Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

The extensive use of antibiotics in livestock farming poses increased concerns for human health as residues of these substances are present in edible tissues. The aim of this study was the determination of the levels of four groups of antibiotics (sulfonamides—SAs, tetracyclines—TCs, streptomycines—STr and quinolones—QNLs) in meat samples (muscles, livers and kidneys from beef, chicken and pork) and the estimation of the dietary exposure to antibiotics from meat consumption and the potential hazard for human health. Fifty-four samples of raw meat were randomly collected in 2018 from the Cretan market, Greece and analyzed both with an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–mass spectrometry (LC–MS). According to the results derived from the ELISA method, only 2% of the meat samples were free from antibiotics, 2% were detected with 4 antibiotics and the great majority of the samples (87%) were detected with 2 to 3 antibiotics. SAs presented the highest detection frequencies for all samples whereas TCs were not detected in any bovine sample. The highest median concentration was detected for STr in bovine muscles (182.10 μg/kg) followed by QNLs (93.36 μg/kg) in pork kidneys whereas the chicken samples had higher burdens of QNLs compared to the other meat samples. LC–MS analysis showed that oxytetracycline (OTC) was the most common antibiotic in all samples. The highest median concentration of all antibiotics was detected for doxycycline (DOX) (181.73 μg/kg in pork kidney) followed by OTC in bovine liver (74.46 μg/kg). Risk characterization was applied for each of the two methods; The hazard quotients (HQ) did not exceed 0.059 for the ELISA method and 0.113 for the LC–MS method for any group of antibiotics, whereas the total hazard indexes (HI) were 0.078 and 0.021, respectively. The results showed the presence of different groups of antibiotics in meat from the Cretan market and that the health risk to antibiotics is low. A risk assessment analysis conducted for meat consumption and corrected for the aggregated exposure revealed no risk for the consumers.

Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends of chromosomes and prevent DNA degradation and recombination, thus ensuring the integrity of the genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing and multiple xenobiotics and bioactive substances. TL has been characterised as a reliable biomarker for the predisposition to developing chronic pathologies and their progression. This narrative review aims to provide arguments in favour of including TL measurements in a complex prognostic and diagnostic panel of chronic pathologies and the importance of assessing the effect of different pharmacologically active molecules on the biology of telomeres. Medicines used in the management of cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy at menopause, danazol, melatonin, and probiotics have been studied for their positive protective effects against TL shortening. All these classes of drugs are analysed in the present review, with a particular focus on the molecular mechanisms involved.

Di(2-ethylhexyl) phthalate (DEHP) is a widespread endocrine-disrupting plasticizer associated with metabolic disorders. To elucidate their mechanistic basis, we developed an Adverse Outcome Pathway Network (AOPN) informed by DEHP-induced perturbations, by integrating multi-omics data, systems biology modeling, and targeted literature evidence. Multi-omics data were generated in 3D human hepatic cells, pancreatic β-cells, and zebrafish larvae exposed to DEHP across biologically relevant concentration ranges. Transcriptomic and metabolomic analyses revealed perturbations in lipid metabolism, mitochondrial function and oxidative stress pathways, including altered sphingolipid signaling and dysregulation of sphingosine-1-phosphate (S1P). Systems biology modeling contextualized these perturbations within metabolic pathways and generated dose-dependent predictions for key intermediates, highlighting potential reinforcing feedback mechanisms such as ATP–ROS interactions that may further destabilize metabolic homeostasis. Integrating experimental and literature evidence identified key event relationships proposed to link early molecular perturbations to downstream adverse metabolic outcomes, including hepatic steatosis, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and obesity. Central mechanistic features of the network converge on lipid remodeling, mitochondrial dysfunction, oxidative stress, serine/S1P pathway disruption, and impaired insulin signaling. Because the individual omics contrasts are based on three replicates per condition, statistical support in this work is evaluated at pathway rather than single-feature level: under Benjamini-Hochberg control almost no individual transcript is significant, whereas the pathways carrying the mitochondrial and lipid-handling key events remain significant in competitive gene-set tests. Cross-system comparison showed that suppression of oxidative-energy metabolism is the only module conserved across all three systems, whereas PPAR signalling and fatty-acid handling are liver-specific and non-monotonic. Together, these data support a coherent, evidence-integrating mechanistic hypothesis linking early molecular events to adverse metabolic outcomes across multiple levels of biological organization, rather than a quantitatively validated causal pathway. To our knowledge, this study provides a novel integrative AOPN framework combining multi-omics data across liver and pancreatic models and reveals previously underappreciated metabolic cross-talk, including involvement of serine and S1P pathways. The proposed framework is explicitly hypothesis-generating and evidence-integrating: it provides a transparent, FDR-audited basis for future quantitative AOP development and supports mechanistically informed chemical risk assessment by identifying early key events, potential biomarkers, and intervention points relevant to human metabolic health.