Project description:Combinatorial synthesis of tryptamine, tyramine, serotonin, dopamine, putrescine, cadaverine, agmatine, histamine, and phenethylamine with acetic anhydride, butyric anhydride, acryloyl chloride, hexanoyl chloride, decanoyl chloride, palmitoyl chloride, and stearoyl chloride respectively. The files also contain the synthesis of tryptamine specifically with acetic anhydride and butyric anhydride respectively.
Project description:Cholesterol performs multiple essential roles in cells. Enhanced cholesterol synthesis and storage in lipid droplets have been linked to cancer aggressiveness, particularly in lipid-rich and hormone-sensitive cancers such as prostate cancer . Cholesterol anabolism and catabolism are finely regulated in tumor cells in response to various nutritional states. Mitochondria have increasingly been recognized as a signal transduction organelle, particularly concerning metabolites derived from mitochondrial activity. The link between mitochondrial regulation and cholesterol synthesis remains inadequately understood. Here, we show that propionyl-CoA promotes cholesterol synthesis, storage, and further progression in prostate cancer cells. We found that propionyl-CoA, mainly produced by isoleucine and valine metabolism in the mitochondria, can translocate through the mitochondrial membrane and serves as a substrate for modifying cleaved SREBP2, stabilizing it and thereby promoting cholesterol synthesis and storage in lipid droplets. This process facilitates cancer metastasis and castration resistant partially through enhancing androgen synthesis in prostate cancer cells. Our results demonstrate that branched-chain amino acid (BCAA) catabolism and propionate metabolism in mitochondria are involved in the regulation of cholesterol synthesis and utilization through metabolite-mediated protein modification. We anticipate that our findings provide a critical link between amino acid metabolism and cholesterol anabolism, highlighting a mechanism that plays a crucial role in the development of castration resistance in prostate cancer patients. This study offers a theoretical rationale for targeting the production of propionyl-CoA, particularly through the metabolism of isoleucine and valine, as an effective strategy to inhibit cholesterol synthesis and its related diseases.
Project description:Despite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often 30 exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results 31 in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker approaches may offer a more reliable diagnosis. Here we investigated the synergistic contributions of circRNA and mRNA signatures derived from blood platelets as biomarkers for lung cancer detection. We developed a comprehensive bioinformatics pipeline permitting analysis of platelet-circRNA and mRNA derived from non-cancer individuals and lung cancer patients. An optimal selected signature is then used to generate the predictive classification model using machine learning algorithm. Using an individual signature of 21 circRNA and 28 mRNA, the predictive models reached an Area Under the Curve (AUC) of 0.88 and 0.81, respectively. Importantly, combinatorial analysis including both types of RNAs resulted in an 8-target signature (6 mRNA and 2 40 circRNA) enhancing the differentiation of lung cancer from controls (AUC of 0.92). Additionally, we identified five biomarkers potentially specific for early-stage detection of lung cancer. Our proof-of-concept study presents the first multi-analyte-based approach for the analysis of platelets-derived biomarkers, providing a potential combinatorial diagnostic signature for lung cancer detection.
Project description:We report the changes in transcriptome that results from RNAi suppression of 7S and 11S storage protein synthesis in soybean seeds, Proteomic results show that other proteins compensate for the storage protein shortfall. The transcriptome analysis show numerous changes result from suppressing storage proteins but compensating proteins are accumulated without parallel changes in the protein's transcription. Total RNA samples prepared from midmaturation wildtype and storage protein RNAi (SP-) soybeans were used to produce cDNA that was subjected to Illumina sequencing. The resulting sequences were assembled and analyzed to characterize the changes in transcriptome that results from suppressing storage protein synthesis/accumulation.
Project description:E3 ubiquitin ligases (E3s) confer specificity of protein degradation through the recognition of specific target substrates for ubiquitination and subsequent degradation, making E3s attractive candidates for drug development. There are over 600 annotated E3s in the human genome, yet the vast majority have no known substrate proteins, due in part to the limited scalability of methods to evaluate the vast number of potential E3-substrate interactions. To address this, we developed COMET (Combinatorial Mapping of E3 Targets), a combinatorial framework that can test the role of many specific E3s in regulating the abundance of many specific substrates, within the context of a single experiment. As a proof-of-concept, we applied COMET to identify specific E3 subunits of the SCF ubiquitin ligase complex that mediate the degradation of target substrates, including short-lived transcription factors (TFs). Our data suggest that many E3-substrate relationships are complex rather than simple 1:1 associations. Further, we provide computational models of E3-substrate interactions from our screen. Looking forward, we anticipate that COMET can be further scaled to enable comprehensive mapping of regulators of protein stability to their target substrates
Project description:Chayote (Sechium edule) fruits are rich in flavonoids, folate, and low-calorie food. However, studies about the flavonoids and regulatory mechanism of flavonoid synthesis in chayote fruits was still unclear. In present study, a transcriptome analysis and metabolite profiling of chayote fruits at three different storage stages were conducted to explore the flavonoid compositions and gene expression associated with flavonoid synthesis. Through the UPLC-MS/MS analysis, a total of 57 flavonoid compounds were detected. Of these, 42 flavonoid glycosides were significantly differential accumulation in chayote fruits at three different storage stages. Many genes associated with flavonoid synthesis were differentially expressed in chayote fruits at three different storage stages through RNA-seq analysis, including structural genes and some TFs. There was a high correlation between RNA-seq analysis and metabolite profiling, and the expression level of candidate genes in the flavonoid synthesis pathway were consistent with the dynamic changes of flavonoids. In addition, one R2R3-MYB transcription factor, FSG0057100, was defined as the critical regulatory gene of flavonoid synthesis. Furthermore, we treated chayote fruits during storage with phenylalanine, and the results show exogenous phenylalanine applications might promote the flavonoid synthesis. Phenylalanine is a effective additive to maintain or improve the total content flavonoids in chayote fruit during storage, can apply the phenylalanine in the postharvest storage of chayote. The above results not only make us better understand the molecular mechanism of flavonoid synthesis in chayote fruits, but also contribute to the promotion and application of chayote products.