The incidence of invasive fungal infections has risen significantly in recent decades as medical interventions have become increasingly aggressive. These infections are extremely difficult to treat due to the extremely limited repertoire of systemic antifungals, the development of drug resistance, and the extent to which the patient's immune function is compromised. Even when the appropriate antifungal therapies are administered in a timely fashion, treatment failure is common, even in the absence of microbial resistance. In this study, we screened a small collection of FDA-approved oncolytic agents for compounds that impact the efficacy of the two most widely used classes of systemic antifungals against , , and We have identified several drugs that enhance fungal growth in the presence of azole antifungals and examine the potential that these drugs directly affect fungal fitness, specifically antifungal susceptibility, and may be contributing to clinical treatment failure.
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http://dx.doi.org/10.1128/AAC.00504-18 | DOI Listing |
Alzheimers Dement
December 2024
University of Pittsburgh, Pittsburgh, PA, USA.
Background: The bi-directional autophagy and inflammation network becomes progressively dysregulated with age, with systemic inflammation as a biomarker of this dysregulation including in Alzheimer's Disease (AD). We hypothesize that interventions which target the shared feature of systemic inflammation in the biology of aging and AD, via regulation of the autophagy-inflammation network, will prevent the conversion to disease pathogenesis in AD as well as improve healthspan and longevity in aging populations. While previous studies report benefits of mTOR inhibition including rapamycin in transgenic mouse models of familial AD, the present studies aim to evaluate this pathway in a model of sporadic, late onset AD (LOAD) and test the contribution of AMP-activated protein kinase (AMPK) as a critical regulator of the mTOR pathway.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background: Studies investigating mTOR signaling provide compelling and reproducible evidence of the extension of lifespan across model organisms by treatment with the mTOR inhibitor rapamycin, and preclinical data suggests neuroprotective benefits of rapamycin in models of Alzheimer's disease (AD). Rapamycin has potent immunosuppressive and autophagy activating effects though it remains unknown whether rapamycin's neuroprotective and lifespan enhancing effects are achieved through modulating systemic inflammation, augmenting autophagy, or via some combination of modifying both these factors. Relatedly, the cellular and molecular mechanisms that contribute to rapamycin's neuroprotective effects in AD remain unclear.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, India.
Plants frequently confront pathogens that disrupt physiological and molecular functions, ultimately reducing agricultural yields. To counter these challenges, plants activate sophisticated defense mechanisms to recognize stress signals while optimizing growth. Phytohormones signaling pathways and their crosstalk are central to regulating plant growth, development and defense.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen, 40002, Thailand.
Celosia argentea is a plant known for producing bioactive compounds, including betalains, which possess various biological and pharmaceutical properties. This study aimed to investigate the effect of biotic and abiotic elicitors on betalains production and their antioxidant activity in cell suspension cultures of C. argentea.
View Article and Find Full Text PDFInt J Food Microbiol
December 2024
National Key Laboratory of Tropical Crop Breeding, School of Tropical Agriculture and Foresty, Hainan University, Haikou 570228, Hainan, China. Electronic address:
During storage and transportation, fruits and vegetables are susceptible to various pathogens, leading to quality degradation and significant economic losses. Currently, chemical pesticides are primarily used for control; however, their overuse poses serious threats to human health and causes environmental pollution. Biocontrol, known for its environmentally friendly characteristics, has been extensively studied.
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