Search Results (34)

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

Assessing the seismic performance of buildings from various epochs is essential for guiding retrofitting policies and educating occupants about their homes’ conditions. However, limited resources pose challenges. Some approaches focus on detailed analyses of a limited number of buildings, while others favor broader coverage with less precision. This paper presents a seismic risk assessment method that balances and integrates the strengths of both, using a comprehensive building survey. We propose a low-cost indicator for evaluating the structural resilience of individual buildings, designed to inform both authorities and property owners, support building rankings, and raise awareness. This indicator classifies buildings by their taxonomy and uses analytical capacity curves (2D or 3D studies) obtained from consulting hundreds of studies to determine the ultimate acceleration (agu) that each building type can withstand before collapse. It also considers irregularities found during the survey (to the exterior and interior) through structural modifiers Δ, and adjusts the peak ground acceleration the building can withstand, agu, based on macroseismic data from past events and based on potential retrofitting, Δ+. Although this method may not achieve high accuracy, it provides a significant approximation for detailed analysis with limited resources and is easy to replicate for similar constructions. The final agu value, considered as resistance, is then compared to the seismic demand at the foundation of the building (accounting for hazard and soil conditions at the building location), resulting in a final R-value. This paper provides specificities to the methodology and applies it to selected areas of the City of Lisbon, clearly supporting the advancement of a more sustainable society. Full article

Objective: This ex vivo study aimed to evaluate the influence of different acquisition protocols, combining voxel size and field of view (FOV), across four cone-beam computed tomography (CBCT) systems, on the accuracy of alveolar bone level measurements for periodontal assessment. Materials and Methods: A dry human mandible was used, with standardized radiopaque markers placed on the cementoenamel junction (CEJ) of the buccal–mesial and buccal–distal aspects of teeth 34 and 43. CBCT scans were performed using four systems—Veraview^® X800, OP300 Pro^®, I-CAT Next Generation^®, and Orthophos XG^®—applying various combinations of field of view (FOV) and voxel resolution available in each device. Reference measurements were obtained in situ using a digital caliper. CBCT images were exported in DICOM format and analyzed with OnDemand3D software (version 4.6) to obtain paracoronal sections. Linear measurements from the CEJ to the alveolar crest were recorded in triplicate and compared to the gold standard using ANOVA and the Dunnett test (α = 0.05). Results: Protocols with smaller voxel sizes and limited FOVs generally yielded measurements closer to the gold standard. However, some larger-FOV protocols with intermediate voxel sizes also achieved comparable accuracy. Among the systems, the I-CAT showed lower agreement within in situ measurements, while others demonstrated reliable performance depending on the acquisition parameters. Conclusions: The findings suggest that CBCT protocols with smaller voxel sizes and reduced FOVs can enhance measurement accuracy in periodontal bone assessments. Nevertheless, intermediate protocols may offer a balance between diagnostic quality and radiation exposure, aligning with the ALADA principle. This study reinforces the need for standardized acquisition parameters tailored to periodontal imaging. Full article

Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish—which share significant genetic homology with humans—we investigated TnP’s effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl₂)-induced hypoxia or light-induced retinal damage (LIRD). Methods: We employed two retinal injury models (CoCl₂-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual–motor response testing and histological examination. Results: CoCl₂ exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)’s thickness. Conclusions: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments. Full article

Arthropod-borne viruses (arboviruses) dengue (DENV), chikungunya (CHIK), and Zika (ZIKV) have been responsible for a high number of outbreaks worldwide. However, their screening in blood donors is not mandatory, and asymptomatic cases might act as an important cause of virus transmission via transfusion. A study was conducted to assess the presence of DENV (serotypes 1–4), ZIKV, and CHIKV in pooled samples (pool size: six) from asymptomatic blood donors. A total of 9463 plasma pools, corresponding to 56,778 blood donations from asymptomatic blood donors who attended donor sessions at HEMORIO and other blood centers in Rio de Janeiro and Espírito Santo, was submitted to automated nucleic-acid extraction and PCR amplification using ZC D-Tipagem molecular assay (Bio-Manguinhos). In general, a pool prevalence of 1% (95/9463) and a donor prevalence of 0.17% (95/56,778) were observed. January and February 2024 had a total of 62 positive pools out of 95 (65.3%). Targets DENV-1 and -2 had a higher prevalence in the studied months—early summer—with 24 and 28 positive pools, respectively. ZC D-Tipagem molecular assay was able to detect the best-known arboviruses circulating in asymptomatic blood donors; this study suggested that ZIKV, CHIK, and DENV are circulating in asymptomatic blood donors before blood donations and can be transmitted to blood transfusion recipients. Full article

Although edible insects (EIs) are encouraged as a sustainable source of protein, their consumption is not as generalised as other types of food that are internationally accepted. While in some regions of the world, EIs are part of the gastronomic and cultural traditions, in other regions, people are not so receptive to this type of food, and some people even express some disgust towards it. Hence, this research focused on the habits of the participants regarding the consumption of insects as well as their perceptions about EIs being or not a part of the local culture or gastronomic patrimony. A questionnaire survey was implemented in fourteen countries (Brazil, Croatia, Greece, Latvia, Lebanon, Lithuania, Mexico, Poland, Portugal, Romania, Serbia, Slovenia, Spain, and Turkey), and globally, 7222 adult participants responded to the questionnaire. SPSS software (version 28) was used to process the data and carry out chi-square tests and Factor Analyses (FA). The obtained results showed significant differences between countries for all the questions included in the survey, either those regarding the habits of the participants or their opinions about the facts linked with EI tradition or cultural aspects. It was found that participants from Mexico consume EIs more than in all other countries and that strong motivations that would lead to consumption among those who do not consume include curiosity and food shortage. The solution obtained with FA considering the ten statements of the scale consisted of two factors: F1—Culture and Tradition of EIs (α = 0.675) and F2—Acceptance of EIs (α = 0.614). In conclusion, the consumption of EIs and the perceptions of people are highly variable according to geographic location and cultural environment. Full article

Aryl Hydrocarbon Receptor (AHR) signaling is crucial for regulating the biotransformation of xenobiotics and physiological processes like inflammation and immunity. Meanwhile, Thalassophryne nattereri Peptide (TnP), a promising anti-inflammatory candidate from toadfish venom, demonstrates therapeutic effects through immunomodulation. However, its influence on AHR signaling remains unexplored. This study aimed to elucidate TnP’s molecular mechanisms on the AHR–cytochrome P450, family 1 (CYP1) pathway upon injury-induced inflammation in wild-type (WT) and Ahr2-knockdown (KD) zebrafish larvae through transcriptomic analysis and Cyp1a reporters. TnP, while unable to directly activate AHR, potentiated AHR activation by the high-affinity ligand 6-Formylindolo [3,2-b]carbazole (FICZ), implying a role as a CYP1A inhibitor, confirmed by in vitro studies. This interplay suggests TnP’s ability to modulate the AHR-CYP1 complex, prompting investigations into its influence on biotransformation pathways and injury-induced inflammation. Here, the inflammation model alone resulted in a significant response on the transcriptome, with most differentially expressed genes (DEGs) being upregulated across the groups. Ahr2-KD resulted in an overall greater number of DEGs, as did treatment with the higher dose of TnP in both WT and KD embryos. Genes related to oxidative stress and inflammatory response were the most apparent under inflamed conditions for both WT and KD groups, e.g., Tnfrsf1a, Irf1b, and Mmp9. TnP, specifically, induces the expression of Hspa5, Hsp90aa1.2, Cxcr3.3, and Mpeg1.2. Overall, this study suggests an interplay between TnP and the AHR-CYP1 pathway, stressing the inflammatory modulation through AHR-dependent mechanisms. Altogether, these results may offer new avenues in novel therapeutic strategies, such as based on natural bioactive molecules, harnessing AHR modulation for targeted and sustained drug effects in inflammatory conditions. Full article

The introduction of women’s, gender, and feminist studies (WGFS) into higher education (HE) curricula has primarily been driven by individual efforts rather than institutional objectives. This article employs a multimethod approach to comprehensively understand the potential contribution of gender equality plans (GEPs) to strengthening the integration of WGFS in HE curricula and pedagogical practices. The study’s documentary corpus includes data from GEPs in implementation, semi-structured interviews with 27 WGFS lecturers, and a web survey of 118 lecturers who teach courses related to or integrating gender aspects. This approach reveals divergent perspectives on the role of GEPs in HEIs, summarized into three categories: cautious optimism, skepticism, and simplistic views. The tensions and constraints associated with the contributions of the GEPs, as perceived by many involved in incorporating gender issues into teaching, outline a vigilant optimism for the future implementation of these mechanisms. Nonetheless, given the historically limited role of institutional initiatives in consolidating WGFS in Portuguese higher education, we argue that the potential contribution of GEPs to this field should not be underestimated, as integrating WGFS into institutional planning can legitimize, support, and leverage efforts that have predominantly been individual. Full article

The increasing number of studies reporting the risks of the exposure to pesticides aligned with the intensified use of such hazardous chemicals has emerged as a pressing contemporary issue, notably due to the potential effects to both the environment and human health. Pesticides, while broadly applied in modern agriculture for pest control and crop protection, have raised concerns due to their unintended effects on non-target organisms. The immune system exerts a key role in the protection against the exposome, which could result in cellular imbalances and tissue damage through the inflammatory response. Pesticides, which encompass a diverse array of chemicals, have been linked to inflammation in experimental models. Therefore, the aim of this review is to discuss the increasing concern over the risks of pesticide exposure focusing on the effects of various chemical classes on inflammation by covering, as broadly as possible, different experimental approaches as well as the multiple or co-exposure of pesticides. Overall, pesticides potentially induce inflammation in different experimental models, manifested through skin irritation, respiratory impairment, or systemic effects. The connection between pesticides and inflammation highlights the importance of proper handling and regulation of these substances and underscores the need for research into safer and sustainable practices to reduce our reliance on synthetic pesticides and fertilizers. Full article

Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies. Full article

The COVID-19 pandemic has brought increased attention to the existing gender asymmetries in academia, which have been extensively studied in the literature. Using the analytical lens of “gendered academic citizenship”, this paper takes a micropolitical perspective to examine how the pandemic has impacted the dynamics of academic work, specifically focusing on the often-overlooked aspect of everyday interactions in the work environment. Through qualitative and quantitative analysis of survey data collected from 1750 lecturers and researchers in Portuguese higher education and research institutions, the study uncovers that women, especially those who are younger, single, have specific caregiving responsibilities, and are in the early stages of their careers, were more vulnerable to experiencing “everyday” microaggressions such as silencing, exclusion, belittlement, being ignored, lack of validation, and invisibility compared to men during the pandemic. These findings suggest that, while the marginalization of women in academia is a longstanding issue, the virtual work model has created a platform for the expression of subtle forms of disempowerment and discrimination against women. These dynamics are perpetuated within the micropolitics of organizations, shaping subjective feelings of belonging and circulating differential levels of recognition within academic institutions. Full article

Women’s, Gender, and Feminist Studies (WGFS) in Portugal emerged relatively late compared to other European countries, and a systematic quantitative analysis of Portuguese research in this field is lacking. This article addresses this gap by conducting a pioneering bibliometric analysis of WGFS publications by scholars based in Portugal between 1995 and 2021, utilizing data from the Web of Science. The analysis reveals several key findings, including a significant growth in WGFS productivity in the 2010s, a high level of internationalization of Portuguese production, and the increasing prominence of specific themes and theoretical perspectives, such as LGBTQIA+ studies and intersectionality. By examining the trajectory of Portuguese scholarship in WGFS since the 1990s, this study provides valuable insights and opens important avenues for future research. Full article

Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16^Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1β in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-β neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence. Full article

Envenomation by venomous fish, although not always fatal, is capable of causing damage to homeostasis by activating the inflammatory process, with the formation of edema, excruciating pain, necrosis that is difficult to heal, as well as hemodynamic and cardiorespiratory changes. Despite the wide variety of pharmacological treatments used to manage acute symptoms, none are effective in controlling envenomation. Knowing the essential role of neutralizing polyclonal antibodies in the treatment of envenoming for other species, such as snakes, this work aimed to produce a polyclonal antiserum in mice and test its ability to neutralize the main toxic effects induced by the venoms of the main venomous Brazilian fish. We found that the antiserum recognizes the main toxins present in the different venoms of Thalassophryne nattereri, Scorpaena plumieri, Potamotrygon gr. Orbignyi, and Cathorops spixii and was effective in pre-incubation trials. In an independent test, the antiserum applied immediately to the topical application of T. nattereri, P. gr orbygnyi, and C. spixii venoms completely abolished the toxic effects on the microcirculation, preventing alterations such as arteriolar contraction, slowing of blood flow in postcapillary venules, venular stasis, myofibrillar hypercontraction, and increased leukocyte rolling and adherence. The edematogenic and nociceptive activities induced by these venoms were also neutralized by the immediate application of the antiserum. Importantly, the antiserum prevented the acute inflammatory response in the lungs induced by the S. plumieri venom. The success of antiserum containing neutralizing polyclonal antibodies in controlling the toxic effects induced by different venoms offers a new strategy for the treatment of fish envenomation in Brazil. Full article

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma. Full article