Accumulation Kinetics and Biological Action of Doxorubicin in Rabbit Intervertebral Discs.

Doxorubicin (DOX) is widely used for the treatment of several tumors, but considerable dose-dependent side effects on many normal tissues, including bones, have been reported. The aim of the present study was to follow for the first time the kinetics of DOX accumulation/clearance in the non-vascularized intervertebral disc (IVD), as well as to assess the drug's biological action in the annulus fibrosus (AF) and nucleus pulposus (NP) IVD cells and tissues. DOX was administered intravenously to rabbits before the isolation of IVDs, in which DOX quantification was performed using a highly sensitive LC-HRMS/MS analytical method.

Current status and challenges of multi-omics research using animal models of atherosclerosis.

Atherosclerosis is an underlying cause of cardiovascular diseases (CVD) which account for most deaths worldwide. Use of diverse preclinical models of atherosclerosis has been implemental in understanding the underlying mechanisms, the implicated cell types, the genes and the molecules at play in the onset and progression of atherosclerotic plaques. Although significant research advancements have been made, further research is necessary to delve into factors influencing plaque types, site preference within the vasculature, interactions with adjacent tissues (liver, pancreas and perivascular adipose tissue), inflammation and sex-based disparities, among others.

Unveiling the Diagnostic Significance of Calprotectin in Serous Ovarian Carcinoma.

: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of great importance in order to improve survival rates.

Transcriptional activation of BmToll9-2 to exogenous dsRNA in the larvae of Bombyx mori.

The Toll pathway plays a crucial role in insect innate immunity, functioning through pattern recognition receptors (PRRs) that detect pathogen associated molecular patterns (PAMPs). Previous studies on BmToll9-2 have primarily investigated its role in sensing bacterial pathogens and activating antimicrobial peptides. In this study, we aimed to investigate the transcriptional regulation of BmToll9-2 in response to exogenous double-stranded RNAs (dsRNAs) in silkworm (Bombyx mori) larvae.

The effect of copper on the antifungal activity of polyethyleneimines against quiescent conidia and germlings of Aspergillus nidulans.

The increase in the number of immunocompromised individuals combined with the severity of fungal infections in the general population has contributed to a significant increase in opportunistic fungal infections, which are often associated with high mortality rates. Although effective, existing antifungal drugs operate via a narrow range of mechanisms, leading to the rapid development of resistance and they primarily target growing host cells. Therefore, the need to develop next-generation antifungal agents that function via a broad range of mechanisms and/or target dormant/quiescent cells is highly important.

Centrosome‑, mitotic spindle‑ and cytokinetic bridge‑specific compartmentalization of AGO2 protein in human liver cells undergoing mitosis: Non‑canonical, RNAi‑dependent, control of local homeostasis.

Argonaute RNA‑induced silencing complex catalytic component 2 (AGO2) is an evolutionary conserved protein involved in microRNA‑dependent gene expression regulation via the RNA interference (RNAi) mechanism. Nevertheless, AGO2 may also be involved in other key processes, such as histone modification, DNA methylation and alternative splicing. Its role in the proper development of organisms is key and no homologue is able to compensate for its loss.

Identification of ISG homologous genes in silkworm and revelation of BmNFIL3 inhibition of BmNPV proliferation through regulation of BmRelish transcription.

It is generally believed that no functional antiviral pathway exists in insects, that is homologous to the interferon signaling system. However, we have previously identified an interferon-stimulated gene (ISG) homologous gene, BmCH25H, in the silkworm and revealed that BmCH25H relied on its hydroxylase activity as an antiviral effector. Therefore, we speculate that there may be additional ISG homologous genes in the silkworm genome, some of which may play an antiviral role.

Activation of in Silkworm () Larval Midgut by and Regulation of Growth.

Insects rely on their innate immune system to defend against pathogens, and the Toll signaling pathway plays an important role in immune regulation. Our previous studies have shown that functions as a positive regulator in the Toll pathway. This study seeks to elucidate the role of , as a sensor to bacterial challenge, in modulating larval development and downstream Toll signaling pathways.

Copper-Chelated Hyperbranched Polyethyleneimines with Antifungal Activity against quiescent conidia and germlings of the opportunistic fungal pathogen Aspergillus nidulans.

The rising number of immunocompromised individuals, combined with the severity of fungal infections in the general population, has contributed to a significant increase in opportunistic fungal infections, which are often associated with high mortality rates. Existing antifungal drugs, although effective, operate via a narrow range of mechanisms, leading to the rapid development of resistance, while they also primarily target growing host cells. Therefore, the need to develop next-generation antifungal agents that function via a broad range of mechanisms and/or to target dormant/quiescent cells is of great importance.

Mating Disruption of (Lepidoptera: Noctuidae) Using Yeast-Derived Pheromones in Cotton Fields.

The use of insect sex pheromones as an alternative technology for pest control in agriculture and forestry offers a promising solution. The development of a novel technology for the biological production of pheromones through yeast fermentation significantly lowers production costs, enabling the adoption of sustainable pest control practices in field crops, a strategy previously reserved for high-value crops. Over three years of monitoring and mating disruption trials in Greek cotton fields, focusing on the cotton bollworm (Hübner) (Lepidoptera: Noctuidae), it was confirmed that yeast-derived pheromones exhibit equal efficacy compared to their chemically synthesized counterparts.

Sex differences in the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice.

Background: Major depressive disorder is one of the main causes of disability worldwide, but its etiopathology remains largely unknown, although several hypotheses have been proposed. Recent studies suggest a potential role for matrix metalloproteinase 9 (MMP-9) in depression, as it is overexpressed in the plasma of depressed patients and normalizes following chronic antidepressant treatment. This study aimed to characterize anxiety and depression-like behaviors in transgenic MMP-9 mice, as well as the expression of different neuroplasticity markers associated with depression, in both sexes.

Fabrication of Antibacterial and Ultraviolet Protective Wool Fabric Using Multi-Walled Carbon Nanotubes Functionalized with Guanidinylated Hyperbranched Polyethyleneimine Derivative.

Wool textiles with multifunctional properties such as self-cleaning, antibacterial, electrical conductivity, UV blocking etc. have recently attracted interest. Among the materials employed towards their development, carbon nanotubes (CNTs) have been widely investigated due to their unique chemical, mechanical and electrical properties, exhibiting also notable UV-blocking properties.

Multistable Synaptic Plasticity Induces Memory Effects and Cohabitation of Chimera and Bump States in Leaky Integrate-and-Fire Networks.

Chimera states and bump states are collective synchronization phenomena observed independently (in different parameter regions) in networks of coupled nonlinear oscillators. And while chimera states are characterized by coexistence of coherent and incoherent domains, bump states consist of alternating active and inactive domains. The idea of multistable plasticity in the network connections originates from brain dynamics where the strength of the synapses (axons) connecting the network nodes (neurons) may change dynamically in time; when reaching the steady state the network connections may be found in one of many possible values depending on various factors, such as local connectivity, influence of neighboring cells etc.

In Vitro Interactions Between Bacteriophages and Antibacterial Agents of Various Classes Against Multidrug-Resistant Metallo-β-Lactamase-Producing Clinical Isolates.

Combination therapy with antibiotics and phages has been suggested to increase the antibacterial activity of both antibiotics and phages. We tested the in vitro activity of five antibiotics belonging to different classes in combination with lytic bacteriophages against multidrug-resistant metallo-β-lactamase (MBL)-producing isolates. A total of 10 non-repetitive well-characterized MBL-producing isolates (5 NDM, 5 VIM) co-resistant to aminoglycosides and quinolones were used.

Natural Product-Derived Senotherapeutics: Extraction and Biological Evaluation Techniques.

Selective targeting of senescent cells has been thus far considered a widespread preventive strategy, as well as a main or adjuvant therapy for age-associated diseases, fueling the research on the discovery of senotherapeutics (i.e., senolytic or senomorphic compounds).

Towards a Rational Basis for the Selection of Probiotics to Improve Silkworm Health and Performance.

Pathogenic infections of silkworms constitute the greatest threat to sericulture. An attractive approach to the improvement in silkworm health and performance comprises the use of probiotics, i.e.

BRF110, an Orally Active Nurr1-RXRα-Selective Rexinoid, Enhances BDNF Expression without Elevating Triglycerides.

We report the discovery of a Nurr1-RXRα heterodimer-selective rexinoid which emerged from the structural modification of aminopyrimidine XCT0135908. Although XCT0135908 demonstrated high selectivity for the Nurr1-RXRα heterodimer over other RXRα dimerization partners, its poor in vivo stability and limited brain penetration hindered its utility. Structure-activity relationship (SAR) studies alongside bioactivity evaluations of a diverse series of substituted pyrimidines led to BRF110, a brain-penetrant compound retaining the selective activation of the Nurr1-RXRα heterodimer.

TGF-β induces cholesterol accumulation to regulate the secretion of tumor-derived extracellular vesicles.

Background: Cancer cells are avid extracellular vesicle (EV) producers. EVs transport transforming growth factor-β (TGF-β), which is commonly activated under late stages of cancer progression. Nevertheless, whether TGF-β signaling coordinates EV biogenesis is a relevant topic that remains minimally explored.

Dantrolene is an HDL-associated paraoxonase-1 activator with immunosuppressive and atheroprotective properties.

Human paraoxonase 1 (PON1), an enzyme bound to high-density lipoprotein (HDL), hydrolyzes oxidized lipids and contributes to HDL atheroprotective functions. Decreased serum paraoxonase and arylesterase activities of PON1 have been reported in patients at increased atherosclerosis risk, such as rheumatoid arthritis patients, and associated with arthritis severity and cardiovascular risk. Agents that can modulate PON1 activity and HDL-mediated effects have not been discovered.

Stimulation of IRES-Dependent Translation by Rocaglamide A Increases the Replication and Virulence of Cricket Paralysis Virus in Lepidopteran Insect Cells.

The discovery that infections of viruses are pervasive among insects has considerable potential for future applications, such as new strategies for pest control through the manipulation of virus-host interactions. However, few studies can be found that aim to minimize (for beneficial insects) or maximize (for pests) virus impact or virulence. Viruses generally employ molecular mechanisms that deviate from the cells' to increase their replication efficiency and to avoid the immune response.

Successful oral RNA interference efficiency in the silkworm Bombyx mori through nanoparticle-shielded dsRNA delivery.

Double-stranded RNA (dsRNA) mediated RNA interference (RNAi) is a tool in functional gene study and pest control. However, RNAi efficiency in Lepidoptera is low compared to the RNAi sensitive Coleoptera. Previous studies on RNAi in the silkworm Bombyx mori, the lepidopteran model insect, were performed by injection only.

TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced /p21 Upregulation.

: Pancreatic Ductal Adeno-Carcinoma (PDAC) is a highly aggressive cancer, with limited treatment options. Disruption of the circadian clock, which regulates key cellular processes, has been implicated in PDAC initiation and progression. Hence, targeting circadian clock components may offer new therapeutic opportunities for the disease.

Similarly to , Is a Positive Regulator of the Humoral Immune Response in the Silkworm, .

Toll receptors play important roles in the development and innate immunity of insects. Previously, we reported the immunological function of in silkworm, , larvae. In this study, we focused on the role of as a regulator in the Toll signaling pathway.

A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence.

Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period.

A pain research strategy for Europe: A European survey and position paper of the European Pain Federation EFIC.

Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce 'research waste', improve the effectiveness of pain research and therapy and promote the uptake of research evidence.