No abstract

A variety of volatile organic compounds (VOCs) are produced and emitted by the human body every day. The identity and concentration of these VOCs reflect an individual’s metabolic condition. Information regarding the production and origin of VOCs, however, has yet to be congruent among the scientific community. This review article focuses on the recent investigations of the source and detection of biological VOCs as a potential for noninvasive discrimination between healthy and diseased individuals. Analyzing the changes in the components of VOC profiles could provide information regarding the molecular mechanisms behind disease as well as presenting new approaches for personalized screening and diagnosis. VOC research has prioritized the study of cancer, resulting in many research articles and reviews being written on the topic. This review summarizes the information gained about VOC cancer studies over the past 10 years and looks at how this knowledge correlates with and can be expanded to new and upcoming fields of VOC research, including neurodegenerative and other noninfectious diseases. Recent advances in analytical techniques have allowed for the analysis of VOCs measured in breath, urine, blood, feces, and skin. New diagnostic approaches founded on sensor-based techniques allow for cheaper and quicker results, and we compare their diagnostic dependability with gas chromatography- and mass spectrometry-based techniques. The future of VOC analysis as a clinical practice and the challenges associated with this transition are also discussed and future research priorities are summarized.

Post-operative assessment of resected tumor margins is critical to ensure the entirety of malignant tissue has been removed from a patient. Microscopic assessment of tissue post-excision is the current gold standard, however the long wait times for proper specimen evaluation limit a surgeon’s ability to be certain they obtained clear margins. To address this need, fluorescence-guided surgery approaches are under development that can yield molecular contrast between healthy and malignant tissues intraoperatively. In head and neck cancer specifically, heterogenous optical properties lead to poor identification in margins greater than 1 mm thick when viewed with single projections. Thus, we demonstrate the use of variable aperture approach to decrease the effects of local optical property variations in the imaged specimen. Here we use Monte Carlo simulations to verify the utility of the idea in a homogenous medium as well in a medium with heterogenous properties. We demonstrate that a ratio metric approach can provide near identical depth discrimination as a single projection in a homogenous medium and is further capable of reducing pixel variability due to local optical properties in a heterogenous medium than a single projection alone.

The development of hepatic insulin resistance (IR) is a critical factor in developing type 2 diabetes (T2D), where insulin fails to inhibit hepatic glucose production but retains its capacity to promote hepatic lipogenesis. Improving insulin sensitivity can be effective in preventing and treating T2D. However, selective control of glucose and lipid synthesis has been difficult. It is known that excess white adipose tissue is detrimental to insulin sensitivity, whereas brown adipose tissue transplantation can restore it in diabetic mice. However, challenges remain in our understanding of liver-adipose communication because the confounding effects of hypothalamic regulation of metabolic function cannot be ruled out in previous studies. There is a lack of in vitro models that use primary cells to study cellular-crosstalk under insulin resistant conditions. Building upon our previous work on the microfluidic primary liver and adipose organ-on-chips, we report for the first time the development of integrated insulin resistant liver-adipose (white and brown) organ-on-chip. The design of the microfluidic device was carried out using computational fluid dynamics; the experimental studies were conducted by carrying out detailed biochemical analysis RNA-seq analysis on both cell types. Further, we tested the hypothesis that brown adipocytes regulated both hepatic insulin sensitivity and lipogenesis. Our results show effective co-modulation of hepatic glucose and lipid synthesis through a platform for identifying potential therapeutics for IR and diabetes.

Metabolism of glucose and lipids is essential for nutrient balance and metabolic homeostasis, and is dynamically regulated by adipose tissue and liver. Dysfunction in regulation of these molecules as well as the secreted factors results in metabolic syndrome and insulin resistance (IR), which is a precursor to type 2 diabetes. Studies have shown that as the main site of adaptive thermogenesis, brown adipose tissue (BAT) improves hepatic insulin sensitivity, whereas white adipose tissue (WAT) can induce hepatic IR. However, how these organs communicate to regulate insulin sensitivity is not completely understood due to the lack of representative experimental models. Animals models are useful but suffer from confounding effects from other organs; traditional in vitro models have limited physiological representation. We have developed an organ-on-chip platform to study the interactions between BAT/WAT and liver under different metabolic states. The adipose-liver organ-chip consists of two interconnected microfluidic devices - brown/white adipocytes were cultured in one device and hepatocytes (insulin sensitive and IR) in the other, both under perfusion. We show that (a) adipocytes exhibited higher intracellular lipid and fatty acid secretion and (b) the hepatocytes secreted higher albumin compared to traditional co-cultures. We found that brown adipocytes secretions restored insulin sensitivity, and improved glucose/lipid metabolism in IR hepatocytes. In contrast, white adipocytes worsened insulin sensitivity and glucose/lipid metabolism. IR hepatocytes lowered Akt-phosphorylation and glucose uptake while upregulated adipocyte fatty acids secretion. Through RNA-seq, we have identified adipose genes responsible for improving hepatic IR. We have discovered potential new targets for improving hepatic insulin sensitivity. The novel organ-chip platform represented the cells physiologically and will be useful in the discovery and validation of new therapeutic targets for T2D. Disclosure N. Tanataweethum: None. A. Trang: None. L. Annepureddy: None. J. Mehta: None. R.N. Cohen: None. A. Bhushan: None. Funding DRTC (P30DK020595)