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We thank Dr. Najjar for his interest [...].
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Enfermedades Cardiovasculares , Dieta Cetogénica , Humanos , Enfermedades Cardiovasculares/epidemiología , NutrientesRESUMEN
The combination of ketogenic diet (KD) with intermittent fasting (IF) has, for years, aroused a great interest in the scientific world and among healthy lifestyle enthusiasts. Its importance is even greater when the study subjects are physically active individuals. The aim of the study was a determination of the effect of strict calculated ketogenic menu combined with IF and with caloric deficit on the selected biochemical markers and body composition in a 23-year-old man performing strength training. At the same time, we decided to conduct the first so-deeply investigated and controlled case study in this respect. The study protocol included a 13-week-long ketogenic diet with intermittent fasting (of delayed time-restricted eating 16:8 type) and caloric deficit. A detailed menu was designed and was used by the man throughout the whole study duration. A number of blood tests were performed before and after the implemented dietary intervention. Additionally, body composition was determined weekly and the concentrations of glucose and ketone bodies, as well as pulse rate and arterial pressure, were measured daily. The most important changes noted included a significant increase in testosterone and vitamin D concentrations and significant reduction in the HOMA-IR index and concentrations of hepatic enzymes, insulin, glucose, iron, urea, and free triiodothyronine (FT3). Moreover, a significant improvement of body composition occurred (the ratio of total body mass to the adipose and muscular tissue and water mass improved). Favourable changes were also noted in heart rate and arterial pressure values. In view of that, the KD with IF and caloric deficit exerted favourable effects on most biochemical parameters and on body composition and caused an almost twofold increase in serum testosterone concentration.
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Background: It is estimated that more than 60 million people in Europe, that is, around 12% of the European population, have at least one tattoo. However, there is still little information on the long-term effects of tattoos. Inks used for tattooing are a mixture of chemicals, with pigments being the main components responsible for the visual effect. The pigments used are not produced specifically as ingredients for tattooing, but mainly/primarily for the needs of industry, where lower purity requirements and quality standards are acceptable. It is therefore necessary to understand the risks associated with tattoos, but also to implement appropriate legal regulations. The aim of this article was to collect and summarise the results of research conducted so far on the type of colourants used in tattoo ink and to analyze the impact of these on human health. In addition, as part of this work, the current legal acts regulating the concentration limits and composition of inks used in tattooing as well as the psychological aspects of tattooing were collected and presented. Methods: Scientific reports and articles from renowned journals from 1994 to 2022, relevant review and research publications in PubMed, and Google Scholar were analyzed. To analyze the available research literature, the Web of Science, Scopus, PubMed databases were used. The following keywords were used to search for publications: tattoos, colourants used in tattoos, side effects of tattoos, legal acts, psychological aspects of tattoos. Results: The result of the literature analysis indicates a risk to health and side effects associated with tattooing the body. There are still no standardised test methods to analyze tattoo inks and assess their safety. Although the art of tattooing has been known for millennia, European legal authorities have not yet implemented effective regulations. Currently, tattoo products in Europe are covered by the general REACH regulation (Resolution ResAP, 2008; EU regulation 2020/2081, 2020). on product safety. The new amendment in force since January 4, 2022 introduces concentration limits for certain substances used in tattoo and permanent makeup inks. However, these provisions do not sufficiently protect either the consumer or the tattoo industry. Conclusions: The results of the research indicate a potentially harmful effect on skin health. A more stringent safety assessment of the colourants used for tattooing is recommended, supported by studies and applicable legislation.
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The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.
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Enfermedades Cardiovasculares , Dieta Cetogénica , Humanos , Dieta Cetogénica/métodos , Enfermedades Cardiovasculares/prevención & control , Lípidos , Dieta , Cuerpos Cetónicos/metabolismoRESUMEN
BACKGROUND: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET. METHODS: Using the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography-mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients. RESULTS: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients (p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = -1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86. CONCLUSIONS: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients' condition, helping with pharmacological treatment or dietary strategies.
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Background: COVID-19 is a new pandemic, which was declared by the World Health Organization in 2019 as a threat to public health. According to numerous reports, it can have negative consequences for pregnant women, labour, and neonates born to infected mothers. The aim of this paper was to gather the evidence and to present a summary of the results of studies concerning COVID-19 in pregnant women and their neonates. Methods: Articles from prestigious journals covering the period from 2020 to February 2023, relevant review papers, and original research articles from PubMed were analysed. In order to analyse the available research literature, the Web of Science, Scopus, and PubMed databases were used, in which the search for articles was conducted using terms ("pregnancy," "coronavirus," "SARS-CoV-2," and "newborn") and using PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analysis) guidelines for clinical trials. Meta-analyses and systematic reviews (2022-2023) on symptoms, neonatal course, and risk of COVID-19 infection have been summarized. Summary of meta-analyses and systematic reviews (2022-2023) on the effect and adverse reaction of the COVID-19 vaccination is presented. Results: As a result of the research conducted, it was confirmed that in most pregnant women, no serious signs of the infection were observed, although isolated cases of death related to COVID-19 in pregnant women were reported. Several authors called attention to the more severe course of the infection in pregnant women with obesity. It seemed that no vertical transmission from mother to child was occurring. Nevertheless, the information was not clinching. The condition of the neonates born to mothers with COVID-19 was in most cases described as normal; however, some papers reported deaths of infected neonates. Conclusions: Due to insufficient data, further research is necessary. Further studies and follow-up are recommended, which would make possible an assessment of remote effects of COVID-19 on pregnancy and vital parameters of the newborn.
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COVID-19 , Complicaciones Infecciosas del Embarazo , Niño , Femenino , Humanos , Recién Nacido , Embarazo , Vacunas contra la COVID-19 , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Parto , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/diagnóstico , SARS-CoV-2RESUMEN
BACKGROUND: The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM). METHODS: UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR. RESULTS: A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways. CONCLUSIONS: This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Vesículas Extracelulares , MicroARNs , Insuficiencia Renal Crónica , Humanos , MicroARNs/genética , Vesículas Extracelulares/metabolismoRESUMEN
The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue; its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.
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Diabetes Mellitus Tipo 2 , Dieta Cetogénica , Humanos , Diabetes Mellitus Tipo 2/prevención & control , Glucosa , Hemoglobina Glucada , InsulinaRESUMEN
The most important function of the skin is to protect the body against harmful mechanical, physical and chemical factors. Its regenerative capacity is sufficient for self-repair in the event of damage, for example, during tattooing, which can be treated as an invasive procedure introducing pigment molecules into skin layers. In the present research on tattoo pigment deposition, the structure of the dermis and epidermis was evaluated using the standard histological technique with hematoxylin and eosin staining. In addition, statistically significant differences between the depth of pigment deposition on the one hand and age, dermis and epidermis thickness and tattoo location on the other were demonstrated.
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Tatuaje , Masculino , Humanos , Tatuaje/efectos adversos , Colorantes , Piel , Coloración y EtiquetadoRESUMEN
Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.
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Enfermedad de Alzheimer , Dieta Cetogénica , Epilepsia , Esclerosis Múltiple , Enfermedad de Parkinson , Humanos , Enfermedad de Alzheimer/metabolismo , Dieta Cetogénica/métodosRESUMEN
Breast cancer (BC) is the most common cancer diagnosed among women in the world, with an ever-increasing incidence rate. Due to the dynamic increase in the occurrence of risk factors, including obesity and related metabolic disorders, the search for new regulatory mechanisms is necessary. This will help a complete understanding of the pathogenesis of breast cancer. The review presents the mechanisms of obesity as a factor that increases the risk of developing breast cancer and that even initiates the cancer process in the female population. The mechanisms presented in the paper relate to the inflammatory process resulting from current or progressive obesity leading to cell metabolism disorders and disturbed hormonal metabolism. All these processes are widely regulated by the action of microRNAs (miRNAs), which may constitute potential biomarkers influencing the pathogenesis of breast cancer and may be a promising target of anti-cancer therapies.
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Neoplasias de la Mama , Enfermedades Metabólicas , MicroARNs , Obesidad , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica , Enfermedades Metabólicas/genética , MicroARNs/genética , Obesidad/complicaciones , Obesidad/genética , Obesidad/patología , Factores de RiesgoRESUMEN
The cervical microbiome (CM) is a complex ecosystem that can change in response to gynecological cancers. We aimed to evaluate changes in the CM of patients who underwent chemoradiation (CRT) therapy for locally advanced cervical cancer. Before and after CRT, cervical swab samples were collected from 16 patients with squamous cell carcinoma of the cervix, and 30 healthy women. All samples were subjected to 16s rRNA-Seq analysis. In healthy premenopausal women the CM comprised mostly Lactobacillus (>90%); the CM community in samples from both pre- and postmenopausal pre-treatment cancer patients was heterogeneous, with a low proportion of Lactobacillus in younger cases. On the genus level, 27 and 11 taxa differentiated healthy controls from cancer patients in pre- and postmenopausal age groups, while 31 and 2 genera differentiated pre- and post-radiation samples and pre-radiation and the follow-up samples, respectively. Microbiome diversity was significantly higher in pre-treatment patients than in healthy controls. The results reveal significant alterations in the CM of cervical cancer patients relative to that in healthy controls; these changes were more striking after CRT. However, further research is needed to determine whether alteration of the CM offers new therapeutic options.
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Several single nucleotide polymorphisms (SNPs) associated with susceptibility to Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have been identified. The aim of this study was to identify susceptibility loci for HL and DLBCL in Polish patients. Altogether, DLBCL (n = 218 and HL patients (n = 224) and healthy individuals (n = 1181) were recruited. Lymphoma diagnosis was based on standard criteria. Genome-wide association study (GWAS) was performed using pooled-DNA samples on llumina Infinium Omni2.5 Exome-8 v1.3, and selected loci were replicated by TaqMan SNP genotyping of individuals. GWAS detected thirteen and seven SNPs associated with DLBCL and HL, respectively. In the replication study, six and seven SNPs reached significance after correction for multiple testing in the DLBCL and HL cohorts, respectively. One and four SNPs associated with DLBCL and HL, respectively, were localized within, and two SNPs-near the major histocompatibility complex (MHC) region. In conclusion, the majority of loci associated with HL and DLBCL aetiology in previous studies have potential roles in immune function. Our pooled-DNA GWAS enabled the identification of several susceptibility loci for DLBCL and HL in the Polish population; some of them were mapped within or adjacent to the MHC, and other associated SNPs were located outside the MHC.
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Estudio de Asociación del Genoma Completo , Linfoma , ADN , Predisposición Genética a la Enfermedad , Humanos , Linfoma/genética , Polonia , Polimorfismo de Nucleótido SimpleRESUMEN
Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.
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Within the endolysosomal pathway in mammalian cells, ESCRT complexes facilitate degradation of proteins residing in endosomal membranes. Here, we show that mammalian ESCRT-I restricts the size of lysosomes and promotes degradation of proteins from lysosomal membranes, including MCOLN1, a Ca2+ channel protein. The altered lysosome morphology upon ESCRT-I depletion coincided with elevated expression of genes annotated to biogenesis of lysosomes due to prolonged activation of TFEB/TFE3 transcription factors. Lack of ESCRT-I also induced transcription of cholesterol biosynthesis genes, in response to inefficient delivery of cholesterol from endolysosomal compartments. Among factors that could possibly activate TFEB/TFE3 signaling upon ESCRT-I deficiency, we excluded lysosomal cholesterol accumulation and Ca2+-mediated dephosphorylation of TFEB/TFE3. However, we discovered that this activation occurs due to the inhibition of Rag GTPase-dependent mTORC1 pathway that specifically reduced phosphorylation of TFEB at S112. Constitutive activation of the Rag GTPase complex in cells lacking ESCRT-I restored S112 phosphorylation and prevented TFEB/TFE3 activation. Our results indicate that ESCRT-I deficiency evokes a homeostatic response to counteract lysosomal nutrient starvation, that is, improper supply of nutrients derived from lysosomal degradation.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Complejos de Clasificación Endosomal Requeridos para el Transporte , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Lisosomas/metabolismo , Mamíferos/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Transducción de SeñalRESUMEN
The diagnosis of primary central nervous system (CNS) lymphoma, which is predominantly of the diffuse large B-cell lymphoma type (CNS DLBCL), is challenging. MicroRNAs (miRs) are gene expression-regulating non-coding RNAs that are potential biomarkers. We aimed to distinguish miR expression patterns differentiating CNS DLBCL and non-malignant CNS diseases with tumor presentation (n-ML). Next generation sequencing-based miR profiling of cerebrospinal fluids (CSFs) and brain tumors was performed. Sample source-specific (CSF vs. brain tumor) miR patterns were revealed. Even so, a set of 17 miRs differentiating CNS DLBCL from n-ML, no matter if assessed in CSF or in a tumor, was identified. Along with the results of pathway analyses, this suggests their pathogenic role in CNS DLBCL. A combination of just four of those miRs (miR-16-5p, miR-21-5p, miR-92a-3p, and miR-423-5p), assessed in CSFs, discriminated CNS DLBCL from n-ML samples with 100% specificity and 67.0% sensitivity. Analyses of paired CSF-tumor samples from patients with CNS DLBCL showed significantly lower CSF levels of miR-26a, and higher CSF levels of miR-15a-5p, miR-15b-5p, miR-19a-3p, miR-106b-3p, miR-221-3p, and miR-423-5p. Noteworthy, the same miRs belonged to the abovementioned set differentiating CNS DLBCL from non-malignant CNS diseases. Our results not only add to the basic knowledge, but also hold significant translational potential.
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Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/genética , Encéfalo/metabolismo , Linfoma/líquido cefalorraquídeo , Linfoma/genética , MicroARNs/líquido cefalorraquídeo , MicroARNs/genética , Adulto , Anciano , Neoplasias Encefálicas/patología , Diagnóstico Diferencial , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Linfoma/patología , Linfoma de Células B Grandes Difuso/líquido cefalorraquídeo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Curva ROCRESUMEN
The gastric microbiota in Crohn's disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls.
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Enfermedad de Crohn/microbiología , Firmicutes/genética , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Bacteroidetes/genética , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/genética , Heces/microbiología , Fusobacterias/genética , Humanos , Proteobacteria/genéticaRESUMEN
BACKGROUND: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. METHODS: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. RESULTS: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. CONCLUSIONS: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.
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Regulación Neoplásica de la Expresión Génica , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Proteínas Supresoras de Tumor/genética , Apoptosis/genética , Estudios de Casos y Controles , Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular , Resistencia a Antineoplásicos/genética , Humanos , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Esferoides Celulares/patología , Cáncer Papilar Tiroideo/tratamiento farmacológico , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
The data demonstrating a correlation between sonographic markers of malignancy of thyroid cancer (TC) and its genetic status are scarce. This study aimed to assess whether the addition of genetic analysis at the preoperative step of TC patients' stratification could aid their clinical management. The material consisted of formalin-fixed paraffin-embedded tumor fragments of 49 patients who underwent thyroidectomy during the early stages of papillary TC (PTC). Tumor DNA and RNA were subjected to next-generation sequencing (NGS) on Ion Proton using the Oncomine™ Comprehensive Assay panel. We observed a significant correlation between BRAF V600E and a higher EU-TIRADS score (p-value = 0.02) with a correlation between hypoechogenicity and taller-than-wide tumor shape in analysed patients. There were no other significant associations between the identified genetic variants and other clinicopathological features. For TC patient's stratification, a strong suspicion of BRAF V600E negativity in preoperative management of TC patients could limit the over-treatment of asymptomatic, very low-risk, indolent disease and leave room for active surveillance.