Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

To evaluate factors associated with human immunodeficiency virus type 1 (HIV-1) proviral DNA load, we conducted a cross-sectional study of 36 chronically HIV-1-infected individuals with undetectable plasma viral RNA. We used real-time polymerase chain reaction to determine the number of HIV-1 proviral DNA copies per 106 peripheral blood mononuclear cells. The mean level of plasma viral RNA when the CD4+ T cell count was above 500 cells/µL without highly active antiretroviral therapy (HAART) was significantly associated with proviral DNA load at the time of undetectable plasma HIV RNA with HAART. Strategies to reduce the level of plasma viral RNA when patients' CD4+ T cell counts are above 500 cells/µL without HAART could help reduce HIV-1 proviral DNA load

Helicity-driven chiral self-sorting supramolecular polymerization with Ag+: right- and left-helical aggregates

The study of chiral self-sorting is extremely important for understanding biological systems and for developing applications for the biomedical field. In this study, we attempted unprecedented chiral self-sorting supramolecular polymerization accompanying helical inversion with Ag+ in one enantiomeric component. Bola-type terpyridine-based ligands (R-L-1 and S-L-1) comprising R- or S-alanine analogs were synthesized. First, R-L-1 dissolved in DMSO/H2O (1 : 1, v/v) forms right-handed helical fibers (aggregate I) via supramolecular polymerization. However, after the addition of AgNO3 (0.2-1.1 equiv.) to the R-L-1 ligand, in particular, it was found that aggregate II with left-handed helicity is generated from the [R-L-1(AgNO3)(2)] complex through the [R-(LAg)-Ag-1](+) complex via the dissociation of aggregate I by a multistep with an off pathway, thus demonstrating interesting self-sorting properties driven by helicity and shape discrimination. In addition, the [R-L-1(AgNO3)(2)] complex, which acted as a building block to generate aggregate III with a spherical structure, existed as a metastable product during the formation of aggregate II in the presence of 1.2-1.5 equiv. of AgNO3. Furthermore, the AFM and CD results of two samples prepared using aggregates I and III with different volume ratios were similar to those obtained upon the addition of AgNO3 to free R-L-1. These findings suggest that homochiral self-sorting in a mixture system occurred by the generation of aggregate II composed of the [R-(LAg)-Ag-1](+) complex via the rearrangement of both, aggregates I and III. This is a unique example of helicity- and shape-driven chiral self-sorting supramolecular polymerization induced by Ag+ starting from one enantiomeric component. This research will improve understanding of homochirality in complex biological models and contribute to the development of new chiral materials and catalysts for asymmetric synthesis

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

SummaryFrequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor

Antibody Detection in Healthcare Workers after Vaccination with Two Doses of the BNT162b2 or ChAdOx1 Vaccine

Background: Due to the COVID-19 pandemic, from 2020, many pharmaceutical companies have developed vaccines. To determine the efficacy of AstraZeneca’s and Pfizer’s vaccines, which were the first and second vaccines to be approved in Korea, respectively, we developed a method to measure their antibody-generating efficacies using immunology analyzers and a rapid antibody test available in Korea. Methods: The antibody-stimulating efficacies of the Pfizer and AstraZeneca vaccines were evaluated using Centaur. XPT SARS-CoV-2 (Siemens Healthineers, Germany), Elecsys. Anti-SARS-CoV-2 S (Roche Diagnostics, Germany), and STANDARD F SARS-CoV-2 nAb FIA (SD Biosensor, Korea). Healthcare workers were enrolled in two groups: the Pfizer (121) and AstraZeneca (117) groups. Antibody levels were measured pre-vaccination, three weeks after vaccination, and 16 weeks after vaccination. Results: The Pfizer group comprised 41 males and 80 females, while the AstraZeneca group comprised 38 males and 79 females. Antibody results were analyzed after excluding four individuals who had recovered from COVID-19. Between weeks 3 and 16, there was no significant difference (P= 0.5, 1.0) between the results of the Roche and Siemens antibody tests in the Pfizer vaccine group. However, the SD biosensor results comparing with the Roche and Siemens antibody tests at three weeks after the initial vaccination showed a significant difference (P < 0.0001). Analysis of the Roche antibody test results before, at three weeks, and at 16 weeks after the administration of the Pfizer and AstraZeneca vaccines revealed a statistically significant difference between before and at three weeks after the first injection (P < 0.0001). After two doses of the Pfizer and AstraZeneca vaccines, antibody formation was above the 90th percentile of the measurement range in all subjects

Rescuing developing thymocytes fromdeath by neglect

The major function of the thymus is to eliminate developing thymocytes that are potentially useless or autoreactive, and select only those that bear functional T cell antigen receptors (TCRs) through fastidious screening. It is believed that glucocorticoids (GCs) are at least in part responsible for cell death during death by neglect. In this review, we will mainly cover the topic of the GC-induced apoptosis of developing thymocytes. We will also discuss how thymocytes that are fated to die by GCs can be rescued from GC-induced apoptosis in response to a variety of signals with antagonizing properties for GC receptor (GR) signaling. Currently, a lot of evidence supports the notion that the decision is made as a result of the integration of the multiple signal transduction networks that are triggered by GR, TCR, and Notch. A few candidate molecules at the converging point of these multiple signaling pathyways will be discussed. We will particularly describe the role of the SRG3 protein as a potent modulator of GC-induced apoptosis in the crosstalk.close

Self-Assembled Triphenylphosphonium-Conjugated Dicyanostilbene Nanoparticles and Their Fluorescence Probes for Reactive Oxygen Species

We report self-assembled novel triphenylphosphonium-conjugated dicyanostilbene-based as selective fluorescence turn-on probes for 1O2 and ClO&#8722;. Mono- or di-triphenylphosphonium-conjugated dicyanostilbene derivatives 1 and 2 formed spherical structures with diameters of ca. 27 and 56.5 nm, respectively, through &#960;-&#960; interaction between dicyanostilbene groups. Self-assembled 1 showed strong fluorescent emission upon the addition of 1O2 and ClO&#8722; compared to other ROS (O2&#8722;, &#8226;OH, NO, TBHP, H2O2, GSH), metal ions (K+, Na+), and amino acids (cysteine and histidine). Upon addition of 1O2 and ClO&#8722;, the spherical structure of 1 changed to a fiber structure (8-nm wide; 300-nm long). Upon addition of 1O2 and ClO&#8722;, the chemical structural conversion of 1 was determined by FAB-Mass, NMR, IR and Zeta potential analysis, and the strong emission of the self-assembled 1 was due to an aggregation-induced emission enhancement. This self-assembled material was the first for selective ROS as a fluorescence turn-on probe. Thus, a nanostructure change-derived turn-on sensing strategy for 1O2 or ClO&#8722; may offer a new approach to developing methods for specific guest molecules in biological and environmental subjects