CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome.

Background: WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is an ultra-rare, combined primary immunodeficiency and chronic neutropenic disorder characterized by a range of clinical presentations, including peripheral neutropenia, lymphopenia, and recurrent infections. WHIM syndrome is most often caused by gain-of-function mutations in the gene encoding C-X-C chemokine receptor 4 (CXCR4). As such, inhibition of CXCR4 with XOLREMDI (mavorixafor), an orally bioavailable CXCR4 antagonist, demonstrated clinically meaningful increases in absolute neutrophil and lymphocyte counts and concomitant reduction in infections in patients with WHIM syndrome, resulting in its recent U.

Antigen-specific T cell immunotherapy by in vivo mRNA delivery.

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis.

Guidance of Nerve Stimulator and Ultrasound for Transforaminal Epidural Steroid Injection in Lumbosacral Radicular Pain : A Single Institution Experience in Vietnam.

Objective: This study aimed to evaluate the clinical feasibility of the combination of ultrasound and nerve stimulator guidance in transforaminal epidural steroid injections (TESIs) to manage lumbosacral chronic radicular pain.

Methods: Using the combination of nerve stimulator and ultrasound guidance, TESIs were performed in 125 segments of 78 patients who presented with chronic lumbar radicular pain. Demographic characteristics and surgical outcomes were recorded on admission, pre-procedural and post-procedural for 1-week, 1-month, 3-month, and 6-month follow-ups.

A Simplified Kinetic Modeling of CO Absorption into Water and Monoethanolamine Solution in Hollow-Fiber Membrane Contactors.

The absorption of CO from CO-N gas mixtures using water and monoethanolamine (MEA) solution in polypropylene (PP) hollow-fiber membrane contactors was experimentally and theoretically examined. Gas was flowed through the lumen of the module, whereas the absorbent liquid was passed counter-currently across the shell. Experiments were carried out under various gas- and liquid-phase velocities as well as MEA concentrations.

Radical Scavenging Is Not Involved in Thymoquinone-Induced Cell Protection in Neural Oxidative Stress Models.

Thymoquinone (TQ), an active compound from seeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to reassess the radical scavenging properties of TQ and explore a potential mode of action. The effects of TQ were studied in models with mitochondrial impairment and oxidative stress induced by rotenone in N18TG2 neuroblastoma cells and rotenone/MPP in primary mesencephalic cells.

The mitochondrial DNA HVI and HVII sequences and haplogroup distribution in a population sample from Vietnam.

Background: Mitochondrial DNA (mtDNA) analysis has been used in forensics and requires well-established population databases for statistical interpretations. However, high-quality mtDNA data from Vietnamese population samples have been limited.

Aim: To examine the mtDNA sequences and haplogroup compositions of a Vietnamese population to provide an mtDNA dataset that can further be used to construct a Vietnamese-specific reference database.

Coupling light to higher order transverse modes of a near-concentric optical cavity.

Optical cavities in the near-concentric regime have near-degenerate transverse modes; the tight focusing transverse modes in this regime enable strong coupling with atoms. These features provide an interesting platform to explore multi-mode interaction between atoms and light. Here, we use a spatial light modulator (SLM) to shape the phase of an incoming light beam to match several Laguerre-Gaussian (LG) modes of a near-concentric optical cavity.

Pyr1-Mediated Pharmacological Inhibition of LIM Kinase Restores Synaptic Plasticity and Normal Behavior in a Mouse Model of Schizophrenia.

The search for effective treatments for neuropsychiatric disorders is ongoing, with progress being made as brain structure and neuronal function become clearer. The central roles played by microtubules (MT) and actin in synaptic transmission and plasticity suggest that the cytoskeleton and its modulators could be relevant targets for the development of new molecules to treat psychiatric diseases. In this context, LIM Kinase - which regulates both the actin and MT cytoskeleton especially in dendritic spines, the post-synaptic compartment of the synapse - might be a good target.

Downregulation of MTSS1 in acute myeloid leukemia is associated with a poor prognosis, chemotherapy resistance, and disease aggressiveness.

Despite recent approval of targeted drugs for acute myeloid leukemia (AML) therapy, chemotherapy with cytosine arabinoside and anthracyclines remains an important pillar of treatment. Both primary and secondary resistance are frequent and associated with poor survival, yet the underlying molecular mechanisms are incompletely understood. In previous work, we identified genes deregulated between diagnosis and relapse of AML, corresponding to therapy naïve and resistant states, respectively.

Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of Retinoic Acid on -ITD/-Driven Acute Myeloid Leukemia Cells.

retinoic acid (atRA) has a dramatic impact on the survival of patients with acute promyelocytic leukemia, but its therapeutic value in other types of acute myeloid leukemia (AML) has so far remained unclear. Given that AML is a stem cell-driven disease, recent studies have addressed the effects of atRA on leukemic stem cells (LSCs). atRA promoted stemness of -driven AML in an -dependent manner but had the opposite effect in -ITD/-driven AML.

retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells.

Acute myeloid leukemia (AML) is an aggressive, often fatal hematopoietic malignancy. retinoic acid (atRA), one of the first molecularly targeted drugs in oncology, has greatly improved the outcome of a subtype of AML, acute promyelocytic leukemia (APL). In contrast, atRA has so far provided little therapeutic benefit in the much larger group of patients with non-APL AML.

Promotes Aggressiveness and Stem Cell-Related Properties of Acute Myeloid Leukemia.

Overexpression of , which encodes the alpha chain of the IL2 receptor, is associated with chemotherapy resistance and poor outcome in acute myeloid leukemia (AML). The clinical potential of anti-IL2RA therapy is, therefore, being explored in early-stage clinical trials. Notwithstanding, only very limited information regarding the biological function of in AML is available.

Investigating Visual-Spatial Abilities in Students and Expert Physical Therapists.

Visual-spatial abilities (VSAs) - the aptitude for mentally processing, retaining, and manipulating visual input - are used by physical therapists in movement analysis. Superior VSAs have been demonstrated in experts compared with novices in other fields, including surgery, anatomy, and aviation, but no literature has investigated VSAs in physical therapy. The purpose of this study was to quantify VSAs in expert and student physical therapists and investigate the differences between the two groups.

Feed‑back loops integrating RELA, SOX18 and FAK mediate the break‑down of the lymph‑endothelial barrier that is triggered by 12(S)‑HETE.

Metastatic cancer cells cross endothelial barriers and travel through the blood or lymphatic fluid to pre‑metastatic niches, leading to their colonisation. 'S' stereoisomer 12S‑hydroxy‑5Z,8Z,10E,14Z‑eicosatetraenoic acid [12(S)‑HETE] is secreted by a variety of cancer cell types and has been indicated to open up these barriers. In the present study, another aspect of the endothelial unlocking mechanism was elucidated.

Immunization with the H5N1 Recombinant Vaccine Candidate Induces High Protection in Chickens against Vietnamese Highly Pathogenic Avian Influenza Virus Strains.

Vietnam is one of the countries most affected worldwide by the highly pathogenic avian influenza (HPAI) virus, which caused enormous economic loss and posed threats to public health. Over nearly two decades, with the antigenic changes in the diversified H5Ny viruses, the limited protective efficacy of the available vaccines was encountered. Therefore, it is necessary to approach a technology platform for the country to accelerate vaccine production that enables quick response to new influenza subtypes.

Cytotoxicity Assessment of Gallium- and Indium-Based Nanoparticles Toward Human Bronchial Epithelial Cells Using an Impedance-Based Real-Time Cell Analyzer.

The semiconductor manufacturing sector plans to introduce III/V film structures (eg, gallium arsenide (GaAs), indium arsenide (InAs) onto silicon wafers due to their high electron mobility and low power consumption. Aqueous solutions generated during chemical and mechanical planarization of silicon wafers can contain a mixture of metal oxide nanoparticles (NPs) and soluble indium, gallium, and arsenic. In this work, the cytotoxicity induced by Ga- and In-based NPs (GaAs, InAs, GaO, InO) and soluble III-V salts on human bronchial epithelial cells (16HBE14o-) was evaluated using a cell impedance real-time cell analysis (RTCA) system.

Effects of graphene oxide and reduced graphene oxide on acetoclastic, hydrogenotrophic and methylotrophic methanogenesis.

This study describes the effects of graphene oxide (GO) and reduced graphene oxide (rGO) on the acetoclastic, hydrogenotrophic and methylotrophic pathways of methanogenesis by an anaerobic consortium. The results showed that GO negatively affected the hydrogenotrophic and acetoclastic pathways at a concentration of 300 mg/L, causing a decrease of ~ 38% on the maximum specific methanogenic activity (MMA) with respect to the controls lacking GO. However, the presence of rGO (300 mg/L) promoted an improvement of the MMA (> 45%) achieved with all substrates, except for the hydrogenotrophic pathway, which was relatively insensitive to rGO.

All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia.

Ecotropic virus integration site 1 (EVI1), whose overexpression characterizes a particularly aggressive subtype of acute myeloid leukemia (AML), enhanced anti-leukemic activities of all-trans retinoic acid (atRA) in cell lines and patient samples. However, the drivers of leukemia formation, therapy resistance, and relapse are leukemic stem cells (LSCs), whose properties were hardly reflected in these experimental setups. The present study was designed to address the effects of, and interactions between, EVI1 and retinoids in AML LSCs.

CGRP Signaling via CALCRL Increases Chemotherapy Resistance and Stem Cell Properties in Acute Myeloid Leukemia.

The neuropeptide CGRP, acting through the G-protein coupled receptor CALCRL and its coreceptor RAMP1, plays a key role in migraines, which has led to the clinical development of several inhibitory compounds. Recently, high expression has been shown to be associated with a poor prognosis in acute myeloid leukemia (AML). We investigate, therefore, the functional role of the CGRP-CALCRL axis in AML.

Microbial toxicity of gallium- and indium-based oxide and arsenide nanoparticles.

III-V semiconductor materials such as gallium arsenide (GaAs) and indium arsenide (InAs) are increasingly used in the fabrication of electronic devices. There is a growing concern about the potential release of these materials into the environment leading to effects on public and environmental health. The waste effluents from the chemical mechanical planarization process could impact microorganisms in biological wastewater treatment systems.

Diazole and triazole inhibition of nitrification process in return activated sludge.

Azoles are emerging contaminants that are resistant to biodegradation during wastewater treatment. Their presence has been widely reported in wastewater effluents and receiving waters. In this work, the potential inhibition of nitrification process by six different azole compounds in wastewater treatment plants was investigated in batch bioassays.

Hybridizing Ag-Doped ZnO nanoparticles with graphite as potential photocatalysts for enhanced removal of metronidazole antibiotic from water.

In this study, the ZnO nanoparticles were doped with Ag and then hybridized on graphite (GP) layer (Ag-ZnO/GP) by a hydrothermal method, which was used as photocatalysts to remove metronidazole (MNZ) antibiotic from aqueous solutions. The fine structure, morphologies, and optical properties of the synthesized composites were first examined. The incorporation of Ag would readily reduce the rate of the recombination of electron-hole pairs and enhance the photocatalytic activity in a wide range of light wavelength.

SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness.

Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival.

12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18.

Metastasising breast cancer cells communicate with adjacent lymph endothelia, intravasate and disseminate through lymphatic routes, colonise lymph nodes and finally metastasize to distant organs. Thus, understanding and blocking intravasation may attenuate the metastatic cascade at an early step. As a trigger factor, which causes the retraction of lymph endothelial cells (LECs) and opens entry ports for tumour cell intravasation, MDA-MB231 breast cancer cells secrete the pro-metastatic arachidonic acid metabolite, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(S)-HETE].