ABSTRACT
Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer [Apt]-conjugated chitosan nanoparticle [NP] for targeted co-delivery of insulin-like growth factor receptor 1 [IGF-1R] Silencer siRNA and docetaxel [DTX] to SKBR3 cells
Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells
Results:The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential [12-14 mV]. siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 [STAT3], matrix metalloproteinases [MMP9], and vascular growth factor [VEGF]
Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug
ABSTRACT
OBJECTIVE@#To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells.@*METHODS@#In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens.@*RESULTS@#Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells.@*CONCLUSIONS@#Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.
ABSTRACT
Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations (2, 10 and 20 μg/mL). B cell activation was assessed through expression of CD69 molecule by flow cytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α (P < 0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.
ABSTRACT
Multiple sclerosis [MS] is an autoimmune disease of the central nervous system [CNS]. The major pathological outcomes of the disease are the loss of blood-brain barrier [BBB] integrity and the development of reactive astrogliosis and MS plaque. For the disease to occur, the non-resident cells must enter into the immune-privileged CNS through a breach in the relatively impermeable BBB. It has been demonstrated that matrix metalloproteinases [MMPs] play an important role in the immunopathogenesis of MS, in part through the disruption of the BBB and the recruitment of inflammatory cells into the CNS. Moreover, MMPs can also enhance the cleavage of myelin basic protein [MBP] and the demyelination process. Regarding the growing data on the roles of MMPs and their tissue inhibitors [TIMPs] in the pathogenesis of MS, this review discusses the role of different types of MMPs, including MMP-2, -3, -7, -9, -12 and -25, in the immunopathogenesis and treatment of MS