The mechanism of action of auranofin analogs in revealed by chemogenomic profiling.

Drug repurposing efforts led to the discovery of bactericidal activity in auranofin, a gold-containing drug used to treat rheumatoid arthritis. Auranofin kills Gram-positive bacteria by inhibiting thioredoxin reductase, an enzyme that scavenges reactive oxygen species (ROS). Despite the presence of thioredoxin reductase in Gram-negative bacteria, auranofin is not always active against them.

Turning on the Antimicrobial Activity of Gold Nanoclusters Against Multidrug-Resistant Bacteria.

In this work, we show that the addition of thiourea (TU) initiated broad-spectrum antimicrobial activity of otherwise inactive D-maltose-capped gold nanoclusters (AuNC-Mal). For example, AuNC-Mal/TU was effective against multidrug-resistant Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 1 μg mL (2.5 μM [Au]) while having 30-60 times lower in vitro cytotoxicity against mammalian cells.

Uridine Diphosphate Glucuronosyl Transferase 2B28 (UGT2B28) Promotes Tumor Progression and Is Elevated in African American Prostate Cancer Patients.

Prostate cancer (PCa) is the second most diagnosed cancer in the United States and is associated with metabolic reprogramming and significant disparities in clinical outcomes among African American (AA) men. While the cause is likely multi-factorial, the precise reasons for this are unknown. Here, we identified a higher expression of the metabolic enzyme UGT2B28 in localized PCa and metastatic disease compared to benign adjacent tissue, in AA PCa compared to benign adjacent tissue, and in AA PCa compared to European American (EA) PCa.

Androgen receptor variant-7 regulation by tenascin-c induced src activation.

Background: Bone metastatic prostate cancer does not completely respond to androgen-targeted therapy and generally evolves into lethal castration resistant prostate cancer (CRPC). Expression of AR-V7- a constitutively active, ligand independent splice variant of AR is one of the critical resistant mechanisms regulating metastatic CRPC. TNC is an extracellular matrix glycoprotein, crucial for prostate cancer progression, and associated with prostate cancer bone metastases.

Establishment of an in-house real-time RT-PCR assay for the detection of severe acute respiratory syndrome coronavirus 2 using the first World Health Organization international standard in a resource-limited country.

Background: The COVID-19 pandemic caused by SARS-CoV-2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real-time RT-PCR are critical for the detection of SARS-CoV-2 in clinical specimens from patients suspected of COVID-19.

Objective: We aimed to establish and validate an in-house real-time RT-PCR for the detection of SARS-CoV-2.

Adipogenesis of ear mesenchymal stem cells (EMSCs): adipose biomarker-based assessment of genetic variation, adipocyte function, and brown/brite differentiation.

Ear mesenchymal stem cells (EMSCs) have been investigated to differentiate into adipocytes, chondrocytes, and muscle cells in vitro. However, the factors controlling adipogenesis of this stem cell population in vitro, function, and type of adipocytes raised from them are still unclear. Here we found that genetics have a modest effect on adipogenic capacity of EMSCs.

New Auranofin Analogs with Antibacterial Properties against Clinical Isolates.

Bacteria of the genus include pathogenic , and the complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species is associated with one of the worst clinical outcomes.

Direct RNA Sequencing Unfolds the Complex Transcriptome of Vibrio parahaemolyticus.

Conventional bacterial genome annotation provides information about coding sequences but ignores untranslated regions and operons. However, untranslated regions contain important regulatory elements as well as targets for many regulatory factors, such as small RNAs. Operon maps are also essential for functional gene analysis.

ELF3 mediates IL-1α induced differentiation of mesenchymal stem cells to inflammatory iCAFs.

Stromal cells in the tumor microenvironment regulate the immune landscape and tumor progression. Yet, the ontogeny and heterogeneity of reactive stromal cells within tumors is not well understood. Carcinoma-associated fibroblasts exhibiting an inflammatory phenotype (iCAFs) have been identified within multiple cancers; however, mechanisms that lead to their recruitment and differentiation also remain undefined.

A graph-based algorithm for detecting rigid domains in protein structures.

Background: Conformational transitions are implicated in the biological function of many proteins. Structural changes in proteins can be described approximately as the relative movement of rigid domains against each other. Despite previous efforts, there is a need to develop new domain segmentation algorithms that are capable of analysing the entire structure database efficiently and do not require the choice of protein-dependent tuning parameters such as the number of rigid domains.

A Noncanonical Hippo Pathway Regulates Spindle Disassembly and Cytokinesis During Meiosis in .

Meiosis in the budding yeast is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires , which encodes an STE20 family GCKIII kinase.

Crystal structures of the RNA triphosphatase from provide insights into how it recognizes the 5'-end of the RNA substrate.

RNA triphosphatase catalyzes the first step in mRNA cap formation, hydrolysis of the terminal phosphate from the nascent mRNA transcript. The RNA triphosphatase from the protozoan parasite , TcCet1, belongs to the family of triphosphate tunnel metalloenzymes (TTMs). TcCet1 is a promising antiprotozoal drug target because the mechanism and structure of the protozoan RNA triphosphatases are completely different from those of the RNA triphosphatases found in mammalian and arthropod hosts.

Risk Factors for Stroke Associated Pneumonia.

Background: Stroke patients are at high risk for stroke-associated pneumonia (SAP). If patients suffer from pneumonia their prognosis will worsen.

Aim: To identify factors that increases the risk of SAP in stroke patients.

Short Tandem Repeats Used in Preimplantation Genetic Testing of Β-Thalassemia: Genetic Polymorphisms For 15 Linked Loci in the Vietnamese Population.

Background: β-thalassemia is one of the most common monogenic diseases worldwide. Preimplantation genetic testing (PGT) of β-thalassemia is performed to avoid affected pregnancies has become increasingly popular worldwide. In which, the indirect analysis using short tandem repeat (STRs) linking with HBB gene to detect different β-globin (HBB) gene mutation is a simple, accurate, economical and also provides additional control of contamination and allele-drop-out ADO.

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells.

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells.

Bone marrow mesenchymal stem/stromal cells (BMSCs), which are known as multipotent cells, are widely used in the treatment of various diseases via their self-renewable, differentiation, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of BMSCs therapy in clinical applications. The number of clinical trials in phase I/II is accelerating; however, they are limited in the size of subjects, regulations, and standards for the preparation and transportation and administration of BMSCs, leading to inconsistency in the input and outcome of the therapy.

Expression of aryl hydrocarbon receptor, inflammatory cytokines, and incidence of rheumatoid arthritis in Vietnamese dioxin-exposed people.

Many Vietnamese citizens have been and continue to be inadvertently exposed to dioxins and dioxin-like compounds deposited in the country during the Vietnam War. Dioxins may be involved in the pathogenesis of inflammatory diseases in part via by affecting expression of aryl hydrocarbon receptor (Ahr) and inflammatory cytokines in animal models. As the role of the Ahr in dioxin-exposed people is not well defined, a study was conducted to examine gene expression levels of Ahr, inflammatory cytokines, and the incidence of diseases in dioxin-exposed citizens who had/still resided near a heavily dioxin-contaminated area in Vietnam.

Effect of Heat Moisture Exchanger on Aerosol Drug Delivery and Airway Resistance in Simulated Ventilator-Dependent Adults Using Jet and Mesh Nebulizers.

Background: Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults.

Methods: An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmHO, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID).

Application of the Mike21C model to simulate flow in the lower Mekong river basin.

Numerical models are useful tools that play an important role in many research projects. Mike21C is one of the most well-established models for simulating a variety of processes, including bank erosion, bed level variations, aggradation, and degradation. Such processes are caused by a variety of activities, such as construction and dredging, as well as seasonal flow fluctuations.

Erratum to: Experimental analysis and numerical simulation of bed elevation change in mountain rivers.

[This corrects the article DOI: 10.1186/s40064-016-2714-3.].

Experimental analysis and numerical simulation of bed elevation change in mountain rivers.

Studies of sediment transport problems in mountainous rivers with steep slopes are difficult due to rapid variations in flow regimes, abrupt changes in topography, etc. Sediment transport in mountainous rivers with steep slopes is a complicated subject because bed materials in mountainous rivers are often heterogeneous and contain a wide range of bed material sizes, such as gravel, cobbles, boulders, etc. This paper presents a numerical model that was developed to simulate the river morphology in mountainous rivers where the maximum bed material size is in the range of cobbles.

Stromal TGF-β signaling induces AR activation in prostate cancer.

AR signaling is essential for the growth and survival of prostate cancer (PCa), including most of the lethal castration-resistant PCa (CRPC). We previously reported that TGF-β signaling in prostate stroma promotes prostate tumor angiogenesis and growth. By using a PCa/stroma co-culture model, here we show that stromal TGF-β signaling induces comprehensive morphology changes of PCa LNCaP cells.