Calcium Phosphate Nanoparticles as Carriers of Low and High Molecular Weight Compounds.

Nanoparticles could improve the bioavailability of active agents of various natures to human, animal, and plant tissues. In this work, we compared two methods on the synthesis of calcium phosphate nanoparticles (CaPs), differed by the synthesis temperature, pH, and concentration of the stabilizing agent, and explored the possibilities of incorporation of a low-molecular-weight peptide analogue enalaprilat, the enzyme superoxide dismutase 1 (SOD1), as well as DNA and dsRNA into these particles, by coprecipitation and sorption. CaPs obtained with and without cooling demonstrated the highest inclusion efficiency for enalaprilat upon coprecipitation: 250 ± 10 μg/mg of CaPs and 340 ± 30 μg/mg of CaPs, respectively.

Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarization.

Aims: Study of the role of mitochondria-generated reactive oxygen species (mtROS) and mitochondrial polarization in mitochondrial fragmentation at the initial stages of myogenesis.

Main Methods: Mitochondrial morphology, Drp1 protein phosphorylation, mitochondrial electron transport chain components content, mtROS and mitochondrial lipid peroxidation levels, and mitochondrial polarization were evaluated on days 1 and 2 of human MB135 myoblasts differentiation. A mitochondria-targeted antioxidant SkQ1 was used to elucidate the effect of mtROS on mitochondria.

A Direct Comparison of Peptide Drug Delivery Systems Based on the Use of Hybrid Calcium Phosphate/Chitosan Nanoparticles versus Unmixed Calcium Phosphate or Chitosan Nanoparticles In Vitro and In Vivo.

Nanocarriers provide a number of undeniable advantages that could improve the bioavailability of active agents for human, animal, and plant cells. In this study, we compared hybrid nanoparticles (HNPs) consisting of a calcium phosphate core coated with chitosan with unmixed calcium phosphate (CaP) and chitosan nanoparticles (CSNPs) as carriers of a model substrate, enalaprilat. This tripeptide analog is an inhibitor of angiotensin-converting enzyme and was chosen by its ability to lower intraocular pressure (IOP).

Holmium-Containing Metal-Organic Frameworks as Modifiers for PEBA-Based Membranes.

Recently, there has been an active search for new modifiers to create hybrid polymeric materials for various applications, in particular, membrane technology. One of the topical modifiers is metal-organic frameworks (MOFs), which can significantly alter the characteristics of obtained mixed matrix membranes (MMMs). In this work, new holmium-based MOFs (Ho-MOFs) were synthesized for polyether block amide (PEBA) modification to develop novel MMMs with improved properties.

Cerebrospinal fluid indices as predictors of treatment response in autoimmune encephalitis.

Background: Cerebrospinal fluid (CSF) indices reflecting intrathecal antibody production and blood-brain barrier impairment are not routinely assessed in patients with autoimmune encephalitis (AE). We aimed to study CSF indices and their association with the prognosis of AE.

Methods: This retrospective cohort study conducted at Amrita Institute of Medical Sciences (AIMS), Kochi, India, included 60 patients aged more than 18 years with definite/probable/possible AE admitted to the Department of Neurology from August 2016 to November 2021.

Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis.

Many muscular pathologies are associated with oxidative stress and elevated levels of the tumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesis defects caused by TNF are mediated in part by reactive oxygen species (ROS), including those produced by mitochondria (mitoROS), but the mechanism of their pathological action is not fully understood. We hypothesized that mitoROS act by triggering and enhancing mitophagy, an important tool for remodelling the mitochondrial reticulum during myogenesis.

Chitosan-Covered Calcium Phosphate Particles Co-Loaded with Superoxide Dismutase 1 and ACE Inhibitor: Development, Characterization and Effect on Intraocular Pressure.

Improvement of the efficiency of drug penetration into the eye tissues is still an actual problem in ophthalmology. One of the most promising solutions is drug encapsulation in carriers capable of overcoming the cornea/sclera tissue barrier. Formulations on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), and an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by simultaneous inclusion of both drugs into calcium phosphate (CaP) particles in situ with subsequent covering of the particles with 5 kDa chitosan.

Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye.

Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients.

Chitosan-covered calcium phosphate particles as a drug vehicle for delivery to the eye.

Formulations on the base of an inhibitor of angiotensin-converting enzyme, enalaprilat, were prepared by the inclusion of the drug into calcium phosphate (CaP)-particles in situ, followed by the covering of the particles with 5 kDa chitosan or 72 kDa glycol chitosan and cross-linking with sodium tripolyphosphate. Physicochemical characterization of the resulted hybrid particles was conducted using dynamic light scattering, as well as scanning and transmission electron microscopy. Enalaprilat-containing particles had a mean hydrodynamic diameter 180 nm and 260 nm and ζ-potential +7 mV and +16 mV for 5 kDa and 72 kDa chitosans, respectively.

Identifying Early Vascular Ageing in Patients With Metabolic Syndrome: Unresolved Issues and a Proposed Novel VAmets Score.

Purpose: To identify the features of early vascular ageing (EVA) in patients with metabolic syndrome (MetS), to assess the accuracy of existing methods for determining vascular age in MetS, and to derive a new score (VAmets) for the calculation of vascular age and predicting EVA in patients with MetS.

Methods: Prospective open cohort study using routinely collected data from general practice. A total of 750 patients (age, 35-80 yrs old) with MetS were examined.

Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy.

Muscles of patients with facioscapulohumeral dystrophy (FSHD) are characterized by sporadic DUX4 expression and oxidative stress which is at least partially induced by DUX4 protein. Nevertheless, targeting oxidative stress with antioxidants has a limited impact on FSHD patients, and the exact role of oxidative stress in the pathology of FSHD, as well as its interplay with the DUX4 expression, remain unclear. Here we set up a screen for genes that are upregulated by DUX4 via oxidative stress with the aim to target these genes rather than the oxidative stress itself.

Interannual monsoon wind variability as a key driver of East African small pelagic fisheries.

Small pelagic fisheries provide food security, livelihood support and economic stability for East African coastal communities-a region of least developed countries. Using remotely- sensed and field observations together with modelling, we address the biophysical drivers of this important resource. We show that annual variations of fisheries yield parallel those of chlorophyll-a (an index of phytoplankton biomass).

One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.

Background: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.

In search for the sources of plastic marine litter that contaminates the Easter Island Ecoregion.

Subtropical gyres are the oceanic regions where plastic litter accumulates over long timescales, exposing surrounding oceanic islands to plastic contamination, with potentially severe consequences on marine life. Islands' exposure to such contaminants, littered over long distances in marine or terrestrial habitats, is due to the ocean currents that can transport plastic over long ranges. Here, this issue is addressed for the Easter Island ecoregion (EIE).

DUX4 Pathological Expression: Causes and Consequences in Cancer.

DUX4, a double homeobox transcription factor, has been mostly studied in facioscapulohumeral dystrophy (FSHD), a pathology linked to a deletion of subtelomeric repeats on chromosome 4q. More recently, however, the gene has been associated with various sarcomas and haematological malignancies. Drugs developed for FSHD could be tested on cancer cells to develop efficient treatment strategies for both pathologies.

Real-world study of efficacy, risk management and reasons for discontinuation of natalizumab for treatment of multiple sclerosis in Russia.

Background: NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far.

Objective: To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia.

MiRNAs from Imprinted Locus at 14q32 are Associated with Multiple Sclerosis: Gender-Specific Expression and Regulation of Receptor Tyrosine Kinases Signaling.

Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent course of multiple sclerosis. It is an autoimmune inflammatory disease of the central nervous system. To investigate the gender-specific involvement of microRNAs (miRNAs) in RRMS pathogenesis, we compared miRNA profiles in peripheral blood mononuclear cells separately in men and women (eight RRMS patients versus four healthy controls of each gender) using high-throughput sequencing.

Genetic differences between primary progressive and relapsing-remitting multiple sclerosis: The impact of immune-related genes variability.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of CNS with a highly heterogeneous clinical course. The role of the genetic variability in determination of MS course is not yet well established. We aimed to estimate the impact of immune-related genes variability in the genetic architecture of two clinically different MS courses - primary progressive (PPMS) and relapsing-remitting (RRMS).

Immune-related miRNA expression patterns in peripheral blood mononuclear cells differ in multiple sclerosis relapse and remission.

MiRNAs were shown to participate in development of autoimmune inflammatory process in multiple sclerosis (MS). To investigate miRNAs involvement in relapse-remission MS course, we analyzed expression of immune-related miRNAs in PBMC of treatment-naïve relapsing and remitting MS patients and healthy controls. The upregulation of miR-126-3p, miR-146b-5p, miR-155, miR-196a-5p, miR-21-5p, miR-223-3p, miR-326 and miR-379-5p in remission compared to relapse was observed; when apply gender stratification, miR-223-3p and miR-379-5p were upregulated only in men.

Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice.

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals.

Nanotraps with biomimetic surface as decoys for chemokines.

A creation of nanotraps that could selectively recognize the chemotactic mediators of leukocyte adhesion and eliminate them from the bloodstream and tissue intercellular matrix is a promising approach for the treatment of various inflammatory and autoimmune diseases. We designed nanotraps as artificial decoy receptors based on poly(lactic acid) (PLA) nanoparticles covered by heparin and bearing on the surface two fragments of CCR5 receptor (N-terminal domain, Nt, and second extracellular loop, ECL2), responsible for chemokine binding. In order to attach Nt and ECL2 to the heparin shell, the corresponding peptides were modified with N- and/or C-terminal oligolysines.

New insights into the burden and costs of multiple sclerosis in Europe: Results for Russia.

Background: In order to assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This, in turn, requires that cost data be regularly updated.

Objective And Methods: This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HQoL).