Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents.

BackgroundRadiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms.MethodsC56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue.ResultsThe irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules.ConclusionWe suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI) dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX) on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg) was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg) to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis) but reduced the normal diet intake (anorexia) whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT) in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.

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Aging is associated with impaired vascular function characterized in part by attenuated vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Due to structural and functional differences between conduit and resistance arteries, the effect of aging on vasorelaxation responses may vary along the arterial tree. Our purpose was to determine age‐related differences in vasorelaxation responses in large and small arteries. Responses to the endothelium‐dependent vasodilator acetylcholine (ACh) and the endothelium‐independent vasodilator sodium nitroprusside (SNP) were assessed in abdominal aorta (AA), iliac arteries (IA), femoral arteries (FA), and gastrocnemius feed arteries (GFA) from young and old male rats. ACh‐mediated vasorelaxation was significantly impaired in old AA and IA. SNP‐mediated vasorelaxation was impaired in old AA. To investigate a potential mechanism for impaired relaxation responses in AA and IA, we assessed eNOS protein content and interactions with caveolin‐1 (Cav‐1), and calmodulin (CaM) via immunoprecipitation and immunoblot analysis. We found no age differences in eNOS content or interactions with Cav1 and CaM. Combined data from all rats revealed that eNOS content was higher in IA compared to AA and FA (p < .001), and was higher in GFA than AA (p < .05). Cav1:eNOS interaction was greater in FA than in AA and IA (p < .01), and in GFA compared to IA (p < .05). No differences in CaM:eNOS were detected. In conclusion, age‐related impairment of vasorelaxation responses occurred in the large conduit, but not small conduit or resistance arteries. These detrimental effects of age were not associated with changes in eNOS or its interactions with Cav‐1 or CaM.

Lactobacillus plantarum is a popular probiotic species due to its safe and beneficial effects on humans; therefore, novel L. plantarum strains have been isolated and identified from various dietary products. Given that bacteria-derived extracellular vesicles (EVs) have been considered as efficient carriers of bioactive materials and shown to evoke cellular responses effectively, L. plantarum-derived EVs are expected to efficiently elicit health benefits. Herein, we identified L. plantarum APsulloc 331261 living in green tea leaves and isolated EVs from the culture medium. We performed quantitative lipidomic analysis of L. plantarum APsulloc 331261 derived EVs (LEVs) using liquid chromatography-mass spectrometry. In comparison to L. plantarum APsulloc 331261, in LEVs, 67 of 320 identified lipid species were significantly increased and 19 species were decreased. In particular, lysophosphatidylserine(18:4) and phosphatidylcholine(32:2) were critically increased, showing over 21-fold enrichment in LEVs. In addition, there was a notable difference between LEVs and the parent cells in the composition of phospholipids. Our results suggest that the lipidomic profile of bacteria-derived EVs is different from that of the parent cells in phospholipid content and composition. Given that lipids are important components of EVs, quantitative and comparative analyses of EV lipids may improve our understanding of vesicle biogenesis and lipid-mediated intercellular communication within or between living organisms.

We propose a facile fluorometric system for detection of gene mutations using graphene oxide (GO). A fluorescent probe DNA anneals to a specific mutant gene and is degraded by the 5'→ 3' exonuclease activity of Taq polymerase during PCR, and the released fluorophore retains fluorescence after addition of GO without quenching.

The increasing prevalence of cholesterol gallstone disease places an economic burden on the healthcare system. To identify novel therapeutics, we assessed the effects of n-3 polyunsaturated fatty acids (PUFA) in combination with UDCA in a mouse model of cholesterol gallstones. Gallstone dissolution, gallbladder wall thickness, mucin gene expression in the gallbladder, and levels of phospholipids, cholesterol, and bile acids in bile and serum were analysed. RNA was extracted from the liver for mRNA sequencing and gene expression profiling. Combination treatment resulted in greater gallstone dissolution compared with the control group, and PUFA and combination treatments reduced the thickness of the gallbladder wall. Expression levels of mucin genes were significantly lower in the UDCA, PUFA, and combination groups. Transcriptome analyses revealed that combination treatment modulated hepatic lipid metabolism. The PUFA and combination groups showed elevated bile phospholipid and bile acid levels and a lower cholesterol saturation index. Combination treatment with PUFA and UDCA dissolves cholesterol gallstones in mice by decreasing mucin production, increasing levels of phospholipids and bile acids in bile, and decreasing cholesterol saturation. Further studies of the therapeutic effects of combination PUFA and UDCA treatment in patients with cholesterol gallstones are warranted.