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With high clinical interest to be applied in regenerative medicine, Mesenchymal Stem/Stromal Cells have been widely studied due to their multipotency, wide distribution, and relative ease of isolation and expansion in vitro. Their remarkable biological characteristics and high immunomodulatory influence have opened doors to the application of MSCs in many clinical settings. The therapeutic influence of these cells and the interaction with the immune system seems to occur both directly and through a paracrine route, with the production and secretion of soluble factors and extracellular vesicles. The complex mechanisms through which this influence takes place is not fully understood, but several functional manipulation techniques, such as cell engineering, priming, and preconditioning, have been developed. In this review, the knowledge about the immunoregulatory and immunomodulatory capacity of MSCs and their secretion products is revisited, with a special focus on the phenomena of migration and homing, direct cell action and paracrine activity. The techniques for homing improvement, cell modulation and conditioning prior to the application of paracrine factors were also explored. Finally, multiple assays where different approaches were applied with varying success were used as examples to justify their exploration.

Organotin compounds are industrial chemicals used as biocides, polyvinyl chloride stabilizers and industrial catalysts for the manufacture of silicone and polyurethane foams. Despite multiple applications, organotin notoriety is due to tributyltin, a potent biocide used in antifouling paints. Because of the intensive use of tributyltin for the protection of ships’ hulls, tributyltin has been largely released into waters, resulting in adverse and even bizarre effects on aquatic organisms, such as imposex in gastropods. However, organotins include other compounds such as tributyltin derivatives, phenyltins and octyltins. Organotin use in plastics, silicone and foams results in their occurrence almost everywhere, e.g., clothes, toys, wallpaper, food containers, household piping and medical devices. Hence, humans are exposed to organotins not solely through ingestion of contaminated seafood but also through direct contact with treated products and by inhalation and ingestion of dust. As a consequence, organotins have been detected in human samples. Toxicity data reveal that organotins are endocrine disruptors, immunotoxicants, carcinogens and obesogens. Here, we review the levels, fate and effects of organotin compounds toward wildlife and humans, starting with a description of organotin applications, with particular incidence in antifouling paints. The global contamination of the marine environment and the deleterious effects of tributyltin onto nontarget organisms are addressed, with particular attention to the imposex phenomenon. The restrictions on tributyltin use in antifouling paints are also described alongside with the new regulations for organotins in consumer products. The sources and pathways of organotins in the environment are discussed, studies in human exposure are presented, and future research is proposed.

Aptamers are single-stranded oligonucleotides, formerly evolved by Systematic Evolution of Ligands by EXponential enrichment (SELEX), that fold into functional three-dimensional structures. Such conformation is crucial for aptamers’ ability to bind to a target with high affinity and specificity. Unnatural nucleotides have been used to develop nucleic acid mimic (NAM) aptamers with increased performance, such as biological stability. Prior knowledge of aptamer-target interactions is critical for applying post-SELEX modifications with unnatural nucleotides since it can affect aptamers’ structure and performance. Here, we describe an easy-to-apply in silico workflow using free available software / web servers to predict the tertiary conformation of NAM, DNA and RNA aptamers, as well as the docking with the target molecule. Representative 2ʹ-O-methyl (2ʹOMe), locked nucleic acid (LNA), DNA and RNA aptamers, with experimental data deposited in Protein Data Bank, were selected to validate the workflow. All aptamers’ tertiary structure and docking models were successfully predicted with good structural similarity to the experimental data. Thus, this workflow will boost the development of aptamers, particularly NAM aptamers, by assisting in the rational modification of specific nucleotides and avoiding trial-and-error approaches.

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.

Sympathetic neuron–associated macrophages act as a local sink for norepinephrine, leading to reduced thermogenesis and increased obesity. The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron–associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment.

Capecitabine (CAP, prodrug) and 5-fluorouracil (5-FU, its active metabolite) are two of the most prominent cytostatics, for which no clear picture can be drawn regarding potential concentrations of effect for freshwater biota, with CAP being grouped in the least studied cytostatic, whereas 5-FU has been classified as of no and of high environmental risk. Accordingly, the present work aimed to assess the ecotoxicity of CAP and 5-FU in three freshwater species, which included a 72-h assay with the producer Raphidocelis subcapitata ; a 96-h assay with the invertebrate secondary consumer Hydra viridissima ; and a 96-h assay with embryos of the vertebrate secondary consumer Danio rerio . The following endpoints were monitored: yield and population growth rate for the algae; mortality, morphological alterations, and post-exposure feeding rates for the cnidarian; and mortality, hatching, and malformations for the fish. Overall, organisms’ sensitivity to CAP decreased in the following order: R. subcapitata  >  H. viridissima  >  D. rerio , whereas for 5-FU, it decreased in the following order: H. viridissima  >  D. rerio  >  R. subcapitata . For CAP, no median lethal effective concentrations (LC/EC 50 ) were possible to compute for D. rerio , with no significant mortality or malformations registered in embryos exposed at concentrations up to 800 mg L −1 . For R. subcapitata , the EC 50 s were 0.077 and 0.63 mg L −1 for yield and growth rate, respectively, and for H. viridissima , the EC 50,30 min for feeding was 22.0 mg L −1 . For 5-FU, no EC 50s could be computed for R. subcapitata , whilst the EC 50s for H. viridissima mortality and feeding were 55.4 and 67.9 mg L −1 , respectively, and for D. rerio , the LC 50,96 h and EC 50,96 h (hatching and abnormalities) were 4546, 4100, and 2459 mg L −1 , respectively. Assuming similar modes of action for both compounds and their co-occurrence, the combined risk quotient of the two chemicals was determined to be 7.97, which represents a risk for freshwater biota. Anticipating the increased consumption of these compounds and cancer development trends worldwide, these impacts may be further aggravated.

A wide range of diseases have been shown to be influenced by the accumulation of senescent cells, from fibrosis to diabetes, cancer, Alzheimer’s and other age-related pathologies. Consistent with this, clearance of senescent cells can prolong healthspan and lifespan in in vivo models. This provided a rationale for developing a new class of drugs, called senolytics, designed to selectively eliminate senescent cells in human tissues. The senolytics tested so far lack specificity and have significant off-target effects, suggesting that a targeted approach could be more clinically relevant. Here, we propose to use an extracellular epitope of B2M, a recently identified membrane marker of senescence, as a target for the specific delivery of toxic drugs into senescent cells. We show that an antibody–drug conjugate (ADC) against B2M clears senescent cells by releasing duocarmycin into them, while an isotype control ADC was not toxic for these cells. This effect was dependent on p53 expression and therefore more evident in stress-induced senescence. Non-senescent cells were not affected by either antibody, confirming the specificity of the treatment. Our results provide a proof-of-principle assessment of a novel approach for the specific elimination of senescent cells using a second generation targeted senolytic against proteins of their surfaceome, which could have clinical applications in pathological ageing and associated diseases.

This work assessed the Blue Carbon (C) stock in the seagrass meadows ( Zostera noltei ) of Ria de Aveiro coastal lagoon (Portugal), and evaluated its spatio-temporal trend over the 2003–2005 to 2013–2014 period. Zostera noltei spatial distribution, restricted to intertidal areas in 2014, was mapped by remote sensing using an unmanned aerial vehicle (UAV) and aerial photography. Zostera noltei biomass was also monitored in situ over a year and its Blue C stock was estimated. By 2014, intertidal meadows covered an area of 226 ± 4 ha and their Blue C stock ranged from 227 ± 6 to 453 ± 13 Mg C. Overall, Ria de Aveiro Z. noltei intertidal meadows increased in extent over the 2003–2005 to 2013–2014 period, corroborating the recent declining trend reversal observed in Europe and contrary to the global decline trend. This spatio-temporal shift might be related to a natural adjustment of the intertidal meadows to past human intervention in Ria de Aveiro, namely large-scale dredging activities, particularly in the 1996–1998 period, combined with the more accurate assessment performed in 2014 using the UAV. This recovery contributes to the effective increase of the Blue C stock in Ria de Aveiro and, ultimately, to supporting climate regulation and improving ecosystem health. However, major dredging activities are foreseen in the system’s management plan, which can again endanger the recovery trend of Z. noltei intertidal meadows in Ria de Aveiro.

One of the leading causes of death is cardiovascular disease, and the most common cardiovascular disease is coronary artery disease. Percutaneous coronary intervention and vascular stents have emerged as a solution to treat coronary artery disease. Nowadays, several types of vascular stents share the same purpose: to reduce the percentage of restenosis, thrombosis, and neointimal hyperplasia and supply mechanical support to the blood vessels. Despite the numerous efforts to create an ideal stent, there is no coronary stent that simultaneously presents the appropriate cellular compatibility and mechanical properties to avoid stent collapse and failure. One of the emerging approaches to solve these problems is improving the mechanical performance of polymeric bioresorbable stents produced through additive manufacturing. Although there have been numerous studies in this field, normalized control parameters for 3D-printed polymeric vascular stents fabrication are absent. The present paper aims to present an overview of the current types of stents and the main polymeric materials used to fabricate the bioresorbable vascular stents. Furthermore, a detailed description of the printing parameters’ influence on the mechanical performance and degradation profile of polymeric bioresorbable stents is presented.

Transformative capacity (TC) is key for addressing climate change impacts. It refers to urban areas’ ability for profound and intentional change to address current challenges and move towards a more desirable and resilient state. However, its varied applications across disciplines can lead to misunderstandings and implementation challenges. Thus, this Semi-Systematic Literature Review (SSLR) on TC within urban studies from 2016 to 2022 aims to overview and synthesise TC literature and its gaps to inform ongoing debates, intersecting it with climate-related research. The results show an increasing interest in TC within two fields of knowledge: resilience studies and transformative research. The review found TC as a catalyst for transformative actions, promoting sustainable pathways, enhancing resilience, and driving fundamental changes in urban climate adaptation. Finally, the prevailing literature gaps concern the TC concept’s fragmentation, excessive research on governance features, and lack of joint research about TC and innovation.