Evolution Driven Microscale Combinatorial Chemistry in Intracellular Mimicking Droplets to Engineer Thermostable RNA for Cellular Imaging.

Fluorescent light-up aptamer/fluorogen pairs are powerful tools for tracking RNA in the cell, however limitations in thermostability and fluorescence intensity exist. Current in vitro selection techniques struggle to mimic complex intracellular environments, limiting in vivo biomolecule functionality. Taking inspiration from microenvironment-dependent RNA folding observed in cells and organelle-mimicking droplets, an efficient system is created that uses microscale heated water droplets to simulate intracellular conditions, effectively replicating the intracellular RNA folding landscape.

Cytotoxic and Noncytotoxic Steroidal Constituents of .

(-)-Cryptanoside A () was identified previously as a major cytotoxic component of the stems of collected in Laos, which mediates its activity by targeting Na/K-ATPase (NKA), with hydrogen bonds formed between its 11- and 4'-hydroxy groups and NKA being observed in its docking profile. In a continuing investigation, and its 17-epimer, (-)-17--cryptanoside A (), and the new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid () and the known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone () pregnane-type steroids were isolated from . In addition, (-)-11,4'-di--acetylcryptanoside A () has been synthesized from the acetylation of .

Molecular Networking, Docking, and Biological Evaluation of Licarin A from as a Potential Cancer Chemopreventive Agent.

Currently, clinically available cancer chemopreventive drug options are limited to mostly tamoxifen and its derivatives, such as raloxifene, and approved specifically for breast cancer. Thus, the availability of chemopreventive drug molecules for other types of malignant cancers would be desirable. In previous reports, the arils of (mace) have been found to exhibit cancer chemopreventive activity.

Discovery of Natural Products for Cancer Prevention.

"Cancer chemoprevention" is a term referring to the slowing or reversal of this disease, using nontoxic natural or synthetic compounds. For about 50 years, there has been a strong scientific interest in discovering plant-derived compounds to prevent cancer, and strategies for this purpose using a concerted series of in vitro, ex vivo, and in vivo laboratory bioassays have been developed. Five examples of the more thoroughly investigated agents of this type are described herein, which are each supported by detailed literature reports, inclusive of ellagic acid, isoliquiritigenin, lycopene, trans-resveratrol, and sulforaphane.

Steroids and Epicoccarines from .

Lichens are symbiotic organisms comprised of mycobionts and photobiont partners. They are known to produce bioactive secondary metabolites and most of these are biosynthesized by mycobionts. Investigations of cultures of isolated lichen-associated fungi have shown promise for the discovery of cytotoxic compounds.

Anti-tumor effects of the eIF4A inhibitor didesmethylrocaglamide and its derivatives in human and canine osteosarcomas.

Inhibition of translation initiation using eIF4A inhibitors like (-)-didesmethylrocaglamide [(-)-DDR] and (-)-rocaglamide [(-)-Roc] is a potential cancer treatment strategy as they simultaneously diminish multiple oncogenic drivers. We showed that human and dog osteosarcoma cells expressed higher levels of eIF4A1/2 compared with mesenchymal stem cells. Genetic depletion of eIF4A1 and/or 2 slowed osteosarcoma cell growth.

Development of Potential Therapeutic Agents from Black Elderberries (the Fruits of L.).

Elderberry ( L.) is a widespread deciduous shrub, of which the fruits (elderberries) are used in the food industry to produce different types of dietary supplement products. These berries have been found to show multiple bioactivities, including antidiabetic, anti-infective, antineoplastic, anti-obesity, and antioxidant activities.

Anti-tumor Effects of the eIF4A Inhibitor Didesmethylrocaglamide and Its Derivatives in Human and Canine Osteosarcomas.

Inhibition of translation initiation using eIF4A inhibitors like (-)-didesmethylrocaglamide [(-)-DDR] and (-)-rocaglamide [(-)-Roc] is a potential cancer treatment strategy as they simultaneously diminish multiple oncogenic drivers. We showed that human and dog osteosarcoma cells expressed high levels of eIF4A1/2, particularly eIF4A2. Genetic depletion of eIF4A1 and/or 2 slowed osteosarcoma cell growth.

The Evolution and Application of a Novel DNA Aptamer Targeting Bone Morphogenetic Protein 2 for Bone Regeneration.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is an FDA-approved growth factor for bone regeneration and repair in medical practice. The therapeutic effects of rhBMP-2 may be enhanced through specific binding to extracellular matrix (ECM)-like scaffolds. Here, we report the selection of a novel rhBMP-2-specific DNA aptamer, functionalization of the aptamer in an ECM-like scaffold, and its application in a cellular context.

Structure-Switching Electrochemical Aptasensor for Rapid, Reagentless, and Single-Step Nanomolar Detection of C-Reactive Protein.

C-reactive protein (CRP) is an acute-phase reactant and sensitive indicator for sepsis and other life-threatening pathologies, including systemic inflammatory response syndrome. Currently, clinical turn-around times for established CRP detection methods take between 30 min to hours or even days from centralized laboratories. Here, we report the development of an electrochemical biosensor using redox probe-tagged DNA aptamers, functionalized onto inexpensive, commercially available screen-printed electrodes.

Cytotoxic leuconoxine-type diazaspiroindole alkaloids isolated from Cryptolepis dubia.

Two leuconoxine-type diazaspiroindole alkaloids, the known compound, (+)-melodinine E (1), and its new analogue, (+)-11-chloromelodinine E (2), were isolated from the stems of Cryptolepis dubia (Burm.f.) M.

Does Dressing Choice Affect Infection Rate in Percutaneous K-Wiring of the Hand and Wrist? - A Systematic Review.

Percutaneous Kirschner wire (K-wire) fixation of hand and wrist fractures is a common trauma procedure, yet there remains little consensus on the best management of wires postoperatively. If wire's ends are left external to the skin, it remains unknown which dressing regimen best reduces infection risk. We felt that a systematic review was required to assess the current consensus on this question within the published literature.

Supporting the Resilience and Mental Health of Missouri Healthcare Workers Through COVID-19 and Beyond: the Gateway2Wellness Program.

The COVID-19 pandemic is over, but US healthcare workers (HCWs) continue to report high levels of work-related exhaustion and burnout but are unlikely to seek help. Digital tools offer a scalable solution. Between February and June 2022, we surveyed Missouri hospital administrators to assess HCW mental health and identify related evidence-based or evidence-informed resources.

Directed Evolution of a G-Quadruplex Peroxidase DNAzyme and Application in Proteomic DNAzyme-Aptamer Proximity Labeling.

DNAzymes have been limited in application by their low catalytic rates. Here, we evolved a new peroxidase DNAzyme mSBDZ-X-3 through a directed evolution method based on the capture of self-biotinylated DNA catalyzed by its intrinsic peroxidase activity. The mSBDX-X-3 DNAzyme has a parallel G-quadruplex structure and has more favorable catalytic properties than all previously reported peroxidase DNAzyme variants.

The Cytotoxic Cardiac Glycoside (-)-Cryptanoside A from the Stems of and Its Molecular Targets.

A cardiac glycoside epoxide, (-)-cryptanoside A (), was isolated from the stems of collected in Laos, for which the complete structure was confirmed by analysis of its spectroscopic and single-crystal X-ray diffraction data, using copper radiation at a low temperature. This cardiac glycoside epoxide exhibited potent cytotoxicity against several human cancer cell lines tested, including HT-29 colon, MDA-MB-231 breast, OVCAR3 and OVCAR5 ovarian cancer, and MDA-MB-435 melanoma cells, with the IC values found to be in the range 0.1-0.

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

Background: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality.

Strategies for the discovery of potential anticancer agents from plants collected from Southeast Asian tropical rainforests as a case study.

Covering up to early 2023The present review summarizes recent accomplishments made as part of a multidisciplinary, multi-institutional anticancer drug discovery project, wherein samples comprising higher plants were collected primarily from Southeast Asia, and also from Central America, and the West Indies. In the introductory paragraphs, a short perspective is provided on the current importance of plants in the discovery of cancer therapeutic agents, and the contributions of other groups working towards this objective are mentioned. For our own investigations, following their collection, tropical plants have been subjected to solvent extraction and biological evaluation for their antitumor potential.

Aptamers as Functional Modules for DNA Nanostructures.

Watson-Crick base-pairing of DNA allows the nanoscale fabrication of biocompatible synthetic nanostructures for diagnostic and therapeutic biomedical purposes. DNA nanostructure design elicits exquisite control of shape and conformation compared to other nanoparticles. Furthermore, nucleic acid aptamers can be coupled to DNA nanostructures to allow interaction and response to a plethora of biomolecules beyond nucleic acids.

Management of diversity and inbreeding when importing new stock into an inbred population.

This article relates to breeding programs that seek to manage genetic diversity. The method maximizes a multicomponent objective function, applicable across breeding scenarios. However, this paper focuses on breeding decisions following immigration of 10 unrelated individuals into a highly inbred simulated population (F ≈ 0.

Bioactive and unusual steroids from Penicillium fungi.

Penicillium fungi are represented by various species and can be found worldwide and thrive in a range of environments, such as in the soil, air, and indoors, and in marine environments, as well as food products. Chemical investigation of species of this genus has led to the discovery of compounds from several structural classes with varied bioactivities. As an example, this genus has been a source of bioactive and structurally unusual steroids.

Tuning Material States and Functionalities of G-Quadruplex-Modulated RNA-Peptide Condensates.

RNA encodes sequence- and structure-dependent interactions to modulate the assembly and properties of biomolecular condensates. RNA G-quadruplexes (rG4s) formed by guanine-rich sequences can trigger the formation of liquid- or solid-like condensates that are involved in many aberrant phase transitions. However, exactly how rG4 motifs modulate different phase transitions and impart distinct material properties to condensates is unclear.

Yield of Facility-based Targeted Universal Testing for Tuberculosis With Xpert and Mycobacterial Culture in High-Risk Groups Attending Primary Care Facilities in South Africa.

Background: We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups.

Methods: Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture.

Effects of Corchorusoside C on NF-κB and PARP-1 Molecular Targets and Toxicity Profile in Zebrafish.

The present study aims to continue the study of corchorusoside C (), a cardenolide isolated from , as a potential anticancer agent. A mechanistic study was pursued in a zebrafish model and in DU-145 prostate cancer cells to investigate the selectivity of towards NF-κB and PARP-1 pathway elements. Compound was found to inhibit the expression of IKKα and NF-κB p65 in TNF-α induced zebrafish and inhibit the expression of NIK in vitro.