👤 Liciane F Medeiros

2,4-Dichlorophenol (2,4-DCP) is a persistent and toxic metabolite derived from the degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and other chlorinated compounds, representing an emerging environmental concern. Despite evidence of its toxicity, its neurotoxic effects in adult organisms remain poorly understood. This study aimed to evaluate the behavioral, biochemical, and molecular responses of adult zebrafish (Danio rerio) following 14-day exposure to environmentally relevant (30 μg L Show less

Repetitive magnetic stimulation (rMS) is used to treat neurological conditions. Understanding its modulatory effects requires investigating cellular processes and molecular pathways Active (75-, 150-, and 300-sec exposure) or sham rMS was administered daily (4 days/300mT-1Hz) to two neuronal [SK-N-BE(2) and SH-SY5Y] and one non-neuronal (HOS) tumor line. Cell viability, cell death, and gene expression of Both neuroblastoma cell lines, SH-SY5Y (150-sec) and SK-N-BE(2) (75-sec), exhibited increased viability compared to the 300-sec group immediately after treatment; however, none of the stimulated groups was different from sham. rMS increased rMS did not affect cell viability or death in these Show less

Alcohol consumption during pregnancy is a major public health concern, as prenatal exposure to ethanol can disrupt embryonic development and lead to Fetal Alcohol Spectrum Disorders (FASD). These disorders are characterized by a wide range of morphological, behavioral, and cognitive impairments, which variability across individuals is strongly influenced by genetic background and environmental conditions. Animal models, particularly zebrafish, offer a powerful tool to investigate how such factors modulate susceptibility to alcohol. In this study, we examined the effects of embryonic alcohol exposure in three zebrafish populations (AB, TU, and OB), assessing developmental parameters, behavior, and gene expression. Results showed that the OB population exhibited higher mortality and pronounced alterations in genes related to metabolism and neurotransmission; AB displayed reduced body and eye growth, along with increased social cohesion under alcohol exposure; while TU was more vulnerable to behavioral effects despite showing morphological resilience. Furthermore, the expression of key genes such as sox2, th1, drd1b, gabra1, and bdnf varied according to both population and alcohol concentration. These findings emphasize the relevance of genetic differences in modulating alcohol's impact and reinforce zebrafish as a valuable translational model for FASD research, paving the way for more refined diagnostic and therapeutic approaches. Show less

In this study, we used optical genome mapping (OGM), conventional karyotyping, and next-generation sequencing to analyze cytogenomic alterations in 91 cases of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Whereas karyotyping detected abnormal karyotypes in 55% of cases, OGM identified cytogenetic abnormalities in 97.8% of the cases and provided clinically relevant information beyond karyotyping in ∼70% of cases. OGM detected gene rearrangements in 80% of cases, including 24 recurrent gene fusions and 21 previously unreported putative gene fusions in T-ALL. Copy number variants were detected in 93% of cases, with interstitial deletions the most common. Gene mutations were detected in 93% of cases, with NOTCH1 being most frequent (in 57% of cases). Combining all data, most T-ALL cases harbored 3 or more cytogenomic aberrations. Specific cytogenomic alterations differed among T-ALL subtypes as follows: rearrangements of BCL11B and PICALM::MLLT10, deletions of 7p, and mutations involving DNMT3A, WT1, TET2, IDH2, and FLT3 were common in early T-precursor and near-early T-precursor subtypes. Rearrangements of TLX1, KMT2A, STIL::TAL1, and NUP214::ABL1, deletions of 9p, and FBXW7 mutations were frequently associated with the cortical subtype. We conclude that integration of OGM and next-generation sequencing with karyotyping enables comprehensive cytogenomic profiling of T-ALL that improves detection of clinically relevant genomic alterations and may inform disease classification and future studies of risk stratification. Show less

The present study investigated the effect of perinatal programming combined with exposure to a western diet on gene expression related to inflammation, neurodegeneration, and synaptic plasticity in the hippocampus of adult rats. Male rats from mothers fed either a standard diet or a western diet during gestation and lactation were used. All pups received only the standard chow diet from the 25th postnatal day (PND), and their body weight was analysed. Rats from the two groups fed the maternal diet were then divided on the 195 Adult rats submitted to a western diet during pregnancy and lactation showed signs of metabolic programming. In addition, glucose and total protein were found to have increased in the serum. The effect of acute exposure to a western diet is increased cholesterol. The western diet decreased gene expression of inflammatory factors ( Acute exposure to a western diet in adulthood alters pre-translational pathways ( Show less

In acute lymphoblastic leukaemia (ALL), cytoplasmic CD3 (cCD3) is a defining marker for T-lineage, and CD19 plus additional B-cell marker(s) for B-lineage. We identified 23 ALL cases in which the lymphoblasts expressed both cCD3 and CD19, making lineage assignment challenging. These cases represented approximately 10% of cCD3+ ALL and expressed a median of two additional B-cell markers other than CD19, including CD79a (76%), CD22 (22%), PAX5 (57%) and CD10 (44%). Two cases were mixed for T/B-lineage ALL, both positive for BCR::ABL1 rearrangement. In the remaining 21 cases, IgH and/or IgK/L rearrangement were detected in 1 of 19 cases and TRG/TRB in 13 of 21 (62%) cases. Other T-ALL characteristic genetic abnormalities included NOTCH1 mutations (7/21, 33%), PHF6 (6/21, 29%), JAK3 (4/21, 19%), PICALM::MLLT10, TLX3::BCL11B, TRB::HOXA13, SPTAN1::NUP214 and deletion of CDKN2A/CDKN2B. In the 16 cases that demonstrated a T-ALL genetic profile, CD22 (2/16, 13%) was found to be a more specific additional B-lineage marker than CD79a (11/15, 73%), PAX5 (8/14, 57%) or CD10 (7/16, 44%). Our data suggest that mixed T/B-ALL is extremely rare, with most cases associated with BCR::ABL1 and blast crisis of myeloproliferative neoplasms. The majority of cases represent early T-precursor lymphoblastic leukaemia expressing aberrant B-cell markers. We also showed persistent CD19 expression in relapsed/residual disease (16/17, 94%), suggesting its potential role as a therapeutic target and as a marker for detection of residual/relapse disease in these ALL cases. Show less

Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent MYD88 and CXCR4 mutations and fluorescence in-situ hybridization showed CCND1 translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas. Show less

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: Show less

Leishmaniasis is a neglected tropical disease, with approximately 1 million new cases and 30,000 deaths reported every year worldwide. Given the lack of adequate medication for treating leishmaniasis, drug repositioning is essential to save time and money when searching for new therapeutic approaches. This is particularly important given leishmaniasis's status as a neglected disease. Available treatments are still far from being fully effective for treating the different clinical forms of the disease. They are also administered parenterally, making it challenging to ensure complete treatment, and they are extremely toxic, in some cases, causing death. Triclabendazole (TCBZ) is a benzimidazole used to treat fasciolosis in adults and children. It presents a lower toxicity profile than amphotericin B (AmpB) and is administered orally, making it an attractive candidate for treating other parasitoses. The mechanism of action for TCBZ is not yet well understood, although microtubules or polyamines could potentially act as a pharmacological target. TCBZ has already shown antiproliferative activity against Cytotoxicity assay was performed by MTT assay. Cell inhibition (CI) values were obtained according to the equation CI = (O.D treatment x 100/O.D. negative control). For Infection evaluation, fixated cells were stained with Hoechst and read at Operetta High Content Imaging System (Perkin Elmer). For growth curves, cell culture absorbance was measured daily at 600 nm. For the synergism effect, Fractional Inhibitory Concentrations (FICs) were calculated for the IC50 of the drugs alone or combined. Mitochondrial membrane potential (DYm), cell cycle, and cell death analysis were evaluated by flow cytometry. Reactive oxygen species (ROS) and lipid quantification were also determined by fluorimetry. Treated parasites morphology and ultrastructure were analyzed by electron microscopy. The selectivity index (SI = CC50/IC50) of TCBZ was comparable with AmpB in promastigotes and amastigotes of Considering that TCBZ has the advantage of being inexpensive and administrated orally, our results suggest that TCBZ, combined with AmpB, is a promising candidate for treating leishmaniasis with reduced toxicity. Show less

Fibromyalgia (FM) is a chronic pain syndrome that affects the central nervous system and generates disability, which is characterized by generalized pain, fatigue, and functional decline. In this review, we aimed to identify the polymorphisms related to the pathophysiology of FM and the clinical characteristics generated by genetic influence. Only original studies with genes related to FM were considered, totaling 27 articles. The genes found were: MTHFR, RGS4, MYT1L, TACR1, SCN9A, DRD3, ADRB2, IL-4, HLA-DRB1, EDN1, CNR1, TAAR1, OPRM1, ADRA1A, ADRB3, BDNF, GRIA4, HTR3A, HTR3B, HTR2A, SERPINA 1 or A1AT, NRXN3, GCH1, MEFV, TRPV3, SLC6A4, ACE I/D, TSPO, COMT, and MAOA. Several genes related to different pain syndromes and altered pain thresholds have been identified and some polymorphisms were related to susceptibility to FM. It was observed that 73.33% of the genes related to FM were also associated with some psychological disorders, such as anxiety, depression, schizophrenia, and obsessive and compulsive disorder, and 40.00% with pain sensitivity and/or migraine, besides other disorders associated (drug addiction, autoimmune disorders, circulatory problems, and metabolic alterations). This review demonstrated an association of FM and genetic polymorphisms that can expand our knowledge about the pathophysiology of this disease. Show less

The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem≥ia. An apoB/apoA1 ratio ≥0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ≥0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients. Show less

Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression. Show less

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1h and 5 days, but not after 12h or 50 days. In the Cx, the GIPR expression increases after 1h, 12h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration. Show less