Modulation of carcinogen-metabolizing enzyme by madinah mint (Mentha spp) in rat liver

Background: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P450 mixed function oxidase system.Materials and methods: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P450 mixed function oxidase) analysisResults: The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (p<0.001) when compared with the control. However, glutathione S-transferase and glucuronosyl transferase activities were significantly decreased (p<0.001 and p<0.01) respectively compared with control. The mutagenic activity of N-nitrosopiperidine was lower in the minttreated hepatic microsomal compared with the controls.Conclusion: It can be concluded that BWME has the potential to suppress the activity of cytochrome enzymes involved in the bioactivation of chemical carcinogen; hence may display chemo preventive activity.Keywords: Carcinogen-PAH-Cytochrome P45

Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.

Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells

Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer

PURPOSE To analyze the role and translational potential for hypermethylation of CpG islands and shores in the regulation of small RNAs within urothelial cell carcinoma (UCC). To examine microRNAs (miR) and mirtrons, a new class of RNA located within gene introns and processed in a Drosha-independent manner. EXPERIMENTAL DESIGN The methylation status of 865 small RNAs was evaluated in normal and malignant cell lines by using 5-azacytidine and microarrays. Bisulfite sequencing was used for CpG regions around selected RNAs. Prognostic and diagnostic associations for epigenetically regulated RNAs were examined by using material from 359 patients, including 216 tumors and 121 urinary samples (68 cases and 53 controls). Functional analyses examined the effect of silencing susceptible RNAs in normal urothelial cells. RESULTS Exonic/UTR-located miRs and mirtons are most susceptible to epigenetic regulation. We identified 4 mirtrons and 16 miRs with CpG hypermethylation across 35 regions in normal and malignant urothelium. For several miRs, hypermethylation was more frequent and dense in CpG shores than islands (e.g., miRs-9/149/210/212/328/503/1224/1227/1229), and was associated with tumor grade, stage, and prognosis (e.g., miR-1224 multivariate analysis OR = 2.5; 95% CI, 1.3-5.0; P = 0.006). The urinary expression of epigenetically silenced RNAs (miRs-152/328/1224) was associated with the presence of UCC (concordance index, 0.86; 95% CI, 0.80-0.93; ANOVA P < 0.016). CONCLUSIONS Hypermethylation of mirtrons and miRs is common in UCC. Mirtrons appear particularly susceptible to epigenetic regulation. Aberrant hypermethylation of small RNAs is associated with the presence and behavior of UCC, suggesting potential roles as diagnostic and prognostic biomarkers

Association of serum asymmetric dimethyl-arginine and troponin I levels as a risk of myocardial infarction in thalassemia

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction. Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined. Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%). Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients.Keywords: CKMB, LDH1, AST, Troponin T, asymmetric dimethylarginie, Thalassemia

Possible hypocholesterolemic effect of ginger and rosemary oils in rats

Background: Hypercholesterolemia is a major risk factor for development of atherosclerosis. The present study was conducted to evaluate the potential effect of ginger oil alone or combined with rosemary oil as hypocholesterolemic agent in rats fed high fat diet.Materials and methods: Healthy female albino rats (n=80) weighting about (150-180 g) were included in this study divided into two equal groups; Group (I): were fed on the basal diet. Group (I) were divided into 4 subgroups each 10: Group (Ia): negative control. Group (Ib): Rats received i.p 2.5 g/Kg b.w of ginger oil. Group (Ic): rats received i.p 2.5 g/Kg b.w of rosemary oil. Group (Id): Rats received i.p 5 g/Kg b.w mixture of ginger oil and rosemary oil (1:1). The second main groups; Group (II): high fat diet (HFD) were fed on the basal diet plus cholesterol (1%), bile salt (0.25%) and animal fat (15%) to induce hypercholesterolemia for six weeks. Group (II) was divided into 4subgroups: Group (IIa): HFD. Group (IIb): HFD were treated with i.p 2.5 g/Kg b.w ginger oil. Group (IIc): (n=10) HFD were treated with i.p 2.5 g/Kg b.w rosemary oil. Group (IId): (n=10) HFD were treated with i.p 5 g/Kg b.w mixture of oils.Results: It was found that HFD rats showed a significant elevation in glucose, total cholesterol, triglyceride, GOT, GPT, alkaline phosphatase and a reduction in serum HDL-c compared with negative control. Treatment with ginger oil, rosemary oil and their mixture modulated the elevation of these parameters. Histopathological examination of the liver tissue of HFD rats showed a lipid deposition and macrophage infiltration and stenosis of hepatic vein. Treatment with mixture oils preserves normal structure of liver.Conclusion: It was concluded that, hypocholesterolemic effect was related to the active oil content as Rosemary oil contain - α-pinene, Camphor, cineole, borneol and Ginger oil contain Linalool, Terpineol ,Borneol , Eucalyptol.Keywords: Ginger Oil, Rosemary Oil, Rats, Hypocholesterolemi

Early and accurate detection of melanoma skin cancer using hybrid level set approach

Digital dermoscopy is used to identify cancer in skin lesions, and sun exposure is one of the leading causes of melanoma. It is crucial to distinguish between healthy skin and malignant lesions when using computerised lesion detection and classification. Lesion segmentation influences categorization accuracy and precision. This study introduces a novel way of classifying lesions. Hair filters, gel, bubbles, and specular reflection are all options. An improved levelling method is employed in an innovative method for detecting and removing cancerous hairs. The lesion is distinguished from the surrounding skin by the adaptive sigmoidal function; this function considers the severity of localised lesions. An improved technique for identifying a lesion from surrounding tissue is proposed in the article, followed by a classifier and available features that resulted in 94.40% accuracy and 93% success. According to research, the best method for selecting features and classifications can produce more accurate predictions before and during treatment. When the recommended strategy is put to the test using the Melanoma Skin Cancer Dataset, the recommended technique outperforms the alternative

MODULATION OF CARCINOGEN-METABOLIZING ENZYME BY MADINAH MINT (Mentha spp) IN RAT LIVER

Background: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P450 mixed function oxidase system. Materials and methods: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P450 mixed function oxidase) analysis Results The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (

Current Management Strategies in Breast Cancer by Targeting Key Altered Molecular Players

Breast Cancer is second largest disease affecting women worldwide. It remains the most frequently reported and leading cause of death among women in both developed and developing countries. Chemoprevention is one the promising approaches which reduces breast cancer. Tamoxifen and raloxifene are commonly used for treatment of breast cancer in women with high risk, although resistance occurs by tamoxifen after five years of therapy and both drugs cause uterine cancer and thromboembolic events. Aromatase inhibitors are coming up as potential option for prevention in treatment with adjuvant trials in practice. The combination of aromatase inhibitors along with tamoxifen can also be beneficial. For this, clinical trials based on large number of patients with optimal dose and lesser side effects have to be more in practice. Despite the clinical trials going on, there is need of better molecular models which can identify high risk population and new agents with better benefit having less side effects and improved biomarkers for treating breast cancer

Hypoxia drives glucose transporter 3 expression through HIF-mediated induction of the long non-coding RNA NICI

Hypoxia inducible transcription factors (HIFs) directly dictate the expression of multiple RNA species including novel and as yet uncharacterized long non-coding transcripts with unknown function. We used pan-genomic HIF-binding and transcriptomic data to identify a novel long non-coding RNA NICI (Non-coding Intergenic Co-Induced transcript) on chromosome 12p13.31 which is regulated by hypoxia via HIF-1 promoter-binding in multiple cell types. CRISPR/Cas9-mediated deletion of the hypoxia-response element revealed co-regulation of NICI and the neighboring protein-coding gene, solute carrier family 2 member 3 (SLC2A3) which encodes the high-affinity glucose transporter 3 (GLUT3). Knock-down or knock-out of NICI attenuated hypoxic induction of SLC2A3 indicating a direct regulatory role of NICI in SLC2A3 expression, which was further evidenced by CRISPR/Cas9-VPR mediated activation of NICI expression. We also demonstrate that regulation of SLC2A3 is mediated through transcriptional activation rather than post-transcriptional mechanisms since knock-out of NICI leads to reduced recruitment of RNA polymerase 2 to the SLC2A3 promoter. Consistent with this we observe NICI-dependent regulation of glucose consumption and cell proliferation. Furthermore, NICI expression is regulated by the VHL tumour suppressor and is highly expressed in clear cell renal cancer, where SLC2A3 expression is associated with patient prognosis, implying an important role for the HIF/NICI/SLC2A3 axis in this malignancy

BALANITES AEGYPTIACA PROTECTION AGAINST PROLIFERATION OF DIFFERENT CANCER CELL LINE

Background: The aim of the present study was to evaluate in vivo anti-tumor activity of Balanites aegyptiaca fruits extracts in addition to its role in cell cycle and apoptosis. Materials and Methods: Antitumor activities of ethylacetae extract (EAE), ethanol extract (EE) and chloroform extract (CE) were tested against different cell line Hep-2, MCF-7, HL-60 and HCV29T. Calculation of the IC50 values for these extracts confirmed that the most potent plant extract was EAE (40 ug/ml) followed by EE (55ug/ml), CE (61ug/ml). Results: The ethanolic and chloroform extracts showed lower difference in their potency, while the EAE was found to be more active indicating for nonpolar active principles responsible for the anti-proliferative activity. The ethanolic extract was three times higher active than the chloroform extract. The results obtained showed that EAE exert a significant anti-proliferative, enhancement of apoptosis and modulation of cell cycle phases compared with vincristine. Conclusion: The presence of alkaloids, flavonoids and Phenolics increase its efficiency as anti-proliferative action. EAE has promising anti-cancer activity with higher activity than EE or CE extract