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Canavalia gladiata ( C. gladiata ) and Arctium lappa ( A. lappa ), used in traditional medicine and food. However, their preventive effects in dextran sulphate sodium (DSS)-induced inflammatory bowel disease (IBD) remain unclear. We found that the C. gladiata and A. lappa mixture suppressed inflammation in LPS-induced RAW 264.7 cells. The mixture increased the population and activation of immune cells, up-regulation of cell cycle, and induction of IgA and IgG production in wild-type mice. Furthermore, the extract mixture prevented clinical IBD symptoms and restored IgA production in IBD mice. Similarly, a mixture of the marker compounds, chicoric acid and lupeol, ameliorated IBD-associated clinical signs, improved the population and activation of immune cells and functional defects in natural killer (NK) cells and reduced production of IgA in these mice. In conclusion, the C. gladiata and A. lappa mixture ameliorated progression of DSS-induced IBD by enhancing immune responses and recovering functional immune cell defects. [ABSTRACT FROM AUTHOR]

Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells. Knockdown of endogenous miR-21 by HGP21 led to decreased proliferation and reduced migration of cancer cells, as well as the induction of apoptosis, with enhanced PTEN levels. Interestingly, in vivo fluorescence signals markedly recovered 3 h after the intravenous delivery of HGP21 and displayed signals more than 5-fold higher than those observed in the HGPscr-treated group of tumor-bearing mice. These findings demonstrate the possibility of using the HGP nanoplatform as a cancer theranostic tool in miRNA-targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: The aerial parts of Saururus chinensis (SC) have been used for the treatment of edema, fever, jaundice, and inflammatory diseases in Korean folk medicine for centuries. However, the mechanism by which SC exerts these anti-tumorigenic activities in human prostate and breast cancer cells has not yet been fully understood. In this study, we report on the methylene chloride fraction from SC exerting cytotoxicity against prostate and breast cancer cells in a dose-dependent manner. Specifically, SC exerted the most potent cytotoxicity in LNCaP and MCF-7 cells. SC was shown to down-regulate various angiogenetic (VEGF), proliferative (Cyclin D1), anti-apoptotic (Bcl-2) gene products in these cells. SC also increased the number of annexin V-positive apoptotic bodies and the sub-G1 DNA contents of the cell cycle undergoing apoptosis through caspase-3 activation in both LNCaP and MCF-7 cells. We further confirmed that caspase-3 plays an important role in SC-induced apoptosis in LNCaP and MCF-7 cells through the use of the caspase-3 inhibitor. Moreover, we observed that SC potentiated paclitaxel-induced apoptosis in MCF-7 cells and sauchinone is a major active constituent of SC, which could induce apoptosis in the cells. Taken together, our data provide the evidence that SC induces apoptosis depending on caspase-3 activation and overcomes the natural biological resistance to chemotherapy found in human prostate and breast cancer cells. [Copyright &y& Elsevier]

• CAEC enhanced immune function by stimulating NK cell activity and IL-10 expression. • CAEC significantly increased NK cell activity at E:T = 25:1 and 50:1 after 8 weeks. • CAEC significantly increased the level of IL-10 after 8 weeks. • CAEC will be able to serve as a functional food for stimulating immunity. The aim of this study was to evaluate the efficacy and safety of CAEC (Canavalia gladiata arctium lappa extract complex) in adults with white blood cells between 3 and 8 × 103 cells/µL by assessing natural killer (NK) cell activity and immune-related biomarkers. Overall, 100 participants (CAEC group = 50, placebo group = 50) were randomised, and administered CAEC or placebo once daily for 8 weeks, with an evaluation visit performed every 4 weeks. NK cell activity, the primary outcome, significantly increased in CAEC when compared with the placebo at effector-to-target (E:T) ratios of 25:1 and 50:1 after 8 weeks. Compared with the placebo group, IL-10 demonstrated significant differences at week 8 in the CAEC group. Our findings demonstrate that CAEC is safe and enhances immune function by stimulating NK cell activity through IL-10 expression. Hence, we anticipate that CAEC can be developed as a functional food for stimulating immunity. [ABSTRACT FROM AUTHOR]

Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Cascade multi-purpose heat pumps are designed to concurrently meet the hot water (HW) and cooling needs, and the HW and heating demands of buildings. However, the capacity of heat pumps deteriorates as the building load increases. At such conditions, the capacity of the heat pump needs to be enhanced to ensure that its rated value is maintained. This study examines the adoption of a variable speed compressor in the low-stage (LS) of a water source cascade multi-purpose heat pump for capacity control at different outdoor conditions in many operating modes. The study showed that the variable speed compressor is highly reliable for the capacity control of the cascade multi-purpose heat pump in all operating modes at varying outdoor temperature conditions. However, the variable speed compressor to be adopted for the capacity control of the cascade multi-purpose heat pump should have a higher capacity and wider range of compressor speeds to meet the rated capacity of the cascade multi-purpose heat pump at severe outdoor temperature conditions in HW mode and heating-HW mode. Furthermore, the variable speed compressor should be installed in the low stage cycle and hot water cycle to ensure precise capacity control, improved system efficiency and energy savings. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cationic alkyl starches were synthesized to observe the adsorption behavior by QCM-D. [•] Adsorbed amount of cationic starches increased compared with cationic surfactants. [•] Tendency for increased rigidity after desorption was observed in all cationic starches. [•] Cationic alkyl starches showed more adsorbed amount and rigidity than cationic starches. [ABSTRACT FROM AUTHOR]

The effects of daucosterol have been identified in cancer therapy and neuronal diseases. However, the regulatory function of daucosterol in DSS-induced colitis has not yet been investigated. In this study, we evaluated the immunological and therapeutic effects of daucosterol in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Unlike vehicle mice, mice pre- or post-treated with daucosterol showed inhibition of body weight loss and the decrease in the disease activity index (DAI). In addition, daucosterol treatment rescued the DSS-induced decrease in colon length and disruption of the epithelial lining. Furthermore, it reduced DSS-induced production of reactive oxygen species (ROS), infiltration of macrophages, and expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Mice with colitis showed a decreased population of Foxp3+ cells, which was upregulated by daucosterol treatment. Furthermore, daucosterol increased natural killer (NK) cell activity and inhibited excessive IgA levels in mice with DSS-induced colitis. Collectively, our findings demonstrated that daucosterol significantly alleviated DSS-induced colitis, indicating the possibility of daucosterol as a therapeutic option for colitis. • Daucosterol prevented clinical symptoms of DSS-induced colitis. • Daucosterol alleviated inflammation in DSS-induced colitis. • Daucosterol recovered the number of Treg cells reduced by DSS-induced colitis. • Daucosterol is good candidate therapeutic for colonic diseases including DSS-induced colitis. [ABSTRACT FROM AUTHOR]

The effective chemotherapeutic drug, doxorubicin (DOX), elicits immunogenic cell death (ICD) and additional anticancer immune responses during chemotherapy. However, it also induces severe side effects and systemic immunosuppression, hampering its wide clinical application. Herein, we constructed cancer-activated DOX prodrug by conjugating the cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly , FRRG) to a doxorubicin (DOX), resulting in FRRG-DOX that self-assembled into cancer-activated DOX prodrug nanoparticles (CAP-NPs). The resulting CAP-NPs were further stabilized with the FDA-approved compound, Pluronic F68. CAP-NPs formed stable prodrug nanoparticles and they were specifically cleaved to cytotoxic DOX molecules only in cathepsin B-overexpressing cancer cells, inducing a cancer cell-specific cytotoxicity. In particular, the CAP-NPs induced ICD through cathepsin B-cleavage mechanism only in targeted cancer cells in vitro. In colon tumor-bearing mice, selectively accumulated CAP-NPs at tumors enhanced antitumor immunity without DOX-related severe toxicity, inflammatory response and systemic immunosuppression. Moreover, cytotoxicity against immune cells infiltrated into tumor microenvironment was significantly reduced compared to free DOX, leading to increased response to checkpoint inhibitor immunotherapy. The combinatorial treatment of CAP-NPs with anti-PD-L1 exhibited high rate of complete tumor regression (50%) compared to free DOX with anti-PD-L1. Concurrently, DOX-related side effects were greatly reduced during chemoimmunotherapy. Collectively, our results suggest that cancer-activated DOX prodrug nanoparticles provide a promising approach to increase clinical benefit by inducing an immune response preferentially only to targeted cancer cells, not to normal cells and immune cells, and potentiates checkpoint inhibitor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]