The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.
BackgroundThe A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy.Methodology/Principal FindingsWe expressed the globular HA receptor binding domain, referred to here as HA63–286-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63–286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model.Conclusions/SignificanceProjections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy.
Colorimetric LAMP for COVID-19 intensified diagnostics: a simple and quantitative method comparable in diagnostic performance to RT-qPCR.
Background Preclinical drug discovery for the treatment of chronic pain is at present challenged by the difficulty to study behaviours comparable to the complex human pain experience in animals. Several reports have demonstrated a frequent association of chronic pain in humans with affective disorders, such as anxiety and depression, and impaired cognitive functions, including memory and decision making, and motivation for goal‐directed behaviours. In this study, we validated different behavioural outcomes to measure the emotional and cognitive manifestations of neuropathic pain induced in mice by partial sciatic nerve ligation. Methods In these mice, we evaluated at different time points the nociceptive responses, the anxiety‐ and depressive‐like behaviours, the anhedonic state, object recognition memory and the operant responding maintained by food and the effects of the repeated administration of pregabalin on these manifestations. Results Our results demonstrated that the presence of allodynia and hyperalgesia in neuropathic pain mice was associated with increased anxiety‐ and depressive‐like behaviours, reduced memory functions, development of an anhedonic state and impaired motivation to obtain food in the operant task. Chronic pregabalin treatment improved the nociceptive, anxiety‐like and anhedonic responses, as well as the memory deficit, but did not modify the depressive‐like alterations and the decreased motivation in these mice. Conclusions These results indicate that some emotional manifestations of chronic pain do not necessarily resolve when pain is relieved and underline the relevance to evaluate multiple behavioural responses associated with chronic pain, including the affective‐motivational and cognitive behaviours, to increase the predictive value of preclinical drug discovery. What does this study add? In this study, we have validated different behavioural outcomes allowing a reliable measurement of the emotional and cognitive manifestations of neuropathic pain induced in mice by partial sciatic nerve ligation. These results underline the relevance to evaluate these multiple pain‐related alterations to improve the predictive value of preclinical drug discovery.
The coronavirus disease 2019 (COVID-19) pandemic has crudely demonstrated the need for massive and rapid diagnostics. By the first week of July, more than 10,000,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization (WHO) for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of~625 to 2×10 5 DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-QPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics.
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