Shapiroabrams1887

In summary, we present a human cellular model of neuronal differentiation exhibiting a novel essential function of NF-κB-c-REL in fate choice between neurogenesis and oligodendrogenesis which will potentially be relevant for multiple sclerosis and schizophrenia.Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies in non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain-null (NSG) mice and established humanized mouse NPC-patient-derived xenograft (NPC-PDX) model successfully. Epstein-Barr virus was detected in the NPC in both NSG and humanized mice as revealed by Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) and immunohistochemical (IHC) staining. In the NPC-bearing humanized mice, the percentage of tumor-infiltrating CD8+ cytotoxic T cells was lowered, and the T cells expressed higher levels of various inhibitory receptors, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) than those in blood. Thmodel, which plausibly serves as a robust platform to test for the efficacy of immunotherapy and may predict clinical outcomes in NPC patients.The paper presents the results of measurements of electrical strength of Midel 1204 natural ester doped with iron nanopowder in a hydrophobic carbon shell. The research was conducted for different concentrations of the dopant. The samples were prepared in the High Voltage Technique Laboratory. After mixing, they were tightly closed, and the first measurements were taken after 5 weeks of dissolution of the dopant in liquid. The tests were repeated after another 2 weeks and 3 weeks of dissolution of nanoparticles. An increase in both mean and maximum breakdown voltage was shown for the tested liquid mixtures. The concentration for which the value of electrical strength begins to decrease was indicated. It was also shown that a longer time of dissolution of nanoparticles causes an increase in the electric strength value for the tested samples.Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by stem-cell-derived clonal over-proliferation of mature myeloid lineages, bone marrow fibrosis, osteosclerosis, defective erythropoiesis, and pro-inflammatory cytokine over-expression. The aim of the present study was to highlight possible differences in the transcriptome among CD34+ cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2V617F MUTATED and 28 JAK2 wild-type). The GO analysis of upregulated genes revealed enrichment for JAK2/STAT1 pathway gene set in PB CD34+ cells of PMF patients with and without the JAK2V617F mutation comparing to the healthy control subjects, and in particular a significant upregulation of immunoproteasome (IP)-belonging genes as PSMB8, PSMB9, and PSMB10. A more detailed investigation of the IFN-gamma (IFNG) pathway also revealed that IFNG, IRF1, and IFNGR2 were significantly upregulated in PB CD34+ cells of PMF patients carrying the mutation for JAK2V617F compared to JAK2 wild-type PMF patients. Finally, we showed an upregulation of HLA-class I genes in PB CD34+ cells from PMF JAK2V617F mutated patients compared to JAK2 wild-type and healthy controls. In conclusion, our results demonstrate that IPs and IFNG pathways could be involved in PMF disease and in particular in patients carrying the JAK2V617F mutation.Blooms of the cyanobacterium Planktothrix agardhii are common in shallow, eutrophic freshwaters. P. agardhii may produce hepatotoxic microcystins (MCs) and many other bioactive secondary metabolites belonging mostly to non-ribosomal oligopeptides. The aim of this work was to study the effects of two extracts (Pa-A and Pa-B) of P. agardhii-predominated bloom samples with different oligopeptide profiles and high concentration of biogenic compounds on another natural P. agardhii population. We hypothesised that the P. agardhii biomass and content of oligopeptides in P. agardhii is shaped in a different manner by diverse mixtures of metabolites of different P. agardhii-dominated cyanobacterial assemblages. For this purpose, the biomass, chlorophyll a and oligopeptides content in the treated P. agardhii were measured. Seven-day microcosm experiments with four concentrations of the extracts Pa-A and Pa-B were carried out. Generally, aeruginosins (AERs), cyanopeptolins (CPs) and anabaenopeptins (APs) were the most numerous peptides; however, only 16% of them were common for both extracts. The addition of the extracts resulted in similar effects on P. agardhii an increase in biomass, Chl-a and MC content in the exposed P. agardhii as well as changes in its oligopeptide profile were observed. MCs present in the extracts did not inhibit accumulation of P. agardhii biomass, and did not have any negative effect on MC and Chl-a content. No evidence for bioaccumulation of dissolved peptides in the P. agardhii exposed was found. As the two tested extracts differed considerably in oligopeptide composition, but contained similar high concentrations of nutrients, it seems that biogenic compounds, not oligopeptides themselves, positively influenced the mixed natural P. agardhii population.The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. CFSE Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.Wendy Havran, Professor and Associate Dean of Graduate Studies at Scripps Research, passed away on January 20th, 2020 following a heart attack [...].To understand the physical demands of sexual intercourse, it is necessary to monitor the kinematic parameters of this activity using relatively non-invasive technology. The aims of this study are to analyze the validity and reliability of an inertial device for monitoring the range of motion at the pelvis during simulated intercourse and compare the range of motion (ROM). Twenty-six adults were monitored during intercourse using an inertial device (WIMU) and a motion capture system (gold standard) in a test that consisted of 4 sets of 20 simulated in-out cycles (IOC) in missionary and cowgirl positions. Men and women were tested separately in a laboratory setting for simulated intercourse aims. There were no differences between the WIMU and the gold standard system at fast pace (p > 0.05), whereas there were differences at slow pace (~2.04°; p ≤ 0.05; d = 0.17). Intraclass correlation coefficients (ICCs) for the relationship between systems was very close to 1 at both paces (slow 0.981; fast 0.998). The test-retest reliability analysis did not show any difference between sets of measurements. In conclusion, WIMU could be considered as a valid and reliable device for IOC range of motion monitoring during sexual intercourse in missionary and cowgirl positions.Alkyl moieties-open chain or cyclic, linear, or branched-are common in drug molecules. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some hydroxy metabolites, which are equiactive with their parent drugs, have been developed into ester prodrugs while carboxy metabolites, which are equiactive to their parent drugs, have been developed into drugs as per se. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. The review provides a basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules, and (ii) pharmacologic activity of the metabolites resulting from hydroxy and/or carboxy functionalization of alkyl moieties.