Kisspeptin signaling in astrocytes modulates the reproductive axis.

Reproduction is safeguarded by multiple, often cooperative regulatory networks. Kisspeptin signaling, via KISS1R, plays a fundamental role in reproductive control, primarily by regulation of hypothalamic GnRH neurons. We disclose herein a pathway for direct kisspeptin actions in astrocytes that contributes to central reproductive modulation. Protein-protein-interaction and ontology analyses of hypothalamic proteomic profiles after kisspeptin stimulation revealed that glial/astrocyte markers are regulated by kisspeptin in mice. This glial-kisspeptin pathway was validated by the demonstrated expression of Kiss1r in mouse astrocytes in vivo and astrocyte cultures from humans, rats and mice, where kisspeptin activated canonical intracellular signaling-pathways. Cellular co-expression of Kiss1r with the astrocyte markers, GFAP and S100-ß, occurred in different brain regions, with higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells, in the G-KiRKO mouse, altered gene expression of key factors in PGE2 synthesis in astrocytes, and perturbed astrocyte-GnRH neuronal appositions, as well as LH responses to kisspeptin and LH pulsatility, as surrogate marker of GnRH secretion. G-KiRKO mice also displayed changes in reproductive responses to metabolic stress induced by high-fat diet, affecting female pubertal onset, estrous cyclicity and LH-secretory profiles. Our data unveil a non-neuronal pathway for kisspeptin actions in astrocytes, which cooperates in fine-tuning the reproductive axis and its responses to metabolic stress.

The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

BACKGROUND: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown. METHODS: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models. RESULTS: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats. CONCLUSIONS: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity. SIGNIFICANCE STATEMENT: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.

An Overview on Flavor Extraction, Antimicrobial and Antioxidant Significance, and Production of Herbal Wines.

Wine has been utilized as a source for medicinal preparations, combined with various herbs, to treat particular ailments and disorders. By utilizing herb extracts, regular but limited consumption of these herbal wines helps to decrease the need for prescription medications to treat a variety of ailments. The diversity and the composition of the yeast micropopulation significantly contribute to the sensory characteristics of wine. A particular metabolic activity characterizes the growth of each wine yeast species, which determines the concentrations of flavor compounds in the final wine. Numerous herbs, such as tulsi, ginger, aloe vera, tea, amla, lemongrass, and peppermint, are used in the preparation of herbal wines, where either the herb or herbal blends are primarily used as the substrate. The variants provided improved accuracy, increased acceptability, and broader uses for the novel product. Herbal wines pave the way to provide nutraceuticals to consumers and protection against pathogenic microorganisms and inflammation through their richness in antioxidants. The existing herbal wines and their health advantages are discussed in this Review, along with some new directions for the herbal wine business.

Grape Pomace-Advances in Its Bioactivity, Health Benefits, and Food Applications.

From a circular economy perspective, the appropriate management and valorization of winery wastes and by-products are crucial for sustainable development. Nowadays, grape pomace (GP) has attracted increasing interest within the food field due to its valuable content, comprising nutritional and bioactive compounds (e.g., polyphenols, organic and fatty acids, vitamins, etc.). Particularly, GP polyphenols have been recognized as exhibiting technological and health-promoting effects in different food and biological systems. Hence, GP valorization is a step toward offering new functional foods and contributing to solving waste management problems in the wine industry. On this basis, the use of GP as a food additive/ingredient in the development of novel products with technological and functional advantages has recently been proposed. In this review, we summarize the current knowledge on the bioactivity and health-promoting effects of polyphenolic-rich extracts from GP samples. Advances in GP incorporation into food formulations (enhancement of physicochemical, sensory, and nutritional quality) and information supporting the intellectual property related to GP potential applications in the food industry are also discussed.

Chitosan for the treatment of inflammationof the oral mucosa: A systematic review / Chitosán para el tratamiento de la inflamación de la mucosa oral: una revisión sistemática

Background: Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, thispolysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosanapplications in the dentistry field has been explored. This work aimed to conduct a systematic review to addressthe clinical efficacy of chitosan for the treatment of oral mucositis.Material and Methods: The design of the included studies were observational studies, randomized clinical trials(RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies wereexcluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source,and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies wererecorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Devel-opment, and Evaluation, GRADE) assessments were carried out.Results: From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a totalof 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibiteda high risk of bias. The quality of the studies was between low and very low.Conclusions: The results of the included studies suggest that chitosan can diminish pain and improve the healingof ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oralmucositis compared with other current therapies.(AU)

Encuesta burnout (¿estás quemado?) en Especialistas de Cardiología SAC / Burnout Survey among SAC Cardiologists

RESUMEN Introducción. Los profesionales de la salud se encuentran expuestos a un fenómeno ocupacional que resulta del estrés crónico en el ámbito laboral llamado síndrome de burnout (SBO). Este se ha convertido en uno de los riesgos laborales psicosociales más importantes en la sociedad actual y genera costos significativos en el ámbito de la salud. Objetivos. Evaluar la prevalencia de SBO por percepción subjetiva y mediante la aplicación del inventario del síndrome del Desgaste Ocupacional "Burnout" de Maslach (MBI) en los especialistas de cardiología del padrón de la Sociedad Argentina de Cardiología (SAC), y las diferencias acordes al sexo. Material y métodos. Estudio observacional, de corte transversal, mediante una encuesta anónima realizada en abril de 2023 a los especialistas del padrón SAC. Se recabaron datos sobre impresión subjetiva de SBO (sentirse "quemado"), sexo, edad, tiempo de ejercicio profesional. Fue opcional completar el inventario MBI (subescalas) para establecer el diagnóstico de burnout. Resultados. Participaron 756 profesionales, 51,4 % fueron mujeres. El 62 % tenían más de 40 años y el 61 % tenía más de 10 años de ejercicio profesional. Del total de médicos encuestados, el 94,4 % eligió realizar el test de Maslach (MBI), siendo esto más frecuente en las mujeres (96,6 % vs 91,3 %, p < 0,001). La prevalencia de SBO por un MBI de alto puntaje (≥67puntos) fue del 75 % y la prevalencia de percepción de SBO fue del 69 % (p < 0,001). De los que se autopercibieron "quemados" (69 %), el 96,8 % contestó el inventario MBI y se confirmó el diagnóstico de SBO por MBI de alto puntaje en el 78 %. De los que se autopercibieron "no quemados" (31 %), el 89,3 % completó el inventario MBI con diagnóstico de SBO en la subescala cansancio emocional (24 %), despersonalización (18 %) y realización personal (10 %) más allá de no tener la impresión subjetiva de estar "quemado". Los menores de 40 años tuvieron más SBO por MBI de alto puntaje (50 % vs 28 %, p= 0,001) al igual que los profesionales con menos de 10 años en el ejercicio de su profesión (45 % vs 20 % en aquellos con tiempo mayor, p < 0,001). El SBO fue más prevalente en las mujeres que en los hombres, tanto por autopercepción (77 % vs 56 %, p < 0,001) como por el inventario de Maslach (80 % vs 74 %, p=0,001), específicamente en la subescala agotamiento emocional (37 % vs 29 %; p < 0,001) y realización personal (37 % vs 41 %, p < 0,001), sin diferencias por sexo en la esfera de despersonalización. Conclusión. El SBO tiene alta prevalencia entre los cardiólogos encuestados, principalmente en mujeres, tanto por autopercepción como por aplicación del inventario MBI. Por otro lado 1 de cada 4 profesionales encuestados que no se autopercibían "quemados" tuvieron un test positivo para SBO. Teniendo en cuenta la alta prevalencia de SBO entre los especialistas en cardiología es imperioso realizar acciones de prevención e intervención concertadas y sostenidas para transformar esta realidad que impacta desfavorablemente tanto en la salud de los pacientes como en la de los propios médicos.

ABSTRACT Background. Healthcare professionals are exposed to an occupational phenomenon as a result of chronic stress in the workplace called burnout syndrome (BOS). Burnout has become one of the most important psychosocial occupational hazards today and generates significant health care costs. Objectives. The aim of our study was to evaluate the subjective perception of the prevalence of BOS among cardiologists of the Argentine Society of Cardiology (SAC) using Maslach Burnout Inventory (MBI), and the differences between sexes. Methods. We conducted an observational, cross-sectional study using an anonymous survey distributed among specialists of the SAC register in April 2023. The information collected included the subjective impression of BOS (feeling "burned out"), sex, age and years of practice. The participants could optionally complete the MBI (subscales) to establish the diagnosis of BOS. Results. A total of 756 professionals participated in the survey; 51.4% were women. Sixty-two percent of the participants were >40 years old, and 61 % had been practicing medicine for more than 10 years. Of all the physicians surveyed, 94.4% completed the MBI, with women more likely to do so than men (96.6% vs. 91.3%, p < 0.001). The prevalence of BOS, assessed by a high MBI score (≥ 67), was 75%, while 69% reported feeling burned out (p < 0.001). Of those who felt burned out (69 %), 96.8 % completed the MBI, and 78% of them received a diagnosis of BOS based on high MBI scores. Of the 31 % who did not feel burned out, 89.3 % completed the MBI. Burnout syndrome was diagnosed in the emotional exhaustion subscale in 24 %, in the depersonalization subscale in 18%, and in the personal accomplishment subscale in 10%. The diagnosis of BOS made by high MBI score was more common in survey participants under 40 years than in older participants (50 % vs. 28 %, p < 0.001) and in professionals who have been practicing medicine for less than 10 years (45 % vs. 20 % in those with more years of practice, p < 0.001). Women were more likely to experience BOS according to their own perception (77 % vs. 56 %, p < 0.001) and MBI score (80 % vs. 74 %, p < 0.001), specifically in the emotional exhaustion (37 % vs. 29 %, p < 0.001) and personal accomplishment (37 % vs. 41 %, p < 0.001) subscales, with No differences by sex in the depersonalization sphere. Conclusion. Burnout syndrome was found to be prevalent among the surveyed cardiologists, particularly in female participants, as indicated by both their own perception and the MBI assessment. In addition, 1 out of 4 professionals surveyed who did not feel "burned out" tested positive for BOS. Given the high prevalence of BOS among cardiologists, coordinated and sustained prevention and intervention actions should be undertaken to change this reality that negatively impacts both patient and physician health.

Partial characterization of canola (Brassica napus L.) protein isolates as affected by extraction and purification methods.

Canola (Brassica napus L.) meal represents a prominent alternative plant-based source for protein isolation. This work aimed to investigate the combined effect of extraction and purification methods for the production of canola protein isolates (CPIs). CPIs were characterized in terms of process yield, protein recovery, basic composition, amino acid profile, in vitro protein digestibility, techno-functional properties, structural properties, and molecular features. The results showed that the Alk-Uf method enhanced yield (16.23 %) and protein recovery (34.88 %). Meanwhile, the Et-Alk-Uf method exhibited the highest crude protein (89.71 %) and free amino nitrogen (4.34 mg g protein-1) contents. Furthermore, protein digestibility (95.5 %) and protein digestibility corrected amino acid score (1.0) were improved using the Et-Alk-Ac method. Conversely, the amino acid composition, secondary structure, and electrophoretic profiles were generally similar for all CPIs. The Alk-Uf and Et-Alk-Uf methods produced isolates with the highest water solubility (∼39.18 %), water absorption capacity (∼3.86 g water g protein-1), oil absorption capacity (∼2.77 g oil g protein-1), and foaming capacity (∼505.26 %). Finally, the foaming stability (93.75 %) and foaming density (34.38 %) were increased when employing the Alk-Ac method. These findings suggest that, in general, the Alk-Uf and Et-Alk-Uf methods can be used to obtain CPIs with high added value for use in food formulations.

Unravelling the functional development of vertebrate pathways controlling gaze.

Animals constantly redirect their gaze away or towards relevant targets and, besides these goal-oriented responses, stabilizing movements clamp the visual scene avoiding image blurring. The vestibulo-ocular (VOR) and the optokinetic reflexes are the main contributors to gaze stabilization, whereas the optic tectum integrates multisensory information and generates orienting/evasive gaze movements in all vertebrates. Lampreys show a unique stepwise development of the visual system whose understanding provides important insights into the evolution and development of vertebrate vision. Although the developmental emergence of the visual components, and the retinofugal pathways have been described, the functional development of the visual system and the development of the downstream pathways controlling gaze are still unknown. Here, we show that VOR followed by light-evoked eye movements are the first to appear already in larvae, despite their burrowed lifestyle. However, the circuits controlling goal-oriented responses emerge later, in larvae in non-parasitic lampreys but during late metamorphosis in parasitic lampreys. The appearance of stabilizing responses earlier than goal-oriented in the lamprey development shows a stepwise transition from simpler to more complex visual systems, offering a unique opportunity to isolate the functioning of their underlying circuits.

Chitosan-Based Nanogels Designed for Betanin-Rich Beetroot Extract Transport: Physicochemical and Biological Aspects.

Nanotechnology has emerged as a possible solution to improve phytochemicals' limitations. The objective of the present study was to encapsulate beetroot extract (BR Ext) within a chitosan (CS)-based nanogel (NG) designed via ionic crosslinking with tripolyphosphate (TPP) for betanin (Bet) delivery, mainly in the ophthalmic environment. BR Ext is rich in betanin (Bet) according to thin layer chromatography (TLC), UV-visible spectroscopy, and HPLC analysis. NG presented a monodisperse profile with a size of 166 ± 6 nm and low polydispersity (0.30 ± 0.03). ζ potential (ζ-Pot) of +28 ± 1 is indicative of a colloidally stable system. BR Ext encapsulation efficiency (EE) was 45 ± 3%. TEM, with the respective 3D-surface plots and AFM, showed spherical-elliptical-shaped NG. The BR Ext release profile was biphasic with a burst release followed by slow and sustained phase over 12 h. Mucoadhesion assay demonstrated interactions between NG with mucin. Moreover, NG provided photoprotection and pH stability to BR Ext. FRAP and ABTS assays confirmed that BR Ext maintained antioxidant activity into NG. Furthermore, in vitro assays using human retinal cells displayed absence of cytotoxicity as well as an efficient protection against injury agents (LPS and H2O2). NGs are a promising platform for BR Ext encapsulation, exerting controlled release for ophthalmological use.

[Reported prevalence of dental caries in Mexican children and teenagers]. / Prevalencia reportada de caries dental en niños y adolescentes mexicanos.

Dental caries is a serious multifactorial oral disease that causes demineralization of the tooth's hard tissues and affects more than half of the world's population. The objective of this exploratory systematic review was to determine the prevalence of dental caries in Mexican children and adolescents, as well as related factors such as sex, nutritional status, type of dentition, education, living conditions, socioeconomic level, and the type of demographic area. The eligibility criteria to be considered were observational studies whose sample included Mexicans 0-15 years of age in which the prevalence or an index of dental caries had been evaluated. Eligible studies were identified through the search carried out in 6 databases and manual search, without publication time restriction. Fifty-four studies were found that met the eligibility criteria. In these included studies it was observed that, in the last decades, the prevalence of caries in Mexican children and adolescents exhibits a tendency to decrease this disease. In the 1980s, caries prevalences of up to 92.8% were reported; between 1990-1999, the highest reported prevalence was 97%; from 2000-2009, the highest reported prevalence was 95%; from 2010 to 2019 the highest prevalence was 94.6%; and from 2020 and 2021, prevalences of up to 88.5% were reported. Although there has been a decrease in the prevalence of caries in Mexican children, this disease continues to be linked to biological, behavioral and socioeconomic determinants.

La caries dental es una enfermedad bucodental multifactorial grave que provoca la desmineralización de los tejidos duros del diente y afecta a más de la mitad de la población mundial. El objetivo de esta revisión sistemática exploratoria fue determinar la prevalencia de caries dental en niños y adolescentes mexicanos, así como los factores relacionados como el sexo, el estado nutricional, el tipo de dentición, la educación, las condiciones de vida, el nivel socioeconómico y el tipo de área demográfica. Los criterios de elegibilidad fueron estudios observacionales cuya muestra incluyera mexicanos de 0 a 15 años en los que se hubiera evaluado la prevalencia o un índice de caries dental. Los estudios elegibles fueron identificados mediante la búsqueda realizada en 6 bases de datos y de manera manual, sin restricción de tiempo de publicación. Se encontraron 54 estudios que cumplieron con los criterios de elegibilidad. En estos estudios incluidos se observó que en las últimas décadas la prevalencia de caries en niños y adolescentes mexicanos exhibe una tendencia a la baja. En la década de 1980, se reportaron prevalencias de caries de hasta 92.8%; entre 1990-1999, la mayor prevalencia reportada fue de 97%; de 2000-2009, la prevalencia más alta reportada fue de 95%; de 2010 a 2019 la mayor prevalencia fue de 94.6%; y de 2020 y 2021, se reportaron prevalencias de hasta 88.5%. Aunque ha habido un decremento en la prevalencia de caries en niños mexicanos, esta enfermedad continúa vinculada a determinantes biológicas, conductuales y socioeconómicas.

Potential probiotic lactobacilli strains isolated from artisanal Mexican Cocido cheese: evidence-based biosafety and probiotic action-related traits on in vitro tests.

The biosafety of four potentially probiotic lactobacilli strains, isolated from artisanal Mexican Cocido cheese, was assessed through in vitro tests aimed to determine (1) the antibiotic susceptibility profile by broth microdilution, (2) the transferability of antibiotic resistance determinants by filter-mating, and (3) the phenotypic and genotypic stability during serial batch sub-culture (100-day period) by evaluating physiological and probiotic features and RAPD-PCR fingerprinting. Lactobacilli strains exhibited multidrug-resistance; however, resistance determinants were not transferred in the filter-mating assay. Significant (p < 0.05) differences were observed in bacterial morphology and some functional and technological properties when strains were serially sub-cultured over 50 generations (G50), compared to the initial cultures (G0). Conversely, the strains did not show mucinolytic and hemolytic activities either at G0 or after 100 generations (G100). Genetic polymorphism and genomic template instability on selected strains were detected, which suggest possible evolutionary arrangements that may occur when these bacteria are largely cultured. Our findings suggest that the assessed strains did not raise in vitro biosafety concerns; however, complementary studies are still needed to establish the safe potential applications in humans and animals.

Benzoxaborole-grafted high molecular weight chitosan from prawn: Synthesis, characterization, target recognition and antibacterial properties.

Boronated polymers are in the focus of dynamic functional materials due to the versatility of the B-O interactions and accessibility of precursors. Polysaccharides are highly biocompatible, and therefore, an attractive platform for anchoring boronic acid groups for further bioconjugation of cis-diol containing molecules. We report for the first time the introduction of benzoxaborole by amidation of the amino groups of chitosan improving solubility and introducing cis-diol recognition at physiological pH. The chemical structures and physical properties of the novel chitosan-benzoxaborole (CS-Bx) as well as two phenylboronic derivatives synthesized for comparison, were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), rheology and optical spectroscopic methods. The novel benzoxaborole grafted chitosan was perfectly solubilized in an aqueous buffer at physiological pH, extending the possibilities of boronated materials derived from polysaccharides. The dynamic covalent interaction between boronated chitosan and model affinity ligands, was studied by means of spectroscopy methods. A glycopolymer derived from poly(isobutylene-alt-anhydride) was also synthesized to study the formation of dynamic assemblies with benzoxaborole-grafted chitosan. A first approximation to apply fluorescence microscale thermophoresis for the interactions of the modified polysaccharide is also discussed. Additionally, the activity of CSBx against bacterial adhesion was studied.

Emerging Technologies to Extract Fucoxanthin from Undaria pinnatifida: Microwave vs. Ultrasound Assisted Extractions.

Macroalgae are an extensive resource for the obtention of bioactive compounds, mainly phenolic compounds, phlorotannins, and pigments. Fucoxanthin (Fx) is the most abundant pigment present in brown algae and has shown several useful bioactivities that can be used to fortify products in the food and cosmetic industries. Nevertheless, to date, there is still insufficient literature reporting on the extraction yield of Fx from U. pinnatifida species from green technologies. In this regard, the present study aims to optimize the extraction conditions to obtain the highest Fx yield from U. pinnatifida through emerging techniques, namely microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE). These methods will be compared with the conventional methodologies of heat-assisted extraction (HAE) and Soxhlet-assisted extraction (SAE). According to our results, even though the extraction yield could be slightly higher when using MAE than UAE, the Fx concentration obtained from the alga was double when using UAE. Thus, the Fx ratio in the final extract reached values of 124.39 mg Fx/g E. However, the optimal conditions should also be considered since UAE needed 30 min to perform the extraction, whereas MAE was able to obtain 58.83 mg Fx/g E in only 3 min and 2 bar, meaning less energy expenditure and minimum cost function. To our knowledge, this study obtains the highest concentrations of Fx ever reported (58.83 mg Fx/g E for MAE and 124.39 mg Fx/g E for UAE), with low energy consumption and short times (3.00 min for MAE and 35.16 min for UAE). Any of these results could be selected for further experiments and proposed for industrial scaling-up.

Arginine Methylation of the PGC-1α C-Terminus Is Temperature-Dependent.

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. Various fragments of PGC-1α corresponding to the C-terminus were used as substrates, and the methylation reactions were analyzed by fluorography and mass spectrometry to determine the extent of methylation throughout the substrates, the location of the methylated PGC-1α arginine residues, and finally, whether temperature affects the deposition of methyl groups. We also employed two prediction programs, PRmePRed and MePred-RF, to search for putative methyltransferase sites. Methylation reactions show that arginine residues R548 and R753 in PGC-1α are methylated at or below 30 °C by PRMT7, while methylation by PRMT1 was detected at these same residues at 30 °C. Computational approaches yielded additional putative methylarginine sites, indicating that since PGC-1α is an intrinsically disordered protein, additional methylated arginine residues have yet to be experimentally verified. We conclude that temperature affects the extent of arginine methylation, with more methylation by PRMT7 occurring below physiological temperature, uncovering an additional control point for PGC-1α.

Key Stress Response Mechanisms of Probiotics During Their Journey Through the Digestive System: A Review.

The survival of probiotic microorganisms during their exposure to harsh environments plays a critical role in the fulfillment of their functional properties. In particular, transit through the human gastrointestinal tract (GIT) is considered one of the most challenging habitats that probiotics must endure, because of the particularly stressful conditions (e.g., oxygen level, pH variations, nutrient limitations, high osmolarity, oxidation, peristalsis) prevailing in the different sections of the GIT, which in turn can affect the growth, viability, physiological status, and functionality of microbial cells. Consequently, probiotics have developed a series of strategies, called "mechanisms of stress response," to protect themselves from these adverse conditions. Such mechanisms may include but are not limited to the induction of new metabolic pathways, formation/production of particular metabolites, and changes of transcription rates. It should be highlighted that some of such mechanisms can be conserved across several different strains or can be unique for specific genera. Hence, this review attempts to review the state-of-the-art knowledge of mechanisms of stress response displayed by potential probiotic strains during their transit through the GIT. In addition, evidence whether stress responses can compromise the biosafety of such strains is also discussed.

Safety Assessment of the Potential Probiotic Bacterium Limosilactobacillus fermentum J23 Using the Mexican Fruit Fly (Anastrepha ludens Loew, Diptera: Tephritidae) as a Novel In Vivo Model.

Safety assessment of probiotics is difficult but essential. In this work, the Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae), was used as in vivo model to assess the biosafety of Limosilactobacillus fermentum J23. In the first set of experiments, the strain was orally administered to adult flies through direct feeding, whereas in the second set of experiments, it was supplemented through the larval rearing medium. Data showed that L. fermentum J23 did not lead to increased mortality or treatment-related toxicity signs in adult female and male flies. Ingestion of L. fermentum J23 by adult female flies led to a statistically significant improvement in locomotor activity compared to the control groups (ca. 59% decrease in climbing time, p < 0.0001). A positive trend in lifespan extension under stress (maximum lifespan = 144 h) was also observed. When L. fermentum J23 was administered to the larvae, the adult emergence (p = 0.0099), sex ratio (p = 0.0043), and flight ability (p = 0.0009) increased significantly by 7%, 31%, and 8%, respectively, compared to the control diet. No statistical effect between the control diet and the L. fermentum J23-based diet for the number of pupae recovered, pupal weight, duration of the pupal stage, lifespan under stress, and morphological development was observed. We conclude that feeding L. fermentum J23 to the novel experimental model A. ludens had no toxic effects and could be safely considered a potential probiotic for food supplements; however, further studies are still needed to establish its biosafety in humans.

Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.

Nutraceutical and Pharmaceutical Behavior of Bioactive Compounds of Miracle Oilseeds: An Overview.

India plays an important role in the production of oilseeds, which are mainly cultivated for future extraction of their oil. In addition to the energic and nutritional contribution of these seeds, oilseeds are rich sources of bioactive compounds (e.g., phenolic compounds, proteins, minerals). A regular and moderate dietary supplementation of oilseeds promotes health, prevents the appearance of certain diseases (e.g., cardiovascular diseases (CVDs), cancers) and delays the aging process. Due to their relevant content in nutraceutical molecules, oilseeds and some of their associated processing wastes have raised interest in food and pharmaceutical industries searching for innovative products whose application provides health benefits to consumers. Furthermore, a circular economy approach could be considered regarding the re-use of oilseeds' processing waste. The present article highlights the different oilseed types, the oilseeds-derived bioactive compounds as well as the health benefits associated with their consumption. In addition, the different types of extractive techniques that can be used to obtain vegetable oils rich from oilseeds, such as microwave-assisted extraction (MAE), ultrasonic-assisted extraction (UAE) and supercritical fluid extraction (SFE), are reported. We conclude that the development and improvement of oilseed markets and their byproducts could offer even more health benefits in the future, when added to other foods.

Impact of quarantine due to COVID-19 pandemic on health and lifestyle conditions in older adults from Centro American countries.

BACKGROUND: The impact of quarantine in older adults have been reported in several studies with contradictory results, reporting from negative effects to no significant outcomes or even beneficial consequences. Heterogeneity in aging plays a role in each region, the aim of this study is to analyze the impact of quarantine on health conditions (physical and mental) and lifestyle in older adults in five Centro American countries during COVID-19 pandemic. METHOD: In this cross-sectional study, n = 712 older adults 60 years and older from Mexico, Guatemala, El Salvador, Honduras and Costa Rica were assessed by telephone. Sociodemographic data, physical and mental health, lifestyle and quarantine conditions were asked previous informed consent. RESULTS: In general, mean of days in quarantine at the moment of the study was 142 days (approximately four months and three weeks). In the analysis of the impact of the days in quarantine effects were found on the frequency of falls, functional ability in Activities of Daily Living (ADL), general cognitive function, memory, orientation, language, frequency of drinking alcohol, having a balanced diet, and being active cognitively. Some differences were found between countries. CONCLUSIONS: Effects of quarantine on older adults in Centro America, requires attention of governments and healthcare to prevent long term morbidity and disability, and to promote healthy aging.

Connecting nutritional deprivation and pubertal inhibition via GRK2-mediated repression of kisspeptin actions in GnRH neurons.

BACKGROUND: Perturbations in the timing of puberty, with potential adverse consequences in later health, are increasingly common. The underlying neurohormonal mechanisms are unfolded, but nutritional alterations are key contributors. Efforts to unveil the basis of normal puberty and its metabolic control have focused on mechanisms controlling expression of Kiss1, the gene encoding the puberty-activating neuropeptide, kisspeptin. However, other regulatory phenomena remain ill-defined. Here, we address the putative role of the G protein-coupled-receptor kinase-2, GRK2, in GnRH neurons, as modulator of pubertal timing via repression of the actions of kisspeptin, in normal maturation and conditions of nutritional deficiency. METHODS: Hypothalamic RNA and protein expression analyses were conducted in maturing female rats. Pharmacological studies involved central administration of GRK2 inhibitor, ßARK1-I, and assessment of gonadotropin responses to kisspeptin or phenotypic and hormonal markers of puberty, under normal nutrition or early subnutrition in female rats. In addition, a mouse line with selective ablation of GRK2 in GnRH neurons, aka G-GRKO, was generated, in which hormonal responses to kisspeptin and puberty onset were monitored, in normal conditions and after nutritional deprivation. RESULTS: Hypothalamic GRK2 expression increased along postnatal maturation in female rats, especially in the preoptic area, where most GnRH neurons reside, but decreased during the juvenile-to-pubertal transition. Blockade of GRK2 activity enhanced Ca+2 responses to kisspeptin in vitro, while central inhibition of GRK2 in vivo augmented gonadotropin responses to kisspeptin and advanced puberty onset. Postnatal undernutrition increased hypothalamic GRK2 expression and delayed puberty onset, the latter being partially reversed by central GRK2 inhibition. Conditional ablation of GRK2 in GnRH neurons enhanced gonadotropin responses to kisspeptin, accelerated puberty onset, and increased LH pulse frequency, while partially prevented the negative impact of subnutrition on pubertal timing and LH pulsatility in mice. CONCLUSIONS: Our data disclose a novel pathway whereby GRK2 negatively regulates kisspeptin actions in GnRH neurons, as major regulatory mechanism for tuning pubertal timing in nutritionally-compromised conditions.