Study of gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni under various mannitol concentrations

Molecular Biology Reports - Stevia rebaudiana produces sweet steviol glycosides that are 300 times sweeter than sugar and have the beneficial effects on human health including anti-hyperglycaemic....     

Immunoliposomes bearing lymphocyte activation gene 3 fusion protein and P5 peptide: A novel vaccine for breast cancer

LAG3-Ig as an immune adjuvant has elicited potent anti-tumor immune responses in several preclinical and clinical studies, but the full potential immunostimulatory of LAG3-Ig has yet to be achieved. We hypothesized that by anchoring LAG3-Ig to the surface of liposomes, the adjuvant activity of LAG3-Ig could be improved. We also investigated the immunotherapy by co-delivery of liposome-coupled LAG3-Ig and P5 tumor antigen in mice model of TUBO breast cancer. We prepared and characterized novel PEGylated liposomes bearing surface conjugated LAG3-Ig and P5. Consistent with our hypothesis, liposomes-conjugated LAG3-Ig via multivalent binding to MHC class II molecules exerted immunostimulatory of LAG3-Ig and markedly induced maturation of dendritic cells more efficiently than free LAG3-Ig. LAG3-Ig-P5-immunoliposomes effectively elicited protective anti-tumor responses more than locally injected soluble LAG3-Ig + P5. The higher percentage of CD4⁺ and CD8⁺ T cells in the spleen and more rapid and pronounced infiltration of these effector cells into the site of the tumor were seen following immunoliposome therapy. Finally, anti-tumor immunity induced by LAG3-Ig-P5-immunoliposomes translated into the more tumor regression and prolonged survival of treated mice, compared to soluble immunotherapy. Taken together, our findings suggest that LAG3-Ig-P5-immunoliposomes can be considered as a valuable candidate for developing a liposome-based therapeutic cancer vaccine in treating HER2/ neu⁺ breast cancer patients.     

Effect of soil texture and its organic content on the efficacy of Trichoderma harzianum (MIAU 145 C) in controlling Meloidogyne javanica and stimulating the growth of kidney beans

The efficiency of Trichoderma harzianum (MIAU 145 C) in promoting kidney bean (cv. Goli) growth in different soil texture (sandy loam, loam and clay loam) and organic matter content (0.5 and 2% of leaf litter) was assessed in a factorial experiment in the absence of Meloidogyne javanica. In another factorial experiment, the effect of soil texture, soil organic content and control measure (no control, 10?ml of T. harzianum containing 10⁶ spore ml^?1 and 2?mg ai cadusafos kg^?1 soil) was determined on nematode-infected kidney bean’s growth, fungus controlling activity and M. javanica reproduction. Except for the shoot length, the fungus improved plant growth. Clay loam was not a proper soil type for the cultivation of kidney bean plants (even in the soil without nematode), but the plant grew better in sandy loam and loam soil. The presence of leaf litter in the soil enhanced plant growth, increased fungal efficiency and increased nematode reproduction. It seems that T. harzianum can activate the plant defence system in sandy loam soil. T. harzianum was more effective in sandy loam or loam soil containing 2% organic matter (leaf litter) and reduced the reproduction factor of the nematode in the tested soil textures equally to the chemical nematicide treatment.     

Lack of association between interleukin-13 gene polymorphisms (−1055 C/T and +2044 G/A) in Iranian patients with lung cancer

Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited; control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes, alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population.     

Mucor hiemalis: a new source for uricase production

Summary One hundred and sixty-five strains of microorganisms with the ability to grow in a medium containing uric acid as a major source of nitrogen were isolated from soil samples during a screening program. Among them, a zygomycete fungus with well-developed columellae was recognized to produce high levels of the enzyme in a short time. Classification of the isolated fungus was carried out according to the morphological and culture characteristics of the organism, and it was identified as Mucor hiemalis. The fungus was able to produce an intracellular urate oxidase in a fermentation medium mainly containing uric acid. Optimized composition of the medium consisted of (l⁻¹ of distilled water) uric acid, 7.0 g; maltose, 6.0 g; Vogel stock solution, 20 and 1 ml of 0.5 M copper sulphate. The optimum pH and temperature for uricase production in the optimized medium were pH 6 and 30 °C, respectively.     

The application of musculoskeletal modeling to investigate gender bias in non-contact ACL injury rate during single-leg landings

The central tenet of this study was to develop, validate and apply various individualised 3D musculoskeletal models of the human body for application to single-leg landings over increasing vertical heights and horizontal distances. While contributing to an understanding of whether gender differences explain the higher rate of non-contact anterior cruciate ligament (ACL) injuries among females, this study also correlated various musculoskeletal variables significantly impacted by gender, height and/or distance and their interactions with two ACL injury-risk predictor variables; peak vertical ground reaction force (VGRF) and peak proximal tibia anterior shear force (PTASF). Kinematic, kinetic and electromyography data of three male and three female subjects were measured. Results revealed no significant gender differences in the musculoskeletal variables tested except peak VGRF (p = 0.039) and hip axial compressive force (p = 0.032). The quadriceps and the gastrocnemius muscle forces had significant correlations with peak PTASF (r = 0.85, p < 0.05 and r = ? 0.88, p < 0.05, respectively). Furthermore, hamstring muscle force was significantly correlated with peak VGRF (r = ? 0.90, p < 0.05). The ankle flexion angle was significantly correlated with peak PTASF (r = ? 0.82, p < 0.05). Our findings indicate that compared to males, females did not exhibit significantly different muscle forces, or ankle, knee and hip flexion angles during single-leg landings that would explain the gender bias in non-contact ACL injury rate. Our results also suggest that higher quadriceps muscle force increases the risk, while higher hamstring and gastrocnemius muscle forces as well as ankle flexion angle reduce the risk of non-contact ACL injury.     

Investigation of the effect of homocysteinylation of substance P on its binding to the NK1 receptor using molecular dynamics simulation

Substance P is a neurotransmitter or modulator in both the central and peripheral nervous systems. In this work, modifications of the lysine in SP by homocysteine and an acetyl group as well as the conformational dynamics of the native and modified SP peptides and their complexes with the NK1 receptor were studied via MD simulation. It was found that modifying SP stabilizes the peptide structure, but the modified SP peptides are less likely to bind to the NK1 receptor, so the resulting complexes are less stable. The RMSD of native SP (~0.33 nm) is about twice as large as that of the modified SP peptides (~0.18 nm), while the RMSD for the receptor complexed with native SP is ~0.3 nm, and that for the receptor complexed with either of the modified peptides is ~0.35 nm, which demonstrates the high stability of the modified SP peptides as well as the receptor complexed with native SP. Such behavior was also observed in other structural analyses. The binding free energies of the native and modified SP peptides with the NK1 receptor were also compared. The ΔG_bind values for the binding of homocysteinylated SP to the NK1 receptor and the binding of the acetylated SP and native SP to the NK1 receptor were ?38.89, ?64.46, and???264.52 kJ mol^?1, respectively. Modification of the lysine of SP decreases the binding affinity of the peptide to the NK1 receptor. In other words, homocysteinylation or acetylation of SP leads to weaker interactions of the peptide with the NK1 receptor compared to those between native SP and NK1. We propose that this phenomenon leads to increased levels of homocysteinylated SP in plasma in many diseases such as breast cancer.

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Graphical abstract Substance P (SP) is a neuropeptide which binds to the NK1 receptor. SP is of great pharmacological interest, as agonists and antagonists of SP can potentially be used to treat many chronic diseases. Therefore, in this work, the lysine (LYS) in SP was theoretically modified with a homocysteine or acetyl group to explore the effects of such a modification on the binding affinity of this peptide with the NK1 receptor and the structural dynamics of the resulting complex