An approach to the effects of longevity, sexual maturity, and reproduction on telomere length and oxidative stress in different Psittacidae species

Introduction: Aging is a multifactorial process that includes molecular changes such as telomere shortening. Telomeres shorten progressively with age in vertebrates, and their shortening rate has a significant role in determining the lifespan of a species. However, DNA loss can be enhanced by oxidative stress. The need for novel animal models has recently emerged as a tool to gather more information about the human aging process. Birds live longer than other mammals of the same size, and Psittacidae species are the most persevering of them, due to special key traits.Methods: We aimed to determine telomere length by qPCR, and oxidative stress status using colorimetric and fluorescence methods in different species of the order Psittaciformes with different lifespans.Results: We found that telomeres shorten with age for both long- and short-lived birds (p < 0.001 and p = 0.004, respectively), with long-lived birds presenting longer telomeres than short-lived ones (p = 0.001). In addition, short-lived birds accumulated more oxidative stress products than long-lived birds (p = 0.013), who showed a better antioxidant capacity (p < 0.001). Breeding was found related to telomere shortening in all species (p < 0.001 and p = 0.003 for long- and short-lived birds). Short-lived birds, especially breeding females, increased their oxidative stress products when breeding (p = 0.021), whereas long-lived birds showed greater resistance and even increased their antioxidant capacity (p = 0.002).Conclusion: In conclusion, the relationship between age and telomere length in Psittacidae was verified. The influence of breeding increased cumulative oxidative damage in short-lived species, while long-lived species may counteract this damage

DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity

Aging is a complex process influenced by internal and external factors. Oxidative stress damages DNA, leading to 8-hydroxy-2’ deoxyguanosine formation (8-OHdG). Telomere shortening is considered a biomarker of aging and oxidative stress may enhance its attrition. The ability to manage and repair oxidative stress varies among species and life histories. Avian species, such as Psittacidae birds, exhibit exceptional lifespans despite their physiological characteristics that might suggest otherwise. This study investigates 8-OHdG levels in serum samples from long- and short-lived birds of the order Psittaciformes, examining their relationship with telomere length and antioxidant capacity based on lifespan strategies. Among 43 individuals analyzed 26 belonged to the “long-lived species” group and 17 belonged to the “short-lived species” one. Relative telomere length (rTL) was measured in DNA isolated from whole blood by qPCR, and oxidative stress markers, such as Total Antioxidant Capacity (TAC) and 8-OHdG, were determined by spectrophotometry in serum samples. Long-lived birds had longer rTL than short-lived ones [1.308 ± 0.11 vs. 0.565 ± 0.13, (p < 0.001)]. On the contrary, short-lived birds showed more DNA damage than their counterparts [3.847 ± 0.351 vs. 2.012 ± 0.308, respectively, (p < 0.001)]. Old birds had shorter rTL than young ones, for both longevity groups (p < 0.001). Although no correlation was found between 8-OHdG levels and age, nor 8-OHdG and telomere length, long-lived birds exhibited 75.42-unit increased TAC levels when increased 8-OHdG concentrations (p = 0.046). These findings highlight distinct patterns of telomere length and oxidative stress influenced by lifespan strategies among avian longevity groups

Discovery of amoebicidal compounds by combining computational and experimental approaches

36 p.-6 fig.-4 tab.Pathogenic and opportunistic free-living amoebae such as Acanthamoeba spp. can cause keratitis (Acanthamoeba keratitis [AK]), which may ultimately lead to permanent visual impairment or blindness. Acanthamoeba can also cause rare but usually fatal granulomatous amoebic encephalitis (GAE). Current therapeutic options for AK require a lengthy treatment with nonspecific drugs that are often associated with adverse effects. Recent developments in the field led us to target cAMP pathways, specifically phosphodiesterase. Guided by computational tools, we targeted the Acanthamoeba phosphodiesterase RegA. Computational studies led to the construction and validation of a homology model followed by a virtual screening protocol guided by induced-fit docking and chemical scaffold analysis using our medicinal and biological chemistry (MBC) chemical library. Subsequently, 18 virtual screening hits were prioritized for further testing in vitro against Acanthamoeba castellanii, identifying amoebicidal hits containing piperidine and urea imidazole cores. Promising activities were confirmed in the resistant cyst form of the amoeba and in additional clinical Acanthamoeba strains, increasing their therapeutic potential. Mechanism-of-action studies revealed that these compounds produce apoptosis through reactive oxygen species (ROS)-mediated mitochondrial damage. These chemical families show promise for further optimization to produce effective antiacanthamoebal drugs.Funding from RICET (RD16/0027/0010) and (RD16/0027/0001), FEDER funds (PI18/01380), MECD (Grant FPU15/1465 to V. S.-P.) is acknowledged, M. R. B. was also funded by RICET and I. S. was funded by Agustin de Betancourt Programme.Peer reviewe

Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective