Expression of Keratinocyte Growth Factor in Periapical Lesions

The epithelial proliferation associated with inflammatory periapical lesions and with periapical cyst formation represents an interesting but poorly understood pathological change. Keratinocyte growth factor (KGF) is a recently identified growth factor that is produced by stromal fibroblasts and acts specifically to stimulate epithelial growth and differentiation. To investigate its possible role in the activation of the normally quiescent rests of Malassez, we examined the expression of KGF by in situ hybridization of sections of normal periodontal ligament (PDL) and of 12 periapical granulomas or cysts. Normal PDL and periapical granulomas with scant inflammatory infiltration showed few cells expressing message for KGF. However, KGFexpressing cells were found in the connective tissue stroma close to dense foci of inflammatory cells and to proliferating epithelial elements and cystic epithelial linings. Examination of tissues by the reverse-transcription polymerase chain reaction (RT-PCR) showed KGF expression in 4 specimens of periapical lesions but low or undetectable levels in normal PDL. These observations suggest that the induction of KGF expression in the stromal cells of periapical lesions may play an important role in stimulating the epithelial proliferation associated with cyst formation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66683/2/10.1177_00220345960750090701.pd

Non-invasive characterization of hybrid gelatin:poly-L-lactide electrospun scaffolds using second harmonic generation and multiphoton imaging

In this work we generated hybrid gelatin:poly-l-lactide electrospun scaffolds and implemented non-invasive methods to characterize them

USING EARTH OBSERVATION TO SUPPORT FIRST AID RESPONSE IN CRISIS SITUATIONS– LESSONS LEARNED FROM THE EARTHQUAKE IN TÜRKIYE/SYRIA (2023)

In the early morning hours on Tuesday, February 6, 2023, the southern part of Türkiye was struck by two large and several smaller earthquakes, causing destruction and casualties over a remarkably large area. In such cases, quick response and well-informed coordination is a key factor to successful first aid responses since damage and the number of people buried or in need often remain unclear in the hours after the disaster. The German Aerospace Center (DLR) responded to the earthquake by rapidly providing a number of information products, all above very high-resolution imagery in an easy-to-use web-based application. Next to satellite and drone imagery, damage information and pre-disaster imagery were provided to the users. Drone imagery was acquired in person for Kirikhan, a city in the south of the disaster area. Access to the viewer was granted to authorized users from public authorities, humanitarian aid organisations, and research institutes. Furthermore, DLR generated information products in the fields of settlement pattern, AI based damage assessment and tectonic movements. These data, as scientifically significant as they are, were not part of the web viewer. Within this paper, the reasons will be assessed as well as the general workflow of the activation. The paper will also discuss what steps need to be taken to ensure research outcomes being integrated into information products for users in future and how to prepare for the next disaster to still ensure a quick response but with an enriched product suite

Observations and modeling of areal surface albedo and surface types in the Arctic

An accurate representation of the annual evolution of surface albedo of the Arctic Ocean, especially during the melting period, is crucial to obtain reliable climate model predictions in the Arctic. Therefore, the output of the surface albedo scheme of a coupled regional climate model (HIRHAM–NAOSIM) was evaluated against airborne and ground-based measurements. The observations were conducted during five aircraft campaigns in the European Arctic at different times of the year between 2017 and 2022; one of them was part of the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in 2020. We applied two approaches for the evaluation: (a) relying on measured input parameters of surface type fraction and surface skin temperature (offline) and (b) using HIRHAM–NAOSIM simulations independently of observational data (online). From the offline method we found a seasonally dependent bias between measured and modeled surface albedo. In spring, the cloud effect on surface broadband albedo was overestimated by the surface albedo parametrization (mean albedo bias of 0.06), while the surface albedo scheme for cloudless cases reproduced the measured surface albedo distributions for all seasons. The online evaluation revealed an overestimation of the modeled surface albedo resulting from an overestimation of the modeled cloud cover. Furthermore, it was shown that the surface type parametrization contributes significantly to the bias in albedo, especially in summer (after the drainage of melt ponds) and autumn (onset of refreezing). The lack of an adequate model representation of the surface scattering layer, which usually forms on bare ice in summer, contributed to the underestimation of surface albedo during that period. The difference between modeled and measured net irradiances for selected flights during the five airborne campaigns was derived to estimate the impact of the model bias for the solar radiative energy budget at the surface. We revealed a negative bias between modeled and measured net irradiances (median: −6.4 W m−2) for optically thin clouds, while the median value of only 0.1 W m−2 was determined for optically thicker clouds.</p

Controlling transmembrane protein concentration and orientation in supported lipid bilayers

The trans-membrane protein – proteorhodopsin (pR) has been incorporated into supported lipid bilayers (SLB). In-plane electric fields have been used to manipulate the orientation and concentration of these proteins, within the SLB, through electrophoresis leading to a 25-fold increase concentration of pR

Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles

Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed.Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H(2)O(2), but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation.Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results suggest that muscle-derived ANGPT2 production may play a positive role in skeletal muscle fiber repair

A prospective, double-blind, randomized, controlled clinical trial comparing standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care only for the treatment of chronic, non-healing ulcers of the lower limb in patients with diabetes mellitus: a study protocol

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the use of adjunctive hyperbaric oxygen therapy improves the healing of diabetic foot ulcers, and decreases the risk of lower extremity amputations. A limited number of studies have used a double blind approach to evaluate the efficacy of hyperbaric oxygen therapy in the treatment of diabetic ulcers. The primary aim of this study is to assess the efficacy of hyperbaric oxygen therapy plus standard wound care compared with standard wound care alone in preventing the need for major amputation in patients with diabetes mellitus and chronic ulcers of the lower limb.</p> <p>Methods/Design</p> <p>One hundred and eighteen (59 patients per arm) patients with non-healing diabetic ulcers of the lower limb, referred to the Judy Dan Research and Treatment Centre are being recruited if they are at least 18 years of age, have either Type 1 or 2 diabetes with a Wagner grading of foot lesions 2, 3 or 4 on lower limb not healing for at least 4 weeks. Patients receive hyperbaric oxygen therapy every day for 6 weeks during the treatment phase and are provided ongoing wound care and weekly assessments. Patients are required to return to the study centre every week for an additional 6 weeks of follow-up for wound evaluation and management. The primary outcome is freedom from having, or meeting the criteria for, a major amputation (below knee amputation, or metatarsal level) up to 12 weeks after randomization. The decision to amputate is made by a vascular surgeon. Other outcomes include wound healing, effectiveness, safety, healthcare resource utilization, quality of life, and cost-effectiveness. The study will run for a total of about 3 years.</p> <p>Discussion</p> <p>The results of this study will provide detailed information on the efficacy of hyperbaric oxygen therapy for the treatment of non-healing ulcers of the lower limb. This will be the first double-blind randomized controlled trial for this health technology which evaluates the efficacy of hyperbaric oxygen therapy in prevention of amputations in diabetic patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00621608">NCT00621608</a></p

Keratinocyte Growth Factor Induces Gene Expression Signature Associated with Suppression of Malignant Phenotype of Cutaneous Squamous Carcinoma Cells

Keratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin. The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs (n = 6) than in normal skin samples (n = 6). Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF. KGF did not stimulate SCC cell proliferation, but it reduced invasion of SCC cells through collagen. Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes, including genes with tumor suppressing properties (SPRY4, DUSP4, DUSP6, LRIG1, PHLDA1). KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes, including genes associated with tumor progression (MMP13, MATN2, CXCL10, and IGFBP3). Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2. Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression. These results provide evidence, that KGF does not promote progression of cutaneous SCC, but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells, as compared to normal keratinocytes

CD33 BiTE molecule-mediated immune synapse formation and subsequent T-cell activation is determined by the expression profile of activating and inhibitory checkpoint molecules on AML cells

Bispecific T-cell engager (BiTE) molecules recruit T cells to cancer cells through CD3ε binding, independently of T-cell receptor (TCR) specificity. Whereas physiological T-cell activation is dependent on signal 1 (TCR engagement) and signal 2 (co-stimulation), BiTE molecule-mediated T-cell activation occurs without additional co-stimulation. As co-stimulatory and inhibitory molecules modulate the strength and nature of T-cell responses, we studied the impact of the expression profile of those molecules on target cells for BiTE molecule-mediated T-cell activation in the context of acute myeloid leukemia (AML). Accordingly, we created a novel in vitro model system using murine Ba/F3 cells transduced with human CD33 ± CD86 ± PD-L1. T-cell fitness was assessed by T-cell function assays in co-cultures and immune synapse formation by applying a CD33 BiTE molecule (AMG 330). Using our cell-based model platform, we found that the expression of positive co-stimulatory molecules on target cells markedly enhanced BiTE molecule-mediated T-cell activation. The initiation and stability of the immune synapse between T cells and target cells were significantly increased through the expression of CD86 on target cells. By contrast, the co-inhibitory molecule PD-L1 impaired the stability of BiTE molecule-induced immune synapses and subsequent T-cell responses. We validated our findings in primary T-cell-AML co-cultures, demonstrating a PD-L1-mediated reduction in redirected T-cell activation. The addition of the immunomodulatory drug (IMiD) lenalidomide to co-cultures led to stabilization of immune synapses and improved subsequent T-cell responses. We conclude that target cells modulate CD33 BiTE molecule-dependent T-cell activation and hence, combinatorial strategies might contribute to enhanced efficacy