Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases

Ahmed, Rakin; Anam, Khairul; Ahmed, Hafiz

doi:10.3390/ijms24098116

Cited by 20 publications

(8 citation statements)

References 194 publications

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“…TcCTL16, a CTL-X protein, contains one CRD domain, four CCPs, and one transmembrane domain. Interestingly, it does not contain a signal peptide but instead contains a transmembrane protein, suggesting that it may be secreted by a non-classical secretory pathway [ 35 ]. Additionally, the non-classical secretory pathway is closely related to cell proliferation, immune response, tumor formation and infectious disease pathology [ 36 ], suggesting that TcCTL16 has extensive functions in T. castanuem .…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of a CTL-X-Type Lectin CTL16 in Development and Innate Immunity of Tribolium castaneum

Wang

Gao

et al. 2023

IJMS

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C-type lectins (CTLs) are a class of proteins containing carbohydrate recognition domains (CRDs), which are characteristic modules that recognize various glycoconjugates and function primarily in immunity. CTLs have been reported to affect growth and development and positively regulate innate immunity in Tribolium castaneum. However, the regulatory mechanisms of TcCTL16 proteins are still unclear. Here, spatiotemporal analyses displayed that TcCTL16 was highly expressed in late pupae and early adults. TcCTL16 RNA interference in early larvae shortened their body length and narrowed their body width, leading to the death of 98% of the larvae in the pupal stage. Further analysis found that the expression level of muscle-regulation-related genes, including cut, vestigial, erect wing, apterous, and spalt major, and muscle-composition-related genes, including Myosin heavy chain and Myosin light chain, were obviously down-regulated after TcCTL16 silencing in T. castaneum. In addition, the transcription of TcCTL16 was mainly distributed in the hemolymph. TcCTL16 was significantly upregulated after challenges with lipopolysaccharides, peptidoglycans, Escherichia coli, and Staphylococcus aureus. Recombinant CRDs of TcCTL16 bind directly to the tested bacteria (except Bacillus subtilis); they also induce extensive bacterial agglutination in the presence of Ca2+. On the contrary, after TcCTL16 silencing in the late larval stage, T. castaneum were able to develop normally. Moreover, the transcript levels of seven antimicrobial peptide genes (attacin2, defensins1, defensins2, coleoptericin1, coleoptericin2, cecropins2, and cecropins3) and one transcription factor gene (relish) were significantly increased under E. coli challenge and led to an increased survival rate of T. castaneum when infected with S. aureus or E. coli, suggesting that TcCTL16 deficiency could be compensated for by increasing AMP expression via the IMD pathways in T. castaneum. In conclusion, this study found that TcCTL16 could be involved in developmental regulation in early larvae and compensate for the loss of CTL function by regulating the expression of AMPs in late larvae, thus laying a solid foundation for further studies on T. castaneum CTLs.

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Section: Discussionmentioning

confidence: 99%

Functional Analysis of a CTL-X-Type Lectin CTL16 in Development and Innate Immunity of Tribolium castaneum

Wang

Gao

et al. 2023

IJMS

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“…Small molecule inhibitors targeting Gal-3 have shown potential as antiviral agents in preclinical studies, reducing viral replication and alleviating virus-induced inflammation [24]. The Gal-3 inhibitor TD139 has demonstrated significant reductions in lung fibrosis and ß-catenin activation in animal models of pulmonary fibrosis and is now in phase IIb trials for the treatment of idiopathic pulmonary fibrosis and COVID-19 [109]. A clinical trial of the inhaled Gal-3 inhibitor GB0139 for the treatment of COVID-19 found that it reduced Gal-3 concentrations and other key prognostic biomarkers associated with severe disease, showing potential to reduce the severity of systemic inflammation and cytokine excess in patients with COVID-19 [110].…”

Section: Small Molecule Inhibitors Of Galectin-3mentioning

confidence: 99%

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

Stojanović

Milovanović

et al. 2023

IJMS

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Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy. The impact of Gal-3 extends to the viral life cycle, encompassing critical phases such as replication, assembly, and release. Notably, Gal-3 also contributes to viral pathogenesis, demonstrating involvement in tissue damage, inflammation, and viral persistence and latency elements. A detailed examination of specific viral diseases, including SARS-CoV-2, HIV, and influenza A, underscores the intricate role of Gal-3 in modulating immune responses and facilitating viral adherence and entry. Moreover, the potential of Gal-3 as a biomarker for disease severity, particularly in COVID-19, is considered. Gaining further insight into the mechanisms and roles of Gal-3 in these infections could pave the way for the development of innovative treatment and prevention options for a wide range of viral diseases.

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“…The complexity of its mechanism of action is due to its interaction with numerous proteins of the cell membrane, extracellular matrix, biological fluids, and intracellularity. Hence, it has been described as being implicating in numerous biological and pathological events [ 54 , 55 , 56 , 57 ], such as inflammatory and fibrotic diseases. Galectin-3 influences the beginning and expansion of the acute inflammatory response by attracting macrophages into injury sites and thus exacerbates chronic inflammation by activating proinflammatory pathways, leading to fibrosis, a development that perpetuates inflammation and abnormal tissue repair.…”

Section: Fibrosismentioning

confidence: 99%

Cellular and Molecular Mechanisms Activated by a Left Ventricular Assist Device

Galeone,

Buccoliero,

Barile

et al. 2023

IJMS

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Left ventricular assist devices (LVADs) represent the final treatment for patients with end-stage heart failure (HF) not eligible for transplantation. Although LVAD design has been further improved in the last decade, their use is associated with different complications. Specifically, inflammation, fibrosis, bleeding events, right ventricular failure, and aortic valve regurgitation may occur. In addition, reverse remodeling is associated with substantial cellular and molecular changes of the failing myocardium during LVAD support with positive effects on patients’ health. All these processes also lead to the identification of biomarkers identifying LVAD patients as having an augmented risk of developing associated adverse events, thus highlighting the possibility of identifying new therapeutic targets. Additionally, it has been reported that LVAD complications could cause or exacerbate a state of malnutrition, suggesting that, with an adjustment in nutrition, the general health of these patients could be improved.

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Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases

Cited by 20 publications

References 194 publications

Functional Analysis of a CTL-X-Type Lectin CTL16 in Development and Innate Immunity of Tribolium castaneum

Functional Analysis of a CTL-X-Type Lectin CTL16 in Development and Innate Immunity of Tribolium castaneum

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

Cellular and Molecular Mechanisms Activated by a Left Ventricular Assist Device

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