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1.
Aquat Toxicol ; 275: 107068, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217790

RESUMEN

Pharmaceutically active compounds (PhACs) have been detected in several aquatic compartments, which has been of environmental concern since PhACs can cause adverse effects on the aquatic ecosystem at low concentrations. Despite the variety of PhACs detected in surface water, ecotoxicological studies are non-existent for many of them, mainly regarding their mixture. In addition, water bodies can continuously receive the discharge of raw or treated wastewater with micropollutants. Thus, PhACs are subject to mixture and interactions, potentiating or reducing their toxicity. Therefore, the present study evaluated the toxicity on Aliivibrio fischeri of seven PhACs, which still needs to be explored in the literature. The effects were evaluated for the PhACs individually and for their binary and tertiary mixture. Also, the experimental effects were compared with the concentration addition (CA) and independent action (IA) models. Finally, an environmental risk assessment was carried out. Fenofibrate (FEN), loratadine (LOR), and ketoprofen (KET) were the most toxic, with EC50 of 0.32 mg L-1, 6.15 mg L-1 and 36.8 mg L-1, respectively. Synergistic effects were observed for FEN + LOR, KET + LOR, and KET + FEN + LOR, showing that the CA and IA may underestimate the toxicity. Environmental risks for KET concerning algae, and LOR e 17α-ethynylestradiol (EE2) for crustaceans and fish were high for several locations. Besides, high removals by wastewater treatment technologies are required to achieve the concentrations necessary for reducing KET and LOR risk quotients. Thus, this study contributed to a better understanding of the toxic interactions and environmental risks of PhACs.


Asunto(s)
Aliivibrio fischeri , Ecotoxicología , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/toxicidad , Aliivibrio fischeri/efectos de los fármacos , Medición de Riesgo , Preparaciones Farmacéuticas/análisis , Pruebas de Toxicidad
2.
Cancers (Basel) ; 16(16)2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39199584

RESUMEN

BACKGROUND: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. METHODS: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4-17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. RESULTS: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = -0.454, p = 0.008) was observed. CONCLUSIONS: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients.

3.
Menopause ; 31(9): 796-800, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38954487

RESUMEN

OBJECTIVE: Premature ovarian insufficiency (POI) affects up to 3% of the global female population, influencing metabolic, cardiovascular, and reproductive health. Medical expertise in diagnosis, effects, and treatment strategies, particularly for gynecologists, is crucial for ensuring improved healthcare for women. The objective of this study is to assess the state of medical knowledge regarding the diagnosis, treatment, and follow-up of POI among Brazilian gynecologists. METHODS: A cross-sectional study was conducted using online questionnaires administered to 16,000 members of the Brazilian Federation of Gynecology and Obstetrics. RESULTS: In total, 460 questionnaires were received from gynecologists who had an average age of 44.49 ± 12.57 years and 19.37 ± 12.95 years of professional experience. Fifty-three percent of gynecologists diagnosed POI correctly, and 49% requested karyotype analysis, while fewer than 10% identified all POI etiologies. Over 90% of gynecologists understood the long-term consequences of POI for bone and cardiovascular health. Despite being a consequence of hypoestrogenism, hormone therapy was recommended only by 20% of doctors, with no more than 50% of them prescribing appropriate doses for young women. Regarding self-perception, 60% of gynecologists declared deficient knowledge regarding how to offer care and guidance to women, with hormone therapy being reported as the most important reason (47%). CONCLUSIONS: Current concepts and guidelines for POI are not adequately understood or applied in Brazilian clinical practice, leading to suboptimal care.


Asunto(s)
Ginecología , Conocimientos, Actitudes y Práctica en Salud , Insuficiencia Ovárica Primaria , Humanos , Femenino , Insuficiencia Ovárica Primaria/terapia , Estudios Transversales , Adulto , Brasil , Persona de Mediana Edad , Encuestas y Cuestionarios , Calidad de la Atención de Salud , Pautas de la Práctica en Medicina/estadística & datos numéricos , Competencia Clínica , Ginecólogos
4.
BMC Womens Health ; 24(1): 388, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965526

RESUMEN

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.


Asunto(s)
Dolor Crónico , Dismenorrea , Dolor Pélvico , Humanos , Femenino , Adulto , Dolor Pélvico/epidemiología , Estudios Transversales , Prevalencia , Adulto Joven , Dolor Crónico/epidemiología , Persona de Mediana Edad , Ecuador/epidemiología , Adolescente , Dismenorrea/epidemiología , Dispareunia/epidemiología , Pueblos Indígenas/estadística & datos numéricos , Encuestas y Cuestionarios
5.
PLoS One ; 19(7): e0306657, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39078824

RESUMEN

Choosing appropriate reference genes or internal controls to normalize RT-qPCR data is mandatory for the interexperimental reproducibility of gene expression data obtained by RT-qPCR in most studies, including those on endometriosis. Particularly for miRNAs, the choice for reference genes is challenging because of their physicochemical and biological characteristics. Moreover, the retrograde menstruation theory, mesenchymal stem cells in menstrual blood (MenSCs), and changes in post-transcriptional regulatory processes through miRNAs have gained prominence in the scientific community as important players in endometriosis. Therefore, we originally explored the stability of 10 miRNAs expressions as internal control candidates in conditions involving the two-dimensional culture of MenSCs from healthy women and patients with endometriosis. Here, we applied multiple algorithms (geNorm, NormFinder, Bestkeeper, and delta Ct) to screen reference genes and assessed the comprehensive stability classification of miRNAs using RefFinder. Pairwise variation calculated using geNorm identified three miRNAs as a sufficient number of reference genes for accurate normalization. MiR-191-5p, miR-24-3p, and miR-103a-3p were the best combination for suitable gene expression normalization. This study will benefit similar research, but is also attractive for regenerative medicine and clinics that use MenSCs, miRNA expression, and RT-qPCR.


Asunto(s)
Endometriosis , Menstruación , Células Madre Mesenquimatosas , MicroARNs , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Femenino , MicroARNs/genética , Endometriosis/genética , Células Madre Mesenquimatosas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Menstruación/genética , Adulto , Perfilación de la Expresión Génica/métodos , Estándares de Referencia , Reproducibilidad de los Resultados , Algoritmos
6.
Artículo en Inglés | MEDLINE | ID: mdl-38765507

RESUMEN

Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaß pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaß pathway in predisposition to endometriosis.


Asunto(s)
Variaciones en el Número de Copia de ADN , Endometriosis , Humanos , Endometriosis/genética , Femenino , Adulto , Cromosomas Humanos Par 3/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético
7.
Microbiology (Reading) ; 170(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38739436

RESUMEN

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 µg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 µg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 µg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 µg ml-1) and P. aeruginosa P2307 (65.00 µg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.


Asunto(s)
Antibacterianos , Endopeptidasas , Glucanos , Polimixina B , Fagos de Salmonella , Endopeptidasas/farmacología , Endopeptidasas/química , Endopeptidasas/metabolismo , Polimixina B/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Fagos de Salmonella/genética , Fagos de Salmonella/fisiología , Fagos de Salmonella/química , Glucanos/química , Glucanos/farmacología , Animales , Pruebas de Sensibilidad Microbiana , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/virología , Ratones , Salmonella typhimurium/virología , Salmonella typhimurium/efectos de los fármacos , Bacteriófagos/fisiología , Bacteriófagos/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Virales/farmacología , Proteínas Virales/química
10.
Curr Issues Mol Biol ; 46(4): 3424-3437, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38666945

RESUMEN

Escherichia coli phytase (AppA) is widely used as an exogenous enzyme in monogastric animal feed mainly because of its ability to degrade phytic acid or its salt (phytate), a natural source of phosphorus. Currently, successful recombinant production of soluble AppA has been achieved by gene overexpression using both bacterial and yeast systems. However, some methods for the biomembrane immobilization of phytases (including AppA), such as surface display on yeast cells and bacterial spores, have been investigated to avoid expensive enzyme purification processes. This study explored a homologous protein production approach for displaying AppA on the cell surface of E. coli by engineering its outer membrane (OM) for extracellular expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of total bacterial lysates and immunofluorescence microscopy of non-permeabilized cells revealed protein expression, whereas activity assays using whole cells or OM fractions indicated functional enzyme display, as evidenced by consistent hydrolytic rates on typical substrates (i.e., p-nitrophenyl phosphate and phytic acid). Furthermore, the in vitro results obtained using a simple method to simulate the gastrointestinal tract of poultry suggest that the whole-cell biocatalyst has potential as a feed additive. Overall, our findings support the notion that biomembrane-immobilized enzymes are reliable for the hydrolysis of poorly digestible substrates relevant to animal nutrition.

11.
Arch Endocrinol Metab ; 68: e230502, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578472

RESUMEN

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.


Asunto(s)
Hiperprolactinemia , Neoplasias Hipofisarias , Prolactinoma , Embarazo , Humanos , Femenino , Hiperprolactinemia/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Brasil , Prolactina , Prolactinoma/diagnóstico
12.
Arch Endocrinol Metab ; 68: e230504, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578473

RESUMEN

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.


Asunto(s)
Hiperprolactinemia , Neoplasias Hipofisarias , Prolactinoma , Embarazo , Humanos , Femenino , Hiperprolactinemia/tratamiento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efectos adversos , Prolactina , Neoplasias Hipofisarias/terapia , Brasil
13.
J Sex Marital Ther ; 50(4): 542-553, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482856

RESUMEN

Hypoactive sexual desire dysfunction (HSDD) is prevalent among women. This retrospective cohort study aimed to verify the results of the strategies used by Gynecologists and Obstetricians (Ob-gyn) residents in the management of female HSDD. For this, we conducted a data collection of patient medical records of women with HSDD from the Human Sexuality Studies outpatient clinic of the Human Reproduction Center, Department of Gynecology and Obstetrics of FMRP-USP, from 2005 to 2019. Among the 437 women included, 361 (82.6%) answered the question concerning the effect of the protocol to which they were submitted, whereas 234 (64.8%) reported improvements in sexual desire. The univariate model showed that patients without chronic pelvic pain were 19.0% less likely to report improvements in HSDD than those with chronic pelvic pain (p = 0.03). Patients without depression and without orgasmic dysfunction were, respectively 32% and 23% more likely to show improvements in their HSDD than those who had depression or orgasmic dysfunction (respectively p = 0.001, p = 0.008). However, the multivariate model did not identify any associations. The assistance regarding HSDD by the Ob-gyn resident in training to deal with female sexual complaints may be effective in improving sexual complaints.


Asunto(s)
Disfunciones Sexuales Psicológicas , Salud Sexual , Humanos , Femenino , Disfunciones Sexuales Psicológicas/terapia , Adulto , Estudios Retrospectivos , Salud de la Mujer , Ginecología , Persona de Mediana Edad , Libido , Disfunciones Sexuales Fisiológicas/terapia , Obstetricia , Dolor Pélvico/terapia
14.
JBRA Assist Reprod ; 28(2): 254-262, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38546118

RESUMEN

OBJECTIVE: To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. METHODS: Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. RESULTS: The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. CONCLUSIONS: In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.


Asunto(s)
Inseminación Artificial , Inducción de la Ovulación , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Masculino , Inducción de la Ovulación/métodos , Pronóstico , Inseminación Artificial/métodos , Índice de Embarazo , Resultado del Embarazo/epidemiología
15.
Environ Res ; 247: 118235, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38266904

RESUMEN

BACKGROUND: Since 2011, over 30 tropical Atlantic nations have experienced substantial landings of holopelagic Sargassum spp. Its decomposition results in the production of hydrogen sulfide (H2S), which, in elevated concentrations, can pose a threat to human health. This study aims to enhance our understanding of the temporal and spatial variability in H2S emissions during the decomposition of Sargassum on beaches. The primary objective is to assess potential exposure risks for local populations, tourists, and cleanup workers. METHODS: H2S levels were monitored using a SENKO sensor (SGTP-H2S; limit of detection 0.1-100 ppm; resolution 0.1 ppm) at four distances from Sargassum accumulation points of (0, 10, 30, and 40 m) in Puerto Morelos, Mexico, during 2022 and 2023. RESULTS: Elevated concentrations of H2S were detected beneath the Sargassum piles, with 23.5% of readings exceeding 5 ppm and occasional spikes above 100 ppm. Above the piles, 87.3% of the measurements remained below 2 ppm, and the remainder fell between 2.1 and 5.2 ppm. At 10 m from the shoreline, 90% of measurements registered below 0.1 ppm, and the remaining 10% were below 2 ppm. Readings at 30 and 40 m consistently recorded levels below 0.1 ppm. H2S concentrations positively correlated with Sargassum pile height, the temperature beneath the piles, and wind speed. CONCLUSIONS: Our findings suggest no immediate and significant exposure risk for residents or tourists. However, Sargassum cleanup workers face a higher exposure risk, potentially encountering concentrations above 5 ppm for nearly one-fourth of the working time.


Asunto(s)
Sulfuro de Hidrógeno , Sargassum , Humanos , Viento , Temperatura , México
16.
Int J Biol Macromol ; 259(Pt 2): 129330, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38218270

RESUMEN

DEAD-box helicases are global regulators of liquid-liquid phase separation (LLPS), a process that assembles membraneless organelles inside cells. An outstanding member of the DEAD-box family is DDX3X, a multi-functional protein that plays critical roles in RNA metabolism, including RNA transcription, splicing, nucleocytoplasmic export, and translation. The diverse functions of DDX3X result from its ability to bind and remodel RNA in an ATP-dependent manner. This capacity enables the protein to act as an RNA chaperone and an RNA helicase, regulating ribonucleoprotein complex assembly. DDX3X and its orthologs from mouse, yeast (Ded1), and C. elegans (LAF-1) can undergo LLPS, driving the formation of neuronal granules, stress granules, processing bodies or P-granules. DDX3X has been related to several human conditions, including neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder. Although the research into the pathogenesis of aberrant biomolecular condensation in neurodegenerative diseases is increasing rapidly, the role of LLPS in neurodevelopmental disorders is underexplored. This review summarizes current findings relevant for DDX3X phase separation in neurodevelopment and examines how disturbances in the LLPS process can be related to neurodevelopmental disorders.


Asunto(s)
Trastorno del Espectro Autista , ARN Helicasas DEAD-box , Trastornos del Neurodesarrollo , Animales , Humanos , Ratones , Trastorno del Espectro Autista/genética , Caenorhabditis elegans/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Trastornos del Neurodesarrollo/genética , ARN/metabolismo , Saccharomyces cerevisiae/metabolismo
17.
Behav Brain Res ; 460: 114817, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38122904

RESUMEN

Environmental factors such as undernutrition and environmental enrichment can promote changes in the molecular and behavioural mechanisms related to cognition. Herein, we investigated the effect of enriched environment stimulation in rats that were malnourished in the pre- and postnatal periods on changes in the gene expression of brain-derived neurotrophic factor and its receptor in the hippocampus, as well as on anxiety traits and memory. Early undernutrition promoted weight reduction, increased the risk analysis, reduced permanence in the open arm of the elevated plus-maze and induced a reduction in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B. However, exposure to an enriched environment from 30 to 90 days' old maintained the malnourished phenotype, leading to weight reduction in the control group. In addition, the enriched environment did not alter the risk assessment in the undernourished group, but it did increase the frequency of labyrinth entries. Sixty-day exposure to the enriched environment resulted in a reversal in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus of malnourished rats and favoured of long-term memory in the object recognition test in the open-field. These results suggest that an enriched environment may have a protective effect in adult life by inducing changes in long-term memory and anxiety traits in animals that were undernourished in early life. Furthermore, reversing these effects of undernutrition involves mechanisms linked to the molecular signalling of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Desnutrición , Embarazo , Femenino , Ratas , Animales , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Tropomiosina/metabolismo , Ambiente , Ansiedad , Vitaminas , Desnutrición/complicaciones , Desnutrición/metabolismo , Hipocampo/metabolismo , Pérdida de Peso , Receptor trkB/metabolismo
18.
Braz. j. biol ; 84: e260065, 2024. tab, graf
Artículo en Inglés | VETINDEX | ID: biblio-1384082

RESUMEN

Achatina fulica is a terrestrial mollusk known as the giant African snail that is related to environmental, economic, urban, and public health problems. As control measures for this mollusk, cooking salt (NaCl) and calcium oxide (CaO) are used, and baits are composed of metaldehyde. However, these measures have environmental toxicity and impact the soil. In this way, natural products have been tested on this mollusk to discover and develop a substance to combat this urban and agricultural pest. This article aims to evaluate studies involving natural products to control the population of Achatina fulica. Articles and works published in books were included in the present work. A total of 1,103 works were found during the search. Of these, 14 works met the objective of these review and were included in this article. The tests do not possess methodological standardization, do not have a maximum concentration to be considered active, or a maximum exposure time. A lack of standardization in the methodology of tests on A. fulica was observed. The performance of tests on other life stages of the mollusk, as well as tests that analyze other parameters, are essential. Only one article analyzed presented phytochemical analysis. No ecotoxicity tests were reported either. Some extracts showed promising results, highlighting the aqueous extract of Capsicum frutescens. More studies investigating the molluscicidal activity of natural products on A. fulica are needed. It is very relevant that the new studies present a phytochemical analysis of the tested extracts, as well as ecotoxicity studies.


Achatina fulica é um molusco terrestre conhecido como caramujo gigante africano que está relacionado a problemas ambientais, econômicos, urbanos e de saúde pública. Como medidas de controle para esse molusco, são utilizados sal de cozinha (NaCl) e óxido de cálcio (CaO), e as iscas são compostas de metaldeído. No entanto, essas medidas têm toxicidade ambiental e impactam o solo. Desta forma, produtos naturais foram testados neste molusco para descobrir e desenvolver uma substância para combater esta praga urbana e agrícola. Este artigo tem como objetivo avaliar estudos envolvendo produtos naturais para controle da população de Achatina fulica. Artigos e trabalhos publicados em livros foram incluídos no presente trabalho. Um total de 1.103 trabalhos foram encontrados durante a pesquisa. Destes, 14 trabalhos atendiam ao objetivo desta revisão e foram incluídos neste artigo. Os testes não possuem padronização metodológica, não possuem concentração máxima para serem considerados ativos ou tempo máximo de exposição. Observou-se uma falta de padronização na metodologia de testes em A. fulica. A realização de testes em outras fases da vida do molusco, bem como testes que analisem outros parâmetros, são essenciais. Apenas um artigo analisado apresentou análise fitoquímica. Também não foram relatados testes de ecotoxicidade. Alguns extratos apresentaram resultados promissores, com destaque para o extrato aquoso de Capsicum frutescens. Mais estudos investigando a atividade molusquicida de produtos naturais sobre A. fulica são necessários. É muito relevante que os novos estudos apresentem uma análise fitoquímica dos extratos testados, bem como estudos de ecotoxicidade.


Asunto(s)
Animales , Caracoles , Productos Biológicos/administración & dosificación , Control de Plagas , Agricultura , Salud Pública
19.
Arch. endocrinol. metab. (Online) ; 68: e230502, 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1556946

RESUMEN

ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

20.
Arch. endocrinol. metab. (Online) ; 68: e230504, 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1556959

RESUMEN

ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

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