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1.
Curr Issues Mol Biol ; 45(5): 3997-4016, 2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37232724

RESUMEN

Cutibacterium acnes (C. acnes) is involved in the pathogenesis of acne by inducing inflammation and biofilm formation, along with other virulence factors. A Camellia sinensis (C. sinensis) callus lysate is proposed to reduce these effects. The aim of the present work is to study the anti-inflammatory properties of a callus extract from C. sinensis on C. acnes-stimulated human keratinocytes and the quorum-quenching activities. Keratinocytes were stimulated with thermo-inactivated pathogenic C. acnes and were treated with the herbal lysate (0.25% w/w) to evaluate its anti-inflammatory effect. C. acnes biofilm was developed in vitro and treated with 2.5 and 5% w/w of the lysate to evaluate quorum sensing and the lipase activity. The results showed that the lysate was able to reduce the production of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine ligand 1 (CXCL1), and decrease the nuclear translocation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB). The lysate did not show bactericidal activity but showed diminished biofilm formation, the lipase activity, and the production of autoinducer 2 (AI-2), a member of a family of signaling molecules used in quorum sensing. Therefore, the proposed callus lysate could have the potential to reduce acne-related symptoms without the eradication of C. acnes, which is part of the natural skin microbiome.

2.
Int J Cancer ; 133(10): 2383-91, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23649867

RESUMEN

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase-polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double-blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases.


Asunto(s)
Neoplasias Endometriales/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Estudios de Casos y Controles , Método Doble Ciego , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Histeroscopía/métodos , Persona de Mediana Edad , Patología Molecular/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Adulto Joven
3.
Antibiotics (Basel) ; 11(12)2022 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-36551409

RESUMEN

Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections.

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