ABSTRACT
Polyurethane materials have good biocompatibility, blood compatibility, mechanical properties, fatigue resistance and processability, and have always been highly valued as medical materials. Polyurethane fibers prepared by electrostatic spinning technology can better mimic the structure of natural extracellular matrices (ECMs), and seed cells can adhere and proliferate better to meet the requirements of tissue repair and reconstruction. The purpose of this review is to present the research progress of electrostatically spun polyurethane fibers in bone tissue engineering, skin tissue engineering, neural tissue engineering, vascular tissue engineering and cardiac tissue engineering, so that researchers can understand the practical applications of electrostatically spun polyurethane fibers in tissue engineering and regenerative medicine.
Subject(s)
Biocompatible Materials , Polyurethanes , Tissue Engineering , Tissue Engineering/methods , Polyurethanes/chemistry , Biocompatible Materials/chemistry , Humans , Tissue Scaffolds/chemistry , Regenerative Medicine , Extracellular Matrix , Bone and Bones , Skin/cytologyABSTRACT
Oxaliplatin-based chemotherapy is the current standard of care in adjuvant therapy for advanced colorectal cancer (CRC). But acquired resistance to oxaliplatin eventually occurs and becoming a major cause of treatment failure. Thus, there is an unmet need for developing new chemical entities (NCE) as new therapeutic candidates to target chemotherapy-resistant CRC. Novel Pt(II) complexes were designed and synthesized as cationic monofunctional oxaliplatin derivatives for DNA platination-mediated tumor targeting. The complex Ph-glu-Oxa sharing the same chelating ligand of diaminocyclohexane (DACH) with oxaliplatin but is equally potent in inhibiting the proliferation of HT29 colon cancer cells and its oxaliplatin-resistant phenotype of HT29/Oxa. The in vivo therapeutic potential of Ph-glu-Oxa was confirmed in oxaliplatin-resistant xenograft model demonstrating the reversibility of the drug resistance by the new complex and the efficacy was associated with the unimpaired high intracellular drug accumulation in HT29/Oxa. Guanosine-5'-monophosphate (5'-GMP) reactivity, double-strand plasmid DNA cleavage, DNA-intercalated ethidium bromide (EB) fluorescence quenching and atomic force microscopy (AFM)-mediated DNA denaturing studies revealed that Ph-glu-Oxa was intrinsically active as DNA-targeting agent. The diminished susceptibility of the complex to glutathione (GSH)-mediated detoxification, which confers high intracellular accumulation of the drug molecule may play a key role in maintaining cytotoxicity and counteracting oxaliplatin drug resistance.
Subject(s)
Antineoplastic Agents/chemistry , Coordination Complexes/chemistry , Drug Resistance, Neoplasm/drug effects , Oxaliplatin/chemistry , Platinum/chemistry , Triazoles/chemistry , Animals , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Binding Sites , Cell Line, Tumor , Cell Survival/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Coordination Complexes/metabolism , Coordination Complexes/pharmacology , DNA/chemistry , DNA/metabolism , Drug Design , Drug Screening Assays, Antitumor , Glutathione/chemistry , Humans , Mice , Mice, Nude , Molecular Dynamics Simulation , Nucleic Acid Conformation , Oxaliplatin/pharmacologyABSTRACT
Demand for biliary stents has expanded with the increasing incidence of biliary disease. The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures. However, these stents are nondegradable and prone to restenosis. Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis. To overcome these shortcomings, improvements were made to the materials and surfaces used for the stents. First, this paper reviews the advantages and limitations of nondegradable stents. Second, emphasis is placed on biodegradable polymer and biodegradable metal stents, along with functional coatings. This also encompasses tissue engineering & 3D-printed stents were highlighted. Finally, the future perspectives of biliary stents, including pro-epithelialization coatings, multifunctional coated stents, biodegradable shape memory stents, and 4D bioprinting, were discussed.
ABSTRACT
AIMS: Nutrition and inflammation status play a vital role in the prognosis of patients with heart failure (HF). This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a novel composite indicator of inflammation and nutrition, and short-term mortality among critically ill patients with HF. METHODS: This retrospective study included 548 critically ill patients with HF from the MIMIC-IV database. ALI was computed using body mass index, serum albumin and neutrophil-lymphocyte ratio. The primary endpoint was all-cause in-hospital mortality, and the secondary endpoint was 90 day mortality. Kaplan-Meier survival curve analysis with long-rank test and Cox proportional hazards regression models were employed to assess the relationship between baseline ALI and short-term mortality risk. The incremental predictive ability of ALI was evaluated by C-statistic, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The average age of 548 patients was 72.2 (61.9, 82.1) years, with 60% being male. Sixty-three patients (11.5%) died in the hospital, and 114 patients (20.8%) died within 90 days of intensive care unit admission. The Kaplan-Meier analysis revealed that the cumulative incidences of both in-hospital and 90 day mortality were significantly higher in patients with lower ALI (log-rank test, in-hospital mortality: P < 0.001; 90 day mortality: P < 0.001). The adjusted Cox proportional hazard model revealed that ALI was inversely associated with both in-hospital and 90 day mortality after adjusting for confounders [hazard ratio (HR) (95% confidence interval) (CI): 0.97 (0.94, 0.99), P = 0.035; HR (95% CI): 0.62 (0.39, 0.99), P = 0.046]. A linear relationship was observed between ALI and in-hospital mortality (P for non-linearity = 0.211). The addition of ALI significantly improved the prognostic ability of GWTG-HF score in the in-hospital mortality [C-statistic improved from 0.62 to 0.68, P = 0.001; continuous NRI (95% CI): 0.44 (0.20, 0.67), P < 0.001; IDI (95% CI): 0.03 (0.01, 0.04), P < 0.001] and 90 day mortality [C-statistic improved from 0.63 to 0.70, P < 0.001; continuous NRI (95% CI): 0.31 (0.11, 0.50), P = 0.002; IDI (95% CI): 0.01 (0.00, 0.02), P = 0.034]. Subgroup analysis revealed stronger correlations between ALI and in-hospital mortality in males and patients aged over 65 years (interaction P = 0.031 and 0.010, respectively). The C-statistic of in-hospital mortality in patients over 65 years was 0.66 (95% CI: 0.58, 0.74). CONCLUSIONS: ALI at baseline can independently predict the risk of short-term mortality in critically ill patients with HF, with lower ALI significantly associated with higher mortality. Further large prospective research with extended follow-up periods is necessary to validate the findings of this study.
ABSTRACT
Oxaliplatin-based chemotherapy has proven to be one of the most effective treatments for advanced or metastatic colorectal cancer. However, increasing clinical resistance to oxaliplatin poses unprecedented challenges for both patients and clinicians. Despite extensive efforts to combat this issue, to date, no new molecules have been discovered that can successfully replace oxaliplatin. With the aim of developing a new generation of Pt(II)-based anticancer agents in response to the challenges of oxaliplatin-induced drug resistance, we performed a systematic screening of new Pt(II)-complexes with a quantitative structure-activity relationship (QSAR) study based on their antiresistance activity against oxaliplatin-resistant colon cancer cells. The results revealed that both the structure and chirality of the chelating ligand had a significant impact on the antiresistance properties of the Pt(II)-complexes. Our study culminated in the identification of chiral R-binaphthyldiamine-ligated Pt(II)-malonatoglycoconjugates that can completely counteract oxaliplatin resistance with excellent in vitro and in vivo potency.
Subject(s)
Antineoplastic Agents , Drug Resistance, Neoplasm , Oxaliplatin , Quantitative Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Humans , Drug Resistance, Neoplasm/drug effects , Oxaliplatin/pharmacology , Animals , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Cell Line, Tumor , Drug Discovery , Mice , Drug Screening Assays, AntitumorABSTRACT
The biomedical application of corannulene π-bowls is historically limited by low solubility and bioavailability despite the potential in their unique electronic properties for new functional materials. Herein, the unexpected role and molecular mechanism of Corranulene π-bowls are uncovered in biomedical applications as an effective anticancer agent for Warburg effect mediated selective tumor targeting. The corannulene triazolyl monosaccharides Cor-sugars exhibit highly potent cytotoxicity against human cancer cells and effectively inhibit xenograft growth of hyperglycolytic tumors. Particularly, the galactose-conjugated Cor-gal exhibits superior in vivo anticancer efficacy in A549 tumor models with outstanding safety profile compared to doxorubicin. Moreover, the combined treatment of Cor-gal with immune checkpoint inhibitor results in an effective synergy in treating H460 human lung carcinoma. An uptake mechanism study reveals that Cor-sugars exploit tumor-specific glucose transporter glucose transporter 1 (GLUT1) for targeted cell delivery and intra-tumoral accumulation through the cancer-specific Warburg effect. Their significant anticancer activity is attributed to multiphasic DNA-binding and cell cycle alteration effects. This study uncovers new molecular properties of corannulene buckybowl and enabling their potential new applications in biomedical engineering.
Subject(s)
Antineoplastic Agents , Neoplasms , Polycyclic Aromatic Hydrocarbons , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Humans , Neoplasms/drug therapyABSTRACT
We report a non-antibody GLUT1 inhibitor probe NBDQ that is 30 times more sensitive than the traditional GLUT1 transportable tracer for cancer cell imaging and Warburg effect-based tumor detection. NBDQ reveals significant advantages in terms of tumor selectivity, fluorescence stability and in vivo biocompatibility in xenograft tumor imaging, including triple-negative breast cancer.