RESUMEN
Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.
Asunto(s)
Trastorno Bipolar , Litio , Humanos , Litio/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Trastorno Bipolar/diagnóstico , Genes de Inmunoglobulinas , Compuestos de Litio/farmacología , Compuestos de Litio/uso terapéutico , Línea CelularRESUMEN
Background and Objectives: Desquamative gingivitis (DG) is a clinical term indicating "peeling gums" and is associated with different oral manifestations. In this study, we aimed to assess the association between DG and autoimmune blistering mucocutaneous diseases (ABMD) with oral manifestations. Materials and Methods: A retrospective study including 88 patients diagnosed between 1998 and 2019 with ABMD (intraepithelial and subepithelial autoimmune blistering diseases) was performed at the Oral Medicine Department, Faculty of Dentistry, "Carol Davila" University of Medicine and Pharmacy in Bucharest. For each patient, the sociodemographic and anamnestic data, as well as clinical features of oral lesions (location), histological evaluation, and direct immunofluorescence data were collected. Results: Most of the patients involved in the study were female (78.4%). In total, 34 patients (38.63%) were diagnosed with subepithelial autoimmune diseases (SAD) and 54 (61.36%) had intraepithelial autoimmune diseases (IAD). Differences in the anatomic distribution of oral involvement were found between SAD and IAD. The presence of DG was significantly more common in patients with SAD compared to those with a diagnosis of IAD. Conclusions: Specific anatomical locations of the oral lesions are significantly associated with different subtypes of ABMD, with gingiva and hard palate mucosa being more involved in SAD and the soft palate and buccal mucosa in IAD. Desquamative gingivitis is a clinical sign that raises diagnostic challenges for several conditions in oral medicine.
Asunto(s)
Enfermedades Autoinmunes , Gingivitis , Humanos , Femenino , Masculino , Encía , Estudios Retrospectivos , Mucosa Bucal , Enfermedades Autoinmunes/complicaciones , Enfermedad Crónica , Gingivitis/complicacionesRESUMEN
Background and Objectives: Noncommunicable diseases (NCDs) are a group of non-transmissible conditions that tend to be of long duration and are the result of a combination of genetic, physiological, environmental, and behavioral factors. Although an association between oral disorders and NCDs has been suggested, the relationship between Burning Mouth Syndrome (BMS) and NCDs and their associated risk factors has not been deeply investigated. In this study, we aim to identify associations between BMS and NCDs in the Romanian population. Materials and Methods: Ninety-nine BMS patients and 88 age-matched controls (aged 50 and over) were clinically evaluated for the presence of eight noncommunicable diseases (NCDs) and their most common risk factors, including hypertension, dyslipidemia, smoking, and obesity. Results: The results of our study showed that the BMS in the Romanian population seems to be significantly associated with cardiovascular diseases (CVDs) (p < 0.001) and two of their risk factors, hypertension (p < 0.001) and dyslipidemia (p < 0.001). Moreover, evaluating the Framingham Risk Score (FRS) in the individuals not affected by CVDs (73 CTRL and 38 BMS), we found that 13.2% of BMS patients reported a moderate risk of developing CVDs in ten years, compared to the controls, all of whom presented a low risk (p = 0.002). Conclusions: Our findings suggest that a multidisciplinary clinical approach, which also includes a cardiovascular evaluation, is essential for the successful management of BMS. Moreover, these data highlighted the importance of introducing an integrated strategy for the prevention and care of NCDs in BMS patients.
Asunto(s)
Síndrome de Boca Ardiente , Enfermedades Cardiovasculares , Dislipidemias , Hipertensión , Enfermedades no Transmisibles , Humanos , Persona de Mediana Edad , Anciano , Síndrome de Boca Ardiente/complicaciones , Síndrome de Boca Ardiente/epidemiología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Hipertensión/complicaciones , Hipertensión/epidemiología , Dislipidemias/complicaciones , Dislipidemias/epidemiologíaRESUMEN
Central nervous system (CNS) tumours have devastating effects and are recurrent, with dismal prognosis (gliomas) or life-threatening by the compression effect (meningiomas). This disease's aetiology remains debatable. Over the last decade, the hypothesis that human viruses may be implicated in these tumours has been proposed. In this study, our aim is to examine the presence of 11 viruses in the most frequent CNS primary tumours. Using polymerase chain reaction (PCR), we assessed the viral presence in archived, paraffin-embedded tumour tissues from 114 patients with glioma and meningioma and in the brain tissue from 40 controls lacking tumour pathology. We focused on candidate neuro-oncogenic types (herpesviridae and polyomaviruses) and on human papillomavirus (HPV). HPV presence, for which involvement in these tumours was hardly investigated, was found to be associated with both tumour categories compared with controls (glioma, p = 0.032; meningioma, p = 0.032), whereas the presence of the neuro-oncogenic viruses was found in a negligible number of both categories, suggesting a lack of association with the tumour presence. Moreover, our study reveals a positive correlation between HPV presence and glioma malignancy, and a negative correlation with meningioma grading. Our results suggest that the presence of HPV seems to be significantly associated with primary tumours of the CNS and its meninges.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Glioma , Neoplasias Meníngeas , Meningioma , Infecciones por Papillomavirus , Encéfalo/patología , Carcinogénesis , Neoplasias del Sistema Nervioso Central/etiología , Neoplasias del Sistema Nervioso Central/patología , Glioma/genética , Humanos , Estudios RetrospectivosRESUMEN
The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF-κB signalling pathway. The characterization of the NF-κB expression profile in CRC is an important topic since the suppression of NF-κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF-κB-related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case-control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR-182-5p was upregulated in T compared with PT, whereas miR-10b-5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF- κB pathway.
Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Regulación Neoplásica de la Expresión Génica , Transducción de Señal/genética , MicroARNs/metabolismo , Neoplasias Colorrectales/patologíaRESUMEN
BACKGROUND: Neuroinflammation plays a prominent role in Alzheimer's disease (AD), both in pathogenesis and disease progression. It has been shown that TLR/MYD88 signaling is involved in the chronic low-grade sterile inflammation associated with AD. Several studies have evidenced high levels of MYD88 in the brain of patients and animal models of AD, but no study has assessed so far its levels in blood. METHODS: In this study we evaluated the blood mRNA levels of MYD88 in a mouse model of AD, and also the putative effect of Rivastigmine treatment on MYD88 expression. Twenty-eight transgenic APP/TAU mice (AT) and twenty-two control C57/BL6j mice (WT) were included in this study, out of which five transgenic AT and five WT mice were treated with Rivastigmine. RESULTS: Increased MYD88 transcript in the whole blood from AT mice as compared to WT controls was found, which seems to increase in time due to disease progression and not to aging. This finding suggests that blood leukocytes are primed to develop TLR/MYD-mediated inflammatory processes. Moreover, results indicate that MYD88 blood levels were not modulated by the diseases-specific treatment with Rivastigmine. CONCLUSIONS: Our results suggest that MYD88 might be a promising blood biomarker to monitor AD progression.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Inflamación/metabolismo , Ratones , Ratones Transgénicos , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Rivastigmina/farmacologíaRESUMEN
Despite intensive research, the pathophysiology of Alzheimer's disease (AD) is still not fully understood, and currently there are no effective treatments. Therefore, there is an unmet need for reliable biomarkers and animal models of AD to develop innovative therapeutic strategies addressing early pathologic events such as neuroinflammation and redox disturbances. The study aims to identify inflammatory and redox dysregulations in the context of AD-specific neuronal cell death and DNA damage, using the APPV717I× TAUP301L (AT) mouse model of AD. The expression of 84 inflammatory and 84 redox genes in the hippocampus and peripheral blood of double transgenic AT mice was evaluated against age-matched controls. A distinctive gene expression profile in the hippocampus and the blood of AT mice was identified, addressing DNA damage, apoptosis and thrombosis, complemented by inflammatory factors and receptors, along with ROS producers and antioxidants. Gene expression dysregulations that are common to AT mice and AD patients guided the final selection of candidate biomarkers. The identified inflammation and redox genes, common to AD patients and AT mice, might be valuable candidate biomarkers for preclinical drug development that could be readily translated to clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Encéfalo/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Ratones , Ratones Transgénicos , Oxidación-ReducciónRESUMEN
Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myeloid cells and extracellular matrix (ECM) remodelling. Currently, there are no specific biomarkers to diagnose the severity and prognosis of muscle lesions. In order to investigate the gene expression profile of extracellular matrix and adhesion molecules, as premises of homo- or heterocellular cooperation and milestones for skeletal muscle regeneration, we performed a gene expression analysis for genes involved in cellular cooperation, migration and ECM remodelling in a mouse model of acute crush injury. The results obtained at two early time-points post-injury were compared to a GSE5413 data set from two other trauma models. Third day post-injury, when inflammatory cells invaded, genes associated with cell-matrix interactions and migration were up-regulated. After day 5, as myoblast migration and differentiation started, genes for basement membrane constituents were found down-regulated, whereas genes for ECM molecules, macrophage, myoblast adhesion, and migration receptors were up-regulated. However, the profile and the induction time varied according to the experimental model, with only few genes being constantly up-regulated. Gene up-regulation was higher, delayed and more diverse following more severe trauma. Moreover, one of the most up-regulated genes was periostin, suggestive for severe muscle damage and unfavourable architecture restoration.
Asunto(s)
Proteínas de la Matriz Extracelular/genética , Matriz Extracelular/genética , Músculo Esquelético/fisiología , Regeneración/genética , Transcriptoma/genética , Animales , Membrana Basal/fisiología , Diferenciación Celular/genética , Movimiento Celular/genética , Regulación hacia Abajo/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Mioblastos/fisiología , Regulación hacia Arriba/genéticaRESUMEN
In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.
Asunto(s)
Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Regulación de la Expresión Génica/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mesalamina/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Femenino , Humanos , Mucosa Intestinal/metabolismo , Lipocalina 2/genética , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/genética , Factor Trefoil-1/genéticaRESUMEN
Preclinical Research Alterations in small non-coding RNAs have been observed in many human disease states including cancer, cardiovascular, developmental, neurological, and psychiatric disorders. These molecules have recently raised the interest of the scientific community for novel therapeutic approaches. Nanotechnologies, including the development of sophisticated nanoparticles, offer new ways for the delivery of small RNA-based therapies. The nanoparticle delivery method appears attractive, but so far most of the work in this area has been conducted in the context of cancer. New therapeutic strategies are needed for psychiatric disorders, where treatment is often ineffective, leading to frequent patient hospitalizations and a growing economic burden. In this article, we discuss the role of small RNAs in psychiatric diseases and how this new knowledge, combined with innovations in nanotechnologies, could lead to the development of novel therapeutic approaches. Drug Dev Res 77 : 453-457, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Trastornos Mentales/terapia , ARN no Traducido/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Trastornos Mentales/genética , Nanomedicina , Nanopartículas , ARN no Traducido/genéticaRESUMEN
Several lines of evidence implicate abnormalities in glutamatergic neural transmission in major depressive disorder (MDD) and treatment response. A high percentage of MDD patients do not respond adequately to antidepressants and are classified as having treatment-resistant depression (TRD). In this study we investigated five GRIK4 variants, previously associated with antidepressants response, in an Italian cohort of 247 MDD no-TRD and 380 TRD patients. We found an association between rs11218030 G allele and TRD. Moreover, significant associations between rs11218030 and rs1954787 and the presence of psychotic symptoms were observed. In conclusion, our data support the involvement of GRIK4 in TRD and in the risk of developing psychotic symptoms during depressive episodes.
Asunto(s)
Trastorno Depresivo Mayor/genética , Trastorno Depresivo Resistente al Tratamiento/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Receptores de Ácido Kaínico/genética , Adulto , Anciano , Alelos , Antidepresivos/uso terapéutico , Estudios de Cohortes , Depresión/genética , Depresión/psicología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana EdadRESUMEN
Frontotemporal lobar degeneration (FTLD) encompasses a spectrum of neurodegenerative disorders characterized by behavioral, executive and language impairment, with a common overlap with parkinsonism and motor-neuron disease. Despite an increased understanding of its genetic background and molecular pathophysiology, FTLD is still an orphan disorder and there are currently no effective therapies available. In this brief overview we report the results obtained by several high-throughput and bioinformatic studies aimed at discovering impairment in the transcriptional profiles in brain and peripheral tissues from FTLD patients and in animal models. Taken together, all these results provide an interesting but still fragmentary list of genes and miRNAs whose role in FTLD should be thoroughly investigated.
Asunto(s)
Degeneración Lobar Frontotemporal/genética , Perfilación de la Expresión Génica/métodos , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Animales , Descubrimiento de Drogas/métodos , Degeneración Lobar Frontotemporal/tratamiento farmacológico , Degeneración Lobar Frontotemporal/patología , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , HumanosRESUMEN
BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. METHODS: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. RESULTS: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. CONCLUSIONS: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.
Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Masculino , Humanos , Femenino , Rumanía/epidemiología , Detección Precoz del Cáncer/métodos , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Sangre Oculta , Heces , Tamizaje Masivo/métodosRESUMEN
Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction. The identification of accessible biomarkers in bodily systems such as blood may lead to more accurate diagnosis, and more effective treatments targeting dysfunctional pathways, and could assist in monitoring the disease evolution. This systematic review aims to highlight the dysregulated microRNAs (miRNAs) in the peripheral blood of patients with psychotic disorders. Using the PRISMA protocol, PubMed and Science Direct databases were investigated and 22 articles were included. Fifty-five different miRNAs were found differentially expressed in the blood of psychotic patients compared to controls. Seventeen miRNAs (miR-34a, miR-181b, miR-432, miR-30e, miR-21, miR-137, miR-134, miR-7, miR-92a, miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096) were dysregulated with the same trend (up- or down-regulation) in at least two studies. Of note, miR-34a and miR-181b were up-regulated in the blood of psychotic patients in seven and six studies, respectively. Moreover, the level of miR-181b in plasma was found to be positively correlated with the amelioration of negative symptoms. The panel of miRNAs identified in this review could be validated in future studies in large and well-characterized cohorts of psychotic patients.
RESUMEN
Background:Oral lichen planus (OLP) is a chronic inflammatory disease that affects the oral mucosa. This disorder has been suggested to be related to an impairment of lipid metabolism and profile. A number of studies indicate a higher incidence of dyslipidemia in OLP patients compared to not-affected individuals. Objectives: The aim of this study was to investigate the correlations between lipid profile alterations and clinical features of oral lichen planus. Patients and methods:A total of 52 patients diagnosed with OLP were enrolled in this study. Data regarding the demography, symptoms, severity of lesions assesed by Thongprasom score and lipid profile status were collected from the medical charts. The study group was divided into two sub-cohorts: Group 1, which included OLP patients with lipid profile within the normal range, and Group 2 comprising OLP patients with alterations of the lipid status. Results:The comparative analysis between the two groups found a statistically significant association between the lipid profile and OLP symptoms. Thus, the most frequent symptom was pain, in OLP patients with normal lipid status (Group 1), and burning, in those with altered lipid status (Group 2) (p=0.050). Moreover, the presence of symptoms was reported by a higher percentage of patients from Group 2 (75%) than Group 1 (68.25%). Patients reporting burning symptomatology showed higher triglyceride levels than those who reported pain (p=0.032). Furthermore, we found that male OLP patients have higher levels of LDL compared with female subjects (p=0.021). Conclusion:Lipid profile changes are not associated with an increased severity of OLP lesions. A statistically significant association was found between burning sensation and higher lipid profile parameters.
RESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer. The symptoms appear in advanced stages, and diagnostic and prognostic tests for the early detection of PDAC and disease evolution are not available. The dysregulation of microRNAs (miRNAs) has been associated with cancer development and progression, and some miRNAs have been reported to promote specific metastasis. In this study we aimed to identify the miRNAs dysregulated in PDAC tumoral tissues and a subset of miRNAs associated with tumoral characteristics, mainly metastasis presence and site. For this, the expression of 84 miRNAs was evaluated by qPCR in 30 tumoral tissues and 16 samples of non-tumoral pancreatic tissues. The comparison revealed 32 dysregulated miRNAs (19 upregulated and 13 downregulated) in the PDAC group. Reactome pathway over-representation analysis revealed that these miRNAs are involved in several biological pathways, including "ESR-mediated signaling", "PIP3 activates AKT signaling", and "Regulation of PTEN", among others. Moreover, our study identified an upregulation of miR-15b-5p and miR-20b-5p in the tumoral tissues of patients with hepatic metastasis, outlining these miRNAs as potential markers for hepatic metastasis. No significant difference in miRNA expression was observed in relation to anatomic location, lymphovascular invasion, lung metastasis, and the presence of diabetes.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , MicroARNs , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Neoplasias PancreáticasRESUMEN
Burning Mouth Syndrome (BMS) is a chronic condition characterized by a burning sensation in the oral mucosa, lasting more than 2 hours daily for more than 3 months, without clinical and/or laboratory evidence. BMS is often comorbid with mood, and psychiatric disorders, and a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic function is occurring. In this work, we aimed to define the neuropsychological profile specific for BMS patients for a better management of this complex disease. We conducted a case-control study comparing 120 BMS patients and 110 non-BMS individuals (CTRL). Sociodemographic data and lifestyle habits, were collected, along with data regarding quality of life (SF-36 scale), stress (PSS), depression and anxiety (MADRS and HADS scales), sleep quality (PSQI scale), and cognitive functions (MoCA, SVF and PVF tests). The statistical analysis revealed a lower general quality of life (p < 0.001), worse sleep quality (p < 0.001) in BMS patients than CTRL. The BMS patients also displayed a higher prevalence of mild depressive symptoms than CTRL applying the MADRS (p < 0.001) and HADS-Depression scales (p = 0.001), whereas no differences in anxiety symptoms were found between the two groups (p = 0.174). Moreover, reduced scores semantic and phonemic verbal fluency tests (p < 0.05) were found, but no change in cognition was observed through MoCA (p = 0.551). Our results highlight that synergy between dentistry and neuropsychiatric assessment is essential for a successful management of BMS.
RESUMEN
BACKGROUND: In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. METHODS: We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. RESULTS: These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models CONCLUSIONS: Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathophysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.
Asunto(s)
Trastorno Depresivo Mayor/genética , Leucocitos/metabolismo , ARN Mensajero/genética , Receptor ErbB-3/genética , Adulto , Animales , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Antidepresivos/farmacología , Biomarcadores/sangre , Estudios de Cohortes , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
The reprogramming of lipid metabolism has been highlighted in colorectal cancer (CRC) studies, suggesting a critical role for the scavenger receptor CD36 and fatty acid synthase (FASN) in this malignancy. In this study, we analyzed the gene expression levels of CD36, FASN, the cell surface glypican 4 (GPC4), and the two transporters SLC27A3 and SLC27A4 in 39 paired tumoral and peritumoral tissues from patients with CRC compared with 18 normal colonic mucosae. Moreover, the levels of seven miRNAs targeting CD36 and most of the analyzed genes were evaluated. We found a significant impairment of the expression of all the analyzed genes except GPC4 as well as the differential expression of miR-16-5p, miR-26b-5p, miR-107, miR-195-5p, and miR-27a-3p in the colonic mucosa of CRC patients. Interestingly, CD36 and miR-27a-3p were downregulated and upregulated, respectively, in tumoral tissues compared to peritumoral and control tissues, with a significant negative correlation in the group of patients developing lymph node metastasis. Our results sustain the relationship between CRC and fatty acid metabolism and emphasize the importance of related miRNAs in developing new therapeutic strategies.