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Due to the increasing number of human skin cancers and the limited effectiveness of therapies, research into innovative therapeutic approaches is of enormous clinical interest. In recent years, the use of cold atmospheric pressure plasma has become increasingly important as anti-cancer therapy. The combination of plasma with small molecules offers the potential of an effective, tumour-specific, targeted therapy. The synthesised glycosylated and non glycosylated thia-analogous indirubin derivatives KD87 and KD88, respectively, were first to be investigated for their pharmaceutical efficacy in comparison with Indirubin-3'-monoxime (I3M) on human melanoma (A375) and squamous cell carcinoma (A431) cells. In combinatorial studies with plasma-activated medium (PAM) and KD87 we determined significantly decreased cell viability and cell adhesion. Cell cycle analyses revealed a marked G2/M arrest by PAM and a clear apoptotic effect by the glycosylated indirubin derivative KD87 in both cell lines and thus a synergistic anti-cancer effect. I3M had a pro-apoptotic effect only in A431 cells, so we hypothesize a different mode of action of the indirubin derivatives in the two skin cancer cells, possibly due to a different level of the aryl hydrocarbon receptor and an activation of this pathway by nuclear translocation of this receptor and subsequent activation of gene expression. [ABSTRACT FROM AUTHOR]

Implantation of biomaterials can cause complications often associated with inflammatory reactions. However, repeated evaluation of the implant site would be burdening for patients. Alternatively, blood examinations with analysis of inflammatory serum markers could potentially be useful to reflect the local cellular response for detection and/or prediction of inflammation-related complications. Therefore, following intramuscular implantation of surface-modified Ti implants in rats, this study aimed at examining possible associations between the post-implantation time course of pro-inflammatory (INFγ, IL-2) and anti-inflammatory (IL-4, IL-10) cytokine serum concentrations and the local peri-implant tissue response after 56 days (pro-inflammatory CD68-positive monocytes/macrophages, anti-inflammatory CD163-positive macrophages, MHC class II-positive cells, activated natural killer cells andmast cells). Multivariate correlation analysis revealed a significant interaction between serum IFNγ and peri-implant tissue CD68-positive monocytes/macrophages (p = 0.001) while no interactions were found for other cytokines and cell types. Additional Pearson correlation analysis of IFNγ serum concentrations on each experimental day vs. the CD68-positive monocytes/macrophages response on day 56 demonstrated a consistently positive correlation that was strongest during the first three weeks. Thus, high early pro-inflammatory IFNγ serum concentration was associated with high late number of pro-inflammatory CD68-positive monocyte/macrophages and low early serum IFNγ with low late CD68-positive monocyte/macrophage numbers. Further studies aimed at examination of patient samples could establish the relevance of this association to predict clinical complications. [ABSTRACT FROM AUTHOR]

Copper (Cu) could serve as antibacterial coating for Ti6Al4V implants. An additional cell-adhesive layer might compensate Cu cytotoxicity. This study aimed at in vitro and in vivo evaluation of low-temperature plasma treatment of Ti6Al4V plates with Ti/Cu magnetron sputtering (Ti6Al4V-Ti/Cu), plasma-polymerized ethylenediamine (Ti6Al4V-PPEDA), or both (Ti6Al4V-Ti/Cu-PPEDA). Ti6Al4V-Ti/Cu and Ti6Al4V-Ti/Cu-PPEDA had comparable in vitro Cu release and antibacterial effectiveness. Following intramuscular implantation of Ti6Al4V-Ti/Cu, Ti6Al4V-PPEDA, Ti6Al4V-Ti/Cu-PPEDA and Ti6Al4V controls for 7, 14 and 56 days with 8 rats/day, peri-implant tissue was immunohistochemically examined for different inflammatory cells. Ti6Al4V-PPEDA had more mast cells and NK cells than Ti6Al4V, and more tissue macrophages, T lymphocytes, mast cells and NK cells than Ti6Al4V-Ti/Cu-PPEDA. Ti6Al4V-Ti/Cu had more mast cells than Ti6Al4V and Ti6Al4V-Ti/Cu-PPEDA. Results indicate that PPEDA-mediated cell adhesion counteracted Cu cytotoxicity. Ti6Al4V-Ti/Cu-PPEDA differed from Ti6Al4V only for mast cells on day 56. Altogether, implants with both plasma treatments had antibacterial properties and did not increase inflammatory reactions. [ABSTRACT FROM AUTHOR]

Surface modification of Titanium (Ti) by low-temperature plasma influences cell-material interactions. Therefore, this study aimed at examining serum cytokine levels and associations after intramuscular implantation ( n = 8 rats/group) of Ti-plates with Plasma Polymerized Allyl Amine (Ti-PPAAm), Plasma Polymerized Acrylic Acid (Ti-PPAAc), and without such layers (Ti-Controls). Pro-inflammatory (IL-2, IFNγ, IL-6) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were measured weekly for 56 days. Ti-PPAAm caused increased IL-2 (d7-14, d35), increased IFNγ (d35) and decreased IL-10 (d35, d49-56). Ti-PPAAc induced divergent anti-inflammatory cytokine changes with increased IL-4 (d28-56) and decreased IL-10 (d42-56). Ti-Controls elicited increased IL-2 (d42) and IFNγ (d35-42, d56). IL-6 was not detected and IL-13 only in three samples, thus they do not influence the response against these Ti implants. Correlation analysis revealed surface-dependent associations between cytokines indicating the involvement of different inflammatory cell populations. Concluding, different plasma modifications induce specific serum cytokine profiles and associations indicating distinct inflammatory responses. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-06523-x, published online 15 February 2022 The Funding section in the original version of this Article was omitted. The original article can be found online at https://doi.org/10.1038/s41598-022-06523-x. [Extracted from the article]

Clinical observations have suggested a relationship between osteoarthritis and a changed estrogen metabolism in menopausal women. Phytoestrogens have been shown to ameliorate various menopausal symptoms. Proteoglycans (PG) consisting of low and high sulfated glycosaminoglycans (GAG) are the main components of articular cartilage matrix, and their synthesis is increased by insulin in growth plate cartilage. We have investigated whether GAG synthesis and sodium [35S]sulfate incorporation in female bovine articular chondrocytes are affected by daidzein, genistein, and/or insulin. For comparative purposes, estradiol incubations were performed. Articular chondrocytes were cultured in monolayers at 5% O2 and 5% CO2 in medium containing serum for 7 days followed by the addition of 10−11 M–10−4 M daidzein, genistein, 17β-estradiol, or 5 μg/ml insulin in a serum-free culture phase of 2 days. Photometrically analyzed GAG synthesis was significantly suppressed by high doses (10−5 M–10−4 M) of daidzein, genistein, and 17β-estradiol. Although insulin raised the sodium [35S]sulfate uptake significantly, different concentrations of daidzein, genistein, or 17β-estradiol showed no significant effects. However, the stimulating effect of insulin on sulfate incorporation was enhanced significantly after preincubation of cells with 10−11 M–10−5 M daidzein or 10−9 M–10−5 M genistein but not by 17β-estradiol. In view of the risks of long-term estrogen replacement therapy, further experiments should clarify the potential benefit of phytoestrogens and insulin in articular cartilage metabolism. [ABSTRACT FROM AUTHOR]

Background: Posterior capsule opacification is the most common complication of primary cataract surgery and is caused by migration and proliferation of residual lens epithelial cells onto the posterior capsule. Interfering with the mechanisms involved in cell adhesion is a suitable approach to prevent posterior capsule opacification. Methods: Mibefradil, a T-type calcium-channel blocker, was used to examine the influence on adhesion-mediating mechanisms in human lens epithelial cells derived from cataract surgery. Adhesion was evaluated by light microscopy on the anterior capsules. Expression of integrin receptors was studied by flow cytometry. The influence on the distribution of integrin receptors on the cell surface and the organization of the cytoskeleton was examined by immunofluorescence using a confocal microscope. Results: The calcium-channel blocker Mibefradil inhibited cell adhesion on the anterior capsule wall at concentrations between 10 and 100 µM. The cells expressed the integrin subunits β1 and α3. Mibefradil distinctly impaired the distribution of these integrins on the cell surface in culture. The cells express the cytoskeletal components actin, vimentin and, very weakly, cytokeratin. The structural organization of the actin filaments and vimentin was strongly disrupted with pronounced fragmentation of the actin filaments in the presence of the calcium-channel blocker. Conclusion: The results suggest that the inhibition of cell adhesion by the calcium-channel blocker Mibefradil involves the impairment of integrin-mediated mechanisms. The use of this calcium antagonist appears to be a suitable therapeutic approach to prevent posterior capsule opacification. [ABSTRACT FROM AUTHOR]