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Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Here, a macrophage infection model was used to unravel the role of the histone deacetylase sirtuin 6 (SIRT6) in Mtb‐triggered regulation of the innate immune response. Mtb infection downregulated microRNA‐26a and upregulated its target SIRT6. SIRT6 suppressed glycolysis and expression of HIF‐1α‐dependent glycolytic genes during infection. In addition, SIRT6 regulated the levels of intracellular succinate which controls stabilization of HIF‐1α, as well as the release of interleukin (IL)‐1β. Furthermore, SIRT6 inhibited inducible nitric oxide synthase (iNOS) and proinflammatory IL‐6 but augmented anti‐inflammatory arginase expression. The miR‐26a/SIRT6/HIF‐1α axis therefore regulates glycolysis and macrophage immune responses during Mtb infection. Our findings link SIRT6 to rewiring of macrophage signaling pathways facilitating dampening of the antibacterial immune response. [ABSTRACT FROM AUTHOR]

A 2D coordination polymer, [Zn2(BDC)4(QPR)2(H2O)]n (Zn(II)‐CP) (BDC2− = 1,4‐benzenedicarboxylato; QPR = 7‐[(pyridin‐4‐ylmethylene)‐amino]‐chromen‐2‐one), is presumably the first reported on coumarinyl‐pyridyl framework with terephthalato linker. The optical band gap, 2.91 eV, is obtained from the Tauc's plot that insists to fabricate an optically stimulated semiconducting device, and the electrical conductivity exhibited (Λ) is 8.07 × 10−3 S m−1 (dark) and 9.26 × 10−3 S m−1 (light). The cytotoxicity in the selected human cancer cell lines like HeLa, MDA‐MB 231, and HepG2 cells in relative to the normal kidney epithelial (NKE) cell line has been examined, and its efficacy is observed highest in inhibiting proliferation of HeLa cells (IC50, 21.02) compared with other cancer cells (IC50: 42.22 [HepG2] and 46.37 [MDA‐MB 231]). Further, the Zn(II)‐CP possess intracellular reactive oxygen species (ROS) generation and caspase‐3/7 activation leading to G2/M cell cycle arrest and apoptotic cell death in HeLa cell line. This novel coumarinyl‐pyridyl ligand appended Zn(II)‐CP has been employed for the fabrication of semiconducting device, which is quite impressive in view of existing energy crisis civilization; in addition, the compound has excellent bio‐activity. [ABSTRACT FROM AUTHOR]

1,1′‐((1E,1′E)‐((2E,2′E)(((phenylazanediyl)bis(4,1‐phenylene))bis‐(methanylylidene))bis‐ (hydrazine‐2,1‐diylidene))bis(methanylylidene))bis(naphthalen‐2‐ol), H2L shows high fluorescence emission (λem, 550 nm; λabs, 420 nm) which is selectively quenched by Cu2+ in presence of many other biologically important ions. The limit of detection (LOD), 7.3 nM is much lower than WHO recommended maximum permissible limit (20 μM) of Cu2+consumption in human body. The binding fashion of the probe to Cu2+ ion is 1 : 2 mole ratio and has been confirmed by Job's plot and ESI‐MS spectral data. The binding constant for Cu2+ is 4.93×1010 M−2 which also indicates sufficient stability and 1 : 2 complexation. On addition of cysteine to L‐Cu2+ensemble,the emission intensity (550 nm) enhances which accounts the release of Cu2+ from the non‐emissive complex and restores the total fluorogenic efficiency of probe, H2L (LOD (Cysteine), 36 nM). Thus, ON‐OFF‐ON mechanism of H2L has been utilized for selective and specific detection of Cu2+ and Cysteine over several other amino acids. In addition to this, the probe is treated on WI‐38 cell line to check cytotoxicity. This chemosensor, H2L has been successfully applied to examine intracellular trace quantity of Cu2+ and Cysteine concentration in Hep G2 Cell lines. [ABSTRACT FROM AUTHOR]

A Zn(II)‐based two‐dimensional (2D) pillar bilayer metal‐organic framework (MOF) [{Zn(aip)(4,4′‐bpy)0.5(MeOH)}⋅(H2O)]n (1), (H2aip=5‐aminoisophthalic acid and 4,4′‐bpy=4, 4′‐bipyridine) has been designed and structurally characterized by single crystal X‐ray diffraction (SCXRD) technique. Compound 1 exhibits considerable antibacterial activity upon Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), for which IC50 values have been obtained as 86.26±1.2 μg/ml and 95.96 ± 2.04 μg/ml respectively. Thus the fabricated MOF has the significant antibacterial property against pathogenic bacterial strains with significantly low IC50 values. Therefore, the compound 1 deserves to be a Bio‐MOF in the world of hybrid materials. [ABSTRACT FROM AUTHOR]

Functional group of a molecule monitors the chemical selectivity and the structure regulates the rate of the reaction. Thus, structure‐function relation controls the overall sensitivity of the chemosensor. In this work, three congeneric Schiff bases with common amine, 2,2/‐(propane‐1,2‐diylbis(oxy))dianiline with methoxy substituted Salicylaldehyde are synthesised and have been used to examine the selectivity and sensitivity to the metal ions in 9:1 (v/v) acetonitrile/water (10 mM HEPES buffer, pH 7.4) medium. The probes display prominent fluorescence turn‐on emission when bonded with Zn2+ over sixteen other metal ions with very low limit of detection (LOD), 2.2 to 12.3 nM. Structure with bulkiness has low sensitivity to Zn2+ which may be due to steric crowding about the binding centres of the chelating motif. The selectivity for Zn2+ ion may ascribe to chelation enhancement of fluorescence (CHEF) effect. The probes are characterized by 1H and 13C NMR, IR, HR‐MS and elemental analysis. The metal: ligand ratio of the Zn(II)‐complexes follows 1:1 molar ratio and has been established by Job's plot, Benesi–Hildebrand plot and HR‐MS data. All the probes have been successfully applied to the detection of intracellular Zn2+ ion in Human liver cancer cell line, HepG2. [ABSTRACT FROM AUTHOR]

The active fraction and/or compounds of Calendula officinalis responsible for wound healing are not known yet. In this work we studied the molecular target of C. officinalis hydroethanol extract (CEE) and its active fraction (water fraction of hydroethanol extract, WCEE) on primary human dermal fibroblasts (HDF). In vivo, CEE or WCEE were topically applied on excisional wounds of BALB/c mice and the rate of wound contraction and immunohistological studies were carried out. We found that CEE and only its WCEE significantly stimulated the proliferation as well as the migration of HDF cells. Also they up-regulate the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in vitro. In vivo, CEE or WCEE treated mice groups showed faster wound healing and increased expression of CTGF and α-SMA compared to placebo control group. The increased expression of both the proteins during granulation phase of wound repair demonstrated the potential role of C. officinalis in wound healing. In addition, HPLC-ESI MS analysis of the active water fraction revealed the presence of two major compounds, rutin and quercetin-3-O-glucoside. Thus, our results showed that C. officinalis potentiated wound healing by stimulating the expression of CTGF and α-SMA and further we identified active compounds. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Macrophages play an important role in the establishment of infection by intracellular pathogens. Mycobacterium tuberculosis is known to inhibit apoptosis and to downregulate immune responses of host cells using various strategies, including activation of peroxisome proliferator-activated receptor (PPAR)γ. Mannose-capped lipoarabinomannan (ManLAM) is one of the known bacterial effectors that plays a role in subversion of host immunity and activation of PPARγ. Here, we have used an unbiased global gene expression profiling approach to understand ( a) how ManLAM regulates host cell immune responses and ( b) the role of PPARγ in modulating ManLAM-induced host cell signaling. We have demonstrated that ManLAM-dependent inhibition of macrophage apoptosis is mediated by the upregulation of the antiapoptotic B-cell CLL/ lymphoma 2 (Bcl2) family member A1. Our in silico analyses suggested that ManLAM-mediated PPARγ signaling is linked to important functions such as phagocytosis, cytoskeleton remodeling, cell survival, and autophagy. We have validated that ManLAM upregulates signal transducer and activator of transcription ( STAT5) α, an important transcriptional regulator of cell survival in a PPARγ-dependent manner. © 2015 IUBMB Life, 67(9):726-736, 2015 [ABSTRACT FROM AUTHOR]

Eukaryotic DNA is compacted in the form of chromatin, in a complex with histones and other non-histone proteins. The intimate association of DNA and histones in chromatin raises the possibility that DNA-interactive small molecules may bind to chromatin-associated proteins such as histones. Employing biophysical and biochemical techniques we have characterized the interaction of a classical intercalator, ethidium bromide (EB) and its structural analogue propidium iodide (PI) with hierarchical genomic components: long chromatin, chromatosome, core octamer and chromosomal DNA. Our studies show that EB and PI affect both chromatin structure and function, inducing chromatin compaction and disruption of the integrity of the chromatosome. Calorimetric studies and fluorescence measurements of the ligands demonstrated and characterized the association of these ligands with core histones and the intact octamer in absence of DNA. The ligands affect acetylation of histone H3 at lysine 9 and acetylation of histone H4 at lysine 5 and lysine 8 ex vivo . PI alters the post-translational modifications to a greater extent than EB. This is the first report showing the dual binding (chromosomal DNA and core histones) property of a classical intercalator, EB, and its longer analogue, PI, in the context of chromatin. [ABSTRACT FROM AUTHOR]

Mithramycin (MTR) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg 2+ . As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo . Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

In order to investigate the ameliorative potential of L-ascorbic acid on intensive swimming exercise induced testicular oxidative stress, 18 Wistar male rats (age: 3 months, weight: 127.5 ± 5.3 g) were randomly divided into the following groups: (i) control group (CG, n = 6); (ii) experimental group (EG, n = 6); and (iii) supplemented group (SG, n = 6). An exercise protocol of 3 h swimming per day, five days per week was followed for 6 weeks in EG and SG with no exercise in CG. In SG, L-ascorbic acid was supplied orally at a dose of 25-mg/kg of bodyweight each day for 6 weeks. A significant decrease ( P < 0.05) was noted in paired testicular weights, epididymal sperm count, testicular Δ5, 3β-hydroxyseroid dehydrogenase, 17β-hydroxyseroid dehydrogenase, plasma levels of testosterone luteinizing hormone, follicle stimulating hormone, prolactin, the numbers of preleptotine spermatocytes, midpachytene spermatocytes and stage 7 spermatids of stage VII seminiferous epithelium cycle in EG when compared with CG. A significant elevation ( P < 0.05) in plasma corticosterone and testicular content of malondialdehyde along with a significant reduction ( P < 0.05) in glutathione, ascorbic acid, α-tocopherol, superoxide dismutase, catalase and glutathione-peroxidase, and glutathione-S-transferase were noted in testes of EG compared with CG. No significant change was noted in final bodyweight or numbers of spermatogonia-A among the groups. Furthermore, L-ascorbic acid supplementation restored the above parameters to the control level. Conclusion: It can be concluded that intensive swimming exercise induced oxidative stress causes dysfunctions in the male reproductive system, which can be protected by L-ascorbic acid. (Reprod Med Biol 2006; 5: 145–153) [ABSTRACT FROM AUTHOR]