Search

Background: IMD-0354 is a kind of hydrophobic small molecule inhibitor of IKKβ, which can effectively inhibit the NF-κB pathway. Besides, IMD-0354 can inhibit a variety of tumor cells in culture, but its poor water solubility and low utilization have limited its clinical application. Methods: In this study, IMD-0354 was synthesized through esterifying the folate acid (FA) conjugated dextran (Dex) as well as the lauryl alcohol (LA). Results:The particle (IMD/FA-Dex-LA) size was 212.13±10.62nm, the encapsulation efficiency was 89.27±6.51%, and the drug loading was 4.25±0.42%. Cell viability studies indicated that the IMD/FA-Dex-LA effectively inhibited survival of B16F10 cells in culture. Meanwhile, Western Blotting results showed that the nuclear transport of NF-κB was reduced after blocking the IKK pathway, which would thereby suppress melanoma cell division and proliferation. Moreover, subcutaneous tumor implantation experiment revealed that, the drug-loading complex had an obvious effect on suppressing melanoma cells. Findings of this study demonstrated that the IMD-0354 loaded FA-Dex-LA was more effective than IMD-0354 alone. Conclusion: In summary, FA-Dex-LA has been successfully synthesized in this study, which can serve as a carrier for hydrophobic drug. Further, it is believed the FA-Dex-LA can potentially applied in cancer treatment.

Can Liu,1 Huiqing Xie,2 Jingang Yu,3 Xiaoqing Chen,3 Shijie Tang,4 Lichun Sun,5 Xiang Chen,6 Defei Peng,7,* Xiangyan Zhang,8,* Jianda Zhou1,* 1Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China; 2Department of Rehabilitation, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China; 3School of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410013, China; 4Cleft Lip and Palate Treatment Center, The Second Affliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515041,China; 5Department of Medicine, School of Medicine, Tulane Health Sciences Center, New Orleans, LA, USA; 6Department of Dermatology, The Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; 7Department of Burns and Plastic Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, China; 8Department of Nursing, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China *These authors contributed equally to this work Background: Nowadays, the combination of microRNA (miR) is attracting increased attention in clinical cancer trials. However, the clinical use of miR is highly limited because of certain properties such as instability, low-specificity distribution, and metabolic toxicity. Methods: In order to improve the anti-tumor efficacy and reduce the side effects of miR in treating melanoma, a combination of graphene oxide (GO), chitosan (CS), and a cellular penetrating peptide, MPG, was prepared with solid dispersion method in this research. The research has analyzed the specific components of nano drug-loading complexes GO-CS and GO-CS-MPG through characterization research and confirmed the bio-safety of the carrier material GO-CS-MPG. Results: The GO-CS-MPG-miR33a/miR199a nano drug-loading complex was successfully constructed and its medical effectiveness was verified. Through the subcutaneous tumor implantation experiment, an evident effect of the drug-loading complex in inhibiting melanoma cells was proven. Conclusion: Results suggest that GO-CS-MPG may have potential applications in melanoma therapy. Keywords: melanoma, graphene oxide, chitosan, cellular penetrating peptide, microRNA

Background: Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated. Object: To determine miR-33's roles in melanoma and confirm whether HIF-1α is a direct target gene of miR-33a. Methods: First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1α is a direct target gene of miR-33a. Results: MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1α is a direct target gene of miR-33a. Conclusion: The newly identified miR-33a/HIF-1α axis might provide a new strategy for the treatment of melanoma.

In this paper, orthogonal projection method OPM is proposed to calculate a few eigenpair derivatives of large real symmetric matrices, if the eigenvalues are simple. By projecting large matrix-valued functions to small subspaces dependent on parameter, linear systems of equations for eigenpair derivatives are greatly reduced from the original matrix size. Error bounds on the eigenpairs and their derivatives computed by OPM are established with trivial conditions, which is one of the main contributions of this paper. It is shown that if the deviations from small subspaces to invariant subspace corresponding to the desired eigenvalues and the derivatives of residuals of the computed eigenpairs tend to zero, then the computed eigenpairs and their derivatives converge to the desired eigenpairs and their derivatives. Next, a strategy to generate small subspaces in OPM is given based on the implicitly restarted Lanczos process IRLP for symmetric matrix-valued function. Convergence of the IRLP-based OPM is analysed in detail, which is the main emphasis of this method. Finally some numerical experiments are reported to show the efficiency of our method.

New methods are presented for computing the derivatives of multiple eigenvalues and the corresponding eigenvectors of unsymmetrical quadratic eigenvalue problems. The expressions of eigenpair derivatives are derived in terms of the eigenvalues and eigenvectors of quadratic eigenvalue problems, and the use of rather undesirable state-space representation is avoided. Hence the cost of computation is greatly reduced. The proposed methods are valid for both the case of distinct eigenvalue derivatives and the case of equal eigenvalue derivatives. Numerical results show that the proposed methods are efficient.