In Congenital Disorder of Glycosylation (CDG) type Ia, homozygous mutations of the PMM2 gene cause phosphomannomutase 2 dysfunction.

Herein, a 10-month-old girl is presented with severe hypotonia along with inappropriately normal mental status and normal facies. High 2-ketoglutaric acid was detected in her urine; therefore the diagnosis of 2-Ketoglutarate dehydrogenase complex (KDHC) deficiency was made for this patient. High dose of vitamin B1 was administered, because thiamine is considered as a co-factor in this inborn error of metabolism. She responded very well to daily administration of 500 mg/day vitamin B1 and stood up without help 5 months later. She had experienced seizure, which responded well to pyridoxine. Now, she is a 3.5-years-old child, who could talk and walk normally. Recently, whole exome sequencing was performed for her, which showed homozygote mutation of PMM2; therefore the diagnosis was changed from KDHC deficiency to PMM2-CDG.

Attention to the pathophysiology of inborn errors of metabolism is necessary, while considering the defective enzymes co-factor may help us to find an option for treatment of such rare diseases.

Attention to the pathophysiology of inborn errors of metabolism is necessary, while considering the defective enzymes co-factor may help us to find an option for treatment of such rare diseases.

EGFR (Epidermal Growth Factor Receptor) and CDK2 (Cyclin Dependent Kinase 2) are important targets in the treatment of many solid tumors and different ligands of these receptors share many common structural features.

The study involved synthesis of benzamide-substituted chalcones and determination of their antiproliferative activity as well as preliminary evaluation of EGFR and CDK2 inhibitory potential using both receptor binding and computational methods.

We synthesized 13 benzamide-substituted chalcone derivatives and tested their antiproliferative activity against MCF-7, HT-29 and U373MG cell-lines using Sulforhodamine B Assay. Four compounds were examined for activity against EGFR and CDK2 kinase. The compounds were docked into both EGFR and CDK2 using Glide software. The stability of the interactions for most active compound was evaluated by Molecular Dynamics Simulation using Desmond software. Abivertinib manufacturer Molecular Docking studies on mutant EGFR (T790M, T790M/L858R, and T790M/C797S) were also carried out.

inhibition, the docking studies on mutants were performed and which indicate that the compounds bind to the mutant EGFR but the amino acid residues involved are similar to the wild-type EGFR and therefore, the selectivity seems to be limited.

These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.

These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.

Dysregulation of microRNAs (miRNAs) figures prominently in radio-sensitivity of non-small cell lung cancer (NSCLC). MiR-129-5p can block the development of a variety of tumors. However, whether miR-129-5p modulates radio-sensitivity of NSCLC cells remains unknown.

This study was aimed to explore the role and the underlying mechanism of miR-129-5p in the radiosensitivity of NSCLC.

Radio-resistant NSCLC cell lines (A549-R and H1299-R) were constructed using A549 and H1299 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to quantify miR-129-5p, SRY-box transcription factor 4 (SOX4) mRNA, and RUNX family transcription factor 1 (RUNX1) mRNA expression levels. Cell apoptosis and cell cycle were detected by flow cytometry. Cell counting kit-8 (CCK-8) assay and colony formation experiments were used to measure cell proliferation. γ-H2AX was examined by Western blot to confirm DNA injury. Dual-luciferase reporter experiments were applied to analyze the interactions among miR-129-5p, RUNX1, and SOX4.

In A549-R and H1299-R cells, compared with the wild type cell lines, miR-129-5p expression was remarkably reduced while SOX4 and RUNX1 expressions were increased. The transfection of miR-129-5p into NSCLC cell lines, markedly induced cell apoptosis, DNA injury, and cell cycle arrest, and inhibited cell proliferation and colony formation. RUNX1 and SOX4 were validated as target genes of miR-129-5p, and the restoration of RUNX1 or SOX4 could counteract the influence of miR-129-5p on A549-R cells.

MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.

MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.

Depression is a most common mental disorder. The symptoms of depression include loss of energy, changes in appetite, more or less sleep, anxiety, low concentration, uncertainty, restlessness, feelings of worthlessness, guilt, or despair, and thoughts of self-harm or suicide. In order to provide safe, efficient and cost-effective medication, the plants based principles in isolation or in combination with traditional antidepressants are attracting increasing attention for depression therapy.

The information regarding the present review and its contents such as collected from published literature materials in different international journals. We have used different search engines such as PubMed, Medline, ResearchGate Google Semantic Scholar and ScienceDirect. For this purpose, the data obtained were properly organized and suitably analyzed to include in this article.

Most of the phytomolecules isolated from the medicinal plants display antidepressant effect through the synaptic regulation of levels of neurf depression and other psychiatric disorders. The potential phytochemicals may be further optimized using in silico tools to develop better antidepressants and antisychotic agents in future.The quinolinic ring, present in several molecules, has a great diversity of biological activities. Therefore, this ring is in the structure composition of several candidates of drugs in preclinical and clinical studies, thus, it is necessary the grouping of these results to facilitate the design of new drugs. For this reason, some of the activities were selected for this review, such as antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic and antiviral. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we list the clinical studies of phases III and IV of antimalarial drugs containing the quinoline nucleus and phase III clinical studies of hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we show some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.