Cytokines communicate and coordinate immunity, allowing the immune cells to understand one another. Aside from cytokines, a wide variety of molecules modify immune cell behavior and immune responses. We present a study of volatile organic compounds (VOCs) and their capacity to influence the NF-κB signaling pathway in monocytes. By using the U937 monocyte cell line and CRISPR/Cas9 gene editing, we created a model of NFKB1-/- human monocytes. The results showed that exosomes from distinct cells and the same cell have unique VOC signatures when stimulated by LPS. To test the effect of certain VOCs on NF-κB, we encapsulated them in nanoparticles (liposomes). An example is 2-butanone-encapsulated liposomes, which reduced NF-κB and lowered the level of proinflammatory cytokines (TNF-α, IL-8 MCP-1, and IL-1β) in LPS-stimulated monocytes. These results suggest potential therapeutic targets for modulating the NF-κB signaling in monocytes.

The different immune system cells communicate and coordinate a response using a complex and evolved language of cytokines and chemokines. These cellular interactions carry out multiple functions in distinct cell types with numerous developmental outcomes. Despite the plethora of different cytokines and their cognate receptors, there is a restricted number of signal transducers and activators to control immune responses. Herein, we report on a new class of immunomodulatory signaling molecules based on volatile molecules (VMs, namely, volatile organic compounds [VOCs]), by which they can affect and/or control immune cell behavior and transcriptomic profile without any physical contact with other cells. The study demonstrates the role of VMs by analyzing non-contact cell communication between normal and cancerous lung cells and U937 monocytes, which are key players in the tumor microenvironment. Integrated transcriptome and proteome analyses showed the suggested regulatory role of VMs released from normal and cancer cells on neighboring monocytes in several molecular pathways, including PI3K/AKT, PPAR, and HIF-1. Presented data provide an initial platform for a new class of immunomodulatory molecules that can potentially mirror the genomic and proteomic profile of cells, thereby paving the way toward non-invasive immunomonitoring.

Cell-to-cell communication has a critical role during tumor development and progression, allowing cancer cells to reprogram not only the surrounding tumor microenvironment, but also cells located at distant sites. This chapter focuses on the potential role of volatile organic compounds (VOCs) as signaling/communication agents that exchange over relatively long distances between cells and/or from one cell to another destination. The chapter also discusses VOC signaling as an alternative and/or complementary perspective to proteomic and genomic approaches in monitoring cancer development.

It is well established that cells behave as “microsocieties” that need strict coordination in communication. Any breakdown in this regulatory network can lead to pathological conditions, primarily when “miscommunication” occurs within the immune system. The different components of the immune system communicate using an intricate language of cytokines, chemokines and other cell interactions to orchestrate a response. Cytokines contribute to the maintenance of immune homeostasis and prevention of immunological disorders by tightly regulating the release of pro-inflammatory signals and, in balance with anti-inflammatory cytokine release, assuring a controlled and localized immune reaction. Although cytokines are indispensable for the exact signaling in the immune system, their biological effects often overlap, and individual cytokines have multiple regulatory functions. This chapter focuses on the potential role of volatile organic compounds (VOCs) as signaling/communication agents that shape different components of the immune system. It also emphasizes the immunomodulatory effects of VOCs, especially on the transcriptional profile of monocytes.

The current letter describes the rational behind breath analysis of lung cancer and the progress made so far by means of mass spectrometry and smart sensor arrays. Additionally, it presents and discusses the potential of breath analysis in enabling inexpensive and non-invasive technology that would allow efficient early detection of cancer; stratifying the population based on their bio-specification for a tailored (personalized) therapy; and bed-side fast assessment of treatment efficacy in order to change the therapeutic approach. At the end, the letter pinpoints the main implementation strengths of the method as a routine diagnostic and monitoring in the digital era.

This review presents and discusses a new frontier for fast, risk-free and potentially inexpensive diagnostics of respiratory diseases by detecting volatile organic compounds (VOCs) present in exhaled breath. One part of the review is a didactic presentation of the overlaying concept and the chemistry of exhaled breath. The other part discusses diverse sensors that have been developed and used for the detection of respiratory diseases (e.g. chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, tuberculosis, cystic fibrosis, obstructive sleep apnoea syndrome and pneumoconiosis) by analysis of VOCs in exhaled breath. The strengths and pitfalls are discussed and criticised, particularly in the perspective in disseminating information regarding these advances. Ideas regarding the improvement of sensors, sensor arrays, sensing devices and the further planning of workflow are also discussed.

ןוינכטה לארשיל יגולונכט ןוכמ / ויב הסדנהל הטלוקפה תיאופר _____________________________________________________________________ TECHNION – Israel Institute Of Technology / The Faculty Of Biomedical Engineering Projects Conference, June 2019 Faculty of Biomedical Engineering, Technion IIT Dear all, The Annual Projects Conference in Biomedical Engineering is hosted by the Faculty of Biomedical Engineering at the Technion – Israel Institute of Technology. As the Dean of the Faculty of Biomedical Engineering and as the project course staff, we are pleased and honored to welcome you here. The conference is hosting 4 th year students who are eager to present their year-long projects and to receive feedback from academic researchers, industrial experts, and their peers. These projects implement the medical, engineering, and scientific tools that the students have acquired and developed during their BSc journey in Biomedical Engineering. The students aim to provide solutions that meet research and development needs in the Biomedical industries and research departments. Through working on their projects, students gained invaluable, hands-on experience. They had to work through technical challenges and adhere to strict standards comparable to those in a real-world setting. We believe that this hands-on experience engages graduates with the Biomedical industry and/or the wide variety of Biomedical research in a very strong way encouraging multidisciplinary work that is vital to the students’ futures. Additionally, we encourage the students to think out of the box to initiate new solutions and help foster their entrepreneurship skills. Above all, these projects are a key element of the faculty vision which strives to strengthen the long-term cooperation between academia and industry leaders. In this booklet we are introducing the abstracts of all presented projects. We wish all students rewarding careers and bright futures. We hope that one day they will take an active part in similar projects as professional mentors from both the industry and academia. Kindest Regards, Prof. Shulamit Levenberg, Faculty Dean Prof. Netanel Korin, Course Instructor

To date, there are limited approaches for the direct and rapid visualization (on site) of tumor tissues for pathological assessment and for aiding cytoreductive surgery. Herein, we have designed FIT-PNAs (forced-intercalation-peptide nucleic acids) to detect two RNA cancer biomarkers. Firstly, a lncRNA (long noncoding RNA) termed CCAT1, has been shown as an oncogenic lncRNA over-expressed in a variety of cancers. The latter, an mRNA termed KRT20, has been shown to be over-expressed in metastases originating from colorectal cancer (CRC). To these FIT-PNAs, we have introduced the bis-quinoline (BisQ) cyanine dye that emits light in the red region (605-610 nm) of the visible spectrum. Most strikingly, spraying fresh human tissue taken from patients during cytoreductive surgery for peritoneal metastasis of colon cancer with an aqueous solution of CCAT1 FIT-PNA results in bright fluorescence in a matter of minutes. In fresh healthy tissue (from bariatric surgeries), no appreciable fluorescence is detected. In addition, a non-targeted FIT-PNA shows no fluorescent signal after spraying this FIT-PNA on fresh tumor tissue emphasizing the specificity of these molecular sensors. This study is the first to show on-site direct and immediate visualization of an RNA cancer biomarker on fresh human cancer tissues by topical application (spraying) of a molecular sensor.

Peptide nucleic acid bis-quinoline conjugates are reported as attractive far-red emitting probes that detect mutated mRNA in living cells at SNP resolution.