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Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.

The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.

Background: Knowledge about extracardiac anomalies (ECA) in fetal congenital heart disease (CHD) can improve our understanding of the developmental origins of various outcomes in these infants. The prevalence and spectrum of ECA, including structural brain anomalies (SBA), on magnetic resonance imaging (MRI) in fetuses with different types of CHD and at different gestational ages, is unknown., Objectives: The purpose of this study was to evaluate ECA rates and types on MRI in fetuses with different types of CHD and across gestation., Methods: A total of 429 consecutive fetuses with CHD and MRI between 17 and 38 gestational weeks were evaluated. ECA and SBA rates were assessed for each type of CHD and classified by gestational age (<25 or ≥25 weeks) at MRI., Results: Of all 429 fetuses with CHD, 243 (56.6%) had ECA on MRI, and 109 (25.4%) had SBA. Among the 191 fetuses with normal genetic testing results, the ECA rate was 54.5% and the SBA rate 19.4%. Besides SBA, extrafetal (21.2%) and urogenital anomalies (10.7%) were the most prevalent ECA on MRI in all types of CHD. Predominant SBA were anomalies of hindbrain-midbrain (11.0% of all CHD), dorsal prosencephalon (10.0%) development, and abnormal cerebrospinal fluid spaces (10.5%). There was no difference in the prevalence or pattern of ECA between early (<25 weeks; 45.7%) and late (≥25 weeks; 54.3%) fetal MRI., Conclusions: ECA and SBA rates on fetal MRI are high across all types of CHD studied, and ECA as well as SBA are already present from midgestation onward., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

"Western diet" containing high concentrations of sugar and fat consumed during pregnancy contributes to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet in animals, a cafeteria (CAF) diet is used. We hypothesized that CAF diet given to rats before, and during pregnancy and lactation differently influences fat content, metabolic and inflammation profiles in offspring. Females were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25), body composition, fat contents were measured, and blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet lead to sex-specific alterations in offspring. At PND25, CAF offspring had: (1) higher percentage of fat content, and were lighter; (2) sex-specific differences in levels of glucose; (3) higher levels of interleukin 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); (4) sex-specific differences in concentration of IL-6 and TNF-α, with an increase in CAF females; (5) higher level of IL-10 in both sexes, with a more pronounced increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet., (© 2021. The Author(s).)

Liposomes are phospholipid-based self-assembled nanoparticles. Various components can be solubilized in the lipid bilayer, encapsulated in the aqueous core or attached to the surface, making liposomes attractive platforms for multimodality functionalization. Here we describe theranostic liposomes delivering a magnetic resonance contrast agent (lipid derivative of gadopentetic acid) and a hydrophobic photosensitizer (zinc phthalocyanine, ZnPc) for photodynamic therapy of cancer. For the first time, this theranostic system was prepared by the microfluidic method. Analogous formulations were produced by thin lipid film hydration (TLH) with down-sizing performed by extrusion for comparison purposes. We demonstrated double the loading capacity of ZnPc into liposomes made by microfluidics compared to TLH/extrusion. Microfluidics resulted in the theranostic nanoliposomes characterized by sizes =2.5x smaller than vesicles prepared by TLH/extrusion. Increased relaxivity was observed for liposomes manufactured by microfluidics compared to TLH, despite a slightly lower Gd chelate recovery. We attributed the improved relaxation to the increased surface area/volume ratio of vesicles and decreased phosphatidylcholine/ZnPc molar ratio, which affected water molecules' diffusion through the liposomal membrane. Finally, we showed photodynamic efficacy of ZnPc loaded into theranostic liposomes in head and neck cancer model, resulting in IC 50 of 0.22 - 0.61 μM, depending on the formulation and cell line used. We demonstrate microfluidics' feasibility to be used for theranostic liposome manufacturing and co-entrapment of therapeutic and imaging components in a single-step process with a high yield., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.

Myocardial infarction (MI) is one of the most frequent causes of death in industrialized countries. Stem cells therapy seems to be very promising for regenerative medicine. Skeletal myoblasts transplantation into postinfarction scar has been shown to be effective in the failing heart but shows limitations such, e.g. cell retention and survival. We synthesized and investigated superparamagnetic iron oxide nanoparticles (SPIONs) as an agent for direct cell labeling, which can be used for stem cells imaging. High quality, monodisperse and biocompatible DMSA-coated SPIONs were obtained with thermal decomposition and subsequent ligand exchange reaction. SPIONs' presence within myoblasts was confirmed by Prussian Blue staining and inductively coupled plasma mass spectrometry (ICP-MS). SPIONs' influence on tested cells was studied by their proliferation, ageing, differentiation potential and ROS production. Cytotoxicity of obtained nanoparticles and myoblast associated apoptosis were also tested, as well as iron-related and coating-related genes expression. We examined SPIONs' impact on overexpression of two pro-angiogenic factors introduced via myoblast electroporation method. Proposed SPION-labeling was sufficient to visualize firefly luciferase-modified and SPION-labeled cells with magnetic resonance imaging (MRI) combined with bioluminescence imaging (BLI) in vivo. The obtained results demonstrated a limited SPIONs' influence on treated skeletal myoblasts, not interfering with basic cell functions.

To investigate whether ZEN transfers from the alimentary tract of fish to the somatic cells of ovaries or the oocytes, mature females of rainbow trout were orally exposed to ZEN at a dose of 1 mg·kg - 1 body mass. At sampling times of 2, 6, 12, 24, 48, and 96 h, tissues of the fish (intestine, liver, ovaries, oocytes, muscles, and plasma) were extracted to determine the concentration of ZEN and its metabolites using immunoaffinity columns and HPLC-FLD. Our results confirm that ZEN is transferred from the alimentary tract to the reproductive system of the fish, and indicate that the mycotoxin concentrates in the somatic cells of the ovaries. Importantly, ZEN transferred to the fishes' oocytes and muscles only to a limited extent. Our additional survey of fish hatcheries and local stores indicated only trace amounts of ZEN residuals in the samples that were collected in Poland and Norway between 2013 and 2015, which probably reflects good hygienic conditions for the feed used in these hatcheries. Furthermore, our results indicate that the health risk from dietary intake of ZEN from fish roe is negligible. However, the potential of ZEN to transfer to the fish ovaries may be of concern for aquaculture., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mitotic gynogenesis results in the production of fully homozygous individuals in a single generation. Since inbred fish were found to exhibit an increased frequency of body deformations that may affect their survival, the main focus of this research was to evaluate the ratio of individuals with spinal deformities among gynogenetic doubled haploids (DHs) brown trout as compared to nonmanipulated heterozygous individuals. Gynogenetic development was induced by the activation of brown trout eggs by UV-irradiated homologous and heterologous (rainbow trout) spermatozoa. The subsequent exposure of the activated eggs to the high hydrostatic pressure disturbed the first cleavage in gynogenetic zygotes and enabled duplication of the maternal haploid set of chromosomes. The survival rate was significantly higher among gynogenetic brown trout hatched from eggs activated with the homologous UV-irradiated spermatozoa when compared to DHs hatched from eggs activated by the heterologous spermatozoa. More than 35% of the gynogenetic larvae exhibited body deformities, mostly lordosis and scoliosis. The percentage of malformed brown trout from the control group did not exceed 15%. The increased number of deformed larvae among DHs brown trout suggested rather a genetic background of the disease related to the fish spine deformities; however, both genetic and environmental factors were discussed as a cause of such conditions in fish.