Dr. Kattesh V. Katti

Professor of Radiology and Physics
Director, Institute of Green Nanotechnology
University of Missouri

“Nano-Ayurvedic Medicine”—An Immunomodulatory Holistic Medicine Approach For Cancer Therapy—Through Green Nanotechnology

Cancer continues to be a major public health problem worldwide and there were an estimated 18 million cancer cases around the world in 2018 of which 9.5 million patients died. By 2040, the global burden is expected to grow to 27.5 million new cancer cases and 16.3 million cancer deaths simply due to the growth and aging of the population. The future burden will probably be even larger due to increasing prevalence of factors that increase risk, such as smoking, unhealthy diet, physical inactivity, and fewer childbirths, especially in economically transitioning countries. A number of new therapeutic interventions to combat various forms of human cancer have been developed over the last several decades. However, cures and lifesaving arrestation of this disease have been rare because tumors bear innate characteristics to become resistant to various forms of treatment. It is becoming increasingly clear that various chemotherapeutic, immunotherapeutic and radiation-based treatment modalities activate NF-κB transcription factors, which are responsible for triggering various pro-tumorigenic cascade of processes within the tumor microenvironment. Tumor progression and the evasion of systemic immune surveillance are all dictated by significantly high levels of various immunosuppressive factors, such as IL-10, IL-6, and TGF-β. Tumor progression is further catalyzed by the immune cells, including regulatory T cells, dendritic cells, MDSCs and TAMs, which are known to express a low level of MHC class I molecules within the tumor microenvironment. Most cancer drugs, in current use which belong to specific targeted or cytotoxic agents, rely on “one gene, one target, one disease” approach despite the fact that cancer is a very complicated multi-target and multi-gene defective disease. However, several examples of phytochemical-based therapeutic approaches have shown the power of cocktail of phytochemicals in traditional Indian Ayurvedic (Chinese and African) medicines to be multi targeted by enhancing the CD4⁺/CD8⁺ T cell ratio in the tumor microenvironment. Herbal-based Ayurvedic medicine are also known to reeducate the macrophage by promoting the M1 differentiation of TAM, suggesting the poly-pharmacological and poly-targeted nature of phyto agents

This lecture will discuss application of innovative Green Nanotechnology discoveries, made in Dr. Katti’s laboratory, to develop novel nanomedicine agents derived from combination of tumor specific phytochemicals encapsulated onto biocompatible gold nanoparticles. The longstanding objective of this approach focuses on providing credible scientific rationale to phytochemical-based herbal (Ayurvedic) medicine—all aimed at developing new Precision Medicine modality referred to as ‘Nano-Ayurvedic Medicine. Green Nanotechnology also allows the development of reproducible formulations of herbal and classical Ayurvedic medicines thus providing a pathway for clinical trials for internal/external validity, to allow the safety and efficacy of specific herbal medicines in a more accurate and scientifically verifiable way. This lecture will discuss details on how green nanotechnology can be used to develop  small-molecule phytochemical(s)-functionalized gold nanoparticles to simultaneously achieve: (i) Inhibition of NfkB activation; (ii) Targeting TAM; and (iii) Inhibition of TNF-α induced p65 phosphorylation; and concomitant immunomodulatory therapeutic action. Details on the new invention of a medical modality, referred to as ‘Nano-Ayurvedic Medicine’, recently approved by the US Patents and Trade Marks Office will be presented. The lecture will also highlight the importance of clinical translation in medical research through recent results from human clinical trials on cancer patients of Nano-Ayurvedic Nanomedicine drugs derived through green nanotechnology. The overall importance of green nanotechnology in graduate education and toward developing nanomedicine agents for use in oncology and antibiotics with specific examples of recently commercialized pharmaceuticals would be presented. 

Dr. Alfonso Mucci

Professor; Department of Earth and Planetary Sciences
University of McGill

Ocean acidification: The indisputable problem and the dissolution of deep-sea carbonates.

In the context of climate change, ocean acidification (OA) is seen as the other carbon dioxide (CO₂) problem. Oceanic uptake of anthropogenic CO₂ decreases the pH, carbonate ion concentration and saturation state of surface ocean waters with respect to calcium carbonate (CaCO₃) minerals. OA is a potential threat to the health of marine ecosystems, notably to calcifying organisms whose ability to secrete their CaCO₃ skeletons might be hindered. OA also triggers the dissolution of carbonate minerals on the seafloor, neutralizing man-made CO₂, but estimates are yet available of the extent and foci of this dissolution.

We combined recent databases of bottom-water chemistry, benthic currents, and CaCO₃ content of deep-sea sediments with a new rate model to derive the global distribution of benthic calcite dissolution rates and obtained primary confirmation of an anthropogenic component. By comparing pre-industrial with present-day rates, we determined that significant anthropogenic dissolution now occurs in the western North Atlantic, accounting for 40-100% of the total seafloor dissolution at its most intense locations. At these locations, the calcite compensation depth has risen ~300 m. Increased benthic dissolution was also revealed at various hot spots in the southern extent of the Atlantic, Indian and Pacific Oceans.

According to the IPCC RCP8.5 or “business as usual” emission model, the oceans will acidify further by the end of this century. Nevertheless, results of a range of Earth System and climate models challenge the paradigm that seafloor CaCO₃ dissolution will grow in extent and intensify as ocean acidification persists. We find that while CaCO₃ dissolution will increase over the 21st century in some areas of the deep ocean, such as the eastern central Pacific Ocean, it is projected to decrease in the Northern Pacific and abyssal Atlantic Ocean.