Open MoA: revealing the mechanism of action (MoA) based on network topology and hierarchy.

MOTIVATION: Many approaches in systems biology have been applied in drug repositioning due to the increased availability of the omics data and computational biology tools. Using a multi-omics integrated network, which contains information of various biological interactions, could offer a more comprehensive inspective and interpretation for the drug mechanism of action (MoA). RESULTS: We developed a computational pipeline for dissecting the hidden MoAs of drugs (Open MoA). Our pipeline computes confidence scores to edges that represent connections between genes/proteins in the integrated network. The interactions showing the highest confidence score could indicate potential drug targets and infer the underlying molecular MoAs. Open MoA was also validated by testing some well-established targets. Additionally, we applied Open MoA to reveal the MoA of a repositioned drug (JNK-IN-5A) that modulates the PKLR expression in HepG2 cells and found STAT1 is the key transcription factor. Overall, Open MoA represents a first-generation tool that could be utilized for predicting the potential MoA of repurposed drugs and dissecting de novo targets for developing effective treatments. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/XinmengLiao/Open_MoA.

Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further. We synthesized a series of JNK-5A analogues with targeted modifications, guided by molecular docking studies. These compounds were evaluated for their activities on PKL expression, cell viability, triacylglyceride (TAG) levels, and the expressions of steatosis-related proteins in the human HepG2 cell line. Subsequently, the efficacy of these compounds was assessed in reducing TAG level and toxicity. Compounds 40 (SET-151) and 41 (SET-152) proved to be the most efficient in reducing TAG levels (11.51 ± 0.90 % and 10.77 ± 0.67 %) and demonstrated lower toxicity (61.60 ± 5.00 % and 43.87 ± 1.42 %) in HepG2 cells. Additionally, all synthesized compounds were evaluated for their anti-cancer properties revealing that compound 74 (SET-171) exhibited the highest toxicity in cell viability with IC50 values of 8.82 µM and 2.97 µM in HepG2 and Huh7 cell lines, respectively. To summarize, compounds 40 (SET-151) and 41 (SET-152) show potential for treating NAFLD, while compound 74 (SET-171) holds potential for HCC therapy.

Effect of roasting times on bioactive compounds, fatty acids, polyphenol and nutrients of amaranth (Amaranthus cruentus L.) seed roasted in pan, and principal component analysis.

In this study, the effect of roasting times on bioactive compounds, antioxidant capacity, fatty acids, polyphenol and nutrients of amaranth seed and oils roasted in pan at 120 °C was investigated. Total phenolic and flavonoid results of the seeds of unroasted (control) and roasted-amaranth were recorded between 48.81 (6 min) and 231.35 mg GAE/100 g (15 min) to 64.29 (6 min) and 144.29 mg/100 g (15 min), respectively. Antioxidant activities of unroasted and roasted-amaranth extracts were recorded between 5.50 (control) and 12.78 mmol/kg (15 min). L* values of amaranth seeds ranged from 51.21 to 78.53. Roasting for 3 min and 6 min was increased the L* values of samples, while roasting for 9-12 min caused a decrease in L* values. Gallic acid results of amaranth seeds were identified between 21.94 (control) and 71.06 mg/100 g (15 min). The linoleic acid results of amaranth seed oils were reported between 44.24 (control) and 45.76% (12 min). The highest amounts of elements in roasted and unroasted amaranth seeds were P, K,Ca, Mg and S. In general, it was observed that both macro and micro-elements of amaranth seed samples increased with the application of heat treatment. However, microelement contents differed depending on the roasting time. Graphical abstract: In this study, the effect of thermal process times on total phenol, flavonoid, antioxidant activity, fatty acids, phenolic and minerals of amaranth seed and oils roasted in pan at 120 °C was investigated.

Unmet clinical needs and challenges in the management of acute leukemia in Turkey: a modified Delphi study.

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient-physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients.

Effect of different oil extraction methods on bioactive compounds, antioxidant capacity and phytochemical profiles of raw flaxseeds (Linum usitatissimum) and after roasting at different temperatures.

BACKGROUND: Factors such as variety, genetics, soil structure and plant diseases affect the oil amount and properties of flaxseed. By applying heat and various extraction treatments to flaxseed, the storage ability of the seed is increased by the removal of moisture, and the stability of phytochemicals in the seed against heat can be determined. RESULTS: Total carotenoid and phenol of flaxseeds changed from 0.13 (control) and 0.61 mg g-1 (120 °C) to 202.64 (control and 90 °C) and 225.69 mg 100 g-1 (120 °C), respectively. While total flavonoid of flaxseed roasted at different temperatures varied between 636.0 (90 °C) and 786.00 mg 100 g-1 (120 °C), antioxidant activity values for raw and roasted flaxseeds between 59.32% (control) and 68.64% (120 °C) were recorded. Oil content of seeds changed between 34.07 and 42.57% (P < 0.05). Viscosity of flaxseed oil extracted using different systems was between 31.95 (cold-pressed; control) and 36.00 mPa s (ultrasonic; 120 °C). The dominant phenolics of flaxseeds were identified as isorhamnetin, resveratrol, quercetin, catechin, apigenin-7-glucoside and campherol. The oils of flaxseeds contained 55.27-58.23 linolenic, 17.40-18.91 oleic, 14.03-14.84 linoleic and 4.97-5.37 palmitic acids, depending on extraction method and roasting temperature. CONCLUSION: Roasting and oil extraction methods did not have a significant effect on free acidity, but was found to affect peroxide value. The predominant phenolic constituents of flaxseed samples were isorhamnetin, resveratrol, quercetin, catechin, apigenin-7-glucoside and campherol, respectively. The major fatty acids of flaxseed oil were determined as linolenic, oleic, linoleic and palmitic. © 2023 Society of Chemical Industry.

The accumulation of element and heavy metal concentrations in different parts of some carrot and radish types.

Vegetables, which are an important part of human nutrition, are very rich in minerals necessary for human health, and heavy metals can be found in vegetables at high rates because they can be easily taken by plant roots and leaves. In this study, the macro, micro element and heavy metal element concentrations accumulated in different parts of some carrot and radish types were investigated. The element concentrations in the samples were analyzed by Inductively coupled plasma optical emission spectrometry (ICP-OES; Varian-Vista Model) equipment. P, K, Ca, Mg and S contents of the head of orange and black carrot samples were determined as 602.30 and 727.23 mg/kg, 19,790.91 and 22,230.21 mg/kg, 1765.66 and 1609.41 mg/kg, 580.34 and 660.79 mg/kg and 376.21 and 4444.46 mg /kg respectively. Also, exterior parts of orange and black carrots contained 281.65 and 336.43 mg/kg P, 7768.37 and 10,109.44 mg/kg K, 169.88 and 272.18 mg/kg Ca, 112.08 and 189.28 mg/kg Mg and 135.43 and 217.60 mg/kg S, respectively. P and K contents of the head parts of radish samples (white, red and black radish) were determined between 302.14 (red radish) and 1111.53 mg/kg (black radish) to 13,717.2 (red radish) and 22,202.4 mg/kg (white radish), respectively. Fe amounts of the roots of radish samples changed between20.47 (red radish) and 45.93 mg/kg (white radish). As and Ba were the most abundant heavy metals in both carrot and radish parts. The Ni contents of the parts of the carrots contain more than 50% lower than the head part. Also, while Pb contents of the parts of orange carrot change between 0.189 µg/g (interior of body) and 0.976 µg/g (shell), Pb amounts of the black carrot parts were recorded between 0.136 (head) and 0.536 µg/g (interior of body). The results obtained differed according to the vegetable type and parts. The head part of the radishes was the richest in zinc, followed by root, shell, exterior of body and interior of body in descending order. In general, the parts where heavy metals were most localized were the head and shell parts. The most localized parts of heavy metals in radishes were the head, shell and root parts. As a result, the most of the edible inner parts of carrots and radishes are thought to have a positive effect on human health, since their heavy metal content is low.

Macro-, micro-, and heavy metal element levels in different parts of celery (Apium graveolens L.) plant.

Potassium (K) was found in the highest amount in the macroelements of the celery plant, followed by P, Ca, Mg, and S in decreasing order. P and K amounts of celery plant parts were measured between 619.57 (leaf of celery) and 1244.80 mg/kg (root of celery) to 5594.83 (head of celery) and 7587.35 mg/kg (root of celery), respectively. Exterior and interior parts of celery body contained 866.51 and 1017.45 mg/kg P, 6786.97 and 7325.07 mg/kg K, 615.13 and 491.59 mg/kg Ca, and 286.34 and 224.74 mg/kg Mg, respectively. In general, the celery part with the richest microelements was the leaves, followed in descending order by the head of celery, exterior of celery body, interior of celery body, and root. Fe and Mn contents of the parts of celery plants were recorded between 0.351 (interior of celery body) and 67.79 mg/kg (leaf of celery) to 2.70 (root) and 6.84 mg/kg (leaf of celery), respectively. The lowest and highest concentrations of each heavy metal were found in different parts of the celery plant. In general, the leaves were the part of the celery plant with the most heavy metals. As and Pb accumulated in large amounts in the inner parts of the celery tuber. The highest Pb (0.530 µg/g) was determined in interior of celery body. The highest Co (0.409 µg/g), Cr (0.377 µg/g), Mo (0.854 µg/g), and Ni (0.741 µg/g) were found in the leaf of celery plant.

Quantitative determination of macro and micro elements and heavy metals accumulated in wild fruits analyzed by ICP-OES method.

The moisture amounts of wild fruits ranged from 51.07 (rosehip) to 88.49% (raspberry (yellow)). Wild strawberry generally contained the highest amounts of P, K and Ca. In addition, the highest Mg result was recorded in wild strawberry, fig and rosehip fruits. P and K amounts of wild edible fruits were recorded between 385 mg/kg (blackberry) and 2538 mg/kg (fig) to 6114 (medlar) and 18,613 mg/kg (wild strawberry), respectively. Depending on the fruit variety and type, the microelements found in the highest amounts were Zn, Cu, Mn and B. Fe resultss of fruits were reported at very low levels. Fe results of wild edible fruits changed between 0.21 (apple) and 1.32 mg/kg ((fig). Zn and Cu values of wild edible fruits were recorded between 1.39 (apple) and 16.4 mg/kg (fig) to 1.54 (apple) and 18.4 mg/kg (wild strawberry), respectively. Cu contents of raspberry (red), raspberry (yellow), blackberry, jujube and medlar fruits were found to be very close to each other. Arsenic (As) contents of wild fruits were recorded to be higher than those of other elements. In addition, some fruits have high heavy metal contents. The heavy metal found in the highest amounts in fruits was As, followed in descending order by Ali Ba, Se, Ni and Pb. The high As content of these fruits is likely due to the As content of the soil where the plants are grown and its contamination with As-rich industrial waste. While As contents of edible wild fruits are detected between 4.21 (rosehip) and 65.7 (wild strawberry), Al results of fruits were reported between 0.03 (rosehip) and 16.0 µg/g (mulberry (white)).

A review on some properties of almond: impact of processing, fatty acids, polyphenols, nutrients, bioactive properties, and health aspects.

This review was focused on the proximate compounds, nutritional values, total phenolic, flavonoid, antioxidant activity, fatty acid profile, polyphenols, health aspects and uses of almond kernel and oils. Almond contained about 24-73% crude oil, 50-84% oleic and 6-37% linoleic acids, 77-3908 mg/kg ß-stosterol and 5-8 mg/100 g ß-tocopherol. Almonds are a good source of mono- and unsaturated fatty acids, phytochemicals, bioactive components, minerals, vitamin E, polyphenols and phytosterols and at the same time almonds have healing effects. Since almond seeds or seed oils have versatile uses, they are consumed on their own or as part of a range of food products. Almonds are considered a healthy snack when consumed due to their potential cardioprotective effects. Since the composition of almonds and its effects on health will be effective both during cultivation and processing, studies should be carried out in a way that preserves the product quality. Graphical abstract: In this study, the proximate compounds, harvest and irrigation effect, nutritional values (protein, amino acids, vitamins minerals), total phenol, flavonoid, antioxidant activity, fatty acid profile, polyphenols, and uses of almond kernel and oils were summarized.

Determination of macro-, micro-element and heavy metal contents localized in different parts of three different colored onions.

The element found at the highest amount in onion samples was sulfur, and followed by K, Ca, P, Na, and Mg in decreasing order. While K contents of white onion parts are determined between 1406.31 (outer most edible) and 1758.72 mg/kg (inner most edible), K contents of the parts of brown onions were measured between 1779.79 (head) and 2495.89 mg/kg (inner most edible). Also, K amounts of purple onions were detected between 2248.73 (shell) and 3064.64 mg/kg (middle edible). In addition, in general, the highest P, S, and K were detected in the middle edible and inner most edible parts of the edible onion samples. While the highest Ca content was localized in brown and purple onion roots, it was most localized in the shell part of white onions. In edible white and brown onions, the highest Na content was found in the inner most edible part. Fe amounts of white and brown onion samples were identified between 7.94 (head) and 20.41 mg/kg (root) to 9.56 (middle edible) and 23.67 mg/kg (head), respectively. Also, Fe contents of the parts of purple onions varied between 13.04 (shell) and 20.61 mg/kg (inner most edible). While the highest Fe and Zn are determined in the middle edible part in edible white onions, the highest Fe and Zn were determined in the outer most edible part in brown onions. In general, the most heavy metals were localized in the bark, head, and root parts of the onions. This had a positive effect on the safe edibility of onions. The heavy metal detected in the highest amount in onion samples was arsenic, followed by Cr, Al, Ni, Se, Ba, Pb, Mo, Co, and Cd in descending order. Generally, purple onion type showed maximum values. Therefore, results of the present study seen to be beneficial in the way that it allowed us to selected some varieties with nutrition value that could be interesting to introduce in gastronomy.

The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.

Effect of different roasting methods on the bioactive properties, phenolic compounds and fatty acid compositions of pomegranate (Punica granatum L. cv. Hicaz) seed and oils.

In this study, whole and ground pomegranate (cv. Hicaz) seeds using conventional and microwave ovens were investigated under different parameter. The results show that the total phenolic contents of whole and ground seeds roasted in oven at (150 °C) and microwave at (720 W) for 10 and 20 min, and 5 and 7.5 min, respectively, were found to be slightly higher than those of the control group. In addition, the same roasting method of microwave at (720 W), ground seed oils showed greater fatty acids contents than those of whole seed oils. According to achieved results, roasting techniques used caused noticeable fluctuations of phenolic and fatty acids contents and that depending on which counterparts of pomegranate seeds treated. In addition, a caution recommended when using microwave oven in roasting pomegranate seeds to prevent undesirable alteration or losing of bioactive properties of this value-added product.

Influence of drying techniques on bioactive properties, phenolic compounds and fatty acid compositions of dried lemon and orange peel powders.

Lemon peel powder (LPP) obtained after drying (microwave, infrared, and oven) showed the lowest (58.72%) DPPH-radical scavenging activity in oven-dried and the highest (67.84%) in infrared-dried LPP while that of fresh lemon peel remained 63.22%. Orange peel powder (OPP) showed the lowest DSA (61.65) after microwave and the lowest (63.54%) after infrared-drying while that of fresh orange peel was 63.48%. Total phenolics were between 114.58 (fresh) and 179.69 mgGAE/100 g (oven) in LPP and between 158.54 (fresh) and 177.92 mgGAE/100 g (infrared) in OPP. The total flavonoid contents were 380.44 (fresh)-1043.04 mg/100 g (oven) in case of LPP and 296.38 (fresh)-850.54 mg/100 g (oven) in case of OPP. The gallic acid contents were 2.39 (fresh)-14.02 mg/100 g (oven) in LPP. The (+)-catechin contents were 1.10 (fresh)-49.57 mg/100 g (oven) for LPP and 0.82 (fresh)-7.63 mg/100 g (infrared) in case of OPP. The oleic acid content was 22.99 (infrared)-58.85% (fresh) in LPP-oil and 28.59 (microwave)-61.65% (fresh) in OPP-oil. The linoleic acid contents were 13.76 (fresh)-36.90% (oven) in LPP-oil and 14.14 (fresh)-37.08% (infrared) in case of OPP-oil. The drying techniques showed profound but variable effects on radical scavenging activity, total phenolics, flavonoid, carotenoids, phenolic compounds and fatty acid composition of both LPP and OPP and oven-drying (60 °C) was the most effective in improving these bioactive constituents.

The influence of industrial refining stages on the physico-chemical properties, fatty acid composition and sterol contents in hazelnut oil.

In this study determined influence of industrial refining stages on the physico-chemical properties, fatty acid composition and sterol contents in hazelnut oil. According to this, while acidity values of hazelnut oil obtained from refining stages change between 0.11 (deodorized) and 1.44 (crude), peroxide values of oil samples were determined between 10.4 meqO2/kg (winterized) and 12.5 meqO2/kg (crude oil). In addition, iodine values of oils taken from each refining stages varied between 85.06 (nötralized) and 87.45 (deodorized). While oleic acid contents of hazelnut oils taken from refining stages change between 84.08% (winterized) and 84.68% (neutralized), linoleic acid contents of oil samples ranged from 6.79% (neutralized) to 8.56% (winterized). Total saturated and unsaturated fatty acids of oil samples changed between 6.84% (deodorized) and 8.00% (neutralized) to 92.00% (neutralized) and 93.16% (deodorized), respectively. While campesterol contents of oil sample change between 3.56% (deodorized) and 4.87% (crude), δ-5,23-stigmastadienol contents of oil varied between 0.48% (deodorized) and 2.87% (neutralized). The highest sterol had ß-sitosterol, its amount changed between 54.98% (deodorized) and 73.96% (crude oil). In addition, δ-7-avenasterol contents of hazelnut oil obtained from refining stages varied between 4.85% (crude oil) and 28.33% (deodorized).

Characterization of physico-chemical and bioactive properties of oils of some important almond cultivars by cold press and soxhlet extraction.

The oleic acid composition of almonds oils expressed by cold press varied from 73.56% in Cristomorto cultivar to 76.59% in Tuono while oleic acid in oils extracted by soxhlet method ranged from 71.86% in Cristomorto and 75.63% in Tuono cultivars. Also, oil from cold press extraction contained 19.51% and 21.86% linoleic acid for Ferragnes and Tuono almond cultivars, respectively, while 18.74 and 20.51% linoleic acid was recorded in Soxhlet extracted oil from Ferragnes and Tuono almonds, respectively. In addition, α-tocopherol contents of the oil samples varied significantly (p < 0.05) from 14.18 to 16.86 mg/100 g in Tuono and 15.71-17.96 mg/100 g in Ferragnes for cold-press and soxhlet extracted oils, respectively. ß-Sitosterol composition of the oil obtained by cold press ranged from 157.94 (Tuono) and 171.68 mg/100 g (Cristomorto) while ß-sitosterol content varied from 148.91 (Tuono) and 159.68 mg/100 g (Cristomorto) for oil extracted by Soxhlet method.

Effect of microwave and oven drying processes on antioxidant activity, total phenol and phenolic compounds of kiwi and pepino fruits.

Kiwi and pepino fruits are most valuable fruits as they contains substantial amounts of nutrients and bioactive compounds. These fruits exhibited several health potentials such as antioxidant, antiinflammatory, antiobesity, antihyperlipidemia, and anticancer properties. However, studies on the effect of microwave and conventional drying methods on the antioxidant activity and bioactive compounds of kiwi and pepino fruits are limited. Therefore, this study was conducted to assess the effect of microwave and oven drying methods on antioxidant activity, total phenolic, and phenolic compounds of kiwi and pepino fruits. Drying of the fruit samples was carried out using conventional (70 °C for 20 h) and microwave (720 W for 3 min) ovens. 1,1-diphenyl-2-picrylhydrazyl scavenging and colorimetric Folin-Ciocalteu assays were used to assess the antioxidant activity and total phenolic contents, respectively, of fresh and dried fruits. Both drying methods significantly (p < 0.05) decreased the moisture contents of both fruits compared to untreated controls. Concomitantly, drying methods also enhanced (p < 0.05) antioxidant activity and total phenolic content of both fruits with the highest improvement being observed for microwave-dried fruits compared to untreated controls. In addition, a significant increase was observed in catechin and 1,2-dihydroxybenzene content of kiwi and pepino after drying process. However, microwave drying method reduced the amount of 3,4-dihydroxybenzoic acid in kiwi (ranging from 34.120 to 9.350 mg/100 g) and pepino (varied from 33.414 to 15.445 mg/100 g). Generally, the highest antioxidant activity and phenolic contents were reported in microwave oven dried samples, followed by samples dried in oven and fresh fruits. The results revealed that microwave drying could be more useful in fruit drying than conventional drying. In addition, dried kiwi and pepino fruits contains substantial quantities of phenolic compounds with high antioxidant activity compared to fresh fruits, and thus they are considered as healthy food.

Effect of almond genotypes on fatty acid composition, tocopherols and mineral contents and bioactive properties of sweet almond (Prunus amygdalus Batsch spp. dulce) kernel and oils.

Oil content of almond kernels ranged from 36.7% in the cultivar T12 to 79.0% in genotype T27. The major fatty acid in almond oil is oleic (62.43% in T7-76.34% in T4) followed by linoleic (13.97% in T4-29.55% in T3) and palmitic (4.97% in T2-7.51% inT3). The main tocopherol in almond oil was α-tocopherol (44.25 mg/100 g in T25-75.56 mg/100 g in T13) that was 44 folds higher than other tocopherols in the oil. Total tocopherol contents of almond oils ranged between 47.42 mg/100 g (T14) and 80.15 mg/100 g (T16). Among macro minerals, K was the highest (5238-14,683 mg/kg), followed by P (3475-11,123 mgkg), Ca (1798-5946 mg/kg), and Mg (2192-3591 mg/kg), whereas Na was the least (334-786 mg/kg) in almond kernel. The total polyphenol was observed in T16 (98.67 mg GAE/100 g), while the least was found in T24 (23.75 mg GAE/100 g). Antioxidant activity was high in T7 (91.18%) and low in T12 (44.59%).

Effect of sonication process of terebinth (Pistacia terebinthus L.) fruits on antioxidant activity, phenolic compounds, fatty acids and tocopherol contents.

The current study investigated the impact of sonication process on antioxidant activity, phenolic compounds, total phenolic, total flavonoid, oil contents, fatty acids profile, and tocopherols of terebinth (Pistacia terebinthus) fruits. The highest antioxidant activity (87.32%), total phenolic (251.25 mg/100 g) and flavonoid (3413.72 mg/100 g) contents were observed in terebinth fruits sonicated for 30 min. The oil contents of terebinth increased from 38.93% (control) to 42.60% (sonicated for 15 min) after sonication process. The quercetin and catechin were the chief phenolic compounds in P. terebinthus extracts and their values were increased from 129.09 to 467.28 mg/100 g (quercetin) and from 5.58 to 21.33 mg/100 g (catechin) in fruits sonicated for 30 min. The major fatty acids of terebinth fruit oil were oleic (48.02-49.15%), linoleic (22.28-23.48%) and palmitic (22.10-23.67%) and sonication processes did not affect the quantities of these fatty acids. γ-Tocopherol was the most abundant isomer with the value of 63.95-122.03 mg/100 g in terebinth fruit oil. It could be concluded that pre-sonication for 30 min was more suitable for enhancing the antioxidants and phenolic compounds of P. terebinthus fruit.

The influence of fermentation and bud sizes on antioxidant activity and bioactive compounds of three different size buds of Capparis ovata Desf. var. canescens plant.

The impact of fermentation and bud size on the antioxidant activity, total phenolic content (TPC), and bioactive compounds of caper buds were investigated. The results showed significant differences in the bioactive properties depending on bud sizes and fermentation process. Antioxidant activity values of fresh caper buds were ranged between 69.61% (bid size) and 72.78% (small size), whereas the values of fermented ones varied between 12.50% (big size) and 39.09% (small size). TPC of fresh caper buds were found in the range of 357.81 mg GAE/100 g (medium size) and 372.22 mg GAE/100 g (small size), while those of fermented buds were ranged from 167.53 mg GAE/100 g (medium) to 246.01 mg GAE/100 g (small). Apigenin-7-glucoside, (+)-catechin, 1,2-dihydroxybenzene, and 3,4-dihydroxybenzoic, syringic, and gallic acids were the major phenolic compounds in both fresh and fermented caper buds. Overall, this study clearly demonstrated that both fermentation process and bud size significantly affected the antioxidant activity, TPC, and phenolic compounds of caper buds.

Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1-1 inhibitor, in tumorigenesis and tumor progression.

Glutathione (GSH) and enzymes related to this antioxidant molecule are often overexpressed in tumor cells and may contribute to drug resistance. Blockade of glutathione transferases (GSTs) has been proposed to potentiate the efficacy of chemotherapeutic drugs in cancer. The aim of this study was to evaluate the effect of chlorophyllin that has antioxidant properties, and also interferes with the activity of GST P1-1, on breast cancers in vitro and in vivo. The in vivo studies were conducted using an N-methyl- N-nitrosourea (MNU)-induced chemical carcinogenesis model in laboratory rats. DNA damage, GST activity, and GSH levels were determined in liver and tumor tissues. Treatment with chlorophyllin increased the GSH levels in the liver and significantly decreased DNA damage in the blood, liver, and tumor tissues. Even though tumorigenesis was delayed in rats receiving chlorophyllin before MNU injections, once the tumors emerged, the progression of tumor appeared to be faster than in the animals that received the carcinogen only. Out of nine breast cell lines, GST P1-1 expression was detected in MCF-12A, MDA-MB-231, and HCC38. Concomitant incubation with chlorophyllin and docetaxel did not significantly affect cell proliferation and viability. Chlorophyllin displayed genoprotective effects that initially delayed tumorigenesis. However, once the tumors were established, it may act as a promoter that facilitates tumor growth, potentially by a mechanism independent of cell proliferation and viability. Our results underline the pros and cons of antioxidant treatment in cancer, even if it has a capacity to inhibit GST P1-1.