Barriers to lung cancer referral, diagnosis, and treatment in Central America and the Caribbean: the health professionals' perspectives.

Purpose: To identify the perspectives from healthcare providers about the limitations in referral, diagnosis, and treatment of lung cancer (LC) patients.

Methods: A cross-sectional study through an Internet-based survey was addressed to physicians of multidisciplinary teams in charge of LC patients from Cuba, Curacao, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Jamaica, Panama, and Trinidad and Tobago. The questions focused on physicians' perspectives concerning waiting times and the availability of diagnostic and staging procedures in their settings, as well as the access to systemic therapies and continuous medical education (CME).

Near infrared (NIR)-spectroscopy and in-vitro dissolution absorption system 2 (IDAS2) can help detect changes in the quality of generic drugs.

While Health authorities in Panama strive to increase generic drug use to contain the rising costs of medicines, there is still hesitation to embrace generic drugs. Thus, regulators and drug companies need to ensure the quality, safety and efficacy of generic drugs. One prevailing concern is the absence of control over lot-to-lot changes, which may impact consistent therapeutic performance.

Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.

Cyclin-dependent kinase 9 (CDK9) promotes transcriptional elongation through RNAPII pause release. We now report that CDK9 is also essential for maintaining gene silencing at heterochromatic loci. Through a live cell drug screen with genetic confirmation, we discovered that CDK9 inhibition reactivates epigenetically silenced genes in cancer, leading to restored tumor suppressor gene expression, cell differentiation, and activation of endogenous retrovirus genes.

Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids.

Tuberculosis represents a significant public health crisis. There is an urgent need for novel molecular scaffolds against this pathogen. We screened a small library of marine-derived compounds against shikimate kinase from Mycobacterium tuberculosis ( MtSK), a promising target for antitubercular drug development.

EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data.

Epigenetics has become a fundamental scientific discipline with various implications for biology and medicine. Epigenetic marks, mostly DNA methylation and histone post-translational modifications (PTMs), play important roles in chromatin structure and function. Accurate quantification of these marks is an ongoing challenge due to the variety of modifications and their wide dynamic range of abundance.

Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone.

Ilimaquinone (IQ), a marine sponge metabolite, has been considered as a potential therapeutic agent for various diseases due to its broad range of biological activities. We show that IQ irreversibly inactivates Mycobacterium tuberculosis shikimate kinase (MtSK) through covalent modification of the protein. Inactivation occurred with an apparent second-order rate constant of about 60 M s.

Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications.

The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs).

Cytoplasmic chromatin triggers inflammation in senescence and cancer.

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear.

Recognition of Histone H3K14 Acylation by MORF.

The monocytic leukemia zinc-finger protein-related factor (MORF) is a transcriptional coactivator and a catalytic subunit of the lysine acetyltransferase complex implicated in cancer and developmental diseases. We have previously shown that the double plant homeodomain finger (DPF) of MORF is capable of binding to acetylated histone H3. Here we demonstrate that the DPF of MORF recognizes many newly identified acylation marks.

LC-MS-Based Quality Assessment of a Traditional Chinese Medicine YANG XIN Formulation.

YANG XIN is a traditional Chinese medicine formulation used for nervous fatigue and consists of a proprietary blend of concentrated extracts from 18 plant ingredients. The 18 constituent plant ingredients, YANG XIN capsules, and formulations 2014-005_1 A and 1B were extracted by consecutive 24-hour macerations with dichloromethane followed by methanol. Metabolite separation was carried out through LC-MS in 40 minutes.

Low Resolution Data-Independent Acquisition in an LTQ-Orbitrap Allows for Simplified and Fully Untargeted Analysis of Histone Modifications.

Label-free peptide quantification in liquid chromatography-mass spectrometry (LC-MS) proteomics analyses is complicated by the presence of isobaric coeluting peptides, as they generate the same extracted ion chromatogram corresponding to the sum of their intensities. Histone proteins are especially prone to this, as they are heavily modified by post-translational modifications (PTMs). Their proteolytic digestion leads to a large number of peptides sharing the same mass, while carrying PTMs on different amino acid residues.

Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.

Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth.

Selective Mycobacterium tuberculosis Shikimate Kinase Inhibitors as Potential Antibacterials.

Owing to the persistence of tuberculosis (TB) as well as the emergence of multidrug-resistant and extensively drug-resistant (XDR) forms of the disease, the development of new antitubercular drugs is crucial. Developing inhibitors of shikimate kinase (SK) in the shikimate pathway will provide a selective target for antitubercular agents. Many studies have used in silico technology to identify compounds that are anticipated to interact with and inhibit SK.

Development of an ESI-LC-MS-based assay for kinetic evaluation of Mycobacterium tuberculosis shikimate kinase activity and inhibition.

A simple and reliable liquid chromatography-mass spectrometry (LC-MS) assay has been developed and validated for the kinetic characterization and evaluation of inhibitors of shikimate kinase from Mycobacterium tuberculosis (MtSK), a potential target for the development of novel antitubercular drugs. This assay is based on the direct determination of the reaction product shikimate-3-phosphate (S3P) using electrospray ionization (ESI) and a quadrupole time-of-flight (Q-TOF) detector. A comparative analysis of the kinetic parameters of MtSK obtained by the LC-MS assay with those obtained by a conventional UV-assay was performed.

Identification of shikimate kinase inhibitors among anti-Mycobacterium tuberculosis compounds by LC-MS.

Increasing drug resistance has challenged the control and treatment of tuberculosis, sparking recent interest in finding new antitubercular agents with different chemical scaffolds and mechanisms of action. Mycobacterium tuberculosis shikimate kinase (MtSK), an enzyme present in the shikimate pathway in bacteria, is essential for the survival of the tubercle bacillus, representing an ideal target for therapeutic intervention given its absence in mammals. In this study, a small library of 404 synthetic antimycobacterial compounds identified and supplied through the NIH Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) high throughput screening program against whole cell M.

Triterpenes from Warszewiczia coccinea (Rubiaceae) as inhibitors of acetylcholinesterase.

Seventy-six plant extracts from the Panamanian flora have been screened for acetylcholinesterase (AChE) inhibitors by thin-layer chromatography (TLC) bioautography. The most promising extracts with AChE inhibitory and free radical scavenging activities at 100 microg were those of Tabernaemontana panamensis (Markgr., Boiteau & L.