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Objective: This study aims to analyze the biomechanical characteristics of posterolateral plateau fractures fixed by a novel anatomical plate using finite element analysis. Methods: A three-dimensional digital model of the full length of right tibiofibula was obtained by CT scanning. A posterolateral tibial plateau fracture model was then created. The acquired fracture model was assembled with 4 groups of internal fixations: Group A, novel anatomical plate; Group B, straight buttress plate; Group C, oblique T-shaped locking plate; Group D, two lag screws. Axial loads of 500, 1,000 and 1,500 N perpendicular to the horizontal plane were used to simulate the stress on the lateral plateau of a 65â kg person standing, walking and fast running. Results: Vertical displacements of the posterolateral fragments in each of the four groups gradually increased under loads from 500â N to 1,500â N. The maximum displacement of the fracture fragment in four groups were all located on the lateral side of the proximal part, and the displacement gradually decreased from the proximal part to the distal end. The maximum displacement values under the axial load of 1,500â N was in the following order: novel anatomical plate (1.2365â mm) < oblique T-shaped locking plate (1.314â mm) < two lag screws (1.3747â mm) < straight buttress plate (1.3932â mm). As the axial load increased, the stress value of the different internal fixation models gradually increased. The stress behavior of the same internal fixation model under different loads was similar. The maximum stress value under the axial load of 1,500â N was in the following order: novel anatomical plate (114.63â MPa) < oblique T-shaped locking plate (277.17â MPa) < two lag screws (236.75â MPa) < straight buttress plate (136.2â MPa). Conclusion: The patients with posterolateral plateau fractures fixed with a novel anatomical plate in standing, walking and fast running can achieve satisfactory biomechanical results, which lays the foundation for future applications. At the same time, clinical fracture types are often diverse and accompanied by damage to the soft tissue. Therefore, the ideal surgical approach and appropriate internal fixation must be selected based on the patient's injury condition.
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OBJECTIVES: To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China. METHODS: HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database. RESULTS: A total of 36â263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions. CONCLUSIONS: HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.
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Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3ß/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.
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Nanopartículas , Estresse Oxidativo , Periodontite , Estresse Oxidativo/efeitos dos fármacos , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Periodontite/patologia , Nanopartículas/química , Humanos , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Minociclina/farmacologia , Minociclina/química , Minociclina/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Antibacterianos/química , Antibacterianos/farmacologia , Lipopolissacarídeos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Espécies Reativas de Oxigênio/metabolismo , ImidazóisRESUMO
Minimally invasive, efficient, and satisfactory treatment for irregular and lacunar bone defects is still a challenge. Alginate hydrogels serve as promising stem cell (SC) delivery systems for bone regeneration but are limited by low cellular viability, poor osteogenic differentiation, and insufficient mechanical support. Herein, we developed a BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres (BCHMs) system via a microfluidic method that possesses 1) a uniform size and good injectability to meet clinical bone defects with complex shapes, 2) high cellular viability maintenance and further osteogenic induction capacity, and 3) improved mechanical properties. As the main matrix, the sodium alginate hydrogel maintains the high viability of encapsulated BMSCs and efficient substance exchange. Enhanced mechanical properties and osteogenic differentiation of the BCHMs in vitro were observed with xonotlite (Ca6Si6O17(OH)2, CSH) nanowires incorporated. Furthermore, BCHMs with 12.5 % CSH were injected into rat femoral bone defects, and satisfactory in situ regeneration outcomes were observed. Overall, it is believed that BCHMs expand the application of polysaccharide science and provide a promising injectable bone substitute for minimally invasive bone repair.
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Hidrogéis , Osteogênese , Ratos , Animais , Hidrogéis/farmacologia , Microesferas , Regeneração Óssea , AlginatosRESUMO
INTRODUCTION: Osteoarthritis (OA) is the most prevalent and debilitating joint disease without an effective therapeutic option. Multiple risk factors for OA have been identified, including abnormal chondrocyte miRNA secretion and circadian rhythms disruption, both of which have been found to cause progressive damage and loss of articular cartilage. Environmental disruption of circadian rhythms in mice predisposes animals to cartilage injury and OA. METHODS: The role of miR-195/497 cluster during OA progression was verified by mouse OA model with intra-articular injection of Agomir and Antagomir. We performed micro-CT analysis, Osteoarthritis Research Society International scores, and histological analysis in mouse knee joints. RNA sequencing was performed on the mouse cartilage cell line to explore the molecular mechanism of the miR-195/497 cluster and proteins in signaling pathway were evaluated using Western blot. Senescence-associated phenotypes were detected by Western blot, senescence ß-galactosidase staining, and immunofluorescence. RESULTS: This study demonstrated that miR-195/497-5p expression is disrupted in OA with senescent chondrocytes. In addition, miR-195/497-5p influenced the circadian rhythm of mice chondrocytes by modulating the expression of the Per2 protein, resulting in the gradual degradation of articular cartilage. We found that the miR-195/497 cluster targets DUSP3 expression. The deletion of the miR-195/497 cluster increased the level of DUSP3 expression and decreased the levels of phosphorylated ERK 1/2 and CREB. Per2 transcription is upregulated by stimulating CREB and ERK 1/2 phosphorylation. CONCLUSION: Our findings identify a regulatory mechanism connecting chondrocyte miR-195/497-5p to cartilage maintenance and repair and imply that circadian rhythm disturbances affected by miR-195/497-5p are risk factors for age-related joint diseases such as OA.
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Cartilagem Articular , Relógios Circadianos , MicroRNAs , Osteoartrite , Camundongos , Animais , Relógios Circadianos/genética , MicroRNAs/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Modelos Animais de DoençasRESUMO
Gram-negative sepsis has become a substantial and escalating global healthcare challenge due to the growing antibiotic resistance crisis and the sluggish development of new antibiotics. LL-37, a unique Cathelicidin species found in humans, exhibits a wide range of bioactive properties, including direct bactericidal effects, inflammation regulation, and LPS neutralization. KR-12, the smallest yet potent peptide fragment of LL-37, has been modified to create more effective antimicrobials. In this study, we designed two myristoylated derivatives of KR-12, referred to as Myr-KR-12N and Myr-KR-12C. These derivatives displayed remarkable ability to spontaneously assemble into nanoparticles when mixed with deionized water. Myristoylated KR-12 derivatives exhibited broad-spectrum and intensified bactericidal activity by disrupting bacterial cell membranes. In particular, Myr-KR-12N showed superior capability to rescue mice from lethal E. coli-induced sepsis in comparison with the conventional antibiotic meropenem. We also confirmed that the myristoylated KR-12 nanobiotic possesses significant LPS binding capacity and effectively reduces inflammation in vitro. In an in vivo context, Myr-KR-12N outperformed polymyxin B in rescuing mice from LPS-induced sepsis. Crucially, toxicological assessments revealed that neither Myr-KR-12N nor Myr-KR-12C nanobiotics induced meaningful hemolysis or caused damage to the liver and kidneys. Collectively, our study has yielded an innovative nanobiotic with dual capabilities of bactericidal action and LPS-neutralization, offering substantial promise for advancing the clinical translation of antimicrobial peptides and the development of novel antibiotics. This addresses the critical need for effective solutions to combat Gram-negative sepsis, a pressing global medical challenge.
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Infecções por Escherichia coli , Sepse , Humanos , Animais , Camundongos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Lipopolissacarídeos/química , Escherichia coli/metabolismo , Catelicidinas/química , Catelicidinas/metabolismo , Catelicidinas/farmacologia , Bactérias , Sepse/tratamento farmacológico , Antibacterianos/química , Testes de Sensibilidade MicrobianaRESUMO
Early fracture fixation is the critical factor in fracture healing. Common internal fracture implants are made of metallic materials, which often affects the imaging quality of CT and MRI. Most patients will choose secondary surgery to remove the internal fixation implants, which causes secondary damage to them. The development of new degradable internal fracture implants has attracted more and more attention from orthopedic surgeons and researchers. Based on these problems, we improved the various properties of medical grade polycaprolactone (PCL) by adding poly(L-lactide) (PLLA). We produced PCL/PLLA strapping bands with different mass ratios by injection molding. We compared the mechanical properties, degradation properties, cell biocompatibility, bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, osteogenic differentiation and fracture fixation effect of these strapping bands. The results showed that the tensile strength and yield force of the strapping bands increased with the increase of the content of PLLA. The addition of PLLA could significantly improve the mechanical strength in the early stage and accelerate the degradation rate of the strapping band. PCL/PLLA (80/20) strapping band had no significant cytotoxicity toward rBMSCs and could promote osteogenic differentiation of rBMSCs. The strapping band could ensure femoral fracture healing of beagles in 3 months and didn't cause damage to the surrounding tissues and main organs. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. We produced novel degradable PCL/PLLA strapping bands with different mass ratios by injection molding. We tested the biological safety of the prepared internal fixation strapping bands for fracture, such as cell experiment in vitro and animal experiment, and studied the degradation behavior in vitro. The strapping bands could ensure femoral fracture healing of beagles. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. A Immunofluorescence staining of rBMSCs (live cells: green; dead cells: red). B Young's modulus change curve during strapping bands degradation. C The implantation process of strapping bands. D Micro-CT images of the beagle's fracture recovery after the operation.
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Fraturas do Fêmur , Osteogênese , Animais , Cães , Humanos , Fixação Interna de Fraturas , Fraturas do Fêmur/cirurgia , Consolidação da Fratura , Materiais BiocompatíveisRESUMO
Introduction: The purpose of this study was to analyze the fracture patterns of different posterior-medial wall types of intertrochanteric fractures by 3-D fracture-mapping technique and to further assess their clinical utility. Methods: In a retrospective analysis of interochanteric fractures treated in a large trauma center, fractures were classified into predesigned groups based on 3D-CT imaging techniques, and a 3-D template of the intertrochanteric region was graphically superimposed on the fracture line. Fracture characteristics were then summarized based on fracture-mapping. Finally, radiographic parameters, function, and range of motion were recorded in different fracture classification states. Results: A total of 348 intertrochanteric fractures were included. There were 111 patients (31.9%) in the posterolateral + posteromedial + medial group, with the most severe fracture displacement (typically characterized by fragmentation of the posteromedial wall into three isolated fragments). There were 102 cases (29.3%) in the posterolateral + posteromedial + simple medial group, and the most common fracture feature was a complete fragment posteromedially. A total of 81 cases (23.3%) were classified into the posterolateral + medial group, with the medial fracture line extending the anterior fracture line but leaving the lesser trochanter intact. In the isolated medial group of 33 cases (9.5%), the fracture type was similar to type IV, but the integrity of the greater trochanter was ensured. In the posteromedial + medial group of 12 cases (3.4%), the fracture was characterized by an interruption when the fracture line of the anterolateral wall extended to the posteromedial wall, often resulting in a complete isolated fragment posteromedially and medially. There were nine patients (2.6%) in the isolated posterolateral group. In addition, we found significantly different radiographic scores and range of motion scores between groups. Discussion: This morphometric study helps us to further characterize posterior-medial fracture patterns of intertrochanteric fractures, which may be closely related to different clinical outcomes. Further studies are needed to verify the reliability of this classification scheme in clinical application.
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The oxidation of pyrite (FeS2) not only adversely affects the environment, but also plays a critical role in the geochemical evolution of Fe and S elements. However, the oxidation rate of FeS2 is often controlled by its exposed crystal facets. Herein, the oxidation behaviors and mechanisms of naturally existing FeS2(100) and FeS2(210) crystals are investigated. The adsorption models of O2 on FeS2(100) and FeS2(210) facets are established, additionally, their corresponding surface energies, O2 adsorption sites and energies are also obtained using Density Functional Theory (DFT) calculations. These results suggest that the FeS2(210) facet more readily reacts with O2 because it has more unsaturated coordination of Fe atoms compared with the FeS2(100) facet. Moreover, electrochemical results such as EIS, Tafel and CV curves further prove that FeS2(210) possesses a higher oxidation rate than that of FeS2(100). The results of chemical oxidation experiments and XPS analyses show that FeS2(210) can produce more total Fe, SO42- and H+ than FeS2(100). Furthermore, various intermediate S species such as SO32-, S2O32-, S3O62-, S4O62- and S5O62- are also detected. This work can provide a basis for understanding the oxidation mechanism of facet-dependent FeS2 and the geochemical evolution of Fe and S elements.
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Ferro , Sulfetos , Ferro/química , Oxirredução , Sulfetos/química , Enxofre/químicaRESUMO
Acute pancreatitis (AP) is a common emergency of the digestive system and serious cases can develop into severe acute pancreatitis (SAP), which ortality rates up to 30%. Sirtuin4 (SIRT4) is a member of the sirtuin family, and plays a key role in inflammation and oxidative stress. However, the potential role of SIRT4 in SAP has yet to be elucidated. In the present study, we found that the expression level of SIRT4 in human AP was downregulated by screening a public database, suggesting that SIRT4 may play a role in AP. Subsequently, we used L-arginine (L-Arg) to induce SAP in SIRT4 knockout (SIRT4_KO) and SIRT4 overexpression (AAV_SIRT4) mice. The results showed that the pancreatic tissue injury and related lung and kidney injury were serious in SIRT4_KO mice after SAP induction, but were significantly reduced in AAV_SIRT4 mice. More importantly, we found that the levels of antioxidant factors GSH and SOD were decreased in SIRT4_KO mice, and the production of oxidative products and lipid peroxidation markers was increased, suggesting that SIRT4 was involved in inflammation and oxidative stress during SAP. Further studies showed that the absence or overexpression of SIRT4 affected the expression level of Hypoxia-inducible factor-1α (HIF-1α) after SAP induction, and regulated the expression of ferroptosis related proteins by mediating HIF-1α/HO-1 pathway. Collectively, our study revealed that SIRT4 plays a protective role in SAP by regulating the HIF-1α/HO-1 pathway to inhibit ferroptosis.
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Ferroptose , Pancreatite , Animais , Humanos , Camundongos , Doença Aguda , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação , Pancreatite/genética , Pancreatite/metabolismoRESUMO
Articular osteochondral defects are quite common in clinical practice, and tissue engineering techniques can offer a promising therapeutic option to address this issue.The articular osteochondral unit comprises hyaline cartilage, calcified cartilage zone (CCZ), and subchondral bone.As the interface layer of articular cartilage and bone, the CCZ plays an essentialpart in stress transmission and microenvironmental regulation.Osteochondral scaffolds with the interface structure for defect repair are the future direction of tissue engineering. Three-dimensional (3D) printing has the advantages of speed, precision, and personalized customization, which can satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. This paper summarizes the anatomy, physiology, pathology, and restoration mechanisms of the articular osteochondral unit, and reviews the necessity for a boundary layer structure in osteochondral tissue engineering scaffolds and the strategy for constructing the scaffolds using 3D printing. In the future, we should not only strengthen the basic research on osteochondral structural units, but also actively explore the application of 3D printing technology in osteochondral tissue engineering. This will enable better functional and structural bionics of the scaffold, which ultimately improve the repair of osteochondral defects caused by various diseases.
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The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during bone regeneration period. These two effects reinforce one another and create an endless loop that is also accompanied by mitochondrial dysfunction. However, there is still no effective and inclusive method targeting at the two aspects and breaking the vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel that is capable of releasing metformin and Zn elements are constructed. This hydrogel treats hyperglycemia while also controlling mitochondrial function, reducing inflammation, and restoring homeostasis. In addition, the synergetic effect from metformin and Zn ions inhibits ROS-inflammation cascade generation and destroys the continuous progress by taking effects in both ROS and inflammation and further keeping organelles' homeostasis. Furthermore, with the recovery of mitochondria and breakdown of the ROS-inflammation cascade cycle, osteogenesis under a diabetic microenvironment is enhanced in vivo and in vitro. In conclusion, the study provides critical insight into the biological mechanism and potential therapy for diabetic bone regeneration.
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Diabetes Mellitus , Hiperglicemia , Estruturas Metalorgânicas , Humanos , Espécies Reativas de Oxigênio/metabolismo , HidrogéisRESUMO
The leaf of Perilla frutescens (L.) Britt (PF) has been reported to negatively affect adipocyte formation, inhibit body-fat formation, and lower body weight. However, its effect on adipocyte browning remains unknown. Thus, the mechanism of PF in promoting adipocyte browning was investigated. The ingredients of PF were acquired from the online database and filtered with oral bioavailability and drug-likeness criteria. The browning-related target genes were obtained from the Gene Card database. A Venn diagram was employed to obtain the overlapped genes that may play a part in PF promoting adipocyte browning, and an enrichment was analysis conducted based on these overlapped genes. A total of 17 active ingredients of PF were filtered, which may regulate intracellular receptor-signaling pathways, the activation of protein kinase activity, and other pathways through 56 targets. In vitro validation showed that PF promotes mitochondrial biogenesis and upregulates brite adipocyte-related gene expression. The browning effect of PF can be mediated by the p38 MAPK pathway as well as PI3K-AKT pathway. The study revealed that PF could promote adipocyte browning through multitargets and multipathways. An in vitro study validated that the browning effect of PF can be mediated by both the P38 MAPK pathway and the PI3K-AKT pathway.
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Perilla frutescens , Perilla frutescens/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adipócitos/metabolismo , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVE: This study aims to analyze the biomechanical characteristics of tile B2 pelvic fractures using finite element analysis when the superior ramus of the pubis was fixed by a plate or hollow screws in standing and sitting positions, respectively. METHODS: A three-dimensional digital model of the tile B2 pelvic fracture was obtained by CT scanning the patient. The main ligament structure was then reconstructed based on the anatomical characteristics to create a finite element model of the tile B2 pelvic fracture. The posterior pelvic ring was fixed by sacroiliac joint screws, while the anterior ring injury of the superior ramus of the pubis was fixed by plates and hollow compression screws, respectively. The degrees of freedom of the bilateral acetabulum or two sides of the ischial tuberosity were constrained in the two models. A vertical load of 600 N was applied to the upper surface of the sacrum to measure the displacement and stress distribution of the pelvis in the standing and sitting positions. RESULTS: The displacement distribution of both the healthy and the affected side of the pelvis was relatively uniform in both the plate group and the hollow screw group according to the finite element simulation results. The maximum displacement value in the sitting position was greater than the standing position, and the maximum displacement value of the hollow screw fixation was greater than that of the plate fixation. In the four groups of fixation models, the maximum displacement value of the pelvis in the hollow screw sitting position group was 1616.80 × 10-3 mm, which was greater than that of the other three groups, and in this group the total displacement value of the hollow screw in the anterior ring was 556.31 × 10-3 mm. The stress distribution of the pelvis in the various models was similar in the four groups of models, in which the maximum stress of the pelvis in the hollow screw sitting position group was the largest, which was 201.33 MPa, while the maximum stress in the standing position was 149.85 MPa greater than that in the sitting position of the hollow screw fixation. CONCLUSION: The anterior ring of patients with Tile B2 pelvic fractures fixed with hollow screws or plates in both standing and sitting positions can achieve satisfactory biomechanical results with significant safety margins for plates and screws.
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Regeneration of bone tissue in the environment of diabetes mellitus (DM) remains one of the clinical challenges, with malfunction of stem cells in a high-glucose microenvironment being the primary obstacle. We designed an injectable sustained-release PDGF-BB nanocomposite hydrogel. PDGF-BB, a star molecule for treating various complications of DM, was used for the first time for DM-associated bone regeneration, and we showed that it restored stem cell proliferation and migration and facilitated osteogenesis inhibition under high glucose stimulation by activating ERK and AKT pathways. To address the requirements for continuous PDGF-BB release in GelMA while also increasing mechanical strength, nanoclay LAPONITE® was added, which may still exhibit pro-osteogenic activity in diabetic environments by releasing bioactive ions (Si4+, Mg2+, and Li+). This injectable hydrogel heals calvarial lesions successfully in diabetic rats and has the potential to be used as a direct and effective tool for treating diabetic patients.
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Diabetes Mellitus Experimental , Ratos , Animais , Becaplermina/farmacologia , Nanogéis , Preparações de Ação Retardada/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Regeneração Óssea , Glucose/farmacologiaRESUMO
Bone defects cause serious psychological and economic burden to patients. Artificially bone repairing materials bring hope to the treatment of bone defects. Electrospun technique has attracted great attention since it can fabricate fibers from nano- to micro- scale continuously. Scaffolds fabricated by electrospun can mimic the structure of extracellular matrix which is beneficial to cell adhesion and migration. Researches have showed that bioactive ions (such as silicon and calcium ions) can promote bone regeneration. In addition, physical cues can affect cellular behavior such as cell adhesion and differentiation. In this study, two kinds of calcium silicate - adopted poly (L-lactic acid) (CS-PLLA) electrospun scaffolds with random/aligned structures were prepared by electrospun to promote bone regeneration. The integration of CS nanowires improved the biological property of PLLA electrospun scaffolds. Furthermore, in vitro results indicated that aligned 1 wt% CS adopted PLLA (PCA1) electrospun scaffolds with better physical properties and facilitated cell adhesion, improved alkaline phosphate (ALP) activity and the expression of osteogenic genes (Osteopontin (OPN), Collagen type 1 (Col-1) and Bone morphogenetic protein-2 (BMP-2)) compared with random 1 wt% CS adopted PLLA (PCR1) electrospun scaffolds. In conclusion, the prepared PCA1 electrospun scaffolds might be a potential candidate for bone regeneration in defect areas.
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Nanofibras , Nanofios , Humanos , Osteogênese , Nanofibras/química , Poliésteres/química , Diferenciação Celular , Alicerces Teciduais/química , Engenharia Tecidual , Proliferação de CélulasRESUMO
Improving the separation efficiency and transfer ability of photoinduced electrons/holes in pyrite (FeS2)-based photocatalytic materials is significant for the photoreduction of hexavalent chromium (Cr(VI)) but still remains a challenge. Herein, a novel homojunction was prepared through in-situ growth of nickel (Ni) doped FeS2 nanoparticles on FeS2 nanobelts (denoted as Ni-FeS2/FeS2). Systematical characterizations revealed that Ni doped FeS2 nanoparticles have been successfully in situ grown along the lattice of FeS2 nanobelts. Photoreduction experiments demonstrated that the Ni-FeS2/FeS2 homojunction with 2 mmol Ni doping contents (denoted as 2Ni-FeS2/FeS2) exhibited the optimum Cr(VI) reduction efficiency among the studied catalysts. Density Functional Theory (DFT) calculated results verified that Ni doping could not only be advantageous for the formation of sulfur vacancies but also modify the band gap and band structure of FeS2 nanoparticles. Moreover, several doping energy levels caused by Ni doping have also appeared near the Fermi level of FeS2 nanoparticles. The migration paths of electrons and the existence of internal electric field (IEF) in homojunction were further verified by the calculation of work function. To sum up, the doping energy levels and IEF that produced by homojunction played important roles in accelerating the separation efficiency of its photogenerated carriers.
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In previous works, both tannic acid (TA) and organosilane-based passivators have been proven to possess good inhibition effects on pyrite oxidation, which could effectively prevent acid mine drainage (AMD) generation at the source. However, the hydrophilicity of TA passivation film and the complex coating process of organosilane-based passivators (high temperature conditions were required during the process carried out) may limit their further practical use. Therefore, to achieve the purpose of better coating treatment of pyrite under mild conditions, TA and γ-mercaptopropyltrimethoxysilane (PropS-SH) were introduced to synergistically passivate pyrite in this work. Electrochemistry tests and chemical leaching experiments both confirmed that PropS-SH-TA coated pyrite had better oxidation resistance than raw pyrite and single PropS-SH or TA coated pyrite. Additionally, the analyses of scanning electron microscopy (SEM) measurements and static water contact angle tests demonstrated that a scaly coating was formed on PropS-SH-TA coated pyrite surface, which may be the reason for the significant improvement of its surface hydrophobicity. Finally, the study on the film-forming mechanism of PropS-SH-TA composite passivator displayed that the benzoquinone derivatives formed by TA could copolymerize with PropS-SH through Michael addition or Schiff base reaction, which constructed a dense hydrophobic film on pyrite surface. The newly formed composite film could provide a better oxidation barrier for pyrite based on TA passivation film.
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Ferro , Compostos de Organossilício , Ferro/química , Sulfetos/química , OxirreduçãoRESUMO
Acute pancreatitis is a common acute inflammatory abdominal disease. When acute pancreatitis progresses to severe acute pancreatitis (SAP), it can lead to systemic inflammation and even multiple organ failure. Thioredoxin-interacting protein (TXNIP) is an important protein involved in redox reactions of the inflammatory response. However, the specific role of TXNIP in SAP remains unclear. In this study, we investigated the role of thioredoxin interacting protein (TXNIP) in acute pancreatitis when induced by high doses of arginine. We found that pancreatic damage and the inflammatory response associated with acute pancreatitis were largely restrained in TXNIP knock-out mice but were enhanced in mice overexpressing TXNIP. Interestingly, the phosphorylation of p38, JNK, and ASK1 diminished in TXNIP-KO mice with pancreatitis in comparison with wild-type mice. The role of oxidative stress in SAP was explored in two models: TXNIP and AVV-TXNIP. TXNIP knockdown or the inhibition of ASK1 by gs-4997 abrogated the increase in p-p38, p-JNK, and p-ASK1 in AR42J cells incubated with L-Arg. The administration of gs-4997 to mice with pancreatitis largely reduced the upregulation of IL-6, IL-1ß, TNF-α, and MCP-1. Systemic inflammatory reactions and injury in the lungs and kidneys were assessed in TXNIP-KO and AVV-TXNIP mice with expected outcomes. In conclusion, TXNIP is a novel mediator of SAP and exerts action by regulating inflammatory responses and oxidative stress via the ASK1-dependent activation of the JNK/p38 pathways. Thus, targeting TXNIP may represent a promising approach to protect against SAP.
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MAP Quinase Quinase Quinase 5 , Pancreatite , Deficiência de Proteína , Tiorredoxinas , Animais , Camundongos , Doença Aguda , Apoptose , MAP Quinase Quinase Quinase 5/metabolismo , Pancreatite/genética , Pancreatite/metabolismo , Tiorredoxinas/metabolismoRESUMO
BACKGROUND: Recently biomaterials utilized for designing scaffolds in tissue engineering are not cost-effective and eco-friendly. As a result, we design and develop biocompatible and bioactive hydrogels for osteo-tissue regeneration based on the natural polysaccharide chitosan. Three distinct hydrogel components were used for this. METHODS: Hydrogels networks were created using chitosan 2% (CTS 2%), carboxymethyl chitosan 2% (CMC 2%), and 50:50 mixtures of CTS and CMC (CTS/CMC 50:50). Furthermore, scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), degradation, and swelling behavior of design hydrogels were studied. Also, the cytocompatibility and osteo-differentiation potency were examined by encapsulating mesenchymal stem cells derived from adipose tissue (AMSCs) on the designed hydrogels. RESULTS: According to the findings, our results showed an acceptable pore structure, functional groups, and degradation rate of the designed hydrogels for in vitro evaluation. In addition, employing CMC instead of CTS or adding 50% CMC to the hydrogel component could improve the hydrogel's osteo-bioactivity without the use of external osteogenic differentiation agents. CONCLUSION: The CMC-containing hydrogel not only caused early osteogenesis but also accelerated differentiation to the maturity phase of osteoblasts.