Ursolic acid represses influenza A virus-triggered inflammation and oxidative stress in A549 cells by modulating the miR-34c-5p/TLR5 axis.

BACKGROUND: Ursolic acid (UA) is a pentacyclic triterpenoid compound with a wide range of anti-tumor, anti-inflammatory, hypotensive and other pharmacological effects. Here, the biological roles and regulatory mechanisms of UA in influenza A virus (IAV)-treated A549 cells were investigated. METHOD: The cytotoxic impacts of UA on A549 cells with or without IAV treatment were determined using MTT and LDH assays. The inflammatory responses and oxidative stress of IAV-treated A549 cells were measured by RT-qPCR, ELISA, DCFH-DA probe, and colorimetric assays. A dual luciferase assay was carried out to validate the molecular interaction between miR-34c-5p and TLR5. Promoter methylation was detected by MSP experiment. Methylation-related proteins were quantified by western blot. Virus replication was assessed by TCID50 and western blot assays. RESULTS: UA significantly ameliorated IAV-triggered cell injury and inflammatory response, virus replication and oxidative stress by elevating cell viability, ROS level and the activities of SOD and GSH-Px but reducing the LDH, MDA, and TCID50 values and the expression of virus-related proteins (NP) and cytokines (TNF-α, IL-1ß, IL-6, and IL-18). Moreover, UA promoted miR-34c-5p expression by repressing DNMTs-mediated methylation. TLR5 was verified to be a direct target of miR-34c-5p and could be downregulated by UA. Rescue experiments revealed that silencing miR-34c-5p diminished the regulatory roles of UA in IAV-treated A549 cells. CONCLUSION: Our data elucidated that UA attenuated IAV-triggered inflammatory responses and oxidative stress in A549 cells by regulating the miR-34c-5p/TLR5 axis, suggesting that UA plays a protective role in IAV-induced pneumonia.

Divergent Synthesis of Contorted Polycyclic Aromatics Containing Pentagons, Heptagon, and/or Azulene.

Divergent synthesis of four contorted aromatics containing pentagons, a heptagon, and/or an azulene from the same difluorenyl pentacenediene precursor were realized in one step. The subtle differences in molecular structure were confirmed by X-ray crystallography. The mechanisms for the control of different products, which involve a ring-expansion rearrangement, Scholl reactions, and/or Mallory cyclization were proposed on the basis of control experiments and DFT calculations. Such development adds good structure versatility and materials accessibility to the study of contorted aromatics.

A Chinese herbal medicine (Modified Guomin Decoction) Influences the differentiation of CD4+ T-cell subsets in OVA-induced asthmatic mice.

OBJECTIVE: Modified Guomin Decoction (MGD) is an effective Chinese herbal medicine for treatment of various allergic diseases, especially allergic asthma. Its water decoction is conventionally used for treatment of allergic bronchitis in China. Up to date, the underlying mechanisms of this herbal combination have not been fully investigated yet. METHODS: In the in vivo study, the mice were treated with Chicken egg ovalbumin (OVA) and aluminum hydroxide gel as the classic allergic asthma animal model. After treatment with MGD, the lung tissues were examined by Histological assessment. The flow cytometric analysis was used to classify the CD4+ T-cell subsets. RT-PCR, Real time fluorescence quota PCR and Western blotting were used to analyze the gene expression of IL-4, IL-5, IFN-γ T-bet/GAIA-3 and Foxp3 in lung tissues. RESULTS: MGD significantly reduced ovalbumin-specific IgE production in mouse serum and suppressed inflammatory cell infiltration, thus, improved the asthma symptoms. The mechanistic studies indicated that MGD treatment mainly modified the differentiation of CD4+ T-cell subsets and improved their functions. These included that MGD enhanced the proportion of Th1-cell, reduced Th2-cell subsets to CD4+ cell and balanced Treg/Th17 cell populations in the asthmatic mice spleen tissues. For Th1-cells, MGD upregulated the gene expression of their cytokine IFN-γ and its transcription factor T-bet while it downregulated the gene expression of their cytokines of IL-4 and IL-5. For Th2-cells, MGD mainly downregulated its transcription factor GATA-3 in lung tissues of asthmatic mice. MGD suppressed the Th17-cell subsets in CD4+ cells and upregulated the expression of Foxp3, a specific transcription factor of Treg-cell.

Clearance of serum solutes by hemofiltration in dogs with severe heat stroke.

BACKGROUND: We have previously reported that hemofiltration (HF) may be an effective additional means of treating heat stroke when rapid cooling is not effective. METHODS: Dogs were assigned to a heat stroke (control) or heat stroke + hemofiltration (HF) group (n = 8 each group). After heat stroke induction, dogs in the HF group received HF for 3 h. Serum concentrations of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-6, blood urea nitrogen (BUN) and creatinine were measured at baseline and 1, 2, and 3 h after heat stroke. Clearance rates of solutes were determined 1, 2, and 3 h after the start of HF. RESULTS: Serum concentrations of all solutes tended to increase with time after heat stroke in the control group, but decreased (BUN, creatinine) or remained relatively unchanged (TNF-α, IL-6, IL-10) with time in the HF group. Concentrations of all solutes were significantly lower in the HF group compared with the control group at 2 and 3 h (P < 0.05). Clearance rates for small molecular weight solutes were high, while those for larger molecular weight solutes were low. CONCLUSION: HF prevents heat stroke-induced increases in serum cytokine concentrations and is effective for clearing small molecular weight solutes from serum, but less effective for clearing larger molecular weight solutes, including TNF-α, IL-6, and IL-10.