Toxicological evaluation of standardized extract: Sub-chronic and mutagenicity studies.

(KP), also known as Krachai-dam in Thailand, belongs to the family Zingiberaceae and has been used traditionally to improve blood flow and treat inflammatory, allergic, and gastrointestinal disorders. The objective of this study was to investigate the safety profile of a standardized hydroalcoholic KP rhizome extract via mutagenicity and sub-chronic toxicity evaluations using and techniques. The in vitro mutagenicity of KP extract was assessed via reverse mutation tests using TA98, TA100, TA1535, and TA1537, and WP2 .

Reactive Enamines and Imines In Vivo: Lessons from the RidA Paradigm.

Metabolic networks are webs of integrated reactions organized to maximize growth and replication while minimizing the detrimental impact that reactive metabolites can have on fitness. Enamines and imines, such as 2-aminoacrylate (2AA), are reactive metabolites produced as short-lived intermediates in a number of enzymatic processes. Left unchecked, the inherent reactivity of enamines and imines may perturb the metabolic network.

Distribution of the cytochrome P450 CYP2C8*2 allele in Brazzaville, Republic of Congo.

Background: Cytochrome P450 (CYP) enzymes are essential in the metabolism of most drugs used today. Single nucleotide polymorphism(s) occurring in CYP genes can adversely affect drug pharmacokinetics, efficacy, and safety. Individuals carrying the CYP2C8*2 c.

Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Lysine Metabolism.

Despite intensive study for 50 years, the biochemical and genetic links between lysine metabolism and central metabolism in remain unresolved. To establish these biochemical links, we leveraged andom arcode rasposon uencing (RB-TnSeq), a genome-wide assay measuring the fitness of thousands of genes in parallel, to identify multiple novel enzymes in both l- and d-lysine metabolism. We first describe three pathway enzymes that catabolize l-2-aminoadipate (l-2AA) to 2-ketoglutarate (2KG), connecting d-lysine to the TCA cycle.

Ag@SiO nanoparticles performing as a nanoprobe for selective analysis of 2-aminoanthracene in wastewater samples via metal-enhanced fluorescence.

Due to severely overlapping emission and or/ excitation spectra of polycyclic aromatic hydrocarbons (PAHs), the specifically recognizing PAHs by the fluorescent technique is still a challenge. Here, synthesized Ag@SiO nanoparticles with 40 ± 4 nm Ag core and 7 ± 1 nm SiO shell performing as a nanoprobe could selectively recognize 2-aminoanthracene (2-AA) via metal-enhanced fluorescence (MEF) within 2 min. The sensing mechanism was based on the facts: (1) there was a perfect spectral overlap between the local surface plasmon resonance (LSPR) peak of Ag@SiO and the absorptive peak of 2-AA, and (2) 2-AA could interact with Ag@SiO nanoparticles through hydrogen bonds between -NH in 2-AA and -OH in SiO shell.

Wildlife, human and environmental costs of using lead ammunition: An economic review and analysis.

A proposed European Union (EU)-wide restriction on the use of lead gunshot for shooting in and over wetlands estimated that the societal benefits of a restriction outweighed costs, despite few identified benefits being quantified economically. A subsequent Annex XV Investigation Report on the evidence of impacts of lead ammunition in terrestrial environments concluded that additional measures to control its use are warranted, although to date this has not been further evaluated. To help inform this process, we review the literature and undertake new analyses to estimate the costs of continued use of lead ammunition associated with impacts on wildlife, people and the environment.

Rational Design, Synthesis and Preliminary Evaluation of Novel Fusarinine C-Based Chelators for Radiolabeling with Zirconium-89.

Fusarinine C (FSC) has recently been shown to be a promising and novel chelator for Zr. Here, FSC has been further derivatized to optimize the complexation properties of FSC-based chelators for Zr-labeling by introducing additional carboxylic groups. These were expected to improve the stability of Zr-complexes by saturating the 8-coordination sphere of [Zr] Zr, and also to introduce functionalities suitable for conjugation to targeting vectors such as monoclonal antibodies.

Antimutagenic, antitumor and estrogen receptor binding activity of the rare plant : An ethnobotanical and chemosystematic approach.

Objective: and other members of the Diapensiaceae family have ethnomedicinal history in both Eastern and Western hemispheres. Based on ethnopharmacological and chemosystematic evidence, pharmacological and toxicological bioassays were conducted on the rare plant Oconee Bell, .

Materials And Methods: Extracts were examined in assays for antimutagenicity, antitumor and estrogen receptor (ER)-binding activity.

Adolescent Lisfranc injury treated with TightRope: A case report and review of literature.

Background: Lisfranc injuries are rare and can be easily missed. This injury is extremely rare in children, with limited published data. Different treatment options have been described; one of the options in adults is the "mini" TightRope™ Syndesmosis Device that provides non-rigid fixation with impressive results.

The midgut V-ATPase subunit A gene is associated with toxicity to crystal 2Aa and crystal 1Ca-expressing transgenic rice in Chilo suppressalis.

Insecticidal crystal (Cry) proteins produced by the bacterium Bacillus thuringiensis (Bt) are toxic to a diverse range of insects. Transgenic rice expressing Cry1A, Cry2A and Cry1C toxins have been developed that are lethal to Chilo suppressalis, a devastating insect pest of rice in China. Identifying the mechanisms underlying the interactions of Cry toxins with susceptible hosts will improve both our understanding of Cry protein toxicology and long-term efficacy of Bt crops.

SLA-VER: study protocol description and preliminar results of the first italian RCT on conservative treatment of distal radial fractures.

Introduction: There is no consensus on which is the best way to maintain initial reduction of a distal radius fractures (DRFs). The aim of this study is to test the hypothesis that below elbow cast (BEC) is equivalent to above elbow cast (AEC) in maintaining initial reduction of DRFs. This paper will report on midterm results.

DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.

Rationale: Mutations in the LMNA gene, encoding LMNA (lamin A/C), are responsible for laminopathies. Dilated cardiomyopathy (DCM) is a major cause of mortality and morbidity in laminopathies.

Objective: To gain insights into the molecular pathogenesis of DCM in laminopathies.

Synthesis, characterization and antidiabetic effects of vanadyl(II) adenosine monophosphate amino acid mixed-ligand complexes.

This research paper is aimed at designing a novel insulin alternative for the treatment of diabetes. Six novel vanadyl(II) compounds, [(AMP)(VO)(AA )]·NH , were synthesized from an equimolar ratio of adenosine monophosphate, VOSO and amino acids (AA ). The magnetic moments and electronic spectra revealed the square pyramidal geometrical structure of the complexes.

Fluorescing Isofunctional Ribonucleosides: Assessing Adenosine Deaminase Activity and Inhibition.

The enzymatic conversion of isothiazolo[4,3-d]pyrimidine-based adenosine ( A) and 2-aminoadenosine ( 2-AA) analogues to the corresponding isothiazolo[4,3-d]pyrimidine-based inosine ( I) and guanosine ( G) derivatives is evaluated and compared to the conversion of native adenosine to inosine. Henri-Michaelis-Menten analyses provides the foundation for a high-throughput screening assay, and the efficacy of the assay is showcased by fluorescence-based analysis of A conversion to I in the presence of known and newly synthesized inhibitors.

High-selectivity profiling of released and labeled N-glycans via polar-embedded reversed-phase chromatography.

N-Glycosylation is the most complex post-translational modification of proteins and involved in many physiological processes and is therefore of major interest in academic research and in the biopharmaceutical industry. Reliable, robust, reproducible, and selective analysis of N-glycans is essential to understand the multitude of biological roles of N-glycosylation. So far, hydrophilic interaction liquid chromatography analysis of 2-AB or 2-AA derivatized N-glycans has been the standard method.

Analyses of variants of the Ser/Thr dehydratase IlvA provide insight into 2-aminoacrylate metabolism in .

RidA is a conserved and broadly distributed protein that has enamine deaminase activity. In a variety of organisms tested thus far, lack of RidA results in the accumulation of the reactive metabolite 2-aminoacrylate (2AA), an obligate intermediate in the catalytic mechanism of several pyridoxal 5'-phosphate (PLP)-dependent enzymes. This study reports the characterization of variants of the biosynthetic serine/threonine dehydratase (EC 4.

A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential.

Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold.

How a Communication Intervention in Zambia Re-Oriented Health Services to the Needs of the Least-Supported.

Despite decades of training health workers in communication, complaints from clients and communities about poor health worker attitudes abound. This was found to be so in Zambia where the More Mobilizing Access to Maternal Health Services in Zambia (MORE MAMaZ) program was trying to ensure the inclusion of under-supported women in a community-based maternal and newborn health program in five intervention districts. Under-supported women suffer a disproportionate burden of child mortality and are poor users of health services.

PA5339, a RidA Homolog, Is Required for Full Growth in Pseudomonas aeruginosa.

The Rid protein superfamily (YjgF/YER057c/UK114) is found in all domains of life. The archetypal protein, RidA from , is a deaminase that quenches the reactive metabolite 2-aminoacrylate (2AA). 2AA deaminase activity is conserved in RidA proteins from humans, plants, yeast, archaea, and bacteria.

Redox-Switchable Bis-fused Tetrathiafulvalene Analogue: Observation and Control of Two Different Reduction Processes from Dication to Neutral State.

Derivatives of a new bis-fused donor composed of TTF and extended TTF with an anthraquinoid spacer (TTFAQ) (2) were successfully synthesized. X-ray structure analysis of the tetrakis(methylthio) derivative 2Aa and its I salt revealed that the TTFAQ moieties of both 2Aa and 2Aa adopt the so-called saddle conformation similar to most neutral TTFAQs. The results obtained from the X-ray structure analysis and cyclic voltammetry suggest that a positive charge in 2Aa is unevenly distributed on the TTF moiety, while both positive charges of 2 are mainly located on the TTFAQ moiety.

Brain Health across the Lifespan: A Systematic Review on the Role of Omega-3 Fatty Acid Supplements.

The brain is the most significant and complex organ of the human body. Increasingly, we are becoming aware that certain nutrients may help to safeguard brain health. An expanse of research has investigated the effects of omega fatty acids in relation to brain health but effects across the lifespan have not been widely evaluated.

Base-promoted diastereoselective α-alkylation of borane N-((S)-1'-phenylethyl)azetidine-2-carboxylic acid ester complexes.

The base-promoted α-alkylation of N-((S)-1-phenylethyl)azetidine-2-carboxylic acid esters 1 was investigated. The use of diastereomerically pure borane complexes 3 as substrates, which are easily prepared from 1, dramatically improved the yields and diastereoselectivities of α-alkylated products 2. For example, the treatment of tert-butyl ester (1S,2S,1'S)-3a with 2.

A bacterial biosensor encoding a genetically modified LuxR receptor exhibits improved detection of Pseudomonas aeruginosa's biomarker molecule 2-aminoacetophenone.

2-Aminoacetophneone (2-AA) is a volatile molecule produced in high amounts by the opportunistic pathogen Pseudomonas aeruginosa. We have previously shown that 2-AA activates the quorum sensing (QS) LuxR receptor of Aliivibrio fischeri. In the present study we were able to improve LuxR's affinity and detection limit for 2-AA by genetic modification of three amino acids within the binding pocket of the receptor.

GM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate.

In a GM-CSF driven myeloid cell deficient mouse model (Csf2) that has preserved insulin sensitivity despite increased adiposity, we used unbiased three-dimensional integration of proteome profiles, metabolic profiles, and gene regulatory networks to understand adipose tissue proteome-wide changes and their metabolic implications. Multi-dimensional liquid chromatography mass spectrometry and extended multiplex mass labeling was used to analyze proteomes of epididymal adipose tissues isolated from Csf2 and Csf2 mice that were fed low fat, high fat, or high fat plus cholesterol diets for 8 weeks. The metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, phospholipids, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet for both genotypes, while mice lacking Csf2 were protected from insulin resistance.

Effects of a small, volatile bacterial molecule on Pseudomonas aeruginosa bacteria using whole cell high-resolution magic angle spinning nuclear magnetic resonance spectroscopy and genomics.

In the present study, high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy was applied to live Pseudomonas aeruginosa (PA) bacterial cells to determine the metabolome of this opportunistic Gram-negative human pathogen, and in particular, its response to the volatile aromatic low molecular weight signaling molecule, 2-aminoacetophenone (2-AA). Multi-dimensional HRMAS NMR is a promising method which may be used to determine the in vivo metabolome of live intact bacterial cells; 2-AA is produced by PA and triggers the emergence of phenotypes that promote chronic infection phenotypes in in vitro and in vivo (animal) models. In the present study, we applied one-dimensional and two-dimensional proton (1H) HRMAS NMR to PA cells which were grown with or without 2-AA in order to examine the associations between metabolites and cellular processes in response to 2-AA.