Objective: Patients with symptomatic uncomplicated diverticular disease (SUDD) may have a disrupted gut microbiota. However, current data are from small sample studies, and reported associations vary widely across studies. We aimed to profile the fecal microbiota in SUDD patients enrolled in primary care.
View Article and Find Full Text PDFPharmacol Biochem Behav
December 2024
Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to identify molecular mechanisms involved in chronic variable stress (CVS)-induced anhedonia and promising targets underlying (R)-ketamine rapid antidepressant response.
View Article and Find Full Text PDFThe abuse of synthetic steroids, such as nandrolone decanoate (ND), is often associated with violent behavior, increasing the risk of traumatic brain injury (TBI). After a TBI, proteins like APP, β-amyloid peptide-42 (Aβ42), and phosphorylated tau (pTau) accumulate and trigger endoplasmic reticulum (ER) stress associated with an unfolded protein response (UPR). The involvement of mitochondrial bioenergetics in this context remains unexplored.
View Article and Find Full Text PDFIntroduction: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.
Methods: Here, we integrated [F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis.
Objective: The present study has the following objectives: 1) identify differentially expressed proteins and pathways in blood samples of BD compared to healthy controls by employing high-throughput proteomics and bioinformatics and 2) characterize disease-related molecular signatures through in-depth analysis of the differentially expressed proteins and pathways.
Methods: Blood samples from BD patients (n=10) classified into high (BD+) or poor functioning (BD-), based on functional and cognitive status, and healthy controls (n=5) were analyzed using mass spectrometry-based proteomic analysis. Bioinformatics was performed to detect biological processes, pathways, and diseases related to BD.
Objective: The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify new bioactive compounds or Food and Drug Administration-approved drugs for the treatment of bipolar disorder (BD).
Methods: Five transcriptomic datasets containing 165 blood samples from individuals with BD were selected from the Gene Expression Omnibus (GEO). The number of participants varied from six to 60, with a mean age between 35 and 48 years and a gender difference between them.
Glutamatergic neurotransmission system dysregulation may play an important role in the pathophysiology of Alzheimer's disease (AD). However, reported results on glutamatergic components across brain regions are contradictory. Here, we conducted a systematic review with meta-analysis to examine whether there are consistent glutamatergic abnormalities in the human AD brain.
View Article and Find Full Text PDFUnlabelled: Alzheimer's disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) mouse models, such as the novel humanized amyloid-β (hAβ)-KI, have been developed to better resemble sporadic human AD.
Methods: Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hAβ-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients.
Fibronectin type III domain-containing protein 5 (FNDC5) and its derived hormone, irisin, have been associated with metabolic control in humans, with described FNDC5 single nucleotide polymorphisms being linked to obesity and metabolic syndrome. Decreased brain FNDC5/irisin has been reported in subjects with dementia due to Alzheimer's disease. Since impaired brain glucose metabolism develops in ageing and is prominent in Alzheimer's disease, here, we examined associations of a single nucleotide polymorphism in the FNDC5 gene (rs1746661) with brain glucose metabolism and amyloid-β deposition in a cohort of 240 cognitively unimpaired and 485 cognitively impaired elderly individuals from the Alzheimer's Disease Neuroimaging Initiative.
View Article and Find Full Text PDFThe γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain conditions, but in Alzheimer's disease (AD) studies have provided contradictory results. Here, we conducted a systematic review with meta-analysis to investigate whether the GABAergic system is altered in AD patients compared to healthy controls (HC), following the PRISMA 2020 Statement.
View Article and Find Full Text PDFBackground: Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH
Introduction: In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathologies. The molecular underpinnings behind this specificity are little explored.
View Article and Find Full Text PDFDecreasing neurotrophic support and impaired mitochondrial bioenergetics are key mechanisms for long-term neurodegeneration and cognitive decline after traumatic brain injury (TBI). We hypothesize that preconditioning with lower and higher volumes of physical exercise upregulates the CREB-BDNF axis and bioenergetic capability, which might serve as neural reserves against cognitive impairment after severe TBI. Using a running wheel mounted in the home cage, mice were engaged in lower (LV, 48 h free access, and 48 h locked) and higher (HV, daily free access) exercise volumes for thirty days.
View Article and Find Full Text PDFVirus Res
March 2023
Coronavirus disease 2019 (COVID-19) is an acute viral disease with millions of cases worldwide. Although the number of daily new cases and deaths has been dropping, there is still a need for therapeutic alternatives to deal with severe cases. A promising strategy to prospect new therapeutic candidates is to investigate the regulatory mechanisms involved in COVID-19 progression using integrated transcriptomics approaches.
View Article and Find Full Text PDFAstrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ ([F]AZD4694) and tau ([F]MK-6240), as well as CSF GFAP and YKL-40 measures.
View Article and Find Full Text PDFMetadata analysis of public microarray datasets using bioinformatics tools has been successfully used in several biomedical fields in the search for biomarkers. In reproductive science, there is an urgent need for the establishment of oocyte quality biomarkers that could be used in the clinical environment to increase the chances of successful outcomes in treatment cycles. Adaptive cellular processes observed in cumulus oophorus cells reflect the conditions of the follicular microenvironment and may thus bring relevant information of oocyte's conditions.
View Article and Find Full Text PDFRoundUp (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models.
View Article and Find Full Text PDFPurpose: To study whether the cumulus cell antioxidant system varies accordingly to patients clinical characteristics' as age, infertility diagnosis, BMI, and stimulation protocol applied and if the antioxidant profile of cumulus cells could be used as a predictor of embryo development.
Methods: A prospective study including 383 human cumulus samples provided by 191 female patients undergoing intracytoplasmic sperm injection during in vitro fertilization treatments from a local in vitro fertilization center and processed in university laboratories. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) enzyme activity levels and reduced glutathione (GSH) levels were measured in cumulus oophorus cells individually collected from each aspirated cumulus-oocyte complex, and the results of each sample were compared considering the oocytes outcome after ICSI and patients clinical characteristics.
Introduction: Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers .
Methods: With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers.
The risk stratification of B-acute lymphoblastic leukemia (B-ALL) is based on clinical and biological factors. However, B-ALL has significant biological and clinical heterogeneity and 50% of B-ALL patients do not have defined prognostic markers. In this sense, the identification of new prognostic biomarkers is necessary.
View Article and Find Full Text PDFBackground: Changes in soluble amyloid-beta (Aβ) levels in cerebrospinal fluid (CSF) are detectable at early preclinical stages of Alzheimer's disease (AD). However, whether Aβ levels can predict downstream AD pathological features in cognitively unimpaired (CU) individuals remains unclear. With this in mind, we aimed at investigating whether a combination of soluble Aβ isoforms can predict tau pathology (T+) and neurodegeneration (N+) positivity.
View Article and Find Full Text PDFBackground: Septic shock is a life-threatening condition that challenges immune cells to reprogram their mitochondrial metabolism towards to increase ATP synthesis for building an appropriate immunity. This could print metabolic signatures in mitochondria whose association with disease progression and clinical outcomes remain elusive.
Method: This is a single-center prospective cohort study performed in the ICU of one tertiary referral hospital in Brazil.