Chemotherapy for tumors: an analysis of the dynamics and a study of quadratic and linear optimal controls

We investigate a mathematical model of tumor-immune interactions with chemotherapy, and strategies for optimally administering treatment. In this paper we analyze the dynamics of this model, characterize the optimal controls related to drug therapy, and discuss numerical results of the optimal strategies. The form of the model allows us to test and compare various optimal control strategies, including a quadratic control, a linear control, and a state-constraint. We establish the existence of the optimal control, and solve for the control in both the quadratic and linear case. In the linear control case, we show that we cannot rule out the possibility of a singular control. An interesting aspect of this paper is that we provide a graphical representation of regions on which the singular control is optimal.     

Antioxidant modulation in response to heavy metal induced oxidative stress in Cladophora glomerata

The present investigation was carried out to study the induction of oxidative stress subjected to heavy metal environment. Lipoperoxides showed positive correlation at heavy metal accumulation sites indicating the tissue damage resulting from the reactive oxygen species and resulted in unbalance to cellular redox status. The high activities of ascorbate peroxidase and superoxide dismutase probably counter balance this oxidative stress. Glutathione and soluble phenols decreased, whereas dehydroascorbate content increased in the algae from polluted sites. The results suggested that alga responded to heavy metals effectively by antioxidant compounds and scavenging enzymes.     

Purification and Characterization of Polygalacturonase-3 from Jamaica cherry (Muntingia calabura Linn)

Endo-polygalacturonase-3 (PG-3), the key enzyme of fruit ripening was purified to near homogeneity as judged by native PAGE from the fruit tissues of Jamaica cherry (Muntingia calabura) using ammonium sulphate fractionation, followed by anion-exchange, gel filtration and affinity chromatography. The molecular mass of the PG-3 enzyme was determined as 85 kD, by size exclusion chromatography. SDS-PAGE of PG-3 revealed two dissimilar bands of 62 and 21 kD as heterogenous subunits. The optimum pH of PG-3 was found to be 4.0. The enzyme had an optimum temperature of 40°C and was relatively stable at 50°C and 60°C. K_m for the substrate polygalacturonic acid was found to be 0.27%. The purified enzyme was a glycoprotein with 6.6 % carbohydrate content.     

Bio-efficacy potential of seaweed Gracilaria firma with copepod,Megacyclops formosanus for the control larvae of dengue vector Aedes aegypti

Mosquitoes are the most critical group of insects in the context of public health, because they transmit numerous diseases, causing millions of deaths annually. The frequent use of systemic insecticides to manage insect pests leads to the destabilization of ecosystems and enhanced resistance to insecticides by pests, suggesting a clear need for alternatives. Marine organisms are a rich source of structurally novel and biologically active metabolites, and cyclopoid copepods are prominent predators in many aquatic ecosystems and have been used as biological agents in successful programs to control mosquito larvae. In this study, we determine the effectiveness of the Taiwanese seaweed Gracilaria firma and different solvent extracts combined with the copepod Megacyclops formosanus for controlling Aedes aegypti. A significant larvicidal potential was recorded after seaweed extract treatment against the dengue vector A. aegypti. Larval mortality was observed after 24 h of exposure in laboratory. All extracts exhibited larvicidal effects; however, the highest larval mortality was observed in the methanol extract of G. firma against A. aegypti larvae (LC₅₀ = 0.251%). The methanol extract of G. firma was more effective than the other extracts and is an ideal eco-friendly approach for the control larvae of the dengue vector A. aegypti.     

Evaluation of antibody response in mice against avian influenza A (H5N1) strain neuraminidase expressed in yeast Pichia pastoris

Avian influenza has raised many apprehension in the recent years because of its potential transmitability to humans. With the increasing emergence of drug-resistant avian influenza strains, development of potential vaccines are imperative to manage this disease. Two structural antigens, haemagglutinin and neuraminidase, have been the target candidates for the development of subunit vaccine against influenza. In an effort to develop a faster and economically beneficial vaccine, the neuraminidase gene of a highly pathogenic avian influenza isolate was cloned and expressed in the methylotrophic yeast Pichia pastoris. The recombinant neuraminidase (rNA) antigen was purified, and its bioactivity was analysed. The rNA was found to be functional, as determined by the neuraminidase assay. Four groups of mice were immunized with different concentrations of purified rNA antigen, which were adjuvanted with aluminium hydroxide. The immune response against rNA was analysed by enzyme-linked immunosorbent assay (ELISA) and neuraminidase inhibition assay. The mice groups immunized with 25 μg and 10 μg of antigen had a significant immune response against rNA. This method can be utilized for faster and cost-effective development of vaccines for a circulating and newer strain of avian influenza, and would aid in combating the disease in a pandemic situation, in which production time matters greatly.     

Poly-lysine peptidomimetics having potent antimicrobial activity without hemolytic activity

Diversity of sequence and structure in naturally occurring antimicrobial peptides (AMPs) limits their intensive structure–activity relationship (SAR) study. In contrast, peptidomimetics have several advantages compared to naturally occurring peptide in terms of simple structure, convenient to analog synthesis, rapid elucidation of optimal physiochemical properties and low-cost synthesis. In search of short antimicrobial peptides using peptidomimetics, which provide facile access to identify the key factors involving in the destruction of pathogens through SAR study, a series of simple and short peptidomimetics consisting of multi-Lys residues and lipophilic moiety have been prepared and found to be active against several Gram-negative and Gram-positive bacteria containing methicillin-resistant Staphylococcus aureus (MRSA) without hemolytic activity. Based on the SAR studies, we found that hydrophobicity, +5 charges of multiple Lys residues, hydrocarbon tail lengths and cyclohexyl group were crucial for antimicrobial activity. Furthermore, membrane depolarization, dye leakage, inner membrane permeability and time-killing kinetics revealed that bacterial-killing mechanism of our peptidomimetics is different from the membrane-targeting AMPs (e. g. melittin and SMAP-29) and implied our peptidomimetics might kill bacteria via the intracellular-targeting mechanism as done by buforin-2.     

Fabrication of conducting electrospun nanofibers scaffold for three-dimensional cells culture

Electrospinning is a versatile method to fabricate nanofibers of a range of polymeric and composite materials suitable as scaffolds for tissue engineering applications. In this study, we report the fabrication and characterization of polyaniline-carbon nanotube/poly(N-isopropyl acrylamide-co-methacrylic acid) (PANI-CNT/PNIPAm-co-MAA) composite nanofibers and PNIPAm-co-MAA nanofibers suitable as a three-dimensional (3D) conducting smart tissue scaffold using electrospinning. The chemical structure of the resulting nanofibers was characterized with FTIR and (1)H NMR spectroscopy. The surface morphology and average diameter of the nanofibers were observed by SEM. Cellular response of the nanofibers was studied with mice L929 fibroblasts. Cell viability was checked on 7th day of cell culture by double staining the cells with calcein-AM and PI dye. PANI-CNT/PNIPAm-co-MAA composite nanofibers were shown the highest cell growth and cell viability as compared to PNIPAm-co-MAA nanofibers. Cell viability in the composite nanofibers was obtained in order of 98% that indicates the composite nanofibers provide a better environment as a 3D scaffold for the cell proliferation and attachment suitable for tissue engineering applications.     

Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells

The altered expression of cell surface chondroitin sulfate (CS) and dermatan sulfate (DS) in cancer cells has been demonstrated to play a key role in malignant transformation and tumor metastasis. However, the functional highly sulfated structures in CS/DS chains and their involvement in the process have not been well documented. In the present study, a structural analysis of CS/DS from two mouse Lewis lung carcinoma (3LL)-derived cell lines with different metastatic potentials revealed a higher proportion of Delta(4,5)HexUA-GalNAc(4,6-O-disulfate) generated from E-units (GlcUA-GalNAc(4, 6-O-disulfate)) in highly metastatic LM66-H11 cells than in low metastatic P29 cells, although much less CS/DS is expressed by LM66-H11 than P29 cells. This key finding prompted us to study the role of CS-E-like structures in experimental lung metastasis. The metastasis of LM66-H11 cells to lungs was effectively inhibited by enzymatic removal of tumor cell surface CS or by preadministration of CS-E rich in E-units in a dose-dependent manner. In addition, immunocytochemical analysis showed that LM66-H11 rather than P29 cells expressed more strongly the CS-E epitope, which was specifically recognized by the phage display antibody GD3G7. More importantly, this antibody and a CS-E decasaccharide fraction, the minimal structure recognized by GD3G7, strongly inhibited the metastasis of LM66-H11 cells probably by modifying the proliferative and invading behavior of the metastatic tumor cells. These results suggest that the E-unit-containing epitopes are involved in the metastatic process and a potential target for the diagnosis and treatment of malignant tumors.