Evaluation of (ɳ6-p-cymene) ruthenium diclofenac complex as anticancer chemotherapeutic agent: interaction with biomolecules,cytotoxicity assays

abstract

The designing of metal-based anticancer therapeutic agents can be optimized in a better and rapid way if the ligands utilized have standalone properties. Therefore, even when the organometallic/coordination complex (i.e., metallodrug) gets dissociated in extreme conditions, the ligand can endorse its biological properties. Herein, we have synthesized and characterized ?⁶-p-cymene ruthenium diclofenac complex. Furthermore, the ruthenium complex interactions with human serum albumin (HSA) and ct-DNA have been studied using various spectroscopic studies viz., UV, fluorescence, and circular dichroism and exhibited a significant binding propensity. Furthermore, in vitro cytotoxicity assays were carried out against human breast cancer “MCF-7” cell line. The ?⁶-p-cymene ruthenium diclofenac complex registered significant cytotoxicity with an IC₅₀ value of ～25.0?µM which is comparable to the standard drugs. The ?⁶-p-cymene ruthenium diclofenac complex was able to decrease the MCF-7 cell proliferation and induced significant levels of apoptosis with relatively low toxicity.     

Modulation of chondrocyte migration and aggregation by insulin-like growth factor-1 in cultured cartilage

The effect of insulin-like growth factor-1 (IGF-1) on the behavior of rabbit chondrocytes in cultured collagen (CL) gels initially seeded with 2 × 10⁵ cells/ml was examined. On day 5, the frequency of migrating cells cultured in presence of 100 ng IGF-1/ml was 0.04, which was 54 % of the frequency in IGF-1-free culture. The presence of IGF-1 caused an increase in the frequency of dividing cells from 0.09 to 0.13. These results suggest that IGF-1 suppressed the migration of chondrocytes in the CL gels while stimulating cell division in the initial culture phase. The proteolytic migration of cells was thought to be suppressed by the down-regulation of membrane type 1 matrix metalloproteinase by IGF-1. This contributed to the formation of aggregates with spherical-shaped cells that produced collagen type II.     

Comparative study of mycelia growth and sporophore yield of Auricularia polytricha (Mont.) Sacc on selected palm oil wastes as fruiting substrate

The potential for using agricultural and industrial by-products as substrate for the production of the edible mushroom, Auricularia polytricha, was evaluated using several formulations of selected palm oil wastes mixed with sawdust and further supplemented with selected nitrogen sources. The best substrate formulations were sawdust (SD) mixed with oil palm frond (OPF; 90:10) added with 15 % spent grain (SG) and sawdust mixed with empty fruit bunch (EFB; 50:50) added with 10 % spent grain (SG) with mycelia growth rate of 8 mm/day and 7 mm/day respectively. These two substrate formulations were then subjected to different moisture content levels (65 %, 75 % and 85 %). Highest total fresh sporophore yield at 0.43 % was obtained on SD?+?OPF (90:10)?+?15 % SG at 85 % moisture content, followed closely by SD?+?EFB (50:50)?+?10 % SG with 0.40 % total yield, also at 85 % moisture content. Each of the substrate formulations at 85 % moisture content gave the highest biological efficiency (BE) at 288.9 % and 260.7 %, respectively. Both yield and biological efficiency of A. polytricha on these two formulations were almost three times higher when compared to sawdust substrate alone, thus proving the potential of these formulations to improve yield of this mushroom.     

Zinc oxide-doped poly(urethane) spider web nanofibrous scaffold via one-step electrospinning: a novel matrix for tissue engineering

Zinc oxide (ZnO) nanostructures have been commonly studied for electronic purposes due to their unique piezoelectric and catalytic properties; however, recently, they have been also exploited for biomedical applications. The purpose of this study was to fabricate ZnO-doped poly(urethane) (PU) nanocomposite via one-step electrospinning technique. The utilized nanocomposite was prepared by using colloidal gel composed of ZnO and PU, and the obtained mats were vacuum dried at 60 °C overnight. The physicochemical characterization of as-spun composite nanofibers was carried out by X-ray diffraction pattern, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, electron probe microanalysis, and transmission electron microscopy, whereas the thermal behavior was analyzed by thermogravimetric analysis. The viability, attachment, and proliferation of NIH 3T3 mouse fibroblast cells on the ZnO/PU composite nanofibers were analyzed by in vitro cell compatibility test. The morphological features of the cells attached on nanofibers were examined by Bio-SEM. We conclude that the electrospun nanofibrous scaffolds with unique spider nets had good biocompatibility. Cytotoxicity experiments indicated that the mouse fibroblasts could attach to the nanocomposite after being cultured. Thus, the current work demonstrates that the as-synthesized ZnO/PU hybrid nanofibers represent a promising biomaterial to be exploited for various tissue engineering applications.     

Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20 mg/kg bwt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3 mg/kg bwt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1β levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type (SDAT).     

Agonist Leukadherin-1 Increases CD11b/CD18-Dependent Adhesion Via Membrane Tethers

Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn²⁺ additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1^−/− neutrophils also showed longer detachment distances and time from ICAM-1-coated atomic force microscopy tips, but significantly lower detachment force, as compared to the Mn²⁺-activated cells, confirming that LA1 primarily increased membrane-tether bonds to enhance CD11b/CD18:ICAM-1 binding, whereas Mn²⁺ induced additional CSK-anchored bond formation. The results suggest that the two types of agonists differentially activate integrins and couple them to the cellular machinery, providing what we feel are new insights into signal mechanotransduction by such agents.     

Four products from Escherichia coli pseudogenes increase hydrogen production

Pseudogenes are considered to be nonfunctional genes that lack a physiological role. By screening 3985 Escherichia coli mutants using chemochromic membranes, we found four pseudogenes involved in hydrogen metabolism. Knockouts of pseudogenes ydfW and ypdJ had a defective hydrogen phenotype on glucose and formate, respectively. Also, the knockout of pseudogene yqiG formed hydrogen from formate but not from glucose. For the yqiG mutant, 100% hydrogen recovery was obtained by the complementation of YqiG via a plasmid. The knockout of pseudogene ylcE showed hydrogen deficiency in minimal media which suggested that the role of YlcE is associated with cell growth. Hence, the products of these four pseudogenes play an important physiological role in hydrogen production in E. coli.     

White light augments chemotherapeutic potential of cyclophosphamide: an in vitro study

Cyclophosphamide (CYC) is a known chemotherapeutic drug used widely for the treatment of leukemias, lymphomas and some solid tumors. Copper is an essential constituent of chromatin and its level is usually elevated in various malignancies. Combined modality chemotherapy involves the use of drug with other components for cancer treatment, such as radiation therapy or surgery. Photosensitizer anticancer drugs can be used in combination with light and may have synergistic effect on cancer. The present study is an attempt to show that CYC acts as prooxidant when used in combination with Cu(II) and white light. We hypothesize that CYC when given as a chemotherapeutic agent possibly interact with endogenous copper associated with chromatin of the cancer cells and generate ROS besides acting as DNA alkylating agent. Thus, during chemotherapy the oxidative stress is possibly generated by the drug through mobilizing endogenous Cu(II) which may attribute to the cytotoxic death of cancer cell.     

Enhancement of nitrogen release properties of urea–kaolinite fertilizer with chitosan binder

The use of controlled release fertilizer (CRF) has become a new trend to minimize environmental pollution. In this study, urea–kaolinite containing 20 wt% urea after one hour dry grinding was mixed with different concentrations of chitosan as a binder to prepare nitrogen-based CRF. Fourier transform infrared spectroscopy confirmed the hydrogen bonding between urea and kaolinite. Covalent interaction between urea–kaolinite and chitosan make the granules stronger. The nitrogen release was measured in 5 days interval using a diacetylmonoxime calorimetric method at a wavelength of 527 nm. The results illustrated that by increasing the chitosan concentration from 3 to 7.5%, nitrogen release decreased from 41.23 to 25.25% after one day and from 77.31 to 59.27% after 30 days incubation in water. Compressive stress at break tests confirmed that granules with chitosan 6% had the highest resistance and were chosen for ammonia volatilization tests. Ammonia volatilization was carried out using the forced-draft technique for a period of 10 weeks. The results showed that the total amount of ammonia loss for conventional urea fertilizer and urea–kaolinite–chitosan granules was 68.63 and 56.75%, respectively. This controlled release product could be applied in agricultural crop production purpose due to its controlled solubility in the soil, high nutrient use efficiency and potential economic benefits.