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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.

Correlation results for the novel transcripts.

Cell cycle regulation (S1); Androgen biosynthesis and androgen receptor [AR] signaling (S2); Validation of PCAT5 expression pattern by RT-PCR (S3); Normalized read counts of four TPCATs are plotted in our BPH, PC, and CRPC samples, and complemented with prostate cancer cell lines, normal tissues, human embryonic stem cells, and prostate cancer samples from three additional data sets (S4); Inferred exon structures for four novel transcripts that were validated with RT­PCR (S5); Open chromatin markers and ERG binding at the locus of PCAT5 (S6); ETV4 and PCAT5 expression after 25nM ETV4-siRNA or scrambled CTRL-siRNA treatment in PC-3 cells (S7); Transfection with PCAT5­specific siRNAs did not affect the growth of PCAT5 negative prostate cancer cell line 22Rv1 (S8); Relative cell viability of PCAT5-siRNA transfected ERG-positive DuCaP cells (S9).

Supplementary Figure Legends from Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer

Description of additional methods and procedures used in the study. Also includes Supplementary References.

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.

The present study’s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC 50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L–1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.

Since calixarenes are more easily synthesized and functionalized than other supramolecules, they are compounds of interest in organic chemistry. In this study, the dihydrazide (3a and 3b) and diamino propyl (6a and 6b) derivatives of p-tert-butylcalix[4]arene and calix[4]arene were synthesized. Then the L-proline methyl ester substituted chlorocyclopropenium was reacted with the calix[4]arene derivatives (3a, 3b, 6a, and 6b) at room temperature in CH2Cl2 to obtain calix[4]arene superbase derivatives (4a, 4b, 7a, and 7b) in 75%, 60%, 70%, and 55% yield, respectively. The synthesized compounds' structure was elucidated using spectroscopic techniques (FTIR, H-1 NMR, and C-13 NMR). The cytotoxic properties of the calix[4]arene superbase derivatives were investigated against different human cancer cell, including A549, DLD-1, HEPG2, and PC-3 and human healthy epithelium cell line PNT1A. The cytotoxicity results showed that calix[4]arene superbase derivatives inhibited the proliferation of DLD-1, A549, HEPG2, and PC-3 cells in a dose-dependent manner. Compound 7a had the highest toxic effect on colorectal carcinoma (IC50: 4.7 mu M), and the IC50 values were 18.5 mu M and 74.4 mu M against human prostate and lung cancer cells, respectively. Furthermore, compound 4b was found more effective on hepatocellular carcinoma cells (IC50: 210.2 mu M). As a result, the synthesized calix[4]arene superbase derivatives can be developed to treat different human cancer cell. They can be considered as a preliminary result for molecular-level research.

Synthesis of 1,8-naphthalimide derivatives and biochemical studies using them as anti-cancer and cellular imaging agents have attracted significant attention in recent years. This study aimed to synthesize two new fluorescent lower rim-functionalized 4-sulfo-1,8-naphthalimide derivatives of calix[4]arenes [4 and 7] and examination of their cytotoxic properties for cancerous cells. For this purpose, p-tert-butylcalix[4]arene bearing dihydrazide [3] or diaminopropyl [6] units on its lower rim were reacted with 4-sulfo-1,8-naphthalic anhydrate. The structure of these synthesized compounds has been characterized using 1H-NMR, 13C-NMR, and FT-IR techniques. To investigate the anti-cancer properties, compounds 4, 7, and N,N-dimethylaminoethyl-1,8-naphthalimide [8] were tested on the human colorectal cancer cell line (DLD-1) as well as healthy colon epithelial cell line (CCD-18Co). The IC50 values of 4 and 7 were determined as 12.95 µM and 16.13 µM, respectively, on DLD-1 cells. Furthermore, following the treatment of CCD-18Co cells with 4 and 7, the IC50 values were determined as 508 µM and 269 µM, respectively. However, it was observed that compound 8 had no cytotoxic effect on both DLD-1 cells and CCD-18Co cells. Furthermore, the fluorescence imaging of human colorectal cancer cells treated with the synthesized compounds [4, 7, and 8] was performed on living cells.

Although quercetin is an effective bioactive compound preventing the progress of several human cancers, its impact is reduced due to low bioavailability. The therapeutic potential of quercetin can be enhanced by its encapsulation with macromolecules. In the current study, stable complexes of water-soluble p-sulfonato calix[4,8]arene N,N-dimethylamine derivatives (calix[4]arene (T-4) and calix[8]arene (O-4)) with quercetin (C-1 and C-2) were synthesized and thoroughly characterized, and their cytotoxic effects were evaluated. The first phase solubility study performed shows that the solubility of quercetin is improved because of the formation of the inclusion complex. The solubility constant (Ks) values of T-4-quercetin and O-4-quercetin complexes were calculated to be 205.77 mM and 111.85 mM, respectively. In vitro cytotoxic assays of both complexes on different cancer cell lines were performed by using an alamarBlue assay. Acquired data revealed that the cytotoxic potential of complexes C-1 and C-2 was increased by 3.95 and 2.98-fold, respectively, compared to quercetin. Molecular docking and molecular dynamics simulations of the complexes were also performed to predict the three-dimensional structure of host–guest interactions as well as to obtain crucial time-dependent insight into the calixarene and quercetin complex formation dynamics.

A disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) proteinase family play an important role in many physiological and physiopathological processes such as the maintenance of locomotor system health in sport horses. In this study, we aimed to determine the changes of ADAMTS-4 and ADAMTS-5 levels in concour horses before and after exercise. The Oldenburg and Selle Français horse-breed types which are healthy, 6-15 years old, around 650-750 kg, and distinct genders were used (n=10). Following the physical examinations, the horses were subjected to 50 minutes of regular exercise program. Blood samples were collected into anticoagulant-free tubes in order to determine ADAMTS-4 and ADAMTS-5 mRNA expression and ELISA levels before and after exercise. There were no differences were observed statistically on ADAMTS-4, neither mRNA expression in spite of 25% downregulated, nor at the ELISA levels. On the other hand, ADAMTS-5 mRNA expression was upregulated 3.88 fold (p

The present study evaluated whether short-term exposure to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) has different effects on rats' behaviour and hippocampal levels of central cholinergic biomarkers. Animals were divided into three equal groups namely; group 1 was sham-exposed group, group 2-3 were exposed to 45 V/m and 65 V/m doses of 2.1 GHz frequency for 1 week respectively. Numerical dosimetry simulations were carried out. Object location and Y-maze were used as behavioural tasks. The protein and mRNA expression levels of AChE, ChAT, and VAChT, in the hippocampus were tested using Western Blotting and Real-Time PCR. The impairment performance of rats subjected to 65 V/m dose of 2.1 GHz RF-EMR in both object location and Y-maze tasks was observed. The hippocampal levels of AChE, ChAT, and VAChT, were significantly lower in rats exposed to 65 V/m dose of 2.1 GHz RF-EMR than others. The stronger effect of "65 V/m" dose on both rat's hippocampal-dependent behavioural performances and hippocampal levels of cholinergic biomarkers may be due to the stronger effect of "65 V/m" dose where rats' snouts were located at the nearest distance from the monopole antenna. Furthermore, the simulated SAR values were high for 65 V/m electric-field strengths. For the first time, we report the potential dose-dependent effects of short-term exposure to 2.1 GHz radiation on rat's behavioural performances as well as hippocampal levels of cholinergic biomarkers. Further studies are needed to understand the mechanisms by which RF-EMR influences the function of the central cholinergic system in the brain.

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.

SUMMARY OBJECTIVE: This study aimed to evaluate the hepatoprotective effect of artichoke leaf extract (Cynara scolymus) in experimental obstructive jaundice. METHODS: Rats were separated into three groups, namely, sham, control, and artichoke leaf extract. Ischemia was created for 60 min, and then liver tissue and blood samples were taken at the 90th minute of reperfusion. Artichoke leaf extract was given at a 300 mg/kg dose 2 h before the operation. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum. Histopathological findings of the liver were scored semiquantitatively. RESULTS: Antioxidant enzyme activities in the artichoke leaf extract group were statistically significantly higher than that in the other two groups. Biochemical parameters, which show hepatocellular damage, were found to be similar in both sham and artichoke leaf extract groups. Although the values in the sham group were higher than the artichoke group in terms of protein and gene expressions, no statistically significant difference was found between these two groups. Regarding the hepatocellular effects of obstructive jaundice, the artichoke leaf extract group showed lower scores than the control group in all histopathological scores. CONCLUSION: The results of this study showed that artichoke leaf extract had a hepatoprotective effect that was associated with the antioxidant and anti-inflammatory effects of artichoke leaf extract.

Purpose: This study aims to compare the cytotoxic, apoptotic, and oxidative effects of preserved and preservative-free forms of brimonidine 0.15% on the human corneal epithelial cell (HCEC) line.Methods: Time-dependent cytotoxicity studies were performed at 5 and 15 minute and 1, 6, and 24 hour with the Alamar Blue method in HCEC treated with test solutions. For apoptotic studies, Annexin-V and 7-AAD staining were performed and flow cytometry was used. To support this, mRNA expressions and protein expressions of BAX, BCL-2, and caspase-3, -9, -12, which are among the proapoptotic genes, were evaluated by qRT-PCR and Western-Blot method, respectively.Results: Cell viability was 76.4% with the preserved solution and 36.05% with the preservative-free solution at the 5th minute. No significant difference was observed with either solution at the 15-minute mark, while cell viability did not change significantly after 1 hour. In the apoptosis evaluation, it was observed that the preservative-free solution increased the early apoptotic activity to a greater degree (2.91-fold, pConclusion: It was demonstrated that the preserved solution is less cytotoxic to the HCEC line in the early period, has less early apoptotic activity, and does not significantly increase ROS levels. Further investigations of individual components are necessary to fully understand the toxicity of these ophthalmic solutions.

Purpose: This study aims to compare the cytotoxic, apoptotic, and oxidative effects of preserved and preservative-free forms of brimonidine 0.15% on the human corneal epithelial cell (HCEC) line. Methods: Time-dependent cytotoxicity studies were performed with the Alamar Blue method. For apoptotic studies, PE Annexin V and 7-amino-actinomycin (7-AAD) staining and flow cytometry were performed. Messenger RNA (mRNA) expressions of Bax, Bcl-2, and caspase-3, -9, -12, and protein expressions of Bax and Bcl-2 were evaluated by quantitative real-time polymerase chain reaction and Western blot method, respectively. Results: Cell viability was 76.4% with the preserved solution and 36.05% with the preservative-free solution at the fifth minute. No significant difference was observed with either solution at the 15-min mark, whereas cell viability did not change significantly after 1 h. In the apoptosis evaluation, it was observed that the preservative-free solution increased the early apoptotic activity to a greater degree (P < 0.05). Preservative-free solution also induced gene expression of proapoptotic Bax, caspase-9 and -12, and protein expression of Bax while reducing the protein expression of anti-apoptotic Bcl-2 (P < 0.0001). Preserved solution induced only the gene expression of caspase-12, and reduced the protein expression of Bcl-2 (P < 0.0001). No significant difference was observed in the reactive oxygen species (ROS) levels of either solution compared with the control group (P > 0.05). Conclusion: It was demonstrated that the preserved solution is less cytotoxic to the HCEC line in the early period, has less early apoptotic activity, and does not significantly increase ROS levels.

SUMMARY OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. METHODS: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. RESULTS: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. CONCLUSIONS: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.

PubMed: 31526236, Naringenin is considered as an important flavonoid in phytochemistry because of its important effect on cancer chemoprevention. Unfortunately its poor solubility has restricted its therapeutic applications. In this study, an efficient water-soluble fluorescent calix[4]arene (compound 5) was synthesized as host macromolecule to increase solubility and cytotoxicity in cancer cells of water-insoluble naringenin as well as to clarify localization of naringenin into the cells. Complex formed by host–guest interaction between compound 5 and naringenin was analyzed with UV–visible, fluorescence, FTIR spectroscopic techniques and molecular modeling studies. Stern–Volmer analysis showed binding constant value of Ksv 3.5 × 107 M?1 suggesting strong interaction between host and guest. Binding capacity shows 77% of naringenin was loaded on compound 5. Anticarcinogenic effects of naringenin complex were evaluated on human colorectal carcinoma cells (DLD-1) and it was found that 5-naringenin complex inhibits proliferation of DLD-1 cells 3.4-fold more compared to free naringenin. Fluorescence imaging studies show 5-naringenin complex was accumulated into the cytoplasm instead of the nucleus. Increased solubility and cytotoxicity of naringenin with fluorescent calix[4]arene makes it one of the potential candidates as a therapeutic enhancer. For deep understanding of host–guest interaction mechanisms, complementary multiscale molecular modeling studies were also carried out. Communicated by Ramaswamy H. Sarma. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

WOS: 000482176800112, PubMed: 31460346, In biology, the activity of enzymes is usually regulated by feedback loops, which enables direct communication between enzymes and the state of the cell. In a similar manner, with the intention to have automated activity regulation, the therapeutic effect of a photosensitizer (BOD1) is shown to be reduced through a negative feedback loop initiated by the photosensitizer. Photodynamic action produces cytotoxic O-1(2) and this reactive oxygen species reacts with ascorbate, generating H2O2. Peroxide-mediated oxidation of the photosensitizer auxiliary group leads to the formation of inactive BOD2 from the parent photosensitizer. BOD1 is shown to accumulate in mitochondria, and cell viability is shown to decrease significantly with BOD1 compared to the loop end product, BOD2. Photoinduced enhancement of fluorescence indicates the formation of inactive BOD2 under cellular conditions, and enhanced fluorescence acts as a reporter for the activity of the photosensitizer. We present the first example of PDT autoinactivation, and such a feedback control mechanism would enable a decrease in post-therapy side effects., BAGEP Award of the Science Academy, This work was supported by the BAGEP Award of the Science Academy.

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential, we developed a nanohybrid delivery platform with a noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulfonatocalix[4]arene, enabling a 62 000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in an acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate noncovalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50-fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetin-loaded nanoparticles altered the expression of 27 genes related to apoptosis.

Since calixarenes are more easily synthesized and functionalized than other supramolecules, they are compounds of interest in organic chemistry. In this study, the dihydrazide (3a and 3b) and diamino propyl (6a and 6b) derivatives of p-tert-butylcalix[4]arene and calix[4]arene were synthesized. Then the L-proline methyl ester substituted chlorocyclopropenium was reacted with the calix[4]arene derivatives (3a, 3b, 6a, and 6b) at room temperature in CH2Cl2 to obtain calix[4]arene superbase derivatives (4a, 4b, 7a, and 7b) in 75%, 60%, 70% and 55% yield, respectively. The synthesized compounds' structure was elucidated by using spectroscopic techniques (FTIR, 1H NMR, and 13C NMR ). The cytotoxic properties of the calix[4]arene superbase derivatives were investigated against different human cancerous cells, including A549, DLD-1, HEPG2, and PC-3, as well as human healthy epithelium cell line PNT1A. The cytotoxicity results showed that calix[4]arene superbase derivatives inhibited the proliferation of DLD-1, A549, HEPG2, and PC-3 cells in a dose-dependent manner. Compound 7a had the highest toxic effect on colorectal carcinoma (IC50: 4.7 µM), and the IC50 values were 18.5 µM and 74.4µM against human prostate and lung cancer cells, respectively. Furthermore, the compound 4b was found more effective on hepatocellular carcinoma cells (IC50: 210.2 µM). As a result, the synthesized calix[4]arene superbase derivatives can be developed to treat different human cancer cells. They can be considered as a preliminary result for molecular-level research.

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.

Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme (GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and high toxicity have directed the scientific community's interest to the development of new therapeutic agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way on the design and development of new therapeutic agents as a result of their unique properties. Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical properties and increased efficacy against glioblastoma multiforme.

Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme (GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and high toxicity have directed the scientific community's interest to the development of new therapeutic agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way on the design and development of new therapeutic agents as a result of their unique properties. Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical properties and increased efficacy against glioblastoma multiforme.

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.

A novel dual channel probe based on bisphenol A-rhodamine (BAR) was successfully designed and synthesized with high selectivity and sensitivity to Zn2+ and Hg2+ ions. BAR exhibited an effectively selective and sensitive recognition toward Zn2+ and Hg2+ ions through two different mechanisms (i.e. ESIPT and FRET) in pure MeCN and MeCN-H2O (v/v = 8/2, 5 mM, HEPES, pH 7.0) over other cations. The complexation properties of BAR with Zn2+ and Hg2+ ions were examined by 1H NMR, 13C NMR and FTIR experiments. The detection limits for Zn2+ and Hg2+ were 2.21 and 2.16 μM, respectively. Furthermore, possible utilization of BAR as bio-imaging fluorescent probe to detect Hg2+ in human prostate cancer cell lines was also observed by Fluorescent Cell Imager.

Utilization of fluorescent techniques in detection of various metal ions actively pursued allow ultrasensitive and selective detections of metal ions and prevent the adverse effect of cations such as aluminum (III) ions. In this study, two novel fluorescent chemosensors containing thiazole derivatives, ((E)-2-(4-hydroxy-3-(((2-hydroxyphenyl)imino)methyl)phenyl)-3-phenyl thiazolidin-4-one) AM1 and (2,3-bis(4-hydroxy-3-((E)-((2hydroxyphenyl)imino) methyl) phenyl) thiazolidin-4-one) AM2, have been fabricated. The probes AM1 and AM2 were prepared using the condensation reaction between 2-hydroxy-5-(4-oxo-3-phenyl thiazolidin-2-yl) benzaldehyde and 2-aminophenol for the probe AM1 and 5,5'-(4-oxothiazolidine-2,3-diyl)bis(2-hydroxy benzaldehyde) and 2-aminophenol for the probe AM2. Afterwards, they were analyzed by various types of NMR and FT-IR spectroscopy, ESI-MS spectra, and elemental anayzer. As a second step, each fabricated chemosensor was able to use turn on fluorescence sensing for detecting of Al3+ ions in ACN/H2O (v/v = 50/50, 10.0 mu M, pH = 7.0) solution. Clear complexes formed between the probe AM1 and Al3+ ions and also the probe AM2 and Al-3 (+) ions was determined by not only H-1 NMR titration study but also calculated by using the Job's plot. The limit of detection (LOD) value was found to be 0.11 mu M(AM1) and 4.4 mu M(AM2) for Al3+ ions. Likewise, cell imaging and in vitro cytotoxicity experiments of Al3+ ions in Human epithelium Lovo cells exhibited that prepared chemosensors had low cytotoxicity and blue fluorescence when they treated with of Al3+ ions in the cellular system. (C) 2020 Elsevier B.V. All rights reserved.

The present study demonstrates the synthesis of water-soluble fluorescent calix[4]arenes ( 6 and 7 ) and its application in living cell imaging for Hg 2 + detection at a low level. The synthesized fluorescent ligands 6 and 7 were characterized by 1 H NMR technique. The fluorescent study showed both water soluble ligands were Hg 2 + selective and follow photo-induced electron transfer (PET) process. From the fluorimeter titration experiment detection limit was calculated as 1.14 × 10 − 5 and 3.42 × 10 − 5 for ligand 6 and 7, respectively. From the Benesi-Hildebrand plot binding constant values were evaluated as 666.7 and 733.3 M − 1 for 6 and 7 , respectively. The interactions between ligands 6 and 7 and Hg 2 + were also demonstrated in living cells, SW-620, using Fluorescent Cell Imager. While ligands 6 and 7 alone show fluorescent properties, they loss their action with the presence of Hg 2 + in SW-620 cells.

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.

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential we developed a nanohybrid delivery platform with noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulphonatocalix[4]arene, enabling a 62,000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate non-covalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50 fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetinloaded nanoparticles altered the expression of 27 genes related to apoptosis.

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.

We report the design and synthesis of a new perylene bisimide derivative containing calix[4]arene units (PB-CX[4]) as “turn on” fluorescent sensor for Hg2+ ion determination. PB-CX[4] showed highly selective and sensitive “turn-on” fluorescent responses toward Hg2+ ion based on photoinduced electron transfer (PET) mechanism in DMF/H2O (v/v, 95/5). The binding analysis using a Job plot suggested that PB-CX[4] formed a 1:2 complex with Hg2+. The association constant (K) of PB-CX[4]–Hg2+ complex was found to be 1.66 × 109 M−2, with a detection limit of 5.56 × 10−7 M. In addition, possible utilization of PB-CX[4] as bio-imaging fluorescent probe to detect Hg2+ in human colon cancer cell lines was also observed by confocal fluorescence microscopy.

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

WOS: 000505596300002, PubMed: 31451296, The unique conformational properties, functionality, low toxicity, and low cost make calixarene-based compounds a valuable candidate against cancer. The aim of the present study is the synthesis of the upper rim and lower rim-functionalized L-proline-based calix[4]arene derivatives and evaluation of their cytotoxic potential for human cancerous cells as well as to determine the death mechanism. Synthesized calix[4]arene (3, 8a, 8b 13a, and 13b) derivatives were characterized by different spectroscopic techniques such as (HNMR)-H-1, (CNMR)-C-13, and FTIR. In vitro effects of compounds 3, 8a, 8b, 13a and 13b were tested on human cancerous cells (HEPG2, PC-3, A-549, and DLD-1) as well as human healthy epithelium cell (PNT1A). Results show that compounds 3, 8a, 8b and 13b have cytotoxic potential on human colorectal carcinoma cells (DLD-1) with IC50, values of 43 mu M, 45.2 mu M, 64.57 mu M, and 29.35 mu M respectively. Apoptosis ratios of cell death were investigated with flow cytometer using 7-AAD and Annexin-V as markers. Cytotoxic potential of 8a was found to be higher due to increased apoptosis, when compared with healthy cells the apoptotic cell death was significantly (p < 0.0001) increased up to 1.7-fold and 2.4-fold in DLD-1 and A549 cells, respectively. In conclusion, these L-proline derived calix[4]arenes with their selective cytotoxic potential on human cancerous cells may be a potential candidate for the treatment of human CRC and lung cancer., Scientific and Technological Research Council of Turkey, Turkey (TUBITAK-Grant) [116Z173]; Research Foundation of Selcuk UniversitySelcuk University [17201066, 17201064], We would like to thank the Scientific and Technological Research Council of Turkey, Turkey (TUBITAK-Grant Number 116Z173) and the Research Foundation of Selcuk University (SUBAP-Grant Number: 17201066 and 17201064) for financial support of this work and is a part of Mehmet Oguz Ph.D. thesis and Alev Gul master thesis.