Plant-based extracts possess biological potential due to their high content of phytochemicals. Nevertheless, photosynthetic pigments (e.g., chlorophylls) that are also present in plant extracts could produce undesirable pro-oxidant activity that might cause a negative impact on their eventual application. Herein, the phenolic content of olive leaf (OLE) and green tea (GTE) extracts was assayed, and their antioxidant and anticancer activities were evaluated before and after the removal of chlorophylls. Regarding phenolic content, OLE was rich in hydroxytyrosol, tyrosol as well as oleuropein, whereas the main compounds present in GTE were gallocatechin, epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallocatechin gallate, and caffeine. Interestingly, fresh extracts’ antioxidant ability was dependent on phenolic compounds; however, the elimination of chlorophyll compounds did not modify the antioxidant activity of extracts. In addition, both OLE and GTE had high cytotoxicity against HL-60 leukemic cell line. Of note, the removal of chlorophyll pigments remarkably reduced the cytotoxic effect in both cases. Therefore, our findings emphasize the remarkable antioxidant and anticancer potential of OLE and GTE and suggest that chlorophylls are of paramount importance for the tumor-killing ability of such plant-derived extracts.

Diabetic retinopathy (DR), a complication of diabetes mellitus (DM), can cause severe visual loss. The retinal pigment epithelium (RPE) plays a crucial role in retinal physiology but is vulnerable to oxidative damage. We investigated the protective effects of selenium (Se) on retinal pigment epithelium (ARPE-19) and primary human retinal microvascular endothelial (ACBRI 181) cells against high glucose (HG)-induced oxidative stress and apoptotic cascade. To achieve this objective, we utilized varying concentrations of D-glucose (ranging from 5 to 80 mM) to induce the HG model. HG-induced oxidative stress in ARPE-19 and ACBRI 181 cells and the apoptotic cascade were evaluated by determining Ca²⁺ overload, mitochondrial membrane depolarization, caspase-3/-9 activation, intracellular reactive oxygen species (ROS), lipid peroxidation (LP), glutathione (GSH), glutathione peroxidase (GSH-Px), vascular endothelial growth factor (VEGF) and apoptosis levels. A cell viability assay utilizing MTT was conducted to ascertain the optimal concentration of Se to be employed. The quantification of MTT, ROS, VEGF levels, and caspase-3 and -9 activation was accomplished using a plate reader. To quantitatively assess LP and GSH levels, GSH-Px activities were utilized by spectrophotometer and apoptosis, mitochondrial membrane depolarization, and the release of Ca²⁺ from intracellular stores were evaluated by spectrofluorometer. Our investigation revealed a significant augmentation in oxidative stress induced by HG, leading to cellular damage through modulation of mitochondrial membrane potential, ROS levels, and intracellular Ca²⁺ release. Incubation with Se resulted in a notable reduction in ROS production induced by HG, as well as a reduction in apoptosis and the activation of caspase-3 and -9. Additionally, Se incubation led to decreased levels of VEGF and LP while concurrently increasing levels of GSH and GSH-Px. The findings from this study strongly suggest that Se exerts a protective effect on ARPE-19 and ACBRI 181 cells against HG-induced oxidative stress and apoptosis. This protective mechanism is partially mediated through the intracellular Ca²⁺ signaling pathway.

Fetal alcohol syndrome (FAS) can occur because of high amount of alcohol intake during pregnancy and is characterized by both physical and neurological problems. Children diagnosed with FAS have difficulties in learning, memory, and coordination. Hippocampus has a major role in memory and learning. We aimed to determine whether alcohol exposure during pregnancy had any effect on offspring by evaluating learning ability as well as oxidative stress and autophagy in the hippocampus and cortex tissues of litters. Attention was also paid to sex differences. To do so, TRPM2, Beclin1, p62, LC3B, IBA1, parvalbumin, GAD65, and mGluR5 expression levels were evaluated by immunohistochemistry. Lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels, as well as total oxidant (TOS) and total antioxidant (TAS) status were determined by ELISA. Learning experiments were evaluated by the Morris water maze (MWM) test. Our findings demonstrated that IBA1, LC3B, GAD65, and mGluR5 expression levels were higher in female rats of the chronic alcohol exposure (CAE) model. Our IHC results revealed that TRPM2 expression levels were significantly increased in both males and females in the CAE group. Likewise, TAS was lower, and TOS was higher in CAE animals. Moreover, MWM outcomes supported a learning deficiency in CAE litters compared to controls and indicated that female offspring outperformed males in learning experiments. Therefore, our results revealed the detrimental effects of alcohol exposure during pregnancy on autophagy signaling in the hippocampus and cortex tissue of litters, which could affect the learning ability of animals.

Caffeic acid phenethyl ester (CAPE) may be considered as alternative treatment for periodontitis and benefit the heart by way of its ameliorative effects. The aim of the study was to evaluate the effects of CAPE on cytokine levels and the oxidative status in the serum and heart tissue in a rat model of periodontitis. Experimental animals were randomly assigned to 3 groups: control group (C; n = 8); periodontitis group (P; n = 10); and periodontitis + CAPE group (PC; n = 10). Caffeic acid phenethyl ester, at a dose of 10 μmol/kg/day, was administered by intraperitoneal injection over a 14-day period. Interleukin (IL)-1β, IL‑10 and tumor necrosis factor-alpha (TNF-α) were assessed in the serum. Glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were assessed in both the serum and the heart tissue homogenate. Increased IL‑1β, IL‑10 and TNF-α serum levels were observed in the P group (p < 0.05). Caffeic acid phenethyl ester significantly decreased alveolar bone loss (ABL) and cytokine levels in the PC group (p < 0.05). Malondialdehyde, one of the strongest oxidants, was significantly decreased in the PC group as compared to the P group (p < 0.05). In both the serum and the heart tissue homogenate there were no differences in MDA levels between the PC and C groups. Furthermore, CAPE significantly increased GSH and GSH-Px levels in the serum and heart tissue (p < 0.05). Caffeic acid phenethyl ester has beneficial effects on the tissues affected by periodontitis.

Purpose of Review: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their effects on the skeletal system, independent of the influence of bone metastases, are not fully understood. This critical review specifically summarizes the current evidence on the systemic skeletal effects of ICIs in patients without bone metastases, focusing on changes in bone turnover markers (BTMs), bone mineral density (BMD), and fracture risk, thereby addressing a significant gap in the literature. It also explores potential mechanisms, such as immune-mediated disruption of bone remodeling and alterations in bone quality. Recent Findings: Preclinical in vivo models consistently report that blocking the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) pathways leads to bone loss and increased osteoclast activity. However, clinical findings are paradoxical; while one study using opportunistic quantitative computed tomography (QCT) reported preserved or even improved BMD in patients on ICI therapy, large cohort studies and pharmacovigilance analyses have revealed a consistently elevated risk of fragility fractures. Current assessment tools have limitations in capturing the true skeletal burden of ICI therapy. Summary: A significant discrepancy exists between preclinical data suggesting bone loss and clinical data showing both stable BMD and increased fracture risk. Addressing these knowledge gaps through prospective, high-resolution studies is critical for improving survivorship care. A clearer understanding is essential for developing strategies to prevent skeletal complications in the growing population of patients receiving immunotherapy.