Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic ...properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood–testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells’ toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature.
We report a case of monkeypox in a physician after an occupational needlestick injury from a pustule. This case highlights risk for occupational transmission and manifestations of the disease after ...percutaneous transmission: a short incubation period, followed by a solitary lesion at the injured site and later by systemic symptoms.
Background: Viruses are the major cause of acute respiratory infections in children, causing important morbimortality. Before the COVID-19 pandemic, in temperate regions, respiratory viruses ...displayed a typical seasonality in transmission. A disruption in this pattern was observed in several countries during the pandemic, with low prevalence during the typical season, and an interseasonal rise. We evaluated the effects of the COVID-19 pandemic in the epidemiology of non-COVID viral respiratory infections in children, in a tertiary care hospital in Portugal. Methods: Between March 2020 and August 2022, nasopharyngeal samples from children with respiratory symptoms in the Emergency Department (ED) and the Pediatric Ward were tested for RSV, influenza and other respiratory viruses, by real-time reverse transcriptase PCR (RT-PCR). Results: A seasonal variation was observed from 2018 to 2020, with prevalence increasing in winter (mainly RSV and influenza). In the winter of 2020/21, when measures to mitigate SARS-CoV-2 transmission were stricter, there was a disruption of the seasonal pattern, with unusually low numbers. In the summer of 2021, when measures were being relaxed, there was an atypical rise. In June 2021, RSV was first detected and peaked in October. Influenza (Influenza A H3) was detected for the first time in February 2022, peaking in March/April. Conclusions: These findings show a disruption of the seasonality of viral respiratory infections in children during the pandemic, with a virtual elimination during the months of usually higher prevalence, and a subsequent out-of-season increase, coinciding with variations in the measures implemented to control the SARS-CoV-2 transmission, and confirming their efficacy.
Zinc oxide nanoparticles (ZnO NPs) are among nanoscale materials, attracting increasing attention owing to their exceptional set of characteristics, which makes these engineered nanoparticles a great ...option for improving the quality and effectiveness of diagnosis and treatment. The capacity of ZnO NPs to induce reactive oxygen species (ROS) production, DNA damage, and apoptosis represents a promise for their use in both cancer therapy and microbial treatment. However, their intrinsic toxicity together with their easy entrance and accumulation in organism have raised some concerns regarding the biomedical use of these NPs. Several studies have reported that ZnO NPs might induce cytotoxic effects on the male reproductive system, compromising male fertility. Despite some advances in this area, the knowledge of the effects of ZnO NPs on male fertility is still scarce. Overall, a brief outline of the major ZnO NPs biomedical applications and promises in terms of diagnostic and therapeutic use will also be explored. Further, this review intends to discuss the effect of ZnO NPs exposure on the male reproductive system and speculate their effects on male (in)fertility.
Metabolomics to Study Human Aging: A Review Martins, Claudia; Magalhães, Sandra; Almeida, Idália ...
Current molecular medicine,
01/2024, Volume:
24, Issue:
4
Journal Article
Peer reviewed
In the last years, with the increase in the average life expectancy, the world's population is progressively aging, which entails social, health and economic problems. In this sense, the need to ...better understand the physiology of the aging process becomes an urgent need. Since the study of aging in humans is challenging, cellular and animal models are widely used as alternatives. Omics, namely metabolomics, have emerged in the study of aging, with the aim of biomarker discovering, which may help to uncomplicate this complex process. This paper aims to summarize different models used for aging studies with their advantages and limitations. Also, this review gathers the published articles referring to biomarkers of aging already discovered using metabolomics approaches, comparing the results obtained in the different studies. Finally, the most frequently used senescence biomarkers are described, along with their importance in understanding aging.
The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE ...is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Therefore, during aging and premature aging, several cellular alterations occur, including nuclear‐specific changes, particularly, altered nuclear transport, increased genomic instability induced by DNA damage, and telomere attrition. Here, we highlight and discuss proteins associated with nuclear transport dysfunction induced by aging, particularly nucleoporins, nuclear transport factors, and lamins. Moreover, changes in the structure of chromatin and consequent heterochromatin rearrangement upon aging are discussed. These alterations correlate with NE dysfunction, particularly lamins’ alterations. Finally, telomere attrition is addressed and correlated with altered levels of nuclear lamins and nuclear lamina‐associated proteins. Overall, the identification of molecular mechanisms underlying NE dysfunction, including upstream and downstream events, which have yet to be unraveled, will be determinant not only to our understanding of several pathologies, but as here discussed, in the aging process.
Growing evidence has drawn attention to the nuclear envelope dysfunction as a hallmark of the aging process. Indeed, during aging and premature aging, several cellular alterations occur, including nuclear‐specific changes, particularly alterations in nuclear transport, chromatin organization, and telomere maintenance. Therefore, nuclear protein alterations are essential determinants of physiological and premature aging and may provide biomarkers for aging status and other pathologies like cancer.
Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and weakness, and multisystemic ...dysfunctions. This disorder is caused by an abnormal expansion of the CTG triplet at the
gene that, when transcribed to expanded mRNA, can lead to RNA toxic gain of function, alternative splicing impairments, and dysfunction of different signaling pathways, many regulated by protein phosphorylation. In order to deeply characterize the protein phosphorylation alterations in DM1, a systematic review was conducted through PubMed and Web of Science databases. From a total of 962 articles screened, 41 were included for qualitative analysis, where we retrieved information about total and phosphorylated levels of protein kinases, protein phosphatases, and phosphoproteins in DM1 human samples and animal and cell models. Twenty-nine kinases, 3 phosphatases, and 17 phosphoproteins were reported altered in DM1. Signaling pathways that regulate cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired, as seen by significant alterations to pathways such as AKT/mTOR, MEK/ERK, PKC/CUGBP1, AMPK, and others in DM1 samples. This explains the complexity of DM1 and its different manifestations and symptoms, such as increased insulin resistance and cancer risk. Further studies can be done to complement and explore in detail specific pathways and how their regulation is altered in DM1, to find what key phosphorylation alterations are responsible for these manifestations, and ultimately to find therapeutic targets for future treatments.
Aging is a complex process which leads to progressive loss of fitness/capability/ability, increasing susceptibility to disease and, ultimately, death. Regardless of the organism, there are some ...features common to aging, namely, the loss of proteostasis and cell senescence. Mammalian cell lines have been used as models to study the aging process, in particular, cell senescence. Thus, the aim of this study was to characterize the senescence-associated metabolic profile of a long-term culture of human fibroblasts using Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. We sub-cultivated fibroblasts from a newborn donor from passage 4 to passage 17 and the results showed deep changes in the spectroscopic profile of cells over time. Late passage cells were characterized by a decrease in the length of fatty acid chains, triglycerides and cholesterol and an increase in lipid unsaturation. We also found an increase in the content of intermolecular β-sheets, possibly indicating an increase in protein aggregation levels in cells of later passages. Metabolic profiling by NMR showed increased levels of extracellular lactate, phosphocholine and glycine in cells at later passages. This study suggests that spectroscopy approaches can be successfully used to study changes concomitant with cell senescence and validate the use of human fibroblasts as a model to monitor the aging process.
Full accessibility to people with reduced mobility, applied to tourism, is difficult to achieve and should not be seen in an absolute way, but as a concern to make tourism services more accessible ...and focused on the specific and individual needs of people as tourists. National and regional entities should adopt good practices to build a tourism of all, for all. The Delphi method was used in order to verify the accessibility and attractiveness of the city of Lisbon as a tourist destination by addressing the following objectives: to analyse the competitiveness of a destination for people with reduced mobility, to analyse if Lisbon is attractive and inclusive, considering its infrastructures, services, hospitality, tourist attractions and accessibility. The results obtained in the study show that Lisbon’s factors and resources are increasingly accessible to people with reduced mobility. Our findings reveal that entertainment, general and tourism infrastructures, accommodation, the various activities and cultural resources and the quality of services present greater accessibility for people with reduced mobility. The factors with less importance were: marketing of a destination, accessibilities, and natural resources.
Studying aging is important to further understand the molecular mechanisms underlying this physiological process and, ideally, to identify a panel of aging biomarkers. Animals, in particular mice, ...are often used in aging studies, since they mimic important features of human aging, age quickly, and are easy to manipulate. The present work describes the use of Fourier Transform Infrared (FTIR) spectroscopy to identify an age-related spectroscopic profile of the cardiac and skeletal muscle tissues of C57BL/6J female mice. We acquired ATR-FTIR spectra of cardiac and skeletal muscle at four different ages: 6; 12; 17 and 24 months (10 samples at each age) and analyzed the data using multivariate statistical tools (PCA and PLS) and peak intensity analyses. The results suggest deep changes in protein secondary structure in 24-month-old mice compared to both tissues in 6-month-old mice. Oligomeric structures decreased with age in both tissues, while intermolecular β-sheet structures increased with aging in cardiac muscle but not in skeletal muscle. Despite FTIR spectroscopy being unable to identify the proteins responsible for these conformational changes, this study gives insights into the potential of FTIR to monitor the aging process and identify an age-specific spectroscopic signature.
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