Exome Sequencing has a high diagnostic rate in sporadic congenital hypopituitarism and reveals novel candidate genes.

CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.

Eco-endocrinological dynamics: Unraveling dexamethasone's influence on the interrenal axis in juvenile carp Cyprinus carpio.

This study delves into the eco-endocrinological dynamics concerning the impact of dexamethasone (DXE) on the interrenal axis in juvenile carp, Cyprinus carpio. Through a comprehensive analysis, we investigated the effects of DXE exposure on oxidative stress, biochemical biomarkers, gene expression, and bioaccumulation within the interrenal axis. Results revealed a concentration-dependent escalation of cellular oxidation biomarkers, including 1) hydroperoxides content (HPC), 2) lipid peroxidation level (LPX), and 3) protein carbonyl content (PCC), indicative of heightened oxidative stress. Concurrently, the activity of critical antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT), significantly increased, underscoring the organism's response to oxidative insult. Notable alterations were observed in biochemical biomarkers, particularly Gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activity, with GGT displaying a significant decrease with increasing DXE concentrations. Gene expression analysis revealed a significant upregulation of stress and inflammation response genes, as well as those associated with sensitivity to superoxide ion presence and calcium signaling, in response to DXE exposure. Furthermore, DXE demonstrated a concentration-dependent presence in interrenal tissue, with consistent bioconcentration factors observed across all concentrations tested. These findings shed light on the physiological and molecular responses of juvenile carp to DXE exposure, emphasizing the potential ecological implications of DXE contamination in aquatic environments. Understanding these dynamics is crucial for assessing the environmental impact of glucocorticoid pollutants and developing effective management strategies to mitigate their adverse effects on aquatic ecosystems.

Physicochemical changes in Amaranthus spp grains, flour, isolated starch, and nanocrystals during germination and malting.

Amaranth is a pseudocereal that contains between 50 and 60% starch, gluten-free protein, and essential amino acids. This study investigates the physicochemical changes in Amaranthus spp. grains, flour, isolated starch and nanocrystals during germination and malting. The moisture content increased from 8.9% to 41% over 2 h of soaking. The percentage of germination increased rapidly, reaching 96% after 60 h, a remarkable advantage over other cereals. The nutrient composition varied, including protein synthesis and lipid degradation. Lipid concentration decreased during malting, except for soaking, which increased by 62%. Scanning electron microscopy shows that germination does not cause morphological changes on the outer surface of the grains, while transmission electron microscopy indicates the presence of isolated nanocrystals with orthorhombic crystal structure confirmed by X-ray diffraction. The viscosity profile shows a decrease in peak viscosity. Therefore, amaranth is a potential pseudocereal that can be used as an additive in the production of fermented beverages.

Physicochemical, nutraceutical, and sensory evaluation of a milk-type plant-based beverage of extruded common bean (Phaseolus vulgaris L.) added with iron.

Milk-type beverages are popular vegan products requiring iron and calcium fortification to improve their nutritional value, as iron deficiency is the world's most prevalent nutritional problem. This research aimed to develop and characterize an extruded common bean (Phaseolus vulgaris L.)-based milk-type beverage added with bean protein isolate and iron. The formulations included flavors (non-flavored, vanilla, and nut) and two iron concentrations (2 and 3 mg FeSO4/100 mL). Extrusion increased the beverages' protein (+17.38 %) and starch digestibility, and reduced their antinutritional compounds (trypsin inhibitors, condensed tannins, and carbonates). Developed beverages' formulations differed from a commercial soybean beverage in their physicochemical properties but were more nutritious (protein: 3.33-3.44 %; fiber: 3.43-4.08 %). Iron-added beverages displayed a medium sensory acceptance (best overall likeness: 5.3-6.2). The developed beverage is a suitable, sensory-accepted, and nutritious bean-based beverage, suggesting novel research lines improving vegan beverage formulations to increase average daily iron intake.

Effect of electric field on physicochemical properties and resistant starch formation in ohmic heating processed corn starch.

This research investigated the impact of ohmic heating (OH) on the physicochemical properties and resistant starch formation in native corn starch. Electric field strengths (EFS) of 50, 75, and 100 V/cm were applied to native starch, at a starch-water ratio of 1:1 w/v. The conductivity of the medium is a crucial factor in ohmic heating. In this study, the conductivity values at 120 °C were measured at 1.5 mS/m. The study revealed two distinct outcomes resulting from the application of different EFS. Firstly, a thermal effect induced gelatinization, resulting in a reduction in the enthalpy of corn starch, an increase in the water absorption index (WAI) and the water solubility index (WSI), and a decrease in peak viscosity. Secondly, a non-thermal effect of OH was observed, leading to the electrolysis of certain starch compounds and water. This electrolysis process generated radicals (-OH) that interacted with starch components, augmenting the percentage of resistant starch. This increase was associated with elevated levels of carbonyl and carboxyl groups at 75 and 100 V/cm.

Assessing the impact of COVID-19 era drug combinations on hepatic functionality: A thorough investigation in adult Danio rerio.

Current and thorough information on the ecotoxicological consequences of pharmaceuticals is accessible globally. However, there remains a substantial gap in knowledge concerning the potentially toxic effects of COVID-19 used drugs, individually and combined, on aquatic organisms. Given the factors above, our investigation assumes pivotal importance in elucidating whether or not paracetamol, dexamethasone, metformin, and their tertiary mixtures might prompt histological impairment, oxidative stress, and apoptosis in the liver of zebrafish. The findings indicated that all treatments, except paracetamol, augmented the antioxidant activity of superoxide dismutase (SOD) and catalase (CAD), along with elevating the levels of oxidative biomarkers such as lipid peroxidation (LPX), hydroperoxides (HPC), and protein carbonyl content (PCC). Paracetamol prompted a reduction in the activities SOD and CAT and exhibited the most pronounced toxic response when compared to the other treatments. The gene expression patterns paralleled those of oxidative stress, with all treatments demonstrating overexpression of bax, bcl2, and p53. The above suggested a probable apoptotic response in the liver of the fish. Nevertheless, our histological examinations revealed that none of the treatments induced an apoptotic or inflammatory response in the hepatocytes. Instead, the observed tissue alterations encompassed leukocyte infiltration, sinusoidal dilatation, pyknosis, fatty degeneration, diffuse congestion, and vacuolization. In summary, the hepatic toxicity elicited by COVID-19 drugs in zebrafish was less pronounced than anticipated. This attenuation could be attributed to metformin's antioxidant and hormetic effects.

Understanding chemical pathways of brown centre formation in laboratory induced and conventionally dried nut-in-shell macadamia kernels.

World tree nut production has increased rapidly by around 50 % in the past decade; however, nut defects cause losses. For example, we know that brown centres are a major internal discolouration defect in macadamia nuts and are linked to the storage of nut-in-shell under improper conditions at high temperature and humidity. However, key chemical changes in brown centre kernels have not been described. In this study, we compared brown centres and white kernels from: 1) samples that were "induced" in the laboratory by storing at high moisture concentration; and 2) samples that were dried immediately after harvest using industry best practice methods recommended by the Australian Macadamia Society (AMS). We measured the moisture concentration, sugar concentration, fatty acid concentration, peroxide value, nutrient concentration and volatile compounds of induced and AMS samples. Our results showed that storing nut-in-shell macadamia under wet and hot conditions increased brown centres compared with samples immediately dried using the AMS regime, 10.33 % vs 1.44 %, respectively. Induced brown centres had significantly higher moisture concentrations than induced white centres. Volatile compounds including nonanoic acid, octanoic acid and 2,3 butanediol were identified and associated with brown centre formation in macadamia kernels and the initiation of lipid oxidation. Our results suggest sugar hydrolysis and the Maillard reaction are associated with brown centres both in laboratory induced samples and those formed using industry best practice drying methods. Our study suggests improper drying and storage at high temperature and high humidity are likely to result in brown centre formation. We recommend brown centre losses can be reduced by appropriate drying and storage practices.

Physicochemical changes in starch during the conversion of corn to tortilla in the traditional nixtamalization process associated with RS2.

This work aimed to study the changes in starch and isolated starch resulting from the conversion of corn to tortilla, focusing on the orthorhombic crystal structure and its association with resistant starch. Scanning electron microscopy images show whole, partially, and completely damaged starch granules in nixtamalized corn, masa, and tortillas. More importantly, whole isolated starch granules were found in nixtamal, masa, and tortillas. Transmission electron microscopy shows the presence of nanocrystals with orthorhombic structures in isolated starch. Some of them remained almost undamaged during the nixtamalization process. The X-ray patterns showed orthorhombic crystals in nixtamal, masa, and tortilla and their isolated starches. The RS increased from 2.61 to 5.31 % from corn to tortilla and from 2.52 to 5.61 % for isolated starches from corn and tortilla during the traditional nixtamalization process. The results suggest that the nanocrystals in corn to tortilla are part of RS2.

Chia Oil Microencapsulation Using Tannic Acid and Soy Protein Isolate as Wall Materials.

The use of proteins to produce oil-containing microcapsules has been previously analyzed; however, their chemical modification, in order to improve their performance as wall materials, is a strategy that has not been widely developed yet. This study aimed to analyze the chemical modification of the proteins through cross-linking reactions with tannic acid and to evaluate their performance as wall materials to the microencapsulation of oils rich in polyunsaturated fatty acids. The cross-linking reaction of isolated soy protein and tannic acid was carried out at pH 10-11 and 60 °C. Subsequently, emulsions were made with a high-speed homogenizer and microcapsules were obtained by spray drying. Microcapsules were characterized by particle size, morphology (SEM), total pore area and % porosity (mercury intrusion methodology), superficial properties (contact angle), and size distribution of oil droplets (by laser diffraction). Additionally, encapsulation efficiency was determined as a function of total and surface oil. Oil chemical stability and quality were studied by Rancimat, hydroperoxide values, and fatty acid profiles. In addition, a storage test was performed for 180 days, and released oil and polyphenols were determined by in vitro gastric digestion. Moreover, the fatty acid composition of the oil and the total polyphenol content and antioxidant capacity of polyphenols were analyzed. The results showed that spray-dried microcapsules had an encapsulation efficiency between 54 and 78%. The oxidative stability exhibited a positive correlation between the amount of polyphenols used and the induction time, with a maximum of 27 h. The storage assay showed that the peroxide value was lower for those cross-linked microcapsules concerning control after 180 days. After the storage time, the omega-3 content was reduced by 49% for soy protein samples, while cross-linked microcapsules maintained the initial concentration. The in-vitro digestion assay showed a decrease in the amount of oil released from the cross-linked microcapsules and an increase in the amount of polyphenols and a higher antioxidant capacity for all samples (for example, 238.10 mgGAE/g and 554.22 mg TE/g for undigested microcapsules with TA 40% versus 322.09 mgGAE/g and 663.61 mg TE/g for digested samples). The microcapsules showed a high degree of protection of the encapsulated oil, providing a high content of polyunsaturated fatty acids (PUFAS) and polyphenols even in prolonged storage times.

Longitudinal anti-SARS-CoV-2 antibody immune response in acute and convalescent patients.

Despite global efforts to assess the early response and persistence of SARS-CoV-2 antibodies in patients infected with or recovered from COVID-19, our understanding of the factors affecting its dynamics remains limited. This work aimed to evaluate the early and convalescent immunity of outpatients infected with SARS-CoV-2 and to determine the factors that affect the dynamics and persistence of the IgM and IgG antibody response. Seropositivity of volunteers from Mexico City and the State of Mexico, Mexico, was evaluated by ELISA using the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein for 90 days, at different time points (1, 15, 45, 60, and 90 days) after molecular diagnosis (RT-qPCR). Gender, age range, body mass index (BMI), comorbidities, and clinical spectrum of disease were analyzed to determine associations with the dynamics of anti-SARS-CoV-2 antibodies. On 90 days post-infection, individuals with moderate and asymptomatic disease presented the lowest levels of IgM, while for IgG, at the same time, the highest levels occurred with mild and moderate disease. The IgM and IgG levels were related to the clinical spectrum of disease, BMI, and the presence/absence of comorbidities through regression trees. The results suggest that the dynamics of anti-SARS-CoV-2 IgM and IgG antibodies in outpatients could be influenced by the clinical spectrum of the disease. In addition, the persistence of antibodies against SARS-CoV-2 could be related to the clinical spectrum of the disease, BMI, and the presence/absence of comorbidities.

Acute exposure to fluoxetine leads to oxidative stress and hematological disorder in Danio rerio adults.

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is consistently introduced into the environment due to its ongoing consumption and inadequate removal by wastewater treatment plants. As a result, the scientific community has displayed a keen interest in investigating the potential toxicological effects associated with this medication. Nevertheless, there is a scarcity of available data regarding the impact of FLX on blood parameters. With this in mind, this study aimed to evaluate the potential toxicological consequences of FLX at environmentally significant concentrations (5, 16, and 40 ng/L) following a 96-hour acute exposure blood parameters in Danio rerio fish. Moreover, the investigation encompassed an assessment of oxidative stress parameters to determine whether the drug could induce disruptions in the REDOX status of the fish. The findings unveiled that FLX prompted the induction of oxidative stress in various organs of the fish, encompassing the liver, gut, brain, and gills. Notably, the gills and brain exhibited heightened susceptibility to the drug's effects compared to other organs. Furthermore, following acute exposure to FLX, there was an upregulation of antioxidant-related genes (sod, cat, gpx, nrf1, and nrf2), thereby providing additional evidence supporting the induction of oxidative stress in the organs of the fish. Lastly, FLX significantly impacted the customary values of various blood parameters, including glucose, blood urea nitrogen, alanine aminotransferase, alkaline phosphatase, red blood cell count, hemoglobin, and hematocrit. Thus, it can be inferred that FLX harmed the overall health status of the fish, resulting in the development of liver disease, anemia, and other associated illnesses.

Sustainable Process for Tortilla Production Using Ohmic Heating with Minimal Impact on the Nutritional Value, Protein, and Calcium Performance.

The nixtamalization process used for tortilla production entails extended processing time and generates pollutant effluents. Ohmic heating (OH) is an emerging technology that uses an alternating electric current for rapid and uniform food heating and mitigates effluent concerns. However, gaps exist in nutrient bioavailability studies. In this work, we assessed OH's impact on tortilla nutritional value, protein, and calcium using a rat model. Twenty-five male Wistar rats were fed one of four diets for 21 days: raw corn (RC) as an experimental control, OH-processed tortillas (OHTs), traditionally processed tortillas (TPTs), commercial tortillas (CTs), and a casein diet (CD) as a growth control. Despite similar protein and macronutrient profiles, OH significantly enhanced insoluble fiber content. The weight gain sequence was OHTs > TPTs > CTs > RC. OHTs exhibited superior protein digestibility (88.52%), which was 3% higher than other diets. The serum albumin (2.63-2.73 g/dL) indicated moderate malnutrition due to the tortilla's lower protein content. Nonetheless, the protein efficiency ratio (1.2-1.74) showed no significant difference from TPTs. Bone characteristics and fracture strength resembled the tortilla-fed groups, surpassing RC. X-ray diffraction and scanning electron microscopy confirmed that the OHT and TPT diets improved male rat bone thickness and crystallinity. The findings suggest the potential for OH as an eco-friendly tortilla production method, maintaining nutritional value comparable to traditional methods.

Changes in the physicochemical properties of isolated starch and plantain (Musa AAB Simmonds) flours for early maturity stage.

This work focuses on the study of the physicochemical changes that take place during the first stage of ripening of plantain, with particular attention to the changes in the orthorhombic and hexagonal nanocrystals present in this starch, and its relation shift with resistance starch. Significant changes were observed in the proximal analysis of plantain flour. A gradual increase in moisture content was attributed to the high content of crystalline structures and molecules that can be removed by drying. Water activity increased with ripening, which was attributed to the hygroscopic nature of the flours. The protein content increased, and the carbohydrate content decreased, indicating the progress of biochemical reactions. The changes in the fat content are consistent with the hydrolysis and resynthesis of lipids during the ripening process. The obtained results indicate a significant influence of the ripening stage on the physicochemical properties of flour and starch of plantain, which is associated with the occurrence of a climacteric peak on the 4th day of ripening. The hydration properties of plantain flour decreased significantly during the ripening days, consistent with the occurrence of a climacteric peak. Water holding capacity (WHC) and water binding capacity (WBC) were affected by the degree of digestion of native starch granules and protein denaturation during fruit ripening. Scanning electron microscopes (SEM) showed that during ripening the surface of the isolated starches do not suffer any significative damage. X-ray diffraction patterns were used to identify crystalline structures and to study the changes in the crystalline structures. These results showed that the starch contains orthorhombic and hexagonal nanocrystals, which play and important role and which show small structural damage during ripening reflected in a decrease in their relative crystallinity. This is the first time that these nanocrystals have been studied and considered in the ripening process. Differential scanning calorimetry was used to study the thermal transition in isolated starch. The results indicated that the gelatinization of starch corresponds to the solvation of orthorhombic and hexagonal nanocrystals, and that during ripening there is a decrease in the enthalpy reflecting some crystal structural damage. Pasting properties were studied using a Starch cell for flours and isolated starches, indicating that the pasting profile is governed by intrinsic and extrinsic factors. The resistant starch does not show significant changes at this stage of maturation. This starch is the one with the highest resistant starch content reported in the literature (38%). It was hypothesized that the resistant starch is directly related to the amount of whole starch granules, and more importantly, directly related to the number concentration of orthorhombic and hexagonal nanocrystals. Therefore, knowledge of the physicochemical and nutritional properties of plantain and flour at each stage of ripening allows better selection according to industrial applications.

Utilization of gallic acid-crosslinked soy proteins as wall material for chia oil microencapsulation.

BACKGROUND: Chia oil represents the vegetable source with the highest content of omega-3 fatty acids. However, the incorporation of polyunsaturated fatty acids into food is limited due to their susceptibility toward oxidation. This investigation aimed to study the microencapsulation of chia oil (CO), using gallic acid (GA) crosslinked-soy protein isolate (SPI) as a wall material and its effect on its oxidative stability. RESULTS: Microcapsules presented a moisture content, water activity, and encapsulation efficiency of around 2.95-4.51% (wet basis); 0.17 and 59.76-71.65%, respectively. Rancimat tests showed that with higher GA content, the induction period increased up to 27.9 h. The storage test demonstrated that the microencapsulated oil with crosslinked wall material has lower values of hydroperoxides and higher induction times concerning the non-crosslinked oil. Finally, the fatty acid profile at this storage time indicated that microcapsules with GA did not have significant changes. In vitro digestion exhibited a reduction in the percentage of bioavailable oil for crosslinked microcapsules, but with no variations in its chemical quality, and an increase in the total polyphenols amount and antioxidant activity. CONCLUSION: The results obtained demonstrated that the microencapsulation of CO using SPI crosslinked with GA as wall material exerted a very important protective effect since a synergistic effect could be described between the microencapsulation effect and the antioxidant power of GA. © 2023 Society of Chemical Industry.

Short-term exposure to dexamethasone at environmentally relevant concentrations impairs embryonic development in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.

In recent years and as a result of the Covid-19 pandemic, the consumption of dexamethasone (DXE) has increased. This favors that this corticosteroid is highly released in aquatic environments, generating deleterious effects in aquatic organisms. The information on the toxic effects of DXE in the environment is still limited. Thus, the objective of this work was to determine whether DXE at short-term exposure can cause alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of DXE until 96 hpf. Alterations to embryonic development were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that DXE concentrations above 35 ng/L are capable of producing alterations to embryonic development in 50 % of the embryo population. Furthermore, DXE was able to induce alterations such as scoliosis, hypopigmentation, craniofacial malformations, pericardial edema and growth retardation, leading to the death of half of the population at 50 ng/L of DXE. Concerning oxidative stress, the results demonstrated that DXE induce oxidative damage on the embryos of C. carpio. In conclusion, DXE is capable of altering embryonic development and generating oxidative stress in common carp C. carpio.

Acute exposure to realistic concentrations of Bisphenol-A trigger health damage in fish: Blood parameters, gene expression, oxidative stress.

Despite much information regarding BPA toxicity in fish and other aquatic organisms, data is still misleading as most studies have utilized concentrations several orders of magnitude higher than those typically found in the environment. As an illustration, eight of the ten studies investigating the impact of BPA on the biochemical and hematological parameters of fish have employed concentrations on the order of mg/L. Therefore, the results may not accurately represent the effects observed in the natural environment. Considering the information above, our study aimed to 1) determine whether or not realistic concentrations of BPA might alter the biochemical and blood parameters of Danio rerio and trigger an inflammatory response in the fish liver, brain, gills, and gut and 2) determine which organ could be more affected after exposure to this chemical. Findings pinpoint that realistic concentrations of BPA prompted a substantial increase in antioxidant and oxidant biomarkers in fish, triggering an oxidative stress response in all organs. Likewise, the expression of different genes related to inflammation and apoptosis response was significantly augmented in all organs. Our Pearson correlation shows gene expression was closely associated with the oxidative stress response. Regarding blood parameters, acute exposure to BPA generated biochemical and hematological parameters increased concentration-dependent. Thus, it can be concluded that BPA, at environmentally relevant concentrations, threatens aquatic species, as it prompts polychromasia and liver dysfunction in fish after acute exposure.

Oxidative stress as regulator of neuronal impairment after exposure to hospital effluents in Danio rerio.

The variety of activities carried out within hospitals results in their final discharges being considered hotspots for the emission of emerging pollutants. Hospital effluents contain different substances capable of altering the health of ecosystems and biota, furthermore, little research has been done to elucidate the adverse effects of these anthropogenic matrices. Taking this into account, herein we aimed to establish whether exposure to different proportions (2 %, 2.5 %, 3 %, and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) can induce oxidative stress, behavioral alterations, neurotoxicity, and disruption of gene expression in Danio rerio brain. Our results demonstrate that the hospital effluent under-study induces an anxiety-like state and alters swimming behavior, as fish exhibited increased freezing episodes, erratic movements and traveled less distance than the control group. In addition, after exposure we observed a meaningful rise in biomarkers related to oxidative damage, such as protein carbonyl content (PCC), lipoperoxidation level (LPX), hydroperoxide content (HPC), as well as an increase in enzyme antioxidant activities of catalase (CAT), and superoxide dismutase (SOD) upon short-term exposure. Moreover, we discovered an inhibition of acetylcholinesterase (AChE) activity in a hospital effluent proportion-dependent manner. Regarding gene expression, a significant disruption of genes related to antioxidant response (cat, sod, nrf2), apoptosis (casp6, bax, casp9), and detoxification (cyp1a1) was observed. In conclusion, our outcomes suggest that hospital effluents enhance the emergence of oxidative molecules, and promote a highly oxidative environment at the neuronal level that favors the inhibition of AChE activity, which consequently explains the anxiety-like behavior observed in D. rerio adults. Lastly, our research sheds light on possible toxicodynamic mechanism by which these anthropogenic matrices may trigger damage in D. rerio brain.

Integrative approach to elucidate the embryological effects of caffeine in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.

Caffeine (CAF) is an alkaloid, which acts as a central nervous system (CNS) stimulant drug. In recent years, CAF has been recurrently detected in water bodies, generating deleterious effects in aquatic organisms. The information on the toxic effects of CAF in the environment is still limited. Thus, the objective of this work was to determine whether CAF at environmentally relevant concentrations (CAF concentrations were selected based on studies on the worldwide occurrence of this compound and on the toxicity of CAF in aquatic species) is capable of inducing alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of CAF until 96 hpf. Alterations to embryonic development and teratogenic effects were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide content and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that CAF concentrations above 500 ng/L are capable of producing teratogenic effects. Furthermore, CAF was able to induce alterations such cardiac malformations, somite alterations, pericardial edema and chorda malformations. Concerning oxidative stress, the results demonstrated that CAF induce oxidative damage on the embryos of C. carpio. Our outcomes also showed up-regulations in genes related to antioxidant activity sod, cat and gpx by CAF exposure. In conclusion CAF at environmentally relevant concentrations is able to alter the embryonic development of common carp by the oxidative stress pathway. Based on the above evidence, it can be inferred that acute exposure to CAF can lead to a toxic response that significantly harms fish's health, adversely affecting their essential organs' functioning.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.