Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased (p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1ß, IL-6, and IL-17 cytokines were significantly increased (p < 0.001), while IL-8 and TNF-α were significantly decreased (p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1ß, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

mir-146a genetic polymorphisms in systemic lupus erythematosus patients: Correlation with disease manifestations.

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy-Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78-6.57 and OR: 2.35; CI: 0.79-6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease.

The Mechanical Autophagy as a Part of Cellular Immunity; Facts and Features in Treating the Medical Disorders.

Autophagy is a cellular housekeeping process that incorporates lysosomal-degradation to maintain cell survival and energy sources. In recent decades, the role of autophagy has implicated in the initiation and development of many diseases that affect humanity. Among these diseases are autoimmune diseases and neurodegenerative diseases, which connected with the lacking autophagy. Other diseases are connected with the increasing levels of autophagy such as cancers and infectious diseases. Therefore, controlling autophagy with sufficient regulators could represent an effective strategy to overcome such diseases. Interestingly, targeting autophagy can also provide a sufficient method to combat the current epidemic caused by the ongoing coronavirus. In this review, we aim to highlight the physiological function of the autophagic process to understand the circumstances surrounding its role in the cellular immunity associated with the development of human diseases.

Schiff base 4-ethyl-1-(pyridin-2-yl) thiosemicarbazide up-regulates the antioxidant status and inhibits the progression of Ehrlich solid tumor in mice.

Cisplatin is an approved cancer therapeutic drug used to treat many solid tumors but its accumulation in the kidney, which causes nephrotoxicity, limits its clinical use. Therefore, investigators seek new alternatives to cisplatin that may be more effective and/or safer. Thiosemicarbazides are of great significance due to their expected biological activity including anticancer activities. The aim of this work is the study of the antitumor effect of Schiff base 4-ethyl-1-(pyridin-2-yl) thiosemicarbazide (HEPTS) on Ehrlich solid tumor-bearing mice in comparison to cancer therapeutic drug cisplatin. The experiment was run using sixty adult female Swiss albino mice. Mice were allocated into six groups (n = 10 mice). Healthy control, EAC control (untreated tumor), EAC + cisplatin, EAC + HEPTS, Healthy + HEPTS, and Healthy + solvent. After scarification, blood samples, liver organs, and solid tumors were collected. Tumor weights and volumes were registered. The concentrations of malondialdehyde (MDA), reduced glutathione (GSH), SOD, catalase (CAT), total antioxidant capacity (TAC), nitric oxide (NO), uric acid, creatinine, and urea were assessed. Median survival time (MST) and the percentage increase in lifespan (%ILS) were also calculated. Treatment of tumorized mice with HEPTS significantly reduced both tumor volume and weight while it significantly increased the MST, antioxidant marks and prolonged the %ILS. It also, significantly reduced MAD, creatinine, urea, uric acid, and NO levels. Compared to cisplatin, HEPTS effects were better. Our results recommend HEPTS as one of the probable cisplatin-alternatives for tumor treatment after more validation.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV / Associação entre polimorfismo do gene da interleucina-6 e regulação do ferro em pacientes em hemodiálise infectados pelo HCV

ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

RESUMO Introdução: A hepcidina está associada à patogênese da anemia por insuficiência renal crônica, considerada um estado inflamatório crônico e também infecção por HCV. A IL-6 estimula a liberação de hepcidina a partir do fígado, suprime a captação intestinal de ferro e libera ferro das reservas internas. Método: Para detectar a associação entre o polimorfismo do gene IL-6 e os marcadores de anemia, 80 pacientes em hemodiálise (HD) [40 pacientes em HD, negativos para HCV; e 40 em HD, positivos para HCV] foram avaliados por exames químicos de rotina e hemograma completo, além da avaliação da hepcidina sérica, parâmetros do ferro [ferro sérico e ferritina sérica] e marcadores de hepatite C. O polimorfismo da IL-6 -174G/C foi determinado por MS-PCR, enquanto os polimorfismos de IL-6 -597G/A e -572 G/C foram detectados por PCR-SSP. Resultados: A hepcidina não esteve significativamente elevada em pacientes com HCV em comparação com pacientes em hemodiálise negativos para HCV. Uma diferença estatisticamente significativa foi detectada entre os pacientes em HD HCV negativos comparados aos positivos nas frequências de IL-6 -174 G/C e -597 G/A (P≤ 0,01 e P≤ 0,001, respectivamente). Por outro lado, foi relatada uma diferença não significativa entre pacientes em HD HCV negativos e positivos nas frequências de IL-6 -572 G/C. Conclusões: Nosso estudo indicou que os polimorfismos de IL-6 -174 G/C e -597 G/A podem desempenhar um papel na suscetibilidade ao HCV em pacientes em HD. Ainda necessitamos de estudos prospectivos adicionais em uma população maior para confirmar nossos achados.

EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV.

BACKGROUNDS: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. METHOD: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. RESULTS: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. CONCLUSIONS: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

Lack of Any Relationship Between Circulating Autoantibodies and Interleukin­6 Levels in Egyptian Patients Infected with the Hepatitis C Virus

Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

Adipocytokines in Patients with Chronic Kidney Disease Stage 5.

BACKGROUND: Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD). METHODS: 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR). RESULTS: Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients. CONCLUSIONS: The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.

Amelioration of adriamycin-induced cardiotoxicity by Salsola kali aqueous extract is mediated by lowering oxidative stress.

OBJECTIVES: To assess the cardioprotective effect of the Salsola kali aqueous extract against adriamycin (ADR)-induced cardiotoxicity in male Swiss albino mice. METHODS: The aqueous extract of S. kali was phytochemically screened by traditional methods for different classes and further evaluated for antioxidant activity in vitro. In vivo, cardioprotective evaluation of the extract was designed to have four groups of mice: (1) control group (distilled water, orally; normal saline, intraperitoneally (i.p.)); (2) ADR group (15 mg/kg, i.p.); (3) aqueous S. kali extract (200 mg/kg, orally); and (4) ADR + S. kali group. ADR (5 mg/kg) was injected three times over 2 weeks while S. kali was orally administered daily for 3 weeks (1 week before and 2 weeks during ADR treatment). Cardioprotective properties were assessed using biochemical and histopathological approaches. RESULTS: ADR caused a significant increase in serum enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase). Myocardial levels of malondialdehyde, nitric oxide, and reduced glutathione, as well as the activities of superoxide dismutase and catalase increased while the activities of glutathione peroxidase and glutathione S-transferase declined. Histopathological examination of heart sections revealed that ADR caused myofibrils loss, necrosis and cytoplasmic vacuolization. DISCUSSION: Pretreatment with S. kali aqueous extract normalized serum and antioxidant enzymes minimized lipid peroxidation and cardiac damage. These results have suggested that the extract has antioxidant activity, indicating that the mechanism of cardioprotection during ADR treatment is mediated by lowering oxidative stress.

Pattern of matrix metalloproteinases-9, P53 and BCL-2 proteins in Egyptian patients with pulmonary Mycobacterium tuberculosis.

Matrix metalloproteinases (MMPs) constitute a large family of enzymes that degrade extracellular matrix proteins (ECM). MMPs are implicated in different pathological conditions such as cancer. Bcl-2 and P53 are key controllers of programmed cell death (PCD) or apoptosis. The aim of the present study was to determine the MMP-9, P53 and Bcl-2 levels in Egyptian patients with Mycobacterium tuberculosis (MTB) (Group I) compared with healthy control individuals (Group II). The concentrations of serum MMP-9 were determined quantitatively using enzyme immunoassay (EIA). P53 and Bcl-2 levels were assayed by flow cytometric analysis using specific monoclones. MMP-9 level was significantly higher in MTB patients compared with healthy control. Similarly, P53 and Bcl-2 levels were increased in MTB patients compared with healthy ones. These data reflect the alteration of MMP-9 level during the course of MTB infection, accompanied with apparent dysregulation of cellular apoptosis as indicated by P53 and Bcl-2 over-expression.

Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: association with cigarette smoking.

OBJECTIVES: To evaluate sperm chromatin and DNA integrities in idiopathic infertile men and determine the possible association(s) of cigarette smoking on oxidative stress markers, antioxidant capacity and semen quality. SUBJECTS AND METHODS: Semen samples from men referring to the andrology laboratory were categorized into 3 groups: fertile non-smokers (n=16), infertile non-smokers (n=36), and infertile smokers (n=34). Semen analysis was performed according to WHO criteria. The percentage of sperm DNA fragmentation index (%DFI) and the percentage of sperm with abnormally high DNA stainability (HDS%; immature spermatozoa) were determined by SCSA using the metachromatic properties of acridine orange. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in seminal plasma and spermatozoa were measured by spectrophotometric assays. RESULTS: The classical semen parameters were negatively correlated with lipid peroxidation in spermatozoa; motility and morphology were negatively correlated with %DFI (p<0.05). HDS% was also negatively correlated with above markers except for morphology (r=-0.352, p=0.081). DFI% and HDS% were significantly higher in the infertile smokers group than in infertile non-smokers (p=0.032; p=0.001 respectively). Cigarette smoking was significantly associated with DFI%, HDS%, TBARS and the fraction of "round-headed" sperm (r=0.796, p=0.0001; r=0.371, p=0.033; r=0.606, r=0.591, p=0.001 respectively), and decreased SOD levels (r=-0.545). CONCLUSION: DFI%, HDS% and round-head sperms are increased in idiopathic infertile men; this increase is associated with cigarette smoking. These defects may be attributed to increased oxidative stress and insufficient scavenging antioxidant enzymes in the seminal fluid of infertile patients.

Tumor necrosis factor-alpha and oxidant status are essential participating factors in unexplained recurrent spontaneous abortions.

BACKGROUND: Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The current study was conducted to determine the possible role of antioxidant status and tumor necrosis factor-alpha (TNF-alpha) in URSA. METHODS: Reduced glutathione (GSH), glutathione reductase (GSH-R), glutathione peroxidase (GSH-PX), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA) and TNF-alpha were assayed in women suffering unexplained first-trimester abortions. Two groups were included, the first represented by 24 women with URSA (number of abortions 3-5) and the second included 16 women with URSA (number of abortions >5). The control group included 20 women within their first trimester of pregnancy and 20 non-pregnant healthy females within their follicular phase. RESULTS: We observed that the antioxidant levels measured were significantly lower in URSA groups than in the control group (p<0.05 for each comparison). Higher TNF-alpha, MDA and NO production were detected in URSA groups compared to controls (p<0.05 for each comparison). URSA 3-5 was associated with significantly higher levels of antioxidants and lower levels of TNF-alpha compared to levels in URSA >5. CONCLUSIONS: Impaired antioxidant defense and an increase in oxidative reactive species may be responsible for recurrent abortion due to possible damage produced by their generation. In addition, the level of TNF-alpha apparently contributes to the pathogenesis of URSA.

Utility of slot-blot-ELISA as a new, fast, and sensitive immunoassay for detection of carcinoembryonic antigen in the urine samples of patients with various gastrointestinal malignancies.

Carcinoembryonic antigen (CEA) is the most widely used clinical tumor marker. CEA immunoassay has found acceptance as a diagnostic adjunct in clinical diagnosis of gastrointestinal tumors (GIT). Several immunoassays have been established for detection of CEA in plasma, serum, tissue, feces, and urine of cancer patients using polyclonal or monoclonal antibodies raised against CEA. Some of these assays display both high sensitivity and specificity for the detection of CEA. However, these assays require special and highly expensive equipment and the procedures require long periods for their completion. In the present study, we established a Slot-Blot Enzyme Linked Immunosorbent Assay (SB-ELISA), based on anti-CEA monoclonal antibody (CEA-mAb), as a new, simple, fast, cheap, and non-invasive immunodiagnostic technique for detection of CEA in the urine of GIT patients. Urine and serum samples were collected from 248 GIT patients (58 with pancreatic cancer, 20 with hepatoma, 23 with ampullary carcinoma, 15 with hilar cholangiocarcinoma, 28 with gastric cancer, 14 with esophageal cancer, and 90 with colorectal cancer). Moreover, urine and serum samples were collected from 50 healthy individuals to serve as negative controls. The traditional ELISA technique was used for determination of CEA in the sera of GIT patients using anti-CEA monoclonal antibody. A comparison between the results of both techniques (ELISA and SB-ELISA) was carried out. The traditional ELISA detected CEA in the sera of 154 out of 248 GIT patients with a sensitivity of 59.8%, 51.7% positive predictive value (PPV) and 75.37% negative predictive value (NPV). In addition, it identified 15 false positive cases out of 50 healthy individuals with a specificity of 70%. The urinary CEA was identified by a Western blotting technique and CEA-mAb at a molecular mass of 180 Kda. The developed SB-ELISA showed higher sensitivity, specificity, PPV, and NPV (70.1%, 78%, 62.4%, and 82.13%, respectively) for detection of CEA in the urine of GIT patients. The semi-quantitative SB-ELISA showed a higher overall efficiency of 72.8% versus 63.4% in the case of the quantitative ELISA, for detection of CEA. In conclusion, SB-ELISA is more efficient for detection of CEA in gastrointestinal tumors. It is a simple, rapid, non-invasive, and sensitive assay. Moreover, all steps of the SB-ELISA are performed at room temperature, without the use of expensive equipment; this may enhance the application of this assay in field studies and mass screening programs.

Prominent free radicals scavenging activity of tannic acid in lead-induced oxidative stress in experimental mice.

Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues leading to biochemical and physiological dysfunction. The present study was designed to investigate the effect of tannic acid on some biochemical parameters in Swiss albino mice exposed to lead acetate. The levels of thiobarbaturic acid-reactive substances (TBARS) as an index of lipid peroxidation, nitric oxide (NO), and serum lead (Pb) were significantly increased following intragastric administration of 50 micromole lead acetate/kg body weight three times a week, every other day for three weeks, compared to the corresponding control values. On the other hand, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione content (GSH) and serum copper (Cu) and zinc (Zn) were significantly diminished relative to the control values. The administration of 20 mg tannic acid/kg body weight three times a week every other day for three weeks, enhanced the endogenous antioxidant capacity of the cells by increasing the activities of antioxidant enzymes (SOD, CAT, GSH-R, GST), GSH content and serum Cu and Zn levels. Compared to the lead acetate-exposed group, the levels of TBARS, NO and Pb were decreased in the lead acetate exposed group treated with tannic acid. These results afford evidence supporting the hypothesis that lead induces oxidative stress in hepatic cells. Moreover, tannic acid has a potential in sustaining global antioxidant effect in hepatic cells leading to decreased oxidative stress and cellular damage initiated through free radical production by lead acetate.

Implications of CEA and p53 overexpression in the poor prognosis of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent and aggressive types of cancer. Several clinicopathologic features have been studied to identify the prognostic factors that can provide information concerning the favorable or the poor outcome of colorectal cancer. In the present study, the relationship between serum CEA, p53 expression, and DNA index to the different clinicopathological characteristics of colorectal cancer patients was sought. Fifty patients with CRC were included in this study. p53 protein was detected immunohistochemically using specific monoclonal antibodies. Samples were investigated for DNA index using flow cytometry. In addition, the serum CEA was determined using ELISA. The results showed that 27/50 (54%) were positive for p53. Concerning CEA reactivity, it was found that 35/50 (70%) were reactive for CEA. These results indicate that CEA is more sensitive than p53 to detect colorectal cancer. There was a statistically significant difference between the recurrent and nonrecurrent groups in the CRC Duke's stages, survival time, serum CEA (p = 0.001, 0.016, < 0.001, respectively). Kaplan-Meier method and log-rank test showed that the mean survival time for cases positive for both p53 and CEA is significantly different from cases positive for CEA only, positive for p53 only, and negative for both p53 and CEA (p = 0.0002). Survival time was statistically significant with respect to sex, p53, CEA, and Duke's stages (p = 0.006, 0.024, 0.001, 0.017, respectively). Cox regression model showed that the prognosis of colorectal cancer is influenced by sex, p53, CEA reactivity, and CRC Duke's stages (p = 0.014, 0.006, 0.019, 0.014, respectively). In conclusion, the use of more than one tumor marker may successfully aid in the prediction of colorectal cancer prognosis.

The effect of endoscopic retrograde cholangiopancreatography on the serum IL-18 and erythrocytes antioxidative capacity in biliary obstructive jaundice.

INTRODUCTION: Obstructive jaundice is an important clinical problem. It may cause transient hemolysis and shortened erythrocyte life span as well as cytokine induction. An increase in lipid peroxidation has been noted as evidence of oxidative damage in red cells due to cholestasis. The influence of endoscopic retrograde cholangiopancreatography (ERCP), mechanical lithotrepsy and stone extraction on the antioxidative capacity of the erythrocyte and immune response is still unclear. METHODS: Superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) content of red blood cells (RBC), and serum interleukin (IL-18) were measured in 20 patients with calcular obstructive jaundice before and 4 weeks after ERCP intervention and compared with 10 matched healthy volunteers. RESULTS: A significant decrease (p<0.05) in SOD and CAT activities and glutathione concentration but a significant increase (p<0.05) in serum IL-18 were observed in cholestatic patients compared with the healthy control and were significantly correlated with variable of hepatic dysfunction (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT). After ERCP, serum IL-18 and antioxidant capacity of red blood cells were significantly improved and returned to normal concentration (p<0.05). CONCLUSIONS: In biliary obstruction, serum IL-18 is increased and antioxidative capacity is decreased, and have a direct correlation with biochemical markers of liver injury. After ERCP intervention, the altered antioxidative capacity as well as serum IL-18 was completely restored to normal.

Inhibition of photohemolysis induced by m-chloroperbenzoic acid by metal complexes with SOD-mimetic activity.

Red blood cells (RBCs) are probably the most common target through the damaging action of reactive oxygen species on the cells. The photohemolysis activity of m-chloroperbenzoic acid (CPBA) was concentration- and exposure time-dependent. Twenty minutes photo exposure time and 200 microm of CPBA concentration were optimum to study the effect of generated superoxide (O2-) and hydroxyl (*OH) radicals on RBCs. RBCs lysis photosensitized by CPBA was investigated in the presence of [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl42H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O respectively, where L is 2-methylaminopyridine, with SOD-mimetic activities with the aim of ascertaining their protective activity towards the photo induced cell damage. The decrease of photolytic activity caused by these complexes was concentration-dependent and the maximum percentage of protective activity was 75, 70, 68, 57 or 24% for [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl4 2H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O complex respectively, against the cell irradiated without addition of metal complexes. The comparison between the decrease of photolytic activity caused by these complexes and their SOD-mimetic activity of these metal complexes showed an appreciable correlation.

DNA strand scission by Fe(III) 2-methylaminopyridine complex and hydrogen peroxide.

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects and also in the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in these processes. The conversion of the closed circular double-stranded supercoiled plasmid pcDNA3 into the nicked circular and linear forms was used to investigate DNA nicking induced by the reactions of an iron complex of 2-methylaminopyridine (L), which exhibited a pronounced superoxide dismutase-mimetic activity and antitumour activity with H2O2. Hence the dose-response curve for the [FeL2Cl2]Cl.H2O-mediated H2O2-dependent DNA nicking was studied. For a fixed concentration of [FeL2Cl2]Cl.H2O (25 microM), the concentration of H2O2 producing a maximum extent of DNA nicking was 100 microM. The effects of these two constituents are synergistic. The biological antioxidants such as glycerol, sodium azide and superoxide dismutase significantly inhibited DNA breakage induced by [FeL2Cl2]Cl.H2O and hydrogen peroxide.

2-Methylaminopyridine-copper (II) complex catalyzes protein degradation.

To investigate the mechanism of scission of proteins by the chemical cleaving agents like metal complexes, bovine serum albumin (BSA) has been treated by the copper(II) complex CuL2SO4, where L is 2-methylaminopyridine. BSA degradation increased with increasing the concentration of the copper complex. Copper complex rapidly degraded BSA at mild acidic and neutral pH values while no degradation occurred at alkaline pH values. Moreover, the degradation was increased at higher temperatures. Copper complex act as a catalyst for the polypeptide hydrolysis. The protein degradation was protected with beta-mercaptoethanol by acting as radical scavenger. H2O2 increased BSA degradation which is apparent by the disappearance of the original band. H2O2 reacts with copper complex to produce a reactive oxygen species (ROS), such as hydroxyl radical or a metal-coordinated oxo or peroxo species, which in turn can initiate cleavage of the peptide backbone nearby.