GPX4 is a key ferroptosis regulator orchestrating T cells and CAR-T-cells sensitivity to ferroptosis.

Induction of ferroptosis, an iron-dependent form of regulated cell death, holds promise as a strategy to overcome tumor resistance to conventional therapies and enhance immunotherapy responses. However, while the susceptibility of tumor cells to ferroptosis is extensively studied, limited data exists on the vulnerability of immune cells to disturbed iron balance and lipid peroxidation. Here, we found that T-cell stimulation rewires iron and redox homeostasis and by increasing levels of reactive oxygen species and labile iron promotes lipid peroxidation and T-cells' ferroptosis.

Inhibition of the HIF-1α Signaling Pathway Promotes Oligodendrocyte Maturation in the In Vitro Model of Perinatal Asphyxia.

Preterm or complicated labor is often accompanied by the asphyxia of the newborn. Temporal limitation of oxygen and nutrient supply can be especially harmful to the developing brain and lead to hypoxic-ischemic encephalopathy. This injury is mainly caused by the reduction in white matter volume and may be triggered by delayed maturation of oligodendrocytes and affected myelination.

Inhibition of BET proteins modulates amyloid-beta accumulation and cognitive performance in middle-aged mice prenatally exposed to maternal immune activation.

Introduction: Given the complex etiological basis of Alzheimer's disease (AD), it is reasonable to hypothesize that neuronal dysfunction and death result from the interplay of numerous factors, both genetic and environmental. Accumulating evidence implicates the immune system and inflammation as key components of the pathomechanism of AD. In the present study, we analyzed the effect of maternal immune activation (MIA) on AD-related pathological changes in middle-aged 12-month-old offspring mice.

Dynamic changes in BDNF, VEGF, and GDNF after transplanting human protein-based scaffolds with Wharton's Jelly MSCs in a rat brain injury model.

Stroke poses a considerable challenge for regenerative medicine due to the complex and multidimensional specificity of the central nervous system, and cell therapy is one of the currently considered treatments. The aim of this study was to determine the pro-regenerative outcome after transplantation of preconditioned and scaffold-encapsulated mesenchymal stem/stromal cells isolated from Wharton's Jelly (WJ-MSCs) in an experimental rat model of brain injury. For this purpose, WJ-MSCs cultured at different oxygen concentrations (21% O or 5% O) were transplanted into the injured rat brain in saline or hydrogel scaffolds derived from human platelet lysate or fibrinogen.

An antibiotic-free antimicrobial combination of bacteriocins and a peptidoglycan hydrolase: and assessment of its efficacy.

Mastitis is an inflammatory disease of the mammary gland usually caused by bacterial pathogens that gain physical access to the glandular epithelium through the teat canal. In bovines, common mastitis-causing agents are environmental or pathogenic bacterial species, including staphylococci, streptococci, enterococci, and gram-negative bacteria such as . Current therapeutic strategies for bovine mastitis typically involve the administration of antibiotic formulations into the infected udder, which can result in increased selection for antibiotic resistance and the accumulation of antibiotic residues in milk.

Lipidated DAPEG Polymers as a Non-Toxic Transfection Agent-Influence of Fatty Acid Side Chain on Transfection Efficacy.

This study describes the synthesis, interaction with DNA, and transfection efficacy of eight lipidated compounds based on a recently published non-lipidated parent molecule, an octamer of 2,3-l-Dap, carrying the guanidine group on its side chain. The compounds obtained were found to be non-toxic up to 5 µM and efficient DNA binders and showed greater transfection efficiency than the parent compound, with two leading molecules containing acetic and decanoic moieties. DLS experiments indicated two groups of interaction with DNA.

Design and Characterization of Antibacterial Peptide Nanofibrils as Components of Composites for Biomaterial Applications.

Purpose: The purpose of this study was to design and synthesize the ug46 peptide, incorporate its fibrils into composite materials, and evaluate its structural and antimicrobial properties. Another objective was to utilize spectroscopy and molecular simulation, enhanced by Machine Vision methods, to monitor the aggregation process of the ug46 peptide and assess its potential as a scaffold for an antimicrobial peptide.

Method: The structural analysis of the ug46 peptide reveals its dynamic conformational changes.

Modulation of N-glycosylation in the PD-1: PD-L1 axis as a strategy to enhance cancer immunotherapies.

The modulation of the N-glycosylation status in immune checkpoints, particularly the PD-1/PD-L1 axis, has emerged as a promising approach to enhance cancer immunotherapies. While immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have achieved significant clinical success, recent studies highlight the critical role of N-glycosylation in regulating their expression, stability, and function. Alterations in N-glycosylation might affect the efficacy of ICIs by modulating the interactions between immune checkpoints and antibodies used in therapy.

A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?

Despite the fact that there are published case reports and model work providing evidence of inflammation in Charcot-Marie-Tooth disorders (CMTs), in clinical practice, CMT and inflammatory neuropathies are always classified as two separate groups of disorders. This sharp separation of chronic neuropathies into two groups has serious clinical implications. As a consequence, the patients harboring CMT mutations are practically excluded from pharmacological anti-inflammatory treatments.

Correction: Xin et al. Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage. 2022, , 2976.

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Plastic nanoparticles interfere with extracellular vesicle pathway in primary astrocytes.

The extensive production and use of plastics in recent decades has led to environmental pollution. It has been discovered that plastic microparticles (MPs) and nanoparticles (NPs), formed under the influence of physical forces, can pose a significant health risk. Increasing evidence indicates that NPs can have various toxic effects, including oxidative stress and cell death.

Peptidomimetic inhibitors of the VEGF-A/NRP-1 complex obtained by modification of the C-terminal arginine.

Inhibitors of the interaction between Neuropilin-1 (NRP-1) and Vascular Endothelial Growth Factor-A (VEGF-A) hold significant promise as therapeutic and diagnostic agents directed against cancers overexpressing NRP-1. In our efforts in this field, a few series of strong and fairly stable peptide-like inhibitors of the general formula Lys(Har)-Xaa-Xaa-Arg have been previously discovered. In the current work, we focused on Lys(Har)-Dap/Dab-Pro-Arg sequence.

Polymers of functionalized diaminopropionic acid are efficient mediators of active exogenous enzyme delivery into cells.

Delivery of active protein especially enzyme is one of the major therapeutic challenge. Replacing or substituted invalid/improper acting protein offer fast and effective treatment of disease. Herein, we describe the synthesis and properties of biotinylated peptidomimetics consisting of oxoacid-modified 2,3, L-diaminopropionic acid residues with guanidine groups on its side chains.

Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20 Philadelphia-positive B-cell precursor acute lymphoblastic leukemia in preclinical models.

Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL) is a high-risk subtype of acute lymphoblastic leukemia characterized by the presence of the BCR::ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) combined with chemotherapy are established as the first-line treatment. Additionally, rituximab, an anti-CD20 monoclonal antibody is administered to adult BCP-ALL patients with ≥20% CD20+ blasts.

Engineering of chimeric enzymes with expanded tolerance to ionic strength.

Antimicrobial resistance poses a significant global threat, reaching dangerously high levels as reported by the World Health Organization. The emergence and rapid spread of new resistance mechanisms, coupled with the absence of effective treatments in recent decades, have led to thousands of deaths annually from infections caused by drug-resistant microorganisms. Consequently, there is an urgent need for the development of new compounds capable of combating antibiotic-resistant bacteria.

Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells.

CD20 located predominantly on the B cells plays a crucial role in their development, differentiation, and activation, and serves as a key therapeutic target for the treatment of B-cell malignancies. The breakthrough of monoclonal antibodies directed against CD20, notably exemplified by rituximab, revolutionized the prognosis of B-cell malignancies. Rituximab, approved across various hematological malignancies, marked a paradigm shift in cancer treatment.

Exploring key genes and pathways associated with sex differences in autism spectrum disorder: integrated bioinformatic analysis.

Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder marked by functional abnormalities in brain that causes social and linguistic difficulties. The incidence of ASD is more prevalent in males compared to females, but the underlying mechanism, as well as molecular indications for identifying sex-specific differences in ASD symptoms remain unknown. Thus, impacting the development of personalized strategy towards pharmacotherapy of ASD.

Concomitant inhibition of the thioredoxin system and nonhomologous DNA repair potently sensitizes Philadelphia-positive lymphoid leukemia to tyrosine kinase inhibitors.

Breakpoint cluster region-Abelson () gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia-positive (Ph) B-cell acute lymphoblastic leukemia (B-ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph B-ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph B-ALL.

S1P receptor modulators affect the toxicity of amyloid β oligomers in microglial and neuronal cells.

A large body of evidence has shown that the amyloid b peptide oligomers (Abo) are predominantly responsible for the neurodegeneration/cognitive impairments in Alzheimer's disease (AD). Abo cause mitochondrial dysfunctions leading to an imbalance between pro- and antiapoptotic proteins and finally to neuronal apoptosis. Further, Abo trigger overactivation of microglia followed by enhanced release of proinflammatory cytokines, which exacerbates neurotoxicity of Abo.

Diagnostics and Treatment of Extrameningeal Solitary Fibrous Tumors.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms that account for less than 2% of all soft tissue masses. In the latest WHO 2020 Classification of Soft Tissue Tumors, extrameningeal SFT was listed as intermediate (rarely metastasizing) or malignant neoplasms. Due to the lack of characteristic clinical features, their diagnosis and treatment remain challenging.

Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones.

Synthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds with anticancer potential. We reasoned that such bifunctional conjugates may have enhanced cytotoxic activity.