Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in clinical care, CKD remains a major public health burden, affecting 10–15% of the population, and its prevalence is constantly growing. Due to its insidious nature, CKD is rarely diagnosed in early stages, and once developed, its progression is unfortunately irreversible. There are many factors that contribute to the setting of the inflammatory status in CKD, including increased production of proinflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, altered metabolism of adipose tissue, and last but not least, gut microbiota dysbiosis, an underestimated source of microinflammation. In this scenario, a huge step forward was made by the increasing progression of omics approaches, specially designed for identification of biomarkers useful for early diagnostic and follow-up. Recent omics advances could provide novel insights in deciphering the disease pathophysiology; thus, identification of circulating biomarker panels using state-of-the-art proteomic technologies could improve CKD early diagnosis, monitoring, and prognostics. This review aims to summarize the recent knowledge regarding the relationship between inflammation and CKD, highlighting the current proteomic approaches, as well as the inflammasomes and gut microbiota dysbiosis involvement in the setting of CKD, culminating with the troubling bidirectional connection between CKD and renal malignancy, raised on the background of an inflammatory condition.

Recently, a large spectrum of biomaterials emerged, with emphasis on various pure, blended, or doped calcium phosphates (CaPs). Although basic cytocompatibility testing protocols are referred by International Organization for Standardization (ISO) 10993 (parts 1–22), rigorous in vitro testing using cutting-edge technologies should be carried out in order to fully understand the behavior of various biomaterials (whether in bulk or low-dimensional object form) and to better gauge their outcome when implanted. In this review, current molecular techniques are assessed for the in-depth characterization of angiogenic potential, osteogenic capability, and the modulation of oxidative stress and inflammation properties of CaPs and their cation- and/or anion-substituted derivatives. Using such techniques, mechanisms of action of these compounds can be deciphered, highlighting the signaling pathway activation, cross-talk, and modulation by microRNA expression, which in turn can safely pave the road toward a better filtering of the truly functional, application-ready innovative therapeutic bioceramic-based solutions.

Caveolin-1 (CAV1) is the scaffold protein of caveolae, which are minute invaginations of the cell membrane that are involved in endocytosis, cell signaling, and endothelial-mediated inflammation. CAV1 has also been reported to have a dual role as either a tumor suppressor or tumor promoter, depending on the type of cancer. Inflammation is an important player in tumor progression, but the role of caveolin-1 in generating an inflammatory milieu remains poorly characterized. We used a caveolin-1-knockout (CAV1^−/−) mouse model to assess the inflammatory status via the quantification of the pro- and anti-inflammatory cytokine levels, as well as the ability of circulating lymphocytes to respond to nonspecific stimuli by producing cytokines. Here, we report that the CAV1^−/−mice were characterized by a low-grade systemic proinflammatory status, with a moderate increase in the IL-6, TNF-α, and IL-12p70 levels. CAV1^−/−circulating lymphocytes were more prone to cytokine production upon nonspecific stimulation than the wild-type lymphocytes. These results show that CAV1 involvement in cell homeostasis is more complex than previously revealed, as it plays a role in the inflammatory process. These findings indicate that the CAV1^−/−mouse model could prove to be a useful tool for inflammation-related studies.

The increasing popularity of herbal supplements emphasizes the need of scientific data regarding their health benefits and possible toxicological concerns. The complexity of botanical extracts, which include thousands of distinct compounds, contributes to the challenging nature of this endeavor. In this study, we explored the hormetic effects of two Trifolium pratense extracts on breast cell lines. Using a wide range of concentrations (0.1 to 3.33 mg/mL), we analyzed how extracts modulate cellular processes such as viability, proliferation, and oxidative stress on breast adenocarcinoma highly invasive estrogen receptor negative (ER-) and noninvasive ER+ cells, as well as on non-tumorigenic ER- normal cells. The cytotoxicity and real-time cell analysis (RTCA) assays showed that both extracts exercised a biphasic dose effect on adenocarcinoma ER+ and normal ER- cell proliferation and oxidative stress. We report a monotonic dose-dependent cytotoxicity on highly invasive adenocarcinoma ER- cells; the induced apoptosis was based on the pro-oxidant activity of extracts. The reactive oxygen species (ROS) generation by high-dose ethanolic extract was observed in all cells, followed by mitochondria dysfunction. Oxidative stress parameters, such as malondialdehyde (MDA) and reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity were affected. Our study demonstrates that T. pratense extracts have chemoprevention potential in normal and tumorigenic breast cells by modulating cellular proliferation and oxidative stress.