In vitro assessment of praziquantel and a novel nanomaterial against protoscoleces of Echinococcus granulosus

The present study describes the activity of a nanomaterial on protoscoleces of Echinococcus granulosus, which exhibited morphological changes and apoptosis. Apoptotic changes were deduced on the basis of effector caspase activation and nucleosomal laddering. Invaginated protoscoleces maintained in vitro became evaginated and had hooks, presumptive suckers and stalks. Degenerative changes of protoscoleces were evidenced after treatment with praziquantel and nano-combination. Protoscoleces treated with praziquantel had distinct attestation of necrosis and nano-combination-treated protoscoleces had signatures of apoptosis.     

Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.     

Anticancer potential of 3-(arylideneamino)-2-phenylquinazoline-4(3H)-one derivatives

Different quinazoline derivatives have showed wide spectrum of pharmacological activities. Some 3-(arylideneamino)-phenylquinazoline-4(3H)-ones have been reported to possess antimicrobial activity. The present study has been undertaken to evaluate the anticancer effect of these quinazolinone derivatives. The quinazolinone derivatives were synthesized as reported earlier. Compounds containing NO(2), OH, OCH(3), or OH and OCH(3) as substituent(s) on the arylideneamino group were named as P(3a), P(3b), P(3c), and P(3d) respectively. Out of these, P(3a) and P(3d) showed better cytotoxic activity than P(3b) and P(3c) on a panel of six cancer cell lines of different origin, namely, B16F10, MiaPaCa-2, HCT116, HeLa, MCF7, and HepG2, though the effect was higher in B16F10, HCT116, and MCF7 cells. P(3a) and P(3d) induced death of B16F10 and HCT116 cells was associated with characteristic apoptotic changes like cell shrinkage, nuclear condensation, DNA fragmentation, and annexin V binding. Also, cell cycle arrest at G1 phase, alteration of caspase-3, caspase-9, Bcl-2 and PARP levels, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in treated B16F10 cells. Treatment with multiple doses of P(3a) significantly increased the survival rate of B16F10 tumor bearing BALB/c mice by suppressing the volume of tumor while decreasing microvascular density and mitotic index of the tumor cells.     

Molecular characterization of <Emphasis Type="Italic">Echinococcus granulosus</Emphasis> of Indian animal isolates on the basis of nuclear and mitochondrial genotype

Sixty-six isolates of larval stage of Echinococcus granulosus, a known pathogenic parasite of man and animals were collected from cattle, buffalo, sheep, and goats. Single-stranded conformation polymorphism (SSCP) for analysis of variation after denaturation of amplicon of intron of actin II (ACTII) revealed six SSCP phenotypes. Intron portion was analyzed considering introns-early and introns-late theories. Isolates belonging to different conformers were further screened for mitochondrial ATPase subunit 6 (ATP6) and NADH dehydrogenase subunit II (nadII) genotypes. Assignment of each isolate to its specific strain was achieved after comparing with standard genotypes of E. granulosus. Variants deduced by nuclear targets did not match with mitochondrial haplotypes. A possible explanation for this observation can be attributed toward interspecific hybridization since cross-fertilization occurs less frequently in hermaphrodite organisms. A phylogenetic tree drawn on the basis of predicted aminoacid sequence of ATP6 and nadII revealed two distinct clusters i.e. E. granulosus sensu stricto and E. ortleppi/cattle strain (EG5). To the best of our knowledge, this is the first report of genetic characterization of two distinct ATP6 and nadII genotypes of zoonotic importance living in sympatry.     

Synthesis, spectroscopy and thermal behavior of new lead(II) complexes derived from S-methyl/benzyldithiocarbazates (SMDTC/SBDTC): X-ray crystal structure of [Pb(SMDTC)(NO3)2]

Lead(II) complexes of S-methyldithiocarbazate (SMDTC), [Pb(SMDTC)(NO₃)₂] (1) and S-benzyldithiocarbazate (SBDTC), [Pb(SBDTC)(NO₃)₂] (2) have been synthesized for the first time and characterized by elemental analysis, IR and TGA techniques. The complexes were obtained by addition of the appropriate ligand to an aqueous ethanolic solution of lead(II) nitrate in 1:1 molar ratio. The X-ray crystal structure of complex 1 has been determined by single crystal X-ray diffractometry. In complex 1, lead(II) is in a nine coordinated sphere with seven oxygen atoms of the nitrate groups and thione sulfur, β-nitrogen of neutral bidentate NS chelating ligand. Three nitrate groups act as bidentate chelating whereas the fourth nitrate group is coordinating to the central lead(II) and at the same time it bridges with neighboring lead(II) atom. Coordination geometry of the central lead(II) atom has a tricapped trigonal prismatic arrangement with streochemically inactive lone pair. The lead atoms are linked into polymeric chains and these chains form twin polymeric ribbons linked through bridging oxygen atoms. The N-H?O hydrogen bond network between N_SMDTC and O_nitrate atom leads to self-assembled molecular conformation and stabilizes the crystal structure. The complex 2 with similar spectral and thermal behavior is expected to have a tricapped trigonal prismatic structure. The thermal behavior studies shows that the complexes start to decompose at relatively low temperature (ca. 110 °C) to give PbS residue.     

Plant Remains from an Archaeological Site as Indicators of Vegetation and Agricultural Practice Between (3320±400) and (2080±80) yr BP in Gangetic West Bengal, India

Diverse plant remains recovered from an archaeological site of Chalcolithic-Early Historic age in the Bhairabdanga area of Pakhanna (latitude 23°25′N, longitude 87°23′E), situated on the west bank of the Damodar river, Bankura district, West Bengal, India, include food grains, wood charcoals, and palynomorphs. Radiocarbon dating of the recovered biological remains reveal the age of the site as (3320±400) to (2080±80) yr BP. The food grains were identified as Oryza sativa L. and Vigna mungo L, and seeds of Brassica cf.campestris L. were also found; these indicate the agricultural practice and food habits of the ancient people living at Pakhanna from the Chalcolithic to the Early Historic period. Sediments including plant remains have been broadly divided into two zones, considering archaeological findings and radiocarbon dating. Analysis of the plant remains (i.e. wood charcoals and palynomorphs) in addition to cultivated food grains has revealed that a rich vegetation cover existed in this area, with a prevailing tropical and humid climate,comprising the timber-yielding plants Shorea sp., Terminalia sp., and Tamarindus sp., with undergrowths of diverse shrubs and herbs during the Chalcolithic period (zone Ⅰ) dated (3320±400) yr BP. Comparatively poorer representation and frequency of plant remains indicate a drier climate during the Early Historic period (zone Ⅱ) dated as (2110±340) to (2080±80) yr BP. Comparisons of the archaeobotanical data recovered from the Chalcolithic and Early Historic period and also a principle components analysis indicate a change in the climate of the area from tropical and humid at (3 320 ± 400) yr BP to tropical and drier conditions at (2110±340) to (2080±80) yr BP. The present-day tropical, dry deciduous vegetation of the area suggests that climate change has occurred in the area since the contemporaneous past. The plant remains database has been utilized to reconstruct the settlement pattern of the community living in the site between (3320±400) and (2080±80) yr BP. The community settled near the riverbank, practicing cultivation.