ABSTRACT
BACKGROUND: Sarcopenia is an age-related condition that causes loss of skeletal muscle mass and disability. Sarcopenia is closely related to the prognosis of patients suffering osteoporotic thoraco-lumbar compression fractures (OTLCF). The purpose of this study was to investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty (PKP) in the treatment of older adults with OTLCF surgery and postoperative mortality. METHODS: From February 2016 to June 2019, 101 patients who met the inclusion and exclusion criteria were included in this study. The grip strength of the dominant hand was measured using an electronic grip tester. The diagnostic cutoff value of grip strength for sarcopenia was <27 kg for males and <16 kg for females. The cross-sectional area (cm2) of the musculature at the level of the pedicle of the thoracic 12th vertebra (T12) was measured by chest CT. The skeletal muscle index (SMI) was calculated by dividing the muscle cross-sectional area at the T12 pedicle level by the square of the height. The diagnostic cut-off value of SMI at T12 level is 42.6 cm2/m2 for males and 30.6 cm2/m2 for females. Sarcopenia was diagnosed when the grip strength and SMI values were both lower than the diagnostic cut-off value. All included patients received PKP treatment for OTLCF. The age, gender, operation time, bleeding volume, time to ground, length of hospital stay, visual analog scale (VAS) score before operation and one month after operation, Oswestry Disability Index (ODI) one month after operation and the incidence of refracture within 36 months after operation were compared between the two groups. The survival curves of the two groups were analyzed by Kaplan Meier. Chi-square test was used to compare the differences in survival rates between the two groups at 12, 24, and 36 months after operation. Univariate and multivariate Cox regression analysis compared multivariate factors on OTLCF postoperative mortality. RESULTS: There was no significant difference in gender, operation time, blood loss and preoperative VAS score between the two groups (χ2 = 1.750, p = 0.186; t = 1.195, p = 0.235; t = -0.582, p = 0.562; t = -1.513, p = 0.133), respectively. The patients in the sarcopenia group were older (t = 3.708, p = 0.000), and had longer postoperative grounding time and hospitalization time (t = 4.360, p = 0.000; t = 6.458, p = 0.000). The VAS scores and ODI scores one month postoperatively were also higher in sarcopenia group (t = 5.900, p = 0.000; t = 7.294, p = 0.000), and there was a statistical difference between the two groups. Interestingly, there was no significant difference in the incidence of spinal refracture within 36 months between the two groups (χ2 = 1.510, p = 0.219). The sarcopenia group had a higher mortality rate at 36 months after operation, and the difference was statistically significant (p = 0.002). Sarcopenia is an independent risk factor for long-term mortality in OTLCF patients received PKP surgery. CONCLUSIONS: Patients with sarcopenia combined with OTLCF have poor postoperative recovery of limb function and a high risk of death in the long-term (36 months) after surgery. Active and effective intervention for sarcopenia is required during treatment.
Subject(s)
Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Sarcopenia , Spinal Fractures , Male , Female , Humans , Aged , Kyphoplasty/adverse effects , Sarcopenia/complications , Spinal Fractures/surgery , Spinal Fractures/complications , Treatment Outcome , Fractures, Compression/surgery , Fractures, Compression/complications , Osteoporotic Fractures/surgery , Retrospective StudiesABSTRACT
Tumor-infiltrating immune cells and fibroblasts are significant components of the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), and they participate in tumor progression as closely as tumor cells. However, the relationship between the features of the TME and patient outcomes and the interactions among TME components are still unclear. In this study, we evaluated the PDAC TME in terms of the quantity and location of cluster of differentiation (CD)4+ T cells, CD8+ T cells, macrophages, stromal maturity, and tumor-stroma ratio (TSR), as evaluated by immunohistochemical staining of serial whole-tissue sections from 116 patients with PDAC. The density of T cells and macrophages (mainly activated macrophages) was significantly higher at the invasive margins (IMs) than at the tumor center (TC). CD4+ T cells were significantly association with all the other tumor-associated immune cells (TAIs) including CD8, CD68 and CD206 positive cells. Tumors of the non-mature (intermediate and immature) stroma type harbored significantly more CD8+ T cells at the IMs and more CD68+ macrophages at the IMs and the TC. The density of CD4+, CD8+, and CD206+ cells at the TC; CD206+ cells at the IMs; and tumor-node-metastasis (TNM) staging were independent risk factors for patient outcomes, and the c-index of the risk nomogram for predicting the survival probability based on the TME features and TNM staging was 0.772 (95% confidence interval: 0.713-0.832). PDAC harbored a significantly immunosuppressive TME, of which the IMs were the hot zones for TAIs, while cells at the TC were more predictive of prognosis. Our results indicated that the model based on the features of the TME and TNM staging could predict patient outcomes.
ABSTRACT
Biomaterials have been widely used as substitutes for diseased tissue in surgery and have gained great success and attention. At present, the biocompatibility of biomaterials such as PET woven fabrics is often evaluated both in vitro and in vivo. However, the current experimental methods cannot reveal the relationship between material surfaces and cell adhesion, and few research works have focused on the mechanisms of how the surface morphology of biomaterials affects cell adhesion and proliferation. Thus, it is meaningful to find out how the altered surfaces could affect cell adhesion and growth. In this study, we employed Ar low-temperature plasma treatment technology to create nano-grooves on the warp yarn of PET woven fabrics and seeded human umbellar vein endothelial cells (HUVEC) on these fabrics. We then assessed the O-glycan and N-glycan profiles of the cells grown on different structures of the polyester woven fabrics. The result showed that the surface morphology of polyester woven fabrics could affect the O-glycan profile but not the N-glycan profile of cultured HUVEC. Taken together, the study describes the effects of the surface morphology of biomaterial on the biosynthesis of cellular glycans and may provide new insights into the design and manufacture of biomaterials used as blood vessels based on the expression profiles of O-glycans on cultured cells.
ABSTRACT
Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 µg/cm2, 7.24 ± 1.56 µg/cm2, 15.63 ± 2.45 µg/cm2, and 26.59 ± 3.48 µg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 µg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 µg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 µg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.
Subject(s)
Heparin , Polytetrafluoroethylene , Blood Vessel Prosthesis , Endothelial Cells , Endothelium, Vascular , Extracellular MatrixABSTRACT
Water permeability of textile vascular grafts has been considered as a key indicator for predicting blood permeability after implantation. However, a correlation between water and blood permeability has not been established yet. Therefore, even though the water permeability of a vascular graft can be tested according to the standard ISO 7198, the results fail to guide a manufacturer or a surgeon to judge whether this vascular graft needs pre-clotting or not prior to implantation. As a result, all commercial graft products show almost zero water permeability, which leads to the loss of advantages that textile vascular grafts have the pore size-controlled porous wall. To solve this problem, four types of woven vascular grafts were designed and manufactured in the present work. Then their permeability to water, simulated plasma, and anticoagulated whole blood were measured at graded pressures from 8 to 16 kPa. Moreover, the correlations among the water permeability, the simulated plasma permeability, and the anticoagulated whole blood permeability were established. The results suggest that relatively steady correlations exist between the water permeability and the anticoagulated whole blood permeability, and that the evaluation of the blood permeability using the water permeability is feasible and objective. The present work provides a quantitative method for evaluating the blood permeability using the water permeability, and the latter is thus endowed with practical significance for guiding designs and clinical pre-clotting operations of textiles vascular grafts.
Subject(s)
Blood Vessel Prosthesis , Water , Permeability , TextilesABSTRACT
Biliary stent has been widely used in the treatment of biliary stricture and obstruction, it can relieve the pain of patients effectively, but bacterial infection and stent obstruction are still troublesome after surgery. We introduce the mechanism of infection and stent blockage caused by bacterial invasion after biliary stent implantation, and expound the formation mechanism of bacterial biofilm and bile sludge in this review. Antibacterial biliary stent is an effective way to inhibit biliary tract infection, the literatures on antibacterial modification of biliary stent with different antibacterial methods in domestic and abroad are reviewed, and the research prospect of antibacterial biliary stent is summarized and prospected.
Subject(s)
Biliary Tract , Cholestasis , Anti-Bacterial Agents/pharmacology , Bile , Humans , StentsABSTRACT
BACKGROUND: Several studies found that hip fracture patient outcome is greatly influenced by the time from admission to surgery. To avoid surgical delay, surgery for hip fracture may be performed at night or weekends. However, after-hours surgery may lead to a reduction in support staff and to surgeon fatigue, which ultimately increases mortality and complications. Therefore, we wanted to compare the outcomes of daytime and after-hours surgery in hip fracture patients. METHODS: A literature search was performed in the Cochrane Library, and the Web of Science, PubMed, Embase, and Springer databases from inception to December 2019. Relevant studies comparing the results of operations performed at different time periods were included. The main clinical outcomes included total complications, mortality, blood loss, surgical time, and length of hospitalization. Data were pooled, and a meta-analysis was completed. RESULTS: Nine retrospective cohort studies and one randomized controlled trial met the inclusion criteria; the studies included a total of 583,290 patients. We found no significant differences in mortality, surgical time or blood loss between daytime and after-hours surgery in hip fracture patients (P > 0.05). Of note, the patients who underwent after-hours surgery had fewer surgical complications (P < 0.001) and a shorter length of hospitalization (P = 0.021) than those who underwent daytime surgery. CONCLUSION: After-hours surgery for hip fracture is safe. To avoid surgical delay, after-hours surgery is still a viable and even necessary option.
Subject(s)
Hip Fractures , Hip Fractures/surgery , Hospitalization , Humans , Operative Time , Retrospective StudiesABSTRACT
OBJECTIVE: To explore the effect of Mimics assisted virtual reduction and personalized additional fixation with proximal femoral nail anti rotation in the treatment of unstable intertrochanteric fracture of lateral wall. METHODS: From January 2015 to June 2018, 11 cases of intertrochanteric fracture with unstable lateral wall injury were analyzed retrospectively, including 3 males and 8 females, aged 64 to 81 years old. There were 3 cases of A3.1, 6 cases of A3.2 and 2 cases of A3.3 according to AO classification. All patients underwent CT scanning, according to the CT scanning data, three-dimensional reconstruction of fracture was performed by Mimics soft. Virtual reduction was performed first, and PFNA was implanted after satisfactory reduction. According to the relationship between the fracture characteristics of the lateral wall and the position of the lag screw tail in the lateral wall, 4 cases were treated with PFNA and titanium cable or steel wire, and 7 cases were treated with PFNA and reconstruction locking plate.The quality of reduction and healing were evaluated by follow up, and Harris score of hip joint was performed in the last reexamination. RESULTS: All patients were followed up for 12 to 18 months. No postoperative infection of incision and loosening of internal fixation occurred. The time of fracture healing was 12 to 20 weeks. At the final follow up, Harris score of hip joint was excellent in 6 cases, good in 3 cases and fair in 2 cases. CONCLUSION: The treatment of intertrochanteric fracture of femur with Mimics assisted virtual reduction and PFNA is helpful to preoperative planning and improve the surgical effect.
Subject(s)
Fracture Fixation, Intramedullary , Hip Fractures , Aged , Aged, 80 and over , Bone Nails , Female , Hip Fractures/surgery , Humans , Male , Middle Aged , Retrospective Studies , Software , Treatment OutcomeABSTRACT
An endothelial cell (EC) monolayer aligned along the direction of blood flow in vivo shows excellent capacity for anti-inflammation and anti-thrombosis. Therefore, aligned electrospun fibers have been much studied in the field of vascular implants since they are considered to facilitate the formation of an aligned EC monolayer, yet few research studies have been comprehensively reported concerning the effects of diameter scales of aligned fibers. In the present work, a series of aligned polycaprolactone (PCL) electrospun fibers with varying diameters ranging from dozens of nanometers to several micrometers were developed, and the effects of the fiber scales on EC behaviors, hemocompatibility as well as inflammatory cell behaviors were investigated, to evaluate their potential performance in the field of vascular implants. Our results showed that platelets exhibited small attachment forces on all fibers, and the anticoagulation property improved with the decrease of the fiber diameters. The impact of fiber diameters on human umbilical vein endothelial cell (HUVEC) adhesion and NO release was limited, while significant on HUVEC proliferation. With the increase of the fiber diameters, the elongation of HUVECs on our samples increased first then decreased, and exhibited maximum elongation degrees on 2738 nm and 2036 nm due to the strong contact guidance effect on these graphical cues; too thick or too fine fibers would weaken the contact guidance effect. Furthermore, we hypothesized that HUVECs cultured on 2036 nm had the smallest spreading area because of their elongation, but 2738 nm restricted HUVECs spreading limitedly. Similarly, NO production of HUVECs showed a similar change trend as their elongation degrees on different fibers. Except for 2036 nm, it exhibited the second highest NO production. For RAW 264.7 cells, poorer cell adhesion and lower TNF-α concentration of 1456 nm indicated its superior anti-inflammation property, while 73 nm showed a contrasting performance. Overall, these findings partly revealed the relationship between different topographies and cell behaviors, providing basic insight into vascular implant design.
Subject(s)
Electrochemistry/methods , Endothelium, Vascular/drug effects , Inflammation/drug therapy , Animals , Anticoagulants/chemistry , Cell Adhesion , Cell Proliferation , Cell Survival , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Mice , Platelet Adhesiveness , Polyesters/chemistry , RAW 264.7 Cells , Serum Albumin, Bovine/chemistry , Tissue Engineering/methods , Tissue Scaffolds , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Developing a small-diameter vascular graft with a satisfactory performance in terms of mechanical and biological properties remains a challenging issue because of comprehensive requirements from clinical applications. Polyvinyl alcohol (PVA)/polyacrylamide (PAAm) hydrogels exhibit many desirable characteristics for small-diameter vascular grafts because of their tunable mechanical properties, especially high compliance. However, poor cells adhesion hinders their application for endothelialization in situ. Therefore, in the present work, polydopamine (PDA) and tetrapeptide Arg-Glu-Asp-Val (REDV) were used to functionalize the hydrogels surface and improve cells adhesion. A series of characterizations were systematically conducted to examine the applicability of coated hydrogels to small-diameter vascular grafts. Results showed that bare and coated hydrogels have appropriate structural stability, and no significant differences in tensile properties could be found after being coated with PDA or PDA-REDV. The hydrophilicity of the hydrogels decreased with the coatings of PDA and especially PDA-REDV to improve protein adsorption, porcine iliac artery endothelial cells (PIECs) adhesion, viability, proliferation, and spreading on the hydrogels. Lower hemolysis percentages and higher blood clotting index values were attained for the hydrogels, suggesting their satisfactory hemocompatibility. Overall, the present work provided insights into the development of a novel hydrogel-based small-diameter vascular graft. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:117-127, 2020.
Subject(s)
Acrylic Resins , Blood Vessel Prosthesis , Endothelial Cells/metabolism , Hydrogels , Materials Testing , Oligopeptides , Polyvinyl Alcohol , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Oligopeptides/chemistry , Oligopeptides/pharmacology , Polyvinyl Alcohol/chemistry , Polyvinyl Alcohol/pharmacology , SwineABSTRACT
Vascular basement membrane (VBM) is a thin layer of fibrous extracellular matrix linking endothelium, and collagen type IV (COL IV) is its main composition. VBM plays a crucial role in anchoring down the endothelium to its loose connective tissue underneath. For vascular grafts, constructing biomimetic VBMs on the luminal surface is thus an effective approach to improve endothelialization in situ. In the present work, three types of polycaprolactone (PCL) membranes were produced and characterized through cell counting kit-8 (CCK-8) assay, adhesion force and elastic modulus test to examine the influence of fiber diameter and membrane composition on vascular endothelial cell (EC) behaviors. The PCL membranes with finer fibers of 54.77â¯nm (PCL-54) could biomimic the nanotopography of VBMs more efficiently than 544.64â¯nm (PCL-544), and they were more suitable for Pig iliac endothelium cells (PIECs) adhesion and proliferation, meanwhile, inducing higher elastic modulus and adhesion force of PIECs. On this foundation, we further immobilized COL IV onto PCL-54 (PCL-COL IV) to biomimic VBMs compositionally. Results showed that PIECs on PCL-COL IV exhibited the highest viability and proliferation. Besides, quantitative data indicated that the elastic modulus of the PIECs on PCL-COL IV (4441.00â¯Pa) was as two times higher than that on PCL-54 (2312.26â¯Pa), and the adhesion force grew to 1120.99â¯pN from 673.58â¯pN of PIECs on PCL-54. In summary, the PCL-COL IV membranes show high similarity with the native VBMs in terms of structure and composition, suggesting a promising potential for surface modification to vascular grafts for improved endothelialization.
Subject(s)
Basement Membrane/metabolism , Collagen Type IV/metabolism , Endothelial Cells/metabolism , Polyesters/metabolism , Animals , Basement Membrane/chemistry , Biomimetics/methods , Cell Adhesion , Cell Proliferation , Cells, Cultured , Collagen Type IV/chemistry , Polyesters/chemistry , SwineABSTRACT
Acute thrombosis remains the main limitation of small-diameter vascular grafts (inner diameter <6 mm) for bridging and bypassing of small arteries defects and occlusion. The use of hydrogel tubes represents a promising strategy. However, their low mechanical strength and high swelling tendency may limit their further application. In the present study, a hydrogel vascular graft of Ca alginate/polyacrylamide reinforced with a braided fiber strut was designed and fabricated with the assistance of a customized casting mold. Morphology, structure, swellability, mechanical properties, cyto- and hemocompatibility of the reinforced graft were characterized. The results showed that the reinforced graft was transparent and robust, with a smooth surface. Scanning electron microscopic examination confirmed a uniform porous structure throughout the hydrogel. The swelling of the reinforced grafts could be controlled to 100%, obtaining clinically satisfactory mechanical properties. In particular, the dynamic circumferential compliance reached (1.7 ± 0.1)%/100 mmHg for 50-90 mmHg, a value significantly higher than that of expanded polytetrafluoroethylene (ePTFE) vascular grafts. Biological tests revealed that the reinforced graft was non-cytotoxic and had a low hemolysis percentage (HP) corresponding to (0.9 ± 0.2)%. In summary, the braided fiber-reinforced hydrogel vascular grafts demonstrated both physical and biological superiority, suggesting their suitability for vascular grafts.
ABSTRACT
This study aimed to explore the neuroprotective effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein on early brain injury caused by subarachnoid hemorrhage (SAH) and the relevant mechanisms in experimental rats, expecting to understand whether MANF was a potential therapeutic target for SAH treatment. A perforation model of SAH was introduced into the study. Recombinant human MANF (rh-MANF) and protein kinase B (Akt) inhibitor (MK2206) were used to explore the effect and the mechanisms. Multiple approaches for systemic assessment were employed in the research, including the Garcia test, the SAH grade, Evans blue (EB) dye leakage, brain-water content (BWC), the rotarod test, and the Morris water-navigation task, as were biotechniques, such as immunohistochemistry, Western blot, transmission electron microscopy, and flow cytometry. MANF was mainly expressed in rat neurons, and its expression increased significantly at 3 h after SAH induction and peaked at 24 h. Stereotactic injection of rh-MANF into the cerebroventricle significantly increased the level of MANF, p-Akt, p-mouse double minute 2 homolog (p-MDM2), and B-cell lymphoma 2 (Bcl-2) in brain tissue, whereas it down-regulated the expression of P53, Bcl-2-associated X protein (Bax), and cleaved caspase-3, which indicated that neuronal apoptosis was remarkably suppressed. Expression of matrix metallopeptidase 9 (MMP-9) was also suppressed by the rh-MANF injection. Furthermore, neurologic deficits, EB dye leakage, and BWC were reduced, and long-lasting neuroprotection was noted with rh-MANF administration. The antiapoptotic and blood-brain barrier (BBB) protective effect could be offset by administering MK2206. MANF could alleviate neuronal apoptosis by activating Akt-dependent prosurvival pathway and abate BBB damage via MMP-9 suppression. MANF showed not only transient but also long-lasting neuroprotective properties. The rh-MANF as a potential drug for treating SAH might be of clinical use.-Li, T., Xu, W., Gao, L., Guan, G., Zhang, Z., He, P., Xu, H., Fan, L., Yan, F., Chen, G. Mesencephalic astrocyte-derived neurotrophic factor affords neuroprotection to early brain injury induced by subarachnoid hemorrhage via activating Akt-dependent prosurvival pathway and defending blood-brain barrier integrity.
Subject(s)
Blood-Brain Barrier , Brain Injuries/prevention & control , Nerve Growth Factors/physiology , Proto-Oncogene Proteins c-akt/metabolism , Subarachnoid Hemorrhage/complications , Animals , Brain Injuries/etiology , Brain Injuries/pathology , Brain Injuries/physiopathology , Cell Line, Tumor , Humans , Male , Rats , Rats, Sprague-Dawley , Subcellular Fractions/pathologyABSTRACT
Stents or stent-grafts are often functionalized with films to enhance cell/surface interactions and improve endothelialization. However, continuous film coatings by common surface modification tactics may preclude cells from migrating along the thickness direction and may change the physical characteristics of stent-grafts. Here, polydopamine nanoparticles (PDA-NPs) are attached on braided stent-grafts tightly, forming a nanostructure on microfilaments. They also serve as the anchor for bioactive REDV peptide immobilization to promote endothelia cells (ECs) activities. The results show that braided stent-grafts decorated with PDA-NPs and REDV demonstrate an excellent endothelialization performance and hemocompatibility due to the micro/nanostructure formed and REDV affinity to ECs. The physical properties of stent-grafts are also not compromised. A potential surface modification strategy for scaffold applications is illustrated.
ABSTRACT
BACKGROUND: Neuroinflammation is closely associated with functional outcome in subarachnoid hemorrhage (SAH) patients. Our recent study demonstrated that fluoxetine inhibited NLRP3 inflammasome activation and attenuated necrotic cell death in early brain injury after SAH, while the effects and potential mechanisms of fluoxetine on neuroinflammation after SAH have not been well-studied yet. METHODS: One hundred and fifty-three male SD rats were subjected to the endovascular perforation model of SAH. Fluoxetine (10 mg/kg) was administered intravenously at 6 h after SAH induction. TAK-242 (1.5 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, immunofluorescence/TUNEL staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were performed. RESULTS: Fluoxetine administration attenuated BBB disruption, brain edema, and improved neurological function after SAH. In addition, fluoxetine alleviated the number of Iba-1-positive microglia/macrophages, neutrophil infiltration, and cell death. Moreover, fluoxetine reduced the levels of pro-inflammatory cytokines, downregulated the expression of TLR4 and MyD88, and promoted the nuclear translocation of NF-κB p65, which were also found in rats with TAK-242 administration. Combined administration of fluoxetine and TAK-242 did not enhance the neuroprotective effects of fluoxetine. CONCLUSION: Fluoxetine attenuated neuroinflammation and improved neurological function in SAH rats. The potential mechanisms involved, at least in part, TLR4/MyD88/NF-κB signaling pathway.
Subject(s)
Brain Injuries/drug therapy , Calcium-Binding Proteins/metabolism , Fluoxetine/therapeutic use , Microfilament Proteins/metabolism , Neuroprotective Agents/therapeutic use , Signal Transduction/drug effects , Toll-Like Receptor 4/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/physiopathology , Brain Edema/drug therapy , Brain Edema/etiology , Brain Injuries/etiology , Brain Injuries/mortality , Brain Injuries/pathology , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Gene Expression Regulation/drug effects , Granulocyte Colony-Stimulating Factor/metabolism , Interleukin-3/metabolism , Male , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Recombinant Fusion Proteins/metabolism , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/mortality , Sulfonamides/therapeutic useABSTRACT
Endoleak and luminal loss related to blood permeation and microthrombus migration remain the main challenges in the aneurysm treatment, although stent-grafts have been widely applied. Stent-grafts provide a boundary to shield blood and microemboli transport, which are correlated with their mass transfer performance. Water permeability of vascular prostheses with woven and knitted structures has been analyzed and documented by many researchers, as well as oxygen and protein transfer. However, it is almost a total lack of blood and microemboli transfer along the braided stent-graft thickness direction. In this research, we provided a methodology for the vascular prostheses mass transfer evaluation. Braided stent-grafts in our former research were conducted on a self-developed testing system to investigate their blood permeability and microthrombus transfer behaviors. The pressure along wall thickness direction can be changed. Analytical models were also established based on pore parameters, making them applicative to different structures. Results revealed that the mass transfer behavior of stent-grafts was positively affected by porosity and pore diameter while negatively influenced by their thickness.
Subject(s)
Blood Vessel Prosthesis , Mechanical Phenomena , Stents , Aortic Aneurysm, Abdominal/surgery , Materials Testing , Prosthesis DesignABSTRACT
Polyethylene glycol terephthalate (PET) fabrics with woven structures have proved to be quite effective for use on large diameter artificial blood vessels. However, their use within small-diameter artificial blood vessels has been associated with poor long-term patency, a problem resulting from slow endothelialization on PET and an over hyperplasia of smooth muscle cells. Previous research from our laboratory has revealed that ICAM-1 can be used as a marker to investigate cell adhesion, an effect which was closely associated with cell behavior on the surface of polycaprolactone (PCL) films. Moreover, we found that the coarseness or pore size of the surface exerts considerable influence on cell adhesion and proliferation on PCL films. In this study, we successfully fabricated six types of PET woven fabrics with varying gradients of tightness and porosities. Levels of ICAM-1 expression (membrane ICAM-1 & soluble ICAM-1) were then determined in these woven fabrics. Our results show that increased levels of mICAM-1 and decreased levels of sICAM-1 expression were obtained in HUVECs seeded on these six samples. These findings indicate that cell adhesion and proliferation on fabric surfaces were strongly influenced by their structural parameters, in particular the initial adhesion between the cell and fabric surface. In addition, we also found that extracellular matrix adhesion tends to prefer flat and tight surfaces, which promotes cell-cell and cell-matrix interactions, as well as the endothelialization on the surface of PET fabrics. These findings provide some novel insights with regard to the design and application of small-diameter artificial blood vessels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 954-964, 2018.
Subject(s)
Biocompatible Materials/chemistry , Blood Vessel Prosthesis , Blood Vessels/anatomy & histology , Polyethylene Glycols/chemistry , Cell Adhesion , Cell Proliferation , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Materials Testing , Polyethylene Terephthalates/chemistry , Porosity , Prosthesis Design , Tissue EngineeringABSTRACT
Stent-grafts in peripheral arteries suffer from complex cyclic loadings in vivo, including pulsatile, axial bending and torsion. Normal fatigue durability evaluation technologies, however, are majorly based on pulsation and thus are short of accuracy under the complicated stress conditions experienced physiologically. While there is a little research focused on the cyclic fatigue of stent-grafts in bending, it remains an almost total lack of deformation or fatigue mechanisms. In this work, composite braided stent-grafts incorporating Nitinol (NiTi) yarns and polyethylene terephthalate (PET) multifilament yarns were cycled in bending by the self-developed testing system to investigate their deformation behaviors. Deformation mechanisms at the yarn level were discussed, and NiTi yarn crossover structure was considered the primary factor affecting the deformation modes. Four yarn-crossover-based deformation modes (accordion buckling, diamond-shaped buckling, neck propagation and microbuckling) revealed the mechanisms of energy absorption of braided stent-grafts on the mesoscopic scale. Further, mechanical modes were applied to help regulate stent designs.
Subject(s)
Arteries , Materials Testing , Stents , Stress, Mechanical , Alloys , Polyethylene Terephthalates , Surface Properties , Temperature , Weight-BearingABSTRACT
The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy.