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2.
J Tissue Eng Regen Med ; 13(8): 1375-1393, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31066518

RESUMEN

Diabetes mellitus is a chronic disease characterized by high levels of glucose in the blood, which leads to metabolic disorders with severe consequences. Today, there is no cure for diabetes. The current management for diabetes and derived medical conditions, such as hyperglycemia, cardiovascular diseases, or diabetic foot ulcer, includes life style changes and hypoglycemia-based therapy, which do not fully restore euglycemia or the functionality of damaged tissues in patients. This encourages scientists to work outside their boundaries to develop routes that can potentially tackle such metabolic disorders. In this regard, acellular and cellular approaches have represented an alternative for diabetics, although such treatments still face shortcomings related to limited effectiveness and immunogenicity. The advent of biomaterials has brought significant improvements for such approaches, and three-dimensional extracellular matrix analogs, such as hydrogels, have played a key role in this regard. Advanced hydrogels are being developed to monitor high blood glucose levels and release insulin, as well as serve as a therapeutic technology. Herein, the state of the art in advanced hydrogels for improving treatment of diabetes, from laboratory technology to commercial products approved by drug safety regulatory authorities, will be concisely summarized and discussed.


Asunto(s)
Diabetes Mellitus/terapia , Hidrogeles/uso terapéutico , Animales , Materiales Biocompatibles/química , Células Inmovilizadas/citología , Humanos , Inmunoterapia , Polimerizacion
3.
Front Microbiol ; 9: 1281, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29946316

RESUMEN

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of human tuberculosis (TB), is estimated to be harbored by up to 2 billion people in a latent TB infection (LTBI) state. The only TB vaccine approved for use in humans, BCG, does not confer protection against establishment of or reactivation from LTBI, so new vaccine candidates are needed to specifically address this need. Following the hypothesis that mycobacterial biofilms resemble aspects of LTBI, we modified BCG by deleting the BCG1419c gene to create the BCGΔBCG1419c vaccine strain. In this study, we compared cytokine profiles, bacterial burden, and lung lesions after immunization with BCG or BCGΔBCG1419c before and after 6 months of aerosol infection with M. tuberculosis H37Rv in the resistant C57BL/6 mouse model. Our results show that in infected mice, BCGΔBCG1419c significantly reduced lung lesions and IL-6 in comparison to the unmodified BCG strain, and was the only vaccine that decreased production of TNF-α and IL-10 compared to non-vaccinated mice, while vaccination with BCG or BCGΔBCG1419c significantly reduced IFN-γ production. Moreover, transcriptome profiling of BCGΔBCG1419c suggests that compared to BCG, it has decreased expression of genes involved in mycolic acids (MAs) metabolism, and antigenic chaperones, which might be involved in reduced pathology compared to BCG-vaccinated mice.

4.
Front Microbiol ; 7: 14, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26834732

RESUMEN

Tuberculosis (TB) remains as a global public health problem. In recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by Mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. There are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in TB control programs worldwide and particularly in less developed nations. Regarding vaccines, despite the availability of a live, attenuated strain (Mycobacterium bovis BCG) since almost a century ago, its variable efficacy and lack of protection against pulmonary and latent disease has prompted basic and applied research leading to preclinical and clinical evaluation of up to 15 new candidates. In this work, I present examples of vaccines based on whole cells grown as biofilms, or specific proteins expressed under such condition, and the effect they have shown in relevant animal models or directly in the natural host. I also discuss why it might be worthwhile to explore these approaches, for constructing and developing new vaccine candidates for testing their efficacy against TB.

5.
Vet J ; 190(1): 181-3, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21036080

RESUMEN

This study combines two methodologies - vector expression of a genomic library and proteomics - to identify immunogenic proteins of Mycobacterium bovis. Immunization of BALB/c mice with a plasmid DNA pool from the library, containing approximately 8000 clones, induced a humoral response that facilitated the detection of 12 antigenic proteins by Western blotting. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry identified four proteins (Cpn60-1, HSP70, EF-Tu, and AdoHcyase). Such genomic immunization offers the possibility of in vivo screening of potential candidate M. bovis antigens.


Asunto(s)
Antígenos Bacterianos/genética , ADN Bacteriano/genética , Biblioteca Genómica , Mycobacterium bovis/genética , Proteómica/métodos , Tuberculosis Bovina/diagnóstico , Animales , Antígenos Bacterianos/inmunología , Western Blotting/veterinaria , Bovinos , Clonación Molecular , Electroforesis en Gel de Poliacrilamida/veterinaria , Espectrometría de Masas/veterinaria , Ratones , Ratones Endogámicos BALB C , Mycobacterium bovis/inmunología , Tuberculosis Bovina/genética , Tuberculosis Bovina/inmunología
6.
Salud Publica Mex ; 52(1): 70-8, 2010.
Artículo en Español | MEDLINE | ID: mdl-20464256

RESUMEN

Mycobacterium tuberculosis, the causal agent of tuberculosis, has affected humankind for approximately 20,000 years. Tuberculosis is a devastating disease, particularly in developing countries. One of its most notable characteristics is latent infection, in which live bacilli persist in the host tissues without clinical manifestations. Thus, the tuberculous bacilli adapt their metabolism to remain viable with low or no replication, avoiding their elimination by the immune system or conventional chemotherapy. Among the several problems that are particularly important to the understanding of this form of tuberculosis, and are not well-known, are the key metabolic steps that allow mycobacteria to remain in a dormant state and its interaction with host immunity. This article reviews some of the most significant biological, clinical and epidemiological aspects of this form of tuberculosis.


Asunto(s)
Tuberculosis Latente/epidemiología , Animales , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Proteínas Bacterianas/fisiología , Países en Desarrollo , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Salud Global , Interacciones Huésped-Patógeno , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/inmunología , Macaca fascicularis , México/epidemiología , Ratones , Modelos Animales , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiología , Prevalencia , Factor sigma/fisiología
7.
Salud pública Méx ; 52(1): 70-78, ene.-feb. 2010. tab
Artículo en Español | LILACS | ID: lil-554365

RESUMEN

Mycobacterium tuberculosis afecta a la humanidad desde hace más de 20 000 años. Su morbimortalidad es elevada, por lo que repercute económicamente en los países en desarrollo. La infección latente, caracterizada por la presencia de bacilos vivos en tejidos del huésped, con ausencia de signos y síntomas clínicos, es una característica de esta enfermedad, ya que la micobacteria puede adaptar su metabolismo para mantenerse viva con baja o nula replicación, dificultando su eliminación de los tejidos por los fármacos antituberculosos y permaneciendo inadvertida al reconocimiento y eliminación por el sistema inmunológico. Varias son las interrogantes de esta forma de tuberculosis (TB): la falta de conocimiento del metabolismo del bacilo en estado durmiente, su relación con la inmunidad del hospedero y la identificación de antígenos como marcadores diagnósticos de infección subclínica durante la latencia. Este artículo resume los aspectos biológicos, clínicos y epidemiológicos más importantes de esta forma de tuberculosis.


Mycobacterium tuberculosis, the causal agent of tuberculosis, has affected humankind for approximately 20 000 years. Tuberculosis is a devastating disease, particularly in developing countries. One of its most notable characteristics is latent infection, in which live bacilli persist in the host tissues without clinical manifestations. Thus, the tuberculous bacilli adapt their metabolism to remain viable with low or no replication, avoiding their elimination by the immune system or conventional chemotherapy. Among the several problems that are particularly important to the understanding of this form of tuberculosis, and are not well-known, are the key metabolic steps that allow mycobacteria to remain in a dormant state and its interaction with host immunity. This article reviews some of the most significant biological, clinical and epidemiological aspects of this form of tuberculosis.


Asunto(s)
Animales , Humanos , Ratones , Tuberculosis Latente/epidemiología , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Proteínas Bacterianas/fisiología , Países en Desarrollo , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Interacciones Huésped-Patógeno , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/inmunología , Macaca fascicularis , México/epidemiología , Modelos Animales , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiología , Prevalencia , Factor sigma/fisiología , Salud Global
8.
J Bacteriol ; 187(23): 7918-30, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16291665

RESUMEN

The formation of attaching and effacing (A/E) lesions on intestinal epithelial cells is an essential step in the pathogenesis of human enteropathogenic and enterohemorrhagic Escherichia coli and of the mouse pathogen Citrobacter rodentium. The genes required for the development of the A/E phenotype are located within a pathogenicity island known as the locus of enterocyte effacement (LEE). The LEE-encoded transcriptional regulators Ler, an H-NS-like protein, and GrlA, a member of a novel family of transcriptional activators, positively control the expression of the genes located in the LEE and their corresponding virulence. In this study, we used C. rodentium as a model to study the mechanisms controlling the expression of Ler and GrlA. By deletion analysis of the ler and grlRA regulatory regions and complementation experiments, negative and positive cis-acting regulatory motifs were identified that are essential for the regulation of both genes. This analysis confirmed that GrlA is required for the activation of ler, but it also showed that Ler is required for the expression of grlRA, revealing a novel regulatory loop controlling the optimal expression of virulence genes in A/E pathogens. Furthermore, our results indicate that Ler and GrlA induce the expression of each other by, at least in part, counteracting the repression mediated by H-NS. However, whereas GrlA is still required for the optimal expression of ler even in the absence of H-NS, Ler is not needed for the expression of grlRA in the absence of H-NS. This type of transcriptional positive regulatory loop represents a novel mechanism in pathogenic bacteria that is likely required to maintain an appropriate spatiotemporal transcriptional response during infection.


Asunto(s)
Citrobacter rodentium/genética , Genes Bacterianos/genética , Islas Genómicas/genética , Regulón , Transactivadores , Secuencia de Bases , Citrobacter rodentium/patogenicidad , ADN Intergénico/genética , Regulación Bacteriana de la Expresión Génica , Prueba de Complementación Genética , Datos de Secuencia Molecular , Virulencia
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