Mitochondria are the primary sites for ATP synthesis and free radical generation in organisms. Abnormal mitochondrial metabolism contributes to many diseases, including obesity, diabetes and cancer. UCP2 is an ion/anion transporter located in mitochondrial inner membrane, and has a crucial role in regulating oxidative stress, cellular metabolism, cell proliferation and cell death. Polymorphisms of the UCP2 gene have been associated with diabetes and obesity because UCP2 is involved in energy expenditure and insulin secretion. Moreover, UCP2 gene expression is often amplified in cancers, and increased UCP2 expression contributes to cancer growth, cancer metabolism, anti‐apoptosis and drug resistance. The present review summarizes the latest findings of UCP2 with respect to obesity, diabetes and cancer.
Background: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. Purpose: We proposed a facile "in situ drug conjugation-induced self-assembly" strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. Methods: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. Results: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. Conclusion: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.
Natrium superionic conductor (NASICON) solid electrolyte has been attracting wide attention due to its high ionic conductivity, low cost, and environmental friendliness. In this work, the chemical stability of the NASICON solid electrolyte with the composition of Na3Zr2Si2PO12 was evaluated in acidic solutions with different pH values, and the corrosion mechanism of the NASICON solid electrolyte was revealed at the multiscale level. Variations in bulk impedance, grain boundary impedance, and surface crack impedance with immersion time were determined by an AC impedance method. Comprehensive studies upon scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) etching, X-ray diffraction (XRD), and Raman spectroscopy, the morphological transformation, degradation limit depth, Cl– penetration effect, and proton exchange between H3O+ and Na+ were examined ranging from macro- and meso- to microscales, respectively. With the decrease of the pH of the solution, the exchange rate between H3O+ and Na+ protons increases. The lack of Na+ within the crystallographic lattice leads to the shrinkage of phosphorus–oxygen tetrahedra, which is the main reason for the decrease of unit cell volume, grain refinement, and surface cracks gradually. This work features multiscale characterizations of crystal structure, grain boundaries, surface morphology changes, and Na+ transport, which deepens our physicochemical understanding of solid electrolytes with high chemical stability.
Increasing the expression of cyclin-cyclin-dependent kinase inhibitors (cyclin-CDK) using small molecule inhibitors is a therapeutic strategy used to suppress cancer cell growth. Decorin (DCN), a functional component of the extracellular matrix, has been implicated in the suppression of cell proliferation by upregulating p21, a cyclin-CDK inhibitor. The purpose of this study was to examine the effect of recombinant decorin on the reactivation of p57KIP2, whose expression is silenced in hepatocellular carcinoma (HCC). Cell viability assay, cell cycle analysis, apoptosis assay and quantitative real time-PCR experiments were performed in three groups of HepG2 human cells: Uninfected HepG2 cells (control group), pcDNA3.1 vector-infected HepG2 cells (pcDNA3.1 group) and pcDNA3.1-DCN-infected HepG2 cells (pcDNA3.1‑DCN group). Our results revealed that recombinant human decorin inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis by increasing the expression of caspase-3 in the pcDNA3.1-DCN group. The expression of p57KIP2 mRNA in the pcDNA3.1-DCN group was higher than in the pcDNA3.1 and control groups (P<0.05); however, there was no statistically significant difference between the control and pcDNA3.1 groups (P>0.05). In conclusion, recombinant human decorin reactivated p57KIP2 expression in HepG2 cells. As the expression level of p57KIP2 is downregulated in HCC, our finding may serve as a basis for the therapy and prognosis of HCC, although further studies are required.
Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.
The aim of the present study was to characterize the expression of uncoupling protein 2 (UCP2) in melanoma and to study the potential mechanisms underlying the involvement of UCP2 in melanomagenesis using human melanoma cell lines. The expression of UCP2 was evaluated in specimens from normal control subjects, patients with compound nevus, and patients with cutaneous and mucosal melanoma. Stable knockdown of UCP2 was achieved in human melanoma cell lines, which were used to examine whether UCP2 knockdown affects the mitochondrial membrane potential and intracellular levels of ATP, reactive oxygen species and lactate. Cell proliferation, invasion, spheroid formation and cisplatin sensitivity were also evaluated in the UCP2 knockdown cells. Finally, the effects of UCP2 knockdown on the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways, which are important oncogenic pathways during melanomagenesis, were evaluated. Relatively high expression of UCP2 was detected in human melanoma specimens, which was correlated with Clark level and Breslow thickness. Knockdown of UCP2 suppressed cell proliferation, invasion and spheroid formation, and increased the sensitivity of melanoma cells to cisplatin. Furthermore, the UCP2 knockdown cells exhibited inhibition of Akt/mTOR signaling and ERK activation. Therefore, human melanoma tissues exhibit relatively high UCP2 expression, which may be implicated in the mechanisms underlying tumor progression. The potential role of UCP2 in melanomagenesis may involve enhancing the Akt/mTOR and mitogen-activated protein kinase/ERK pathways.
Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, and their physicochemical characteristics were analyzed. Compared with template peptide ToAP2, the modified peptides had much shorter length, lower molecular weight but significantly greater stability, which in return resulted in increases in the aliphatic index, hydrophilicity, and protein binding ability. Here, we show that the three derived peptides inhibit the growth of Sporothrix globosa, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of S. globosa and enhanced apoptosis, which was evidenced by the upregulation of apoptosis-related protein caspase-3. The scanning electron microscopy analysis revealed deformation and rupture of S. globosa. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in S. globosa upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the in vivo study, we further demonstrated that ToAP2D inhibited the S. globosa infection of mice footpads, and its efficiency was nearly comparable to itraconazole. In summary, our results suggest that antimicrobial peptide ToAP2D has the potential for sporotrichosis therapy.
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