Evaluation of the antimicrobial and antioxidant activities of essential oils, extracts and their main components from oregano from Madeira Island, Portugal

Origanum vulgare subsp. virens growing wild in Madeira Island, Portugal was studied within the ongoing investigations on polymorphic Lamiaceae species. The antimicrobial activity of the essential oils and n-hexane extracts of origanum was determined against 10 strains of bacteria and yeasts, found as human pathogenic or food spoilage microorganisms. The essential oils, n-hexane extracts and isolated compounds showed moderately activity, compared to standard antibiotics, inhibiting all tested bacteria except Pseudomonas aeruginosa. The most sensitive microorganism was Mycobacterium smegmatis, reaching MIC ¼ 25 mg mL 1 . The results obtained suggest a potential application of these oils in pre venting the human pathogenic and food spoilage due to microorganism’s growth. The essential oils and n-hexane extracts have greater RSC than polar extracts, probably due to the high contents in thymol, which demonstrated the highest activity in the DPPH assay. All studied origanum samples showed a large content in non-esterified 1-hexacosanol, C26H54O, accumulated mainly in bracts and flowersinfo:eu-repo/semantics/publishedVersio

Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT) process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors.</p> <p>Findings</p> <p>We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE) was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus.</p> <p>Conclusions</p> <p>The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.</p

Ergebnisse und Herausforderungen der Arbeit in Theorie-Praxis-Netzwerken

In diesem Kapitel ziehen wir eine Zwischenbilanz nach fünf Jahren Arbeit in Theorie-Praxis-Netzwerken im Rahmen des Projekts „Zukunftszentrum Lehrkräftebildung-Netzwerk“ (ZZL-Netzwerk) der „Qualitätsoffensive Lehrerbildung“ (2016 bis 2021). Wir bilanzieren, welche Arbeitsweisen und Formen der Kooperation sich in dem Projekt bewährt haben (Abschnitt 1), welche Ergebnisse und Produkte entstanden sind (Abschnitt 2) und welche theoretischen und praktischen Erkenntnisse gewonnen werden konnten (Abschnitt 3). Die besonderen Herausforderungen, die sich für die weitere Arbeit in dem Projekt stellen, werden in Abschnitt 4 beschrieben. Das Kapitel schließt mit einem kurzen Fazit (Abschnitt 5)

Application of an artificial intelligence-based tool in [18F]FDG PET/CT for the assessment of bone marrow involvement in multiple myeloma

Purpose: [18F]FDG PET/CT is an imaging modality of high performance in multiple myeloma (MM). Nevertheless, the inter-observer reproducibility in PET/CT scan interpretation may be hampered by the different patterns of bone marrow (BM) infiltration in the disease. Although many approaches have been recently developed to address the issue of standardization, none can yet be considered a standard method in the interpretation of PET/CT. We herein aim to validate a novel three-dimensional deep learning-based tool on PET/CT images for automated assessment of the intensity of BM metabolism in MM patients. Materials and methods: Whole-body [18F]FDG PET/CT scans of 35 consecutive, previously untreated MM patients were studied. All patients were investigated in the context of an open-label, multicenter, randomized, active-controlled, phase 3 trial (GMMG-HD7). Qualitative (visual) analysis classified the PET/CT scans into three groups based on the presence and number of focal [18F]FDG-avid lesions as well as the degree of diffuse [18F]FDG uptake in the BM. The proposed automated method for BM metabolism assessment is based on an initial CT-based segmentation of the skeleton, its transfer to the SUV PET images, the subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, six different SUV thresholds (Approaches 1–6) were applied for the definition of pathological tracer uptake in the skeleton [Approach 1: liver SUVmedian 7 1.1 (axial skeleton), gluteal muscles SUVmedian 7 4 (extremities). Approach 2: liver SUVmedian 7 1.5 (axial skeleton), gluteal muscles SUVmedian 7 4 (extremities). Approach 3: liver SUVmedian 7 2 (axial skeleton), gluteal muscles SUVmedian 7 4 (extremities). Approach 4: ≥ 2.5. Approach 5: ≥ 2.5 (axial skeleton), ≥ 2.0 (extremities). Approach 6: SUVmax liver]. Using the resulting masks, subsequent calculations of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in each patient were performed. A correlation analysis was performed between the automated PET values and the results of the visual PET/CT analysis as well as the histopathological, cytogenetical, and clinical data of the patients. Results: BM segmentation and calculation of MTV and TLG after the application of the deep learning tool were feasible in all patients. A significant positive correlation (p &lt; 0.05) was observed between the results of the visual analysis of the PET/CT scans for the three patient groups and the MTV and TLG values after the employment of all six [18F]FDG uptake thresholds. In addition, there were significant differences between the three patient groups with regard to their MTV and TLG values for all applied thresholds of pathological tracer uptake. Furthermore, we could demonstrate a significant, moderate, positive correlation of BM plasma cell infiltration and plasma levels of β2-microglobulin with the automated quantitative PET/CT parameters MTV and TLG after utilization of Approaches 1, 2, 4, and 5. Conclusions: The automated, volumetric, whole-body PET/CT assessment of the BM metabolic activity in MM is feasible with the herein applied method and correlates with clinically relevant parameters in the disease. This methodology offers a potentially reliable tool in the direction of optimization and standardization of PET/CT interpretation in MM. Based on the present promising findings, the deep learning-based approach will be further evaluated in future prospective studies with larger patient cohorts

Analyzing Longitudinal wb-MRI Data and Clinical Course in a Cohort of Former Smoldering Multiple Myeloma Patients: Connections between MRI Findings and Clinical Progression Patterns

The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future

Lower Extremity Energy Absorption and Biomechanics During Landing, Part II: Frontal-Plane Energy Analyses and Interplanar Relationships

Greater sagittal-plane energy absorption (EA) during the initial impact phase (INI) of landing is consistent with sagittal-plane biomechanics that likely increase anterior cruciate ligament (ACL) loading, but it does not appear to influence frontal-plane biomechanics. We do not know whether frontal-plane INI EA is related to high-risk frontal-plane biomechanics

Lower Extremity Energy Absorption and Biomechanics During Landing, Part I: Sagittal-Plane Energy Absorption Analyses

Eccentric muscle actions of the lower extremity absorb kinetic energy during landing. Greater total sagittal-plane energy absorption (EA) during the initial impact phase (INI) of landing has been associated with landing biomechanics considered high risk for anterior cruciate ligament (ACL) injury. We do not know whether groups with different INI EA magnitudes exhibit meaningful differences in ACL-related landing biomechanics and whether INI EA might be useful to identify ACL injury-risk potential

The influences of sex and posture on joint energetics during drop landings

Previous observations suggest that females utilize a more erect initial landing posture than males with sex differences in landing posture possibly related to sex-specific energy absorption (EA) strategies. However, sex-specific EA strategies have only been observed when accompanied by sex differences in initial landing posture. This study: 1) investigated the potential existence of sex-specific EA strategies, and 2) determined the influences of sex and initial landing posture on the biomechanical determinants of EA. The landing biomechanics of eighty subjects were recorded during drop landings in Preferred, Flexed, and Erect conditions. No sex differences in joint EA were identified after controlling for initial landing posture. Males and females exhibited greater ankle EA during Erect vs. Flexed landings with this increase driven by 12% greater ankle velocity, but no change in ankle extensor moment. No differences in hip and knee EA were observed between conditions. However, to achieve similar knee EA, subjects used 7% greater mean knee extensor moment but 9% less knee angular velocity during Flexed landings. The results suggest that sex-specific EA strategies do not exist, and that the magnitude of knee joint EA can be maintained by modulating the relative contributions of joint moment and angular velocity to EA.Keywords: Energy absorption, Kinetics, Kinematics, Landing biomechanic

Efficient In Vitro Generation of IL-22-Secreting ILC3 From CD34+ Hematopoietic Progenitors in a Human Mesenchymal Stem Cell Niche

Innate lymphoid cells (ILCs) and in particular ILC3s have been described to be vital for mucosal barrier functions and homeostasis within the gastrointestinal (GI) tract. Importantly, IL-22-secreting ILC3 have been implicated in the control of inflammatory bowel disease (IBD) and were shown to reduce the incidence of graft-versus-host disease (GvHD) as well as the risk of transplant rejection. Unfortunately, IL-22-secreting ILC3 are primarily located in mucosal tissues and are not found within the circulation, making access to them in humans challenging. On this account, there is a growing desire for clinically applicable protocols for in vitro generation of effector ILC3. Here, we present an approach for faithful generation of functionally competent human ILC3s from cord blood-derived CD34+ hematopoietic progenitors on layers of human mesenchymal stem cells (MSCs) generated in good manufacturing practice (GMP) quality. The in vitro-generated ILC3s phenotypically, functionally, and transcriptionally resemble bona fide tissue ILC3 with high expression of the transcription factors (TF) RorγT, AHR, and ID2, as well as the surface receptors CD117, CD56, and NKp44. Importantly, the majority of ILC3 belonged to the desired effector subtype with high IL-22 and low IL-17 production. The protocol thus combines the advantages of avoiding xenogeneic components, which were necessary in previous protocols, with a high propensity for generation of IL-22-producing ILC3. The present approach is suitable for the generation of large amounts of ILC3 in an all-human system, which could facilitate development of clinical strategies for ILC3-based therapy in inflammatory diseases and cancer