Visible light enhances the antimicrobial effect of some essential oils

The photodisinfection is a topical, broad spectrum antimicrobial technology, targeting bacteria, virus, fungi, and protozoa effective for single cells as for biofilms. Natural molecules have been studied less than synthetic agents in the process but they are currently receiving great interest. Therefore, the aim of this study is to evaluate for the first time if non-coherent blue and red light enhances the antimicrobial activity of some essential oils when standard strains for antibiotic or fungicide tests are enlightened in vitro. Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans collection strains were irradiated with monochromatic visible light from light emitting diodes in the presence of 5% and 0.5% eucalyptus (Eucalyptus globulus), clove (Eugenia caryophyllata), and thyme (Thymus vulgaris) essential oils. Microbial levels were measured by plate count on culture media. In this preliminary report, the results differ according to the kind and concentration of antimicrobial oils, the wavelength of light, and the prokaryotic or eukaryotic microorganism. The results support the idea that mainly blue light enhances the innate antimicrobial activity of the essential oils, especially phenols, and could offer a very efficient and natural way to combat microorganisms in several industries and medical applications.Postprint (author's final draft

Contenidos de isomeros trans de los acidos grasos en productos carnicos. (III) Tejido adiposo y grasa intramuscular de vacuno

Se presentan los resultados obtenidos para la determinación de ácidos grasos en una serie de muestras de tejidos subcutáneo y muscular, procedentes de canales de vacuno, por aplicación de la cromatografía en fase gaseosa, para los que se obtuvieron unos valores medios de 58.7% de ácidos saturados, 39.1 % de monoinsaturados y 2.7% de polinsaturados, en el tejido adiposo, y de 44.7% de saturados, 46.1% de monoinsaturados y 9.4% de polinsaturados, en el tejido muscular. Los contenidos de ácidos grasos trans muestran diferencias significativas entre ambos tejidos (medias del 7% de ácidos trans totales en grasa intramuscular y 10.5% en grasa de depósito). El C18: 1t presenta una distribución paralela a la del total de ácidos trans, mientras que para el C16: 1 trans se observa un comportamiento claramente diferente, ya que no se presentan estas diferencias significativas entre ambos tejidos. En cuanto a los factores estudiados que pueden influir en el contenido de isómeros trans, cabe destacar que la raza fue aquél que ofrecía más diferencias, mientras que entre los diversos orígenes (explotaciones ganaderas) y entre categorías de canal se presentaron menos diferencias en relación a los contenidos de estos isómeros. También es importante destacar que las correlaciones que se han observado entre los contenidos de ácidos trans y los totales de ácidos saturados, mono y polinsaturados presentan un signo contrario, según el tipo de tejido. Así, un aumento del % de ácidos trans va aparejado con un aumento de saturados y una disminución de polinsaturados en el tejido muscular, mientras que va aparejado con una disminución de saturados y un aumento de mono y polinsaturados en el tejido adiposo

Viability qPCR, a new tool for Legionella risk management

Background Viability quantitative Polymerase Chain Reaction (v-qPCR) is a recent analytical approach for only detecting live microorganisms by DNA amplification-based methods This approach is based on the use of a reagent that irreversibly fixes dead cells DNA. In this study, we evaluate the utility of v-qPCR versus culture method for Legionellosis risk management. Methods The present study was performed using 116 real samples. Water samples were simultaneously analysed by culture, v-qPCR and qPCR methods. Results were compared by means of a non-parametric test. Results In 11.6% of samples using both methods (culture method and v-qPCR) results were positive, in 50.0% of samples both methods gave rise to negative results. As expected, equivalence between methods was not observed in all cases, as in 32.1% of samples positive results were obtained by v-qPCR and all of them gave rise to negative results by culture. Only in 6.3% of samples, with very low Legionella levels, was culture positive and v-qPCR negative. In 3.5% of samples, overgrowth of other bacteria did not allow performing the culture. When comparing both methods, significant differences between culture and v-qPCR were in the samples belonging to the cooling towers-evaporative condensers group. The v-qPCR method detected greater presence and obtained higher concentrations of Legionella spp. (p < 0.001). Otherwise, no significant differences between methods were found in the rest of the groups. Conclusions The v-qPCR method can be used as a quick tool to evaluate Legionellosis risk, especially in cooling towers-evaporative condensers, where this technique can detect higher levels than culture. The combined interpretation of PCR results along with the ratio of live cells is proposed as a tool for understanding the sample context and estimating the Legionellosis risk potential according to 4 levels of hierarchy

SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy

Soluble epoxide hydrolase inhibitors: design, synthesis, in vitro profiling and in vivo evaluation in murine models of pain

Trabajo presentado en el ASPET Annual Meeting at Experimental Biology 2022, celebrado en Philadelphia, PA (Estados Unidos), del 2 al 5 de abril de 2022This research by the Grant PID2020-118127RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” to S.V. Financial support from Fundació Bosch i Gimpera, Universitat de Barcelona (F2I grant), to S.V., and from the Xunta de Galicia (ED431G 2019/02 and ED431C 2018/21) to M.I.L. are acknowledged. Partial support was provided by NIH-NIEHS River Award R35 ES03443, NIH-NIEHS Superfund Program P42 ES004699, NINDS R01 DK107767, and NIDDK R01 DK103616 to B.D.H. S.C. acknowledges a PhD fellowship from the Universitat de Barcelona (APIF grant)

Synthesis, in Vitro Profiling, and in Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors

The soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a murine model of capsaicin-induced allodynia. The two compounds showed an anti-allodynic effect in a dose-dependent manner. Moreover, the most potent compound presented robust analgesic efficacy in the cyclophosphamide-induced murine model of cystitis, a well-established model of visceral pain. Overall, these results suggest painful bladder syndrome as a new possible indication for sEHI, opening a new range of applications for them in the visceral pain field

A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer

The immunohistochemical determination of HER-2 to identify patients with advanced breast cancer candidates for Trastuzumab treatment proved neither accurate nor fully reliable, possibly because none of the current reagents detects the specific antigenic site target of Trastuzumab. To circumvent this problem, we conjugated the NH2 groups of Trastuzumab with biotin, and the compound obtained, designated BiotHER, was added directly to tissue sections. Biotin-labelling was revealed with horseradish peroxidase-conjugated streptavidin. Specificity and sensitivity of BiotHER immunostaining with respect to HER-2 amplification were tested on 164 breast carcinoma samples. BiotHER staining was detected on the tumour cell membrane of 12% of all specimens and in 49% specimens with gene amplification, while absent in nonamplified tumours. Predictivity of BiotHER status with respect to the clinical outcome was analysed in 54 patients with HER-2 amplified advanced breast cancer treated with Trastuzumab plus chemotherapy. BiotHER staining, detected in 50% of tumours with HER-2 amplification, was an independent predictor of clinical outcome. In fact, BiotHER positivity was independently associated with increased likelihood of tumour response and reduced risk of tumour progression and death. Biotinylated Trastuzumab can thus be used for immunohistochemical detection of HER-2 overexpression in breast cancer, and has the potential to identify patients likely to benefit from Trastuzumab treatment

Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17

Carbonic anhydrase IX (CA IX) is a transmembrane protein whose expression is strongly induced by hypoxia in a broad spectrum of human tumours. It is a highly active enzyme functionally involved in both pH control and cell adhesion. Its presence in tumours usually indicates poor prognosis. Ectodomain of CA IX is detectable in the culture medium and body fluids of cancer patients, but the mechanism of its shedding has not been thoroughly investigated. Here, we analysed several cell lines with natural and ectopic expression of CA IX to show that its ectodomain release is sensitive to metalloprotease inhibitor batimastat (BB-94) and that hypoxia maintains the normal rate of basal shedding, thus leading to concomitant increase in cell-associated and extracellular CA IX levels. Using CHO-M2 cells defective in shedding, we demonstrated that the basal CA IX ectodomain release does not require a functional TNFα-converting enzyme (TACE/ADAM17), whereas the activation of CA IX shedding by both phorbol-12-myristate-13-acetate and pervanadate is TACE-dependent. Our results suggest that the cleavage of CA IX ectodomain is a regulated process that responds to physiological factors and signal transduction stimuli and may therefore contribute to adaptive changes in the protein composition of tumour cells and their microenvironment