Emodin Attenuates Lipopolysaccharide-Induced Injury via Down-Regulation of miR-223 in H9c2 Cells.

Emodin is a natural product extracted from Rheum palmatum. There are few recent studies on emodin in the treatment of myocarditis. This study aimed to investigate the effect of emodin on lipopolysaccharide (LPS)-induced inflammatory injury in cardiomyocytes. H9c2 cells were treated with 10 µM of LPS and different concentrations (0, 1, 5, 10, 15, and 20 µM) of emodin. The expression of miR-223 was changed by transient transfection. Thereafter, cell viability, apoptosis, the expression of CyclinD1 and Jnk-associated proteins, and the release of pro-inflammatory factors were assessed by cell Counting Kit-8, flow cytometry analysis, quantitative real-time polymerase chain reaction Western blot, and enzyme-linked immunosorbent assay respectively. The results showed that 20 µM of emodin significantly decreased H9c2 cells viability. LPS significantly damaged H9c2 cells, as cell viability was reduced, CyclinD1 was down-regulated, apoptosis was induced, the release of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-alpha were increased, and the phosphorylation of Jnk and c-Jun were promoted. Emodin protected H9c2 cells against LPS-induced inflammatory injury. miR-223 expression was significantly up-regulated by LPS exposure, while emodin lessened this up-regulation. LPS-injured H9c2 cells were attenuated by the overexpression of miR-223; emodin has protective actions on LPS-injured H9c2 cells and targets. Besides, SP600125 (an inhibitor of Jnk) eliminated miR-223-modulated inflammatory injury in H9c2 cells. These data demonstrated that emodin could attenuate LPS-induced inflammatory injury and deactivate Jnk signaling pathway through down-regulation of miR-223.

Purification and immunogenicity study of human papillomavirus 58 virus-like particles expressed in Pichia pastoris.

Two human papillomavirus (HPV) prophylactic vaccines are currently available in the market: Gardasil and Cervarix. These two vaccines work against tumor high-risk subtypes HPV 16 and HPV 18. However, they do not include other high-risk subtypes such as HPV 58. Epidemiological research in China shows that HPV 58 is a prevalent high-risk subtype, second only to HPV 16 and HPV 18. Thus, for cervical cancer prevention in China, developing a vaccine against HPV 58 is necessary. In this study, HPV 58 virus-like particles (VLPs) were expressed in the Pichia pastoris, and subsequently purified through pretreatment and a three-step purification process consisting of strong cation exchange chromatography, size-exclusion chromatography, and hydroxyapatite chromatography. The highly purified HPV 58 VLPs were confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electron microscopy, dynamic laser scattering, and ultracentrifugation. The purified VLPs were used to immunize mice to test their ability to induce humoral immunity. Enzyme-linked immunosorbent assays were performed on the sera of the immunized mice and significantly high anti-HPV 58 VLP antibody titers were observed. The immunogenicity study demonstrates that the purified HPV 58 VLPs are HPV vaccine candidates.

User experience and usability when the automated driving system fails: Findings from a field experiment.

We are entering an era of automated vehicles (AVs), which has potential to improve road safety considerably. A compelling user experience is crucial to AV adoption in the future commercial market. The automated driving system (ADS) that replaces human drivers should be perceived as very useful before the latter are willing to give up their control and entrust their lives to the ADS. However, compared with the growing number of studies on public acceptance of AVs, there has been limited research focusing on user experience and usability. We examined AV and ADS user experience and usability, ADS failures' influence on them, and their influences on re-riding willingness. We conducted a field study using a real AV and a large-scale test track. We invited participants (N = 261) to travel in the AV as passengers in a low-speed environment. Participants were randomly assigned into the normal condition or the fault condition (its participants were exposed to an ADS failure). We measured participants' positive experience (feeling relaxed, safe, and comfortable) and negative experience (feeling tense and risky) while riding in the AV and perceived usability of the ADS based on the System Usability Scale. In both conditions, participants reported moderate positive experience and perceived usability but a relatively high level of willingness to ride in our AV again. The ADS failure reduced positive experience and perceived usability, and it increased negative experience. Positive experience and perceived usability, but not negative experience, influenced re-riding willingness. Compared with male participants, female participants reported less positive experience and lower perceived usability. We discuss implications of our results as well as limitations of this research.

Nanomedicine potentiates mild photothermal therapy for tumor ablation.

The booming photothermal therapy (PTT) has achieved great progress in non-invasive oncotherapy, and paves a novel way for clinical oncotherapy. Of note, mild temperature PTT (mPTT) of 42-45 °C could avoid treatment bottleneck of the traditional PTT, including nonspecific injury to normal tissues, vasculature and host antitumor immunity. However, cancer cells can resist mPTT via heat shock response and autophagy, thus leading to insufficient mPTT monotherapy to ablate tumor. To overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT, synergistic therapies towards cancer cells have been conducted with mPTT. This review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment, including strategies for enhanced single-mode mPTT and mPTT plus synergistic therapies. Moreover, challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed.

Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy.

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a "one-step" modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) "sandwich". After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.

Knockdown CRNDE alleviates LPS-induced inflammation injury via FOXM1 in WI-38 cells.

OBJECTIVE: Pneumonia is the leading global cause of mortality and morbidity in children and elderly people worldwide. The lncRNA colorectal neoplasia differentially expressed (CRNDE) plays an important role in the human development and disease progression. The present study was aimed to investigate the effect of CRNDE on LPS-induced injuries in WI-38 cells and explore the potential mechanism. METHODS: WI-38 cells were treated with LPS to induce injuries. The expression of CRNDE and FOXM1 in WI-38 cells were altered by transient transfection assay. Cell viability was measured by CCK-8 assay and cell apoptosis was detected by flow cytometry assay and western blot. The levels of inflammatory cytokines were assessed by ELISA and western blot. Furthermore, western blot analysis was performed to detect the expression levels of NF-κB and JAK/STAT pathway-related proteins. RESULTS: LPS exposure induced cell injuries and increased CRNDE expression in WI-38 cells. CRNDE overexpression enhanced cell injuries in WI-38 cells with significantly reducing cell viability, increasing cell apoptosis and inflammatory cytokines levels. In addition, CRNDE overexpression further activated the NF-κB and JAK/STAT pathways in LPS-injured WI-38 cells. Inversely, opposite results were observed in CRNDE inhibition treatment group. Interestingly, FOXM1 was up-regulated by CRNDE and FOXM1 silence blocked the effect of CRNDE overexpression in cell apoptosis, inflammation and activation of NF-κB and JAK/STAT signaling pathways. CONCLUSION: This study demonstrated that CRNDE overexpression accelerated LPS-induced apoptosis and inflammation via up-regulation of FOXM1 in WI-38 cells.