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This study investigated whether propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation. Thirty clean male SD rats were randomly divided into a control (n=10), a model (n=10) and a propofol group (n=10). The model and propofol groups were injected with lipopolysaccharide (LPS) via the caudal vein to establish animal models of myocardial injury. At the same time, the control group was injected with normal saline via the caudal vein. At 30 min after the injections, the propofol group was treated with a continuous intravenous infusion of propofol, the control and model groups were injected with normal saline, and the three groups were treated continuously for 4 h. The changes in levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected via enzyme-linked immunosorbent assay (ELISA). The mRNA expression level of nuclear factor-κB (NF-κB) in myocardial tissues was detected via quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of NF-κB, Bax and Bcl-2 in atrial muscles in each group were measured via Western blotting. The damage of myocardial tissues was detected via hematoxylin eosin (H&E) staining of tissues. Our results showed that compared with those in control group, the levels of IL-1, IL-6 and TNF-α in serum in the model and propofol groups were significantly higher; however, the levels in the model group, were significantly higher than those in the propofol group (P<0.01). The mRNA and protein expression levels of NF-κB in the propofol group were significantly lower than those in the model group (P<0.01). Likewise, the protein expression levels of Bax were significantly lower, while those of Bcl-2 were significantly increased. H&E staining showed that the myocardial tissues in the model group were damaged significantly, but the damage in the propofol group was significantly less severe. Based on our findings, it seems propofol can indeed protect against endotoxin-induced myocardial injury through its inhibition of the NF-κB-mediated inflammatory pathway.

Objectives Fibrotic cataract, including posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC), renders millions of people visually impaired worldwide. However, the underlying mechanism remains poorly understood. Here, we report a miRNA‐based regulatory pathway that controls pathological fibrosis of lens epithelium. Materials and methods Expression of miR‐22‐3p and histone deacetylase 6 (HDAC6) in normal and PCO patient samples were measured by qPCR. Human lens epithelial explants were treated with TGF‐β2 in the presence or absence of miR‐22‐3p mimics or inhibitor. Cell proliferation was determined by MTS assay, and migration was tested by transwell assay. Expression of HDAC6 and EMT‐related molecules were analysed by Western blot, qPCR and immunocytochemical experiments. Results We identify miR‐22‐3p as a downregulated miRNA targeting HDAC6 in LECs during lens fibrosis and TGF‐β2 treatment. Mechanistically, gain‐ and loss‐of‐function experiments in human LECs and lens epithelial explants reveal that miR‐22‐3p prevents proliferation, migration and TGF‐β2 induced EMT of LECs via targeting HDAC6 and thereby promoting α‐tubulin acetylation. Moreover, pharmacological targeting of HDAC6 deacetylase with Tubacin prevents fibrotic opaque formation through increasing α‐tubulin acetylation under TGF‐β2 stimulated conditions in both human lens epithelial explants and the whole rat lenses. Conclusions These findings suggest that miR‐22‐3p prevents lens fibrotic progression by targeting HDAC6 thereby promoting α‐tubulin acetylation. The ‘miR‐22‐HDAC6‐α‐tubulin (de)acetylation’ signalling axis may be therapeutic targets for the treatment of fibrotic cataract.

PURPOSE.Lens fibrosis involves aberrant growth, migration, and transforming growth factorb (TGFb)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). In this study, we investigated the role of the bromo-and extra-terminal domain (BET) inhibitor in lens fibrotic disorder to identify drug-based therapies.METHODS. Rat lens explants, rabbit primary lens epithelial cells (rLECs), human lens explants and human SRA01/04 cells were treated with TGFb2 in the presence or absence of the BET bromodomain inhibitor JQ1 or the MYC inhibitor 10058-F4. Proliferation was determined by MTS assay. Cell migration was measured by wound healing and transwell assays. The expression levels of fibronectin (FN), a-smooth muscle actin (a-SMA), E-cadherin, and phosphorylated downstream Smads were analyzed by Western blot, qRT-PCR, and immunocytochemical experiments. Transcriptome analysis was conducted to explore the molecular mechanism.RESULTS. Blockage of BET bromodomains with JQ1 significantly suppressed rLECs proliferation by inducing G1 cell cycle arrest. Furthermore, JQ1 attenuated TGFb2-dependent upregulation of mesenchymal gene expression and phosphorylation of Smad2/3 during the progression of EMT, whereas E-cadherin expression was preserved. JQ1 repressed MYC expression, which was dose-and time-dependently upregulated by TGFb2. Inhibiting MYC with either the smallmolecule inhibitor 10058-F4 or genetic knockdown phenocopied the effects of JQ1 treatment. MYC overexpression partially reversed the JQ1-regulated EMT-related alteration of gene expression. Both JQ1 and 10058-F4 blocked the expression of TGFb receptor II and integrin av in rLECs and abolished TGFb2-induced opacification and subcapsular plaque formation in rat lens explants. CONCLUSIONS.Our results demonstrate the antifibrotic role of JQ1 in maintaining the epithelial characteristics of LECs and blocking TGFb2-induced EMT, possibly by downregulating MYC, thereby providing new avenues for treating lens fibrosis.

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Herein, we reported nitroxide radical-modified CuS nanoparticles (CuS–NO˙ NPs), and they exhibited a typical absorption peak at 1182 nm.

Background The giant panda (Ailuropoda melanoleuca) is a well-known, rare and endangered species. Baylisascaris schroederi is a pathogenic ascarid. Infection with B. schroederi may cause death in giant pandas. At present, the immune evasion mechanism of B. schroederi is little known. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, we focused on the analysis of the regulation of B. schroederi migratory larvae CPI (rBsCPI-1) on mice immune cells. Methods First, the pattern recognition receptors on the surface of peripheral blood mononuclear cells (PBMCs) and the signal pathways that transduce extracellular signals into the nucleus activated by rBsCPI-1 were identified. Then, the regulatory effects of rBsCPI-1 on PBMCs physiological activities were detected. Finally, the effects of rBsCPI-1 on TLR signaling pathway activation and NF-κB phosphorylation in mice immunized with recombinant protein were analysed. Results The results suggested that rBsCPI-1 secreted by B. schroederi migratory larvae is mainly recognized by TLR2 and TLR4 on PBMCs. Extracellular signals are transduced into the nucleus through the MAPK and NF-κB signaling pathways, enhancing the phagocytosis, migration, and apoptosis of PBMCs; meanwhile, rBsCPI-1 induces high expression of NO. Thus, rBsCPI-1 plays a role in immune regulation. In addition, the high expression of negative regulatory factors also ensured that TLR activation is maintained at the optimal level. Conclusions rBsCPI-1 can transduce regulatory signals into immune cells by activating the TLR2/4-NF-κB/MAPK signaling pathway, having a certain regulatory effect on the physiological activities. Meanwhile, rBsCPI-1 can maintain the immune response in a balance by limiting the over-activation of the TLRs signaling pathway and thus contributes to B. schroederi immune evasion. Graphical Abstract