Phthalimide Derivative Shows Anti-angiogenic Activity in a 3D Microfluidic Model and No Teratogenicity in Zebrafish Embryos

This study highlights how the use of in vitro 3D model can allow rapid screening and selection of new and safer drugs. Introduction Angiogenesis is a complex and finely regulated process that consists of the growth of new capillary blood vessels from pre-existing vessels to create communication pathways among tissues. The coordination of different activities such as endothelial cell proliferation and migration, metalloproteinase function, integrin expression and pericyte stabilization is essential for angiogenesis (Folkman, 1984). The “angiogenic switch” is “on” when the balance between pro-angiogenic and anti-angiogenic molecules is disrupted in favor of angiogenesis. A variety of physiological processes rely on angiogenesis such as embryogenesis, female reproductive cycle, organ differentiation and wound healing (Duran et al., 2011). However, angiogenesis also plays an important role in many diseases such as ischemic diseases, vascular malformations, inflammatory disorders, obesity and tumors (Folkman, 1971; Carmeliet and Jain, 2000). In particular, angiogenesis plays a vital role in invasive tumor growth and metastasis and represents an essential mechanism to target and control cancer progression. Angiogenesis allows the recruitment of new blood vessels that become the principal route through which the tumor cells enter the circulation, after leaving the primary tumor site (Zetter, 1998). In addition, the new vessels promote primary tumor gr...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Most fetal ovarian cysts increase in size during the late stages of pregnancy. Early treatment of a huge neonatal cyst may reduce the risk of gastrointestinal obstruction. AbstractMost fetal ovarian cysts increase in size during the late stages of pregnancy. Early treatment of a huge neonatal cyst may reduce the risk of gastrointestinal obstruction.
Source: Clinical Case Reports - Category: General Medicine Authors: Tags: CLINICAL IMAGE Source Type: research
ConclusionHCV core and IL-22 and SOCS-3 molecules are found to be correlated statistically under this study. Concluded from this study that HCV core protein plays a potential role in diverging the hepatocytes from normal to carcinogenic. One cell signaling path cannot decide, the direct role of a single viral protein in developing viral induced hepatocarcinogenesis. Interpreting the complex network of cell signaling involved in HCC development is impractical to study under single study. That is why step by step unmasking the interactive role of few molecules under single study is the ideal way to resolve the impact of vira...
Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
In this study, we found that Lnc-OC1 was significantly higher in PCOS granulosa cells (GCs) compared to non-PCOS GCs. Lnc-OC1 knockdown inhibited cell viability and promoted cell apoptosis, expression of aromatase mRNA and production of estradiol in KGN cells. In PCOS mice, Lnc-OC1 promoted the serum insulin release, production of angiogenesis-related factors and IκBα phosphorylation, which could be partially restored by Lnc-OC1 shRNA. These results suggest that Lnc-OC1 plays an important part in the pathogenesis of PCOS.
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
ConclusionsOur study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.Graphical abstract
Source: Molecular Metabolism - Category: Endocrinology Source Type: research
This article aims to classify the severity grading assessments for both insulin resistance (IR) syndrome and status of pancreatic beta (β) islet cells’ function using the homeostasis model assessment method (that is; homeostasis model assessment-insulin resistance [HOMA-IR] and homeostasis model assessment-pancreatic beta (β) islet cells’ function [HOMA-B] indices) with the focus of disseminating this information rapidly for clinical use by physicians in their patients with dysfunctional regulation of glucose metabolism. It will also assist clinicians to prevent and screen for these individuals who ar...
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
Publication date: Available online 15 February 2020Source: Pharmacological ResearchAuthor(s): Yuanlin Wu, Jing Li, Parham Jabbarzadeh Kaboli, Jing Shen, Xu Wu, Yueshui Zhao, Huijiao Ji, Fukuan Du, Yejiang Zhou, Yongzhou Wang, Hanyu Zhang, Jianhua Yin, Qinglian Wen, Chi Hin Cho, Mingxing Li, Zhangang XiaoAbstractNatural killer (NK) cells are immune cells which are able to kill tumor and virus-infected cells and play an important role in both innate immunity and acquired immunity. Tumor immunotherapy is an emerging model of tumor treatment in the clinic. It is a re-emerging type of anticancer immunotherapy with the purpose o...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 15 February 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Juliusz Bianga, Magali Perez, Damien Mouvet, Caroline Cajot, Philippe De Raeve, Arnaud DelobelAbstractA new analytical method based on ICP-MS/MS is proposed for the characterization of synthetic phosphorothioate oligonucleotides. Absolute quantification of oligonucleotides is challenging, as well as the determination of phosphodiester to phosphorothioate ratio for phosphorothioate oligonucleotides. Both are considered as critical quality attributes and should be determined using robust validated methods. T...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research
AbstractWarfarin is a narrow therapeutic index anticoagulant drug, and several generic formulations have been approved worldwide. However, there has been no report evaluating the bioequivalence of warfarin sodium according to US Food and Drug Administration draft guidance. We designed a 2 ‐sequence and 4‐period crossover study to compare the pharmacokinetic profile and assess bioequivalence between the test warfarin sodium tablet and reference product Coumadin (2.5 mg) in 56 healthy Chinese subjects under fasting and fed conditions. The plasma concentration of warfarin was analy zed by a validated liquid chromatog...
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Manuscript Source Type: research
Publication date: Available online 16 February 2020Source: Journal of Ayurveda and Integrative MedicineAuthor(s): Varghese Thomas, S.N.Venugopalan Nair, D.K. Ved, Darshan ShankarAbstractIndia's medical heritage across its two streams of experiential knowledge viz. the classical (codified) and folk (oral) reveals an incredible range and depth of knowledge of medicinal plants. In the classical stream of Ayurveda, across the period from 1500 BCE to 1900 CE, there is information of more than 12,000 distinct Sanskrit plant names with overlaps across texts. This information is captured in more than 200 texts viz. 6 samhitas, 57 ...
Source: Journal of Ayurveda and Integrative Medicine - Category: Complementary Medicine Source Type: research
Authors: Bartelt A, Widenmaier SB Abstract The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in ...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
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