Subject(s)
Bariatric Surgery , Prader-Willi Syndrome , Humans , Adolescent , Prader-Willi Syndrome/surgeryABSTRACT
IMPORTANCE: Bacterial surface glycans are an attractive therapeutic target in response to antibiotics; however, current knowledge of the corresponding mechanisms is rather limited. Antimicrobial susceptibility testing, genome sequencing, and MALDI-TOF MS, commonly used in recent years to analyze bacterial resistance, are unable to rapidly and efficiently establish associations between glycans and resistance. The discovery of new antimicrobial strategies still requires the introduction of promising analytical methods. In this study, we applied lectin microarray technology and a machine-learning model to screen for important glycan structures associated with carbapenem-resistant P. aeruginosa. This work highlights that specific glycopatterns can be important biomarkers associated with bacterial antibiotic resistance, which promises to provide a rapid entry point for exploring new resistance mechanisms in pathogens.
Subject(s)
Anti-Infective Agents , Pseudomonas Infections , Humans , Pseudomonas aeruginosa/genetics , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Pseudomonas Infections/microbiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Biomarkers , Microbial Sensitivity Tests , PolysaccharidesABSTRACT
Receptor-interacting protein kinase 1 (RIPK1) is up-regulated in patients with neurodegenerative diseases. Our study aimed to explore the underlying mechanisms that involved in the neurotoxic function of RIPK1 in Parkinson's disease (PD). MPP+/MPTP-induced PD cellular and mice models were used in this study. The results showed that RIPK1 was high expressed and activated in MPP+-treated SH-SY5Y cells and MPTP-induced PD mice. Overexpression of RIPK1 facilitated cell apoptosis, necrosis, inflammation response, ROS production and mitochondrial dysfunction in MPP+- treated SH-SY5Y cells, while the RIPK1 inhibitor Nec-1s has an opposite effect. In addition, the Apoptosis-signaling kinase-1 (ASK1)/c-Jun N-terminal kinase (JNK) signalling pathway was activated during the overexpression of RIPK1, and inhibiting the ASK1/JNK signal by the ASK1 inhibitor partially reversed the decline of cell viability, the increase of cell apoptosis, necrosis and inflammation induced by RIPK1 overexpression in MPP+-treated SH-SY5Y cells. Further studies suggested that the inhibition of RIPK1 by Nec-1s largely alleviated the behavioural impairment in PD mice. Hence, our study indicated that the RIPK1 inhibitor Nec-1s has neuroprotective effects against PD through inactivating the ASK1/JNK signalling pathway.