Biomodelling Angiogenesis

2016 ◽  
Vol 7 (2) ◽  
pp. 127-134
Author(s):  
Nikolai A Verlov ◽  
Alexander P Trashkov ◽  
Maria A Pahomova ◽  
Nikolai V Haitsev ◽  
Evgeni I Malyshev

Success or failure of studies in various areas of biology depend on the presence or absence of convenient and effective adequate models of pathologic processes with fair predictability. In spite of variability of models used in contemporary angiology neither of them can be considered to be “golden standard” or etalon for elaborating new methods targeted at blood vessels. The need for a score of different models for studies of each stage of angiogenesis is one of major difficulties in forming a universal concept describing angiogenesis in humans and animals. A hypothesis of malignant neoplasma growth inhibition by means of blocking angiogenesis inducing factors, their receptors or direct destruction of microvessels’ wall is a starting point for profound angiogenesis studies using various in vitro and in vivo models. A wide spectrum of oncogenesis models allows to scrutinize it from various angles revealing general principles of neoplasma development, mechanisms of its interaction with normal tissues and organs, including the circulation system. Using transgenic с animals helped to disclose the key role of angiogenesis in the development of the organism as well as get results maximally close to the effects characteristic of studies of various aspects of angiogenesis in human beings.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rui Chen ◽  
Yingmin Liang ◽  
Mary Sau Man Ip ◽  
Kalin Yanbo Zhang ◽  
Judith Choi Wo Mak

Chronic obstructive pulmonary disease (COPD), characterized by oxidative stress and inflammation, is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. Dendrobium officinale polysaccharides (DOPs) are the main active ingredients extracted from Dendrobium officinale, which have been reported to have antioxidant and anti-inflammatory activity as well as inhibition of mucin gene expression. This study is aimed at investigating the effect of DOPs on CS-induced mucus hypersecretion and viscosity in vitro and in vivo. For in vitro study, primary normal human bronchial epithelial cells (HBECs) differentiated at the air-liquid interface (ALI) culture for 28 days were stimulated with cigarette smoke medium (CSM) in the absence or presence of various concentrations of DOPs or N-acetylcysteine (NAC) for 24 hours. For in vivo study, male Sprague-Dawley rats were randomized to sham air (SA) as control group or CS group for 56 days. At day 29, rats were subdivided and given water as control, DOPs, or NAC as positive control as a mucolytic drug via oral gavage for the remaining duration. Samples collected from apical washing, cell lysates, bronchoalveolar lavage (BAL), and lung tissues were evaluated for mucin gene expression, mucus secretion, and viscosity. DOPs ameliorated the CS-induced mucus hypersecretion and viscosity as shown by the downregulation of MUC5AC mRNA, MUC5AC secretary protein, and mucus viscosity via inhibition of mucus secretory granules in both in vitro and in vivo models. DOPs produced its effective effects on the CS-induced mucus hypersecretion and viscosity via the inhibition of the mucus secretory granules. These findings could be a starting point for considering the potential role of DOPs in the management of the smoking-mediated COPD. However, further research is needed.


2021 ◽  
Author(s):  
Jian Gao ◽  
Ling-Xian Zhang ◽  
Yong-Qiang Ao ◽  
Chun Jin ◽  
Peng-Fei Zhang ◽  
...  

Abstract Background: Tumor invasion and immune evasion are the main mechanisms underlying the progression of non-small-cell lung cancer (NSCLC). In addition, abnormally expressed circular RNAs (circRNAs) contribute to the malignant phenotype of NSCLC. Thus, further investigation of the mechanism of dysregulated circRNAs may provide new insight into the treatment of NSCLC.Methods: circRNA sequencing was used to explore the different expression profiles of circRNAs in 4 NSCLC tissues and paired normal tissues. Then, the expression of key circRNAs in NSCLC tissues and matched normal tissues was further evaluated via in situ hybridization and in cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). Next, in vitro and in vivo models of NSCLC were employed to uncover the functions and mechanisms of key circRNAs in NSCLC progression and treatment.Results: circASCC3 (hsa_circ_0077495) was overexpressed in NSCLC tissues compared to paired normal tissues, and the upregulation of circASCC3 indicated a dismal prognosis in patients with NSCLC. Overexpressed circASCC3 enhanced the malignant phenotype of NSCLC cells in vitro and led to an immunosuppressive microenvironment in vivo. Mechanistically, circASCC3 sponged miR-432-5p to increase the expression of complement C5a, which induced the progression and dysfunctional immune status of NSCLC. Moreover, the combination of the C5aR inhibitor PMX-53 and anti-programmed cell death 1 (PD-1) antibody achieved synergistic effects in NSCLC models overexpressing circASCC3.Conclusion: These results uncover the contributions of circASCC3 to NSCLC progression and immunosuppression and provide a potential strategy for overcoming resistance to anti-PD-1 therapy.


2021 ◽  
Vol 25 ◽  
Author(s):  
Parul Grover ◽  
Monika Bhardwaj ◽  
Garima Kapoor ◽  
Lovekesh Mehta ◽  
Roma Ghai ◽  
...  

: The heterocyclic compounds have a great significance in medicinal chemistry because they have extensive biological activities. Cancer is globally the leading cause of death and it is a challenge to develop an appropriate treatment for the management of cancer. Continuous efforts are being made to find a suitable medicinal agent for cancer therapy. Nitrogen-containing heterocycles have received noteworthy attention due to their wide and distinctive pharmacological activities. One of the most important nitrogen-containing heterocycles in medicinal chemistry is ‘quinazoline’ that possesses a wide spectrum of biological properties. This scaffold is an important pharmacophore and is considered a privileged structure. The various substituted quinazolines displayed anticancer activity against different types of cancer. This review highlights the recent advances in quinazoline based molecules as anticancer agents. Several in-vitro and in-vivo models used along with the results are also included. A subpart briefing natural quinazoline containing anticancer compounds is also incorporated in the review.


Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1508
Author(s):  
Danica Jović ◽  
Vesna Jaćević ◽  
Kamil Kuča ◽  
Ivana Borišev ◽  
Jasminka Mrdjanovic ◽  
...  

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.


TECHNOLOGY ◽  
2016 ◽  
Vol 04 (04) ◽  
pp. 240-248 ◽  
Author(s):  
Sangcheol Na ◽  
Myeongwoo Kang ◽  
Seokyoung Bang ◽  
Daehun Park ◽  
Jinhyun Kim ◽  
...  

Neural circuits, groups of neurons connected in directional manner, play a central role in information processing. Advances in neuronal biology research is limited by a lack of appropriate in vitro methods to construct and probe neuronal networks. Here, we describe a microfluidic culture platform that directs the growth of axons using “neural diode” structures to control neural connectivity. This platform is compatible with live cell imaging and can be used to (i) form pre-synaptic and postsynaptic neurons by directional axon growth and (ii) localize physical and chemical treatment to pre- or postsynaptic neuron groups (i.e. virus infection and etc.). The “neural diode” design consist of a microchannel that split into two branches: one is directed straight toward while the other returns back toward the starting point in a closed loop to send the axons back to the origin. We optimized the “neural diode” pattern dimension and design to achieve close to 70% directionality with a single unit of the “diode”. When repeated 3 times, near perfect (98–100% at wide range of cell concentrations) directionality can be achieved. The living neural circuit was characterized using Ca imaging and confirmed their function. The platform also serves as a straightforward, reproducible method to recapitulate a variety of neural circuit in vitro that were previously observable only in brain slice or in vivo models. The microfluidic neural diode may lead to better models for understanding the neural circuit and neurodegenerative diseases.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark Joseph Desamero ◽  
Shigeru Kakuta ◽  
Yulan Tang ◽  
James Kenn Chambers ◽  
Kazuyuki Uchida ◽  
...  

AbstractThe protective property of propolis across a wide spectrum of diseases has long been realized, yet the anti-tumor efficacy of this bioactive substance from Philippine stingless bees has remained poorly understood. Here, we showed the tumor-suppressing potential of crude ethanolic extract of Philippine stingless bee propolis (EEP) in in vitro models of gastric cancer highlighting the first indication of remarkable subtype specificity towards differentiated-type human gastric cancer cell lines but not the diffuse-type. Mechanistically, this involved the profound modulation of several cell cycle related gene transcripts, which correlated with the prominent cell cycle arrest at the G0/G1 phase. To reinforce our data, a unique differentiated-type gastric cancer model, A4gnt KO mice, together with age-matched 60 week-old C57BL/6 J mice were randomly assigned to treatment groups receiving distilled water or EEP for 30 consecutive days. EEP treatment induced significant regression of gross and histological lesions of gastric pyloric tumors that consistently corresponded with specific transcriptional regulation of cell cycle components. Also, the considerable p21 protein expression coupled with a marked reduction in rapidly dividing BrdU-labeled S-phase cells unequivocally supported our observation. Altogether, these findings support the role of Philippine stingless bee propolis as a promising adjunct treatment option in differentiated-type gastric cancer.


Author(s):  
Diana Boraschi ◽  
Dongjie Li ◽  
Yang Li ◽  
Paola Italiani

The immunological safety of drugs, nanomaterials and contaminants is a central point in the regulatory evaluation and safety monitoring of working and public places and of the environment. In fact, anomalies in immune responses may cause diseases and hamper the physical and functional integrity of living organisms, from plants to human beings. In the case of nanomaterials, many experimental models are used for assessing their immunosafety, some of which have been adopted by regulatory bodies. All of them, however, suffer from shortcomings and approximations, and may be inaccurate in representing real-life responses, thereby leading to incomplete, incorrect or even misleading predictions. Here, we review the advantages and disadvantages of current nanoimmunosafety models, comparing in vivo vs. in vitro models and examining the use of animal vs. human cells, primary vs. transformed cells, complex multicellular and 3D models, organoids and organs-on-chip, in view of implementing a reliable and personalized nanoimmunosafety testing. The general conclusion is that the choice of testing models is key for obtaining reliable predictive information, and therefore special attention should be devoted to selecting the most relevant and realistic suite of models in order to generate relevant information that can allow for safer-by-design nanotechnological developments.


2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 


2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.


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