Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK.

Novel derivatives of the 2-(quinoline-4-carbonyl)hydrazide scaffold carrying the acrylamide moiety were synthesized and tested for their cytotoxic efficacy against the breast carcinoma MCF-7 cell line. The most active members 6a, 6b and 6h revealed significant antiproliferative action with an IC50 value of 3.39, 5.94 and 2.71 µM, respectively, which were more potent than the reference drug Dox (IC50 = 6.18 µM). Aiming to enlighten the antiproliferative activity, compounds 6a and 6h were examined for their inhibitory potential against EGFR kinase. The results demonstrated that compound 6h displayed potent inhibitory activity, as concluded from the IC50 value (IC50 = 0.22 µM) compared to the standard drug Lapatinib (IC50 value of 0.18 µM). Compound 6h was found to induce significant cellular cycle arrest at the G1 phase and provoke apoptosis. Besides, compound 6h triggered apoptosis via upregulating p53 and initiator caspase 9 by 7.4- and 8.7-fold, respectively, compared to DMSO controls.

Association of interleukin6 rs1800796 gene polymorphism and serum level with bladder cancer in Egyptian population.

BACKGROUND: Urinary bladder cancer (UBC)is a common tumor of the urinary tract. OBJECTIVES: To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. DESIGN AND METHODS: One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. RESULTS: The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. CONCLUSION: It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.

Association of PLCE1 (rs7922612) and COL4A3 (rs375290088) Genetic Variants with the Risk of Nephrotic Syndrome in Egyptian Pediatric Patients.

Nephrotic syndrome is one of the most prevalent pediatric kidney illnesses seen in pediatric nephrology clinics. Steroid resistance in children with nephrotic syndrome is a primary cause of renal failure and is characterized by nephrotic range proteinuria that does not respond to conventional steroid therapy. The current work was intended to investigate the possible role of the Phospholipase C epsilon 1 (rs7922612) and collagen4 alpha 3 (rs375290088) single nucleotide polymorphisms as risk factors for developing nephrotic syndrome among Egyptian children. The study was conducted on 100 children with nephrotic syndrome and 100 age- and sex-matched healthy individuals. Geno typing was performed by two methods of polymerase chain reaction for the analysis of PLCE1 (rs7922612) and COL4A3 (rs375290088) variants. We observed a higher percentage of the heterozygous and homozygous variant genotypes of PLCE1 (rs7922612) SNP in NS patients in comparison with the controls (P < 0.001 for both). The frequencies of the PLCE1 (rs7922612) variant showed a statistically significant elevated risk of NS using several genetic models, including the dominant (OR = 9.12), recessive (OR = 2.31), and allelic (OR = 1.62) models (P < 0.001 for each). In addition, the PLCE1 (rs7922612) genotypes and alleles frequencies did not differ significantly between SRNS compared to SSNS cases. Furthermore, there was no significant difference regarding COL4A3 (rs375290088) polymorphism, neither between the NS and control groups nor between SDNS and SRNS. PLCE1 (rs7922612) is considered an independent risk factor for nephrotic syndrome in Egyptian pediatrics.COL4A3 (rs375290088) polymorphism is not correlated to Egyptian NS patients.

Recent advances on quinoxalines as target-oriented chemotherapeutic anticancer agents through apoptosis.

The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target-oriented chemotherapeutics.

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients.

Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

N-allyl quinoxaline derivative exhibited potent and selective cytotoxicity through EGFR/VEGFR-mediated apoptosis: In vitro and in vivo studies.

The cytotoxic activity, EGFR/VEGFR2 target inhibition, apoptotic activity, RT-PCR gene expression, in vivo employing a solid-Ehrlich carcinoma model, and in silico investigations for highlighting the binding affinity of eight quinoxaline derivatives were tested for anticancer activities. The results showed that compound 8 (N-allyl quinoxaline) had potent cytotoxicity against A594 and MCF-7 cancer cells with IC50 values of 0.86 and 1.06 µM, respectively, with noncytotoxic activity against WISH and MCF-10A cells having IC50 values more than 100 µM. Furthermore, it strongly induced apoptotic cell death in A549 and MCF-7 cells by 43.13% and 34.07%, respectively, stopping the cell cycle at S and G1-phases. For the molecular target, the results showed that compound 8 had a promising EGFR inhibition activity with an IC50 value of 0.088 µM compared to Sorafenib (IC50 = 0.056 µM), and it had a promising VEGFR2 inhibition activity with an IC50 value of 0.108 µM compared to Sorafenib (IC50 = 0.049 µM). Treatment with compound 8 ameliorated biochemical and histochemical parameters near normal in the in vivo investigation, with a tumor inhibition ratio of 68.19% compared to 64.8% for 5-FU treatment. Finally, the molecular docking study demonstrated the binding affinity through binding energy and interactive binding mode inside the EGFR/VEGFR2 proteins. Potent EGFR and VEGFR2 inhibition of compound 8 suggests its potential for development as a selective anticancer drug.

The Potential Impact of MYH9 (rs3752462) and ELMO1 (rs741301) Genetic Variants on the Risk of Nephrotic Syndrome Incidence.

The kidney lost a lot of protein in the urine when you have nephrotic syndrome (NS). Clinical manifestations mostly common in NS include massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic nephrotic syndrome is currently classified into steroid-dependent (SDNS) and steroid-resistant (SRNS) based on the initial response to corticosteroid therapy at presentation. Several reports examined the association of the MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs741301 G > A) variant as risk factors for Nephrotic Syndrome. This study aimed to determine the potential effect of the MYH9 gene (rs3752462, C > T) and ELMO1 gene (rs741301) variant on the risk of (NS) among Egyptian Children. This study included two hundred participants involving 100 nephrotic syndrome (NS) cases and 100 healthy controls free from nephrotic syndrome (NS). The MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs G > A741301) variant were analyzed by ARMS-PCR technique. Nephrotic syndrome cases include 74% SRNS and 26% SDNS. Higher frequencies of the heterozygous carrier (CT) and homozygous variant (TT) genotypes of the MYH9 (rs3752462, C > T) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the MYH9 (rs3752462, C > T variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.85, p < 0.001), dominant (OR 3.97, p < 0.001) models, and the recessive model OR 5.94, p < 0.001). Higher frequencies of the heterozygous carrier (GA) and homozygous variant (AA) genotypes of ELMO1gene (rs G > A741301) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the ELMO1 (rs G > A741301) variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.15, p < 0.001), dominant models (OR 2.8, p < 0.001), and the recessive model (OR 4.17, p = 0.001). Both MYH9 and ELMO1 gene variants are significantly different in NS in comparison with the control group (p < 0.001). The MYH9 gene (rs3752462, C > T) and ELMO1gene (rs G > A741301) variants were considered independent risk factors for NS among Egyptian Children.

Association of CYP1A1 T3801C (rs4646903) variant with the susceptibility and progression of B-chronic lymphocytic Leukemia (B-CLL) in the Egyptian population.

BACKGROUND: The frequency of hematological malignancies is increasing universally, and over the last few decades, a significant increase in the incidence of B-chronic lymphocytic leukemia (B-CLL) has been observed. Many studies have revealed the involvement of genetic predisposition along with environmental exposure to genotoxic xenobiotics in the leukemogenesis process of B-CLL. CYP1A1 is a vital member of the cytochromes P450 (CYPs) superfamily, which is involved in pro-carcinogens activation into reactive intermediates during phase I xenobiotic biotransformation. AIM: This study aimed to determine the possible role of the CYP1A1*2A (T3801C, rs4646903) single nucleotide polymorphism (SNP) as a risk factor for developing B-CLL, as well as the impact of this SNP on the disease progression and the clinical outcome. PATIENTS AND METHODS: The study was conducted on 100 patients newly diagnosed with B-CLL, and 100 healthy individuals with matched ages and sex, served as the control group. CYP1A1 (T3801C) genotyping of all patient and control samples was performed using the PCR-based Restriction Fragment Length Polymorphism (RFLP-PCR) method. In addition, serum levels of both IL-6 and TNF-α were estimated by the ELISA technique. RESULTS: Higher frequencies of the heterozygous carrier (TC) and homozygous variant (CC) genotypes of the CYP1A1 (T3801C) variant were observed in B-CLL patients compared to the controls (P < 0.001 for both). The frequencies of the CYP1A1 (T3801C) variant indicated a significant elevated risk of B-CLL under various genetic models, including allelic (OR = 8.8, P < 0.001) and dominant (OR = 9.3, P < 0.001) models. In addition, the median IL-6 level was significantly higher in patients with (TC) and (CC) genotypes than in patients with (TT) genotype (P = 0.001 and P < 0.001, respectively). Also, the median TNF-α level was significantly higher in patients with (TC) and (CC) genotypes than in patients with (TT) genotype (P < 0.001 for both). CONCLUSION: Our results showed that the CYP1A1*2A (T3801C, rs4646903) SNP increases the susceptibility to B-CLL incidence and is associated with poor disease progression.

Down regulation of fatty acid synthase via inhibition of PI3K/AKT/mTOR in ovarian cancer cell line by novel organoselenium pseudopeptide.

Ovarian cancer (OC) is the 7th most common cancer in women world-wide and the 3rd most common female cancer. For the treatment of OC, there is no successful therapeutic. The medications that are currently available have significant side effects and a low therapeutic index. This work aimed to evaluate the anticancer activity of organoselenium pseudopeptide compound against OC cell lines. After treatment with 50 â€‹µM of compound 4 (CPD 4), the viability was determined. The anticancer activity was further investigated by different methods including cell cycle and apoptosis analysis, colony formation assay, zymography, comet assay and Western blot. In comparison to a positive control, compound 4 showed cytotoxicity toward A2780CP cells rather than A2780 and SKOV-3 â€‹cells. Compound 4 was more selective to OC cells rather than HSF cells. Moreover, Compound 4 was able to inhibit cell migration and proliferation. The anticancer effect of compound 4 was found to be partially via cell cycle arrest, overexpression of p27 â€‹cell cycle inhibitor and induction of apoptosis through DNA fragmentation and activated production of ROS. Compound 4 had a differential effect on the modulation of PI3K/AKT/mTOR signaling pathway in the OC treated cell lines, also inhibited lipogenesis process via downregulation of FASN expression. Conclusion: This work highlights the unique role of Compound 4 against OC via modulation of oxidative stress, inhibition of survival PI3K/AKT/mTOR pathway. Compound 4 was found to be a promising alternative therapy for the treatment of OC in this investigation.

PPARÉ£2, aldose reductase, and TCF7L2 gene polymorphisms: relation to diabetes mellitus.

Purpose: Diabetes mellitus (DM) is a growing global health concern. Genetic factors play a pivotal role in the development of diabetes. Therefore, the present work aimed to study the relation between peroxisome proliferator-activate receptors (PPARɣ2) (rs3856806), aldose reductase (AR) (rs759853), transcription factor 7 like 2 (TCF7L2) (rs7903146) gene polymorphism with diabetes in the Egyptian population. Methods: The study included 260 diabetics and 120 healthy subjects. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. Results: Regression analysis revealed that PPARɣ2 TT, TCF7L2 TT were suggested to be independent risk predictors for T1DM and TCF7L2 TC, CC genotype were suggested to be independent protective factors against T1DM development. On the other hand, PPARɣ2 TT, AR TT genotypes were suggested to be independent risk predictors for T2DM susceptibility, and PPARɣ2 CT genotypes were suggested to be independent protective factors against T2DM development. Conclusion: The present study revealed that PPARγ2 (rs3856806), TCF7L2 (rs7903146) and AR (rs759853) gene polymorphism may play an important role in the susceptibility of diabetes. Therefore, these polymorphisms may have a prognostic value for diabetes in the Egyptian population. Further work is required to confirm the role of these polymorphisms in diabetes.

Anticancer Activity of Extremely Effective Recombinant L-Asparaginase from Burkholderia pseudomallei.

L-asparaginase (E.C. 3.5.1.1) purified from bacterial cells is widely used in the food industry, as well as in the treatment of childhood acute lymphoblastic leukemia. In the present study, the Burkholderia pseudomallei L-asparaginase gene was cloned into the pGEX-2T DNA plasmid, expressed in E. coli BL21 (DE3) pLysS, and purified to homogeneity using Glutathione Sepharose chromatography with 7.26 purification fold and 16.01% recovery. The purified enzyme exhibited a molecular weight of ~33.6 kDa with SDS-PAGE and showed maximal activity at 50°C and pH 8.0. It retained 95.1, 89.6%, and 70.2% initial activity after 60 min at 30°C, 40°C, and 50°C, respectively. The enzyme reserved its activity at 30°C and 37°C up to 24 h. The enzyme had optimum pH of 8 and reserved 50% activity up to 24 h. The recombinant enzyme showed the highest substrate specificity towards L-asparaginase substrate, while no detectable specificity was observed for L-glutamine, urea, and acrylamide at 10 mM concentration. THP-1, a human leukemia cell line, displayed significant morphological alterations after being treated with recombinant L-asparaginase and the IC50 of the purified enzyme was recorded as 0.8 IU. Furthermore, the purified recombinant L-asparaginase improved cytotoxicity in liver cancer HepG2 and breast cancer MCF-7 cell lines, with IC50 values of 1.53 and 18 IU, respectively.

Biochemical studies of adiponectin gene polymorphism in patients with obesity in Egyptians.

BACKGROUND: Adiponectin gene polymorphisms have recently been reported to be associated with obesity. In Egypt, obesity has expanded especially with the changing nourishment propensities and the inexorably inactive ways of life, with almost 70 percent of the Egyptian populations being obese. AIM: To assess the relationship of the adiponectin gene (ADIPOQ) polymorphism in patients with Obesity in Egyptians. SUBJECTS AND METHODS: This study included 100 patients with obesity and 97 random controls. RESULTS: Adiponectin rs1501299 polymorphism showed significant difference cases with different obesity grades where the T/T genotype was relatively higher in higher classes of obesity (Class II and III; (66.7% and 55.6% respectively, p = 000), which determines the susceptibility to obesity. CONCLUSION: Adiponectin rs1501299 polymorphism might be a candidate gene, which determines the susceptibility to obesity. Larger studies are necessary to confirm these findings in various populations.

Diminished CCl4 -induced hepatocellular carcinoma, oxidative stress, and apoptosis by co-administration of curcumin or selenium in mice.

Hepatocellular carcinoma (HCC) is a lethal disease, and in HCC advanced stages, there is limited therapeutic efficacy. HCC results in a complication of fibrosis or cirrhosis. In this study, the protective effect of curcumin and selenium versus hepatocellular carcinoma caused by CCl4 in experimental animals was investigated. In all, 70 mice were divided into seven groups to study the effect of curcumin and selenium on CCl4 -induced hepatocellular carcinoma. After treatment time, different animal groups were sacrificed, serum and liver samples were collected and processed for assay of biochemical and molecular parameters. Our results showed that CCl4 administration induced various alterations such as significant elevation in the serum levels of ALT, AST, and hepatic contents of malondialdehyde (MDA), and depletion in the levels of antioxidant parameters. CCl4 induced apoptosis in the hepatic cells indicated by an increased level of p53, CD4, CD8, Bax, and Annexin V/PI in addition to significant decrease in the level of Bcl-2. Administration of curcumin and selenium restored this abnormal variation in these biochemical parameters to normal values. Our study addressed that curcumin or selenium may be helpful in the protection against liver damage induced by CCl4 . The hepatoprotective impact of curcumin or selenium might be mediated primarily by its potent antioxidant activity. PRACTICAL APPLICATIONS: Hepatocellular carcinoma (HCC) ranked third common cause of death, primary liver cancer. Exposure to CCl4 was found to induce significant hepatotoxicity, characterized by fibrosis, bile duct proliferation, cirrhosis, and reduced hepatic function The work was prepared to investigate the protecting capacity of curcumin, selenium alone, and in combination against HCC induced by CCl4 in the experimental animal model. This study proved the protective effect of curcumin and selenium, alone and in combination with each other, where curcumin showed multiple pharmacological activities, including anti-inflammation and antioxidant, and have an essential role in inhibiting the progression of HCC.

Association of GSTP1 p.Ile105Val (rs1695, c.313A > G) Variant with the Risk of Breast Carcinoma among Egyptian Women.

Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant with the elevated risk of multiple cancerous diseases involving breast carcinoma, but with inconclusive findings. The primary purpose of this study is to test the association of this essential variant with the risk of breast carcinoma among Egyptian females. This case-control study was conducted based on 200 participants involving 100 women diagnosed with breast carcinoma and 100 unrelated cancer-free controls from the same district. The genomic DNA for all participants was genotyped utilizing T-ARMS-PCR procedure. The frequencies of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant indicated a statistically significant with the elevated risk of breast carcinoma under various genetic models, including allelic (OR = 2.48, P-value < 0.001) and dominant (OR = 2.36, P-value = 0.003) models. In conclusion, the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant was considered as an independent risk factor for breast carcinoma among Egyptian women.

Evaluation of some oxidative markers in diabetes and diabetic retinopathy.

AIMS: Diabetes mellitus and diabetic retinopathy (DR) are major public health concerns globally. Oxidative stress plays a central role in the pathogenesis of diabetes and DR. The aim of this study was to investigate the association of malondialdehyde, uric acid and bilirubin with diabetes and diabetic retinopathy development. METHODS: This study was conducted on 110 diabetics (with and without retinopathy). Beside 40 healthy individuals as a control group. The level of three markers (malondialdehyde, uric acid and bilirubin) was estimated in the studied groups. Receiver operating characteristic analysis and a logistic regression model was performed. RESULTS: The present study revealed significantly higher uric acid and malondialdehyde levels, while bilirubin showed significantly lower levels in diabetics compared to control and similarly in diabetic retinopathy compared to those without DR. Furthermore, combination of the three markers increased the accuracy and effect size for differentiation between diabetes with and without DR. In addition, higher levels of uric acid and malondialdehyde were associated with risk of diabetes and DR development. CONCLUSION: This study concluded that higher levels of uric acid and malondialdehyde were associated with increase in the risk of diabetes and DR development, while bilirubin wasn't associated with decreasing the risk of diabetes or DR. However, the combination of malondialdehyde, uric acid and bilirubin may be a valuable addition to the current options for the prognosis of DR. In addition, malondialdehyde may be independent predictor of diabetes and DR as well as uric acid may be used as independent biomarker to predict the risk of DR.

Anticancer activity of new cationic arylthiophenes against hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer-related death in the world. No effective curative option exists for the treatment of HCC. The available drugs exhibit severe toxic effects and low therapeutic index. AIM: This work aimed to examine different monocationic arylthiophene derivatives for possible use as chemotherapeutic agents against HCC. METHODS: The IC50 values for the compounds were determined. The mechanism of cytotoxicity was further investigated using different methods. RESULTS: Compound 2j proved to retain the highest cytotoxicity in comparison to as a positive control. The selectivity index of compound 2j revealed the safety to normal cells. Moreover, compound 2j was able to inhibit HepG2 cells´ migration and division. The anticancer effect of compound 2j was found to be partially via cell cycle arrest, activation of the tumour suppressor p53 protein, and induction of apoptosis via both intrinsic and extrinsic pathways. Compound 2j has a potential sensitization activity and significantly reduced the IC50 values for the anticancer drugs doxorubicin, cisplatin, and taxol. CONCLUSION: The tested arylthiophenes showed a potent cytotoxicity against HepG2 cells and were safe to normal cells. The most active compound 2j was found to be able to inhibit cell division and migration and also to induce apoptosis. Compound 2j also proved to have a sensitization effect on standard anticancer drugs.

Association of transcription factor 7-like 2 (rs7903146) gene polymorphism with diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common diabetic complications. Genetic factors play an important role in the development and progression of DR. So, the present study aimed to investigate the association of TCF7L2 (rs7903146) gene polymorphism with the risk of DR in type1 and type2 DM (T1DM and T2DM) in the Egyptian population. MATERIALS AND METHODS: This work is a case-control study in which 550 diabetic patients were enrolled. Among them, 280 diabetics with DR (120 T1DM and 160 with T2DM) and 270 diabetic patients without DR (120 T1DM and 150 with T2DM). Besides, 120 healthy subjects as a control group. Genotyping of TCF7L2 (rs7903146) (C/T) was done following DNA extraction using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: C allele and CC genotype of TCF7L2 (rs7903146) were significantly associated with increased risk for DR within T2DM in multiplicative and recessive models. While dominant model showed no significant association with DR. Although TC may be associated with a decreased risk for DR in T1DM and T2DM in over dominant model, there was no significant association of TCF7L2 (rs7903146) with the risk of DR susceptibility within T1DM in multiplicative, dominant, and recessive models. CONCLUSION: The present study revealed the association of TCF7L2 (rs7903146) polymorphism with DR susceptibility within diabetic patients. Therefore, TCF7L2 (rs7903146) gene polymorphism may have a prognostic value for diabetic retinopathy in the Egyptian population. Further work is required to confirm the association of this polymorphism as a risk for DR.

Oxidative stress in CLL patients leads to activation of Th9 cells: an experimental and comprehensive survey.

Older adults are mostly affected by chronic lymphocytic leukemia (CLL). The present study aimed to evaluate oxidative stress in CLL and to assess its impact on IL-9, Th9 cells levels and prognosis of cases. Seventy Egyptian CLL patients and 15 healthy controls were included. Th9 cell and immunophenotyping of abnormal B cells were assessed by flow cytometry, IL-9 level using ELISA, IL-9 mRNA by qRT-PCR, cytogenetics using FISH, and oxidative stress parameters were determined spectrophotometrically and with native gel electrophoresis. Oxidative stress was elevated in CLL that correlated with abnormal immunophenotyping, cytogenetic changes, bad prognosis, Th9 cells, and overexpression of IL-9. Levels of IL-9 and Th9 cells were strongly correlated with oxidative stress and bad prognostic markers in CLL, indicating that these cells may contribute to CLL by novel mechanisms that could include oxidant injury.

An Approach to Treatment of Liver Cancer by Novel Glycyrrhizin Derivative.

BACKGROUND: Liver cancer is a life threating disease as it is the fifth most common cancer and the third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment. METHODS: This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 µM of each compound, cell viability was determined. RESULTS: The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18ß-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-ß-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 µM, respectively. Both the compounds showed higher selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA which might be attributed to its higher activity and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation. CONCLUSION: This work highlights the cytotoxicity of glycyrrhizin and its derivatives for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18ß-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer.

Synthesis and Biological Evaluation of Bisthiazoles and Polythiazoles.

Small heterocyclic compounds containing nitrogen and sulfur atoms, such as thiazole derivatives, represent a significant class of organic azoles that exhibit promising bioactivities and have a great potential in medicinal and agricultural fields. A convenient and high-yielding synthetic approach for a range of organic molecules is presented. The nuclease-like activities of compounds were studied with the aid of E. coli AB1157 DNA and agarose gel electrophoresis. The antioxidant evaluation of the compounds was carried out with different antioxidant techniques, such as ABTS and NO scavenging efficiency. The antibacterial behavior was evaluated against various bacterial strains, both Gram-positive and -negative, and the minimum inhibitory concentration (MIC) values of these compounds were determined. The antiproliferative activities and IC50 values of the synthesized organic molecules compounds against HEPG-2, MCF-7, and HCT-116 cell lines were evaluated.