Bioactive compounds as an alternative for the sugarcane industry: Towards an integrative approach.

Here, a comprehensive review of sugarcane industrialization and its relationship with bioactive compounds (BCs) detected in various products and by-products generated during its processing is presented. Furthermore, it is discussed how these compounds have revealed important antioxidant, antineoplastic, antidiabetic, and antimicrobial activities. From this bibliographic research highlights the significance of two types of BCs of natural origin (phenolic compounds (PCs) and terpenoids) and a group of compounds synthesized during industrial transformation processes (Maillard reaction products (MRPs)). It was found that most of the studies about the BCs from sugarcane have been conducted by identifying, isolating, and analyzing ones or a few compounds at a specific period, this being a conventional approach. However, given the complexity of the synthesis processes of all these BCs and the biological activities they can manifest in a specific biological context, novel approaches are needed to address these analyses holistically. To overcome this challenge, integrating massive and multiscale methods, such as omics sciences, seems necessary to enrich these studies. This work is intended to contribute to the state of the art that could support future research about the exploration, characterization, or evaluation of different bioactive molecules from sugarcane and its derivatives.

Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.

Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-ß pathway.

Structural and functional computational analysis of nicotine analogs as potential neuroprotective compounds in Parkinson disease.

As the mechanism of interaction between nicotinic receptors with nicotine analogs is not yet fully understood, information at molecular level obtained from computational calculations is needed. In this sense, this work is a computational study of eight nicotine analogs, all with pyrrolidine ring modifications over a nicotine-based backbone optimized with B3LYP-D3/aug-cc-pVDZ. A molecular characterization was performed focusing on geometrical parameters such as pseudo-rotation angles, atomic charges, HOMO and LUMO orbitals, reactivity indexes and intermolecular interactions. Three analogs, A2 (3-(1,3-dimethyl-4,5-dihydro-1h-pirazole-5-yl) pyridine), A3 (3-(3-methyl-4,5-dihydro-1H-pyrazol-5-yl)-pyridine) and A8 (5-methyl-3-(pyridine-3-yl)-4,5-dihydroisoxazole), were filtered suggesting putative neuroprotective activity taking into account different reactivity values, such as their lowest hardness: 2.37 eV (A8), 2.43 eV (A2) and 2.56 eV (A3), compared to the highest hardness value found: 2.71 eV for A5 (3-((2S,4R)-4-(fluoromethyl)-1-methylpyrrolidine-2-il) pyridine), similar to the value of nicotine (2.70 eV). Additionally, molecular docking of all 8 nicotine analogs with the α 7 nicotinic acetylcholine receptor (α 7 nAChR) was performed. High values of interaction between the receptor and the three nicotine analogs were obtained: A3 (-7.1 kcal/mol), A2 (-6.9 kcal/mol) and A8 (-6.8 kcal/mol); whereas the affinity energy of nicotine was -6.4 kcal/mol. Leu116 and Trp145 are key residues in the binding site of α 7 nAChR interacting with nicotine analogs. Therefore, based upon these results, possible application of these nicotine analogs as neuroprotective compounds and potential implication at the design of novel Parkinson's treatments is evidenced.

Structure, clustering and functional insights of repeats configurations in the upstream promoter region of the human coding genes.

BACKGROUND: Repetitive DNA sequences (Repeats) are significant regions in the human genome that have a specific genomic distribution, structure, and several binding sites for genome architecture and function. In consequence, the possible configurations of Repeats in specific and dynamic regions like the gene promoters could define footprints for molecular mechanisms, pathways, and cell function beyond their density in the genome. Here we explored the distribution of Repeats in the upstream promoter region of the human coding genes with the aim to identify specific configurations, clusters and functional meaning of those elements. Our method includes structural descriptions, hierarchical clustering, pathway association, and functional enrichment analysis. RESULTS: We report here several configurations of Repeats in the upstream promoter region (UPR), which define 2729 patterns for the 80% of the human coding genes. There are 47 types of Repeats in these configurations, where the most frequent were Alu, Low_complexity, MIR, Simple_repeat, LINE/L2, LINE/L1, hAT-Charlie, and ERV1. The distribution, length, and the high frequency of Repeats in the UPR defines several patterns and clusters, where the minimum frequency of configuration among Repeats was higher than 0.7. We found those clusters associated with cellular pathways and ontologies; thus, it was plausible to determine groups of Repeats to specific functional insights, for example, pathways for Genetic Information Processing or Metabolism shows particular groups of Repeats with specific configurations. CONCLUSION: Based on these findings, we propose that specific configurations of repetitive elements describe frequent patterns in the upstream promoter for sets of human coding genes, which those correlated to specific and essential cell pathways and functions.

Amelogénesis imperfecta en una familia / Amelogenesis imperfecta in a family

Introducción: la amelogénesis imperfecta consiste en un grupo de desórdenes hereditarios que afectan el desarrollo del esmalte dental, de tal forma que se ve comprometida la apariencia clínica de todos o casi todos los dientes, tanto temporales como permanentes. Objetivo: informar las características y condiciones clínicas de la dentición de tres individuos de una misma familia con diagnóstico presuntivo de amelogénesis imperfecta. Presentación de casos: se realizó examen intrabucal a tres individuos con rango de consanguinidad de primer grado (madre y dos hijos) quienes presentaban alterado estructuralmente el esmalte de los dientes. De acuerdo con las características clínicas dentales y el método de Witkop, los individuos fueron diagnosticados de forma presuntiva con amelogénesis imperfecta hipomadura tipo II (madre), caracterizada por hipomaduración del esmalte y fragmentación por desgaste en los bordes incisales; amelogénesis imperfecta hipoplásica tipo I (hijo mayor), con amplias zonas de dentina expuesta opaca y con manchas pardas generalizadas; y amelogénesis imperfecta hipomadura tipo II (hijo menor), con predominio de lesiones en forma de copo de nieve o motas de algodón. Conclusiones: el diagnóstico clínico de la amelogénesis imperfecta basado en métodos fenotípicos resulta impreciso debido a la imposibilidad de establecer el origen de las alteraciones macroestructurales del esmalte. Sin embargo, de acuerdo con la descripción de los tres casos, son las afecciones en la cantidad y calidad del esmalte las que permiten realizar un diagnóstico clínico presuntivo, que guía la implementación de un tratamiento odontológico direccionado a la solución del compromiso estético y a la prevención del compromiso del órgano dentino-pulpar. En esta presentación de casos, la manifestación fenotípica de la enfermedad pasó de la madre a ambos hijos, siendo la amelogénesis imperfecta hipomadura dominante en el hijo menor(AU)

Introduction: amelogenesis imperfecta consists of a group of hereditary disorders that affect the development of the dental enamel in such a way that the clinical appearance of all or almost all primary and permanent teeth is compromised. Objective: report the clinical characteristics and conditions of the dentition of three individuals from the same family with a presumptive diagnosis of amelogenesis imperfecta. Case presentation: intraoral examination was performed of three first-degree relatives (mother and two children) with structurally altered tooth enamel. Based on their clinical dental characteristics and the results of the Witkop method, the individuals were presumptively diagnosed with hypomaturation amelogenesis imperfecta type II (mother), characterized by enamel hypomaturation and fragmentation by wear on the incisal edges; hypoplastic amelogenesis imperfecta type I (elder son), with large areas of opaque exposed dentin and generalized brown spots; and hypomaturation amelogenesis imperfecta type II (younger son), with a predominance of lesions in the shape of snowflakes or cotton wads. Conclusions: clinical diagnosis of amelogenesis imperfecta based on phenotypic methods is imprecise, since it is not possible to establish the origin of the macrostructural alterations of the enamel. However, according to the description of the three cases, quantitative and qualitative damage to the enamel makes it possible to establish a presumptive clinical diagnosis which will guide the implementation of a dental treatment aimed at resolving the aesthetic commitment and preventing involvement of the dentine-pulp complex. In this case presentation, the phenotypic manifestation of the disease passed from the mother to both children, and hypomaturation amelogenesis imperfecta was dominant in the younger son(AU)

Draft Genome Sequence of Streptococcus anginosus BVI, a New Vaginal Pathogen Candidate.

Streptococcus anginosus is a pathogen implicated in urogenital and gastroinstestinal tract infections. Here, we report the draft genome sequence of S. anginosus BVI, isolated from a bacterial vaginosis patient attending a prenatal care unit in Cali, Colombia. The genome sequence of BVI consists of 2,014,025 bp, encoding 2,008 predicted proteins.

Vaginosis bacteriana por Gardnerella vaginalis: Nuevas enseñanzas desde la ecología molecular / Bacterial vaginosis by Gardnerella vaginalis: New lessons from molecular ecology

La vaginosis bacteriana (VB), es la afección vaginal más frecuente en las mujeres en edad reproductiva generada por un desbalance en el ecosistema vaginal que ocasiona complicaciones severas para la salud reproductiva. Existen hipótesis de origen biológico que relacionan la presencia de organismos como Gardnerella vaginalis, Prevotella sp, Atopobium vaginae como la causa más frecuente relacionada con la vaginosis, los cuales logran desplazar poblacionalmente microorganismos con capacidad protectora del epitelio vaginal como Lactobacillus crispatus y Lactobacillus jensenii. En la actualidad y de acuerdo a la OMS, la vaginosis bacteriana estaría implicada en alteraciones durante el embarazo como parto pre termino, bajo peso al nacer, corioamnionitis, ruptura prematura de membranas (RPM), endometritis post parto, entre otras. En los últimos años, con base estudios apoyados en datos de patrones moleculares, así como tecnología de análisis de genomas, surge una visión mucho más completa de condiciones ecológicas y agentes participantes en la vaginosis bacteriana.

Bacterial vaginosis (BV) is the most common vaginal condition in women of reproductive age generated due to an imbalance in the vaginal ecosystem that causes severe reproductive health complications. There are biological origin hypothesis linking the presence of organisms such as Gardnerella vaginalis, Prevotella sp, Atopobium vaginae as the most common cause related vaginosis, which manage to replace the microorganisms population wich protective abilities within the vaginal epithelium as Lactobacillus crispatus and Lactobacillus jensenii. At present, and according to WHO, bacterial vaginosis would be involved in disturbances during pregnancy and preterm delivery, low birth weight, chorioamnionitis, premature rupture of membranes (PROM), postpartum endometritis, among others. In recent years, based on data from molecular studies based on molecular patterns and genome analysis technology, a much more broaden picture of environmental conditions and agents involved in bacterial vaginosis has arise.

Exploration of noncoding sequences in metagenomes.

Environment-dependent genomic features have been defined for different metagenomes, whose genes and their associated processes are related to specific environments. Identification of ORFs and their functional categories are the most common methods for association between functional and environmental features. However, this analysis based on finding ORFs misses noncoding sequences and, therefore, some metagenome regulatory or structural information could be discarded. In this work we analyzed 23 whole metagenomes, including coding and noncoding sequences using the following sequence patterns: (G+C) content, Codon Usage (Cd), Trinucleotide Usage (Tn), and functional assignments for ORF prediction. Herein, we present evidence of a high proportion of noncoding sequences discarded in common similarity-based methods in metagenomics, and the kind of relevant information present in those. We found a high density of trinucleotide repeat sequences (TRS) in noncoding sequences, with a regulatory and adaptive function for metagenome communities. We present associations between trinucleotide values and gene function, where metagenome clustering correlate with microorganism adaptations and kinds of metagenomes. We propose here that noncoding sequences have relevant information to describe metagenomes that could be considered in a whole metagenome analysis in order to improve their organization, classification protocols, and their relation with the environment.