Investigation on the insecticidal efficacy of novel pellet formulation against Callosobruchus maculatus (F.) (Col.: Bruchidae) in three different heights and compared with phosphine

Applying essential oils, fumigant toxicity in stored products pests control has sharpened recently. Since these products have low penetration power and vapour pressure, their use in crop depth is restricted. The aim of this work was using controlled release technology to solve this problem. In this research, 1,8-cineole-based pellets were prepared by dry mixing method and physical load of 1,8-cineole on strach, which followed by pressing the mixture, using pellet maker apparatus, to form pellets. Insecticidal efficacy of produced pellets was investigated against adults (1–3?days old) Callosobruchus maculatus F. (Col.: Bruchidae) compared with phostoxin under 28?±?2?°C and darkness in laboratory condition. LC₅₀ and LC₉₅ of pellets against C. maculatus in 24?h were 0/017 and 0/050?ml active ingredient per L air, respectively. LC₅₀ and LC₉₅ of phosphine pellets against C. maculatus in 24?h were 0/124 and 1/852?ml active ingredient per L air, respectively.     

In vitro cytotoxicity studies of parent and nanoencapsulated Holmium-2,9-dimethyl-1,10-phenanthroline complex toward fish-salmon DNA-binding properties and antibacterial activity

Abstract

In this study, the interaction of Holmium (Ho) complex including 2, 9-dimethyl-1,10-phenanthroline, also called Neocuproine (Neo), [Ho(Neo)₂Cl₃.H₂O], as fluorescence probe with fish-salmon DNA (FS-DNA) is studied during experimental investigations. Multi-spectroscopic methods are utilized to determine the affinity binding constants (K_b) of complex–FS-DNA. It is found that fluorescence of Ho complex is strongly quenched by the FS-DNA through a static quenching procedure. Under optimal conditions in Tris(trishydroxymethyl-aminomethane)–HCl buffer at 25?°C with pH?≈?7.2, intrinsic binding constant K_b of Ho complex is 6.12?±?0.04?×?10⁵ M^?1. Also, the binding site number and Stern–Volmer quenching constant are calculated. There are different approaches, including iodide quenching assay, salt effect and thermodynamical assessment to determine the features of the binding mode between Ho complex and FS-DNA. Also, the parent and starch and lipid nanoencapsulated Ho complex, as potent antitumor candidates, were synthesized. The main structure of Ho complex is maintained after encapsulation using starch and lipid nanoparticles. 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method was used to assess the anticancer properties of Ho complex and its encapsulated forms on human cancer cell lines of human lung carcinoma cell line and breast cancer cell line. In conclusion, these compounds could be considered as new antitumor candidates.

Communicated by Ramaswamy H. Sarma     

Melatonin: An important anticancer agent in colorectal cancer

Colorectal cancer is one of the most common cancers among the elderly, which is also seen in the forms of hereditary syndromes occurring in younger individuals. Numerous studies have been conducted to understand the molecular and cellular pathobiology underlying colorectal cancer. These studies have found that cellular signaling pathways are at the core of colorectal cancer pathology. Because of this, new agents have been proposed as possible candidates to accompany routine therapy regimens. One of these agents is melatonin, a neuro-hormone known best for its essential role in upholding the circadian rhythm and orchestrating the many physiologic changes it accompanies. Melatonin is shown to be able to modulate many signaling pathways involved in many essential cell functions, which if deregulated cause an accelerated pace towards cancer. More so, melatonin is involved in the regulation of immune function, tumor microenvironment, and acts as an antioxidant agent. Many studies have focused on the beneficial effects of melatonin in colorectal cancers, such as induction of apoptosis, increased sensitivity to chemotherapy agents and radiotherapy, limiting cellular proliferation, migration, and invasion. The present review aims to illustrate the known significance of melatonin in colorectal cancer and to address possible clinical use.     

Analytical Approach to the Surface Plasmon Resonance Characteristic of Metal Nanoparticle Dimer in Dipole-Dipole Approximation

This theoretical study deals with the effect of bi-particle interaction on the surface plasmon resonance (SPR) in a dimer which includes two identical metal nanoparticles (NPs). Considering the dipole-dipole interaction in a Drude-like model, an appropriate equation is derived for the permittivity of each NP. The restoration force related to the classical confinement originating from the finite size of NPs is considered, and an appropriate adjustment coefficient is considered for this term through analyzing experimental data. Two different polarizations are considered for the laser beam electric field, and it is shown that the orientation of the electric field has an essential role in the linear optical properties of a dimer. Numerical investigation is accomplished for a dimer of gold NPs with two different diameters of 4 nm and 20 nm. For the parallel polarization, dipole-dipole interaction leads to the redshift of SPR wavelength and increase in its peak value, while for the perpendicular polarization, the absolute opposite results are derived. For all cases, it is shown that SPR wavelength functionality with respect to the geometric factor a/d (NP radius to the separation) can be presented by a cubic equation that fits better than an exponential one suggested by the earlier studies which demonstrates the dipole-dipole characteristic of the interaction. Qualitatively, our results are in good agreement with the other experimental studies.

     

Nutrient Regulation by Continuous Feeding Removes Limitations on Cell Yield in the Large-Scale Expansion of Mammalian Cell Spheroids

Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications.     

A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue

To evaluate the potential of three stem cells for cell therapy and tissue engineering applications, the biological behavior and osteogenic capacity of the newly introduced cord-blood-derived, unrestricted somatic stem cells (USSC) were compared with those of mesenchymal stem cells isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC). There was no significant difference between the rates of proliferation of the three stem cells. During osteogenic differentiation, alkaline phosphatase (ALP) activity peaked on day 7 in USSC compared to BM-MSC which showed the maximum value of ALP activity on day 14. However, BM-MSC had the highest ALP activity and mineralization during osteogenic induction. In addition, AT-MSC showed the lowest capacity for mineralization during differentiation and had the lowest ALP activity on days 7 and 14. Although AT-MSC expressed higher levels of collagen type I, osteonectin and BMP-2 in undifferentiated state, but these genes were expressed higher in BM-MSC during differentiation. BM-MSC also expressed higher levels of ALP, osteocalcin and Runx2 during induction. Taking together, BM-MSC showed the highest capacity for osteogenic differentiation and hold promising potential for bone tissue engineering and cell therapy applications.     

Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial activity of 7-prenyloxycoumarins against promastigotes

Two new sesquiterpene coumarins, named szowitsiacoumarin A (1) and szowitsiacoumarin B (2), and a phenylpropanoid derivative, 2-epihelmanticine (3), together with nine known compounds, auraptene (4), umbelliprenin (5), galbanic acid (6), methyl galbanate (7), farnesiferol B (8), farnesiferol C (9), persicasulfide A (10), beta-sitosterol and stigmasterol were isolated from the roots of Ferula szowitsiana. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D-((1)H and (13)C) and 2D-NMR experiments (DQF-COSY, HSQC, HMBC, and ROESY) as well as HR-MALDI-MS analysis. Since the configuration of 2-epihelmanticine was previously only partly determined, a relative configurational analysis of its four stereocenters was carried out on the basis of the recently reported J-based method. The inhibiting activity of prenylated coumarins, auraptene (4) and umbelliprenin (5), in addition to galbanic acid (6), as major component, and of the Me(2)CO extract of Ferula szowitsiana (Apiaceae) roots has been evaluated against promastigotes of Leishmania major. Umbelliprenin and auraptene showed significant activity with IC(50) values of 4.9microg/ml (13.3microM) and 5.1microg/ml (17.1microM) after 48h incubation, respectively.     

The potential of plant systems to break the HIV‐TB link

Tuberculosis (TB) and human immunodeficiency virus (HIV) can place a major burden on healthcare systems and constitute the main challenges of diagnostic and therapeutic programmes. Infection with HIV is the most common cause of Mycobacterium tuberculosis (Mtb), which can accelerate the risk of latent TB reactivation by 20‐fold. Similarly, TB is considered the most relevant factor predisposing individuals to HIV infection. Thus, both pathogens can augment one another in a synergetic manner, accelerating the failure of immunological functions and resulting in subsequent death in the absence of treatment. Synergistic approaches involving the treatment of HIV as a tool to combat TB and vice versa are thus required in regions with a high burden of HIV and TB infection. In this context, plant systems are considered a promising approach for combatting HIV and TB in a resource‐limited setting because plant‐made drugs can be produced efficiently and inexpensively in developing countries and could be shared by the available agricultural infrastructure without the expensive requirement needed for cold chain storage and transportation. Moreover, the use of natural products from medicinal plants can eliminate the concerns associated with antiretroviral therapy (ART) and anti‐TB therapy (ATT), including drug interactions, drug‐related toxicity and multidrug resistance. In this review, we highlight the potential of plant system as a promising approach for the production of relevant pharmaceuticals for HIV and TB treatment. However, in the cases of HIV and TB, none of the plant‐made pharmaceuticals have been approved for clinical use. Limitations in reaching these goals are discussed.     

Rapid Rebound of the Treg Compartment in DEREG Mice Limits the Impact of Treg Depletion on Mycobacterial Burden,but Prevents Autoimmunity

The development of an effective vaccine against tuberculosis (Tb) represents one of the major medical challenges of this century. Mycobacterium bovis Bacille Calmette-Guerin (BCG), the only vaccine available at present, is mostly effective at preventing disseminated Tb in children, but shows variable protection against pulmonary Tb, the most common form in adults. The reasons for this poor efficacy are not completely understood, but there is evidence that T regulatory cells (Tregs) might be involved. Similarly, Tregs have been associated with the immunosuppression observed in patients infected with Tb and are therefore believed to play a role in pathogen persistence. Thus, Treg depletion has been postulated as a novel strategy to potentiate M. bovis BCG vaccination on one side, while on the other, employed as a therapeutic approach during chronic Tb infection. Yet since Tregs are critically involved in controlling autoimmune inflammation, elimination of Tregs may therefore also incur the danger of an excessive inflammatory immune response. Thus, understanding the dynamics and function of Tregs during mycobacterial infection is crucial to evaluate the potential of Treg depletion as a medical option. To address this, we depleted Tregs after infection with M. bovis BCG or Mycobacterium tuberculosis (Mtb) using DEREG mice, which express the diphtheria toxin (DT) receptor under the control of the FoxP3 locus, thereby allowing the selective depletion of FoxP3⁺ Tregs. Our results show that after depletion, the Treg niche is rapidly refilled by a population of DT-insensitive Tregs (diTregs) and bacterial load remains unchanged. On the contrary, impaired rebound of Tregs in DEREG × FoxP3^GFP mice improves pathogen burden, but is accompanied by detrimental autoimmune inflammation. Therefore, our study provides the proof-of-principle that, although a high degree of Treg depletion may contribute to the control of mycobacterial infection, it carries the risk of autoimmunity.