Fabrication and Stability Improvement of Monoglyceride Oleogel/Polyglycerol Polyricinoleate-Stabilized W/O High Internal Phase Pickering Emulsions.

To decrease the lipid content in water-in-oil (W/O) emulsions, high internal phase Pickering W/O emulsions (HIPPE) were fabricated using magnetic stirring using a combination of monoglyceride (MAG) oleogel and polyglycerol polyacrylate oleate (PGPR) as stabilizers. Effects of MAGs (glyceryl monostearate-GMS, glycerol monolaurate-GML and glycerol monocaprylate-GMC) and internal phase components on the formation and properties of HIPPEs were investigated. The results showed that milky-white stabilized W/O HIPPE with up to 85 wt% aqueous phase content was successfully prepared, and the droplet interfaces presented a network of MAG crystals, independent of the MAG type. All HIPPEs exhibited great stability under freeze-thaw cycles but were less plastic. Meanwhile, GML-oleogel-based HIPPEs had larger particle size and were less thermal stable than GMS and GMC-based HIPPEs. Compared to guar gum, the internal phase components of sodium chloride and sucrose were more effective in reducing the particle size of HIPPEs, improving their stability and plasticity, and stabilizing them during 100-day storage. HIPPEs presented great spreadability, ductility and plasticity after whipping treatment. This knowledge provides a new perspective on the use of oleogels as co-stabilizers for the formation of W/O HIPPEs, which can be used as a potential substitute for creams.

Flavonoid extract Kushenol a exhibits anti-proliferative activity in breast cancer cells via suppression of PI3K/AKT/mTOR pathway.

BACKGROUND: Kushenol A is natural flavonoid extract discovered in recent years, with potential anti-tumor activity. Its role in breast cancer is poorly understood. METHODS: To investigate biological function of Kushenol A in breast cancer (BC), Cell Counting Kit-8 assay, colony formation assay, flow cytometry, western blotting, qPCR analysis, and xenograft mouse model were performed. RESULTS: We found that Kushenol A treatment reduced proliferative capability and induced G0/G1 phase cell cycle arrest and apoptosis of BC cells in a concentration-dependent manner. Besides, Kushenol A treatment contributed to the upregulation of apoptosis-related and cell cycle-associated genes. In nude mice, Kushenol A administration repressed BC xenograft tumor growth. Mechanistically, phosphorylation levels of AKT and mTOR were markedly attenuated in Kushenol A-treated BC cells; however, there were no significant differences in total AKT and mTOR expressions. Moreover, PI3K inhibitor combined with Kushenol A exhibited synergistic inhibitory activity on cell proliferation. CONCLUSIONS: Taken together, our findings suggested that Kushenol A suppressed BC cell proliferation by modulating PI3K/AKT/mTOR signaling pathway. Kushenol A may be a promising therapeutic drug for treating BC.

Gut Microbiota Characteristics of People with Obesity by Meta-Analysis of Existing Datasets.

Obesity is a complex chronic, relapsing, progressive disease. Association studies have linked microbiome alterations with obesity and overweight. However, the results are not always consistent. An integrated analysis of 4282 fecal samples (2236 control (normal weight) group, 1152 overweight, and 894 simple obesity) was performed to identify obesity-associated microbial markers. Based on a random effects model and a fixed effects model, we calculated the odds ratios of the metrics, including bacterial alpha-diversity, beta-diversity, Bacteroidetes/Firmicutes ratio, common genera, and common pathways, between the simple obesity and control groups as well as the overweight and control groups. The random forest model was trained based on a single dataset at the genus level. Feature selection based on feature importance ranked by mean decrease accuracy and leave-one-out cross-validation was conducted to improve the predictive performance of the models. Chao1 and evenness possessed significant ORs higher than 1.0 between the obesity and control groups. Significant bacterial community differences were observed between the simple obesity and the control. The ratio of Bacteroidetes/Firmicutes was significantly higher in simple obesity patients. The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower. The random forest model achieved a high accuracy (AUC = 0.83). The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased. This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity.

Structural analysis and in vitro antitumor effect of polysaccharides from Pholiota adiposa.

Pholiota adiposa is an edible chestnut mushroom with many health benefits, such as antioxidant and anticancer activity. In this paper, polysaccharides were extracted from Pholidota adiposa using an acid extraction process. The crude polysaccharide was purified using DEAE-cellulose chromatography, and two polysaccharide fractions of SPAP2-1 and SPAP2-2 were obtained. The structure was characterized using UV, GPC, GC, FT-IR, methylation, and NMR analysis. Monosaccharide component analysis indicated that SPAP2-1 (19 kDa) and SPAP2-2 (20 kDa) contained mannose, glucose, and galactose with different molecular ratios. Their antitumor effects were investigated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay, Annexin V-fluorescein isothiocyanate (FITC), propidium iodide (PI) staining, and flow cytometry. By analyzing the changes in the cells, SPAP2-1 caused damage and changed the proliferation rate of HeLa cells. SPAP2-1 showed strong interference to the cell cycle of HeLa cells and induced cell apoptosis. Overall, these results suggested that polysaccharides from Pholiota adiposa, especially SPAP2-1, may have the potential to be used as a tumor cell inhibitor, which needs further study.

Comparative transcriptome analysis of the gills and hepatopancreas from Macrobrachium rosenbergii exposed to the heavy metal Cadmium (Cd2+).

Heavy metal Cadmium (Cd2+) pollution has become a severe environmental problem for aquatic organisms. In crustaceans, gills (Gi) and hepatopancreas (Hp) play a vital role in the toxicology. However, in Macrobrachium rosenbergill, there are few researches about gill and hepatopancreases responding to Cd2+ stress at a molecular level. In this study, transcriptomic analysis was applied to characterize gene expression profiles of gills and hepatopancreas of M. rosenbergill after Cd2+ exposure for 0 h, 3 h and 3 d. Six cDNA libraries (Gi 0 h, Gi 3 h, Gi 3 d, Hp 0 h, Hp 3 h, and Hp 3 d) were constructed and a total of 66,676 transcripts and 48,991 unigenes were annotated. Furthermore, differentially expressed genes (DEGs) were isolated by comparing the Cd2+ treated time-point libraries (3 h and 3 d group) with the control library (0 h group). The results showed that most of the DEGs were down-regulated after Cd2+ exposure and the number of DEGs among gill groups were significantly higher than those among hepatopancreas groups. GO functional and KEGG pathway analysis suggested many key DEGs in response to the Cd2+ stress, such as metallothionein and Hemocyanin. Additionally, a total of six DEGs were randomly selected to further identify their expressional profile by qPCR. The results indicated that these DEGs were involved in the response to Cd2+. This comparative transcriptome provides valuable molecular information on the mechanisms of responding to Cd2+ stress in M. rosenbergii, which lays the foundation for further understanding of heavy metal stress.

Covalent conjugation of extracellular vesicles with peptides and nanobodies for targeted therapeutic delivery.

Natural extracellular vesicles (EVs) are ideal drug carriers due to their remarkable biocompatibility. Their delivery specificity can be achieved by the conjugation of targeting ligands. However, existing methods to engineer target-specific EVs are tedious or inefficient, having to compromise between harsh chemical treatments and transient interactions. Here, we describe a novel method for the covalent conjugation of EVs with high copy numbers of targeting moieties using protein ligases. Conjugation of EVs with either an epidermal growth factor receptor (EGFR)-targeting peptide or anti-EGFR nanobody facilitates their accumulation in EGFR-positive cancer cells, both in vitro and in vivo. Systemic delivery of paclitaxel by EGFR-targeting EVs at a low dose significantly increases drug efficacy in a xenografted mouse model of EGFR-positive lung cancer. The method is also applicable to the conjugation of EVs with peptides and nanobodies targeting other receptors, such as HER2 and SIRP alpha, and the conjugated EVs can deliver RNA in addition to small molecules, supporting the versatile application of EVs in cancer therapies. This simple, yet efficient and versatile method for the stable surface modification of EVs bypasses the need for genetic and chemical modifications, thus facilitating safe and specific delivery of therapeutic payloads to target cells.

microRNA exchange via extracellular vesicles in cancer.

Cells utilize different means of inter-cellular communication to function properly. Here, we review the crosstalk between cancer cells and their surrounding environment through microRNA (miRNA)-containing extracellular vesicles (EVs). The current findings suggest that the export of miRNAs and uptake of miRNA-containing EVs might be an active process. As post-transcriptional regulators of gene expression, cancer-derived miRNAs that are taken up by normal cells can change the translational profile of the recipient cell towards a transformed proteome. Stromal cells can also deliver miRNAs via EVs to cancer cells to support tumour growth and cancer progression. Therefore, gaining a better understanding of EV-mediated inter-cellular communication in the tumour microenvironment might lead to the development of novel diagnostic and therapeutic strategies.