Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life.

radiation sensitivity assessment for individual head and neck cancer patients using deep learning-based automated nuclei and DNA damage foci detection.

Introduction: Tumor biopsy tissue response to irradiation is potentially an interesting biomarker for tumor response, therefore, for treatment personalization. Tumor response can be characterized by DNA damage response, expressed by the large-scale presence of DNA damage foci in tumor nuclei. Currently, characterizing tumor nuclei and DNA damage foci is a manual process that takes hours per patient and is subjective to inter-observer variability, which is not feasible in for clinical decision making.

Ex Vivo Functional Assay for Evaluating Treatment Response in Tumor Tissue of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient.

Correction: Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes.

Correction for 'Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes' by Fabio Perissinotto et al., Nanoscale, 2021, 13, 5224-5233, DOI: .

Structural insights into fusion mechanisms of small extracellular vesicles with model plasma membranes.

Extracellular vesicles (EVs) are a potent intercellular communication system. Such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications.

Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo.

The lack of approved anti-inflammatory and neuroprotective therapies in otology has been acknowledged in the last decades and recent approaches are heralding a new era in the field. Extracellular vesicles (EVs) derived from human multipotent (mesenchymal) stromal cells (MSC) can be enriched in vesicular secretome fractions, which have been shown to exert effects (eg, neuroprotection and immunomodulation) of their parental cells. Hence, MSC-derived EVs may serve as novel drug candidates for several inner ear diseases.

Extracellular Vesicles Can Deliver Anti-inflammatory and Anti-scarring Activities of Mesenchymal Stromal Cells After Spinal Cord Injury.

Spinal cord injury is characterized by initial neural tissue disruption that triggers secondary damage and extensive non-resolving inflammation, which aggravates loss of function and hinders recovery. The early onset of inflammation following traumatic spinal cord injury underscores the importance of acute intervention after the initial trauma. Injections of mesenchymal stromal cells (MSCs) can reduce inflammation following spinal cord injury.

Heparin Differentially Impacts Gene Expression of Stromal Cells from Various Tissues.

Pooled human platelet lysate (pHPL) is increasingly used as replacement of animal serum for manufacturing of stromal cell therapeutics. Porcine heparin is commonly applied to avoid clotting of pHPL-supplemented medium but the influence of heparin on cell behavior is still unclear. Aim of this study was to investigate cellular uptake of heparin by fluoresceinamine-labeling and its impact on expression of genes, proteins and function of human stromal cells derived from bone marrow (BM), umbilical cord (UC) and white adipose tissue (WAT).

Manufacturing and characterization of extracellular vesicles from umbilical cord-derived mesenchymal stromal cells for clinical testing.

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) may deliver therapeutic effects that are comparable to their parental cells. MSC-EVs are promising agents for the treatment of a variety of diseases. To reach the intermediate goal of clinically testing safety and efficacy of EVs, strategies should strive for efficient translation of current EV research.

An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles.

The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs) is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs) exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient.

Numerical analysis of ammonia homogenization for selective catalytic reduction application.

Selective catalytic reduction based on urea water solution as ammonia precursor is a promising method for the NO abatement form exhaust gasses of mobile diesel engine units. It consists of injecting the urea-water solution in the hot flue gas stream and reaction of its products with the NO over the catalyst surface. During this process flue gas enthalpy is used for the urea-water droplet heating and for the evaporation of water content.

A Good Manufacturing Practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles.

Background Aims: Extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) may contribute to biological processes such as tissue regeneration, immunomodulation and neuroprotection. Evaluation of their therapeutic potential and application in future clinical trials demands thorough characterization of EV content and production under defined medium conditions, devoid of xenogenic substances and serum-derived vesicles. Addressing the apparent need for such a growth medium, we have developed a medium formulation based on pooled human platelet lysate (pHPL), free from animal-derived xenogenic additives and depleted of EVs.

Putative new West Nile virus lineage in Uranotaenia unguiculata mosquitoes, Austria, 2013.

West Nile virus (WNV) is becoming more widespread and markedly effecting public health. We sequenced the complete polyprotein gene of a divergent WNV strain newly detected in a pool of Uranotaenia unguiculata mosquitoes in Austria. Phylogenetic analyses suggest that the new strain constitutes a ninth WNV lineage or a sublineage of WNV lineage 4.

Full-length genome analysis of Čalovo strains of Batai orthobunyavirus (Bunyamwera serogroup): implications to taxonomy.

Batai virus (BATV) is a poorly studied arthropod-borne virus belonging to the genus Orthobunyavirus (Bunyamwera serogroup) within the family Bunyaviridae. It has been associated with human influenza-like febrile illness in several Asian, African, and European countries. Čalovo virus (CVOV), isolated in 1960 in Slovakia, has been classified as BATV based on high antigenic similarity, and since then both CVOV and BATV were used as synonyms.

Molecular characterization of the African orthobunyavirus Ilesha virus.

Ilesha virus is an arthropod-borne virus belonging to the genus Orthobunyavirus of the Bunyaviridae family. Ilesha virus has been isolated from humans in several African countries, mostly in relation with febrile illness and erythema, though there are reported cases of fatal meningoencephalitis and hemorrhagic fever. In the present study, we report the complete genomic sequence of all three Ilesha virus segments (S, M, L) and characterize the open reading frames.

Barkedji virus, a novel mosquito-borne flavivirus identified in Culex perexiguus mosquitoes, Israel, 2011.

Barkedji virus, named after the area of its first identification in Senegal, is a newly discovered flavivirus (FV), for which we propose the abbreviation BJV. In the present study, we report the first-time detection of BJV in Culex perexiguus mosquitoes in Israel in 2011 and determination of its almost complete polyprotein gene sequence. We characterized the BJV genome and defined putative mature proteins, conserved structural elements and potential enzyme motifs along the polyprotein precursor.

Influenza C virus NS1 protein counteracts RIG-I-mediated IFN signalling.

The nonstructural proteins 1 (NS1) from influenza A and B viruses are known as the main viral factors antagonising the cellular interferon (IFN) response, inter alia by inhibiting the retinoic acid-inducible gene I (RIG-I) signalling. The cytosolic pattern-recognition receptor RIG-I senses double-stranded RNA and 5'-triphosphate RNA produced during RNA virus infections. Binding to these ligands activates RIG-I and in turn the IFN signalling.

A seven plasmid-based system for the rescue of influenza C virus.

We report the establishment of a reverse-genetics system for the rescue of recombinant influenza C/JJ/50 virus from seven plasmids. The nucleotide sequence of the whole C/JJ/50 genome was determined and full-length cDNAs were cloned into an RNA pol I/pol II-based bidirectional vector. Transfection of Vero cells and subsequent amplification on MDCK cells yielded viral HA titres of 128.

Functional interaction in establishment of ribosomal integrity between small subunit protein rpS6 and translational regulator rpL10/Grc5p.

Functional ribosomes synthesize proteins in all living cells and are composed of two labile associated subunits, which are made of rRNA and ribosomal proteins. The rRNA of the small 40S subunit (SSU) of the functional eukaryotic 80S ribosome decodes the mRNA molecule and the large 60S subunit (LSU) rRNA catalyzes protein synthesis. Recent fine structure determinations of the ribosome renewed interest in the role of ribosomal proteins in modulation of the core ribosomal functions.

Conformation-based design of two cyclic physalaemin analogues.

Two new cyclic analogues of physalaemin were designed on the basis of the conformation found in DMSO solution. Glp-Ala-cyclo(-Asp-Pro-Asn-Lys-)-Phe-Tyr-Gly-Leu-Met-NH2 (1) was synthesized by cyclization of physalaemin. In 2 the Asp residue was replaced by Glu.

Synthesis, conformational studies, and molecular dynamics calculations of two cyclic tetrapeptides with 17- and 18-membered rings.

Two cyclic tetrapeptides [Boc-cyclo(-Xxx-Pro-Asn-Lys-)OMe (Xxx = Asp or Glu)] were synthesized and investigated by NMR spectroscopy. They were designed in order to mimic the salt bridge found in physalaemin. Isomers of the urethane bond were observed in DMSO solution.

pH dependent conformation of physalaemin.

The undecapeptide physalaemin was investigated by n.m.r.

[Nitrefazole, a 4-nitroimidazole derivative with a marked inhibitory effect on aldehyde dehydrogenase. Synthesis and structural assignment].

2-Methyl-4-nitro-1-(4-nitrophenyl)imidazole (nitrefazole) is a drug which causes a strong and long lasting inhibition of aldehyde dehydrogenase, an enzyme involved in the metabolism of alcohol. The synthesis of this compound as well as that of the isomeric 5-nitro analogue are described. It can be shown by means of detailed 1H- and 13C-NMR studies of both isomers and some other structurally related compounds that the nitro group in nitrefazole is in position 4 of the imidazole ring, whereas the other pharmacologically active nitroimidazoles like metronidazole are mainly substituted in position 5 (or in exceptional cases in position 2).

Further compounds from the pedal gland of the bontebok (Damaliscus dorcas dorcas).

The identification of four further major constituents of the pedal gland exudate of the bontebok, Damaliscus dorcas dorcas, viz. alpha-terpineol, 2-n-heptylpyridine, m-cresol and (A)-6-dodecen-4-olide and the investigation of the stereochemistry of the double bond in (Z)-6-dodecen-4-olide by means of iterative computer analysis are described. An improved synthesis of this compound is outlined.