Transposable elements alter gene expression and may impact response to cisplatin therapy in ovarian cancer.

Cisplatin is widely employed for cancer treatment; therefore, understanding resistance to this drug is critical for therapeutic practice. While studies have delved into differential gene expression in the context of cisplatin resistance, findings remain somewhat scant. We performed a comprehensive investigation of Transposable Elements (TEs) expression and their impact in host genes in two cisplatin-treated ovarian cancer cell lines. RNA-seq, ATAC-seq, and in-depth bioinformatics analysis were used to compare cisplatin-sensitive and -resistant ovarian cancer cell lines. Our results reveal that cisplatin therapy alters the expression of protein-coding genes, but also key TEs, including LINE1, Alu, and endogenous retroviruses, in both cisplatin-sensitive and -resistant cell lines. By co-expressing with downstream genes or by creating chimeric transcripts with host genes at their insertion sites, these TEs seem to control the expression of protein-coding genes, including tumor-related genes. Our model uncovers TEs influencing the expression of cancer genes and cancer pathways. Collectively, our findings indicate that TEs alterations associated with cisplatin treatment occur in critical cancer genes and cellular pathways synergically. This research highlights the importance of considering the entire spectrum of transcribed elements in the genome, especially TE expression, for a complete understanding of complex models like cancer response to treatment.

Descripción de pacientes con displasia del desarrollo de cadera en Hospital Clínico Herminda Martin, Chillán, entre los años 2020-2021 / Description of patients with developmental dysplasia of the hip at the Hospital Clínico Herminda Martin, Chillán, between the years 2020-2021

Introducción: La displasia del desarrollo de la cadera (DDC), una patología multifactorial más prevalente en el sexo femenino, afecta a lactantes, y el diagnóstico y tratamiento oportuno permiten evitar consecuencias posteriores, morbimortalidad significativa y una carga en salud importante. Objetivo: Conocer la realidad local en relación con el diagnóstico y tratamiento de la DDC, describiendo demográficamente a los pacientes evaluados por médicos especialistas, específicamente traumatólogos infantiles del Hospital Clínico Herminda Martin (HCHM) en Chillán. Materiales y métodos: Se llevó a cabo un estudio descriptivo transversal de una cohorte de pacientes evaluados mediante radiografías en el HCHM por sospecha de DDC, entre junio de 2020 y julio de 2021. Se recopilaron variables como sexo, tipo de compromiso del desarrollo de la cadera y tratamiento utilizado. Resultados: De 146 pacientes evaluados, el 83.6% correspondían al sexo femenino, mientras que el 16.4% eran del sexo masculino. En cuanto a los tratamientos ortopédicos, el 82.7% fueron mujeres y el 17.2% hombres, siendo las correas de Pavlik el tratamiento más utilizado. Solo 7 pacientes requirieron tratamiento quirúrgico. Discusión: Los resultados obtenidos se respaldan en la evidencia internacional, reflejando realidades similares a la situación local. La relevancia de este estudio radica en la falta de una base de datos nacional o local actualizada sobre la patología, sumado a la ventaja de informar acerca de los tratamientos disponibles y la adherencia a ellos. Esto permite reflejar el comportamiento de la población local durante los años 2020-2021. Las limitaciones incluyen el seguimiento, debido a restricciones por la pandemia y la falta de datos previos.

Introduction: Developmental dysplasia of the hip (DDH), a multifactorial pathology more prevalent in females, affects infants, where timely diagnosis and treatment avoid subsequent consequences, significant morbidity, and mortality, as well as the health burden it generates. Objective: To understand the local reality regarding the diagnosis and treatment of DDH by describing the demographic characteristics of patients evaluated by medical specialists, specifically child traumatologists from the Hospital Clínico Herminda Martin (HCHM) in Chillán. Materials and Methods: A cross-sectional descriptive study was conducted on a cohort of patients evaluated through radiographs at HCHM due to suspected DDH between June 2020 and July 2021. Variables collected included sex, type of hip development compromise, and treatment used. Results: Out of 146 patients, 83.6% were female and 16.4% were male. In terms of orthopedic treatments, 82.7% were females, and 17.2% were males, with Pavlik straps being the most used orthopedic treatment. Only 7 patients underwent surgical treatment. Discussion: The obtained results align with international evidence, reflecting realities similar to the local situation. The study's significance lies in the absence of an updated national or local database on the pathology. Additionally, it provides insights into available treatments and patient adherence, offering a snapshot of the local population's behavior during 2020-2021. Limitations include patient follow-up challenges due to pandemic restrictions and the lack of pre-existing data.

Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster.

The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM) and 4-Vinylcyclohexene diepoxide (VCD) are the two downstream metabolites of 4-vinylcyclohexene (VCH), an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10-1000 µM) in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST) activity in the flies exposed to VCM and VCD (p<0.05). These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1), kelch-like erythroid-derived cap-n-collar (CNC) homology (ECH)-associated protein 1 (Keap-1), mitogen activated protein kinase 2 (MAPK-2), catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1) and thioredoxin reductase 1 (TrxR-1) (p<0.05). VCM and VCD inhibited acetylcholinesterase (AChE) and delta aminolevulinic acid dehydratase (δ-ALA D) activities in the flies (p<0.05). Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD.

Identification of influential events concerning the Antarctic ozone hole over southern Brazil and the biological effects induced by UVB and UVA radiation in an endemic treefrog species.

The increased incidence of solar ultraviolet radiation (UV) due to ozone depletion has been affecting both terrestrial and aquatic ecosystems and it may help to explain the enigmatic decline of amphibian populations in specific localities. In this work, influential events concerning the Antarctic ozone hole were identified in a dataset containing 35 years of ozone measurements over southern Brazil. The effects of environmental doses of UVB and UVA radiation were addressed on the morphology and development of Hypsiboas pulchellus tadpole (Anura: Hylidae), as well as on the induction of malformation after the conclusion of metamorphosis. These analyzes were complemented by the detection of micronucleus formation in blood cells. 72 ozone depletion events were identified from 1979 to 2013. Surprisingly, their yearly frequency increased three-fold during the last 17 years. The results clearly show that H. pulchellus tadpole are much more sensitive to UVB than UVA light, which reduces their survival and developmental rates. Additionally, the rates of micronucleus formation by UVB were considerably higher compared to UVA even after the activation of photolyases enzymes by a further photoreactivation treatment. Consequently, a higher occurrence of malformation was observed in UVB-irradiated individuals. These results demonstrate the severe genotoxic impact of UVB radiation on this treefrog species and its importance for further studies aimed to assess the impact of the increased levels of solar UVB radiation on declining species of the Hylidae family.

Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster.

4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 µM-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (δ-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, δ-ALA-D, and AChE activities (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant balance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity.

Neuroprotective effect of diphenyl diselenide in a experimental stroke model: maintenance of redox system in mitochondria of brain regions.

Acute stroke is a major risk for morbidity and mortality in aging population. Mitochondrion has been the focus of a wide stroke-related research. This study investigated if treatment or pre-treatment with diphenyl diselenide (PhSe)2 can prevent mitochondrial damage in cerebral structures of rats induced by an ischemia and reperfusion (I/R) model. Adult male Wistar rats were assigned into five experimental groups: sham operation, ischemia/reperfusion, pre-treated + I/R, treated + I/R, and Sham + (PhSe)2. Neurological score showed the damage caused by I/R, which was partially prevented by (PhSe)2. Moreover, mitochondria of hippocampus and cortex were impaired by I/R through an increase of reactive oxygen species production, mitochondrial membrane potential (ΔΨm) and electrons flow alteration, activity of complex I deregulation as well as mitochondrial swelling. However, the ischemic damage did not induce an increase in pro-apoptotic proteins expression, but demonstrated an enhanced expression of Hsp70. The mitochondrial redox state was also altered (GSH/GSSG ratio, MnSOD, and GPx activities). Our results revealed that all treatments with (PhSe)2 significantly reduced the mitochondrial damage induced by I/R. These findings suggest that neuroprotective properties of (PhSe)2 may be attributed to the maintenance of mitochondrial redox balance.

Analysis of FOXP3 gene and protein expressions in renal allograft biopsies and their association with graft outcomes.

BACKGROUND: The transcription factor FOXP3 is increased in acute renal rejection, but its influence on graft outcomes is unclear. This study correlated FOXP3 with dendritic cells and graft outcomes. METHODS: We assessed 96 kidney transplants undergoing allograft biopsy for cause. FOXP3 mRNA was analyzed by real-time polymerase chain reaction (PCR) and FOXP3 protein and DCsCD83(+) by immunohistochemistry. Graft function and survival were assessed at 5 years post-transplantation, as well as by independent predictors of graft loss. RESULTS: Intragraft FOXP3 gene and protein expression were significantly correlated (r = 0.541, p < 0.001). Both FOXP3 mRNA and protein were increased in patients with acute rejection (AR). High expression of FOXP3 mRNA or protein in biopsies did not correlate with clinical variables, but there was a trend to higher positive variation in the glomerular filtration rate (GFR) from biopsy to last follow-up. Patients with FOXP3-mRNA(high) had more DCsCD83(+) in biopsy, but these cells did not associate with AR. Five-year graft survival was not influenced by either FOXP3 mRNA or protein expressions. CONCLUSIONS: FOXP3 mRNA and protein had a good correlation in archival renal graft tissue. Increased FOXP3 expression was found in AR and FOXP3 associated with high numbers of DCs. However, both FOXP3 mRNA and protein was not associated with better allograft outcomes.

Spi2 gene polymorphism is not associated with recurrent airway obstruction and inflammatory airway disease in thoroughbred horses.

The aim was to detect the presence of polymorphisms at exons 1, 2, 3 and 4 of the Spi2 gene, and evaluate a possible association between them and recurrent airway obstruction (RAO) or inflammatory airway disease (IAD) in thoroughbred horses, through single-strand conformational-polymorphism (SSCP) screening. Although polymorphism was not detected in exons 1, 2 and 3, three alleles and six genotypes were identified in exon 4. The frequencies of allele A (0.6388) and genotype AA (0.3888) were higher in horses affected by RAO, although no association was found between polymorphism and horses with either RAO or IAD.

The hobo-related elements in the melanogaster species group.

The hobo-related sequences (hRSs) were considered as degenerate and inactive elements until recently, when one mobilizable copy was described. Using this sequence as the initial seed to search for homologous sequences in 12 available Drosophila genomes, in addition to searching for these sequences by PCR and Southern blot in nine other species, we found homologous sequences in every species of the Drosophila melanogaster species subgroup. Some evidence suggests that these non-autonomous sequences were kept mobilizable for at least 0.4 million years. Also, some very short sequences with miniature inverted-repeat transposable element (MITE) characteristics were found among these hRSs. These hRSs and their 'MITE-like' counterparts could provide a good example of the steps proposed in models that describe the MITEs origin.