Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML

LKB1 is a significant tumor suppressor and epigenetic regulator playing a vital role in different types of cancers. SHMT1 and GLDC are two critical genes of the epigenetic pathway influenced by LKB1. As epigenetic is the major cause of AML pathogenesis, this study aimed at investigating LKB1, SHMT1, and GLDC gene expression levels in acute myeloid leukemia patients. The present study was conducted on LKB1, SHMT1, and GLDC gene expression levels in 60 de novo AML samples and 30 normal controls using real-time RT-PCR. The results showed that LKB1 and SHMT1 have respectively a significantly lower (P < 0.05) and higher (P < 0.05) expression level than that of normal controls. Furthermore, the correlation between LKB1 with SHMT1 and GLDC was significant and positive (P value: 0.015, r: 0.299). Positive findings confirm that metabolic pathways alongside the LKB1 association drive the epigenetic axis and its substrate production. Therefore, it can be concluded that the newly-discovered pathway in the pathogenesis of this disease provides new insights into the design of therapeutic targets.     

Corrective exercise for intrinsic foot muscles versus the extrinsic muscles to rehabilitate flat foot curving in adolescents: randomized-controlled trial

Sport Sciences for Health - Extrinsic and intrinsic foot muscles actively support the foot’s arches, particularly the medial longitudinal arch. Previous studies have focused on strengthening...     

The Cameriere,Haavikko, Demirjian,and Willems methods for the assessment of dental age in Croatian children

International Journal of Legal Medicine - This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental...     

Validation of the Italian,European, North German,Malaysian, and South African black formulas on Cameriere method using panoramic radiographs in Kenyan children

International Journal of Legal Medicine - This study aimed to validate the accuracy of five different formulas based on the Cameriere method for age estimation in Kenyan children. We analyzed...     

Chemokine CCR3 ligands-binding peptides derived from a random phage-epitope library

Eosinophils are major effectors cells implicated in a number of chronic inflammatory diseases in humans, particularly bronchial asthma and allergic rhinitis. The human chemokine receptor C-C receptor 3 (hCCR3) provides a mechanism for the recruitment of eosinophils into tissue and thus has recently become an attractive biological target for therapeutic intervention. In order to develop peptides antagonists of hCCR3-hCCL11 (human eotaxin) interactions, a random bacteriophage hexapeptide library was used to map structural features of hCCR3 by determining the epitopes of neutralizing anti-hCCR3 mAb 7B11. This mAb t is selective for hCCR3 and exhibit potent antagonist activity in receptor binding and functional assays. After three rounds of biopanning, four mAb7B11-binding peptides were identified from a 6-mer linear peptide library. The phage bearing the peptides showed specific binding to immobilized mAb 7B11 with over 94% of phages bound being competitively inhibited by free synthetic peptides. In FACScan analysis all selected phage peptides were able to strongly inhibit the binding of mAb 7B11 to hCCR3-transfected preB-300-19 murine cells. Furthermore, synthetic peptides of the corresponding phage epitopes were effective in blocking the antibody–hCCR3 interactions and to inhibit the binding of hCCL11 to hCCR3 transfectants. Chemically synthesized peptides CKGERF, FERKGK, SSMKVK and RHVSSQ, effectively competed for ¹²⁵I-hCCL11 binding to hCCR3 with IC₅₀ ranging from 3.5 to 9.7 μM. Calcium release and chemotaxis of hCCR3 transfectants or human eosinophils were inhibited by all peptides in a dose-dependent manner. Furthermore, they showed inhibitory effects on chemotaxis of human eosinophils induced by hCCL11, hCCL5, hCCL7, hCCL8, and hCCL24. Specificities of all selected peptides were assessed with hCXCR1, hCXCR2, hCXCR3, and hCCR5 receptors. Peptides CKGERF and FERKGK showed inhibitory effects on eosinophil chemotaxis in a murine model of mCCL11-induced peritoneal eosinophilia. The development of peptides inhibiting the interactions between hCCR3 and its chemokine ligands will facilitate the development of small peptides antagonists with the hope of ameliorating chronic inflammatory diseases in humans.     

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Exercise testing induces fatal thromboembolism from mechanical mitral valve

Thromboembolism is still one of the most important complications of prosthetic heart valves. Embolism to a major coronary branch is rare, but acute proximal occlusions can be fatal, even when the coronary arteries are otherwise normal and intervention is rapid. We report a fatal complication of an exercise test in a patient who had a St. Jude bileaflet mitral valve. After an exercise test, a 42-year-old woman with a mechanical prosthetic valve had a severe hemodynamic collapse with acute ST segment changes. Coronary angiography showed a totally occluded left main coronary artery with TIMI grade 0 to 1 flow. Rapid injection of contrast material and the passage of a floppy guidewire through the thrombus restored a TIMI grade 3 flow. Angiography showed no coronary atherosclerostic involvement. Despite successful coronary reperfusion, intra-aortic balloon counterpulsation, and intensive medication, the patient died. This case demonstrates that exercise testing should be applied with great caution in patients with prosthetic valves, and only after a careful evaluation of valve function. We recommend transesophageal echocardiography prior to exercise testing in these patients.