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Huber, H.

Publications and source records attributed to Huber, H..

2 recordsLinked to original sources

Photodynamic inactivation of pathogenic bacteria on human skin by applying a potent photosensitizer in a hydrogel

The antibiotic crisis increasingly threatens the health systems world-wide. Especially as there is an innovation gap in the development of novel antibiotics, treatment options for bacterial infections become fewer. The photodynamic inactivation (PDI) of bacteria appears to be a potent, new technology that may support the treatment of colonized or infected skin. In photodynamic inactivation, a dye - called photosensitizer - absorbs light and generates reactive singlet oxygen. This singlet oxygen is then capable of killing bacteria independent of species or strain and their antibiotic resistance profile. In order to provide a practical application for the skin surface, the photosensitizer was included in an aqueous hydrogel (photodynamically active hydrogel). The efficacy of this gel was initially tested on an inanimate surface and then on the human skin ex vivo. NBTC staining and TUNEL assays were carried out on skin biopsies to investigate potential harmful effects of the surface PDI to the underlying skin cells. The photosensitizer in the gel sufficiently produced singlet oxygen while showing only little photobleaching. On inanimate surfaces as well as on the human skin, the number of viable bacteria was reduced by over or nearly up to 4 log10 steps, equal to 99.99% reduction or even more. Furthermore, histological staining showed no harmful effects of the gel towards the tissue. The application of this hydrogel represents a valuable method in decolonizing human skin including the potential to act against superficial skin infections. The presented results are promising and should lead to further investigation in a clinical study to check the effectivity of the photodynamically active hydrogel on patients.

microbiology↗

Phosphatases are predicted to govern prolactin-mediated JAK-STAT signaling in pancreatic beta cells

Patients with diabetes are unable to produce a sufficient amount of insulin to properly regulate their blood-glucose levels. One potential method of treating diabetes is to increase the number of insulin-secreting beta cells in the pancreas to enhance insulin secretion. It is known that during pregnancy, pancreatic beta cells proliferate in response to the pregnancy hormone, prolactin. Leveraging this proliferative response to prolactin may be a strategy to restore endogenous insulin production for patients with diabetes. To investigate this potential treatment, we previously developed a computational model to represent the prolactin-mediated JAK-STAT signaling pathway in pancreatic beta cells. However, this model does not account for variability in protein expression that naturally occurs between cells. Here, we applied the model to understand how heterogeneity affects the dynamics of JAK-STAT signaling. We simulated a sample of 10,000 heterogeneous cells with varying initial protein concentrations responding to prolactin stimulation. We used partial least squares regression to analyze the significance and role of each of the varied protein concentrations in producing the response of the cell. Our regression models predict that the concentrations of the cytosolic and nuclear phosphatases strongly influence the response of the cell. The model also predicts that increasing prolactin receptor strengthens negative feedback mediated by the inhibitor SOCS. These findings reveal biological targets that can potentially be used to modulate the proliferation of pancreatic beta cells to enhance insulin secretion and beta cell regeneration in the context of diabetes.

systems biology↗