Search Results (13)

Background: Bovine alphaherpesvirus 1 (BoAHV-1) is a major respiratory and reproductive pathogen in cattle worldwide. Both innate and adaptive immune responses contribute to protection against this virus; however, virus-host interactions remain partly undefined. In this study, the impact of BoAHV-1 infection on calves’ immune responses was investigated in detail. Methods: Six calves were intranasally infected with wild-type BoAHV-1, and blood samples were collected longitudinally. Leukocyte subset dynamics were assessed by complete haematological assay and flow cytometry, while multiplex ELISA was used to quantify serum levels of ten cytokines. For each parameter, post-infection values (days 2, 4, 8, 10, and 14) were compared with pre-infection baseline values (day 0). Results: Infection induced an initial phase of immunosuppression, reflected by decreased circulating αβ and γδ-T cells. However, infected animals rapidly developed a protective immune response, characterised by increased circulating classical and intermediate monocytes and elevated levels of the related chemokine MIP-1β. Early post-infection, rises in serum IFN-γ and IL-10 were also detected. Conclusions: Our data suggest that monocyte recruitment and increased serum levels of IFN-γ and IL-10 are positively associated with the ability to overcome infection. A better understanding of the immunopathogenic mechanisms underlying BoAHV-1 infection will support the development of more effective vaccines against this virus. Full article

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive “micro-to-macro” approach for the refinement of clinical practices and delivery of personalised therapies. Full article

This article presents the findings of a scientific study investigating the efficacy of various assessment techniques used to evaluate the adaptability and productive qualities of Aberdeen Angus cattle on three prominent farms in the northern region of the Republic of Kazakhstan. A comprehensive analysis of the haematological and biochemical parameters of experimental groups of cattle with different genotypes (American, Canadian, and Estonian selection) was conducted. The studies revealed notable variability in haematological and biochemical indicators, contingent on the origin. Concurrently, the dynamics of the aforementioned indicators did not exceed the physiological norms. The modern allelofund was characterised with the help of microsatellite markers, and the level of genetic diversity of Aberdeen Angus cattle of different genotypes was estimated. The research uncovered the genealogical structure of the populations, the purity of the populations, the provenance, the polymorphism level, the heterozygosity indices, and the Wright fixation index (Fis). The genotyping of cattle of the Aberdeen Angus breed on 15 microsatellite markers yielded the establishment of 80 alleles in the Kolos-firm LLP, 77 alleles in the Vishnevskoe LLP, and 92 alleles in the Sever-Agro N LLP. The total expected heterozygosity was He = 0.673, while the observed heterozygosity was Ho = 0.710. Full article

Viral infections caused by exposure to viruses such as Epstein–Barr, cytomegalovirus, or Parvovirus B19 have always been considered predisposing environmental factors for the onset of autoimmune diseases. More recently, autoimmune mechanisms such as molecular mimicry, T-cell activation, transient immunosuppression and inflammation have also been observed in cases of SARS-CoV-2 infection. Several newly diagnosed autoimmune disorders have been reported post-COVID-19, such as COVID-19-associated multisystemic inflammatory syndrome in children (MIS-C), type 1 diabetes mellitus, systemic lupus erythematosus, or rheumatoid arthritis. In this article, we present a new case of paediatric systemic lupus erythematosus (SLE) with haematological (macrophage activation syndrome), renal (stage 2), cutaneous (urticarial vasculitis) and digestive involvement, onset three and a half months post-COVID-19. In the dynamics, de novo infection generated by Epstein–Barr exposure was associated. The diagnosis was confirmed based on EULAR/ACR 2019 criteria. The aim of the article is to present a possible correlation between SARS-CoV-2 and Epstein–Barr as extrinsic factors in triggering or activating paediatric systemic lupus erythematosus. Keywords: paediatric systemic lupus erythematosus; post-COVID-19; Epstein–Barr; SARS- CoV-2; case report; paediatric patient. Full article

Biosorption successfully remediates saline water contaminated with legacy contaminants, but its effects on the health of marine organisms remain unclear. Therefore, our aim was to address this knowledge gap with data on the accumulation ability, as well as the cytogenetic and biochemical effects in turbot (Scophthalmus maximus). To this end, we exposed turbot for seven days to a mixture of remediated metals (Rem treatments: Cd, Hg, and Pb), with and without the presence of nanoparticles (NP), and compared them with the maximum allowable concentrations (MAC treatment) for effluent discharges. We determined the metal accumulation in the blood and kidney and evaluated haematological changes (red blood cell count, haemoglobin, and mean cell haemoglobin (MCH)) and genotoxicity (erythrocytic nuclear abnormalities assay) in the blood. The results showed that remediation with non-living macroalgae significantly reduced the metallic blood and kidney burdens in the Rem treatments. Furthermore, no genotoxic potential occurred in the Rem and MAC treatments in parallel with the reduction in MCH levels in the Rem treatments, which would reflect hematopoietic disturbances in the MAC. Our results validate biosorption remediation as we achieved a considerable reduction in metal loads while maintaining the health status of fish, highlighting the importance of testing water remediation methods in the biota. Full article

Animal nutrition plays an important role in the therapy of many diseases, including heart failure. The aim was to assess whether 6 months of feeding an AEP + ADH enriched diet (from fish meat) in dogs suffering from heart failure due to mitral degeneration impacts the dogs’ metabolic profile and clinical status. Twenty small breed dogs were included: 50% were in stage B2 of MMVD and 50%, in stage C according to ACVIM. Dogs were randomly divided into two groups. One group receiving a standard diet, the second one a diet enriched with EPA + DHA (from fish meat). All dogs continued to receive appropriate therapy throughout the study. Control examinations were performed at the start of the study, after 3 and 6 months of appropriate feeding. Examinations included ECG, ECHO, blood hemathology and biochemistry, morphometric measurements, body fat index and subcutaneous fat tissue thickness. Serum samples were analyzed with a high-performance liquid chromatography system. Data were analyzed using the Progenesis QI (PQI, Non-linear Dynamics). The results showed no differences in clinical, cardiological, haematological and biochemical parameters between the two study groups. An effect on the metabolomic profile following a continued diet enriched in DHA + EPA (from fish meat) was more pronounced with time. After 6 months of feeding the diete enriched with DHA + EPA (from fish meat), there was a favorable reduction in glycerophosphocholine and xanthine levels, but an adverse increase in lactate and furvan and a decrease in alanine was not stopped. Full article

Multiple myeloma is an incurable plasma cell neoplastic disease representing about 10–15% of all haematological malignancies diagnosed in developed countries. Proteasome is a key player in multiple myeloma and proteasome inhibitors are the current first-line of treatment. However, these are associated with limited clinical efficacy due to acquired resistance. One of the solutions to overcome this problem is a polypharmacology approach, namely combination therapy and multitargeting drugs. Several polypharmacology avenues are currently being explored. The simultaneous inhibition of EZH2 and Proteasome 20S remains to be investigated, despite the encouraging evidence of therapeutic synergy between the two. Therefore, we sought to bridge this gap by proposing a holistic in silico strategy to find new dual-target inhibitors. First, we assessed the characteristics of both pockets and compared the chemical space of EZH2 and Proteasome 20S inhibitors, to establish the feasibility of dual targeting. This was followed by molecular docking calculations performed on EZH2 and Proteasome 20S inhibitors from ChEMBL 25, from which we derived a predictive model to propose new EZH2 inhibitors among Proteasome 20S compounds, and vice versa, which yielded two dual-inhibitor hits. Complementarily, we built a machine learning QSAR model for each target but realised their application to our data is very limited as each dataset occupies a different region of chemical space. We finally proceeded with molecular dynamics simulations of the two docking hits against the two targets. Overall, we concluded that one of the hit compounds is particularly promising as a dual-inhibitor candidate exhibiting extensive hydrogen bonding with both targets. Furthermore, this work serves as a framework for how to rationally approach a dual-targeting drug discovery project, from the selection of the targets to the prediction of new hit compounds. Full article

Oesophageal adenocarcinoma (OAC) has a dismal prognosis, where curable disease occurs in less than 40% of patients, and many of those with incurable disease survive for less than a year from diagnosis. Despite the widespread use of systematic chemotherapy in OAC treatment, many patients receive no benefit. New treatments are urgently needed for OAC patients. There is an emerging interest in epigenetic regulators in cancer pathogenesis, which are now translating into novel cancer therapeutic strategies. Histone-modifying enzymes (HMEs) are key epigenetic regulators responsible for dynamic covalent histone modifications that play roles in both normal and dysregulated cellular processes including tumorigenesis. Several HME inhibitors are in clinical use for haematological malignancies and sarcomas, with numerous on-going clinical trials for their use in solid tumours. This review discusses the current literature surrounding HMEs in OAC pathogenesis and their potential use in targeted therapies for this disease. Full article

Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease. This review focuses on biofluids as a promising source of proteomic biomarkers in haematologic malignancies and a key component of future diagnostic, prognostic, and disease-monitoring applications. Full article

In the last decades, HOX proteins have been extensively studied due to their pivotal role in transcriptional events. HOX proteins execute their activity by exploiting a cooperative binding to PBX proteins and DNA. Therefore, an increase or decrease in HOX activity has been associated with both solid and haematological cancer diseases. Thus, inhibiting HOX-PBX interaction represents a potential strategy to prevent these malignancies, as demonstrated by the patented peptide HTL001 that is being studied in clinical trials. In this work, a computational study is described to identify novel potential peptides designed by employing a database of non-natural amino acids. For this purpose, residue scanning of the HOX minimal active sequence was performed to select the mutations to be further processed. According to these results, the peptides were point-mutated and used for Molecular Dynamics (MD) simulations in complex with PBX1 protein and DNA to evaluate complex binding stability. MM-GBSA calculations of the resulting MD trajectories were exploited to guide the selection of the most promising mutations that were exploited to generate twelve combinatorial peptides. Finally, the latter peptides in complex with PBX1 protein and DNA were exploited to run MD simulations and the ΔG_binding average values of the complexes were calculated. Thus, the analysis of the results highlighted eleven combinatorial peptides that will be considered for further assays. Full article

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N′-N′-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants’ concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits’ body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit’s vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir. Full article

Developing precision medicine is a major trend in clinical oncology. The main adverse effects of ifosfamide, actinomycin D and vincristine (IVA) treatment for rhabdomyosarcoma are haematological toxicities such as neutropenia or thrombocytopenia. The severity of these effects vary among patients but their dynamic profiles are similar. A non-empirical adjustment of the chemotherapy dose to avoid severe toxicities could help secure the treatment administration. Twenty-four patients with rhabdomyosarcoma treated with IVA chemotherapy courses were selected. Before and during each cycle, routine multiple blood cell counts were performed allowing for a dynamic study of the haematological toxicities. We developed a machine learning analysis using a gradient boosting regression technique to forecast the ifosfamide induced haematological toxicities as a function of neutrophils and platelets initial levels and the initial ifosfamide dose. To validate models’ accuracy, predicted and observed neutrophils and platelets levels were compared. The model was able to reproduce the dynamic profiles of the haematological toxicities. Among all cycles, the mean absolute errors between predicted and observed neutrophils and platelets levels were 1.0 and 72.8 G/L, respectively. Adjusting a patient’s ifosfamide dose based upon the predicted haematological toxicity levels at the end of a treatment cycle could enable tailored treatment. Full article

Poly(vinyl alcohol)/hyaluronic acid cryogels loaded with methotrexate were studied. The physical–chemical characterization of cryogels was performed by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimetry and dynamic mechanical thermal analysis. Acute toxicity and haematological parameters were determined by “in vivo” tests. The biocompatibility tests proved that the obtained cryogels showed significantly decreased toxicity and are biocompatible. The pH-responsiveness of the swelling behaviour and of the methotrexate release from the poly(vinyl alcohol)/hyaluronic acid (PVA/HA) cryogels were studied in a pH interval of 2–7.4. A significant change in properties was found at pH 5.5 specific for treatment of affected skin in psoriasis disease. Full article