The axolotl (Ambystoma mexicanum) has a great capacity to regenerate its tissues; however, the fidelity and success of its regenerative process diminish with age. Retrotransposons make up the largest portion of the axolotl genome, and their expression may be involved in this age-related decline. Through an integrative analysis of repetitive element expression using RNA sequencing, it is shown that Ty3 retrotransposons are highly upregulated in the axolotl as an effect of chronological aging. Other non-long-terminal-repeat transposons, including long interspersed nuclear element 1, function as hubs of gene coexpression networks involved in muscle development and regulation of apoptosis and connective tissue replacement, which are also suppressed in adulthood. By contrast, it is found that during regeneration of the limb, these pathways and the expression of Ty3 retrotransposons are distinctly downregulated. Although the blastema can readjust most of the transposon differential expression in adulthood, several elements remain affected and may have an impact in the immune response during regeneration. This analysis provides a profile of retrotransposon expression through chronological aging and during limb regeneration in the axolotl and indicates that transposons are responsive to physiological changes in a tissue-specific way and may participate in the gene coregulatory networks underlying the regenerative process.

Chronic consumption of high fat diets (HFD) is a risk factor for the development of metabolic diseases such as obesity and diabetes, and it is also associated with cognitive impairment and Alzheimer´s disease. Palmitic acid (PA) is a major component of HFD, and high concentrations of this saturated fatty acid exerts pleiotropic actions in cells. The PA effects have been largely studied in peripheral tissues where is considered a driving force for the development of many metabolic diseases such as obesity, insulin resistance and Type II diabetes. In the brain, particularly in neurons, it is able to increase oxidative metabolism, induce insulin resistance, and alter gene expression. However, little is known about how PA-induced metabolic alterations may affect gene expression mechanisms in neurons. One of the most studied PA-dependent mechanisms is associated with the lipid-induced activation of the transcription factors, PPAR-γ and PGC-α, but fewer studies have analyzed the PA-dependent regulation of epigenetic mechanisms. In this study, we identified PA-linked changes in the class I histone deacetylases (HDACs) content associated with chromatin acetylation and with differential expression of the BDNF-encoding gene and the non-coding retrotransposon, LINE1 in differentiated human neuroblastoma cells.

The axolotl is an animal with remarkable regenerative abilities, making it an ideal model for studying potential regenerative therapies in mammals, including humans. However, the molecular mechanisms involved in regeneration remain unclear. We conducted a transcriptomic analysis of juvenile axolotls’ limbs and their blastema and compared the results with aged axolotls that failed to regenerate after amputation. We identified a set of genes involved in cell differentiation, transcriptional regulation, cartilage development, bone morphogenesis, and extracellular matrix remodeling. Four highly expressed genes ( FSTL1, ADAMTS17, GPX7 , and CTHRC1 ) were identified in regenerating tissue, but underexpressed in aged axolotls. Structural and homology analysis showed that these genes are conserved and have important roles in development, bone morphogenesis, and cartilage formation. Our findings propose a novel set of axolotl genes involved in tissue regeneration that could be a starting point for further studies in other vertebrates. Graphical abstract

The axolotl, known for its remarkable regenerative abilities, is an excellent model for studying regenerative therapies. Nevertheless, the precise molecular mechanisms governing its regenerative potential remain uncertain. In this study, we collected samples from axolotls of different ages, including 8-year-old individuals and 8-month-old juveniles, obtaining their blastemas 10 days after amputation. Subsequently, we conducted a transcriptomic analysis comparing our samples to a set of previously published experiments. Our analysis unveiled a distinctive transcriptional response in the blastema, characterized by differential gene expression associated with processes such as bone and tissue remodeling, transcriptional regulation, angiogenesis, and intercellular communication. To gain deeper insights, we compared these findings with those from aged axolotls that showed no signs of regeneration 10 days after amputation. We identified four genes—FSTL1, ADAMTS17, GPX7, and CTHRC1—that showed higher expression in regenerating tissue compared to aged axolotls. Further scrutiny, including structural and homology analysis, revealed that these genes are conserved across vertebrate species. Our discoveries point to a group of proteins relevant to tissue regeneration, with their conservation in vertebrates suggesting critical roles in development. These findings also propose a novel gene set involved in axolotl regeneration, laying a promising foundation for future investigations across vertebrates.

The rise in life expectancy has significantly increased the occurrence of age-related chronic diseases, leading to escalating expenses for both society and individuals. Among the main factors influencing health and lifespan, lifestyle takes a forefront position. Specifically, nutrition, mental activity, and physical exercise influence the molecular and functional mechanisms that contribute to the prevention of major age-related diseases. Gaining deeper insights into the mechanisms that drive the positive effects of healthy lifestyles is valuable for creating interventions to prevent or postpone the development of chronic degenerative diseases. This review summarizes the main mechanisms that underlie the positive effect of lifestyle factors in counteracting the major age-related diseases involving brain health, musculoskeletal function, cancer, frailty, and cardiovascular diseases, among others. This knowledge will help to identify high-risk populations for targeted intervention trials and discover new biomarkers associated with healthy aging.

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.

Purpose Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53 . Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. Methods We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT , MGMT and TP53 , and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). Results In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. Conclusions The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Chromatin maintenance and remodeling are processes that take place alongside DNA repair, replication, or transcription to ensure the survival and adaptability of a cell. The environment and the needs of the cell dictate how chromatin is remodeled; particularly where and which histones are deposited, thus changing the canonical histone array to regulate chromatin structure and gene expression. Chromatin is highly dynamic, and histone variants and their chaperones play a crucial role in maintaining the epigenetic regulation at different genomic regions. Despite the large number of histone variants reported to date, studies on their roles in physiological processes and pathologies are emerging but continue to be scarce. Here, we present recent advances in the research on histone variants and their chaperones, with a focus on their importance in molecular mechanisms such as replication, transcription, and DNA damage repair. Additionally, we discuss the emerging role they have in transposable element regulation, aging, and chromatin remodeling syndromes. Finally, we describe currently used methods and their limitations in the study of these proteins and highlight the importance of improving the experimental approaches to further understand this epigenetic machinery.

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on catalytic activity. Abnormal expression of DNMT3B isoforms is frequently observed in several types of cancer, such as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma. However, the expression patterns and consequences of DNMT3B isoforms in OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms expression by qPCR in 63 OC samples and their association with disease-free survival (DFS), overall survival (OS), and tumor progression. We included OC patients with the main histological subtypes of EOC and patients in all the disease stages and found that DNMTs were overexpressed in advanced stages (p-value < 0.05) and high-grade OC (p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in advanced stages (p-value = 0.0251) and high-grade serous ovarian carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004) serous ovarian carcinoma (SOC). Finally, we observed that overexpression of DNMT3B isoforms was associated with poor prognosis in OC and SOC. DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value = 0.038) in SOC patients. In addition, the ovarian carcinoma cell lines OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2 sequences in the pericentromeric region. In summary, our results suggest that DNMT3B3 expression is altered in OC.

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research.

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ Cell Tumor (TGCT) patients are platinum resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum sensitive and 14 were platinum resistant. We incorporated analyses of mutational burden, driver mutations, SNV and CNV signatures. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplification of 2q11.1 as a novel variant with chemosensitivity biomarker potential. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. Our data sheds light into understanding platinum resistance in a poorly characterized population.

Transcription Factors (TFs) are crucial proteins that regulate gene expression in the cell. They bind to regulatory sequences and promote the transcription of genomic elements. The identification of TFs binding sites is often the first step towards a detailed understanding of their function, which has important implications to comprehend the cell, its development and differentiation. This chapter focuses on the bioinformatic analyses used to identify specific TF binding sites. It introduces the different high-throughput experimental techniques currently used to elucidate the regulatory elements such as, ChIP-seq, SELEX-seq, ChIP-on-chip, CUT&RUN or CUT&Tag, and the computational methods used to identify and/or predict the regulatory sequences targeted by TFs. The topics described here are the different TF binding motif representations, from Position Weight Matrices to Transcription Factor Flexible Models; the de novo motif discovery approaches, including the enumerative, probabilistic, nature-inspired, deep learning and ensemble algorithms; and motif prediction methods, which can consider phylogenetic foot printing or co-expression data, among others. An overview of the different tools used and their pros and cons in practice is discussed in order to understand the general workflow of TFBS studies and their experimental basis, both necessary to identify the limitations of the field.

Objectives: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. Methods: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. Results: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. Conclusions: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Marijuana (Cannabis sp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.