Drought stress induced by polyethylene glycol (PEG) in local maize at the early seedling stage.

Drought stress adversely impacts growth, crop production, reproductive organ development, and yield characteristics in maize. As a drought-sensitive crop, maize (Zea mays L.) shows considerable varietal differences. A study was conducted at the Tissue Culture Laboratory, Department of Biology, Faculty of Mathematics and Natural Sciences, University of North Sumatra, Medan, Indonesia in order to identify drought-tolerant maize varieties. During germination and early seedling growth, 16 local accessions were evaluated for drought tolerance. Based on local climate and soil conditions, these specific accessions were chosen. The varieties were tested against five levels of drought stress imposed by Polyethylene glycol 6000 (PEG-6000) at 10, 20, 30, 40, and 50%. An experiment with three replications was conducted using a completely randomized design. In the study, local maize accessions (BI3, SB5, DS2, and MN3) and the hybrid variety (H) showed the capability of tolerating drought stress. Generally, germination time, germination percent and vigor index, root and shoot length, shoot ratio, and fresh and dry weight were decreased by increasing PEG concentrations (up to 50%). According to ANOVA results, shoot water content was not significantly affected by the PEG, nor was the interaction between the PEG and the accessions. The root water content, however, was significantly affected by PEG, and the interaction between PEG and accessions. Although interactions between accessions with low PEG concentrations improved germination characteristics, the root histology of the accessions varied. According to drought tolerance indexes, five maize accessions are drought-tolerant, including H (0.683), SB5 (0.617), DS2 (0.565), MN3 (0.512), and BI3 (0.504). The drought-tolerant varieties are recommended in regions with low rainfall or low water sources since they are less water-intensive and produce higher yields.

Nanobugs as Drugs: Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV-1 Virus.

The survival strategies of infectious organisms have inspired many therapeutics over the years. Indeed the advent of oncolytic viruses (OVs) exploits the uncontrolled replication of cancer cells for production of their progeny resulting in a cancer-targeting treatment that leaves healthy cells unharmed. Their success against inaccessible tumors however, is highly variable due to inadequate tumor targeting following systemic administration. Coassembling herpes simplex virus (HSV1716) with biocompatible magnetic nanoparticles derived from magnetotactic bacteria enables tumor targeting from circulation with magnetic guidance, protects the virus against neutralizing antibodies and thereby enhances viral replication within tumors. This approach additionally enhances the intratumoral recruitment of activated immune cells, promotes antitumor immunity and immune cell death, thereby inducing tumor shrinkage and increasing survival in a syngeneic mouse model of breast cancer by 50%. Exploiting the properties of such a nanocarrier, rather than tropism of the virus, for active tumor targeting offers an exciting, novel approach for enhancing the bioavailability and treatment efficacy of tumor immunotherapies for disseminated neoplasms.

Macrophage Regulation of the Development of Castration-Resistant Prostate Cancer.

Androgen deprivation therapy (ADT) is the front-line treatment for early and metastatic prostate cancer, and the development of tumor resistance to it has major clinical consequences. Cancer cells start to proliferate and tumors begin to regrow, requiring the administration of more generic anticancer treatments like surgery, radiotherapy, and/or chemotherapy. Tumor-associated macrophages are known to drive tumor resistance to a number of anti-cancer therapies. El-Kenawi and colleagues now demonstrate a novel mechanism underpinning their ability to do so in prostate tumors during ADT. This involves the accumulation of cholesterol by macrophages in tumors and its transfer to cancer cells, where it acts as a precursor for androgen biosynthesis and results in the activation of androgen receptors.See related article by El-Kenawi and colleagues, p. 5477.

Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors.

Oncolytic viruses (OV) have been shown to activate the antitumor functions of specific immune cells like T cells. Here, we show OV can also reprogram tumor-associated macrophage (TAM) to a less immunosuppressive phenotype. Syngeneic, immunocompetent mouse models of primary breast cancer were established using PyMT-TS1, 4T1, and E0771 cell lines, and a metastatic model of breast cancer was established using the 4T1 cell line. Tumor growth and overall survival was assessed following intravenous administration of the OV, HSV1716 (a modified herpes simplex virus). Infiltration and function of various immune effector cells was assessed by NanoString, flow cytometry of dispersed tumors, and immunofluorescence analysis of tumor sections. HSV1716 administration led to marked tumor shrinkage in primary mammary tumors and a decrease in metastases. This was associated with a significant increase in the recruitment/activation of cytotoxic T cells, a reduction in the presence of regulatory T cells and the reprograming of TAMs towards a pro-inflammatory, less immunosuppressive phenotype. These findings were supported by in vitro data demonstrating that human monocyte-derived macrophages host HSV1716 replication, and that this led to immunogenic macrophage lysis. These events were dependent on macrophage expression of proliferating cell nuclear antigen (PCNA). Finally, the antitumor effect of OV was markedly diminished when TAMs were depleted using clodronate liposomes. Together, our results show that TAMs play an essential role in support of the tumoricidal effect of the OV, HSV1716-they both host viral replication via a novel, PCNA-dependent mechanism and are reprogramed to express a less immunosuppressive phenotype.

Magnetic-silk/polyethyleneimine core-shell nanoparticles for targeted gene delivery into human breast cancer cells.

The lack of efficient and cost-effective methods for gene delivery has significantly hindered the applications of gene therapy. In this paper, a simple one step and cost effective salting-out method has been explored to fabricate silk-PEI nanoparticles (SPPs) and magnetic-silk/PEI core-shell nanoparticles (MSPPs) for targeted delivery of c-myc antisense oligodeoxynucleotides (ODNs) into MDA-MB-231 breast cancer cells. The size and zeta potential of the particles were controlled by adjusting the amount of silk fibroin in particle synthesis. Lower surface charges and reduced cytotoxicity were achieved for MSPPs compared with PEI coated magnetic nanoparticles (MPPs). Both SPPs and MSPPs were capable of delivering the ODNs into MDA-MB-231 cells and significantly inhibited the cell growth. Through magnetofection, high ODN uptake efficiencies (over 70%) were achieved within 20 min using MSPPs as carriers, exhibiting a significantly enhanced uptake effect compared to the same carriers via non-magnetofection. Both SPPs and MSPPs exhibited a significantly higher inhibition effect against MDA-MB-231 breast cancer cells compared to human dermal fibroblast (HDF) cells. Targeted ODN delivery was achieved using MSPPs with the help of a magnet, making them promising candidates for targeted gene therapy applications.