Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy in humans and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy.
Timely lysosome escape is of paramount importance for endocytosed nanomedicines to avoid premature degradation under the acidic and hydrolytic conditions in lysosomes. Herein, we report an exciting finding that phenylboronic acid (PBA) modification can greatly facilitate the lysosome escape of cylindrical polymer brushes (CPBs). On the basis of our experimental results, we speculate that the mechanism is associated with the specific interactions of the PBA groups with lysosomal membrane proteins and hot shock proteins. The featured advantage of the PBA modification over the known lysosome escape strategies is that it does not cause significant adverse effects on the properties of the CPBs; on the contrary, it enhances remarkably their tumor accumulation and penetration. Furthermore, doxorubicin was conjugated to the PBA-modified CPBs with a drug loading content larger than 20%. This CPBs-based prodrug could eradicate the tumors established in mice by multiple intravenous administrations. This work provides a novel strategy for facilitating the lysosome escape of nanomaterials and demonstrates that PBA modification is an effective way to improve the overall properties of nanomedicines including the tumor therapeutic efficacy.
Blood–brain barrier (BBB)‐crossing ability of drugs is of paramount importance for the treatments of central nervous system diseases. However, the known methods for drug transport across the BBB are generally complicated and inefficient, and exhibit serious side effects in some cases. Herein, we report an exciting finding that fluorination and betaine modification can significantly augment the BBB‐crossing ability of cylindrical polymer brushes (CPBs), which was demonstrated by the comparison with the CPBs modified with alkyl and poly(ethylene glycol) chains, respectively. We surmise that fluorination enhances the BBB penetration of the CPBs by increasing the hydrophobicity and reducing the surface energy, and betaine medication achieves this function via a betaine transporter BGT1 expressed on brain capillaries. By means of an in vitro BBB model, we demonstrated that the CPBs penetrated the BBB through transendothelial transport. This work provides a novel strategy for enhancing the BBB‐crossing ability of nanomaterials.
Fertility is a significant concern among adolescent and young adult (AYA) cancer survivors and their caregivers, especially after their completion of cancer treatment programs. Concerns about fertility affect not only cancer patients' psychological well-being, but also all aspects of their medical treatments, including treatment protocol, decision-making, and treatment adherence. In this scoping review, the PubMed, CINAHL, Web of Science, Embase, CNKI, and Wanfang electronic databases were searched according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. The searches identified 669 articles, 54 of which met the inclusion criteria. Reviewers extracted the data on the study characteristics, measurements, positive factors, negative factors, and additional themes. This scoping review included studies from 10 countries. Most studies were quantitative using a cross-sectional design. The prevalence of reproductive concerns among AYA cancer survivors ranged from 44% to 86%, and 28% to 44% of the survivors experienced moderate to severe concerns. The specific implementation of fertility consultation, including timing, consult frequency, and content, deserves ongoing exploration.
Well-designed second near-infrared (NIR-II) fluorophores are promising in optical diagnosis and therapy of tumors. In this work, we synthesized a donor−acceptor−donor (D−A−D) NIR-II fluorophore named BBTD-BET with dithienylethene as an electron donor and benzobisthiadiazole as an electron acceptor. To the best of our knowledge, this is the first report of using dithienylethene, a typical photochromic molecule, as a building block for NIR-II fluorophores. We studied the geometrical configuration, electronic state, and optical properties of BBTD-BET by both theoretical and experimental means. BBTD-BET had absorption and emission in the NIR-I and NIR-II spectral ranges, respectively. Using PEGylated BBTD-BET as a theranostic agent, we achieved NIR-II fluorescence/photoacoustic (PA) dual-modal imaging and attained high imaging resolution, desired signal-to-noise ratio, and excellent photothermal therapy (PTT) efficacy. After one PTT treatment, the tumors established in mice were eradicated. This work provides a novel organic conjugated molecule integrating NIR-II/PA dual-modal imaging and PTT functionalities that is very promising in the theranostic of tumors.
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