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Sucul alanlarda yaşayan birincil üreticiler olan deniz algleri, önemleri nedeniyle birçok araştırmaya konu olmakla birlikte ilaç, kozmetik, gıda, yakıt ve tekstil endüstrilerinde önemli rol oynayan ökaryotik ve ötrofik organizmalardır. Makroalgler, potansiyel farmakolojik kullanımları olan birkaç makro besin, mikro besin ve diğer önemli biyolojik olarak aktif bileşikler (örneğin polifenoller, enzimler ve antibiyotikler) üretmesiyle bilinmektedir. Bu araştırmada, Codium fragile (Suringar) Hariot 1889’un metanol, etanol, aseton ve su ekstrelerinin kimyasal bileşimi, antimikrobiyal ve antioksidan aktiviteleri (3 yöntem ile), toplam fenolik (TPC) ve flavonoid (TFC) içeriklerini araştırmayı amaçlandı. LC-ESI-MS/MS analizleri gallik asit, 4-hidroksibenzaldehit, 4-hidroksibenzoik asit, p-kumarik asit, salisilik asit, biokanin A ve diosgenin içeren yedi bileşiğin tanımlanmasına izin verdi. Ekstrelerin TPC ve TFC değerleri sırasıyla 10,34±0,13-64,67±0,02 µg GAEs/mg ekstre ve 12,73±2,68-36,78±1,08 µg QEs/mg ekstre olarak hesaplandı. Metanol, etanol ve aseton ekstreleri gram negatif ve gram pozitif bakterilere karşı farklı seviyelerde aktivite göstermiştir (MİK: 3.125-1.562 mg/mL). Su ekstresi ABTS•+ (%70,43±14,85) ve DPPH• (%72,61±11,44) testlerine en yüksek aktiviteyi gösterirken, aseton ekstresi CUPRAC (absorbans: 0,60±0,15) testinde en yüksek aktiviteyi gösterdi. Elde ettiğimiz sonuçlar, C. fragile'in gıda koruyucuları ve diğer endüstriyel ve farmasötik alanlarda doğal bir biyoaktif madde kaynağı olarak değerlendirilebileceğini onaylamaktadır., Marine algae, which are the primary producers living in aquatic areas, are the subject of many studies due to their importance as they are eukaryotic and eutrophic organisms that play a crucial role in the pharmaceutical, cosmetic, food, fuel, and textile industries. Macroalgae are known in producing several macronutrients, micronutrients, and other important biologically active compounds (e.g. polyphenols, enzymes, and antibiotics) with potential pharmacological uses. In this research, we aimed to investigate the chemical composition, antimicrobial and antioxidant activities (with three assays), total phenolic (TPC) and flavonoid (TFC) contents of the methanol, ethanol, acetone, and water extracts of Codium fragile (Suringar) Hariot. The LC-ESI-MS/MS assessment allowed the identification of seven compounds containing gallic acid, 4-hydroxybenzaldehyde, 4-hidroxybenzoic acid, p-coumaric acid, salicylic acid, biochanin A, and diosgenin. TPC and TFC of the extracts were calculated as in the range of 10.34±0.13-64.67±0.02 µg GAEs/mg extract and 12.73±2.68-36.78±1.08 µg QEs/mg extract, respectively. All extracts of C. fragile showed antimicrobial activity against all test pathogens at different levels. The methanol, ethanol, and acetone extracts showed different levels of activity against gram-negative and gram-positive bacteria (MIC: 3.125-1.562 mg/mL). The water extract showed the highest activity in ABTS•+ (70.43±14.85%) and DPPH• (72.61±11.44%) assays while the acetone extract exhibited the best activity in CUPRAC (absorbance: 0.60±0.15) assay. The results we obtained approved that C. fragile could be valued as a natural source of bioactive agents for food preservatives and in other industrial and pharmaceutical fields.

Background: Prostate cancer(PCa) has the second-highest morbidity and mortality rates in men. Possessing facile surface chemistry and unique optical properties make silica nanoparticles(SiO2-NPs) promising cancer therapy materials. Objective: This study aimed to investigate the effects of SiO2-NPs and their derivatives, including SiNP-NH2, SiNP-Cl, and SiNP-SH against PCa and clarify their molecular mechanism on cell death, gene, and protein expressions. Methods: Following the synthesis and derivation of SiO2-NPs, their characterization was carried out using TEM, DLS, BET, and FT-IR. Cytotoxic properties of the compounds were investigated against different human cancerous cells, including HUH-7, A549, DLD-1, HeLa, NCI-H295R, and PC-3, as well as human healthy epithelium cell line PNT1A. Results: SiNP-NH2, SiNP-Cl, and SiNP-SH dose-dependently inhibited the proliferation of PC-3 cells with an IC50 value as 55.46 μg/mL, 55.09 μg/mL and 72.89 μg/mL, respectively. SiNP-SH significantly(p2-NPs and its derivatives. Conclusion: Our results demonstrated that –SH functioned SiO2-NPs can prevent the proliferation of human PCa by increasing apoptosis by upregulating gene and protein expression of p53(TP53) as well as caspase-3, caspase-9, and caspase-12 in the apoptotic pathway. Besides, the increased level of Smad-4 has also implicated the decreased cell proliferation. Hence, low sized SiNP-SH nanoparticles might be a suitable candidate for the treatment of human PCa.

Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatment of colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p -coumaric acid ( p -CA), on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO on controlled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p -CAis the main compound of EVO. EVO and p -CA inhibit the proliferation of human colon cancer cells DLD-1 and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells. mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p -CA. EVO and p -CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p -CA.

Phytochemicals, extracts, and mixtures obtained from plants have been offered as an option for cancer treatment and prevention for modern drug discovery in recent years. For this purpose, in this study, anti-colorectal cancer effects of the hexane, acetone, methanol, and water extracts obtained by sequential extraction from Euphorbia helioscopia L., Ferula elaeochytris Korovin, and Sideritis albiflora Hub.-Mor. on DLD-1 cell line were investigated in vitro by using Alamar blue assay. Dose-dependent inhibition was detected in the viability of DLD-1 cell line. In all three plants species, E. helioscopia (IC50: 140.83±0.31 µg/mL), F. elaeochytris (IC50: 67.93±0.12 µg/mL), and S. albiflora (IC50: 85.12±0.10 µg/mL) methanol extracts showed higher anti-colorectal effects on DLD-1 cell line compared to other extracts tested for the same species. In addition, the IC50 value of doxorubicin used as a standard was found as 6.10±0.55 µg/mL. With the results obtained, as the first report highlighting in vitro anti-colorectal cancer effects of the studied plant species on DLD-1 cell line, promising marks were obtained from the analysis of the extracts as anti-cancer sources for plant-derived drug applications., Bitkilerden elde edilen fitokimyasallar, ekstreler ve karışımlar, son yıllarda modern ilaç keşfi için kanser tedavisinde ve önlenmesinde bir seçenek olarak sunulmuştur. Bu amaçla, bu çalışmada sıralı ekstraksiyon kullanılarak Euphorbia helioscopia L., Ferula elaeochytris Korovin ve Sideritis albiflora Hub.-Mor. bitkilerinden elde edilen hekzan, aseton ve metanol ekstrelerinin DLD-1 hücre hattı üzerindeki anti-kolorektal kanser etkileri Alamar mavisi testi kullanılarak in vitro olarak incelendi. DLD-1 hücre hattının canlılığında doza bağlı inhibisyon tespit edildi. Üç bitki türünün hepsinde, E. helioscopia (IC50: 140.83±0.31 µg/mL), F. elaeochytris (IC50: 67.93±0.12 µg/mL) ve S. albiflora (IC50: 85.12±0.10 µg/mL) metanol ekstreleri aynı türler için test edilen diğer ekstrelere kıyasla DLD-1 hücre hattı üzerine daha yüksek anti-kolorektal kanser etkisi gösterdi. İlaveten, standart olarak kullanılan doksorubisinin IC50 değeri 6.10±0.55 µg/mL olarak belirlendi. İncelenen bitki türlerinin DLD-1 hücre hattı üzerindeki in vitro anti-kolorektal kanser etkilerini vurgulayan bu ilk çalışma ile bitki kaynaklı ilaç uygulamaları için anti-kanser kaynakları olarak ekstraktların analizinden umut verici sonuçlar ortaya çıkarıldı.

An ecofriendly and efficient procedure for the synthesis of silver nanoparticles (AgNPs) was performed using aqueous extract of Enteromorpha intestinalis as reducing, capping, and stabilizing agents. AgNPs were characterized by UV spectroscopy, Fourier transform infrared (FTIR), high-resolution transmission electron microscope (HRTEM), and EDX. Moreover, the optimum conditions for the green synthesis were studied and the antimicrobial activity were estimated by agar well diffusion and broth dilution methods. UV vis spectroscopy confirmed the formation of AgNPs due to their surface plasmon resonance. The optimum conditions for the biosynthesis of AgNPs were using 2.5 g or 5 g/100 ml (w/v) of algal biomasses for extraction, and 1 mM of silver ions within 72 h. Transmission electron micrographs showed that AgNPs were spherical in shape and with a mean average size of 9.17 ± 3.2 nm. FTIR revealed the that protein and polysaccharides are responsible for AgNPs synthesis. Additionally, AgNPs exhibited antimicrobial activity against all tested microorganisms. The minimum Inhibitory concentration for all bacteria and Candida albicans ATCC26555 was 6.25 µg/ml except Klebsiella Pneumoniae ATCC70603 and Staphylococcus aureus ATCC4330 was 12.5 µg/ml. Further studies will be recommended to estimate the cytotoxicity of these AgNPs on the human cell line. The future use of algae as green nanofactory will be important in medical applications.

In the study, fluorescent imaging of live cells was performed using fluorescent carbon quantum dots derived from edible mushrooms species; Agaricus bisporus, Pleurotus ostreatus, and Suillus luteus as a fluorophore agent. Carbon quantum dots were synthesized through a facile and low-cost method based on microwave irradiation of dried mushroom samples in hydrogen peroxide solution under optimized conditions (microwave energy, solution type, duration of microwave treatment, amount of mushroom). Upon purification with centrifugation, microfiltration, and dialysis, the lyophilized carbon quantum dots were identified through UV-visible, fluorescence and FT-IR, X-ray photoelectron spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy, and quantum yield calculation. Cell viability assessment of the carbon quantum dots was evaluated against human epithelial cell line PNT1A using the Alamar Blue Assay. In vitro fluorescence cell imaging studies demonstrated that the carbon dots could dynamically penetrate the cell membrane and nuclear membrane and localize in both the cytoplasm and the nucleus.

Objective: The aim of this study was to investigate antioxidant, enzyme inhibitory and cytotoxic activities of Agropyron repens and Crataegus monogyna methanol extracts with total phenolic and flavonoid contents. Materials and Methods: Total phenolic and flavonoid contents of A. repens and C. monogyna methanol extracts were measured according to Folin Ciocalteu and aluminum nitrate methods, respectively. Antioxidant and enzyme inhibitory activities of the methanol extracts were tested spectrophotometrically. Also, cytotoxic activities of the methanol extracts against DLD-1 and CCD-18Co were investigated by using Alamar Blue assay. Results: C. monogyna methanol extract with the highest total phenolic and flavonoid contents (68.13±0.34 µg GAEs/mg extract and 36.91±0.17 µg QEs/mg extract, respectively) had the best antioxidant activity in β-carotene-linoleic acid (IC50: 32.72±0.15 µg/mL), CUPRAC (A0.50: 282.69±0.25 µg/mL), DPPH• (IC50: 71.69±0.85 µg/mL), and ABTS•+ (IC50: 40.43±0.55 µg/ mL) assays. A. repens methanol extract showed the highest effect against AChE (18.73±0.47 %), BChE (37.59±1.07 %), urease (89.18±0.84%), α-glucosidase (6.71±0.23 %), whereas C. monogyna methanol extract showed the highest effect against tyrosinase (30.52±1.00%) and α-amylase (37.24±0.06 %). Also, A. repens (IC50: 57.38 µg/mL) and C. monogyna (IC50: 54.04 µg/ mL) methanol extracts showed close cytotoxic activity on DLD-1. Conclusion: Antioxidant, cytotoxic, and enzyme inhibitory activities of A. repens and C. monogyna methanol extracts were investigated with total phenolic and flavonoid contents in this study. The results obtained with this study strengthen the potential of the studied plants as a new source for the discovery of antioxidant, cytotoxic, and enzyme inhibitor agents.

Porodaedalea pini is a medicinally important mushroom with antioxidant, cytotoxic, immunostimulating, antitumor, antiviral and immunomodulating activities. Therefore, in this study, P. pini methanol extract and isolated compounds from the methanol extract were tested for cytotoxic activities against DLD-1 (colorectal cancer) and CCD-18Co (human colon fibroblast cell line) by using Alamar Blue assay. Cytotoxic activity on DLD-1 was decreased in the order of P. pini methanol extract> 4-(3,4-dihydroxyphenyl)but-3-en-2-one (3)> pinoresinol (2)> ergosta-7,24(28)-dien-3β-ol (1). P. pini methanol extract was determined to have the best cytotoxic activity with the lowest IC50 value on DLD-1 (IC50: 25.33±0.29 µg/mL) and the highest IC50 value on CCD-18Co (434.30±1.45 µg/mL). Within the scope of the findings, it is thought that P. pini mushroom can be used as a new and natural agent in the treatment of colorectal cancer.

The metal complexes of Zn(II), Ni(II), Cu(II) and Pb(II) with asymmetrical Schiff bases were synthesized. The asymmetrical Schiff base was obtained through the condensation of 1,2-phenylenediamine, 4-methyl-1,2-phenylenediamine, 2-hydroxy-1-napthaldehyde and biphenyl-4-carbaldehyde. The new Schiff base ligands (L1' and L2') and their metal complexes were characterized by TG/DTG, FT-IR, 1H-NMR, UV–Vis, ESR, powder XRD, elemental analysis, magnetic moment and fluorescence studies. The powder XRD studies indicate that Co(II) and Cu(II) complexes are amorphous, while Ni(II) and Zn(II) complexes are crystalline. The anticarcinogenic effects of L1' and L2' were also investigated against colon (SW-620) and cervical cancer (HeLa) cell lines and compound L2' was found to possess the highest anticarcinogenic potential, with 16.7 µM and 27.5 µM of IC50 values for HeLa and SW620 cells, respectively.

WOS: 000396702900011, In the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mu M/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P) H: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109R012], This study was supported by a grant from The Scientific and Technological Research Council of Turkey (109R012).

Calixarenes are supramolecular structures characterized by their "calix" shape and their easy synthetic accessibility. They are amphiphilic in nature, thus they can bear in their structure both hydrophobic and hydrophilic features as well as charged groups. They are characterized by architectural plasticity responsible for their unique fine-tuned properties that can be shaped for an array of applications. Herein, we will focus, on their diverse available applications, and give special emphasis on biocatalysis and cancer therapy as two modern directions and emerging fields of interest that have been sporadically explored in the literature and can pave the way for the discovery of novel therapeutics. This review provides the first exhaustive examination on the enhanced catalytic activity and selectivity of calixarene-based encapsulated biocatalysts towards the synthesis of bioactive molecules. The application of functionalized calixarenes in cancer therapy is also analyzed towards the spatiotemporal control they can offer in targeted drug delivery.

In the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms,and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001). © 2016 Taylor & Francis Group, LLC.

Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions. Cancer Res; 75(19); 4026–31. ©2015 AACR.

Prostate cancer is the third most common cause of male cancer death in developed countries, and one of the most comprehensively characterized human cancers. Roughly 60% of prostate cancers harbor gene fusions that juxtapose ETS-family transcription factors with androgen regulated promoters. A second subtype, characterized by SPINK1 overexpression, accounts for 15% of prostate cancers. Here we report the discovery of a new prostate cancer subtype characterized by rearrangements juxtaposing the SMAD inhibitor SKIL with androgen regulated promoters, leading to increased SKIL expression. SKIL fusions were found in 6 of 540 (1.1%) prostate cancers and 1 of 27 (3.7%) cell lines and xenografts. 6 of 7 SKIL-positive cancers were negative for ETS overexpression, suggesting mutual exclusivity with ETS fusions. SKIL knockdown led to growth arrest in PC-3 and LNCaP cell line models of prostate cancer, and its overexpression led to increased invasiveness in RWPE-1 cells. The role of SKIL as a prostate cancer oncogene lends support to recent studies on the role of TGF-β signaling as a rate-limiting step in prostate cancer progression. Our findings highlight SKIL as an oncogene and potential therapeutic target in 1-2% of prostate cancers, amounting to an estimated 10,000 cancer diagnoses per year worldwide. This article has supplementary files, which can be found here:http://dx.doi.org/10.18632/oncotarget.3359

The present study was designed to evaluate different doses of ellagic acid (EA)in vivoin rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.

Epilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxyresorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content. © 2014 Springer International Publishing Switzerland.

The aim of this study was to investigate the effects of plant phenolic compound tannic acid (TA) on proliferative, metastatic, invasive properties of prostate cancer (PCa) cells; PC-3 and LNCaP, as well as drug metabolizing and antioxidant enzymes. Characterization of TA was done by using FT-IR and NMR. TA dose dependently inhibited the proliferation of PC-3 and LNCaP cells with IC50 values 35.3 mu M and 29.1 mu M, respectively. Wound healing assay showed that TA significantly inhibited (92.7%) migration of PCa cells (p

Context: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes. Objective: This study investigated in vivo effects of Epilobium hirsutum (EH) on CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA expressions in liver. Materials and methods: Male Wistar Albino rats were injected with EH at a dose of 37.5mg/kg i.p. daily for 9d. CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA levels were determined by enzyme assays, Western blotting and qPCR, respectively. Results: CYP1A1 associated ethoxyresorufin-O-deethylase activity of control and EH-treated animals were found as 6.54±1.21 and 4.48±1.67nmol/min/mg, respectively. CYP2E1 associated aniline 4-hydroxylase of control and EH group were 0.537±0.011 and 0.109±0.01nmol/min/mg, respectively. However, EH treatment increased the GPx and NQO1 activities from 0.069±0.015 to 0.107±0.026nmol/min/mg and from 163.34±92 to 588.3±14nmol/min/mg, respectively. Furthermore, protein and mRNA expression analysis revealed that CYP1A1 and CYP2E1 levels were decreased while those of NQO1 and GPx increased after EH treatment. Discussion and conclusion: Our current data suggest that the metabolism of xenobiotics, including drugs, may be altered due to changes in the expression and activity of these proteins by EH. © 2013 Informa Healthcare USA, Inc.

In the present study, to better understand the role of different nitric oxide synthase (NOS) isoforms in hippocampus-dependent forms of learning, we examined the expression of neural, endothelial, and inducible NOS in the hippocampus of young-adult rats classified as "poor" and "good" learners on the basis of their performance in the partially baited 12-arm radial maze. Taking into consideration strain-dependent differences in learning skills and NOS expression, experiments were performed on two different lines of laboratory rats: the inbred Wistar (W) and the outcrossed Wistar/Spraque-Dawley(W/S) line. The hippocampal levels of NOS proteins were assessed by Western Blotting. In the present study, genetically more homogenous W rats showed a slower rate of learning compared to the genetically less homogenous outcrossed W/S rats. The deficient performance in the W rat group compared to outcrossed W/S rats, and in "poor" learners of both groups compared to "good" learners was due to a higher percentage of reference memory errors. The overall NOS levels were significantly higher in W group compared to outcrossed W/S rats. In both rat lines, the rate of learning positively correlated with hippocampal levels of nNOS and negatively correlated with iNOS levels. Hippocampal eNOS levels correlated negatively with animals' performance but only in the W rats. These results suggest that all 3 NOS isoforms are implemented but play different roles in neural signaling. (C) 2012 Elsevier B.V. All rights reserved.

Background: Prostate cancer (PC) is the second most common cancer among men. Most PC-related deaths are due to invasive tumors that are treated with therapies inhibiting androgen production or androgen receptor (AR) activity. After an initial response, tumors invariably progress to castration resistant prostate cancers (CRPCs) for which no effective cure exists. Methods and Results: We used transcriptome sequencing to study fresh-frozen tissue specimens from 12 benign prostatic hyperplasias (BPHs), 28 PCs, and 13 CRPCs. Reference-based transcriptome assembly uncovered 145 previously unannotated intergenic PC and CRPC associated long non-coding transcripts (lncRNAs) or isoforms. One third of the transcripts were CRPC-specific. We showed that one of the novel transcripts, Prostate Cancer Associated Transcript 5 (PCAT5), expressed in half of the tumors, was likely regulated by ERG, the key transcription factor in ∼50% of prostate cancers. Genome-wide expression analysis of a PCAT5-positive prostate cancer cell line after PCAT5 knockdown suggested significant alterations in proliferation pathways. In vitro validation of the pathway alterations revealed concordantly dramatic effects in phenotype: stalling of cell growth, migration, invasion, and colony forming potential, and increase in the rate of apoptosis. Conclusions: We identified the key differences between PC and CRPC in transcriptome level, and validated the oncogenic potential of a novel lncRNA in ERG-positive prostate cancers, PCAT5. Our study presents a number of putative lncRNA biomarkers for CRPC, and opportunities for therapeutic intervention. Citation Format: Antti Ylipää, Kati Kivinummi, Matti Annala, Annika Kohvakka, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi, Matti Nykter. Transcriptome sequencing reveals PCAT5 - new ERG-regulated non-coding transcript in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 148. doi:10.1158/1538-7445.AM2015-148

Prostate cancer is the third most common source of male cancer deaths in developed countries. The standard of care for aggressive prostate cancer is androgen ablation, which prolongs survival until the tumor acquires a castration resistant phenotype. The molecular pathology underlying prostate cancer progression is not yet fully understood. We used integrative high throughput sequencing to study cancer-associated alterations in 53 prostate cancer related neoplasia at the DNA, RNA and epigenetic levels. The cohort included both hormone-naive and castration resistant prostate cancers, along with two neuroendocrine prostate cancers. We identified two new fusion genes, one of which associated with neuronal differentiation and castration resistance. We also identified a number of novel prostate cancer associated transcripts, including transcripts specific to castration resistant tumors. Based on ChIP-seq data from prostate cancer cell lines, many of the novel transcripts were regulated by known oncogenes such as ERG and AR. Methylation sequencing revealed a near-identical pattern of promoter hypermethylation in both hormone-naive and castration resistant tumors. Enrichment of hypermethylation was observed at EZH2 binding sites, supporting the role of EZH2 in the recruitment of DNA methyltransferase in prostate cancer. Promoter hypermethylation suppressed the expression of hundreds of genes, but a subset of genes characterized by promoter H3K27 trimethylation responded to hypermethylation with increased expression. Citation Format: Matti J. Annala, Kati K. Waltering, Antti Ylipää, Kimmo Kartasalo, Kirsi Tuppurainen, Serdar Karakurt, Leena Latonen, Outi Saramäki, Simo-Pekka Leppänen, Janne Seppälä, Hanna E. Rauhala, Teuvo LJ Tammela, Olli Yli-Harja, Wei Zhang, Tapio Visakorpi, Matti Nykter. Integrative sequencing reveals novel alterations in untreated and castration resistant prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5217. doi:10.1158/1538-7445.AM2013-5217