Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial.

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 107 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.

Specific IgA, But Not IgG, in Human Milk From COVID-19-infected Mothers Neutralizes SARS-CoV-2.

This study highlights the importance of human milk in providing anti-severe acute respiratory syndrome coronavirus 2 immunity to newborns. The highest protective activity of human milk against COVID-19 was found in colostrum from infected mothers. Neutralizing activity was associated with high levels of specific IgA. Depletion of IgA, but not IgG, from milk samples completely abolished the ability of human milk to neutralize severe acute respiratory syndrome coronavirus 2.

Actitudes asociadas a las prácticas de inyección de riesgo en personas que se inyectan drogas en Palma de Mallorca / Attitudes associated with risky injection practices in people who inject drugs in Palma de Mallorca

El objetivo de este estudio fue explorar las actitudes de las personas que se inyectan drogas (PID) y realizan prácticas de inyección de riesgo, identificando los factores subyacentes a su discurso que sustentan esas actitudes. Se planteó una investigación cualitativa con un diseño de grupos de discusión con PID (n = 34) y entrevistas a expertos(as) (n = 3). Los grupos y entrevistas fueron grabados, transcritos y analizados bajo el enfoque de la teoría fundamentada y el método del análisis temático. Se identificaron 17 categorías de riesgo, agrupadas en seis dimensiones: Consumo de drogas, Conocimiento, Confianza en otras personas, Acceso a jeringuillas nuevas, Situación personal y Azar. Estas dimensiones modularían la magnitud de las actitudes hacia las distintas prácticas de inyección de riesgo o actuarían como barreras que socavan la intención de las PID de inyectarse de manera segura. El discurso analizado sugiere que muchas PID han desarrollado actitudes poco negativas, neutras o incluso positivas hacia algunas prácticas de inyección de riesgo, principalmente hacia su realización en situaciones determinadas y aun conociendo las consecuencias negativas que estas entrañan. Proponer una descripción diferenciada de las actitudes asociadas a las prácticas de inyección de riesgo no sólo contribuye a profundizar en su explicación, sino que permitirá una mayor adecuación de los programas preventivos a las necesidades específicas de las PID. (AU)

The goal of this study was to explore the attitudes of people who inject drugs (PWID) and carry out risky practices, identifying underlying factors in their speech that sustain those attitudes. We proposed a qualitative research design with PWID focus groups (n = 34) and interviews with experts (n = 3). The interviews were recorded, transcribed, and analyzed following the principles of grounded theory and thematic analysis methodology. A total of 17 risk categories were identified and grouped into six dimensions: Drug Consumption, Knowledge, Trust In Other People, Access To Unused Syringues, Personal Situation, and Random. These dimensions would modulate the magnitude of the attitudes towards the different risky injection practices or act as barriers that limit the intention of PWID to inject themselves in a safe way. The analysis of the narratives suggests that many PWID have developed slightly negative, neutral, or even positive attitudes towards some risky injection practices, mainly towards carrying them out in certain situations and even when knowing of their negative consequences. Characterizing the attitudes associated with risky injection practices not only contributes to understanding them more thoroughly but will also allow preventive programs to be better suited to the specific needs of PWID. (AU)

Human milk immune factors, maternal nutritional status, and infant sex: The INSPIRE study.

OBJECTIVES: Breastfeeding is an energetically costly and intense form of human parental investment, providing sole-source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers-Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFß2, and IL-10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers-Willard hypothesis and consider the application of the hypothesis to milk composition. METHODS: We analyzed concentrations of immune factors in 358 milk samples collected from women residing in 10 international sites using linear mixed-effects models to test for an interaction between maternal condition, including population as a random effect and infant age and maternal age as fixed effects. RESULTS: IgG concentrations were significantly lower in milk produced by women consuming diets with low diversity with male infants than those with female infants. No other significant associations were identified. CONCLUSIONS: IgG concentrations were related to infant sex and maternal diet diversity, providing minimal support for the hypothesis. Given the lack of associations across other select immune factors, results suggest that the Trivers-Willard hypothesis may not be broadly applied to human milk immune factors as a measure of maternal investment, which are likely buffered against perturbations in maternal condition.

High-intensity interval training prevents muscle mass loss in overweight Chilean young adults during a hypocaloric-Mediterranean diet: a randomized trial.

The hypocaloric Mediterranean diet (MD) mainly reduces fat mass but inevitably causes a loss of skeletal muscle mass. High-intensity interval training (HIIT) seems to have advantages in preserving muscle mass during a hypocaloric regime. Our study compares body composition and metabolic changes in overweight and obese Chilean women and men after 3 months of weight loss treatment with a Mediterranean-type hypocaloric diet, HIIT, or a combination of both. The study included 83 overweight or obese women and men between the ages of 25 and 50. The subjects were randomly assigned to one of the three intervention groups: (1) MD, (2) EX, and (3) MD + EX. Baseline and post-intervention measurements included: (a) body composition by dual-beam densitometry, muscle, and fat measurements by thigh ultrasound and computed tomography; (b) handgrip and quadriceps muscle strength; (c) exercise performance by peak oxygen consumption, peak load, work efficiency, and exercise energy expenditure; and (d) metabolic parameters. Out of 83 participants, the retention rate was 49% due to low compliance with the interventions. As expected, the MD group resulted in significantly greater weight loss (MD -7%, EX -0.6% and MD + EX -5.3%) and appendicular fat mass loss (MD -11.1%, EX -2.9, MD + EX -10.2%) but was associated with significant lean tissue loss (2.8%), which was prevented by HIIT (EX -0.1 and MD + EX -0.6%). Metabolic and glycoxidative parameters remained unchanged, irrespective of changes in body composition. Hypocaloric diets remain the most effective means to lose weight and body fat. However, it induces a loss of lean body mass when not accompanied by exercise training. This study shows that HIIT prevents the loss of muscle mass caused by a hypocaloric Mediterranean diet.

Ligilactobacillus salivarius MP100 as an Alternative to Metaphylactic Antimicrobials in Swine: The Impact on Production Parameters and Meat Composition.

The metaphylactic use of antimicrobials in swine farms contributes to the emergence of antibiotic-resistant bacteria, which constitutes a major challenge for public health. Alternative strategies are required to eradicate their routine use. In a previous study, metaphylactic antimicrobials were replaced by the administration of Ligilactobacillus salivarius MP100 to sows and piglets for two years. This practice positively modified the fecal microbiota and metabolic profiles in the farm. In this work, the farm dataset was used to compare the productivity-related parameters between a 2-year period of routine metaphylactic antibiotherapy and the first 2 years of a replacement with the probiotic strain. The probiotic period improved these productivity-related parameters, from litter size to growth performance. In addition, samples of Longissimus lumborum, including skin and subcutaneous fat, were obtained from the animals ingesting the probiotic strain and controls (metaphylactic antibiotherapy) and analyzed for their pH, water holding capacity, composition, and metabolic profiling. The probiotic intake did not negatively affect the meat composition and was associated with an increase in inosine concentration and a slight tendency for increasing the intramuscular fat content. These factors are considered as biomarkers of meat quality. In conclusion, the substitution of metaphylactic antimicrobials with the administration of the probiotic strain was associated with beneficial productivity and meat quality outcomes.

A randomized pilot trial assessing the reduction of gout episodes in hyperuricemic patients by oral administration of Ligilactobacillus salivarius CECT 30632, a strain with the ability to degrade purines.

Introduction: Hyperuricemia and gout are receiving an increasing scientific and medical attention because of their relatively high prevalence and their association with relevant co-morbidities. Recently, it has been suggested that gout patients have an altered gut microbiota. The first objective of this study was to investigate the potential of some Ligilactobacillus salivarius strains to metabolize purine-related metabolites. The second objective was to evaluate the effect of administering a selected potential probiotic strain in individuals with a history of hyperuricemia. Methods: Inosine, guanosine, hypoxanthine, guanine, xanthine, and uric acid were identified and quantified by high-performance liquid chromatography analysis. The uptake and biotransformation of these compounds by a selection of L. salivarius strains were assessed using bacterial whole cells and cell-free extracts, respectively. The efficacy of L. salivarius CECT 30632 to prevent gout was assessed in a pilot randomized controlled clinical trial involving 30 patients with hyperuricemia and a history of recurrent gout episodes. Half of the patients consumed L. salivarius CECT 30632 (9 log10 CFU/day; probiotic group; n = 15) for 6 months while the remaining patients consumed allopurinol (100-300 mg/daily; control group; n = 15) for the same period. The clinical evolution and medical treatment received by the participants were followed, as well as the changes in several blood biochemical parameters. Results: L. salivarius CECT 30632 was the most efficient strain for inosine (100%), guanosine (100%) and uric acid (50%) conversion and, therefore, it was selected for the pilot clinical trial. In comparison with the control group, administration of L. salivarius CECT 30632 resulted in a significant reduction in the number of gout episodes and in the use of gout-related drugs as well as an improvement in some blood parameters related to oxidative stress, liver damage or metabolic syndrome. Conclusion: Regular administration of L. salivarius CECT 30632 reduced serum urate levels, the number of gout episodes and the pharmacological therapy required to control both hyperuricemia and gout episodes in individuals with a history of hyperuricemia and suffering from repeated episodes of gout.

Improving gene regulatory network inference and assessment: The importance of using network structure.

Gene regulatory networks are graph models representing cellular transcription events. Networks are far from complete due to time and resource consumption for experimental validation and curation of the interactions. Previous assessments have shown the modest performance of the available network inference methods based on gene expression data. Here, we study several caveats on the inference of regulatory networks and methods assessment through the quality of the input data and gold standard, and the assessment approach with a focus on the global structure of the network. We used synthetic and biological data for the predictions and experimentally-validated biological networks as the gold standard (ground truth). Standard performance metrics and graph structural properties suggest that methods inferring co-expression networks should no longer be assessed equally with those inferring regulatory interactions. While methods inferring regulatory interactions perform better in global regulatory network inference than co-expression-based methods, the latter is better suited to infer function-specific regulons and co-regulation networks. When merging expression data, the size increase should outweigh the noise inclusion and graph structure should be considered when integrating the inferences. We conclude with guidelines to take advantage of inference methods and their assessment based on the applications and available expression datasets.

Fabrication of Activated Carbon Decorated with ZnO Nanorod-Based Electrodes for Desalination of Brackish Water Using Capacitive Deionization Technology.

Capacitive deionization (CDI) is a promising and cost-effective technology that is currently being widely explored for removing dissolved ions from saline water. This research developed materials based on activated carbon (AC) materials modified with zinc oxide (ZnO) nanorods and used them as high-performance CDI electrodes for water desalination. The as-prepared electrodes were characterized by cyclic voltammetry, and their physical properties were studied through SEM and XRD. ZnO-coated AC electrodes revealed a better specific absorption capacity (SAC) and an average salt adsorption rate (ASAR) compared to pristine AC, specifically with values of 123.66 mg/g and 5.06 mg/g/min, respectively. The desalination process was conducted using a 0.4 M sodium chloride (NaCl) solution with flow rates from 45 mL/min to 105 mL/min under an applied potential of 1.2 V. Furthermore, the energy efficiency of the desalination process, the specific energy consumption (SEC), and the maximum and minimum of the effluent solution concentration were quantified using thermodynamic energy efficiency (TEE). Finally, this work suggested that AC/ZnO material has the potential to be utilized as a CDI electrode for the desalination of saline water.

Immunomodulation of the Vaginal Ecosystem by Ligilactobacillus salivarius CECT 30632 Improves Pregnancy Rates among Women with Infertility of Unknown Origin or Habitual Abortions.

In this study, the probiotic potential of Ligilactobacillus salivarius CECT 30632 was assessed, including properties specifically related with gynecological targets. This strain displayed co-aggregative and antimicrobial activity against a wide spectrum of vaginal pathogens while being respectful with the growth of vaginal lactobacilli. The strain produced a high concentration of lactic acid and displayed α-amylase activity when assayed in vitro. It showed a noticeable survival rate after exposition to conditions similar to those present in the human digestive tract and was adhesive to both vaginal and intestinal cells. Subsequently, their capacity to increase pregnancy rates among women with habitual abortion or infertility of unknown origin was studied. Administration of L. salivarius CECT 30632 (~9 log10 CFU) daily for a maximum of six months to these women was safe and led to a successful pregnancy rate of 67.5% (80% and 55% for women with repetitive abortion and infertile women, respectively). Significant differences in Nugent score, vaginal pH, and vaginal concentrations of lactobacilli, TGF-ß, and VEFG were observed when the samples collected before the intervention were compared with those collected after the treatment among those women who got pregnant. Therefore, this strain can modulate the vaginal ecosystem and lead to better fertility outcomes.

Hotspots of geogenic arsenic and manganese contamination in groundwater of the floodplains in lowland Amazonia (South America).

Arsenic enrichment in groundwater resources in deltas and floodplains of large sediment-rich rivers is a worldwide natural hazard to human health. High spatial variability of arsenic concentrations in affected river basins limits cost-effective mitigation strategies. Linking the chemical composition of groundwater with the topography and fluvial geomorphology is a promising approach for predicting arsenic pollution on a regional scale. Here we correlate the distribution of arsenic contaminated wells with the fluvial dynamics in the Amazon basin. Groundwater was sampled from tube wells along the Amazon River and its main tributaries in three distinct regions in Peru and Brazil. For each sample, the major and trace element concentrations were analyzed, and the position of the well within the sedimentary structure was determined. The results show that aquifers in poorly weathered sediments deposited by sediment-rich rivers are prone to mobilization and accumulation of aqueous arsenic and manganese, both in sub-Andean foreland basins, and in floodplains downstream. Two zones at risk are distinguished: aquifers in the channel-dominated part of the floodplain (CDF) and aquifers in the overbank deposits on the less-dynamic part of the floodplain (LDF). Some 70 % of the wells located on the CDF and 20 % on the LDF tap groundwater at concentrations exceeding the WHO guideline of 10 µg/L arsenic (max. 430 µg/L), and 70 % (CDF) and 50 % (LDF) exceeded 0.4 mg/L manganese (max. 6.6 mg/L). None of the water samples located outside the actual floodplain of sediment-rich rivers, or on riverbanks of sediment-poor rivers exceed 5 µg/L As, and only 4 % exceeded 0.4 mg/L Mn. The areas of highest risk can be delineated using satellite imagery. We observe similar patterns as in affected river basins in South and Southeast Asia indicating a key role of sedimentation processes and fluvial geomorphology in priming arsenic and manganese contamination in aquifers.

Attitudes associated with risky injection practices in people who inject drugs in Palma de Mallorca. / Actitudes asociadas a las prácticas de inyección de riesgo en personas que se inyectan drogas en Palma de Mallorca.

The goal of this study was to explore the attitudes of people who inject drugs (PWID) and carry out risky practices, identifying underlying factors in their speech that sustain those attitudes. We proposed a qualitative research design with PWID focus groups (n = 34) and interviews with experts (n = 3). The interviews were recorded, transcribed, and analyzed following the principles of grounded theory and thematic analysis methodology. A total of 17 risk categories were identified and grouped into six dimensions: Drug Consumption, Knowledge, Trust In Other People, Access To Unused Syringues, Personal Situation, and Random. These dimensions would modulate the magnitude of the attitudes towards the different risky injection practices or act as barriers that limit the intention of PWID to inject themselves in a safe way. The analysis of the narratives suggests that many PWID have developed slightly negative, neutral, or even positive attitudes towards some risky injection practices, mainly towards carrying them out in certain situations and even when knowing of their negative consequences. Characterizing the attitudes associated with risky injection practices not only contributes to understanding them more thoroughly but will also allow preventive programs to be better suited to the specific needs of PWID.

El objetivo de este estudio fue explorar las actitudes de las personas que se inyectan drogas (PID) y realizan prácticas de inyección de riesgo, identificando los factores subyacentes a su discurso que sustentan esas actitudes. Se planteó una investigación cualitativa con un diseño de grupos de discusión con PID (n = 34) y entrevistas a expertos(as) (n = 3). Los grupos y entrevistas fueron grabados, transcritos y analizados bajo el enfoque de la teoría fundamentada y el método del análisis temático. Se identificaron 17 categorías de riesgo, agrupadas en seis dimensiones: Consumo de drogas, Conocimiento, Confianza en otras personas, Acceso a jeringuillas nuevas, Situación personal y Azar. Estas dimensiones modularían la magnitud de las actitudes hacia las distintas prácticas de inyección de riesgo o actuarían como barreras que socavan la intención de las PID de inyectarse de manera segura. El discurso analizado sugiere que muchas PID han desarrollado actitudes poco negativas, neutras o incluso positivas hacia algunas prácticas de inyección de riesgo, principalmente hacia su realización en situaciones determinadas y aun conociendo las consecuencias negativas que estas entrañan. Proponer una descripción diferenciada de las actitudes asociadas a las prácticas de inyección de riesgo no sólo contribuye a profundizar en su explicación, sino que permitirá una mayor adecuación de los programas preventivos a las necesidades específicas de las PID.

Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty.

Orthologs separate after lineages split from each other and paralogs after gene duplications. Thus, orthologs are expected to remain more functionally coherent across lineages, while paralogs have been proposed as a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS), as proxy for functional divergence. We used five working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering. The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, suggesting that orthologs generally tend to be more functionally stable than paralogs. The differences in dN/dS ratios remained suggesting the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes with high codon usage biases, low coverage of either of the aligned sequences, or sequences with very high similarities. Separation by percent identity of the encoded proteins showed that the differences between the dN/dS ratios of orthologs and paralogs were more evident at high sequence identity, less so as identity dropped. The last results suggest that the differences between dN/dS ratios were partially related to differences in protein identity. However, they also suggested that paralogs undergo functional divergence relatively early after duplication. Our analyses indicate that choosing orthologs as probably functionally coherent remains the right approach in comparative genomics.

Active revegetation after mining: what is the contribution of peer-reviewed studies?

Knowing the state of the art on research related to post-mining active revegetation can help to improve revegetation success and identify research gaps. We performed a systematic review about active revegetation after mining and identified 203 relevant studies. Most studies were performed in the USA (34%), in regions with a temperate climate (59%) and in abandoned coal mines (45%). The studies were focused on the plantation of woody species (59%) or sowing of herbaceous species (39%). The most widely evaluated treatments were the addition of amendments (24%) and fertilizers (21%), mainly with positive and neutral effects; in general, organic amendments presented more positive effects than inorganic amendments and fertilizers. We also identified studies on the effects of plowing, inoculation of microorganisms, nurse plants, herbivore exclusion and watering. The results of these treatments should be taken with caution, because they can vary according to the functional strategies of the introduced species and the local context, such as the degree of nutrient limitation in the mining area and abiotic conditions. Further research is needed in non-temperate climates, involving long-term monitoring and with detailed descriptions of the interventions to better interpret results and general implications of active revegetation of mining areas.

Desalination Using the Capacitive Deionization Technology with Graphite/AC Electrodes: Effect of the Flow Rate and Electrode Thickness.

Capacitive deionization (CDI) is an emerging water desalination technology whose principle lies in ion electrosorption at the surface of a pair of electrically charged electrodes. The aim of this study was to obtain the best performance of a CDI cell made of activated carbon as the active material for water desalination. In this work, electrodes of different active layer thicknesses were fabricated from a slurry of activated carbon deposited on graphite sheets. The as-prepared electrodes were characterized by cyclic voltammetry, and their physical properties were also studied using SEM and DRX. A CDI cell was fabricated with nine pairs of electrodes with the highest specific capacitance. The effect of the flow rate on the electrochemical performance of the CDI cell operating in charge-discharge electrochemical cycling was analyzed. We obtained a specific absorption capacity (SAC) of 10.2 mg/g and a specific energetic consumption (SEC) of 217.8 Wh/m3 at a flow rate of 55 mL/min. These results were contrasted with those available in the literature; in addition, other parameters such as Neff and SAR, which are necessary for the characterization and optimal operating conditions of the CDI cell, were analyzed. The findings from this study lay the groundwork for future research and increase the existing knowledge on CDI based on activated carbon electrodes.

SMART-LAMP: A Smartphone-Operated Handheld Device for Real-Time Colorimetric Point-of-Care Diagnosis of Infectious Diseases via Loop-Mediated Isothermal Amplification.

Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.

System Principles Governing the Organization, Architecture, Dynamics, and Evolution of Gene Regulatory Networks.

Synthetic biology aims to apply engineering principles for the rational, systematical design and construction of biological systems displaying functions that do not exist in nature or even building a cell from scratch. Understanding how molecular entities interconnect, work, and evolve in an organism is pivotal to this aim. Here, we summarize and discuss some historical organizing principles identified in bacterial gene regulatory networks. We propose a new layer, the concilion, which is the group of structural genes and their local regulators responsible for a single function that, organized hierarchically, coordinate a response in a way reminiscent of the deliberation and negotiation that take place in a council. We then highlight the importance that the network structure has, and discuss that the natural decomposition approach has unveiled the system-level elements shaping a common functional architecture governing bacterial regulatory networks. We discuss the incompleteness of gene regulatory networks and the need for network inference and benchmarking standardization. We point out the importance that using the network structural properties showed to improve network inference. We discuss the advances and controversies regarding the consistency between reconstructions of regulatory networks and expression data. We then discuss some perspectives on the necessity of studying regulatory networks, considering the interactions' strength distribution, the challenges to studying these interactions' strength, and the corresponding effects on network structure and dynamics. Finally, we explore the ability of evolutionary systems biology studies to provide insights into how evolution shapes functional architecture despite the high evolutionary plasticity of regulatory networks.

Glucocorticoid Receptor ß Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism.

Glucocorticoids (GC) are steroids hormones that drive circulating glucose availability through gluconeogenesis in the liver. However, alternative splicing of the GR mRNA produces two isoforms, termed GRα and GRß. GRα is the classic receptor that binds to GCs and mediates the most described actions of GCs. GRß does not bind GCs and acts as a dominant-negative inhibitor of GRα. Moreover, GRß has intrinsic and GRα-independent transcriptional activity. To date, it remains unknown if GRß modulates glucose handling in hepatocytes. Therefore, the study aims to characterize the impact of GRß overexpression on glucose uptake and storage using an in vitro hepatocyte model. Here we show that GRß overexpression inhibits the induction of gluconeogenic genes by dexamethasone. Moreover, GRß activates the Akt pathway, increases glucose transports mRNA, increasing glucose uptake and glycogen storage as an insulin-mimetic. Our results suggest that GRß has agonist-independent insulin-mimetic actions in HepG2 cells.

Interactions between human milk oligosaccharides, microbiota and immune factors in milk of women with and without mastitis.

Lactational mastitis is an excellent target to study possible interactions between HMOs, immune factors and milk microbiota due to the infectious and inflammatory nature of this condition. In this work, microbiological, immunological and HMO profiles of milk samples from women with (MW) or without (HW) mastitis were compared. Secretor status in women (based on HMO profile) was not associated to mastitis. DFLNH, LNFP II and LSTb concentrations in milk were higher in samples from HW than from MW among Secretor women. Milk from HW was characterized by a low bacterial load (dominated by Staphylococcus epidermidis and streptococci), high prevalence of IL10 and IL13, and low sialylated HMO concentration. In contrast, high levels of staphylococci, streptococci, IFNγ and IL12 characterized milk from MW. A comparison between subacute (SAM) and acute (AM) mastitis cases revealed differences related to the etiological agent (S. epidermidis in SAM; Staphylococcus aureus in AM), milk immunological profile (high content of IL10 and IL13 in SAM and IL2 in AM) and milk HMOs profile (high content of 3FL in SAM and of LNT, LNnT, and LSTc in AM). These results suggest that microbiological, immunological and HMOs profiles of milk are related to mammary health of women.

Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder.

Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.