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Human genetic variants can affect TB and HIV drug metabolism, which may lead to toxicity or treatment failure. We evaluated associations between genetic variants of antiretroviral therapy (ART) and HIV-1 outcomes among TB/HIV patients. We included RePORT-Brazil participants with TB/HIV who initiated standard TB treatment [2 months of isoniazid/rifampicin (or rifabutin)/pyrazinamide/ethambutol, then 4 months or more of isoniazid/rifampicin (or rifabutin)], and ART.
View Article and Find Full Text PDFThe relentless emergence of antibiotic-resistant pathogens, particularly Gram-negative bacteria, highlights the urgent need for novel therapeutic interventions. Drug-resistant infections account for approximately 5 million deaths annually, yet the antibiotic development pipeline has largely stagnated. Venoms, representing a remarkably diverse reservoir of bioactive molecules, remain an underexploited source of potential antimicrobials.
View Article and Find Full Text PDFExposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity.
View Article and Find Full Text PDFThe capsaicin receptor, TRPV1, mediates the detection of harmful chemical and thermal stimuli. Overactivation of TRPV1 can lead to cellular damage or death through excitotoxicity, a phenomenon associated with painful neuropathy and the paradoxical use of capsaicin as an analgesic. We exploited capsaicin-evoked death to conduct a systematic analysis of excitotoxicity through a genome-wide CRISPRi screen, thereby revealing a comprehensive network of regulatory pathways.
View Article and Find Full Text PDFEngineered IL-21-Expressing Nanovesicles for Co-Delivery of GOX and Ferrocene to Induce Synergistic Anti-Tumor Effects.
Adv Healthc Mater
January 2025
School of Life Sciences, Anhui Medical University, Hefei, Anhui, 230032, China.
Glucose oxidase (GOX)-induced starvation is a safe treatment for tumor. However, the non-specific targeting of GOX and the plasticity of tumor metabolism lead to toxic side effects and low tumor mortality. Thus, it is necessary to develop a synergistic strategy with high tumor targeting specificity to enhance the mortality of GOX.
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