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1.
Elife ; 122024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298260

RESUMEN

Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described. Arpin mRNA and protein are expressed in EC and downregulated by pro-inflammatory cytokines. Arpin depletion in Human Umbilical Vein Endothelial Cells causes the formation of actomyosin stress fibers leading to increased permeability in an Arp2/3-independent manner. Instead, inhibitors of ROCK1 and ZIPK, kinases involved in the generation of stress fibers, normalize the loss-of-arpin effects on actin filaments and permeability. Arpin-deficient mice are viable but show a characteristic vascular phenotype in the lung including edema, microhemorrhage, and vascular congestion, increased F-actin levels, and vascular permeability. Our data show that, apart from being an Arp2/3 inhibitor, arpin is also a regulator of actomyosin contractility and endothelial barrier integrity.


Asunto(s)
Actomiosina , Permeabilidad Capilar , Células Endoteliales de la Vena Umbilical Humana , Animales , Humanos , Actomiosina/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones , Serpinas/metabolismo , Serpinas/genética , Ratones Noqueados , Quinasas Asociadas a rho/metabolismo , Quinasas Asociadas a rho/genética , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/genética , Fibras de Estrés/metabolismo , Células Endoteliales/metabolismo , Proteínas Portadoras
2.
Nat Cell Biol ; 26(9): 1613-1622, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39223377

RESUMEN

The growing availability of single-cell and spatially resolved transcriptomics has led to the development of many approaches to infer cell-cell communication, each capturing only a partial view of the complex landscape of intercellular signalling. Here we present LIANA+, a scalable framework built around a rich knowledge base to decode coordinated inter- and intracellular signalling events from single- and multi-condition datasets in both single-cell and spatially resolved data. By extending and unifying established methodologies, LIANA+ provides a comprehensive set of synergistic components to study cell-cell communication via diverse molecular mediators, including those measured in multi-omics data. LIANA+ is accessible at https://github.com/saezlab/liana-py with extensive vignettes ( https://liana-py.readthedocs.io/ ) and provides an all-in-one solution to intercellular communication inference.


Asunto(s)
Comunicación Celular , Transducción de Señal , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Programas Informáticos , Animales , Transcriptoma , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos
3.
Basic Res Cardiol ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311911

RESUMEN

Inflammation, fibrosis and metabolic stress critically promote heart failure with preserved ejection fraction (HFpEF). Exposure to high-fat diet and nitric oxide synthase inhibitor N[w]-nitro-l-arginine methyl ester (L-NAME) recapitulate features of HFpEF in mice. To identify disease-specific traits during adverse remodeling, we profiled interstitial cells in early murine HFpEF using single-cell RNAseq (scRNAseq). Diastolic dysfunction and perivascular fibrosis were accompanied by an activation of cardiac fibroblast and macrophage subsets. Integration of fibroblasts from HFpEF with two murine models for heart failure with reduced ejection fraction (HFrEF) identified a catalog of conserved fibroblast phenotypes across mouse models. Moreover, HFpEF-specific characteristics included induced metabolic, hypoxic and inflammatory transcription factors and pathways, including enhanced expression of Angiopoietin-like 4 (Angptl4) next to basement membrane compounds, such as collagen IV (Col4a1). Fibroblast activation was further dissected into transcriptional and compositional shifts and thereby highly responsive cell states for each HF model were identified. In contrast to HFrEF, where myofibroblast and matrifibrocyte activation were crucial features, we found that these cell states played a subsidiary role in early HFpEF. These disease-specific fibroblast signatures were corroborated in human myocardial bulk transcriptomes. Furthermore, we identified a potential cross-talk between macrophages and fibroblasts via SPP1 and TNFɑ with estimated fibroblast target genes including Col4a1 and Angptl4. Treatment with recombinant ANGPTL4 ameliorated the murine HFpEF phenotype and diastolic dysfunction by reducing collagen IV deposition from fibroblasts in vivo and in vitro. In line, ANGPTL4, was elevated in plasma samples of HFpEF patients and particularly high levels associated with a preserved global-longitudinal strain. Taken together, our study provides a comprehensive characterization of molecular fibroblast activation patterns in murine HFpEF, as well as the identification of Angiopoietin-like 4 as central mechanistic regulator with protective effects.

4.
Eur J Sport Sci ; 24(9): 1350-1364, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39172795

RESUMEN

This systematic review aimed to establish the effectiveness of exercise interventions, alone or in combination with dietary modifications, on working memory (WM) in individuals living with overweight and obesity. A comprehensive literature search was conducted using the Scopus, PubMed, Springer-Link, RefSeek, and Cochrane Library databases to identify relevant publications up to January 18, 2024. Data on participants' characteristics, intervention settings, and key outcomes related to WM were extracted. The quality of the studies was assessed using the PEDro scale. A total of 15 articles met pre-established inclusion criteria, involving participants across nine countries with a range of 12-125 individuals and ages spanning from 6 to 80 years old. Among the studies analyzed, 10 exclusively investigated exercise interventions, whereas five explored the combined effects. Notably, 70% of the exercise interventions (7 out of 10) exhibited positive improvements in WM. Likewise, 60% of the combined interventions (3 out of 5) demonstrated favorable enhancements in WM. No differences were found between the two protocols. Common features between the protocols were identified and described. Both protocols showed favorable and promising effects on WM in this clinical population. Nonetheless, the limited evidence addressing the combination of exercise and diet in the same research approach reduces the generalizability of the findings. This review offers valuable insights for future clinical and research applications in people with overweight and obesity.


Asunto(s)
Memoria a Corto Plazo , Obesidad , Sobrepeso , Humanos , Terapia Combinada , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Memoria a Corto Plazo/fisiología , Obesidad/terapia , Obesidad/dietoterapia , Sobrepeso/terapia , Sobrepeso/dietoterapia
5.
Cureus ; 16(7): e65106, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39171025

RESUMEN

Introduction Obesity can develop from childhood through adulthood and is influenced by genetics, family, and environmental factors. Parenting educational style is believed to contribute to an individual's future weight status. This study aims to assess the connection between parenting educational style and weight-related issues. Methods The study involved 487 participants, including either the mother and/or father and their school-age child, aged 6-11, at a primary care unit in Mexico. Fifty-two records were excluded due to incomplete questionnaires, electronic records, and refusal of informed consent. The study group consisted of 435 adults and children who completed an adapted version of the Parenting Styles and Dimensions Questionnaire (PSDQ) tailored for the Mexican population. The researchers also gathered anthropometric measurements of the primary caregiver (parent) and the child from the electronic record to calculate their BMI and nutritional status. We used IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA) to analyze the data. The Pearson Chi-square and Fisher's exact test were applied to examine interaction terms between variables, revealing a statistically significant p-value of <0.05. Results Out of the 435 patients examined, there were 229 (52.6%) children and 206 (47.3%) adult patients. Grade 2 obesity was present in 90 (39.3%) school-age children and 104 (50.5%) adult patients. The family's parenting educational style, as determined by the PSDQ questionnaire, was found to be permissive in 143 (69.4%) patients, authoritarian in 33 (16.0%) patients, and authoritative in 30 (14.6%) patients. Conclusions Parenting educational style and the PSDQ tool can be used to assess how parents influence the development of obesogenic home environments. We observed that a permissive parenting educational style was linked to a more obesogenic environment, whereas an authoritative parenting educational style was linked to a less obesogenic environment.

6.
BMC Neurosci ; 25(1): 37, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174899

RESUMEN

BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. CONCLUSION: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.


Asunto(s)
Caquexia , Progresión de la Enfermedad , Ratones Endogámicos BALB C , Sistema Nervioso Simpático , Animales , Caquexia/metabolismo , Caquexia/patología , Caquexia/etiología , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Masculino , Ratones , Proteína Desacopladora 1/metabolismo , Línea Celular Tumoral , Canales Iónicos/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Oxidopamina , Simpatectomía Química , Interleucina-6/metabolismo , Índice de Masa Corporal , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/metabolismo
7.
Microorganisms ; 12(8)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39203465

RESUMEN

Acute hepatopancreatic necrosis disease, caused by Vibrio parahaemolyticus strains carrying the pirA and pirB toxin genes (VpAHPND), has been causing great economic losses in Asia and America in the shrimp farming industry. Numerous strains are resistant to antibiotics. However, supplementation with probiotic antagonists has become a more desirable treatment alternative. Fourteen strains of microorganisms were assessed for their potential to inhibit VpAHPND in vitro activity. The bacteria with the highest activity were challenged with VpAHPND-infected Pacific white shrimp Litopenaeus vannamei. Furthermore, the genomic characteristics of probiotic bacteria were explored by whole-genome sequencing. We identified the Sonora strain as Bacillus pumilus, which possesses positive proteolytic and cellulolytic activities that may improve shrimp nutrient uptake and digestion. Challenge trials showed a low cumulative mortality (11.1%). B. pumilus Son has a genome of 3,512,470 bp and 3734 coding sequences contained in 327 subsystems. Some of these genes are related to the biosynthesis of antimicrobial peptides (surfactins, fengycin, schizokinen, bacilibactin, and bacilysin), nitrogen and phosphorus metabolism, and stress response. Our in vitro and in vivo findings suggest that B. pumilus Sonora has potential as a functional probiotic.

8.
Plants (Basel) ; 13(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39204613

RESUMEN

Chagas disease, caused by the protozoan Trypanosoma cruzi, represents an important and worldwide public health issue, particularly in Latin America. Limitations of conventional treatment with benznidazole and nifurtimox underscore the urgent need for new therapeutic strategies for this disease. Schinus molle, a tree used in traditional medicine for various ailments, has demonstrated promising antiparasitic activity. The in vitro anti-T. cruzi activity of Schinus molle crude methanol extract, partitions, and fractions, as well as their cytotoxicity in Vero cells and Artemia salina, and hemolytic activity in human erythrocytes were assessed. Most of the extracts possessed anti-T. cruzi effects, with Sm-CF3 being the fraction with the highest activity (IC50 = 19 µg/mL; SI = 6.8). Gas chromatography-mass spectrometry analysis identified 20 compounds, with fatty acyls comprising the predominant chemical class (55%). We also identified the antiparasitic compounds cis-5,8,11,14,17-eicosapentaenoic acid and trans-Z-α-bisabolene epoxide, suggesting their potential contribution to the observed anti-T. cruzi activity. In conclusion, our findings support the therapeutic potential of S. molle as a source of novel antiparasitic agents against T. cruzi.

9.
Int J Mol Sci ; 25(16)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39201493

RESUMEN

Beauveria bassiana has potential for Aedes aegypti biological control. However, its efficacy depends on the strain's geographic location, host susceptibility, and virulence. The present study aimed to evaluate the effectiveness of B. bassiana strain BBPTG4 conidia in controlling Ae. aegypti adults and its detection via introns profile on exposed mosquito corpses. Morphologic characteristics among strains were highly similar. Comprehensive testing of these strains demonstrated that BBPT4 exhibited the ideal biological activity for Ae. aegypti control, with a median lethal time (TL50) of 7.5 d compared to ~3 d and ~10 d for BB01 and BB37 strains, respectively. Infected mosquitoes died after GHA and BBPTG4 exposure, and corpses were analyzed for infecting strains detection. Differences among the seven evaluated strains were determined, assessing five different insertion group I intron profiles in BBTG4, BB01, GHA, BB37, and BB02 strains. Mosquitoes infected by BBPTG4 and non-exposed (negative control) intron profiles were obtained. We detected the presence of introns in the BBPTG4 strain, which were not present in non-exposed mosquitoes. In conclusion, B. bassiana strains showed similarities in terms of their cultural and microscopic morphological characteristics and biologicals virulence level, but different intron profiles. BBPTG4 strain-infected Ae. aegypti adult corpses, showing specific amplicons, enabled us to identify B. bassiana at the strain level among infected mosquitoes. However, monitoring and detection of field-infected insects is essential for further verification.


Asunto(s)
Aedes , Beauveria , Beauveria/genética , Beauveria/patogenicidad , Animales , Aedes/microbiología , Intrones/genética , Fenotipo , Genotipo , Variación Genética , Control Biológico de Vectores , Control de Mosquitos/métodos , Virulencia/genética , Mosquitos Vectores/microbiología
10.
Bone ; 187: 117211, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39053792

RESUMEN

Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Ratas Wistar , Animales , Masculino , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Ratas , Difosfonatos/farmacología , Difosfonatos/efectos adversos , Guanidinas/farmacología , Guanidinas/uso terapéutico
11.
Front Psychol ; 15: 1355434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39049947

RESUMEN

Objective: To determine how cognitive domains mediate the link between fitness components, their global score (GFS), and adolescents' academic achievement (ACA) across various school subjects. Methods: In this study, 1,296 adolescents aged 10-14 participated. GFS was computed by three fitness components (strength, muscular, and cardiorespiratory fitness) through the ALPHA-fitness test battery. ACA was determined by five school subjects (Language, English, Mathematics, Science, and History) and two academic scores (a) "Academic Average" (five subjects) and (b) "Academic-PISA" (Language, Mathematics, and Science). A principal component analysis was performed to establish four factors (working memory [WM], cognitive flexibility [CF], inhibitory control [IC], and fluid reasoning [FR]). A parallel mediation approach was implemented with 5,000 bootstrapped samples controlled for sex, maturity, central obesity, having breakfast before cognitive tasks, schools, and school vulnerability. Total, direct, indirect effects, and mediation percentages were estimated. Results: Overall, the finding showed a full parallel mediation effect for Language (92.5%) and English (53.9%), while a partial mediation for Mathematics (43.0%), Science (43.8%), History (45.9%), "Academic Average" (50.6%), and "Academic-PISA" (51.5%). In particular, WM, IC, and FR mediated all school subjects except mathematics, where IC was not significant. CF has not mediated any relationship between GF and academic performance. Conclusion: This study underscores the pivotal role of cognitive domains, specifically WM, IC, and FR, in mediating the link between physical fitness and academic performance in adolescents. These insights have relevant implications for educational and public health policies.

12.
Clin Transl Gastroenterol ; 15(9): e1, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38916225

RESUMEN

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic limited access to colonoscopy. To advance colorectal cancer health equity, we conducted a quality improvement study on colonoscopy wait times in 2019-2023 for underinsured (Medicaid, uninsured) compared with insured patients at an academic medical center providing colonoscopy for surrounding Federally Qualified Health Centers. METHODS: Retrospective chart reviews were performed on adult outpatient colonoscopies in the preintervention period (2019-2021). In 2022, an institutional grant funded bilingual patient navigation to reduce colonoscopy wait times. Postintervention data were collected prospectively from May 2022 to May 2023 in 2 phases. Multivariable regression analyses were conducted for colonoscopy wait times as a primary outcome. RESULTS: Analysis of 3,403 screening/surveillance and 1,896 diagnostic colonoscopies revealed significantly longer colonoscopy wait times for underinsured compared with insured patients after 2019. For screening/surveillance colonoscopies, wait time differences between underinsured and insured patients in the second postintervention phase were reduced by 34.21 days (95% confidence interval [CI]: 11.07-57.35) compared with the postpandemic period and by 56.36 days (95% CI: 34.16-78.55) compared with the first postintervention phase. For diagnostic colonoscopies, wait time differences in the second postintervention phase were reduced by 27.57 days (95% CI: 9.96-45.19) compared with the postpandemic period and by 20.40 days (95% CI: 1.02-39.77) compared with the first postintervention phase. DISCUSSION: Colonoscopy wait times were significantly longer for underinsured compared with insured patients following the COVID-19 pandemic. This disparity was partially ameliorated by patient navigation. Monitoring outpatient colonoscopy wait times in underinsured patients is important for advancing health equity.


Asunto(s)
COVID-19 , Colonoscopía , Pacientes no Asegurados , Mejoramiento de la Calidad , Listas de Espera , Humanos , Colonoscopía/estadística & datos numéricos , Colonoscopía/economía , COVID-19/epidemiología , COVID-19/diagnóstico , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Pacientes no Asegurados/estadística & datos numéricos , Estados Unidos , Neoplasias Colorrectales/diagnóstico , SARS-CoV-2 , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Anciano , Adulto , Detección Precoz del Cáncer/economía , Factores de Tiempo
13.
Nucleic Acids Res ; 52(14): 8100-8111, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38943333

RESUMEN

Transcriptomics is widely used to assess the state of biological systems. There are many tools for the different steps, such as normalization, differential expression, and enrichment. While numerous studies have examined the impact of method choices on differential expression results, little attention has been paid to their effects on further downstream functional analysis, which typically provides the basis for interpretation and follow-up experiments. To address this, we introduce FLOP, a comprehensive nextflow-based workflow combining methods to perform end-to-end analyses of transcriptomics data. We illustrate FLOP on datasets ranging from end-stage heart failure patients to cancer cell lines. We discovered effects not noticeable at the gene-level, and observed that not filtering the data had the highest impact on the correlation between pipelines in the gene set space. Moreover, we performed three benchmarks to evaluate the 12 pipelines included in FLOP, and confirmed that filtering is essential in scenarios of expected moderate-to-low biological signal. Overall, our results underscore the impact of carefully evaluating the consequences of the choice of preprocessing methods on downstream enrichment analyses. We envision FLOP as a valuable tool to measure the robustness of functional analyses, ultimately leading to more reliable and conclusive biological findings.


Asunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Humanos , Perfilación de la Expresión Génica/métodos , Transcriptoma/genética , Línea Celular Tumoral , Programas Informáticos , Insuficiencia Cardíaca/genética , Flujo de Trabajo , Neoplasias/genética , Análisis de Datos , Benchmarking
14.
Int J Mol Sci ; 25(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38791551

RESUMEN

Rotavirus is the main cause of acute diarrhea in children up to five years of age. In this regard, probiotics are commonly used to treat or prevent gastroenteritis including viral infections. The anti-rotavirus effect of Bifidobacterium longum and Chlorella sorokiniana, by reducing viral infectivity and improving IFN-type I response, has been previously reported. The present study aimed to study the effect of B. longum and/or C. sorokiniana on modulating the antiviral cellular immune response mediated by IFN-γ, IL-10, SOCS3, STAT1, and STAT2 genes in rotavirus-infected cells. To determine the mRNA relative expression of these genes, HT-29 cells were treated with B. longum and C. sorokiniana alone or in combination, followed by rotavirus infection. In addition, infected cells were treated with B. longum and/or C. sorokiniana. Cellular RNA was purified, used for cDNA synthesis, and amplified by qPCR. Our results demonstrated that the combination of B. longum and C. sorokiniana stimulates the antiviral cellular immune response by upregulating IFN-γ and may block pro-inflammatory cytokines by upregulating IL-10 and SOCS3. The results of our study indicated that B. longum, C. sorokiniana, or their combination improve antiviral cellular immune response and might modulate pro-inflammatory responses.


Asunto(s)
Bifidobacterium longum , Chlorella , Interferón gamma , Interleucina-10 , Probióticos , Infecciones por Rotavirus , Proteína 3 Supresora de la Señalización de Citocinas , Humanos , Células HT29 , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Probióticos/farmacología , Rotavirus/fisiología , Infecciones por Rotavirus/inmunología , Infecciones por Rotavirus/virología , Factor de Transcripción STAT1/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo
15.
Int J Mol Sci ; 25(7)2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38612895

RESUMEN

Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.


Asunto(s)
MicroARNs , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Transducción de Señal , Proliferación Celular/genética , Movimiento Celular/genética , ARN Interferente Pequeño , MicroARNs/genética , Agitación Psicomotora , ARN Bicatenario , Proteínas Ligadas a GPI/genética
16.
Neuromolecular Med ; 26(1): 11, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38592597

RESUMEN

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.


Asunto(s)
Trastorno Depresivo Mayor , Suicidio , Masculino , Humanos , Colesterol 24-Hidroxilasa , Trastorno Depresivo Mayor/genética , Frecuencia de los Genes , Polimorfismo de Nucleótido Simple
17.
Front Public Health ; 12: 1363015, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566792

RESUMEN

Background: Excessive sedentary time has been negatively associated with several health outcomes, and physical activity alone does not seem to fully counteract these consequences. This panorama emphasizes the essential of sedentary time interruption programs. "The Up Project" seeks to assess the effectiveness of two interventions, one incorporating active breaks led by a professional and the other utilizing a computer application (self-led), of both equivalent duration and intensity. These interventions will be compared with a control group to evaluate their impact on physical activity levels, sedentary time, stress perception, occupational pain, and cardiometabolic risk factors among office workers. Methods: This quasi-experimental study includes 60 desk-based workers from universities and educational institutes in Valparaiso, Chile, assigned to three groups: (a) booster breaks led by professionals, (b) computer prompts that are unled, and (c) a control group. The intervention protocol for both experimental groups will last 12 weeks (only weekdays). The following measurements will be performed at baseline and post-intervention: cardiometabolic risk based on body composition (fat mass, fat-free mass, and bone mass evaluated by DXA), waist circumference, blood pressure, resting heart rate, and handgrip strength. Physical activity and sedentary time will be self-reported and device-based assessed using accelerometry. Questionnaires will be used to determine the perception of stress and occupational pain. Discussion: Governments worldwide are addressing health issues associated with sedentary behavior, particularly concerning individuals highly exposed to it, such as desk-based workers. Despite implementing certain strategies, there remains a noticeable gap in comprehensive research comparing diverse protocols. For instance, studies that contrast the outcomes of interventions led by professionals with those prompted by computers are scarce. This ongoing project is expected to contribute to evidence-based interventions targeting reduced perceived stress levels and enhancing desk-based employees' mental and physical well-being. The implications of these findings could have the capacity to lay the groundwork for future public health initiatives and government-funded programs.


Asunto(s)
Fuerza de la Mano , Lugar de Trabajo , Humanos , Ejercicio Físico/fisiología , Ocupaciones , Dolor
18.
Nutrients ; 16(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38474736

RESUMEN

A Mediterranean diet (MedDiet) has emerged as a crucial dietary choice, not only in attenuating various adolescents' metabolic health issues but it has also been associated with improved cognitive and academic achievement. However, few studies have established patterns of food consumption linked to both cognitive and academic achievement in adolescents living in a developing country with non-Mediterranean-based food. Methods: This cross-sectional study included 1296 Chilean adolescents (50% girls) aged 10-14 years. The MedDiet Quality Index was used to assess adherence to the MedDiet in children and adolescents. Through cluster analysis, four distinct dietary patterns were identified: Western diet (WD = 4.3%); low fruit and vegetables, high-sugar diet (LFV-HSD = 28.2%); low fruit and vegetables, low-sugar diet (LFV-LSD = 42.2%); and the MedDiet (25.3%). A mixed-model analysis was conducted to compare these clusters and their relationships with cognitive and academic achievements. Principal component analysis was performed to identify four primary cognitive domains: working memory, cognitive flexibility, inhibitory control, and fluid reasoning. Academic achievement was determined with five school subjects (Language, English, Mathematics, Science, and History) and included the Academic-PISA score derived from the mean scores in Language, Mathematics, and Science. Results: A marked difference was observed between the four clusters, which was mainly related to the consumption of sugar, ultra-processed foods, fruits, and vegetables. According to cognitive performance, the MedDiet group showed higher performance across all domains than the LFV-HSD, LFV-LSD, and WD groups. Regarding academic achievement, the WD underperformed in all analyses compared to the other groups, while the MedDiet was the unique profile that achieved a positive difference in all academic subjects compared to the WD and LFV-HSD groups (p < 0.05). Conclusions: These findings suggest that higher adherence to Mediterranean-style-based patterns and better food quality choices are associated with improved cognitive and academic achievements.


Asunto(s)
Éxito Académico , Dieta Mediterránea , Femenino , Niño , Humanos , Adolescente , Masculino , Estudios Transversales , Verduras , Cognición , Análisis por Conglomerados , Azúcares
19.
Physiology (Bethesda) ; 39(3): 0, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38319138

RESUMEN

The application of single-cell molecular profiling coupled with spatial technologies has enabled charting of cellular heterogeneity in reference tissues and in disease. This new wave of molecular data has highlighted the expected diversity of single-cell dynamics upon shared external queues and spatial organizations. However, little is known about the relationship between single-cell heterogeneity and the emergence and maintenance of robust multicellular processes in developed tissues and its role in (patho)physiology. Here, we present emerging computational modeling strategies that use increasingly available large-scale cross-condition single-cell and spatial datasets to study multicellular organization in tissues and complement cell taxonomies. This perspective should enable us to better understand how cells within tissues collectively process information and adapt synchronized responses in disease contexts and to bridge the gap between structural changes and functions in tissues.


Asunto(s)
Células , Tejidos , Tejidos/citología
20.
J Electrocardiol ; 83: 95-105, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38387106

RESUMEN

Electrocardiographic patterns of right bundle branch and fascicular blocks were comprehensively analyzed in a two-phase study. The research aimed to address the scarcity of literature and the absence of standardized diagnostic criteria for these conditions. It revealed a weak correlation between the cardiac axis and age and highlighted the high misdiagnosis rate of these blocks. Furthermore, it discussed the challenges in fulfilling existing diagnostic criteria. The study emphasizes the need for a more precise understanding of right ventricular conduction disorders and the importance of developing robust diagnostic criteria.


Asunto(s)
Bloqueo de Rama , Electrocardiografía , Humanos , Bloqueo de Rama/diagnóstico , Sistema de Conducción Cardíaco , Ventrículos Cardíacos
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