Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and propolis on atherosclerosis. In our study, C57BL/6J mice (n = 16) were used in the control and sham groups. In contrast, ApoE^-/- mice (n = 48) were used in the case, water extract of propolis (WEP), ethanolic extract of propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1β, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased (p < 0.003). Our study results show that propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.

Aim: To date, various molecules have been investigated to reduce the effect of renal ischemia/reperfusion (I/R) injury. However, none have yet led to clinical use. The present study aimed to investigate the protective effect of cordycepin (C) on renal I/R injury in an experimental rat model. Materials and methods: Twenty-four mature Sprague Dawley female rat was randomly divided into three groups: Sham, I/R, I/R+C. All animals underwent abdominal exploration. To induce I/R injury, an atraumatic vascular bulldog clamp was applied to the right renal pedicle for 60 minutes (ischemia) and later clamp was removed to allow reperfusion in all rats, except for the sham group. In the I/R + C group, 10 mg/kg C was administered intraperitoneally, immediately after reperfusion. After 4 hours of reperfusion, the experiment was terminated with right nephrectomy. Histological studies and biochemical analyses were performed on the right nephrectomy specimens. EGTI (endothelial, glomerular, tubulointerstitial) histopathology scoring and semi-quantitative analysis of renal cortical necrosis were used for histological analyses and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total oxidant status (TOS) for biochemical analyses. Results: Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. The I/R group had higher histopathological scores than the I/R + C group. In the biochemical analysis of the tissues, SOD, MDA, TOS values were found to be statistically different in the I/R group compared to the I/R + C group (p: 0.004, 0.004, 0.001 respectively). Conclusions: Intraperitoneal cordycepin injection following ischemia preserve renal tissue against oxidative stress in a rat model of renal I/R injury.

Objective: In this study, we aimed to evaluate the potential effects of white tea (WT) in the atherosclerosis process characterized by oxidative stress, inflammation, and dyslipidemia. Methods: In our study, apolipoprotein E knockout (ApoE^−/−) mice (RRID: IMSR_JAX:002052) and C57BL/6J mice (RRID: IMSR_JAX:000664) were used. In the atherosclerosis model induced by an atherogenic diet (AD), WT was administered via oral gavage at two different concentrations. The animals were sacrificed by decapitation under anesthesia, and their serum and aortic tissues were collected. Total cholesterol (TC), triglyceride (TG), interleukin (IL)-1β, IL-6, IL-10, IL-12, tumor necrosis factor-α (TNF-α), interferon-γ, myeloperoxidase, paraoxonase-1, lipoprotein-associated phospholipase A2, oxidized low-density lipoprotein (Ox-LDL), lectin-like oxidized LDL receptor (LOX-1), a disintegrin, and metalloprotease (ADAM) 10 and 17 activities were determined via colorimetric, enzyme-linked immunoassay, and fluorometric methods. Results: WT supplementation decreased serum Ox-LDL, LOX-1, TC, and TG levels by approximately 50%. TNF- and IL-6 levels were reduced by approximately 30% in the aortic arch. In addition, ADAM10/17 enzyme activities were found to be reduced by approximately 25%. However, no change in the AD-induced fibrotic cap structure was observed in the aortic root. Conclusions: The findings indicate that white tea effectively reduced oxidative stress, inflammation, and dyslipidemia in atherosclerosis but does not affect atheroma plaque morphology.

Background and Objectives: ADAM17, a sheddase that regulates cytokine and receptor ectodomains, amplifies inflammatory signaling. Acute liver injury (ALI) is driven by dysregulated inflammation, accompanied by both oxidative and endoplasmic reticulum (ER) stress responses. We investigated whether pharmacological inhibition of ADAM17 with GW280264X mitigates lipopolysaccharide (LPS)-induced acute liver injury by targeting these pathways. Methods: Male C57BL/6J mice received intraperitoneal LPS (10 mg/kg). GW280264X (500 µg/kg, i.p.) was administered at one and three hours post-LPS treatment. At the fifth hour, serum and liver samples were collected to determine serum ALT/AST levels and to perform hematoxylin and eosin (H&E) staining. Inflammatory (TNF-α), oxidative (MDA, 4-HNE, Fe²⁺, GSH; NRF2/KEAP1), endoplasmic reticulum (ER) stress (GRP78, ATF6, CHOP), and ferroptosis-related (GPX4, SLC7A11) markers, along with ADAM17 protein levels, were analyzed using ELISA, colorimetric assays, and Western blotting. Results: LPS triggered hepatic injury. This was accompanied by marked elevations in TNF-α, oxidative indices (MDA, 4-HNE, Fe²⁺) and ER stress proteins (GRP78, ATF6, CHOP), together with depletion of hepatic GSH. GW280264X significantly reduced AST levels, attenuated inflammatory, oxidative, and ER stress responses, and improved hepatic histopathology. GPX4 and SLC7A11 tended to increase following treatment, but the changes did not reach statistical significance and should be interpreted cautiously due to the limited sample size (n = 5). Similarly, ADAM17 protein levels tended to decrease, although the change was not statistically significant. Conclusions: Pharmacological inhibition of ADAM17 with GW280264X may confer early hepatoprotection in LPS-induced ALI by attenuating inflammatory, oxidative and ER stress pathways. ADAM17 inhibition yielded partial and statistically non-significant protective effects at this early stage; therefore, these findings should be considered exploratory. Future studies with larger sample sizes and longer observation periods are warranted to confirm the durability and mechanistic basis of this response.

Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. Methods: A total of 13 patients diagnosed with urosepsis, based on an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score and positive urine culture, were included in the study. Daily blood samples were collected from patients for 10 days, and serum levels of GDF15, procalcitonin (PCT), and presepsin (P-SEP) were measured by ELISA. C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, and neutrophil, lymphocyte, and platelet counts were determined using autoanalyzers. Temporal changes were analyzed using the Friedman test, and correlations were analyzed using Spearman’s test. Results: GDF15 levels began to decrease from Day 3, with a significant decline observed from Day 7 compared to Day 1 (p < 0.001). Similar decreasing trends were observed in CRP and PCT levels, whereas presepsin levels did not exhibit significant changes. Significant positive correlations were identified between GDF15 and CRP (r = 0.65, p = 0.015), BUN (r = 0.57, p = 0.041), and creatinine (r = 0.62, p = 0.024), and a significant negative correlation was observed with eGFR (r = −0.62, p = 0.024). No significant correlation was found between GDF15 and presepsin (p > 0.05). Conclusions: GDF15 is a biomarker sensitive to the resolution phase of inflammation and organ dysfunction in sepsis, demonstrating significant temporal changes. It holds potential as an indicator for monitoring clinical progression and assessing prognosis.