SARS-CoV-2 strains and clinical profiles of COVID-19 patients in a Southern Brazil hospital.

Introduction: The COVID-19 pandemic had a widespread global impact and presented numerous challenges. The emergence of SARS-CoV-2 variants has changed transmission rates and immune evasion, possibly impacting the severity. This study aims to investigate the impact of variants on clinical outcomes in southern Brazil.

Use of dipyrone during pregnancy and risk of congenital anomalies: a systematic review.

Purpose: This study aimed to summarize the evidence on the teratogenic effects of dipyrone used during pregnancy.

Methods: Databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science, Lilacs, SciELO, SCOPUS, OasisBR, and OpenGray) were reviewed until September 2023. We included studies that compared pregnant women who used dipyrone during any gestational period with those who used other analgesics or did not use any analgesics during the same gestational period.

From bench to in silico and backwards: What have we done on genetics of recurrent pregnancy loss and implantation failure and where should we go next?

Human reproduction goes through many challenges to its success and in many cases it fails. Cases of pregnancy loss are common outcomes for pregnancies, and implantation failures (IF) are common in assisted reproduction attempts. Although several risk factors have already been linked to adverse outcomes in reproduction, many cases remain without a definitive cause.

Possible New Candidates Involved to Thalidomide-Related Limbs and Cardiac Defects: A Systems Biology Approach.

Thalidomide is a known teratogen that causes malformations especially in heart and limbs. Its mechanism of teratogenicity is still not fully elucidated. Recently, a new target of thalidomide was described, TBX5, and was observed a new interaction between HAND2 and TBX5 that is disrupted in the presence of thalidomide.

Bioinformatics Methods for Transcriptome Analysis on Teratogenesis Testing.

Teratogenesis testing can be challenging due to the limitations of both in vitro and in vivo models. Test-systems, based especially on human embryonic cells, have been helping to overcome the difficulties when allied to omics strategies, such as transcriptomics. In these test-systems, cells exposed to different compounds are then analyzed in microarray or RNA-seq platforms regarding the impacts of the potential teratogens in the gene expression.

Brazilian women in Bioinformatics: Challenges and opportunities.

Bioinformatics is a growing research field that received great notoriety in the years of the COVID-19 pandemic. It is a very integrative area, comprising professionals from science, technology, engineering, and mathematics (STEM). In agreement with the other STEM areas, several women have greatly contributed to bioinformatics ascension; however, they had to surpass prejudice and stereotypes to achieve recognition and leadership positions, a path that studies have demonstrated to be more comfortable to their male colleagues.

Challenges to the effectiveness of next-generation sequencing in formalin-fixed paraffin-embedded tumor samples for non-small cell lung cancer.

Introduction: Next-generation sequencing (NGS) of Formalin-Fixed and Paraffin-Embedded (FFPE) specimens is routine in precision oncology practice. However, results are not always conclusive, and it is important to identify which factors may influence FFPE tumor sequencing success.

Materials And Methods: Here, we evaluated the influence of pre-analytical factors on 705 samples of non-small cell lung cancer specimens that underwent NGS testing.

Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome?

Purpose: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway.

HLA haplotypes and differential regional mortality caused by COVID-19 in Brazil: an ecological study based on a large bone marrow donor bank dataset.

The coronavirus disease 2019 (COVID-19) mortality rates varied among the states of Brazil during the course of the pandemics. The human leukocyte antigen (HLA) is a critical component of the antigen presentation pathway. Individuals with different HLA genotypes may trigger different immune responses against pathogens, which could culminate in different COVID-19 responses.

An Efficient Extraction Method Allowing the Genetic Evaluation of Host DNA from Samples Collected for Virus Infection Diagnosis in Viral Transport Medium.

During the COVID-19 pandemic, an extraordinary number of nasopharyngeal secretion samples inoculated in viral transport medium (VTM) were collected and analyzed to detect SARS-CoV-2 infection. In addition to viral detection, those samples can also be a source of host genomic material, providing excellent opportunities for biobanking and research. To describe a simple, in-house-developed DNA extraction method to obtain high yield and quality genomic DNA from VTM samples for host genetic analysis and assess its relative efficiency by comparing its yield and suitability to downstream applications to two different commercial DNA extraction kits.

Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein-protein interaction network analyses.

Introduction: Zika virus (ZIKV) is a human teratogen that causes congenital Zika syndrome (CZS). AXL, TLR3, and STAT2 are proteins involved in the ZIKV's entry into cells (AXL) and host's immune response (TLR3 and STAT2). In this study, we evaluated the role of genetic polymorphisms in these three genes as risk factors to CZS, and highlighted which proteins that interact with them could be important for ZIKV infection and teratogenesis.

A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.

Several molecular mechanisms of thalidomide embryopathy (TE) have been investigated, from anti-angiogenesis to oxidative stress to cereblon binding. Recently, it was discovered that thalidomide and its analogs, named immunomodulatory drugs (IMiDs), induced the degradation of C2H2 transcription factors (TFs). This mechanism might impact the strict transcriptional regulation of the developing embryo.

Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection.

Severe COVID-19 is a systemic disorder involving excessive inflammatory response, metabolic dysfunction, multi-organ damage, and several clinical features. Here, we performed a transcriptome meta-analysis investigating genes and molecular mechanisms related to COVID-19 severity and outcomes. First, transcriptomic data of cellular models of SARS-CoV-2 infection were compiled to understand the first response to the infection.

Downregulation of Microcephaly-Causing Genes as a Mechanism for ZIKV Teratogenesis: A Meta-analysis of RNA-Seq Studies.

Zika virus (ZIKV) is a neurotropic teratogen that causes congenital Zika syndrome (CZS), characterized by brain and eye anomalies. Impaired gene expression in neural cells after ZIKV infection has been demonstrated; however, there is a gap in the literature of studies comparing whether the differentially expressed genes in such cells are similar and how it can cause CZS. Therefore, the aim of this study was to compare the differential gene expression (DGE) after ZIKV infection in neural cells through a meta-analysis approach.

Role of gut microbiota in infectious and inflammatory diseases.

Thousands of microorganisms compose the human gut microbiota, fighting pathogens in infectious diseases and inhibiting or inducing inflammation in different immunological contexts. The gut microbiome is a dynamic and complex ecosystem that helps in the proliferation, growth, and differentiation of epithelial and immune cells to maintain intestinal homeostasis. Disorders that cause alteration of this microbiota lead to an imbalance in the host's immune regulation.

Precision medicine implementation challenges for testing in chronic kidney disease in admixed populations.

Chronic Kidney Disease (CKD) is a public health problem that presents genetic and environmental risk factors. Two alleles in the Apolipoprotein L1 () gene were associated with chronic kidney disease; these alleles are common in individuals of African ancestry but rare in European descendants. Genomic studies on Afro-Americans have indicated a higher prevalence and severity of chronic kidney disease in people of African ancestry when compared to other ethnic groups.

Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.

Background: Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings.

Molecular Mechanisms of ZIKV-Induced Teratogenesis: A Systematic Review of Studies in Animal Models.

Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos.

Genetic evaluation of HAND2 gene and its effects on thalidomide embryopathy.

Background: HAND2 is a transcription factor important for embryonic development, required for limbs and cardiovascular development. Thalidomide is a drug responsible to a spectrum of congenital anomalies known as Thalidomide Embryopathy (TE), which includes mainly limb and heart defects. It is known that HAND2 interaction with TBX5, an important protein for limbs and heart development, is inhibited by Thalidomide.

Transcriptome meta-analysis of valproic acid exposure in human embryonic stem cells.

Valproic acid (VPA) is a widely used antiepileptic drug not recommended in pregnancy because it is teratogenic. Many assays have assessed the impact of the VPA exposure on the transcriptome of human embryonic stem-cells (hESC), but the molecular perturbations that VPA exerts in neurodevelopment are not completely understood. This study aimed to perform a transcriptome meta-analysis of VPA-exposed hESC to elucidate the main biological mechanisms altered by VPA effects on the gene expression.