ABSTRACT
OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.
Subject(s)
Arthritis, Rheumatoid , Cell Movement , Cell Proliferation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice, Inbred DBA , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Arthritis, Rheumatoid/therapy , Arthritis, Rheumatoid/metabolism , Mice , Mesenchymal Stem Cells/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Mesenchymal Stem Cell Transplantation/methods , Phosphatidylinositol 3-Kinases/metabolism , Humans , Interferon-gamma/metabolism , Umbilical Cord/cytology , Arthritis, Experimental/therapy , Arthritis, Experimental/metabolism , MaleABSTRACT
This study presents an efficient strategy for constructing 1,2-difunctionalized quinoline derivatives via the multicomponent cascade coupling of N-heteroaromatics with alkyl halides and different terminal alkynes. This reaction was achieved through sequential functionalization at the one- and two-positions of quinolines, which displayed a broad substrate scope, environmental friendliness, excellent functional group tolerance, high atom efficiency, and chemoselectivity. The multicomponent coupling involved the abnormal construction of new C-N, CâC, and CâO bonds in one pot. The applicability of this method was further demonstrated by the late-stage functionalization of complex drug molecules under the established conditions.
ABSTRACT
We herein describe a practical direct amination of phenols through a palladium-catalyzed hydrogen-transfer-mediated activation method to synthesize the secondary and tertiary amines. In this conversion, environmentally friendly water and inexpensive ammonium formate were used as solvent and reductant, respectively. A range of amines, including aliphatic amines, aniline, secondary amines, and diamines, could be coupled effectively by this method to achieve mono/dual amination and cyclization of phenols. This study not only provides a green and mild strategy for the synthesis of secondary and tertiary naphthylamines but also expands the synthesis of chloroquine in organic chemistry.
