Emidonol is a Russian antioxidant drug, widely used in veterinary medicine both for prophylactic purposes and under pathological conditions associated with oxygen deficiency. The product of its biotransformation in animals is meldonium, which is a metabolic modulator and has been included on the Prohibited List by the World Anti-Doping Agency (WADA) since 2016. In the presented research, volunteers once consumed samples of milk from cows that had undergone a 15-day course of the veterinary drug Emidonol® 10%, obtained from one of the farms in the Moscow region.
View Article and Find Full Text PDFInjuries of the respiratory system caused by viral infections (e.g., by influenza virus, respiratory syncytial virus, metapneumovirus, or coronavirus) can lead to long-term complications or even life-threatening conditions.
View Article and Find Full Text PDFCancer is unquestionably a global healthcare challenge, spurring the exporation of novel treatment approaches. In recent years, nanomaterials have garnered significant interest with the greatest hopes for targeted nanoformulations due to their cell-specific delivery, improved therapeutic efficacy, and reduced systemic toxicity for the organism. The problem of successful clinical translation of nanoparticles may be related to the fact that most in vitro tests are performed at pH values of normal cells and tissues, ranging from 7.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
October 2024
N-Heterocyclic carbenes (NHC) are well-recognized ligands of choice for preparing robust transition metal species. However, their use for fabrication of biomedically relevant nanoparticles has been limited to the synthesis of non-targeted particles showing increased tolerance to different aqueous coagulants. In this work, the first example of carbene-coated metal nanoparticles suitable for in vivo applications is presented.
View Article and Find Full Text PDFCurrently, various functionalized nanocarrier systems are extensively studied for targeted delivery of drugs, peptides, and nucleic acids. Joining the approaches of genetic and chemical engineering may produce novel carriers for precise targeting different cellular proteins, which is important for both therapy and diagnosis of various pathologies. Here we present the novel nanocontainers based on vectorized genetically encoded (Mx) encapsulin, confining a fluorescent photoactivatable mCherry (PAmCherry) protein.
View Article and Find Full Text PDFRecent developments in the field of nanomedicine have introduced a wide variety of nanomaterials that are capable of recognizing and killing tumor cells with increased specificity. A major limitation preventing the widespread introduction of nanomaterials into the clinical setting is their fast clearance from the bloodstream via the mononuclear phagocyte system (MPS). One of the most promising methods used to overcome this limitation is the MPS-cytoblockade, which forces the MPS to intensify the clearance of erythrocytes by injecting allogeneic anti-erythrocyte antibodies and, thus, significantly prolongs the circulation of nanoagents in the blood.
View Article and Find Full Text PDFTargeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are promising agents for liquid biopsy-a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification.
View Article and Find Full Text PDFMacrophages play an important role in the adaptive immune system. Their ability to neutralize cellular targets through Fc receptor-mediated phagocytosis has relied upon immunotherapy that has become of particular interest for the treatment of cancer and autoimmune diseases. A detailed investigation of phagocytosis is the key to the improvement of the therapeutic efficiency of existing medications and the creation of new ones.
View Article and Find Full Text PDFAbnormal mRNAs of the hybrid BCR-ABL gene in the majority of cases initiate the synthesis of proteins with a mass of 210 kDa (p210), 190 kDa (p190), and 230 kDa (p230). Expression of the p210 variant is most common in CML (95% of cases), while the p190 and p230 variants are less common (1-4%). On the contrary, p190 predominates in ALL.
View Article and Find Full Text PDFReducing the undesirable systemic effect of photodynamic therapy (PDT) can be achieved by incorporating a photosensitizer in microparticles (MPs). This study is devoted to the preparation of biocompatible biodegradable MPs with the inclusion of the natural photosensitizer Radachlorin (RС) and an assessment of the possibility of their use for PDT. RC-containing MPs (RС MPs) with poly(lactic-co-glycolic acid) copolymer (PLGA) matrix were prepared by a double emulsion solvent evaporation methods.
View Article and Find Full Text PDFThe unloading of postural muscles leads to the changes in myosins heavy chains isoforms (MyHCs) mRNAs transcription pattern, that cause severe alterations of muscle functioning. Several transcription factors such as NFATc1 and TEAD1 upregulate slow MyHC mRNA transcription, and p38 MAP kinase can phosphorylate NFAT and TEAD1, causing their inactivation. However, the role p38 MAP kinase plays in MyHCs mRNAs transcription regulation in postural soleus muscle during unloading remains unclear.
View Article and Find Full Text PDFWe studied the effect of histone deacetylase 1 (HDAC1) inhibition on titin content and expression of TTN gene in rat m. soleus after 3-day gravitational unloading. Male Wistar rats weighing 210±10 g were randomly divided into 3 groups: control, 3-day hindlimb suspension, and 3-day hindlimb suspension and injection of HDAC1 inhibitor CI-994 (1 mg/kg/day).
View Article and Find Full Text PDFUnloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq).
View Article and Find Full Text PDFWe studied the effect of acrylamide on the content of intracellular ATP in the cells of bacteria of the genera Rhodococcus and Alcaligenes, the luminescence of the genetically engineered strain Escherichia coli K12 TG1 (pXen7), and the survival of bacteria of various systematic groups. According to the level of decrease in the concentration of intracellular ATP, it was found that the strain with lower amidase activity (R. erythropolis 6-21) and Gram-negative proteobacteria A.
View Article and Find Full Text PDFThe development of synthetic ways to fabricate nanosized materials with a well-defined shape, narrow-sized distribution, and high stability is of great importance to a rapidly developing area of nanotechnology. Here, we report an unusual reaction between amorphous two-line ferrihydrite and concentrated sulfuric or other mineral and organic acids. Instead of the expected dissolution, we observed the formation of new narrow-distributed brick-red nanoparticles (NPs) of hematite.
View Article and Find Full Text PDFTo test the hypothesis that p38α-MAPK plays a critical role in the regulation of E3 ligase expression and skeletal muscle atrophy during unloading, we used VX-745, a selective p38α inhibitor. Three groups of rats were used: non-treated control (C), 3 days of unloading/hindlimb suspension (HS), and 3 days HS with VX-745 inhibitor (HSVX; 10 mg/kg/day). Total weight of soleus muscle in HS group was reduced compared to C (72.
View Article and Find Full Text PDFNanoparticles (NPs) that can provide additional functionality to the nanoagents derived from them, , cytotoxicity or imaging abilities, are in high demand in modern nanotechnology. Here, we report new spindle-like iron oxide nanoparticles doped with Eu that feature magnetic resonance imaging (MRI) contrasting properties together with shape-related cytotoxicity (unusual for such low 2.4% Eu content).
View Article and Find Full Text PDFSmart materials that can switch between different states under the influence of chemical triggers are highly demanded in biomedicine, where specific responsiveness to biomarkers is imperative for precise diagnostics and therapy. Superior selectivity of drug delivery to malignant cells may be achieved with the nanoagents that stay "inert" until "activation" by the characteristic profile of microenvironment cues ( tumor metabolites, angiogenesis factors, microRNA/DNA, ). However, despite a wide variety and functional complexity of smart material designs, their real-life applications are hindered by very limited sensitivity to inputs.
View Article and Find Full Text PDFNanosized metal-organic frameworks (nMOFs) have shown great promise as high-capacity carriers for a variety of applications. For biomedicine, numerous nMOFs have been proposed that can transport virtually any molecular drug, can finely tune their payload release profile, etc. However, perspectives of their applications for the targeted drug delivery remain relatively unclear.
View Article and Find Full Text PDFUnderstanding the intricacies of particle-cell interactions is essential for many applications such as imaging, phototherapy, and drug/gene delivery, because it is the key to accurate control of the particle properties for the improvement of their therapeutic and diagnostic efficiency. Recently, high-throughput methods have emerged for the detailed investigation of these interactions. For example, imaging flow cytometry (IFC) collects up to 60,000 images of cells per second (in 12 optical channels) and provides information about morphology and organelle localization in combination with fluorescence and side scatter intensity data.
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