The Physiology and Proteomics of Drought Tolerance in Maize: Early Stomatal Closure as a Cause of Lower Tolerance to Short-Term Dehydration?

Understanding the response of a crop to drought is the first step in the breeding of tolerant genotypes. In our study, two maize (Zea mays L.) genotypes with contrasting sensitivity to dehydration were subjected to moderate drought conditions. The subsequent analysis of their physiological parameters revealed a decreased stomatal conductance accompanied by a slighter decrease in the relative water content in the sensitive genotype. In contrast, the tolerant genotype maintained open stomata and active photosynthesis, even under dehydration conditions. Drought-induced changes in the leaf proteome were analyzed by two independent approaches, 2D gel electrophoresis and iTRAQ analysis, which provided compatible but only partially overlapping results. Drought caused the up-regulation of protective and stress-related proteins (mainly chaperones and dehydrins) in both genotypes. The differences in the levels of various detoxification proteins corresponded well with the observed changes in the activities of antioxidant enzymes. The number and levels of up-regulated protective proteins were generally lower in the sensitive genotype, implying a reduced level of proteosynthesis, which was also indicated by specific changes in the components of the translation machinery. Based on these results, we propose that the hypersensitive early stomatal closure in the sensitive genotype leads to the inhibition of photosynthesis and, subsequently, to a less efficient synthesis of the protective/detoxification proteins that are associated with drought tolerance

Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids

One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.Funding Agencies|MIIC, PDF grant; Linkoping University, Sweden; EU H2020 Marie Sklodowska-Curie Individual Fellowship [706694]; European CommissionEuropean Commission Joint Research Centre; Wolfson College, University of CambridgeUniversity of Cambridge; MIIC Strategic Postdoc Grant; MIIC Seed Grant at Linkoping University (LiU), Sweden; Swedish Cancer SocietySwedish Cancer Society [2017/301]; County Council of Ostergotland; Research Funds of Linkoping University Hospital</p

Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids

One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.Funding Agencies|MIIC, PDF grant; Linkoping University, Sweden; EU H2020 Marie Sklodowska-Curie Individual Fellowship [706694]; European CommissionEuropean Commission Joint Research Centre; Wolfson College, University of CambridgeUniversity of Cambridge; MIIC Strategic Postdoc Grant; MIIC Seed Grant at Linkoping University (LiU), Sweden; Swedish Cancer SocietySwedish Cancer Society [2017/301]; County Council of Ostergotland; Research Funds of Linkoping University Hospital</p

Antiinflammatory, Analgesic and Antipyretic Activities of Mimusops elengi Linn

In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o) was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesic effect was evaluated using acetic acid-induced writhing and Eddy’s hot plate models and antipyretic activity was assessed by Brewer’s yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o) significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer’s yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity