Sphingolipid metabolism-related genes as diagnostic markers in pneumonia-induced sepsis: the AUG model DOI Creative Commons
Jing Wu, Xiaomin Li, Zhihao Chen

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 20, 2025

Abstract Pneumonia-induced sepsis (PIS) is a life-threatening condition with high mortality rates, necessitating the identification of biomarkers and therapeutic targets. Sphingolipid, particularly ceramides, are pivotal in modulating immune responses determining cell fate. In this study, we identified novel gene signature related to sphingolipid metabolism, comprising ACER3 , UGCG GBA which key enzymes involved synthesis metabolism ceramides. This signature, termed “AUG model”, demonstrated strong diagnostic performance modest prognostic efficacy across both training (GSE65682) validation (E-MTAB-1548 E-MTAB-5273) datasets. A clinical cohort 20 PIS patients, 31 pneumonia cases, 11 healthy controls further validated increased expression AUG genes at mRNA protein levels peripheral blood samples upon admission. Our comprehensive analysis bulk single-cell transcriptome datasets revealed that these implicated death pathways, including autophagy apoptosis. Additionally, cell-communication indicated enhanced macrophage migration inhibitory factor (MIF) signaling may be associated dysregulated potentially driving inflammatory cascade. study identifies predictive model for PIS, highlighting role metabolism-related disease progression suggesting potential targets management.

Language: Английский

Bioinformatics and system biology approaches to identify pathophysiological impact of COVID-19 to the progression and severity of neurological diseases DOI Open Access
Md Habibur Rahman, Humayan Kabir Rana, Silong Peng

et al.

Computers in Biology and Medicine, Journal Year: 2021, Volume and Issue: 138, P. 104859 - 104859

Published: Sept. 23, 2021

Language: Английский

Citations

35
Elevation in sphingolipid upon SARS-CoV-2 infection: possible implications for COVID-19 pathology DOI Creative Commons
Einat B. Vitner, Roy Avraham, Boaz Politi

et al.

Life Science Alliance, Journal Year: 2021, Volume and Issue: 5(1), P. e202101168 - e202101168

Published: Nov. 11, 2021

Understanding pathways that might impact coronavirus disease 2019 (COVID-19) manifestations and outcomes is necessary for better management therapeutic development. Here, we analyzed alterations in sphingolipid (SL) levels upon infection with severe acute respiratory syndrome 2 (SARS-CoV-2). SARS-CoV-2 induced elevation of SL both cells sera infected mice. A significant increase glycosphingolipid was early post infection, which essential viral replication. This could be reversed by treatment glucosylceramide synthase inhibitors. Levels sphinganine, sphingosine, GA1, GM3 were significantly increased the murine model infection. The potential involvement SLs COVID-19 pathology discussed.

Language: Английский

Citations

34
TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection DOI Creative Commons
Meisam Yousefi,

Wai Suet Lee,

Biaoguo Yan

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(8), P. e1010763 - e1010763

Published: Aug. 8, 2022

Transmembrane Protein 41B (TMEM41B) and Vacuole Membrane 1 (VMP1) are two ER-associated lipid scramblases that play a role in autophagosome formation cellular metabolism. TMEM41B is also recently validated host factor required by flaviviruses coronaviruses. However, the exact underlying mechanism of promoting viral infections remains an open question. Here, we both VMP1 essential dependency factors for all four serotypes dengue virus (DENV) human coronavirus OC43 (HCoV-OC43), but not chikungunya (CHIKV). While HCoV-OC43 failed to replicate entirely TMEM41B- VMP1-deficient cells, detected diminished levels DENV these cell lines, which were accompanied upregulation innate immune dsRNA sensors, RIG-I MDA5. Nonetheless, this did correspondingly induce downstream effector TBK1 activation Interferon-beta expression. Despite low replication, classical replication organelles undetectable infected TMEM41B-deficient suggesting sensors likely consequence aberrant rather than causal reduced infection. Intriguingly, uncovered inhibitory effect deficiency on HCoV-OC43, can be partially reversed using exogenous fatty acid supplements. In contrast, cannot rescued metabolite treatment. line with observed phenotypes, found cells harbor higher compromised mitochondria, especially results severe dysregulations mitochondrial beta-oxidation. Using metabolomic profiling approach, revealed distinctive global metabolome, particularly lipidome, cells. Our findings highlight central modulating multiple pathways, including mobilization, beta-oxidation, metabolic regulations, facilitate

Language: Английский

Citations

26
Saliva metabolomic profile of COVID-19 patients associates with disease severity DOI Open Access
Narjes Saheb Sharif‐Askari, Nelson C. Soares,

Hajer A. Mohamed

et al.

Metabolomics, Journal Year: 2022, Volume and Issue: 18(11)

Published: Oct. 22, 2022

Language: Английский

Citations

26
Receptor-dependent effects of sphingosine-1-phosphate (S1P) in COVID-19: the black side of the moon DOI Open Access
Hayder M. Al‐kuraishy, Gaber El‐Saber Batiha, Ali I. Al‐Gareeb

et al.

Molecular and Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 478(10), P. 2271 - 2279

Published: Jan. 18, 2023

Language: Английский

Citations

14
Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity DOI Creative Commons
Samar Sami Alkafaas,

Abanoub Mosaad Abdallah,

Mai Helmy Hassan

et al.

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 6, 2024

Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, > 6 million deaths. Symptoms included strain complications, leading to pneumonia. SARS-CoV-2 attaches the ACE-2 receptor of host cell membrane enter. Targeting entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes conversion sphingolipid (sphingomyelin) ceramide. Ceramide molecules aggregate/assemble on plasma form "platforms" facilitate viral intake into cell. Impairing ASMase activity will eventually disrupt In this review, we identified metabolism sphingolipids, sphingolipids' role in signal transduction cascades, infection mechanisms. Also, outlined structure underlying mechanisms inhibiting 40 with aid inhibitors acid (FIASMAs). silico molecular docking analyses FIASMAs revealed dilazep (S = - 12.58 kcal/mol), emetine 11.65 pimozide 11.29 carvedilol 11.28 mebeverine 11.14 cepharanthine 11.06 hydroxyzin 10.96 astemizole 10.81 sertindole 10.55 bepridil 10.47 kcal/mol) have higher inhibition than candidate drug amiodarone 10.43 making them better options for inhibition.

Language: Английский

Citations

6
Exploring the causal effects of depression and antidepressants on COVID-19 DOI Creative Commons
Li Fu, Ancha Baranova, Hongbao Cao

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 359, P. 350 - 355

Published: May 25, 2024

Language: Английский

Citations

5
The Manifold Roles of Sphingolipids in Viral Infections DOI Creative Commons

Elita Avota,

Jochen Bodem,

Janice Chithelen

et al.

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 29, 2021

Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions sphingolipids with various viruses at different steps their replication cycles. This includes structural during entry plasma membrane or endosomal membranes, early leading sphingolipid-mediated signal transduction, internal membranes and lipids replication, virus assembly budding. Targeted interventions in sphingolipid metabolism – as far they can be tolerated by cells organisms may open novel possibilities support antiviral therapies. Human immunodeficiency type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such influenza A (IAV), measles (MV), hepatitis C (HCV), dengue virus, Ebola severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), investigations still beginnings. As many inhibitors already clinical use against diseases, repurposing studies applications some appear a promising approach.

Language: Английский

Citations

27
Recent Progress in the Development of Opaganib for the Treatment of Covid-19 DOI Creative Commons
Charles D. Smith,

Lynn W. Maines,

Staci N. Keller

et al.

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 2199 - 2211

Published: July 1, 2022

Abstract: The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across world. Although antivirals active against mild disease have been identified recently, new drugs treat moderate severe patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for treatment of cancer inflammatory diseases. Recent work demonstrates that opaganib also has antiviral activity several viruses SARS-CoV-2. A recently completed multinational Phase 2/3 trial in hospitalized with demonstrated can be safely administered these patients, more importantly, resulted 62% decrease mortality large subpopulation moderately Covid-19. Furthermore, acceleration clearance was observed opaganib-treated patients. Understanding biochemical mechanism anti-SARS-CoV-2 essential optimizing protocols. inhibits three enzymes metabolism: sphingosine kinase-2 (SK2); dihydroceramide desaturase (DES1); glucosylceramide synthase (GCS). Herein, we describe tripartite model which suppresses infection replication inhibiting SK2, DES1 GCS. potential impact modulation signaling on multi-organ dysfunction discussed. Keywords: opaganib, ABC294640, sphingolipid, kinase, desaturase,

Language: Английский

Citations

18
Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection DOI Creative Commons
Sifen Lu,

Yongzhao Zhou,

Ya Hu

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: June 2, 2023

Background and objectives Disease severity prognosis of coronavirus disease 2019 (COVID-19) with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially microbiome patient. Here, we aimed explore characteristics microbiota COVID-19 patients compare them those similar symptoms. Methods was diagnosed in through detection severe acute respiratory syndrome 2 (SARS-CoV-2) quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization performed metatranscriptomic sequencing analyses swab specimens from 144 patients, 100 infected viruses, 40 healthy volunteers. Results The diversity SARS-CoV-2 infection different that infections. Prevotella Aspergillus could play a role differentiation between also influence mechanism potentially involved sphingolipid metabolism regulation pathway. Conclusion characterization caused viruses. act as biomarker for diagnosis host immune response evaluation infection. In addition, cross-talk among , SARS-CoV-2, pathways provide basis precise diagnosis, prevention, control, treatment COVID-19.

Language: Английский

Citations

10