Cross talk between genetics and biochemistry in the pathogenesis of hepatocellular carcinoma.

The liver is a crucial organ in the regulation of metabolism, signaling, and homeostasis. Using recent advanced sequencing technologies, several mutations of genes in major metabolic and signaling pathways have been discovered in the pathogenesis of hepatocellular carcinoma (HCC). These gene signatures alter expression and ultimately affect biochemical pathways by modifying enzyme/protein levels, resulting in numerous clinical outcomes related to HCC.

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection.

To investigate the effect of genetic variations in the angiotensin converting enzyme (ACE), interferon (IFNG) and tumor necrosis factor (TNF-α) genes on the severity of coronavirus disease (COVID-19). Between September and December 2021, 33 patients with COVID-19 were included in this prospective study. The patients were classified and compared according to disease severity: mild&moderate (n = 26) vs severe&critical (n = 7).

A Crosstalk Between Dual-Specific Phosphatases and Dual-Specific Protein Kinases Can Be A Potential Therapeutic Target for Anti-cancer Therapy.

While protein tyrosine kinases (PTKs) play an initiative role in growth factor-mediated cellular processes, protein tyrosine phosphatases (PTPs) negatively regulates these processes, acting as tumor suppressors. Besides selective tyrosine dephosphorylation of PTKs via PTPs may affect oncogenic pathways during carcinogenesis. The PTP family contains a group of dual-specificity phosphatases (DUSPs) that regulate the activity of Mitogen-activated protein kinases (MAPKs), which are key effectors in the control of cell growth, proliferation and survival.

Regulation and Effect of Telomerase and Telomeric Length in Stem Cells.

Telomeres are the protective end caps of eukaryotic chromosomes and they determine the proliferative lifespan of somatic cells, as the protectors of cell replication. Telomere length in leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a biomarker of human ageing.

HDAC Inhibition Overcomes Acute Resistance to MEK Inhibition in BRAF-Mutant Colorectal Cancer by Downregulation of c-FLIPL.

Purpose: Activating mutations in the BRAF oncogene are found in 8% to 15% of colorectal cancer patients and have been associated with poor survival. In contrast with BRAF-mutant (MT) melanoma, inhibition of the MAPK pathway is ineffective in the majority of BRAFMT colorectal cancer patients. Therefore, identification of novel therapies for BRAFMT colorectal cancer is urgently needed.

Four novel mutations in the β-galactosidase gene identified in infantile type of GM1 gangliosidosis.

Objectives: The aim of this study is to find out mutations of Turkish GM1 gangliosidosis patients and to make genotype-phenotype correlations.

Design And Methods: β-galactosidase activities were measured by using fluorometric substrate. Mutation screening of 16 exons of β-galactosidase gene and mutation detection were done by PCR-SSCP and DNA sequencing, respectively.

Two novel alpha-galactosidase A mutations causing Fabry disease: A missense mutation M11V in a heterozygote woman and a nonsense mutation R190X in a hemizygote man.

Objectives: To evaluate the nature of the molecular lesions in the alpha-galactosidase A gene of two patients having Fabry disease.

Methods: Enzyme analyses were done using 4-methylumbellyferyl alpha-galactoside as substrate. Single stranded conformational polymorphism analysis and DNA sequencing were performed following PCR amplification of seven exons of alpha-galactosidase A gene.

Methotrexate-induced apoptosis is enhanced by altered expression of methylenetetrahydrofolate reductase.

Folates are essential for DNA synthesis and methylation reactions. The antifolate methotrexate (MTX) is a widely used chemotherapeutic drug which inhibits DNA synthesis and induces apoptosis. Changes in activity of a critical folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), might alter the chemosensitivity to MTX, as the MTHFR substrate is required for nucleotide synthesis and its product is used in homocysteine remethylation to methionine.

Protective role of 27bp repeat polymorphism in intron 4 of eNOS gene in lacunar infarction.

Association of the three potential endothelial nitric oxide synthase gene (eNOS) polymorphisms (T-786C in promoter region, G894T in exon 7 and tandem 27-bp repeats in intron 4) with an increased risk of lacunar infarction (LI) were investigated. Genotypes of 70 patients and 81 healthy controls were determined through PCR with or without RFLP. Flow-mediated dilatation (FMD) was performed to assess endothelial-dependent vasodilatation, whereas the endothelial-independent vasodilatation was assessed with nitroglycerin (NTG).

Altered expression of methylenetetrahydrofolate reductase modifies response to methotrexate in mice.

Objective: Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism (677C-->T) in methylenetetrahydrofolate reductase (MTHFR) encodes an enzyme with reduced activity. Response to the antifolate methotrexate (MTX) may be modified in 677TT individuals because MTHFR converts nonmethylated folates, used for thymidine and purine synthesis, to 5-methyltetrahydrofolate, used in homocysteine remethylation to methionine.

Increased hexosaminidase activity in antipsychotic-induced extrapyramidal side effects: possible association with higher occurrence in bipolar disorder patients.

Dystonic movements and Parkinsonism are frequently seen in gangliosidoses and these conditions have been reported to modify dopaminergic plasticity. We investigated whether the activity of hexosaminidase, a type-two ganglioside (GM2) degrading enzyme, correlates with drug-induced extrapyramidal system (EPS) side effects in psychiatric patients. We compared hexosaminidase activity in the lymphocytes of 29 EPS-positive patients, 13 EPS-negative patients, and 30 healthy volunteers.