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Vitamin D deficiency is a common finding and there is a suggested association with hypertension. Resistant hypertension is a clinical problem observed in 5-30% of hypertensive patients. Renal denervation (RDN) has been used for patients with resistant hypertension and has proven to lower blood pressure. Our primary goal was to assess the vitamin D serum concentration as a predictor of blood pressure response to RDN in highly selected patients.This prospective, nonrandomized, single-center study included 24 patients treated with RDN. Based on their one-year response after RDN, patients were classified as responders or non-responders at six months or at 12 months.The median follow-up was 52 months (range, 14-91 months). After RDN, 17 patients (70.8%) had a reduction5 mmHg in the mean systolic blood pressure, at the first six months of follow-up. At 12 months, 20 patients (83.3%) were responders. Vitamin D levels at baseline (15.1±4.8 vs. 24.2±8.8 ng/ml) and at six months (16.6±7.2 vs. 25±9.2 ng/ml) were lower in early non-responders compared to early responders (p=0.008), without significant variation during follow-up. Even though Vitamin D levels were lower in the total responder's group, no statistically significant differences were found (p=ns).In patients with resistant hypertension, low vitamin D concentrations were associated with an absence of early response to RDN.

Drug delivery using nanoparticles (NPs) represents a potential approach for therapy in cancer, such gastric cancer (GC) due to their targeting ability and controlled release properties. The use of advanced nanosystems that deliver anti-cancer drugs specifically to tumor cells may strongly rely on the expression of cancer-associated targets. Glycans aberrantly expressed by cancer cells are attractive targets for such delivery strategy. Sialylated glycans, such as Sialyl-Tn (STn) are aberrantly expressed in several epithelial tumors, including GC, being a potential target for a delivery nanosystem. The aim of this study was the development of NPs surface-functionalized with a specific antibody targeting the STn glycan and further evaluate this nanosystem effectiveness regarding its specificity and recognition capacity. Our results showed that the NPs surface-functionalized with anti-STn antibody efficiently are recognized by cells displaying the cancer-associated STn antigen under static and live cell monitoring flow conditions. This uncovers the potential use of such NPs for drug delivery in cancer. However, flow exposure was disclosed as an important biomechanical parameter to be taken into consideration. Here we presented an innovative and successful methodology to live track the NPs targeting STn antigen under shear stress, simulating the physiological flow. We demonstrate that unspecific binding of NPs agglomerates did not occur under flow conditions, in contrast with static assays. This robust approach can be applied for

This review provides insights on the impact of glycosylation in cancer biology and its influence in the current approaches of targeted cancer therapies in the clinical setting. The roles of glycosylation in cancer signaling, tumor progression, and metastasis are reviewed as well as glycans and glycan-binding proteins in tumor immunomodulation. Moreover, the latest reports on glycans influencing targeted therapeutic approaches in cancer are summarized. Finally, we discuss the future challenges of the field, outlining potential applications of glycan-based biomarkers for patient stratification and strategies for improving personalized cancer treatment.

Organic UV-filters are emergent contaminants continuously released into the aquatic ecosystems. These compounds are persistent showing potential for bioaccumulation. Partial life-cycle tests may underestimate the toxicity of UV-filters especially since these compounds have shown to act as endocrine disruptors. In the present study, the benthic aquatic insect Chironomus riparius was exposed to a gradient of Benzophenone-3 (BP3) concentrations over two generations to assess effects over a full life cycle from the first-instar larvae in the parental (P) generation (emergence, fecundity and fertility) until emergence in the subsequent generation (filial - F1). Recovery from exposure was also assessed after one generational exposure. Our results showed that concentrations of up to 8mg BP3/kg, elicited no effects regarding emergence rate and development time of C. riparius in the P generation. Our results also showed that C. riparius fecundity was not affected by BP3 exposure, but a strong dose-response relationship was observed for fertility with none of the egg ropes hatching at 8mg BP3/kg. Regarding effects observed in the F1 generation, emergence and development time were impaired by continuous exposure to BP3. Moreover, reduced emergence and changes in development time were observed in the F1 generation maintained in control/clean conditions but whose parents were exposed to BP3. Results found in this two-generational study clearly show reproductive effects of BP3 on C. riparius that would not be detected using standard tests. Full life cycle and multigenerational assays are critical to properly evaluate the population level effects of endocrine disrupting compounds such as organic UV-filters. published

The high levels of microplastics (MPs) found in freshwaters, particularly in riverine sediments, may impose a threat to the macroinvertebrate communities with possible consequences at ecosystem-level. The present study aimed to assess the effects of a mixture of different sizes of polyethylene microplastics (PE-MPs) on the composition and structure of macroinvertebrate communities and key-functions, such as primary production and leaf litter decomposition. MPs were mixed in the sediment at three different concentrations (0.1, 1, and 10 g kg-1) already found in freshwater sediments to enhance the relevance of the work. After eight days of exposure to PE-MPs, the observed changes in macroinvertebrate community structure were mostly due to the reduction in the abundance of deposit-feeders and grazers that were reduced by ca 31-50% and 34-39%, in the two highest MPs concentrations respectively, in comparison with the control treatment after 8 days of exposure. MPs internal concentrations were detected only in organisms exposed to plastic particles within artificial streams with chironomids and mayflies presenting higher MPs internal levels (average of 115 particles/individual found in chironomids, 166/individual for Baetis sp. and 415 particles/individual for Ephemerella sp.) suggesting higher ingestion of plastic microparticles. Nevertheless, the alterations in the community structure did not translate into impairments in the functional endpoints analysed, leaf litter decomposition and primary production, that were expected due to possible sub-lethal effects (e.g., feeding inhibition) on detritivores and grazers. This study represents one of the few assessments of MPs effects on freshwater benthic macroinvertebrate community structure and the first that simultaneously considered ecosystem-level functional endpoints. Further research combining different microplastics and longer exposure periods are needed to raise knowledge on potential ecological consequences of MPs to freshwaters.

Made available in DSpace on 2022-04-29T08:33:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-15 European Commission Fundação para a Ciência e a Tecnologia Ministério da Ciência, Tecnologia e Ensino Superior Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) European Regional Development Fund Centro de Investigação em Materiais Cerâmicos e Compósitos Centro de Estudos Ambientais e Marinhos, Universidade de Aveiro Microplastics and nanomaterials are applied in a myriad of commercial and industrial applications. When leaked to natural environments, such small particles might threaten living organisms' health, particularly when considering their potential combination that remains poorly investigated. This study investigated the physiological and biochemical effects of polyethylene (PE; 64-125 μm in size, 0.1, 1.0, and 10.0 mg·L−1) single and combined with an engineered nanomaterial applied in antifouling coatings, the copper-aluminium layered double hydroxides (Cu-Al LDH; 0.33, 1.0, and 3.33 mg·L−1) in the flatfish Solea senegalensis larvae (8 dph) after 3 h exposure, in a full factorial design. Particles ingestion, histopathology, and biochemical biomarkers were assessed. Fish larvae presented

Freshwater riverbeds are a major repository of microplastics (MPs) from inland activities. Benthic macroinvertebrates that live in close contact with sediments seem to ingest a considerable amount of such plastic particles. The effects of MPs on life-history traits are relatively well-known, but the suborganismal mechanisms underlying such effects remain unclear. This study addressed the potential effects of low-density polyethylene (LDPE) MPs on Chironomus riparius larvae at cellular and molecular levels. Fourth instar C. riparius larvae were exposed to 0.025 and 2.5 g/kg LDPE of dry sediment (sizes:32 and 32-45 μm; with irregular shape) under laboratory conditions for 48 h. These short-term exposures to environmental concentrations of LDPE MPs induced changes in the energy reserves (mostly by decreasing carbohydrates and increasing lipids), increased antioxidant and detoxification responses (tGSH, CAT, and GST), and induced increases in the activity of AChE (related to neurotransmission). In addition, at the gene level, exposure to MPs modified mRNA levels of InR, Dis, EcR, Dronc, Met (endocrine system), Def (immune system), PARP, ATM, NLK, and Decay (DNA repair), generating important alterations in the C. riparius development and response to unfavorable situations. This study provides new evidence of the effects of LDPE MPs at the suborganismal level, filling the gap in knowledge regarding the mechanisms underlying the toxicity of MPs and spotlighting gene expression analyses as early indicators of MP toxicity in C. riparius which were confirmed by Integrated biomarker response analyses highlighting the gene expression as sensible and useful endpoints for LPDE pollution in freshwaters. These results, coupled with previous investigations on responses at the organismal level, emphasizes the potential adverse effects of LDPE MPs on C. riparius, which may compromise freshwater benthic communities, considering its ecological role within these habitats.

Despite the frequent detection of organic ultraviolet-filters (UV-filters) in freshwater sediments, there is a lack of ecotoxicological data undermining a correct risk assessment for these emerging contaminants. The present study assessed the effects of three of the most commonly used UV-filters (benzophenone-3 - BP3; 3-(4-methylbenzylidene)camphor - 4-MBC and octocrylene - OC) on Chironomus riparius life history and biochemical responses. Standard ecotoxicological assays confirmed that all compounds impaired growth of C. riparius larvae and induced developmental effects such as delayed emergence and a reduction of imagoes weight. Concerning the biochemical responses analysed no evidences of oxidative damage in lipids or neurotoxicity (tested assessing acetylcholinesterase activity) were observed for any of the tested compounds. However, 4-MBC exposure induced a decrease in catalase activity and an increase in glutathione-S-transferase activity at 14.13mg/Kg while OC exposure caused an increase in total glutathione levels at 0.23 and 18.23mg/Kg. Exposure to all UV-filters tested, increased energy consumption on C. riparius with significant differences above 1.00mg/Kg for BP3, 0.09mg/Kg for 4-MBC and 2.13mg/Kg for OC. These results suggest that environmental relevant concentrations of UV-filters can cause deleterious effects to aquatic benthic species, such as C. riparius, and call for further research concerning effects of organic UV-filters on natural invertebrate communities and ecosystem functioning.

Physiological responses allow populations to cope with metal contamination and can be involved in the evolution of tolerance under historical metal contamination scenarios. Here we investigate physiological aspects that might be underlying the heritable high tolerance to cadmium (Cd) in two Chironomus riparius populations collected from historically metal contaminated sites in comparison to two populations from reference sites. To evaluate differences in the physiological response to short-term Cd exposure, protein expression profiles, metallothioneins [MTs] and several antioxidant defences such as total glutathione (GSHt), catalase (CAT) and glutathione-S-transferases [GSTs], were measured in all four populations reared for at least 8 generations under laboratory clean conditions. Cd-induced oxidative damage in lipids and energy related parameters (energy consumption and energy reserves) were also assessed. Results showed two major gradients of protein profiles according to Cd concentration and population tolerance. Furthermore, Cd-tolerant populations showed higher baseline levels of MTs and GSHt while Cd-sensitive populations, collected from reference sites, showed significant induction of GSHt levels with Cd exposure that were nonetheless insufficient to avoid increased oxidative damage to lipids. Cd exposure had no clear effects on the antioxidant enzymes or energy reserves but triggered a general increase in energy consumption. Finally, energy consumption was higher in Cd-tolerant populations across experimental conditions. Altogether, results demonstrate that inherited Cd-tolerance in these midge populations is related, at least in part, with different constitutive levels and plasticity of different defence mechanisms confirming the validity of using multiple physiological traits when studying evolution of tolerance.

The insecticide thiamethoxam (TMX) is a systemic neonicotinoid widely used for pest control in several agricultural crops. TMX mimics the action of acetylcholine causing uncontrolled muscular contraction eventually leading to insect death. TMX is being found in freshwater ecosystems at concentrations of up to 225µg/L. Still, chronic toxicity data for freshwater invertebrates is limited. Therefore, the aim of this study was to evaluate the acute and chronic effects (at organismal and biochemical levels) of TMX on the freshwater insect Chironomus riparius. C. riparius life history responses were significantly affected by TMX exposure, namely with a decrease in growth and delay in emergence. Concerning the biochemical responses, after a short exposure (48h) to TMX, our results showed that low concentrations of TMX significantly reduced CAT activity and LPO levels of C. riparius. No effects were observed in AChE, GST and ETS activities. Effects in terms of survival, development rates and biochemical responses of C. riparius exposed to low concentrations of TMX observed in this study suggest potential deleterious effects of this neonicotinoid on aquatic insects inhabiting freshwaters environments near agricultural areas.

Stream ecosystems face ever-increasing pressures by the presence of emergent contaminants, such as, personal care products. N, N-diethyl-3-methylbenzamide (DEET) is a synthetic insect repellent that is being found in surface waters environments in concentrations up to 33.4 μg/L. Information concerning DEET's toxicity in the aquatic environment is still limited and focused only on its acute effects on model species. Our main objective was to assess the effects of DEET exposure to a caddisfly non-target species using sub-lethal endpoints. For that, we chose Sericostoma vittatum, an important shredder in Portuguese freshwaters that has been already used in different ecotoxicological assays. Besides acute tests, S. vittatum were exposed during 6 days to a gradient of DEET concentrations (8, 18 and 40.5 mg/L) to assess effects on feeding behaviour and biochemical responses, such as, lipid peroxidation levels (LPO), catalase and acetylcholinesterase (AChE) activities, and also assess effects on energy reserves and consumption. Acute tests revealed a 48 h-LC50 of 80.12 mg/L and DEET exposure caused feeding inhibition with a LOEC of 36.80 mg/L. Concerning the biochemical responses, DEET caused no effects in LPO nor on catalase activity. A non-significant decrease in AChE activity was observed. Regarding energetic reserves, exposure to DEET caused a significant reduction in S. vittatum carbohydrates levels. These results add important information for the risk assessment of insect repellents in the aquatic environment and suggest that reported environmental concentrations of DEET are not toxic to non-target freshwater insects.

Paraquat (PQ) is still used in several countries worldwide as an herbicide for weed control in agricultural production, ponds, reservoirs and irrigation canals. Thus, PQ is frequently found in surface water systems and is potentially toxic to aquatic organisms, since it can cause mitochondrial dysfunction altering in the redox state of cells. This study aimed to investigate the chronic effects of PQ to Chironomus riparius and Girardia tigrina, and compare their physiological strategies to cope with environmental stress. The mean emergence time was the most sensitive endpoint for Chironomids, with the lowest observed effect concentrations (LOEC) being 0.02 for males and 0.1 mg PQ L−1 for females. Moreover, PQ reduced the body weight of male and female imagoes, with LOECs of 0.5 and 2.5 mg PQ L−1, respectively. Paraquat also decreased the respiration rate (LOEC = 2.5 mg PQ L−1) and total glutathione (tGSH) content (LOEC = 0.5 mg PQ L−1). Thus, the aerobic production of energy was not affected and allowed chironomids to cope with oxidative stress induced by PQ, but with consequent physiological costs in terms of development rates and weight of adults. In planarians, PQ decreased the locomotion and feeding activity, and delayed photoreceptor regeneration (LOECs = 2.5 mg PQ L−1 for all endpoints). Despite increased aerobic energy production (LOEC = 0.5 mg PQ L−1), planarians were not able to cope with oxidative stress induced by the highest PQ concentrations, since lipid peroxidation levels were significantly increased (LOEC = 2.5 mg PQ L−1) concomitantly with a significant decrease of tGSH (LOEC = 2.5 mg PQ L−1). These results showed that planarians were unable to cope with oxidative stress induced by PQ with consequent impairments of behavior and regeneration despite an increased aerobic energy production.

Plastics have been on top of the political agenda in Europe and across the world to reduce plastic leakage and pollution. However, the COVID-19 pandemic has severely disrupted plastic reduction policies at the regional and national levels and induced significant changes in plastic waste management with potential for negative impacts in the environment and human health. This paper provides an overview of plastic policies and discusses the readjustments of these policies during the COVID-19 pandemic along with their potential environmental implications. The sudden increase in plastic waste and composition due to the COVID-19 pandemic underlines the crucial need to reinforce plastic reduction policies (and to implement them into action without delays), to scale up in innovation for sustainable and green plastics solutions, and to develop dynamic and responsive waste management systems immediately. Policy recommendations and future research directions are discussed., Thanks are due to CESAM (UIDP/50017/2020+UIDB/50017/2020), with the financial support from FCT/MCTES through national funds; and to the research project comPET (PTDC/CTA-AMB/30361/2017) funded by FEDER, through COMPETE 2020 - Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE), through FCT/MCTES, and also to the Integrated Program of SR&T D' Smart Valorisation of Endogenous Marine Biological Resources Under a Changing Climate’ (reference Centro-01-0145-FEDER-000018), co-funded by Centro (2020) program, Portugal 2020, European Union, through the European Regional Development Fund. J.C.P. and A.L.P.S. were funded by Portuguese Science Foundation (FCT) through scholarship PD/BD/135581/2018 and PD/BPD/114870/2016 + CEECIND/01366/2018, respectively; under POCH funds, co-financed by the European Social Fund and Portuguese National Funds from MEC. T.R.W. was funded by a NSERC Discovery Grant RGPIN-2018-04119, and D.C. was funded by a research contract within the project comPET (nr. Contract: 5662).

In the last decades, the use of organic ultraviolet-filters (UV-filters) has increased worldwide, and these compounds are now considered emerging contaminants of many freshwater ecosystems. The present study aimed to assess the effects of 3-(4-methylbenzylidene) camphor (4-MBC) on a freshwater invertebrate community and on associated ecological functions. For that, artificial streams were used, and a natural invertebrate benthic community was exposed to sediments contaminated with two concentrations of 4-MBC. Effects were evaluated regarding macroinvertebrate abundance and community structure, as well as leaf decomposition and primary production. Results showed that the macroinvertebrate community parameters and leaf decomposition rates were not affected by 4-MBC exposure. On the other hand, primary production was strongly reduced. This study highlights the importance of higher tier ecotoxicity experiments for the assessment of the effects of low concentrations of organic UV-filters on freshwater invertebrate community structure and ecosystem functioning.

Despite being considered environmentally safe, a deeper environmental risk assessment is needed for microbial insecticides; special attention should be devoted to their sublethal toxicity to non-target species. This study evaluated effects of VectoBac® 12AS - VB (based on the bacterium Bacillus thurigiensis var. israelensis) and Naturalis®-L - NL (based on the fungus Beauveria bassiana) on the aquatic insect Chironomus riparius life- history and biochemical responses. Acute tests estimated a 48 h-LC50 (median lethal concentration) of 1.85 μg/L (VB) and 34.7 mg/L (NL). Under sub- lethal exposure, VB decreased adults' emergence (LOEC – lowest observed effect concentration of 80 ng/L) while NL impaired larval growth (LOEC of 0.32 mg/L) and delayed emergence (LOEC of 2 mg/L for males and 0.8 mg/L for females). Despite not being monotonic, phenoloxidase activity increased (LOEC of 20 ng/L (VB) and 2 mg/L (NL)), suggesting activation of the immune system. There were no indications of oxidative damage nor neurotox- icity. Catalase activity was stimulated with all VB treatments, possibly associated with detoxification of immune response products. Under NL exposure, glutathione-S-transferase activity increased but did not show a dose- dependent response and, total glutathione decreased in the highest concentration. Exposure to both formulations caused the increase in protein content, while carbohydrate and lipids were not altered. This study revealed the susceptibility of C. riparius to VB and NL at concentrations below the ones recommended for field application, with potential population-level effects. These results add important information for the risk assessment of these microbial insecticides in aquatic ecosystems, considering relevant sublethal endpoints and raising concern about the adverse effects on non-target aquatic organisms. published

Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "Simple- Cell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer. This work was supported by The Danish Research Councils, The Mizutani Foundation, The Danish National Research Foundation (DNRF107) and Fundacão para a Ciência e a Tecnologia (FCT) and COMPETE (Programa Operacional Temático Factores de Competitividade, comparticipado pelo fundo comunitário europeu FEDER) in the framework of the projects: PTDC/BBB-EBI/0786/2012; EXPL/CTM-BIO/0762/2013. Grants were received from FCT (SFRH/BD/73717/2010 to DC), (SFRH/BPD/75871/2011 to AM), (SFRH/BPD/96510/2013 to CG) and (SFRH/BPD/66288/2009 to JAF). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education, and is partially supported by FCT.

In Portugal, Eucalyptus plantations replaced native species and presently occupy at least 26% of the total forest area. These changes in the biodiversity affect riparian corridors and eucalyptus leaves are nowadays common primary sources of energy and carbon for aquatic benthic communities. The diverse and complex chemical composition of eucalyptus leaf litter and the resulting leachates may alter the homeostatic balance of exposed aquatic organisms. The present study focused on the evaluation of ecotoxicological responses of Chironomus riparius to Eucalyptus globulus leaf leachates at different levels of biological organization, including larval survival, growth and emergence, and biochemical endpoints, namely biomarkers related to cholinergic neurotransmission (acetylcholinesterase, AChE, activity), oxidative stress (catalase, CAT, and glutathione- S -transferases, GSTs, activities), total glutathione contents (tGSH), and peroxidative damage (lipid peroxidation, LPO) and also to oxygen consumption rate (electron transport system, ETS). The here-obtained results showed that E. globulus leaf leachates, in comparison with leaf leachates of the autochthonous species Alnus glutinosa , impaired C. riparius growth and development rates, altering their emergence patterns, and also changed key biochemical pathways, namely with putative effects on energetic balance, and neurophysiology.

Introduction Glycosylation alterations are frequently found in cancer and specific aberrant glycan structures are associated with tumour development and progression.1 The characterisation of glycosylation modifications occurring in cancer is of high interest and represents a source of putative new biomarkers for cancer detection, therapeutic intervention and patient stratification. Material and methods Glycomics, glycoproteomics, glycoprofiling, and in situ Proximity Ligation Assays of glycoengineered cancer cell models and tissue samples from gastrointestinal cancer patients were performed. Results and discussions This presentation reports the recent discoveries applying several novel approaches for: (A) the characterisation of glycosylation changes in the cancer cells; (B) the identification of the aberrant expression of specific glycan structures in cancer, like terminal sialylated glycans, which lead to the activation of tyrosine kinase receptors, such as HER2, MET, and RON;2,3,4,5 (C) the identification of altered glycosylated proteins, carrying simple mucin-type carbohydrate structures, in engineered cancer cell models and in sera of cancer patients.5,6 Conclusion These results demonstrate aberrant glycan structures as key functional players in tumour biology and highlight their potential as novel biomarkers and as therapeutic targets in the clinical management of cancer patients.1,5,6