Isothermal Technologies for HPV Detection: Current Trends and Future Perspectives.

The human papillomavirus (HPV) is a non-enveloped DNA virus transmitted through skin-to-skin contact that infects epithelial and mucosal tissue. It has over 200 known genotypes, classified by their pathogenicity as high-risk and low-risk categories. High-risk HPV genotypes are associated with the development of different types of cancers, including cervical cancer, which is a leading cause of mortality in women. In clinical practice and the market, the principal tests used to detect HPV are based on cytology, hybrid detection, and qPCR. However, these methodologies may not be ideal for the required timely diagnosis. Tests have been developed based on isothermal nucleic acid amplification tests (INAATs) as alternatives. These tests offer multiple advantages over the qPCR, such as not requiring specialized laboratories, highly trained personnel, or expensive equipment like thermocyclers. This review analyzes the different INAATs applied for the detection of HPV, considering the specific characteristics of each test, including the HPV genotypes, gene target, the limit of detection (LOD), detection methods, and detection time. Additionally, we discuss the tests available on the market that are approved by the Food and Drug Administration (FDA). Finally, we address the challenges and potential solutions for the large-scale implementation of INAATs, particularly in rural or underserved areas.

Genetic Variants Associated with Suicide Risk in the Mexican Population: A Systematic Literature Review.

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4, SAT-1, TPH-2, ANKK1, GSHR, SCARA50, RGS10, STK33, COMT, and FKBP5. This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.

The role of damage associated molecular pattern molecules (DAMPs) and permeability of the blood-brain barrier in depression and neuroinflammation.

Depression is a heterogeneous mental disorder characterized by feelings of sadness and loss of interest that render the subject unable to handle basic daily activities such as sleeping, eating, or working. Neurobiological traits leading to depression include genetic background, early life abuse, life stressors, and systemic and central inflammatory profiles. Several clinical and preclinical reports documented that depression shows an increase in pro-inflammatory markers such as interleukin (IL-)1ß, IL-6, IL-12, tumor necrosis factor (TNF), and interferon (IFN)-γ; and a decrease in anti-inflammatory IL-4, IL-10, and transforming growth factor (TGF)-ß species. Inflammatory activation may trigger and maintain depression. Dynamic crosstalk between the peripheral immune system and the central nervous system (CNS) such as activated endothelial cells, monocytes, monocyte-derived dendritic cells, macrophages, T cells, and microglia has been proposed as a leading cause of neuroinflammation. Notably, pro-inflammatory cytokines disrupt the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic, noradrenergic, dopaminergic, and glutamatergic neurotransmission. While still under investigation, peripheral cytokines can engage brain pathways and affect the central synthesis of HPA hormones and neurotransmitters through several mechanisms such as activation of the vagus nerve, increasing the permeability of the blood-brain barrier (BBB), altered cytokines transport systems, and engaging toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). However, physiological mechanisms that favor time-dependent central inflammation before or during illness are not totally understood. This review will provide preclinical and clinical evidence of DAMPs and the BBB permeability as contributors to depression and neuroinflammation. We will also discuss pharmacologic approaches that could potentially modulate DAMPs and BBB permeability for future interventions against major depression.

Prevalence of the SNP rs10774671 of the OAS1 gene in Mexico as a possible predisposing factor for RNA virus disease.

The COVID-19 pandemic has revealed the susceptibility of certain populations to RNA virus infection. This variety of agents is currently the cause of severe respiratory diseases (SARS-CoV2 and Influenza), Hepatitis C, measles and of high prevalence tropical diseases that are detected throughout the year (Dengue and Zika). The rs10774671 polymorphism is a base change from G to A in the last nucleotide of intron-5 of the OAS1 gene. This change modifies a splicing site and generates isoforms of the OAS1 protein with a higher molecular weight and a demonstrated lower enzymatic activity. The low activity of these OAS1 isoforms makes the innate immune response against RNA virus infections less efficient, representing a previously unattended risk factor for certain populations. OBJECTIVE: Determine the distribution of rs10774671 in the open population of Mexico. METHODS: In 98 healthy volunteers, allelic and genotypic frequencies were determined by qPCR using allele specific labeled probes, and the Hardy-Weinberg equilibrium was determined. RESULTS: The A-allele turned out to be the most prevalent in the analyzed population. CONCLUSIONS: Our population is genetically susceptible to RNA virus disease due to the predominant presence of the A allele of rs10774671 in the OAS1 gene.

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Identification of a Novel Pathogenic Rearrangement Variant of the APC Gene Associated with a Variable Spectrum of Familial Cancer.

Familial adenomatous polyposis (FAP) is an autosomal-dominant condition characterized by the presence of multiple colorectal adenomas, caused by germline variants in the adenomatous polyposis coli (APC) gene. More than 300 germline variants have been characterized. The detection of novel variants is important to understand the mechanisms of pathophysiology. We identified a novel pathogenic germline variant using next-generation sequencing (NGS) in a proband patient. The variant is a complex rearrangement (c.422+1123_532-577 del ins 423-1933_423-1687 inv) that generates a complete deletion of exon 5 of the APC gene. To study the variant in other family members, we designed an endpoint PCR method followed by Sanger sequencing. The variant was identified in the proband patient's mother, one daughter, her brother, two cousins, a niece, and a second nephew. In patients where the variant was identified, we found atypical clinical symptoms, including mandibular, ovarian, breast, pancreatic, and gastric cancer. Genetic counseling and cancer prevention strategies were provided for the family. According to the American College of Medical Genetics (ACMG) guidelines, this novel variant is considered a PVS1 variant (very strong evidence of pathogenicity), and it can be useful in association with clinical data for early surveillance and suitable treatment.

miRNA signature associated with R-CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma.

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R-CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) profile expression in the retina of spotted gar (Lepisosteus oculatus) and bioinformatics mining.

Olfactomedin-like (OLFML) proteins are members of the olfactomedin domain-containing secreted glycoprotein (OLF) family. OLFML2A and OLFML2B are representative molecules of these glycoproteins. Olfactomedins are critical for the development and functional organization of the nervous system and retina, which is a highly conserved structure in vertebrates, having almost identical anatomical and physiological characteristics in multiple taxa. Spotted gar, a member of the Lepisosteidae family, is a freshwater fish that inhabits rivers, bayous, swamps, and brackish waters. Recently, the complete genome has been sequenced, providing a unique bridge between fish medical models to human biology, making it an excellent animal model. This study was aimed to understanding the evolution OLFML2A and OLFML2B in the retina of spotted gar through looking for the expression of these genes. Spotted gar retina was analyzed with hematoxylin-eosin staining assays to provide an overall view of the retina structure and an immunofluorescence assay to identify OLFML2A and OLFML2B protein expression. A phylogenetic tree was created using the neighbor-joining method. Forces that direct the evolution of the fish genes were tested. Spotted gar retina, as in other vertebrates, is made of several layers. OLFML2A and OLFML2B proteins were detected in the rod and cone photoreceptor layer (PRL), outer nuclear layer (ONL), and inner nuclear layer (INL). Phylogenetic tree analysis confirms the orthology within the OLFML2A gene. Purifying selection is the evolutionary force that directs the OLFML2A genes. OLFML2A genes have a well-conserved function over time and species.

Understanding the HPV integration and its progression to cervical cancer.

Cervical cancer is one of the main causes of female cancer death worldwide, and human papilloma virus (HPV) its causal agent. To investigate viral oncogenesis several studies have focused on the effects of HPV oncoproteins E6 and E7 and the mechanisms by which these proteins stimulate the cellular transformation process. However, phenomena such as the physical state of the viral genome (episomal or integrated) and the effects of this integration on cell proliferation contribute new clues to understand how HPV infection causes carcinogenesis. New molecular technologies are currently facilitating these discoveries. This paper reviews the tumor development process initiated by HPV, recent findings on the process of viral integration into the host genome, new methods to detect HPV integration, and derived associated effects.

[Institutional Biobank as a pillar of medical science]. / El Biobanco Institucional como pilar de las ciencias médicas.

A biobank facility is one of the most valuable means that academic medical organizations have to offer researchers for improving the competitiveness of their medical research. We describe the implementation of our institutional biobank. Our efforts focused on the design and equipment of work areas, staff training, quality control, bioethical and regulatory issues, generating research collaborations and developing funding strategies. We implemented an institutional biobank at the School of Medicine of the Autonomous University of Nuevo León, Mexico. The biobank has supported more than a dozen research protocols with over 3 000 individuals enrolled and almost 6 000 sampled biospecimens stored. The institutional biobank has become an essential bridge and effective catalyst for research synergies between basic and clinical sciences and it is on its way to becoming a National Laboratory.

El Biobanco Institucional como pilar de las ciencias médicas / Institutional Biobank as a pillar of medical science

Resumen: Los biobancos constituyen puentes efectivos entre grupos de investigación básicos y clínicos para generar conocimientos y aplicaciones que eleven su competitividad internacional. Se revisaron las tareas realizadas y los logros alcanzados durante la implementación del Biobanco Institucional de la Universidad Autónoma de Nuevo León (UANL). Se abordó el equipamiento, entrenamiento del personal, aspectos bioéticos y regulatorios, y procesos de laboratorio y de gestión de calidad, entre otros. A partir del apoyo a más de una docena de proyectos de investigación, la inscripción de más de 3 000 individuos y la colecta, procesamiento y almacenamiento de casi 6 000 bioespecímenes, el Biobanco Institucional contribuye de manera importante a la integración de las actividades de asistencia, docencia e investigación básica y clínica del Hospital Universitario y de la Facultad de Medicina de la UANL. Se iniciaron planes para transitar del Biobanco Institucional hacia el Laboratorio Nacional.

Abstract: A biobank facility is one of the most valuable means that academic medical organizations have to offer researchers for improving the competitiveness of their medical research. We describe the implementation of our institutional biobank. Our efforts focused on the design and equipment of work areas, staff training, quality control, bioethical and regulatory issues, generating research collaborations and developing funding strategies. We implemented an institutional biobank at the School of Medicine of the Autonomous University of Nuevo León, Mexico. The biobank has supported more than a dozen research protocols with over 3 000 individuals enrolled and almost 6 000 sampled biospecimens stored. The institutional biobank has become an essential bridge and effective catalyst for research synergies between basic and clinical sciences and it is on its way to becoming a National Laboratory.

Structure and evolution of the gorilla and orangutan growth hormone loci.

In primates, the unigenic growth hormone (GH) locus of prosimians expressed primarily in the anterior pituitary, evolved by gene duplications, independently in New World Monkeys (NWM) and Old World Monkeys (OWMs)/apes, to give complex clusters of genes expressed in the pituitary and placenta. In human and chimpanzee, the GH locus comprises five genes, GH-N being expressed as pituitary GH, whereas GH-V (placental GH) and CSHs (chorionic somatomammotropins) are expressed (in human and probably chimpanzee) in the placenta; the CSHs comprise CSH-A, CSH-B and the aberrant CSH-L (possibly a pseudogene) in human, and CSH-A1, CSH-A2 and CSH-B in chimpanzee. Here, the GH locus in two additional great apes, gorilla (Gorilla gorilla gorilla) and orangutan (Pongo abelii), is shown to contain six and four GH-like genes, respectively. The gorilla locus possesses six potentially expressed genes, gGH-N, gGH-V and four gCSHs, whereas the orangutan locus has just three functional genes, oGH-N, oGH-V and oCSH-B, plus a pseudogene, oCSH-L. Analysis of regulatory sequences, including promoter, enhancer and P-elements, shows significant variation; in particular the proximal Pit-1 element of GH-V genes differs markedly from that of other genes in the cluster. Phylogenetic analysis shows that the initial gene duplication led to distinct GH-like and CSH-like genes and that a second duplication provided separate GH-N and GH-V. However, evolution of the CSH-like genes remains unclear. Rapid adaptive evolution gave rise to the distinct CSHs, after the first duplication, and to GH-V after the second duplication. Analysis of transcriptomic databases derived from gorilla tissues establishes that the gGH-N, gGH-V and several gCSH genes are expressed, but the significance of the many CSH genes in gorilla remains unclear.

Draft Genome Sequence of an Atypical Strain of Streptococcus pneumoniae Serotype 19A Isolated from Cerebrospinal Fluid.

We present here the draft genome sequence of ITALIC! Streptococcus pneumoniaestrain MTY32702340SN814 isolated in Monterrey, Mexico, from a girl with bacterial meningitis. The strain belongs to the atypical and multidrug-resistant serogroup 19A. This is the first report in the literature of sequence type 3936 (ST3936) in ITALIC! S. pneumoniaeserotype 19A.

Complete Genome Sequence of Streptococcus pneumoniae Serotype 19A, a Blood Clinical Isolate from Northeast Mexico.

We report here the draft genome sequence of aStreptococcus pneumoniaestrain isolated in Monterrey, Mexico, MTY1662SN214, from a man with purpura fulminans. The strain belongs to the invasive and multidrug-resistant serogroup 19A, sequence type 320 (ST320). The draft genome sequence consists of 60 large contigs, a total of 2,069,474 bp, and has a G+C content of 39.7%.

Phenotypic and molecular identification of Fonsecaea pedrosoi strains isolated from chromoblastomycosis patients in Mexico and Venezuela.

Chromoblastomycosis is a chronic granulomatous disease caused frequently by fungi of the Fonsecaea genus. The objective of this study was the phenotypic and molecular identification of F. pedrosoi strains isolated from chromoblastomycosis patients in Mexico and Venezuela. Ten strains were included in this study. For phenotypic identification, we used macroscopic and microscopic morphologies, carbohydrate assimilation test, urea hydrolysis, cixcloheximide tolerance, proteolitic activity and the thermotolerance test. The antifungal activity of five drugs was evaluated against the isolates. Molecular identification was performed by sequencing the internal transcribed spacer (ITS) ribosomal DNA regions of the isolated strains. The physiological analysis and morphological features were variable and the precise identification was not possible. All isolates were susceptible to itraconazole, terbinafine, voriconazole and posaconazole. Amphotericin B was the least effective drug. The alignment of the 559-nucleotide ITS sequences from our strains compared with sequences of GenBank revealed high homology with F. pedrosoi (EU285266.1). In this study, all patients were from rural areas, six from Mexico and four from Venezuela. Ten isolates were identified by phenotypic and molecular analysis, using ITS sequence and demonstrated that nine isolates from Mexico and Venezuela were 100% homologous and one isolate showed a small genetic distance.

Complete genome sequence of Nocardia brasiliensis HUJEG-1.

In Mexico, actinomycetoma is mainly caused by Nocardia brasiliensis, which is a soil inhabitant actinobacterium. Here, we report for the first time the draft genome of a strain isolated from a human case that has largely been found in in vitro and experimental models of actinomycetoma, N. brasiliensis HUJEG-1.