RELAXIN: A MAGICAL THERAPY FOR HEALTHY HEART

Relaxin (a peptide hormone) has emerged as a cardioprotective agent and plays a vital role in normal cardiac function. By activation a complex network of signaling cascade, relaxin is responsible for creating a healthy environment for heart functioning. Under pathological conditions, such as cardiomyopathy and heart failure, expression level of relaxin is increased dramatically to protect heart. By promoting angiogenesis, vasodilatation, improving ischemia/reperfusion injury and remodeling, relaxin has emerged as a magical agent to address cardiac abnormalities. Over the past 3 decades, various cardioprotection strategies are in use to deal with cardiac diseases, however till date no effective therapy is in clinical practice. Relaxin has emerged as a novel therapeutic agent to have beneficial action during various pathological conditions. In this review, we have discussed different cardioprotective roles of relaxin that marks it, as an effective agent to tackle heart related diseases.Â

THE WARBURG EFFECT: A POSSIBLE ROLE OF CAP INDEPENDENT TRANSLATION

Cancer is a complex multistep process involving tremendous changes at molecular and cellular properties of a cancerous cell. One of the main characteristics associated with the tumor cells include preferential use of glycolysis over oxidative phosphorylation to meet the high energy needs. This process is observed even in the presence of ample oxygen to fuel mitochondrial respiration and is considered to be the root cause of tumor growth and a potential hallmark of cancer. It has been found that tumor cells shows increased glycolytic capacity than normal cells and produce lactate rather than pyruvate in the process. During cancers, the expression levels of glycolytic enzymes are increased and different mechanisms like increased transcription or altered post-translational regulation has been proposed. Since hypoxia is a well known model in cancers and therefore role of capindependent translation cannot be ignored. Furthermore, elucidation of the underlying reasons behind the increased expression of glycolytic enzymes in cancer will help us to better understand and cure cancer. This review focuses on the possible role of cap independent translation in mediating increased expression of glycolytic enzymes in cancers. Key word: Cancer, Warburg Effect, glycolytic enzymes, Cap independent translation, hypoxi

TARGETING HIF-1 PATHWAY: A THERAPEUTIC APPROACH TO KILL CANCER CELLS

Tumorous growth often faces hypoxic (low oxygen tension) conditions and the adaptations of these cells to hypoxic conditions determine their survival. The cancer cells respond to hypoxia by altering the expression of different genes and Hypoxia-Inducible Factor (HIF)-1 is one of it. HIF-1 is a transcriptional factor that response to hypoxia (low oxygen tension) conditions quickly. Expression of HIF-1 gene is essential for increase in vascularization of hypoxic region such as tumor and thus aid in proliferation and survival of cancerous cells. Moreover, HIF-1 signaling in cancer cells has a diverse influence on the metastatic cascade. Targeting HIF-1 is therefore one of the most promising approach to treat cancer. In this review, we have focused on the potential of targeting HIF-1 pathway as therapeutic intervention to treat cancer. Key words: HIF-1 Pathway, Cancer, Hypoxia-Inducibl

Ultrasonography (USG) as an adjuvant diagnostic aid in fascial space infections

The aim: to evaluate the efficiency of USG as an adjuvant diagnostic aid in fascial space infections and help draw a treatment plan as per the diagnosis made by USG examination Materials and methods: 60 patients having odontogenic superficial fascial space infection of the maxillofacial region were included. All of the patients included in our study were properly examined clinically with proper work up done, ordering different radiographs necessary to ascertain odontogenic cause most patients diagnosed with cellulitis were given medical line of treatment, and those with abscess were subjected to incision and drainage. Informed consent was obtained from all the participants involved in the study. Results: in this study, total of 60 patients were studied. Out of 60 patients of odontogenic facial space infections, 24 were male and 36 were female. Buccal space was the most common space involved (24;40 %) followed by submandibular space (9;15.0 %) than Canine space (6;10 %). In a total of 60 cases, clinical diagnosis of cellulitis was made in 18 cases (30 %) and that of abscess in 42 patients (70.0 %). All patients were subjected to the USG examination in which cellulitis was diagnosed in 24 cases (40 %) and abscess in 36 cases (60 %). Conclusion: USG could be considered to be a valuable adjuvant to clinical examination in patients with fascial space infection and help in delivering better treatment, after intervention 34 cases were found to be abscess while USG found 36 cases hence clearly proving the superiority of USG in diagnosis of abscess than clinical examination. It has its own advantages like minimal cost, repeated examinations, and readily available in especially in developing countries where people could not easily afford better imaging modalitie

Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells.

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.This study was supported by AIIMS Intramural grant (Grant number: A514) and AIIMS IITD Grant (AI-34) from All India Institute of Medical Sciences (AIIMS) New Delhi, Delhi India to Mayank singh. Sidra Medicine Precision Program provides research funding to Mohammad Haris (5081012002). Muzafar A. Macha is supported by Ramalingaswami Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi

Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells

Neosetophomone B (NSP–B), a meroterpenoid fungal secondary metabolite, was investigated for its anticancer potential in leukemic cell lines (K562 and U937). NSP-B treatment of leukemic cells suppressed cell viability by triggering apoptotic cell death. Apoptosis induced by NSP-B is triggered by mitochondrial signaling and caspase activation. Additionally, NSP-B treatment of leukemic cells causes AKT's inactivation accompanied by downregulation of SKP2 oncogene and MTH1 with a concomitant increase of p21Cip1and p27Kip1. Furthermore, NSP-B causes suppression of antiapoptotic proteins, including cIAP1, cIAP2, XIAP, survivin and BCl-XL. Overall, NSP-B reduces cell viability by mitochondrial and caspase-dependent apoptosis. The inhibition of AKT and SKP2 axis could be a promising therapeutic target for leukemia treatment.This work was supported by grant funded by the Medical Research Center (MRC), Hamad Medical Corporation, Doha, Qatar (MRC-01-21-301). The authors thank Qatar National Library for open access support of this article

Bioinformatics Analysis Reveals FOXM1/BUB1B Signaling Pathway as a Key Target of Neosetophomone B in Human Leukemic Cells: A Gene Network-Based Microarray Analysis

Abnormal expression of Forkhead box protein M1 (FOXM1) and serine/threonine kinase Budding uninhibited by benzimidazoles 1 (BUB1B) contributes to the development and progression of several cancers, including chronic myelogenous leukemia (CML). However, the molecular mechanism of the FOXM1/BUB1B regulatory network and the role of Neosetophomone-B (NSP-B) in leukemia remains unclear. NSP-B, a meroterpenoid fungal secondary metabolite, possesses anticancer potential in human leukemic cells lines; however, the underlying mechanism has not been elucidated. The present study aimed to explore the role of NSP-B on FOXM1/BUB1B signaling and the underlying molecular mechanism of apoptosis induction in leukemic cells. We performed gene expression profiling of NSP-B-treated and untreated leukemic cells to search for differentially expressed genes (DEGs). Interestingly BUB1B was found to be significantly downregulated (logFC -2.60, adjusted p = 0.001) in the treated cell line with the highest connectivity score among cancer genes. Analysis of TCGA data revealed overexpression of BUB1B compared to normal in most cancers and overexpression was associated with poor prognosis. BUB1B also showed a highly significant positive correlation with FOXM1 in all the TCGA cancer types. We used human leukemic cell lines (K562 and U937) as an in vitro study model to validate our findings. We found that NSP-B treatment of leukemic cells suppressed the expression of FOXM1 and BUB1B in a dose-dependent manner. In addition, NSP-B also resulted in the downregulation of FOXM1-regulated genes such as Aurora kinase A, Aurora kinase B, CDK4, and CDK6. Suppression of FOXM1 either by siRNA or NSP-B reduced BUB1B expression and enhanced cell survival inhibition and induction of apoptosis. Interestingly combination treatment of thiostrepton and NSP-B suppressed of cell viability and inducted apoptosis in leukemic cells via enhancing the activation of caspase-3 and caspase-8 compared with single-agent treatment. These results demonstrate the important role of the FOXM1/BUB1B pathway in leukemia and thus a potential therapeutic target.Medical Research Center Grant no; MRC-01-21-301 (SU), Hamad Medical Corporation, Doha Qatar. The publication of this article was funded by the Qatar National Library

Learning with a network of competing synapses

Competition between synapses arises in some forms of correlation-based plasticity. Here we propose a game theory-inspired model of synaptic interactions whose dynamics is driven by competition between synapses in their weak and strong states, which are characterized by different timescales. The learning of inputs and memory are meaningfully definable in an effective description of networked synaptic populations. We study, numerically and analytically, the dynamic responses of the effective system to various signal types, particularly with reference to an existing empirical motor adaptation model. The dependence of the system-level behavior on the synaptic parameters, and the signal strength, is brought out in a clear manner, thus illuminating issues such as those of optimal performance, and the functional role of multiple timescales.Comment: 16 pages, 9 figures; published in PLoS ON

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161