Immunometabolic disorders in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic autoimmune disease connected with complex and unclear disorders of the immune system, which causes inflammation of body tissues and internal organs. It leads to the formation of anti-nuclear antibodies (ANA) and immune complexes. Numerous immune system disorders and dysfunctions in the biochemical processes can occur in the course of the disease, and a wide range of abnormalities associated with cellular respiratory processes and mitochondrial function have been documented.

New tacrine-acridine hybrids as promising multifunctional drugs for potential treatment of Alzheimer's disease.

The synthesis, biological tests, and computer modeling of a series of novel promising tacrine hybrids for the therapy of Alzheimer's disease are reported. Firstly, new tacrine-acridine hybrids with different carbon linker lengths were synthesized. Secondly, all the compounds were tested in vitro for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzyme activity.

Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk.

Background: Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development.

Novel tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid moiety induce cell cycle arrest and apoptosis in lung cancer cells by activation of DNA damage signaling.

Lung cancer is still the leading cause of cancer-related death worldwide, indicating a necessity to develop more effective therapy. Acridine derivatives are potential anticancer agents due to their ability to intercalate DNA as well as inhibit enzymes involved in replication and transcription. Recently, we have evaluated anticancer activity of 32 novel acridine-based compounds.

The role of base excision repair in pathogenesis of breast cancer in the Polish population.

Breast cancer (BC) is leading type of cancer among group of women, which determines almost 23% of invasive cancers. It has been reported repeatedly that the level of oxidative stress is higher for BC in comparison to cancer-free woman. The goal of the present study was to evaluate the role of base excision repair (BER) pathway in the development of BC.

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population.

DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped.

The role of base excision repair in the development of primary open angle glaucoma in the Polish population.

Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients.

The role of the 148 Asp/Glu polymorphism of the APE1 gene in the development and progression of primary open angle glaucoma development in the Polish population.

Glaucoma is an ocular disorder that is characterized by progressive degeneration of the optic nerve and loss of visual field (VF). Recent data have suggested that the level of oxidative DNA damage in human trabecular meshwork is significantly increased in glaucomatous patients as compared to controls. It was also noted that progressive loss of visual field may by connected with elevated levels of oxidative DNA lesions.

Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma.

Background: Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This hypothesis may suggest an association of base excision repair with the risk of primary open angle glaucoma development.

Purpose: The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG.

Role of base-excision repair in the treatment of childhood acute lymphoblastic leukaemia with 6-mercaptopurine and high doses of methotrexate.

Methotrexate (MTX) and 6-mercaptopurine (6MP) are the most commonly used drugs in the therapy of childhood acute lymphoblastic leukaemia (ALL). The main genotoxic effect of MTX resulting from inhibition of thymidylate synthase is mis-incorporation of uracil into DNA, which is considered essential for the effectiveness of the Protocol M in ALL IC BFM 2002/EURO LB 2002 regimens. In this study, we investigated the level of basal and induced DNA damage as well as the effectiveness of DNA repair in lymphocytes of children with ALL at four time-points during therapy with MTX and 6MP.

The association of polymorphisms in DNA base excision repair genes XRCC1, OGG1 and MUTYH with the risk of childhood acute lymphoblastic leukemia.

The aim of this study was to evaluate the association of polymorphisms in genes encoding three key proteins of DNA base excision repair (BER): the OGG1 Ser326Cys, the MUTYH Tyr165Cys and the XRCC1 Arg399Gln with the risk of childhood acute lymphoblastic leukemia (ALL). Our study included 97 children patients with ALL (mean age 5.4±2.