Search bioRxivSearch

Biology subjects

Lopes, M.

Publications and source records attributed to Lopes, M..

2 recordsLinked to original sources

Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival During Cancer Cachexia Syndrome

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that Toll-like receptor 4 (TLR4) mediates AT remodeling, in particular, AT browning and inflammatory response in mice bearing Lewis lung carcinoma (LLC). LLC tumor-bearing (TB) TLR4-/- mice were spared from AT remodeling due to a reduced macrophage infiltration and adipocyte atrophy. TLR4-/- mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 reproduced the main protective effect against AT remodeling found in TLR4-/- TB mice. Moreover, the treatment was effective in prolonging the survival and attenuating tumor mass growth when compared to non-treated-TB animals. Further, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising therapeutic target for cancer-induced AT remodeling.\n\nHIGHLIGHTSO_LIGenetic ablation and pharmacological inhibition of TLR4 attenuate adipose tissue remodeling during cancer-associated cachexia;\nC_LIO_LITLR4 suppression play an essential role in the browning phenotype induced by cachexia;\nC_LIO_LIAdministration of TLR4 drug inhibitor increase survival and reduces tumor mass growth in tumor bearing mice;\nC_LIO_LITLR4 pathway is a promising target for cancer-cachexia therapeutic intervention.\nC_LI

cancer biology

Unraveling rice tolerance mechanisms against Schizotetranychus oryzae mite infestation

Infestation of Schizotetranychus oryzae (Acari: Tetranychidae) causes great losses in rice productivity. Infestation in Puita INTA-CL cultivar reduced the number of seeds/plant, percentage of full seeds, 1,000 seeds weight, and seed length, whereas infestation in IRGA423 increased 1,000 seeds weight and seed length. Reduction in seed weight/plant caused by infestation was higher in Puita INTA-CL than IRGA423. Thus, Puita INTA-CL was established as susceptible, and IRGA423 as tolerant to S. oryzae infestation. Photosynthetic parameters were less affected by infestation in IRGA423 than in Puita INTA-CL. Infestation also caused accumulation of H2O2, decreased cell membrane integrity and accelerated senescence in leaves of Puita INTA-CL, while leaves of IRGA423 presented higher levels of phenolics compounds. Using proteomic analysis, we identified proteins related to plant defense, such as jasmonate synthesis, and related to other mechanisms of tolerance such as oxidative stress, photosynthesis, and DNA structure maintenance, more abundant in IRGA423 after seven days of infestation. We detected higher levels of silicon (as amorphous silica cells) in leaves of infested IRGA423 plants compared to Puita INTA-CL, an element previously linked to plant defense. Our data shows that IRGA423 presents tolerance to S. oryzae infestation, and that multiple mechanisms might be employed by this cultivar.\n\nHighlightThis is the first report evaluating the defense responses (tolerance and susceptiblity) of two contrasting rice cultivars to Schizotetranychus oryzae mite infestation.

plant biology