ABSTRACT
Diagnosis of developmental dysplasia of the hip (DDH) mostly relies on physical examination and ultrasound, and both methods are operator-dependent. Late detection can lead to complications in young adults. Current evidence supports the involvement of environmental and genetic factors, such as single nucleotide variants (SNVs). Incorporating genetic factors into diagnostic methods would be useful for implementing early detection and management of affected individuals. Our aim was to analyze environmental factors and SNVs in DDH patients. We included 287 DDH cases and 284 controls. Logistic regression demonstrated an association for sex (OR 9.85, 95% CI 5.55-17.46, p = 0.0001), family history (OR 2.4, 95% CI 1.2-4.5, p = 0.006), fetal presentation (OR 3.19, 95% CI 1.55-6.54, p = 0.002), and oligohydramnios (OR 2.74, 95%CI 1.12-6.70, p = 0.026). A model predicting the risk of DDH including these variables showed sensitivity, specificity, PPV, and NPV of 0.91, 0.53, 0.74, and 0.80 respectively. The SNV rs1800470 in TGFB1 showed an association when adjusted for covariables, OR 0.49 (95% CI 0.27-0.90), p = 0.02. When rs1800470 was included in the equation, sensitivity, specificity, PPV and NPV were 0.90, 0.61, 0.84, and 0.73, respectively. Incorporating no-operator dependent variables and SNVs in detection methods could be useful for establishing uniform clinical guidelines and optimizing health resources.
ABSTRACT
Triple negative breast cancer (TNBC) is an aggressive type of cancer that accounts for ~23% of breast tumors in Mexico. In an attempt to understand in an improved way the behavior of TNBC, throughout the years, gene expression in these tumors has been studied. Lehman et al identified 6 subtypes of gene expression in TNBC with distinct characteristics. In the present study, it was aimed to assess clinical, pathological and prognostic characteristics of TNBC in a Mexican-based cohort. A total of 55 patients diagnosed with TNBC at Mexico's National Institute of Cancer (INCan) were included. Tumor needle biopsy samples were obtained and subjected to microarray analysis. Patients were thus classified into one of the 6 TNBC molecular subtypes. The prognostic, clinical and pathological information of patients was obtained, and differences across molecular subtypes were sought. Out of the 55 included patients, the following subtypes were identified: 9 basal-like-1, 11 basal-like-2 (BSL2), 16 immunomodulatory (IM), 12 mesenchymal, 6 androgen receptor-like and 1 mesenchymal stem-like. Mean follow-up time was 47.1 months. The IM molecular subtype had the best overall survival (OS) (median OS was not reached). BSL2 had the worst OS (15 months). A complete pathologic response to neoadjuvant chemotherapy was obtained more often in the IM subtype (P=0.032). No significant associations were found between any of the clinical or pathological characteristics and the TNBC molecular subtypes. The results obtained from the present study should be considered when seeking to implement a clinical-molecular model for TNBC patient care, particularly in Hispanic-based populations, as they have been frequently underrepresented in clinical studies assessing TNBC molecular subtypes.
ABSTRACT
Research on the microbiome has drawn an increasing amount of attention over the past decade. Even more so for its association with disease. Neurodegenerative diseases, such as Alzheimer's disease (AD) have been a subject of study for a long time with slow success in improving diagnostic accuracy or identifying a possibility for treatment. In this work, we analyze past and current research on microbiome and its positive impact on AD treatment and diagnosis. We present a bibliometric analysis from 2012 to 2021 with data retrieved on September 2, 2021, from the Scopus database. The query includes "Gut AND (Microbiota OR Microbiome) AND Alzheimer*" within the article title, abstract, and keywords for all kinds of documents in the database. Compared with 2016, the number of publications (NPs) on the subject doubled by 2017. Moreover, we observe an exponential growth through 2020, and with the data presented, it is almost certain that it will continue this trend and grow even further in the upcoming years. We identify key journals interested in the subject and discuss the articles with most citations, analyzing trends and topics for future research, such as the ability to diagnose the disease and complement the cognitive test with other clinical biomarkers. According to the test, mild cognitive impairment (MCI) is normally considered an initial stage for AD. This test, combined with the role of the gut microbiome in early stages of the disease, may improve the diagnostic accuracy. Based on our findings, there is emerging evidence that microbiota, perhaps more specifically gut microbiota, plays a key role in the pathogenesis of diseases, such as AD.
ABSTRACT
No genetic basis is currently established that differentiates hypermobility spectrum disorders (HSD) from hypermobile Ehlers-Danlos syndrome (hEDS). Diagnosis is entirely based on clinical parameters with high overlap, leading to frequent misdiagnosis of these two phenotypes. This study presents a landscape of DNA mutations through whole-exome sequencing of patients clinically diagnosed with generalized HSD. In this study, three genes (MUC3A, RHBG, and ZNF717) were mutated in all five patients evaluated. The functional enrichment analysis on all 1162 mutated genes identified the extracellular matrix (ECM) structural constituent as the primary overrepresented molecular function. Ingenuity pathway analysis identified relevant bio-functions, such as the organization of ECM and hereditary connective tissue disorders. A comparison with the matrisome revealed 55 genes and highlighted MUC16 and FREM2. We also contrasted the list of mutated genes with those from a transcriptomic analysis on data from Gene Expression Omnibus, with only 0.5% of the genes at the intersection of both approaches supporting the hypothesis of two different diseases that inevitably share a common genetic background but are not the same. Potential biomarkers for HSD include the five genes presented. We conclude the study by describing five potential biomarkers and by highlighting the importance of genetic/genomic approaches that, combined with clinical data, may result in an accurate diagnosis and better treatment.
Subject(s)
Connective Tissue Diseases , Ehlers-Danlos Syndrome , Joint Instability , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/genetics , Genomics , Humans , Joint Instability/genetics , Membrane Transport Proteins/genetics , Exome SequencingABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.
Subject(s)
Idiopathic Pulmonary Fibrosis , MicroRNAs , Epithelial-Mesenchymal Transition/genetics , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Myofibroblasts/metabolism , Signal TransductionABSTRACT
In 2015, emergent cases of localized cutaneous leishmaniasis (LCL) were reported in Tinum, Yucatan, Mexico. As part of an eco-epidemiological study to characterize the elements that trigger Leishmania infection in that area, we conducted a field study to investigate the occurrence of Leishmania infection in wild rodents. From November 2019 to February 2020, rodents were caught from three sites located in the municipality of Tinum, Yucatan. For each specimen, clinical signs suggestive of Leishmania infection were recorded. Samples from the tail, liver, and spleen were taken for the identification of Leishmania DNA by PCR. Twenty rodents belonging to two species were caught including Heteromys gaumeri (55%, 11/20) and Ototylomys phyllotis (45%, 9/20). Fifty-five percent of the animals presented white spots on the tail, 15% had splenomegaly, and 5% had hepatomegaly. Fifty-five percent (11/20) of the animals were found infected by Leishmania. Heteromys gaumeri was caught in all trapping sites and was the most infected species (63.6%, 7/11). The percentage of infection for O. phyllotis was 44.4% (4/9). Leishmania (Leishmania) mexicana was identified as the infecting species in two H. gaumeri. This study provides, for the first time, evidence of Leishmania infection in wild rodents from the Yucatan state. Heteromys gaumeri and O. phyllotis may be involved in the transmission cycle of L. mexicana in this emergent focus; however, further longitudinal studies are needed to confirm their role as primary reservoirs.
ABSTRACT
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Seven subtypes have been described based on gene expression patterns. Herein, we characterized the tumor biology and clinical behavior of the immunomodulatory (IM) subtype. METHODS: Formalin-fixed paraffin-embedded tumor samples from 68 high-risk (stage III-IV) TNBC patients were analyzed through microarrays, immunohistochemistry, and DNA sequencing. RESULTS: The IM subtype was identified in 24% of TNBC tumor samples and characterized by a higher intratumoral (intT) and stromal (strml) infiltration of FOXP3+ TILs (Treg) compared with non-IM subtypes. Further, PD-L1+ (>1%) expression was significantly higher, as well as CTLA-4+ intT and strml expression in the IM subtype. Differential expression and gene set enrichment analysis identified biological processes associated with the immune system. Pathway analysis revealed enrichment of the ß-catenin signaling pathway. The non-coding analysis led to seven Long Intergenic Non-Protein Coding RNAs (lincRNAs) (6 up-regulated and 1 down-regulated) that were associated with a favorable prognosis in the TNBC-IM subtype. The DNA sequencing highlighted two genes relevant to immune system responses: CTNNB1 (Catenin ß-1) and IDH1. CONCLUSION: the IM subtype showed a distinct immune microenvironment, as well as subtype-specific genomic alterations. Characterizing TNBC at a molecular and transcriptomic level might guide immune-based therapy in this subgroup of patients.
ABSTRACT
Deer encompass a group of large-sized vertebrates that serve as hosts for a wide variety of ectoparasites, mainly ticks. In Mexico, ticks have relevance as vectors of pathogenic microorganisms, and 20 species of hard ticks are associated with four species of deer, although only a single study has been conducted to detect bacterial agents associated with ticks from deer in the country. In February, 2019 three white-tailed deers (Odocoileus virginianus) were hunted from the locality of Chiná from the municipality of Campeche, Mexico. The sampled deers were parasitized by 26 ticks belonged to three species: Amblyomma mixtum (5â, 1â), Amblyomma ovale (2â, 1â), and Ixodes sp. cf. Ixodes affinis (15â, 2â). Specimens were screened individually for Anaplasma, Borrelia, Ehrlichia, and Rickettsia DNA by the amplification of several fragments of 16S rRNA, gltA, 17-kDa, and flaB genes. This study report for the first time the presence of Rickettsia sp. cf. Rickettsia monacensis in Ixodes sp. cf. Ixodes affinis in Mexico.
Subject(s)
Deer/parasitology , Ixodes/microbiology , Rickettsia/isolation & purification , Anaplasma/isolation & purification , Animals , Borrelia/isolation & purification , Ehrlichia/isolation & purification , Female , Male , Mexico , RNA, Bacterial , RNA, Ribosomal, 16SABSTRACT
Calcitriol and transforming growth factors beta (TGF-ß) are involved in several biological pathways such as cell proliferation, differentiation, migration and invasion. Their cellular effects could be similar or opposite depending on the genetic target, cell type and context. Despite the reported association of calcitriol deficiency and disruption of the TGF-ß pathway in prostate cancer and the well-known independent effects of calcitriol and TGF-ßs on cancer cells, there is limited information regarding the cellular effects of calcitriol and TGF-ß in combination. In this study, we in vitro analyze the combinatory effects of calcitriol and TGF-ß on cell growth and apoptosis using PC-3 and DU145 human prostate cancer cell lines. Using high-throughput microarray profiling of PC-3 cells upon independent and combinatory treatments, we identified distinct transcriptional landscapes of each intervention, with a higher effect established by the combinatorial treatment, following by TGF-ß1 and later by calcitriol. A set of genes and enriched pathways converge among the treatments, mainly between the combinatory scheme and TGF-ß1, but the majority were treatment-specific. Of note, CYP24A1, IGFBP3, CDKN1A, NOX4 and UBE2D3 were significantly up-regulated upon the combinatorial treatment whereas CCNA1, members of the CT45A and APOBEC3 family were down-regulated. By public RNA signatures, we were able to confirm the regulation by the co-treatment over cell proliferation and cell cycle. We finally investigated the possible clinical impact of genes modulated by the combinatorial treatment using benchmark prostate cancer data. This comprehensive analysis reveals that the combinatory treatment impairs cell growth without affecting apoptosis and their combinatory actions might synergize and improved their individual effects to reprogram prostate cancer signaling.
Subject(s)
Antineoplastic Agents/pharmacology , Calcitriol/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Prostatic Neoplasms/drug therapy , Transforming Growth Factor beta1/pharmacology , Transforming Growth Factor beta2/pharmacology , Vitamins/pharmacology , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Calcitriol/analogs & derivatives , Cell Movement , Cell Proliferation , Drug Therapy, Combination , Gene Expression Profiling , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathologyABSTRACT
OBJECTIVE: Human mesenchymal stem cells (hMSCs) are a promising source for regenerative medicine, especially mesodermal lineages. Clinical applications require an understanding of the mechanisms for transcriptional control to maintain the desired cell type. The aim of this study was to identify novel markers for differentiation of hMSCs into bone or cartilage with the use of Kartogenin, by RNA analysis using microarray technology, and explore the role of RhoA-Rho associated protein kinase (ROCK) inhibition in these. METHODS: Commercial human bone marrow derived primary mesenchymal stem cells were purchased from ATCC. Cells were differentiated in vitro in 2-dimensional cultures using Kartogenin as the main cartilage inducer and bone morphogenetic protein 2 for bone differentiation; cells were cultured with and without ROCK inhibitor Y-27632. After 21 days of culture, whole RNA was extracted and analyzed via Affimetrix microarrays. The most significant hits were validated by quantitative polymerase chain reaction. RESULTS: We found a total of 1,757 genes that were either up- or downregulated on differentiation, when compared to P1 hMSC (control) at day 0 of differentiation. Two members of the Serpin superfamily, SERPINA9 and SERPINB2, were significantly upregulated in the cartilage groups, whereas they were unchanged in the bone groups with and without ROCK inhibition. CONCLUSIONS: SERPINA9 and SERPINB2 are novel differentiation markers, and molecular regulator candidates for hMSC lineage commitment toward bone and cartilage, providing a new tool for regenerative medicine. Our study highlights the roles of these 2 genes, with significant upregulation of both in cell cultures stimulated with Kartogenin.
Subject(s)
Antigens, Differentiation/genetics , Cartilage/cytology , Cell Lineage/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mesenchymal Stem Cells/cytology , Neoplasm Proteins/metabolism , Serpins/metabolism , Anilides , Bone Morphogenetic Protein 2 , Cell Differentiation/genetics , Cells, Cultured , Humans , Phthalic Acids , RNA/isolation & purification , Up-Regulation/geneticsABSTRACT
Bovine tuberculosis (bTB) caused by Mycobacterium bovis has a significant economic impact worldwide each year. Control of bTB is based on skin testing and removal of reactors. However, additional strategies are required to control this disorder. Natural disease resistance has been defined as the inherent capacity of an individual to resist disease when exposed to pathogens without previous exposure or immunization. However, little is known about natural disease resistance against Mycobacterium bovis in cattle. In this study, we aimed to identify candidate biomarkers to detect host resistance to M. bovis. We used a microbicidal assay to identify the resistance phenotype. A genomic microarray analysis was carried out on RNA from 2 resistant (R) and 2 susceptible (S) cows. Our results evidenced 69 differentially expressed genes. A subset of six genes that showed differential up (IL1RN), and down-regulation (VNN, GATM, ARHGEF11, NAAA and HSPA2) were selected for further analysis. To further validate the candidate biomarkers, we identified the R phenotype in 31 cattle (9 R and 22â¯S). Macrophage mRNA was isolated from this group of cattle. Expression of candidate biomarkers was evaluated by qPCR 2-ΔCt and ROC curves to determine their diagnostic potential. Candidates IL1RN and ARHGEF11 discriminates between R and S cattle. Furthermore, combination of candidates ARHGEF11: VNN: HSPA2 discriminate between R from S with AUC 0.7993 and agreement index of 0.853 (pâ¯≤â¯0.01). Our data suggest that candidate biomarkers may support the preliminary screening to identify natural resistance in herds against Mycobacterium bovis in Holstein-Friesian cattle.
Subject(s)
Biomarkers/metabolism , Mycobacterium bovis/immunology , Tuberculosis, Bovine/immunology , Animals , Cattle , Female , Genomics , Immunity, Innate , Male , Microarray Analysis/veterinary , Tuberculosis, Bovine/microbiologyABSTRACT
Myiasis represents a group of neglected tropical diseases caused by the infestation of vertebrate tissues by dipterous larvae. We herein report an imported case of foruncular myasis caused by Dermatobia hominis in Mexico City. The species was confirmed by DNA sequencing and phylogenetic reconstruction analysis.
Subject(s)
Diptera/genetics , Diptera/parasitology , Larva , Myiasis/diagnosis , Skin Diseases, Parasitic/diagnosis , Actinobacteria , Adult , Animals , Humans , Mexico , Phylogeny , Sequence Analysis, DNA , TravelABSTRACT
Leishmania protozoa are the etiological agents of visceral, cutaneous and mucocutaneous leishmaniasis. In specific geographical regions, such as Latin America, several Leishmania species are endemic and simultaneously present; therefore, a diagnostic method for species discrimination is warranted. In this attempt, many qPCR-based assays have been developed. Recently, we have shown that L. (L.) infantum and L. (L.) amazonensis can be distinguished through the comparison of the Cq values from two qPCR assays (qPCR-ML and qPCR-ama), designed to amplify kDNA minicircle subclasses more represented in L. (L.) infantum and L. (L.) amazonensis, respectively. This paper describes the application of this approach to L. (L.) mexicana and introduces a new qPCR-ITS1 assay followed by high-resolution melt (HRM) analysis to differentiate this species from L. (L.) amazonensis. We show that L. (L.) mexicana can be distinguished from L. (L.) infantum using the same approach we had previously validated for L. (L.) amazonensis. Moreover, it was also possible to reliably discriminate L. (L.) mexicana from L. (L.) amazonensis by using qPCR-ITS1 followed by an HRM analysis. Therefore, a diagnostic algorithm based on sequential qPCR assays coupled with HRM analysis was established to identify/differentiate L. (L.) infantum, L. (L.) amazonensis, L. (L.) mexicana and Viannia subgenus. These findings update and extend previous data published by our research group, providing an additional diagnostic tool in endemic areas with co-existing species.
ABSTRACT
Haemaphysalis leporispalustris is a hard tick species that have been recorded mainly parasitizing rabbits and birds across the Nearctic and Neotropical regions. Particularly in Mexico, most of the records come from historical collection journeys from before the 1960s. In this paper, we bring new geographical records for this species in Mexico to provide the first genetic data in the country through the amplification of the 16S, COI, and 18S genes, and the detection of a rickettsial agent as well.
Subject(s)
Ixodidae/parasitology , Rickettsia/isolation & purification , Animals , Female , Gene Amplification , Ixodidae/genetics , Male , Mexico , RabbitsABSTRACT
Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers. In this study, the gene expression of human sperm subpopulations with high (F1) and low (F2) motility from healthy normozoospermic (N) and asthenozoospermic (A) individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed genes. Results from A-F1 versus N-F1, A-F2 versus N-F2, N-F1 versus N-F2, and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus controls. Gene ontology (GO) analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes (BPs), several of which are associated with sperm physiology. In addition, gene set enrichment analysis of the same contrast showed 110 BPs, 36 cellular components, and 31 molecular functions, several of which are involved in sperm motility. A leading-edge analysis of selected GO terms resulted in several downregulated genes encoding to dyneins and kinesins, both related to sperm physiology. Furthermore, the predicted activation state of asthenozoospermia was increased, while fertility, cell movement of sperm, and gametogenesis were decreased. Interestingly, several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia activation. Conversely, GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs, although the gene set enrichment analysis detected six enriched BPs, one cellular component, and two molecular functions. Overall, the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.
Subject(s)
Asthenozoospermia/genetics , Spermatozoa/metabolism , Asthenozoospermia/metabolism , Case-Control Studies , Gene Expression Profiling , Humans , Male , Oligonucleotide Array Sequence Analysis , RNA/genetics , RNA/metabolism , Real-Time Polymerase Chain Reaction , Spermatozoa/physiologyABSTRACT
Helicobacter pylori is associated with the development of several lesions in the human stomach. This chronic infection produces gastritis, which can progress to intestinal metaplasia and gastric cancer. To date, there is very little information regarding gene-expression in the different phases of progression caused by chronic H. pylori infection. In this study, we performed a genome-wide gene-expression analysis in gastric biopsies of patients chronically infected with H. pylori, using the potential of high-throughput technologies that have not been fully exploited in this area. Here we illustrate the potential correlation of H. pylori infection with the gene expression changes in follicular gastritis, chronic gastritis and intestinal metaplasia. We also suggest its potential as biomarkers of each condition. An exploratory set of 21 biopsies from patients with follicular gastritis, chronic gastritis, and intestinal metaplasia were analyzed by gene-expression microarrays in order to identify the biological processes altered in each lesion. The microarray data was corroborated by real-time PCR, while 79 Formalin-Fixed Paraffin-Embeded samples were analyzed by immunohistochemistry. Follicular gastritis exhibited significant enrichment in genes associated with glutamate signaling, while chronic gastritis showed a down-regulation in metallothionein 1 and 2 and in oxidative phosphorylation-related genes, which could be associated with the chronic infecton of H. pylori. Intestinal metaplasia exhibited an over-expression of gastrointestinal stem cell markers, such as LGR5 and PROM1, as well as messenger RNA and nucleic acid metabolism-related genes. The gene-expression patterns found in this study provide new comparative information about chronic gastritis, follicular gastritis and intestinal metaplasia that may play an important role in the development of gastric cancer.
ABSTRACT
BACKGROUND: The treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified. METHODS: Blood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment. RESULTS: We observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals. CONCLUSIONS: Changes in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment.
Subject(s)
Gene Expression , Interleukin-2 Receptor alpha Subunit/genetics , Latent Tuberculosis/genetics , Latent Tuberculosis/microbiology , Ubiquitin Thiolesterase/genetics , Adult , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Biomarkers , Female , Humans , Interferon-gamma Release Tests , Interleukin-2 Receptor alpha Subunit/metabolism , Isoniazid/pharmacology , Isoniazid/therapeutic use , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Tuberculin Test , Ubiquitin Thiolesterase/metabolism , Young AdultABSTRACT
Abstract Free-ranging and feral dogs represent a group of unattended companion animals. They impact wild animal populations by predating native species, displacing predators and introducing exotic pathogens. The aim of this work was to describe the molecular occurrence of Rickettsia, Ehrlichia, Anaplasma, Mycoplasma and Bartonella in feral dogs. The study was carried out in the last relict of a protected area in Mexico City. Blood clots samples from 19 dogs were obtained and analyzed for detection of specific fragments of the 16S-rRNA gene for Anaplasma, Ehrlichia and Mycoplasma and citrate synthase (gltA) for Bartonella and Rickettsia. Our results showed that DNA from three bacteria species (Bartonella vinsonii subsp. berkhoffii, Ehrlichia canis and Mycoplasma haemocanis) was present with frequencies ranging from 5.3 to 15.8%. This is the first record of B. vinsonii subsp. berkhoffii and M. haemocanis in dogs from México, and also the first finding of Ehrlichia canis in Mexico City. It is important to perform surveillance of feral dog populations in order to identify the impact of these pathogens on wild animal populations and Public Health in order to establish prevention and protection programs.
Resumo Cães errantes e selvagens representam um grupo de animais de companhia livres. Eles impactam as populações de animais selvagens pela predação de espécies nativas, deslocando predadores e introduzindo patógenos exóticos. O objetivo deste trabalho foi descrever a ocorrência molecular de Rickettsia, Ehrlichia, Anaplasma, Mycoplasma e Bartonella em cães selvagens. O estudo foi realizado no último ecossistema de uma área protegida na Cidade do México. Amostras de coágulos sanguíneos de 19 cães foram obtidas e analisadas para detecção de fragmentos específicos do gene 16S-rRNA para Anaplasma, Ehrlichia e Mycoplasma e citrato sintase (gltA) para Bartonella e Rickettsia. Nossos resultados mostraram que o DNA de três espécies de bactérias (Bartonella vinsonii subsp. berkhoffii, Ehrlichia canis e Mycoplasma haemocanis) estava presente com frequências variando de 5,3 a 15,8%. Este é o primeiro registro de B. vinsonii subsp. berkhoffii e M. haemocanis em cães do México, e também a primeira descrição de Ehrlichia canis na Cidade do México. É importante realizar a vigilância das populações de cães selvagens para identificar o impacto desses patógenos nas populações de animais silvestres e na Saúde Pública, a fim de estabelecer programas de prevenção e proteção.
Subject(s)
Animals , Male , Female , Dogs , Rickettsia/isolation & purification , Bartonella/isolation & purification , Gram-Negative Bacterial Infections/veterinary , Dog Diseases/microbiology , Ehrlichia/isolation & purification , Anaplasma/isolation & purification , Mycoplasma/isolation & purification , Phylogeny , Rickettsia/genetics , Bartonella/genetics , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/epidemiology , Dog Diseases/epidemiology , Ehrlichia/genetics , Anaplasma/genetics , Animals, Wild , Mexico/epidemiology , Mycoplasma/geneticsABSTRACT
We found Rickettsia parkeri in Amblyomma ovale ticks collected in Veracruz, Mexico, in 2018. We sequenced gene segments of gltA, htrA, sca0, and sca5; phylogenetic reconstruction revealed near-complete identity with R. parkeri strain Atlantic Rainforest. Enhanced surveillance is needed in Mexico to determine the public health relevance of this bacterium.