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JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
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Management of diabetic chronic wound exudate is a serious challenge in healthcare worldwide since it is related to the speed of diabetic wound healing. However, current foam dressings not only absorb fluid to generate swelling and compress the wound to hinder wound healing but also are very thick and less comfortable to use. Herein, a superabsorbent self-pumping ultrathin dressing is reported to accelerate diabetic wound healing by achieving superior exudate absorption and management in an ultrathin state. The self-pumping dressing is composed of a drainage layer loaded with anthocyanidin and a thermoplastic polyurethane absorbent layer embedded with superabsorbent particles. The dressing realizes the self-pumping process of unidirectional exudate draining to the absorption layer through the drainage layer without significant dressing swelling to compress the diabetic wound. The dressing is experimentally proven to unidirectionally drain excessive exudate with inflammatory factors and modulate the conversion of macrophages from M1 to M2 in diabetic wounds, thereby promoting the healing of diabetic skin ulcers faster than commercial foam dressings. Therefore, the dressing provides a new idea and novel method for accelerating diabetic skin ulcer healing.
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Antocianinas , Bandagens , Diabetes Mellitus Experimental , Macrófagos , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos , Diabetes Mellitus Experimental/terapia , Antocianinas/química , Antocianinas/farmacologia , Ratos , Masculino , Células RAW 264.7 , Poliuretanos/químicaRESUMO
PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.
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Densidade Óssea , Osso Esponjoso , Úmero , Tomografia Computadorizada por Raios X , Humanos , Densidade Óssea/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Reprodutibilidade dos Testes , Úmero/diagnóstico por imagem , Úmero/fisiologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/fisiopatologia , Osso Esponjoso/fisiologia , Algoritmos , Imagens de Fantasmas , Adulto , Osteoporose/fisiopatologia , Osteoporose/diagnóstico por imagem , Idoso de 80 Anos ou maisRESUMO
Purpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats. Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition. Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance. Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing.
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Quitosana , Diabetes Mellitus , Nanopartículas Metálicas , Humanos , Camundongos , Ratos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Quitosana/química , Ouro/química , Staphylococcus aureus/metabolismo , Hidrogéis/química , Escherichia coli , Células NIH 3T3 , Nanopartículas Metálicas/química , Cicatrização , Colágeno/metabolismo , Bactérias/metabolismo , InflamaçãoRESUMO
Uncontrolled hemorrhage results in various complications and is currently the leading cause of death in the general population. Traditional hemostatic methods have drawbacks that may lead to ineffective hemostasis and even the risk of secondary injury. Therefore, there is an urgent need for more effective hemostatic techniques. Polymeric hemostatic materials, particularly hydrogels, are ideal due to their biocompatibility, flexibility, absorption, and versatility. Functional hemostatic hydrogels can enhance hemostasis by creating physical circumstances conducive to hemostasis or by directly interfering with the physiological processes of hemostasis. The procoagulant principles include increasing the concentration of localized hemostatic substances or establishing a physical barrier at the physical level and intervention in blood cells or the coagulation cascade at the physiological level. Moreover, synergistic hemostasis can combine these functions. However, some hydrogels are ineffective in promoting hemostasis or have a limited application scope. These defects have impeded the advancement of hemostatic hydrogels. To provide inspiration and resources for new designs, this review provides an overview of the procoagulant principles of hemostatic hydrogels. We also discuss the challenges in developing effective hemostatic hydrogels and provide viewpoints.
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Hemostáticos , Humanos , Hemostáticos/farmacologia , Hidrogéis/farmacologia , Hemostasia , Coagulação Sanguínea , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controleRESUMO
Self-pumping dressings become one of the optimal solutions for the controlled management of chronic diabetic wound exudate and wound healing. However, present self-pumping dressings are not only prone to breakage of the loose hydrophobic layer but also have cumbersome and complicated preparation steps, which hinder the application of self-pumping dressings in diabetic wound treatment. Herein, a novel self-pumping structure of superabsorbent Janus dressing is designed to improve the strength of the hydrophobic layer and promote diabetic wound healing. The Janus dressing consists of a hydrophobic layer with a drainage agent (drainage layer) and a fluffy 3D nanofiber cotton (absorbent layer). Regardless of the thickness of the drainage layer, the drainage agent in the drainage layer provides the fluid to penetrate the drainage layer to the absorbent layer for unidirectional fluid draining. In design proof, the superabsorbent Janus dressing provides unidirectional drainage of inflammatory exudate and regulation of macrophage polarization, resulting in faster diabetic wound healing than single-layer dressings. Thus, the Janus dressing demonstrates important clinical implications to offer a novel design and preparation strategy for accelerating diabetic wound healing.
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Bandagens , Diabetes Mellitus , Humanos , Cicatrização , Exsudatos e Transudatos , Interações Hidrofóbicas e HidrofílicasRESUMO
Achieving precision treatment in bone tissue engineering (BTE) remains a challenge. Photothermal therapy (PTT), as a form of precision therapy, has been extensively investigated for its safety and efficacy. It has demonstrated significant potential in the treatment of orthopedic diseases such as bone tumors, postoperative infections and osteoarthritis. However, the high temperatures associated with PTT can lead to certain limitations and drawbacks. In recent years, researchers have explored the use of biomaterials for mild photothermal therapy (MPT), which offers a promising approach for addressing these limitations. This review provides a comprehensive overview of the mechanisms underlying MPT and presents a compilation of photothermal agents and their utilization strategies for bone tissue repair. Additionally, the paper discusses the future prospects of MPT-assisted bone tissue regeneration, aiming to provide insights and recommendations for optimizing material design in this field.
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Diabetic wounds are chronically hard-healing wounds. Bacterial infection, persistent inflammation and impaired angiogenesis are key factors affecting diabetic wound healing. Herein, inspired by pomegranate, Au/Ag nanodots (Au/AgNDs) with fluorescent and photothermal properties were adopted as the pomegranate-like core, and the polyvinyl alcohol hydrogel as the pomegranate-like shell to obtain the multifunctional nanocomposite wound dressing for promoting diabetic wounds healing and real-time self-monitoring the dressing state. On the one hand, the antibacterial and photothermal therapy synergistic strategy based on the nanocomposite has an excellent treatment effect on diabetic wounds by highly antibacterial, anti-inflammation, accelerating collagen deposition and angiogenesis. On the other hand, the nanocomposite can be used as "smart messenger" to determine the appropriate time for dressing replacement. With the release of Au/AgNDs from the nanocomposite, the photothermal performance and antibacterial activity of the wound dressing were reduced, and the fluorescence intensity decreased. The change of fluorescence intensity can be visualized by the naked eye, which guides the appropriate time for dressing replacement, and avoids secondary wound damage caused by frequent and blind dressing replacement. This work provides an effective strategy for the treatment of diabetic wounds and intelligent self-monitoring of the state of dressings in clinical practice.
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Técnicas Biossensoriais , Diabetes Mellitus , Nanocompostos , Bandagens , Cicatrização , Antibacterianos , Diabetes Mellitus/terapiaRESUMO
Fungal diseases have posed a great challenge to global health, but have fewer solutions compared to bacterial and viral infections. Development and application of new treatment modalities for fungi are limited by their inherent essential properties as eukaryotes. The microorganism identification and drug sensitivity analyze are limited by their proliferation rates. Moreover, there are currently no vaccines for prevention. Polymer science and related interdisciplinary technologies have revolutionized the field of fungal disease management. To date, numerous advanced polymer-based systems have been developed for management of fungal diseases, including prevention, diagnosis, treatment and monitoring. In this review, we provide an overview of current needs and advances in polymer-based strategies against fungal diseases. We high light various treatment modalities. Delivery systems of antifungal drugs, systems based on polymers' innate antifungal activities, and photodynamic therapies each follow their own mechanisms and unique design clues. We also discuss various prevention strategies including immunization and antifungal medical devices, and further describe point-of-care testing platforms as futuristic diagnostic and monitoring tools. The broad application of polymer-based strategies for both public and personal health management is prospected and integrated systems have become a promising direction. However, there is a gap between experimental studies and clinical translation. In future, well-designed in vivo trials should be conducted to reveal the underlying mechanisms and explore the efficacy as well as biosafety of polymer-based products.
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Antifúngicos , Micoses , Humanos , Antifúngicos/uso terapêutico , Polímeros/uso terapêutico , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/prevenção & controle , FungosRESUMO
Although the past decade has witnessed unprecedented medical advances, achieving rapid and effective hemostasis remains challenging. Uncontrolled bleeding and wound infections continue to plague healthcare providers, increasing the risk of death. Various types of hemostatic materials are nowadays used during clinical practice but have many limitations, including poor biocompatibility, toxicity and biodegradability. Recently, there has been a burgeoning interest in organisms that stick to objects or produce sticky substances. Indeed, applying biological adhesion properties to hemostatic materials remains an interesting approach. This paper reviews the biological behavior, bionics, and mechanisms related to hemostasis. Furthermore, this paper covers the benefits, challenges and prospects of biomimetic hemostatic materials.
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Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.
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Formigas , Membros Artificiais , Nanopartículas Metálicas , Animais , Prata/farmacologia , Biomimética , Osseointegração , Antibacterianos/farmacologiaRESUMO
The R2R3-MYB transcription factors are widely involved in the regulation of plant growth, biotic and abiotic stress responses. Meanwhile, seed germination, which is stimulated by internal and external environments, is a critical stage in the plant life cycle. However, the identification, characterization, and expression profiling of the Populus euphratica R2R3-MYB family in drought response during seed germination have been unknown. Our study attempted to identify and characterize the R2R3-MYB genes in P. euphratica (PeR2R3-MYBs) and explore how R2R3-MYBs trigger the drought and abscisic acid (ABA) response mechanism in its seedlings. Based on the analysis of comparative genomics, 174 PeR2R3-MYBs were identified and expanded driven by whole genome duplication or segment duplication events. The analysis of Ka/Ks ratios showed that, in contrast to most PeR2R3-MYBs, the other PeR2R3-MYBs were subjected to positive selection in P. euphratica. Further, the expression data of PeR2R3-MYBs under drought stress and ABA treatment, together with available functional data for Arabidopsis thaliana MYB genes, supported the hypothesis that PeR2R3-MYBs involved in response to drought are dependent or independent on ABA signaling pathway during seed germination, especially PeR2R3-MYBs with MYB binding sites (MBS) cis-element and/or tandem duplication. This study is the first report on the genome-wide analysis of PeR2R3-MYBs, as well as the other two Salicaceae species. The duplication events and differential expressions of PeR2R3-MYBs play important roles in enhancing the adaptation to drought desert environment. Our results provide a reference for prospective functional studies of R2R3-MYBs of poplars and lay the foundation for new breeding strategies to improve the drought tolerance of P. euphratica.
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Arabidopsis , Populus , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Populus/genética , Populus/metabolismo , Genes myb , Proteínas de Plantas/metabolismo , Secas , Estudos Prospectivos , Melhoramento Vegetal , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , FilogeniaRESUMO
Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after SCI, and, if so, whether reversing CL alteration leads to neuroprotection after SCI. Using lipidomic analysis, we uncovered CL alterations at an early stage of SCI. Over 50 distinct CL species were identified, of which 50% showed significantly decreased abundance after SCI. The decreased CL species contained mainly polyunsaturated fatty acids that are highly susceptible to peroxidation. In parallel, 4-HNE, a lipid peroxidation marker, significantly increased after SCI. We found that mitochondrial oxidative stress not only induced CL oxidation, but also resulted in CL loss by activating cPLA2 to hydrolyze CL. CL alterations induced mitochondrial dysfunction and neuronal death. Remarkably, pharmacologic inhibition of CL alterations with XJB-5-131, a novel mitochondria-targeted electron and reactive oxygen species scavenger, reduced cell death, tissue damage and ameliorated motor deficits after SCI in adult rats. These findings suggest that CL alteration could be a novel mechanism that mediates injury-induced neuronal death, and a potential therapeutic target for ameliorating secondary SCI.
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Cardiolipinas , Traumatismos da Medula Espinal , Ratos , Animais , Cardiolipinas/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Morte Celular , Mitocôndrias/metabolismo , Fosfolipídeos/metabolismo , HomeostaseRESUMO
Brachial plexus avulsion (BPA), which commonly occurs in neonatal birth injuries and car accidents, severely disrupts spinal cord segments and nerve roots. Avulsion is usually located in the transitional zone at the junction of spinal nerve roots and starting point of the spinal cord, which places heavy disability burdens on patients due to sensory and motor function loss in the innervated areas. Primary mechanical injuries and secondary pathogenesis, such as inflammatory infiltration and oxidative stress, lead to inefficient management and poor prognosis. Astaxanthin (AST) has a strong ability to bleach singlet oxygen and capture free radicals, quench singlet oxygen and trap free radicals, and folic acid (FC) can effectively inhibit the inflammatory response. This study aimed to investigate the therapeutic effects of AST and FC on BPA. The 24 h after BPA was considered the acute phase of the injury, and the combination of AST and FC had the best therapeutic effect due to the synergistic effect of AST's antioxidant and FC's anti-inflammatory properties. At 6 weeks after BPA, AST-FC promoted the recovery of biceps motor functions, increased myofiber diameter, enlarged the amplitude of musculocutaneous nerve-biceps compound action potential, and improved Terzis grooming test (TGT) scores. Meanwhile, more functional ventral horn motor neurons in the spinal cord were maintained. In conclusion, AST-FC combined therapy has a potential role in the clinical management of BPA since it can effectively alleviate oxidative stress and the inflammatory response in the acute phase of BPA, increase the survival rate of neurons, and promote neuronal regeneration and recovery of motor functions in the late stage of BPA.
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Three different types of entropy weight methods (EWMs), i.e., EWM-A, EWM-B, and EWM-C, have been used by previous studies for integrating prediction models. These three methods use very different ideas on determining the weights of individual models for integration. To evaluate the performances of these three EWMs, this study applied them to developing integrated short-term traffic flow prediction models for signalized intersections. At first, two individual models, i.e., a k-nearest neighbors (KNN)-algorithm-based model and a neural-network-based model (Elman), were developed as individual models to be integrated using EWMs. These two models were selected because they have been widely used for traffic flow prediction and have been approved to be able to achieve good performance. After that, three integrated models were developed by using the three different types of EWMs. The performances of the three integrated models, as well as the individual KNN and Elman models, were compared. We found that the traffic flow predicted with the EWM-C model is the most accurate prediction for most of the days. Based on the model evaluation results, the advantages of using the EWM-C method were deliberated and the problems with the EWM-A and EWM-B methods were also discussed.
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Articular cartilage has limited self-regeneration ability for lacking of blood vessels, nerves, and lymph that makes it a great challenge to repair defects of the tissue and restore motor functions of the injured or aging population. Platelet derivatives, such as platelet-rich plasma, have been proved effective, safe, and economical in musculoskeletal diseases for their autologous origin and rich in growth factors. The combination of platelet derivatives with biomaterials provides both mechanical support and localized sustained release of bioactive molecules in cartilage tissue engineering and low-cost efficient approaches of potential treatment. In this review, we first provide an overview of platelet derivatives and their application in clinical and experimental therapies, and then we further discuss the techniques of the addition of platelet derivatives and their influences on scaffold properties. Advances in cartilage tissue engineering with platelet derivatives as signal factors and structural components are also introduced before prospects and concerns in this research field. In short, platelet derivatives have broad application prospects as an economical and effective enhancement for tissue engineering-based articular cartilage repair.
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As the most common cancer in men worldwide, prostate cancer has a serious impact on people's health. Until now, the development of a platform for integrating tumor targeting, imaging and an effective treatment for prostate cancer has remained challenging. Herein, a nano-system is designed to improve both diagnosis and treatment for prostate cancer. We successfully synthesized an AuNCs-LHRHa nano-system by combining PEI-modified gold nanoclusters (AuNCs) with LHRH analogues (LHRHa). Due to the good tunable optical properties and photothermal properties of AuNCs, the nano-system can not only achieve efficient fluorescence/computed tomography dual-mode imaging, but can also be used for photothermal therapy (PTT). After modifying the LHRHa antibody of a prostate tumor, AuNCs-LHRHa can be more effectively recognized by the gonadotropin-releasing hormone receptors (GnRH-R) on the membrane of RM-1 cells, enhancing the tumor cell uptake of the nano-system, improving the targeting accuracy and PTT therapy efficacy for prostate cancer. It is hoped that the nano-system, which combines dual-mode imaging and targeted therapy, will provide a promising strategy for the integration of FL/CT diagnosis and PTT therapy for GnRH-R positive prostate cancer.
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Terapia Fototérmica , Neoplasias da Próstata , Ouro , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
Understanding the reorganization of neural circuits spared after spinal cord injury in the motor cortex and spinal cord would provide insights for developing therapeutics. Using optogenetic mapping, we demonstrated a transhemispheric recruitment of neural circuits in the contralateral cortical M1/M2 area to improve the impaired forelimb function after a cervical 5 right-sided hemisection in mice, a model mimicking the human Brown-Séquard syndrome. This cortical reorganization can be elicited by a selective cortical optogenetic neuromodulation paradigm. Areas of whisker, jaw, and neck, together with the rostral forelimb area, on the motor cortex ipsilateral to the lesion were engaged to control the ipsilesional forelimb in both stimulation and nonstimulation groups 8 weeks following injury. However, significant functional benefits were only seen in the stimulation group. Using anterograde tracing, we further revealed a robust sprouting of the intact corticospinal tract in the spinal cord of those animals receiving optogenetic stimulation. The intraspinal corticospinal axonal sprouting correlated with the forelimb functional recovery. Thus, specific neuromodulation of the cortical neural circuits induced massive neural reorganization both in the motor cortex and spinal cord, constructing an alternative motor pathway in restoring impaired forelimb function.
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Córtex Motor , Traumatismos da Medula Espinal , Animais , Membro Anterior , Camundongos , Córtex Motor/patologia , Córtex Motor/fisiologia , Tratos Piramidais/patologia , Tratos Piramidais/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapiaRESUMO
Cancer remains a formidable global problem with a high mortality rate. There are many effective anti-cancer drugs in clinical use, among which paclitaxel (PTX) has good effects on non-small cell lung cancer, ovarian cancer, and breast cancer. However, when applied to the clinic, PTX still has many limitations, such as poor water solubility, drug resistance, and side effects on healthy tissues. A gold nanodots-paclitaxel-polylysine (AuNDs-PTX-PLL) core-shell nano-system of integrated diagnosis and treatment is constructed to achieve intelligent responsive drug delivery. On the one hand, the problem of poor water-solubility and drug resistance of PTX are solved. On the other hand, the nano-system has an excellent intelligent response effect. Drugs can only be released in the weakly acidic environment of the tumor, which reduces the damage and side effects to normal tissues. Moreover, the nano-system can be used for real-time tracking and auxiliary diagnosis for the tumor through the multi-mode imaging mode, such as fluorescence, photoacoustic, and computed tomography to achieve accurate visualization. The photothermal effect of AuNDs is beneficial to promote the release of drugs. The nano-system integrates multi-mode imaging, chemotherapy, intelligent drug release in tumor weakly acidic environment, and has excellent practical application prospects in tumor diagnosis and treatment.