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The cytotoxic effects of linalool and eugenol on HeLa and Caco-2 cancer cells were investigated. The expression of the Fyn, Hck, and ADAMTS genes and Bcl-2, Bax, VEGF proteins were determined through the real-time-qPCR and Western blot analysis, respectively. IC50 values of linalool on HeLa cell were 799.6, 1228, and 1239 mu g/mL after 24, 48, and 72 h, respectively, whereas those of eugenol were 388, 94.35, and 73.78 mu g/mL. IC50 values in Caco-2 cells were 887.7, 1259, and 1356 mu g/mL for linalool whereas those of eugenol were 452.7, 578.3, and 433.3 mu g/mL after 24, 48, and 72 h, respectively. As a control, Hek-293 IC50 values were 1047 and 556.7 mu g/mL for linalool and eugenol, respectively. Linalool at 1024 mu g/mL concentration increased Bax and Bcl-2 levels significantly in both cell lines (p < 0.001). However, eugenol treatment did not alter Bax levels (p > 0.05), but it decreased Bcl-2 levels significantly (p < 0.001). Additionally, 1024 mu g/mL linalool exposure increased Fyn gene expression in Caco-2 cells, which was not observed for HeLa cells. Unlike linalool, eugenol upregulated ADAMTS1 gene expression and decreased VEGF levels in HeLa cells. On the contrary, in Caco-2 cells, eugenol treatment did not affect ADAMTS1 levels, whilst linalool upregulated ADAMTS1 levels, especially at 1024 mu g/mL concentration. VEGF levels increased in Caco-2 cells following eugenol treatment. ADAMTS3 levels decreased in Caco-2 cells with exception of 1024 mu g/mL linalool treatment. These results indicated the anti-proliferative, apoptotic effects of plant-derived natural compounds. It is also revealed that eugenol might also display antiangiogenic properties on HeLa cells in addition to its apoptotic effects.

© 2022 Wiley-VCH GmbH.Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1β levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.

In this study, silver nanoparticles (AgNPs) were synthesized economically and simply using an environmentally friendly method with the extract obtained from agricultural waste olive leaves. AgNPs synthesized according to the analysis data were determined to have maximum absorbance at 433.5 nm wavelength, spherical appearance, 7.2 nm crystal nano size and -19.9 mV zeta potential. It was determined by the microdilution method with Minimum Inhibition Concentration (MIC) that AgNPs exert a suppressive effect on the growth of pathogen gram-negative, positive bacteria and yeast at very low concentrations. The cytotoxic effects of the particles were investigated on healthy cell lines (HDF) and cancerous cell lines (U118, CaCo-2, Skov-3). AgNPs showed up to 70% suppression in cancer cell lines.

In this study, investigation on the essential oils and ethanol extracts of naturally grown and cultivatedSatureja macrantha samples were reported. The essential oil, flavour and terpenoid-steroid-flavonoid contents of S.macrantha samples were determined by GC-MS and their phenolic contents by LC-MS/MS. Besides, the biologicalactivities of the samples were investigated for their antioxidant, anti-Alzheimer, antimicrobial, cytotoxic,antityrosinase, antiurease, antielastase and anticollagenase properties. The phenolic content and antioxidant capacityof the cultivated sample were higher than those of the naturally grown sample. According to the GC-MS results,terpinene-4-ol (30.9%) and p-cymene (56.7%) were determined as the major components in the essential oils of thenaturally grown and cultivated S. macrantha, respectively. The flavour analysis results showed that cis-sabinenehydrate (20.7%) and carvacrol (42.2%) were found to be the major components in the naturally grown and cultivatedsamples, respectively. While the naturally grown sample was rich in abietane diterpenoids (ferruginol (17.5 mganalyte/g extract) and sugiol (4.2 mg analyte/g extract)), these components were not detected in the cultivatedsample. The rosmarinic acid content (0.20 and 24.87 mg analyte/g extract, respectively) of the cultivated samplewas found to be significantly higher than that of the natural sample. The biological activities of the samples weredetermined to be changed in parallel with their chemical contents that are due to factors such as climatic conditions,and soil structure.

Since ancient time, Salvia L. species have been commonly used to treat colds, bronchitis, tuberculosis, heart diseases, and menstrual and digestive disorders in traditional medicine all around the world. They have been also used as tea and spice. Studies indicated that diterpenes and triterpenes isolated from Salvia species possess various pharmacological and biological effects such as anti-inflammatory, antiviral, cytotoxic, antioxidant, and hepatotoxic activities. Flavones were also shown to have antimicrobial, antioxidant, and cytotoxic potentials. Salvia extracts also exhibit anti-Alzheimer, antiseptic, cardiovascular, antihypertensive, and antituberculous effects. To investigate the effects of 63 secondary metabolites from Salvia species on cell viability and apoptosis, Salvia secondary metabolites including 25 phenolics, 4 fatty acids, 19 abietane diterpenoids, 12 triterpenoids, and three steroids were examined on healthy cell line (PDF), breast cancer (MCF-7), and colon cancer (HT-29) cell lines using MTT method. In addition, the effects of rosmarinic acid, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, carnosic acid, carnosol, cryptotanshinone, beta-sitosterol, and ursolic acid on pro-apoptotic Bax and antiapoptotic Bcl-2 protein expression levels were investigated by Western Blot method. Practical applications Phenolic compounds (apigenin, chrysin, and luteolin) and diterpenes (especially dihydrotanshinone I, carnosic acid, and carnosol), and almost all of the triterpenes exhibited high toxic effects on healthy cell line. Cytotoxic effects of cryptotanshinone, 12-hydroxy abieta-1,3,5(10),8,11,13-hexaene, 12-demethylmulticauline, 6,7-dehydroroyleanone, acetyl royleanone, ferruginol, ursolic acid, and 3-acetyl lupeol were relatively higher than their toxic effects. Acetyl royleanone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone were found to have anticancer potential based on their modulating effects on the expression levels of Bax and Bcl-2 proteins which play important roles in the regulation of apoptosis. The results of the present study showed that acetyl royleanone, cryptotanshinone, 6,7-dehydroroyleanone, carnosic acid, and cryptotanshinone have potential to be used in the pharmaceutical industry.

Although chemotherapy (CT) has some adverse effects on healthy tissues and cells, it is widely preferred for treating patients with cancer. Drug resistance is one of the major impediments to successful cancer treatment. Electrochemotherapy (ECT) is a technique where cancer cells are rendered permeable to medications. Thanks to this permeability, the dose of the medication required for cancer treatment decreases. Our aim in this study is to examine the effects of short-term extremely low-frequency magnetic fields (ELF-MFs) on CT and ECT treatments in Caco-2 colon cancer cells. The Caco-2 cancer cells were treated with 5-fluorouracil (5-FU, 50 mu M) and ECT (strength:1125 V/cm, duration:100 mu s, frequency:1 Hz), alone as well as in combinations with ELF-MF (4 mT, 10 min). MTT assay was used to determine the efficacy of the treatments. Our findings in the study showed that ECT was much more successful than 5-FU treatment alone in Caco-2 colon cancer cells. Application of 4 mT ELF-MF after CT significantly increased the viability of the Caco-2 cancer cells compared to the CT group alone (p < .05). An increase in the viability of cells treated with 4 mT after ECT was observed compared to ECT alone. Similarly, there was an increase in the viability of cells treated with MF prior to ECT treatment (p < .05). The results show that exposure to ELF-MF at 4 mT flux density significantly reduces CT and ECT treatment efficacy in Caco-2 colon cancer cells.

WOS:000691376800017 Abstract: To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. Cannabinoids, the main constituents of cannabis (Cannabis sativa L.), are therapeutic compounds that have received international attention in the health field due to their therapeutic properties. Recently, they have been tested for the treatment of COVID-19 due to their antiviral properties. Indeed, cannabinoid-type compounds, and in particular cannabidiol (CBD), isolated from glandular trichomes found in the calyx of cannabis flowers with reported antiviral properties is hypothesized to be a therapeutic option in the ministration of SARS-CoV-2 consorted with COVID-19 disease. The relevant articles were determined from the database search published mainly in Web of Science, Google scholar, PubMed, Crossref, and ClinicalTrials.gov database during the pandemic period. The articles were evaluated for the therapeutic potentials, mechanisms of action of cannabinoids, the roles of the ECS in the immune system, impact of cannabinoids in SARS-CoV-2 septic, especially if they address the application of cannabinoids as drugs for the curability and management of SARSCoV-2 and its novel variants. Although the evidence needed to be considered using cannabinoids in the control and treatment of viral diseases is currently in its infancy, they already offer an opportunity for clinicians due to their effects in relieving pain, improving appetite, and improving childhood epilepsy, especially in cancer and human immunodeficiency virus (HIV/AIDS) patients. In addition to these, the most recent scientific evidence emphasizes their use in the treatment of the coronavirus infected patients. In brief, all preclinic and clinic studies that have been reported show that, through the cannabinoid system, cannabinoids, particularly CBD, have many mechanisms that are effective in the treatment of patients infected by SARS-CoV-2. Thus, more extensive studies are necessary in this area to fully identify the effects of cannabinoids on SARS-CoV-2.

This study examined the effects of black cumin seed oil treatment on oxidative stress and the expression of radixin and moesin in the liver of experimental diabetic rats.Eighteen rats were divided into 3 equal groups (control, diabetes, treatment). The control group was not exposed to any experimental treatment. Streptozotocin was administered to the rats in the diabetes and treatment groups. A 2.5 mL/kg dose of black cumin seed oil was administered daily for 56 days to the treatment group. At the conclusion of the experiment, the blood level of malondialdehyde (MDA) and glutathione (GSH) was measured. The expression level and the cellular distribution of radixin and moesin in the liver were analyzed.The plasma MDA (3.05±0.45 nmol/mL) and GSH (78.49±20.45 μmol/L) levels in the diabetes group were significantly different (p0.01) from the levels observed in the control group (MDA: 1.09±0.31 nmol/mL, GSH: 277.29±17.02 μmol/L) and the treatment group (MDA: 1.40±0.53 nmol/mL, GSH: 132.22±11.81 μmol/L). Immunohistochemistry and western blotting analyses indicated that while the level of radixin was not significantly between the groups (p0.05) and moesin expression was significantly downregulated (p0.05) in the experimental group, the treatment was ineffective.The administered dose was sufficient to prevent oxidative stress, but was not sufficient to alleviate the effects of diabetes on moesin expression in hepatic sinusoidal cells.

Recycling wastes and providing their use in useful fields attract attention every day. In our study, with the extract prepared from the parts of the Cynara scolymus L. (artichoke) plant that is not suitable for human consumption, silver nanoparticles were easily synthesized in an ec-friendly, energy-free way. Characterization of the obtained nanoparticles was done with a UV-visible spectrophotometer (UV-Vis.), fourier transform infrared spectroscopy (FTIR), X-ray diffraction diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), and zeta potential analysis data. In these data, it was determined that AgNPs have a maximum absorbance at 458.8 nm wavelength, a crystal nanosize of 28.78 nm, and a spherical appearance. The zeta potential of (-) 16.9 mV indicates that silver nanoparticles exhibit a stable structure. Particles show antimicrobial effects on pathogenic species at concentrations of 0.03-0.25 μg/ml, and it was determined by using the minimum inhibition concentration (MIC) microdilution method. By examining their cytotoxic effects on U118, CaCo-2, and Skov-3 cancer cell lines and healthy HDF cell lines by the MTT method, concentrations of inhibitive effects on survival were determined.

Zn(II) complex of Schiff base derived from the condensation of 4-aminopyrimidine-2(1H)-one with salicylaldehyde was prepared and characterized by various physico‐chemical and spectral methods for structure determination. The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-fluorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal fibroblast cells (HDF) was used as control for biocompatibility. Then, the effectiveness of electroporation (EP) on cytotoxic activities of these compounds has been examined. The cytotoxicities of the 5-FU and new Zn(II) complex, alone or in combination with electroporation, were determined by MTT assay. The Zn(II) complex showed good cytotoxicity against T98G and U118 brain tumor cell lines with IC50 = 282.47 and 297.91 μM respectively, while it was safe on HDF healthy cells with IC50 = 826.72 μM. The 5-FU exhibited less cytotoxicity compared to the Zn(II) complex against T98G (IC50 = 382.35 μM) and U118 (IC50 = 396.56 μM) tumor cell lines. The combined application of Zn (II) + EP decreased the IC50 value by 5.96-fold in T98G cells and 4.76-fold in U118 cells. EP showed a similar effect in its combined application with 5-FU, resulting in a decrease of the IC50 value of 4.22-fold in the T98G cells and 3.84-fold in the U118 cells. In a conclusion, the Zn(II) complex exhibited an anticancer potential against both brain tumor cell lines (T98G and U118) and EP greatly increased the cytotoxicity of Zn(II) complex and 5-FU on these chemotherapy-resistant cells.

The propose of this study is to investigate the chemical constituents of nine Euphorbia species; namely, E. aleppica, E. eriophora, E. macroclada, E. grisophylla, E. seguieriana subsp. seguieriana, E. craspedia, E. denticulata, E. falcata and E. fistulosa by LC-MS/MS as well as their antioxidant, anticholinesterase, tyrosinase inhibitory, urease inhibitory and cytotoxic activities. Among 59 extracts prepared from the different parts of the mentioned Euphorbia species, E. seguieriana subsp. seguieriana leaf (IC50: 10.41 +/- 0.93 mu g/mL) in lipid peroxidation inhibitory by beta-carotene-linoleic acid assay exhibited the highest activity, while E. grisophylla root in DPPH free radical scavenging (IC50: 0.79 +/- 0.01 mu g/mL), E. grisophylla seed in ABTS cation radical scavenging (IC50: 8.93 +/- 0.02 mu g/mL), E. fistulosa root both in acetyl- and butyryl-cholinesterase inhibitory (53.71 +/- 1.89% and 77.63 +/- 0.60% inhibition, respectively), E. denticulata leaf in urease inhibitory (96.89 +/- 2.00% inhibition), and E. macroclada mixed in tyrosinase inhibitory (86.99 +/- 3.77% inhibition) activities. However in cytotoxic activity studies, E. denticulata against PDF fibroblast cell lines (IC50: 23.04 +/- 0.03 mu g/mL), E. craspedia against HT-29 cancer cell line (IC50: 13.74 +/- 0.02 mu g/mL), E. fistulosa against MCF-7 and DLD-1 cancer cell lines (IC50: 14.04 +/- 0.04 mu g/mL and IC50: 20.23 +/- 0.08 mu g/mL, respectively) indicated quite good activity. According to the LC-MS/MS results, these species were rich in quinic acid, malic acid and tannic acid, rutin, hesperidin and hyperoside. Incidentally, it was found that the E. eriophora possessed very strong irritating potential. A chemometric approach using principal component analysis (PCA) and hierarchical clustering analysis (HCA) techniques were also studied on collected data to reveal the relationship between chemical contents of different parts of these Euphorbia species, and their biological activities, together with regional differences. Overall, these species could be suggested as valuable sources of natural-bioactive agents for developing new functional, pharmacological and health promoting ingredients.

Preeclampsia is a severe multisystem disorder, and its pathophysiology is still not completely understood. Autophagy, a recycling process that maintains cellular homoeostasis during differentiation and development, is controversial regarding increased or decreased autophagic activity in preeclampsia. The aim of this study was to determine whether autophagy is increased in the placentas of women with preeclampsia by examining the protein levels of autophagy markers (Beclin 1 and SQSTM1/p62) and phosphorylation of cyclin E. For this purpose, placentas from preeclampsia (n=10) and control (n=10) pregnancies were included in this study. The protein expression of autophagy-related markers Beclin1, SQSTM1/p62 and phosphorylation status of cyclin E were detected by Western blot. Our data showed that the protein levels of both Beclin 1 and SQSTM1/p62 were significantly increased, while the phosphorylation level of cyclin E was significantly decreased in placentas with preeclampsia compared to those derived from controls. The results of this study suggest that the autophagic activity is perpetually increased in preeclampsia and cyclin E protein stabilisation might be involved in the induction of autophagy.

The importance of Salvia L. species, being used as traditional medicine, in the scientific world is increasing day by day. The relationship between health and traditional-modern life, promotes the creation of new value added food products. Within this context, in this study, it was aimed to biologically and chemically investigate the essential oil and ethanol extracts of the Salvia multicaulis Vahl. Chemical and biological study results of naturally grown and cultivated (uninvestigated in the literature) samples of S. multicaulis were compared. The essential oil, aroma and terpenoid-steroid contents of the species were determined by gas chromatography-mass spectrometry (GC–MS) and phenolic content by liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS). In addition, the bioactivities of the extracts were screened for antioxidant, cytotoxic, antialzheimer, antiurease, antityrosinase, antielastase and anticollagenase activities. It was found that the enzyme activities of the essential oil and the antioxidant activities of all ethanol extracts of the species were quite high. It was determined that especially essential oil and the ethanol extracts of the leaf parts exhibited high cytotoxic effect in cancer cell lines (PDF (Healthy primary dermal fibroblast cell line), HT-29 (colon cancer cell line), MCF-7 (breast cancer cell line), Caco-2 (colon cancer cell line) and Skov-3 (ovary cancer cell line)). According to the GC–MS results, in the natural specimen 1,8-cineole (33.05 %) and d -limonene (21.18 %), in the cultivated sample 1,8-cineole (42.35 %) and α-pinene (15.74 %) were detected to be as the major components of the essential oil and aroma, respectively. It was observed that both natural and cultivated samples were rich in β-Sitosterol. Moreover, the root extract of natural samples was found to be richer than the other extracts in terms of abieatane diterpene (ferruginol, cryptanol, sugiol, and inuroyleanone) compounds. According to the LC–MS/MS results, it is seen that both natural and cultivated samples are very rich in rosmarinic acid. Especially, the flower part of the natural sample (98.10 mg analyte/g extract) was found to contain more rosmarinic acid than the other parts. Due to the high total phenolic and rosmarinic acid content, cytotoxic, anti-aging, and antioxidant potential of the ethanol extract of the leaf parts of the species, it has the potential to be used as a food supplement, food preservative and in the pharmaceutical industry.

Background: Behcet’s Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD. Objective: The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients. Methods: Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot. Results: The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients. Conclusion: SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients.

Background/aim: In this experimental study, we aimed to evaluate the late period effects of the combination of Ankaferd Blood Stopper (ABS), which has bone wound healing effects, and ß-tricalcium phosphate (TCP) on the regeneration of bone tissue through histopathological, immunohistochemical, and radiological (dual energy X-ray absorptiometry - DEXA) methods in nondiabetic rats.Materials and methods: Sixty-four Wistar albino male rats were used. In the calvaria of the rats, a bone defect 7.0 mm in diameter was created. These rats were divided into 4 different groups. Group 1 was the control group without any treatment, a 0.125 mL B-TCP graft was applied to Group 2, a 0.125 mL ABS was applied to Group 3, and a 0.125 mL (ß-TCP + ABS) mixture was applied to group 4. Half of the rats were sacrificed on day 28 and the other half on day 56. Histopathological, immunohistochemical, and DEXA analyses of the specimens were performed after the experiment.Results: As a result of the histopathological analysis, osteoblastic activity and new bone formation were found to be significantly higher in Group 2, Group 3, and Group 4 than the control group on day 28 (P < 0.05). However, inflammatory cell infiltration and vascular dilatation and hemorrhage decreased significantly compared to the control group (P < 0.05). The histopathological analysis in rats on day 56 showed that osteoblastic activity in Group 2 and Group 4 was significantly higher than in the control group, but there was a statistically significant decrease in inflammatory cell infiltration and vascular dilatation and hemorrhage compared to the control group (P < 0.05). New bone formation in Group 2, Group 3, and Group 4 was significantly higher than in the control group. Western blotting findings revealed that the osteonectin and osteopontin expression on day 28 was increased significantly in Group 2 and Group 4. DEXA analyses revealed that BMC values in Group 2 and Group 4 on day 28 were significantly higher than in the control group (P < 0.05). There was no significant difference in bone mineral density values on the 28th and 56th days (P > 0.05). Conclusion: The use of both ß-TCP + ABS and only ABS had positive effects on wound healing and bone formation in nondiabetic rats.