Search Results (8)

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on 20 July 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and October 2024, Wezlana^® (Amgen ABP 654), Uzpruvo^® (Alvotech AVT04) and Pyzchiva^® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma^® (Celltrion Healthcare CT-P43) was approved by the EMA in August 2024. Otulfi^® (Fresenius Kabi/Formycon) was approved by the FDA in October 2024. Several other potential biosimilar candidates are under development, including BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g., Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review summarizes the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs. Full article

Voles are the most common vertebrate pests in European agriculture. Identifying their distribution and abundance patterns provides valuable information for future management. Barn Owl diet analysis is one of the optimum methods used to record small mammal distribution patterns on large spatial scales. From 2003 to 2005, a total of 10,065 Barn Owl pellets were collected and analyzed from 31 breeding sites in the largest agroecosystem in Greece, the Thessaly plains. A total of 29,061 prey items were identified, offering deep insight into small mammal distribution, specifically voles. Four discrete vole species (Harting’s vole Microtus hartingi, East European vole Microtus levis, Thomas’s pine vole Microtus thomasi, and Grey dwarf hamster Cricetulus migratorius) comprised 40.5% (11,770 vole prey items) of the total Barn Owl prey intake. The presence and abundance of the voles varied according to underlying environmental gradients, with soil texture and type playing a major role. M. levis showed no significant attachments to gradients, other than a mild increase in Mollisol soils. It was syntopic in all sites with M. hartingi, which was the dominant and most abundant small mammal species, preferring non-arable cultivated land, natural grasslands, set-aside fields, and fallow land. M. thomasi was strictly present in western Thessaly and strongly associated with a sandy-clay soil texture and Alfisol soils. C. migratorius was the least represented vole (162 items), exclusively present in eastern Thessaly and demonstrating a stronger association with cereals, Mollisol soils, and an argillaceous-clay soil texture. This is the first study in Greece at such a large spatial scale, offering insights for pest rodents’ distribution in intensive agroecosystems and their response to environmental gradients including soil parameters. Full article

Farmland species face many threats, including habitat loss and malnutrition during key periods of their life cycle. This is aggravated in conventionally managed monocultures, leading to nutrient deficiencies that impair the survival and reproduction of farmland wildlife. For instance, protein deficiencies in wheat or vitamin B3 deficiency in maize reduce by up to 87% the reproductive success of the critically endangered common hamster (Cricetus cricetus), a flagship species of European farmlands. It is urgent to identify and implement agricultural practices that can overcome these deficiencies and help restoring hamsters’ reproductive success. As part of a conservation program to diversify farming habitats in collaboration with farmers, we tested whether associations between wheat or maize and three supplemental crops (soybean, sunflower and fodder radish) supported hamsters’ performance during hibernation and reproduction. We observed that maize–sunflower, maize–radish and wheat–soybean associations minimized hamsters’ body mass loss during hibernation. The wheat–soybean association led to the highest reproductive success (N = 2 litters of 4.5 ± 0.7 pups with a 100% survival rate to weaning), followed by maize–sunflower and maize–radish. These crop associations offer promising opportunities to overcome nutritional deficiencies caused by cereal monocultures. Their agronomic potential should promote their implementation on a large scale and benefit farmland biodiversity beyond the common hamster. Full article

Small carnivores are susceptible to regularly accumulating small- to medium-sized mammal remains in both natural and archaeological sites. However, compared to nocturnal birds of prey, these accumulations are still poorly documented and are generally based on a limited number of samples, including those of relatively small size. Here, we present an analysis of European hamster remains from a rescue excavation at Ittenheim (Bas-Rhin, Grand-Est, France), which were recovered from an infilled burrow, three meters below the current surface. The remains are well preserved and exhibit large proportions of tooth marks. Comparisons with a new and existing reference collection combined with an analysis of all recovered faunal remains suggest the accumulation reflects the action of young red foxes. This is supported by the fact that, although these young individuals leave teeth mark, they do not necessarily consume all parts of medium-sized prey species, including the European hamster. Conversely, the remains of smaller rodents, such as microtine, show distinct patterns of digestion and tooth marks. Carnivore bone accumulations from scats are generally poorly preserved; however, our results demonstrate prey size plays a major role, both qualitatively and quantitatively, in skeletal representation, bone preservation, and bone surface modifications. The present paper underlines the need for more diversified taphonomic reference collections based on an integrative approach designed to evaluate multi-taxa accumulations. Full article

The common hamster is a critically endangered species, but it is also perceived as a pest. Searching for an economic reason for its protection can be an argument to prevent its extinction. The purpose of this paper is to reveal the identification services provided by hamsters in the agricultural ecosystem and the determination of their correlation with human welfare. We propose the methods that can be applied for this purpose, and we check if the knowledge of the species is sufficient in order to use available methods for estimating the value of the services. The common hamster is a provider of supporting, regulating, and cultural services. Estimating their value is difficult because (1) available knowledge on the species’ ecology requires an update, in many aspects, due to changes to agricultural practices that have taken place since the 1970s (e.g., assessment of actual losses to cereal, vegetable, or root crops), and also extending by context, enabling the economic valuation of services (e.g., determination of impact range on various habitat components); it is also necessary to identify the correlations between profits and losses caused by this species; (2) there is a low level of public knowledge on the presence of hamsters and their role in the ecosystem. Education, primarily for consumers, followed by the promotion of hamsters as an umbrella and key species for agricultural areas, may result in the development of cultural services, which will increase the economic value of the services provided by hamsters. Full article

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications. Full article

The genotoxicity of anatase/rutile TiO₂ nanoparticles (TiO₂ NPs, NM105 at 3, 15 and 75 µg/cm²) was assessed with the mammalian in-vitro Hypoxanthine guanine phosphoribosyl transferase (Hprt) gene mutation test in Chinese hamster lung (V79) fibroblasts after 24 h exposure. Two dispersion procedures giving different size distribution and dispersion stability were used to investigate whether the effects of TiO₂ NPs depend on the state of agglomeration. TiO₂ NPs were fully characterised in the previous European FP7 projects NanoTEST and NanoREG2. Uptake of TiO₂ NPs was measured by transmission electron microscopy (TEM). TiO₂ NPs were found in cytoplasmic vesicles, as well as close to the nucleus. The internalisation of TiO₂ NPs did not depend on the state of agglomeration and dispersion used. The cytotoxicity of TiO₂ NPs was measured by determining both the relative growth activity (RGA) and the plating efficiency (PE). There were no substantial effects of exposure time (24, 48 and 72 h), although a tendency to lower RGA at longer exposure was observed. No significant difference in PE values and no increases in the Hprt gene mutant frequency were found in exposed relative to unexposed cultures in spite of evidence of uptake of NPs by cells. Full article

For many years, it was of interest to identify the sequences encoding the two melatonin receptors (MT₁ and MT₂) from various species. After publishing the basic molecular characterization of the human, rat, mouse, sheep, and platypus MT₁, MT₂, or Mel1c receptors, we began cloning the genes from other animals, such as birds, bats, and vipers. The goal was to advance the receptor crystallization, which could greatly contribute the understanding of the sequence/stability relationship. European hamster MT₁ receptor was cloned for the first time from this gender, was expressed in stable form in cells, and its binding characterized with a sample of 19 melatonin ligands. Siberian hamster (Phodopus sungorus) expresses a non-functional MT₂. We observed that unlike this hamster, the European hamster (Cricetus cricetus) does not have a stop codon in the MT₂ sequence. Thus, we undertook the tedious task of cloning the MT₂ receptor. We partially succeeded, sequencing the complete exon 2 and a fragment of exon 1 (from putative amino acids 12 to 38 and 77 to 323), after several years of efforts. In order to show that the protein parts we cloned were capable to sustain some binding capacities, we designed a chimeric MT₂ receptor using a consensus sequence to replace the unknown amino acids, based on other small rodent MT₂ sequences. This chimeric construct could bind melatonin in the nanomolar range. This work is meant to be the basis for attempts from other laboratories of the community to determine the complete natural sequence of the European hamster MT₂ receptor. The present work is the first to show that, among the hamsters, if the Siberian is a natural knockout for MT₂, the European one is not. Full article