Evaluation of suppressor behavior of guanidine-derived metformin and galegine as novel potential drugs for cancer treatment: an in silico study.

There are some natural products from plants that can prevent and treat disease. Metformin, a derivative of galegine, is the basic drug to treat diabetes. Moreover, this molecule has anticancer properties that inhibit cancer cell growth and proliferation. In this study, the main interactions of galegine and metformin with various cancer-involved proteins, including mitochondrial alpha-glycerophosphate dehydrogenase, yeast NADH dehydrogenase, and transforming growth factor-ß1, were surveyed by molecular docking and molecular dynamics simulations. The results showed that each of the proteins makes complexes with the ligands via favorable non-bonded interactions, especially hydrogen bond interactions. There is greater stability for complexes containing galegine based on the root mean square deviation results. The higher structure compactness is also found in galegine receptors than in metformin receptors. Calculation of ΔGbinding, using the MM/PBSA methodology, shows that the binding energy values for metformin and galegine in interaction with each of the receptors are almost the same, and galegine has similar binding properties with metformin in interaction with the studied protein receptors. Therefore, galegine, a natural ingredient with better binding properties to cancer-involved proteins than metformin (with various side effects), can be applied as a new drug for cancer treatment.

Application of nanoparticles in breast cancer treatment: a systematic review.

It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The main treatment method for different types of cancer is chemotherapy with drugs. Because of less water solubility of chemotherapy drugs or their inability to pass through membranes, their body absorbs them inadequately, which lowers the treatment's effectiveness. Drug specificity and pharmacokinetics can be changed by nanotechnology using nanoparticles. Instead, targeted drug delivery allows medications to be delivered to the targeted sites. In this review, we focused on nanoparticles as carriers in targeted drug delivery, their characteristics, structure, and the previous studies related to breast cancer. It was shown that nanoparticles could reduce the negative effects of chemotherapy drugs while increasing their effectiveness. Lipid-based nanocarriers demonstrated notable results in this instance, and some products that are undergoing various stages of clinical trials are among the examples. Nanoparticles based on metal or polymers demonstrated a comparable level of efficacy. With the number of cancer cases rising globally, many researchers are now looking into novel treatment approaches, particularly the use of nanotechnology and nanoparticles in the treatment of cancer. In order to help clinicians, this article aimed to gather more information about various areas of nanoparticle application in breast cancer therapy, such as modifying their synthesis and physicochemical characterization. It also sought to gain a deeper understanding of the mechanisms underlying the interactions between nanoparticles and biologically normal or infected tissues.

Green synthesized Ag nanoparticles stimulate gene expression and paclitaxel production in Corylus avellana cells.

Synthesis of nanoparticles (NPs) through plant extracts has been suggested as an effective and nature-friendly method. Paclitaxel is one of the most valuable secondary metabolites with therapeutic uses, and hazelnut has been suggested as one of the sustainable resources for producing this metabolite. In the present study, we synthesized Ag NPs using the ethanolic extract of C. avellana leaves and were characterized using UV-visible, FTIR, XRD, EDX, DLS, SEM, and TEM analyses. In addition, we investigated the effect of green synthesized Ag (GS Ag) NPs (5 and 10 mg/L), para-aminobenzoic acid (PABA) (20 mg/L), and AgNO3 (10 mg/L) on cell viability, physiological characteristics, gene expression, and biosynthesis of secondary metabolites in hazelnut cell cultures. The results showed that 10 mg/L Ag NPs and AgNO3 significantly affected the cell viability, the content of ROS, peroxidation of lipids, antioxidant capacity, secondary metabolite production, and expression pattern of the genes involved in the taxanes biosynthesis pathway in the hazelnut cells. The cytotoxicity increased by increasing the GS Ag NPs concentration from 5 to 10 mg/L, which was associated with reduced membrane integrity and cell viability. Elicitation of the cells with 10 mg/L Ag NPs combined with 20 mg/L PABA (as a precursor) remarkably excited the expression of TAT and GGPPS genes and the production of secondary metabolites as well as paclitaxel. So that the highest expression of TAT and GGPPS genes (3.71 and 3.69) and the highest amount of taxol (230.21 µg g-1 FW) and baccatin (1025.8 µg g-1 FW) were observed in this treatment. KEY POINTS: • For the first time, we assessed and reported the molecular and physiological responses of C. avellana cells to GS Ag NPs, AgNO3, and PABA. • In hazel cells, GS Ag NPs stimulate several physiological and molecular responses. • In addition to increasing antioxidant activity, GS Ag NPs significantly increased the expression of genes involved in the paclitaxel biosynthesis pathway and the production of secondary metabolites.

Factors affecting the growth, antioxidant potential, and secondary metabolites production in hazel callus cultures.

Hazelnut is one of the most important nut plants recently suggested as a sustainable source for paclitaxel. In the present study, the effect of the concentration and combination of PGRs, different basal medium and ultrasonic waves on callus induction and growth, physiological characteristics, and taxol and baccatin III production in hazelnut callus cultures were investigated. The results indicated that combining 2,4-D (2 mg/L) and Kin (0.2 mg/L) with the sonication of explants for 1 min provides an optimized condition for callus induction and growth. Hazelnut explants exhibited different callus production and biochemical and metabolic characteristics depending on the basal medium type, ultrasound treatment, and inclusion of ascorbic acid in the medium. So that, the highest percentage of callogenesis (100%) observed in ½ MS + 1 min US, ½ MS + 150 mg/L AA, B5 + 1 min US and B5 + 150 mg/L AA, and also ½ MS salt + Nitsch vitamins + 150 mg/L AA. Furthermore, the highest callus growth (7.86 g FW) was obtained from ½ MS + 1 min US. The highest amount of baccatin III production (147.98 and 147.85 mg/L) was obtained from the WPM and MS basal media; the highest taxol production (44.89 mg/L) was observed in the WPM basal medium. The cultures in the MS, WPM, and MS salts + Nitsch vitamins media, had the highest H2O2 and MDA content, antioxidant enzymes activity, and phenolic compounds. In conclusion, culture media nutrient composition and concentration not only affect the cell growth and physiological status of the cultures but also improve secondary metabolites production and accumulation.

Improving galegine production in transformed hairy roots of Galega officinalis L. via elicitation.

Galega officinalis L. is an herbaceous legume used to treat symptoms associated with hyperglycemia or diabetes mellitus because of its dominant alkaloid, galegine. In this study, we induced hairy roots in this plant using Rhizobium rhizogenes strain A4, and investigated the effect of type, concentration, and duration of elicitor application on galegine content and some phytochemical characteristics in the hairy roots. Hence, the best growing hairy root line in terms of growth rate was selected and subcultured for treatment with elicitors. Then, at the end of the log phase of growth, chitosan (100, 200, and 400 mg/L), salicylic acid (100, 200, and 300 mM), and ultrasound (1, 2, and 4 min) were applied to hairy roots culture medium. High-performance liquid chromatography (HPLC) showed that the content of galegine was significantly increased after elicitation compared with the control. Thus, the highest content of galegine (14.55 mg/g FW) was obtained 2 days after elicitation when ultrasonic waves were applied to the hairy root culture medium for 4 min. Also, elicitation resulted in a significant increase in the content of total phenol, flavonoid, H2O2 and MDA compared with the control. So that the highest total flavonoid content was obtained in hairy roots that were treated with ultrasonic waves for 4 min and harvested 2 days after elicitation; while, application of 400 mg/L chitosan for 4 days resulted in the highest total phenol (16.84 mg/g FW).

Phaseolus vulgaris genome possesses CAMTA genes, and phavuCAMTA1 contributes to the drought tolerance.

Calmodulin-binding transcription activators (CAMTAs) are a family of transcription factors that play an important role in plants' response to the various biotic and abiotic stresses. The common bean (Phaseolus vulgaris L.) is one of the most important crops in the world and plays a pivotal role in sustainable agriculture. To date, the composition of CAMTA genes in genomes of Phaseolus species and their role in resistance to drought stress are not known. In this study, five PhavuCAMTA genes were characterized in common bean genome through bioinformatics analysis, the morphological and biochemical response of 23 Ph.vulgaris genotypes to different levels of drought stress were evaluated and the expression patterns of PhCAMTA1 in the leaf tissues of sensitive and tolerant genotypes were analysed. Gene structure, protein domain organization and phylogenetic analyses showed that the CAMTAs of Phaseolus were structurally similar and clustered into three groups as other plant CAMTAs. Genotypes showeda differential response to drought stress. Thus, the plant height, number of nodes and flower, total chlorophyll and total protein content, and activity of antioxidant enzymes (ascorbate peroxidase and catalase) in plants significantly influenced by genotype and drought stress interaction. Moreover, the resistant and susceptible genotypes were identified according to three-dimensional plots and the expression patterns of PhavuCAMTA1 gene were studied using real-time quantitative polymerase chain reaction. The results of the present study serve as the basis for future functional studies on the Phaseolus CAMTA family.

Effect of ultrasonic waves on crocin and safranal content and expression of their controlling genes in suspension culture of saffron (Crocus sativus L.).

The expression of biosynthesis controlling genes of crocin and safranal in saffron (Crocus sativus) can be influenced by ultrasonic waves. Sterilized saffron corms were cultured in a ½-MS medium supplemented by 2-4-D and BAP.  Saffron callus cells were treated with ultrasonic waves in a cellular suspension culture under optimal growth conditions. The samples were collected at 24 and 72 hours after treatment in three replications. The secondary metabolites were measured by high-performance liquid chromatography and the gene expression was analysed by the real-time polymerase chain reaction. Results indicate that this elicitor can influence the expressions of genes CsBCH, CsLYC and CsGT-2; the ultrasonic waves acted as an effective mechanical stimulus to the suspension cultures. The analysis of variance of the ultrasonically produced amounts of safranal and crocin indicates that there is a significant difference between once- and twice-treated samples in that the amount of safranal was the highest within the samples taken from the twice-treated suspension culture at 72 h after the ultrasound treatment, and the crocin was maximised after 24 h passed the twice-applied ultrasound treatment.

Ultrasound-enhanced gene delivery to alfalfa cells by hPAMAM dendrimer nanoparticles.

Cationic polyamidoamine (PAMAM) dendrimers are highly branched nanoparticles with unique molecular properties, which make them promising nanocarriers for gene delivery into cells. This research evaluated the ability of hyperbranched PAMAM (hPAMAM)-G2 with a diethylenetriamine core to interact with DNA, its protection from ultrasonic damage, and delivery to alfalfa cells. Additionally, the effects of ultrasound on the efficacy of hPAMAM-G2 for the delivery and expression of the gus A gene in the alfalfa cells were investigated. The electrophoresis retardation of plasmid DNA occurred at an N/P ratio (where N is the number of hPAMAM nitrogen atoms and P is the number of DNA phosphorus atoms) of 3 and above, and hPAMAM-G2 dendrimers completely immobilized the DNA at an N/P ratio of 4. The analysis of the DNA dissociated from the dendriplexes revealed a partial protection of the DNA from ultrasound damage at N/P ratios lower than 2, and with increasing N/P ratios, the DNA was better protected. Sonication of the alfalfa cells in the presence of ssDNA-FITC-hPAMAM increased the ssDNA delivery efficiency to 36%, which was significantly higher than that of ssDNA-FITC-hPAMAM without sonication. Additionally, the efficiency of transfection and the expression of the gus A gene were dependent on the N/P ratio and the highest efficiency (1.4%) was achieved at an N/P ratio of 10. The combination of 120 s of ultrasound and hPAMAM-DNA increased the gusA gene transfection and expression to 3.86%.

Investigation of diversity in Aegilops biuncialis and Aegilops umbellulata by A-PAGE.

Aegilops species, wild relatives of wheat, are one of the important genetic resources in wheat breeding. In this study 13 populations of Aegilops biuncialis along with 2 populations of progenitor species Aegilops umbellulata were analysed in six replications using of acid polyacrylamide gel electrophoresis. The results showed that TN-01-293 population had a high gluten and grind quality because of high percentage of γ-45.31 and γ-43.5 (high gluten quality index) in the observed band. Also, Ahar population from A. biuncialis was introduced to light gluten because of low percentage of γ-45.31 and γ-43.5 bands of quality. All studied populations can be used in breeding programmes for improving quality of bread wheat because of lack of γ-42 and γ-40 bands (low quality indices) and including high frequency of band in ω region. Through using PopGen 1.32 software, diversity is estimated . The maximum value of genetic diversity among populations resulted 49%.

Enhanced thebaine production in Papaver bracteatum cell suspension culture by combination of elicitation and precursor feeding.

In this study, the effect of methyl jasmonate (MJ) and ultrasound (US), individually and in combination with L-tyrosine, on the stimulation of thebaine production in Papaver bracteatum cell suspension cultures was studied. The addition of L-tyrosine did not significantly affect the cell biomass, but significantly increased the thebaine yield of cells compared with the control. The synergistic effects of MJ and L-tyrosine in the combined treatment of 100 µM MJ and 2 mM L-tyrosine increased the thebaine yield of cells up to 84.62 mg L(- 1) at 6 days after treatment. Sonication of the cells for 20 s caused a significant decrease in cell growth and biomass, whereas the thebaine yield increased up to 39.60 mg L(- 1) at 6 days after treatment. The combination of US (10 s) and L-tyrosine feeding (2 mM) significantly increased the production of thebaine in comparison to individual utilisation of 2 mM L-tyrosine and US (10 s).

Karyotype and C-banding patterns of mitotic chromosomes in Heteranthelium piliferum.

The C-banded karyotype of Heteranthelium piliferum species was studied in a natural population from northwest of Iran using aceto-iron-hematoxilin staining and C-banding technique. Chromosome measurements including long arm, short arm and chromosome lengths, arm ratio index, relative chromosome length, heterochromatin percent per chromosome and per chromosome set were made. It was revealed that the karyotype of this species is symmetric and consists of 7 pairs of metacentric chromosomes. Arm ratio index values ranged from 1.01 in chromosome G to 1.44 in chromosome D. One of the chromosomes had a satellite located on the end of its long arm (chromosome G). The Q genome of this species like A, B, D, S, M and M, genomes in diploid species of Aegilops-Trticum group, H genome in Hordeum, E genome in Agropyron and R genome in Secale has metacentric or sub-metacentric chromosomes.