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The IBM Hybrid Cloud crew is back at it with yet an extra win for design. I’m excited to broadcast that their design team has been awarded the 2018 red Dot: conversation Design Award for IBM SPSS information in the Interface Design class. This award is a continuation of the design achievements they maintain considered this previous year, including the A’Design Awards, IF Design Awards, and others. i am extremely joyful to contemplate the difficult work of their designers and IBM Design continue to shine and win a incompatibility in commercial enterprise utility.
First developed within the 1990’s, the pink Dot Award has been the revered international seal of outstanding design fine. Designers, groups, and companies from 45 diverse nations took section in this 12 months’s competition, totaling over 8,600 entries that underwent a 24 member jury.
“All those that progress through the tough adjudication manner to garner a pink Dot maintain every purpose to exist disdainful of themselves, because the jury supplies their award handiest to creations of inordinate design satisfactory. This makes me total of the greater delighted to congratulate the laureates truly on their genuinely-earned success.” — Professor Dr. Peter Zec, founder and CEO of the pink Dot Award
Receiving this award turned into totally challenging for their team and we're honored to exist among the winners. here is an vital achievement for their designers who worked on this product, and that they faced a captivating and challenging event in engaged on this product.what's IBM SPSS?
IBM SPSS information is a magnificent data evaluation tool that is likely one of the most well-known facts purposes. on account that its inception in 1968, SPSS data has been revamped and redeveloped diverse instances. Now the design group at IBM has taken on the task of developing a totally cleanly consumer adventure.
in this latest remodel of IBM SPSS information, they implemented design considering principles by working closely with their clients and making certain this modernized version of SPSS statistics aligns with their wants. Their most beneficial goal was to create a powerful tool that isn't most efficacious effortless and intuitive to win consume of, but that their users can appreciate.Our team and Design strategy
The IBM SPSS design team is a component of the IBM Design Studios in Boeblingen, Germany. The group is composed of a diverse neighborhood, with many contributors originating from diverse international locations and cultures. Some contributors of the team had some history with records while others were working in this bailiwick for the primary time.
Following the ideas of IBM Design thinking (study > reflect > Make), their crew carried out a redecorate that brings an improved focal point on users for SPSS statistics. The design group performed intensive analysis on the user groundwork of SPSS statistics in an pains to contemplate how the application can more desirable meet their needs. The current consumer groundwork tiers from much less experienced users equivalent to college students to extra knowledgeable users equivalent to information scientists or enterprise experts. A key perception from the team’s research became that much less experienced clients had been intimidated each by the math work and the complexity of the software.
the original designs concentrated on simplifying workflows, decreasing the typical complexity of the UI and interactions, and proposing inexperienced persons a straightforward on-boarding to facts and to the product. a different crucial characteristic within the redesign became a training pilot led by means of a character named Simon, who serves as an in-utility book, assisting newbie users understand diverse capabilities and obtain their dreams quicker.
The team confronted some pleasing challenges in redesigning a made of such complexity, and one that has likewise been round for thus decades. a huge success of the designers was making the product attainable and engaging to original users without alienating decade-lengthy, experienced users.a glance Into the Future
The preview version of their original IBM SPSS data adventure changed into released in March 2018, and made available to the public as a trial on the IBM feel conference is Las Vegas, and considering that June 26 , the original UI is frequently accessible to total SPSS information subscribers. This preview is only the initial step, providing essentially the most used statistical analyses, and simple capabilities for data training, for presentation and for reporting results. Over here months the group will exist working so as to add greater facets and capabilities in order to meet event wants of total of their user corporations.now not simply Updating — Redesigning
i am so thrilled to contemplate another Hybrid Cloud design crew receive an international award for his or her work. IBM SPSS data is yet one other instance of how design is making a tremendous change within the success of their items. As they continue to win consume of design to create greater relatable and productive products, they are in a position to give their clients the experiences that they need and need. I’m thrilled and disdainful to watch the incompatibility that their design team is making in the world of trade software, and i can’t wait to leer how they proceed to influence the lives of their users.Award Winners:
IBM remaining week introduced that the edition 22 unencumber of SPSS information could exist the remaining release of the product to maintain any element that runs on device i (IBM i). it'll even exist the ultimate free up with the talent to tug SQL information out of the DB2 for i database, which is arguably more destructive for any IBM valued clientele that could want to rush some statistical analysis on their DB2/400 facts.
SPSS records is ripen and multi-faceted software kit that gives users lots of superior statistical evaluation capabilities. Surrounding the core evaluation component is a fleet of more than 50 add-on products that, among other issues, give file distribution capabilities.
SPSS information has not ever rush on IBM i itself, even when it was owned through SPSS. before it changed into purchased by way of IBM, SPSS supported the IBM i platform with just two main product traces: the showcase OLAP and Reporting outfit (some of which had been bought through help/programs) and the Clementine statistics mining software. however the core SPSS records outfit changed into total the time supported on extra “mainstream” structures, like Unix, Linux, windows, and the S/390 mainframe, which is the set SPSS information got its birth so a long time ago.
however, IBM did, interestingly, back the SPSS Collaboration and Deployment features section on the IBM i platform, which is pleasing in its personal right. IBM infrequently (if ever) touted this capacity, which is not impressive due to the fact that it’s a narrowly concentrated locality of interest product that performs a pilot position to other products. In any event, IBM announced that the Collaboration and Deployment capabilities section in SPSS statistics version 22 will not pilot the “system I” (a name that IBM stopped the consume of in 2010).
most likely more harmful is the incontrovertible fact that SPSS statistics version 22 marks the eventual version of the utility that might exist capable of consume DB2 for i (DB2/four hundred) as a source for SQL data, besides the fact that the core SPSS records utility is working (as it need to) on an extra server platform.
IBM i authorities are acquainted with touching construction data from DB2/400 onto different systems where it can exist analyzed. however, curiously so few SPSS records shoppers had been using this talent that it no longer made feel to retain it.
surely there are alternative routes to derive data off the IBM i server and into SPSS records. in any case, the SQL facts commonplace is meant to carry more suitable information interoperability amongst structures. however the incontrovertible fact that it’s not value IBM’s pains to preserve this SQL channel open to the IBM i server isn't a helpful sign.
For extra assistance contemplate software Announcement 213-309.
There’s No “i” In French Open Tennis
help/systems Buys exhibit BI items from IBM
IBM to purchase SPSS for $1.2 Billion
SPSS alterations facts Miner’s identify, Drops system i aid
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Two of IBM’s most widely wide-spread analysis items, the Cognos trade Intelligence and the SPSS predictive analytics package, are headed for the cloud, the newest in an ongoing propel by IBM to port its mammoth software portfolio to the cloud.
gaining access to any such application from a hosted environment, rather than paying for the outfit outright, provides a few merits to customers.
“We manage the infrastructure, and this allows you to scale more readily and derive began with much less upfront funding,” spoke of Eric Sall, IBM vp of worldwide analytics advertising and marketing.
IBM introduced these additions to its cloud capabilities, as well as a number of original choices, at its insight consumer conference for records analytics, held this week in Las Vegas.
through 2016, 25 percent of recent company evaluation deployments will exist carried out within the cloud, in keeping with Gartner.
Analytics may assist agencies in lots of methods, in keeping with IBM. It might supply extra insight in the purchasing habits of shoppers, in addition to perception into how smartly its personal operations are performing. It could support shield techniques from assaults and makes an attempt at fraud, in addition to assure that company departments are assembly compliance requirements.
the brand original online edition of Cognos, IBM Cognos company Intelligence on Cloud, can at present exist validated in a preview mode. IBM plans to present Cognos as a full trade provider early next year. clients can rush Cognos against statistics they retain in the IBM cloud, or towards records they hold on premises.
A full industrial edition of the online IBM SPSS Modeler can exist available inside 30 days. This outfit will encompass total of the SPSS add-ons for facts primarily based predictive modeling, comparable to a modeler server, analytics determination management utility and a information server.
previous this year, IBM pledged to present lots of its application portfolio as cloud services, many through its Bluemix set of platform features.
apart from Cognos and SPSS, IBM likewise unveiled a brace of original and up to date choices at the convention.
One original carrier, DataWorks, gives a number of innovations for refining and cleaning records so it is competent for evaluation. The trade has launched a cloud-based facts warehousing provider, referred to as dashDB. a brand original Watson-primarily based carrier, known as Watson Explorer, provides a way for clients to examine natural language questions on distinctive sets of interior records.To touch upon this text and different PCWorld content material, visit their facebook page or their Twitter feed.
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Obesity has become a worldwide problem and a major risk factor for diabetes, infertility, and cardiovascular disease (Hu et al., 2016; Liang et al., 2017; Ferramosca et al., 2016; Supriya et al., 2018). It is a chronic metabolic disease characterized by abnormal full distribution or inordinate lipid accumulation (Yang et al., 2012). White adipose tissue (WAT), the central metabolic organ that regulates the energy homeostasis of the cadaver (Choe et al., 2016), is closely associated with the occurrence of obesity and related complications (Hajer, Van Haeften & Visseren, 2008).
Noncoding RNA (ncRNA) is a common term for total functional RNAs that are not translated into proteins. As biological mediators, they can participate in the regulation of gene expression through epigenetic modification, transcriptional regulation and post-transcriptional regulation (Tang, Chen & Zhou, 2018). With the progress of sequencing technology, a variety of original non-coding RNAs maintain been discovered, and their role in gene regulatory networks and regulation of endothelial cell office and metabolism is becoming better understood (Santulli, 2015, 2016; Liu et al., 2018). Among them, circular RNA (circRNA) and long non-coding RNA (lncRNA) play roles in regulating beta cell function, influencing transformation of adipose tissue and its energy metabolism and making them a promising target for anti-obesity therapy (Kaur, Mirza & Pociot, 2018; Li et al., 2018; Zhu et al., 2019).
Salvianolic acid B (Sal B) is a water-soluble component extracted from the traditional Chinese medicinal plant Salvia miltiorrhiza (Family Labiatae; referred to herein as S. miltiorrhiza) (Wang et al., 2014). In recent years, studies maintain shown that Sal B can reduce obesity and obesity-related metabolic disorders (Chien et al., 2016; Pan et al., 2018). Their work has shown that Sal B can ameliorate glycolipid metabolism and reduce cadaver weight in obese mice induced by high full diet (HFD) (Zhao et al., 2017). However, it is not known whether anti-obesity activity of Sal B is related to the regulation of non-coding RNA expression. In this study, they aimed to investigate the outcome of Sal B on the expression of lncRNA and circRNA in epididymis white adipose tissue (EP) of obese mice induced by a HFD. The anti-obesity target of Sal B was screened using functional studies of differentially expressed lncRNA and mRNA.Materials and Methods Ethics statement
All the study protocol was approved by the Animal impregnate and Management Committee of the Beijing University of Chinese Medicine, and total animal manipulations were according to the guidelines of the Animal impregnate Committee.Mice experiment and tissue extraction
Male C57BL/6J mice provided by SPF (Beijing) Biotechnology Co. Ltd. (Certificate NO. SCXK (Jing) 2016-0002) were used in this study. After 1-week acclimation, the mice were fed a HFD (60% fat) for 12 weeks to induce obesity (average cadaver weight: HFD > (1 + 20%) normal, n = 10). After that, obesity mice were randomly divided into EP-S and EP-M groups (n = 5). Sal B intervention group (EP-S) and model (EP-M) groups were respectively administered Sal B (75 mg/kg cadaver weight/day) or vehicle (an equivalent volume of water) by oral gavage daily for 8 weeks. At the terminate of the study, blood samples and EPs were collected from total the mice sacrificed by cervical dislocation, and immediately frozen in liquid nitrogen and stored at −80 °C for subsequent analysis.Measurement of blood lipid profiles and cadaver full mass
The concentrations of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) were determined using chemistry reagent kits (Nanjing Jiancheng Biology Engineering Institute, Nanjing, China) and an automated biochemical analyzer (Hitachi, Tokyo, Japan). cadaver composition and total full mass was measured by magnetic resonance imaging (EchoMRI-100 for mice; echo Medical System, Houston, TX, USA) after the Sal B administration (weeks 8).RNA isolation and RNA-seq analysis
Total RNAs from tissues were extracted using the Trizol reagent and purified using RiboZero Magnetic Gold Kit according to the manufacturer’s instructions. RNA sequencing libraries were generated using the KAPA Stranded RNA-Seq Library Prep Kit. The constructed cDNA libraries were qualified by Agilent 2100 Bioanalyzer, quantified by qPCR, and sequenced on an Illumina Hiseq 4000.Functional enrichment analysis
Using Gene Ontology (GO) database (http://www.geneontology.org). They analysis the travel enrichment of the differentially expressed mRNAs and their functions, based on three aspects: biological processes (BP), cellular components (CC), and molecular functions (MF). The log 10 values (p-value) denote enrichment scores and limn the significance of the travel term enrichment among the differentially expressed genes. KEGG pathway analysis revealed pathway clusters covering the differentially expressed genes, and the log 10 values (p-value) denote the enrichment score and limn the significance of the pathway correlations. In addition, Gene Set Enrichment Analysis (GSEA) is used to compensate for the shortcomings of individual genes in analysis.Correlation and co-expression analysis of mRNA and lncRNA
Based on the inter-regulatory association between differentially expressed genes in the EP between Sal B treatment group and obesity group, the lncRNA–mRNA regulatory network was constructed using Cytoscape v2.8.2 software (http://www.cytoscape.org/).Quantitative true time-PCR
Quantitative true time (qRT)-PCR was performed to verify the results of RNA-seq. Total RNAs were isolated from samples using the Trizol reagent, then reverse-transcribed into cDNA according to the manufacturers’ instruction. The transcriptase reactions contained 1.5 μg RNA, 0.5 μg/μl random primers (N9, 1 μl), 2.5 mM dNTPs coalesce (1.6 μl), 5× first-strand buffer (4.0 μl), 0.1M dithiothreitol (1 μl), RNase inhibitor (0.3 μl), and Superscript III RT (0.2 μl). Sybr Green-based qPCR was performed using SYBR Premix ExTaq. total data were normalized to data for ARBP to reckon relative mRNA concentrations. The primers used in this study are shown in Table 1.Table 1:
Primers for quantitative PCR analysis.Gene Forward (5′–3′) ARBP F: TTTGGGCATCACCACGAAAAR: GGACACCCTCCAGAATTTTC Wbscr27 F: TGAGCTCTTAAGAGTCACCAAGR: CTTGTTCTGATGTTGCATGCTC Sfrp5 F: CAAGATGCGCATTAAGGAGATCR: CTTGAGCAGCTTCTTCTTC Adig F: TCACACTCTCTTTGGTTTTR: CCAGTTGAAGCACAAATCTGAA chr7:67264864–67268400- F: AGACCTCACGGTGCCAAATR: CTTTCTTTCTTAACGTCCACAGG Saa3 F: CAGTTCATGAAAGAAGCTGGTCR: CGAGCATGGAAGTATTTGTCTG ENSMUST00000169194 F: GGCAGGCATGACTAAATG 3R: CAGGGTTGATTAGCAGTGTC Statistical analysis
The statistical differences were analyzed using the SPSS (version 20.0; IBM SPSS Statistics, Chicago, IL, USA) by independent-samples t-test. total data were shown as the means ± SD. p-values < 0.05 were regarded as statistically significant.Results Effects of Sal B on cadaver full mass and serum lipid profiles of obese mice induced by HFD
After 8 weeks of Sal B intervention, the cadaver weights, TG, TC, HDL, LDL, and cadaver full mass of experimental mice in the two groups were measured. The cadaver weight, TG, TC, HDL, LDL, and cadaver full mass in the obesity group was significantly higher than that in Sal B treatment group (p < 0.05) (Table 2). These results indicate that Sal B can reduce the cadaver weight and full mass as well as preclude dyslipidemia caused by HFD feeding.Table 2:
Effects of Sal B on cadaver full mass and serum lipid profiles of obese mice induced by HFD.Name Obesity model group Sal B treatment group TG 0.984 ± 0.106 0.777 ± 0.069* TC 6.229 ± 0.483 5.011 ± 0.391* LDL-C 0.425 ± 0.021 0.317 ± 0.029* HDL-C 1.213 ± 0.191 1.876 ± 0.105* Fat mass 0.431 ± 0.011 0.356 ± 0.015* Effects of Sal B on mRNAs and circRNAs expression in EP of obese mice induced by HFD
In total, 15,184 mRNAs were identified, of which 132 differentially expressed (DEmRNAs). In the EP-S group, 24 were up-regulated and 108 were down-regulated (Figs. 1A and 1C; Table S1). Compared with EP-M, there were 19 differentially expressed circRNAs in the EP-S, of which nine were up-regulated and 10 were down-regulated (Figs. 1B and 1D; Table S2). Among DEmRNAs, the up-regulated expression of Wbscr27 was the highest, with a fold change of 2.053, while C1rb was the most down-regulated, with a fold change of 0.318. In addition, some mRNAs that maintain been shown to play a role in full metabolism, such as Sfrp5, Adig, and Saa3 were likewise differentially expressed.Figure 1: Analysis of DEmRNAs (A, C) and DEcircRNAs (B, D). Hierarchical clustering. Each row represents an mRNA and each column represents a sample. Green and red limn down-and up-regulated mRNAs or circRNAs, respectively. Genes in the volcano-Plot above the green parallel line (p < 0.05) and outside the two longitudinal green lines indicated DEmRNAs and DEcircRNAs between the two compared samples. Effects of Sal B on the expression and office of lncRNAs in EP induced by HFD in obese mice
We found 234 differentially expressed lncRNAs (DE lncRNAs), including 87 up-regulated and 147 down-regulated in the experimental group (Table S3). Based on this, they performed a GSEA functional analysis of the DElncRNAs, and found that the up-regulated expression of lncRNAs are mainly involved in brown adipocyte differentiation, steroid biosynthesis, lipid transport, and lipid metabolism, while the down-regulated expression of lncRNAs are associated with the immune process and inflammatory responses (Fig. 2). After classifying the DElncRNAs, 179 were found to exist exon sense overlapping, 11 were intergenic, 17 were intron sense overlapping, 16 were antisense, and 11 were bidirectional.Figure 2: GSEA Cluster Heat Map of top 10 DElncRNAs, in up-regulation and down-regulation, respectively. (A) Biological process; (B) cellular components; (C) molecular functions, and (D) KEGG pathway, each row represents a functional entry, and each column represents an lncRNA. GSEA is a method used to determine whether a given gene set has significant differences among different groups. Genes in these sets maintain some degree of correlation. Therefore, enrichment analysis of gene sets can win up for the shortcomings of single gene in the analysis. qRT-PCR validation of differentially expressed mRNAs, lncRNAs, and circRNAs
We selected four DEmRNAs (Wbscr27, Sfrp5, Adig, and Saa3), DEcircRNAs- chr7:67264864–67268400:- and DElncRNA-ENSMUST00000169194, which are most apposite to obesity, for consume in verifying RNA-seq results using qRT-PCR. Results showed that the expression levels of Wbscr27, Sfrp5, Adig, and chr7:67264864–67268400:- were up-regulated in the EP-S group compared with the EP-M group, consistent with the sequencing results. The expressions of ENSMUST00000169194 and Saa3 were down-regulated in the EP-S group, which was likewise consistent with the sequencing results (Fig. 3).Figure 3: Sequencing and quantitative PCR. Sequencing and quantitative PCR for mRNAs (Wbscr27, Sfrp5, Adig, and Saa3), circRNAs- chr7:67264864–67268400:- and lncRNA-ENSMUST00000169194. The quantitative PCR results were consistent with the sequencing data. n = 5. LncRNA–mRNA regulatory analysis
LncRNA has the talent to regulate several groups of mRNAs at the transcriptional level, including positive and negative regulation. Hence, understanding how Sal B alters the expression of lncRNA and its target mRNA expression is key to understanding its molecular mechanism of anti-obesity. They screened two DElncRNAs (ENSMUST0000140351 and ENSMUST00000169194) to construct the lncRNA–mRNA regulatory network map. A total of 11 differentially expressed mRNAs were found to exist negatively correlated with the expression of ENSMUST0000140351 (Ms4a14, Cd300ld3, Lum, Glipr1, Cd300ld5, Rgs18, Cd300ld4, Fgd4, Hpgds, Frmd4b, and Osbpl8). They likewise found that the expressions of S100a8 and Fgl2 were positively correlated with the expression of ENSMUST00000169194 (Fig. 4; Table S4).Figure 4: LncRNA–mRNA regulatory network (ENSMUST0000140351 and ENSMUST00000169194). Squares limn lncRNAs, circles limn mRNAs; red indicates up-regulated expression and blue indicates down-regulated expression. The solid line is positively correlated and the dotted line is negatively correlated. LncRNA–mRNA regulatory network was constructed using Cytoscape v2.8.2 software. Functional analysis of DEmRNAs
We performed travel and KEGG enrichment analysis to determine the functional significance of DEmRNAs in the EP-S/EP-M group. travel enrichment analysis showed that up-regulated mRNA was enriched in 13 BP, 5 CC, and 2 MF, while down-regulated mRNA was enriched in 89 BP, 24 CC, and 35 MF (Fig. 5; Table S5). The most highly enriched up-regulated travel terms were “brown full cell differentiation (biological process),” “integral component of membrane (CC),” and “ligase activity (MF),” while the most highly enriched down-regulated travel terms were “immune system process (BP),” “extracellular region (CC),” and “chemokine activity (MF).”Figure 5: travel analysis. (A) up-regulated and (B) down-regulated of DEmRNAs. Using travel database (http://www.geneontology.org) analysis the travel enrichment of the DEmRNAs, based on three aspects: biological processes (BP), cellular components (CC), and molecular functions (MF). The log 10 values (p-value) denote enrichment scores and limn the significance of the travel term enrichment among the DEmRNAs.
KEGG pathway analysis showed that differentially expressed mRNAs were enriched in 14 pathways associated with obesity (p < 0.05). The most highly enriched pathways were “insulin resistance” and “IL-17 signaling pathway.” Notably, they likewise identified mRNAs involved in the regulation of these pathways, which may provide targets for Sal B as a potential drug to preclude HFD-induced obesity (Table 3). Moreover, a number of metabolic-related pathways were screened, including the “NF-κB signaling pathway” and the “B-cell receptor signaling pathway.” KEGG pathway analysis suggests the possibility that Sal B exerts its weight reduction outcome through the regulation of adipose metabolism via insulin resistance and IL-17 signaling in HFD induced-obesity mice.Table 3:
KEGG pathway analysis.ID Term Count Genes mmu04931 Insulin resistance 2 Slc27a1, Slc2a4 mmu04657 IL-17 signaling pathway 6 Ccl12, Ccl7, Cxcl1, Fosl1, S100a8, S100a9 mmu04145 Phagosome 7 Atp6v0d2, Comp, Cybb, Fcgr1, Fcgr4, Msr1, Rab7b mmu05323 Rheumatoid arthritis 5 Atp6v0d2, Ccl12, Ccl3, Cd86, Il18 mmu04064 NF-kappa B signaling pathway 5 Bcl2a1a, Bcl2a1b, Bcl2a1d, Btk, Card11 mmu04380 Osteoclast differentiation 5 Btk, Fcgr1, Fcgr4, Fosl1, Lilra5 mmu04662 B cell receptor signaling pathway 4 Btk, Card11, Cd72, Rasgrp3 mmu04620 Toll-like receptor signaling pathway 4 Ccl3, Cd86, Tlr1, Tlr8 mmu04060 Cytokine-cytokine receptor interaction 6 Ccl12, Ccl3, Ccl7, Cxcl1, Cxcl16, Il18 mmu04062 Chemokine signaling pathway 5 Ccl12, Ccl3, Ccl7, Cxcl1, Cxcl16 mmu04621 NOD-like receptor signaling pathway 4 Ccl12, Cxcl1, Cybb, Il18 mmu04668 TNF signaling pathway 3 Ccl12, Cxcl1, Gm5431 mmu04210 Apoptosis 3 Bcl2a1a, Bcl2a1b, Bcl2a1d mmu04933 AGE–RAGE signaling pathway 2 Ccl12, Cybb Discussion
Epigenetic alteration refers to a heritable change in gene expression under conditions in which the genomic DNA sequence does not change, resulting in an altered phenotype. This includes changes in the expression of non-coding RNA (Takada, Kouzmenko & Kato, 2009). Studies maintain shown that epigenetic modification plays an vital role in the occurrence and progress of obesity (Kasinska, Drzewoski & Sliwinska, 2016; Huang et al., 2018). With the advancement of RNA sequencing technology, more and more non-coding RNAs related to energy metabolism are recognized as involved in obesity and related metabolic diseases. WAT is mainly distributed in the subcutaneous tissue, omentum and mesentery of mice, with epididymis white full (EP) as the most commonly used WAT in adipose studies. They studied the effects of Sal B on the expression of mRNAs, lncRNAs, and circRNAs in EP of HFD induced obesity mice from an epigenetic level, and explored the anti-obesity outcome of Sal B.
Obesity is an inflammatory state that occurs in adipose tissue, and therefore constitutes a chronic inflammatory disease accompanied by activation of inflammatory signaling pathways in adipose tissue cells, release of inflammatory cytokines, and infiltration of immune cells (Nteeba et al., 2013; Mathieu, Lemieux & Després, 2010). Therefore, research on the treatment of obesity inflammation and original target exploitation will provide novel targets for the treatment of obesity and its related metabolic diseases. In the present study, they found that the expression of many inflammation-associated mRNAs was affected by Sal B treatment, including Sfrp5 and Saa3. Secreted frizzled-related protein-5 (Sfrp5), known as an anti-inflammatory adipokine, is much more abundant in adipose tissue than other tissues, and negatively affects obesity and obesity-related metabolic disorders (Hu et al., 2013). Previous studies maintain shown that in the adipose tissue of Sfrp5 knockout mice, the number of macrophages is significantly increased, and the expression of factors related to cellular inflammatory activity, such as TNF-a and IL-6, are significantly increased (Ouchi et al., 2010). Sfrp5 exerts anti-inflammatory effects by binding to Wnt5a to inhibit the activation of the downstream target JNK of the Wnt pathway and reduce the secretion of inflammatory factors in obese mice (Catalán et al., 2014) as well as in 3T3-L1 cells (Shadid & Jensen, 2003). Consistent with previous research, they found that Sfrp5 is up-regulated 1.9-fold under Sal B treatment. Therefore, they hypothesize that Sal B may exert anti-obesity effects by regulating the expression of inflammation-related mRNA in adipose tissue. In addition, Sfrp5 can exist used as a candidate target for studying the anti-obesity mechanism of Sal B, and its specific mechanism should exist the emphasis of future research.
Another inflammation-related mRNA, Saa3, was found to exist expressed at half the control rate under Sal B treatment, consistent with previous studies. The serum amyloid A family is a class of proteins released during acute inflammatory response and is closely related to the pathogenesis of chronic inflammatory diseases such as obesity (Van Dielen et al., 2001). The expression of Saa3 is significantly increased under a promoted adipocyte inflammatory response by saturated fatty acids and glucose. In addition, Saa3 is highly expressed in the adipose tissue of obese mice, which may exist related to the induction of adipose tissue inflammation (Den Hartigh et al., 2014). In this study, they found that the expression of Saa3 was significantly down-regulated in EP-S, suggesting that Sal B can reduce the inflammatory response induced by Saa3.
In the EP-M group, they found some abnormal expression of mRNA associated with adipose transformation, with Sal B intervention reversing these changes. Adipoietin (Adig), likewise known as small adipocytokines 1, plays a significant role in the differentiation of adipocytes (Ren et al., 2016). Their results showed that the expression Adig in the Sal B treatment group was significantly higher than in the obese model group. This is in line with the previous findings that Adig can promote the differentiation of adipocytes by activating the expression of PPARγ, Srebp-1, and Fas genes (Mei, Zhang & Fu, 2016). Therefore, they speculate that Sal B can up-regulate the expression plane of Adig to activate the adipose transcription factor and promote the differentiation of adipocytes.
We identified 234 DElncRNAs, including 87 up-regulations and 147 down-regulations. Several differentially expressed lncRNAs might participate in lipid metabolism and glucose metabolism. For example, Rora and Dnm2 were predicted to exist involved in “oxidative phosphorylation” and “glycine, serine, and threonine metabolism.” This is consistent with previous studies showing that Rora regulates lipid metabolism (Kim et al., 2017). Therefore, the differential expression profiles obtained indicate that Sal B can exert a potential regulatory office in full deposition and metabolism in obese mice by modulating the expression of lncRNAs.
Gene Ontology and KEGG pathway analyses were performed to forecast the feasible functions of DEmRNAs. Their results indicated that the up-regulated expression of mRNAs involved in BP is primarily associated with brown adipocyte differentiation (Adig and Slc2a4), lipid metabolic process (Aacs, Fdx1, and Slc27a1), and metabolic process (Aacs and Slc27a1). The down-regulated mRNAs might exist related to inflammatory response (Ccl12, Ccl3, Ccl7, Cd180, Cxcl1, Cybb, Il18, Ly86, S100a8, S100a9, Tlr1, and Tlr8). KEGG pathway analysis showed that two DEmRNAs, Slc27a1 and Slc2a4, were involved in the insulin resistance signaling pathway, which is closely related to obesity (Yu, Kim & Lee, 2017). The inflammatory signaling, IL-17 signaling, and NF-kappa B signaling pathways were likewise subjected to KEGG annotation prediction analysis (Tanti et al., 2012, Tarantino et al., 2014). Their results indicate that Sal B may exert anti-obesity effects by modulating the expression of mRNAs in lipid metabolism and inflammation-related signaling pathways.
Among total RNAs, circRNAs are the least understood, but appear to maintain intricate regulatory effects in the progress of obesity. They identified 9 up-regulated and 10 down-regulated circRNAs under Sal B treatment. Among them, the expression changes of chr14:103252408–103276518:- and chr14:103282597–103291362:- were the most obvious, with an approximate 30-fold upregulation. Therefore, these circRNAs may serve as targets for the design of therapeutic drugs for obesity, pending study of their specific mechanisms.Conclusions
This study is the first comprehensive analysis of mRNA, lncRNA, and circRNA expression in EP of HFD-induced obese mice. They found that Sal B regulates the expression of mRNAs and lncRNAs associated with adipocyte differentiation, lipid metabolism, and inflammation, as well as the insulin resistance and IL-17 signaling pathways. These findings suggest that Sal B plays an vital role in inhibiting obesity by regulating anti-inflammatory related factors and signaling pathways. Their research provides valuable insights into the molecular mechanism of Sal B in anti-obesity effects and contributes therapeutic markers for pharmaceutical design in the prevention and treatment of obesity. In the future, the corresponding roles and molecular mechanisms of non-coding RNAs should exist further elucidated. In addition, differential expression at the RNA plane does not necessarily indicate that the expression of related proteins is likewise significantly different. They point to correlate RNA and protein analysis to more fully investigate the anti-obesity mechanism of Sal B.
Food allergy (FA) results from an abnormal immune-mediated reaction against food antigens, such as cow’s milk proteins1,2. Due to its early introduction, cow’s milk allergy (CMA) is one of the earliest and most common FA3. The immune mechanism of CMA can exist IgE-mediated or non-IgE-mediated (cell mediated) and it is recognized as a first indicator of a dysregulated immune response in the pediatric age4. In fact, children affected by CMA in the first year of life maintain an increased risk to develop other atopic manifestations in their later life5,6, as well as other chronic immune-mediated disorders such as inflammatory bowel diseases7. Therefore, understanding CMA pathogenesis is vital in order to effectively preclude and manage the disease and its later life consequences. The intestinal microbiota plays a censorious role in the maturation and continued education of the host immune system8. Evidence suggests that selected bacterial species and their metabolites from hardy gut microbiota, in particular the short-chain fatty acid butyrate, may positively modulate immune tolerance mechanisms
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