Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti–programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
Introduction Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.
India would require around 311 million tons of food grains (cereals and pulses) during 2030 to feed around 1.43 billion people, and the requirement expectedly would further increase to 350 million tons by 2050 when India's population would be around 1.8 billion. To achieve food security in the country, the attempts need to focus on both area expansion under agriculture as well as rise in crop productivity. Massive urbanization is putting pressure on agricultural lands, resulting in shrinking of land holdings. The possibility of area expansion under agriculture, therefore, exists in restoring the degraded lands. Nearly 147 million ha of land is subjected to soil degradation, including 94 million ha from water erosion, 23 million ha from salinity/alkalinity/acidification, 14 million ha from water-logging/flooding, 9 million ha from wind erosion and 7 million ha from a combination of factors due to different forces. Government of India has fixed a target of restoring 26 million ha of degraded lands, including salt-affected soils, by the year 2030 to ensure food security for the people. Around 6.74 million ha area in the country is salt-affected. Estimates suggest that every year nearly 10% additional area is getting salinized, and by 2050, around 50% of the arable land would be salt-affected. Saline soils occupy 44% area covering 12 states and one Union Territory, while sodic soils occupy 47% area in 11 states. The ICAR-Central Soil Salinity Research Institute and many State Agricultural Universities are engaged in studying salt-affected soils and developing reclamation technologies and strategies. Several innovative technologies have been developed and on-farm tested. Gypsum-based sodic soil reclamation, sub-surface drainage of waterlogged saline lands, salt tolerant crop varieties and improved agroforestry techniques are some of the well-adapted technologies in the country. Reclamation of 2.18 million ha of salt-affected soils (2.07 million ha barren sodic soils and 0.11 million ha saline soils) has contributed more than 17 million tons of food grains per annum to the country's food basket, with additional annual income of Rs. 15.5 billion, and employment generation of 2.8 million man-days. Other technologies of management of salt-affected soils, viz. alternate land-use systems, saline aquaculture, cultivation of salt tolerant crop varieties, agro-forestry, phytoremediation, bioremediation etc. have positively impacted food and nutritional security, women empowerment, involvement of landless laborers and minimizing rural migration etc. The ongoing consistent research efforts for the management and reclamation of such soils would hopefully continue ensuring food security in the country. The Government needs to make policies favorable for implementation of reclamation technologies in the country.
Majority of infectious microorganism make their gateway to the host through mucosal surfaces, such as gastrointestinal tract, nasal and vaginal tract. Mucosal immune response structured as sIgA can effectively prevent the attachment and invasion of the microorganism from mucosal surface and thereby serves as an efficient tool against infectious disease. There has been an increased demand for the development of novel vaccine that leads to the induction of immune response in systemic circulation as well as at mucosal surfaces against infectious disease. Mucosal delivery of vaccine provides basis for induction of both mucosal as well as systemic immune responses against the infectious organisms. However, a variety of factors such as mucociliary clearance, presence of deteriorating enzymes, pH extremes (GIT), low permeation and metabolic degradation limit the mucosal delivery of vaccine. Numerous strategies have been explored in the meadow of mucosal vaccination for the purpose of efficient antigen delivery through mucosal route(s). Polymeric carrier(s) such as nanoparticles and microparticles loaded with the antigen can serve as the basis for creation of important formulations for improved vaccine. Biodegradable and mucoadhesive polymeric carrier(s) seems to be most promising candidate for mucosal vaccine delivery. Several polymers from natural and synthetic origin, such as polylactide-co-glycolide, chitosan, alginate, carbopol, gelatin etc., have been explored for the efficient mucosal vaccine delivery and significant results have been obtained. This review outlines the polymers used in mucosal vaccine delivery with special reference to mucoadhesive/biodegradable polymers. This article also covers the recent patent granted in the field on polymeric carrier mediated mucosal vaccination.
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