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Introduction: The Fabaceae family is one of the most abundant in Costa Rica, with at least 136 genera and 593 species, many of which are important for agriculture, forestry, and ornamental purposes. Objective: To understand species distribution and extent of collection efforts from the country’s two main herbaria. Methods: We cleaned databases from 1887 to 2022 at the University of Costa Rica (USJ) and the National Herbarium (CR). Results: We documented the presence of 154 genera of Fabaceae, with Inga being the most abundant and diverse. The largest collection effort occurred in 1993, with records of 112 genera and 321 species. We identified 19 species that had not been collected for more than 40 years. Puntarenas emerged as the province with the highest number of genera and species records (117 and 406, respectively), while at the cantonal level, La Cruz, Bagaces, and Osa presented the largest numbers of genera (89, 84, and 79, respectively). Most records are from the Tropical Humid Forest life zone (biotemperature 18-24 °C; precipitation 2 000-4 000 mm). The largest number of species was associated with non-climbing evergreen trees (228 species), followed by non-climbing evergreen shrub/trees (74 species). Additionally, we identified 5 species classified as critically endangered, 29 as endangered, and 21 as near threatened. Conclusion: Our herbarium analysis of Fabaceae in Costa Rica revealed a rich diversity (154 genera, predominantly Inga), with a spatial bias towards Puntarenas and the Tropical Humid Forest. Key findings include 19 long-uncollected species and considerable numbers of threatened species, underlining the need for further conservation efforts and exploration to address taxonomic gaps. more...

The diagnosis of thyroid cancer (TC) has increased dramatically in recent years. Papillary TC is the most frequent type and has shown a good prognosis. Conventional treatments for TC are surgery, hormonal therapy, radioactive iodine, chemotherapy, and targeted therapy. However, resistance to treatments is well documented in almost 20% of all cases. Genomic sequencing has provided valuable information to help identify variants that hinder the success of chemotherapy as well as to determine which of those represent potentially druggable targets. There is a plethora of targeted therapies for cancer, most of them directed toward point mutations; however, chromosomal rearrangements that generate fusion genes are becoming relevant in cancer but have been less explored in TC. Therefore, it is relevant to identify new potential inhibitors for genes that are recurrent in the formation of gene fusions. In this review, we focus on describing potentially druggable variants and propose both point variants and fusion genes as targets for drug repositioning in TC. more...

The most frequently diagnosed histological types of cervical cancer (CC) are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. A molecular profile that distinguishes each histological subtype and predicts the prognosis would be of great benefit to CC patients. Methods: The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes (DEGs) between ADC and SCC. The DEGs were validated on a publicly available Mexican-Mestizo patient transcriptome dataset (GSE56303). The global biological pathways involving the DEGs were obtained using the Webgestalt platform. The associations of the DEGs with Overall Survival (OS) were assessed. Finally, three DEGs were validated by RT-qPCR in an independent cohort of Mexican patients. Results. The molecular profiles of ADC and SCC of the CC patients of the TCGA database and the Mexican-Mestizo cohort (GSE56303) were determined obtaining 1768 and 88 DEGs, respectively. Strikingly, 70 genes were concordant—with similar Log2FoldChange values—in both cohorts. The 70 DEGs were involved in IL-17, JAK/STAT, and Ras signaling. Kaplan-Meier OS analysis from the Mexican-Mestizo cohort showed that higher GABRB2 and TSPAN8 and lower TMEM40 expression were associated with better OS. Similar results were found in an independent Mexican cohort. Conclusions: Molecular differences were detected between the ADC and SCC subtypes; however, further studies are required to define the appropriate prognostic biomarker for each histological type. more...

What factors account for polarization in constitutional conventions comprised of party members and many independents without prior legislative experience? Using the 4,669 roll call votes in the 155-member constitutional convention in Chile (2021–2), comprised of more independents than party members, we explore the determinants of ideological polarization. Relying on absolute values for the WNominate scores, we find that party members are less polarized than independents and that prior legislative experience does not impact polarization. In institutionalized party systems that allow independents to compete with party members on a level playing field, a larger presence of independents in legislatures might help increase ideological polarization while a larger number of party members helps reduce ideological polarization in roll call votes. [ABSTRACT FROM AUTHOR] more...

IntroductionMetastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies.MethodsWe sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing.ResultsOverall, we found 22 variants –9 of them reported for the first time– and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort.DiscussionOur results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population. more...

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1β, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination. more...

Objective/context: We explore if legislators use roll call votes in the Chamber of Deputies in Chile as a tool to respond to the power of the president in the legislative process. Is there evidence of solidarity among legislators in their roll call votes? Do they vote more cohesively in legislator-initiated bills than in president-initiated bills? Methodology: With 5216 roll call votes by the 120 members of the Chamber of Deputies in Chile in the 2006-2010 and 2010-2014 terms, we look for evidence of legislative solidarity in how bills are voted. We use WUnity and WRice indicators and inferential analysis—ordinary least square regressions— to test 4 hypotheses. Conclusions: Government coalitions show more cohesion than opposition coalitions, though the rightwing coalition showed more cohesion than the leftwing coalition both as an opposition and a government coalition. Originality: We contribute to the studies on the behavior of legislatures in Latin America to assess if, given the president’s legislative powers, legislators use their roll call votes as a tool to express solidarity with other legislators voting in favor of legislator-initiated bills, using roll call votes as a way to counter balance the powerful legislative tools of presidents. more...

Despite efforts to promote health policies focused on screening and early detection, cervical cancer continues to be one of the leading causes of mortality in women; in 2020, estimated 30,000 deaths in Latin America were reported for this type of tumor. While the therapies used to treat cervical cancer have excellent results in tumors identified in early stages, those women who are diagnosed in locally advanced and advanced stages show survival rates at 5 years of more...

Breast cancer is the most common cancer in women. Despite advances in diagnosis and prognosis, distal metastases occur in these patients in up to 15% of cases within 3 years of diagnosis. The main organs in which BC metastasises are the bones, lungs, liver, and brain. Unfortunately, 90% of metastatic patients will die, making this an incurable disease. Researchers are therefore seeking biomarkers for diagnosis and metastasis in different organs. Optimally, such biomarkers should be easy to detect using, preferably, non-invasive methods, such as using miRNA molecules, which are small molecules of about 22 nt that have as their main function the post-transcriptional regulation of genes. Furthermore, due to their uncomplicated detection and reproducibility in the laboratory, they are a tool of complementary interest for diagnosis, prognosis, and treatment. With this in mind, in this review, we focus on describing the most current studies that propose using miRNA independently as a potential biomarker for the diagnosis and prediction of brain, lung, liver, and bone metastases, as well as to open a window of opportunity to deepen this area of study to eventually use miRNAs molecules in clinical practice for the benefit of BC patients. more...

BackgroundIn Cervical cancer (CC), in addition to HPV infection, the most relevant alteration during CC initiation and progression is the aberrant activation of Wnt/β-catenin pathway. Several inhibitory drugs of this pathway are undergoing preclinical and clinical studies. Long non-coding RNAs (lncRNAs) are associated with resistance to treatments. In this regard, understanding the efficiency of drugs that block the Wnt/β-catenin pathway in CC is of relevance to eventually propose successful target therapies in patients with this disease.MethodsWe analyzed the levels of expression of 249 components of the Wnt/β-catenin pathway in a group of 109 CC patients. Three drugs that blocking specific elements of Wnt/β-catenin pathway (C59, NSC668036 and ICRT14) by TOP FLASH assays and qRT-PCR were tested in vitro in CC cells.Results137 genes of the Wnt/β-catenin pathway were up-regulated and 112 down-regulated in CC patient’s samples, demonstrating that this pathway is dysregulated. C59 was an efficient drug to inhibit Wnt/β-catenin pathway in CC cells. NSC668036, was not able to inhibit the transcriptional activity of the Wnt/β-catenin pathway. Strikingly, ICRT14 was neither able to inhibit this pathway in HeLa cells, due to HOTAIR interaction with β-catenin, maintaining the Wnt/β-catenin pathway activated.ConclusionsThese results demonstrate a mechanism by which HOTAIR evades the effect of ICRT14, a Wnt/β-catenin pathway inhibitory drug, in HeLa cell line. The emergence of these mechanisms reveals new scenarios in the design of target therapies used in cancer. more...

In light of the post-genomic era, epigenetics brings about an opportunity to better understand how the molecular machinery works and is led by a complex dynamic set of mechanisms, often intricate and complementary in many aspects. In particular, epigenetics links developmental biology and genetics, as well as many other areas of knowledge. The present work highlights substantial scopes and relevant discoveries related to the development of the term from its first notions. To our understanding, the concept of epigenetics needs to be revisited, as it is one of the most relevant and multifaceted terms in human knowledge. To redirect future novel experimental or theoretical efforts, it is crucial to compile all significant issues that could impact human and ecological benefit in the most precise and accurate manner. In this paper, the reader can find one of the widest compilations of the landmarks and epistemic considerations of the knowledge of epigenetics across the history of biology from the earliest epigenetic formulation to genetic determinism until the present. In the present work, we link the current body of knowledge and earlier pre-genomic concepts in order to propose a new definition of epigenetics that is faithful to its regulatory nature. [ABSTRACT FROM AUTHOR] more...

Abstract Background Invasion and metastasis are determinant events in the prognosis of Colorectal cancer (CRC), a common neoplasm worldwide. An important factor for metastasis is the acquired capacity of the cell to proliferate and invade adjacent tissues. In this paper, we explored the role of micro-RNA-26a in the regulation of proliferation and migration in CRC-derived cells through the negative regulation of PTEN, a key negative regulator of the AKT pathway. Methods Expression levels of PTEN and mir-26a were surveyed in normal and CRC-derived cell lines; paraffin embedded human tissues, TCGA CRC expression data and a Balb/c mice orthotopic induced CRC model. CRC was induced by an initial intraperitoneal dose of the colonic carcinogen Azoxymethane followed by inflammatory promoter Dextran Sulfate Sodium Salt. Luciferase assays provide information about miR-26a–PTEN 3′UTR interaction. Proliferation and migration by real time cell analysis and wound-healing functional analyses were performed to assess the participation of mir-26a on important hallmarks of CRC and its regulation on the PTEN gene. Results We observed a negative correlation between PTEN and mir-26a expression in cell lines, human tissues, TCGA data, and tissues derived from the CRC mouse model. Moreover, we showed that negative regulation of PTEN exerted by miR-26a affected AKT phosphorylation levels directly. Functional assays showed that mir-26a directly down-regulates PTEN, and that mir-26a over-expressing cells had higher proliferation and migration rates. Conclusions All this data proposes an important role of mir-26a as an oncomir in the progression and invasion of CRC. Our data suggested that mir-26a could be used as a biomarker of tumor development in CRC patients, however more studies must be conducted to establish its clinical role. more...

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide in both sexes. Current therapies include surgery, chemotherapy, and targeted therapy; however, prolonged exposure to chemical agents induces toxicity in patients and drug resistance. So, we implemented a therapeutic strategy based on the combination of doxorubicin, metformin, and sodium oxamate called triple therapy (Tt). We found that Tt significantly reduced proliferation by inhibiting the mTOR/AKT pathway and promoted apoptosis and autophagy in CRC derived cells compared with doxorubicin. Several autophagy genes were assessed by western blot; ULK1, ATG4, and LC3 II were overexpressed by Tt. Interestingly, ULK1 was the only one autophagy-related protein gradually overexpressed during Tt administration. Thus, we assumed that there was a post-transcriptional mechanism mediating by microRNAs that regulate UKL1 expression during autophagy activation. Through bioinformatics approaches, we ascertained that ULK1 could be targeted by mir-26a, which is overexpressed in advanced stages of CRC. In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1α transcription factor recognition sites. We developed two different HIF-1α stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1α enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1α detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1α and that in turn regulates mir-26a transcription. more...

The widespread dysregulation that characterizes cancer cells has been dissected and many regulation pathways common to multiple cancer types have been described in depth. Wnt/β-catenin signaling and autophagy are among these principal pathways, which contribute to tumor growth and resistance to anticancer therapies. Currently, several therapeutic strategies that target either Wnt/β-catenin signaling or autophagy are in various stages of development. Targeted therapies that block specific elements that participate in both pathways; are subject to in vitro studies as well as pre-clinical and early clinical trials. Strikingly, drugs designed for other diseases also impact these pathways, which is relevant since they are already FDA-approved and sometimes even routinely used in the clinic. The main focus of this mini-review is to highlight the importance of drug repositioning to inhibit the Wnt/β-catenin and autophagy pathways, with an emphasis on the interplay between them. The data we found strongly suggested that this field is worth further examination. more...

IntroductionBLK has been identified as a risk factor to rheumatoid arthritis (RA) primarily in Asian or European-derived populations. However, this finding has not been evaluated in other populations such as Latin-Americans, except for Colombians. On the other hand, BANK1 single nucleotide variants (SNVs) have been scarcely studied in RA patients.ObjectiveThe aim of this study was to determine whether the BLK rs2736340T/C, rs13277113A/G, and BANK1 rs10516487G/A (R61H) and rs3733197G/A (A383T) polymorphisms are risk factors to RA in a sample of patients from Central Mexico.Materials and MethodsWe studied 957 women; 487 controls and 470 patients with RA by means of a TaqMan® SNP genotyping assay with fluorescent probes for the BLK rs13277113A/G, rs2736340T/C and BANK1 10516487G/A (R61H) and rs3733197G/A (A383T) variants.ResultThe BLK rs2736340T/C and rs13277113A/G variants were associated with risk for RA: C vs T; OR 1.39, p = 0.001, and G vs A; OR 1.37, p = 0.004, respectively. In addition, there was also an association between BANK1 R61H and RA: A vs G; OR 1.49, p = 0.003, but no with BANK1 A383T. We also identified an interaction significant between genotypes of BLK rs2736340T/C-BANK1 rs10516487G/A and RA: OR 1.65, p = 0.0001.ConclusionsOur data suggest that both BLK and BANK1 confer susceptibility to RA in Mexican patients. The individual association of BANK1 rs1054857G/A with RA had not been previously reported in a particular population (except for pooled patients from several countries), therefore, our study presents the first evidence of association between this BANK1 variant and RA. more...

Cancer is a complex disease, and its study requires deep understanding of several biological processes and their regulation. It is an accepted fact that non-coding RNAs are vital components of the regulation and cross-talk among cancer-related signaling pathways that favor tumor aggressiveness and metastasis, such as neovascularization, angiogenesis, and vasculogenic mimicry. Both long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) have been described as master regulators of cancer on their own; yet there is accumulating evidence that, besides regulating mRNA expression through independent mechanisms, these classes of non-coding RNAs interact with each other directly, fine-tuning the effects of their regulation. While still relatively scant, research on the lncRNA-miRNA-mRNA axis regulation is growing at a fast rate, it is only in the last 5 years, that lncRNA-miRNA interactions have been identified in tumor-related vascular processes. In this review, we summarize the current progress of research on the cross-talk between lncRNAs and miRNAs in the regulation of neovascularization, angiogenesis and vasculogenic mimicry. more...

Vasculogenic mimicry (VM) is a novel cancer hallmark in which malignant cells develop matrix-associated 3D tubular networks with a lumen under hypoxia to supply nutrients needed for tumor growth. Recent studies showed that microRNAs (miRNAs) may have a role in VM regulation. In this study, we examined the relevance of hypoxia-regulated miRNAs (hypoxamiRs) in the early stages of VM formation. Data showed that after 48 h hypoxia and 12 h incubation on matrigel SKOV3 ovarian cancer cells undergo the formation of matrix-associated intercellular connections referred hereafter as 3D channels-like structures, which arose previous to the apparition of canonical tubular structures representative of VM. Comprehensive profiling of 754 mature miRNAs at the onset of hypoxia-induced 3D channels-like structures showed that 11 hypoxamiRs were modulated (FC>1.5; p < 0.05) in SKOV3 cells (9 downregulated and 2 upregulated). Bioinformatic analysis of the set of regulated miRNAs showed that they might impact cellular pathways related with tumorigenesis. Moreover, overall survival analysis in a cohort of ovarian cancer patients (n = 485) indicated that low miR-765, miR-193b, miR-148a and high miR-138 levels were associated with worst patients outcome. In particular, miR-765 was severely downregulated after hypoxia (FC < 32.02; p < 0.05), and predicted to target a number of protein-encoding genes involved in angiogenesis and VM. Functional assays showed that ectopic restoration of miR-765 in SKOV3 cells resulted in a significant inhibition of hypoxia-induced 3D channels-like formation that was associated with a reduced number of branch points and patterned tubular-like structures. Mechanistic studies confirmed that miR-765 decreased the levels of VEGFA, AKT1 and SRC-α transducers and exerted a negative regulation of VEGFA by specific binding to its 3‘UTR. Finally, overall survival analysis of a cohort of ovarian cancer patients (n = 1435) indicates that high levels of VEGFA, AKT1 and SRC-α and low miR-765 expression were associated with worst patients outcome. In conclusion, here we reported a novel hypoxamiRs signature which constitutes a molecular guide for further clinical and functional studies on the early stages of VM. Our data also suggested that miR-765 coordinates the formation of 3D channels-like structures through modulation of VEGFA/AKT1/SRC-α axis in SKOV3 ovarian cancer cells. more...

Breast cancer is the neoplasm with the highest number of deaths in women. Although the molecular mechanisms associated with the development of this tumor have been widely described, metastatic disease has a high mortality rate. In recent years, several studies show that microRNAs or miRNAs regulate complex processes in different biological systems including cancer. In the present work, we describe a group of 61 miRNAs consistently over-expressed in breast cancer (BC) samples that regulate the breast cancer transcriptome. By means of data mining from TCGA, miRNA and mRNA sequencing data corresponding to 1091 BC patients and 110 normal adjacent tissues were downloaded and a miRNA–mRNA network was inferred. Calculations of their oncogenic activity demonstrated that they were involved in the regulation of classical cancer pathways such as cell cycle, PI3K–AKT, DNA repair, and k-Ras signaling. Using univariate and multivariate analysis, we found that five of these miRNAs could be used as biomarkers for the prognosis of overall survival. Furthermore, we confirmed the over-expression of two of them in 56 locally advanced BC samples obtained from the histopathological archive of the National Cancer Institute of Mexico, showing concordance with our previous bioinformatic analysis. more...

Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%–85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood. Here, we investigated whether a microRNA profile could be associated with pathological complete response in triple-negative breast cancer patients receiving 5-fluorouracil, adriamycin, cyclophosphamide–cisplatin/paclitaxel as a novel neoadjuvant chemotherapy. In the discovery cohort, the expression of 754 microRNAs was examined in tumors from 10 triple-negative breast cancer patients who achieved pathological complete response and 8 without pathological complete response using TaqMan Low-Density Arrays. Unsupervised hierarchical cluster analysis identified 11 microRNAs with significant differences between responder and no-responder patients (fold change ≥ 1.5; p more...