Assessment of Illumina® Human mtDNA Genome assay: workflow evaluation with development of analysis and interpretation guidelines

International Journal of Legal Medicine - Mitochondrial DNA (mtDNA) is a small but significant part of the human genome, whose applicability potential has gradually increased with the advent of...     

Transcription factor HIF1A: downstream targets,associated pathways,polymorphic hypoxia response element (HRE) sites,and initiative for standardization of reporting in scientific literature

Tumor Biology - Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes...     

Drug-induced Fatty Liver Disease: Pathogenesis and Treatment

Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.     

Advances in diagnosis of chronic liver diseases in pediatric patients

Background

Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recognition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available.

Methods

A non-systematic literature search was performed to summarize the current knowledge about transient elastography (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population.

Results

Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized.

Conclusions

TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient’s demographics, disease etiology, and essential laboratory parameters.

     

The association of the decline in glomerular filtration rate with aggressive endometrial cancers

International Urology and Nephrology - Most site-specific cancer incidence is increased with the decrease of glomerular filtration rate (GFR). We analyzed endometrial cancers depending on different...     

Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors

We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC₅₀ = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 μM), and efflux impaired E. coli strain (MIC = 0.78 μM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.     

Identification of new impurities of enalapril maleate on oxidation in the presence of magnesium monoperoxyphthalate

Stress stability testing and forced degradation were used to determine the stability of enalapril maleate (EM) and to find a degradation pathway for the drug. The degradation impurities, formed under different stressed conditions, were investigated by HPLC and UPLC–MS methods. HPLC analysis showed several degradation impurities of which several were already determined, but on oxidation in the presence of magnesium monoperoxyphthalate (MMPP) several impurities of EM were observed which were not yet characterized. The HPLC methods for determination of EM were validated. The linearity of HPLC method was established in the concentration range between 0.5 and 10 μg/mL with correlation coefficient greater than 0.99. The LOD of EM was 0.2 μg/mL and LOQ was 0.5 μg/mL. The validated HPLC method was used to determine the degradation impurities in samples after stress stability testing and forced degradation of EM. In order to identify new degradation impurities of EM after forced degradation UPLC–MS/MSⁿ, Orbitrap has been used. It was found that new impurities are oxidation products: (S)-1-((S)-2-((S)-1-ethoxy-4-(o,m,p-hydroxyphenyl)-1-oxobutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid, (2S)-1-((2S)-2-((2S)-1-ethoxy-4-hydroxy-1-oxo-4-phenylbutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid. (S)-2-(3-phenylpropylamino)-1-(pyrrolidin-1-yl)propan-1-one was identified as a new degradation impurity.