Dose‐dependent actions of curcumin in experimentally induced myocardial necrosis: a biochemical,histopathological, and electron microscopic evidence

Curcumin, an active component of turmeric, is a well‐known antioxidant due to its reactive oxygen species (ROS) scavenging property. However, some in vitro studies have suggested that curcumin induces generation of ROS at higher doses and thus exerts pro‐oxidant effect. We demonstrate, for the first time, the dose‐dependent effects of curcumin in isoprenaline‐induced model of myocardial necrosis in rats. The animals were assigned to control, isoprenaline and three curcumin treatment groups. Curcumin (100, 200, and 400 mg/kg) and vehicle (dimethyl sulfoxide) were administrated orally for 15 days and isoprenaline (85 mg/kg, s.c.) was given to curcumin treated and isoprenaline group on 13th and 14th day, respectively. Thereafter, on 15th day, the animals were sacrificed for biochemical analysis along with histopathological and ultrastructural examination. There was an increase in glutathione, superoxide dismutase (SOD), creatine kinase‐MB (CK‐MB) and lactate dehydrogenase (LDH) levels, decrease in thiobarbituric acid reactive substances (TBARS), and preservation of myocardial architecture in the curcumin (100 and 200 mg/kg) treated groups. However, at 400 mg/kg dose there was ineffectual protection against isoprenaline‐induced myocardial damage. Instead, there was significant lipid peroxidation as evident by increased levels of TBARS (93.87 ± 9.93, p < 0.0001) and decrease in CK‐MB (206.32 ± 13.54, p < 0.0001) and LDH (134.26 ± 9.13, p < 0.01) as compared to the two lower doses. Hence, it can be concluded that curcumin augments endogenous antioxidant system at lower doses but mediates ROS induction at higher concentration leading to myocardial damage. Copyright © 2009 John Wiley & Sons, Ltd.     

Preclinical evaluation of DO3P-AME-DO3P: a polyazamacrocyclic methylene phosphonate for diagnosis and therapy of skeletal metastases

A phosphonate derivative 10'-bis(acetamido)-ethane-bis[1,4,7-tri(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane] (DO3P-AME-DO3P), was synthesized with 90% yield in high purity. It was labeled with (99m)Tc in 97.5% efficiency and specific activity of 112-250 MBq/μmol. The binding affinity of (99m)Tc-DO3P-AME-DO3P towards bone minerals was tested in vitro by using hydroxy apatite as a bone model with absorption of 93% during the first hour of the experiment. Receptor binding assay on human bone cell line SAOS-2 demonstrated K(d) value of 1.07 nM. Cell binding studies of DO3P-AME-DO3P on osteoblasts and osteoclasts cells performed in vitro displayed preferential affinity of the compound towards osteoclast (167.95 ± 3.56% dose/mg protein). The serum stability of (99m)Tc complex was found to be 96.8% after 24 h. Blood kinetics of (99m)Tc-DO3P-AME-DO3P performed on normal rabbits showed fast clearance with t(1/2)(F) = 15 min ± 0.014 min and t(1/2)(S) = 4 h 3 min ± 0.09 min. Biodistribution studies carried out in normal BALB/c mice showed bone-to-blood ratio of 20 and bone-to-muscle ratio of 33. The bone tissue demonstrated highest concentration of bound radioactivity with 10.73% ID/g at 1 h post injection. The protonation and stability constants were determined by pH-potentiometry titrations. The stability constants of DO3P-AME-DO3P with Lu(III), Sm(III), and Ho(III) were 19.7, 21.8, and 20.2 determined by "out of cell" method. The excellent bone seeking properties of DO3P-AME-DO3P make it a candidate of choice for SPECT imaging and preferential uptake of the compound in osteoclasts in comparison to osteoblasts; BMM and BMC can be used to understand the pathway of pathogenesis of osteoporosis and skeletal metastases.     

Correlating on-line monitoring parameters, pH, DO and ORP with nutrient removal in an intermittent cyclic process bioreactor system

The paper presents the study correlating the profile of on-line monitoring parameters and nutrient removal in an intermittent cyclic process bioreactor (ICPBR) system, thereby utilizing the parameters as operational tool. A laboratory scale ICPBR was employed to treat low C/N ratio domestic wastewater from a township. The study was conducted for correlating biological nutrient removal and on-line monitored parameters pH, dissolved oxygen (DO) and oxidation-reduction potential (ORP). The results revealed that pH, DO and ORP related with the dynamic behavior of nutrient concentration (NH4-N, NO3-N, and PO4-P) during treatment in an ICPBR system. The variation in pH and ORP of the reactor liquor correlate to conversion of ammonia (NH4-N) and nitrate (NO3-N) concentrations, respectively. As the bioconversion of ammonia nitrogen and phosphorus are related to the varying profile of the on-line monitored parameters, the profiles could possibly be used as onsite process control parameters.     

Genetic screening in couples experiencing recurrent assisted procreation failure

Infertility is a major health problem affecting about 10-20% of couples in the reproductive age group. Male factor is assumed to be responsible in about 50% cases of infertility. The origin of reduced testicular sperm function is unknown in about 50-70% of cases and for such couples assisted reproduction techniques (ART) are a boon. Male infertility is often due to poor semen quality and may be associated with genetic defects. ART has revolutionized management of infertility and intracytoplasmic sperm injection (ICSI) is the ART procedure of choice in 60-80% cases. Despite major technological advancements and professional expertise in ART, the success rate and carry-home live birth rate of ICSI is low (18-25%). This study was aimed to understand the genetic etiopathology of recurrent ART failure. For this, 110 couples with 3 or more failed ART cycles were recruited. A detailed history was taken and only idiopathic ART failure cases were enrolled for this study. They were subjected to cytogenetic and Yq microdeletion analysis. Genetic abnormalities were detected in 19 couples. Since a large number (18.2%) cases harboured genetic abnormalities, it is important for all couples opting for ART to undergo a thorough genetic analysis to prevent recurrent emotional, physical and financial stress.     

Blockchain for IoV in 6G environment: review solutions and challenges

Cluster Computing - In this era of modern digital technologies, the Internet of Vehicles (IoVs) is omnipresent and can be used for varied purposes. However, these devices have scalability,...     

Cadmium Remediation by Arbuscular Mycorrhizal Fungus–Colonized Celery Plants Supplemented with Ethylenediaminetetraacetic Acid

A pot trial using Glomus mosseae along with EDTA (ethylenediaminetetraacetic acid) was conducted for the phytoextraction of cadmium (Cd) by celery (Apium graveolens Linn.) plants from soil artificially contaminated with Cd under glass house conditions. The experiment is a 2 × 2 × 4 factorial design with two levels of G. mosseae inoculations (G. mosseae inoculated and uninoculated), two EDTA concentrations (without and with 2.5 mmol kg^?1 soil EDTA) and four Cd concentrations (0, 5, 10, and 20 mg kg^?1 soil). The results indicate the formation of an effective symbiosis between G. mosseae and celery in the contaminated soil. However, an increase in Cd input level and EDTA addition showed strong phytotoxic effect on celery plants and G. mosseae, as a considerable decrease in the frequency of root colonization and spore density was noticed. However, the plants were able to withstand the stressed condition due to the benefits provided by G. mosseae through increased P accumulation, chlorophyll content, and plant growth, resulting in an increase in Cd accumulation, which was good enough for the phytoextraction purpose. Thus, celery plants inoculated with G. mosseae and later supplemented with EDTA could be an effective and potentially suitable practice for the remediation of Cd-contaminated sites.     

Gain of native conformation of Aurora A S155R mutant by small molecules

Aurora A is a mitotic serine/threonine kinase protein that is a proposed target of the first-line anticancer drug design. It has been found to be overexpressed in many human cancer cells, including hematological, breast, and colorectal. Here, we focus on a particular somatic mutant S155R of Aurora kinase A protein, whose activity decreases because of loss of interaction with a TPX2 protein that results in ectopic expression of the Aurora kinase A protein, which contributes chromosome instability, centrosome amplification, and oncogenic transformation. The primary target of this study is to select a drug molecule whose binding results in gaining S155R mutant interaction with TPX2. The computational methodology applied in this study involves mapping of hotspots (for uncompetitive binding), virtual screening, protein–ligand docking, postdocking optimization, and protein–protein docking approach. In this study, we screen and validate ZINC968264, which acts as a potential molecule that can improve the loss of function occurred because of mutation (S155R) in Aurora A. Our approaches pave a suitable path to design a potential drug against physiological condition manifested because of S155R mutant in Aurora A.