Multiple Sclerosis Biomarkers Detection by a BiLSTM Deep Learning Model for miRNA Data Analysis DOI
Nehal M. Ali,

Mohamed Shaheen,

Mai S. Mabrouk

et al.

2022 International Arab Conference on Information Technology (ACIT), Journal Year: 2022, Volume and Issue: unknown, P. 1 - 6

Published: Nov. 22, 2022

High-throughput data technology has enabled studies on microRNA analysis to evolve in the field of early disease diagnosis. Multiple Sclerosis is one most known chronic autoimmune diseases that can cause severe disabilities, including partial blindness, motor and considerable psychological impact. This work introduces a complete BiLSTM deep learning model for analyzing miRNA patients provide detection this disease. The introduced based preprocessing flow published earlier by authors. experiments were conducted dataset 215 transcriptomic samples treated untreated patients. implicated results quite promising, as produced sensitivity, specificity, precision, accuracy, F1 scores (0.785,0.789,0.788, 0.8, 0.79) respectively, achieved. To ensure robustness, obtained accuracy was compared two other state-of-art models, proposed relatively outperformed literature models.

Language: Английский

Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation DOI Creative Commons

Leigh Ellen Fremuth,

Huimin Hu, Diantha van de Vlekkert

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115204 - 115204

Published: Jan. 1, 2025

Neuraminidase 1 (NEU1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, NEU1 regulates immune cells, primarily those of monocytic lineage. Here, we examine how Neu1 influences microglia by modulating sialylation full-length Trem2 (Trem2-FL), a multifunctional receptor that microglial survival, phagocytosis, cytokine production. When is deficient/downregulated, Trem2-FL remains sialylated, accumulates intracellularly, excessively cleaved into C-terminal fragment (Trem2-CTF) an extracellular soluble domain (sTrem2), enhancing their signaling capacities. Sialylated (Sia-Trem2-FL) does not hinder Trem2-FL-DAP12-Syk complex assembly but impairs signal transduction through Syk, ultimately abolishing Trem2-dependent phagocytosis. Concurrently, Trem2-CTF-DAP12 complexes dampen NF-κB signaling, while sTrem2 propagates Akt-dependent cell survival NFAT1-mediated production TNF-α CCL3. Because are implicated neurodegenerative/neuroinflammatory diseases, including Alzheimer disease sialidosis, activity represents therapeutic approach to broadly regulate microglia-mediated neuroinflammation.

Language: Английский

Citations

2
Neuraminidase 1 promotes renal fibrosis development in male mice DOI Creative Commons
Qianqian Chen, Kang Liu, Ning Shi

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 27, 2023

Abstract The functions of the influenza virus neuraminidase has been well documented but those mammalian neuraminidases remain less explored. Here, we characterize role 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated fibrotic kidneys patients mice. Functionally, tubular epithelial cell-specific knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, collagen deposition Conversely, overexpression exacerbates progressive fibrosis. Mechanistically, interacts with TGFβ type I receptor ALK5 at 160-200aa region stabilizes leading to SMAD2/3 activation. Salvianolic B, a component Salvia miltiorrhiza , found strongly bind effectively protect mice from NEU1-dependent manner. Collectively, this study characterizes promotor for suggests potential avenue targeting treat kidney diseases.

Language: Английский

Citations

27
Sialidase Inhibitors with Different Mechanisms DOI Creative Commons

Joseph M. Keil,

Garrett R. Rafn,

Isaac Turan

et al.

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(20), P. 13574 - 13593

Published: Oct. 17, 2022

Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal terminal Sia (desialylation). By desialylation, sialidase can modulate functionality target compound and is thus often involved in biological pathways. Inhibition sialidases with inhibitors an important approach for understanding function underlying mechanisms could serve as a therapeutic well. Transition-state analogues, such anti-influenza drugs oseltamivir zanamivir, major inhibitors. In addition, difluoro-sialic acids were developed mechanism-based Further, fluorinated quinone methide-based suicide substrates reported. Sialidase product analogue also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, human sialidases. This Perspective describes different their activities future potential, which include transition-state inhibitors, substrate

Language: Английский

Citations

35
Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases DOI Creative Commons

Katarzyna Drzewicka,

Zbigniew Zasłona

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 14, 2024

Metabolic changes are coupled with alteration in protein glycosylation. In this review, we will focus on macrophages that pivotal the pathogenesis of pulmonary fibrosis and sarcoidosis thanks to their adaptable metabolism an attractive therapeutic target. Examples presented review demonstrate glycosylation regulates metabolism-driven immune responses macrophages, implications for fibrotic processes granuloma formation. Targeting proteins regulate glycosylation, such as fucosyltransferases, neuraminidase 1 chitinase could effectively block immunometabolic driving inflammation fibrosis, providing novel avenues interventions.

Language: Английский

Citations

7
Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy DOI Creative Commons
Yingyan Yu, Wenjie Peng

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 16

Published: May 3, 2023

Malignant tumors are complex structures composed of cancer cells and tumor microenvironmental cells. In this structure, cross-talk interact, thus jointly promoting development metastasis. Recently, immunoregulatory molecule-based immunotherapy has greatly improved treatment efficacy for solid cancers, enabling some patients to achieve persistent responses or cure. However, owing the drug-resistance low response rate, against available targets PD-1/PD-L1 CTLA-4 limited benefits. Although combination therapies have been proposed enhance severe adverse effects observed. Thus, alternative immune checkpoints must be identified. The SIGLECs a family receptors (known as glyco-immune checkpoints) discovered in recent years. This review systematically describes molecular characteristics SIGLECs, discusses progress areas including synthetic ligands, monoclonal antibody inhibitors, Chimeric antigen receptor T (CAR-T) cells, with focus on strategies blocking sialylated glycan-SIGLEC axis. Targeting can expand scope provide multiple options new drug development.

Language: Английский

Citations

12
Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management DOI Open Access
Patrycja Jastrząb,

Karolina Narejko,

Halina Car

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(20), P. 5103 - 5103

Published: Oct. 22, 2023

A cellular sialome is a physiologically active and dynamically changing component of the cell membrane. Sialylation plays crucial role in tumor progression, alterations sialylation patterns have been described as modulators chemotherapy effectiveness. However, precise mechanisms through which altered contributes to drug resistance cancer are not yet fully understood. This review focuses on intricate interplay between treatment. It presents sialic acids modulating cell-cell interactions, extracellular matrix (ECM), immunosuppressive processes within context cancer. The issue also discussed, that involve transporters, microenvironment, metabolism analyzed. explores drugs therapeutic approaches may induce modifications with primary focus their impact sialyltransferases or sialidases. Despite advancements glycobiology glycoengineering, an interdisciplinary effort required decipher comprehend biological characteristics consequences sialylation. Additionally, understanding modulatory sialoglycans sensitivity applying this knowledge clinical practice for benefit patients.

Language: Английский

Citations

9
Sialylation: fate decision of mammalian sperm development, fertilization, and male fertility DOI
Shiqi Yi, Ying Feng,

Yan Wang

et al.

Biology of Reproduction, Journal Year: 2023, Volume and Issue: 109(2), P. 137 - 155

Published: June 28, 2023

Abstract Sperm development, maturation, and successful fertilization within the female reproductive tract are intricate orderly processes that involve protein translation post-translational modifications. Among these modifications, sialylation plays a crucial role. Any disruptions occurring throughout sperm’s life cycle can result in male infertility, yet our current understanding of this process remains limited. Conventional semen analysis often fails to diagnose some infertility cases associated with sperm sialylation, emphasizing need comprehend investigate characteristics sialylation. This review reanalyzes significance development evaluates impact damage on fertility under pathological conditions. Sialylation serves vital role journey sperm, providing negatively charged glycocalyx enriching molecular structure surface, which is beneficial reversible recognition immune interaction. These particularly during maturation tract. Moreover, enhancing mechanism underlying promote relevant clinical indicators for detection treatment.

Language: Английский

Citations

8
Systems medicine framework for repurposable drug combinations for COVID-19 comorbidities DOI Creative Commons
S. Saranya,

L. Thamanna,

P. Chellapandi

et al.

Medicine in Omics, Journal Year: 2024, Volume and Issue: 11, P. 100038 - 100038

Published: May 22, 2024

Currently, vaccines have shown efficacy against new SARS-CoV-2 variants. This study aimed to develop a systems medicine framework that can predict and validate drug combinations be repurposed for treating COVID-19 its comorbidities, specifically type 2 diabetes hypertension. found gut microbes could potentially influence the action of drugs, innate immune response, intestinal dysfunction, susceptibility virus in individuals with these comorbidities. It was also discovered spike protein interacts 57 human genes, many which are linked food-borne bacteria. An analysis disease enrichment showed arthritis hypertension were frequently observed as comorbidities patients infected SARS-CoV-2. Several including Fluvoxamine, Donepezil, Ifenprodil, been identified repurposable drugs Moreover, nitazoxanide tocilizumab (antivirals), bacitracin (antibacterial), gliclazide (antidiabetics) potential drugs. Tocilizumab effective diabetes. A combination lidocaine has suggested

Language: Английский

Citations

1
Unveiling the Impact of Endogenous Sialidases on Human Non-Infectious Disease Pathogenesis DOI Open Access

R. Surkova,

Anastasia V. Poznyak, Dmitry Kashirskikh

et al.

OnLine Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 24(3), P. 302 - 312

Published: March 1, 2024

In our review, we have compiled existing information regarding the role of endogenous sialidases (neuraminidases) in initiation and development various non-infectious processes humans. Precisely, pathologies cardiovascular system, tumor formations, neurological metabolic disorders, hereditary diseases. Sialidases appeared to be widely involved a variety human pathologies. An increase or decrease enzymatic activity sialidase can triggering factor pathogenesis these disorders. This led us conclusion that enzymes this family are essential for normal functioning organisms. Therefore, with detailed study characteristics functions sialidase, it is possible develop new effective diagnostic methods, treatment strategies, prevention many important linking all sialidase-related features different diseases, which set direction further studies.

Language: Английский

Citations

0
Neuraminidase 1 regulates the cellular state of microglia by modulating the sialylation of Trem2 DOI Open Access
Leigh E. Fremuth, Huimin Hu, Diantha van de Vlekkert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Summary Neuraminidase 1 (Neu1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, Neu1 regulates immune cells, primarily those of monocytic lineage. Here we examined how influences microglia by modulating sialylation full-length Trem2 (Trem2-FL), a multifunctional receptor that microglial survival, phagocytosis, cytokine production. When was deficient/downregulated, Trem2-FL remained sialylated, accumulated intracellularly, excessively cleaved into C-terminal fragment (Trem2-CTF) an extracellular soluble domain (sTrem2), enhancing their signaling capacities. Sialylated (Sia-Trem2-FL) did not hinder Trem2-FL–DAP12–Syk complex assembly but impaired signal transduction through Syk, ultimately abolishing Trem2-dependent phagocytosis. Concurrently, Trem2-CTF–DAP12 complexes dampened NFκB signaling, while sTrem2 propagated Akt-dependent cell survival NFAT1-mediated production TNFα CCL3. Because are implicated neurodegenerative/neuroinflammatory diseases, including Alzheimer disease (AD) sialidosis, activity represents therapeutic approach to broadly regulate microglia-mediated neuroinflammation.

Language: Английский

Citations

0