Facile Design of Superparamagnetic Core-Shell EDC-Ascorbate-Fe3O4 Nanocomposites for Targeted Delivery of Doxorubicin to Triple Negative Breast Tumor by Fenton Reaction

Triple negative breast cancer (TNBC) phenotype accounts for its significant resistance to chemotherapy and other therapeutic procedures. So, the establishment of better and effective therapeutic procedures has become a challenge during recent years. Doxorubicin is a potent chemotherapeutic candidate but its prominent side effects can be subsided via its combination with nanocarriers. So, the present study was aimed to design ascorbic acid modified biopolymeric EDC/NHS-modified magnetic nanoparticles (MNP@MNP@AA-EDC/NHS-DOX for doxorubicin drug delivery to the triple negative breast cancers cell lines of MDA-MB-231, MDA-MB-468 and HCC1937. Monodisperse Fe3O4 MNPs were prepared by chemical co-precipitation method. According to the SEM and DLS results, MNP@AA-EDC/NHS-DOX, MNPs@AA, MNP@AA-MNP@AA-EDC/NHS and MNP@AA-EDC/NHS-DOX had average particle diameter of 53, 79 and 95 nm, respectively. While, XRD analysis showed that the MNP material had the strongest Fe crystal peak, while surface modified MNP@AA-EDC/NHS-DOX did not alter the characteristic properties of MNPs. VSM magnetization analysis revealed that MNP@AA-EDC/NHS-DOX exhibited sufficient paramagnetic potential in the presence of external magnetic field. The TG analysis showed that thermal decomposition capacity of present nanocomposites was: MNPs > MNP@AA-EDC/NHS > AA-MNPs > MNP@AA-EDC/NHS-DOX. AA-modified MNPs did not completely lose their thermal stability as compared to other modifications. Alamar blue analysis revealed that the bare MNPs did have non-significant cytotoxicity in MDA-MB-231, MDA-MB-468 and HCC1937 cell lines (p > 0.001). While, MNP@AA-EDC/NHS-DOX at 0.1, 1.0 and 10 μg/mL DOX concentrations showed significantly lowered cell survival percentages as compared to the free DOX regimens after 24 and 72h. While, HCC1937 cell line had the most accumulation of free (1.42 > 0.93 > 0.9 pg DOX/cell) and conjugated DOX (2.64 > 2.2 > 1.91 pg DOX/cell) after 6 h of incubation period as compared to MDA-MB-468 and MDA-MB-231, respectively (* p < 0.05). Present results provide a new insight into the design of paramagnetic targeted drug delivery nanocomposite system to overcome the obstacles and side effects of conventional chemotherapeutic agents

Triterpenic and phenolic acids production changed in Salvia officinalis via in vitro and in vivo polyploidization: A consequence of altered genes expression

The induction of polyploidy is an efficient technique for creating a diversity of genetic, phenotypic, and phytochemical novelties in plant taxa. Sage (Salvia officinalis L.) is a well-known medicinal plant rich of valuable bioactive molecules such as triterpenic and phenolic acids. In the present study, the effect of in vitro and in vivo polyploidization on morphological characteristics, anatomical structures, phytochemical traits, and expression level of the genes involved in the biosynthesis of major triterpenic acids (ursolic, betulinic, and oleanolic acids) of the plant was studied. The sterile seeds treated with different concentrations (0, 0.05, 0.1, and 0.2%) of colchicine for 24 and 48 h were considered for polyploidy induction. Flow cytometry and chromosome counting were used to confirm the ploidy level of diploid (2n = 2x = 14, 2C DNA = 1.10 pg) and tetraploid (2n = 4x = 28, 2C DNA = 2.12 pg) plants after seven months. The highest polyploidy induction was obtained by applying 0.1% (w/v) colchicine for 48 h with an efficiency of 19.05% in vitro tetraploidy. Polyploids showed differences in leaf shape and color, leaf and stem thickness, trichrome density, root length, plant height, and number of leaves compared to diploid plants. There was also a significant decrease in rosmarinic acid content in polyploid (plants) as compared to diploid plants. Although a significant decrease in ursolic acid content was observed in polyploids, betulinic acid content associated with the expression levels of genes encoding enzymes being active in triterpene biosynthesis such as squalene epoxidase (SQE) and lupeol synthase (LUS). The expression of SQE and LUS was significantly increased in in vitro tertaploids (2.9-fold) and in vivo mixoploids (2.4-fold). The results confirm the idea that induced polyploidy can randomly alter breeding traits of plants as well as the content of bioactive compounds

Induced polyploidy and broad variation in phytochemical traits and altered gene expression in Salvia multicaulis

Induced polyploidy is nowadays an important strategy in plant breeding and for the development of new crops. Salvia multicaulis Vahl is a valuable medicinal plant that produce precious bioactive metabolites including triterpenic acids (TAs) and phenolic compounds. Hence, at first, for selecting elite lines, both HPLC and GC-MC analyses were performed on fourteen S. multicaulis lines. Then, seeds of selected lines of S. multicaulis were exposed to different concentrations (0.00, 0.05, 0.1, and 0.2 %) of colchicine for 24 or 48 h. The flow cytometric analysis and chromosome counting were used to confirm ploidy level of tetraploid control (2n = 4x = 28, 2C DNA = 1.36 pg) and hexaploid (2n = 6x = 42, 2C DNA = 1.97 pg) plants after seven-month. For the first time, the effects of in vitro polyploidization on morphological characteristics, TAs and phenolic acid contents as well as on the expression of six TAs biosynthesis related genes were investigated. The highest efficiency of hexaploidy (12.76 %) was achieved 48 h after exposure to 0.1 % colchicine concentration. The hexaploid plants showed different growth traits compared with those of tetraploid control plant; indeed, hexaploid plants had leaves with a darker green color, a lower trichome density, and lower plant height and root length. Moreover, there was a significant increase in rosmarinic acid and caffeic acid content in hexaploid plants compared with tetraploid control plants. Also, the increase of oleanolic acid (1.33 fold) content in hexaploids was associated with a significant increased expression of squalene synthase (SQS) and β-amyrin synthase (BAS) genes in hexaploid plants. Nevertheless, a significant decreased expression of squalene epoxidase (SQE), mixed-function amyrin synthase (MFAS), and lupeol synthase (LUS) was observed in hexaploid plants, that led to a reduced content of ursolic acid and betulinic acid compared with tetraploid control plants. These results confirmed that polyploidization is a breeding method with stochastic results in secondary metabolites production and gene expression related to biosynthetic pathways

Phenolics diversity among wild populations of Salvia multicaulis: as a precious source for antimicrobial and antioxidant applications

The genus Salvia L. belongs to the Lamiaceae family including several known species rich in natural compounds that are extensively used in pharmaceutical, food, and cosmetic industries. Salvia multicaulis populations contain a broad diversity of flavonoids and phenolic acids. The present study aimed to explore biological and pharmacological effects including antimicrobial and antioxidant activities of nineteen S. multicaulis populations (SMPs) grown in Iran for the first time. High content of rosmarinic acid (RA) in SMP12 (Gazan) (5.65 ± 0.33 mg/g DW) caused high antimicrobial activity against two bacteria (Staphylococcus aureus, Escherichia coli) and the fungus Candida albicans, while methanolic extract of SMP1 (Taleghan) showed high antioxidant activity due to high content of salvianolic acid A (SAA) and quercetin (0.53 ± 0.04 and 0.49 ± 0.12 mg/g DW, respectively). Altogether these results can be considered for further commercial exploitations to meet the demands of the food and pharmaceutical industries

Polarized Deeply Inelastic Scattering (DIS) Structure Functions for Nucleons and Nuclei

We extract parton distribution functions (PDFs) and structure functions from recent experimental data of polarized lepton-DIS on nucleons at next-to-leading order (NLO) Quantum Chromodynamics. We apply the Jacobi polynomial method to the DGLAP evolution as this is numerically efficient. Having determined the polarized proton and neutron spin structure, we extend this analysis to describe 3He and 3H polarized structure functions, as well as various sum rules. We compare our results with other analyses from the literature.Comment: LaTeX, 12 pages, 11 figures, 6 tables. Update to match published versio

Pion mass dependence of the Kl3K_{l3} semileptonic scalar form factor within finite volume

We calculate the scalar semileptonic kaon decay in finite volume at the momentum transfer $t_{m} = (m_{K} - m_{\pi})^2$, using chiral perturbation theory. At first we obtain the hadronic matrix element to be calculated in finite volume. We then evaluate the finite size effects for two volumes with $L = 1.83 fm$ and $L= 2.73 fm$ and find that the difference between the finite volume corrections of the two volumes are larger than the difference as quoted in \cite{Boyle2007a}. It appears then that the pion masses used for the scalar form factor in ChPT are large which result in large finite volume corrections. If appropriate values for pion mass are used, we believe that the finite size effects estimated in this paper can be useful for Lattice data to extrapolate at large lattice size.Comment: 19 pages, 5 figures, accepted for publication in EPJ

Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkPlant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation

Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review

Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications. © 2020, © 2020 Taylor & Francis Group, LLC

Proportion and mortality of Iranian diabetes mellitus, chronic kidney disease, hypertension and cardiovascular disease patients with COVID-19: a meta-analysis

Background: Currently, the number of patients with SARS-COV-2 infection has increased rapidly in Iran, but the risk and mortality of SARS-COV-2 infection in Iranian patients with diabetes mellitus (DM), chronic kidney disease (CKD), hypertension and cardiovascular diseases (CVDs) still not clear. The aim of this meta-analysis was to estimate the proportion and mortality of SARS-COV-2 in these patients. Methods: A comprehensive literature search was carried out in PubMed, Web of Sciences, Cochrane Library, EMBASE, CNKI, SciELO, and other databases to identify all relevant studies published up to 10 January, 2020. The proportion and mortality in the patients were assessed by odd ratio (OR) and the corresponding 95 confidence interval (95 CI). Results: A total of ten case-series including 11,755 cases with SARS-COV-2 infection and 942 deaths were selected. Among them, there were total of 791 DM patients with 186 deaths, 225 CKD patients with 45 deaths, 790 hypertension cases with 86 deaths, and 471 CVDs cases with 60 deaths. Pooled data revealed that the proportion of SARS-COV-2 infection in the patients with hypertension, DM, CVDs and CKD were 21.1 , 16.3 , 14.0 and 5.0 , respectively. Moreover, the SARS-COV-2 infection were associated with an increased risk of mortality in DM (OR = 0.549, CI 95 0.448�0.671, p � 0.001) and CKD (OR = 0.552, 95 CI 0.367�0.829, p = 0.004) patients, but not hypertension and CVDs. There was no publication bias. Conclusions: Our pooled data showed that the proportion of SARS-COV-2 infection was the highest in the Iranian patients with hypertension (21.1 ) followed by DM (16.3 ), CVDs (14.0 ) and CKD (5.0 ). Moreover, DM and CKD in patients with SARS-COV-2 infection were associated with a 0.549 and 0.552-fold increase in mortality, respectively. Clinicians in Iran should be aware of these findings, to identifying patients at higher risk and inform interventions to reduce the risk of death. Moreover, well-designed, large-scale and multicenter studies are needed to improve and validate our findings. © 2021, Springer Nature Switzerland AG