scholarly journals MicroRNA and mRNA Sequencing Analyses Reveal Key Hepatic Metabolic Pathways Responsive to Maternal Malnutrition in Full-Term Fetal Pigs

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 829-829
Author(s):  
Feng Wang ◽  
Christian Maltecca ◽  
Xiaoqiu Wang ◽  
Jack Odle ◽  
Lin Xi
Keyword(s):  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Agricultural Research ◽  
Negative Impact ◽  
Full Term ◽  
Differentially Expressed ◽  
Hepatic Tissue ◽  
Sequencing Analysis ◽  
Maternal Malnutrition ◽  
Maternal Undernutrition

Abstract Objectives Maternal and infant undernutrition is highly prevalent in developing countries, leading to serious fetus/infant mortality, intrauterine growth restriction, stunting, and severe wasting. However, the effects of maternal undernutrition have generally focused on the reduced maternal nutrient supply to the fetus. The potential impairment of fetal metabolic pathways has not been well studied. Methods Pregnant gilts (Landrace x Yorkshire x Duroc) received the NRC gestation diet with (n = 4) or without (n = 4) 50% intake restriction at insemination day and 70% for the following gestation period. Full term fetuses were obtained via C-section, two piglets were selected from each gilt in both groups and subject to hepatic tissue collection. MicroRNA and mRNA deep sequencing analysis was performed using the Illumina GAIIx system. The mRNA-miRNA correlation and associated signaling pathways were analyzed via CLC workbench, Ingenuity Pathway Analysis Software. Results A total of 42 differentially expressed miRNAs were identified between intake-restriction and full-nutrition group. Among of these, mir-206, mir-133b, mir-1246, mir-1843 and mir-7139 are the most downregulated and mir-10b, mir-708 and mir-222 are the most upregulated miRNAs. A total of 1215 mRNAs were identified to differentially expressed between two groups. Two metabolic pathways: retinol biosynthesis and oxidative phosphorylation were significantly modified, and the modification was associated with the miRNA changes induced by the maternal feed restriction. Briefly, the retinol biosynthesis pathway was upregulated (p < 0.01), in which those differential expressed mir-221, mir-4492, mir-1281 and mir-4492 were predicted targeting genes AADAC, CES3, PNPLA3 and RDH13 in the pathway. The oxidative phosphorylation pathway was upregulated (p < 0.05), and those differential expressed mir-1843, mir-222 and mir-184 were predicted targeting genes ATP5F1C, NDUFA1, NDUFB10, and NDUFS7 in this pathway. Conclusions These results provide the framework for further understanding of negative impact of maternal malnutrition on hepatic metabolic pathways via miRNA-RNA interactions in full-term fetal pigs. Funding Sources Supported in part by the Bill and Melinda Gates Foundation (GCE OPP1061037) and by the North Carolina Agricultural Research Service.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

Transcriptional identification of differentially expressed genes during the prepupal–pupal transition in the oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

2021 ◽  
pp. 1-14
Author(s):  
Peirong Li ◽  
Xinru Li ◽  
Wei Wang ◽  
Xiaoling Tan ◽  
Xiaoqi Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Metabolic Pathways ◽  
Developmental Stages ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Mythimna Separata ◽  
Kegg Pathway Analysis ◽  
Oriental Armyworm ◽  
Lepidoptera Noctuidae

Abstract The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.

scholarly journals Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 325
Author(s):  
Carolina Venturoli ◽  
Ilaria Piga ◽  
Matteo Curtarello ◽  
Martina Verza ◽  
Giovanni Esposito ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Pathways ◽  
Negative Impact ◽  
Digital Pathology ◽  
Pyruvate Dehydrogenase Kinase ◽  
Ovarian Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 1

Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways—comprising both oxidative phosphorylation and glycolysis—in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.

scholarly journals Transcriptomic and Metabolic Profiling of High-Temperature Treated Storage Roots Reveals the Mechanism of Saccharification in Sweetpotato (Ipomoea batatas (L.) Lam.)

2021 ◽  
Vol 22 (13) ◽  
pp. 6641
Author(s):  
Chen Li ◽  
Meng Kou ◽  
Mohamed Hamed Arisha ◽  
Wei Tang ◽  
Meng Ma ◽  
...  
Keyword(s):  
High Temperature ◽  
Metabolic Pathways ◽  
Transcriptome Sequencing ◽  
Ipomoea Batatas ◽  
Sequencing Analysis ◽  
Storage Roots ◽  
Metabolic Analysis ◽  
Cooking Process

The saccharification of sweetpotato storage roots is a common phenomenon in the cooking process, which determines the edible quality of table use sweetpotato. In the present study, two high saccharified sweetpotato cultivars (Y25, Z13) and one low saccharified cultivar (X27) in two growth periods (S1, S2) were selected as materials to reveal the molecular mechanism of sweetpotato saccharification treated at high temperature by transcriptome sequencing and non-targeted metabolome determination. The results showed that the comprehensive taste score, sweetness, maltose content and starch change of X27 after steaming were significantly lower than those of Y25 and Z13. Through transcriptome sequencing analysis, 1918 and 1520 differentially expressed genes were obtained in the two periods of S1 and S2, respectively. Some saccharification-related transcription factors including MYB families, WRKY families, bHLH families and inhibitors were screened. Metabolic analysis showed that 162 differentially abundant metabolites related to carbohydrate metabolism were significantly enriched in starch and sucrose capitalization pathways. The correlation analysis between transcriptome and metabolome confirmed that the starch and sucrose metabolic pathways were significantly co-annotated, indicating that it is a vitally important metabolic pathway in the process of sweetpotato saccharification. The data obtained in this study can provide valuable resources for follow-up research on sweetpotato saccharification and will provide new insights and theoretical basis for table use sweetpotato breeding in the future.

scholarly journals Transcriptome analysis identifies differentially expressed genes in the progenies of a cross between two low phytic acid soybean mutants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hangxia Jin ◽  
Xiaomin Yu ◽  
Qinghua Yang ◽  
Xujun Fu ◽  
Fengjie Yuan
Keyword(s):  
Developmental Stage ◽  
Phytic Acid ◽  
Differentially Expressed Genes ◽  
Transcriptome Analysis ◽  
Defense Mechanisms ◽  
Developmental Stages ◽  
Sucrose Metabolism ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Seed Developmental Stage

AbstractPhytic acid (PA) is a major antinutrient that cannot be digested by monogastric animals, but it can decrease the bioavailability of micronutrients (e.g., Zn and Fe). Lowering the PA content of crop seeds will lead to enhanced nutritional traits. Low-PA mutant crop lines carrying more than one mutated gene (lpa) have lower PA contents than mutants with a single lpa mutant gene. However, little is known about the link between PA pathway intermediates and downstream regulatory activities following the mutation of these genes in soybean. Consequently, we performed a comparative transcriptome analysis using an advanced generation recombinant inbred line with low PA levels [2mlpa (mips1/ipk1)] and a sibling line with homozygous non-mutant alleles and normal PA contents [2MWT (MIPS1/IPK1)]. An RNA sequencing analysis of five seed developmental stages revealed 7945 differentially expressed genes (DEGs) between the 2mlpa and 2MWT seeds. Moreover, 3316 DEGs were associated with 128 metabolic and signal transduction pathways and 4980 DEGs were annotated with 345 Gene Ontology terms related to biological processes. Genes associated with PA metabolism, photosynthesis, starch and sucrose metabolism, and defense mechanisms were among the DEGs in 2mlpa. Of these genes, 36 contributed to PA metabolism, including 22 genes possibly mediating the low-PA phenotype of 2mlpa. The expression of most of the genes associated with photosynthesis (81 of 117) was down-regulated in 2mlpa at the late seed developmental stage. In contrast, the expression of three genes involved in sucrose metabolism was up-regulated at the late seed developmental stage, which might explain the high sucrose content of 2mlpa soybeans. Furthermore, 604 genes related to defense mechanisms were differentially expressed between 2mlpa and 2MWT. In this study, we detected a low PA content as well as changes to multiple metabolites in the 2mlpa mutant. These results may help elucidate the regulation of metabolic events in 2mlpa. Many genes involved in PA metabolism may contribute to the substantial decrease in the PA content and the moderate accumulation of InsP3–InsP5 in the 2mlpa mutant. The other regulated genes related to photosynthesis, starch and sucrose metabolism, and defense mechanisms may provide additional insights into the nutritional and agronomic performance of 2mlpa seeds.

scholarly journals Next-Generation Sequencing Analysis of the Tineola bisselliella Larval Gut Transcriptome Reveals Candidate Enzymes for Keratin Digestion

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1113
Author(s):  
Michael Schwabe ◽  
Sven Griep ◽  
Henrike Schmidtberg ◽  
Rudy Plarre ◽  
Alexander Goesmann ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Disulfide Bonds ◽  
Differentially Expressed ◽  
Intestinal Microbiome ◽  
Sequencing Analysis ◽  
High Quality ◽  
Transcriptomic Data ◽  
Next Generation Sequencing Analysis ◽  
Generation Sequencing ◽  
Tineola Bisselliella

The clothes moth Tineola bisselliella is one of a few insects that can digest keratin, leading to the destruction of clothing, textiles and artwork. The mechanism of keratin digestion is not yet fully understood, partly reflecting the lack of publicly available genomic and transcriptomic data. Here we present a high-quality gut transcriptome of T. bisselliella generated from larvae reared on keratin-rich and keratin-free diets. The overall transcriptome consists of 428,221 contigs that were functionally annotated and screened for candidate enzymes involved in keratin utilization. As a mechanism for keratin digestion, we identified cysteine synthases, cystathionine β-synthases and cystathionine γ-lyases. These enzymes release hydrogen sulfite, which may reduce the disulfide bonds in keratin. The dataset also included 27 differentially expressed contigs with trypsin domains, among which 20 were associated with keratin feeding. Finally, we identified seven collagenases that were upregulated on the keratin-rich diet. In addition to this enzymatic repertoire potentially involved in breaking down keratin, our analysis of poly(A)-enriched and poly(A)-depleted transcripts suggested that T. bisselliella larvae possess an unstable intestinal microbiome that may nevertheless contribute to keratin digestion.

scholarly journals Randomized clinical trial of the effect of the onset time of skin-to-skin contact at birth, immediate compared to early, on the duration of breastfeeding in full term newborns

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sergio I Agudelo ◽  
Oscar A Gamboa ◽  
Eduardo Acuña ◽  
Lina Aguirre ◽  
Sarah Bastidas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Exclusive Breastfeeding ◽  
Negative Impact ◽  
Onset Time ◽  
Full Term ◽  
Breastfeeding Duration ◽  
Bivariate Analysis ◽  
Skin Contact ◽  
Term Newborns ◽  
Skin To Skin

Abstract Background Skin-to-skin contact (SSC) compared to separation at birth has a positive effect on breastfeeding. However, separation at birth is common with negative impact on breastfeeding. The aim was to determine the effect of immediate SSC compared to early SSC on the duration of exclusive breastfeeding. Methods A randomized multicentre parallel clinical trial was conducted in two hospitals in Cundinamarca (Colombia) between November 2018 and January 2020. Low-risk full term newborns at birth were included. Neonates were assigned to immediate (in the first minute after birth) or early onset (start exactly at 60 min of life) skin to skin contact. Monthly follow-up was performed until 6 months of age. The primary outcome was the percentage of exclusively breastfed infants at 6 months (time in months with human milk as the only source of food). Secondary outcomes were the percentage of infants with exclusive breastfeeding at 3 months, duration in months of exclusive breastfeeding, neonate’s breastfeeding ability, percentage of weight change between birth and the first week of life and hospitalization in the neonatal unit in the first week. A bivariate analysis was performed to determine the variables associated with exclusive breastfeeding at 6 months. A survival analysis was performed to evaluate the effect of the onset of SSC on exclusive breastfeeding duration. Results A total of 297 newborns were included: 49.8% (n = 148) in the immediate SSC group, and 50.2% (n = 149) in the early SSC group. The mean duration of exclusive breastfeeding in both groups was 5 months. There were no differences between the groups in the percentage of exclusive breastfeeding at 6 months (relative risk [RR] 1.06, 95% CI 0.72, 1.58) or in the duration of exclusive breastfeeding (hazard ratio [HR] 0.98, 95% CI 0.74, 1.28). Conclusions The percentage of infants and the duration of exclusive breastfeeding in the first 6 months of age were the same between the two groups of SSC interventions. Given the current barriers to its implementation, the results of this study could positively impact the use of SSC at birth and standardize the intervention and improve breastfeeding indicators. Trial registration ClinicalTrials.gov NCT02687685.

scholarly journals Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Tingfu Du ◽  
Shuaiyao Lu ◽  
Qinfang Jiang ◽  
Yun Li ◽  
Kaili Ma
Keyword(s):  
Rhesus Macaque ◽  
Differentially Expressed ◽  
Hepatic Tissue ◽  
Expression Change ◽  
Macaque Model ◽  
Genome Wide ◽  
Proteomic Study ◽  
Pathway Analyses ◽  
High Sucrose

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ-) induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

Molecular predictors of response to selinexor in advanced unresectable de-differentiated liposarcoma (DDLS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11509-11509
Author(s):  
Christopher James Walker ◽  
Hua Chang ◽  
Jianjun Liu ◽  
Bruno Vincenzi ◽  
Andrea Napolitano ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
B Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Tumor Control ◽  
Double Blind Study ◽  
Sequencing Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Validation Set

11509 Background: Patients (pts) with recurrent inoperative DDLS have a poor prognosis and limited treatment options. Selinexor is an oral, selective inhibitor of nuclear export (SINE) compound approved for previously treated pts with myeloma and diffuse large B-cell lymphoma. SEAL was a Phase 2-3 randomized, double-blind, study of selinexor versus placebo in pts with progressive DDLS and 2-5 prior systemic therapies. SEAL showed significantly prolonged progression-free survival (PFS, HR = 0.70, p = 0.0228) with well managed toxicity. A biomarker predictive of clinical activity could be used to optimize selection of pts with DDLS for selinexor. Methods: Pts were randomized 2:1 for Phase 3: 188 received twice weekly selinexor (60mg) and 97 received placebo. Three exploratory biomarker analyses (RNA sequencing of biopsies) from selinexor-treated pts were performed: discovery set of sensitive (n = 8) or resistant (n = 9) tumors; a validation set of pts with favorable (n = 19) or poor (n = 14) tumor control based on PFS, and paired lesions from a pt who harbored both a responsive and resistant lesion. Tumor biopsies from 24 pts on placebo with short ( < 5 months, n = 18) and long ( > 6 months, n = 6) PFS were RNA sequenced. Gene expressions were compared using a negative binomial distribution with DeSeq2. Pathway analyses were performed using Gene Set Enrichment Analysis (GSEA) with MSigDB Cancer Gene Neighborhoods. Results: RNA sequencing analysis comparing 17 sensitive and resistant tumors identified 114 differentially expressed genes (adjusted p-values < 0.05). Expression of CALB1, which encodes the calcium-binding protein calbindin, was significantly lower in sensitive tumors (adjusted P [Padj] = 7.5x10-20), and expression of GRM1, which encodes a metabotropic glutamate receptor that activates phospholipase C, was higher in selinexor sensitive tumors (Padj= 0.003). These findings were confirmed in an independent validation set (Padj = 0.01 – 0.02). In the pt with paired sensitive and resistant lesions, CALB1 expression was 52-fold lower in the sensitive tumor. In a comparison of placebo-treated pts, neither CALB1 or GRM1 was differentially expressed between pts with short or long PFS, indicating they are markers of response to selinexor treatment, rather than general markers of disease aggressiveness. Gene set enrichment analyses revealed that selinexor sensitive tumors in the discovery and validation sets showed upregulation of cancer genes related to SNRK and the netrin 1 receptor tumor suppressor DCC. The resistant tumors showed upregulated EIF3S2 translation initiator-related genes. Conclusions: Selinexor sensitive DDLS tumors showed low expression of CALB1 and high GRM1. If validated, pts with DDLS whose tumors match this expression profile are especially likely to benefit from selinexor. Clinical trial information: NCT02606461.

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