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1.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38928446

RESUMO

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.


Assuntos
Biologia Computacional , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Feminino , Gravidez , Biologia Computacional/métodos , Redes Reguladoras de Genes , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Perfilação da Expressão Gênica , Transdução de Sinais/genética , Regulação da Expressão Gênica
2.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673986

RESUMO

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.


Assuntos
Ritmo Circadiano , Demência Vascular , Estresse Oxidativo , Animais , Humanos , Relógios Circadianos/genética , Demência Vascular/tratamento farmacológico , Demência Vascular/metabolismo , Demência Vascular/patologia , Demência Vascular/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Terapia de Alvo Molecular
3.
Int J Mol Sci ; 24(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38139395

RESUMO

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.


Assuntos
Infecções por HIV , HIV-1 , Transtornos Neurocognitivos , Sirtuína 3 , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Animais , Ratos , Produtos do Gene tat/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/virologia , Neurônios/metabolismo , Biogênese de Organelas , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Sirtuína 3/genética , Sirtuína 3/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
4.
Int J Mol Sci ; 23(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35054829

RESUMO

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain-blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer's and Parkinson's disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.


Assuntos
Infecções por HIV/psicologia , Doenças Neurodegenerativas/metabolismo , Sirtuínas/metabolismo , Estresse do Retículo Endoplasmático , Regulação da Expressão Gênica , Infecções por HIV/metabolismo , Humanos , Qualidade de Vida , Resposta a Proteínas não Dobradas
5.
Mol Biol Rep ; 48(5): 4247-4252, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34097204

RESUMO

Among the host restriction factors against HIV, SERINC5 has been described in vitro, but the mRNA level of SERINC5 in vivo has been little studied. We compare SERINC5 expression in subjects with HIV-1 (highly active antiretroviral treatment (HAART) and HAART-naïve) with and without suppression of viral load. A cross-sectional study was performed with 107 individuals distributed as follows: 24 with HAART-naïve and detectable viral load (> 50 copies/mL), 13 with HAART and detectable viral load (> 50 copies/mL), 50 with HAART and undetectable viral load (≤ 50 copies/mL), and 20 without HIV-1. SERINC5 expression in buffy coats was determined using RT-qPCR. The viral load was determined using real-time PCR and the amount of CD4 + and CD8 + T-lymphocytes was measured using flow cytometry. The data were normalized with the Shapiro-Wilk test and the Kruskal-Wallis test was subsequently performed. The relative expression was compared with a T-test and the remaining data with the Mann-Whitney U-test. ANCOVA multiple linear regression analysis was performed between characteristics of patients with SERINC5 expression. The mean and SD of the SERINC5 expression in the three groups with HIV-1 was 0.9 ± 0.2 and without HIV-1 was 1.7 ± 0.14 (P < 0.001). Multiple linear regression did not show the participation of CD4 +, CD8 + , viral load, infection time, or treatment time. No differences in the SERINC5 expression were found among the studied groups of patients with HIV-1. When comparing the groups with and without HIV-1 infection, SERINC5 was downregulation in the HIV-1 groups.


Assuntos
Buffy Coat/metabolismo , Regulação para Baixo/genética , Infecções por HIV/sangue , Infecções por HIV/genética , HIV-1/genética , Proteínas de Membrana/genética , Carga Viral/métodos , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/métodos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Resultado do Tratamento , Adulto Jovem
6.
Genet Mol Biol ; 43(3): e20200017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584920

RESUMO

MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.

7.
Rev Invest Clin ; 68(6): 292-298, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28134940

RESUMO

BACKGROUND: Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1ß and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. METHODS: In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. RESULTS: The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1ß concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. CONCLUSIONS: The neuronal cell loss caused by endotoxic shock and interleukin-1ß levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.


Assuntos
Citocinas/metabolismo , Eritropoetina/farmacologia , Fármacos Neuroprotetores/farmacologia , Choque Séptico/prevenção & controle , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Hipocampo/patologia , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Melatonina/farmacologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
8.
Int Arch Allergy Immunol ; 163(4): 252-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24713632

RESUMO

BACKGROUND: Restrictive, very low-energy diets focused on rapid weight loss have proven to be effective in improving asthma outcome in obese patients, but their use in children and pubescents is controversial due its potential consequences in growth. More conservative, normocaloric schemes are suggested as a more suitable dietary approach for these patients. METHODS: A randomized clinical trial was run of 51 pubertal adolescents with asthma and obesity, who were allocated to either an interventional 28-week program of normocaloric diet based on normal requirements for height and meal planning (n = 26) or a non-interventional (free diet) control group (n = 25). Asthma-related quality of life (AR-QOL, assessed by the Standardized Pediatric Asthma Quality of Life Questionnaire, PAQLQ[S]) and clinical indicators of asthma control were measured before and after the intervention period. RESULTS: Diet intervention was associated with a significant improvement in AR-QOL in relation to baseline (Δ PAQLQ[S] scores) compared with controls, both in overall score (p < 0.001) and its subdomains (activity limitation, p < 0.001; symptoms, p < 0.002; emotional function, p < 0.001). The group with normocaloric diet observed a significant decrease in body mass index z-score, which correlated positively with the improvement in AR-QOL (Spearman's r = 0.51, p < 0.01), in addition to have significantly fewer events of acute attacks of asthma and nighttime awakenings, plus a non-significant reduction in the use of inhaled corticosteroids. No significant changes were observed in the pulmonary function tests. CONCLUSION: The normocaloric dietary intervention was associated with improvement of AR-QOL and some aspects of asthma control. Such structured dietary programs could probably have a role as a complementary non-pharmacological therapeutic strategy in obese pubertal adolescents with asthma.


Assuntos
Asma/dietoterapia , Dieta Redutora , Obesidade Infantil/dietoterapia , Qualidade de Vida , Adolescente , Índice de Massa Corporal , Criança , Terapias Complementares , Comportamento Alimentar , Feminino , Humanos , Masculino , Cooperação do Paciente , Inquéritos e Questionários , Redução de Peso
9.
Mutagenesis ; 29(6): 427-31, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25232046

RESUMO

The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future.


Assuntos
Anorexia Nervosa/patologia , Bulimia Nervosa/patologia , Micronúcleos com Defeito Cromossômico , Mucosa Bucal/patologia , Adolescente , Adulto , Antropometria , Estudos de Casos e Controles , Feminino , Humanos , Adulto Jovem
10.
Neuroscience ; 549: 76-83, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38734304

RESUMO

Stroke is one of the leading causes of disability worldwide, where the Hippocampus (HPC) is affected. HPC organizes memory, which is a cognitive domain compromised after a stroke, where cerebrolysin (CBL) and Nicotinamide (NAM) have been recognized as potentially therapeutic. In this study, we aimed to evaluate the efficacy of a combined administration of CBL and NAM in a rat stroke model. Male Sprague-Dawley rats (n = 36) were divided into four groups: saline (pMCAO - Saline), CBL (pMCAO + CBL), NAM (pMCAO + NAM), and experimental (pMCAO + CBL-NAM) (n = 9 per group). A permanent middle cerebral artery occlusion (pMCAO) was induced through electrocauterization of the middle cerebral artery, followed by the administration of CBL (2.5 ml/kg), NAM (500 mg/kg) or combined immediately after skin suture, as well as at 24, 48, and 72 h post-surgery. The rats were evaluated in the novel object recognition test; hippocampal infarct area measurement; reconstruction of neurons from CA1 for Sholl analysis; and, measurement of brain-derived neurotrophic factor (BDNF) levels near the infarct zone. Our findings revealed that the administration of CBL or NAM induced infarct reduction, improved cognition, and increased BDNF levels. Moreover, a combination of CBL and NAM increased dendritic intersection in CA1 pyramidal neurons. Thus, the combined administration of CBL and NAM can promote cognitive recovery after a stroke, with infarct reduction, cytoarchitectural changes in HPC CA1 neurons, and BDNF increase. Our findings suggest that this combination therapy could be a promising intervention strategy for stroke.


Assuntos
Aminoácidos , Cognição , Hipocampo , Infarto da Artéria Cerebral Média , Neurônios , Fármacos Neuroprotetores , Niacinamida , Ratos Sprague-Dawley , Animais , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Aminoácidos/farmacologia , Aminoácidos/administração & dosagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Niacinamida/farmacologia , Niacinamida/administração & dosagem , Cognição/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Quimioterapia Combinada , Modelos Animais de Doenças
11.
Brain Res ; 1825: 148694, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38048977

RESUMO

Stroke is a pathology related to the vascular system in the brain and it is one of the main causes of disability, representing a burden on public health. This lesion provokes a disorganization of sensory-motor and cognitive systems, the latter associated with hippocampal activity, a structure in which α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA N-methyl-D-aspartate (NMDA) receptors are important for the integration of information. Several molecules have been studied for their capacity to enhance recovery from a stroke, including cerebrolysin that could potentially be reinforced by environmental enrichment. Here, stroke was induced in 40 male rats and 24 h later, they were administered cerebrolysin (2.5 ml/kg), put in an environmentally enriched arena or given both treatments, for 10 days. Subsequently, motor functioning was assessed with the Bederson test and the cognitive domain was assessed through novel object recognition. Hematoxylin/eosin staining was then used to assess the infarct size, and AMPA-GRIA1 and NMDA-R1 subunits in the hippocampus were measured by ELISA. In motor and cognitive performance, the administration of cerebrolysin and environmental enrichment enhanced recovery. Moreover, the infarct size decreased in all the groups that received a treatment, but an increase occurred in AMPA-GRIA1 only in experimental group regarding to control group, while NMDA-R1 had no differences. These results suggest that cerebrolysin and environmental enrichment could act in synergy to recover after a stroke, leading to a smaller infarct area and the presence of more AMPA-GRIA1 subunits in the hippocampus of experimental group. These data encourage further studies in which neurorehabilitation approaches can be combined with cerebrolysin administration to treat the motor and cognitive symptoms of stroke.


Assuntos
Aminoácidos , N-Metilaspartato , Acidente Vascular Cerebral , Ratos , Animais , Masculino , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologia , N-Metilaspartato/farmacologia , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Hipocampo/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Infarto , Cognição
12.
Mult Scler Relat Disord ; 82: 105373, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154347

RESUMO

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.


Assuntos
Metaloproteinase 9 da Matriz , Esclerose Múltipla , Gravidez , Humanos , Feminino , Esclerose Múltipla/genética , Transcriptoma , Mapas de Interação de Proteínas , Biologia Computacional , Proteínas Sanguíneas , Chaperonas Moleculares
13.
Biomedicines ; 12(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38540215

RESUMO

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

14.
Int J Gynaecol Obstet ; 162(1): 244-255, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36637233

RESUMO

BACKGROUND: The menarche plays an important role in a woman's life, as its onset may generate the development of certain pathologies in the future. OBJECTIVES: To review the updated bibliography about risk factors related to the age of onset of menarche. SEARCH STRATEGY: A systematic search review of PubMed, Scopus, EMBASE, EBSCO-Host, Springer Link, and Clinical Key from November 2021 to May 2022. DATA COLLECTION AND ANALYSIS: From each article a descriptive summary organized by first author, year of publication, type of article, characteristics of the study, and results was extracted. The results of the different articles were compared before using them in the current literature review. MAIN RESULTS: A total of 15 824 articles were collected, from which 33 articles were used following the inclusion and exclusion criteria. It was found that an early estrogen stimulus triggers a predisposing factor for pathologies such as insulin resistance, asthma and short stature. In contrast, a late estrogenic stimulus generates low bone mineral density. CONCLUSIONS: The importance of menarche as a protective or triggering factor of pathologies helps us to implement preventive measures to avoid these future pathologies.


Assuntos
Resistência à Insulina , Menarca , Feminino , Humanos , Fatores de Risco , Fatores Etários
15.
Artigo em Inglês | MEDLINE | ID: mdl-37567649

RESUMO

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.

16.
Brain Sci ; 13(3)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36979318

RESUMO

The main histopathological hallmarks of Parkinson's disease (PD) are the degeneration of the dopaminergic neurons of the substantia nigra pars compacta and the loss of neuromelanin as a consequence of decreased dopamine synthesis. The destruction of the striatal dopaminergic pathway and blocking of striatal dopamine receptors cause motor deficits in humans and experimental animal models induced by some environmental agents. In addition, neuropsychiatric symptoms such as mood and anxiety disorders, hallucinations, psychosis, cognitive impairment, and dementia are common in PD. These alterations may precede the appearance of motor symptoms and are correlated with neurochemical and structural changes in the brain. This paper reviews the most crucial pathophysiology of neuropsychiatric alterations in PD. It is worth noting that PD patients have global task learning deficits, and cognitive functions are compromised in a way is associated with hypoactivation within the striatum, anterior cingulate cortex, and inferior frontal sulcus regions. An appropriate and extensive neuropsychological screening battery in PD must accurately assess at least five cognitive domains with some tests for each cognitive domain. This neuropsychological screening should consider the pathophysiological and clinical heterogeneity of cognitive dysfunction in PD.

17.
J Clin Med ; 11(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35806869

RESUMO

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS.

18.
Int J Ment Health Addict ; 20(2): 895-906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33169075

RESUMO

The presence of COVID-19 has had psychological consequences among health personnel; these include fear, anxiety, and depression. In the current study, we used the Fear of COVID-19 Scale (FCV-19S) to assess the response to fear within health staff in Mexico. This was a cross-sectional survey study in which we administered the Spanish version of the FCV-19S to hospital staff. The FCV-19S is a seven-item questionnaire that assesses the severity of fear caused by COVID-19. A total of 2860 participants-1641 female and 1218 male personnel from three hospitals-were included in the study. The internal reliability of the scale was good, with Cronbach's alpha of .902. A confirmatory factor analysis (CFA) was conducted on the seven items of the FCV-19S, showing good model fit (χ 2 (7) = 29.40, p < .001; CFI = .99; TLI = .99; RMSEA = .03; SRMR = .010; AIC = 71.40). We found a global FCV-19S mean score of 19.3 ± 6.9, with a significant difference in scores between women and men. Our survey shows a significantly higher level of fear in nursing and administrative personnel, which may be explained by the nursing staff being in close contact with infected patients and the administrative staff lacking understanding of the possible implications of the infection, compared with nonclinical hospital personnel. Our results are consistent with those of other researchers. We must remember that fear is a reaction and that we must be courageous enough to trust validated infection prevention practices to provide the highest standard of care, in the safest environment that we can, for as long as we can.

19.
Nutr Hosp ; 38(2): 366-373, 2021 Apr 19.
Artigo em Espanhol | MEDLINE | ID: mdl-33615820

RESUMO

INTRODUCTION: Introduction and objective: pregnancy is a stage of life with high nutritional vulnerability and increased levels of maternal oxidative stress. Total antioxidant capacity (CAT) identifies the protective effect of a balanced diet rich in foods of plant origin with antioxidant activity. The aim of this study was to relate CAT with dietary intake and body mass index (BMI) in pregnant women in the Community of Madrid. Methods: a cross-sectional, comparative study was conducted in 89 pregnant women and 61 healthy women of reproductive age. Age, place of origin, weight, height, BMI, macronutrient and micronutrient intake, and dietary CAT by food frequency were recorded; CAT was classified as desirable (≥ 19,301.0 µm/g) or undesirable (< 19,301.0 µm/g); the statistical analysis, including χ², Student's t-test or Mann Whitney U-test, was made using the SPSS program v.23. Results: differences were found in caloric profile, intake of antioxidant micronutrients, and dietary CAT (p < 0.05). Mean CAT in pregnant women was 23,163.0 ± 10,829.0 µm/g, whereas in non-pregnant women it was 25,916.0 ± 9,703.0 µm/g (p = 0.035). Pregnant women with a desirable CAT (56.2 %) preferred to consume fruits and vegetables, and 65.6 % of non-pregnant women preferred bread, pasta and cereals (p = 0.02). Hand fruit, citrus fruits, green leafy vegetables, and tomato were preferentially consumed by both groups. In pregnant women, poor nutritional status, overweight, and obesity rates of 36.0 % were found versus 28.0 % in non-pregnant women (p < 0.001). Conclusion: the BMI of pregnant women is not related to dietary CAT or the relatively low consumption of antioxidant components.


INTRODUCCIÓN: Introducción y objetivo: el embarazo es una etapa de la vida con alta vulnerabilidad nutricional y aumento de los niveles de estrés oxidativo en la madre. La capacidad antioxidante total (CAT) identifica el efecto protector de la dieta equilibrada, rica en alimentos de origen vegetal con actividad antioxidante. El objetivo de este estudio fue relacionar la CAT con la ingesta dietética y el índice de masa corporal (IMC) en mujeres gestantes pertenecientes a la Comunidad de Madrid. Métodos: se realizó un estudio transversal comparativo de 89 mujeres gestantes y 61 mujeres sanas en edad reproductiva. Se registraron la edad, el lugar de origen, el peso, la estatura, el IMC, la ingesta de macronutrientes y micronutrientes, y la CAT dietética por frecuencia alimentaria; la CAT se clasificó como deseable (≥ 19.301,0 µm/g) y no deseable (< 19.301,0 µm/g); el análisis estadístico, con la prueba del χ², la prueba de la t de Student o la prueba de la U de Mann Whitney, se realizó de acuerdo con la normalidad de las variables en la población estudiada. Se utilizó el programa SPSS, versión 23. Resultados: se encontraron diferencias en el perfil calórico, la ingesta de micronutrientes antioxidantes y la CAT dietética (p < 0,05). La CAT promedio en las gestantes fue de 23.163,0 ± 10.829,0 µm/g, frente a 25.916,0 ± 9.703,0 µm/g en las no gestantes (p = 0,035). Las gestantes con CAT deseable (56,2 %) preferían consumir frutas y verduras, mientras que el 65,6 % de las mujeres no gestantes preferían el pan, la pasta y los cereales (p = 0,03). La fruta de mano, los frutos cítricos, las verduras de hoja verde y el tomate eran consumidos preferentemente por ambos grupos. En las mujeres gestantes, en cuanto al estado nutricional deficiente, la tasa de sobrepeso y obesidad fue del 36,0 %, frente al 28,0 % entre las no gestantes (p < 0,001). Conclusión: el IMC de las mujeres gestantes no está relacionado con la CAT dietética ni con el relativo bajo consumo de componentes antioxidantes.


Assuntos
Antioxidantes/administração & dosagem , Índice de Massa Corporal , Ingestão de Alimentos , Micronutrientes/administração & dosagem , Adulto , Estudos de Casos e Controles , Estudos Transversais , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Frutas/química , Humanos , Nutrientes/administração & dosagem , Estado Nutricional , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Estresse Oxidativo , Gravidez , Complicações na Gravidez/epidemiologia , Gestantes , Espanha , Verduras/química
20.
Animals (Basel) ; 11(11)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34827910

RESUMO

Micronuclei (MN) are used to assess genotoxic exposure, whereas nuclear buds (NBs) have been linked to genotoxic events. Crocodylus moreletii was studied to identify MN and NBs. Three groups were formed: Group 1 (water) and groups 2 and 3 (7 or 10 mg/kg of cyclophosphamide). A drop of blood was obtained daily from the claw tip at 0 to 120 h. Spontaneous micronucleated erythrocytes (MNEs) and erythrocytes with nuclear buds (NBEs) were counted. The frequencies of micronucleated young erythrocytes (MNYEs) and NB young erythrocytes (NBYEs) were evaluated, including the ratio of young erythrocytes (YE)/1000 total erythrocytes. No significant differences were observed in the YE proportion on sampling days; group 1 did not show differences for any parameter, whereas group 2 showed significant differences in MNEs and NBEs, and group 3 showed differences in NBEs and NBYEs. Some mitotic activity in circulation was observed in YEs. In conclusion, NBEs could be a more sensitive biomarker to genotoxic damage than MNEs. The identification of these biomarkers leads us to propose Crocodylus moreletii as a possible environment bioindicator because these parameters could be useful to analyze the in vivo health status of these reptiles and for biomonitoring genotoxic pollutants in their habitats.

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