Yttrium oxide nanoparticles ameliorates calcium hydroxide and calcium titanate nanoparticles induced genomic DNA and mitochondrial damage, ROS generation and inflammation.

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.

Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.

BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.

Genotoxicity and oxidative stress induction by calcium hydroxide, calcium titanate or/and yttrium oxide nanoparticles in mice.

Intensive uses of Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the effect of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs and Y2O3NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)2NPs or CaTiO3NPs alone together with high Ca(OH)2NPs induced reactive oxygen species (ROS) generation and a slight CaTiO3NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs up to the negative control level. Oral administration of Y2O3NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)2NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO3NPs and Y2O3NPs separately or simultaneously together with Ca(OH)2NPs. Conclusion: Ca(OH)2NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO3NPs administration. However, administration of Y2O3NPs alone was non-genotoxic and coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)2NPs and CaTiO3NPs. Thus co-administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs is recommended to counter Ca(OH)2NPs and CaTiO3NPs induced genotoxicity and oxidative stress.

Novel grape seed extract nanoparticles attenuate amikacin-induced nephrotoxicity in rats.

Amikacin (AMK), an antibiotic, is prescribed for treating various bacterial diseases like urinary tract infections, encephalitis, asthma and joint infections. The most significant side effects, which affect 1 to 10% of consumers, are kidney injury and ototoxicity. Several studies discussed the role of grape seed extract (GSE) in renoprotection against AMK. The current study aimed to extract Muscat of Alexandria grape seeds followed by its characterization to determine its bioactive components and elements. GSE nanoparticles was prepared and tested, in vitro, to determine its safety for the in vivo experiment. Experimental groups were control group I, AMK group II, GSE (50 mg/kg)-AMK group III, GSE (100 mg/kg)-AMK group IV, GSE NPs (25 mg/kg)-AMK group V and GSE NPs (50 mg/kg)-AMK group VI. Groups 2-6 received 100 mg/kg/day of AMK by intramuscular injection for two weeks for the induction of experimental nephrotoxicity. Groups 3-6 received daily doses of GSE or GSE NPs by oral gavage, concurrently, with AMK for two weeks. GSE was rich in polyphenol compounds like proanthocyanidins, phenolic acids like gallic and egallic acids, catechine and epicatechine. GSE NPs have a smooth surface and a size that ranged from 40 to 70 nm; and have an anti-oxidant, anti-inflammatory, anti-cytotoxic and anti-microbial in vitro effects. It reduced oxidative stress and inflammation that followed AMK administration; and attenuated the AMK-induced nephrotoxicity. GSE NPs were safe to be used in vivo as a renoprotective agent against AMK; where, it reduced the oxidative stress and inflammation.

Associations Between Serum Soluble Toll-like Receptors 4 and 9 and Breast Cancer in Egyptian Patients.

BACKGROUND: Toll-like receptors (TLRs) play an important role in regulation of immune cells and are vital in tumorigenesis due to its crucial role in inflammatory microenvironment regulation, as they promote the synthesis and release of inflammatory cytokines and chemokines. Toll-like receptors 4 and TLRs 9 were found to be highly expressed in breast cancer. The aim of this study is to investigate the soluble toll-like receptors 4 and 9 (sTLR4 and sTLR9) as potential biomarkers for diagnosis and prognosis of breast cancer and their association with the clinicopathological parameters of breast cancer. PATIENTS AND METHOD: In this retrospective case-control study, 186 female subjects were recruited and divided into three groups, Group I: 62 healthy control, Group II: 62 subjects diagnosed with non-metastatic breast cancer, and Group III: 62 subjects diagnosed with metastatic breast cancer. Enzyme-linked immunosorbent assay (ELISA) technique was used to quantify the levels of sTLR4 and sTLR9 in serum. RESULTS: Both non-metastatic and metastatic groups showed significant higher levels of both serum sTLR4 and sTLR9 expression compared to healthy controls. Only sTLR9 was significantly increased among metastatic patients compared to non-metastatic group. Serum levels of sTLR9 and sTLR4 were still significantly associated with breast cancer in a multiple logistic regression model (P = <.001). ROC curves showed that both sTLR4 and sTLR9 can be a significant parameter to discriminate between normal females and breast cancer patients. CONCLUSION: Soluble toll-like receptors 4 and sTLR9 are over-expressed in patients with metastatic and non-metastatic BC than in benign cases. The expression levels of sTLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness suggested to be prognostic biomarkers. Toll-like receptors may represent therapeutic targets in breast cancer.

Immunohistochemical Expression of CD90, CD133, and TPM1 in Relation to Gastric Cancer and H. pylori Association.

BACKGROUND: Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Multiple malignancies overexpress CD90, making it a helpful diagnostic and prognostic marker. CD133 is suggested to be related to poor prognosis in GC. Tropomyosin-1 (TPM1) tumor-suppressor gene low expression may predict poor survival in GC. Our study aimed to investigate CD90, CD133, and TPM1 immunohistochemical expression in GC in relation to diagnosis, prognosis, and Helicobacter pylori (H. pylori) infection. METHODS: 144 paraffin blocks containing gastric cancerous (108 cases), and non-cancerous (36 cases) tissue were analyzed histopathologically for the type of lesion, grade, and stage of malignancy and by using an immunohistochemical assay for studying the expression of CD90, CD133, and TPM1. Data analysis was carried out using the Statistical Package for the Social Sciences (SPSS) version 20.0. RESULTS: The obtained results showed a significantly higher expression of CD90 and CD133 while showing a significantly lower expression of TPM1 in malignant samples compared to benign ones. CD90 was significantly higher in grade-3, stage-3, and N3 (p<0.05), with no significant difference concerning positive and negative H. pylori samples. CD133 percentage and H-score were significantly higher in grade-2 and stage-4 tumors than in other grades and stages, while being insignificantly higher in N3 and H. pylori-positive cases. TPM1 expression levels were significantly downregulated in GC and H. pylori-positive cases (p<0.05). TPM1 downregulation was associated with grade progression, increased depth of invasion, and tumor node metastasis. CONCLUSION: CD90, CD133, and TPM1 immunohistochemical expression in the gastric biopsy are related firmly to grades and stages of GC as well as H. pylori infection, so they could be of prognostic value. Further studies on a larger sample size are recommended.

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats.

BACKGROUND: Nowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE. METHODS: Firstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days. RESULTS: The results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress. CONCLUSION: Co-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Induction of ROS mediated genomic instability, apoptosis and G0/G1 cell cycle arrest by erbium oxide nanoparticles in human hepatic Hep-G2 cancer cells.

The remarkable physical and chemical characteristics of noble metal nanoparticles, such as high surface-to-volume ratio, broad optical properties, ease of assembly, surfactant and functional chemistry, have increased scientific interest in using erbium oxide nanoparticles (Er2O3-NPs) and other noble metal nanostructures in cancer treatment. However, the therapeutic effect of Er2O3-NPs on hepatic cancer cells has not been studied. Therefore, the current study was conducted to estimate the therapeutic potential of Er2O3-NPs on human hepatocellular carcinoma (Hep-G2) cells. Exposure to Er2O3-NPs for 72 h inhibited growth and caused death of Hep-G2 cells in a concentration dependent manner. High DNA damage and extra-production of intracellular reactive oxygen species (ROS) were induced by Er2O3-NPs in Hep-G2 cells. As determined by flow cytometry, Er2O3-NPs arrested Hep-G2 cell cycle at the G0/G1 phase and markedly increased the number of Hep-G2 cells in the apoptotic and necrotic phases. Moreover, Er2O3-NPs caused simultaneous marked increases in expression levels of apoptotic (p53 and Bax) genes and decreased level of anti-apoptotic Bcl2 gene expression level in Hep-G2 cells. Thus it is concluded that Er2O3-NPs inhibit proliferation and trigger apoptosis of Hep-G2 cells through the extra ROS generation causing high DNA damage induction and alterations of apoptotic genes. Thus it is recommended that further in vitro and in vivo studies be carried out to study the possibility of using Er2O3-NPs in the treatment of cancer.

Eco-physiological response and genotoxicity induced by crude petroleum oil in the potential phytoremediator Vinca rosea L.

BACKGROUND: Phytoremediation is determined as an emerging green technology suitable for the safe remediation and restoration of polluted terrestrial and aquatic environments. In this study, the assessment of an ornamental plant, Vinca rosea L., as a phytoremediator of crude oil in polluted soils was conducted. In an open greenhouse experiment, plants were raised in sandy-clayey soils treated with 1, 3, 5, and 7% oil by weight. The experiment was conducted over 5 months. RESULTS: Total petroleum hydrocarbon (TPH) degradation percentage by V. rosea after a 5-month growth period ranged from 86.83 ± 0.44% to 59.05% ± 0.45% in soil treated with 1 and 7%, respectively. Plants raised in polluted soils demonstrated a dramatic reduction in germination rates, in addition to growth inhibition outcomes shown from decreased plant height. An increase in branching was observed with an increase in oil pollution percentages. Moreover, the phytomass allocated to the leaves was higher, while the phytomass witnessed lower values for fine roots, flowering and fruiting when compared to the controls. Apart from the apparent morphological changes, there was a decrease in chlorophyll a/b ratio, which was inversely proportional to the oil pollution level. The contents of carotenoids, tannins, phenolics, flavonoids, and antioxidant capacity were elevated directly with an increase in oil pollution level. The start codon-targeted (SCoT) polymorphisms and inter-simple sequence repeat (ISSR) primers showed the molecular variations between the control and plants raised in polluted soils. The genetic similarity and genomic DNA stability were negatively affected by increased levels of crude oil pollution. CONCLUSIONS: The ability of V. rosea to degrade TPH and balance the increased or decreased plant functional traits at the macro and micro levels of plant structure in response to crude oil pollution supports the use of the species for phytoremediation of crude oil-polluted sites. The genotoxic effects of crude oil on V. rosea still require further investigation. Further studies are required to demonstrate the mechanism of phenolic, flavonoid, and antioxidant compounds in the protection of plants against crude oil pollution stress. Testing different molecular markers and studying the differentially expressed genes will help understand the behavior of genetic polymorphism and stress-resistant genes in response to crude oil pollution.

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats.

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (ß) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1ß and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated ß cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1ß and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting ß cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.

Molecular Detection of Genetic Susceptibility to Bladder Cancer in Egyptian Patients.

OBJECTIVE: Genome-wide association studies (GWAS) have identified a number of genetic variants associated with the susceptibility of bladder cancer (BC) in European and Chinese populations. Here, we assessed the association of two of these variants, rs9642880 and rs710521 in an Egyptian patients and also examined the expression of c-Myc.The basis was due to the absence of studies on Egyptian patients to determine the association between rs9642880& rs710521 and bladder cancer risk, particularly due to the known role of the variant (rs9642880) in the Progression and development of bladder cancer. METHODS: Urine samples were collected from onehundred and fiftybladder cancer patients under particular standards and fifty healthy controls. Genomic DNA was extracted,  rs9642880 G>T and rs710521 A>G polymorphisms were amplified, assessed via restriction fragment length polymorphism(RFLP) and sequenced. Urine retrieved results were compared to the histopathological diagnosis of tissue biopsies and to the results of C-Myc immunohistochemistry. Data were statistically analyzed using Microsoft Excel 2016, association between significant genotypes of the two studied variables and bladder cancer risk was performed. RESULTS: We found that the TT genotype of rs9642880 G>T was strongly associated with the risk of bladder cancer, andfor rs710521 A>G, AG genotype was also identified to has an association with bladder cancer risk.All 150 tumor sections showed positive immunoreactivity for c-Myc in the nucleus and the cytoplasm. CONCLUSION: Identifying the association to risk of bladder cancer using genetic analysis will help in the early detection of the disease.

Enhanced cytotoxic activity of beta carotene conjugated liposomes towards breast cancer cell line: comparative studies with cyclophosphamide.

This work aims to evaluate cyclophosphamide (Cyclo) cytotoxic efficacy combined with liposomes in the presence or absence of beta carotene (beta) by detecting the effects of these compounds on the breast cancer cell line (MCF-7) DNA damage. The IC50 value for beta in cytotoxic assay with MCF-7 treated cells was 21.15 µg/ml, while with liposomal beta (LipoBeta) being 121 µg/ml. The free Cyclo IC50 value was 719.86 µg/ml, its liposomal form (LipoCyclo) was 172 µg/ml. The results indicated that in contrast with Cyclo and control values, all comet assay parameters for the LipoBeta were significantly increased (P < 0.05). In MCF-7 cells treated with beta, the findings show a higher intensity of comet tail than those treated with LipoBeta. The presence of several double-strand breaks suggests this high intensity relative to the head. The molecular combination between Cyclo and liposomes in the presence or absence of beta was characterized. Dynamic light scattering measurements confirmed the mono-dispersity of all samples. The incorporation of Cyclo or beta into liposomes exhibited a slight shift to higher temperature compared to the main peak of empty liposomes that exists at 101.5°C which creates a conformational disorder within the phospholipids. The FTIR study showed structural alterations in vesicles after liposome encapsulation.

IL-8 secreted by tumor associated macrophages contribute to lapatinib resistance in HER2-positive locally advanced breast cancer via activation of Src/STAT3/ERK1/2-mediated EGFR signaling.

Locally advanced breast cancer (LABC) is an aggressive disease characterized by late clinical presentation, large tumor size, treatment resistance and low survival rate. Expression of EGFR/HER2 and activation of intracellular tyrosine kinase domains in LABC are associated with poor prognosis. Thus, target therapies such as the anti-receptor tyrosine kinases lapatinib drug have been more developed in the past decade. The response to lapatinib involves the inhibition of RTKs and subsequently signaling molecules such as Src/STAT3/Erk1/2 known also to be activated by the cytokines in the tumor microenvironment (TME). The aim of the present study is to identify the major cytokine that might contribute to lapatinib resistance in EGFR+/HER2+ LABC patients. Indeed, tumor associated macrophages (TAMs) are the main source of cytokines in the TME. Herein, we isolated TAMs from LABC during modified radical mastectomy (MRM). Cytokine profile of TAMs revealed that IL-8 is the most prominent highly secreted cytokine by TAMs of LABC patients. Using in-vitro cell culture model we showed that recombinant IL-8 (50 and 100 ng/mL) at different time intervals interfere with lapatinib action via activation of Src/EGFR and signaling molecules known to be inhibited during treatment. We proposed that to improve LABC patients' response to lapatinib treatment it is preferred to use combined therapy that neutralize or block the action of IL-8.

HSP70 as a Diagnostic and Prognostic Marker in Egyptian Women With Breast Cancer.

BACKGROUND: Heat shock protein 70 (HSP70) is a significant cellular stress response protein that has intrinsic and extrinsic pathways to protect cells against apoptosis. It is one of the most induced proteins in cancer cells. The aim of the present study is to investigate the significant role of the HSP70 expression in Egyptian patients with breast cancer (BC) and its potential to be as a diagnostic and prognostic marker. MATERIALS AND METHODS: HSP70 was examined in 155 cases in this prospective study; patients were subdivided into 3 groups: 60 patients with malignant metastatic disease, 60 patients with malignant non-metastatic disease, and 35 patients with benign lesions as control. HSP70 expression was detected using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). RESULTS: Most cases of breast cancer expressed HSP70 in both serum (98.3%) and tumor tissue (90%). A strong positive correlation was found between HSP70 IHC and ELISA (r = 0.811). The mean HSP70 levels, as detected in both patients' serum by ELISA and tumor tissue by IHC, was significantly higher in patients with BC than in benign cases (P = .001). HSP70 was significantly higher in patients with metastatic BC than in those with non-metastatic BC (P = .001). HSP70 showed positive correlation with tumor size (pT stage) and number of lymph node metastases (P ≤ .001). CONCLUSION: HSP70 is over-expressed in patients with metastatic and non-metastatic BC than in benign cases. A high level of HSP70 either in patient's serum or in tumor tissue correlated significantly with advanced disease in patients with BC. This present study suggests that HSP70 can serve as a BC biomarker for early screening, diagnosis, and follow-up.

Tissue-based long non-coding RNAs "PVT1, TUG1 and MEG3" signature predicts Cisplatin resistance in ovarian Cancer.

OBJECTIVES: The current study aimed to investigate the potentiality of three lncRNAs "Plasmacytoma variant translocation 1(lnc-PVT1), Taurine upregulated gene type 1(lnc-TUG1) and Maternally expressed gene 3 (lnc-MEG-3)", to predict Cisplatin resistance in ovarian cancer (OC), in addition, to access their prognostic significance. METHODS: The expression level of lncRNAs were measured in 100 formalin-fixed paraffin-embedded tissue (FFET) samples of OC patients who were treated by Cisplatin-based chemotherapy using qPCR. RESULTS: The results showed that lnc_PVT1 was significantly upregulated by 2.3 folds in Cisplatin resistant tissues, while, lnc-TUG1 and lnc-MEG3 were downregulated by 1.2 and 3 folds, respectively. In addition, the three lncRNAs exhibited high sensitivity and specificity in predicting chemo-resistance and they were negatively associated with OS and progression-free survival (p < 0.001). CONCLUSION: The lnc-PVT1, lnc-TUG1, and lnc-MEG3 transcriptome signatures could be used for predicting resistance to Cisplatin in OC patients.

Green Technology for Remediation of Water Polluted with Petroleum Crude Oil: Using of Eichhornia crassipes (Mart.) Solms Combined with Magnetic Nanoparticles Capped with Myrrh Resources of Saudi Arabia.

Crude oil pollution of water bodies is a worldwide problem that affects water ecosystems and is detrimental to human health and the diversity of living organisms. The objective of this study was to assess the ability of water hyacinth (Eichhornia crassipes (Mart.) Solms) combined with the presence of magnetic nanoparticles capped with natural products based on Myrrh to treat fresh water contaminated by crude petroleum oil. Magnetic nanoparticles based on magnetite capped with Myrrh extracts were prepared, characterized, and used to adsorb heavy components of the crude oil. The hydrophobic hexane and ether Myrrh extracts were isolated and used as capping for magnetite nanoparticles. The chemical structures, morphologies, particle sizes, and magnetic characteristics of the magnetic nanoparticles were investigated. The adsorption efficiencies of the magnetic nanoparticles show a greater efficiency to adsorb more than 95% of the heavy crude oil components. Offsets of Water hyacinth were raised in bowls containing Nile River fresh water under open greenhouse conditions, and subjected to varying crude oil contamination treatments of 0.5, 1, 2, 3, and 5 mL/L for one month. Plants were harvested and separated into shoots and roots, oven dried at 65 °C, and grounded into powder for further analysis of sulphur and total aromatic and saturated hydrocarbons, as well as individual aromatic constituents. The pigments of chlorophylls and carotenoids were measured spectrophotometrically in fresh plant leaves. The results indicated that the bioaccumulation of sulphur in plant tissues increased with the increased level of oil contamination. Water analysis showed significant reduction in polyaromatic hydrocarbons. The increase of crude oil contamination resulted in a decrease of chlorophylls and carotenoid content of the plant tissues. The results indicate that the water hyacinth can be used for remediation of water slightly polluted by crude petroleum oil. The presence of magnetite nanoparticles capped with Myrrh resources improved the remediation of water highly polluted by petroleum crude oil.

Interaction between 12p chromosomal abnormalities and Lnc-HOTAIR mediated pathway in acute myeloid leukemia.

OBJECTIVES: To investigate the correlation of homeobox (HOX) transcript antisense RNA expression with clinicopathological features and the clinical prognosis of the patients with chromosome 12p abnormalities associated acute myeloid leukemia (AML). We also investigate the association of 12p chromosomal on the expression of HOTAIR, miRNA-193a, and c-kit gene as targeting genes for HOTAIR in AML. METHODS: AML patients with 12p chromosomal abnormalities were recruited and compared to AML with other chromosomal abnormalities rather than 12p. The long noncoding RNA (lncRNA) "HOTAIR," miR-193a, and c-Kit genes expression were measured in bone marrow samples using Syber green based real-time polymerase chain reaction. RESULTS: We found a significant difference for the expression levels of HOTAIR, c-kit, and miR-193a between 12p abnormalities associated AML and those without. The survival analysis revealed that patient's with low expression levels of HOTAIR and c-kit had significantly better survival and leukemia free survival. In contrast, miR-193a was associated with better overall survival but not leukemia free survival. CONCLUSION: 12p abnormalities associated AML were associated with worse prognosis. Our results proved that HOTAIR, miR-193a, and c-kit genes are independent prognostic predictors in 12p chromosomal associated AML; therefore it may represent a novel therapeutic application in AML in the future.

The prognostic significance of the long non-coding RNAs "CCAT1, PVT1" in t(8;21) associated Acute Myeloid Leukemia.

Long non-coding RNA (LncRNA) is recently linked to various types of cancers, CCAT and PVT1 are two LncRNAs linked to t(8;21) associated Acute Myeloid Leukemia, the interplay between CCAT, PVT1 and the MYC proto-oncogene implicated in t(8;21) could present an opportunity for using LncRNA as prognostic biomarker or a target for therapy, We investigated the expression levels of LncRNAs in 70 patients; 30 with t(8;21) positive AML and 40 with t(8;21) negative AML, We found that CCAT1 and PVT1 are expressed in higher levels in t(8;21) positive -AML by 5.3 folds compared to t(8;21) negative group; the expression values were significantly associated with high-risk clinical criteria; moreover, they are associated with lower overall survival (OS) rate and leukemia-free survival (LFS), however we didn't find a statistically significant cut-off value of LncRNAs using the Cox regression analysis for Lnc_PVT1 except with LFS, we conclude that high expression levels of CCAT1 and PVT1 are associated with poor prognosis while being poor prognostic biomarkers in t(8;21) associated AML.

Dysregulation of miR-125b predicts poor response to therapy in pediatric acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most well-known sort of leukemia in children. In spite of favorable survival rates, some patients relapse and achieve a poor outcome. METHODS: We analyzed miR-125b and Bcl-2 expressions in pediatric patients with ALL and evaluated their clinical utility as molecular markers for the prediction of disease outcomes. RESULTS: Downregulation of miR-125b and increased Bcl-2 expression levels in pediatric patients with ALL were associated with poor prognosis at diagnosis. At day 28 of induction, miR-125b was significantly increased, whereas Bcl-2 was downregulated. Loss of miR-125b during diagnosis and its elevation after therapy are strongly correlated with short leukemia-free survival and worse survival. Moreover, the combination of miR-125b with Bcl-2 markers can clearly enhance the prediction of the disease outcome. Finally, a univariate analysis highlighted the independent prognostic value of miR-125 in a pediatric patient with ALL. CONCLUSIONS: miR-125b and Bcl-2 together are potent predictors for the prognosis and, therefore, can be used as therapeutic targets in childhood ALL.

Differential Expression of RAGE, EGFR and Ki-67 in Primary Tumors and Lymph Node Deposits of Breast Carcinoma

Background: Breast cancer is a complex disease that results from the inheritance of a number of susceptible genes. Intensive search wok was conducted world-wide on molecular bases of breast cancer in order to achieve the best therapeutic modalities; however, breast cancer still remains a challengeable task. It is very important to determine if the biological parameters in metastatic regional lymph nodes are similar to that in the primary breast cancer because therapy is indicated for patients with synchronous metastatic regional lymph nodes of breast cancer. Difference in therapeutic response in cases of breast cancer may be assumed partially to variability in the biological behavior of tumor tissue in primary breast cancer and lymph node metastasis. Aim: Our aim is to evaluate any variability in the expression of three types of tissue markers in both the primary breast tumors and corresponding axillary lymph nodes in order to expect the targeted therapeutic effect on both sites. Material and Methods: Three markers from different categories; RAGE, EGFR and Ki-67 were immunohistochemicalyl studied for their expression in biopsy specimens from primary breast tumors and their corresponding axillary lymph nodes. Results: There was a statistically significant difference in the expression of these markers between benign and malignant breast lesions.Although we found some differences in the expression of the three studied markers between primary breast cancer and corresponding axillary lymph nodes, yet these variations were mostly not statistically significant. Conclusion: Our findings support the validity of anti-RAGE and anti-EGFR therapy for treatment of both primary and nodal metastatic breast cancer in immunopositive cases.