Alliin (S-allyl cysteine sulfoxide) is a bioactive sulfoxide compound derived from garlic. To evaluate the preventive effect of alliin against metabolic risk factors in diet induced obese (DIO) mice, ...we treated the C57BL/6J DIO mice with drinking water with or without alliin (0.1 mg/ml) for 8 weeks. Results showed that alliin had no significant effect on the body weight, adiposity or energy balance. However, alliin treatment enhanced glucose homeostasis, increased insulin sensitivity and improved the lipid profile in the DIO mice. This was, at least partly, attributable to alliin induced modulation of the intestinal microbiota composition, typically decreased Lachnospiraceae and increased Ruminococcaceae. From above, we conclude that alliin has nutraceutical or even medicinal potential in prevention of diabetes and lipid metabolic disorders.
Increasing energy expenditure through activation of brown adipose tissue (BAT) is a critical approach to treating obesity and diabetes. In this study, rutin, a natural compound extracted frommulberry ...and a drug used as a capillary stabilizer clinically formany years without any side effects, regulated whole‐body energymetabolism by enhancing BAT activity. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both genetically obese (Db/Db) and diet‐induced obesity (DIO) mice. Rutin also induced brown‐like adipocyte (beige) formation in subcutaneous adipose tissue in both obesity mouse models. Mechanistically, we found that rutin directly bound to and stabilized SIRT1, leading to hypoacetylation of peroxisome proliferator‐activated receptor γ coactivator‐1α protein, which stimulated Tfam transactivation and eventually augmented the number of mitochondria and UCP1 activity in BAT. These findings reveal that rutin is a novel small molecule that activates BAT and may provide a novel therapeutic approach to the treatment of metabolic disorders.—Yuan, X., Wei, G., You, Y., Huang, Y., Lee, H. J., Dong, M., Lin, J., Hu, T., Zhang, H., Zhang, C., Zhou, H., Ye, R., Qi, X., Zhai, B., Huang, W., Liu, S., Xie, W., Liu, Q., Liu, X., Cui, C., Li, D., Zhan, J., Cheng, J., Yuan, Z., Jin, W. Rutin ameliorates obesity through brown fat activation. FASEB J. 31, 333–345 (2017) www.fasebj.org
MicroRNAs (miRNAs), a ubiquitous class of short RNAs, play vital roles in physiological and biochemical processes in plants by mediating gene silencing at post-transcriptional (PTGS) level. Tomato is ...a model system to study molecular basis of fleshy fruit ripening and senescence, ethylene biosynthesis and signal transduction owing to its genetic and molecular tractability. To study the functions of miRNAs in tomato fruit ripening and senescence, and their possible roles in ethylene response, the next generation sequencing method was employed to identify miRNAs in tomato fruit. Bioinformatics and molecular biology approaches were combined to profile the miRNAs expression patterns at three different fruit ripening stages and by exogenous ethylene treatment.
In addition to 7 novel miRNA families, 103 conserved miRNAs belonging to 24 families and 10 non-conserved miRNAs matching 9 families were identified in our libraries. The targets of many these miRNAs were predicted to be transcriptional factors. Other targets are known to play roles in the regulation of metabolic processes. Interestingly, some targets were predicted to be involved in fruit ripening and softening, such as Pectate Lyase, beta-galactosidase, while a few others were predicted to be involved in ethylene biosynthesis and signaling pathway, such as ACS, EIN2 and CTR1. The expression patterns of a number of such miRNAs at three ripening stages were confirmed by stem-loop RT-PCR, which showed a strong negative correlation with that of their targets. The regulation of exogenous ethylene on miRNAs expression profiles were analyzed simultaneously, and 3 down-regulated, 5 up-regulated miRNAs were found in this study.
A combination of high throughput sequencing and molecular biology approaches was used to explore the involvement of miRNAs during fruit ripening. Several miRNAs showed differential expression profiles during fruit ripening, and a number of miRNAs were influenced by ethylene treatment. The results suggest the importance of miRNAs in fruit ripening and ethylene response.
Summary
The development and ripening of tomato fruit are complex processes involving many gene regulatory pathways at the transcriptional and post‐transcriptional level. Ripening inhibitor (RIN) is a ...vital transcription factor, which targets numerous ripening‐related genes at the transcriptional level during tomato fruit ripening. MicroRNAs (miRNAs) are a class of short noncoding RNAs that play important roles in post‐transcriptional gene regulation. To elucidate the potential regulatory relationship between rin and miRNAs during fruit development and ripening, we identified known miRNAs and profiled their expression in wild‐type tomato and rin mutant using a deep sequencing approach combined with quantitative RT‐PCR. A total of 33 known miRNA families were identified, of which 14 miRNA families were differently accumulated. Subsequent promoter analysis showed that possible RIN‐binding motifs (CArG‐box) tended to occur frequently in the promoter regions of partial differently expressed miRNAs. In addition, ethylene may participate in the regulation of miRNAs accumulation during tomato fruit ripening. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay confirmed the direct binding of RIN to the promoter of MIR172a. Collectively, these results showed a close correlation between miRNA expression and RIN as well as ethylene, which further elucidated the regulatory roles of miRNAs during fruit development and ripening and enriched the regulatory network of RIN in tomato fruit.
Gastric cancer is a prevalent malignancy with a high degree of heterogeneity, which has led to a poor therapeutic response. Though there are numerous HER2-targeted medicines for HER2+ gastric cancer, ...many trials have not indicated an improvement in overall survival. Here 29 ERBB2 amplification (ERBB2-Amp) type gastric cancer samples with WES and RNA-seq data were selected for investigation, which copy-number aberration (CNA) was +2. Initially, the somatic mutation and copy number variant (CNV) of them, which might cause resistance to HER2-targeted therapies, were systematically investigated evaluated, as well as their mutation signatures. Moreover, 37 modules were identified using weighted gene co-expression network analysis (WGCNA), including the blue module related to DFS status and lightcyan module correlated with ARHGAP26_ARHGAP6_CLDN18 rearrangement. In addition, focal adhesion and ECM-receptor interaction pathways were considerably enriched in the turquoise module with ERBB2 gene. ExportNetworkToCytoscape determined that MIEN1 and GRB7 are tightly connected to ERBB2., Finally, 14 single-cell intestinal gastric cancer samples were investigated, and it was shown that the TFAP2A transcription factor regulon was highly expressed in ERBB2high group, as was the EMT score. Overall, our data provide comprehensive molecular characteristics of ERBB2-Amp type gastric cancer, which offers additional information to improve HER2-targeted gastric cancer treatment.
“Cu-DNAzyme” and “G4-DNAzyme” were used to develop a “turn-off” dual-DNAzyme colorimetric biosensor, which could be used to detect Cu2+ by employing exonuclease III-mediated cyclical assembly (EMCA). ...EMCA was based on the cleavage activity of Cu2+ to transfer the linkage sequences of the substrate strand and enzyme strand into the transition sequence. The horseradish peroxidase (HRP)-mimicking activity of the G4-DNAzyme was lost after binding with the complementary transition sequence and was hydrolyzed by Exo III. These results demonstrate that the proposed colorimetric biosensor was an effective method for ultradetection of trace metals in a high original signal background. Due to the high sensitivity of the biosensor, the limit of detection (LOD) of Cu2+ is 0.16 nM. This design offers a general purpose platform that could be applied for the detection of any metal ion target through adjustment of metal-dependent DNA-cleaving DNAzymes, which is of great significance for the rapid determination of food safety.
Silver ions are regarded as one of the most hazardous metal contaminants, endangering both the ecological environment and human health. Traditional silver ions detection technologies are hampered by ...their high cost, time-consuming nature, and labor-intensive operation. DNA aptamers play an essential part in the field of biosensors due to their ease of synthesis, ease of modification, and low cost. This paper focuses on reviewing the research progress of DNA aptamer-based biosensors in silver ions detection. According to the types of signal transduction, they are classified into four forms of signal transduction: fluorescent biosensors, colorimetric biosensors, electrochemical biosensors, and surface-enhanced Raman spectroscopy biosensors. In addition, this paper gives a perspective on the application prospects outlook and development directions of DNA aptamer-based biosensors, in order to provide theoretical ideas for the future development of more sensitive DNA aptamer biosensors for rapid detection of silver ions.
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•Biosensor based on DNA aptamer for silver ion detection were reviewed.•Biosensors with different signal outputs for detection were introduced.•A reasonable prospect was given for the development of silver ion biosensors.
Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a natural product in garlic, has multiple biological and ...pharmacological functions. However, the role of allicin in the regulation of metabolic organs, particularly BAT activation, has not been well studied. Here, we show that allicin imparts a significant effect by inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in obese mice. These observations strongly correlate with the activation of BAT. Notably, allicin plays a role in BAT activation, which may partly contribute to the Sirt1-PGC1α-Tfam pathway. In addition, allicin can significantly increase the succinylation levels of UCP1 in BAT by inhibiting sirt5, whereas excess allicin induces autophagy/mitophagy and mitochondrial dysfunction. Thus, our findings point to allicin as a promising therapeutic approach for the treatment of obesity and metabolic disorders.
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•Allicin reduces adiposity and maintains glucose homeostasis•Allicin activates the brown adipocytes and increases the energy expenditure•Allicin enhances BAT activity partly through SIRT1-PGC1a-Tfam signaling pathway•Allicin regulates mitophagy via suppressed sirt5-mediated succinylation accumulation
Biological Sciences; Human Physiology; Molecular Physiology
Tomato fruit are sensitive to chilling injury (CI) during cold storage. Several factors have been discovered to be involved in chilling injury of tomato fruit. Plant hormones play an important ...regulatory role, however, the relationship between chilling injury and N6-methyladenosine (m6A) methylation of transcripts in plant hormone pathways has not been reported yet. In order to clarify the complex regulatory mechanism of m6A methylation on chilling injury in tomato fruit, Nanopore direct RNA sequencing was employed. A large number of enzymes and transcription factors were found to be involved in the regulation process of fruit chilling injury, which were associated with plant hormone, such as 1-aminocyclopropane 1-carboxylate synthase (ACS), aspartate aminotransferase (AST), auxin response factor (ARF2), ethylene response factor 2 (ERF2), gibberellin 20-oxidase-3 (GA20ox) and jasmonic acid (JA). By conjoint analysis of the differential expression transcripts related to chilling injury and m6A methylation differential expression transcripts 41 differential expression transcripts were identified involved in chilling injury including 1-aminocyclopropane-1-carboxylate oxidase (ACO) and pectinesterase (PE) were down-regulated and heat shock cognate 70 kD protein 2 (cpHSC70), HSP70-binding protein (HspBP) and salicylic acid-binding protein 2 (SABP2) were up-regulated. Our results will provide a deeper understanding for chilling injury regulatory mechanism and post-harvest cold storage of tomato fruit.
Small RNAs have emerged as critical regulators in the expression and function of eukaryotic genomes at the post‐transcriptional level. To elucidate the functions of microRNA (miRNAs) and endogenous ...small‐interfering RNAs (siRNAs) in tomato fruit ripening process, the deep sequencing and bioinformatics methods were combined to parse the small RNAs landscape in three fruit‐ripening stages (mature green, breaker and red‐ripe) on a whole genome. Two species‐specific miRNAs and two members of TAS3 family were identified, 590 putative phased small RNAs and 125 cis‐natural antisense (nat‐siRNAs) were also found in our results which enriched the tomato small RNAs repository and all of them showed differential expression patterns during fruit ripening. A large amount of the targets of the small RNAs were predicted to be involved in fruit ripening and ethylene pathway. Furthermore, the promoters of the conserved and novel miRNAs were found to contain the conserved motifs of TATA‐box and CT microsatellites which were also found in Arabidopsis and rice, and several species‐specific motifs were found in parallel.
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