Effect of complexation of oxidised corn starch with mineral elements on physicochemical properties

The objective of this study was to determine the effect of complexation of oxidised starch with mineral elements on its physicochemical properties. Corn starch was oxidised with sodium hypochlorite and, afterwards, modified with ions of potassium, magnesium and iron. Thus, native and modified starches were analysed for: contents of mineral elements, colour parameters (L*a*b*), water binding capacity and solubility in water at temperature of 60 and 80 °C. Thermodynamic characteristics of gelatinisation by DSC, molecular weight distribution by GPC, intrinsic viscosity and pasting properties by RVA were studied. The efficiency of incorporation of metal ions into oxidised corn starch was about 30%, 20% and 20% for potassium, magnesium and iron ions, respectively. The complexation with potassium ions caused the greatest changes in the molecular weight distribution and the intrinsic viscosity of starches and viscosity of starch pastes. Only modification of starch with iron ions affected the colour parameters of the starch. Incorporation of metal ions into starch resulted also in changes in its water binding capacity and solubility in water.     

Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.     

Oligomerization of Human Cystatin C—An Amyloidogenic Protein: An Analysis of Small Oligomeric Subspecies

Human cystatin C (HCC), an amyloidogenic protein, forms dimers and higher oligomers (trimers, tetramers and donut like large oligomers) via a domain-swapping mechanism. The aim of this study was the characterization of the HCC oligomeric states observed within the pH range from 2.2 to 10.0 and also in conditions promoting oligomerization. The HCC oligomeric forms obtained in different conditions were characterized using size exclusion chromatography, dynamic light scattering and small-angle X-ray scattering. The marked ability of HCC to form tetramers at low pH (2.3 or 3.0) and dimers at pH 4.0–5.0 was observed. HCC remains monomeric at pH levels above 6.0. Based on the SAXS data, the structure of the HCC tetramer was proposed. Changes in the environment (from acid to neutral) induced a breakdown of the HCC tetramers to dimers. The tetrameric forms of human cystatin C are formed by the association of the dimers without a domain-swapping mechanism. These observations were confirmed by their dissociation to dimers at pH 7.4.     

Vascularization Strategies in 3D Cell Culture Models: From Scaffold-Free Models to 3D Bioprinting

The discrepancies between the findings in preclinical studies, and in vivo testing and clinical trials have resulted in the gradual decline in drug approval rates over the past decades. Conventional in vitro drug screening platforms employ two-dimensional (2D) cell culture models, which demonstrate inaccurate drug responses by failing to capture the three-dimensional (3D) tissue microenvironment in vivo. Recent advancements in the field of tissue engineering have made possible the creation of 3D cell culture systems that can accurately recapitulate the cell–cell and cell–extracellular matrix interactions, as well as replicate the intricate microarchitectures observed in native tissues. However, the lack of a perfusion system in 3D cell cultures hinders the establishment of the models as potential drug screening platforms. Over the years, multiple techniques have successfully demonstrated vascularization in 3D cell cultures, simulating in vivo-like drug interactions, proposing the use of 3D systems as drug screening platforms to eliminate the deviations between preclinical and in vivo testing. In this review, the basic principles of 3D cell culture systems are briefly introduced, and current research demonstrating the development of vascularization in 3D cell cultures is discussed, with a particular focus on the potential of these models as the future of drug screening platforms.     

ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male’s HLA-C1C1 or HLA-C1C2 protected from RIF (p/p_corr. = 0.005/0.044, OR = 0.343; p/p_corr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male’s HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.     

The Size-Dependent Effects of Silver Nanoparticles on Germination,Early Seedling Development and Polar Metabolite Profile of Wheat (Triticum aestivum L.)

The phytotoxicity of silver nanoparticles (Ag NPs) to plant seeds germination and seedlings development depends on nanoparticles properties and concentration, as well as plant species and stress tolerance degrees. In the present study, the effect of citrate-stabilized spherical Ag NPs (20 mg/L) in sizes of 10, 20, 40, 60, and 100 nm, on wheat grain germination, early seedlings development, and polar metabolite profile in 3-day-old seedlings were analyzed. Ag NPs, regardless of their sizes, did not affect the germination of wheat grains. However, the smaller nanoparticles (10 and 20 nm in size) decreased the growth of seedling roots. Although the concentrations of total polar metabolites in roots, coleoptile, and endosperm of seedlings were not affected by Ag NPs, significant re-arrangements of carbohydrates profiles in seedlings were noted. In roots and coleoptile of 3-day-old seedlings, the concentration of sucrose increased, which was accompanied by a decrease in glucose and fructose. The concentrations of most other polar metabolites (amino acids, organic acids, and phosphate) were not affected by Ag NPs. Thus, an unknown signal is released by small-sized Ag NPs that triggers affection of sugars metabolism and/or distribution.     

Development and Comprehensive Characteristics of Thermosensitive Liquid Suppositories of Metoprolol Based on Poly(lactide-co-glycolide) Nanoparticles

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.     

COVID-19, Vaccination,and Female Fertility in the Czech Republic

The fast-track process to approve vaccines against COVID-19 has raised questions about their safety, especially in relation to fertility. Over the last 2 years, studies have appeared monitoring female fertility, especially from assisted reproduction centers or in animal experiments. However, studies monitoring healthy populations are still limited. The aim of our study was to monitor the relevant parameters of female fertility (sex and other steroids, LH, FSH, SHBG, Antimüllerian hormone and antral follicle count) before and then 2–4 months after the third dose of vaccination against COVID-19 in a group of 25 healthy fertile woman. In addition, anti-SARS-CoV-2 and anti-SARS-CoV-2S antibodies were determined. We did not observe significant changes in the measured parameters before and after the third dose of vaccination. By comparing levels of the analytes with antibodies indicating a prior COVID-19 infection, we found that women who had experienced the disease had statistically lower levels of estrone, estradiol, SHBG and 5α-dihydroprogesterone, and conversely, higher levels of androgen active dehydroepiandrosterone and dihydrotestosterone. Our results confirm that vaccination does not affect female fertility, and that what fertile women should be worried about is not vaccination, but rather COVID-19 infection itself.     

The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System—A Systematic Review

Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut–brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut–brain axis based on selected diseases, i.e., Alzheimer’s disease, Parkinson’s disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut–brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota–gut–brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome.