Targeted therapy aiming at the metastatic signal pathway, such as that triggered by receptor tyrosine kinase (RTK), for the prevention of tumor progression is promising. However, RTK-based targeted ...therapy frequently suffered from drug resistance due to the co-expression of multiple growth factor receptors that may raise compensatory secondary signaling and acquired mutations after treatment. One alternative strategy is to manipulate the common negative regulators of the RTK signaling. Among them, Raf kinase inhibitory protein (RKIP) is highlighted and focused on this review. RKIP can associate with Raf-1, thus suppressing the downstream mitogen-activated protein kinase (MAPK) cascade. RKIP also negatively regulates other metastatic signal molecules including NF-κB, STAT3, and NOTCH1. In general, RKIP achieves this task via associating and blocking the activity of the critical molecules on upstream of the aforementioned pathways. One novel RKIP-related signaling involves reactive oxygen species (ROS). In our recent report, we found that PKCδ-mediated ROS generation may interfere with the association of RKIP with heat shock protein 60 (HSP60)/MAPK complex via oxidation of HSP60 triggered by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. The departure of RKIP may impact the downstream MAPK in two aspects. One is to trigger the Mt→cytosol translocation of HSP60 coupled with MAPKs. The other is to change the conformation of HSP60, favoring more efficient activation of the associated MAPK by upstream kinases in cytosol. It is worthy of investigating whether various RTKs capable of generating ROS can drive metastatic signaling via affecting RKIP in the same manner.
Objective: Optoacoustic (photoacoustic) tomography is aimed at reconstructing maps of the initial pressure rise induced by the absorption of light pulses in tissue. In practice, due to inaccurate ...assumptions in the forward model, noise, and other experimental factors, the images are often afflicted by artifacts, occasionally manifested as negative values. The aim of this work is to develop an inversion method which reduces the occurrence of negative values and improves the quantitative performance of optoacoustic imaging. Methods: We present a novel method for optoacoustic tomography based on an entropy maximization algorithm, which uses logarithmic regularization for attaining non-negative reconstructions. The reconstruction image quality is further improved using structural prior-based fluence correction. Results: We report the performance achieved by the entropy maximization scheme on numerical simulation, experimental phantoms, and in-vivo samples. Conclusion: The proposed algorithm demonstrates superior reconstruction performance by delivering non-negative pixel values with no visible distortion of anatomical structures. Significance: Our method can enable quantitative optoacoustic imaging, and has the potential to improve preclinical and translational imaging applications.
Both protein kinase C (PKC) and reactive oxygen species (ROS) are well-known signaling messengers cross-talking with each other to activate mitogen-activated protein kinases (MAPKs) for progression ...of hepatocellular carcinoma (HCC). However, the underlying mechanisms are not well elucidated. Especially, whether mitochondrial ROS (mtROS) is involved and how it triggers MAPK signaling are intriguing. In this study, we found mtROS generation and phosphorylation of MAPKs were mediated by PKCδ in HCCs treated with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Heat shock protein 60 (HSP60), one of the chaperones in mitochondria was the major protein oxidized in TPA-treated HCCs. Moreover, depletion of HSP60 or expression of HSP60 cysteine mutant prevented TPA-induced phosphorylation of MAPKs. To delineate how HSP60 mediated MAPK activation, the role of Raf kinase inhibitor protein (RKIP), a negative regulator of MAPK, was investigated. TPA dissociated RKIP from HSP60 in both mitochondria and cytosol, concurrently with translocation of HSP60 and MAPK from mitochondria to cytosol, which was associated with robust phosphorylation of MAPKs in the cytosol. Moreover, TPA induced opposite phenotypical changes of HCCs, G1 cell cycle arrest, and cell migration, which were prevented by mtROS scavengers and depletion of PKCδ and HSP60. Consistently, TPA increased the migration-related genes, hydrogen peroxide inducible clone5, matrix metalloproteinase-1/3, lamininγ2, and suppressed the cell cycle regulator cyclin E1 (CCNE1) via PKCδ/mtROS/HSP60/MAPK-axis. Finally, c-jun and c-fos were required for TPA-induced expression of the migration-related genes and a novel microRNA, miR-6134, was responsible for TPA-induced suppression of CCNE1. In conclusion, PKCδ cross-talked with mtROS to trigger HSP60 oxidation for release of RKIP to activate MAPK, regulating gene expression for migration, and G1 cell cycle arrest in HCC. Targeted therapy aiming at key players like PKCδ, RKIP, and HSP60 is promising for preventing HCC progression.
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•PKC∂ and mitochondrial ROS crosstalk with each other for HCC cell migration.•Upon HSP60 oxidation, Raf-kinase inhibitory protein dissociates itself from HSP60.•Oxidized HSP60 shows mitochondria to cytosol translocation with its client proteins.•Activation of HSP60 client proteins ERK and JNK occurred robustly in the cytosol.•Novel miR-6134 targeted Cyclin E1 to exert G1 cell cycle arrest.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The domain of graphene's application is highly multifaceted in the recent years but developing quintessential quality of graphene is quite challenging for industrial sectors via facile route. In this ...article, an indigenous one step production of graphene from graphite powder by mere stirring and using eco‐friendly aqueous solvent is reported. This fabrication process also bypass the conventional multistep involved previously. The role of sodium dodecyl sulfate (SDS) as a surfactant and the effect of stirring at different time intervals are studied, which clearly indicates that the surfactant facilitates the dispersion of the precursor in water at room temperature and the prolonged stirring helps to break the labile van der Waals forces within the graphitic structure.
Graphene nanosheets are prepared from natural graphite powder by stirring for 15 and 25 hours at room temperature. It is observed that 25 hours of stirring leads better quality of graphene. This environment‐friendly process involves aqueous medium and surfactant avoiding the multi‐steps. The average particle size after 25 hours is found to be 69.2 nm. The SEM confirms clear isolation of graphitic layers after 25 hours of stirring.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•B-HLH proteins bind the E-Box 8-mer CGCAN|NTG better to carboxylcytosine in the CG dinucleotide.•The Tcf3|Ascl1 heterodimer preferentially binds to 5caC better than either homodimer.•Increased ...binding of 5caC to B-HLH proteins was confirmed by circular dichroism thermal denaturation.•5caC increased Tcf3|Ascl1 heterodimer binding ∼10-fold.•5hmC and 5fC did not change binding.
Three oxidative products of 5-methylcytosine (5mC) occur in mammalian genomes. We evaluated if these cytosine modifications in a CG dinucleotide altered DNA binding of four B-HLH homodimers and three heterodimers to the E-Box motif CGCAG|GTG. We examined 25 DNA probes containing all combinations of cytosine in a CG dinucleotide and none changed binding except for carboxylation of cytosine (5caC) in the strand CGCAG|GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3|Ascl1 heterodimer which increased binding ∼10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective:Optoacoustic (photoacoustic) tomography is aimed at reconstructing maps of the initial pressure rise induced by the absorption of light pulses in tissue. In practice, due to inaccurate ...assumptions in the forward model, noise and other experimental factors, the images are often afflicted by artifacts, occasionally manifested as negative values. The aim of the work is to develop an inversion method which reduces the occurrence of negative values and improves the quantitative performance of optoacoustic imaging. Methods: We present a novel method for optoacoustic tomography based on an entropy maximization algorithm, which uses logarithmic regularization for attaining non-negative reconstructions. The reconstruction image quality is further improved using structural prior based fluence correction. Results: We report the performance achieved by the entropy maximization scheme on numerical simulation, experimental phantoms and in-vivo samples. Conclusion: The proposed algorithm demonstrates superior reconstruction performance by delivering non-negative pixel values with no visible distortion of anatomical structures. Significance: Our method can enable quantitative optoacoustic imaging, and has the potential to improve pre-clinical and translational imaging applications.
SAtellite-based Marine Process Understanding, Development, Research and Applications (SAMUDRA) for blue economy, a technology development program of the Space Applications Centre, is an umbrella ...program covering research and applications geared toward physical and biological oceanography making use of current and future satellite observations for developing the nation’s blue economy. The main motivation behind this project was to develop satellite and numerical model-based information and value-added products and to demonstrate the implementation of developed applications for operational requirements. The program also aimed at improving existing methodologies for various applications by utilizing space-based inputs. Several field campaigns with the use of NavIC-enabled instruments and NABHMITRA were conducted for measuring biophysical parameters and validation of developed applications in the coastal regions. One of the key aspects of this project was development of web-based customized tools/dissemination system for providing the information to the end users. Some of the key/notable achievements of SAMUDRA were development of a portal OceanEye (tailor-made web-portal for Shipping Corporation of India), storm-surge/inundation system, oil-spill trajectory modeling, level-next potential fishing zone algorithm and rip current alert system.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Simple and mucopurulent chronic bronchitis (SMCB) is characterized by recurrent mucoid or mucopurulent sputum production in absence of localized suppurative disease. This observational ...open label study was undertaken to evaluate the effects of homoeopathic medicine in SMCB.
Methods: 1902 patients were screened from 07centres out of which 1305 were excluded. 597 patients were enrolled as per the inclusion and exclusion criteria. A total of 14 pre-defined homeopathic medicines were shortlisted for prescription after repertorizing the pathological symptoms of SMCB. Outcomes were changes in symptoms score using chronic bronchitis symptom scale (CBSS) and changes in FEV1/ FVC ratio using spirometry over a period of two years. Appearance of any change (relief/ worse)/ status quo was immediately followed by placebo/ change in dilution/ change in remedy. Statistical analysis was done using SPSS version 21.
Results: 532 patients were analyzed under intention to treat principle using last observation carry forward method. Mean CBS score reduced from 29.86±4.5 at baseline to 12.33±7.6 at completion of 2 years. Repeated measures ANOVA, at time points 0 (baseline), 3, 6, 9, 12 , 15, 18, 21 and 24 months, showed significant reduction in CBS scores Wilk’s Lambda 0.104, F=564, df 524; p=00001. The FEV1 and FEV1/FVC was maintained within normal limits. 86% prescriptions included Lycopodium, Arsenicum album, Pulsatilla, Phosphorus, Stannum metallicum, Calcarea carbonica, Silicea, Bryonia alba.
Conclusion: The result suggests effectiveness of homoeopathic treatment in early stage of SCMB patients. However, controlled trials are required for further validation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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