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1.
Pediatr Rheumatol Online J ; 18(1): 24, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183841

RESUMO

Kawasaki disease (KD) is an acute febrile multisystem vasculitis and has been recognized to be one of the most common causes of acquired heart disease in children. Although gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain are not uncommon in KD patients, KD with lower gastrointestinal bleeding is quite rare. Here, we describe a 3-year-old boy with typical KD who had lower gastrointestinal bleeding caused by rectal ulcers on the third day of aspirin therapy.

2.
J Pediatr Surg ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32164985

RESUMO

BACKGROUND: The optimal regimen for enteral nutritional support in the management of children with short bowel syndrome (SBS) is not well characterized. A high fat, enteral diet is theoretically beneficial due to increased caloric density and enhanced structural adaptation. We therefore sought to determine the long-term effects of a high fat diet (HFD) on liver injury, a common complication of SBS, compared to a standard chow (SC) diet. METHODS: Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6 mice underwent a sham operation or a 50% or 75% proximal small bowel resection (SBR). Mice in each group were then fed either a HFD (35% kcal fat) or SC (13% kcal fat). At post-operative week 15, markers of liver injury were quantified. RESULTS: Liver triglyceride levels were increased from 7- to 19-fold in mice on the HFD compared to mice fed SC in the sham, 50%, and 75% resection groups. Serum ALT (2.2-fold increase in 75% resected mice compared to sham controls) and AST (2.0- and 2.7-fold increases in 50% and 75% resected mice, respectively) levels as well as fibrotic liver staining were elevated only in resected mice fed a HFD. CONCLUSION: Long-term enteral feeding of HFD in our murine SBS model is associated with hepatic steatosis and liver injury. Our observation that liver steatosis and injury occur independent of parenteral nutrition suggests that enteral feeding composition and magnitude of intestinal loss may make a significant contribution to intestinal failure-associated liver disease.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32196846

RESUMO

Controlling the surface composition of shaped bimetallic nanoparticles could offer precise tunability of geometric and electronic surface structure for new nanocatalysts. To achieve this goal, we design a platform for studying the intermixing process in a shaped nanoparticle, using multilayered Pd-Ni-Pt core-shell nanocubes as precursors. We find that, under mild conditions, the intermixing between Ni and Pt could be tuned by changing layer thickness and number, triggering intermixing while preserving nanoparticle shape. Intermixing of the two metals is monitored using transmission electron microscopy. The surface structure evolution is characterized using electrochemical methanol oxidation. DFT calculations suggest that the low-temperature mixing is enhanced by shorter diffusion lengths and strain introduced by the layered structure. The platform and insights presented here represent an advance toward the realization of shape-controlled multimetallic nanoparticles tailored to each potential application.

4.
J Zhejiang Univ Sci B ; 21(2): 93-121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115909

RESUMO

Salinity affects more than 6% of the world's total land area, causing massive losses in crop yield. Salinity inhibits plant growth and development through osmotic and ionic stresses; however, some plants exhibit adaptations through osmotic regulation, exclusion, and translocation of accumulated Na+ or Cl-. Currently, there are no practical, economically viable methods for managing salinity, so the best practice is to grow crops with improved tolerance. Germination is the stage in a plant's life cycle most adversely affected by salinity. Barley, the fourth most important cereal crop in the world, has outstanding salinity tolerance, relative to other cereal crops. Here, we review the genetics of salinity tolerance in barley during germination by summarizing reported quantitative trait loci (QTLs) and functional genes. The homologs of candidate genes for salinity tolerance in Arabidopsis, soybean, maize, wheat, and rice have been blasted and mapped on the barley reference genome. The genetic diversity of three reported functional gene families for salt tolerance during barley germination, namely dehydration-responsive element-binding (DREB) protein, somatic embryogenesis receptor-like kinase and aquaporin genes, is discussed. While all three gene families show great diversity in most plant species, the DREB gene family is more diverse in barley than in wheat and rice. Further to this review, a convenient method for screening for salinity tolerance at germination is needed, and the mechanisms of action of the genes involved in salt tolerance need to be identified, validated, and transferred to commercial cultivars for field production in saline soil.

5.
Forensic Sci Int ; 309: 110195, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32120191

RESUMO

Traditional vehicle accident reconstructions do not take into account all existing uncertainties and may over- or under-estimate the injury risk. The objective of this study was to introduce a new uncertainty analysis method by applying Response Surface-Monte Carlo Methods (RS-MCM) to predict head injury risk in real electric two wheelers (ETW) to vehicle accidents. Vehicle impact velocity ranges in three detailed ETWs accidents (including video records and injury reports) were estimated using direct linear transformation (DLT) or video frame (VF) methods. A response surface methodology (RSM) was used to obtain an approximate model of the each real ETW accident, and a vehicle impact velocity distribution was estimated by applying the Monte Carlo Method (MCM) to the resulting model. If the velocity distribution was in agreement with the initial estimated velocity, the reconstruction quality was deemed acceptable. The injury severity was then assessed using the initial conditions resulting from the range of potential head impact conditions identified in the reconstruction activities. The identified head linear and angular impact velocities were input to finite element analyses to the THUMS Ver4.02 pedestrian head model and resulting in head injury criteria (HIC). The HIC values were further explored using the same RSM method used earlier to establish impact conditions. The distribution of reconstructed AIS levels show good agreement with the injury results from forensic reports. The results illustrated that the RS-MCM enriches the information for head trauma injury mechanisms caused by the vehicle collisions or ground impact.

6.
Food Chem ; 320: 126624, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32208181

RESUMO

A ratiometric fluorescence (FL) sensor was fabricated by coordinating 2, 6-pyridinedicarboxylic acid (DPA) sensitized Tb3+ (Tb-DPA) with NH2 and COOH on the surface of the N-doped carbon dots (N-CDs) for detecting Hg2+ in seafood. The sensor exhibited two FL emissions at 436 nm (N-CDs) as the response signal and at 543 nm (Tb-DPA) as the reference signal when excited at 290 nm. After adding Hg2+, the FL emission at 436 nm was significantly quenched and the FL emission at 543 nm was negligibly changed. The electron transfer (ET) between COO- of N-CDs and Hg2+ led to the FL quenching of N-CDs. The FL ratio (F436/F543) exhibited a good linear relationship in the Hg2+ concentrations of 1161.51 µM with a low limit of detection (LOD) of ~37 nM. The sensor presented high selectivity, satisfactory accuracy and precision toward Hg2+ in seafood with recoveries of 86.45-114.47% and RSDs of 0.20-1.92%.

7.
Anticancer Res ; 40(3): 1419-1426, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132038

RESUMO

BACKGROUND/AIM: Anti-cancer drug resistance restricts the efficacy of chemotherapy in malignant tumors. Casein kinase 2α (CK2α) is highly expressed in 5-fluorouracil (5FU)-resistant colorectal cancer (CRC) cells. We hypothesized that inhibition of CK2α might reduce CRC resistance to 5FU. MATERIALS AND METHODS: To investigate the role of CK2α in 5FU-resistant CRC cells, we assessed cell viability, apoptosis, cyclin-dependent kinase 4 (CDK4) activity, cell-cycle progression, invasion, and sphere formation in 5FU-resistant CRC cells. RESULTS: CK2α levels were significantly increased in 5FU-resistant CRC cells compared to those in wild-type CRC cells. During exposure to 5FU, viability, CDK4 activity, cell-cycle progression, invasion, and sphere formation were enhanced, while apoptosis was decreased in 5FU-resistant CRC cells. These effects were mediated by the inhibiting effects of CK2α on endoplasmic reticulum (ER) stress. Combination of CK2α knockdown with 5FU treatment promoted apoptosis of 5FU-resistant CRC cells by inducing ER stress. CONCLUSION: 5FU treatment in combination with a CK2α inhibitor may exert a synergistic effect against drug-resistant cancer cells.

8.
Phys Chem Chem Phys ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32133473

RESUMO

The influence of an external electric field (EEF) on the deprotonation reaction of Fe3+-solvated molecules was studied using reactive molecular dynamics (ReaxFF MD) simulations. It was examined in terms of changes in structural properties, kinetics, system energy, and reaction products under an EEF, and the results were further verified experimentally. The research results show that the presence of an EEF will affect the distribution of water molecules around Fe3+ and provide energy for the fracturing of O-H bonds. The increase in the state of reaction products represented by H+ also suggests that the EEF can promote the deprotonation reaction of Fe3+-solvated molecules. The viscosity of the system is significantly increased under an EEF. The experimental results for verification show that the pH of the FeCl3 solution is reduced under the action of an EEF, which means that the hydrolysis of Fe3+ has been promoted. The experimental results are consistent with the results of the MD simulations.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32133546

RESUMO

The aim of this study was to evaluate the effectiveness of various head injury criteria and associated risk functions in prediction of vulnerable road users (VRUs) severe head injuries caused by ground impact during vehicle collisions. Ten VRU accidents with video information were reconstructed by using Chalmers Pedestrian Model, vehicle multi-body system models and the THUMS (Ver. 4.0.2) finite element model. The head kinematics were used to calculate injury risks for seven head kinematics-based criteria: head angular velocity and acceleration, linear acceleration, head injury criterion (HIC), head impact power (HIP) and two versions of brain injury criterion (i.e., BRIC and BrIC). In addition, the intracranial responses were used to estimate seven tissue injury criteria, Von Mises stress, shear stress, coup pressure (C.P.) and countercoup pressure (CC.P.), maximum principal strain (MPS), cumulative strain damage measure (CSDM), and dilatation damage measure (DDM). A review of the medical reports for all cases indicated that each individual suffered severe head injuries and died. The injury risks predicted through simulations were compared to the head injuries recorded in the medical or forensic reports. The results indicated that 75-100% of the reconstructed ground impact accidents injuries were correctly predicted by angular acceleration, linear acceleration, HIC, C.P., MPS and CSDM0.15. Shear stress, CC.P. and CSDM0.25 correctly predicted 50-75% of the reconstructed accidents injuries. For angular velocity, HIP, BRIC and BrIC, the injuries were correctly predicted for less than 50% of the reconstructed accidents. The Von Mises stress and DDM did not correctly predict any reconstructed accidents injuries. The results could help to understand the effectiveness of the brain injury criteria for future head injury evaluation.

10.
Acta Biomater ; 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126308

RESUMO

Titanium-based endosseous implants with high antibacterial and osseointegration activities are extremely required in clinics. To achieve this line, herein the doped coatings with three kinds of Zn doses were micro-arc oxidized (MAOed) on Ti. They were examined to reveal a bilayered structure, in which the outer layer consisted completely of the amorphism comprising elements of Ti, O and Zn with Zn doped in the form of weaken Zn-O bonds, and the underlying layer was partially crystallized with nanocrystalline TiO2 and Zn2TiO4 to embed an amorphous matrix. While the Zn doped doses of the surface amorphous layers increased with elevating the MAOed voltages, the weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of reactive oxide species (ROS) on the coatings. The enhanced HO• and O2-• formation on the elevated voltage MAOed coatings caused serious break of the cell walls and plasma membranes of S. aureus. In parallel, the enhanced Zn2+ release and extracellular H2O2 formation led to the enhanced intracellular ROS level of S. aureus, further aggravating the damage of plasma membrane, resulting in bacteria death. On contrary to the overdose of Zn doped coating, the moderate doses of Zn doped coatings did not induce additional intracellular ROS and attenuate viability and proliferation of osteoblasts in vitro, and promoted osseointegration in both S. aureus-uninfected and infected rat tibias, which ascribed to the strong antibacterial activity and un-attenuated cell function of the coatings in the infected case. STATEMENT OF SIGNIFICANCE: (1) The Zn-doped coatings revealed a bilayered structure of the surface layer comprising the Ti, O and Zn constructed amorphism with Zn in the form of weaken Zn-O bonds, and the underlying layer comprising nanocrystalline TiO2 and Zn2TiO4 to embed amorphous matrix. (2) The weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of ROS on the coatings. (3) The enhanced Zn2+ release and ROS formation on the coatings killed S. aureus by inducing serious break of their cell walls and plasma membranes. This effect in combination of un-attenuated osteoblast proliferation endowed the moderate Zn doped coatings with enhanced osseointegration in S. aureus-infected rat tibias.

11.
Cancer Biomark ; 27(2): 243-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083573

RESUMO

BACKGROUND: Prognostic biomarkers are promising targets for cancer prevention and treatment. OBJECTIVE: We try to filtrate survival-related genes for non-small cell lung cancer (NSCLC) via transcriptome analysis. METHODS: Transcriptome data and clinical information of Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), mainly subtypes of NSCLC, were obtained from The Cancer Genome Atlas (TCGA) program. Differentially expressed genes (DEGs) analyzed by DESeq2 package were regarded as candidate genes. For survival analysis, univariate and multivariate Cox regression were applied to select biomarkers for overall survival (OS) and progression-free survival (PFS), where univariate analysis was for preliminary filtration and multivariate analysis considering age, gender, TNM parameters and clinical stage was for ultimate determination. Gene ontology (GO) analysis and pathway enrichment were used for biological annotation. RESULTS: We ultimately acquired a series of genes closely related to prognosis. For LUAD, we determined 314 OS-related genes and 275 PFS-related genes, while 54 OS-related genes and 78 PFS-related genes were chosen for LUSC. The final biological analysis indicated important function of proliferative signaling in LUAD but for LUSC, only cornification process had statistical meaning. CONCLUSIONS: We strictly determined prognostic genes of NSCLC, which would contribute to its carcinogenesis investigation and therapeutic methods improvement.

12.
Mil Med Res ; 7(1): 4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Infecção Hospitalar , Controle de Infecções , Programas de Rastreamento , Equipamento de Proteção Individual , Pneumonia Viral , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas , Medicina Baseada em Evidências , Hidratação , Humanos , Controle de Infecções/normas , Pulmão/diagnóstico por imagem , Epidemiologia Molecular , Cuidados de Enfermagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
13.
Artigo em Inglês | MEDLINE | ID: mdl-32089265

RESUMO

Ischemic injury is a major risk factor for fibrosis. However, the precise mechanisms by which fibrosis is regulated and induced under ischemic oxidative stress conditions are unknown. To address this, we investigated the effect of melatonin on ischemia-induced fibrosis. In a hindlimb ischemia mouse model, ischemia induced fibrosis by increasing inflammation and the expression of extracellular matrix (ECM) proteins. Melatonin prevented ischemia-induced fibrosis in the injured tissues. In particular, melatonin suppressed the fibrosis-mediated inflammatory reaction in myoblasts through the microRNA-149 (miR-149)/indoleamine 2,3-dioxygenase-1 (IDO-1) signaling pathway. The melatonin-induced increase in miR-149 inhibited the expression of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and ECM components, such as collagen I and fibronectin. In addition, melatonin increased antioxidative activity and mitochondrial function in myoblasts via the miR-149/peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) signaling axis, and the anti-fibrotic effects of melatonin were blocked by inhibition of miR-149. These findings indicate that melatonin is a key target molecule in fibrosis related to ischemic diseases and that miR-149 might be a novel target for the treatment of ischemia-induced fibrosis.

14.
Ann Transplant ; 25: e918076, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32015300

RESUMO

BACKGROUND The aim of this study was to investigate the clinical features and treatment strategies of transplant renal artery stenosis (TRAS) with kidneys from donation after cardiac death (DCD). MATERIAL AND METHODS We collected the clinical data of donors and recipients of single-center DCD-induced TRAS from January 2015 to June 2017. RESULTS All the 8 cases of TRAS were from hypertensive cerebrovascular accident DCD-originated kidneys. The mean donor age was 53.5 (45~57) years, with mean BMI 27.8 (26.4~32.3) kg/m², atherosclerosis index 5.8 (4.9~7.0), and renal atherosclerotic plaque. Clinical features of TRAS were: refractory hypertension with elevated serum creatinine >50%, and negative urine protein and occult blood. Ultrasound of transplanted kidneys showed renal blood flow index 0.49 (0.43~0.55). Angiography confirmed the diagnosis of renal artery trunk or secondary branch stenosis. There were 2 cases of moderate stenosis and 6 cases of severe stenosis. Six patients underwent stent implantation and 2 patients underwent balloon dilatation. Seven patients had serum creatinine recovery after interventional therapy during follow-up. The transplanted kidney of 1 patient ruptured 6 h after interventional therapy and was then resected. CONCLUSIONS The incidence of TRAS with hypertensive cerebrovascular accident DCD-originated kidneys is relatively high, which is a warning to kidney transplant physicians. Digital subtraction angiography (DSA) is the most reliable diagnostic means of TRAS and can be performed concurrently with intervention therapy. If the donor has severe atherosclerosis, plaques that are visible to the unaided eye in the renal artery trunk should be removed as completely as possible.

15.
Colloids Surf B Biointerfaces ; 187: 110773, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926789

RESUMO

Improved implant-bone interface interaction for rapid formation of strong and long-lasting bond is significantly important in orthopedic clinics. Herein, Ca-doped TiO2 nanotube film (M-CaNTs) with enhanced adhesion strength was fabricated on titanium (Ti) surface by an anodization-hydrothermal treatment. Results showed that TiO2 nanotube film (M-NTs) fabricated by modified anodization was amorphous, exhibiting 100-nm diameter and 12-nm tube wall thickness. After hydrothermal treatment, the nanotubular structure of M-CaNTs kept integrated, but was volume-expanded, exhibiting a decreased diameter (∼ 60 nm) and an increased wall thickness (∼ 30 nm). The formation of M-CaNTs proceeded preferentially at the interior surfaces of the closely aligned nanotubes, involving an in situ dissolution-recrystallization process. Though the adhesion strength of M-CaNTs was weakened by the volume-expansion derived internal stress, it was still higher than that of the traditionally obtained one. In the in vitro investigations, the combination of nanotubular structure and Ca2+ could expectedly enhance the attachment, spreading and proliferation of MC3T3-E1 cells, as well as promote the expressions of bone-specific genes, intracellular proteins and ALP activity, which in turn accelerated collagen secretion and ECM mineralization. This work provides an attractive potential for the surface modification of Ti-based implants in clinical application.

16.
EBioMedicine ; 52: 102633, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31981984

RESUMO

BACKGROUND: Fabry disease (FD) is a recessive X-linked lysosomal storage disorder caused by α-galactosidase A (GLA) deficiency. Although the mechanism is unclear, GLA deficiency causes an accumulation of globotriaosylceramide (Gb3), leading to vasculopathy. METHODS: To explore the relationship between the accumulation of Gb3 and vasculopathy, induced pluripotent stem cells generated from four Fabry patients (FD-iPSCs) were differentiated into vascular endothelial cells (VECs). Genome editing using CRISPR-Cas9 system was carried out to correct the GLA mutation or to delete Thrombospondin-1 (TSP-1). Global transcriptomes were compared between wild-type (WT)- and FD-VECs by RNA-sequencing analysis. FINDINGS: Here, we report that overexpression of TSP-1 contributes to the dysfunction of VECs in FD. VECs originating from FD-iPSCs (FD-VECs) showed aberrant angiogenic functionality even upon treatment with recombinant α-galactosidase. Intriguingly, FD-VECs produced more p-SMAD2 and TSP-1 than WT-VECs. We also found elevated TSP-1 in the peritubular capillaries of renal tissues biopsied from FD patients. Inhibition of SMAD2 signaling or knock out of TSP-1 (TSP-1-/-) rescues normal vascular functionality in FD-VECs, like in gene-corrected FD-VECs. In addition, the enhanced oxygen consumption rate is reduced in TSP-1-/- FD-VECs. INTERPRETATION: The overexpression of TSP-1 secondary to Gb3 accumulation is primarily responsible for the observed FD-VEC dysfunction. Our findings implicate dysfunctional VEC angiogenesis in the peritubular capillaries in some of the complications of Fabry disease. FUNDING: This study was supported by grant 2018M3A9H1078330 from the National Research Foundation of the Republic of Korea.

17.
Mar Drugs ; 18(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963176

RESUMO

Four novel bioactive tetrahydroanthra-γ-pyrone compounds, shellmycin A-D (1-4), were isolated from the marine Streptomyces sp. shell-016 derived from a shell sediment sample collected from Binzhou Shell Dike Island and Wetland National Nature Reserve, China. The structures of these four compounds were established by interpretation of 1D and 2D NMR and HR-MS data, in which the absolute configuration of 1 was confirmed by single crystal X-ray diffraction, and compound 3 and 4 are a pair of stereoisomers. Compound 1-4 exhibited cytotoxic activity against five cancer cell lines with the IC50 value from 0.69 µM to 26.3 µM. Based on their structure-activity relationship, the putative biosynthetic pathways of these four compounds were also discussed.

18.
ACS Appl Mater Interfaces ; 12(5): 5462-5475, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927945

RESUMO

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated ß-cyclodextrin (ß-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

19.
ACS Appl Mater Interfaces ; 12(5): 6590-6597, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31935058

RESUMO

Collagen I (Col-I) is widely used in the fabrication of biomaterials due to its biocompatibility; however, Col-I based biomaterials are susceptible to mechanical failure during handling, which limits their applicability to biomaterials. Chemical or physical treatment can improve the mechanical properties of collagen; however, these processes can create issues of cytotoxicity or denaturation. We report here an alternative strategy to improve the stability and mechanical properties of Col-I while preserving its native structure, through thermal treatment in fluorous media. Thermal treatment of Col-I in fluorous solvent generates compact, stable films with significantly increased mechanical strength. Furthermore, the use of fluorous media significantly reduces the extent of swelling and the rate of proteolytic degradation, but it preserves the high cell biocompatibility.

20.
ACS Nano ; 14(2): 2077-2089, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31990179

RESUMO

Periprosthetic infection is considered the main cause of implant failure, which is expected to be solved by fabricating an antibacterial coating on the surface of the implant. Nevertheless, systemic antibiotic treatment still represents the mainstream method for preventing infection, and few antibacterial coatings are applied clinically. This is because the externally introduced traditional antibacterial coatings suffer from the risk of invalidation and tissue toxicity induced by the consumption of antibacterial agents, degradation, and shedding. In this work, we proposed a rapid photo-sonotherapy by creating an oxygen deficiency on a titanium (Ti) implant through sulfur (S)-doping (Ti-S-TiO2-x), which endowed the implants with great sonodynamic and photothermal ability. Without introducing an external antibacterial coating, it reached a high antibacterial efficiency of 99.995% against Staphylococcus aureus under 15 min near-infrared light and ultrasound treatments. Furthermore, bone infection was successfully treated after combination treatments, and improved osseointegration was observed. Importantly, the S-doped Ti implant immersed in water for 6 months showed an unchanged structure and properties, suggesting that the Ti implant with intrinsic modification showed stable antibacterial performance under exogenous stimuli with a high antibacterial performance in vivo. This photo-sonotherapy based on sulfur doping is also promising for cancer therapy with biosafety.

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