Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.

Cordycepin, or 3'-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3' position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3' position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin's mechanism of action.

Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old / Signo de Frank asociado con la gravedad de la cardiopatía isquémica en adultos de edad inferior o igual a 65 años

Background and objective Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. Patients and methods A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. Results We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 28–65). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.98–5.38), p≤0.001, male gender OR 2.28; 95% CI (1.20–4.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.11–2.97), p=0.017. Conclusions There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention (AU)

Antecedentes y objetivo El signo de pliegue diagonal de la oreja o signo de Frank se ha asociado con cardiopatía isquémica. El objetivo de este trabajo fue evaluar la relación del signo de Frank con la gravedad de la cardiopatía isquémica en adultos≤65años en el noreste de México. Pacientes y métodos Se realizó un estudio transversal en pacientes ≤65años sometidos a coronariografía de manera consecutiva en un periodo de 5 meses en 2022. Se relacionó la enfermedad arterial coronaria (EAC) grave con el signo de Frank y los factores de riesgo cardiovascular tradicionales. Para determinar la asociación se realizó análisis bivariado y multivariado mediante regresión logística que incluyó las variables con valor de p<0,05. El análisis estadístico se realizó con el programa SPSS versión 22. Resultados Se incluyeron 311 pacientes≤65años, de los cuales el 80% fueron hombres. La mediana de edad fue 57 años (rango de 28-65 años). El 62% de los pacientes presentó el signo de Frank. Las principales características clínicas en pacientes con signo de Frank fueron diabetes mellitus tipo 2 (55%), p=0,003, dislipidemia (53%), p=0,026 y tabaquismo (68%), p=0,002. En el análisis multivariado las variables independientes asociadas a EAC grave fueron el signo de Frank (OR: 3,26; IC 95%: 1,98-5,38; p≤0,001), sexo masculino (OR: 2,28; IC 95%: 1,20-4,35; p=0,012) y dislipidemia (OR: 1,81; IC 95%: 1,11-2,97; p=0,017). Conclusiones Existe asociación independiente del signo de Frank con la presencia de EAC grave en pacientes≤65años, que puede ser útil para el cribado y la prevención (AU)

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.

Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer.

[Educational intervention on organ and tissue donation at UMAE No. 34]. / Intervención educativa sobre donación de órganos y tejidos en la UMAE No. 34.

Background: The lack of information associated with donation is devastating for those patients in need of a transplant and requires a solution based on changing social perception through educational interventions. Objective: Determine the level of knowledge of the general population after an educational intervention about organ and tissue donation at the Hospital de Cardiología UMAE No. 34. Methods: Educational intervention study with measurement before and after, prospective. Instrument validated using the Kuder-Richardson formula with a reliability coefficient of 0.74. The study population was made up of the general population in the waiting rooms at UMAE No. 34, only the associations with values of p < 0.05 were considered statistically significant. Results: 266 evaluation instruments were applied to 133 participants. The educational intervention contributed to an increase in the level of knowledge (p = 0.0001). The level of knowledge after the intervention was higher in the younger participants (p = 0.013) and in those with a university studies (p = 0.0001). The relation between age and the level of subsequent knowledge showed favorable significance in the intention to donate in younger participants with high subsequent knowledge (p = 0.046). Conclusions: An educational intervention on donation of organs and tissues for transplant purposes is an effective strategy to increase and reinforce the knowledge of the general population.

Introducción: la falta de información relacionada con la donación de órganos y tejidos resulta devastadora para aquellos pacientes en necesidad de un trasplante, y requiere de una solución basada en el cambio de percepción social mediante intervenciones educativas. Objetivo: determinar el nivel de conocimiento de la población general posterior a una intervención educativa sobre la donación de órganos y tejidos en el Hospital de Cardiología No. 34. Métodos: estudio de intervención educativa con medición antes y después, prospectivo. Instrumento validado mediante fórmula de Kuder-Richardson con coeficiente de fiabilidad de 0.74. La población de estudio se conformó por la población general en las salas de espera de la UMAE No. 34. Las asociaciones con valores de p < 0.05 se consideraron estadísticamente significativas. Resultados: se aplicaron 266 instrumentos de evaluación en 133 participantes. La intervención educativa contribuyó a aumentar el nivel de conocimiento (p = 0.0001). El nivel de conocimiento posterior a la intervención fue mayor en los participantes jóvenes (p = 0.013) y en aquellos con estudios universitarios (p = 0.0001). La relación entre la edad y el nivel de conocimiento posterior mostró significancia favorable en la intención de donación en jóvenes con conocimiento posterior alto (p = 0.046). Conclusiones: una intervención educativa sobre la donación de órganos y tejidos con fines de trasplantes es una estrategia eficaz para aumentar y reforzar el conocimiento de la población general.

Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old.

BACKGROUND AND OBJECTIVE: Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. PATIENTS AND METHODS: A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. RESULTS: We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 28-65). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.98-5.38), p≤0.001, male gender OR 2.28; 95% CI (1.20-4.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.11-2.97), p=0.017. CONCLUSIONS: There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention.

Identification of variants in genes associated with hypertrophic cardiomyopathy in Mexican patients.

The objective of this work was to identify genetic variants in Mexican patients diagnosed with hypertrophic cardiomyopathy (HCM). According to world literature, the genes mainly involved are MHY7 and MYBPC3, although variants have been found in more than 50 genes related to heart disease and sudden death, and to our knowledge there are no studies in the Mexican population. These variants are reported and classified in the ClinVar (PubMed) database and only some of them are recognized in the Online Mendelian Information in Men (OMIM). The present study included 37 patients, with 14 sporadic cases and 6 familial cases, with a total of 21 index cases. Next-generation sequencing was performed on a predesigned panel of 168 genes associated with heart disease and sudden death. The sequencing analysis revealed twelve (57%) pathogenic or probably pathogenic variants, 9 of them were familial cases, managing to identify pathogenic variants in relatives without symptoms of the disease. At the molecular level, nine of the 12 variants (75%) were single nucleotide changes, 2 (17%) deletions, and 1 (8%) splice site alteration. The genes involved were MYH7 (25%), MYBPC3 (25%) and ACADVL, KCNE1, TNNI3, TPM1, SLC22A5, TNNT2 (8%). In conclusion; we found five variants that were not previously reported in public databases. It is important to follow up on the reclassification of variants, especially those of uncertain significance in patients with symptoms of the condition. All patients included in the study and their relatives received family genetic counseling.

[Donation in the Cardiology Hospital No. 34]. / Donación en el Hospital de Cardiología No. 34.

BACKGROUND: Chronic degenerative diseases have become a challenge for the Mexican health system. Faced with this problem, health institutions have focused on the therapeutic potential of organ and tissue donation and transplantation. OBJECTIVE: To analyze the experience of the donation program and to identify areas of opportunity at the Hospital de Cardiología No. 34 (Hospital of Cardiology Number 34), in Monterrey, Nuevo León, Mexico. MATERIAL AND METHODS: Observational, cross-sectional, and retrospective study. The study population was made up by deaths and successful interviews. Only groupings with values of p < 0.05 were considered statistically significant. RESULTS: A global of 1947 deaths were registered and a total of 210 interviews were carried out; 83 (39.5%) family members accepted to donate and 127 (60.5%) refused to donate. Only 3 associations between variables had significant statistical value. The year was an important determinant in the increase in effective donations (p = 0.010), and so was the month of the year (p = 0.037), obtaining more positive interviews in the second half of the year; finally, the shift also contributed to the family response (p = 0.012), with the morning shift being the best shift to conduct a successful family interview. CONCLUSIONS: It is imperative to conduct studies that analyze and describe the experience of donation programs to promote and encourage the value of donation.

INTRODUCCIÓN: las enfermedades crónico-degenerativas se han convertido en un desafío para el sistema de salud mexicano. Frente a este problema, las instituciones sanitarias se han enfocado en el potencial terapéutico de la donación y el trasplante de órganos y tejidos. OBJETIVO: analizar la experiencia del programa de donación e identificar áreas de oportunidad en el Hospital de Cardiología No. 34, en Monterrey, Nuevo León, México. MATERIAL Y MÉTODOS: estudio observacional, transversal y retrospectivo. La población de estudio se conformó por defunciones y entrevistas exitosas. Únicamente agrupaciones con valores de p < 0.05 se consideraron estadísticamente significativas. RESULTADOS: se registró un global de 1947 defunciones y se efectuaron en total 210 entrevistas; 83 (39.5%) disponentes secundarios aceptaron donar y 127 (60.5%) se negaron. Solo tres asociaciones entre variables tuvieron valor estadístico significativo. El año fue un determinante importante en el incremento de las donaciones efectivas (p = 0.010) y también lo fue el mes del año (p = 0.037), pues se obtuvieron más entrevistas positivas en el segundo semestre del año; finalmente, el turno también contribuyó en la respuesta familiar (p = 0.012) y fue el turno matutino el mejor para hacer una entrevista familiar exitosa. CONCLUSIONES: es imperativo llevar a cabo estudios que analicen y describan la experiencia del programa de donación para promover y fomentar el valor de la donación.

Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure.

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0-F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1-F3), and a decrease in the quality of sperm (F0-F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium abscessus: a model to study antimycobacterial agents.

BACKGROUND: Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model using organotypic cultures of murine precision-cut lung slices, an experimental model in which metabolic activity, and all the usual cell types of the organ are found while the tissue architecture and the interactions between the different cells are maintained. METHODS: Precision cut lung slices (PCLS) were prepared from the lungs of wild type BALB/c mice using the Krumdieck® tissue slicer. Lung tissue slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 µg/mL) and tigecycline (0.25, 1 and 4 µg/mL), at 12, 24 and 48 h. Afterwards, CFUs were determined plating on blood agar to measure the surviving intracellular bacteria. The viability of PCLS was assessed by Alamar Blue assay and corroborated using histopathological analysis. RESULTS: PCLS were successfully infected with a virulent strain of M. abscessus as demonstrated by CFUs and detailed histopathological analysis. The time-course infection, including tissue damage, parallels in vivo findings reported in genetically modified murine models for M. abscessus infection. Tigecycline showed a bactericidal effect at 48 h that achieved a reduction of > 4log10 CFU/mL against the intracellular mycobacteria, while imipenem showed a bacteriostatic effect. CONCLUSIONS: The use of this new organotypic ex vivo model provides the opportunity to test new drugs against M. abscessus, decreasing the use of costly and tedious animal models.

Curcumin Attenuates the Pathogenicity of Entamoeba histolytica by Regulating the Expression of Virulence Factors in an Ex-Vivo Model Infection.

Infection with the enteric protozoan Entamoeba histolytica is still a serious public health problem, especially in developing countries. Amoebic liver abscess (ALA) is the most common extraintestinal manifestation of the amoebiasis, and it can lead to serious and potentially life-threatening complications in some people. ALA can be cured by metronidazole (MTZ); however, because it has poor activity against luminal trophozoites, 40-60% of treated patients get repeated episodes of invasive disease and require repeated treatments that can induce resistance to MTZ, this may emerge as an important public health problem. Anti-virulence strategies that impair the virulence of pathogens are one of the novel approaches to solving the problem. In this study, we found that low doses of curcumin (10 and 50 µM) attenuate the virulence of E. histolytica without affecting trophozoites growth or triggering liver injury. Curcumin (CUR) decreases the expression of genes associated with E. histolytica virulence (gal/galnac lectin, ehcp1, ehcp5, and amoebapore), and is correlated with significantly lower amoebic invasion. In addition, oxidative stress is critically involved in the etiopathology of amoebic liver abscess; our results show no changes in mRNA expression levels of superoxide dismutase (SOD) and catalase (CAT) after E. histolytica infection, with or without CUR. This study provides clear evidence that curcumin could be an anti-virulence agent against E. histolytica, and makes it an attractive potential starting point for effective treatments that reduce downstream amoebic liver abscess.

Protective effects of phenolic acids on mercury-induced DNA damage in precision-cut kidney slices.

OBJECTIVES: Precision-cut tissue slices are considered an organotypic 3D model widely used in biomedical research. The comet assay is an important screening test for early genotoxicity risk assessment that is mainly applied on in vitro models. The aim of the present study was to provide a 3D organ system for determination of genotoxicity using a modified method of the comet assay since the stromal components from the original tissue make this technique complicated. MATERIALS AND METHODS: A modified comet assay technique was validated using precision-cut hamster kidney slices to analyze the antigenotoxic effect of the phenolic compounds caffeic acid, chlorogenic acid, and rosmarinic acid in tissue slices incubated with 15 µM HgCl2. Cytotoxicity of the phenolic compounds was studied in Vero cells, and by morphologic analysis in tissue slices co-incubated with HgCl2 and phenolic compounds. RESULTS: A modification of the comet assay allows obtaining better and clear comet profiles for analysis. Non-cytotoxic concentrations of phenolic acids protected kidney tissue slices against mercury-induced DNA damage, and at the same time, were not nephrotoxic. The highest protection was provided by 3 µg/ml caffeic acid, although 6 µg/ml rosmarinic and 9 µg/ml chlorogenic acids also exhibited protective effects. CONCLUSION: This is the first time that a modification of the comet assay technique is reported as a tool to visualize the comets from kidney tissue slices in a clear and simple way. The phenolic compounds tested in this study provided protection against mercury-induced genotoxic damage in precision-cut kidney slices.

Development of a Novel Ex-vivo 3D Model to Screen Amoebicidal Activity on Infected Tissue.

Amoebiasis is a parasitic disease that causes thousands of deaths every year, its adverse effects and resistance to conventional treatments have led to the search of new treatment options, as well as the development of novel screening methods. In this work, we implemented a 3D model of intestine and liver slices from hamsters that were infected ex vivo with virulent E. histolytica trophozoites. Results show preserved histology in both uninfected tissues as well as ulcerations, destruction of the epithelial cells, and inflammatory reaction in intestine slices and formation of micro abscesses, and the presence of amoebae in the sinusoidal spaces and in the interior of central veins in liver slices. The three chemically synthetized compounds T-001, T-011, and T-016, which act as amoebicides in vitro, were active in both infected tissues, as they decreased the number of trophozoites, and provoked death by disintegration of the amoeba, similar to metronidazole. However, compound T-011 induced signs of cytotoxicity to liver slices. Our results suggest that ex vivo cultures of precision-cut intestinal and liver slices represent a reliable 3D approach to evaluate novel amoebicidal compounds, and to simultaneously detect their toxicity, while reducing the number of experimental animals commonly required by other model systems.

Antitumoral Effect of Laurinterol on 3D Culture of Breast Cancer Explants.

Macroalgae represent an important source of bioactive compounds with a wide range of biotechnological applications. Overall, the discovery of effective cytotoxic compounds with pharmaceutical potential is a significant challenge, mostly because they are scarce in nature or their total synthesis is not efficient, while the bioprospecting models currently used do not predict clinical responses. Given this context, we used three-dimensional (3D) cultures of human breast cancer explants to evaluate the antitumoral effect of laurinterol, the major compound of an ethanolic extract of Laurencia johnstonii. To this end, we evaluated the metabolic and histopathological effects of the crude extract of L. johnstonii and laurinterol on Vero and MCF-7 cells, in addition to breast cancer explants. We observed a dose-dependent inhibition of the metabolic activity, as well as morphologic and nuclear changes characteristic of apoptosis. On the other hand, a reduced metabolic viability and marked necrosis areas were observed in breast cancer explants incubated with the crude extract, while explants treated with laurinterol exhibited a heterogeneous response which was associated with the individual response of each human tumor sample. This study supports the cytotoxic and antitumoral effects of laurinterol in in vitro cell cultures and in ex vivo organotypic cultures of human breast cancer explants.

Breast Organotypic Cancer Models.

Breast cancer is the most common cancer type diagnosed in women, it represents a critical public health problem worldwide, with 1,671,149 estimated new cases and nearly 571,000 related deaths. Research on breast cancer has mainly been conducted using two-dimensional (2D) cell cultures and animal models. The usefulness of these models is reflected in the vast knowledge accumulated over the past decades. However, considering that animal models are three-dimensional (3D) in nature, the validity of the studies using 2D cell cultures has recently been questioned. Although animal models are important in cancer research, ethical questions arise about their use and usefulness as there is no clear predictivity of human disease outcome and they are very expensive and take too much time to obtain results. The poor performance or failure of most cancer drugs suggests that preclinical research on cancer has been based on an over-dependence on inadequate animal models. For these reasons, in the last few years development of alternative models has been prioritized to study human breast cancer behavior, while maintaining a 3D microenvironment, and to reduce the number of experiments conducted in animals. One way to achieve this is using organotypic cultures, which are being more frequently explored in cancer research because they mimic tissue architecture in vivo. These characteristics make organotypic cultures a valuable tool in cancer research as an alternative to replace animal models and for predicting risk assessment in humans. This chapter describes the cultures of multicellular spheroids, organoids, 3D bioreactors, and tumor slices, which are the most widely used organotypic models in breast cancer research.

Expression of NK Cell Surface Receptors in Breast Cancer Tissue as Predictors of Resistance to Antineoplastic Treatment.

BACKGROUND: Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells. However, the role of NK cells in resistance to systemic therapy in breast cancer remains unclear. The present project aims to evaluate the gene expression profile of human NK cells in breast cancer tissue resistant to treatment with taxanes-anthracyclines. METHODS: Biopsies from tumor tissues were obtained from patients with breast cancer without prior treatment. Histopathological analysis and ex vivo exposure to antineoplastic chemotherapeutics were carried out. Alamar blue and lactate dehydrogenase release assays were performed for quantitative analysis of tumor viability. Gene expression profiles from tumor tissues without prior exposure to therapeutic drugs were analyzed by gene expression microarrays and verified by polymerase chain reaction. RESULTS: A significant decrease in gene expression of cell-surface receptors related to NK cells was observed in tumor samples resistant to antineoplastic treatment compared with those that were sensitive to treatment. CONCLUSION: A decrease in NK cell infiltration into tumor tissue might be a predictive marker for failure of chemotherapeutic treatment in breast cancer.

Modeling tuberculosis pathogenesis through ex vivo lung tissue infection.

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Several in vitro and in vivo experimental models have been used to study TB pathogenesis and induction of immune response during Mycobacterium tuberculosis infection. Precision cut lung tissue slices (PCLTS) is an experimental model, in which all the usual cell types of the organ are found, the tissue architecture and the interactions amongst the different cells are maintained. PCLTS in good physiological conditions, monitored by MTT assay and histology, were infected with either virulent Mycobacterium tuberculosis strain H37Rv or the TB vaccine strain Mycobacterium bovis BCG. Histological analysis showed that bacilli infecting lung tissue slices were observed in the alveolar septa, alveolar light spaces, near to type II pneumocytes, and inside macrophages. Mycobacterial infection of PCLTS induced TNF-α production, which is consistent with previous M. tuberculosis in vitro and in vivo studies. This is the first report of using PCLTS as a system to study M. tuberculosis infection. The PCLTS model provides a useful tool to evaluate the innate immune responses and other aspects during the early stages of mycobacterial infection.

[Myocardial infarction in young mexicans associated to metabolic syndrome]. / Infarto agudo al miocardio en jóvenes mexicanos asociado a síndrome metabólico.

BACKGROUND: Acute coronary diseases are catastrophic, especially in young patients. OBJECTIVE: To determine the risk of metabolic syndrome (MS) for premature acute myocardial infarction (AMI), combined with familial, behavioral, and nutritional factors in the northeast of Mexico. MATERIAL AND METHODS: This is a case control study of patients less than 47 years of age with no personal history of angina, AMI, or cerebrovascular disease. Cases corresponded to patients with AMI (incident and primary cases; n = 55) and controls were blood donors located at the same hospital (n = 55). Behavioral, nutritional, and cardiometabolic risk factors were measured. Multivariate logistic regression was used for estimating odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: MS increased the risk for premature AMI (95% CI: 1.73-39.5) eightfold, followed by smoking (OR: 7.76; 95% CI: 1.27-47.3), family history of AMI or sudden death (OR: 11.0; 95% CI: 2.03-60.4), and sedentary lifestyle (OR: 2.26; 95% CI: 2.52-9.80), independent of potential confounders. CONCLUSIONS: The study highlights the magnitude of the risk of MS for AMI in Mexican young adults. The phenomenon of coronary diseases among young adults needs essential attention from the health sector.

Organotypic culture of breast tumor explants as a multicellular system for the screening of natural compounds with antineoplastic potential.

Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control) decreased significantly (P < 0.05); however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.