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We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(<i>η</i>⁶-<i>p</i>-cymene)(1,2-dicarba-<i>closo</i>-dodecarborane-1,2-dithiolato)] (<b>1/2</b>), [Ir(<i>η</i>⁵-pentamethylcyclopentadiene)(1,2-dicarba-<i>closo</i>-dodecarborane-1,2-dithiolato)] (<b>3</b>), [Os/Ru(<i>η</i>⁶-<i>p</i>-cymene)(benzene-1,2-dithiolato)] (<b>4/5</b>) and [Ir(<i>η</i>⁵-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (<b>6</b>)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes <b>3</b> and <b>6</b> were found to be non-cytotoxic. The anti-inflammatory activity of <b>1–6</b> was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes <b>3</b> and <b>6</b> trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action

data sheet from Anti-inflammatory activity of electron-deficient organometallics

We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(<i>η</i>⁶-<i>p</i>-cymene)(1,2-dicarba-<i>closo</i>-dodecarborane-1,2-dithiolato)] (<b>1/2</b>), [Ir(<i>η</i>⁵-pentamethylcyclopentadiene)(1,2-dicarba-<i>closo</i>-dodecarborane-1,2-dithiolato)] (<b>3</b>), [Os/Ru(<i>η</i>⁶-<i>p</i>-cymene)(benzene-1,2-dithiolato)] (<b>4/5</b>) and [Ir(<i>η</i>⁵-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (<b>6</b>)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes <b>3</b> and <b>6</b> were found to be non-cytotoxic. The anti-inflammatory activity of <b>1–6</b> was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes <b>3</b> and <b>6</b> trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action

Mass spectrometry analysis of a nitric oxide adduct from Anti-inflammatory activity of electron-deficient organometallics

Figure S1. Mass spectrum of complex [2-NO] in acetone solution, recorded in ESI- mode

Influence of Mussel-Derived Bioactive BMP-2-Decorated PLA on MSC Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo

Osteoinductive activity of the implant in bone healing and regeneration is still a challenging research topic. Therapeutic application of recombinant human bone morphogenetic protein-2 (BMP-2) is a promising approach to enhance osteogenesis. However, high dose and uncontrolled burst release of BMP-2 may introduce edema, bone overgrowth, cystlike bone formation, and inflammation. In this study, low-dose BMP-2 of 1 μg was used to design PLA-PD-BMP for functionalization of polylactic acid (PLA) implants via mussel-inspired polydopamine (PD) assist. For the first time, the binding property and efficiency of the PD coating with BMP-2 were directly demonstrated and analyzed using an antigen–antibody reaction. The obtained PLA-PD-BMP surface immobilized with this low BMP-2 dose can endow the implants with abilities of introducing strong stem cell adhesion and enhanced osteogenicity. Furthermore, in vivo osteoinduction of the PLA-PD-BMP-2 scaffolds was confirmed by a rat ectopic bone model, which is marked as the “gold standard” for the evidence of osteoinductive activity. The microcomputed tomography, Young’s modulus, and histology analyses were also employed to demonstrate that PLA-PD-BMP grafted with 1 μg of BMP-2 can induce bone formation. Therefore, the method in this study can be used as a model system to immobilize other growth factors onto various different types of polymer substrates. The highly biomimetic mussel-derived strategy can therefore improve the clinical outcome of polymer-based medical implants in a facile, safe, and effective way

Table_1_Protective Ability of Biogenic Antimicrobial Peptide Microcin J25 Against Enterotoxigenic Escherichia Coli-Induced Intestinal Epithelial Dysfunction and Inflammatory Responses IPEC-J2 Cells.DOCX

<p>Poison of intestinal induce severe health problems in human infants and young animals due to contaminating foods and feedstuffs. With the emergence of public health concerns and high-speed diffuse of drug-opposition of bacteria, the adoption of antimicrobial peptides as potential candidates in treating pathogen infections raised up. Nature Microcin J25 (MccJ25), a class of lasso peptides separated from a fecal strain of E. coli, has been replied to display powerful antimicrobial behavior. Herein, the study was to assess the usefulness of biogenic MccJ25 in the prophylaxis of ETEC K88 infection in IPEC-J2 cells. In vitro antimicrobial activity against ETEC K88 and cytotoxicity of biogenic MccJ25 were determined first. To further understand how biogenic MccJ25 mediates its impact, ETEC K88 adhesion in cells, membrane permeability [as indicated by reduced release of lactate dehydrogenase (LDH)], transepithelial electrical resistance (TEER), barrier function, and proinflammatory cytokines levels were determined in IPEC-J2 cells after treatment with biogenic MccJ25 and challenge with ETEC K88. Biogenic MccJ25 had a minimum inhibitory concentration of 0.25 μg/mL against ETEC K88, decreased ETEC K88 adhesion in cells and did not cause cytotoxicity toward cells. Furthermore, biogenic MccJ25 protects against ETEC-induced barrier dysfunction by increasing the TEER, decreasing the LDH and promoting tight junction proteins (TJPs) by promoting the assembly of occludin and claudin-1 in the tight junction complex. Biogenic MccJ25 was further found to relieve inflammation responses through modulation of interleukine-6, IL-8 and tumor necrosis factor-α levels via inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor κB activation. In summary, biogenic MccJ25 can protects against ETEC K88-induced intestinal damage and inflammatory response, recommend the hidden adoption of biogenic MccJ25 as a novel prophylactic agent to reduce pathogen infection in animals, food or humans.</p