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Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.

Objective: To analyze the clinical records of patients with gastric adenocarcinoma, treated at two different public health institutions in Mexico to determine survival rates. Methods: Cox proportional-hazards model was fitted to identify the factors involved in survival of patients. Result: The results show that subjects aged 41 to 50 years of age had a 56% lower risk of death from gastric cancer compared to those

Background Antibody-mediated immune response plays an important role in protection against reinfection. In the case of SARS-CoV-2 infection, the maximum duration of antibody response is still unknown. In this work, the generation of neutralizing antibodies (NAbs) and IgG antibodies against the S1 subunit (S1 IgG ) of SARS-CoV-2 and their possible duration were determined through decay models. Methods 132 participants with SARS-CoV-2 infection were classified according to the severity of the disease. Seroconversion and persistence of S1 IgG antibodies and NAbs were determined by ELISA, samples were taken at two different times post-infection and duration of those antibodies was estimated using Linear Mixed Models (LMMs). Results The highest amount of S1 IgGs antibodies was associated with age (41 years or older), greater severity of COVID-19 and male gender. NAbs production was associated with the same variables, except for age. The percentage of NAbs decay is higher in the asymptomatic group (P = 0.033), while in S1 IgG antibodies decay, no statistical difference was found between the 4 severity groups. An exponential decay model was built by using a LMM and similarly, two dispersion regions where constructed. The duration of S1 IgG antibodies was 744 days (668–781) for first region and 744 days (453–1231) for the second. Regarding NAbs, an adaptative LMM was used to model a logistic function, determining a duration of 267 days (215–347). Conclusion Humoral immunity to SARS-CoV-2 infection depends on the severity of the disease, gender and age. This immune response could be long-lasting as for other coronaviruses. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01705-7.

Objetivos: Determinar si el lugar de residencia y el grado de marginación se encuentran asociados a la supervivencia al cáncer de próstata. Materiales y métodos: Se incluyeron a todos los pacientes diagnosticados con cáncer de próstata (CP) en el periodo 2013-2017 en un hospital de tercer nivel de atención de Veracruz, México. Los casos expuestos fueron los pacientes que habitualmente residían en zonas rurales, los no expuestos fueron los de zonas urbanas. Se recolectaron variables según características clínico epidemiológicas e histopatológicas. Para medir la supervivencia se utilizó el método de Kaplan Meier y la prueba de Log Rank. Los factores pronósticos fueron determinados calculando hazard ratio ajustado (HRa) en un análisis multivariado mediante el método de riesgos proporcionales de Cox. Resultados: Se analizaron 186 casos de CP. La supervivencia global a 5 años fue de 48,3%. Los hombres que residían en zonas urbanas tuvieron una probabilidad de supervivencia mayor que quienes residían en zonas rurales (HRa 1,67, IC 95%: 1,16-2,41). Asimismo, las personas que vivían en lugares catalogados como zonas de baja marginación tuvieron una mayor probabilidad de supervivencia que quienes vivían en zonas de alta marginación (HRa 2,32, IC 95%: 1,47-3,66). Conclusiones: El lugar de residencia rural se identificó como un factor de mal pronóstico para la supervivencia de pacientes con CP independientemente de otras variables sociodemográficas y clínicas; los pacientes que vivían en lugares con grados de marginación más elevados tuvieron un pronóstico desfavorable de supervivencia.

The respiratory syncytial virus (RSV) is one of the main etiological agents in acute respiratory infections. To date, the replicative cycle of this virus is not completely known, and the events as well as the role of cellular and viral proteins that participate in the infectious cycle of RSV are still a matter of intense research. An important protein that is a control point for many viruses is the helicase eIF4AI, which participates at the beginning of the cap-dependent translation of eukaryotes and cap-independent translation of certain viral mRNAs. Recently, eIF4AI has been considered as a potential viral therapeutic target. In order to understand the role of eIF4AI during the infectious cycle of RSV, we evaluated the effect of eIF4AI knockdown on the amount of positive-strand viral RNA and viral progeny of this virus. Our results showed a decrease for both parameters, suggesting a possible involvement of eIF4AI during replicative cycle of RSV. In addition, using confocal microscopy, it was observed that eIF4AI colocalized with RSV viral protein, supporting the possible participation of eIF4AI during the replicative cycle of RSV. Keywords: eIF4AI; RSV; translation; antiviral.

En las últimas décadas la esperanza de vida del ser humano ha aumentado notablemente como consecuencia del avance en el desarrollo científico y tecnológico. Sin embargo, en México aún existen diversas problemáticas en salud que deben ser atendidas con un enfoque desde la salud pública. Pretendemos en esta obra divulgar algunas de estas problemáticas, describir su impacto actual y mostrar sus desafíos a futuro. La lectura de este libro pretende en parte demostrar la complejidad de los procesos salud-enfermedad y la necesidad de desarrollar aproximaciones multi y transdisciplinarias para su solución. Finalmente, quisiéramos mencionar que pretendemos que esta obra sea la primera de una serie de esfuerzos de divulgación editorial a cargo de expertos, con el objetivo de que el público en general adquiera conocimiento y se desarrolle acciones de empoderamiento con la finalidad de que exija una mejor atención a estas problemáticas de salud y cuide su salud tanto a nivel individual como colectivo.

RESUMEN Objetivo: Efectuar una revision sistematica de estudios originales revisados por pares que contengan datos acerca de la identificacion de SARS-CoV-2 en muestras clinicas de liquido amniotico, placenta o membranas, sangre del cordon umbilical y leche humana de mujeres con diagnostico clinico o confirmado de COVID-19. Para ser incluidos en esta revision sistematica, los estudios debieron ser aceptados despues de la publicacion de la guia para el manejo de pacientes con COVID-19 de la Organizacion Mundial de la Salud (disponible el 13 de marzo de 2020). Resultados: Se incluyeron 17 estudios en los que se identificaron 143 muestras clinicas (38 de liquido amniotico, 34 de placentas o membranas, 39 de sangre del cordon umbilical y 32 de leche humana), de las cuales nueve resultaron positivas para ARN de SARS-CoV-2 (una de liquido amniotico obtenida antes de romper las membranas; seis de placenta o membranas, aunque los autores indican la posibilidad de contaminacion por sangre materna en tres de ellas, y dos de leche humana). Conclusiones: Siguiendo nuestros criterios de busqueda no encontramos estudios que demuestren la deteccion de SARS-CoV-2, en conjunto con el aislamiento viral y la evaluacion de la capacidad infectiva de las particulas virales, en muestras clinicas de liquido amniotico, placenta o membranas, sangre del cordon umbilical y leche humana, de mujeres con diagnostico clinico o confirmado de COVID-19. Sin embargo, la transmision vertical no puede descartarse y se requieren estudios de mayor tamano que empleen idealmente tecnicas de localizacion in situ de ARN y proteina de SARS-CoV-2, asi como de aislamiento viral que compruebe la capacidad infectiva de las particulas virales.

Introduction Young women under 30 years with breast cancer (BC) are an emerging challenge. The purpose is to identify prognostic factors for survival in young women under 30 years of age with BC. Material and methods A retrospective cohort study was conducted among women younger than or equal to 40 years with BC and who were treated at the State Cancer Center during the period 2012–2017. Overall survival was assessed using the Kaplan–Meier method and the log-rank test. Univariate and multivariate analysis assessed survival predictors using Cox proportional hazards regression model. Results 282 young women were included. The >30-year-old subgroup showed a significant association with excess weight ( P = .002) compared to the 5 cm HR = 2.3; 95% CI 1.03 to 5.1), and advanced clinical stages (HR = 6.6 95% CI 1.3 to 35.5) persisted as predictors. Conclusions Being very young (

The causes of the broad spectrum of severity in COVID-19 are unknown. A protective effect through humoral immunity from previous infections by viruses of the SARS-CoV-2 family could explain a mild form of this disease. This study aimed to address whether the presence of antibodies against human seasonal coronaviruses (HCoVs) could prevent severe manifestations of COVID-19. A cross-sectional study was carried out in 165 participants. The presence of pre-existent antibodies against the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 were detected. From all of the seasonal HCoVs studied, it was only found that being seropositive to HCoV-229E presented an association (p = 0.012) with developing mild clinical symptoms of COVID-19 or being asymptomatic. Multinomial regression analysis showed that being seropositive to HCoV-229E is associated with mild or moderate clinical symptoms for COVID-19. Statistical analysis also showed that being female is associated with being asymptomatic for SARS-CoV-2 infection or developing mild COVID-19. A subgroup analysis taking only seropositive to HCoV-229E revealed that females are more likely to develop asymptomatic SARS-CoV-2 infection (OR = 27.242, 95% CI 2.092–354.706, p = 0.012). Our results suggest that previous infections by HCoV-229E could prevent more serious clinical manifestations of COVID-19, but these are not the only variables that influence this event.

Objective To evaluate the use of a sequencing procedure for the entire rpoB gene of Mycobacterium tuberculosis to identify mutations pre-rifampicin resistance determining region (RRDR), within RRDR, and post-RRDR in isolates circulating in a region affected by tuberculosis (TB). Methods Five primers were designed, with which five DNA fragments of rpoB were obtained, sequenced by Sanger, and analysed in silico in order to identify mutations over the entire rpoB gene in rifampicin-sensitive and rifampicin-resistant TB. Results It was possible to analyse the entire rpoB gene in five rifampicin-sensitive and 15 rifampicin-resistant isolates. Thirty-six mutations were identified. Two mutations were found pre-RRDR, nine within-RRDR and 25 post-RRDR. The most frequent mutations within RRDR were S531L (53%), followed by S512T (20%), all of which were found in rifampicin-resistant isolates. Of the 25 mutations found post-RRDR, 14 were only in resistant isolates, and the most frequent was D853N, which was present in 85% of isolates. Mutations E818K, D836N and T882P were observed in 80% of the rifampicin-resistant and rifampicin-sensitive isolates. Conclusions The proposed sequencing method allowed identification of mutations in the entire rpoB gene. This procedure represents a useful tool for diagnosing rifampicin resistance. The number of mutations that were found raises new questions about the diversity of mutations in the rpoB gene and their role in rifampicin resistance in regions where TB is endemic.

Background Chronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications. Methods A cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessments, as well chronic kidney disease diagnosis according to the KDIGO guideline. Urinary MMP-9 was quantified by ELISA and adjusted using urinary creatinine (UCr). Results A total of 111 patients were included. Most participants were women (66%). Mean age was 61 ± 10 years and median T2DM duration was estimated at 11 years. Through multivariate analysis, MMP-9/UCr was found to be associated with albumin concentration and albumin to creatinine ratio. Discussion Validation of non-invasive biomarkers of chronic kidney disease among T2DM patients is necessary. Here, we demonstrate MMP-9/UCr as a potential biomarker of albumin concentration and albumin to creatinine ratio in Mexican patients with T2DM.

To determine if the place of residence and the level of social marginalization are associated with prostate cancer survival.All patients diagnosed with prostate cancer (PC) in the period from 2013 to 2017 in a tertiary healthcare hospital in Veracruz, Mexico were included. Patients resided in rural and urban areas. Variables were collected according to clinical-epidemiological and histopathological characteristics. The Kaplan Meier method and the Log Rank test were used to measure survival. Prognostic factors were determined by calculating the adjusted hazard ratio (HRa) in a multivariate analysis using the Cox proportional risk method.A total of 186 PC cases were analyzed. Overall, after 5 years, 48.3% of the patients survived. Men living in urban areas had a higher probability of survival than those living in rural areas (HRa 1.67, 95% CI 1.16-2.41). Similarly, people living in areas classified as low- marginalization zones had a higher probability of survival than those living in areas with a high level of social marginalization (HRa 2.32, 95% CI 1.47-3.66).To reside in a rural place was identified as a negative prognostic factor for the survival of patients with PC regardless of other sociodemographic and clinical variables; patients living in high-marginalization places had an unfavorable survival prognosis.Determinar si el lugar de residencia y el grado de marginación se encuentran asociados a la supervivencia al cáncer de próstata.Se incluyeron a todos los pacientes diagnosticados con cáncer de próstata (CP) en el periodo 2013-2017 en un hospital de tercer nivel de atención de Veracruz, México. Los casos expuestos fueron los pacientes que habitualmente residían en zonas rurales, los no expuestos fueron los de zonas urbanas. Se recolectaron variables según características clínico epidemiológicas e histopatológicas. Para medir la supervivencia se utilizó el método de Kaplan Meier y la prueba de Log Rank. Los factores pronósticos fueron determinados calculando hazard ratio ajustado (HRa) en un análisis multivariado mediante el método de riesgos proporcionales de Cox.Se analizaron 186 casos de CP. La supervivencia global a 5 años fue de 48,3%. Los hombres que residían en zonas urbanas tuvieron una probabilidad de supervivencia mayor que quienes residían en zonas rurales (HRa 1,67; IC 95%: 1,16-2,41). Asimismo, las personas que vivían en lugares catalogados como zonas de baja marginación tuvieron una mayor probabilidad de supervivencia que quienes vivían en zonas de alta marginación (HRa 2,32; IC 95%: 1,47-3,66).El lugar de residencia rural se identificó como un factor de mal pronóstico para la supervivencia de pacientes con CP independientemente de otras variables sociodemográficas y clínicas; los pacientes que vivían en lugares con grados de marginación más elevados tuvieron un pronóstico desfavorable de supervivencia.

M. tuberculosis stimulates matrix metalloproteinases secretion in the host; however, the patterns of matrix metalloproteinase 9 (MMP-9) and 2 (MMP-2) isoforms are unknown. Therefore, the aim of this study was to evaluate the activities of these isoforms in sputum samples of patients with varying degrees of mycobacterial load. Sputum samples were recovered from individuals with positive and negative diagnosis of tuberculosis. Bacillary load was determined by bacilloscopy, and presence and activity of MMP-2 and MMP-9 isoforms determined by gelatin zymography. Of the recovered samples; 39 were from individuals without tuberculosis and 48 with tuberculosis; 12 had low bacillary and 36 high bacillary load. Participation of MMP-2 isoforms were not observed, but in MMP-9, there was a decrease in the latent, associated with lipocalin and homodimeric isoforms. In contrast, there was a rise in the active isoform, all with statistical significance. In conclusion our results show that MMP-2 isoforms do not seems to be directly involved with tuberculosis evolution of infection. However, variations in MMP-9 isoforms were observed, which coincided with the progression of tuberculosis infection. These results raise questions regarding how MMP-9 isoforms might influence the formation and progression of granuloma, and their use as markers of progression of tuberculosis infection.

Cell migration is the process by which cells move through tissues, and it is crucial to carry out a wide variety of physiological and pathological processes. The study methods to evaluate cell migration are very useful tools for biomedical research. Among these methods, the wound and healing assay is one of the simplest, most economical and is widely used in research. However, one of its disadvantages is that the width and shape of the wound can vary among experimental samples since the scraping is carried out manually, representing a difficult variable to control. In the present article a variant of the razor scrape assay is addressed, which eliminates this variation in the width of the wound, thus facilitating the measurement and comparison using the total area of cell migration.•A method that can be carried out under standard culture conditions.•Avoids the disadvantage of variation in width and shape of the wound.•It constitutes a simple, cheap option and multiple advantages over the traditional method., Graphical abstract Image, graphical abstract

Background The disease Zika is considered as emergent. The infection can be acquired through different routes: a bite from the Aedes mosquito, sexual contact, from mother to child during pregnancy and by blood transfusion. The possibility of Zika transmission through human lactation has been considered. Zika is a disease of great concern for public health because it has been associated with neonatal and postnatal microcephaly, among other birth defects. Objectives To review published evidence of the probable transmission of Zika through human lactation. Data sources Electronic databases: Cochrane Central Register of Controlled Trials, EBSCO, Gale, Science Direct, Scopus, US National Library of Medicine (PubMed) and Web of Science. World Health Organization and Centers for Disease Control and Prevention web pages. Study eligibility criteria To be eligible, studies of any design had to provide primary data of human breast milk as a potential fluid for the transmission of Zika, or primary or secondary follow-up data of infants with at least one previous published study that complied with the first criterion of eligibility. Participants Studies about women with suspected, probable or confirmed Zika during pregnancy, or the postnatal period and beyond. Studies about infants who breastfeed directly from the breast or where fed with the expressed breast milk of the suspected, probable or confirmed women with Zika. Results This study only chose data from research papers; no patients were taken directly by the authors. A total of 1,146 were screened and nine studies were included in the qualitative synthesis, from which a total of 10 cases were identified, with documented follow-up in three of these cases. Through the timing of maternal Zika infection, five cases were classified as prenatal (time before delivery), one as immediate postnatal (period from 0 to 4 days after birth); no cases were classified as medium postnatal (period from 5 days to 8 weeks after birth); two were classified as long postnatal (period from 8 weeks to 6 months after birth) and two as beyond six months after birth. Conclusion Human milk may be considered as a potentially infectious fluid, but we found no currently documented studies of the long-term complications in infants up to 32 months of age, with suspected, probable or confirmed Zika through human lactation, or evidence with respect to the human pathophysiology of the infection acquired through human lactation. In the light of the studies reviewed here, the World Health Organization recommendation of June 29th 2016, remains valid: “the benefits of breastfeeding for the infant and mother outweigh any potential risk of Zika virus transmission through breast milk.”

The helicase eIF4A is part of the cellular eIF4F translation initiation complex. The main functions of eIF4A are to remove secondary complex structures within the 5′-untranslated region and to displace proteins attached to mRNA. As intracellular parasites, viruses regulate the processes involved in protein synthesis, and different mechanisms related to controlling translation factors, such as eIF4A, have been found. The inhibitors of this factor are currently known; these substances could be used in the near future as part of antiviral pharmacological therapies in instances of replication cycles in which eIF4A is required. In this review, the particularities of how some viruses make use of this initiation factor to synthesize their proteins are discussed.

Respiratory syncytial virus (RSV) requires protein biosynthesis machinery to generate progeny. There is evidence that RSV might alter some translation components since stress granules are formed in their host cells. Consistent with these observations, we found that RSV induces dephosphorylation of 4EBP1 (eIF4E-binding protein), an important cellular translation factor. Our results show no correlation between the 4EBP1 dephosphorylation time and the decrease in the global rate of protein synthesis. Interestingly, treatment with rapamycin stimulates virus generation. The results suggest that RSV is a virus that still contains unknown mechanisms involved in the translation of their mRNAs through the alteration or modification of some translation factors, such as 4EBP1, possibly to favor its replicative cycle.

17 páginas, 1 figura, 7 tablas, BACKGROUND: Whole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico. METHODS: WGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized. FINDINGS: Prediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively. Lastly, four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition. CONCLUSIONS: The results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis., CFM-M was a CONACYT fellow of the Maestría en Ciencias de la Salud of the Instituto de Ciencias de la Salud Universidad Veracruzana. RZ-C and IC were partially funded by I-COOP-2017- COOPB2032. RMS was funded by CONACyT-Problemas nacionales grant no. 2015-01-147. XS was funded by GACD-FONCICYT Conacyt No.264693.

To assess the knowledge, attitudes, and practices about the Zika virus in both students and workers at the University of Veracruz, an online survey was conducted. The participants were divided into two groups: one according to sex, the other according to whether they were workers or students. Their answers were classified into knowledge, attitudes, and practices and they were rated as low, medium, and high. The results showed that knowledge about Zika prevailing among the university population is considered as medium in 79.4% of the study population. Most respondents know that the mosquito spreads the Zika virus (98.8%) and the clinical characteristics, while sexual transmission by the virus is little known (36.85%). Both the univariate analysis (OR (CI5) 0.227 (0.070&ndash, 0.735), p = 0.013] and multivariate analysis (OR (CI95) 0.234 (0.071&ndash, 778), p = 0.018] showed that belonging to the health sciences area is related to having a greater knowledge about Zika. Despite the existing knowledge, a low level of prevention practices prevails in the whole community (55%). A medium level of knowledge about Zika prevailed, while proper implementation of preventive measures for Zika is low, despite the fact that the state of Veracruz&mdash, the place where the University is located&mdash, is an endemic area.

Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

The most frequent mutations associated with rifampin and isoniazid resistance in Mycobacterium are the substitutions at codons 531 and 315 in the rpoB and katG genes, respectively. Hence, the aim of this study was to characterize these mutations in Mycobacterium isolates from patients suspected to be infected with drug-resistant (DR) pulmonary tuberculosis (TB) in Veracruz, Mexico. Drug susceptibility testing of 25 clinical isolates revealed that five were susceptible while 20 (80%) were DR (15% of the annual prevalence for Veracruz). Of the DR isolates, 15 (75%) were resistant to rifampin, 17 (85%) to isoniazid and 15 (75%) were resistant to both drugs (MDR). Sequencing analysis performed in the isolates showed that 14 (93%) had mutations in the rpoB gene; seven of these (47%) exhibited a mutation at 531 (S-->L). Ten (58%) of the 20 resistant isolates showed mutations in katG; nine (52%) of these 10 exhibited a mutation at 315 (S-->T). In conclusion, the DR profile of the isolates suggests a significant number of different DR-TB strains with a low frequency of mutation at codons 531 and 315 in rpoB and katG, respectively. This result leads us to consider different regions of the same genes, as well as other genes for further analysis, which is important if a genetic-based diagnosis of DR-TB is to be developed for this region.

Endocrine studies have shown prolactin (PRL) and testosterone (T) regulate prostate function. Both hormones are involved in the diseases of this gland as hyperplasia, dysplasia, and metastatic cancer. Since it has been reported metalloproteinases (MMPs) are underlying processes of metastasis and these are regulated by PRL and T. By histological studies we have detected PRL and T induce hyperplasia in many areas of the rat prostate within one month of treatment. In this work, we evaluated membrane type-1 matrix metalloproteinase (MT1-MMP) mRNA and enzymatic activity of MMP-2 and MMP-9 MMPs at the ventral (PV) and dorsolateral (PDL) prostate of the rat in response to treatments induced with PRL and T for one month. Our preliminary results show not differences of MT1-MMP mRNA expression in all groups at PV and PDL. Although there is a trend of increased MT1-MMP mRNA in groups T and PRL+T at PV, probably in response to an increase of androgen receptor. MMP-2 and MMP-9 were found. In all groups, inactive MMP-2...

Expression of the tissue inhibitor of metalloproteinases-1 (Timp-1) gene can be induced by either phorbol myristate acetate (PMA) or transforming growth factor β1 (TGF-β1), although the signalling pathways involved are not clearly defined. Canonically, histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) or sodium butyrate (NaB) increase total cellular histone acetylation and activate expression of susceptible genes. Remarkably, PMA and TGF-β1 stimulation of Timp-1 show a differential response to TSA or NaB. TSA or NaB potentiate PMA-induced Timp-1 expression but repress TGF-β1-induced Timp-1 expression. The repression of TGF-β1-induced Timp-1 by TSA was maximal at 5 ng·mL−1, while for the superinduction of PMA-induced Timp-1 expression, the maximal dose is > 500 ng·mL−1 TSA. A further HDACi, valproic acid, did not block TGF-β1-induced Timp-1 expression, demonstrating that different HDACs impact on the induction of Timp-1. For either PMA or TGF-β1 to induce Timp-1 expression, new protein synthesis is required, and the induction of AP-1 factors closely precedes that of Timp-1. The effects of the HDACi can be reiterated in transient transfection using Timp-1 promoter constructs. Mutation or deletion of the AP-1 motif (−59/−53) in the Timp-1 promoter diminishes PMA-induction of reporter constructs, however, the further addition of TSA still superinduces the reporter. In c-Jun–/– cells, PMA still stimulates Timp-1 expression, but TSA superinduction is lost. Transfection of a series of Timp-1 promoter constructs identified three regions through which TSA superinduces PMA-induced Timp-1 and we have demonstrated specific protein binding to two of these regions which contain either an avian erythroblastosis virus E26 (v-ets) oncogene homologue (Ets) or Sp1 binding motif.

Matrix metalloproteinases (MMPs) and adamalysins (ADAMs) cleave many extracellular proteins, including matrix, growth factors, and receptors. We profiled the RNA levels of every MMP, several ADAMs, and inhibitors of metalloproteinases (TIMPs and RECK) in numerous mouse tissues during development and in the uterus during pregnancy. Observations include: most secreted MMPs are expressed at low to undetectable levels in tissues, whereas membrane-bound MMPs, ADAMs and inhibitors are abundant; almost every proteinase and inhibitor is present in the uterus or placenta at some time during gestation; the mouse collagenases mColA and mColB are found exclusively in the uterus and testis; and each tissue has its unique signature of proteinase and inhibitor expression.

Background. During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC.Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC.Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (CT) values, as very high (CT≤25), high (CT=26–30), moderate (CT=31–35), low (CT=36–39), or not detected (CT=40). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC.Results. We found a high expression ofMMP1,MMP2,MMP14,TIMP1,andTIMP3; moderate one ofMMP9andMMP25,and low one ofMMP13andMMP24in both tissues. In absolute mRNA levels, significant differences were found in expression ofMMP2,MMP24,andMMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC.Conclusions. We consider thatMMP2,MMP24,andMMP25and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

Summary The Salmonella typhi ompS1 gene codes for an outer membrane protein of the OmpC/OmpF porin family. It is expressed at very low levels, relative to the major porins. However, deletion analysis of the 58 regulatory region showed that the gradual removal of nucleotides π310 to π88, upstream from the P1 major transcriptional start-point, resulted in a stepwise increase in expression, reaching levels 10-fold above those for the ompC major porin gene. Hence, this 222 bp segment contains cis-acting regulatory elements involved in negative control. Primer extension analysis revealed the presence of three promoters: P1 activity was OmpR dependent; P2 was expressed at a lower level in the absence of OmpR; and P3 had a minor constitutive activity. OmpR bound preferentially to box II, an 18 bp F1/C1 canonical site, the removal (π88 to π66) of which resulted in a decrease in expression thus supporting its role in positive control. Expression of ompS1 was not induced by a set of stress conditions, including a shift in osmolarity, nor was the IHF regulator involved in negative control. An ompS1 homologue was found in E. coli K-12, which contains a nonsense codon and a shift in the reading frame, whereas Salmonella typhimurium contains an open reading frame in this region. Thus, S. typhi ompS1 provides novel features in OmpR regulation.

Gastric cancer is a complex disease that involves a range of biological individuals and tumors with histopathological features. The pathogenesis of this disease is multi-factorial and includes the interaction of genetic predisposition with environmental factors. Gastric cancer is normally diagnosed in advanced stages where there are few alternatives to offer and the prognosis is difficult to establish. Metastasis is the leading cause of cancer deaths. Identification of key genes and signaling pathways involved in metastasis and recurrence could predict these events and thereby identify therapeutic targets. In this context, the extracellular matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) represent a potential prognostic tool, because both genetic families regulate growth, angiogenesis, invasion, immune response, epithelial mesenchymal transition and cellular survival. Proteolytic parameters based on MMP/TIMP expression could be useful in the identification of patients with a high probability of developing distant metastases or peritoneal dissemination for each degree of histological malignancy. It is also probable that these parameters can allow improvement in the extent of surgery and dictate the most suitable therapy. We reviewed papers focused on human gastric epithelial cancer as a model and focus on the potential use of MMPs and TIMPs as molecular markers; also we include literature regarding gastric cancer risk factors, classification systems and MMP/TIMP regulation.

Helicobacter pylori (H. pylori) is the etiologic agent of gastritis; it has been estimated that 50 % of the world’s population could be infected by this bacteria. Gastritis may progress to chronic atrophic gastritis, a condition associated with the development of gastric cancer (GC). Several matrix metalloproteases (MMP) and tissue inhibitors of MMPs (TIMP) as well as disintegrins and metalloproteases (ADAM) have been reported as being involved in gastritis. Among other processes, these protein families participate in remodeling the extracellular matrix, cell signaling, immune response, angiogenesis, inflammation and epithelial mesenchymal transition. This systematic review analyzes the scientific evidence surrounding the relationship between members of the MMP, TIMP and ADAM families and infection by H. pylori in gastritis, considering both in vitro and in vivo studies. Given the potential clinical value of certain members of the MMP, TIMP and ADAM families as molecular markers in gastritis and the association of gastritis with GC, the need for further study is highlighted.

The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available.

The human matrix metalloproteinase (MMP) gene family includes 24 genes whose regulated expression, together with that of four tissue inhibitors of metalloproteinases (TIMPs), is essential in tissue remodelling and cell signalling. Quantitative real-time-PCR (qPCR) analysis was used to evaluate the shared and unique patterns of control of these two gene families in human MRC-5 and WI-38 fibroblasts in response to the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA). The requirement for ongoing translation was analysed using three protein synthesis inhibitors, anisomycin, cycloheximide and emetine. PMA induced MMP1, 3, 8, 9, 10, 12, 13, 14 and TIMP1 and TIMP3 RNAs after 4-8 h, and induction of all except MMP9 and TIMP3 was blocked by all protein synthesis inhibitors. However, even though all inhibitors effectively blocked translation, PMA-induction of MMP9 and TIMP3 was blocked by emetine but was insensitive to cycloheximide and anisomycin. Anisomycin alone induced MMP9 and TIMP3, along with MMP25 and MMP19. The extracellular signal-regulated kinases (ERKs)-1/2 were strongly activated by PMA, while anisomycin activated the c-Jun N-terminal kinase (JNK) and p38 pathways, and cycloheximide activated p38, but emetine had no effect on the stress-activated mitogen-activated protein kinase (MAPK) pathways. The involvement of the p38 and JNK pathways in the selective effects of anisomycin and cycloheximide on MMP/TIMP expression was supported by use of pharmacological inhibitors. These data confirm that most inducible MMPs and TIMP1 behave as "late" activated, protein synthesis-dependent genes in fibroblasts. However, the requirement of protein synthesis for PMA-induction of MMPs and TIMPs is not universal, since it is abrogated for MMP9 and TIMP3 by stimulation of the stress-activated MAPK pathways. The definition of clusters of co-regulated genes among the two gene families will aid in bioinformatic dissection of control mechanisms.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibroblast expansion and extracellular matrix accumulation. However, the mechanisms involved in matrix remodeling have not been elucidated. In this study, the authors aimed to evaluate the expression of the tissue inhibitors of matrix metalloproteinases (TIMPs) in human fibroblasts and whole tissues from IPF and normal lungs. They also determined the role of mitogen-activated protein kinase (MAPK) in TIMP3 expression. TIMP1, TIMP2, and TIMP3 were highly expressed in lung fibroblasts. Transforming growth factor (TGF)-beta1, a profibrotic mediator, induced strong up-regulation of TIMP3 at the mRNA and protein levels. The authors examined whether the MAPK pathway was involved in TGF-beta1-induced TIMP3 expression. TGF-beta1 induced the phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2. Biochemical blockade of p38 by SB203580, but not of the ERK MAPK pathway, inhibited the effect of this factor. The effect was also blocked by the tyrosine kinase inhibitor genistein and by antagonizing TGF-beta1 receptor type I (activin-linked kinase [ALK5]). In IPF tissues TIMP3 gene expression was significantly increased and the protein was localized to fibroblastic foci and extracellular matrix. Our findings suggest that TGF-beta1-induced TIMP3 may be an important mediator in lung fibrogenesis.

This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican population.

AIM: To investigate factors associated with gastric cancer (GC) in the Mexican population using a validated questionnaire. METHODS: We designed and validated in Spanish a Questionnaire to Find Factors Associated with Diseases of the Digestive Tract using GC as a model. A cross-sectional study using 49 subjects, with confirmed histopathological GC diagnosis, and 162 individuals without GC participated. Odds ratio and 95% CIs were estimated in univariate and multivariate analysis adjusted for possible confounding factors. In order to match age groups, a multivariate sub-analysis was performed in subjects ≥ 39 years of age and in females and males separately. RESULTS: In the univariate analysis, we found an association between GC and education to primary level or below, low socioeconomic status, the use of dental prostheses, omission of breakfast, consumption of very hot food and drink, addition of salt to prepared foods, consumption of salt-preserved foods and the pattern of alcohol consumption. We found protection against GC associated with the use of mouthwash, food refrigeration and regular consumption of fruit and vegetables. In the multivariate sub-analysis with subjects of ≥ 39 years, the omission of breakfast was identified as a risk factor for GC. CONCLUSION: Our study suggests an association between the omission of breakfast and the failure to refrigerate food with GC in the Mexican population.

AIM: To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. METHODS: MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). RESULTS: 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. CONCLUSION: MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish.

Background Acute respiratory infections (ARIs) cause illness. Children under five years of age are highly vulnerable to these infections. Viral coinfection or multiple viral infection is a variable that can have a significant impact on the evolution of these diseases. Methods This cross-sectional study was carried out in Mexican children (under five years of age) who had an ARI and who were treated by an emergency service in a hospital in Guadalajara, Jalisco, Mexico. The viral etiology, as well as the presence of multiple viral infections, was determined. A structured questionnaire was used to obtain demographic and clinical information. Odds ratio (OR) was calculated, and univariate and multivariate analyses using logistic regression were performed. Results In the study population, metapneumovirus (hMPV) was the most frequent virus (22%), followed by adenovirus (hAD) (16%), respiratory syncytial virus (RSV) (14%), rhinovirus (hRV) (12%), bocavirus (hBoV) (9%), influenza virus (IF) (7%), and parainfluenza (PIF) (4%). The frequency of viral coinfections was 31.62%, and multiple logistic regression analysis revealed that hMPV, RSV, PIF, and hBoV were independently associated with multiple viral infection. No difference was found in the clinical manifestation of children with simple and multiple infections. Simple hMPV infection was associated with patients who presented with severe ARI. Using a multivariate analysis, we found that overcrowding is associated with coinfection when the viral etiology was hRV (OR = 2.56, 95% confidence interval (CI) 1.07 to 6.13), IF (OR = 2.56, 95% CI 1.07 to 6.13), PIF (OR = 2.96, 95% CI 1.15 to 7.65), hAD (OR = 2.56, 95% CI 1.07 to 6.13), and hBoV (OR = 2.9, 95% CI 1.14 to 7.34). Conclusions Viral coinfections are frequent in children requiring treatment by an emergency service. However, the severity of ARI is similar to that of children with a simple infection. The hMPV is common and may confer a significant disease burden in the Mexican population. Finally, overcrowding is a housing characteristic that favors the development of coinfections. Electronic supplementary material The online version of this article (doi:10.1186/s13052-015-0133-7) contains supplementary material, which is available to authorized users.