Astrocyte-Mediated Neuroinflammation in Neurological Conditions

Biomolecules, Год журнала: 2024, Номер 14(10), С. 1204 - 1204

Опубликована: Сен. 25, 2024

Astrocytes are one of the key glial types central nervous system (CNS), accounting for over 20% total cells in brain. Extensive evidence has established their indispensable functions maintenance CNS homeostasis, as well broad involvement neurological conditions. In particular, astrocytes can participate various neuroinflammatory processes, e.g., releasing a repertoire cytokines and chemokines or specific neurotrophic factors, which result both beneficial detrimental effects. It become increasingly clear that such astrocyte-mediated neuroinflammation, together with its complex crosstalk other immune cells, designates neuronal survival functional integrity neurocircuits, thus critically contributing to disease onset progression. this review, we focus on current knowledge responses astrocytes, summarizing common features Moreover, highlight several vital questions future research promise novel insights into diagnostic therapeutic strategies against those debilitating diseases.

Язык: Английский

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Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy

Science Bulletin, Год журнала: 2024, Номер 69(17), С. 2745 - 2755

Опубликована: Июль 15, 2024

Язык: Английский

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Novel formats of antibody conjugates: recent advances in payload diversity, conjugation, and linker chemistry

Expert Opinion on Biological Therapy, Год журнала: 2023, Номер 23(11), С. 1053 - 1065

Опубликована: Ноя. 2, 2023

Introduction In the field of bioconjugates, focus on antibody – drug conjugates (ADCs) with novel payloads beyond traditional categories potent cytotoxic agents is increasing. These innovative ADCs exhibit various molecular formats, ranging from small-molecule payloads, such as immune agonists and proteolytic agents, to macromolecular oligonucleotides proteins.

Язык: Английский

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A review of RNA nanoparticles for drug/gene/protein delivery in advanced therapies: Current state and future prospects

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 295, С. 139532 - 139532

Опубликована: Янв. 5, 2025

Язык: Английский

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Potential Theranostics of Breast Cancer with Copper-64/67 Sarcophagine-trastuzumab

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Over-expression of Human Epidermal Growth Factor Receptor 2 (HER2) is associated with a significant proportion breast cancers. Targeting HER2 possible monoclonal antibody called trastuzumab but metastatic positive tumours can develop resistance to this treatment. One approach more potent therapeutic agents which retain the selectivity attach β- emitting radionuclide, such as copper-67, for radioimmunotherapy. It also β+ copper-64 antibodies diagnostic imaging positron emission tomography (PET). In work, cage amine sarcophagine (Sar) chelator conjugated give Sar-trastuzumab be radiolabelled either or copper-67 at room temperature in minutes [64Cu]CuSar-trastuzumab and [67Cu]CuSar-trastuzumab respectively. The potential was evaluated mice bearing HER2+ SKOV-3 showing that tracer has very high tumour uptake retention 48 hours after injection. variant, [67Cu]CuSar-trastuzumab, highly therapeutically efficacious same model no signs radiotoxicity. combination PET guide radionuclide therapy [67Cu]CuSar-trastzumab theranostic treatment cancer other disease become resistant conventional immunotherapy.

Язык: Английский

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Amplification-Free Ratiometric Electrochemical Aptasensor for Point-of-Care Detection of Therapeutic Monoclonal Antibodies

Analytical Chemistry, Год журнала: 2023, Номер 95(37), С. 14094 - 14100

Опубликована: Сен. 6, 2023

The rapid quantification of therapeutic monoclonal antibodies (mAbs) is great significance to their pharmacokinetics/pharmacodynamics (PK/PD) research and the personalized medication for disease treatment. Taking advantage direct decoration tens redox tags target interest, we illustrate herein an amplification-free ratiometric electrochemical aptasensor point-of-care (POC) detection trace amounts mAbs. POC mAbs involved use methylene blue (MB)-conjugated aptamer as affinity element with ferrocene (Fc) via boronate crosslinking, in which MB-derived peak current was used reference signal, Fc tag output signal. As each mAb carries diol sites site-specific tags, crosslinking enabled detection, cost-effective quite simple operation. In presence bevacizumab (BevMab) target, resulting signal (i.e., IFc/IMB value) exhibited a good linear response over range 0.025-2.5 μg/mL, limit (LOD) 6.5 ng/mL. Results indicated that aptamer-based recognition endowed high selectivity, while readout satisfactory reproducibility robustness. Moreover, applicable serum samples. together, holds promise

Язык: Английский

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Self-Assembly of Epitope-Tagged Proteins and Antibodies for Delivering Biologics to Antigen Presenting Cells

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 33 - 38

Опубликована: Дек. 26, 2023

Inspired by the immune system's own strategy for macrophage activation, we describe here a simple self-assembly generating artificial complexes. The built-in recognition domains in antibody, viz. Fab and Fc domains, are judiciously leveraged cargo conjugation to generate nanoassembly targeting, respectively. A responsive linker is engineered into releasing protein inside macrophages, while ensuring stability during delivery. design principles versatile be applicable range of biologics, from small toxins large enzymes, with high loading capacity. This platform has potential delivering biologics cells implications immunotherapy.

Язык: Английский

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Development and Characterization of a Portable Flow Microreactor for Enhanced Bioconjugation Applications

Organic Process Research & Development, Год журнала: 2024, Номер 28(5), С. 1806 - 1813

Опубликована: Янв. 4, 2024

The reliance of pharmaceutical production on batch reactors dating back to the 20th century has exposed vulnerabilities in supply chains essential medicines, which were exacerbated by recent global challenges such as COVID-19 pandemic and geopolitical tensions. Modern alternatives flow microreactors (FMRs) promise streamlined chemical small channels, enabling precise local with advantages efficiency, environmental friendliness, potential cost reduction. In particular, field bioconjugate synthesis expanded rapidly alongside traditional small-molecule drugs. This study describes development optimization a Portable FMR system designed fit size constraints suitcase. was successfully tuned withstand practical applications, performance stabilized using feedback mechanism based actual measurements relative pressure (or viscosity). mixing capability verified Villermaux–Dushman reaction. Bioconjugate synthesis, exemplified PEGylation interleukin-6, showcased successful mono-PEGylation while reducing aggregation rates. Additionally, antibody–drug conjugates efficiently accomplished tandem-mode reactor system, highlighting advancements this field. To best our knowledge, is first report suitcase-sized device syntheses.

Язык: Английский

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Crab-shaped DNA tetrahedral nanomachine for silencing undruggable mRNA targets in prostate cancer

Nano Today, Год журнала: 2024, Номер 55, С. 102187 - 102187

Опубликована: Фев. 2, 2024

Cancer-associated gene fusions and mutations have emerged as a promising wellspring of therapeutic neoantigens. However, the lack precise expeditious drug design pipeline has unfortunately missed opportunity for timely treatment. Due to intricate arbitrary nature these fusions, navigating terrain 3D protein structures presents additional challenges. Despite significant advancements in targeted therapy, there are still number targets that cannot be effectively targeted, hindering further efficacy. Moreover, conditional efficacy RNA interference through siRNA is compromised by off-target phenomena, leading associated toxic side effects. To address limitations, we developed meticulously engineered DNA nanostructure form captivating crab-shaped tetrahedron. This not only ensures efficient with mRNA, but also facilitates ease rapidity synthesis. Additionally, it demonstrates an unprecedented ability suppress expression previously considered "undruggable", which crucial therapies. Through vivo experimentation within murine prostate cancer model, shown effectiveness overcoming resistance, thus clearly displaying its substantial potential clinical translation applications.

Язык: Английский

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Peptide and Protein Cysteine Modification Enabled by Hydrosulfuration of Ynamide

ACS Central Science, Год журнала: 2024, Номер 10(9), С. 1742 - 1754

Опубликована: Авг. 21, 2024

Efficient functionalization of peptides and proteins has widespread applications in chemical biology drug discovery. However, the chemoselective site-selective modification remains a daunting task. Herein, highly efficient chemo-, regio-, stereoselective hydrosulfuration ynamide was identified as an method for precise by uniquely targeting thiol group cysteine (Cys) residues. This novel could be facilely operated aqueous buffer fully compatible with wide range proteins, including small model large full-length antibodies, without compromising their integrity functions. Importantly, this reaction provides Z-isomer corresponding conjugates exclusively superior stability, offering approach to peptide protein therapeutics. The potential application further exemplified Cys-bioconjugation variety ynamide-bearing functional molecules such molecule drugs, fluorescent/affinity tags, PEG polymers. It also proved redox proteomic analysis through Cys-alkenylation. Overall, study bioorthogonal tool Cys-specific functionalization, which will find broad synthesis peptide/protein conjugates.

Язык: Английский

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