Halochromic Bacterial Cellulose/Anthocyanins Hybrid Polymer Film with Wound-Healing Potential.

Polymer-based dressings deriving from natural biomaterials have advantages such as nontoxicity, biocompatibility, and mechanical stability, which are essential for efficient wound healing and microbial infection diagnostics. Here, we designed a prototype of an intelligent hydrogel dressing on the base of bacterial cellulose (BC) for monitoring wound microbial infection due to the uploaded natural pH dye-sensor, anthocyanins (ANC) of elderberry fruit ( L.).

Comprehensive Review of Chronic Stress Pathways and the Efficacy of Behavioral Stress Reduction Programs (BSRPs) in Managing Diseases.

The connection between chronic psychological stress and the onset of various diseases, including diabetes, HIV, cancer, and cardiovascular conditions, is well documented. This review synthesizes current research on the neurological, immune, hormonal, and genetic pathways through which stress influences disease progression, affecting multiple body systems: nervous, immune, cardiovascular, respiratory, reproductive, musculoskeletal, and integumentary. Central to this review is an evaluation of 16 Behavioral Stress Reduction Programs (BSRPs) across over 200 studies, assessing their effectiveness in mitigating stress-related health outcomes.

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level.

The role of USP1 deubiquitinase in the pathogenesis and therapy of cancer.

Ubiquitin-specific protease 1 (USP1) is an important deubiquitinating enzyme (DUB) involved in the maintenance of genome integrity, cell cycle, and cell homeostasis. USP1 overexpression is a characteristic feature of various cancers, correlating with a poor prognosis. The review summarizes the recent knowledge in understanding the role of deubiquitinase USP1 in the stabilization of oncoproteins and tumor suppressors, as a critical event in cancer development and progression.

PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer's disease.

Disrupted tau proteostasis and transneuronal spread is a pathological hallmark of Alzheimer's disease. Neurodegenerative diseases remain an unmet medical need and novel disease modifying therapeutics are paramount. Our objective was to develop a mechanistic mathematical model to enhance our understanding of tau antibody pharmacokinetics and pharmacodynamics in animals and humans.

Germanium Nanoparticles Prepared by Laser Ablation in Low Pressure Helium and Nitrogen Atmosphere for Biophotonic Applications.

Due to particular physico-chemical characteristics and prominent optical properties, nanostructured germanium (Ge) appears as a promising material for biomedical applications, but its use in biological systems has been limited so far due to the difficulty of preparation of Ge nanostructures in a pure, uncontaminated state. Here, we explored the fabrication of Ge nanoparticles (NPs) using methods of pulsed laser ablation in ambient gas (He or He-N mixtures) maintained at low residual pressures (1-5 Torr). We show that the ablated material can be deposited on a substrate (silicon wafer in our case) to form a nanostructured thin film, which can then be ground in ethanol by ultrasound to form a stable suspension of Ge NPs.

Nuclear localization of BCR and cortactin indicates their potential role in regulation of actin branching in nucleus.

Aim: To study cellular localization of full-length breakpoint cluster region (BCR), Pleckstrin homology domain of BCR and cortactin and determine whether they can coexist in cell nucleus.

Materials And Methods: HEK293T cell line was transfected with pECFP-BCR, pEGFP-PH and pmTagRFP-N1-CTTN using polyethyleneimine. Live cells were imaged in cell culture dishes with glass coverslip attached to the bottom with Leica SP8 STED 3D confocal microscope in the environmental chamber.

Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells.

Aim: To analyze interaction of ubiquitin specific peptidase 1 (USP1) with Bcr-Abl and to assess the relation between USP1 functional activity and Bcr-Abl expression in K562 chronic myeloid leukemia cells.

Materials And Methods: The interaction between USP1 and Bcr-Abl in K562 cells was analyzed by co-immunoprecipitation, Western blot analysis, and confocal microscopy.

Results: A direct interaction between Bcr-Abl oncoprotein and USP1 protein in K562 cells was established by co-immunoprecipitation.

Tailoring Photoluminescence from Si-Based Nanocrystals Prepared by Pulsed Laser Ablation in He-N Gas Mixtures.

Using methods of pulsed laser ablation from a silicon target in helium (He)-nitrogen (N) gas mixtures maintained at reduced pressures (0.5-5 Torr), we fabricated substrate-supported silicon (Si) nanocrystal-based films exhibiting a strong photoluminescence (PL) emission, which depended on the He/N ratio. We show that, in the case of ablation in pure He gas, Si nanocrystals exhibit PL bands centered in the "red - near infrared" (maximum at 760 nm) and "green" (centered at 550 nm) spectral regions, which can be attributed to quantum-confined excitonic states in small Si nanocrystals and to local electronic states in amorphous silicon suboxide (a-SiO) coating, respectively, while the addition of N leads to the generation of an intense "green-yellow" PL band centered at 580 nm.

Development of Anti-CD74 Antibody-Drug Conjugates to Target Glucocorticoids to Immune Cells.

Glucocorticoids (GCs) are excellent anti-inflammatory drugs but are dose-limited by on-target toxicity. We sought to solve this problem by delivering GCs to immune cells with antibody-drug conjugates (ADCs) using antibodies containing site-specific incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone propionate to human antigen-presenting immune cells to afford GR activation that was dependent on the targeted antigen.

Colocalization of USP1 and РН domain of Bcr­Abl oncoprotein in terms of cronic myeloid leukemia cell rearrangements.

The development of chronic myeloid leukemia (CML) is the result of a reciprocal translocation between chromosomes 9 and 22 due to the emergence of Philadelphia chromosome. The product of this mutation is a hybrid oncoprotein Bcr-Abl. According to the results of mass spectrometric analysis, USP1 protein was identified as a potential candidate for interaction with the PH domain Bcr-Abl oncoprotein.

Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo.

IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4.

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction.

[Antiherpetic effect of RNA-tilorone molecular complex in cell culture].

The authors studied the antiviral effect of an interferonogenic yeast RNA-tilorone molecular complex (MC) compared to the Virolex, videly used antiherpetic drug, and standard interferon (IFN) alpha/beta inducer poly(I)poly(C) in Vero cells culture infected with herpes simplex type I virus (HSV-1). The tilorone contained by MC has been shown to be twice less toxic and twice more active against HSV than its free molecules. The value of chemotherapeutic index (CI) of Virolex in experiments with Vero cells reaches 2500, CI poly(I)poly(C) and MC being 324; the last value meets the requirements for promising drugs.

MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis.

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1(+)CD11b(+) population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines.

Molecular epidemiology of HIV Type 1 in Ukraine: birthplace of an epidemic.

During the 1990s, HIV-1 spread rapidly through drug networks in Ukraine and from there throughout the former Soviet Union. To examine the origins of this epidemic, the genetics of HIV-1 in Ukraine were studied. Proviral DNA from PBMC was extracted and PCR amplified.

Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential.

Interleukin-4 (IL-4), a major T-helper type 2 (Th2) cytokine, primes dendritic cells (DCs) for IL-12 production, suggesting a negative feedback loop to prevent dysregulated Th2 inflammation, such as allergy. We previously showed that human thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes of atopic dermatitis, activates CD11c(+) DCs to induce the differentiation of naive CD4(+) and CD8(+) T cells into proallergic effectors. Here we show that TSLP primes DCs to produce large amounts of IL-12 after CD40 ligand stimulation, similar to IL-4 priming of DCs.

Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors.

Type 1 interferon-producing cells (IPCs), also known as plasmacytoid dendritic cell (DC) precursors, represent the key effectors in antiviral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic stem cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE, and graft-versus-host disease.

Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.

Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell-derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13-producing effectors exhibiting poor cytolytic activity.

Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.

Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic cells (DCs) and induced production of the T(H)2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve T(H) cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma.

The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor.

Plasmacytoid predendritic cells or type 1 interferon (IFN)-producing cells (IPCs) have recently been identified in mice. Although culture systems giving rise to different murine dendritic cell subsets have been established, the developmental regulation of murine plasmacytoid IPCs and the culture conditions leading to their generation remain unknown. Here we show that large numbers of over 40% pure CD11c(+)CD11b(-)B220(+)Gr-1(+) IPCs can be generated from mouse bone marrow cultures with FLT3-ligand.

Virus-inhibitory effect of a yeast RNA-tilorone molecular complex in cell cultures.

The virus-inhibitory activity of a molecular complex (MC) of tilorone and yeast RNA was studied in vitro on three virus-cell systems: vesicular stomatitis virus (VSV) - murine fibroblast L929 cells, Venezuelan equine encephalittis virus (VEEV) - swine embryo kidney (SEK) cells and encephalomyocarditis virus (EMCV) - established piglet testicular (EPT) cells. In all these systems the MC exerted an antiviral effect similar to that of polynucleotide interferon (IFN) inducers such as poly(I)-poly(C), larifan and ridostin. The antiviral effect of the MC was similar when the compound was applied before or after virus adsorption to cells.

[Effect of interferonogenic molecular complex of yeast RNA--tilorone on DNA, RNA and protein synthesis in vitro].

In the experiments in vitro using the primary mononuclear cells (MNC) culture of the human peripheral blood the influence of interferonogenic yeast RNA-tilorone molecular complex on the DNA, RNA and protein synthesis was studied. The complex was shown to inhibit the insertion of 3H-thymidine, 3H-uridine and 3H-leucine into DNA, RNA and protein of MNC total pool (by 13, 1 and 40% respectively); that was practically conformed with this synthesis inhibition upon to a natural origin polynucleotide interferon inducers--lariphan (9, 0 and 57% respectively) and ridostin (9, 0 and 56% respectively) action, and at the same time rather less than poly(I)-poly(C) (14, 5 and 62% respectively). In the case of preliminary cell stimulation by the mitogen PHA the complex revealed comitogenic action at a concentration 25 micrograms/ml, that corresponded to optimal for interferonogenesis; the increase of the doses till 100-1000 micrograms/ml lead to in the reversal effect.

Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.

Toll-like receptors (TLRs) are ancient microbial pattern recognition receptors highly conserved from Drosophila to humans. To investigate if subsets of human dendritic cell precursors (pre-DC), including monocytes (pre-DC1), plasmacytoid DC precursors (pre-DC2), and CD11c(+) immature DCs (imDCs) are developed to recognize different microbes or microbial antigens, we studied their TLR expression and responses to microbial antigens. We demonstrate that whereas monocytes preferentially express TLR 1, 2, 4, 5, and 8, plasmacytoid pre-DC strongly express TLR 7 and 9.