Photoimmunotherapy (PIT) combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed and synthesized, in a highly convergent manner, the silicon phthalocyanine dye WB692-CB2, which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines. In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen (PSMA).
View Article and Find Full Text PDFThe expression of E-cadherin on Langerhans cells (LC) is required for adequate dendrite intercalation between epidermal keratinocytes. Upon disruption of epidermal homeostasis by tape stripping, E-cadherin competent LC extend dendrites reaching up to the epidermal surface, while E-cad deficient LC lack this ability.
View Article and Find Full Text PDFIntroduction: While TLR ligands derived from microbial flora and pathogens are important activators of the innate immune system, a variety of factors such as intracellular bacteria, viruses, and parasites can induce a state of hyperreactivity, causing a dysregulated and potentially life-threatening cytokine over-response upon TLR ligand exposure. Type I interferon (IFN-αβ) is a central mediator in the induction of hypersensitivity and is strongly expressed in splenic conventional dendritic cells (cDC) and marginal zone macrophages (MZM) when mice are infected with adenovirus. This study investigates the ability of adenoviral infection to influence the activation state of the immune system and underlines the importance of considering this state when planning the treatment of patients.
View Article and Find Full Text PDFBackground: In England, a range of mental health crisis care models and approaches to organising crisis care systems have been implemented, but characteristics associated with their effectiveness are poorly understood.
Aims: To (a) develop a typology of catchment area mental health crisis care systems and (b) investigate how crisis care service models and system characteristics relate to psychiatric hospital admissions and detentions.
Method: Crisis systems data were obtained from a 2019 English national survey.
(1) Background: With shifts in daily dietary habits, concerns have arisen regarding potential impacts on metabolic health. This study sought to investigate the interplay between nutrient intake and its effects on the anthropometric and inflammatory profiles of young individuals. (2) Methods: Our approach examined the interrelation of caloric, macronutrient, and vitamin intakes with inflammatory markers, serum cholesterol, triglycerides, and other key metrics.
View Article and Find Full Text PDFMaintaining homeostasis is central to organismal health. Deviation is detected by a variety of sensors that react to alarm signals arising from injury, infection, and other inflammatory triggers. One important element of this alarm system is the innate immune system, which recognizes pathogen-/microbe- or damage-associated molecular patterns via pattern recognition receptors localized in the cytosol or in membranes of innate immune cells such as macrophages, dendritic cells, and mast cells but also of T cells, B cells, and epithelial cells.
View Article and Find Full Text PDFWith the demand for renewable energy and efficient devices rapidly increasing, a need arises to find and optimize novel (nano)materials. With sheer limitless possibilities for material combinations and synthetic procedures, obtaining novel, highly functional materials has been a tedious trial and error process. Recently, machine learning has emerged as a powerful tool to help optimize syntheses; however, most approaches require a substantial amount of input data, limiting their pertinence.
View Article and Find Full Text PDFInt J Environ Res Public Health
December 2022
Physical exercise can induce changes in gas exchange and ventilation kinetics. Of these, some will lead to various adaptations which can influence performance and health. We conducted a single-center observational study on 40 participants.
View Article and Find Full Text PDFAtopic diseases, including atopic dermatitis (AD) and asthma, affect a large proportion of the population, with increasing prevalence worldwide. AD often precedes the development of asthma, known as the atopic march. Allergen sensitization developed through the barrier-defective skin of AD has been recognized to be a critical step leading to asthma, in which thymic stromal lymphopoietin (TSLP) was previously shown to be critical.
View Article and Find Full Text PDFThe blood-brain barrier (BBB) represents one of the biggest hurdles for CNS related drug delivery, preventing permeation of most molecules, and therefore poses a major challenge for researchers in finding effective treatments for CNS diseases. The low permeability of molecules through the BBB is linked on one hand to the extreme tightness by tight junction (TJ) formation limiting the paracellular transport, and on the other hand to the presence of ATP-driven efflux pumps which actively transport unwanted compounds out of the brain. In this study we evaluated the applicability of the immortalized human cell line hCMEC/D3 for ABC transporter studies, focusing on the most expressed ABC transporters at the human BBB: P-glycoprotein (PGP, ABCB1), multidrug resistance protein 4 (MRP4, ABCC4) and breast cancer resistance protein (BCRP, ABCG2).
View Article and Find Full Text PDFBackground: Inpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day units; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature.
View Article and Find Full Text PDF: During physical exercise, the electrical signal of the muscle fibers decreases due to repeated muscle contractions held at different intensities. The measured signal is strongly related to the motor unit activation rate, which is dependent on the chemical mediators and the available energy. By reducing the energy availability, adenosine triphosphate (ATP) production will decrease and therefore the muscle fibers activation rate will be negatively affected.
View Article and Find Full Text PDFRecessive dystrophic epidermolysis bullosa (RDEB), a genetic skin blistering disease, is a paradigmatic condition of tissue fragility-driven multi-organ fibrosis. Here, longitudinal analyses of the tissue proteome through the course of naturally developing disease in RDEB mice revealed that increased pro-inflammatory immunity associates with fibrosis evolution. Mechanistically, this fibrosis is a consequence of altered extracellular matrix organization rather than that of increased abundance of major structural proteins.
View Article and Find Full Text PDFAstacin-like proteinases (ALPs) are regulators of tissue and extracellular matrix (ECM) homeostasis. They convey this property through their ability to convert ECM protein pro-forms to functional mature proteins and by regulating the bioavailability of growth factors that stimulate ECM synthesis. The most studied ALPs in this context are the BMP-1/tolloid-like proteinases.
View Article and Find Full Text PDFBackground: Contact sensitizers may interfere with correct protein folding. Generation of un-/misfolded proteins can activate the IRE-1 or PERK signaling pathways initiating the unfolded protein response (UPR) and thereby determine inflammatory immune responses. We have analyzed the effect of sensitizers with different potencies on the induction of UPR activation/inhibition and the subsequent generation of a pro-inflammatory micromilieu in vitro as well as the effect of UPR modulation on the inflammatory response in the murine contact hypersensitivity (CHS) in vivo.
View Article and Find Full Text PDFBackground: Low-molecular weight chemicals or metal ions can cause allergic contact dermatitis, an inflammatory skin disease. Mice lacking Toll-like receptors 2 and 4 (TLR2/4 mice) are resistant to contact hypersensitivity (CHS). In the Western population obesity is increasing, which is known to have a proinflammatory impact.
View Article and Find Full Text PDFAllergies are highly prevalent hypersensitivity responses to usually harmless substances. They are mediated by the immune system which causes pathologic responses such as type I (rhinoconjunctivitis, allergic asthma, atopy) or type IV hypersensitivity (allergic contact dermatitis). The different types of allergy are mediated by effector and memory T cells and, in the case of type I hypersensitivity, B cells.
View Article and Find Full Text PDF(1) Background: Worldwide, public health policies focus on studying dietary patterns and the related anthropometric changes in children. Their aim is to improve the measures meant to reduce global malnutrition rates. Our goal was to study the main changes in the inflammatory status related to anthropometric changes and total daily energy intake.
View Article and Find Full Text PDF(1) Background: Daily caloric intake should aim to reduce the risk of obesity or poor anthropometric development. Our study objective was to analyze the association between food consumption, inflammatory status and anthropometric development; (2) Methods: We performed a prospective observational analytical research during September 2020 and April 2021 on a group of 160 healthy subjects, aged between 6 and 12 years old, by analyzing food ingestion, the basal metabolic rate, anthropometric development and the inflammatory status; (3) Results: IL-6 was significantly correlated to the sum of skinfolds, along with both serum proteins and triglycerides. The skin folds were significantly correlated with the caloric intake and with total fat intake, next to saturated and trans fats.
View Article and Find Full Text PDFIron-based Fe-Mn-Al-Ni shape-memory alloys are of rather low materials cost and show remarkable pseudoelastic properties. To further understand the martensitic transformation giving rise to the pseudoelastic properties, different Fe-Mn-Al-Ni alloys have been heat treated at 1473 K and quenched in ice water. The martensite, which is formed from a body-centred cubic austenite, is commonly described as face-centered cubic (f.
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