Integrated analysis reveals NLRC4 as a potential biomarker in sepsis pathogenesis
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LCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments
Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis. Despite increasing data supporting the hypothesis of neuronal damage, the exact mechanism of sepsis-related cognitive disorders and therapeutic strategies remain unclear and need further investigation. In this study, a sepsis model was established in C57 mice using lipopolysaccharide (LPS). The findings demonstrated that LPS exposure induced neuronal loss, synaptic and cognitive deficits accompanied by mitochondrial damage. Bioinformatics and western blot analyses demonstrated a significant increase in Lipocalin-2 (LCN2) during sepsis as a key hub gene involved in immune and neurological inflammation. Interestingly, the recombinant LCN2 protein exhibited similar effects on synaptic dysfunction and cognitive deficits in C57 mice. Conversely, downregulating LCN2 effectively nullified the impact of LPS, leading to the amelioration of synaptic and cognitive deficits, neuronal loss, and reactive oxygen species (ROS)-associated mitochondrial damage. These findings suggest a novel etiopathogenic mechanism of SAE, which is initiated by the increased LCN2, leading to neuronal loss and cognitive deficit. Inhibition of LCN2 could be therapeutically beneficial in treating sepsis-induced synaptic and cognitive impairments.
SEPSIS – a complete guide
What is sepsis? Sepsis arises due to the body’s abnormal response to an infection. The immune system usually works to fight germs (such as bacteria,…
Neuroinflammatory fluid biomarkers in patients with Alzheimer’s disease: a systematic literature review
Neuroinflammation is associated with both early and late stages of the pathophysiology of Alzheimer’s disease (AD). Fluid biomarkers are gaining significance in clinical practice for diagnosis in presymptomatic stages, monitoring, and disease prognosis. This systematic literature review (SLR) aimed to identify fluid biomarkers for neuroinflammation related to clinical stages across the AD continuum and examined long-term outcomes associated with changes in biomarkers.
Why do travelers discontinue using integrated ride-hailing platforms? The role of perceived value and perceived risk
Despite integrated ride-hailing platforms have provided many benefits to travelers, there are also various potential risks. This study aims to examine travelers’ discontinuance behavioral intention toward integrated ride-hailing platforms. The research framework was established by extending the theory of planned behavior (TPB) with perceived value and perceived risk. Perceived value was classified into utilitarian, hedonic, and social values, while perceived risk was classified into privacy, performance, security, and financial risks. Additionally, the factors of switch cost and personal innovativeness were included. An empirical analysis was carried out using partial least-squares structural equation modeling (PLS-SEM) based on a survey conducted in Nanjing, China. Furthermore, a multi-group analysis (MGA) was performed to examine behavioral differences across demographic variables. The findings suggest that discontinuous behavioral intention is influenced by subjective norms, perceived behavioral control, and attitude. Among them, perceived behavioral control shows the strongest impact (−0.190). Perceived value, including utilitarian, hedonic, and social dimensions, negatively influences discontinuance intention, whereas the four variables of risk perception positively affect discontinuance intention. Notably, social value, performance risk, and privacy risk act higher total effects on discontinuance intention. Switch cost is negatively associated with attitude (−0.222), and positively affects discontinuance intention (0.189). Personal innovativeness has positive and stronger effects on perceived value (0.237), negative effects on perceived risk (−0.174), and negative effects on discontinuance intention. Regarding MGA results, older travelers demonstrate a stronger impact of social value on perceived value, higher-income groups exhibit greater sensitivity to security risks, and frequent travelers prioritize utilitarian value.
Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy
Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.
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