Scientific, sustainability and regulatory challenges of cultured meat

Producing meat without the drawbacks of conventional animal agriculture would greatly contribute to future food and nutrition security. This Review Article covers biological, technological, regulatory and consumer acceptance challenges in this developing field of biotechnology. Cellular agriculture is an emerging branch of biotechnology that aims to address issues associated with the environmental impact, animal welfare and sustainability challenges of conventional animal farming for meat production. Cultured meat can be produced by applying current cell culture practices and biomanufacturing methods and utilizing mammalian cell lines and cell and gene therapy products to generate tissue or nutritional proteins for human consumption. However, significant improvements and modifications are needed for the process to be cost efficient and robust enough to be brought to production at scale for food supply. Here, we review the scientific and social challenges in transforming cultured meat into a viable commercial option, covering aspects from cell selection and medium optimization to biomaterials, tissue engineering, regulation and consumer acceptance

The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation

Impact of the COVID-19 Pandemic Surge on Radiation Treatment: Report From a Multicenter New York Area Institution.

Purpose During the COVID-19 surge months of March and April 2020, our New York multicenter health system experienced an influx of cases with COVID-19. We sought to study the impact of the surge period on patients with cancer prescribed radiation treatment (RT). Methods We reviewed our secure departmental quality assurance database for all patients who underwent RT planning simulations from March 6, 2020, through April 30, 2020. A priority level between 1 and 3 was prospectively assigned to each case based on faculty consensus to determine which patients required immediate RT. In May 2020, each faculty physician again retrospectively reviewed their patients from the database and provided additional commentary on how the COVID-19 pandemic had affected each patient\u27s care. All statistics are descriptive. Results A total of 412 RT courses in 406 unique patients were simulated for linear accelerator-based external beam RT. The median age was 66 years. Treatment intent was curative in 70.6% and palliative in 29.4%. Of the 412 cases, 66.7% were priority 1, 25% priority 2, and 7.8% priority 3. Two hundred thirty-nine cases (58%) underwent standard-of-care diagnosis, workup, and treatment plan. Seventeen patients (4.1%) electively canceled their RT, and 17 others (4.1%) electively delayed RT start. Thirty-four (8.3%) were prescribed hypofractionation to shorten their RT course, and 22 (5.3%) had a change in modality. Incomplete or delayed workup was identified in 19 cases (4.6%). Conclusion The COVID-19 pandemic surge resulted in 42% of our patients having a non-standard-of-care pathway. This outcome demonstrates a significant impact of the COVID-19 crisis on routine cancer care