BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

CTNNB1 syndrome mouse models.

CTNNB1 syndrome is a rare neurodevelopmental disorder, affecting children worldwide with a prevalence of 2.6-3.2 per 100,000 births and often misdiagnosed as cerebral palsy.

A study on the compressive strength of three-dimensional direct printing aligner material for specific designing of clear aligners.

Background: The demand for orthodontic treatment using clear aligners has been gradually increasing because of their superior esthetics compared with conventional fixed orthodontic therapy. This study aimed to evaluate and compare the compressive strength of three-dimensional direct printing aligners (3DPA) with that of conventional thermo-forming aligners (TFA) to determine their clinical applicability. In the experimental group, the 3DPA material TC-85 (TC-85 full) was used to create angular protrusions called rectangular pressure areas (RPA).

Synthesis and evaluation of nitrochromene derivatives as potential antileishmanial therapeutics through biological and computational studies.

Leishmaniasis is a parasitic disease caused by protozoan organisms belonging to the Leishmania genus, affecting many individuals worldwide, with the burden surpassing one million cases. This disease leads to considerable morbidity and mortality, predominantly within tropical and subtropical regions. The current therapeutic options for leishmaniasis are far from ideal, as they fail to achieve a level of efficacy that can be deemed universally effective.

Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.

Deciphering the sources of variability in drug responses requires to understand the processes modulating drug pharmacokinetics. However, pharmacological research suffers from poor reproducibility across clinical, animal, and experimental models. Predictivity can be improved by using Organs-on-Chips, which are more physiological, human-oriented, micro-engineered devices that include microfluidics.

Bioinspired artificial antioxidases for efficient redox homeostasis and maxillofacial bone regeneration.

Reconstructing large, inflammatory maxillofacial defects using stem cell-based therapy faces challenges from adverse microenvironments, including high levels of reactive oxygen species (ROS), inadequate oxygen, and intensive inflammation. Here, inspired by the reaction mechanisms of intracellular antioxidant defense systems, we propose the de novo design of an artificial antioxidase using Ru-doped layered double hydroxide (Ru-hydroxide) for efficient redox homeostasis and maxillofacial bone regeneration. Our studies demonstrate that Ru-hydroxide consists hydroxyls-synergistic monoatomic Ru centers, which efficiently react with oxygen species and collaborate with hydroxyls for rapid proton and electron transfer, thus exhibiting efficient, broad-spectrum, and robust ROS scavenging performance.

S1PR3-driven positive feedback loop sustains STAT3 activation and keratinocyte hyperproliferation in psoriasis.

Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and persistent inflammation. Although persistent activation of signal transducer and activator of transcription 3 (STAT3) is implicated in its pathogenesis, the mechanisms underlying the sustained STAT3 activation remain poorly understood. Here, we identify sphingosine-1-phosphate receptor 3 (S1PR3) as a critical regulator of STAT3 activation and psoriasis pathogenesis, orchestrating a self-amplifying circuit that sustains keratinocyte hyperproliferation and chronic inflammation.

A high-valence bismuth(V) nanoplatform triggers cancer cell death and anti-tumor immune responses with exogenous excitation-free endogenous HO- and O-independent ROS generation.

Reactive oxygen species with evoked immunotherapy holds tremendous promise for cancer treatment but has limitations due to its dependence on exogenous excitation and/or endogenous HO and O. Here we report a versatile oxidizing pentavalent bismuth(V) nanoplatform (NaBiO-PEG) can generate reactive oxygen species in an excitation-free and HO- and O-independent manner. Upon exposure to the tumor microenvironment, NaBiO-PEG undergoes continuous H-accelerated hydrolysis with •OH and O generation through electron transfer-mediated Bi-to-Bi conversion and lattice oxygen transformation.

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production.

Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards.

Serologic diagnosis of Entamoeba histolytica infection based on the gradient-based digital immunoassay.

Background: Entamoeba histolytica is a parasite that could cause severe amebiasis, an extremely contagious parasitic disease with critical clinical symptoms. Timely diagnosis and treatment of E. histolytica are crucial for preventing complications and fatalities.

Disclosing long-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma therapy.

Frequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-free latanoprost-loaded (0.005 % w/v) synthetic phosphatidylcholine (1,2-dioleoyl-sn-glycero-3-phosphocholine 0.

Design of hybrid aptamer-molecularly imprinted polymer nanoparticles for selective binding of oxidized low-density lipoprotein in an ELISA-mimic system.

Oxidized low-density lipoprotein (oxLDL) is the leading cause of atherosclerosis and cardiovascular disease development. An enzyme-linked immunosorbent assay (ELISA)-mimic system for sensitive and specific oxLDL determination was developed using selective aptamer-molecularly imprinted polymer nanoparticles (AP-MIP NP) coupled with an immunology-based colorimetric assay. The AP-MIP NP were synthesized using solid-phase molecular imprinting by incorporating aptamers into the MIP NP cavities.

Exploring the Anti-Adherence Potential of Skt35 to Combat Catheter-Associated Staphylococcus aureus Infections: Efficacy, Toxicity and Mechanism of Action.

Catheter-associated urinary tract infections (CAUTIs), often caused by biofilm-forming Staphylococcus aureus, present significant clinical challenges. Skt35, a dioxopiperidinamide derivative of cinnamic acid, was investigated for its potential antibacterial and antibiofilm activities against S. aureus biofilms.

Different processing methods affect the chemical composition and in vitro anti-tumor activity of ginseng.

Ginseng and its processed products are valued as health foods for their nutritional benefits. The traditional forms of processed ginseng include white ginseng, dali ginseng (DLG), red ginseng (RG), and black ginseng (BG). However, the impact of processing on the chemical composition and anti-tumor efficacy of these products is not well understood.

Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.

Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties.

Targeting senescence and GATA4 in age-related cardiovascular disease: a comprehensive approach.

The growing prevalence of age-related cardiovascular diseases (CVDs) poses significant health challenges, necessitating the formulation of novel treatment approaches. GATA4, a vital transcription factor identified for modulating cardiovascular biology and cellular senescence, is recognized for its critical involvement in CVD pathogenesis. This review collected relevant studies from PubMed, Google Scholar, and Science Direct using search terms like 'GATA4,' 'cellular senescence,' 'coronary artery diseases,' 'hypertension,' 'heart failure,' 'arrhythmias,' 'congenital heart diseases,' 'cardiomyopathy,' and 'cardiovascular disease.

Acute leukemia in children: evaluating the necessity of routine biochemical analysis of cerebrospinal fluid.

Unlabelled: Biochemical analyses of cerebrospinal fluid (CSF) are routinely performed at diagnosis in many pediatric oncology and hematology centers when acute leukemia is diagnosed. However, the clinical relevance of these analyses remains unclear. We conducted a retrospective analysis of biochemical CSF data from children diagnosed with acute leukemia at two French hospitals between 2016 and 2023 assessing the results in relation to the presence or absence of leukemic neuromeningeal involvement and the correlation between cytological and biochemical analyses.

An ultrasensitive colorimetric/fluorescent/photothermal sensing platform for the detection of D-amino acids based on carbon dots nanozymes with enhanced peroxidase-like activity.

Based on the enhanced peroxidase-like activity of carbon dots nanozymes (CDszymes), with a specific oxidation reaction of D-amino acid oxidase catalysing the formation of HO from D-amino acid, an ultrasensitive sensing platform, was constructed for the quantitative detection of D-amino acids in saliva. With the increase of D-amino acids concentration, the blue color of catalytic product gradually deepend, the fluorescence CDszymes gradually quenched, and the temperature gradually increased. Using D-alanine as D-amino acid models, the detection limits of D-alanine in colorimetric/photothermal/fluorescent mode were 0.

Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers.

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers.

A silicon rhodamine 1,2-dioxetane chemiluminophore for near-infrared imaging.

Near-infrared (NIR) chemiluminescent probes have attracted increasing attention in recent years due to their attractive properties for imaging. Herein, we developed a NIR chemiluminophore silicon rhodamine (SiRCL-1) based on the intramolecular energy transfer process from excited state benzoate to a silicon rhodamine emitter under aqueous conditions. SiRCL-1 exhibited dual emission peaks at 540 nm and 680 nm with a high signal penetration through tissue at 680 nm (>30 mm) and long-lasting luminescence (>50 min), demonstrating its significance as a chemiluminescence scaffold for biological application.

Rapid identification of pathogenic bacteria from clinical positive blood cultures virus-like magnetic bead enrichment and MALDI-TOF MS profiling.

Reducing the time required for the detection of bacteria in blood samples is a critical area of investigation in the field of clinical diagnosis. Positive blood culture samples often require a plate culture stage due to the interference of blood cells and proteins, which can result in significant delays before the isolation of single colonies suitable for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. In this study, we developed a non-specific enrichment strategy based on SiO-encapsulated FeO nanoparticles combined with MALDI-TOF MS for direct identification of bacteria from aqueous environments or positive blood culture samples.

Bioengineered NanoAid synergistically targets inflammatory pro-tumor processes to advance glioblastoma chemotherapy.

Through transcriptomic analysis of patient-derived glioblastoma tissues, we identify an overactivation of inflammatory pathways that contribute to the development of a tumor-promoting microenvironment and therapeutic resistance. To address this critical mechanism, we present NanoAid, a biomimetic nanoplatform designed to target inflammatory pro-tumor processes to advance glioblastoma chemotherapy. NanoAid employs macrophage-membrane-liposome hybrids to optimize the delivery of COX-2 inhibitor parecoxib and paclitaxel.

The biomechanical effect of the O-A angle on the aortic valve under left ventricular assist device support: a primary fluid-structure interaction study.

Background: Left ventricular assist device (LVAD) has been widely used as an alternative treatment for heart failure, however, aortic regurgitation is a common complication in patients with LVAD support. And the O-A angle (the angle between LVAD outflow graft and the aorta) is considered as a vital factor associated with the function of aortic valve. To date, the biomechanical effect of the O-A angle on the aortic valve remains largely unknown.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies.

Luteolin is widely distributed phytochemical, a flavonoid, in kingdom plantae. Luteolin with potential antioxidant activity prevent ROS-induced damages and reduce oxidative stress which is mainly responsible in pathogenesis of many diseases. Several chemo preventive activities and therapeutic benefits are associated with luteolin.