14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis.

Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis.

Temporal dynamics of nitric oxide wave in early vasculogenesis.

Endothelium-derived nitric oxide (NO) is a mediator of angiogenesis. However, NO-mediated regulation of vasculogenesis remains largely unknown. In the present study, we show that the inhibition of NO significantly attenuated endothelial migration, ring formation, and tube formation.

Subgroup and subtype-specific outcomes in adult medulloblastoma.

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium.

Systems level insights into the impact of airborne exposure on SARS-CoV-2 pathogenesis and COVID-19 outcome - A multi-omics big data study.

Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that led to more than 800,00 deaths and continues to be a major threat worldwide. The scientific community has been studying the risk factors associated with SARS-CoV-2 infection and pathogenesis. Recent studies highlight the possible contribution of atmospheric air pollution, specifically particulate matter (PM) exposure as a co-factor in COVID-19 severity.

Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action.

Aims: The SARS-coV-2 pandemic continues to cause an unprecedented global destabilization requiring urgent attention towards drug and vaccine development. Thalidomide, a drug with known anti-inflammatory and immunomodulatory effects has been indicated to be effective in treating a SARS-coV-2 pneumonia patient. Here, we study the possible mechanisms through which thalidomide might affect coronavirus disease-19 (COVID-19).

Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q.

Background: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.

Methods: Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival.

Results: Across all cohorts, 663 PF-EPN-A were identified.

Ectopic release of nitric oxide modulates the onset of cardiac development in avian model.

Heart development is one of the earliest developmental events, and its pumping action is directly linked to the intensity of development of other organs. Heart contractions mediate the circulation of the nutrients and signalling molecules to the focal points of developing embryos. In the present study, we used in vivo, ex vivo, in vitro, and in silico methods for chick embryo model to characterize and identify molecular targets under the influence of ectopic nitric oxide in reference to cardiogenesis.

Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity.

Adaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat.

An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.

OTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which OTX2 represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an OTX2 regulatory network that controls Group 3 medulloblastoma cell fate.

Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity.

Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hypothesized thalidomide targets FGFRs.

Mechanistic insights into the differential effects of thalidomide and lenalidomide in metastatic prostate cancer.

Aim: To understand why thalidomide and lenalidomide exhibit different responses in metastatic prostate cancer (mPCa) treatment.

Methods: We analyzed the perturbation signatures of thalidomide, lenalidomide, flutamide treated mPCa cell line from Library of Integrated Network-based Cellular Signatures database and transcriptome of docetaxel-treated mPCa patients.

Results: Flutamide and docetaxel downregulated 'Steroid Biosynthesis', 'Cell cycle' and PCa specific transcription factor networks.

Thalidomide remodels developing heart in chick embryo: discovery of a thalidomide mediated hematoma in heart muscle.

Despite of medical disaster caused by thalidomide in 1960s, the drug came to clinical use again for the treatment of erythema nodosum leprosum (ENL) and multiple myeloma. Recently, a new generation of children affected by thalidomide intake by their mothers during pregnancy has been identified in Brazil. In the past few years, there is the great enhancement in our understanding of the molecular mechanisms and targets of thalidomide with the help of modern OMICS technologies.

A proteome-wide systems toxicological approach deciphers the interaction network of chemotherapeutic drugs in the cardiovascular milieu.

Onco-cardiology is critical for the management of cancer therapeutics since many of the anti-cancer agents are associated with cardiotoxicity. Therefore, the major aim of the current study is to employ a novel method combined with experimental validation to explore off-targets and prioritize the enriched molecular pathways related to the specific cardiovascular events other than their intended targets by deriving relationship between drug-target-pathways and cardiovascular complications in order to help onco-cardiologists for the management of strategies to minimize cardiotoxicity. A systems biological understanding of the multi-target effects of a drug requires prior knowledge of proteome-wide binding profiles.

Nitric oxide signaling regulates tumor-induced intussusceptive-like angiogenesis.

Existing animal models for screening tumor angiogenic process have various setbacks that necessitate further investigations. In this study, we developed an ex-ovo egg yolk angiogenesis model to screen the angiogenic potency of tumor cells (HeLa and SiHa cell lines). The egg yolk angiogenesis assay was applied to study the nitric oxide (NO) influence on switching from sprouting angiogenesis (SA) to intussusceptive angiogenesis (IA) under tumor microenvironment.

Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis.

Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data.

Oxidative environment causes molecular remodeling in embryonic heart-a metabolomic and lipidomic fingerprinting analysis.

Environmental factors including pollution affect human health, and the unifying factor in determining toxicity and pathogenesis for a wide array of environmental factors is oxidative stress. Here, we created the oxidative environment with 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH) and consequent cardiac remodeling in chick embryos. The metabolite fingerprint of heart tissue was obtained from Fourier transform infrared (FTIR) spectroscopic analysis.

Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques.

Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies.

The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo.

Background: Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13.

Harvesting clues from genome wide transcriptome analysis for exploring thalidomide mediated anomalies in eye development of chick embryo: Nitric oxide rectifies the thalidomide mediated anomalies by swinging back the system to normal transcriptome pattern.

Thalidomide, the notorious teratogen is known to cause various developmental abnormalities, among which a range of eye deformations are very common. From the clinical point of view, it is necessary to pinpoint the mechanisms of teratogens that tune the gene expression. However, to our knowledge, the molecular basis of eye deformities under thalidomide treatmenthas not been reported so far.