leila hosseinzadeh

Despite significant advancements in structural engineering, unfortunately we continue to witness severe loss of life and extensive damage caused by earthquake. Therefore, providing solutions to counteract this natural event and mitigate its effects has always been a focus of researchers. Structural control systems, such as dampers and isolators, have gained significant popularity due to their remarkable ability to reduce the seismic response of structures. In this research, a comprehensive review of the development and application of tubular yielding steel dampers has been the focus. Dampers are classified based on their behavioral characteristics and geometric configuration, and tubular dampers are among the most commonly used dampers. Based on conducted research, it can be concluded that most tubular dampers have a simple and cost-effective manufacturing technology, and the possibility of replacing damaged components after an earthquake is available for each of these types of dampers. On the other hand, tubular dampers offer advantages such as high energy absorption and dissipation capacity, consistent performance under cyclic loading, high ductility, and high strength and stiffness. In this article, a comparison between different types of yielding tubular dampers has been conducted. It is worth noting that despite the advantages of tubular dampers, their widespread use in the country is not yet evident. Moreover, the existing codes and standards lack design provisions for such energy dissipation systems, which is a significant gap considering the importance of the subject.

Nowadays, herbal medicine has been utilized to treat various diseases such as cancer, which showed successful therapeutic efficacy in previous studies. This study for the first time evaluated the cytotoxic potential of cinnamaldehyde (CIN) alone and in combination with doxorubicin (DOX), a well-known potent anti-tumor agent, on the proliferation of prostatic cancer cell line (PC3).

Experimental approach: 

The cytotoxicity and apoptotic activities of CIN and DOX, either separately or together, were determined on PC3 cells by the MTT test and Annexin V/PI assay, respectively. To further investigate which apoptotic pathway participated in cell death a collection of prominent markers of apoptosis induction including caspase-3/7 activations, mitochondrial membrane potential (MMP), and phosphatidyl serine translocation were detected.

The different concentrations of CIN and DOX significantly inhibited the proliferation of PC3 cells in a concentration-dependent way within a 24-h treatment. In addition, the induction of apoptosis by CIN was accompanied by an increase in the activation of caspase-3/7 in PC3 cells with IC50 concentrations of 12.5 and 10 μg/mL for CIN and DOX, respectively. Moreover, the morphological observations obtained from flow cytometry MMP and caspase-3/7 activity assays, altogether, revealed the potential effect of CIN on apoptosis induced in PC3 cells by DOX.

Conclusions and implications: 

Taken together, the current study concluded that the combination of CIN and DOX could lead to the production of a potential therapeutic agent for prostate cancer. However, further in vivo and clinical studies are still needed to validate this combination in prostate cancer therapy.

The steel shear wall is a lateral load resistant system that has received attention in recent decades. Steel shear walls are used in two ways: hardened and unhardened walls. Although the post-buckling behavior of the steel shear wall causes the post-buckling loading but this plate buckling is not always desirable. One of the useful solutions to prevent lateral buckling is the use of walls with corrugated plates. In this research, the behavior of a steel shear walls consisting of two flat plates and one corrugated plate was studied in two states of conventional structural steel (A36) and low yield point steel(LYP). The use of low yield strength steel improved the seismic performance of the steel shear wall system. Taking into account the changes in the thickness of the plate and different aspect ratio, LYP steel increased the values of stiffness, ultimate strength, and energy absorption by about 74%, 51% and 36%. The effect of increasing the plate thickness on the stiffness parameter for infill panel with A36 steel is more than that of LYP steel. Increasing the thickness of the plates increased the stiffness, ultimate strength, and energy absorption of the system for A36 steel by about 45%, 35%, and 44%, and for LYP steel by about 35%, 62%, and 53%, and also increase in the dimensional ratio of stiffness, strength and increased the energy absorption of the system for A36 steel by 51%, 36% and 38% respectively and for LYP steel by 52%, 46% and 49% respectively.

Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population.  In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rs10995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results.

Falcaria vulgaris is a medicinal plant with culinary uses and widespread therapeutic applications. Despite already proven as a very promising dietary supplement, its safety and possible effects on the human body are yet to define. This study was designed to investigate the acute and subchronic toxic effects of hydroethanolic F. vulgaris in male and female Wistar rats.

Experimental: 

To evaluate the safety of a hydroethanolic extract of F. vulgaris, acute and subchronic toxicity in Wistar rats treated with extract was investigated. For investigation of acute toxicity of F. vulgaris, both genders of rats were treated for 45 days with a single dose of the extract (4000 mg/ kg) via gavage. Also for sub-chronic testing, the extract was administrated orally at the doses of 150, 300, and 450 mg/kg for 45 days. At the end of the study, the animals were sacrificed and the hematological, biochemical, and histopathological parameters were assayed.

After a single oral administration of F. vulgaris (4000 mg/kg), no mortality was observed in both control and groups in either sex. Also, histopathological inspection of vital organs and tissues revealed no obvious alteration in these organs. The obtained results showed a significant reduction in the weight of heart and liver in male rats that received the highest dose of the extract. The level of red blood cell distribution width (dose of 450 mg/kg) from the hematological parameters and the level of serum creatinine (dose of 150 and 450 mg/kg) from the biochemical parameters increased significantly in male rats. On the contrary, during treatment the concentration of all examined minerals remained unchanged. Histopathological inspection indicated that liver, kidney, and testis were found to be affected by subchronic exposure to F. vulgaris extract.

The results of the acute study revealed that F. vulgaris may be nontoxic even at doses less than 4000 mg/kg body weight. However, the result of subchronic study confirmed the liver dysfunctions in Wistar rats and also suggested the significant effect of F. vulgaris on testicular tissue, which may cause serious male infertility. The ability to impair male fertility by such a medicinal plant has not been reported yet. It can be concluded that the no observed adverse effect level (NOAEL) of F. vulgaris are 150 and 450 mg/kg for male and female rats, respectively.

Cancer development is a multi-stage process in which apoptosis plays an important role. Apoptotic agents from natural products like phenolic compounds can be used effectively in the treatment of cancer. Berberis vulgaris L. fruits are a rich source of natural phenolic compounds and have been evaluated for their apoptotic effects.

this study was carried out to evaluate the apoptotic effect of B. vulgaris fruits in normal and cancerous cells by investigating p53, Bax, and Bcl-2 genes expression and identifying an active compound.

B. vulgaris fruits were extracted with ethanol using maceration method. To yield an active compound, the extract was divided into fractions and subfractions that could be evaluated using chromatography techniques, and the purified compound structure was determined by nuclear magnetic resonance (NMR). The cytotoxic activity of the selected fraction against 3T3 and MCF-7 cell lines along with its effect on the mRNA apoptosis regulating genes like p53, Bax, and Bcl-2 were investigated subsequently.

Results showed that B. vulgaris extract increased the mRNA level of p53 and Bax and decreased Bcl-2 mRNA level in cancer cell lines. The structure of the purified compound was determined as the 3-caffeoylquinic acid (chlorogenic acid).

B. vulgaris fruit has in vitro antineoplastic activity by stimulating cellular apoptosis via increasing the levels of p53 and Bax proteins and decreasing Bcl-2 and comprises chlorogenic acid as one of its phenolic phytochemicals.

Artemisia is an important genus of Iranian flora. The current study on the aerial parts of A. turanica was conducted to determine the most potent extract and its fractions in the cytotoxic assays.

The cytotoxic e"ects of 13 fractions (1–13) from dichloromethane extract on three cancer cell lines (KB, HeLa, and U87MG) were assessed. Preliminary phytochemical analysis of more potent cytotoxic fractions was carried out using thin-layer chromatography (TLC) and di"erent spray reagents.

Dichloromethane extract showed the best bioactivity against cancerous cell lines. Fractions 4, 6, 7, and 9 of this extract had potential e"ective components in the inhibition of the proliferation of KB cancer cells. In addition, fractions 4 and 6 were able to inhibit the growth of HeLa cell line. The active fractions decreased the mitochondrial membrane potential level, and played a critical role in caspase-3 and 9 activation and generation of reactive oxygen species. The cytotoxic activity of these fractions was found to be not significant toward U87MG cells. TLC analysis suggested the probable presence of terpenoids as the main component of most of the selected fractions.

The species is suggested as the potential source of cytotoxic phytochemicals.

Deformed memory alloys due to special behaviors such as superelastic behavior (complete recovery of strain during loading and unloading in the form of a hysteresis curve) and memory behavior (recovery of strain during heating due to phase transformation from stable phase to low temperature to stable phase At high temperatures) has attracted the attention of researchers in the last decade. In addition to the above behaviors, these materials have other suitable properties such as high resistance to fatigue and corrosion, stability of its behavior-strain and energy dissipation ability. One of the ways to manage damage in the structure and reduce seismic needs is to use rocking systems. In these systems, relative motion occurs mainly between the legs of the columns and their corresponding foundations, where energy absorbers are made. In the rocking motion of the body, the structure deforms to an elastic level and moves almost as a rigid body, and after the earthquake, the weight of the building causes the structure to return to its original place.

Ulcerative colitis (UC) is a chronic, idiopathic, and recurrent disease with unknown etiology. Achillea wilhelmsii has been introduced as a herbal remedy for gastrointestinal ulcers and UC in traditional Persian medicine.

We examined the effectiveness of A. wilhelmsii aqueous extract against acetic-acid-induced UC in rats. Settings and Design: Fifty-six male Wister albino rats weighing 180–200 g were randomly divided into eight groups and after induction of UC were treated with five doses of aqueous extract of A. wilhelmsii.

After induction of UC by acetic acid, the aerial parts of A. wilhelmsii (6.25, 12.5, 25, 50, and 100mg/kg) were administered orally. On 11th day, the animals were euthanized by overdose of ether inhalation and the intestinal tissue was rapidly dissected for macroscopic, histological, and microscopic scores. Statistical Analysis Used: Data were analyzed by stats Directver.2.7.9 (SAS, Cary, North Carolina). One-way analysis of variance (ANOVA) followed by Newman–Keul’s post hoc test for multiple comparisons. A value of P < 0.05 was considered as significant level. Results were expressed as mean ± standard error of the mean (SEM).

All doses of A. wilhelmsii extract significantly reduced macroscopic and microscopic scores of colitis without significant changes in bodyweight of animals.

Treatment of the rats with A. wilhelmsii extract improved UC via its anti-inflammatory, antioxidant, and antimicrobial activities. According to the results of this study, A. wilhelmsii has a therapeutic effect against acetic-acid-induced UC in the animal model.

Iran is considered as one of the most seismically active regions in the world. Therefore, the need for seismic strengthening of the existing structures is essential. One of the suitable methods in seismic reinforcement of buildings is the use of dampers. Dampers are components, which are mostly utilized to increase damping and deplete seismic energy. Numerous studies have indicated that dampers can reduce seismic displacement. In this way, the performance of most of the load-bearing members of the structure remains in the elastic range. In this research, the effect of using slit steel dampers (SSD) on concrete structures was evaluated. Therefore, four models of SSD were selected as following: 3 single slit, 3 double slit, 5 single slit and 5 double slit in three thickness of 6, 8 and 10 mm, which were placed in a concrete frame with a single diagonal brace at the connection of the brace to the column beam. The effects of increasing the number of slits from 3 to 5, from single to double and increasing the thickness were studied. The results exhibited that by increasing the thickness of dampers, the area of force-displacement diagram, stiffness and strength were increased in frames. The frames, which are consisted of double 3-slit dampers presented better performance than 5-slit dampers. So that, the reduction of rigidity of frame with single 5-slit dampers in a thickness of 10 mm, was 4.9% in comparison with double samples. In addition, it is decreased in stiffness by 2.9% and 7.3% for single and double models, respectively

After the Northridge earthquake, it was determined that the beam-to-column connections in the moment frames were weak and needed to be revised. In recent years, the use of bolted connections have expanded and replaced almost welded connections. The US Code of Conduct (AISC358-16) introduced a new connection called the Simpson Connection, which is a semi-rigid connection with the idea of ​​damage control. Progressive connection is a new and smart type of screw connection that includes a weakened plate, end plate, corner as well as a buckle plate. The main purpose of this study is to investigate the linear and nonlinear behavior of Simpson connectivity using ABAQUS software. The baseline sample was selected from the model outlined in US Code (AISC358-16). To gain a better understanding of the new Simpson junction model, 14 numerical specimens were modeled and the strengths and weaknesses of the models including ductility, stiffness, strength, and energy absorption of the models were compared. In this connection, the geometry of weakened plate and its performance is important. In so doing, variables such as mid-length, mid-width, initial length, as well as stiffeners were evaluated in the initial length of the weakened plate. The model with a thickness of 30 mm thicker than the other models with respect to the mentioned characteristics, showed acceptable results including anchor tolerance of 1010 kN.m and energy absorption of 55.53 kN/mm which showed that its use is suitable for areas with high seismicity.

In the present study, we tried for the first time to examine whether cinnamaldehyde (CA), with herbal nature, can be co-administrated with doxorubicin (DOX, as an anticancer drug) toward U87MG glioblastoma cells to potentiate its cytotoxic effect and overcome or reduce its side effects.
Experimental approach: The cytotoxic effect of DOX and CA, either individually or in combination,   were evaluated on U87MG cells using the MTT method. The mechanism of action was studied by investigating the mode of cell death using caspase-3 and 9 activations, mitochondrial membrane potential (MMP) as well as sub G1 analysis. The expression of apoptosis- related genes (Bcl-2 and Bax) was also examined.

Cellular toxicity assay revealed that CA and DOX can potentially reduce the viability of U87MG cells with IC50 at 11.6 and 5 µg/mL, respectively. Exposure with the combination of CA and DOX significantly increased cytotoxic effect of DOX on U87MG cells. The results of SUBG1, MMP, and also caspase-3 and -9 activity assays, in association with the results corresponding to the Bax and Bcl-2 gene expressions, altogether revealed that CA can induce apoptosis on U87MG cells. Moreover, apoptogenic effects of DOX were found to be potentiated by CA.

The results of this study revealed the promising cytotoxic and apoptogenic role of CA on U87MG cells. Additionally, our findings demonstrated that CA is able to enhance the apoptosis induced by DOX on human glioblastoma cells. Collectively, these data suggested that  co-exposure of CA and DOX could be effective for treatment of glioblastoma, but further in vivo and clinical studies are still needed to prove these results.

A green and efficient one-pot, four-component synthesis of 4-phenyl-4,5-dihydropyranopyrazolone derivatives 5a–5l is described in ethanol-water with activated potassium carbonate and evaluation of anticancer activity on cancer cell lines and apoptosis mechanism is also investigated. This method provides several advantages such as environmental friendliness, shorter reaction time, excellent yields, and simple workup procedure. The in vitro cytotoxic activity of the synthesized compounds was investigated against cancer cell lines (PC-3, MCF-7, and A-2780) in comparison with doxorubicin, a well-known anticancer drug, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide colorimetric assay. Also apoptosis studies were investigated by caspase-3 and caspase-9 enzymes and mitochondrial membrane potential. Our compounds showed acceptable and moderate cytotoxicity compared with doxorubicin in the studied cell lines. The compounds 5g in PC3 cell line (half maximal inhibitory concentration (IC50= 104 µM)), 5g and 5i in MCF7 cell line (IC50 = 23 and 87 µM, respectively), and 5g–5i in A2780 cell line (IC50 = 60, 50, and 31 µM, respectively) showed the best results close to the control drug doxorubicin. The compound 5h showed significant result in the activation of caspase-3 and caspase-9 enzymes in comparison with the control. Only the 5g in MCF7 cells and the 5g–5i derivatives in A2780 cells caused increased mitochondrial membrane potential compared to the control group.

In the present study, we tried for the first time to examine the anti-proliferative andanti-apoptogenic effect of Glabridin (Glab) toward three groups of cancer cells (SKNMC,H1299, and A2780). Furthermore, the possibility of co-administration of Glab with doxorubicin(DOX) to these cells was also examined to find out whether Glab can potentiate the cytotoxiceffect of this chemotherapy agent. Different cellular assays (MTT, caspase-3 activity, MMP, RT-PCR analysis) were carriedout on the cancer cells treated with Glab. Cellular toxicity assay revealed that Glab can potentially reduce the viability of thesecells with IC50 concentrations up to 10, 12, and 38 μM toward A2780, SKNMC, and H1299 celllines, respectively. The results of MMP and caspase-3 activity assays, in association with theresults corresponding to the BAX and Bcl-2 gene expressions, altogether revealed that Glab canexert apoptogenic effect on these cells. The intrinsic mitochondrial pathway was found to bethe main mechanism, in which Glab induced apoptosis toward H1299 cells and SKNMC cells,while the apoptosis mechanism for A2780 cells could be probably through extrinsic pathway.Glab also potentiated the cytotoxic effect of DOX and its accumulation in H1299 cell line. The results of this study revealed the promising cytotoxic role of Glab on differentcarcinoma cells. These data also suggested that co-chemotherapy method using Glab could beeffective for treatment of cancer, but further in-vivo and clinical studies are still needed to assurethese results.

Different types of Artemisia aucheri extracts were reported to have various biological activities including a cytotoxic effect on some cancer cell lines. We investigated the antiproliferative activity of isolated sesquiterpenoids from petroleum ether extract of Artemisia aucheri (A. aucheri)aerial parts on SK-N-MC, MCF-7, and A2780 cell lines. Phytochemicals from the petroleum ether cold macerated extract were isolated using normal phase vacuum liquid chromatography and high pressure liquid chromatography (VLC and HPLC) and the structures of the components were determined by spectroscopic means. Cell viability was determined by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Activation of caspases-3 and -9 was evaluated using a spectrophotometer. Mitochondrial membrane potential (MMP) was measured using rhodamine 123 fluorescent dye. Two tetrahydrofuran- type sesquiterpenoids, hydroperoxide of davanone (1) and hydroxydavanone (2) were isolated and characterized. Between these compounds, compound 1 exhibited the most potent activity against the MCF-7, SK-N-MC and A2780 cell lines with IC50 value of 8.45 ± 0.81 µg/mL, 9.60 ± 1.32 µg/mL and 10.9 ± 2.03 µg/mL in A2780, MCF-7 and SK-N-MC cells, respectively. Compound 1 inhibited cell growth of human cancer cells by induction of apoptosis. To the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of two davanone derivatives isolated from A. aucheri in human cancer cells. Overall, our data suggest that hydroperoxide of davanone (1) should be further studied in-vivo as a potential antitumor agent.

In high-rise buildings, by increasing the number of floors, designers are forced to use the tubular system or to combine it with other systems. The “shear lag” phenomenon and also architectural problems due to the low distance between the columns are disadvantages of this system. Concentrically bracings due to their high shear-stiffness combining with tubular system improve the behavior of this system due to the disadvantages mentioned. But the main disadvantage of this system is the sudden change of lateral deformation against wind and earthquake forces. In this paper, a new idea is introduced that uses a steel shear wall at the two ends of the frame and a general bracing between them. These two walls act as a strong moment anchor against overturning moment of building, and due to their high stiffness, absorb the major shear forces. So, the shear lag decreases. The results show that lateral deformation is reduced in the proposed system, and the axial forces and bending moment also have a significant reduction, which indicates the high efficiency of this system.

Lately, bismuth-based nanomaterials have been widely utilized in medical researches such as imaging, drug delivery and radio-sensitization. Despite their advantages, bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study, we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines. Bi2O3 NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10, 20, 50 and 100 μg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also, apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis, respectively. Bi2O3 NPs were successfully synthesized with average size of 19.2 ± 6.5 nm, then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 μg/ml for both compounds. Results indicated low cytotoxicity of the prepared NPs at lower incubation periods, which is very important for their further applications. However, 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.

Date, Phoenix dactylifera, is a commonly used food in arid and semiarid regions of the world including Iran. Date seeds, are low-cost agriculture by-products and used for several medicinal uses and animal food, however, there are no records on its likely toxic effects. To investigate the safety of P. dactylifera, we investigated its acute and sub-chronic toxicity in Wistar rats in both sexes. Animals were treated with four different single doses (5g/kg) of P. dactylifera extract oral gavage (per oral, p.o.), and checked for symptoms of toxicity two weeks after dispensation. In the sub-chronic toxicity study, P. dactylifera seeds were administered in three different doses (500, 1000, 1500 mg/kg) through 45 days. Fatality, clinical symptoms, body weight alteration, gross findings, organ weights, hematological and biochemical criteria, and histological specifications were screened all along the study. We found no fatality or morbidity in clinical manifestations, corpse weight, or necropsy evidence in none of the rats in the acute study. Regarding the outcome of the sub-chronic assay, a meaningful decline in urea concentration in male animals and no significant differences observed in other hematological criteria in both sexes. No significant histopathological difference in lung and heart tissue of different groups were observed but there are kidney cortex congestion and hepatocyte focal degeneration in female and male rats taking elevated doses (1500 mg/kg) of palm kernel extract, respectively. Analyses of the obtained results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the no observed adverse effect level of P. dactylifera was defined to be 1000 mg/kg for male and female rats.

This study evaluated the anti-atherosclerosis effect of aqueous extract and polysaccharide-enriched fraction of Prosopis farcta on adhesion and inflammatory cascades in vascular endothelial cells and related molecular mechanisms. Cellular toxicities of LPS, plant extract and polysaccharide-enriched fraction were analyzed in vitro using the MTT method. The ROS accumulation, mRNA expression of ICAM1 and VCAM1, and COX activity were measured in HUVEC cells. These results revealed a new underlying mechanism for anti-atherosclerosis effect of P. farcta and polysaccharide-enriched fraction by attenuating inflammatory cascade mediated by COX expression, modulating expression of cell-adhesion molecules including VCAM-1 and ICAM-1, and diminishing oxidative stress agents.

The antiproliferative effect of dichloromethane extract of Artemisia aucheri (A. aucheri) has been demonstrated previously on human cancerous cell lines. In the current study, further fractionation was carried out on the dichloromethane extract of A. aucheri and their cytotoxic effects were evaluated on three human cancer cell lines; SKNMC, MCF-7, and A2780. Cell viability was determined by MTT assay and activation of caspases was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the genes expression. Detection of DNA fragmentation was carried out by flow cytometry. The obtained results showed that fractions 5 and 7 (F5 and F7) have a potent cytotoxic effect, especially against MCF-7 cells. F5 and F7 also induced apoptosis through the DNA fragmentation and mitochondrial membrane potential (MMP) disruption in MCF-7 cells. The caspase-3, 9 enzyme activities were also increased after exposure to F5 and F7. Moreover, caspase-8 activity increased significantly after exposure to F7 but not F5. The level of mRNA expressions of Bax and Smac/DIABLO was increased after exposure to both fractions. A detectable decrease was also observed in the mRNA expression of Bcl-2 after exposure to F7. No change was observed in the level of mRNA expressions of tumor suppressor P53 after exposure to F7. Therefore, the cell cycle arrest and apoptosis induced by F7 could probably be mediated through a p53-independent mechanism. Taken together, these observations demonstrated that the cytotoxic effect of F5 and F7 on MCF-7 cells is likely exerted via apoptotic cell death.

Fatty acids (FAs), the key structural elements of dietary lipids, are notable in the nutritional value of plants. Black cumin, a popular anti-inflammatory and antioxidant food seasoning, contains nonpolar constituents such as FAs.
Seeds were extracted using hexane and their cytoprotective activity was assessed against doxorubicin (DOX)-mediated oxidative stress and apoptosis in PC12 cell line.
In spite of the cellular death induced by DOX toward PC12 cells, bioassay-guided purification showed that pretreatment with FAs mixtures (24h) attenuated DOX-mediated apoptosis, which could be attributed to the inhibited caspase 3 activity and enhanced mitochondrial membrane potential. Palmitic acid, caprylic acid and oleic acid each 1/3 in the mixture, also suppressed DOX-induced ROS generation.
Our observation indicated that the subtoxic concentration of FAs from Nigella sativa could effectively protect the cells against oxidative stress, due to their antioxidant activity, and could be regarded as a dietary supplement.

This paper introduces a green and simple hydrothermal synthesis to prepare carbon quantum dots (CQDs) from walnut oil with a high quantum yield. In addition, cytotoxic and apoptogenic properties of the CQDs were analyzed on human cancer cell lines.
The optical properties and morphological characteristic were investigated by the TEM, XRD, FT-IR, UV-vis and photoluminescence (PL).The cytotoxic potential of walnut CQDs was evaluated on PC3, MCF-7 and HT-29 human carcinoma cell lines using the MTT methods. The mechanism of action was studied by investigating the mode of cell death using the activation of caspase-3 and 9 as well as mitochondrial membrane potential (MMP). Cellular uptake of the CQDs was detected by fluorescence microscope. CQDs had an average size of 12 nm and a significant emission at 420 nm at an excitation wavelength of 350 nm was recorded.
The prepared CQDs possessed a good fluorescent quantum yield of 14.5% with quinine sulfate (quantum yield 54%) as a reference and excellent photo as well as pH stabilities. The walnut CQDs were proved to be an extremely potent cytotoxic agent, especially against MCF-7 and PC-3 cell lines. Induction of apoptosis by CQDs was accompanied by an increase in the activation of caspase-3. Caspase-9 activity did not increase after exposure to the CQDs. Additionally; the MMP did not show any significant loss.
The results of our study can corroborate the cytotoxic and apoptotic effect of walnut CQDs in the PC3 and MCF-7 cancer cell lines.

In this study, a novel small interfering RNA (siRNA) delivery system based on encapsulation of lipolexes was introduced. A Lipofectamine-2000–siRNA complex was encapsulated in particles of poly (D,L-lactic-co-glycolic acid; PLGA) by double micro-emulsion. Parameters such as surfactant concentration, the volume of the inner water phase and the outer water phase were evaluated to achieve high loading efficiency, small particle size and low polydispersity. The ratio of the internal to the external phase has a significant effect on the particle size and encapsulation efficiency. The various concentration of surfactant has a different effect on the particle size. In order to achieve optimum conditions for siRNA delivery, the luciferase siRNA was used as a reporter gene. The prepared formulations have a particle sizes in the range of 222 ± 5.2 nm to 900 ± 20 nm and loading efficiency in the range of 4% to 29%. lipoplex loaded PLGA particles (LPPs) had a zeta potential values ranging from −23±2.5 to −29±1.5 mV. S1 and S3 formulations showed greater efficiency compared to the lipoplexes. The gene silencing pattern of LPPs was different from lipoplex. The cytotoxicity of lipoplex loaded PLGA particles (LPPs) was lower than lipoplexes in H1299 cell line. LPPs showed better stability and higher level transfection in the presence of heparin than lipoplexes. The EGFR silencing of S1 formulation was greater than other formulation in A431 cell line. All together these properties suggest that lipoplex loaded PLGA particles have strong potential as a gene carrier for in vivo silencing angiogenesis and treatment of cancer.

In this study, we evaluated the cytotoxic potential of fractions (F1-F5) isolated from hexane extract of the seeds of N. sativa on human ovarian carcinoma cell line, A2780. F2 showed an outstanding potent cytotoxic effect against A2780 cells. Next, this fraction was purified to obtain six sub-fractions (SF1-SF6) and their cytotoxic effects were then evaluated. The obtained results showed that SF2 had strong cytotoxic effect against A2780 cell line. The effective subfraction (SF2) was determined to be linoleic acid (LA) according to spectroscopic analyses. In the next set of experiments, the apoptotic potentials of LA were investigated. Induction of apoptosis by LA was accompanied by an increase in activation of caspase-3, -9 and reduction in mitochondrial membrane potential (MMP) in A2780 cells. It can be concluded that LA, inhibited the growth of human ovarian carcinoma cells, A2780 and induced mitochondrial-related apoptosis.

Osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural coumarin derivative, has exhibited various pharmacological properties. In addition, the possibility of its development as a promising lead compound for drug discovery has been proposed. However, there is little toxicological information regarding safety of repeated exposure to this coumarin.
The present study evaluated the potential toxicity of osthole after acute and subchronic administration in rodents. In addition, we investigated the effect of osthole on different hepatic CYP gene expressions in male rats receiving the highest dose of osthole.
In the acute toxicity study, single doses of osthole (100, 500, and 1000 mg/kg) were administered intraperitoneally to mice and the mice were then monitored for 14 days. In the subchronic toxicity study, osthole was administered orally to rats at doses of 5, 25, and 50 mg/kg/day for 45 days.
The results of acute study indicated that LD50 of osthole is about 710 mg/kg. There was no significant difference in body weight, relative organ weight, and hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes including in creatinine, potassium, glucose, albumin, and urea levels. The results of histopathological studies showed that all the removed organs, specially kidney, were affected by subchronic exposure to osthole. The change in the kidney included peritubular capillary congestion, hemorrhage in renal parenchyma, mild tubular dilatation, and mild interstitial infiltration of inflammatory cells. Furthermore, osthole treatment caused an induction in CYP1A2, CYP2E1, and CYP2C11.
Finally, concerning the common classification of relative toxicity of chemicals, acute toxicity results suggested that osthole is a moderately toxic substance when administered i.p. The obtained data from subchronic study supported the evidence of renal function impairment by osthole. The no-observed adverse-effect level (NOAEL) of the extract for both male and female rats is considered less than 5 mg/kg.