Rapamycin inhibits corneal inflammatory response and neovascularization in a mouse model of corneal alkali burn.

Alkali burn-induced corneal injury often causes inflammation and neovascularization and leads to compromised vision. We previously reported that rapamycin ameliorated corneal injury after alkali burns by methylation modification. In this study, we aimed to investigate the rapamycin-medicated mechanism against corneal inflammation and neovascularization. Our data showed that alkali burn could induce a range of different inflammatory response, including a stark upregulation of pro-inflammatory factor expression and an increase in the infiltration of myeloperoxidase- and F4/80-positive cells from the corneal limbus to the central stroma. Rapamycin effectively downregulated the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), toll-like receptor 4 (TLR4), nucleotide binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3), and Caspase-1, and suppressed the infiltration of neutrophils and macrophages. Inflammation-related angiogenesis mediated by matrix metalloproteinase-2 (MMP-2) and rapamycin restrained this process by inhibiting the TNF-α upregulation in burned corneas of mice. Rapamycin also restrained corneal alkali burn-induced inflammation by regulating HIF-1α/VEGF-mediated angiogenesis and the serum cytokines TNF-α, IL-6, Interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The findings of this study indicated rapamycin may reduce inflammation-associated infiltration of inflammatory cells, shape the expression of cytokines, and balance the regulation of MMP-2 and HIF-1α-mediated inflammation and angiogenesis by suppressing mTOR activation in corneal wound healing induced by an alkali injury. It offered novel insights relevant for a potent drug for treating corneal alkali burn.

Reducing cadmium accumulation in shrimp using Escherichia coli with surface-displayed peptide.

Cadmium (Cd) is a hazardous metal that can accumulate in aquatic organisms and endanger human health via the food chain. In this study, genetic engineering was used to display a peptide with Cd-binding potential on the surface of Escherichia coli cells. This whole-cell adsorbent exhibited high affinity for Cd ions (Cd2+) in the solution. The Cd2+ adsorption capacity of the whole-cell adsorbent was three-fold that of the control cells in a 20 µM Cd2+ solution, and 97.2% ± 2.38% of the Cd2+ was removed. The whole-cell adsorbent was fed to shrimp (Neocaridina denticulata), and the surface-engineered E. coli successfully colonized the shrimp intestine, which showed significantly less Cd accumulation than the group not fed surface-engineered E. coli. The whole-cell adsorbent evidently protected shrimp from the toxicity of Cd2+ by adsorbing it. Moreover, the whole-cell adsorbent mitigated the changes in microbial community structure in the shrimp gut caused by the exposure of Cd2+. These findings suggest that this strategy is effective for controlling the contamination of Cd2+ in shrimp.

Hg2+-binding peptide decreases mercury ion accumulation in fish through a cell surface display system.

Mercury is a potentially toxic trace metal that poses threats to aquatic life and to humans. In this study, a mercury-binding peptide was displayed on the surface of Escherichia coli cells using an N-terminal region ice nucleation protein anchor. The surface-engineered E. coli facilitated selective adsorption of mercury ions (Hg2+) from a solution containing various metal ions. The Hg2+ adsorption capacity of the surface-engineered cell was four-fold higher than that of the original E. coli cells. Approximately 95% of Hg2+ was removed from solution by these whole-cell sorbents. The transformed strains were fed to Carassius auratus, so that the bacteria could colonize fish intestine. Engineered bacteria-fed C. auratus showed significantly less (51.1%) accumulation of total mercury when compared with the group that had not been fed engineered bacteria. The surface-engineered E. coli effectively protected fish against the toxicity of Hg2+ in aquatic environments by adsorbing more Hg2+. Furthermore, the surface-engineered E. coli mitigated microbial diversity changes in the intestine caused by Hg2+ exposure, thereby protecting the intestinal microbial community. This strategy is a novel approach for controlling Hg2+ contamination in fish.

Reducing methylmercury accumulation in fish using Escherichia coli with surface-displayed methylmercury-binding peptides.

Seafood consumption is widely considered as the primary route for human exposure to the neurotoxin methylmercury (MeHg) that is produced by certain anaerobic microorganisms and can bioaccumulate to high concentration levels in natural aquatic food webs. In this study, a novel methylmercury-binding peptide with seven amino acids was displayed on the cell surfaces of Escherichia coli strain W-1, which was isolated from fish feces and fused with ice nucleation protein. These cells exhibited high affinity and selectivity toward methylmercury. They efficiently removed more than 96% of 12 µM methylmercury, and accumulation of methylmercury in the engineered strain was four times higher than that in the wild type. Transmission electron microscopy confirmed methylmercury accumulation on cell membranes. Carassius auratus was fed by engineered bacteria, which showed a decrease in methylmercury concentration in muscles of about 36.3 ± 0.7%; whereas an increase in methylmercury concentration was observed in the feces (36.7 ± 0.8%) in comparison to the control group. The engineered strain in the gut captured methylmercury and prevented it's absorption by muscles, while some bacteria with methylmercury were excreted in the feces. The surface-engineered E. coli effectively protected fish from methylmercury contamination.

A Comprehensive Review on the Biological and Pharmacological Activities of Rhodanine Based Compounds for Research and Development of Drugs.

At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have exhibited wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery. Here, we review some deadly defects of clinical medicines to the therapy of diseases and important advances on rhodanine derivatives in drug researches (e.g. as anti-diabetic, anti-viral, antiinflammatory, anti-microbial, anti-tumor agents and inhibitors for Alzheimer Disease), indicating that rhodanine heterocycle could be used as a significant pharmacophore to develop novel pharmacological active molecules. It is believed that the review is of importance for new ideas in the development of and rational designs of rhodanine-based drugs.