TPEN selectively eliminates lymphoblastic B cells from bone marrow pediatric acute lymphoblastic leukemia patients.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients.

Combinational treatment of TPEN and TPGS induces apoptosis in acute lymphoblastic and chronic myeloid leukemia cells in vitro and ex vivo.

TPEN and TPGS have recently shown selective cytotoxic effects in vitro and ex vivo leukemia cells. In this study, we aimed to test the synergistic effect of combined TPEN and TPGS agents (thereafter, T2 combo) on Jurkat (clone-E61), K562, Ba/F3, and non-leukemia peripheral blood lymphocytes (PBL). The ED50 doses (i.

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers.

Multiple-Allele MHC Class II Epitope Engineering by a Molecular Dynamics-Based Evolution Protocol.

Epitopes that bind simultaneously to all human alleles of Major Histocompatibility Complex class II (MHC II) are considered one of the key factors for the development of improved vaccines and cancer immunotherapies. To engineer MHC II multiple-allele binders, we developed a protocol called PanMHC-PARCE, based on the unsupervised optimization of the epitope sequence by single-point mutations, parallel explicit-solvent molecular dynamics simulations and scoring of the MHC II-epitope complexes. The key idea is accepting mutations that not only improve the affinity but also reduce the affinity gap between the alleles.

Ab initio metadynamics determination of temperature-dependent free-energy landscape in ultrasmall silver clusters.

Ab initio metadynamics enables the extraction of free-energy landscapes having the accuracy of first-principles electronic structure methods. We introduce an interface between the PLUMED code that computes free-energy landscapes and enhanced-sampling algorithms and the Atomic Simulation Environment (ASE) module, which includes several ab initio electronic structure codes. The interface is validated with a Lennard-Jones cluster free-energy landscape calculation by averaging multiple short metadynamics trajectories.

Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations.

Individual and synergic effect of carbamazepine and diclofenac in the removal of organic matter from an expanded granular bed anaerobic reactor.

Due to the negative effects caused to the natural environment by the presence of pharmaceutical-type traces and other pollutants in wastewater, it is necessary to develop and optimize efficient treatment systems. This study evaluated the effect of carbamazepine (CBZ) and diclofenac (DCF) on the behavior of seven EGSB (expanded granular sludge bed) anaerobic reactors at laboratory scale, using chromatographic and physicochemical analyses of the influent, effluent, and the biomass contained in the reactors. The results showed that CBZ had a greater effect on the removal and behavior of microorganisms than DCF, with average efficiencies of 34.

Monitoring of cyanobacteria and cyanotoxins in a Colombian tropical reservoir.

Anthropogenic pollution and global climate change have resulted in favorable environmental conditions for increased frequency and duration of cyanobacterial blooms in aquatic systems. Cyanobacteria can produce toxic metabolites called cyanotoxins, which have become a worldwide concern as they threaten human and animal health. The presence of cyanobacteria and four cyanotoxins were evaluated in a Colombian reservoir.

Linking toxicity and predation in a venomous arthropod: the case of (Scorpiones: Buthidae), a generalist predator scorpion.

Background: Scorpions are arachnids that have a generalist diet, which use venom to subdue their prey. The study of their trophic ecology and capture behavior is still limited compared to other organisms, and aspects such as trophic specialization in this group have been little explored.

Methods: In order to determine the relationship between feeding behavior and venom toxicity in the scorpion species , 33 specimens were offered prey with different morphologies and defense mechanisms: spiders, cockroaches and crickets.

(-)-Epigallocatechin-3-Gallate Diminishes Intra-and Extracellular Amyloid-Induced Cytotoxic Effects on Cholinergic-like Neurons from Familial Alzheimer's Disease PSEN1 E280A.

Alzheimer's disease (AD) is a complex neurodegenerative disease characterized by functional disruption, death of cholinergic neurons (ChNs) because of intracellular and extracellular Aβ aggregates, and hyperphosphorylation of protein TAU (p-TAU). To date, there are no efficient therapies against AD. Therefore, new therapies for its treatment are in need.

Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS).

Promising Hybrids Derived from S-Allylcysteine and NSAIDs Fragments against Colorectal Cancer: Synthesis, Evaluation, Drug-Likeness and ADME/tox Studies.

We synthesized twelve hybrids, -allyl Cysteine methyl, ethyl and propyl ester-based non-steroidal anti-inflammatory drugs and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of all compounds was evaluated against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids , and displayed the best anticancer activity with IC values between 0.

Phenolic-rich extract of avocado Persea americana (var. Colinred) peel blunts paraquat/maneb-induced apoptosis through blocking phosphorylation of LRRK2 kinase in human nerve-like cells.

It is increasingly evident that LRRK2 kinase activity is involved in oxidative stress (OS)-induced apoptosis-a type of regulated cell death and neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that a phenolic-rich extract of avocado Persea americana var. Colinred peel (CRE, 0.

Phytochemical Screening of (Spruce) Woodson (Apocynaceae) Latex, In Vitro Cytotoxicity and Incision Wound Repair in Mice.

, also known as "Bellaco caspi", is a medicinal plant whose latex, stem bark, and leaves possess phenolic acids, lupeol, β-dihydro-plumbericinic acid, plumericin, and plumeride, among other components. Some of these have been linked to such biological activities as antiulcer, anti-inflammatory, and wound healing. The aim of this study was to determine the phytochemical compounds of latex, as well as its in vitro cytotoxicity and wound healing effect in mice.

The expansion of human T-betCD21 B cells is T cell dependent.

Accumulation of human CD21 B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21 B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-betCD21 B cells.

Microbiota, Prostatitis, and Fertility: Bacterial Diversity as a Possible Health Ally.

Background: In health, microorganisms have been associated with the disease, although the current knowledge shows that the microbiota present in various anatomical sites is associated with multiple benefits.

Objective: This study aimed to evaluate and compare the genitourinary microbiota of chronic prostatitis symptoms patients and fertile men.

Materials And Methods: In this preliminary study, ten volunteers have included 5 volunteers with symptoms of chronic prostatitis (prostatitis group) and five fertile volunteers, asymptomatic for urogenital infections (control group) matched by age.

Chemopreventive Potential of a Chromone from ALSTROEMERIACEAE) against Colorectal Cancer.

Chemoprevention with natural products may provide important alternatives in the search for new drugs to treat cancer. Thus, the ethanol extract of and its secondary metabolite (chromone) were evaluated in SW480 and SW620 human adenocarcinoma colon cells to identify a possible effect on cell growth, antiproliferative and/or proapoptotic activity. The ethanol extract did not show growth inhibition of these cell lines 48 h after treatment; besides, it required higher concentration and time to have an antiproliferative effect.

Enzymatic synthesis of capric acid-rich structured lipids and their effects on mice with high-fat diet-induced obesity.

The objective of this study was to produce structured lipids (SLs) by enzymatic acidolysis using Rhizopus oryzae lipase covalently immobilized in a low-cost material. Grape seed oil was used to synthesize SLs containing the medium-chain fatty acid (C10:0) capric acid. SL synthesis led to 38.

Mental health outcomes in communities exposed to Armed Conflict Experiences.

Background: Populations exposed to Armed Conflict Experiences (ACE) show different levels of impact in their mental health (i.e. clinical and positive components); however, there is limited evidence related to mental health of general population (civilians not classified as victims) exposed to ACE.

Application of ensemble pharmacophore-based virtual screening to the discovery of novel antimitotic tubulin inhibitors.

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug is available. The colchicine site is composed of three interconnected sub-pockets that fit their ligands and modify others' preference, making the design of molecular hybrids (that bind to more than one sub-pocket) a difficult task.

Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.

Melatonin Increases Life Span, Restores the Locomotor Activity, and Reduces Lipid Peroxidation (LPO) in Transgenic Knockdown Parkin Drosophila melanogaster Exposed to Paraquat or Paraquat/Iron.

Parkinson's disease (PD) is a complex progressive neurodegenerative disorder involving impairment of bodily movement caused by the specific destruction of dopaminergic (DAergic) neurons. Mounting evidence suggests that PD might be triggered by an interplay between environmental neurotoxicants (e.g.

MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach.

Background: Scorpions are widely known for the neurotoxic effects of their venoms, which contain peptides affecting ionic channels. Although Colombia is recognized for its scorpion diversity, only a few studies are available describing the venom content.

Methods: In this descriptive study, we analyzed the MS/MS sequence, electrophoretic and chromatographic profile linked to a bioinformatics analysis of the scorpions (Chactidae), (Hormuridae), (Buthidae) and (Buthidae) from Colombia.

Latent Tri-lineage Potential of Human Menstrual Blood-Derived Mesenchymal Stromal Cells Revealed by Specific In Vitro Culture Conditions.

Human menstrual blood-derived mesenchymal stromal cells (MenSCs) have become not only an important source of stromal cells for cell therapy but also a cellular source for neurologic disorders in vitro modeling. By using culture protocols originally developed in our laboratory, we show that MenSCs can be converted into floating neurospheres (NSs) using the Fast-N-Spheres medium for 24-72 h and can be transdifferentiated into functional dopaminergic-like (DALNs, ~ 26% TH + /DAT + flow cytometry) and cholinergic-like neurons (ChLNs, ~ 46% ChAT + /VAChT flow cytometry) which responded to dopamine- and acetylcholine-triggered neuronal Ca inward stimuli when cultured with the NeuroForsk and the Cholinergic-N-Run medium, respectively in a timely fashion (i.e.