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1.
iScience ; 27(3): 109191, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38433928

RESUMO

The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

2.
J Vis Exp ; (201)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38047572

RESUMO

Acquiring fresh and well-characterized tumor tissue samples is critical for conducting high-quality "omics" studies. However, it can be particularly challenging in the context of prostate cancer (PC) due to the unique nature of this organ and the high heterogeneity associated with this tumor. On the other hand, histopathologically characterizing samples before their storage without causing significant tissue alterations is also an intriguing challenge. In this context, we present a new method for acquiring, mapping, characterizing, and micro-dissecting resected prostate tissue based on anatomopathological criteria. Unlike previously published protocols, this method reduces the time required for histopathological analysis of the prostate specimen without compromising its structure, which is crucial for assessing surgical margins. Furthermore, it enables the delineation and micro-macro dissection of fresh prostate tissue samples, with a focus on histological tumor areas defined by pathological criteria such as Gleason score, precursor lesions (high-grade prostatic intraepithelial neoplasia - PIN), and inflammatory lesions (prostatitis). These samples are then stored in a Biobank for subsequent research analyses.


Assuntos
Neoplasia Prostática Intraepitelial , Neoplasias da Próstata , Masculino , Humanos , Bancos de Espécimes Biológicos , Reprodutibilidade dos Testes , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasia Prostática Intraepitelial/patologia , Próstata/cirurgia , Próstata/patologia
3.
Environ Microbiol ; 25(12): 2988-3010, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37718389

RESUMO

Plants produce a variety of secondary metabolites in response to biotic and abiotic stresses. Although they have many functions, a subclass of toxic secondary metabolites mainly serve plants as deterring agents against herbivores, insects, or pathogens. Microorganisms present in divergent ecological niches, such as soil, water, or insect and rumen gut systems have been found capable of detoxifying these metabolites. As a result of detoxification, microbes gain growth nutrients and benefit their herbivory host via detoxifying symbiosis. Here, we review current knowledge on microbial degradation of toxic alkaloids, glucosinolates, terpenes, and polyphenols with an emphasis on the genes and enzymes involved in breakdown pathways. We highlight that the insect-associated microbes might find application in biotechnology and become targets for an alternative microbial pest control strategy.


Assuntos
Alcaloides , Insetos , Animais , Insetos/fisiologia , Plantas/metabolismo , Alcaloides/metabolismo , Herbivoria/fisiologia , Simbiose
4.
Medisur ; 12(5): 709-716, oct. 2014.
Artigo em Espanhol | LILACS | ID: lil-760299

RESUMO

Fundamento: la morbilidad por diabetes mellitus se incrementa de modo sostenido. Esta enfermedad se caracteriza por el deterioro progresivo de múltiples funciones metabólicas y es propensa a desarrollar enfermedades bucales. Objetivo: caracterizar el estado de salud bucal de pacientes diabéticos. Métodos: se realizó un estudio descriptivo, de serie de casos, durante el período de enero de 2010 a marzo de 2011, con una población de 120 pacientes diabéticos atendidos en la Clínica Estomatológica Docente Mártires de Sagua. Algunas de las variables analizadas fueron: tiempo de evolución de la diabetes mellitus, enfermedades bucodentales, indicadores epidemiológicos, higiene bucal, entre otros. Resultados: las afecciones bucodentales más frecuentes fueron: enfermedad periodontal, caries dental, disfunción masticatoria y estomatitis subprótesis. La relación entre el tiempo de evolución de la diabetes mellitus y las enfermedades bucodentales, mostró alta significación estadística. Los valores del índice de COP-D aumentaron en la misma medida que la edad. El índice de mortalidad dentaria mostró un promedio total de 13,8, con mayor afectación del grupo de 80 y más años con 24,5. Los factores de riesgo más sobresalientes fueron: higiene bucal deficiente, antecedentes de caries, dientes ausentes sin remplazo, entre otros. Conclusión: los pacientes diabéticos deben tener presente el control de su enfermedad, así como tomar especial cuidado respecto a su higiene bucal, pues con ello disminuyen el riesgo de caer en complicaciones que pueden estar relacionadas con enfermedades bucodentales.


Background: morbidity due to diabetes mellitus is increasing steadily. This disease is characterized by progressive impairment of multiple metabolic functions and is likely to cause oral diseases. Objective: to characterize the oral health status of diabetic patients. Methods: a case series study involving 120 diabetic patients treated at the Mártires de Sagua Teaching Dental Clinic was conducted from January 2010 to March 2011. The variables analyzed included: duration of diabetes mellitus, oral diseases, epidemiological indicators, oral hygiene, among others. Results: the most common oral diseases were: periodontal disease, dental cavities, masticatory dysfunction and denture stomatitis. The relationship between the duration of diabetes mellitus and oral diseases showed high statistical significance. DMFT values increased with age. Tooth mortality rate showed an overall average of 13.8, the group aged 80 years and over was the most affected with 24.5. The most significant risk factors were: poor oral hygiene, history of dental cavities, missing teeth without replacement, among others. Conclusion: diabetic patients should consider the control of their disease and take care of their oral hygiene, thus the risk of complications related to oral diseases decreases.

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