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1.
Article in English | MEDLINE | ID: mdl-38299284

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.


Subject(s)
Endocrine Disruptors , Environmental Pollutants , Endocrine Disruptors/adverse effects , Humans , Environmental Pollutants/toxicity , Environmental Exposure/adverse effects , Animals , Risk Assessment , Pregnancy , Endocrine System/drug effects
2.
Cureus ; 13(11): e19389, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34925991

ABSTRACT

To the best of our knowledge, there have been few reports in the literature about perineal injury without an associated pelvic fracture. In this report, we are going to discuss the mechanism, management, and outcome of two cases of perineal injury associated with car accidents. The two cases, one male and one female, presented with sustained isolated soft tissue injuries to the perineum. Both cases revealed a separated anorectum from the coccyx and sacrum without detectable damage to the lumen or surrounding sphincter. Pelvis fracture was not present in either case nor did the urinary bladder or urethra show signs of injury. A defunctioning (temporary) colostomy medical innervation was done to both and the perineal wound was left to heal. At last, both patients were satisfied with the final outcome.

3.
J Med Chem ; 63(13): 6784-6801, 2020 07 09.
Article in English | MEDLINE | ID: mdl-32433887

ABSTRACT

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as in vivo tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first in vivo validation of CaMK1D as a target for diabetes therapeutics.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 1/antagonists & inhibitors , Diet/adverse effects , Drug Discovery , Insulin Resistance , Obesity/drug therapy , Obesity/metabolism , Protein Kinase Inhibitors/pharmacology , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 1/chemistry , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Models, Molecular , Obesity/chemically induced , Protein Conformation , Protein Kinase Inhibitors/therapeutic use
4.
Nucleic Acids Res ; 42(5): e30, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24170810

ABSTRACT

In eukaryotic cells, the shortening and removal of the poly(A) tail of cytoplasmic mRNA by deadenylase enzymes is a critical step in post-transcriptional gene regulation. The ribonuclease activity of deadenylase enzymes is attributed to either a DEDD (Asp-Glu-Asp-Asp) or an endonuclease-exonuclease-phosphatase domain. Both domains require the presence of two Mg2+ ions in the active site. To facilitate the biochemical analysis of deadenylase enzymes, we have developed a fluorescence-based deadenylase assay. The assay is based on end-point measurement, suitable for quantitative analysis and can be adapted for 96- and 384-well microplate formats. We demonstrate the utility of the assay by screening a chemical compound library, resulting in the identification of non-nucleoside inhibitors of the Caf1/CNOT7 enzyme, a catalytic subunit of the Ccr4-Not deadenylase complex. These compounds may be useful tools for the biochemical analysis of the Caf1/CNOT7 deadenylase subunit of the Ccr4-Not complex and indicate the feasibility of developing selective inhibitors of deadenylase enzymes using the fluorescence-based assay.


Subject(s)
Enzyme Assays/methods , Enzyme Inhibitors/pharmacology , Ribonucleases/antagonists & inhibitors , Transcription Factors/antagonists & inhibitors , Exoribonucleases/metabolism , Fluorescence , HeLa Cells , Humans , Repressor Proteins , Ribonucleases/metabolism , Small Molecule Libraries , Transcription Factors/analysis , Transcription Factors/metabolism
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