Objective: To explore the molecular mechanisms of fat metabolism and deposition in pigs, an experiment was conducted to identify hepatic mRNAs and miRNAs expression and determine the potential interaction of them in two phenotypically extreme pig breeds. Methods: mRNA and miRNA profiling of liver from 70-day Jinhua (JH) and Landrace (LD) pigs were performed using RNA sequencing. Blood samples were taken to detect results of serum biochemistry. Bioinformatics analysis were applied to construct differentially expressed miRNA-mRNA network. Results: Serum total triiodothyronine and total thyroxine were significantly lower in Jinhua pigs, but the content of serum total cholesterol (TCH) and low-density lipoprotein cholesterol were strikingly higher. A total of 467 differentially expressed genes (DEGs) and 35 differentially expressed miRNAs (DE miRNAs) were identified between JH and LD groups. Gene ontology analysis suggested that DEGs were involved in oxidation-reduction, lipid biosynthetic and lipid metabolism process. Interaction network of DEGs and DE miRNAs were constructed, according to target prediction results. Conclusion: We generated transcriptome and miRNAome profiles of liver from JH and LD pig breeds which represent distinguishing phenotypes of growth and metabolism. The potential miRNA-mRNA interaction networks may provide a comprehensive understanding in the mechanism of lipid metabolism. These results serve as a basis for further investigation on biological functions of miRNAs in the porcine liver.
EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.
Cho, Sung Woo;Kim, Hyoung Kyu;Sung, Ji Hee;Han, Jin
BMB Reports
/
제54권9호
/
pp.464-469
/
2021
Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)+ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)+ and PDGFRα+ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα+ CLCs and hiPSC-derived KDR+PDGFRα+ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.
Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.
Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA+ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA+ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.
Cellulases are a group of biocatalyst enzymes that are capable of degrading cellulosic biomass present in the natural environment and produced by a large number of microorganisms, including bacteria and fungi, etc. In the current study, we isolated, screened and characterized cellulase-producing bacteria from soil. Three cellulose-degrading species were isolated based on clear zone using Congo red stain on carboxymethyl cellulose (CMC) agar plates. These bacterial isolates, named as HB2, HS5 and HS9, were subsequently characterized by morphological and biochemical tests as well as 16S rRNA gene sequencing. Based on 16S rRNA analysis, the bacterial isolates were identified as Bacillus cerus, Bacillus subtilis and Bacillus stratosphericus. Moreover, for maximum cellulase production, different growth parameters were optimized. Maximum optical density for growth was also noted at pH 7.0 for 48 h for all three isolates. Optical density was high for all three isolates using meat extract as a nitrogen source for 48 h. The pH profile of all three strains was quite similar but the maximum enzyme activity was observed at pH 7.0. Maximum cellulase production by all three bacterial isolates was noted when using lactose as a carbon rather than nitrogen and peptone. Further studies are needed for identification of new isolates in this region having maximum cellulolytic activity. Our findings indicate that this enzyme has various potential industrial applications.
[Purpose] Epidemiological evidence has shown that leisure-time physical activity and structured exercise before and after breast cancer diagnosis contribute to reducing the risk of breast cancer recurrence and mortality. Thus, in this review, we aimed to summarize the physical activity-dependent regulation of systemic factors to understand the biological and molecular mechanisms involved in the initiation, progression, and survival of breast cancer. [Methods] We systematically reviewed the studies on 1) the relationship between physical activity and the risk of breast cancer, and 2) various systemic factors induced by physical activity and exercise that are potentially linked to breast cancer outcomes. To perform this literature review, PubMed database was searched using the terms "Physical activity OR exercise" and "breast cancer", until August 5th, 2020; then, we reviewed those articles related to biological mechanisms after examining the resulting search list. [Results] There is strong evidence that physical activity reduces the risk of breast cancer, and the protective effect of physical activity on breast cancer has been achieved by long-term regulation of various circulatory factors, such as sex hormones, metabolic hormones, inflammatory factors, adipokines, and myokines. In addition, physical activity substantially alters wholebody homeostasis by affecting numerous other factors, including plasma metabolites, reactive oxygen species, and microRNAs as well as exosomes and gut microbiota profile, and thereby every cell and organ in the whole body might be ultimately affected by the biological perturbation induced by physical activity and exercise. [Conclusion] The understanding of integrative mechanisms will enhance how physical activity can ultimately influence the risk and prognosis of various cancers, including breast cancer. Furthermore, physical activity could be considered an efficacious non-pharmacological therapy, and the promotion of physical activity is probably an effective strategy in primary cancer prevention.
In this study we investigate physical and chemical characteristics of immature and mature skipjack tuna (Katsuwonus pelamis) roes in fresh and dried forms. Fresh roes were studied for histological structure and also dried by three methods: hot air drying (HD), vacuum drying (VD) and freeze drying (FD). The obtained roe powders were analysed for proximate composition, color value, fatty acid composition, amino acid profile, equivalent umami concentration (EUC) and protein pattern. Unyolked oocytes were more common in immature roes, while fully yolked oocytes were more common in mature roes. All dried tuna roes contained high content of protein and lipid (69.31%-70.55% and 11.14%-16.02%, respectively). The powders obtained by FD provided the highest lightness value (L*). The main fatty acid found in all roe powders was docosahexaenoic acid (DHA) (23.49%-27.02%). Glutamic acid, leucine, and aspartic acid were the three most abundant amino acids found in the powders (13.58-14.61, 8.06-8.42, and 7.81-8.39 g/100 g of protein, respectively). The mature roe powder obtained from HD provided the highest EUC value (73.09 g monosodium glutamate/100 g of samples). The protein band at molecular weight of 97 kDa (vitelline) represented the major protein. Therefore, dried tuna roe could be a functional ingredient source of protein and lipid rich in DHA and it also has potential to be used as taste enhancer with umami compound.
Purpose: Human milk oligosaccharides (HMOs) may be genetically determined based on the secretor and Lewis status of the mother. This study aims to determine the HMO profile and the secretor and Lewis gene status of Indonesian lactating mothers. Methods: Baseline data of 120 mother-infant pairs between 0-4 months post-partum obtained from a prospective longitudinal study was used. The concentrations of 2'-fucosyllactose (2'FL), lacto-N-fucopentaose I (LNFP I), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 3'-sialyllactose (3'SL), and 6'-sialyllactose (6'SL) were measured. Genetic analysis was performed for mothers using targeted next-generation sequencing and Sanger sequencing. Wild-type AA with the rs1047781 (A385T) polymorphism was categorized as secretor positive, while heterozygous mutant AT was classified as a weak secretor. The presence of rs28362459 (T59G) heterozygous mutant AC and rs3745635 (G508A) heterozygous mutant CT genes indicated a Lewis negative status, and the absence of these genes indicated a positive status. Subsequently, breast milk was classified into various groups, namely Group 1: Secretor+Lewis+ (Se+Le+), Group 2: Secretor-Lewis+ (Se-Le+), Group 3: Secretor+Lewis-(Se+Le-), and Group 4: Secretor-Lewis- (Se-Le-). Data were analyzed using the Mann-Whitney and Kruskal-Wallis rank tests, and a p-value of 0.05 indicated statistical significance. Results: A total of 58.3% and 41.7% of the samples had positive and weak secretor statuses, respectively. The proportion of those in Group 1 was 85%, while 15% were Group 3. The results showed that only 2'FL significantly differed according to the secretor status (p-value=0.018). Conclusion: All Indonesian lactating mothers in this study were secretor positive, and most of them had a Lewis-positive status.
Objective: The objective of the present study was to investigate the effect of dietary betaine (BT) supplementation on the hepatic transcriptome profiles in broiler chickens raised under heat stress (HS) conditions. Methods: A total of 180 (21-d-old) Ross 308 male broiler chicks were allotted to 1 of 3 treatment groups with 6 replicated cages in a completely randomized design. One group was kept under thermoneutral conditions at all times and was fed a basal diet (PC). Other 2 groups were exposed to a cyclic heat stress condition. One of the 2 groups under heat stress conditions was fed the basal diet as a negative control (NC), whereas the other group was fed the basal diet supplemented with 0.2% BT. All chickens were provided with diets and water ad libitum for 21 d. Following the experiment, the liver samples were collected for RNA sequencing analysis. Results: Broiler chickens in NC and BT group had decreased (p<0.05) growth performance. In the transcriptome analysis, the number of differentially expressed genes were identified in the liver by HS conditions and dietary BT supplementation. In the comparison between NC and PC treatments, genes related to energy and nucleic acid metabolism, amino acid metabolism, and immune system were altered by HS, which support the reason why heat-stressed poultry had decreased growth performance. In the comparison between NC and BT treatments, genes related to lipid metabolism, carbohydrate metabolism, and immune system were differently expressed under HS conditions. Conclusion: HS negatively impacts various physiological processes, including DNA replication, metabolism of amino acids, lipids, and carbohydrates, and cell cycle progression in broiler chickens. Dietary BT supplementation, however, offers potential counteractive effects by modulating liver function, facilitating gluconeogenesis, and enhancing immune systems. These findings provide a basis for understanding molecular responses by HS and the possible benefits of dietary BT supplementation in broiler chickens exposed to HS.
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