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DN is recognized as not only a leading cause of end stage renal disease (ESRD) but also an independent risk factor for cardiovascular disease (CVD). Novel therapeutic approaches to diabetic nephropathy (DN) are needed, or else, healthcare resources will be overwhelmed by the expected worldwide increase in associated cases of ESRD and CVD. Reactive oxygen species (ROS) and advanced glycation end product (AGE) are implicated in the development of DN. Hydrogen sulfide (H2S) is known for its antioxidant and antiapoptotic characteristics. Simultaneously diabetics have lower H2S levels. Thus, it is worth investigating the use of H2S in treatment of DN. To investigate the potential therapeutic role of H2S in DN. Sixty male rats were divided into four groups: control, DN, DN+NaHS30 µmol/kg/day and DN+NaHS100 µmol/kg/day. Fasting blood sugar (FBS), kidney function tests, SIRT1 activity, superoxide dismutase activity (SOD), malondialdehyde (MDA) and expression of caspase3 and p53 in renal tissues were assessed. Kidney was examined histopathologically. DN rats had higher FBS, renal dysfunction, decreased SIRT1 and SOD activity levels, increased caspase3 and p53 relative expression and increased MDA in renal tissues. NaHS increased SIRT1 and reversed biochemical, apoptotic, oxidant and pathologic parameters characteristic of DN, with better results using a dose of 100 µmol/kg/day. H2S has a protective role against DN through decreasing FBS, ROS, apoptosis and upregulating SIRT1, thus preserving renal cells from further damage caused by DM.

Summary Background: The aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer. Methods: This case control study was done on 88 breast cancer patients, 40 with fibroadenoma and 80 healthy subjects. Genotyping of the LAPTM4B polymorphism was determined by PCR. Serum LAPTM4B level was measured using ELISA. Results: There was a significant difference in the (*1/2+ *2/2) genotypes in breast cancer patients (59.1) compared to the control subjects (43.8%) (P=0.047; OR=1.86; 95% CI=1.01–3.43). The frequency of the allele 2* of the LAPTM4B gene was significantly higher in breast cancer patients (36.4%) than in the control (25.6%) (p=0.034; OR=1.66; 95% CI=1.04–2.65). Genotypes (*1/2+*2/2) were significantly associated with the differential classification of TNM. Serum level of LAPTM4B was significantly higher in breast cancer patients than in control and fibroadenoma and in fibroadenoma patients than in control. In breast cancer patients, serum LAPTM4B was significantly higher in stage III and in large tumor size. Serum LAPTM4B was significantly higher in the cancer patients’ genotypes (*1/2+*2/2). Conclusions: Genetic polymorphism of LAPTM4B is a potential risk factor for the development of breast cancer. Serum LAPTM4B may be used as a diagnostic and prognostic marker for breast cancer.

Background Diabetic nephropathy is one of the major causes of end-stage renal disease. As impaired fibrinolysis can increase renal fibrosis, we investigated the relationship of impaired fibrinolysis, as assessed by the ratio of plasminogen activator inhibitor-1 (PAI-1) to tissue-type plasminogen activator (t-PA) with urinary albumin excretion (UAE) and renal disease progression in type 2 diabetes. Patients and methods A total of 50 patients with type 2 diabetes and 10 healthy control individuals were included in the study. Participants were subdivided according to UAE. Group 1 (G1) represented control individuals. Group 2 (G2) included patients without albuminuria. Group 3 (G3) included patients with microalbuminuria. Group 4 (G4) included patients with macroalbuminuria. Creatinine clearance and UAE were calculated. PAI-1 and t-PA were measured using an enzyme-linked immunosorbent assay kit, and the PAI-1/t-PA ratio was calculated as an index of impaired fibrinolysis. Results PAI-1 was highly elevated significantly in G4 when compared with the other groups, with a mean of 87.40 ± 17.03 IU/ml against 28.00 ± 6.98 IU/ml in G1, 46.4 ± 7.99 IU/ml in G2, and 64.10 ± 18.26 IU/ml in G3 (P < 0.001). Also, the serum level of t-PA in G4 was highly elevated significantly when compared with G1 and G2 with means of 16.85 ± 5.63 IU/ml against 7.95 ± 1.91 IU/ml and 10.45 ± 2.63 IU/ml, respectively (P < 0.001). The ratio of PAI-1/t-PA in G4 was significantly higher when compared with G1 (mean of 5.94 ± 2.81 against 3.54 ± 0.43; P = 0.01). PAI-1 and t-PA showed a significant positive correlation with UAE. Receiver operating characteristics curve analysis revealed that only PAI-1 and t-PA were significant discriminated factors for microalbuminuria and macroalbuminuria (P < 0.001). Conclusion Serum levels of PAI-1 and t-PA and the PAI-1/t-PA ratio were significantly increased in diabetic patients with higher UAE. Impaired fibrinolysis and increased UAE were associated with renal disease progression.

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended.

As many other metals, aluminum is a widely recognized neurotoxicant and its link with neurodegenerative disorders has been the subject of scientific debate. One proposal focuses on amyloid β deposition (amyloidogenesis) as the key player in triggering neuronal dysfunction the so-called amyloid cascade hypothesis. We undertook this study first to investigate the cognition status of workers exposed to Al dust in an Al factory in Southern Cairo, second, to evaluate serum amyloid precursor protein (APP) and cathepsin D (CD) enzyme activity to study the possible role of Al in amyloidogenesis, and finally to explore the relation between these potential biomarkers and cognitive functions. The study was conducted on 54 exposed workers and 51 matched controls. They were subjected to questionnaire, neurological examination and a cognitive test battery, Addenbrooke's Cognitive Examination - Revised (ACE-R). Serum Al, APP and CD enzyme activity were measured. A significant increase of serum Al was found in the exposed workers with an associated increase in serum APP and decrement in CD activity. The exposed workers displayed poor performance on the ACE-R test. No significant correlation was detected between ACE-R test total score and either APP or CD activity. We concluded that occupational exposure to Al is associated with cognitive impairment. The effect of occupational Al exposure on the serum levels of APP and CD activity may be regarded as a possible mechanism of Al in amyloidogenesis. However, our findings do not support the utility of serum APP and CD activity as screening markers for early or preclinical cognitive impairment.

Background Anesthesia and surgery starts a series of stress responses in the body. Subsequently, loss of normal anabolic actions of insulin and development of insulin resistance occur. Resulting hyperglycemia has been considered by an evidence based study as a risk factor for perioperative morbidity and mortality. We tested whether a single preoperative dose of alanyl-glutamine would prevent such responses in addition to maintaining glutathione level; an important factor for maintaining cellular redox potential. Methods A total of 40 cancer patients were enrolled in this study who received an infusions of 500 ml of Normal Saline started an hour before surgery and continued throughout the surgery. The Dipeptiven® group (20 patients): 2 ml Dipeptiven®/kg were added to saline, while the control group (20 patients): nothing was added to saline. Blood samples were taken a preoperative sample and two postoperative samples (immediately after immergence from anesthesia and 24 h after surgery). These samples were analyzed for plasma glucose, plasma insulin to calculate insulin resistance by HOMA test. Plasma reduced glutathione level was also analyzed in the same time points. Results We found that insulin resistance and glucose level were less in the tested time points in the Dipeptiven® group of patients when compared with the control group. Furthermore, plasma glutathione level was higher in the Dipeptiven® group than the control group. Conclusion Preoperative alanyl-glutamine is helpful in amelioration of insulin resistance and improvement of plasma glutathione levels in the early postoperative period.

Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. © 2013 BioFactors, 40(1):132–137, 2014

Background Breast cancer (BC) is a major worldwide health care problem that mostly afflicts the elderly population in the more developed countries. It is not known how common is breast cancer among elderly Egyptian patients and whether this differs from the disease in younger patients. Aims To study the clinico-pathological features of BC in elderly Egyptian patients (⩾65 years of age) among the population of an Egyptian Governorate, Gharbiah, and to compare these features with those of younger patients ( Methods This is a cross sectional study that compares elderly BC (EBC) and the non-elderly BC (NEBC) using the information from the Gharbiah Population-based Cancer registry (GPCR) during the years 1999–2007. Results Out of 6078 BCs, 12% were EBCs and 88% were NEBCs. Between 1999 and 2007, the crude incidence rate (CIR, per 100,000 populations) of EBC increased from 47 to 71 and that of NEBC increased from 16 to 17. Compared to NEBC patients, EBC patients were more likely to have a positive family history and present with a distant disease and less likely to present with a localized disease. EBCs were more likely to have lung metastases and less likely to have liver metastases. Histology, grade, hormone and HER-2 receptor statuses were comparable in both groups. Apart from hormonal therapies, the elderly were less likely to receive surgery, radiotherapy or chemotherapy. Conclusion EBC patients in Egypt present with advanced disease and are less likely to receive surgery, radiotherapy or chemotherapy compared to NEBC patients.

This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs) and a novel curcumin derivative (NCD) on HepG2 cells (hepatoma cell line) and to investigate their effect on Notch1 signaling pathway target genes. HepG2 cells were divided into HepG2 control group, HepG2 cells treated with MSC conditioned medium (MSCs CM), HepG2 cells treated with a NCD, HepG2 cells treated with MSCs CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a NCD). Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time, reverse transcription-polymerase chain reaction (RT-PCR) in HepG2 cells. In addition, HepG2 proliferation assay was performed in all groups. Notch1 and its target genes (Hes1 and cyclin D1) were downregulated in all treated groups with more suppressive effect in the groups treated with both MSCs and NCD. Also, treated HepG2 cells showed significant decrease in cell proliferation rate. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can be considered as a therapeutic target in HCC.

Purpose: To estimate the effect of fasting during Ramadan (the ninth lunar month) on adherence to oral hormonal therapies (OHT) among breast cancer (BC) patients. Patients and Methods: During Ramadan 2010, 139 BC patients were interviewed at the Egyptian National Cancer Institute. They were asked about fasting as well as intake of OHT in Ramadan and in the preceding month. Results: The median age was 50 years and most patients were postmenopausal with good perfor- mance status and non-metastatic disease. The median number of fasting days was 18% and 93% of patients were fasting 80% or more of Ramadan. Tamoxifen and aromatase inhibitors were used in 64% and 36%, respectively. Adherence to OHT during Ramadan and its preceding month were 94.2% and 95.7%, respectively (p = 0.77). In univariate analysis, non-adherence prior to Ramadan and shorter duration of OHT were predictors of non-adherence during Ramadan (P < 0.001, 0.003, respectively). Fasting, age, performance status, presence of metastases and type of hormonal therapy were not good predictors of adherence. Conclusions: While most of patients receiving OHT for BC are fasting during Ramadan, this does not negatively impact compliance with treatment. a 2012 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage.to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity.The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins.The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE.Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.

Objectives The aim of this work was to explore the value of serum vascular endothelial growth factor-A (VEGF-A) in patients with metastatic triple negative breast cancer (TNBC) treated with chemotherapy. The primary end point was overall survival (OS). Secondary end points were response rate (RR), progression-free survival (PFS) and VEGF-A level at baseline, mid-therapy and at the end of therapy. Design and methods Female patients aged 18 years or above with histologically proven metastatic TNBC were included. Serum VEFG-A levels were measured at baseline, after the 3rd and 6th cycles of FAC chemotherapy regimen (Fluorourcil, Adriamycin, and Cyclophamide). Results The overall RR was 57%. The median PFS and OS were 7 and 11.2 months, respectively (95% CI: 4.3–9.7 and 3.8–18.5 months, respectively). Patients whose disease progressed despite therapy had a significantly higher baseline VEGF-A level than those who did not progress. VEGF-A level did not drop with continuation of therapy. Patients with high VEGF-A level had a significantly lower PFS but not OS than patients with low levels. Conclusion The outcome of metastatic TNBC is poor with FAC chemotherapy regimen. Alternative chemotherapeutic regimens and novel therapeutic approaches including targeting of VEGF and/or its receptors are warranted.

Background: Urotensin II (U-II) and its receptor, UT, are widely expressed throughout the body. It is known to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to Endothelin 1 (ET-1). Objective: To investigate the possible association of the polymorphism of UTS2 gene (Thr21Met and Ser89Asn) with the susceptibility to SSc and pattern of disease manifestations in Egyptian patients. Results: We found that the Thr21Met MM genotypes of the UTS2 gene were significantly increased in SSc patients (20%) compared to the control subjects (5%) (p=0.013) There was a significant difference in the MM and NN genotypes in diffuse SSc patients (35.7%, 67.9%) compared to limited SSc patients (6.2%, 25%) (p=0.004, 0.001) .The frequency of the N allele of the UT89 gene polymorphism was significantly higher in the SSc patients (58.3%) than in the control subjects (36.7%) (p=0.001). Significant associations were found between Thr21Met MM and Ser89Asn NN genotypes with pitting scars, digital ischemia, pulmonary hypertension, gastrointestinal manifestations and Anti Scleroderma-70 Antibody. Significant associations were found between Thr21Met M allele with pitting scars, digital ischemia and Anti Scleroderma-70 Antibody, while Ser89Asn N allele showed also in addition a significant association with Raynaud's phenomenon and renal manifestations. Conclusion: The results suggest that UTS2 Thr21Met and Ser89Asn genetic polymorphisms may be important risk factors in the development of SSc susceptibility in the Egyptian population, and an indicator of many disease manifestations such as pulmonary hypertension, severe skin and lung involvement in patients with SSc.

AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP). METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group I included 25 patients with SBP and group II included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin (IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups I and II (P = 0.001 and 0.02 respectively). Group I was associated with a significantly higher frequency of AG genotype [control 8 (40%) vs SBP 19 (76.0%), P < 0.001], and group II was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1 (5%) vs cirrhotic 16 (64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups (I and II) [control 10 (25%) vs SBP 27 (54%), P < 0.001 and vs cirrhotic 37 (74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group I than in group II. Group I showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.

Background:Brick manufacturing constitutes an important industrial sector in Egypt with considerable exposure to silica.Objectives:We aimed for evaluating hepatic functions in silica-exposed workers in the clay brick industry, and the possible role of matrix remodeling and immunological factors.Methods:A case–control study, 87 workers as exposed and 45 as control subjects. Questionnaire, clinical examination, and laboratory investigations: liver functions, matrix metalloproteinase-9, immunoglobulins G and E, and anti-liver kidney microsomal antibody.Results:In the exposed workers, mean levels of liver functions, matrix metalloproteinase-9 (MMP-9), and IgG and IgE were significantly higher. In the silicotic subgroup the mean level of GGT was almost twice the level in the non-silicotic subjects. Logistic regression showed that abnormal GGT and ALT were associated with production workers.Conclusion:Workers in the clay brick industry showed evidence of liver disease that could be related to matrix rem...

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) are pivotal cytokines in the pathogenesis of systemic lupus erythematosus (SLE). To investigate the possible association of the polymorphism of the TNF promoter gene −308 and that of the LTA gene 252 with susceptibility to SLE and with phenotypic disease features in Egyptian patients. A case control study involving 100 SLE patients and 100 unrelated healthy controls. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect genetic polymorphism. We found that TNF−308 genotype AA was significantly increase by 26 % in SLE patients compared to 10 % in the control group (p = 0.003; OR 3.16; CI 1.43–6.98) and the frequency of the A allele of the TNF promoter −308 was significantly higher in the SLE patients (42 %) than in the control subjects (24 %) (p < 0.001; OR 2.29; 95 % CI 1.49–3.52). Genotype LTA 252 GG showed a significant increase by 22 % in SLE patients compared to 6 % in the control group (p = 0.001; OR 4.42; 95 % CI 1.71–11.44), and the frequency of the G allele of the LTA was significantly higher in the SLE patients (38 %) than in the control subjects (21 %) (p < 0.001; OR 2.31; 95 % CI 1.48–3.6). Genotype (AA+GA) of TNF was significantly associated with clinical manifestations as malar rash, arthritis, oral ulcers, serositis and systemic lupus erythematosus disease activity index. Genotype (GG+GA) of LTA was significantly associated with arthritis. These results suggest that TNF and LTA genetic polymorphisms contribute to SLE susceptibility in the Egyptian population and are associated with disease characteristics. TNF−308 and LTA+252 polymorphic markers may be used for early diagnosis of SLE and early prediction of clinical manifestations, like arthritis.

Background Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. Subjects and Methods A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (−1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). Results We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p

Background: The aim of this work was to analyse the past trends of biomedical and cancer publications from Qatar listed on PubMed for the years 2000–2012. These findings were then compared with the corresponding global number of publications. Methods: PubMed was searched for cancer publications, clinical trials, publications on humans or other species. Searching for “Qatar*” in the “Affiliation” field yielded the lowest number of publications; searching for “Qatar*” in the “Affiliation” or in “Title/Abstract” yielded a moderate number of results and searching for “Qatar*” in the “Affiliation” or “Title/Abstract” or “Text Word” fields yielded the highest number of publications. The annual percentage change (APC) from one year to the next was calculated for the population and each type of publication. Information on the population of Qatar was gathered from the website of Qatar Statistics Authority to determine the correlation of papers published per 1000 population. Results: The number of publications retrieved from PubMed was not particularly different for each variation of search carried out. However, the most representative number of publications was retrieved upon searching for “Qatar*” in the “Affiliation” or in “Title/Abstract” fields. Between the years 2000 and 2012, the total number of biomedical publications from Qatar increased 24 times with an average APC of 33.4%, which was found to be more than the APC of the population in Qatar which averaged at 9%. The number of biomedical publications per 1000 population increased from 0.02 in 2000 to 0.15% in 2012. Most publications retrieved were humans studies and occasionally were for other animal species. Cancer publications in Qatar represented 16.9% of the total publications and the number of cancer publications per 1000 population increased from 0% in 2000 to 0.02% in 2012. Publications classified as clinical trials represented 4.6% of Qatar biomedical publications. Publication of cancer clinical trials were very rare (0.4%). Conclusions: Despite the obvious increase in Qatar biomedical and cancer publications in PubMed, the absolute numbers were relatively small. While strategies are in place, leaders of Qatar biomedical research need to consider increasing cancer research and clinical trials to meet the country's needs. Linking research output to researchers, research facilities and research funding is needed.

Background and study aims Hepatocellular carcinoma (HCC) is a fatal malignancy. Effective curative surgery is achieved when HCC is detected earlier. Proteosomes, the main non-lysosomal proteolytic structures organising the cellular mechanisms of cleaving proteins, can be considered a tumour marker in many kinds of malignancies. The aim of this study was to assess the plasma proteosome level in HCC and cirrhosis and, accordingly, evaluate its potential diagnostic ability in the detection of HCC in cirrhosis. Patients and methods This study included 60 patients, divided into two groups: the HCC group and the liver cirrhosis group. Twenty normal subjects served as a control group. Serum levels of proteosome and alpha-foetoprotein (AFP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Results Plasma proteosome levels were significantly higher in patients with HCC and in patients with cirrhosis without HCC when compared to controls individually (p > 0.002 and p > 0.001, respectively) but did not reach a significant differentiating level between them (area under curve (AUC) = 0.641, p = 0.061). Moreover, the plasma proteosome level was not correlated with the severity of HCC by the Milan criteria or with AFP level. In addition, it was not significantly related to laboratory or Child-Pugh scoring. Moreover, the combined use of plasma proteosome level and AFP measurements for the diagnosis of HCC was not effective. Conclusions In this study, the plasma proteosome level was comparably recorded in both patients with cirrhosis and patients with HCC (mean value ± standard deviation were 5.796 ± 1.46 and 7.176 ± 2.48 μg ml−1, respectively), not reaching a significant differentiating level between them, although predictability of HCC using the plasma proteosome level was significant (p = 0.017).

Background PubMed is a free web literature search service that contains almost 21 millions of abstracts and publications with almost 5 million user queries daily. The purposes of the study were to compare trends in PubMed-indexed cancer and biomedical publications from Egypt to that of the world and to predict future publication volumes. Methods The PubMed was searched for the biomedical publications between 1991 and 2010 (publications dates). Affiliation was then limited to Egypt. Further limitation was applied to cancer, human and animal publications. Poisson regression model was used for prediction of future number of publications between 2011 and 2020. Results Cancer publications contributed 23% to biomedical publications both for Egypt and the world. Egyptian biomedical and cancer publications contributed about 0.13% to their world counterparts. This contribution was more than doubled over the study period. Egyptian and world’s publications increased from year to year with rapid rise starting the year 2003. Egyptian as well as world’s human cancer publications showed the highest increases. Egyptian publications had some peculiarities; they showed some drop at the years 1994 and 2002 and apart from the decline in the animal: human ratio with time, all Egyptian publications in the period 1991-2000 were significantly more than those in 2001-2010 (P Conclusions The Egyptian contribution to world’s biomedical and cancer publications needs significant improvements through research strategic planning, setting national research priorities, adequate funding and researchers’ training.

BACKGROUND: Breast cancer (BC) is the commonest among women in Egypt as well as in many other countries. Cyclo-oxygenase-2 (COX-2) and 12-lipo-oxygenase (12-LOX) are over-expressed in 30-40% of patients and carry a poor prognosis. The objectives of this study were to correlate COX-2 and 12-LOX expression with various clinico-pathologic patients' characteristics and their impact on overall survival (OS) and disease free survival (DFS) in Egyptian women with operable BC. MATERIALS AND METHODS: This prospective study included 57 consecutive BC cases presenting to the Egyptian National Cancer Institute. Sections from BC and nearby normal tissues were examined for expression of COX-2 and 12-LOX using reverse transcriptase polymerase chain reaction. RESULTS: The patients' median age was 45 years. Fifty-three percent were premenopausal. Stage II and III disease represented 25 and 75% respectively. Adjuvant chemotherapy, radiotherapy and tamoxifen were used in 90, 75 and 60% respectively. Sixty percent had hormone-receptor positive tumors and 28% over-expressed HER2/neu. Forty-nine and sixty-five percent showed over-expression of COX-2 and 12-LOX respectively. Patients with higher TNM stage or who developed visceral metastases had significantly higher COX-2 expression. For the whole group of patients, the median DFS was 37 months, while the median OS was not reached. OS or DFS did not differ significantly between patients with normal and over-expression of COX-2. DFS but not OS was significantly higher in 12-LOX over-expression compared to normal expression. CONCLUSION: COX-2 over-expression was associated with poor prognostic criteria in BC, but did not affect DFS or OS. 12-LOX over-expression was associated with better DFS, but not OS.

Background Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions. Materials and methods Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation. Results NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver. Conclusion The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.

Background: Curcumin, a polyphenol from turmeric, has potent anticancer properties in human cancer cell lines. Nevertheless, its multitargeting clinical application in cancer and other diseases is hampered by

Human mesenchymal stem cells (hMSCs) are mostly studied for their potential clinical use. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. The present study was conducted to evaluate the tumor suppressive effects of human mesenchymal stem cells (hMSCs) on human hepatoma cell line (HepG2) and their signaling mechanisms. To fulfill this objective, the influence of hMSCs on genes concerned with apoptosis, mitogenesis as well as on the proliferation of HepG2 cell line was investigated using either hMSCs-conditioned or using hMSCs and HepG2 co-culture conditioned media. Cell survival was evaluated using cell proliferation (MTT) assay kit. Gene expression of survivin, proliferating cell nuclear antigen (PCNA), β-Catenin, telomerase and VEGF was assessed by real time reverse transcription-polymerase chain reaction (RT-PCR). HpG2 cells cultured with either hMSCs-conditioned media or with hMSCs&HepG2 co-culture conditioned media showed decreased proliferation and decreased expression of survivin, PCNA, β-Catenin and telomerase. However, both media had increased expression of VEGF. Treatment of HepG2 cells by either hMSCs conditioned media or by hMSCs and HepG2 co-culture condition media led to a significant decrease in cell proliferation and down regulation of genes concerned with antiapoptosis, mitogenesis, and cell proliferation. This indicates that hMSCs can suppress tumorigenesis through factors produced in their conditioned media.

Chronic renal failure (CRF) is a common disease with high morbidity and mortality. The inadequacy of current treatment modalities and insufficiency of donor organs for cadaveric transplantation have driven a search for improved methods of dealing with renal failure. This raises the concept of cell-based therapy using mesenchymal stem cells (MSCs). The purpose of this work is to evaluate the effect of MSCs in rats with CRF and to detect the level of B-cell lymphoma 2 (Bcl-2) and basic fibroblast growth factor (bFGF) as possible antiapoptotic and anti-inflammatory paracrine mediators of MSCs action. This study was carried on female albino rats, which were divided into 3 groups, control group, CRF group and CRF/MSCs group. MSCs were derived from bone marrow of male albino rats and were characterized morphologically and by RT-PCR for CD29. Serum urea, creatinine, Na, K, systolic blood pressure and 24-hour urinary albumin were estimated for all groups, Y-chromosome gene (Sry) was detected by PCR in renal tissue. Also Bcl-2 and bFGF were examined by RT-PCR in renal tissue of all studied groups and the kidney was examined pathologically. The results of this work showed that CRF rats receiving MSCs showed significantly lowered serum urea, creatinine and urinary albumin levels compared to the CRF group. Also improvement of serum Na and K was observed in CRF/MSCs group compared to CRF group. As regard Bcl-2 and bFGF they were highly expressed in renal tissue of CRF/MSCs group compared to the CRF group. The (Sry) gene was detected by PCR in the renal tissue of CRF/MSCs group. These results demonstrate a potential of MSCs to ameliorate the kidney function in rats with CRF possibly through the antiapoptotic and anti-inflammatory paracrine mediators of MSCs.

Background Several studies highlight curcumin’s benefit as a hypoglycemic agent, however; a limited number of reports present the importance of curcumin in improvement of pancreatic islets in diabetes. The aim of the present study is to evaluate the antidiabetic effect of a novel curcumin derivative and its effect on pancreatic islet regeneration in type I diabetes-induced by STZ. Materials and methods Rats were divided into diabetic rats and diabetic rats treated orally with the novel curcumin derivative (NCD) for 40 days. Fasting blood samples were withdrawn periodically from all rats to estimate plasma glucose, insulin and C-peptide for 10 months. Histopathology was performed to allow the assessment of pancreatic islet morphology. Insulin and CD105 were detected immunohistochemically. Results In diabetic rats, the plasma glucose, insulin and C-peptide levels remained within the diabetic range for about 4 months, after which a gradual decrease in glucose and increase in insulin and C-peptide was observed, which reached almost normal levels after 10 months. NCD treated diabetic rats showed significantly lowered plasma glucose and increased plasma insulin and C-peptide levels. This was followed by a further significant decrease in plasma glucose and increase in plasma insulin and C-peptide after two months from oral administration of the NCD. The plasma insulin and C-peptide continued to increase for ten months reaching levels significantly higher than the basal level. Histopathological examination of diabetic rat pancreas revealed absence of islets of Langerhans, minimal adipose tissue infiltration and localized lymphocytic infiltrates. However, after 6 months of induction of diabetes, rat pancreas showed the appearance of small well formed islets and positive insulin cells but no CD105 positive cells. NCD treated rats showed the appearance of primitive cell collections, large insulin positive cells and CD105 positive cells in the adipose tissue infiltrating the pancreatic tissues. This was followed by the gradual appearance of insulin positive cells in the islets while, CD 105 positive cells remained in the adipose tissue. After 5 and 10 months from the onset of diabetes, rat pancreas showed, well developed larger sized islets with disappearance of primitive cell collections and CD 105 positive cells. Also, insulin positive islets of variable size with disappearance of insulin positive cells in adipose tissue were detected. Conclusion The NCD possesses antidiabetic actions and enhanced pancreatic islets regeneration.

Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.