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BACKGROUND/OBJECTIVES: Estrogens and HPV are necessary for cervical cancer (CC) development. The levels of the G protein-coupled estrogen receptor (GPER) increase as CC progresses, and HPV oncoproteins promote GPER expression. The role of this receptor is controversial due to its anti- and pro-tumor effects. This study aimed to determine the effect of GPER activation, using its agonist G-1, on the transcriptome, cell migration, and invasion in SiHa cells and non-tumorigenic keratinocytes transduced with the HPV16 E6 or E7 oncogenes. METHODS: Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays. RESULTS: Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. CONCLUSIONS: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia.
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The literature regarding the life course and queer migration has shown that many gay men and lesbians seek large cities to live their lives away from the prying eyes of their families and build their sexual identity. In the global south, little is known about the effects that sexuality can have on the migratory trajectories of individuals. In that sense, what happens to the lives of those that have never left their hometowns and have had to find ways to experience their sexuality in these places. Therefore, the aim of this paper is to discuss queer migration, the impact on the lives of the individuals that left their hometowns, others that at one point came back and those that never left in the first place. Based on 21 life course interviews with self-identified LGB individuals in small/medium towns in Brazil, this paper shows how aspects such as closeness to family, educational trajectory, financial stability affects the migration trajectories of LGB individuals that live in small/medium cities. The results show that families are an important influence in the decision-making to migrate, to stay or to return to your hometown.
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In recent years there has been a decline in the incidence of gastric cancer, however the high mortality rate has remained constant. The present study evaluated the potential effects of the retinoid fenretinide on the viability and migration of two cell lines, AGS and NCI-N87, that represented primary and metastatic intestinal gastric cancer subtypes, respectively. It was determined that a similar2 dose of fenretinide reduced the viability of both the primary and metastatic cell lines. In addition, it was demonstrated that combined treatment with fenretinide and cisplatin may affect the viability of both primary and metastatic gastric cancer cells. Furthermore, a wound healing assay demonstrated an inhibitory effect for fenretinide on cell migration. As part of the characterization of the mechanism of action, the effect of fenretinide on reactive oxygen species production and lipid droplet content was evaluated, with the latter as an indirect means of assessing autophagy. These results support the hypothesis of combining using fenretinide with conventional therapies to improve survival rates in advanced or metastatic gastric cancer.
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PURPOSE: Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism. METHODS: The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth. RESULTS: SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo. CONCLUSION: SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.
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BACKGROUND: As the migratory flow to the USA has intensified in recent months, health problems associated have been identified. The aim of this work was the identification of malaria cases imported into Mexican territory. METHODS: Operational definitions of suspected and confirmed cases were used for investigation of malaria cases. Detection of parasitic entities by thick blood smear and molecular biology served as a confirmatory test. With the characteristics of the cases, a heat map was made to determine common clinical pictures. Finally, epidemiological analysis of cases was performed for the construction of timelines of imported malaria and the tracing of migratory routes. RESULTS: Twelve migrants from four countries were treated for presenting clinical symptoms with suspected dengue or malaria. Malaria was confirmed and two Plasmodium species were identified. From the epidemiological dates of arrival in Mexico, onset of symptoms and migratory routes, we speculate that ten cases acquired P. vivax during their crossing through Honduras, El Salvador or Guatemala. For the Guinea cases, we conclude that there was African importation of P. falciparum. CONCLUSION: The epidemiological panorama of malaria cases imported into Mexico show the need to join efforts to ensure universal access to health services, with the objective of timely detection of imported cases.
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BACKGROUND: Venezuelan migration has experienced an unprecedented increase in the last decade, with approximately 7.7 million Venezuelan-born individuals residing in other countries as of 2024. Our study aims to identify the potential and actual demand for healthcare services (SRH) in the Venezuelan diaspora's four primary destinations within the Andean Countries: Colombia, Ecuador, Peru, and Chile. METHODS: Using official data from administrative records, censuses, and sample surveys reported by the host countries and international agencies, we estimate the annual evolution of Venezuelan-born women of reproductive age (WRA) and their offspring. Additionally, we conduct two case studies focusing on Colombia and Chile to analyse the groups most vulnerable to unmet health needs. RESULTS: The population of WRA has increased to between 5 and 6.8%, and births have risen to approximately 3-8% in host countries due to Venezuelan migration. Yet, we found a general decrease in health coverage for certain age groups of Venezuelan female migrants in host countries for the period 2017-2022, particularly in Chile. By 2022, an estimated 20% of healthcare needs remained unmet among children, girls, and younger Venezuelan women, contributing to greater health inequalities between Venezuelan-born adolescents and those from other countries of birth. CONCLUSIONS: Our findings highlight the escalating demand for and limited access to healthcare services among Venezuelan WRA in their destinations. Unmet healthcare needs are particularly prevalent among younger women by 2022, underscoring the urgency for health system to incorporate gender-responsive, equitable interventions and ensuring health rights for high-risk migrant groups such as infants, children, adolescents, and younger women. Addressing these challenges remains a critical task for the regional public health agenda in Latin America.
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Salud Pública , Humanos , Femenino , Venezuela , Perú , Adolescente , Adulto , Chile , Colombia , Adulto Joven , Persona de Mediana Edad , Ecuador , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Niño , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Migrantes/estadística & datos numéricosRESUMEN
This article discusses Earth's Rights as an environmental justice mechanism of reparation, protection, and justice for indigenous communities, environmental defenders, and other populations in Latin America. We argue that Earth's rights encompass and include the right to health and can be integrated into international human rights frameworks to protect all forms of life, responding to colonial legacies of discrimination and violence. We respond to the scarcity of literature discussing Earth's rights in relation to situations where human rights and Earth's rights are violated. We ground our argument in the theoretical conceptualization of Latin American proposals of Earth's rights and its potential for actionable policy approaches that include human health as inevitably interconnected to our planet's well-being. We address the environmental injustices that affect the right to health and argue that an Earth's rights framework can support reparations for historically marginalized communities.
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Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.
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The conservation status of monarch butterflies in North America is a topic of intense scrutiny and debate. It is clear that winter colonies in Mexico are declining, yet some recent studies suggest that summer breeding populations are relatively stable and similar to historical abundances. One possible explanation for these discordant patterns is that fall migration success has been recently disrupted. Here, we use a relatively unexplored citizen-scientist dataset on the size of monarch "roosts," which are resting aggregations on vegetation, to infer changes in monarch abundance along the fall migration route over the last 17 y. We found that the timing of migration remained relatively unchanged while the flyway has generally become warmer and greener. Warmer and greener conditions were associated with larger roosts, yet we found steady, dramatic declines in roost sizes through time that were independent of climate and landscape factors. Roost sizes have declined as much as 80%, with losses increasing from north to south along the migration route. These findings suggest that failure during the fall migration could explain the apparent drop in monarch numbers from summer breeding to overwintering populations. This in turn suggests that conservation efforts that support fall migration success are most needed, such as providing high quality nectar plants along the migration route or limiting the planting of nonnative milkweeds that enhance monarch parasite loads. Overall, it appears the fall migration of monarch butterflies is under imminent threat, even if the species' overall survival is not.
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Migración Animal , Mariposas Diurnas , Estaciones del Año , Animales , Mariposas Diurnas/fisiología , Migración Animal/fisiología , México , Dinámica PoblacionalRESUMEN
Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.
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Apoptosis , Movimiento Celular , Proliferación Celular , Cloruro de Litio , Neoplasias del Cuello Uterino , Humanos , Cloruro de Litio/farmacología , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Movimiento Celular/efectos de los fármacos , Femenino , Células HeLa , Línea Celular Tumoral , Antineoplásicos/farmacología , Carbonato de Litio/farmacología , Ciclo Celular/efectos de los fármacos , Reposicionamiento de MedicamentosRESUMEN
Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients.
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Proteínas Quinasas Activadas por AMP , Carcinoma Hepatocelular , Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas , Ácido Tióctico , Proteína p53 Supresora de Tumor , Humanos , Ácido Tióctico/farmacología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Células Hep G2 , Proteínas Quinasas Activadas por AMP/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Invasividad Neoplásica , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Gene flow is important for maintaining the genetic diversity required for adaptation to environmental disturbances, though gene flow may be limited by site fidelity in small coastal sharks. Bonnethead sharks (Sphyrna tiburo)-a small coastal hammerhead species-demonstrate site fidelity, as females are philopatric while males migrate to mediate gene flow. Consequently, bonnetheads demonstrate population divergence with distance, and Atlantic populations are genetically distinct from those of the Gulf of Mexico. Indeed, Florida forms a vicariant zone between these two bodies of water for many marine species, including some sharks. However, while bonnetheads are expected to have limited dispersal, the extent and rate of bonnethead migration remain uncertain. Thus, we aimed to determine their dispersal capacity by evaluating connectivity between disparate populations from the Gulf of Mexico and Atlantic Ocean. Using 10,733 SNPs derived from 2bRAD sequences, we evaluated genetic connectivity between Tampa Bay on the Gulf Coast of Florida and Biscayne Bay on the Atlantic coast of Florida. While standard analyses of genetic structure revealed slight but significant differentiation between Tampa Bay and Biscayne Bay populations, demographic history inference based on the site frequency spectrum favored a model without divergence. However, we also estimate that if population divergence occurred, it would have been recent (between 1500 and 4500 years ago), with continuous unidirectional gene flow from Tampa Bay to Biscayne Bay. Our findings support the hypothesis that bonnetheads can migrate over relatively large distances (>300 miles) to find mates. Together, these results provide optimism that under proper management, a small-bodied globally endangered shark can undergo long migrations to sustain genetic diversity.
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Inflammatory bowel diseases (IBDs) involve chronic inflammation of the gastrointestinal tract, where effector CD4+ T-cells play a central role. Thereby, the recruitment of T-cells into the colonic mucosa represents a key process in IBD. We recently found that CCR9 and DRD5 might form a heteromeric complex on the T-cell surface. The increase in CCL25 production and the reduction in dopamine levels associated with colonic inflammation represent a dual signal stimulating the CCR9:DRD5 heteromer, which promotes the recruitment of CD4+ T-cells into the colonic lamina propria. Here, we aimed to analyse the molecular requirements involved in the heteromer assembly as well as to determine the underlying cellular mechanisms involved in the colonic tropism given by the stimulation of the CCR9:DRD5 complex. The results show that dual stimulation of the CCR9:DRD5 heteromer potentiates the phosphorylation of the myosin light chain 2 (MLC2) and the migration speed in confined microchannels. Accordingly, disrupting the CCR9:DRD5 assembly induced a sharp reduction in the pMLC2 in vitro, decreased the migratory speed in confined microchannels, and dampened the recruitment of CD4+ T-cells into the inflamed colonic mucosa. Furthermore, in silico analysis confirmed that the interface of interaction of CCR9:DRD5 is formed by the transmembrane segments 5 and 6 from each protomer. Our findings demonstrated that the CCR9:DRD5 heteromeric complex plays a fundamental role in the migration of CD4+ T-cells into the colonic mucosa upon inflammation. Thereby, the present study encourages the design of strategies for disassembling the formation of the CCR9:DRD5 as a therapeutic opportunity to treat IBD.
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Linfocitos T CD4-Positivos , Mucosa Intestinal , Receptores CCR , Receptores de Dopamina D5 , Transducción de Señal , Receptores CCR/metabolismo , Receptores CCR/genética , Humanos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Receptores de Dopamina D5/metabolismo , Receptores de Dopamina D5/genética , Mucosa Intestinal/metabolismo , Colon/metabolismo , Movimiento Celular , Dopamina/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/inmunologíaRESUMEN
This study explored the migration of follicular fluid (FF)-derived extracellular vesicles (EVs) of the uterine environment to the bloodstream and their interaction with neutrophils in vivo and in vitro. For the in vivo experiment, six Nellore heifers (Bos indicus) received an intrauterine infusion seven days after ovulation with 1X PBS only (sham group; n=1), 1X PBS stained with lipophilic dye PKH26 (control group; n=2), or FF-derived EVs stained with PKH26 (treated group; n=3). Plasma was collected at 0, 10, 30, 60-, 180-, 360-, 720-, and 1440-min post-infusion to obtained EVs for analysis by nano flow cytometry. Labeled EVs were present in the bloodstream at 30- and 60-min post-infusion in the treatment group. Additionally, plasma derived-EVs from all groups were positive for Calcein-AM, Alix, Syntenin, and Calnexin, which confirm the presence of EVs. The second experiment utilized the plasma-derived EVs from the heifers from 30 and 60 min timepoints to evaluate if neutrophils can uptake EVs in vitro. As results, it was possible to observe the presence of labeled EVs in neutrophils treated with plasma derived-EVs from the treatment group. In summary, our results suggest that labeled EVs can migrate from the uterine environment rapidly and interact with circulating immune cells in bovine.
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En Latinoamérica y El Caribe la presencia de niños, niñas y adolescentes en los flujos migratorios internacionales es creciente. Los efectos que la migración genera sobre la salud de estos grupos han sido poco estudiados. El objetivo de este artículo es indagar en las principales evidencias reportadas respecto al acceso y uso de servicios de salud por parte de niños, niñas y adolescentes migrantes en América Latina y El Caribe. Esto, con la finalidad de reflexionar sobre el rol que cumplen los determinantes sociales de la salud de diverso nivel, en las condiciones de salud de estos grupos. También se busca identificar recomendaciones para su abordaje desde los sistemas de salud y la política pública. Para ello se realizó una revisión narrativa de 52 publicaciones sobre la base de un proceso de búsqueda de literatura científica de la base de datos y Google Académico. Se identificaron cinco temas relevantes: uso de urgencias asociado a falta de acceso a salud, a servicios preventivos y a otros determinantes sociales de la salud; exposición a enfermedades infecciosas prevenibles; salud mental; salud sexual y reproductiva; y vacunaciones y salud dental. Concluimos que la evidencia muestra la necesidad de abordar las inequidades y desventajas que están acumulando estos grupos, desde una óptica de determinantes sociales de la salud y de políticas que consideren la salud como derecho humano independiente de la situación migratoria de los niños, niñas y adolescentes, así como la de sus padres o cuidadores principales.
The presence of children and adolescents in migratory flows is growing in Latin America and the Caribbean. Little is known about migration's effects on these groups' health. This article aims to investigate the evidence available on the access and use of healthcare services by migrant children and adolescents in Latin America and the Caribbean. We seek to explore the role of social determinants of health at different levels in the health conditions of these groups. Also, to identify potential recommendations for healthcare systems and public policy to address them. For this purpose, a narrative review of 52 publications was carried out based on a search of scientific literature in the Web of Science and Google Scholar databases. Five relevant topics were identified: use of emergency care associated with lack of healthcare access, preventive services, and other social determinants of health; exposure to preventable infectious diseases; mental health; sexual and reproductive health; and vaccinations and dental health. We conclude that the evidence shows the need to address the inequities and disadvantages faced by migrant children from a perspective of social determinants of health and policies that consider health as a human right regardless of the migratory status of children and adolescents, as well as that of their parents or primary caregivers.
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Background: The crisis in Venezuela has forced almost eight million people to flee to mainly neighbouring countries, including Brazil. Half of the displaced Venezuelans are women and girls, with adolescent girls facing distinctive challenges to their sexual and reproductive health during displacement and settlement. The aim of this study is to understand the barriers and facilitators for the sexual and reproductive health of adolescent Venezuelan girls residing in Brazil. Methods: The study used qualitative methods, including semi-structured interviews with 19 Venezuelan migrant adolescent girls conducted in Boa Vista and Manaus. We analysed transcripts using thematic analysis, and mapped findings to a theoretical framework based on the Bronfenbrenner Socio-ecological Model, which we adapted to explore how intersectional vulnerabilities at the individual level interact with contextual factors creating barriers and facilitators for health and rights of migrant adolescent girls. Results: Venezuelan adolescent migrants in Brazil face practical and structural barriers in realising their sexual and reproductive health and rights in four areas: menstruation; family planning, contraception and sexually transmitted infection; prenatal, childbirth and postnatal care; and preventing gender-based violence. The reported barriers were lack of knowledge around sexual and reproductive health rights, exposure to violence and lack of access to age-appropriate healthcare services. Mitigating factors included education (both in the family setting and at school); prevention activities undertaken by health services; care provision from non-governmental organisations and international agencies; and best practices in local health services. Conclusions: Host states must take action to enhance the right to sexual and reproductive health for adolescent migrants to allow them to make autonomous, independent and informed choices. A socioecological perspective on sexual and reproductive health and rights can help formulate intersectional policies that interconnect different levels of adolescent migrants' experience.
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Trichomonas vaginalis causes trichomoniasis, the most common non-viral sexually transmitted disease worldwide. As an extracellular parasite, adhesion to host cells is essential for the development of infection. During attachment, the parasite changes its tear ovoid shape to a flat ameboid form, expanding the contact surface and migrating through tissues. Here, we have identified a novel structure formed at the posterior pole of adherent parasite strains, resembling the previously described uropod, which appears to play a pivotal role as an anchor during the attachment process. Moreover, our research demonstrates that the overexpression of the tetraspanin T. vaginalis TSP5 protein (TvTSP5), which is localized on the cell surface of the parasite, notably enhances the formation of this posterior anchor structure in adherent strains. Finally, we demonstrate that parasites that overexpress TvTSP5 possess an increased ability to adhere to host cells, enhanced aggregation and reduced migration on agar plates. Overall, these findings unveil novel proteins and structures involved in the intricate mechanisms of T. vaginalis interactions with host cells.
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Proteínas Protozoarias , Trichomonas vaginalis , Trichomonas vaginalis/genética , Humanos , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Adhesión Celular , Tetraspaninas/metabolismo , Tetraspaninas/genética , Membrana Celular/metabolismo , Interacciones Huésped-Parásitos , Extensiones de la Superficie Celular/metabolismo , AnimalesRESUMEN
Snake venoms are a complex mixture of proteins and polypeptides that represent a valuable source of potential molecular tools for understanding physiological processes for the development of new drugs. In this study two major PLA2s, named PLA2-I (Asp49) and PLA2-II (Lys49), isolated from the venom of Bothrops diporus from Northeastern Argentina, have shown cytotoxic effects on LM3 murine mammary tumor cells, with PLA2-II-like exhibiting a stronger effect compared to PLA2-I. At sub-cytotoxic levels, both PLA2s inhibited adhesion, migration, and invasion of these adenocarcinoma cells. Moreover, these toxins hindered tubulogenesis in endothelial cells, implicating a potential role in inhibiting tumor angiogenesis. All these inhibitory effects were more pronounced for the catalytically-inactive toxin. Additionally, in silico studies strongly suggest that this PLA2-II-like myotoxin could effectively block fibronectin binding to the integrin receptor, offering a dual advantage over PLA2-I in interacting with the αVß3 integrin. In conclusion, this study reports for the first time, integrating both in vitro and in silico approaches, a comparative analysis of the antimetastatic and antiangiogenic potential effects of two isoforms, an Asp49 PLA2-I and a Lys49 PLA2-II-like, both isolated from Bothrops diporus venom.
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Bothrops , Venenos de Crotálidos , Fosfolipasas A2 , Animales , Bothrops/metabolismo , Ratones , Fosfolipasas A2/metabolismo , Fosfolipasas A2/química , Fosfolipasas A2/farmacología , Línea Celular Tumoral , Venenos de Crotálidos/química , Movimiento Celular/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Adhesión Celular/efectos de los fármacos , Femenino , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/citología , Metástasis de la Neoplasia , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inhibidores , Fibronectinas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/química , Humanos , Lisina/química , Lisina/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/metabolismo , AngiogénesisRESUMEN
Parasites comprise a substantial portion of global biodiversity and play critical roles in shaping ecosystems by modulating trophic networks and affecting their hosts' abundance and distribution. The dynamics of host migration introduce new complexity to these relationships. From the host perspective, migratory behavior can either act as a defense mechanism or augment exposure to a broader spectrum of pathogens. Conversely, for parasites, host migration represents a mechanism for their dispersion and an opportunity to infect new host species. This study investigates the complex interplay between migration and parasite-host interactions, focusing on the interaction between hosts and avian malaria and malaria-like parasites in the Brazilian Atlantic Rain Forest. We captured 1466 birds representing 70 different species, uncovering 322 infections with Plasmodium/Haemoproteus parasites. We observed variations in migration timing and fluctuations in host abundance across months. By comparing the observed patterns of interaction of migratory and non-migratory birds to patterns of interaction expected at random, we show that migration affects the roles hosts take in the parasite-host network. Interestingly, despite the fact migratory species hosted more exclusive and distinct parasites, migrants did not occupy central network positions, which are mostly occupied by resident birds. Overall, we highlight the role of resident birds as a key species within parasite-host communities and the high specialization among avian haemosporidians and their hosts.
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Migración Animal , Aves , Interacciones Huésped-Parásitos , Animales , Brasil , Ecosistema , Plasmodium/fisiologíaRESUMEN
The presence of children and adolescents in migratory flows is growing in Latin America and the Caribbean. Little is known about migration's effects on these groups' health. This article aims to investigate the evidence available on the access and use of healthcare services by migrant children and adolescents in Latin America and the Caribbean. We seek to explore the role of social determinants of health at different levels in the health conditions of these groups. Also, to identify potential recommendations for healthcare systems and public policy to address them. For this purpose, a narrative review of 52 publications was carried out based on a search of scientific literature in the Web of Science and Google Scholar databases. Five relevant topics were identified: use of emergency care associated with lack of healthcare access, preventive services, and other social determinants of health; exposure to preventable infectious diseases; mental health; sexual and reproductive health; and vaccinations and dental health. We conclude that the evidence shows the need to address the inequities and disadvantages faced by migrant children from a perspective of social determinants of health and policies that consider health as a human right regardless of the migratory status of children and adolescents, as well as that of their parents or primary caregivers.
En Latinoamérica y El Caribe la presencia de niños, niñas y adolescentes en los flujos migratorios internacionales es creciente. Los efectos que la migración genera sobre la salud de estos grupos han sido poco estudiados. El objetivo de este artículo es indagar en las principales evidencias reportadas respecto al acceso y uso de servicios de salud por parte de niños, niñas y adolescentes migrantes en América Latina y El Caribe. Esto, con la finalidad de reflexionar sobre el rol que cumplen los determinantes sociales de la salud de diverso nivel, en las condiciones de salud de estos grupos. También se busca identificar recomendaciones para su abordaje desde los sistemas de salud y la política pública. Para ello se realizó una revisión narrativa de 52 publicaciones sobre la base de un proceso de búsqueda de literatura científica de la base de datos y Google Académico. Se identificaron cinco temas relevantes: uso de urgencias asociado a falta de acceso a salud, a servicios preventivos y a otros determinantes sociales de la salud; exposición a enfermedades infecciosas prevenibles; salud mental; salud sexual y reproductiva; y vacunaciones y salud dental. Concluimos que la evidencia muestra la necesidad de abordar las inequidades y desventajas que están acumulando estos grupos, desde una óptica de determinantes sociales de la salud y de políticas que consideren la salud como derecho humano independiente de la situación migratoria de los niños, niñas y adolescentes, así como la de sus padres o cuidadores principales.