Soft tissue sarcomas are malignant tumors characterized by heterogeneity and are associated with a high mortality rate. Histopathological grading is considered a pivotal factor in prognostication and treatment planning. While core needle biopsy exhibits high accuracy in determining tumor histology, it fails in some cases, potentially misclassifying high-grade tumors as low-grade.
View Article and Find Full Text PDFThis study aimed to develop a method allowing high-dimensional and technically uniform screening of surface markers on cells of hematopoietic origin. High-dimensional screening of cell phenotypes is primarily the domain of single-cell RNA sequencing (RNAseq), which allows simultaneous analysis of the expression of thousands of genes in several thousands of cells. However, rare cell populations can often substantially impact tissue homeostasis or disease pathogenesis, and dysregulation of rare populations can easily be missed when only a few thousand cells are analyzed.
View Article and Find Full Text PDFIntroduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor.
View Article and Find Full Text PDFNeuropathic pain (NP), resulting from damage to the somatosensory system, is characterized by either spontaneous or evoked pain. In the context of NP, wherein aberrant signaling pathways contribute to the perception of pain, the thalamus emerges as a key player. This structure is integral to the pain network that includes connections to the dorsal horn of the spinal cord, highlighting its role in the affective-motivational aspects of pain perception.
View Article and Find Full Text PDFBackground: The multimodal properties of mesenchymal stromal cells (MSCs), particularly their ability to modulate immune responses is of high interest in translational research. Pro-inflammatory, hypoxic, and 3D culture priming are promising and often used strategies to improve the immunosuppressive potency of MSCs, but the underlying mechanisms are not well understood. Therefore, the aims of this study were (i) to compare the effects of pro-inflammatory, hypoxic, and 3D culture priming on the in vitro immunosuppressive potential of MSCs, (ii) to assess if immunosuppressive priming effects are temporally preserved under standard and translationally relevant culture conditions, and (iii) to investigate if the three priming strategies engage the same immunosuppressive mechanisms.
View Article and Find Full Text PDFFront Cell Dev Biol
October 2023
The pain in patients with Modic type 1 changes (MC1) is often due to vertebral body endplate pain, which is linked to abnormal neurite outgrowth in the vertebral body and adjacent endplate. The aim of this study was to understand the role of MC1 bone marrow stromal cells (BMSCs) in neurite outgrowth. BMSCs can produce neurotrophic factors, which have been shown to be pro-fibrotic in MC1, and expand in the perivascular space where sensory vertebral nerves are located.
View Article and Find Full Text PDFCrohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. Extensive screening studies have revealed the accumulation of immune cell subsets with unique plasticity and immunoregulatory properties in patients with CD. We performed phenotypic and functional studies on inflamed and non-inflamed bioptic tissue to investigate the presence of distinct T cells in the intestinal mucosa of CD patients.
View Article and Find Full Text PDFThe molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain enhancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2, CBP/CREBBP, p300/EP300, and HIST1H1 in >95% of cases.
View Article and Find Full Text PDFFollicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of or its overexpression are associated with FL transformation (tFL).
View Article and Find Full Text PDFThe molecular pathogenesis of follicular lymphoma (FL) was partially revealed by the discovery of BCL2 translocations to the region encoding the immunoglobulin heavy chain, which accompany the vast majority of cases. This aberration leads to the ectopic and constitutive expression of anti-apoptotic BCL2 protein in B-cells. Nevertheless, the aberration alone is not sufficient for FL development, which suggests necessity of further genetic aberrations acquisition for neoplastic transformation to FL.
View Article and Find Full Text PDFBackground: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL).
View Article and Find Full Text PDFThe MINERvA experiment observes an excess of events containing electromagnetic showers relative to the expectation from Monte Carlo simulations in neutral-current neutrino interactions with mean beam energy of 4.5 GeV on a hydrocarbon target. The excess is characterized and found to be consistent with neutral-current π^{0} production with a broad energy distribution peaking at 7 GeV and a total cross section of 0.
View Article and Find Full Text PDFThe first direct measurement of electron neutrino quasielastic and quasielasticlike scattering on hydrocarbon in the few-GeV region of incident neutrino energy has been carried out using the MINERvA detector in the NuMI beam at Fermilab. The flux-integrated differential cross sections in the electron production angle, electron energy, and Q^{2} are presented. The ratio of the quasielastic, flux-integrated differential cross section in Q^{2} for ν_{e} with that of similarly selected ν_{μ}-induced events from the same exposure is used to probe assumptions that underpin conventional treatments of charged-current ν_{e} interactions used by long-baseline neutrino oscillation experiments.
View Article and Find Full Text PDFTwo different nuclear-medium effects are isolated using a low three-momentum transfer subsample of neutrino-carbon scattering data from the MINERvA neutrino experiment. The observed hadronic energy in charged-current ν_{μ} interactions is combined with muon kinematics to permit separation of the quasielastic and Δ(1232) resonance processes. First, we observe a small cross section at very low energy transfer that matches the expected screening effect of long-range nucleon correlations.
View Article and Find Full Text PDFNeutrino-induced coherent charged pion production on nuclei νμA→μ(±)π(∓)A is a rare, inelastic interaction in which a small squared four-momentum |t| is transferred to the recoil nucleus, leaving it intact in the reaction. In the scintillator tracker of MINERvA, we remove events with evidence of particles from nuclear breakup and reconstruct |t| from the final-state pion and muon. We select low |t| events to isolate a sample rich in coherent candidates.
View Article and Find Full Text PDFWe present measurements of ν(μ) charged-current cross section ratios on carbon, iron, and lead relative to a scintillator (CH) using the fine-grained MINERvA detector exposed to the NuMI neutrino beam at Fermilab. The measurements utilize events of energies 2
We report a study of ν(μ) charged-current quasielastic events in the segmented scintillator inner tracker of the MINERvA experiment running in the NuMI neutrino beam at Fermilab. The events were selected by requiring a μ- and low calorimetric recoil energy separated from the interaction vertex. We measure the flux-averaged differential cross section, dσ/dQ², and study the low energy particle content of the final state.
View Article and Find Full Text PDFWe have isolated ν(μ) charged-current quasielastic (QE) interactions occurring in the segmented scintillator tracking region of the MINERvA detector running in the NuMI neutrino beam at Fermilab. We measure the flux-averaged differential cross section, dσ/dQ², and compare to several theoretical models of QE scattering. Good agreement is obtained with a model where the nucleon axial mass, M(A), is set to 0.
View Article and Find Full Text PDFA series of 5-alkynyl- and 5-aryl-4,6-dithianonanedioic acids and related compounds has been prepared for evaluation of leukotriene antagonist activity. The alkynyl compounds were prepared by thioacetal exchange from the corresponding acetylenic acetals. The aryl derivatives were synthesized from the appropriate benzaldehydes, most of which were prepared by one of three general routes: Meyers' oxazolin method, a palladium coupling procedure, and a hydroxybenzaldehyde alkylation.
View Article and Find Full Text PDFAnti-human Ig (immunoglobulin) E induced the release of 2.84 +/- 0.33 ng/ml of immunoreactive leukotrienes (iLTs) from passively sensitized, fragmented rhesus monkey lung, whereas tissue not challenged with anti-IgE released 0.
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