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Hardeep Singh Tuli,1 Vivek Kumar Garg,2 Jinit K Mehta,3 Ginpreet Kaur,3 Ranjan K Mohapatra,4 Kuldeep Dhama,5 Katrin Sak,6 Ajay Kumar,7 Mehmet Varol,8 Diwakar Aggarwal,1 Uttpal Anand,9 Jagjit Kaur,10 Ross Gillan,11 Gautam Sethi,12 Anupam Bishayee11 1Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, India; 2Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, Punjab, India; 3Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, Shri Vile Parle Kelavani Mandal, Narsee Monjee Institute of Management Studies, Mumbai, Maharashtra, India; 4Department of Chemistry, Government College of Engineering, Keonjhar, Odisha, India; 5Division of Pathology, Indian Council of Agricultural Research-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India; 6NGO Praeventio, Tartu, Estonia; 7Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India; 8Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey; 9Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 10Centre of Excellence in Nanoscale Biophotonics, Graduate School of Biomedical Engineering, Faculty of Engineering, The University of New South Wales, Sydney, Australia; 11College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA; 12Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Anupam Bishayee; Hardeep Singh Tuli, Email abishayee@lecom.edu; abishayee@gmail.com; hardeep.biotech@gmail.comAbstract: Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice (Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.Keywords: licorice, cancer, apoptosis, cell cycle, angiogenesis, treatment, nano-delivery

Secreted by pancreatic β-cells, insulin is the major anabolic hormone, regulating the metabolism of fats, proteins, and carbohydrates. Defects in insulin production or action can lead to diabetes characterized by derangements in glucose handling and metabolic disease. Diabetes affects 420 million people worldwide, increasing morbidity, mortality and placing a burden on healthcare of nations. There is a need for rapid and accurate monitoring of insulin levels to optimize diabetes management and facilitate early diagnosis of insulin related chronic diseases. Conventional strategies such as HPLC, MALDI-TOF, ELISA, etc. used for insulin detection are not suitable for point-of-care testing (POCT) as they are expensive, and require sample preparation, sophisticated instruments, and skilled personnel. Our goal was to develop techniques to allow POCT for insulin in real time. In this study we developed two lateral flow assays (LFAs) based POCT platforms using aptamers as the biorecognition molecules for colorimetric and fluorescent detection of insulin. A range of conditions were tested such as concentrations of aptamers, reporter molecules used, volume of sample required, and assay time to obtain quantify insulin levels using a standard LFA reader. The colorimetric LFAs had linear detection range of 0.01-1 ng.mL-1 and LOD of 0.01 ng.mL-1. The fluorescent LFAs exhibited a linear detection range of 0-4 ng.mL-1 and 0.1 ng.mL-1 LOD. Various signal amplification strategies were incorporated, ie., gold-silver amplification technique and rolling circular amplification (RCA) to further enhance the signal. The developed colorimetric LFAs were successfully used for insulin quantification in rat blood, human blood, and human saliva samples. Although insulin levels were quantified within 12 min, some issues arose such as coagulation, need for dilution, and non-uniform flow through the test strips. Further work is required to optimize blood handling to progress an insulin POCT in real time. Future work could develop a multiplexed strip for detection of different analytes such as HbA1c, glucose, and C-peptide for better management of diabetes, along with a smartphone reader App. This research goes some way to addressing the challenge of providing a reliable and rapid approach for highly sensitive and specific detection of insulin for POCT applications.