The anti-aging mechanism of ginsenosides with medicine and food homology.

With the acceleration of global aging and the rise in living standards, the achievement of healthy aging is becoming an imperative issue globally. Ginseng, a medicinal plant that has a long history of dietary intake and remarkable medicinal value, has become a research hotspot in the field of food and medicine. Ginsenosides, especially protopanaxadiol-type saponins and protopanaxatriol-type saponins, are among the most important active ingredients in ginseng. Ginsenosides have been found to exhibit powerful and diverse pharmacological activities, such as antiaging, antitumor, antifatigue and immunity enhancement activities. Their effects in antiaging mainly include (1) promotion of metabolism and stem cell proliferation, (2) protection of skin and nerves, (3) modulation of intestinal flora, (4) maintenance of mitochondrial function, and (5) enhancement of telomerase activity. The underlying mechanisms are primarily associated with the intervention of the signaling pathways in apoptosis, inflammation and oxidative stress. In this review, the mechanism of action of ginsenosides in antiaging as well as the potential values of developing ginsenoside-based functional foods and antiaging drugs are discussed.

Expression of a novel dual-functional polypeptide and its pharmacological action research.

AIMS: To develop a dual-functional medicine for hypoglycemic and anti-thrombus. MAIN METHODS: The long-acting glucagon like peptide-1 (5×GLP-1) and nattokinase (NK) were cloned by SOE PCR and gained the GLP-1 and NK fusion polypeptide after transformed into E. coli. Use of mice models for the hypoglycemic and anti-thrombus activity of the fusion polypeptide. Balb/C mice were given the carrageenan by intraperitoneal injection to induce tail thrombus models. Type 2 diabetes mellitus mice model was used to research the hypoglycemic function of the fusion polypeptide. KEY FINDINGS: Results showed that the fusion polypeptide could significantly prevent thrombus formation after oral administration. Continuous administration for 15 days, fasting blood glucose levels of the experimental group decreased to nearly normal levels. SIGNIFICANCE: The present study investigated the expression, purification and functional activity of the rolGLP-1 and NK fusion polypeptide, which provided a foundation for further studying the detailed pharmaceutical mechanism and drug development.

Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy.

BACKGROUND: Progressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype. METHODS: We focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)-NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD. RESULTS: Synthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which-following endocytosis driven by CD44+ cells-promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%-45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition. CONCLUSIONS: Nanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.

Particle-based artificial three-dimensional stem cell spheroids for revascularization of ischemic diseases.

Development of new approaches to biomimetically reconstruct vasculature networks remains challenging in regenerative medicine. We introduce a particle-based artificial stem cell spheroid (ASSP) technology that recapitulates paracrine functions of three-dimensional (3D) SSPs for vasculature regeneration. Specifically, we used a facile method to induce the aggregation of stem cells into 3D spheroids, which benefited from hypoxia microenvironment-driven and enhanced secretion of proangiogenic bioactive factors. Furthermore, we artificially reconstructed 3D spheroids (i.e., ASSP) by integration of SSP-secreted factors into micro-/nanoparticles with cell membrane-derived surface coatings. The easily controllable sizes of the ASSP particles provided superior revascularization effects on the ischemic tissues in hindlimb ischemia models through local administration of ASSP microparticles and in myocardial infarction models via the systemic delivery of ASSP nanoparticles. The strategy offers a promising therapeutic option for ischemic tissue regeneration and addresses issues faced by the bottlenecked development in the delivery of stem cell therapies.

Microplastic pollution in water and sediment in a textile industrial area.

Microplastics pollution in the environment is closely determined by the surrounding industrial and human activities. In present study, we investigated microplastics in water and sediment samples collected from a textile industrial area in Shaoxing city, China. The abundance of microplastics varied from 2.1 to 71.0 items/L in surface water samples, and from 16.7 to 1323.3 items/kg (dw) in sediment samples. The polymer type was dominated by polyester both in water (95%) and sediment (79%) samples. The majority of the detected microplastics was predominantly colored fibers smaller than 1 mm in diameter. The high level of microplastic pollution detected in local freshwater and sediment environments was attributed to the production and trading activities of textile industries, for which severe regulations should be envisaged in the future to effectively reduce the local microplastic pollution.

Construction of a Pichia pastoris strain efficiently secreting irisin and assessment of its bioactivity in HepG2 cells.

Irisin, a circulating myokine, has been shown to effectively ameliorate insulin resistance and type 2 diabetes mellitus by administration of the recombinant protein. Therefore, it is important to efficiently produce active irisin protein and further characterize its potential mechanism against hepatic insulin resistance. In this study, we obtained a multi-copy irisin-expressing P. pastoris strain through an optimized method, which is pH 5.5, 1.8% methanol for 96 h, for producing a high amount of recombinant irisin protein following a series of screening and optimization procedures. The higher-glycosylated irisin, which is supposed to be the active form was obtained by dialysis and ion-exchange chromatography purification method. Both of the laser scanning confocal microscope and the atomic force microscope not only detected the high-effectiveness entering cells of FITC-irisin but also localized it on the membrane of HepG2 cells. Immunofluorescence staining further suggested that irisin could localize in the cytoplasm but not in the nucleus. We further showed that glycosylated irisin rescued palmitate-induced reduction in Glut2 expression and cell viability, inhibited the apoptosis, potentially by activating PI3K/AKT pathway. In summary, we developed an efficient irisin-expressing P. pastoris strain and optimal expression condition, visualized its distribution, demonstrated biological activity and potential mechanisms in hepatic cells.

Comparison of microplastic pollution in different water bodies from urban creeks to coastal waters.

Although freshwater and estuary systems are recognized as origins and transport pathways of plastics to the oceans, there is a lack of comparison of microplastics in different water bodies or river networks. In the present study, the spatial distribution of microplastics was compared across different water bodies, including city creeks (Shanghai), rivers (Suzhou River and Huangpu River), an estuary (Yangtze Estuary) and coastal waters (East China Sea) in the Yangtze Delta area. Significant spatial differences of microplastic abundances were revealed across the sampling areas. The results showed that the abundance of microplastics was higher (1.8-2.4 items/L) in freshwater bodies than that in estuarine and coastal water (0.9 items/L). In the Suzhou River and the Huangpu River, microplastics showed trends of increasing abundance downstream, where the peak of microplastic pollution is closer to the city center and the estuary. In respect of abundance, microplastics are likely to be transported from pollution sources to sink areas via river networks. The proportion of fibers was the highest in city creeks (88%), followed by the Suzhou River (85%), the Huangpu River (81%), the Yangtze Estuary (66%) and the East China Sea (37%). Similarly, polyesters dominated in city creeks and rivers. The results suggest that both the abundance and properties of microplastic pollution varies across different water bodies. Microplastic pollution in small freshwater bodies is more serious than in estuarine and coastal waters. Therefore, we support prioritization of water monitoring for microplastics within entire river networks, instead of single water body surveys.

HBX protein promotes LASP-1 expression through activation of c-Jun in human hepatoma cells.

LIM and SH3 domain protein 1 (LASP-1) is known to participate in the progression of hepatocellular carcinoma (HCC). We previously showed that ectopic expression of hepatitis B virus (HBV) X protein (HBX) enhanced the expression of LASP-1, which promoted proliferation and migration of HCC cells. Here, we further demonstrated the molecular mechanism underlying upregulation of LASP-1, mediated by HBX, in HBV-infected HCC cells. Through a luciferase activity assay, we discovered that the LASP-1 promoter region regulated by HBX contained an AP-1 binding element in human hepatoma cells. Interestingly, c-Jun, one subunit of AP-1, was mainly responsible for activation, mediated by HBX, of the LASP-1 promoter. Furthermore, HBX was shown not only to interact with phosphorylated c-Jun in HCC cells but also to activate c-Jun by increasing the activation of PI3-K/JNK signaling. Chromatin immunoprecipitation (ChIP) assay demonstrated that HBX was capable of binding to the LASP-1 promoter with c-Jun. Further, the expression levels of HBX were shown to be significantly positively correlated with that of LASP-1 and phosphorylatedc-Jun in HBV-related HCC tissues by immunohistochemistry analysis. In addition, the N-terminus of HBX was found to be responsible for the activation of c-Jun, as well as the expression of LASP-1. Taken together, these results suggest that HBX contributes to LASP-1 expression via the activation of c-Jun to increase the promoter activity of LASP-1 in HBV-related HCC cells.

The enhanced expression of death receptor 5 (DR5) mediated by HBV X protein through NF-kappaB pathway is associated with cell apoptosis induced by (TNF-α related apoptosis inducing ligand) TRAIL in hepatoma cells.

BACKGROUND: HBV X protein (HBX) is associated with cell apoptosis mediated by TNF-α related apoptosis inducing ligand (TRAIL), while the role of HBX on the expressions of TRAIL receptors death receptor 4 (DR4) and DR5 are unclear. In this study, we detected the cell apoptosis induced by TRAIL as well as gene and protein expressions of DR4 and DR5 in Huh-7 cells steadily transfected with HBX (Huh-7-HBX cells). In addition, we investigated the activation of different pathways associated with the expressions of TRAIL receptors in Huh-7-HBX cells. METHODS: The apoptosis of Huh-7-HBX cells induced by TRAIL was evaluated by flow cytometry analysis. The levels of DR4 and DR5 expression in cells were determined by real-time PCR and western blotting analysis. The activities of JNK pathway and NF-kappaB (NF-κB) pathway were demonstrated by western blotting assay. RESULTS: Compared to control cells, the percentage of cell apoptosis was increased in Huh-7-HBX cells. The increased expressions of DR4 and DR5 on gene and protein levels were observed in Huh-7-HBX cells. Further researches suggested that activation of JNK pathway was increased but not involved in the expression of TRAIL receptors in HBX positive cells. The activation of NF-κB pathway increased and was responsible for DR5 expression and cell apoptosis in HBX positive cells. CONCLUSIONS: These results demonstrate that increased apoptosis induced by TRAIL is associated with increased expression of DR5 that mediated by HBX through NF-κB pathway. This finding provides a critical insight into the mechanism of hepatocyte apoptosis mediated by HBX in HBV infection.