High frequency of alpha7-HPV in Colombian Caribbean coast women: cervical cancer screening analysis.

BACKGROUND: Cervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening. METHODS: A cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and - 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value < 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software. RESULTS: We included 450 women, mean age 40 (SD±11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18-31.63). Menopause was protective (OR=0.31; 95% CI 0.11-0.89). CONCLUSIONS: Our study reveals a notable prevalence of multiple (2-4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.

Additive effects of the combined expression of soluble forms of GAS1 and PTEN inhibiting glioblastoma growth.

The overexpression of GAS1 (Growth Arrest Specific 1) in glioma cells induces cell cycle arrest and apoptosis. We previously demonstrated that the apoptotic process set off by GAS1 is caused by its capacity to inhibit the Glial cell-derived neurotrophic factor (GDNF)-mediated intracellular survival signaling pathway. Whereas on the other hand, PTEN is a tumor suppressor, inactive in many tumors, and both GAS1 and PTEN inhibit the PI3K/AKT pathway. Therefore, it is relevant to investigate the potential additive effect of the overexpression of GAS1 and PTEN on tumor growth. In particular, we employed secreted forms of both GAS1 (tGAS1) and PTEN (PTEN-LONG, or PTEN-L) and tested their combined effect on glioma cells. We observed that the co-expression of both the proteins inhibited the growth of U-87 MG human glioblastoma cells more effectively than when independently expressed, and decreased the activity of both AKT and ERK1/2. Interestingly, the combination of the soluble forms was always the most effective treatment. To improve the transfer of tGAS1 and PTEN-L, we employed a lentiviral vector with a p2A peptide-enabled dual expression system that allowed the generation of the two proteins using a single promoter (CMV), in equimolar amounts. The viral vector reduced the growth of U-87 MG cells in vitro and had a striking effect in inhibiting their proliferation after inoculating it into the immunosuppressed mice. The present results support a potential adjuvant role for the combined use of tGAS1 and PTEN-L in the treatment of glioblastoma.

Expression of Gas1 in Mouse Brain: Release and Role in Neuronal Differentiation.

Growth arrest-specific 1 (Gas1) is a pleiotropic protein that induces apoptosis of tumor cells and has important roles during development. Recently, the presence of two forms of Gas1 was reported: one attached to the cell membrane by a GPI anchor; and a soluble extracellular form shed by cells. Previously, we showed that Gas1 is expressed in different areas of the adult mouse CNS. Here, we report the levels of Gas1 mRNA protein in different regions and analyzed its expressions in glutamatergic, GABAergic, and dopaminergic neurons. We found that Gas1 is expressed in GABAergic and glutamatergic neurons in the Purkinje-molecular layer of the cerebellum, hippocampus, thalamus, and fastigial nucleus, as well as in dopaminergic neurons of the substantia nigra. In all cases, Gas1 was found in the cell bodies, but not in the neuropil. The Purkinje and the molecular layers show the highest levels of Gas1, whereas the granule cell layer has low levels. Moreover, we detected the expression and release of Gas1 from primary cultures of Purkinje cells and from hippocampal neurons as well as from neuronal cell lines, but not from cerebellar granular cells. In addition, using SH-SY5Y cells differentiated with retinoic acid as a neuronal model, we found that extracellular Gas1 promotes neurite outgrowth, increases the levels of tyrosine hydroxylase, and stimulates the inhibition of GSK3ß. These findings demonstrate that Gas1 is expressed and released by neurons and promotes differentiation, suggesting an important role for Gas1 in cellular signaling in the CNS.

Gas1 expression in parietal cells of Bowman's capsule in experimental diabetic nephropathy.

Gas1 (Growth Arrest-Specific 1) is a pleiotropic protein with novel functions including anti-proliferative and proapoptotic activities. In the kidney, the expression of Gas1 has been described in mesangial cells. In this study, we described that renal parietal cells of Bowman's capsule (BC) and the distal nephron cells also express Gas1. The role of Gas1 in the kidney is not yet known. There is a subpopulation of progenitor cells in Bowman's capsule with self-renewal properties which can eventually differentiate into podocytes as a possible mechanism of regeneration in the early stages of diabetic nephropathy. We analyzed the expression of Gas1 in the parietal cells of Bowman's capsule in murine experimental diabetes. We found that diabetes reduced the expression of Gas1 and increased the expression of progenitor markers like NCAM, CD24, and SIX1/2, and mesenchymal markers like PAX2 in the Bowman's capsule. We also analyzed the expression of WT1 (a podocyte-specific marker) on BC and observed an increase in the number of WT1 positive cells in diabetes. In contrast, nephrin, another podocyte-specific protein, decreases its expression in the first week of diabetes in the glomerular tuft, which is gradually restored during the second and third weeks of diabetes. These results suggest that in diabetes the decrease of Gas1 promotes the activation of parietal progenitor cells of Bowman's capsule that might differentiate into podocytes and compensate their loss observed in this pathology.

[Obesity, a risk factor for ascending bacterial infection during pregnancy]. / Obesidad, factor de riesgo de infección bacteriana ascendente durante el embarazo.

BACKGROUND: Obesity in pregnancy is associated with significantly higher rates of infection. AIM: To compare the infectious morbidity in pregnant women with normal and altered body mass index (BMI). MATERIAL AND METHODS: Cross sectional retrospective study of 6,150 patients who had delivery or second trimester abortion during 2012. The patients were classified according to BMI as underweight, normal weight, overweight and obese. We compared the frequency of pregnancy and perinatal complications related to ascending bacterial infection (ABI). The data was obtained from the hospital’s databases. RESULTS: Obese patients had higher rates of pregnancy and perinatal complications related to ABI compared to patients with normal weight. The odds ratios (OR) and 95% confidence intervals (CI) for second trimester abortion were 3.45 (1.63-7.31) p < 0.01, for preterm delivery 2.42 (1.51-3.87) p < 0.01, for labor and puerperium infections 3.42 (2.06-5.68) p < 0.01 and for early neonatal infectious and perinatal mortality 4.46 (1.75-11.37) p < 0.01. A logistic regression analysis revealed that obesity is an independent risk factor for second trimester abortion related to ABI with an OR of 3.18 (CI 95% 1.46-6.91), premature delivery related to ABI with an OR of 2.51 (CI 95% 1.54-4.09) and for delivery and postpartum infections with an OR of 4.44 (CI 95% 2.62 to 7.51). CONCLUSIONS: Obese pregnant women had a 2.5 to 4.5 times increased risk of infectious morbidity compared to normal weight patients. Obesity is an independent risk factor for second trimester abortion and preterm delivery related to ABI and delivery and postpartum infectious.

Neural stem cells producing an inducible and soluble form of Gas1 target and inhibit intracranial glioma growth.

BACKGROUND AIMS: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor and current treatments have not improved its prognosis. Therefore, new strategies and therapeutic agents should be investigated. Growth arrest specific-1 (Gas1) is a protein that induces cell arrest and apoptosis of gliomas and a soluble form, tGas1, increases these effects acting in both autocrine and paracrine manners. Moreover, neural stem cells (NSCs) can be used as a vehicle to transport therapeutic molecules because they have innate tropism towards tumors. METHODS: Lentiviral vectors were used to obtain NSCs capable of expressing tGas1 in a regulated manner. The ability of engineered NSCs to track and reach GBM in vivo, produce tGas1, and their efficacy decreasing tumor growth and increasing the overall health and survival time of nude mice implanted with GBM were assessed. RESULTS: The overexpression of tGas1 from NSCs decreased viability and induced cell arrest and apoptosis of GBM cells and also, albeit in a reduced manner, of NSCs themselves. NSCs migrate from one cerebral hemisphere to the contralateral, reach GBM, express the tGas1 transgene when induced by tetracycline and produce the protein. Tumor volume decreased by 77% compared with controls, and tGas1 improved the overall health and increased the survival time of mice implanted with GBM by 75%. CONCLUSIONS: We demonstrated that tGas1 has an antineoplastic effect, and the results support the potential of tGas1 as an adjuvant for the treatment of gliomas.

Trypanosoma cruzi in domestic and wild mammals in the northeast region of Colombia.

Trypanosoma cruzi hosts can serve as a source of infection for animals, vectors, and humans, contributing to the establishment of Chagas disease (CD) in a given area. Traditionally, the Department of Córdoba has not been considered a transmission area for CD; however, the report of several acute cases of Chagas disease highlights the importance of studying the dynamics of disease transmission in this region. This study aimed to detect T. cruzi in domestic and wild mammals in the department of Córdoba. In 2017, a cross-sectional descriptive study was conducted in six villages in two municipalities in the department of Córdoba. Blood samples from dogs living in the zones were collected in EDTA vacutainer tubes for domestic mammals. Wild mammals were collected using Sherman and Tomahawk traps and mist nets in crops and peridomiciles. T. cruzi DNA was detected using the kinetoplast DNA (kDNA) variable region and the tandem repeat satellite region of T. cruzi as molecular targets. We sampled 168 dogs and 146 wild mammals. The detected prevalence of T. cruzi was 6.37%; the TcI lineage was found in D. marsupialis, H. anomalus, and one canine. A specimen of D. marsupialis with TcI and TcII lineages was also identified. T. cruzi DNA was detected in domestic and wild animals in the study area, indicating the circulation of the parasite in peridomestic environments. D. marsupialis may represent an important host in maintaining this region's wild and domestic cycle.

How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

Introduction: The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. Methods: A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. Results: The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Conclusion: Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

Characterization of the pattern of expression of Gas1 in the kidney during postnatal development in the rat.

Growth Arrest-Specific 1 (Gas1) is a pleiotropic protein with different functions, in the adult kidney Gas1 acts as an endogenous inhibitor of cell proliferation but it is also necessary for the maintenance and proliferation of Renal Progenitor Cells (RPC) during early development, thus it fulfills important functions in the adult kidney. However, it is not known whether or not Gas1 is expressed during postnatal development, a critical stage for renal maturation. For this reason, the main objective of this work was to characterize the expression pattern of Gas1 in the different regions of the kidney by immunofluorescence and Western blot analysis during the postnatal development of the rat. We found that Gas1 is present and has a differential expression pattern in the various regions of the nephron during postnatal development. We observed that the highest levels of expression of Gas1 occur in the adult, however, Gas1 is also expressed in RPC and interestingly, the expression of RPC markers such as the Neural cell adhesion molecule (NCAM) and Cluster of differentiation 24 (CD24) were found to have an inverse pattern of expression to Gas1 (decreases as the kidney matures) during postnatal renal maturation, this indicates a role for Gas1 in the regulation of renal cell proliferation at this stage of development.

Expression of growth arrest specific 1 (Gas1) in the distal tubules and collecting ducts in normal kidney and in the early stages of diabetic nephropathy.

The Growth Arrest-Specific protein 1 (Gas1) has been recently described in kidney as an endogenous inhibitor of cell proliferation in mesangial cells and with an important role in the maintenance of nephron progenitor cells. Furthermore, the expression of Gas1 was demonstrated in NCAM + progenitor parietal cells of Bowman's capsule. Thus, the aim of this study was to analyze the expression of Gas1 in the collecting ducts (CD) of healthy rats and to examine whether high glucose levels modify its expression during the early stages of diabetes in STZ-treated rats. Immunofluorescence reveals that principal cells AQP2 + express Gas1 in both healthy and diabetic conditions. Western blot from enriched fractions of medullary CD suggests that diabetes promotes the increase of Gas1. AQP2 + cells are also positive for the expression of CD24 and CD1133 in diabetic rats. In addition, diabetes modifies the cell morphology in the CD and favors the increase of principal cells (AQP2+/Gas1+), induces a significant decrease of intercalated cells (V-ATPase+/Gas1-) and the presence of intermediate cells (Gas1+/V-ATPase+) which express both principal and intercalated cell markers. The expression of Gas1 in the distal tubules was also determined by immunofluorescence, western blot and ELISA in diabetic rats. The results identify Gas1 as a specific marker of principal cells in healthy and diabetic rats and suggest that diabetes promotes the expression of Gas1. Gas1 may have an important role in the maintenance and differentiation to principal cells in the CD during early stages of diabetes.

IL-4, IL-10, CCL2 and TGF-ß as potential biomarkers for severity in Plasmodium vivax malaria.

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules is thought to contribute to pathogenesis and has been proposed as a possible predictor for disease complications. The objective of this study was to evaluate the cytokine profile of P. vivax malaria patients with different clinical outcomes to identify possible immune biomarkers for severe P. vivax malaria. The study included patients with non-severe (n = 56), or severe (n = 50) P. vivax malaria and healthy controls (n = 50). Patient plasma concentrations of IL-4, IL-2, CXCL10, IL-1ß, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, CXCL8 and active TGF-ß1 were determined through flow cytometry. The levels of several cytokines and chemokines, CXCL10, IL-10, IL-6, IL-4, CCL2 and IFN-γ were found to be significantly higher in severe, compared to non-severe P. vivax malaria patients. Severe thrombocytopenia was positively correlated with IL-4, CXCL10, IL-6, IL-10 and IFN-γ levels, renal dysfunction was related to an increase in IL-2, IL-1ß, IL-17A and IL-8, and hepatic impairment with CXCL10, MCP-1, IL-6 and IFN-γ. A Lasso regression model suggests that IL-4, IL-10, CCL2 and TGF-ß might be developed as biomarkers for severity in P. vivax malaria. Severe P. vivax malaria patients present specific cytokine and chemokine profiles that are different from non-severe patients and that could potentially be developed as biomarkers for disease severity.

Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas.

Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection; nutritional status; and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI); however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR = 1.20) compared to POZOI (PR = 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.

Adenoviral astrocyte-specific expression of BDNF in the striata of mice transgenic for Huntington's disease delays the onset of the motor phenotype.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. The most characteristic structural feature of this disease is neurodegeneration accompanied by gliosis in the striatum. BDNF has been proposed to protect striatal neurons from degeneration, because it is an important survival factor for these neurons from development to adulthood. Considering the extensive gliosis and the survival effects of BDNF, we constructed an adenovirus to express a BDNF cDNA in astrocyte cells using a promoter of the glial fibrillary acidic protein gene. Cells stably transfected in vitro with a BDNF cDNA driven by this promoter expressed BDNF and responded to external stimuli increasing BDNF production. When the vector was applied into the striata of mice transgenic for HD, long-term expression of the transgene was observed, associated with a delay of onset of the motor phenotype of the R6/2 HD transgenic mice. The present data indicate that the striatal expression of BDNF is a potential adjuvant for the treatment of HD.

Liver and kidney dysfunction, hypoglycemia, and thrombocytopenia in Plasmodium vivax malaria patients at a Colombian Northwest region.

Plasmodium vivax has high morbidity, it is the Plasmodium species with the greatest worldwide distribution, and its ability to trigger severe symptoms is currently recognized. The present study aims to compare the clinical and epidemiological characteristics of patients with P. vivax malaria, with and without complication criteria, in an endemic area for malaria transmission in northwest Colombia. A descriptive cross-sectional study was carried out between 2017 and 2019, patients with P.vivax severe malaria (n = 50), non-severe malaria (n = 56) and healthy controls (n = 50) were included. Sociodemographic, clinical, hematological, and biochemical characteristics were analyzed. Clinical follow-up was carried out in a group of patients with severe malaria. The statistical analysis was carried out in GraphPad Prism; the Chi-square test analyzed categorical variables, comparisons of variables for the three groups were carried out by the Kruskal-Wallis test and comparison between two groups by the Mann-Whitney test. A multiple correspondence analysis described the relationship between variables, which was carried out through the R software. One hundred fifty-six individuals were linked to the study, 76 women and 80 men, between 3 and 71 years old. For 50% of the patients, it was their first malaria episode; 42% of the patients classified with severe malaria required hospitalization, compared to 7.1% of the patients with non-severe malaria. Parasitaemia was similar in both clinical groups; however, 10% of severe patients presented high parasitemia, between 20,000-135,000. The most frequent clinical characteristics in patients with severe malaria were severe thrombocytopenia in 54%, hypoglycemia in 48%, and liver and kidney failure in 30%. Biochemical and hematological parameters returned to normal in 90% of the patients with severe malaria on the third day after starting treatment. Thrombocytopenia, hypoglycemia, and liver and kidney dysfunctions were the most frequent P. vivax malaria complications in this study. Hemoglobin concentration and parasite count were not related to the clinical condition of patients. Thrombocytopenia was the most frequent finding in patients with malaria, and its severity presented an inverse relationship with the number of previous malaria episodes.

Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays a pivotal role in liver fibrosis, because it activates hepatic stellate cells, stimulating extracellular matrix deposition. Cyclooxygenase-2 (COX-2) has been associated with TGF-beta because its inhibition decreases TGF-beta expression and collagen production in some cultured cell types. AIM: The aim of this work was to evaluate the ability of celecoxib (a selective COX-2 inhibitor) to prevent and to reverse the liver fibrosis induced by CCl(4). METHODS: We established experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl(4) administration and CCl(4) plus pharmacological treatment in both prevention and reversion models. We determined: alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, COX and metalloproteinase-2 and -9 activities, lipid peroxidation, glutathione levels, glycogen and collagen content and TGF-beta expression. RESULTS: Celecoxib prevented and aided to the recovery of livers with necrotic and cholestatic damage. Celecoxib exhibited anti-oxidant properties by restoring the redox equilibrium (lipid peroxidation and glutathione levels). Glycogen was decreased by CCl(4), while celecoxib partially prevented and reversed this effect. Celecoxib inhibited COX-2 activity, decreased TGF-beta expression, induced metalloproteinase-2 activity and, consequently, prevented and reversed collagen accumulation. CONCLUSION: Our findings indicate that celecoxib exerts strong antifibrogenic and fibrolytic effects in the CCl(4) model of cirrhosis.

Simultaneous Treatment with Soluble Forms of GAS1 and PTEN Reduces Invasiveness and Induces Death of Pancreatic Cancer Cells.

INTRODUCTION: Pancreatic carcinoma cells exhibit a pronounced tendency to invade along and through intra and extrapancreatic nerves, even during the early stages of the disease, a phenomenon called perineural invasion (PNI). Thus, we sought to determine the effects of the simultaneous expression of soluble forms of GAS1 and PTEN (tGAS1 and PTEN-L) inhibiting tumor growth and invasiveness. MATERIALS AND METHODS: We employed a lentiviral system to simultaneously express tGAS1 and PTEN-L; in order to determine the effects of the treatments, cell viability and apoptosis as well as the expression of the transgenes by ELISA and intracellular signaling as ascertained by the activation of AKT and ERK1/2 were measured; cell invasiveness was determined using a Boyden chamber assay; and the effects of the treatment were measured in vivo in a mouse model. RESULTS: In the present work, we show that the combined treatment with tGAS1 and PTEN-L inhibits the growth of pancreatic cancer cells, by reducing the activities of both AKT and ERK 1/2, decreases cell invasiveness, and restrains tumor growth in a mouse model. CONCLUSION: The combined administration of tGAS1 and PTEN-L could be a valuable adjunct therapy for the treatment of pancreatic cancer.

DENV and ZIKV detection in patients with acute febrile syndrome in Córdoba, Colombia.

OBJECTIVE: To determine simultaneous circulation of DENV serotypes and ZIKV in Córdoba, Colombia, during 2015 and 2016. MATERIAL AND METHODS: A total of 294 samples from patients with clinical diagnosis of febrile syndrome compatible with dengue were collected between June 2015 and December 2016. All samples were tested for DENV and ZIKV by RT-PCR using C6/36 cells culture supernatant. RESULTS: Thirty-three percent of the samples were positive (97/294); from these, 61.8% were positive for DENV and 31% were positive for Zika. The predominant serotype was DENV-2 (70.1%), followed by DENV-3 (8.9%), DENV-4 (6%), and DENV-1 (3%). DENV/ZIKV coinfection was identified in 7.2% of the cases associated with DENV-1 and DENV-3 serotypes. The confirmed cases of dengue, Zika, and DENV/ZIKV coinfections were clinically mild and self-limited. CONCLUSIONS: We reported the co-circulation of all four DENV serotypes, with a higher frequency of DENV-2, and ZIKV introduction in Córdoba department-Colombia in August 2015. This scenario favored the appearance of DENV/ZIKV coinfections.

Utilidad del complejo posterior para el diagnóstico prenatal de sintelencefalia

Introducción y objetivo: Demostrar el valor del plano axial del complejo posterior, como apoyo a la detección antenatal de sintelencefalia, variante de holoprosencefalia. Método: Se incluyeron todas las pacientes con diagnóstico de sintelencefalia evaluadas desde el año 2008. En todos los casos se consignaron los datos clínicos, de neurosonografía (NSG), de resonancia magnética (RM) y genética. Resultados: Cuatro casos fueron diagnosticados en el segundo trimestre y en todos se realizó estudio genético y RM. Tres tuvieron en su evolución anomalías extra-SNC y dos de ellos alteraciones cromosómicas, una de ellas incompatible con la vida extrauterina. Lo hallazgos descritos en neuroimagen para esta afección fueron detectados en la NSG, con una excelente correlación con RM, ya fuera esta última realizada en periodo fetal o posnatal. Conclusión: El diagnóstico prenatal de variantes de holoprosencefalia es difícil, considerando la existencia de una fusión medial más acotada que en las formas clásicas. El presente estudio demuestra la utilidad del plano del complejo posterior para la sospecha diagnóstica de sintelencefalia.

Introduction and objective: To demonstrate the value of the axial plane of the posterior complex, as a clue for the antenatal detection of synthelencephaly, a variant of holoprosencephaly. Method: All patients diagnosed with syntelencephaly evaluated since 2008 were included. In all cases, clinical, neurosonography (NSG), magnetic resonance imaging (MRI) and genetic data were recorded. Results: Four cases were diagnosed in the second trimester and in all of them a genetic study and MRI were performed. Three had extra-CNS anomalies in their evolution and two of them chromosomal anomalies, one of them incompatible with extrauterine life. Neuroimaging findings described for this condition were detected by NSG, with an excellent correlation with MRI, whether the latter was performed in the fetal or postnatal period. Conclusion: The prenatal diagnosis of holoprosencephaly variants is difficult, considering the existence of a more limited medial fusion than in the classical forms. The present study demonstrates the usefulness of the posterior complex plane for the diagnostic suspicion of synthelencephaly.

Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress.

Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcumin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappaB activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) mRNA, and NF-kappaB activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-1beta, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappaB to the nucleus; CCl4 induced NF-kappaB DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappaB activation and thus production of proinflammatory cytokines.

Gas1 reduces Ret tyrosine 1062 phosphorylation and alters GDNF-mediated intracellular signaling.

The present results show that the expression of Growth Arrest Specific1 (Gas1) in SH-SY5Y neuroblastoma cells significantly inhibits the increased phosphorylation of tyrosine 1062 of the Ret receptor tyrosine kinase induced by glial-cell-line-derived neurotrophic factor (GDNF). We also observed that Gas1 significantly reduces the activation of Akt. GDNF and members of its family of ligands (GFLs), signal through a molecular complex consisting of one of its receptors (GFRalphas) and the Ret receptor tyrosine kinase. GDNF is a key component to preserve several cell populations in the nervous system, including dopaminergic and motor neurons, and also participates in the survival and differentiation of peripheral neurons such as enteric, sympathetic and parasympathetic. On the other hand, Gas1 is a molecule involved in cell arrest that can induce apoptosis when over-expressed in different cell lines, including cells of neuronal and glial origin. Although, Gas1 is widely expressed during development, its role in vivo has not yet been clearly defined. We recently showed the structural homology between Gas1 and GFRalphas, thus suggesting that the physiological role of Gas1 is that of modulating the biological responses induced by GDNF and/or other members of this family of signaling molecules. The results of this work are consistent with the hypothesis of Gas1 acting as a negative modulator of GDNF signaling.