Prolonged survival of venereal Tritrichomonas foetus parasite in the gastrointestinal tract, bovine fecal extract, and water.

IMPORTANCE: Nowadays, the routine herd diagnosis is usually performed exclusively on bulls, as they remain permanently infected, and prevention and control of Tritrichomonas foetus transmission are based on identifying infected animals and culling practices. The existence of other forms of transmission and the possible role of pseudocysts or cyst-like structures as resistant forms requires rethinking the current management and control of this parasitic disease in the future in some livestock regions of the world.

Role of cytoneme structures and extracellular vesicles in Trichomonas vaginalis parasite-parasite communication.

Trichomonas vaginalis, the etiologic agent of the most common non-viral sexually transmitted infection worldwide. With an estimated annual prevalence of 276 million new cases, mixed infections with different parasite strains are expected. Although it is known that parasites interact with their host to enhance their own survival and transmission, evidence of mixed infections call into question the extent to which unicellular parasites communicate with each other. Here, we demonstrated that different T. vaginalis strains can communicate through the formation of cytoneme-like membranous cell connections. We showed that cytonemes formation of an adherent parasite strain (CDC1132) is affected in the presence of a different strain (G3 or B7RC2). Our findings provide evidence that this effect is contact-independent and that extracellular vesicles (EVs) are responsible, at least in part, of the communication among strains. We found that EVs isolated from G3, B7RC2, and CDC1132 strains contain a highly distinct repertoire of proteins, some of them involved in signaling and communication, among other functions. Finally, we showed that parasite adherence to host cells is affected by communication between strains as binding of adherent T. vaginalis CDC1132 strain to prostate cells is significantly higher in the presence of G3 or B7RC2 strains. We also observed that a poorly adherent parasite strain (G3) adheres more strongly to prostate cells in the presence of an adherent strain. The study of signaling, sensing, and cell communication in parasitic organisms will enhance our understanding of the basic biological characteristics of parasites, which may have important consequences in pathogenesis.

Extracellular vesicle-localized miR-203 mediates neural crest-placode communication required for trigeminal ganglia formation.

While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, we show that the microRNA-(miR)203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. Reciprocally, loss of miR-203 function in placode, but not neural crest, cells perturbs trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses a miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.

Tritrichomonas foetus Cell Division Involves DNA Endoreplication and Multiple Fissions.

Tritrichomonas foetus and Trichomonas vaginalis are extracellular flagellated parasites that inhabit animals and humans, respectively. Cell division is a crucial process in most living organisms that leads to the formation of 2 daughter cells from a single mother cell. It has been assumed that T. vaginalis and T. foetus modes of reproduction are exclusively by binary fission. However, here, we showed that multinuclearity is a phenomenon regularly observed in different T. foetus and T. vaginalis strains in standard culture conditions. Additionally, we revealed that nutritional depletion or nutritional deprivation led to different dormant phenotypes. Although multinucleated T. foetus are mostly observed during nutritional depletion, numerous cells with 1 larger nucleus have been observed under nutritional deprivation conditions. In both cases, when the standard culture media conditions are restored, the cytoplasm of these multinucleated cells separates, and numerous parasites are generated in a short period of time by the fission multiple. We also revealed that DNA endoreplication occurs both in large and multiple nuclei of parasites under nutritional deprivation and depletion conditions, suggesting an important function in stress nutritional situations. These results provide valuable data about the cell division process of these extracellular parasites. IMPORTANCE Nowadays, it's known that T. foetus and T. vaginalis generate daughter cells by binary fission. Here, we report that both parasites are also capable of dividing by multiple fission under stress conditions. We also demonstrated, for the first time, that T. foetus can increase its DNA content per parasite without concluding the cytokinesis process (endoreplication) under stress conditions, which represents an efficient strategy for subsequent fast multiplication when the context becomes favorable. Additionally, we revealed the existence of novel dormant forms of resistance (multinucleated or mononucleated polyploid parasites), different than the previously described pseudocysts, that are formed under stress conditions. Thus, it is necessary to evaluate the role of these structures in the parasites' transmission in the future.

Physical activity and sitting time in adults after positive diagnosis for COVID-19: a cross-sectional study / Atividade física e tempo sentado em adultos após diagnóstico positivo para COVID-19: um estudo transversal

This study aimed to: a) investigate the most common signs and symptoms reported by people infect-ed by the COVID-19, b) compare total time and weekly level of physical activity of people between pre- and post-infection period, and c) examine the association between physical activity levels and signs and symptoms reported during the disease cycle. Twenty-two adult people (14 males and 8 females, mean age 37.9 ± 16.8 years) living in Ribeirão Preto, Brazil participated in this study. Par-ticipants received a positive diagnosis for COVID-19 by PCR. Physical activity and sitting time was assessed using the International Physical Activity Questionnaire. Variables such as body mass index and the clinical condition of the disease (signs and symptoms) were collected. The most frequent signs and symptoms reported by active and inactive individuals, respectively, were loss of taste (77.8% and 25%), headache (66.7% and 25%), coughing (66.7% and 25%), difficulty breathing (61.1% and 25%), and sore throat (61.1% and 75%). A 120-minute reduction (p = 0.010) in the total time of weekly physical activity and a 155-minute reduction (p = 0.003) of weekly moderate physical activity was observed in the pre- and post-diagnostic COVID-19 infection comparison. There was further an association between difficulty breathing and being physically inactive (odds ratio = 0.222; 95%CI: 0.094 ­ 0.527). Our findings suggest that COVID-19 had a negative impact on physical activity and that being physically active may reduce the likelihood of presenting with difficulty breathing if infected with the SARS-CoV-2 and associated disease COVID-19

Este estudo teve como objetivo: a) investigar os sinais e sintomas mais comuns relatados por pessoas infectadas por COVID-19, b) comparar o tempo total e o nível semanal de atividade física das pessoas no período pré e pós-infecção, c) examinar a associação entre os níveis de atividade física e os sinais e sintomas relatados du-rante o ciclo da doença. Participaram deste estudo 22 pessoas (14 do sexo masculino e oito do feminino, idade média 37,9 ± 16,8 anos) residentes na cidade de Ribeirão Preto, Brasil. Todos receberam diagnóstico positivo para COVID-19 via PCR. A atividade física e o tempo sentado foram avaliados por meio do Questionário Internacional de Atividade Física. Variáveis como índice de massa corporal e o quadro clínico da doença (sinais e sintomas), foram coletadas. Os sinais e sintomas mais frequentes foram perda do paladar (77,8% e 25%), dor de cabeça (66,7% e 25%), tosse (66,7% e 25%), dificuldade para respirar (61,1% e 25%) e dor gar-ganta (61,1% e 75%), para indivíduos ativos e inativos, respectivamente. Uma redução de 120 minutos (p = 0,010) no tempo total de atividade física semanal e de 155 minutos (p = 0,003) de atividade física moderada semanal foi observada na comparação pré e pós-diagnóstico por COVID-19. Houve associação entre dificul-dade para respirar e ser fisicamente inativo (odds ratio = 0,222; IC95%: 0,094 ­ 0,527). Nossos resultados sugerem que a COVID-19 teve impacto negativo na atividade física e que pessoas fisicamente ativas podem reduzir a probabilidade de apresentar dificuldade para respirar quando diagnosticadas por COVID-19

Ultrastructural and Functional Analysis of a Novel Extra-Axonemal Structure in Parasitic Trichomonads.

Trichomonas vaginalis and Tritrichomonas foetus are extracellular flagellated parasites that inhabit humans and other mammals, respectively. In addition to motility, flagella act in a variety of biological processes in different cell types, and extra-axonemal structures (EASs) have been described as fibrillar structures that provide mechanical support and act as metabolic, homeostatic, and sensory platforms in many organisms. It has been assumed that T. vaginalis and T. foetus do not have EASs. However, here, we used complementary electron microscopy techniques to reveal the ultrastructure of EASs in both parasites. Such EASs are thin filaments (3-5 nm diameter) running longitudinally along the axonemes and surrounded by the flagellar membrane, forming prominent flagellar swellings. We observed that the formation of EAS increases after parasite adhesion on the host cells, fibronectin, and precationized surfaces. A high number of rosettes, clusters of intramembrane particles that have been proposed as sensorial structures, and microvesicles protruding from the membrane were observed in the EASs. Our observations demonstrate that T. vaginalis and T. foetus can connect to themselves by EASs present in flagella. The protein VPS32, a member of the ESCRT-III complex crucial for diverse membrane remodeling events, the pinching off and release of microvesicles, was found in the surface as well as in microvesicles protruding from EASs. Moreover, we demonstrated that the formation of EAS also increases in parasites overexpressing VPS32 and that T. vaginalis-VPS32 parasites showed greater motility in semisolid agar. These results provide valuable data about the role of the flagellar EASs in the cell-to-cell communication and pathogenesis of these extracellular parasites.

VPS32, a member of the ESCRT complex, modulates adherence to host cells in the parasite Trichomonas vaginalis by affecting biogenesis and cargo sorting of released extracellular vesicles.

Trichomonas vaginalis is a common sexually transmitted extracellular parasite that adheres to epithelial cells in the human urogenital tract. Extracellular vesicles (EVs) have been described as important players in the pathogenesis of this parasite as they deliver proteins and RNA into host cells and modulate parasite adherence. EVs are heterogeneous membrane vesicles released from virtually all cell types that collectively represent a new dimension of intercellular communication. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery contributes to several key mechanisms in which it reshapes membranes. Based on this, some components of the ESCRT have been implicated in EVs biogenesis in other cells. Here, we demonstrated that VPS32, a member of ESCRTIII complex, contribute to the biogenesis and cargo sorting of extracellular vesicles in the parasite T. vaginalis. Moreover, we observe that parasites overexpressing VPS32 have a striking increase in adherence to host cells compared to control parasites; demonstrating a key role for this protein in mediating host: parasite interactions. These results provide valuable information on the molecular mechanisms involved in extracellular vesicles biogenesis, cargo-sorting, and parasite pathogenesis.

Unveiling the role of EVs in anaerobic parasitic protozoa.

The anaerobic or microaerophilic protozoan parasites such as the enteric human pathogens Entamoeba histolytica, Giardia intestinalis, Cryptosporidium parvum, Blastocystis hominis and urogenital tract parasites Trichomonas vaginalis are able to survival in an environment with oxygen deprivation. Despite living in hostile environments these pathogens adopted different strategies to survive within the hosts. Among them, the release of extracellular vesicles (EVs) has become an active endeavor in the study of pathogenesis for these parasites. EVs are heterogenous, membrane-limited structures that have played important roles in cellular communication, transferring information through cargo and modulating the immune system of the host. In this review, we described several aspects of the recently characterized EVs of the anaerobic protozoa, including their role in adhesion, modulation of the immune response and omics analysis to understand the potential of these EVs in the pathogenesis of these diseases caused by anaerobic parasites.

Toward incorporating epigenetics into regulation of gene expression in the parasite Trichomonas vaginalis.

Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract, causing a highly prevalent sexually transmitted infection. The parasite must change its transcriptional profile in order to establish and maintain infection. However, few core regulatory elements and transcription factors have been identified to date and little is known about other mechanisms that may control these rapid changes in gene expression during parasite infection. In the last years, epigenetic mechanisms involved in the regulation of gene expression have been gaining major attention in this parasite. In this review, we summarize and discuss the major advances of the last few years with regard to epigenetics (DNA methylation, post-translational histone modifications, and histone variants) in the parasite T. vaginalis. These studies can shed light into our current understanding of this parasite's biology with far-reaching implications for the prognosis and treatment of trichomoniasis.

Extracellular vesicles released by anaerobic protozoan parasites: Current situation.

Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism for transferring information between cells and organisms across all three kingdoms of life. Parasitic unicellular eukaryotes use EVs as vehicles for intercellular communication and host manipulation. Pathogenic protozoans are able to modulate the immune system of the host and establish infection by transferring a wide range of molecules contained in different types of EVs. In addition to effects on the host, EVs are able to transfer virulence factors, drug-resistance genes and differentiation factors between parasites. In this review we cover the current knowledge on EVs from anaerobic or microaerophilic extracellular protozoan parasites, including Trichomonas vaginalis, Tritrichomonas foetus, Giardia intestinalis and Entamoeba histolytica, with a focus on their potential role in the process of infection. The role of EVs in host: parasite communication adds a new level of complexity to our understanding of parasite biology, and may be a key to understand the complexity behind their mechanism of pathogenesis.

Expression of DNA repair genes in oral squamous cell carcinoma using reverse transcription-quantitative polymerase chain reaction.

OBJECTIVE: The aim of this study was to evaluate the expression of DNA repair genes in cases of oral squamous cell carcinoma (OSCC). STUDY DESIGN: Expression of the MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes was evaluated by reverse transcription-quantitative polymerase chain reaction in the OSCC group (32 patients) and the control group (15 patients). The groups were compared by using the Mann-Whitney test, with Bonferroni correction. Associations between gene expression levels and clinical data were explored by using Pearson's and Spearman's correlation coefficients, with P value less than .05 indicating a significant difference. RESULTS: The MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes were downregulated in the OSCC group compared with the control group, with significant values for MLH1 (P < .0001); MSH2 (P = .038); MLH3 (P < .0001); ATM (P < .0001); MRE11A (P < .0001); XRCC1 (P = .0004); and PMS2 (P = .008). Analysis of the correlation between gene expression and clinical data only revealed a significant negative correlation between age and expression of the PMS2 gene. CONCLUSIONS: Expression of the DNA repair genes MLH1, MSH2, MLH3, ATM, MRE11 AMRE11A, XRCC1, and PMS2 was reduced in OSCC.

Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5-methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA in T. vaginalis is associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.

Abordaje de adicciones a nuevas tecnologías: una propuesta de prevención en contexto escolar y tratamiento de rehabilitación / An approach to addiction to new technologies: a proposal for prevention in the school environment and rehabilitation treatment

El vertiginoso avance de las nuevas tecnologías de la información y la comunicación (TIC's) ha generado, además de innumerables beneficios a la sociedad, cambios en nuestros hábitos de vida que no siempre son fáciles de asimilar de manera saludable. Estos hábitos son un caldo de cultivo en el que pueden desarrollarse malos usos de las TIC's, llegando a situaciones en las que se puede hablar de una adicción comportamental. El presente trabajo expone la experiencia del Centro de Tratamiento Triora MonteAlminara de Málaga en el desarrollo de una propuesta para el abordaje integral de esta problemática. Este proyecto incluye dos líneas fundamentales: la prevención en centros educativos y sociales, dirigida a jóvenes, familiares y profesorado; y el tratamiento de personas afectadas por este problema, con intervenciones como el ingreso terapéutico, orientación familiar y tratamiento ambulatorio individual y/o grupal, en función de las particularidades de cada proceso

The vertiginous progress of new information and communication technologies (ICTs) has generated, in addition to countless benefits to society, changes in our lifestyle habits that are not always easy to assimilate in a healthy way. These habits are a breeding ground in which poor and dysfunctional uses of ICT can be developed, resulting in what can be considered a behavioral addiction. The present research presents the experience of the Triora MonteAlminara Treatment Center of Malaga in developing a proposal for an integral approach to this problem. This project includes two fundamental lines of work: prevention in educational and social centers, aimed at young people, relatives and educational staff; and the treatment of people affected by this problem, with therapeutic interventions such as treatment center admission, family counseling and individual and/or group outpatient treatment, according to the particularities of each personal process

Protein Palmitoylation Plays an Important Role in Trichomonas vaginalis Adherence.

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in T. vaginalis In order to study the extent and function of S-acylation in T. vaginalis biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of Trichomonas vaginalis pathogenesis.

Membrane-shed vesicles from the parasite Trichomonas vaginalis: characterization and their association with cell interaction.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor-ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.

TfVPS32 Regulates Cell Division in the Parasite Tritrichomonas foetus.

The flagellated protist Tritrichomonas foetus is a parasite that causes bovine trichomonosis, a major sexually transmitted disease in cattle. Cell division has been described as a key player in controlling cell survival in other cells, including parasites but there is no information on the regulation of this process in T. foetus. The regulation of cytokinetic abscission, the final stage of cell division, is mediated by members of the ESCRT (endosomal sorting complex required for transport) machinery. VPS32 is a subunit within the ESCRTIII complex and here, we report that TfVPS32 is localized on cytoplasmic vesicles and a redistribution of the protein to the midbody is observed during the cellular division. In concordance with its localization, deletion of TfVPS32 C-terminal alpha helices (α5 helix and/or α4-5 helix) leads to abnormal T. foetus growth, an increase in the percentage of multinucleated parasites and cell cycle arrest at G2/M phase. Together, these results indicate a role of this protein in controlling normal cell division.

Epigenetics regulates transcription and pathogenesis in the parasite Trichomonas vaginalis.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Different T. vaginalis strains vary greatly in their adherence and cytolytic capacities. These phenotypic differences might be attributed to differentially expressed genes as a consequence of extra-genetic variation, such as epigenetic modifications. In this study, we explored the role of histone acetylation in regulating gene transcription and pathogenesis in T. vaginalis. Here, we show that histone 3 lysine acetylation (H3KAc) is enriched in nucleosomes positioned around the transcription start site of active genes (BAP1 and BAP2) in a highly adherent parasite strain; compared with the low acetylation abundance in contrast to that observed in a less-adherent strain that expresses these genes at low levels. Additionally, exposition of less-adherent strain with a specific histone deacetylases inhibitor, trichostatin A, upregulated the transcription of BAP1 and BAP2 genes in concomitance with an increase in H3KAc abundance and chromatin accessibility around their transcription start sites. Moreover, we demonstrated that the binding of initiator binding protein, the transcription factor responsible for the initiation of transcription of ~75% of known T. vaginalis genes, depends on the histone acetylation state around the metazoan-like initiator to which initiator binding protein binds. Finally, we found that trichostatin A treatment increased parasite aggregation and adherence to host cells. Our data demonstrated for the first time that H3KAc is a permissive histone modification that functions to mediate both transcription and pathogenesis of the parasite T. vaginalis.

Osseointegration of hydroxyapatite implants in rat tibial defects with sciatic nerve injury / Oseointegración de implantes de hidroxiapatita en defectos tibiales de ratas con lesión del nervio ciático

Bone metabolism is influenced by different factors and muscle activity acts as a stimulator of bone plasticity. Conditions such as nerve injuries can compromise bone physiology due to muscle inactivity. Preview studies have shown that nerve damage reduces P substance and calcitonin gene-related peptides, also known as neuropeptides that may have a key role on bone healing. Therefore, this study evaluated the osseointegration of hydroxyapatite implants in tibial defects of rats submitted to unilateral sciatic nerve section. Twelve Wistar rats were divided into two groups (G1 and G2). In G1, the sciatic nerve was left intact and in G2 the left sciatic nerve was completely sectioned. An experimental tibial bone defect was then created in both groups and filled with hydroxyapatite granules. The animals were sacrificed 2 months after implantation and samples were submitted to macroscopic inspection and histological analysis. Good radiopacity of the hydroxyapatite granules and radiographic definition of the bone defect were noted. Histologic analysis revealed formation of new bone adjacent to the hydroxyapatite granules in G1 and, to a lesser extent, in G2 in which the proliferation of connective tissue predominated at the implant site. The formation of new bone stimulated by hydroxyapatite in bone defects can be expected even in animals with limb paralysis due to nerve injury; however, bone formation occurs at a slower speed in these animals and the volume of newly formed bone is lower.

El metabolismo óseo está influenciado por diferentes factores y la actividad muscular como un estimulador de la plasticidad ósea. Condiciones tales como lesiones nerviosas pueden comprometer la fisiología ósea debido a la inactividad muscular. Estudios previos han demostrado que el daño nervioso reduce la sustancia P y el péptido relacionado con el gen de la calcitonina, también conocidos como neuropéptidos que pueden tener un papel clave en la cicatrización ósea. Este estudio evaluó la oseointegración de los implantes de hidroxiapatita en defectos tibiales de ratas sometidas a la sección del nervio ciático unilateralmente. Doce ratas Wistar se dividieron en dos grupos (G1 y G2). En G1, el nervio ciático se dejó intacto y en el G2 el nervio ciático izquierdo fue completamente seccionado. Un defecto óseo tibial fue creado experimentalmente en ambos grupos y se rellenó con gránulos de hidroxiapatita. Los animales se sacrificaron 2 meses después de la implantación y las muestras fueron sometidas a inspección macroscópica y el análisis histológico. Se observó buena radiopacidad de los gránulos de hidroxiapatita y definición radiográfica del defecto óseo. El análisis histológico reveló neoformación ósea adyacente a los gránulos de hidroxiapatita en G1 y, en menor medida en G2, donde la proliferación de tejido conectivo predominó en el sitio de implante. La neoformación ósea estimulada por hidroxiapatita en defectos óseos se puede esperar incluso en animales con parálisis de los miembros producto de una lesión nerviosa; sin embargo, la formación de hueso se produce a menor velocidad en estos animales y su volumen es menor.

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.