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HS-1793 is a novel derivative of resveratrol, a compound known for its numerous beneficial effects, including anticancer activity, anti-inflammatory response, antimicrobial, antiaging, anti-cardiovascular disease activity, neuroprotective activity, etc. Despite its wide and interesting properties, resveratrol suffers from a crucial flaw because it is low bioavailable. For this reason, many other derivatives were explored and among them, HS-1793 has caught the attention of researchers. HS-1793 is a synthetic derivative of resveratrol discovered in 2007 that has been shown to have anti-cancer and anti-inflammatory properties. In addition, the compound showed a positive profile in metabolic processes, with adequate pharmacokinetics and pharmacodynamics. This review highlights current research on HS-1793, evaluating in vitro and in vivo works and lays the foundation for novel explorative trials in human diseases.

Purpose of Review: This consensus statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF) provides the official view on the role of exercise as a non-pharmacological approach in lipedema. In detail, this consensus statement SISMeS - SIF aims to provide a comprehensive overview of lipedema, focusing, in particular, on the role played by physical exercise (PE) in the management of its clinical features., Recent Findings: Lipedema is a chronic disease characterized by abnormal fat accumulation. It is often misdiagnosed as obesity, despite presenting distinct pathological mechanisms. Indeed, recent evidence has reported differences in adipose tissue histology, metabolomic profiles, and gene polymorphisms associated with this condition, adding new pieces to the complex puzzle of lipedema pathophysiology. Although by definition lipedema is a condition resistant to diet and PE, the latter emerges for its key role in the management of lipedema, contributing to multiple benefits, including improvements in mitochondrial function, lymphatic drainage, and reduction of inflammation. Various types of exercise, such as aquatic exercises and strength training, have been shown to alleviate symptoms and improve the quality of life of patients with lipedema. However, standardized guidelines for PE prescription and long-term management of patients with lipedema are lacking, highlighting the need for recommendations and further research in this area in order to optimise therapeutic strategies., (© 2024. The Author(s).)

Over the past decade, global reports have shown a rise in the harmful effects of microplastics (MPs) on marine fish. This study analysed marine species' biochemical biomarker responses to microplastic exposure, finding that MPs can induce oxidative stress in marine fish through meta-regression results. Overall, exposure to MPs resulted in the activation of antioxidant defence mechanisms, such as superoxide dismutase, catalase and glutathione reductase, detoxification enzymes such as glutathione-S-transferase, the detection of malondialdehyde, and inhibition of acetylcholinesterase. Moreover, results highlight oxidative stress biomarkers were activated in wild species that had ingested MPs, indicating potential harm to marine fish, as confirmed in experimental studies. Furthermore, even though MPs' exposure is better regulated in an experimental setting, it is challenging to replicate actual exposure and environmental factors. The study's findings show the need for more investigation into the hazardous consequences of exposure to environmental MPs on species surveyed in the maritime environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aging is a normal physiological process influenced by the combination of multiple mechanisms, primarily oxidative stress and neuroinflammation, which impact general physiology and brain function. Phenolic compounds have demonstrated the ability to slow down the aging process of the brain due to their antioxidant and anti-inflammatory effects. This study assessed the protective properties of catechin and polyphenon-60 in non-pathologically aged rats regarding visuo-spatial learning and the oxidative status of the frontal cortex. Old animals were treated with catechin or green tea extract (polyphenon-60) for 36 days, daily. Healthy old and young rats were used as controls. During the first training phase, treated rats executed the test better, locating the target in less time compared with the controls. Biomarkers of oxidative stress (catalase activities, superoxide dismutase, glutathione reductase, and glutathione S-transferase) were reduced in the brain of old animals, although their activities were partially improved after both antioxidant treatments. Furthermore, the rise in the production of reactive oxygen species and malondialdehyde levels-a marker of lipid peroxidation-in the frontal cortex of aged animals was significantly ameliorated after the interventions. In conclusion, old rats exhibited enhanced cognitive function and reduced stress levels following the administration of catechin and polyphenon-60.

Hyperbaric oxygen therapy (HBOT) is the clinical application of oxygen at pressures higher than atmospheric pressure. HBOT has been effectively used to manage diverse clinical pathologies, such as non-healing diabetic ulcers. The aim of the present study was to analyse the effects of HBOT on the plasma oxidative and inflammation biomarkers and growth factors in patients with chronic diabetic wounds. The participants received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20, before and 2 h after the HBOT. An additional (control) blood sample was collected 28 days after wound recovery. No significant differences were evident in haematological parameters, whereas the biochemical parameters progressively decreased, which was significant for creatine phosphokinase (CPK) and aspartate aminotransferase (AST). The pro-inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β), progressively decreased throughout the treatments. Biomarkers of oxidative stress--plasma protein levels of catalase, extracellular superoxide dismutase, myeloperoxidase, xanthine oxidase, malondialdehyde (MDA) levels and protein carbonyls--were reduced in accordance with wound healing. Plasma levels of growth factors--platelet-derived growth factor (PDFG), transforming growth factor β (TGF-β) and hypoxia-inducible factor 1-alpha (HIF-1α)-- were increased as a consequence of HBOT and reduced 28 days after complete wound healing, whereas matrix metallopeptidase 9 (MMP9) progressively decreased with the HBOT. In conclusion, HBOT reduced oxidative and pro-inflammatory mediators, and may participate in activating healing, angiogenesis and vascular tone regulation by increasing the release of growth factors.

Ethnopharmacological Relevance: The genus Eryngium is known for producing a wide range of bioactive compounds with proved medicinal properties. In the last years, research has focused on E. maritimum, with previous studies reporting anticancer, antimicrobial, antioxidant, and anti-inflammatory activities. Ethnobotanical literature suggests that it has been traditionally used to treat a wide range of illnesses, having antitussive, diuretic and aphrodisiac properties. Being rhizome one of the most bioactive organs, much of the available references from traditional uses suggest that it has been specifically used to treat renal diseases. In this sense, inflammation and oxidative processes play a major role in kidney dysfunctions, which could be associated to the mechanism of action of the plant extracts., Aim of the Study: The main aim of the study was to investigate the effects of E. maritimum rhizome extract on the antioxidant and inflammatory response in human immune cells., Material and Methods: Rhizome extracts were obtained from plants growing in Mallorca (Balearic Islands), and its composition was determined using HPLC-DAD, highlighting simple phenolic compounds such as trans-ferulic acid, catechin, chlorogenic acid, epicatechin and rosmarinic acid as the major constituents. Total antioxidant capacity was determined using the FRAP assay. Jurkat cells were cultured to analyse cytotoxicity by cell viability assay. In parallel, cells were stimulated with phytohemagglutinin and treated with different extract concentrations. Gene and protein expression, as well as nitrite and cytokine levels were evaluated as indicators of metabolic responses., Results: The plant extract showed a high diversity of pharmacologically bioactive compounds with potential therapeutic uses. The extract presented null cytotoxicity and exerted antioxidant and anti-inflammatory effects on Jurkat cells by inducing an antioxidant response and reducing cytokine and nitric oxide release and the expression of pro-inflammatory genes., Conclusion: The present findings suggest that E. maritimum is a promising phytotherapeutic species because of its strong antioxidant and anti-inflammatory potential, which could explain some of its traditional uses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bromelain is a key enzyme found in pineapple ( Ananas comosus (L.) Merr .); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pezzani, Jiménez-Garcia, Capó, Sönmez Gürer, Sharopov, Rachel, Ntieche Woutouoba, Rescigno, Peddio, Zucca, Tsouh Fokou, Martorell, Gulsunoglu-Konuskan, Ydyrys, Bekzat, Gulmira, Hano, Sharifi-Rad and Calina.)

Obesity involves a chronic state of low-grade inflammation, which is linked to the development of several comorbidities. Recently, the very low-calorie ketogenic diet (VLCKD) has gained great interest in the treatment of obesity, almost ousting the ancient and healthy Mediterranean diet (MD). However, because these dietary regimens exploit different pathophysiological mechanisms, we hypothesize that adherence to the MD may play a role in determining the efficacy of the VLCKD. We enrolled 318 women (age 38.84 ± 14.37 years; BMI 35.75 ± 5.18 kg/m²) and assessed their anthropometric parameters, body compositions, and adherence to the MD (with the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire) at baseline. The anthropometric parameters and body composition were repeated at the end of the VLCKD. At the end of the VLCKD, the women with high adherence to the MD achieved the best results in terms of weight loss and improved body composition. Specifically, the women who were above the median of fat mass (FM)% reduction had the best MD pattern, characterized by a higher consumption of extra virgin olive oil (EVOO), fruits, vegetables, and red wine, as well as a higher adherence to the MD than the women who were below the same median. In a multiple regression analysis, the PREDIMED score was the main predictor of the FM% reduction score and came in first, followed by fruit, EVOO, and glasses of wine, in predicting the percentage reduction in FM. A PREDIMED score value of > 5 could serve as a threshold to identify patients who are more likely to lose FM at the end of the VLCKD. In conclusion, high adherence to the MD resulted in higher VLCKD efficacy. This could be due to the antioxidant and anti-inflammatory properties of the MD, which are capable of establishing a metabolic set-up that is favorable to the onset of more effective ketosis.

Plastic debris is a growing environmental problem on a global scale, as plastics and microplastics (MPs) can be ingested by marine organisms, inducing toxic effects. The aim of this study was to assess MP intake and antioxidant responses in three bioindicator species: red mullet, bogue, and anchovy ( Mullus surmuletus, Boops boops , and Engraulis encrasicolus , respectively) for plastic contamination in the Mediterranean Sea. MP intake was assessed in the gastrointestinal tract of the fish. Further, several enzymes from both the liver and brain were analysed. The antioxidant defences, catalase (CAT) and superoxide dismutase (SOD), as well as the detoxifying enzyme glutathione-S-transferase (GST), were measured in both tissues. The acetylcholine esterase (AchE), as an indicator of neuronal damage, was measured in the brain. Malondialdehyde (MDA) was analysed as a marker of oxidative damage in the brain and liver samples. Total MP intake and MP typology differed between the three species, with M. surmuletus showing the lowest intake of MPs, while B. boops showed the highest intake of MPs. An increase in both antioxidant enzymes was evidenced in E. encrasicolus liver activity with respect to MP intake. In brain samples, an increase in CAT activity was found in M. surmuletus and B. boops as a consequence of MP ingestion. SOD activity in the brain increased in B. boops and E. encrasicolus that had ingested MPs. GST activity increased in the liver of M. surmuletu s' and in brains of B. boops that had ingested MPs. The intake of MPs is species related, as well as being inherently linked to the habitat they live in and being able to induce a light activation of species-specific detoxifying and antioxidant mechanisms.

We have applied a multispecies ecosystem approach to analyse the ingestion of anthropogenic particles (AP) in the gastrointestinal tract of 313 individuals (17 fish species and 8 invertebrate species) from pelagic, demersal and benthic habitats in a marine protected area off the Western Mediterranean (Cabrera National Park). We have quantified and characterized the ingestion at several taxonomic levels of fish, sea urchins, sea cucumbers, bivalves, and jellyfish in relation to biotic/abiotic factors based on taxonomic groups, trophic guilds (functional groups) and habitats. AP ingestion occurrence ranged from 26 to 100% with no significant differences among taxonomic groups. The fish within the MPA showed an overall ingestion occurrence ranging from 0 to 100%, the echinoderms from 29 to 100%, the bivalves from 72 to 96% and the jellyfish 36% ingestion. The ecosystem approach applied to evaluate overall AP ingestion within the species reported that for trophic guilds, the omnivorous species ingested the highest amounts of anthropogenic items, while herbivores ingested significantly fewer items than all other trophic guilds. Moreover, no significant differences were found amongst habitats, indicating a homogeneous spatial distribution of APs at all studied habitats. The multispecies approach provided insight into the high APs exposure to species within Cabrera MPA, highlighting the potential harm linked with marine litter that threatens marine biodiversity.

Marine aquaculture is considered a potential source of microplastics (MPs). MPs can induce oxidative stress and damage in marine species. In this study we evaluated the impact of MPs intake in the commercial fish, Sparus aurata, from aquaculture facilities and the antioxidant response associated to this MPs ingestion in caged specimens for 120 days. Sampling was carried out at the beginning of the study (T 0 ), at 60 days (T 60 ) and at 120 days (T 120 ). At each sampling stage, gastrointestinal tract, blood, plasma, liver and muscle samples were obtained to analyse MPs intake (gastrointestinal tract), oxidative stress markers (blood, plasma and liver) and plasticizers bioaccumulation (muscle). Fish sampled at T 60 presented the highest MPs intake and plasticizers accumulated in muscle over time, but with a different pattern according to type: bisphenols and phthalates. This indicates MPs ingestion induces a differential tissue response in S. aurata. Similarly, stress biomarkers presented a differential response throughout the study, depending on the analysed tissue. In the case of oxidative damage markers, for malondialdehyde (MDA) an increase throughout the study was observed both in liver and blood cells but with a progressive decrease in plasma. In the case of phase I detoxifying enzyme activities in liver, 7-ethoxyresorufin O-deethylase (EROD), 7-benzyloxy-4-[trifluoromethyl]-coumarin-O-debenzyloxylase (BFCOD) and carboxylesterases (CE), showed a comparable decrease at T 60 with a slight recovery at T 120 . In contrast, glutathione-S-transferase (GST) activity was significantly enhanced at T 60 compared to the other sampling stages. In conclusion, MPs ingestion occurs in aquaculture reared seabream where potentially associated plasticizers accumulate in the muscle and both could be responsible for plasma and liver oxidative stress damage and alterations on detoxifying biomarkers responses., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The growing plastic production and its continuous use is a significant problem. In addition, aquaculture practices have experienced a considerable growth and plastic is widely used in these activities, hence plasticizers must be considered due to their potential ecotoxicological impacts on species. Mussels placed inside an Integrated Multi-Trophic Aquaculture (IMTA) system and at two control locations were employed to quantify the ingestion of anthropogenic particles and associated chemical plasticizers, such as bisphenol A (BPA) jointly to bisphenol F (BPF) and bisphenol S (BPS), and phthalates represented by diethyl phthalate (DEP), dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP). In addition, some metabolism and oxidative stress related parameters were measured in mussels' whole soft tissue. Anthropogenic particle ingestion of mussels increased over time at the three locations and the following order of abundance of pollutants was observed: BPA> BPF> DEHP> DBP> BPS> DEP. Even though no differences according to location were found for pollutants' occurrence, time trends were evidenced for BPA and DEHP. On the other hand, a location effect was observed for biomarkers with highest values detected in mussels located at the vicinities of the aquaculture facility. In addition, a reduced detoxification activity was observed over time parallel to BPA decrease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects., Methods: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS)., Results: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1., Conclusions: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.

Diabetes is part of metabolic diseases and is characterized by high blood sugar levels over a prolonged period as result of an insulin-deficient production or an inappropriate response to insulin by our cells. This chronic disease was the direct cause of 1.6 million deaths in 2016 as reported by the World Health Organization. Emodin is a natural product and active ingredient of various Chinese herbs with the chemical formula 1,3,8-trihydroxy-6-methylanthraquinone. Diacerein is another naturally occurring anthraquinone (1,8-diacetoxy-3-carboxyanthraquinone) commonly used as commercial drug to treat osteoarthritis. These two anthraquinone derivatives have been shown to exert antidiabetic activities. Emodin seems to enhance the glucose tolerance and insulin sensibility via activation of PPAR γ and modulation of metabolic-related genes. Diacerein seems to decrease inflammatory cytokines and increase insulin secretion enhancing insulin sensibility and therefore improving glucose control. Other naturally occurring anthraquinone derivatives, such as catenarin (1,4,6,8-tetrahydroxy-3-methylanthraquinone), have been shown to have antidiabetic activities although few studies have been performed. The synthesis of new emodin derivatives is increasing, but these new molecules have not been tested for diabetes treatment. In the current work, available literature on anthraquinone derivatives' effects in diabetes disease is reviewed. Moreover, we discuss the chemistry, food sources, bioavailability, and toxicity of the naturally occurring anthraquinone with antidiabetic effects., Competing Interests: The authors state that they have no conflicts of interest., (Copyright © 2021 Miquel Martorell et al.)

The constant increase in plastic pollution has attracted great attention in recent years due to its potential detrimental effects on organisms and ecosystems. While the consequences of ingestion of large plastic litter are mostly understood, the impacts resulting from a long-term exposure and a recovery period of microplastics (MPs) are still limited. The aims were to monitor oxidative stress, detoxification and inflammatory biomarkers in liver, plasma and erythrocytes of Sparus aurata exposed during 90 days to low-density polyethylene (LDPE)-MPs enriched diet (10% by weight) followed by 30 days of depuration. Exposure to LDPE-MPs progressively activates the antioxidant and detoxification system and induces an inflammatory response in liver and plasma, whereas no significant changes were observed in erythrocytes. The plasma activities of catalase, myeloperoxidase (MPO), lysozyme and the levels of malondialdehyde (MDA) as maker of lipid peroxidation significantly increased after exposure to LDPE-MPs for 90 days compared to the control group. The activities of all antioxidant enzymes - catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase-, the detoxification enzyme glutathione s-transferase, MPO, the production of reactive oxygen species and the levels of MDA were also significantly increased in liver after MPs exposure. Additionally, all these biomarkers tended to recover during the depuration period, most of them reaching similar levels to those of the control group. In conclusion, the ingestion of a diet containing LDPE-MPs for 90 days induced a progressive increase in oxidative stress and inflammation biomarkers in liver and plasma of S. aurata but not in erythrocytes, which tended to regain control values when not exposed to MPs for 30 days. The present study contributes to a better understanding of the toxic effects of MPs in S. aurata and highlights the usefulness of plasma that can be obtained in a minimally invasive way to monitor these effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neurodegenerative disorders, particularly in the elderly population, represent one of the most pressing social and health-care problems in the world. Besides the well-established role of both oxidative stress and inflammation, alterations of the immune response have been found to be closely linked to the development of neurodegenerative diseases. Interestingly, various scientific evidence reported that an altered gut microbiota composition may contribute to the development of neuroinflammatory disorders. This leads to the proposal of the concept of the gut-brain-immune axis. In this scenario, polyphenols play a pivotal role due to their ability to exert neuroprotective, immunomodulatory and microbiota-remodeling activities. In the present review, we summarized the available literature to provide a scientific evidence regarding this neuroprotective and immunomodulatory effects and the interaction with gut microbiota of polyphenols and, the main signaling pathways involved that can explain their potential therapeutic application in neurodegenerative diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Oxidative stress (OxS) has been linked to several chronic diseases and is recognized to have both major causes and consequences. The use of antioxidant-based nutraceuticals has been licensed as an optimal tool for management of OxS-related diseases. Currently, great interest is focused on the valorization of agri-food by-products as a source of bioactive compounds, including polyphenols. In this sense, we evaluated the efficacy of a novel nutraceutical formulation based on polyphenolic extract from Aglianico cultivar grape pomace (registered as Taurisolo ® ). In particular, we tested both native and in vitro gastrointestinal digested forms. The two extracts have been used to treat ex vivo neutrophils from subjects with metabolic syndrome, reporting a marked antioxidant activity of Taurisolo ® , as shown by its ability to significantly reduce both the levels of reactive oxygen species (ROS) and the activities of catalase and myeloperoxidase in the cell medium after stimulation of neutrophils with phorbol 12-myristate 13-acetate (PMA). Interestingly, we observed an increase in intracellular enzymatic activities in PMA-treated cells, suggesting that Taurisolo ® polyphenols might be able to activate nuclear factors, up-regulating the expression of this target antioxidant gene. In addition, Taurisolo ® reversed the increase in malondialdehyde induced by PMA; reduced the expression of pro-inflammatory genes such as cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNFα) and myeloperoxidase (MPO); and induced the expression of the anti-inflammatory cytokine IL-10. Overall, these results suggest the efficacy of Taurisolo ® in contrasting the OxS at blood level, providing evidence for its therapeutic potential in the management of OxS-related pathological conditions in humans.

Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60%-70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.

Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal weight, overweight and obesity. Methods: One hundred and fifty adults (55-80-years-old; 60% women) from the Balearic Islands, Spain, were recruited and classified according to body mass index (BMI). Anthropometric measurements were carried out, fasting blood samples were collected and plasma and PBMCs were obtained. Biochemical parameters, hemogram, antioxidant enzyme activities and protein levels, reactive oxygen species production (ROS), malondialdehyde (MDA), and cytokine (tumour necrosis factor, TNFα, and interleukin 6, IL-6) levels were measured. Results: Glycaemia, triglyceridemia, abdominal obesity, and waist-to-height ratio (WHtR) were higher, and HDL-cholesterol was lower in obese patients. MDA and TNFα plasma levels were higher in the obese compared to normal-weight group, while the levels of IL-6 were higher in both obese and overweight subjects with respect to normal-weight peers. The activities of all antioxidant enzymes in PBMCs as well as the production ROS progressively increased with BMI. The protein levels of catalase in PBMCs were higher in obese and glutathione reductase in obese and overweight subjects compared to normal-weight peers. No other differences were observed. Conclusion: The current results show that overweight and obesity are related to an increase in pro-oxidant and proinflammatory status in plasma and PBMCs. The studied biomarkers may be useful for monitoring the progression/reversal of obesity.

The loggerhead turtle, Caretta caretta, is a very vulnerable species to human action which means that numerous specimens arrive at the recovery centres to be treated until they can be returned to the natural environment. The aim of the present study was to investigate the physiological evolution of C. caretta specimens that have entered a recovery centre by using oxidative stress biomarkers. Plasma and peripheral blood mononuclear cells of specimens were obtained at different periods: the day of arrival at the recovery centre (day 1), at 3, 9, and 30 days later, and a final sample collected before the animal was returned to the sea. The average residence time in the centre until the return to the sea was 58.5 ± 6.1 days. The activities of antioxidant enzymes - catalase (CAT), superoxide dismutase (SOD), glutathione reductase, and glutathione peroxidase activities in immune cells and CAT and SOD in plasma - progressively decreased throughout the recovery time. Similarly, H 2 O 2 production by immune cells after lipopolysaccharide (LPS) and zymosan activation progressively decreased with the recovery process. Also, malondialdehyde (MDA), as a marker of lipid peroxidation, and the activity of the pro-oxidant myeloperoxidase were significantly decreased throughout the recovery process. In conclusion, the results evidenced that the turtles presented a high level of oxidative stress upon arrival at the recovery centre, which was normalized along with their rehabilitation. Oxidative stress biomarkers are a good tool to monitor the recovery process in C. caretta complementary to the veterinary control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Triterpenes are a large group of secondary metabolites mainly produced by plants with a variety of biological activities, including potential antitumor effects. Hepatocellular carcinoma (HCC) is a very common primary liver disease spread worldwide. The treatment can consist of surgical intervention, radiotherapy, immunotherapy and chemotherapeutic drugs. These drugs mainly include tyrosine multikinase inhibitors, although their use is limited by the underlying liver disease and displays side effects. For that reason, the utility of natural compounds such as triterpenes to treat HCC is an interesting line of research. No clinical studies are reported in humans so far., Objective: The aim of the present work is to review the knowledge about the effects of triterpenes as a possible coadjuvant tool to treat HCC., Results: In vitro and xenograft models have pointed out the cytotoxic and anti-proliferative effects as well as improvements in tumor growth and development of many triterpenes. In addition, they have also shown to be chemosensitizing agents when co-administered with chemotherapeutic agents. The mechanisms of action are diverse and involve the participation of mitogen-activated protein kinases, including JNK, p38 MAPK and ERK, and the survival-associated PI3K / Akt signaling pathway. However, no clinical studies are still reported in humans., Conclusion: Triterpenes could become a future strategy to address HCC or at least improve results when administered in combination with chemotherapeutic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide, directly related to the progressive increase in body weight and obesity. The accumulation of lipids in patients with NAFLD contributes to the development of insulin resistance, inflammatory response and oxidative stress in hepatocytes and alteration of the circulating lipid and glycaemic profile. However, to date, there are no effective pharmacological treatments for patients with NAFLD. Lifestyle changes and dietary modifications aimed at weight loss are the best current alternatives; therefore, new approaches should be considered. Resveratrol, a natural polyphenol of the stilbene group, is a potential candidate for the management of NAFLD for its anti-inflammatory, antioxidant properties, and calorie restriction-like effects., Methods: In this review, the available information on the potential therapeutic effects of resveratrol on NAFLD, found mainly in animal models and in some clinical trials, is summarizes., Results: In vitro and animal model studies have shown beneficial effects of resveratrol treatment on NAFLD. Resveratrol reduces the hepatic accumulation of lipids and improves lipid and glycaemic metabolism. Some of the mechanisms of action are the signalling pathways of AMP-activated protein kinase, sirtuin 1 and nuclear factor κB. However, the results obtained in clinical trials are inconclusive., Conclusion: Although preclinical trials have shown promising results of resveratrol against NALFD, the lack of clear results in clinical trials makes it necessary to conduct more studies with a larger number of patients and for a longer time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pollution derived from human activities and the arrival of invasive species are common worldwide and affect coastal marine ecosystems negatively, and more especially in a semi-closed sea such as the Mediterranean Sea. The aim of the study was to evaluate oxidative stress biomarkers in the gonadal tissue of the sea urchin Paracentrotus lividus (Lamarck, 1816) sampled in different areas of Sant Antoni de Portmany (Ibiza Island, Spain) with different anthropic activities, and in an area deeply covered by the invasive red algae Lophocladia lallemandii. The densities of P. lividus were higher in the area with the greatest anthropogenic influence, while the area invaded by L. lallemandii showed the lowest density. A significant increase in the activities of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) and the phase II detoxifying enzyme glutathione S-transferase (GST) was found in the most impacted area by the human activity. Moreover, malondialdehyde (MDA) and nitrite levels were also increased in the most impacted area. Similarly, the presence of L. lallemandii induced oxidative stress in P. lividus evidenced by a significant increase in all analysed biomarkers. In conclusion, changes in oxidative stress biomarkers are a good proxy to evaluate the impacts induced by anthropogenic activities and by the presence of invasive algae to P. lividus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The endemic fan mussel ( Pinna nobilis ) in the Mediterranean Sea is at high risk of disappearance due to massive mortality events. The aim of the study was to evaluate the antioxidant response of P. nobilis collected in the Balearic Islands (Western Mediterranean) before and after the mass mortality event. Individuals collected before (between 2011 and 2012) and after (between 2016 and 2017) the event were analyzed by histological, molecular, and biochemical methods to compare pathogenic loads and biochemical responses. All the individuals collected during 2016-2017 presented symptoms of the disease and were positive for Haplosporidium pinnae , while acid-fast bacteria or/and Gram-negative bacteria were detected in some individuals of both sampling periods. The activities of the antioxidant enzymes catalase and superoxide dismutase in the gills were significantly lower in P. nobilis affected with the parasite compared to those in the asymptomatic ones, while levels of malondialdehyde, as an indicator of lipid peroxidation, were higher in infected individuals. When analyzing the differential effects of H. pinnae and Mycobacterium sp. on P. nobilis , it was observed that significant effects on biomarkers were only observed in the presence of H. pinnae . Co-infection of P. nobilis by H. pinnae with other pathogens such as Mycobacterium sp. constitutes a serious problem due to its high mortality rate in the Balearic Island waters. This concerning situation for P. nobilis is favored by a reduction in antioxidant defenses related to H. pinnae infection that induces oxidative stress and cell damage.

The concentrations of cadmium (Cd), mercury (Hg) and lead (Pb) were determined in muscular tissue of eleven loggerhead turtles (Caretta caretta) from the Balearic Islands (Spain, Western Mediterranean). The metal levels found in the present study were similar or lower than concentrations detected in Andalusia (mainland Spain), Italy, Canary Islands (Spain) or Japan. As the main source of metals in the loggerhead turtle is the diet, low metal burdens could be explained by its opportunistic feeding way. No significant differences were found in metal concentrations between juveniles and subadults in any of the heavy metals analysed. Furthermore, no significant correlation was detected between heavy metal concentrations and straight carapace length (SCL) of the studied individuals. These results could derive from the homogeneity in age and size of the turtles sampled, so further studies including adults are needed in order to assess the heavy metal accumulation with turtle growth.

Environmental pollution from plastic debris is a major global concern, being a potential threat to marine organisms and ecosystems. The accumulation of microplastics (MPs) in the oceans has notable ecological implications due to their long persistence, their potential ecotoxicity, and their ability to adsorb other pollutants and act as vectors of pathogens. Nevertheless, whereas the number of investigations documenting the presence of MPs in wild fish has increased, less studies have addressed the toxicological effects associated with the ingestion of MPs in long-term laboratory conditions. The aim of the present study was to assess the physiological response of gilthead seabream (Sparus aurata) exposed to low-density polyethylene (LDPE) MPs during a 90-day exposure followed by an extra 30 days of depuration through the application of oxidative stress biomarkers in the gut. No changes were observed in the Fulton condition factor of fish associated with MP intake. The activities of antioxidant enzymes and glutathione s-transferase and the levels of reduced glutathione progressively increased throughout the study in the MPs-fed group compared to the control group, reaching the highest values at 90 days. Similarly, the activity of the pro-inflammatory enzyme, myeloperoxidase, and the levels of oxidative damage markers -malondialdehyde and protein carbonyls-also increased after 90 days of exposure to an enriched diet with MPs. During the 30-day depuration period, all the biomarkers analysed tended to normalize, with the majority recovering values similar to those of the control group. In conclusion, MPs exposure during 90 days to S. aurata induced oxidative stress and a pro-inflammatory response in gut, and were able to recover after the exposure to MPs was removed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)