The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma (HCC). The foremost objective of ...this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of HCC and to identify the computational bioinformatics frameworks of these missense variants. A total of 250 participants were enrolled in this study, including 150 HCC patients and 100 cancer‐free controls. The genomic DNA was characterized and genotyped by applying the PCR‐CTPP method. The frequency of the APEX1 (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12–2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42–0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (p > .05). Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC.
Regioselective alkylation of 2-thiouracils 1a-c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-{(2,2-Dimethyl-1,3-dioxolan-4-yl) ...methylthio}pyrimidin-4(1H)-ones 3a-c and 4-{(2,2-Dimethyl-1,3-dioxolan-4-yl)methylthio} pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a-c and 9a,b whose deprotection afforded 6a-c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a-c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a-c and 15a,b which were deprotected to give 13a-c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a-c were treated with two equivalents of 2 to give 2,4-bis{(2,2-dimethyl-1,3-dioxolan-4-yl)methylthio}pyrimidines 18a-c. Deprotection of compounds 18a-c gave 2,4-bis(2,3-dihydroxypropyl)thiopyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: According to GLOBOCAN estimates, breast cancer was found to be the most often diagnosed cancer in women worldwide, (11.7%) and the fourth leading cause of cancer mortality (6.9%). The ...present study was aimed to evaluate the involvement of oxidative stress on breast cancer carcinogenesis in Egyptian population.
Methods: Lipid peroxidation as evidenced by malondialdehyde (MDA) and nitric oxide (NO) stress as well as the status of the antioxidants superoxide dismutase (SOD) and total antioxidant capacity (TAC) were estimated in serum of 163 breast cancer patients. Correlations between oxidative/ antioxidant profile and different prognostic variables in BC patients were estimated.
Results: Lipid peroxidation in BC was enhanced in response to cancer stage and tumor size (p < 0.01). Similarly, NO was increase in response to NPI, Her2/neu and cancer stage (p < 0.02). Inversely in antioxidant, SOD was decrease in response to Her2/neu only (p < 0.002). While, TAC was increase in response to cancer stage and tumor size (p < 0.01). We found that oxidative/antioxidant status was dependent on NPI, Her2/neu, cancer stage and tumor size of BC patients.
Conclusion: Higher oxidative stress generation and lower SOD activity were found in our study, which supports the oxidative stress concept in breast carcinogenesis.
A series of peptide and dipeptide derivatives conjugated with an indole residue were synthesized. The prepared compounds were tested for antimicrobial activity against two different bacterial and one ...antifungal species displaying different degrees of antimicrobial activities or inhibitory actions.
Objective: Obesity has been described as a worldwide increasing health problem and risk factor of various disorders including type 2 diabetes mellitus (T2DM). So, our study aim to determine of common ...variants of fat mass and obesity associated gene polymorphisms rs1421085 and rs 9939609; confers risk of obesity and type 2 diabetic mellitus in Egyptian females.Methods: In this population rs1421085 and rs9939609 polymorphisms of fat mass and obesity (FTO) gene were genotyped in 105 obese patients and 100 healthy controls with ages 14-60 y were collected from Medicine Specialized Hospital, Mansoura University, Egypt during the period between Jul.-Oct. 2016, genotyping of SNPs was performed by restriction fragment length polymorphism (RFLP) assay, fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA IR), body mass index (BMI), waist-to-hip ratio (WHR) lipid profile was determined.Results: There was the significantly higher frequency of the AA compared to controls p=0.0001) of genotypers9939609. Also, cases have shown a significantly higher frequency of the C allele, p<0.00001) of rs1421085 genotype polymorphisms increased the risks of obesity. On the other hand, there were no significant correlations between genotypes and obesity-related (anthropometric body composition) parameters. Only the fasting blood glucose was significantly higher in the TA p=0.004).Conclusion: The FTO rs9939609 and rs1421085 single nucleotide polymorphisms (SNPs) was associated with increased risk of obesity in type 2 diabetic populations on Egyptian females.
Background: According to GLOBOCAN estimates, breast cancer was found to be the most often diagnosed cancer in women worldwide, (11.7 %) and the fourth leading cause of cancer mortality (6.9 %).
Aim: ...The purpose of this study is to investigate the role of the Angiotensin I-converting enzyme (ACE) gene polymorphism in breast cancer prediction risk in Egyptian population.
Methods: Polymorphism detection analysis was performed on 163 subjects from breast cancer (BC) patients, 79 with Benign Breast Disease group (BBD) patients and 202 controls (C). ACE I/D (rs1799752) polymorphism were detected using polymerase chain reaction (PCR).
Results: The observed genotype frequencies were II 10.9%, ID 78.2% and DD 10.9% in healthy control, II 8.6%, ID 79.1% and DD 12.3% in BC patients and II 12.6%, ID 78.4% and DD 9% in BBD patients. There were no association between ACE gene polymorphisms, between the BC or BBD groups when compared to the control group (ORDD= 1.43, 95 % CI= (0.58-3.52), P= 0.29) and (ORDD= 1.29, 95 % CI= (0.57-2.95), P= 0.37) respectively. There was no risk estimate in BC or BBD when DD vs II + ID (Recessive) or ID vs II+ DD (Over-dominant) were compared to control. Allele frequencies show the same figure. From the different histological BC hormonal markers the Her2 was showing significant association in ID genotype of ACE I/D (rs1799752) (P= 0.04) and dominant model (II vs ID + DD, P= 0.03). Concerning different BC prognostic models, the poor prognostic one of Her2 enriched model (ER-ve PR-ve Her2+ve) show significant association in ACE genotype ID and dominant model (II vs ID + DD), (P= 0.01) when compared to the good prognostic hormonal status.
Conclusion: It seems that this is the first study that interested in correlate the ACE gene polymorphisms in different BC variants characters in Egyptian patients. ACE I/D (rs1799752) polymorphism ID genotype have strong association to breast cancer carcinogenesis, poor prognosis and metastasis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.
Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl ...2,3-O-isopropylidene-5-O-p-toluenesulfonyl-
β
-D-ribofuranoside (2). The alkylation of 2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D-ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d. Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected compounds was studied.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Condensation of the silylated pyrimidines 5a-c with methyl 2-deoxy-3,5-di-O-toluoyl-D-pentofuranoside 6, using trimethylsilyltriflate as catalyst gave anomeric mixtures of 2′-deoxynucleosides 7a-c, ...the pure
α
- and
β
-anomers were separated and deprotected with sodium methoxide in methanol to give 1-(2′-deoxy-
α
-D- pentafuranosyl)-4-hydroxy-5-substituted-6(1H)-pyrimidinones 10a,b and 13a and their corresponding
β
-anomers 11a,b and 13b.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A series of peptide derivatives conjugated with N
1
-protected tryptophan residue was synthesized. The prepared compounds were tested for antimicrobial activity against four different bacterial ...species displaying different degrees of antibacterial activities or inhibitory actions.
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