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Study Design: Retrospective Study., Objective: At the North American Spine Society (NASS) conference, participants may influence spine surgery practices and patient care through their contributions. Therefore, their financial conflicts of interest are of notable interest. This study aims to compare the demographics and payments made to participating surgeons., Methods: A list of 151 spine surgeons was created based on those who participated in the 2022 NASS conference. Demographic information was obtained from public physician profiles. General payments, research payments, associated research funding, and ownership interest were collected for each physician. Descriptive statistics and two-tailed t-tests were used., Results: In 2021, 151 spine surgeon participants received industry payments, totaling USD 48 294 115. The top 10% of orthopedic surgeons receiving payments accounted for 58.7% of total orthopedic general value, while the top 10% of neurosurgeons accounted for 70.1%. There was no significant difference between these groups' general payment amounts. Surgeons with 21-30 years of experience received the most general funding. There was no difference in funding between surgeons in academic or private settings. For all surgeons, royalties accounted for the largest percentage of the general value exchanged, while food/beverage accounted for the largest percentage of transactions., Conclusion: Our study found that only years of experience had a positive association with general payments, and most monetary value belonged to a small handful of surgeons. These participants receiving significant money may promote techniques requiring products of companies providing their compensation. Future conferences may require disclosure policy changes so attendees understand the degree of funding participants receive., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The chaperone protein EROS ("Essential for Reactive Oxygen Species") was recently discovered in phagocytes. EROS was shown to regulate the abundance of the ROS-producing enzyme NADPH oxidase isoform 2 (NOX2) and to control ROS-mediated cell killing. Reactive oxygen species are important not only in immune surveillance, but also modulate physiological signaling responses in multiple tissues. The roles of EROS have not been previously explored in the context of oxidant-modulated cell signaling. Here we show that EROS plays a key role in ROS-dependent signal transduction in vascular endothelial cells. We used siRNA-mediated knockdown and developed CRISPR/Cas9 knockout of EROS in human umbilical vein endothelial cells (HUVEC), both of which cause a significant decrease in the abundance of NOX2 protein, associated with a marked decrease in RAC1, a small G protein that activates NOX2. Loss of EROS also attenuates receptor-mediated hydrogen peroxide (H 2 O 2 ) and Ca 2+ signaling, disrupts cytoskeleton organization, decreases cell migration, and promotes cellular senescence. EROS knockdown blocks agonist-modulated eNOS phosphorylation and nitric oxide (NO ● ) generation. These effects of EROS knockdown are strikingly similar to the alterations in endothelial cell responses that we previously observed following RAC1 knockdown. Proteomic analyses following EROS or RAC1 knockdown in endothelial cells showed that reduced abundance of these two distinct proteins led to largely overlapping effects on endothelial biological processes, including oxidoreductase, protein phosphorylation, and endothelial nitric oxide synthase (eNOS) pathways. These studies demonstrate that EROS plays a central role in oxidant-modulated endothelial cell signaling by modulating NOX2 and RAC1., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Backgrounds and Aims: The role of inflammation in driving atherosclerosis is well-established. It exerts systemic effects beyond the local site of plaque formation. In the context of coronary artery disease (CAD), the proteins that show altered levels in the plasma, are potentially important for understanding the key regulatory mechanism in the pathogenesis of atherosclerosis. A case-control study revealed that plasma soluble Peptidoglycan Recognition Protein 2 (PGLYRP2) primarily produced by the liver, is increased in subjects with CAD. Furthermore, the concentration of PGLYRP2 in the blood correlates with the severity of coronary artery disease. Thus, it raises interest in understanding the exact role of the protein in aortic inflammation and plaque progression., Methods: We evaluated the plasma concentration of PGLYRP2 in three distinct groups: patients with CAD (N = 68), asymptomatic individuals (N = 34), and healthy volunteers (N = 20). Furthermore, we investigated the correlation between disease severity and PGLYRP2 levels in CAD patients. To identify potential binding partners of PGLYRP2, we employed computational analysis. We verified the PGLYRP2-NOD2 interaction in macrophage cells and elucidated the inflammatory pathways activated by PGLYRP2 within these cells. To assess the impact of PGLYRP2, we examined its effects in the atherosclerotic mice model (ApoE -/ - )., Results: In this study, we report for the first time that Nucleotide-binding Oligomerization domain 2 (NOD2) which is expressed on the surface of macrophages, is a receptor of PGLYRP2. The N-terminal domain of PGLYRP2 directly binds to NOD2 and activates the NOD2-RIP2-NFκB cascade that promotes the secretion of proinflammatory cytokines like TNFα, IL1β, and IL-8. In the atherosclerotic mice model (ApoE -/- ) we demonstrate that elevated PGLYRP2 level is parallel with increased proinflammatory cytokines in the plasma when fed a High Cholesterol Diet (HCD). Immunohistochemical analysis reveals that PGLYRP2 is co-localized with NOD2 on the macrophages at the site of the lesion., Conclusions: Taken together, our data demonstrate that NOD2 acts as a receptor of PGLYRP2 on macrophages, which mediates the activation of the NOD2-RIP2-NFκB pathway and promotes inflammation, thus significantly contributing to the development and progression of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TG Cdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TG Cdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich's ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TG Cdh5 mice could provide mechanistic insights into Friedreich's ataxia., (© 2023. The Author(s).)

Statins have manifold protective effects on the cardiovascular system. In addition to lowering LDL cholesterol levels, statins also have antioxidant effects on cardiovascular tissues involving intracellular redox pathways that are incompletely understood. Inhibition of HMG-CoA reductase by statins not only modulates cholesterol synthesis, but also blocks the synthesis of lipids necessary for the post-translational modification of signaling proteins, including the GTPase Rac1. Here we studied the mechanisms whereby Rac1 and statins modulate the intracellular oxidant hydrogen peroxide (H 2 O 2 ) via NADPH oxidase (Nox) isoforms. In live-cell imaging experiments using the H 2 O 2 biosensor HyPer7, we observed robust H 2 O 2 generation in human umbilical vein endothelial cells (HUVEC) following activation of cell surface receptors for histamine or vascular endothelial growth factor (VEGF). Both VEGF- and histamine-stimulated H 2 O 2 responses were abrogated by siRNA-mediated knockdown of Rac1. VEGF responses required the Nox isoforms Nox2 and Nox4, while histamine-stimulated H 2 O 2 signals are independent of Nox4 but still required Nox2. Endothelial H 2 O 2 responses to both histamine and VEGF were completely inhibited by simvastatin. In resting endothelial cells, Rac1 is targeted to the cell membrane and cytoplasm, but simvastatin treatment promotes translocation of Rac1 to the cell nucleus. The effects of simvastatin both on receptor-dependent H 2 O 2 production and Rac1 translocation are rescued by treatment of cells with mevalonic acid, which is the enzymatic product of the HMG-CoA reductase that is inhibited by statins. Taken together, these studies establish that receptor-modulated H 2 O 2 responses to histamine and VEGF involve distinct Nox isoforms, both of which are completely dependent on Rac1 prenylation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Frost and freezing temperatures have posed an obstacle to tropical woody evergreen plants over evolutionary time scales. Thus, along tropical elevation gradients, frost may influence woody plant community structure by filtering out lowland tropical clades and allowing extra-tropical lineages to establish at higher elevations. Here we assess the extent to which frost and freezing temperatures influence the taxonomic and phylogenetic structure of naturally patchy evergreen forests (locally known as shola ) along a mid-upper montane elevation gradient in the Western Ghats, India. Specifically, we examine the role of large-scale macroclimate and factors affecting local microclimates, including shola patch size and distance from shola edge, in driving shola metacommunity structure. We find that the shola metacommunity shows phylogenetic overdispersion with elevation, with greater representation of extra-tropical lineages above 2000 m, and marked turnover in taxonomic composition of shola woody communities near the frost-affected forest edge above 2000 m, from those below 2000 m. Both minimum winter temperature and patch size were equally important in determining metacommunity structure, with plots inside very large sholas dominated by older tropical lineages, with many endemics. Phylogenetic overdispersion in the upper montane shola metacommunity thus resulted from tropical lineages persisting in the interiors of large closed frost-free sholas, where their regeneration niche has been preserved over time.

In the present study, an attempt has been made to design a solar light driven N-rGO-ZnO- CoPc(COOH) 8 nanocomposite for the degradation of cyanide. The morphological and structural characterization of the synthesized nanocomposite was performed by XRD, FT-IR, XPS, UV-vis DRS, FESEM, TEM, EDS, PL spectra and BET surface area. The results revealed that almost 91% degradation and 86% toxicity removal occurred at 25 mgL -1 of initial cyanide concentration by the N-rGO-ZnO-CoPc(COOH) 8 nanocomposite under illumination of solar light within 120 min. Analysis of free radicals reveals that the generation of OH . radicals was the predominant species in the photocatalytic degradation process. The cyanide degradation follows pseudo-first order kinetics. The estimated apparent rate constant (K app ) of the above nanocomposite was 3 times higher than that of the ZnO photocatalyst alone together with a very good recycle activities. This might be due to the application of metallpthalocyanine photosensitizer CoPc(COOH) 8 which enhances the rate of visible light absorption efficiency and activates the higher band gap ZnO photocatalyst under visible light. In addition, the presence of residual oxygen in N-rGO also promotes nucleation and anchor sites for interfacial contact between ZnO and N-rGO for effective charge transfer. Further, the N-rGO-ZnO-CoPc(COOH) 8 photocatalytic system showed significant antibacterial activities against mixed culture systems. Therefore, the N-rGO-ZnO-CoPc(COOH) 8 nanocomposite may be an alternative solar light driven photocatalyst system for the removal of cyanide from the wastewater along with its strong disinfectant activities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Synchronous liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have traditionally been contraindicated. More recent clinical practice has begun to promote this aggressive treatment in select patients., Objective: This study aimed to investigate the perioperative and oncological outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, with and without liver resection, in the management of metastatic colorectal cancer., Data Sources: Medline, Embase, and Cochrane Library databases were searched up to July 2020., Study Selection: Cohort studies comparing outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with and without liver resection for metastatic colorectal cancer were reviewed. No randomized controlled trials were available., Intervention: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without synchronous liver resection were compared., Main Outcome Measures: The primary outcome measures were perioperative mortality and major morbidity. Secondary outcomes included 3- and 5-year overall survival and 1- and 3-year disease-free survival., Results: Fourteen studies fitted the inclusion criteria, with 8 studies included in the meta-analysis. On pooled analysis, there was no significant difference in perioperative morbidity and mortality between the two groups. Patients that underwent concomitant liver resection had worse 1- and 3-year disease-free survival and 3- and 5-year overall survival., Limitations: Only a limited number of studies were available, with a moderate degree of heterogeneity., Conclusions: The addition of synchronous liver resection to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of resectable metastatic colorectal cancer was not associated with increased perioperative major morbidity and mortality in comparison with cytoreduction and hyperthermic intraperitoneal chemotherapy alone. However, the presence of liver metastases was associated with inferior disease-free and overall survival. These data support the continued practice of liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in the management of select patients with such stage IV disease., (Copyright © The ASCRS 2021.)

Reverse cholesterol transport (RCT) plays a critical role in removing cholesterol from the arterial wall. However, very few reports directly relate chronic inflammation and RCT with atherosclerosis. The present study was undertaken to investigate clinical implications of significantly altered circulating proteins in subjects with ST-segment elevation myocardial infarction (STEMI) in the manifestation of atherosclerotic events. Using a case-control design, more than 2500 proteins in both STEMI and healthy control subjects were identified by Orbitrap mass spectrometer. Quantitative proteomics study revealed downregulation of 26 proteins while expression of 38 proteins increased significantly in STEMI subjects compared to healthy controls. Pathway enrichment analyses indicated that most of the identified proteins were related to chronic inflammation, atherosclerosis, and RCT. Altered proteins such as AZGP1, ABCA5, Calicin, PGLYRP2, HAVCR2 and C17ORF57 were further validated by Western blotting analysis of human plasma. Pathophysiological significance was studied using macrophage derived foam cell for their critical role in RCT which indicated the imbalance of RCT via the interaction of AZGP1 with CD36. In summary, this study revealed a unique relationship of some novel proteins apparently responsible for impaired RCT and chronic inflammation leading to atherothrombosis and myocardial infarction. SIGNIFICANCE: In the present study we identified ≥2500 unique circulating proteins in healthy control and clinically diagnosed STEMI subjects among which 423 proteins were found to be common in both the groups. We further show 64 proteins significantly different between healthy control and STEMI subjects. Proteomic analyses reveal a panel of proteins associated with atherosclerosis and STEMI. One of the proteins, AZGP1, an adipokine, is likely to act as the missing link between chronic inflammation and cholesterol transport. Deregulation of reverse cholesterol transport might be orchestrated by AZGP1, CD36, ABCA5, and PPARɣ in STEMI subjects. The present study employs shotgun and quantitative proteomics followed by in vitro validations demonstrating a biochemical basis for reverse cholesterol transport in the local milieu of the luminal wall of the artery which are critical for plaque build-up and atherosclerosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)-/- mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE-/- mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Notwithstanding recent evidences, paternal environment is thought to be a potential but unlikely source of fitness variation that can affect trait evolution. Here we studied intergenerational effects of males' exposure to varying adult density in Drosophila melanogaster laboratory populations.We held sires at normal (N), medium (M) and high (H) adult densities for 2 days before allowing them to mate with virgin females. This treatment did not introduce selection through differential mortality. Further, we randomly paired males and females and allowed a single round of mating between the sires and the dams. We then collected eggs from the dams and measured the egg size. Finally, we investigated the effect of the paternal treatment on juvenile and adult (male) fitness components.We found a significant treatment effect on juvenile competitive ability where the progeny sired by the H-males had higher competitive ability. Since we did not find the treatment to affect egg size, this effect is unlikely to be mediated through variation in female provisioning.Male fitness components were also found to have a significant treatment effect: M-sons had lower dry weight at eclosion, higher mating latency, and lower competitive mating success.While being the first study to show both adaptive and non-adaptive effect of the paternal density in Drosophila , our results highlight the importance of considering paternal environment as important source of fitness variation., Competing Interests: None declared.

The pituitary function is regulated by a complex system involving the hypothalamus and biological networks within the pituitary. Although the hormones secreted from the pituitary have been well studied, comprehensive analyses of the pituitary proteome are limited. Pituitary proteomics is a field of postgenomic research that is crucial to understand human health and pituitary diseases. In this context, we report here a systematic proteomic profiling of human anterior pituitary gland (adenohypophysis) using high-resolution Fourier transform mass spectrometry. A total of 2164 proteins were identified in this study, of which 105 proteins were identified for the first time compared with high-throughput proteomic-based studies from human pituitary glands. In addition, we identified 480 proteins with secretory potential and 187 N-terminally acetylated proteins. These are the first region-specific data that could serve as a vital resource for further investigations on the physiological role of the human anterior pituitary glands and the proteins secreted by them. We anticipate that the identification of previously unknown proteins in the present study will accelerate biomedical research to decipher their role in functioning of the human anterior pituitary gland and associated human diseases.

The ErbB signalling pathway has been studied extensively owing to its role in normal physiology and its dysregulation in cancer. Reverse engineering by mathematical models use the reductionist approach to characterize the network components. For an emergent, system-level view of the network, we propose a data analytics pipeline that can learn from the data generated by reverse engineering and use it to re-engineer the system with an agent-based approach. Data from a kinetic model that estimates the parameters by fitting to experiments on cell lines, were encoded into rules, for the interactions of the molecular species (agents) involved in biochemical reactions. The agent model, a digital representation of the cell line system, tracks the activation of ErbB1-3 receptors on binding with ligands, resulting in their dimerization, phosphorylation, trafficking and stimulation of downstream signalling through P13-Akt and Erk pathways. The analytics pipeline has been used to mechanistically link HER expression profile to receptor dimerization and activation of downstream signalling pathways. When applied to drug studies, the efficacy of a drug can be investigated in silico. The anti-tumour activity of Pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, was simulated by blocking 80% of the cellular HER2 available, to observe the effect on signal activation.

Motivation: Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments., Results: A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies., Availability and Implementation: Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material ., Contact: liz.csir@gmail.com., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Human antithrombin is a blood derivative widely used in the treatment of coagulation dysfunction. Affinity chromatography using heparin (HEP) derivatives is usually used for antithrombin purification. In this study, an affinity procedure based on a magnetic Dacron-HEP composite is proposed. Dacron was firstly converted to Dacron-hydrazide and magnetised by co-precipitation with of Fe 2+ /Fe 3+ (mDAC). HEP was activated by carbodiimide and N-hydroxysuccinimide and covalently linked to mDAC (mDAC-HEP). EDX and infrared spectra analyses confirmed each synthesis step of mDAC-HEP. This composite exhibited superparamagnetism behaviour. Human plasma was incubated with mDAC-HEP (fresh and stored over a long period) and washed with phosphate buffer containing increasing concentrations of NaCl. Human plasma antithrombin activity was reduced by approximately 20% in the presence of the 1.0M NaCl fraction, and this eluate was able to prolong coagulation time (aPTT) using both preparations. Electrophoresis of the eluates revealed bands corresponding to the expected size of antithrombin (58kDa). The mDAC-HEP particles are reusable. This method presents the following advantages: easy, low-cost synthesis of the composite, magnet-based affinity purification steps, and reusability., (Copyright © 2016 Elsevier B.V. All rights reserved.)

3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS in A375 cells (IC50-24.01 μM), with that in SK-MEL-2 (IC50-67.6 μM), another melanoma cells which highly over-express MITF-M. The compound arrests the cells at S-G2 transition state of the cell cycle, as resveratrol. Our results indicate that DETS is a powerful antioxidant, having anticancer efficacy comparable with that of resveratrol, and is a potential candidate to be explored by in vivo studies and in-depth mechanistic evaluation. To our knowledge, this is the first report on the antioxidant and anticancer properties of DETS.

Identifying interactions between proteins in a complex is essential to analyze their role in various cellular activities and structural stability. Therefore, effective algorithms and computer programs are required for the better understanding of various interactions exist at the protein-protein interface. The protein inter-chain interaction (PICI) server was developed to identify these interaction sites and various interactions that contribute to the specificity and strength of the protein complex by using Protein Interaction Identification Algorithm (PIIA). The multi-parametric approach of this algorithm involves the interface area between the subunits, the atomic coordinate distance, the linearity of bonds, the orientation of aromatic side-chains, and physicochemical properties of the residues. Particular advantages of PICI include its ability to identify various strong and weak interactions, including those which have not been considered before by any other server. Representation of interface data in text tables, 3D interaction visualizer, colored sequence viewer, and a dynamic colored graphical matrix display makes it distinct from similar web servers. Users can analyze interactions within multi-chain proteins by their PDBids or by uploading a structure atomic coordinate file and can download the result in plain text or XML format.

The prevalence of diabetes and heart diseases is increasing in the world. Nutraceuticals of natural origin are gaining importance as an alternative to modern drugs for the management of metabolic syndrome. In the present study, punicic acid (PA), a major bioactive found in pomegranate seed, was subjected for biological characterization with respect to peroxisome proliferator-activated receptor gamma (PPARγ) agonist property in an in vitro system (3T3-L1 adipocytes). We evaluated the adipogenic potential of various concentrations (5, 10 and 30 μM) of PA by studying triglyceride accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity in adipocytes, which were found to be increased moderately compared with the positive control, i.e. rosiglitazone (RG). Glucose uptake activity (↑225.93% ± 2.55% for 30 μM of PA), and the prevention of reactive oxygen species (ROS) generation (↓57 ± 1.83% for 30 μM of PA) in adipocytes with PA were also evaluated. We also found that PA increased adiponectin secretion and upregulated GLUT4 expression and translocation in adipocytes. Molecular modelling studies revealed a high binding affinity of PA to the PPARγ ligand binding domain. An in vitro ligand binding assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) also proved PA as a PPARγ agonist. Finally, we conclude that PA is a potential nutraceutical and should be encouraged for use both as a prophylactic and therapeutic agent.

Protein-peptide interactions, where one partner is a globular protein (domain) and the other is a flexible linear peptide, are key components of cellular processes predominantly in signaling and regulatory networks, hence are prime targets for drug design. To derive the details of the protein-peptide interaction mechanism is often a cumbersome task, though it can be made easier with the availability of specific databases and tools. The Peptide Binding Protein Database (PepBind) is a curated and searchable repository of the structures, sequences and experimental observations of 3100 protein-peptide complexes. The web interface contains a computational tool, protein inter-chain interaction (PICI), for computing several types of weak or strong interactions at the protein-peptide interaction interface and visualizing the identified interactions between residues in Jmol viewer. This initial database release focuses on providing protein-peptide interface information along with structure and sequence information for protein-peptide complexes deposited in the Protein Data Bank (PDB). Structures in PepBind are classified based on their cellular activity. More than 40% of the structures in the database are found to be involved in different regulatory pathways and nearly 20% in the immune system. These data indicate the importance of protein-peptide complexes in the regulation of cellular processes., (Copyright © 2013. Production and hosting by Elsevier Ltd.)

IL-15 is a pleotropic cytokine, which plays an important role in natural killer (NK) cell activity, T cell proliferation, and T cell cytotoxic activity. Dendritic cells (DCs) are the major antigen presenting cells in the immune system and presumed to play an important role in immune recognition of allo and xenotransplantation. We showed that IL-15 activated human peripheral blood DC is cytotoxic to human and porcine aortic endothelial cells. Unlike DCs, CD14+ monocytes show no cytotoxicity against the endothelial cells. This cytotoxic potential of IL-15 activated DC against endothelial cells is dose dependent and increases significantly upon treatment of endothelial cells with inflammatory cytokines like TNF-α or IFN-γ. The cytotoxic potential of IL-15 activated DC is associated with apoptosis of endothelial cells, as indicated by the increased Annexin V staining, caspase activation and loss of mitochondrial membrane potential. Further it was observed that DC mediated cytotoxicity against endothelial cell is mediated via granzyme B possibly secreted by the activated DCs., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Among the many abnormally expressed proteins in ovarian cancer, the prominent cancer in women, ID1 (inhibitors of DNA binding protein 1) is a potential one among other several targets. Interaction of ID1 with ETS-1 (transcriptional activator of p16(INK4a)) suppresses the transcription of p16(INK4a) and causes abnormal cell proliferation. A peptide aptamer (ID1/3-PA7) has been designed to prevent this interaction and thereby leading to the transcription of p16(INK4a). However, the structural basis behind the molecular interaction of ID1 with ETS-1 (agonist) and ID1/3-PA7 (antagonist) is poorly understood. In order to understand this structural recognition and their interaction mechanism, in silico methods were used. From this interaction analysis, the residues of ETS-1 involved in interaction with the p16(INK4a) promoter were found to be targeted by ID1. Subsequently, ETS-1 binding residues of ID1 were found to be targeted by its aptamer- ID1/3-PA7. These results suggest that both ETS-1 and ID1/3-PA7 binds at the same region harbored by the residues-H97, D100, R103, D104, L107, A144, C145, D149, D150 and C154 of ID1. All these observations correlate with the experimental reports, suggesting that the identified residues might play a crucial role in promulgating the oncogenic effects of ID1. In silico alanine scanning mutagenesis also confirms the role of identified hot spot residues in p16(INK4a) regulation. Finally, the molecular dynamic simulation studies reveal the prolonged stability of the aforementioned interacting complexes. The obtained results throw light on the structure and residues of ID1 involved in transcriptional regulation of p16(INK4a).

The hepatoprotective activity of a fraction of the leaf extract of A.indica against carbon tetrachloride : liquid paraffin (1:1) induced liver damage in rats at doses of 100 mg/kg and 200 mg/kg was evaluated. A significant dose dependent hepatoprotective activity was evidenced by lowering of the elevated levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), acid phosphatase (ACP) and alkaline phosphatase (ALP) in the serum of CCl(4) : liquid paraffin (1:1) treated rats.