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mtDNA từ thực vật y học qua nanovesicles kích thích con đường cGAS-STING để tái tạo đại thực bào liên quan đến khối u cho sự thoái lui của khối u
Tóm tắt
Nanovesicles từ thực vật (PDNVs) đã được đề xuất như một cơ chế chính cho sự tương tác và giao tiếp giữa các vương quốc, nhưng các thành phần tác động được bao gói trong các vesicles và các cơ chế liên quan vẫn còn phần lớn chưa được biết đến. Cây thuốc Artemisia annua được biết đến như một tác nhân chống sốt rét, đồng thời thể hiện một phạm vi hoạt động sinh học rộng lớn bao gồm các tính chất điều hòa miễn dịch và chống khối u với các cơ chế cần được làm rõ hơn. Trong nghiên cứu này, chúng tôi đã tách và tinh chế các hạt giống như exosome từ A. annua, được đặc trưng bởi hình dạng quy mô nano và được bao bọc trong màng, do đó được gọi là nanovesicles từ artemisia (ADNVs). Đáng chú ý, các vesicles này đã chứng minh khả năng ức chế sự phát triển của khối u và tăng cường miễn dịch chống khối u trong mô hình chuột mắc ung thư phổi, chủ yếu thông qua việc tái cấu trúc vi mô khối u và tái lập trình các đại thực bào liên quan đến khối u (TAMs). Chúng tôi đã xác định DNA ti thể từ thực vật (mtDNA), khi được hấp thu vào TAMs qua các vesicles, như một phân tử tác động chính để kích hoạt con đường cGAS-STING, dẫn đến sự chuyển biến của các đại thực bào pro-tumor sang kiểu hình chống khối u. Hơn nữa, dữ liệu của chúng tôi cho thấy việc sử dụng ADNVs đã cải thiện đáng kể hiệu quả của thuốc ức chế PD-L1, một loại thuốc ức chế điểm kiểm soát miễn dịch điển hình, ở chuột mang khối u. Tóm lại, nghiên cứu hiện tại, lần đầu tiên theo hiểu biết của chúng tôi, đã giải mã một sự tương tác giữa các vương quốc trong đó mtDNA từ thực vật y học, qua nanovesicles, kích thích tín hiệu miễn dịch trong các tế bào miễn dịch của động vật có vú nhằm thiết lập lại miễn dịch chống khối u và thúc đẩy việc tiêu diệt khối u.
Từ khóa
#nanovesicles #mtDNA #cGAS-STING #đại thực bào #ung thưTài liệu tham khảo
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