Investigating Cellulose Binding of Peptides Derived from Carbohydrate Binding Module 1.

Carbohydrate-binding modules (CBM) have emerged as useful tools for a wide range of tasks, including the use as purification tags or for cellulose fiber modification. For this purpose, the CBM needs to be attached to a target protein leading to large constructs. We investigated if short peptides from the carbohydrate binding site of CBMs can bind in a similar way as native, full-length CBMs to nanocrystalline cellulose (NCC) or cotton linter paper.

Clinical applications of next-generation sequencing-based ctDNA analyses in breast cancer: defining treatment targets and dynamic changes during disease progression.

The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non-invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real-time monitoring of the effectiveness of cancer therapies as well as the identification of resistance mechanisms to guide targeted therapy. Although the field of ctDNA studies offers a wide range of applications, including in early disease, in this review we mainly focus on the role of ctDNA in the dynamic molecular characterization of unresectable locally advanced and metastatic BC (mBC).

Design and synthesis of peptides as stabilizers of histone deacetylase 4.

Histone deacetylase 4 (HDAC4) contributes to gene repression by complex formation with HDAC3 and the corepressor silencing mediator for retinoid or thyroid hormone receptors (SMRT). We hypothesized that peptides derived from the class IIa specific binding site of SMRT would stabilize a specific conformation of its target protein and modulate its activity. Based on the SMRT-motif 1 (SM1) involved in the interaction of SMRT with HDAC4, we systematically developed cyclic peptides that exhibit K values that are 9 to 56 times lower than that of the linear SMRT peptide.

Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease.

Aims: Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients.

Aging impairs the neurovascular interface in the heart.

Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium is characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed the impact of aging on the cardiac neurovascular interface. We report that aging reduces nerve density in the ventricle and dysregulates vascular-derived neuroregulatory genes.

Gene Fusions in Non-Small-Cell Lung Cancer: Real-World Screening Data of 1068 Unselected Patients.

(1) Background: The main objectives of our study are (i) to determine the prevalence of () fusions in a routine diagnostic setting in NSCLC (non-small cell lung cancer) and (ii) to investigate the feasibility of screening approaches including immunohistochemistry (IHC) as a first-line test accompanied by fluorescence in situ hybridization (FISH) and RNA-(ribonucleic acid-)based next-generation sequencing (RNA-NGS). (2) Methods: A total of 1068 unselected consecutive patients with NSCLC were screened in two scenarios, either with initial IHC followed by RNA-NGS ( = 973) or direct FISH testing ( = 95). (3) Results: One hundred and thirty-three patients (14.

Effect of macrocyclization and tetramethylrhodamine labeling on chemokine binding peptides.

Receptor-derived peptides have played an important role in elucidating chemokine-receptor interactions. For the inflammatory chemokine CXC-class chemokine ligand 8 (CXCL8), a site II-mimetic peptide has been derived from parts of extracellular loops 2 and 3 and adjacent transmembrane helices of its receptor CXC-class chemokine receptor 1 (Helmer et al., RSC Adv.

pH-Dependent Release of Vancomycin from Modularly Assembled Collagen Laminates.

To prevent surgical site infections, antibiotics can be released from carriers made of biomaterials, such as collagen, that support the healing process and are slowly degraded in the body. In our labs we have developed collagen laminates that can be easily assembled and bonded on-site, according to medical needs. As shown previously, the asymmetric assembly leads to different release rates at the major faces of the laminate.

High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune cell infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how immune cell phenotypes vary across different patient subgroups is lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution by integrating 1,283,972 single cells from 556 samples and 318 patients across 29 datasets, including our dataset capturing cells with low mRNA content.

Pheochromocytoma Turned Malignant During Pregnancy in a Patient With Neurofibromatosis Type I - A Case Report and Systematic Review of the Current Literature.

Background/aim: Pheochromocytomas (PHEOs) are a rare entity in the common population but have higher prevalence in neurofibromatosis type I (NFI) patients. In combination with pregnancy there are several reports on perioperative complications due to endocrine tumor activity; however, case reports on the malignant course of the disease could not be identified.

Case Report: We report the case of a pregnant female patient with diagnosed NF1, who was referred to our hospital with metastatic PHEO.

Interstitial Pulmonary Fibrosis and Extensive Dendriform Ossification with Persistent Viral Load: A Rare Presentation of Post-COVID-19 Condition in Need of Lung Transplantation.

The incidence, presentation, and predisposing factors of post-acute sequelae of COVID-19 (PASC) are currently poorly understood. Lung explants may provide a rare insight into terminal SARS-CoV-2-associated lung damage and its pathophysiology. A 62-year-old man presented with progressively worsening respiratory symptoms after recovering from mild COVID-19 3 months earlier.

Mechanical characterization of rose bengal and green light crosslinked collagen scaffolds for regenerative medicine.

Collagen is one of the most important biomaterials for tissue engineering approaches. Despite its excellent biocompatibility, it shows the non-negligible disadvantage of poor mechanical stability. Photochemical crosslinking with rose bengal and green light (RGX) is an appropriate method to improve this property.

An Additively Manufactured Sample Holder to Measure the Controlled Release of Vancomycin from Collagen Laminates.

The controlled release of antibiotics prevents the spread of pathogens and thereby improves healing processes in regenerative medicine. However, high concentrations may interfere with healing processes. It is therefore advantageous to use biodegradable materials for a controlled release.

Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness.

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer's disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice.

A spark of hope: histopathological and functional recovery after critical COVID-19.

Background: There are substantial concerns about fibrotic and vascular pulmonary sequelae after coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).AQ1 Histopathology reports of lung biopsies from COVID-19 survivors are scarce.

Case: We herein report results of functional and histopathological studies in a 70 year-old man undergoing a co-incidental tumor lobectomy six months after long-term mechanical ventilation for COVID-19 pneumonia.

Pathological Fracture of the Tibia as a First Sign of Hyperparathyroidism - A Case Report and Systematic Review of the Current Literature.

Background/aim: Pathological fractures are rare, suspicious and in some cases mentioned as the first sign of a malignant tumor. We present an uncommon case with a pathological fracture of the tibia diaphysis as the first sign of severe hyperparathyroidism.

Case Report: We report the case of a female patient who was referred to the emergency department with a history of progressively worsening pain in the lower left leg and an inability to fully bear weight.

Sapropterin (BH4) Aggravates Autoimmune Encephalomyelitis in Mice.

Depletion of the enzyme cofactor, tetrahydrobiopterin (BH4), in T-cells was shown to prevent their proliferation upon receptor stimulation in models of allergic inflammation in mice, suggesting that BH4 drives autoimmunity. Hence, the clinically available BH4 drug (sapropterin) might increase the risk of autoimmune diseases. The present study assessed the implications for multiple sclerosis (MS) as an exemplary CNS autoimmune disease.

Cell-based actin polymerization assay to analyze chemokine inhibitors.

Chemokines play an important role in various diseases as signaling molecules for immune cells. Therefore, the inhibition of the chemokine-receptor interaction and the characterization of potential inhibitors are important steps in the development of new therapies. Here, we present a new cell-based assay for chemokine-receptor interaction, using chemokine-dependent actin polymerization as a readout.

Immobilisation of CXCL8 gradients in microfluidic devices for migration experiments.

The release of inflammatory chemokines leads to the formation of chemokine gradients that result in the directed migration of immune cells to the site of injury. In this process, cells respond to soluble gradients (chemotaxis) as well as to immobilised gradients (haptotaxis). Surface-bound chemokine gradients are mostly presented by endothelial cells and supported by glycosaminoglycans (GAGs), such as heparan sulfate, involving the GAG binding site of chemokines.

Rose Bengal Crosslinking to Stabilize Collagen Sheets and Generate Modulated Collagen Laminates.

For medical application, easily accessible biomaterials with tailored properties are desirable. Collagen type I represents a biomaterial of choice for regenerative medicine and tissue engineering. Here, we present a simple method to modify the properties of collagen and to generate collagen laminates.

Epitope Identification and Affinity Determination of an Inhibiting Human Antibody to Interleukin IL8 (CXCL8) by SPR- Biosensor-Mass Spectrometry Combination.

The polypeptide chemokine Interleukin-8 (IL8) plays a crucial role in inflammatory processes in humans. IL8 is involved in chronic inflammatory lung diseases, rheumatoid arthritis, and cancer. Previous studies have shown that the interaction of IL8 with its natural receptors CXCR1 and CXCR2 is critical in these diseases.

Top-level gene copy number gain defines a subtype of poorly differentiated pulmonary adenocarcinomas with poor prognosis.

Background: amplifications occur in human tumors, including non-small cell lung cancer (NSCLC). MET inhibitors have demonstrated some clinical activity in amplified NSCLC, presumably with a gene dose effect. However, the definition of MET positivity or amplification as a potential oncogenic driver is still under debate.

Toxic Effect of Vancomycin on Viability and Functionality of Different Cells Involved in Tissue Regeneration.

To prevent infections local delivery of antibiotics is a useful tool. Especially in bone fractures, vancomycin impregnated bone cements are often used allowing high concentrations of antibiotics at the infection side without high serum concentrations. However, besides potential pathogens, cells involved in tissue regeneration may also be affected by the drug.

Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer.

Background: Targeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response.