Diallyl Trisulfide Prevents Adipogenesis and Lipogenesis by Regulating the Transcriptional Activation Function of KLF15 on PPARγ to Ameliorate Obesity.

SCOPE: Diallyl trisulfide (DATS) is a bioactive compound in garlic. The anti-obesity effect of garlic oil has been reported, but the role and mechanism of DATS in preventing obesity remain to be explored. METHODS AND RESULTS: Studies with high-fat-diet-induced obese mice and 3T3-L1 adipocytes are performed. The results show that DATS significantly reduces lipid accumulation and repairs disordered metabolism in vivo by restraining adipogenesis and lipogenesis, and promoting lipolysis and fatty acid oxidation in white adipose tissue. In cells, DATS plays different roles at different stages of adipocyte differentiation. Notably, DATS reduces lipid accumulation mainly by inhibiting adipogenesis and lipogenesis at the late stage. KLF15 is knocked down in 3T3-L1 cells, which eliminate the inhibitory effect of DATS on adipogenesis and lipogenesis. The dual-luciferase reporter and ChIP assays indicate that DATS can inhibit the transcriptional activation function of KLF15 on PPARγ by inhibiting the binding of KLF15 to PPARγ promoter. The function comparison of structural analogs and the intervention of dithiothreitol show that disulfide bond is crucial for DATS to work. CONCLUSION: DATS prevents obesity by regulating the transcriptional activation function of KLF15 on PPARγ.

Research Progress of Safety of Zearalenone: A Review.

Zearalenone, a mycotoxin produced by fungi of the genus Fusarium, widely exists in animal feed and human food. The structure of zearalenone is similar to estrogen, so it mainly has estrogenic effects on various organisms. Products contaminated with zearalenone can pose risks to animals and humans. Therefore, it is imperative to carry out toxicological research on zearalenone and evaluate its risk to human health. This paper briefly introduces the production, physical, and chemical properties of zearalenone and the research progress of its toxicity kinetics, focusing on its genetic toxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, carcinogenicity, endocrine interference, and its impact on intestinal health. Finally, the progress of the risk assessment of human exposure is summarized to provide a reference for the follow-up study of zearalenone.

Artemether Ameliorates Non-Alcoholic Steatohepatitis by Repressing Lipogenesis, Inflammation, and Fibrosis in Mice.

Background: Non-alcoholic fatty liver disease (NAFLD) is a widespread disease, but no recognized drug treatment exists. Previous studies have shown that artemether (Art) can ameliorate carbon tetrachloride (CCl4)-induced liver fibrosis in mice. This study sets out to observe the therapeutic impact of Art on non-alcoholic steatohepatitis (NASH). Methods: Model mice were provided with a methionine- and choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 28 weeks, respectively, and then treated with Art. RNA sequencing (RNA-Seq) analyzed gene expression changes caused by Art treatment. The molecular mechanism of the therapeutic effects of Art on NASH was studied in the mouse liver and HepG2 cells. Results: Art treatment significantly attenuated hepatic lipid accumulation and liver damage in MCD diet- or HFD-induced NASH mice. The RNA-Seq analysis revealed lipid metabolism as a major pathway suppressed by Art administration, in addition to the regulation of inflammation pathways. Mechanistically, Art reduced lipid accumulation by repressing de novo lipogenesis of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD1), promoting lipolysis of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α), adipose triglyceride lipase (ATGL), and carnitine palmitoyltransferase I (CPT-1a) in NASH mouse liver and HepG2 cells. In addition, Art inhibited the secretion of pro-inflammatory factors and reduced inflammatory infiltration by effectively inhibiting M1 macrophage activation. Furthermore, Art inhibited transforming growth factor-beta 1 (TGF-ß), and the SMAD signaling pathway mediates the development of liver fibrosis. Inclusion: Art improved fat deposition by repressing de novo lipogenesis and promoting lipolysis in vivo and in vitro. Furthermore, Art improved inflammation and fibrosis with a significant effect. It is a prospective therapeutic agent for NASH.

Extraction and Identification of Three New Urechis unicinctus Visceral Peptides and Their Antioxidant Activity.

The viscera of Urechis unicinctus with polypeptides, fatty acids, and amino acids are usually discarded during processing to food. In order to improve the utilization value of the viscera of Urechis unicinctus and avoid resource waste, antioxidant polypeptides were isolated from the viscera of Urechis unicinctus. First, a protein hydrolysate of Urechis unicinctus (UUPH) was prepared by ultrasonic-assisted enzymatic hydrolysis, and the degree of hydrolysis was as high as 79.32%. Subsequently, three new antioxidant peptides (P1, P2, and P3) were purified from UUPH using ultrafiltration and chromatography, and their amino acid sequences were identified as VTSALVGPR, IGLGDEGLRR, TKIRNEISDLNER, respectively. Then, the antioxidant activity of the polypeptide was predicted by the structure-activity relationship and finally verified by experiments on eukaryotic cells. The P1 peptide exhibited the strongest antioxidant activity among these three antioxidant peptides. Furthermore, P1, P2, and P3 have no toxic effect on RAW264.7 cells at the concentration of 0.01~2 mg/mL and can protect RAW264.7 cells from H2O2-induced oxidative damage in a concentration-dependent manner. These results suggested that these three new antioxidant peptides were isolated from the viscera of Urechis unicinctus, especially the P1 peptide, which might serve as potential antioxidants applied in health-derived food or beverages. This study further developed a new use of the by-product of Urechis unicinctus, which improved the comprehensive utilization of marine biological resources.

Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications.

INTRODUCTION: miRNA-derivative clinical nucleotide drugs (mdCNDs) effectively treat several diseases, with numerous undergoing clinical trials. In early-stage trials in disease therapeutics, such as malignant pleural mesothelioma and hepatic virus C infection, mdCND's therapeutic potency is undeniably good for effectiveness and safety. AREAS COVERED: Fifteen mdCNDs undergoing clinical trials are introduced in this review. MiRNA modifications methods have been summarized, including phosphorothioate, cholesterol, locked nucleic acid, 2'-O-methyl, N,N-diethyl-4-(4-nitronaphthalen1-ylazo)-phenylamine modifications, and many more. Moreover, delivery systems, including self-assembled, inorganic ions nanoparticles, exosomes, and lipid-based nanosystems for mdCNDs targeted delivery, are presented. Among that, EnGeneIC, N-Acetylgalactosamine, liposomal nanoparticles, and cholesterol-conjugated for mdCNDs delivery are currently undergoing clinical trials. The pH, light, temperature, redox-responsive, enzyme, and specific-substance modes to trigger the release of miRNAs to target sites on-demand and the prospects of mdCNDs are discussed in this review. EXPERT OPINION: mdNCDs are one type of promising clinical drugs, however, it is still in the infancy. During the development process, it is imperative to advance in modifying miRNAs, especially at the 5'-end, to enhance targetability and stability against nucleases, develop a stimuli-responsive mode to control the release of mdCNDs to tissue cell-type-specific sites.

DNA Methylation Changes and Its Associated Genes in Mulberry (Morus alba L.) Yu-711 Response to Drought Stress Using MethylRAD Sequencing.

Drought stress remains one of the most detrimental environmental cues affecting plant growth and survival. In this work, the DNA methylome changes in mulberry leaves under drought stress (EG) and control (CK) and their impact on gene regulation were investigated by MethylRAD sequencing. The results show 138,464 (37.37%) and 56,241 (28.81%) methylation at the CG and CWG sites (W = A or T), respectively, in the mulberry genome between drought stress and control. The distribution of the methylome was prevalent in the intergenic, exonic, intronic and downstream regions of the mulberry plant genome. In addition, we discovered 170 DMGs (129 in CG sites and 41 in CWG sites) and 581 DMS (413 in CG sites and 168 in CWG sites). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicates that phenylpropanoid biosynthesis, spliceosome, amino acid biosynthesis, carbon metabolism, RNA transport, plant hormone, signal transduction pathways, and quorum sensing play a crucial role in mulberry response to drought stress. Furthermore, the qRT-PCR analysis indicates that the selected 23 genes enriched in the KEGG pathways are differentially expressed, and 86.96% of the genes share downregulated methylation and 13.04% share upregulation methylation status, indicating the complex link between DNA methylation and gene regulation. This study serves as fundamentals in discovering the epigenomic status and the pathways that will significantly enhance mulberry breeding for adaptation to a wide range of environments.

Insights into nucleic acid-based self-assembling nanocarriers for targeted drug delivery and controlled drug release.

Over the past few decades, rapid advances of nucleic acid nanotechnology always drive the development of nanoassemblies with programmable design, powerful functionality, excellent biocompatibility and outstanding biosafety. Nowadays, nucleic acid-based self-assembling nanocarriers (NASNs) play an increasingly greater role in the research and development in biomedical studies, particularly in drug delivery, release and targeting. In this review, NASNs are systematically summarized the strategies cooperated with their broad applications in drug delivery. We first discuss the self-assembling methods of nanocarriers comprised of DNA, RNA and composite materials, and summarize various categories of targeting media, including aptamers, small molecule ligands and proteins. Furthermore, drug release strategies by smart-responding multiple kinds of stimuli are explained, and various applications of NASNs in drug delivery are discussed, including protein drugs, nucleic acid drugs, small molecule drugs and nanodrugs. Lastly, we propose limitations and potential of NASNs in the future development, and expect that NASNs enable facilitate the development of new-generation drug vectors to assist in solving the growing demands on disease diagnosis and therapy or other biomedicine-related applications in the real world.

Bioactive components from Moringa oleifera seeds: production, functionalities and applications - a critical review.

A readily distinguishable and indigenous member of the plant kingdom in the Indian subcontinent is the 'drumstick tree', i.e. Moringa oleifera Lam. In addition to India, this drought-tolerant and rapidly evolving tree is currently extensively disseminated across the globe, including subtropical and tropical areas. The plant boasts a high nutritional, nutraceutical and therapeutic profile, mainly attributing to its significant repertoire of the biologically active components in different parts: protein, flavonoids, saponins, phenolic acids, tannin, isothiocyanate, lipids, minerals, vitamins, amongst others. M. oleifera seeds have been shown to elicit a myriad of pharmacological potential and health benefits, including: antimicrobial, anticancer, antidiabetic, antioxidant, antihypertensive, anti-inflammatory and cardioprotective properties. Additionally, the seed cakes obtained from post-extraction process are utilized for: coagulation, flocculation and sedimentation purposes, benefiting effluent management and the purification of water, mainly because of their capability in eliminating microbes and organic matter. Despite the extraordinary focus on other parts of the plant, especially the foliage, the beneficial aspects of the seeds have not been sufficiently highlighted. The health benefits of bioactive components in the seeds are promising and demonstrate enough potential to facilitate the development of functional foods. In this review, we present a critical account of the types, characteristics, production and isolation of bioactive components from M. oleifera seeds. Furthermore, we appraise the: pharmacological activities, cosmetic, biodiesel, lubricative, modern farming, nutritive and wastewater treatment applications of these functional ingredients. We infer that there is a need for further human/clinical studies and evaluation, despite their health benefits. Additionally, the safety issues need to be adequately clarified and assessed, in order to establish a conventional therapeutic profile.

Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells.

Ochratoxin A (OTA) is one of the mycotoxins, which widely pollutes food systems and seriously threatens human health. OTA's target organ is the kidney. Exosome, as one of the extracellular vesicles, could be secreted by all kinds of cells. It contains different proteins, nucleic acid, and lipid, which are decided by their donor cells and could be uptake by the recipient cells, release their contents, and affect the recipient cell's life activity. In this study, a 24 h-treatment with 5 µM OTA was found to significantly reduce the cell viability of HEK293 cells and meanwhile to provide a sufficient quantity of exosomes, thus this concentration and time were selected for subsequent experiments. In addition, exosomes extracted by ultracentrifugation had higher purity, fewer impurities, and uniform morphology than that by the ExoQuick-TC kit. Furthermore, these exosomes increased ROS levels and decreased mitochondrial membrane potential in HEK293 cells. By RNA-seq, the cytotoxicity mechanisms induced by OTA-treated HEK293 cell-derived exosomes (EXO-OTA) and OTA were mainly the metabolism of proteins and the cell cycle respectively. Also, it proved that exosomes deliver partial OTA-induced cytotoxicity.