Resumo em Inglês:

Abstract Aplastic anemia (AA) is a disease characterized by a severe reduction of the erythroid lineage. Its molecular mechanisms have been studied using technologies such as whole-exome sequencing via NGS; however, this remains a costly and limited-access strategy for developing countries. In this study, 17 de novo patients diagnosed with AA were analyzed. Genomic DNA was isolated from each patient to perform the Multiplex Ligation-dependent Probe Amplification (MLPA) technique, which uses different probes to detect numerical alterations in the exons of the genes of interest (GATA2, RUNX1, C/EBPα, hTERT). In 70.9% cases, a molecular abnormality was found. GATA2 was the most frequently altered gene (58.8%), followed by TERT (47.0%), RUNX1 (41.1%), and finally C/EBPα (35.3%). Detecting these molecular alterations could help to understand the progression of AA to other hematologic malignancies due to the genomic instability associated with this panel of genes involved in various hematopoietic maturation processes.

Resumo em Inglês:

Abstract Lung cancer is a highly prevalent disease and the leading cause of cancer-related deaths worldwide. Among non-small cell lung carcinomas (NSCLC), adenocarcinoma is one of the most common subtypes. This retrospective study aimed to analyze the prevalence of epidermal growth factor receptor (EGFR) mutations and programmed death-ligand 1 (PD-L1) expression in patients with confirmed lung adenocarcinoma, based on pathology reports from 2019 to 2024. Patients were assessed by sex, age, PD-L1 expression, and presence of EGFR and ALK mutations. A total of 895 patients were included, mostly male, with an average age of 65.85 years. EGFR mutations were identified in 24.4% of the cases, predominantly exon 19 deletions (50.2%), with women accounting for 70.3% of those mutations. PD-L1 expression, determined by the tumor proportion score (TPS), was high (TPS ≥ 50%) in 28.9%, low (1 ≤ TPS ≤ 49%) in 26.3%, and absent (TPS < 1%) in 44.8% of patients. ALK mutations were found in 5.1% of cases, mostly among younger individuals. Findings on EGFR mutations were consistent with the national and international literature. However, PD-L1 expression rates were higher than those typically reported in Brazilian studies, highlighting regional variation in biomarker prevalence.

Resumo em Inglês:

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB, or Sanfilippo syndrome type B) is a lysosomal storage disorder caused by variants in the NAGLU gene, leading to heparan sulfate accumulation. This study analyzed 27 MPS IIIB Brazilian patients diagnosed via the MPS Brazil Network (2014-2022). Diagnosis involved biochemical tests [NAGLU enzyme activity, urinary glycosaminoglycans (GAG)], showing expected low activity of the enzyme and high concentration of GAGs. Molecular analysis of the NAGLU gene by Sanger sequencing or Targeted Next-Generation Sequencing confirmed the diagnosis. Forty-nine variants were found across patient alleles, comprising twenty-two different variants. Two variants were described for the first time: p.Gly79Arg and p.Leu598Pro (both missense). In silico tools predicted the novel variants as damaging/deleterious. The study identified 90.7% of the expected mutant alleles, observing variant heterogeneity and a higher frequency of missense variants. This characterization enhances understanding of the Brazilian MPS IIIB genetic landscape and is instrumental to the design of diagnostic and screening strategies.

Resumo em Inglês:

Abstract Obesity is a global public health issue, increasingly affecting young adults. Its association with other diseases highlights the urgency of developing prevention strategies. Genetic factors play a significant role in susceptibility to obesity, making the identification of risk-associated variants essential for prevention strategies. Therefore, this study aimed to analyze LEP, LEPR, and FTO variants as potential genetic risk factors for obesity in Brazilians aged 18-35 years. The participants were classified with, or without obesity/overweight. Genotyping was performed by ASO-PCR, RFLP, and DNA sequencing. A questionnaire was applied to collect anthropometric data, and personal and family medical history. Preliminary analyses indicated that obesity was significantly associated with individuals over 25 years of age; therefore, to specifically investigate early-onset obesity, the primary genetic association analyses were restricted to the 18-25 age group. A significant association was found between the LEP rs7799039 variant and BMI ≥ 25 Kg/m², and LEP rs17151919 was strongly associated with BMI ≥ 30 Kg/m² in this age group. These findings underscore the importance of identifying genetic variants that increase the risk of obesity in young adults and suggest contributing to the development of more effective and personalized prevention strategies, integrating knowledge from genetics, medicine, and nutrition.

Resumo em Inglês:

Abstract Understanding shark reproductive modes is crucial for conservation, as these K-strategist species are vulnerable to overexploitation. The spiny dogfish (Squalus acanthias), a small shark listed as ‘vulnerable’ by the IUCN, has a 22-month gestation period and a reproductive output ranging from 1 to 21 pups per litter. This study aimed to investigate multiple paternity in S. acanthias using Single Nucleotide Polymorphism (SNP) markers. Samples from six litters, comprising 40 individuals collected in Argentina, were analyzed using a ddRADseq library. SNP markers were screened with the STACKS pipeline, and kinship and paternity were analyzed using COANCESTRY and COLONY software. Results revealed 1,021 to 1,620 SNPs per litter, with multiple paternity detected in all litters. The number of sires per litter ranged from 2 to 4. No correlation was found between litter size and multiple paternity, suggesting this behavior may enhance genetic diversity. The species’ size and sex segregation, coupled with females in shallower waters, increase their vulnerability to fishing pressure. Overfishing and bycatch exacerbate the reduction in sexually mature individuals, threatening population recovery. This study highlights the need for management policies that incorporate reproductive strategies, especially for species like S. acanthias with complex life histories and low recovery rates.

Resumo em Inglês:

Abstract Over the past two decades, molecular data have revealed a complex evolutionary history for the Neotropical felid genus Leopardus. A particularly problematic subset has been the L. tigrinus complex, which has been demonstrated to comprise more than one species. Recent molecular data indicated that it is not even monophyletic, comprising distinct Leopardus lineages with a similar morphology, which likely underlies the assumption that they formed a single species. To further investigate its composition and evolutionary history, we generated mtDNA data from multiple individuals sampled in Andean regions of Colombia and Peru. The Colombian samples formed a well-supported clade that was the sister-group of the Costa Rican lineage. Remarkably, the Peruvian L. tigrinus samples formed a different clade, placed at a distinct location within the Leopardus phylogeny, as a sister-group to (L. pardalis + L. wiedii). This unexpected result extends the inference of non-monophyly of the L. tigrinus complex, and raises the possibility that additional taxonomic entities may be contained in this genus.

Resumo em Inglês:

Abstract Tissue Factor (TF) can inhibit osteoclastogenesis. Moderate autophagy is an essential factor for osteoclastogenesis. As a molecule present in human monocytes, TF can inhibit autophagic activity through B-cell lymphoma-2 (BCL2) overexpression; this suggests that the anti-osteoclastogenic role of TF may occur in human monocytes and be associated with BCL2-dependent autophagy. Our study aimed to explore the relationship between TF-regulated BCL2-autophagy signaling and osteoclast-differentiation fate of human monocytes. Cell enrichment based on fluorescence-activated cell sorting (FACS) was used to enrich TF-associated monocytic clusters. Then, a series of functional assays were performed to investigate the roles of TF in monocytic parameters associated with osteoclast precursors (OCPs). The results showed that under osteoclastic induction, the osteoclastogenic ability and autophagic activity in enriched TF- monocytes were enhanced whereas TF+ monocytes exhibited opposite results. BCL2 expression and the interaction between BCL2-Beclin1 in TF- monocytes decreased while those of TF+ monocytes were contrary. The osteoclastogenic ability of TF- monocytes decreased again with autophagy inhibition with Beclin1 underexpression. The osteoclastogenic ability of TF+ monocytes increased again with enhanced autophagy with BCL2 inhibition and Beclin1 overexpression. Overall, TF increases BCL2-Beclin1 stability by upregulating BCL2 expression, thereby decreasing Beclin1-dependent autophagy and subsequent monocytic osteoclastogenesis in human monocytes.

Resumo em Inglês:

Abstract Dry eye disease (DED) is often associated with corneal epithelial injury under hyperosmotic stress, which contributes to epithelial cell apoptosis and delay wound healing. Human Umbilical Cord Mesenchymal Stem Cell-derived Small Extracellular Vesicles (hUC-MSCs-sEVs) have emerged as promising therapeutic agents due to their anti-inflammatory, anti-apoptotic, and regenerative properties. In this study, we isolated and characterized hUC-MSCs-sEVs and assessed their therapeutic potential in hyperosmotic corneal epithelial injury. We demonstrated that hUC-MSCs-sEVs significantly promoted human corneal epithelial cell proliferation and repair under hyperosmotic conditions, reducing oxidative stress and preserving mitochondrial function. Additionally, hUC-MSCs-sEVs inhibited the expression of pro-inflammatory cytokines IL-6 and IL-1β, as well as downregulated the cGAS-STING signaling pathway, a critical mediator of inflammation. These findings suggest that hUC-MSCs-sEVs may offer a novel therapeutic strategy for treating hyperosmotic stress-induced corneal epithelial damage by mitigating oxidative stress, preserving mitochondrial integrity, and modulating inflammatory responses.