Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus.

CDK4/6 inhibitors (CDK4/6i) and oncolytic viruses are promising therapeutic agents for the treatment of various cancers. As single agents, CDK4/6 inhibitors that are approved for the treatment of breast cancer in combination with endocrine therapy cause G1 cell cycle arrest, whereas adenoviruses induce progression into S-phase in infected cells as an integral part of the their life cycle. Both CDK4/6 inhibitors and adenovirus replication target the Retinoblastoma protein albeit for different purposes.

Reduced Acquisition Time [F]GE-180 PET Scanning Protocol Replaces Gold-Standard Dynamic Acquisition in a Mouse Ischemic Stroke Model.

Aim: Understanding neuroinflammation after acute ischemic stroke is a crucial step on the way to an individualized post-stroke treatment. Microglia activation, an essential part of neuroinflammation, can be assessed using [F]GE-180 18 kDa translocator protein positron emission tomography (TSPO-PET). However, the commonly used 60-90 min post-injection (p.

Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice.

In accordance with the 'refinement' component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to determine whether s-ketamine could provide adequate surgical tolerance at a 50% dose relative to that of ketamine racemate and whether antagonism of medetomidine could be initiated 15 min earlier. The second aim was to investigate the potential improvement in analgesia for both anaesthetic protocols by adding butorphanol or metamizole.

Functional analysis of bioactivated and antiinfective PDLLA - coated surfaces.

Common scaffold surfaces such as titanium can have side effects; for example, infections, cytotoxicity, impaired osseointegration, or low regeneration rates for bone tissue. These effects lead to poor implant integration or even implant loss. Therefore, bioactive implants are promising instruments in tissue regeneration.

MagnetofectionTM platform: from magnetic nanoparticles to novel nucleic acid therapeutics.

Nucleic acid delivery to cells to make them produce a desired protein or to shut down the expression of endogenous genes opens unique possibilities for research and therapy. During the last decade, to realize the potential of this approach, nanomagnetic methods for delivering and targeting nucleic acids have been developed, methods which are often referred to as Magnetofection. Our research group at the Institute of Experimental Oncology and Therapy Research, located at the University Hospital Klinikum rechts der Isar in the center of Munich, Germany, develops new magnetic nanomaterials and, their formulations with gene-delivery vectors and technologies to allow localized and efficient gene delivery in vitro and in vivo for a variety of research, diagnostic and therapeutic applications.

Characterization of Intestinal Lactobacillus reuteri Strains as Potential Probiotics.

This study was conducted to evaluate the probiotic properties of Lactobacillus reuteri isolated from human infant feces (less than 3 months). Out of thirty-two representative L. reuteri strains isolated from the infant human feces, nine isolates (i.

A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.

Purpose: In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study.

Effects of nanoparticle coatings on the activity of oncolytic adenovirus-magnetic nanoparticle complexes.

Limitations to adenovirus infectivity can be overcome by association with magnetic nanoparticles and enforced infection by magnetic field influence. Here we examined three core-shell-type iron oxide magnetic nanoparticles differing in their surface coatings, particle sizes and magnetic properties for their ability to enhance the oncolytic potency of adenovirus Ad520 and to stabilize it against the inhibitory effects of serum or a neutralizing antibody. It was found that the physicochemical properties of magnetic nanoparticles are critical determinants of the properties which govern the oncolytic productivities of their complexes with Ad520.

Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.

Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse.

Successful anatomic repair of fetoscopic access sites in the mid-gestational rabbit model using amnion cell engineering.

Background/aim: Our aim was to evaluate the impact of in vitro cultured amnion cells, injected and/or seeded in different scaffolds, on in vivo fetal membrane repair.

Materials And Methods: Amnion cells, isolated from allogeneic fetal membranes, were cultured on three different scaffolds for 14 to 21 days. In 33 mid-gestational rabbits, fetoscopic access sites were randomly allocated to four closure study groups: conventional collagen plug, as well as collagen plug, collagen foil, and fibrin glue as scaffolds for the cultured amnion cells.

Diversity of bacillus species isolated from okpehe, a traditional fermented soup condiment from Nigeria.

The diversity of Bacillus species isolated from the fermented soup condiment okpehe in Nigeria was studied using a combination of phenotypic and genotypic methods. Fifty strains presumptively characterized as Bacillus spp. using the API 50 CHB test were further identified by PCR of randomly amplified polymorphic DNA (RAPD) and by amplified ribosomal DNA restriction analysis (ARDRA) genotyping methods.

Weissella beninensis sp. nov., a motile lactic acid bacterium from submerged cassava fermentations, and emended description of the genus Weissella.

Four Gram-positive, catalase-negative, short rod-shaped or coccoid, heterofermentative lactic acid bacterial strains (2L24P13(T), 1L48P15, 1L24P31 and 1L24P34) with unusual phenotypic and genotypic properties were isolated from submerged fermenting cassava on MRS agar. All strains were motile, grew at 15 degrees C, produced dl-lactic acid from glucose with gas formation and produced ammonia from arginine. Acid was produced from d-fructose, d-galactose, d-glucose, lactose, maltose, d-mannose, melibiose, d-raffinose, sucrose, N-acetylglucosamine and d-mannitol, but not from d-arabinose or xylose.

Functional properties of lactic acid bacteria isolated from ethnic fermented vegetables of the Himalayas.

A total of 94 strains of Lactic acid bacteria (LAB), previously isolated from ethnic fermented vegetables and tender bamboo shoots of the Himalayas, were screened for functional properties such as acidification capacity, enzymatic activities, degradation of antinutritive factors and oligosaccharides, production of biogenic amines, hydrophobicity and adherence to mucus secreting HT29 MTX cells. Strong acidification and coagulation activities of LAB strains were recorded. Most of the LAB strains showed antimicrobial activities against the used indicator strains; however, only Lb.

The influence of the stable expression of BMP2 in fibrin clots on the remodelling and repair of osteochondral defects.

Growth factors like BMP2 have been tested for osteochondral repair, but transfer methods used until now were insufficient. Therefore, the aim of this study was to analyse if stable BMP2 expression after retroviral vector (Bullet) transduction is able to regenerate osteochondral defects in rabbits. Fibrin clots colonized by control or BMP2-transduced chondrocytes were generated for in vitro experiments and implantation into standardized corresponding osteochondral defects (n=32) in the rabbit trochlea.

Pediococcus argentinicus sp. nov. from Argentinean fermented wheat flour and identification of Pediococcus species by pheS, rpoA and atpA sequence analysis.

A Gram-positive, small coccus-shaped lactic acid bacterium, strain LMG 23999(T), was isolated from Argentinean wheat flour. 16S rRNA gene sequence analysis revealed that the phylogenetic position of the novel strain was within the genus Pediococcus, with Pediococcus stilesii, Pediococcus pentosaceus and Pediococcus acidilactici as its closest relatives (97.7, 97.

A fibrin glue composition as carrier for nucleic acid vectors.

Purpose: Gene delivery from biomaterials has become an important tool in tissue engineering. The purpose of this study was to generate a gene vector-doted fibrin glue as a versatile injectable implant to be used in gene therapy supported tissue regeneration.

Methods: Copolymer-protected polyethylenimine(PEI)-DNA vectors (COPROGs), naked DNA and PEI-DNA were formulated with the fibrinogen component of the fibrin glue TISSUCOL and lyophilized.

A genus-specific PCR method for differentiation between Leuconostoc and Weissella and its application in identification of heterofermentative lactic acid bacteria from coffee fermentation.

A genus-specific PCR analysis method was developed for a rapid and reliable differentiation between the two heterofermentative lactic acid bacteria genera Leuconostoc and Weissella. Primer sets specific for target regions of the 16S rRNA genes were designed and the specificity of the PCR was evaluated using the type strains of 13 species of Leuconostoc and 11 species of Weissella. In addition, the newly developed genus-specific PCR analysis was applied to characterize 72 lactic acid bacteria (LAB) strains isolated from coffee fermentation and which were presumptively classified as Leuconostoc or Weissella species.

Functional characteristics of Lactobacillus spp. from traditional Maasai fermented milk products in Kenya.

In this study functional characteristics of 23 representative Lactobacillus strains isolated from the Maasai traditional fermented milk 'Kule naoto' were determined. The Lb. acidophilus group strains showed resistance to gastric juice and bile.

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas.

Diversity of predominant lactic acid bacteria associated with cocoa fermentation in Nigeria.

The fermentation of cocoa relies on a complex succession of bacteria and filamentous fungi, all of which can have an impact on cocoa flavor. So far, few investigations have focused on the diversity of lactic acid bacteria involved in cocoa fermentation, and many earlier investigations did not rely on polyphasic taxonomical approaches, which take both phenotypic and genotypic characterization techniques into account. In our study, we characterized predominant lactic acid bacteria from cocoa fermentations in Nigeria, using a combination of phenotypic tests, repetitive extragenic palindromic PCR, and sequencing of the 16S rRNA gene of representative strains for accurate species identification.

Microbiological and biochemical profile of cv. Conservolea naturally black olives during controlled fermentation with selected strains of lactic acid bacteria.

The effect of controlled fermentation processes on the microbial association and biochemical profile of cv. Conservolea naturally black olives processed by the traditional anaerobic method was studied. The different treatments included (a) inoculation with a commercial starter culture of Lactobacillus pentosus, (b) inoculation with a strain of Lactobacillus plantarum isolated from a fermented cassava product and (c) uninoculated spontaneous process.

Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega.

Background: Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility.

Hypothesis: Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible.

Animals: Twenty domestic cats.

Functional properties of Lactobacillus plantarum strains isolated from Maasai traditional fermented milk products in Kenya.

Lactobacillus plantarum was the major species among the lactic acid bacterial strains isolated from traditional fermented milk of the Maasai in Kenya. Selected strains were characterized for their functional properties using in vitro standard procedures. All strains expressed acid tolerance at pH 2.

Leuconostoc holzapfelii sp. nov., isolated from Ethiopian coffee fermentation and assessment of sequence analysis of housekeeping genes for delineation of Leuconostoc species.

A Gram-positive, ovoid lactic acid bacterium, strain LMG 23990(T), was isolated from Ethiopian coffee fermentation. 16S rRNA gene sequence analysis indicated that the novel strain belongs to the genus Leuconostoc, with Leuconostoc citreum and Leuconostoc lactis as the closest neighbours (99.6 and 99.

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial.