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      A lysosome-targeted fluorescent probe with large Stokes shift for visualizing biothiols in vivo and in vitro

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          Summary

          Lysosomal biothiols play critical roles in numerous cellular processes and diseases. Researching an effective method for real-time labeling biothiols in lysosomes is of great significance and urgency, as it could provide essential information for the diagnosis of relevant diseases. In this study, we developed a lysosome-targeted fluorescent probe (LY-DCM-P) with a large Stokes shift of 150 nm for the sensitive and selective detection of biothiols in vivo and in vitro. Additionally, LY-DCM-P showed low cytotoxicity and excellent lysosome-targeted ability. The probe was successfully employed to monitor fluctuations in lysosomal biothiols in various living systems, enabling enormous potential to accurately monitor the occurrence and progress of biothiol-related diseases.

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          Highlights

          • A lysosome-targeted fluorescent probe LY-DCM-P was constructed to detect biothiols

          • LY-DCM-P exhibits red fluorescence (670 nm) upon binding to biological thiols

          • LY-DCM-P can be used for rapid and highly selective detection of biological thiols

          • LY-DCM-P has effectively monitored the endogenous biothiols in living systems

          Abstract

          Chemistry; Physics; Biological sciences

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          Most cited references42

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          In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus

          Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
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            Fluorescent Probes with Multiple Binding Sites for the Discrimination of Cys, Hcy, and GSH.

            Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play crucial roles in maintaining redox homeostasis in biological systems. This Minireview summarizes the most significant current challenges in the field of thiol-reactive probes for biomedical research and diagnostics, emphasizing the needs and opportunities that have been under-investigated by chemists in the selective probe and sensor field. Progress on multiple binding site probes to distinguish Cys, Hcy, and GSH is highlighted as a creative new direction in the field that can enable simultaneous, accurate ratiometric monitoring. New probe design strategies and researcher priorities can better help address current challenges, including the monitoring of disease states such as autism and chronic diseases involving oxidative stress that are characterized by divergent levels of GSH, Cys, and Hcy.
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              Lysosomes as targets for cancer therapy.

              Tumor invasion and metastasis are associated with altered lysosomal trafficking and increased expression of the lysosomal proteases termed cathepsins. Emerging experimental evidence suggests that such alterations in lysosomes may form an "Achilles heel" for cancer cells by sensitizing them to death pathways involving lysosomal membrane permeabilization and the release of cathepsins into the cytosol. Here, we highlight recent results on cancer-related changes in the composition and function of lysosomes, focusing on possible implications for the development of novel cancer therapeutics that target tumor cell lysosomes.
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                Author and article information

                Contributors
                Journal
                iScience
                iScience
                iScience
                Elsevier
                2589-0042
                07 November 2024
                20 December 2024
                07 November 2024
                : 27
                : 12
                : 111334
                Affiliations
                [1 ]Hubei Key Laboratory for Precision Synthesis of Small Molecule Pharmaceuticals & Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P.R. China
                Author notes
                []Corresponding author wuzj@ 123456hubu.edu.cn
                [∗∗ ]Corresponding author renjun@ 123456hubu.edu.cn
                [∗∗∗ ]Corresponding author efwang@ 123456hubu.edu.cn
                [2]

                These authors contributed equally

                [3]

                Lead contact

                Article
                S2589-0042(24)02559-8 111334
                10.1016/j.isci.2024.111334
                11615578
                39634562
                f3e360b2-894c-4925-ad62-ebd2882c1f21
                © 2024 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 August 2024
                : 18 September 2024
                : 4 November 2024
                Categories
                Article

                chemistry,physics,biological sciences
                chemistry, physics, biological sciences

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