Evaluation of the inhibitory power of extracts obtained from medicinal plants on on pathogenic enterobacteria relevant in public health

Los extractos vegetales pueden ser obtenidos de diferentes partes de las plantas como hojas, tallos, flores y raíces. El interés por los extractos vegetales ha aumentado notablemente por sus propiedades bactericidas, fungicidas y antioxidantes. Por tal motivo, el objetivo del presente trabajo consistió en evaluar el poder inhibitorio de sustancias extraídas de cuatro plantas medicinales: Schinus molle (molle), Sesamum indicum (sésamo) Cinnamomum zeylanicum (canela) y Minthostachys mollis (muña) frente a diez bacterias enterobacterias patógenas. Los extractos se obtuvieron con o sin maceración empleando solventes orgánicos y por extracción acuosa. La metodología de extracción que presentó mayor poder inhibitorio fue la realizada con solventes orgánicos, mientras que las extracciones acuosas fueron las que presentaron un poder menor. En los ensayos de inhibición, el extracto de canela fue el que presentó mayor poder inhibitorio frente a los enterobacterias patógenas, mientras que la combinación de canela con sésamo (1:1) mostró un efecto sinérgico, potenciando la actividad antibacteriana. Además, la canela presentó actividad bactericida frente a Salmonella ser. typhimurium y Salmonella ser. enteritidis.Vegetable extracts can be obtained from different parts of plants such as leaves, stems, flowers and roots. Interest in vegetable extracts has increased significantly due to their bactericidal, fungicidal and antioxidant properties. For this reason, the objective of this work was to evaluate the inhibitory power of the vegetable substances extracted from four medicinal plants: Schinus molle (molle), Sesamum indicum (sesame) Cinnamomum zeylanicum (cinnamon) and Minthostachys mollis (muña) against ten pathogenic enterobacteria. The extracts were obtained with or without maceration with organic solvents and by aqueous extraction. The extraction methodology that presented the highest inhibitory power was that carried out with organic solvents, while the aqueous extractions were those that presented lower inhibitory power. In the inhibition assays, cinnamon extract showed the greatest inhibitory power against pathogenic enterobacteria, while the cinnamon extract combined with sesame (1:1) showed a synergistic effect enhancing antibacterial activity. In addition, cinnamon presented bactericidal effect against Salmonella ser. typhimurium and Salmonella ser. enteritidis.Facultad de Ciencias Veterinaria

Evaluation of the inhibitory power of extracts obtained from medicinal plants on on pathogenic enterobacteria relevant in public health

Los extractos vegetales pueden ser obtenidos de diferentes partes de las plantas como hojas, tallos, flores y raíces. El interés por los extractos vegetales ha aumentado notablemente por sus propiedades bactericidas, fungicidas y antioxidantes. Por tal motivo, el objetivo del presente trabajo consistió en evaluar el poder inhibitorio de sustancias extraídas de cuatro plantas medicinales: Schinus molle (molle), Sesamum indicum (sésamo) Cinnamomum zeylanicum (canela) y Minthostachys mollis (muña) frente a diez bacterias enterobacterias patógenas. Los extractos se obtuvieron con o sin maceración empleando solventes orgánicos y por extracción acuosa. La metodología de extracción que presentó mayor poder inhibitorio fue la realizada con solventes orgánicos, mientras que las extracciones acuosas fueron las que presentaron un poder menor. En los ensayos de inhibición, el extracto de canela fue el que presentó mayor poder inhibitorio frente a los enterobacterias patógenas, mientras que la combinación de canela con sésamo (1:1) mostró un efecto sinérgico, potenciando la actividad antibacteriana. Además, la canela presentó actividad bactericida frente a Salmonella ser. typhimurium y Salmonella ser. enteritidis.Vegetable extracts can be obtained from different parts of plants such as leaves, stems, flowers and roots. Interest in vegetable extracts has increased significantly due to their bactericidal, fungicidal and antioxidant properties. For this reason, the objective of this work was to evaluate the inhibitory power of the vegetable substances extracted from four medicinal plants: Schinus molle (molle), Sesamum indicum (sesame) Cinnamomum zeylanicum (cinnamon) and Minthostachys mollis (muña) against ten pathogenic enterobacteria. The extracts were obtained with or without maceration with organic solvents and by aqueous extraction. The extraction methodology that presented the highest inhibitory power was that carried out with organic solvents, while the aqueous extractions were those that presented lower inhibitory power. In the inhibition assays, cinnamon extract showed the greatest inhibitory power against pathogenic enterobacteria, while the cinnamon extract combined with sesame (1:1) showed a synergistic effect enhancing antibacterial activity. In addition, cinnamon presented bactericidal effect against Salmonella ser. typhimurium and Salmonella ser. enteritidis.Facultad de Ciencias Veterinaria

Therapy free of cells vs human mesenchymal stem cells from umbilical cord stroma to treat the inflammation in OA

[Abstract] Osteoarthritis (OA) is closely linked to the increase in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) is implicated in cartilage degradation. In the last decade, extracellular vesicles (EV) in combination with the use of miRNAs to modify post-transcriptional expressions of multiple genes have shown their utility in new therapies to treat inflammatory diseases. This work delves into the anti-inflammatory effect of extracellular vesicles derived from mesenchymal stem cells (MSC) previously modified to inhibit the expression of miR-21. We compare the efficacy of two treatments, MSC with their miR-21 inhibited through lentiviral transfection and their EV, against inflammation in a new OA animal model. The modified MSC and their EV were intraperitoneally injected in an OA animal model twice. One month after treatment, we checked which therapy was the most effective to reduce inflammation compared with animals untreated. Treated OA model sera were analyzed for cytokines and chemokines. Subsequently, different organs were analyzed to validate the results obtained. EV were the most effective treatment to reduce chemokines and cytokines in serum of OA animals as well as SASP, in their organs checked by proteomic and genomic techniques, compared with MSC alone in a statistically significant way. In conclusion, MSC-miR-21--derived EV showed a higher therapeutic potential in comparison with MSCs-miR-21-. They ameliorate the systemic inflammation through inactivation of ERK1/2 pathway in OA in vivo model. Workflow of the realization of the animal model of OA by injecting cells into the joint cavity of the left knee of the animals, which produces an increase in serum cytokines and chemokines in the animals in addition to the increase in SASP and markers of inflammation. Inhibition of miR-21 in MSCs, from the stroma of the human umbilical cord, by lentivirus and extraction of their EVs by ultracentrifugation. Finally, application of MSC therapy with its miR-21 inhibited or its EVs produces a decrease in serum cytokines and chemokines in the treated animals, in addition to an increase in SASP and markers of inflammation. The cell-free therapy being the one that produces a greater decrease in the parameters studied.Xunta de Galicia; ED481D-2021-020Instituto de Salud Carlos III; PI20/0049

Estado gingival y presencia de bacterias del complejo rojo en escolares de 12 años

The objective of this study was to determine the gingival state and presence of red complex bacteria in saliva samples of 12-year-old schoolchildren. A calibrated periodontist evaluated biofilm index (BI) (Silness and Löe, 1964), presence of calculus, and gingival index (GI) (Silness and Löe, 1967) in sixty two 12-year-old students of Carmen Lyra School. Saliva samples were collected from each student. The DNA of each sample was extracted and amplified by the polymerase chain reaction (PCR) technique, using specific primers. The BI was 1.18. Calculus was present in 40.40% of the schoolchildren examined; 19.4% was supragingival calculus and 21% both supragingival and subgingival calculus. The GI was 0.97, which according to Silness and Löe is mild gingivitis. Gingivitis was present in 96.8% of the children examined. Regarding the PCR tests: 18 of the samples (31.58%) did not present any of the bacteria analyzed and the remaining 39 samples (68.42%) were positive for at least the presence of red complex bacteria. Within the limitations of this study, it is concluded that the prevalence of gingivitis and calculus is high in the sample examined, and the gingival state observed in the study population, may be related to the presence of red complex bacteria.El objetivo de este estudio era determinar el estado gingival y la presencia de bacterias del complejo rojo en muestras de saliva de niños de 12 años de la Escuela Carmen Lyra. Una periodoncista calibrada evaluó en 62 estudiantes de 12 años de la Escuela Carmen Lyra, el índice de biofilme (IB) (Silness y Löe, 1964), la presencia de cálculo y el índice gingival (IG) (Silness y Löe, 1967). Se recolectaron muestras de saliva de cada estudiante. El ADN de cada muestra fue extraído y amplificado por medio de la prueba PCR, empleando primers específicos, para determinar la presencia de bacterias del complejo rojo. El IB fue de 1.18. El cálculo estuvo presente en el 40.40% de la muestra, se encontró 19.4% de cálculo en supragingival y 21% tanto en supragingival como en subgingival. El IG fue de 0.97, que de acuerdo con Silness y Löe es una gingivitis leve. La gingivitis estuvo presente en el 96.8 % de los niños examinados. Con respecto a las pruebas PCR: 18 de las muestras (31.58 %) no presentaron ninguna de las bacterias analizadas y las 39 muestras restantes (68.42 %) fueron positivas por lo menos a la presencia de las bacterias del complejo rojo. Dentro de las limitaciones de este estudio, se concluye que la prevalencia de gingivitis y cálculo es alta en la muestra examinada y el estado gingival observado puede estar relacionado con la presencia de bacterias del complejo rojo.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Vicerrectoría de Docencia::Salud::Facultad de Odontologí

Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis

[Abstract] Background: In the present study, we explored potential protein biomarkers useful to predict the therapeutic response of knee osteoarthritis (KOA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes. Methods: A shotgun proteomic analysis by iTRAQ labelling and liquid chromatography–mass spectrometry (LC-MS/MS) was performed using sera from 40 patients enrolled in the Multicentre Osteoarthritis interVEntion trial with Sysadoa (MOVES). The panel of proteins potentially useful to predict KOA patient’s response was clinically validated in the whole MOVES cohort at baseline (n = 506) using commercially available enzyme-linked immunosorbent assays kits. Logistic regression models and receiver-operating-characteristics (ROC) curves were used to analyze the contribution of these proteins to our prediction models of symptomatic drug response in KOA. Results: In the discovery phase of the study, a panel of six putative predictive biomarkers of response to CS+GH (APOA2, APOA4, APOH, ITIH1, C4BPa and ORM2) were identified by shotgun proteomics. Data are available via ProteomeXchange with identifier PXD012444. In the verification phase, the panel was verified in a larger set of KOA patients (n = 262). Finally, ITIH1 and ORM2 were qualified by a blind test in the whole MOVES cohort at baseline. The combination of these biomarkers with clinical variables predict the patients’ response to CS+GH with a specificity of 79.5% and a sensitivity of 77.1%. Conclusions: Combining clinical and analytical parameters, we identified one biomarker that could accurately predict KOA patients’ response to CS+GH treatment. Its use would allow an increase in response rates and safety for the patients suffering KOA.Insituto de Salud Carlos III; PI14/01707Instituto de Salud Carlos III; PI16/02124Insituto de Salud Carlos III; PI17/00404Instituto de Salud Carlos III; DTS17/00200Instituto de Salud Carlos III; CIBER-CB06/01/0040Insituto de Salud Carlos III; RETIC-RIER-RD16/0012/000

The new pharmacological chaperones PBXs increase α-galactosidase a activity in Fabry disease cellular models

Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal α-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize α-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of α-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of α-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.Fundación Biomédica Galicia Sur | Ref. OT-02-CNFXunta de Galicia | Ref. CN2012 / 18

Action Mechanisms of Small Extracellular Vesicles in Inflammaging [Review]

This article belongs to the Special Issue Extracellular Vesicles Research in Inflamm-Aging[Abstract] The accumulation process of proinflammatory components in the body due to aging influences intercellular communication and is known as inflammaging. This biological mechanism relates the development of inflammation to the aging process. Recently, it has been reported that small extracellular vesicles (sEVs) are mediators in the transmission of paracrine senescence involved in inflammatory aging. For this reason, their components, as well as mechanisms of action of sEVs, are relevant to develop a new therapy called senodrugs (senolytics and senomorphic) that regulates the intercellular communication of inflammaging. In this review, we include the most recent and relevant studies on the role of sEVs in the inflammatory aging process and in age-related diseases such as cancer and type 2 diabetes.J.F.L. was funded by Xunta de Galicia, Grant Number ED481D-2021-020. M.C.A. received a grant from the Spanish National Health Institute Carlos III (PI20/00497)Xunta de Galicia; ED481D-2021-02

NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells

Introduction Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. Methods In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA ⁻ ) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. Results In vitro , we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo , NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo , they exhibited functional properties of leukemia initiating cells. Discussion The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL

Effects of diet on the outcomes of rheumatic and musculoskeletal diseases (RMDs): systematic review and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs

BackgroundA EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed.MethodsSystematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage).ResultsIn total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression.ConclusionThe current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing

Prevalence of Systemic Lupus Erythematosus in Spain: Higher than Previously Reported in other Countries?

[Abstract] Objectives: Prevalence of SLE varies among studies, being influenced by study design, geographical area and ethnicity. Data about the prevalence of SLE in Spain are scarce. In the EPISER2016 study, promoted by the Spanish Society of Rheumatology, the prevalence estimate of SLE in the general adult population in Spain has been updated and its association with sociodemographic, anthropometric and lifestyle variables has been explored. Methods: Population-based multicentre cross-sectional study, with multistage stratified and cluster random sampling. Participants were contacted by telephone to carry out a questionnaire for the screening of SLE. Investigating rheumatologists evaluated positive results (review of medical records and/or telephone interview, with medical visit if needed) to confirm the diagnosis. To calculate the prevalence and its 95% CI, the sample design was taken into account and weighing was calculated considering age, sex and geographic origin. Multivariate logistic regression models were defined to analyse which sociodemographic, anthropometric and lifestyle variables included in the telephone questionnaire were associated with the presence of SLE. Results: 4916 subjects aged 20 years or over were included. 16.52% (812/4916) had a positive screening result for SLE. 12 cases of SLE were detected. The estimated prevalence was 0.21% (95% CI: 0.11, 0.40). SLE was more prevalent in the rural municipalities, with an odds ratio (OR) = 4.041 (95% CI: 1.216, 13.424). Conclusion: The estimated prevalence of SLE in Spain is higher than that described in most international epidemiological studies, but lower than that observed in ethnic minorities in the United States or the United Kingdom