Temporal expression of thyroid hormone regulating genes (tsh-b, tsh-r, dio2 and dio3) and their correlation with annual reproductive cycle of the Indian freshwater catfish, Heteropneustes fossilis (Bloch).

Photoperiod and temperature are well-established environmental cues for gonadal growth in seasonally reproducing organisms. The photoperiod is known to regulate seasonal reproduction via induction of thyroid hormone regulating genes in the saccus vasculosus (SV) of fishes. However, SV is absent in many seasonally breeding fishes, including Heteropneustes fossilis. H. fossilis is a long-day breeding catfish in which gonadal recrudescence begins six months earlier than spawning. The present study attempted to analyse the expression of thyroid hormone-regulating genes (tsh-b, tsh-r, dio2 and dio3) in the brain, liver and ovary. In the brain, upregulated expression of thyrotropin-beta subunit (tsh-b), deiodinase2 (dio2) and deiodinase3 (dio3) genes is concomitant with the increasing photoperiod and temperature in nature, which may appear to regulate seasonal reproduction. Both deiodinases, dio2 and dio3, were also upregulated in the liver and ovarian tissue during the gonadal growth phase. The upregulation of deiodinases may enhance the metabolism and activity of tissues, thereby facilitating their respective roles. The expression of these genes was also assessed in the brain, liver, ovary, kidney, skin, spleen and gill tissues during the spawning period. The ubiquitous expression of deiodinases may point to enhanced activity in their organ-specific role. The present study speculates that expression of tsh-b, tsh-r, dio2 and dio3 genes during the reproductive phase of H. fossilis might be involved in the regulation of seasonal reproduction

EFFECT OF QUERY FORMATION ON WEB SEARCH ENGINE RESULTS

ABSTRACT Query in a search engine is generally based on natural language. A query can be expressed in more than one way without changing its meaning as it depends on thinking of human being at a particular moment. Aim of the searcher is to get most relevant results immaterial of how the query has been expressed. In the present paper, we have examined the results of search engine for change in coverage and similarity of first few results when a query is entered in two semantically same but in different formats. Searching has been made through Google search engine. Fifteen pairs of queries have been chosen for the study. The t-test has been used for the purpose and the results have been checked on the basis of total documents found, similarity of first five and first ten documents found in the results of a query entered in two different formats. It has been found that the total coverage is same but first few results are significantly different

Molecular pathways regulated by areca nut in the etiopathogenesis of oral submucous fibrosis

Many oral mucosal lesions are due to substance abuse, such as tobacco and areca nut, amongst others. There is considerable evidence that oral lesions/disorders such as some leukoplakias, most erythroplakias, and submucous fibrosis have malignant potential, with a conversion rate of 5%-10% over a 10-year period. There have been several reports on possible biomarkers that predict malignant conversion of the oral lesions associated with these disorders. Management of these is mostly surgical removal of the lesion followed by observation, and in some cases treatment by antioxidants and anti-inflammatory agents. Oral submucous fibrosis is due to excessive deposition of extracellular matrix in the connective tissue plus, particularly, collagens. The deposition of collagen leads to stiffness of the affected regions and results in difficulty in mouth opening. Areca nut chewing is proposed as the most probable etiological factor in the manifestation of oral submucous fibrosis. Several studies suggest involvement of proinflammatory cytokines, dysregulated by areca nut, in the development of the disease. Amongst these, transforming growth factor-beta is in the forefront, which is also shown to be involved in fibrosis of other organs. This review addresses the molecular mechanisms involved in oral submucous fibrosis development and provides a model for the regulation of transforming growth factor-beta by areca nut. It provides an exemplar of the role of modern molecular techniques in the study of oral disease

Role of areca nut induced JNK/ATF2/Jun axis in the activation of TGF-beta pathway in precancerous Oral Submucous Fibrosis

Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-beta driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-beta activation and its effects contributing to OSF. However, the mechanism for activation of TGF-beta signaling in OSF is still unknown. In this study we demonstrate activation of TGF-beta signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process. In good correlation; pJNK was detected in OSF tissues but not in normal tissues. Moreover, activation of JNK was found to be dependent on muscarinic acid receptor induced Ca2+/CAMKII as well as ROS. JNK dependent phosphorylation of ATF2/c-Jun transcription factors resulted in TGF-beta transcription and its signaling. pATF2/p-c-Jun were enriched on TGF-beta promoter and co-localized in nuclei of epithelial cells upon areca nut treatment. In corroboration, OSF tissue sections also had nuclear pATF2 and p-c-Jun. Our results provide comprehensive mechanistic details of TGF-beta signaling induced by etiological agent areca nut in the manifestation of fibrosis which can lead to new therapeutic modalities for OSF

Mitochondria-Targeting Iron(III) Catecholates for Photoactivated Anticancer Activity under Red Light

Iron(III) catecholates Fe(R-bpa)(R-dopa)Cl] (1, 2) with a triphenylphosphonium (TPP) moiety, where R-bpa is 2-(TPP-N,N-bis((pyridin-2-yl)methyl)ethanamine) chloride (TPPbpa) and R-dopa is 4-{2-(anthracen-9-yl)methylamino]ethyl}benzene-1,2-diol (andopa, 1) or 4-{2-(pyren-1-yl)-methylamino]ethyl}benzene-1,2-diol (pydopa, 2), were synthesized and their photocytotoxicity studied. Complexes 3 and 4 with phenyl-N,N-bis(pyridin-2-yl)methyl]methanamine (phbpa) were used as controls. The catecholate complexes showed an absorption band near 720 nm. The 5e(-) paramagnetic complexes showed a Fe-III/Fe-II irreversible response near -0.45 V and a quasi-reversible catechol/semiquinone couple near 0.5 V versus saturated calomel electrode (SCE) in DMF/0.1 M tetrabutylammonium perchlorate. They showed photocytotoxicity in red/visible light in HeLa, HaCaT, MCF-7, and A549 cells. Complexes 1 and 2 displayed mitochondrial localization, reactive oxygen species (ROS) generation under red light, and apoptotic cell death. Control complexes 3 and 4 exhibited uniform distribution throughout the cell. The complexes showed DNA photocleavage under red light (785 nm), forming hydroxyl radicals as the ROS

Iron(III) salicylates of dipicolylamine bases showing photo-induced anticancer activity and cytosolic localization

An iron(III) salicylate having a dipicolylamine base (andpa) with a photoactive anthracenyl moiety is prepared, characterized, and studied for its photo-induced anticancer activity and cellular localization in HeLa and MCF-7 cells. Its phenyl analogue is structurally characterized by X-ray crystallography. The complex has a ternary structure in which the dipicolylamine ligand and salicylic acid in dianionic form (sal) display respective tridentate and bidentate mode of coordination in Fe(sal)(phdpa)Cl] (1). Complex Fe(sal)(andpa)Cl] (2) having a pendant anthracenyl moiety shows significant photocytotoxicity in visible light (400-700 nm) giving IC50 values of 8.6 +/- 0.7 and 3.4 +/- 0.9 mu M in HeLa and MCF-7 cells, while being essentially nontoxic in the dark (IC50 > 100 mu M). The complex shows cytosolic localization in the cancer cells. Formation of hydroxyl radicals ((OH)-O-center dot) as the reactive oxygen species is evidenced from the pUC19 DNA photocleavage studies. (C) 2015 Elsevier Ltd. All rights reserved

Polypyridyl iron(II) complexes showing remarkable photocytotoxicity in visible light

Iron(II) complexes of polypyridyl ligands (B), viz. Fe(B)(2)]Cl-2 (1 and 2) of N, N, N-donor 2-(2-pyridyl)-1,10-phenanthroline (pyphen in 1) and 3-(pyridin-2-yl)dipyrido3,2-a:2',3'-c]phenazine (pydppz in 2), are prepared and characterized. They are 1:2 electrolytes in aqueous DMF. The diamagnetic complexes exhibit metal to ligand charge transfer band near 570 nm in DMF. The complexes are avid binders to calf thymus DNA giving binding constant (K (b)) values of similar to 10(6) M-1 suggesting significant intercalative DNA binding of the complexes due to presence of planar phenanthroline bases. Complex 2 exhibits significant photocytotoxicity in immortalized human keratinocyte cells HaCaT and breast cancer cell line MCF-7 giving IC50 values of 0.08 and 13 mu M in visible light (400-700 nm). Complex 2 shows only minor dark toxicity in HaCaT cells but is non-toxic in dark in MCF-7 cancer cells. The light-induced cellular damage follows apoptotic pathway on generation of reactive oxygen species as evidenced from the dichlorofluorescein diacetate (DCFDA) assay

Mitochondria-Targeted Anticancer Activity of BODIPY-Appended Iron(III) Catecholates in Red Light

Iron(III) catecholates of dipicolylamine (dpa) bases having appended Benzyl (in bzdpa) or BODIPY (borondipyrromethene) moiety (in L-1 and L-2), viz. Fe(Bzdpa)(cat)Cl] (1), Fe(L-1)(cat)Cl] (2) and Fe(L-2)(cat)Cl] (3), were prepared and characterized (H(2)cat = catechol). The iron(III) complexes with a ligand-to-metal charge transfer (LMCT) band within 600-800 nm were studied for their photocytotoxicity in visible (400-700 nm) and red (600-720 nm) light. Complex 2 with a BODIPY fluorophore in L-1 gave IC50 values of 2.2 +/- 0.5 and 15.0 +/- 0.7 mu M in visible and red light, respectively, in HeLa cells. Complex 3 with a diiodo-BODIPY moiety showed excellent PDT activity giving respective IC50 values of 0.8 +/- 0.2 and 12.6 +/- 1.1 mu M. They are less toxic in dark (IC50: >= 85 mu M). A similar activity was observed in MCF-7 cancer cells. The BODIPY complexes showed significant mitochondrial localization. Annexin FITC assay showed apoptotic cell death involving reactive oxygen species (ROS). Photo-generation of ROS was evidenced from dichlorofluorescein diacetate (DCFDA) assay. Mechanistic studies on DNA photocleavage reactions showed the presence of two types of ROS. Singlet oxygen formation from BODIPY was evidenced from the 1,3-diphenylisobenzofuran (DPBF) experiments. Hydroxyl radical was generated on red light photo-activation of the LMCT band within photodynamic therapy (PDT) spectral window