Diabetic kidney disease is a serious complication of diabetes mellitus, often leading to chronic kidney disease and ultimately end-stage renal disease. Inflammation, besides deranged mineral metabolism, plays a role in the pathophysiology of diabetic kidney disease. The present study investigated the relationship between IL-6 an important pro-inflammatory cytokine, and Klotho an anti-aging protein with renoprotective function in diabetic kidney disease progression. A study was carried out on 60 patients with ESRD caused by diabetic kidney disease on maintenance hemodialysis and 40 apparently healthy control individuals. IL-6 and Klotho serum levels were measured using the enzyme-linked immunosorbent assay method. Some biochemical indicators, such as intact parathyroid hormone, 1.25-dihydroxyvitamin D3, blood urea, and creatinine, were also measured. The main findings (mean ± SE) showed that the levels of IL-6 and iPTH levels were considerably higher in DKD patients (18.360 ± 2.323 pg/mL; 239.222 ± 24.073 pg/dL) than in controls (4.341 ± 0.393 pg/mL; 26.077 ± 1.609 pg/dL), indicating persistent inflammation and secondary hyperparathyroidism. Conversely, serum 1.25(OH)2D3 and Klotho levels were considerably lower in the DKD group (14.911 ± 0.991 ng/dL and 213.500 ± 25.905 pg/mL, respectively) than in controls (29.125 ± 1.195 ng/dL and 453.587 ± 33.797 pg/mL), indicating kidney function impairment and mineral metabolism disturbance. There was a notable weak inverse relationship between IL-6 and Klotho (r = –0.271, p = 0.036). This suggests that Klotho low levels may increase inflammatory responses and adversely affect renal function. In conclusion, the research demonstrates how IL-6 and Klotho affect one another in diabetic kidney disease. This suggests their application as potential biomarkers for disease progression and targets for therapy in preventing inflammation and maintaining kidney function.
Cisplatin (CP) is an effective antineoplastic agent whose clinical application is constrained by organ toxicities, including liver injury. Although the underlying mechanisms of CP-associated hepatotoxicity have been widely explored, the characteristics of early biochemical and molecular responses following acute exposure remain incompletely defined. The present study aimed to examine early alterations in oxidative stress, inflammatory response, and apoptosis-related pathways following acute CP exposure and to evaluate their potential relevance for subsequent hepatotoxic progression. In this study, early alterations in oxidative balance, inflammatory mediators, and apoptosis-related proteins were examined in rat liver tissue after single-dose CP administration at 5, 7.5, and 12 mg/kg. Liver samples collected 3 days post-treatment were analyzed using ELISA-based assays, routine biochemical methods, and Western blotting for Bax and Bcl-2 expression. The results indicated a dose-related disruption of redox homeostasis, evidenced by elevated lipid peroxidation markers and reduced antioxidant activity. In parallel, pro-inflammatory cytokines showed an increasing trend across treatment groups. Apoptotic signaling was also affected, with enhanced Bax expression and reduced Bcl-2 levels, particularly at higher doses. These molecular findings were accompanied by increases in liver-associated enzyme activities. Overall, the data suggest that acute CP exposure induces measurable early changes at the biochemical and molecular levels in hepatic tissue. These alterations may represent initial responses associated with the development of hepatotoxicity. However, further studies incorporating extended observation periods and structural analyses are needed to better define the temporal progression and mechanistic relevance of these findings.
It was proved that adenosine deaminase (ADA) accumulates in synovial fluids (SFs) in rheumatoid arthritis (RA), reducing the anti-inflammatory adenosine concentration and exacerbating inflammation. Therefore, ADA inhibiting as an inflammation supporting agent may be beneficial in RA treatment. The quest for the new enzyme inhibitors is a relevant task. The aim of this work was to investigate the influence of the water and ethanol extracts of Origanum vulgare L. (OVL) from Armenian landscape on ADA activity. The influence of the extracts on ex vivo ADA activity in two groups of SFs from RA patients with differing the enzyme activity demonstrated more effective inhibition in SFs with higher ADA activity for both extracts. Two isoforms of ADA were purified to elucidate which one is the main factor responsible for the observed enzyme inhibition. There was no significant difference in inhibition of large isoform of ADA from human erythrocytes and RA SFs. The evaluated IC50 values for small isoform of ADA (SADA) evidenced 1.5 times more effective inhibition in vitro citrullinated enzyme compared to the non-citrullinated one. Considering the accumulation of citrullinated SADA in RA SFs enhances inflammation by metabolizing adenosine, the obtained results suggest OVL is a promising source of anti-inflammatory agent for the development of new therapeutic medicines for RA.
Women infertility is a common reproductive system disorder. Diagnosis and treatment are characterized by limited availability and high costs. This paper intends to evaluate the levels of endogenous antioxidant proteins metallothionein 2 (MT2) and metallothionein 4 (MT4) in the serum of both infertile and fertile women, as well as to assess the association between these proteins and total oxidant capacity (TOC), total antioxidant capacity (TAC), oxidative stress index (OSI), serum anti-Müllerian hormone (AMH), and serum testosterone. This case-control study involved one hundred eighty Iraqi women, categorized into three categories: primary infertile women (P group), secondary infertile women (S group), and healthy fertile women (C group). With regard to the control group, the results demonstrated a significant rise in serum MT2 levels within the primary infertile group, while serum MT4 level displayed a noticeable decrease in the infertile groups. The rise in MT2 could serve as a means to compensate for a decline in MT4, pointing out the potential antioxidant contribution of these proteins in the progression of infertility. A receiver operating characteristic (ROC) outcome demonstrated excellent sensitivity and specificity, alongside an elevated AUC for MT2, MT4, and other biomarkers in a diagnosis of women infertility.
Extracellular vesicles (EVs) represent a promising tool for diagnostics and therapy, but high heterogeneity limits their practical use. In this work, a comparative study of the physicochemical properties of native EVs secreted by HEK-293T cells and exosome-like nanovesicles (EMNVs) obtained by extrusion of whole HEK-293T cells was carried out. Using transmission electron microscopy, dynamic and electrophoretic light scattering, and surface-enhanced Raman spectroscopy, the authors found that EMNVs form a more homogeneous population with an average diameter of 115 nm and a high negative charge (−22.9 mV), whereas native EVs are more heterogeneous in size and have a lower zeta potential (−12.1 mV). Spectral analysis revealed the presence of nucleic acid signals in native EVs and their absence in EMNVs, indicating differences in molecular composition due to different biogenesis mechanisms. The obtained data demonstrate that EMNVs are a more standardized and colloidally stable alternative to native EVs, making them a promising platform for the development of drug-delivery systems.
