Although nanomedicines can passively target tumor through the enhanced permeability and retention (EPR) effect, their distribution and retention are limited by complex tumor microenvironment. Herein, a self-delivery supramolecular nanoplatform with shape-transforming capacity (Ce6-CD/ Fc-pep-PEG) is constructed by the host-guest interaction between chlorin e6-conjugated β-cyclodextrin (Ce6-CD) and ferrocene-modified FFVLG 3 C-PEG conjugates (Fc-pep-PEG). Following passive accumulation mediated by the EPR effect, hydrophobic Fc is oxidized to water-soluble Fc + by endogenous ROS in tumor sites. The resulting Fc + -pep-PEG fragment dissociated from Ce6-CD and recombined to nanofibers through the intermolecular hydrogen bonds among FFVLG 3 C peptide chains, thus enhancing the retention. Meanwhile, the Ce6-CD fragment still maintained the form of spherical micelles with a relatively smaller size to penetrate into the deep tumor regions. Moreover, the cascade Fenton reaction catalyzed by Fc generated •OH and O 2 to relieve hypoxia and amplify PDT efficiency. In turn, ROS generated by PDT promoted shape-transformation and continuous occurrence of Fenton reaction. In vitro and in vivo evaluations verify that through the positive feedback loop, Ce6-CD/ Fc-pep-PEG can induce a potent antitumor immune response and achieve ROS-potentiated elimination of primary tumor and bone metastasis.
Cigarette smoke (CS) increases up-regulation of TLR4-mediated signaling and induces TLR4-dependent inflammation in lungs. CS exposure–induced HMGB1 translocation and release of HMGB1 controls CS-induced inflammatory response. MGB1 induces TLR4-mediated proinflammatory cytokine production and activates NF-κB and JNK/p38 pathways.
Emerging evidence has shown the age-related changes in gut microbiota, but few studies were conducted to explore the effects of age on the gut microbiota in patients with major depressive disorder (MDD). This study was performed to identify the age-specific differential gut microbiota in MDD patients. In total, 70 MDD patients and 71 healthy controls (HCs) were recruited and divided into two groups: young group (age 18-29 years) and middle-aged group (age 30-59 years). The 16S rRNA gene sequences were extracted from the collected fecal samples. Finally, we found that the relative abundances of Firmicutes and Bacteroidetes were significantly decreased and increased, respectively, in young MDD patients as compared with young HCs, and the relative abundances of Bacteroidetes and Actinobacteria were significantly decreased and increased, respectively, in middle-aged MDD patients as compared with middle-aged HCs. Meanwhile, six and 25 differentially abundant bacterial taxa responsible for the differences between MDD patients (young and middle-aged, respectively) and their respective HCs were identified. Our results demonstrated that there were age-specific differential changes on gut microbiota composition in patients with MDD. Our findings would provide a novel perspective to uncover the pathogenesis underlying MDD.
The platelet-derived growth factor (PDGF) signaling pathway has been found to play important roles in the development and progression of human cancers by regulating the processes of cell proliferation, apoptosis, migration, invasion, metastasis, and the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Moreover, PDGF signaling has also been found to alter the expression profile of miRNAs, leading to the reversal of EMT phenotype. Although the role of miRNAs in cancer has been documented, there are very few studies documenting the cellular consequences of targeted re-expression of specific miRNAs. Therefore, we investigated whether the treatment of human pancreatic cancer cells with PDGF could alter the expression profile of miRNAs, and we also assessed the cellular consequences. Our study demonstrates that miR-221 is essential for the PDGF-mediated EMT phenotype, migration, and growth of pancreatic cancer cells. Down-regulation of TRPS1 by miR-221 is critical for PDGF-mediated acquisition of the EMT phenotype. Additionally, the PDGF-dependent increase in cell proliferation appears to be mediated by inhibition of a specific target of miR-221 and down-regulation of p27Kip1.
We applied an atmospheric pressure differential mobility analyzer (DMA) coupled to a time-of-flight mass spectrometer to examine the stability, mass-mobility relationship, and extent of hydration of dimethylamine-sulfuric acid cluster ions, which are of relevance to nucleation in ambient air. Cluster ions were generated by electrospray ionization and were of the form: [H((CH3)2NH)x(H2SO4)y](+) and [(HSO4)((CH3)2NH)x(H2SO4)y](-), where 4 ≤ x ≤ 8, and 5 ≤ y ≤ 12. Under dry conditions, we find that positively charged cluster ions dissociated via loss of both multiple dimethylamine and sulfuric acid molecules after mobility analysis but prior to mass analysis, and few parent ions were detected in the mass spectrometer. Dissociation also occurred for negative ions, but to a lesser extent than for positive ions for the same mass spectrometer inlet conditions. Under humidified conditions (relative humidities up to 30% in the DMA), positively charged cluster ion dissociation in the mass spectrometer inlet was mitigated and occurred primarily by H2SO4 loss from ions containing excess acid molecules. DMA measurements were used to infer collision cross sections (CCSs) for all identifiable cluster ions. Stokes-Millikan equation and diffuse/inelastic gas molecule scattering predicted CCSs overestimate measured CCSs by more than 15%, while elastic-specular collision model predictions are in good agreement with measurements. Finally, cluster ion hydration was examined by monitoring changes in CCSs with increasing relative humidity. All examined cluster ions showed a modest amount of water molecule adsorption, with percentage increases in CCS smaller than 10%. The extent of hydration correlates directly with cluster ion acidity for positive ions.
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