Evaluation of the immunological functions of placental alkaline phosphatase in vivo using ALPP transgenic miceChen, Ng, Chen
et alFront Immunol (2025) 16, 1499388
Abstract: Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions.Copyright © 2025 Chen, Ng, Chen, Pan, Cheng, Wu, Hsueh, Chiang and Lin.
p53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injuryLiu, Wang, Shen
et alMech Ageing Dev (2024) 222, 112000
Abstract: Spinal cord injury (SCI)-induced hindlimb dysfunction affects the physical and mental health of patients. There is growing evidence suggesting that the recovery capacity of elderly SCI patients is poorer than that of young individuals. However, the specific molecular mechanisms remain unclear.RNA expression profiles of SCI samples were collected from the GEO database, and key genes involved in the progression of SCI were identified by the limma package in R software. A diagnostic model based on SCIDEG was constructed using LASSO regression analysis. Subsequently, correlation analysis was conducted to identify biological pathways influenced by the key genes. Furthermore, SCI animal models were established in different age groups to examine the expression of relevant genes and verify the molecular mechanism of p53/HIF-1α axis.We initially identified 34 ischemia-hypoxia-related genes potentially involved in the progression of SCI. Subsequently, we constructed a diagnostic model based on SCIDEGs using LASSO regression analysis. This model highlighted 9 key genes (TP53, SFTPA1, MASP2, KRT14, IL9, HIF1A, HGFAC, FUT7, and ALPP), which demonstrated high diagnostic accuracy in both the training set (AUC=1) and the validation set (AUC=0.855). Further cross-analysis with ischemia-reperfusion-related datasets confirmed the involvement of HIF1A and TP53. We also observed significant enrichment of HIF1A in organoids composed of mature neurons, which induced neuronal damage. In subsequent spinal cord injury animal models of different age groups, we found that HIF-1α expression was downregulated in the spinal cord tissues of elderly animals. Additionally, we discovered that TP53 activation induces cellular senescence in aging neurons and suppresses HIF-1α expression and autophagy levels within these cells.In summary, our study suggests that the p53/HIF-1α signaling pathway plays a critical role in regulating neuronal aging and autophagy in the pathogenesis of SCI. Importantly, HIF-1α may represent a promising therapeutic target for SCI treatment.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in ChildrenSherman, Karmali, Kumar
et alOpen Forum Infect Dis (2024) 11 (11), ofae626
Abstract: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Impact of Knack Manoeuvre Among Women with Urinary Incontinence: A Quasi Experimental StudyJagadeeswari, Kalabarathi, Bhuvaneswari
J Pharm Bioallied Sci (2024) 16 (Suppl 3), S2000-S2002
Abstract: The Objective of the study is to assess the effectiveness of Knack manoeuvre among women with urinary incontinence.A quasi-experimental study with a repeated measures design was used to conduct study at Saveetha Medical College Hospital. Experimental group received Knack manoeuvre for 6 months and control group received routine care. The sample size was 100, which was recruited by purposive sampling technique. The data were collected with structured questionnaire, and questionnaire for urinary incontinence diagnosis and biophysiological parameters were assessed by abdominal leak peak pressure (ALPP).The study results depict that frequency and percentage distribution of pretest and post-test level of ALPP. Between group comparison of post-test at 6 months of control and experimental showed significance (P < 0.001). There was a progressive decrease in ALPP of control and experimental groups.To our knowledge, this is the first prospective nonrandomized study that assesses the efficacy of the Knack manoeuvre on urine incontinence by assessing biophysiological parameters.Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.
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