Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation.

BACKGROUND: Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. METHODS: The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 µg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. RESULTS: XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. CONCLUSION: XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Dietary supplement of Yunkang 10 green tea and treadmill exercise ameliorate high fat diet induced metabolic syndrome of C57BL/6 J mice.

BACKGROUND: Diet and exercise play important roles in ameliorating metabolic syndrome. Yunkang 10 (Camellia sinensis var. assamica) is a most cultivated tea variety for making tea in the Southwestern China. Currently, there is no report of healthy effects of Yunkang 10 green tea (YKGT) and treadmill exercise (Ex) on high fat diet induced metabolic syndrome (MetS). We aimed to investigate the beneficial effects and molecular mechanism of YKGT and Ex using high fat diet induced MetS of C57BL/6 mice. METHODS: Catechins and caffeine in water extract of YKGT were measured via high performance liquid chromatography (HPLC). 10-week old mice were fed with high fat diet (HFD) for 10 weeks to induce obese mice. Then the obese mice were fed with continuous high fat diet (HFD), HFD with YKGT, HFD with Ex, and HFD with both YKGT and Ex for 8 weeks, respectively. The another group of 10-week old mice fed with low fat diet (LFD) were used as control. RESULTS: HPLC data revealed that YKGT has abundantly high concentration of epigallocatechin gallate (EGCG) and caffeine compared to Longjing 43 (Camellia sinensis var. sinensis) green tea. YKGT and Ex significantly decreased the level of blood glucose, serum total cholesterol (TC), triglyceride (TG), insulin, and alanine aminotransferase activity (ALT) when compared to HFD group. The fatty liver and hepatic pro-inflammatory gene expression in the YKGT, Ex and YKGT+Ex groups was mitigated significantly compared with HFD group, respectively. The phosphorylation of inhibitor of nuclear factor kappa-B kinase α/ß (IKKα/ß) and inhibitor of nuclear factor kappa-B α (IkBα) protein in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway was also decreased in YKGT or YKGT+Ex groups. The combination of YKGT and Ex prevented gene expression for lipid synthesis in the liver tissue, and significantly upregulated mRNA level of glucose transport genes in the skeletal muscles, when compared to the HFD group. CONCLUSIONS: This study demonstrated that YKGT supplement or exercise appeared to reverse preexisting metabolic syndrome, and effectively relieved the fatty liver and hepatic inflammatory response induced by high fat diet. YKGT supplement and treadmill exercise together had better beneficial effects than only one intervention.

One-Pot Synthesis of MoS2 Nanoflakes with Desirable Degradability for Photothermal Cancer Therapy.

Developing biodegradable photothermal agent holds great significance for potential clinical translation of photothermal therapy. In the current study, one-pot hydrothermal synthesis of MoS2 nanoflakes with desirable degradation capability was presented. The participation of poly(acrylic acid) (PAA) in hydrothermal process could not only facilitate the modification of polyethylene glycol (PEG), but also bestow degradability to the prepared MoS2 nanoflakes. Moreover, the PEGylated hybrid nanoflakes (MoS2-PPEG) also exhibited excellent stability in various medium and outstanding photothermal properties. Interestingly, MoS2-PPEG behaved distinctly different degradation rate in diverse condition. The rapid degradation of MoS2-PPEG was observed in neutral pH solution, whereas much slower degradation occurred in an acidic tumor microenvironment. Furthermore, data indicated that the major degradation product of MoS2-PPEG was water-soluble Mo-based ion. Meanwhile, the good in vitro biocompatibility of MoS2-PPEG was also confirmed in terms of cytotoxicity and hemolysis. With favorable photothermal performance, MoS2-PPEG can efficiently killing cancer cells in vitro and suppress the tumor growth in vivo. More importantly, the gradual decreasing content of MoS2-PPEG in organs and detectable Mo element in urine of mice suggested that the degradability of MoS2-PPEG might facilitate its excretion to some degree. Hence, the degradable MoS2 nanoflakes prepared by one-pot hydrothermal routine may provide insight for further biomedical applications of inorganic photothermal agent.

Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

Au/polypyrrole@Fe3O4 nanocomposites for MR/CT dual-modal imaging guided-photothermal therapy: an in vitro study.

Construction of multifunctional nanocomposites as theranostic platforms has received considerable biomedical attention. In this study, a triple-functional theranostic agent based on the cointegration of gold nanorods (Au NRs) and superparamagnetic iron oxide (Fe3O4) into polypyrrole was developed. Such a theranostic agent (referred to as Au/PPY@Fe3O4) not only exhibits strong magnetic property and high near-infrared (NIR) optical absorbance but also produces high contrast for magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Importantly, under the irradiation of the NIR 808 nm laser at the power density of 2 W/cm(2) for 10 min, the temperature of the solution containing Au/PPY@Fe3O4 (1.4 mg/mL) increased by about 35 °C. Cell viability assay showed that these nanocomposites had low cytotoxicity. Furthermore, an in vitro photothermal treatment test demonstrates that the cancer cells can be efficiently killed by the photothermal effects of the Au/PPY@Fe3O4 nanocomposites. In summary, this study demonstrates that the highly versatile multifunctional Au/PPY@Fe3O4 nanocomposites have great potential in simultaneous multimodal imaging-guided cancer theranostic applications.

Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs.

Engaging functional biomaterial scaffolds to regulate stem cell differentiation has drawn a great deal of attention in the tissue engineering and regenerative medicine community. In this study, biomimetic composite nanofibrous scaffolds of hydroxyapatite/chitosan (HAp/CTS) were prepared to investigate their capacity for inducing murine mesenchymal stem cells (mMSCs) to differentiate into the osteogenic lineage, in the absence and presence of an osteogenic supplementation (i.e., ascorbic acid, ß-glycerol phosphate, and dexamethasone), respectively. Using electrospun chitosan (CTS) nanofibrous scaffolds as the control, cell morphology, growth, specific osteogenic genes expression, and quantified proteins secretion on the HAp/CTS scaffolds were sequentially examined and assessed. It appeared that the HAp/CTS scaffolds supported better attachment and proliferation of the mMSCs. Most noteworthy was that in the absence of the osteogenic supplementation, expression of osteogenic genes including collagen I (Col I), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) were significantly upregulated in mMSCs cultured on the HAp/CTS nanofibrous scaffolds. Also increased secretion of the osteogenesis protein markers of alkaline phosphatase and collagen confirmed that the HAp/CTS nanofibrous scaffold markedly promoted the osteogenic commitment in the mMSCs. Moreover, the presence of osteogenic supplementation proved an enhanced efficacy of mMSC osteogenesis on the HAp/CTS nanofibrous scaffolds. Collectively, this study demonstrated that the biomimetic nanofibrous HAp/CTS scaffolds could support and enhance the adhesion, proliferation, and particularly osteogenic differentiation of the mMSCs. It also substantiated the potential of using biomimetic nanofibrous scaffolds of HAp/CTS for functional bone repair and regeneration applications.