） and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling， followed by gene oncology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group， XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci （ACF，P<0.01）. As revealed by HE staining， XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes （446 up-regulated and 169 down-regulated） between the model group and the blank group and 54 differentially expressed genes （29 up-regulated and 25 down-regulated） between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene （Nek7， P<0.01）， Mucin 16 （Muc16， P<0.01）， SiahE3 ubiquitin protein ligase family member 3 （Siah3， P<0.01）， regenerating islet-derived protein 3-gamma （Reg3g， P<0.01）， RNA polymerase Ⅱ elongation factor-associated factor 2 （Eaf2， P<0.01）， transforming growth factor‐alfa gene （TGF-α， P<0.05）， secretoglobin family 1A member 1 （Scgb1a1， P<0.05）， family with sequence similarity 227 member B （Fam227B， P<0.05）， cytochrome P450 family 2 subfamily c polypeptide 40 （Cyp2c40， P<0.01）， and ankyrin repeat and EF-hand domain containing protein 1 （Ankef1， P<0.05）. Enrichment analysis showed that intestinal epithelial cell proliferation， metabolism of xenobiotics by cytochrome P450， and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness， heat， stasis， and toxin in mice， which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.

Research progress of omics technology in the field of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is one of the common and severe ocular complications of diabetes mellitus, representing a leading cause of blindness among working-age people. Currently, the pathogenesis of DR is not been explained, and the treatment effect is quite limited in advanced stage. In recent years, it has been revealed in some studies that DR could produce a particularly remarkable performance in genomics, transcriptomics, epigenomics, proteomics and metabolomics. With the rapid development of high-throughput sequencing and detection technology, different omics techniques can explore the occurrence and development mechanism of DR from different omics levels. This paper introduces the research progress of DR in different omics techniques,as well as the new direction of integration analysis in multiomics with DR, and finally discusses the current existing problems and future prospects of omics technology. Therefore, the application of different omics techniques to explore the occurrence and development of DR on different levels contributes a novel idea to unraveling the pathophysiological mechanism of DR and identifying new biomarkers and therapeutic targets.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome / 中国结合医学杂志

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics.@*METHODS@#Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A@*RESULTS@#Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA@*CONCLUSION@#Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.

Drug target inference by mining transcriptional data using a novel graph convolutional network framework

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.

Differential miRNA expression in the peripheral blood of patients with Keshan disease and its mechanism / 中华地方病学杂志

Objective:Through differential miRNA expression profiles and bioinformatics in the peripheral blood of patients with Keshan disease (KD) and healthy control, to explore the possible pathogenesis of KD.Methods:Ten patients with chronic KD (KD group) were selected in the severe disease area of KD in Wulian County, and 10 healthy subjects (control group) were selected in non-KD area of Dongchangfu District, Shandong Province. Blood sample of elbow vein was collected and plasma was separated. RNA-seq technology was used to construct the differential expression profiles of miRNA in KD and control groups. Target mRNAs were screened using Starbase, miRTarBase, miRDB and TargetScan. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to investigate the possible pathogenesis of KD.Results:Compared the control group and KD group, 132 differentially expressed miRNAs were screened out, including 90 upregulated and 42 downregulated miRNAs. Through Starbase, miRTarBase, miRDB and TargetScan, 53 miRNAs were obtained, 737 targeted mRNAs were obtained. GO analysis showed that the differential genes were mainly involved in the biological processes of Ras protein signal transduction, transmembrane transport, cell cycle regulation, cell adhesion, etc. KEGG pathway analysis showed that the differential genes were mainly involved in viral infection, endocytosis, adhesion spot and actin regulation.Conclusion:In this study, RNA-seq technology is used to obtain differential miRNA expression profiles of KD patients and healthy control, and target pathogenic genes and signaling pathways that may be related to KD are screened out.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis / 中国天然药物

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg

Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

Genomics and functional genomics in Leishmania and Trypanosoma cruzi: statuses, challenges and perspectives

The availability of Trypanosomatid genomic data in public databases has opened myriad experimental possibilities that have contributed to a more comprehensive understanding of the biology of these parasites and their interactions with hosts. In this review, after brief remarks on the history of the Trypanosoma cruzi and Leishmania genome initiatives, we present an overview of the relevant contributions of genomics, transcriptomics and functional genomics, discussing the primary obstacles, challenges, relevant achievements and future perspectives of these technologies.

Different development phase of transcription proteomics and metabolomics of flower of Lonicera macranthoides / 中国中药杂志

In order to study the regulation mechanism of secondary metabolites biosynthesis in Lonicera macranthoides, the key genes involved in the regulation of biosynthesis and the mechanism of differential metabolites were explored. In this study, high-throughput sequencing technology was used for transcriptome sequencing of L. macranthoides at different development stages. By using Liquid chromatography-tandem mass spectrometry(LC-MS/MS) technology, the laws of qualitative, quantitative and synthetic accumulation of its metabolites were studied, and the key enzyme genes for the biosynthesis of phenolic acid and flavonoids were screened out according to the differentially expressed genes. A total of 111 differentially accumulate metabolites(DAM) and 6 653 differentially expressed genes(DGE) were obtained by metabonomics and transcriptomics analysis. The metabolites and key enzyme genes in the Erqing(KE) were significantly different from those in the Dabai(KD) and Yinhua(KY) stages. In the phenylalanine biosynthesis pathway, the ion abundance of chlorogenic acid, naringin, quercetin, rutin, coniferol and other metabolites decreased with the development of flowers, while the ion abundance of ferulic acid, coumarin and syringoside increased with the development of flowers. Key enzyme genes such as CHS, HCT, CCR, FLS and COMT positively regulate the downstream metabolites, while PAL, C4H and 4CL negatively regulate the downstream metabolites. This study provides candidate genes and theoretical basis for the further exploration of key enzymes in the biosynthesis of secondary metabolites and for the regulation of the accumulation of secondary metabolites in L. macranthoides by molecular biological methods.

A peep into the transcriptome studies of the industrially important brown algae with special focus on Macrocystis genus / Una mirada a los estudios de transcriptoma en algas pardas de importancia industrial, en especial del género Macrocystis

Abstract Brown algae are a commercial source of different polysaccharides/hydrocolloids that has been used to produce food, pharmaceutical, and several other useful biotechnological stuff. Nevertheless, transcriptomics has become a tool that not only provides valuable information for the understanding of the physiological processes of a species but also allows the identification of industrially important candidate genes. This study describes the transcriptome of brown algae and their industrial application with a special focus on Macrocystis integrifolia.

Resumen Las algas pardas son una fuente comercial de diferentes polisacáridos / hidrocoloides utilizados para producir alimentos, productos farmacéuticos y otros productos biotecnológicos útiles. Por otra parte, la transcriptómica se ha convertido en una herramienta que no solo proporciona información valiosa para la comprensión de los procesos fisiológicos de una especie, sino que también permite la identificación de genes candidatos industrialmente importantes. Este estudio describe el transcriptoma de algas pardas y su aplicación industrial con un enfoque especial en Macrocystis integrifolia.

Integrated chemical and transcriptomic analyses unveils synthetic characteristics of different medicinal root parts of Angelica sinensis / 中草药·英文版

Objective: Why are different medicinal parts including heads, bodies and tails of Angelicae Sinensis Radix (ASR) distinct in pharmaceutical activities? Here we explored their discrepancy in chemical constituents and transcriptome. Methods: ASR were separated into three medicinal parts: heads (rootstocks with petiole traces of ASR), bodies (taproots of ASR) and tails (lateral roots of ASR), and chemical and transcriptomic analyses were conducted simultaneously. Results: High performance liquid chromatography (HPLC) fingerprint results showed that five widely used active ingredients (ferulic acid, senkyunolide H, senkyunolide A, n-butylphathlide, and ligustilide) were distributed unevenly in the three ASR medicinal parts. Partial least squares-discriminant analysis (PLS-DA) demonstrated that the heads can be differentiated from the two other root parts due to different amounts of the main components. However, the content of ferulic acid (a main quality marker) was significantly higher in tails than in the heads and bodies. The transcriptome analysis found that 25,062, 10,148 and 29,504 unigenes were specifically expressed in the heads, bodies and tails, respectively. WGCNA analysis identified 17 co-expression modules, which were constructed from the 19,198 genes in the nine samples of ASR. Additionally, we identified 28 unigenes involved in two phenylpropanoid biosynthesis (PB) pathways about ferulic acid metabolism pathways, of which 17 unigenes (60.7%) in the PB pathway were highly expressed in the tails. The expression levels of PAL, C3H, and CQT transcripts were significantly higher in the tails than in other root parts. RT-qPCR analysis confirmed that PAL, C3H, and CQT genes were predominantly expressed in the tail parts, especially PAL, whose expression was more than doubled as compared with that in other root parts. Conclusion: Chemical and transcriptomic analyses revealed the distribution contents and pivotal transcripts of the ferulic acid biosynthesis-related pathways. The spatial gene expression pattern partially explained the discrepancy of integral medicinal activities of three medicinal root parts.

Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency / 中国结合医学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach.@*METHODS@#Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction.@*RESULTS@#A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B.@*CONCLUSIONS@#CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

Biologia de Sistemas de RNAs Não-Codificadores Longos na Vacinação / Systems biology of Long Non-Coding RNAs in vaccination

Entender os mecanismos responsáveis pela proteção induzida por vacinas contribui para o desenvolvimento de novas vacinas. Uma abordagem de pesquisa denominada Vacinologia de Sistemas surgiu para endereçar essa tarefa. A aplicação da Vacinologia de Sistemas gerou informações amplas relacionadas a respostas vacinais e foi aplicada no estudo de diversas vacinas. Apesar de estarem envolvidos em diversos processos imunológicos, RNAs Não-Codificadores Longos (lncRNAs) ainda não foram estudados no contexto da imunidade induzida por vacinas. Neste trabalho, fizemos a análise de mais de 2.000 amostras de transcritoma de sangue periférico, oriundas de 17 diferentes coortes vacinadas, com foco na identificação de lncRNAs potencialmente envolvidos com a resposta induzida por vacinas contra gripe e contra febre amarela. Criamos também um banco de dados online, em que todos os nossos resultados podem ser facilmente acessados. Nossos resultados indicaram que diversos lncRNAs participam de múltiplas vias imunológicas relacionadas a respostas induzidas por vacinas. Entre esses, o transcrito FAM30A se destaca por ter alta expressão em células B e ser correlacionado com a expressão de genes de imunoglobulina localizados no mesmo locus genômico. Identificamos também alterações na expressão de lncRNAs em dados de RNA-seq de uma coorte de crianças imunizadas com uma vacina atenuada contra gripe, o que sugere um papel de lncRNAs na resposta a diferentes vacinas. Nossos achados trazem evidências de que lncRNAs tem um papel significativo na resposta imune induzida por vacinas

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of Systems Vaccinology provides detailed information on host responses to vaccination and has been successfully applied in the study of the molecular mechanisms of several vaccines. Long Non-Coding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from these analyses can be easily accessed. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children vaccinated with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination

Comprehensive transcriptomics and proteomics analyses of rice stripe virus-resistant transgenic rice

Stable transgenic rice line (named KRSV-1) with strong resistance against rice stripe virus was generated using the genesequence of disease-specific protein by RNA interference. Comprehensive safety assessment of transgenic plants has turnedinto a significant field of genetic modification food safety. In this study, a safety assessment of KRSV-1 was carried out in astepwise approach. The molecular analysis exhibited that KRSV-1 harbored one copy number of transgene, which wasintegrated into the intergenic non-coding region of chromosome 2 associated with inter-chromosomal translocations of 1.6-kb segments of chromosome 8. Then, transcriptomics and proteomics analyses were carried out to detect the unintendedeffects as a result of the integration of the transgene. Although 650 dramatically differentially expressed genes (DDEGs)and 357 differentially expressed proteins were detected between KRSV-1 and wild-type (WT) by transcriptomics andproteomics analyses, no harmful members in the form of toxic proteins and allergens were observed. Encouragingly, thenutritional compositions of seeds from KRSV-1 were comparable with WT seeds. The results of this entire study ofmolecular analysis, transcriptome and proteome profile of KRSV-1 revealed that no detrimental changes in the form of toxicproteins and allergens were detected in the transgenic rice line due to the integration of the transgene.

Co-Expression Network Analysis Identifies Possible Hub Genes in Aging of the Human Prefrontal Cortex / Análisis de redes de coexpresión identifica posibles genes clave en el envejecimiento de la corteza prefrontal humana / Análise de redes de co-expressão identifica possíveis genes chave no envelhecimento do córtex pré-frontal humano

Abstract Introduction : Aging is the main risk factor for the development of chronic diseases such as cancer, diabetes, Parkinson's disease, and Alzheimer's disease. The central nervous system is particularly susceptible to progressive functional deterioration associated with age, among the brain regions the prefrontal cortex (PFC) has one of the highest involvements. Transcriptomics studies of this brain region have identified the decrease in synaptic function and activation of neuroglia cells as fundamental characteristics of the aging process. The aim of this study was to identify hub genes in the transcriptomic deregulation in the PFC aging to advance in the knowledge of this process. Materials and methods : A gene co-expression analysis was carried out for 45 people 60 to 80 years old compared with 38 people 20 to 40 years old. The networks were visualized and analyzed using Cytoscape; citoHubba was used to determine which genes had the best topological characteristics in the co-expression networks. Results : Five genes with high topological characteristics were identified. Four of them -HPCA, CACNG3, CA10, PLPPR4- were repressed and one was over-expressed -CRYAB-. Conclusion: The four repressed genes are expressed preferentially in neurons and regulate the synaptic function and the neuronal plasticity, while the overexpressed gene is typical of glial cells and is expressed as a response to neuronal damage, facilitating myelination and neuronal regeneration.

Resumen Introducción : el envejecimiento es el principal factor de riesgo para el desarrollo de enfermedades crónicas como el cáncer, la diabetes, el Parkinson y el Alzheimer. El sistema nervioso central es particularmente susceptible al deterioro funcional progresivo asociado con la edad, entre las regiones cerebrales con mayor compromiso se encuentra la corteza prefrontal (CPF). Estudios de transcriptómica de esta región han identificado como características fundamentales del proceso de envejecimiento la disminución de la función sináptica y la activación de las células de la neuroglia. No es claro cuáles son las causas iniciales, ni los mecanismos moleculares subyacentes a estas alteraciones. El objetivo de este estudio fue identificar genes clave en la desregulación transcriptómica en el envejecimiento de la CPF para avanzar en el conocimiento de este proceso. Materiales y métodos : se hizo un análisis de coexpresión de genes de los transcriptomas de 45 personas entre 60 y 80 años con el de 38 personas entre 20 y 40 años. Las redes fueron visualizadas y analizadas usando Cytoscape, se usó citoHubba para determinar qué genes tenían las mejores características topológicas en las redes de coexpresión. Resultados : se identificaron cinco genes con características topológicas altas. Cuatro de ellos -HPCA, CACNG3, CA10, PLPPR4- reprimidos y uno sobreexpresado -CRYAB-. Conclusión : los cuatro genes reprimidos se expresan preferencialmente en neuronas y regulan la función sináptica y la plasticidad neuronal, mientras el gen sobreexpresado es típico de células de la glía y se expresa como respuesta a daño neuronal facilitando la mielinización y la regeneración neuronal.

Resumo Introdução : o envelhecimento é o principal fator de risco pra o desenvolvimento de doenças crónicas como o câncer, a diabetes, o Parkinson e o Alzheimer. O sistema nervoso central é particularmente susceptível ao deterioro funcional progressivo associado à idade, uma das regiões do cérebro com maior compromisso é o pré-frontal (CPF). Estudos de transcritoma desta região têm identificado como características fundamentais do processo de envelhecimento a diminuição da função sináptica e ativação das células da neuroglia. Não é claro quais são as causas iniciais, nem os mecanismos moleculares subjacentes a estas alterações. O objetivo deste estudo foi identificar genes chave na desregulação transcritoma no envelhecimento da CPF para avançar no conhecimento deste processo. Materiais e métodos : se fez uma análise de co-expressão de genes dos transcritomas de 45 pessoas entre 60 e 80 anos com o de 38 pessoas entre 20 e 40 anos. As redes foram visualizadas e analisadas usando Cytoscape, usou-se citoHubba para determinar que genes tinham as melhores características topológicas nas redes de co-expressão. Resultados : identificaram-se cinco genes com características topológicas altas. Quatro deles -HPCA, CACNG3, CA10, PLPPR4- reprimidos e um superexpresso -CRYAB-. Conclusão : os quatro genes reprimidos se expressam preferencialmente em neurônios e regulam a função sináptica e plasticidade neuronal, enquanto o gene superexpresso é típico de células da glia e se expressa como resposta ao dano neuronal facilitado a mielinização e a regeneração neuronal.

Overview of genomics and post-genomics research on type 2 diabetes mellitus: Future perspectives and a framework for further studies

In this review, we briefly outlined salient features of pathophysiology and results of the genetic association studies hithertoconducted on type 2 diabetes. Primarily focusing on the current status of genomic research, we briefly discussed the limitedprogress made during the post-genomic era and tried to identify the limitations of the post-genomic research strategies. Wesuggested reanalysis of the existing genomic data through advanced statistical and computational methods and recommended integrated genomics-metabolomics approaches for future studies to facilitate understanding of the gene-environment interactions in the manifestation of the disease. We also propose a framework for research that may be apt fordetermining the effects of urbanization and changing lifestyles in the manifestation of complex genetic disorders like type 2diabetes in the Indian populations and offset the confounding effects of both genetic and environmental factors in thenatural way

Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke / 中国实验方剂学杂志

Objective:To obtain the regulatory relationship between genes by screening the differentially expressed long non-coding ribonucleic acid(lncRNA), microRNA(miRNA) and messenger RNA(mRNA) in serum of patients with Yin and Yang syndromes of acute ischemic stroke, and to discuss the material basis and biological mechanism of formation of Yin and Yang syndromes of acute ischemic stroke from the transcriptome level. Method:The microarray chips were adopted to detect expression of lncRNA, mRNA and miRNA in serum of ischemic stroke patients with Yin and Yang syndromes and non-stroke subjects(10 cases each). Differential expression profiles related to Yin and Yang syndromes were selected by conjoint analysis. Further, the obtained differential genes were subjected to antisense lncRNA and mRNA co-expression analysis, gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) functional pathway analysis, and the intergenic regulatory relationship was obtained to predict the target genes of lncRNA. Partial differential genes in 40 patients(10 with Yang syndrome and 30 with Yin syndrome) were verified by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). Result:The expression of 227 lncRNA, 54 mRNA and 4 miRNA were closely related to Yang syndrome, 394 lncRNA and 206 mRNA were closely related to Yin syndrome. Antisense lncRNA RP11-647P12.1 and RP11-677M14.2 may regulate the expression of neuron-derived neurotrophic factor(NDNF) and neurogranin(NRGN) by up-regulating the expression level in Yang syndrome. The differential expression of mRNA between Yin syndrome and Yang syndrome was mainly related to neurotransmitter receptor activity regulation, endocrine hormone regulation, inflammatory response, renin-angiotensin system and other pathways. Conclusion:There are differences in the expression profiles of lncRNA, miRNA and mRNA between Yin syndrome and Yang syndrome in acute ischemic stroke, which may be regulated by multiple pathways, such as blood pressure regulation, adrenergic receptor regulation, renin-angiotensin system and γ-aminobutyric acid(GABA). The transcriptome characteristics provide scientific basis for studying the biological basis of Yin syndrome and Yang syndrome in acute ischemic stroke.

Research ideas and methods of protein and peptides in animal medicine based on transcriptomics-proteomics-peptidomics integrated association analysis strategy / 中草药

Animal medicine is an important part of traditional Chinese medicine, and its unique efficacy is irreplaceable in clinical application. In consideration of the main problems in the research of animal medicine, such as the uncertainty of chemical composition, pharmacodynamic components and toxic components, and the inadequacy of quality control system, this article established a research method of protein and peptides in animal medicine based on transcriptomics-proteomics-peptidomics integrated association analysis strategy, which mainly include the construction of protein database based on transcriptomics, high resolution mass spectrometry analysis, identification and activity evaluation of protein and peptide components. It attempts to provide a practical research method for the analysis and identification of protein and peptide components in animal medicine and technical support for further solving the key issues of animal medicine research.