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1.
J Am Chem Soc ; 145(6): 3312-3317, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36728932

RESUMO

Developing magnetic ultrasoft robots to navigate through extraordinarily narrow and confined spaces like capillaries in vivo requires synthesizing materials with excessive deformability, responsive actuation, and rapid adaptability, which are difficult to achieve with the current soft polymeric materials, such as elastomers and hydrogels. We report a magnetically actuatable and water-immiscible (MAWI) coacervate based on the assembled magnetic core-shell nanoparticles to function as a liquid robot. The degradable and biocompatible millimeter-sized MAWI coacervate liquid robot can remain stable under changing pH and salt concentrations, release loaded cargoes on demand, squeeze through an artificial capillary network within seconds, and realize intravascular targeting in vivo guided by an external magnetic field. We believe the proposed "coacervate-based liquid robot" can implement demanding tasks beyond the capability of conventional elastomer or hydrogel-based soft robots in the field of biomedicine and represents a distinct design strategy for high-performance ultrasoft robots.


Assuntos
Robótica , Água , Desenho de Equipamento , Fenômenos Físicos , Elastômeros , Fenômenos Magnéticos
2.
Int J Neurosci ; 133(5): 492-495, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33931000

RESUMO

BACKGROUND:  In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of one exceptional case of a nidus-type FTAVS and surgical treatment of the lesion. CASE DESCRIPTION: The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable. CONCLUSIONS: A nidus-type arteriovenous shunt could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.


Assuntos
Fístula Arteriovenosa , Cauda Equina , Humanos , Cauda Equina/diagnóstico por imagem , Cauda Equina/cirurgia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/patologia , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância Magnética , Angiografia Digital/métodos
3.
Neurosciences (Riyadh) ; 28(1): 42-47, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36617452

RESUMO

OBJECTIVES: To explore the clinicopathological features and prognosis of multifocal high-grade gliomas (M-HGGs) with H3F3A mutation in adults. METHODS: Four adult patients with H3F3A-mutant M-HGGs who were treated at our institution from August 2020 to December 2021 were reviewed, including clinical, pathological and radiologic data. A series of 16 adult patients with M-HGGs without H3F3A mutation was used as a comparative group. Progression-free survival (PFS) and overall survival (OS) were compared between the groups using the Kaplan-Meier method. RESULTS: All patients were IDH wild-type and TERT wild-type, and P53 was overexpressed. A patient with the H3 G34R mutation and 1 of 3 patients with the H3 K27 M mutation had MGMT promoter methylation. The lesions with the H3 G34R mutation were located in the cerebral hemisphere; the lesions with H3 K27 alterations were mainly in the midline structure, and the cerebral hemisphere could also be involved. One patient underwent subtotal resection (STR), and 3 patients underwent biopsy. All patients received radiotherapy, and the median PFS and OS were 9.5 months and 14.5 months, respectively. The clinical outcomes were similar to those of non-H3F3A-mutated M-HGGs patients (median PFS and OS were 7.0 months and 18.0 months, respectively). CONCLUSION: We describe the clinicopathological features and outcomes of 4 adult M-HGGs patients with H3F3A mutation, and found this mutation doesn't appear to have a negative outcome with the administration of current therapies.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Prognóstico , Mutação/genética
4.
Stroke ; 52(12): 3873-3882, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34412511

RESUMO

BACKGROUND AND PURPOSE: Paravertebral arteriovenous shunts (PVAVSs) are rare. Whether the intradural venous system is involved in drainage may lead to differences in clinical characteristics through specific pathophysiological mechanisms. This study aims to comprehensively evaluate the natural history and clinical outcomes of PVAVSs with or without intradural drainage. METHODS: Sixty-four consecutive patients with PVAVSs from 2 institutes were retrospectively reviewed. Lesions were classified as type A (n=28) if the intradural veins were involved in drainage; otherwise, they were classified as type B (n=36). The clinical course from initial presentation to the last follow-up was analyzed. RESULTS: The patients with type A shunts were older at presentation (52.5 versus 35.5 years, P<0.0001) and more likely to have lower spinal segments affected than patients with type B PVAVSs (67.8% versus 13.9%, P=0.00006). After presentation, the deterioration rates related to gait and sphincter dysfunction were significantly higher in patients with type A than type B shunts (gait dysfunction: 71.8%/y versus 17.0%/y, P=0.0006; sphincter dysfunction: 63.7%/y versus 11.3%/y, P=0.0002). According to the angiogram at the end of the latest treatment, 79% of type A and 75% of type B PVAVSs were completely obliterated. If the lesions were partially obliterated, a significantly higher clinical deterioration rate was observed in patients with type A shunts than those with type B shunts (69.9%/y versus 3.2%/y, P=0.0253). CONCLUSIONS: Type A PVAVSs feature rapid progressive neurological deficits; therefore, early clinical intervention is necessary. For complex lesions that cannot be completely obliterated, surgical disconnection of all refluxed radicular veins is suggested.


Assuntos
Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/terapia , Malformações Vasculares do Sistema Nervoso Central/patologia , Malformações Vasculares do Sistema Nervoso Central/terapia , Medula Espinal/irrigação sanguínea , Adulto , Idoso , Embolização Terapêutica/métodos , Feminino , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/patologia , Procedimentos Cirúrgicos Vasculares/métodos
5.
BMC Surg ; 21(1): 117, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676461

RESUMO

BACKGROUND: Osteopetrosis is a genetic disease characterized by defects in osteoclast formation and function. There were a few cases of subtrochanteric femur fractures treated with dynamic hip screw (DHS) in patients with osteopetrosis, but unfortunately the healing outcome was rather poor. CASE PRESENTATION: We present our experience for treating a patient with intermediate autosomal recessive osteopetrosis (IRO) suffering from subtrochanteric femur fracture. In this case, we successfully used dynamic hip screw (DHS) internal fixation through meticulous preoperative planning and postoperative care, as well as application of surgical techniques. The patient displayed stable internal fixation with no limitation of activities during follow-up for 15 months. In addition to this case, a review of previous case reports showed an increasing number of case reports demonstrating that surgical treatment-related complications could be avoided preoperatively, intraoperatively, and postoperatively. CONCLUSION: DHS for this patient, who suffered from subtrochanteric fractures with osteopetrosis, was successfully implemented. In the light of a comprehensive literature review, preoperative planning, surgical techniques, and postoperative rehabilitation care can significantly reduce the complications.


Assuntos
Fraturas do Quadril , Osteopetrose , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Humanos , Osteopetrose/complicações , Resultado do Tratamento
6.
Curr Osteoporos Rep ; 18(6): 621-632, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33030684

RESUMO

PURPOSE OF REVIEW: The goals of this review are two folds: (1) to describe the recent understandings on the roles of calcitonin gene-related peptide-α (CGRP) in bone homeostasis and the underlying mechanisms of related neuronal regulation and (2) to propose innovative CGRP-modulated approaches for enhancing bone regeneration in challenging bone disorders. RECENT FINDINGS: CGRP is predominantly produced by the densely distributed sensory neuronal fibers in bone, declining with age. Under mechanical and biochemical stimulations, CGRP releases and exerts either physiological or pathophysiological roles. CGRP at physiological level orchestrates the communications of bone cells with cells of other lineages, affecting not only osteogenesis, osteoclastogenesis, and adipogenesis but also angiogenesis, demonstrating with pronounced anabolic effect, thus is essential for maintaining bone homeostasis, with tuned nerve-vessel-bone network. In addition, its effects on immunity and cell recruitment are also crucial for bone fracture healing. Binding to the G protein-coupled receptor composited by calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) on cellular surface, CGRP triggers various intracellular signaling cascades involving cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Peaking at early stage post-fracture, CGRP promotes bone formation, displaying with larger callus. Then CGRP gradually decreases over time, allowing normal or physiological bone remodeling. By elevating CGRP at early stage, low-intensity pulsed ultrasound (LIPUS), electrical stimulation, and magnesium-based bio-mineral products may promisingly accelerate bone regeneration experimentally in medical conditions like osteoporosis, osteoporotic fracture, and spine fusion. Excess CGRP expression is commonly observed in pathological conditions including cancer metastatic lesions in bone and fracture delayed- or non-healing, resulting in persistent chronic pain. To date, these discoveries have largely been limited to animal models. Clinical applications are highly desirable. Compelling evidence show the anabolic effects of CGRP on bone in animals. However, further validation on the role of CGRP and the underlying mechanisms in human skeletons is required. It remains unclear if it is type H vessel connecting neuronal CGRP to osteogenesis, and if there is only specific rather than all osteoprogenitors responsible to CGRP. Clear priority should be put to eliminate these knowledge gaps by integrating with high-resolution 3D imaging of transparent bulk bone and single-cell RNA-sequencing. Last but not the least, given that small molecule antagonists such as BIBN4096BS can block the beneficial effects of CGRP on bone, concerns on the potential side effects of humanized CGRP-neutralizing antibodies when systemically administrated to treat migraine in clinics are arising.


Assuntos
Regeneração Óssea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Homeostase/fisiologia , Osteogênese/fisiologia , Animais , Consolidação da Fratura/fisiologia , Humanos , Transdução de Sinais
7.
Small ; 15(51): e1904486, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31755651

RESUMO

Magnesium (Mg) alloys have been promised for biomedical implants in orthopedic field, however, the fast corrosion rate and mode challenge their clinical application. To push Mg alloys materials into practice, a composite coating with biodegradable and high compatible components to improve anticorrosion property of an Mg alloy (i.e., AZ31) is designed and fabricated. The inner layer is micro-nano structured Mg(OH)2 through hydrothermal treatment. Then stearic acid (SA) is introduced to modify Mg(OH)2 for better reducing the gap below a surface-degradation polymer layer of poly(1,3-trimethylene carbonate). Benefited by the SA modification effect, this sandwiched coating avoids corrosive medium penetration via enhancing the adhesion strength at the interface between outer and inner layers. Both in vitro and in vivo tests indicate that the composite coating modified AZ31 perform a better anticorrosion behavior and biocompatibility compared to bare AZ31. Strikingly, a 1.7-fold improvement in volume of newly formed bone is observed surrounding the composite coating modified implant after 12 week implantation. The sandwiched biocompatible coating strategy paves a hopeful way for future translational application of Mg alloys orthopedic materials in clinics.


Assuntos
Implantes Absorvíveis , Ligas/química , Magnésio/química , Materiais Revestidos Biocompatíveis/química , Ácidos Esteáricos/química
8.
Ann Rheum Dis ; 78(4): 551-561, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30745310

RESUMO

OBJECTIVES: Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional relationship in OA progression in chondrocyte lineage. METHODS: The role of Wnt16 during skeletal development was examined by Col2a1-Wnt16 transgenic mice and Wnt16fl/fl;Col2a1-Cre (Wnt16-cKO) mice. OA progression was assessed by micro-CT analysis and Osteoarthritis Research Society International score after anterior cruciate ligament transection (ACLT) surgery with Wnt16 manipulation by adenovirus intra-articular injection. The molecular mechanism was investigated in vitro using 3D chondrocyte pellet culture and biochemical analyses. Histological analysis was performed in mouse joints and human cartilage specimens. RESULTS: Wnt16 overexpression in chondrocytes in mice significantly inhibited chondrocyte hypertrophy during skeletal development. Wnt16 deficiency exaggerated OA progression, whereas intra-articular injection of Ad-Wnt16 markedly attenuated ACLT-induced OA. Cellular and molecular analyses showed that, instead of ß-catenin and calcium pathways, Wnt16 activated the planar cell polarity (PCP) and JNK pathway by interacting mainly with AP2b1, and to a lesser extend Ror2 and CD146, and subsequently induced PTHrP expression through phosphor-Raptor mTORC1 pathway. CONCLUSIONS: Our findings indicate that Wnt16 activates PCP/JNK and crosstalks with mTORC1-PTHrP pathway to inhibit chondrocyte hypertrophy. Our preclinical study suggests that Wnt16 may be a potential therapeutic target for OA treatment.


Assuntos
Artrite Experimental/patologia , Osteoartrite/patologia , Proteínas Wnt/fisiologia , Animais , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Diferenciação Celular/fisiologia , Polaridade Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Condrócitos/patologia , Condrócitos/fisiologia , Progressão da Doença , Humanos , Hipertrofia/prevenção & controle , Sistema de Sinalização das MAP Quinases/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/fisiologia , Camundongos Transgênicos , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Proteína Relacionada ao Hormônio Paratireóideo/fisiologia , Proteínas Wnt/deficiência , Proteínas Wnt/metabolismo
9.
Nanomedicine ; 13(1): 111-121, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27621054

RESUMO

Specific detection of various tumor types remains crucial for designing effective treatment strategies. We demonstrate photoacoustic imaging (PAI) using high-affinity and high-specificity peptide-based probes for accurate and specific diagnosis of osteosarcoma. Herein, two new tumor-specific oligopeptides, termed PT6 and PT7, were identified using phage display-based screening on an osteosarcoma cell line (UMR-106). The identified oligopeptides were able to detect clinical osteosarcoma samples on tissue microarrays. Oligopeptide-conjugated PEGylated gold nanorods (PGNR) were designed to specifically target UMR-106 cells. More importantly, PAI revealed that both PGNR-PT6 and PGNR-PT7 could bind selectively to subcutaneous UMR-106 xenografts after systemic administration and enhance the contrast of osteosarcoma images by 170% and 230%, respectively, compared to tumor-bearing mice injected with PGNRs conjugated to scrambled oligopeptides. PAI employing PGNRs conjugated to specifically designed nanoprobes may provide a new method for tumor type-specific diagnosis of osteosarcoma.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Osteossarcoma/diagnóstico por imagem , Biblioteca de Peptídeos , Técnicas Fotoacústicas , Animais , Linhagem Celular Tumoral , Ouro/química , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Camundongos , Transplante de Neoplasias , Oligopeptídeos
10.
Nanomedicine ; 12(6): 1453-62, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27046663

RESUMO

Imaging is routinely used for clinical and diagnostic purposes, but techniques capable of high specificity and resolution for the early detection of nerve injury are still limited. In this study, we found that heat shock protein 27 (HSP27) becomes highly upregulated within 3 to 7 days of nerve injury. Taking advantage of this expression pattern, we conjugated gold nanorods (GNRs) to HSP27-specific antibodies to generate a nanoprobe (GNR-HSP27Abs) that could be targeted to the site of nerve injury and detected by near-infrared photoacoustic imaging. Notably, photoacoustic images acquired 12hours after local administration of GNR-HSP27Abs demonstrated that the nanoprobe can distinguish between injured and uninjured nerves in rats. Taken together, these findings expand the application of nanoprobe-targeted photoacoustic imaging to the detection of injured nerves, and prompt further development of this novel imaging platform for clinical application.


Assuntos
Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Análise Espectral , Traumatismos do Sistema Nervoso/diagnóstico por imagem , Animais , Anticorpos , Ouro , Proteínas de Choque Térmico HSP27 , Nanotubos , Ratos
11.
Biomed Mater ; 19(4)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38815612

RESUMO

Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.


Assuntos
Implantes Absorvíveis , Ligas , Magnésio , Insuficiência Renal Crônica , Animais , Magnésio/química , Ligas/química , Ratos , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/metabolismo , Masculino , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Teste de Materiais , Rim/metabolismo , Rim/patologia , Aço Inoxidável/química , Corrosão
12.
Sci Adv ; 10(10): eadk6084, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457498

RESUMO

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.


Assuntos
Cartilagem Articular , Nanopartículas , Osteoartrite , Ratos , Animais , Óxido de Magnésio/farmacologia , Magnésio/farmacologia , Fosfatidilinositol 3-Quinases , Osteoartrite/tratamento farmacológico
13.
Bone ; 183: 117094, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582289

RESUMO

The present study aimed to establish and evaluate a preclinical model of steroid-associated osteonecrosis (SAON) in mice. Sixteen 24-week-old male C57BL/6 mice were used to establish SAON by two intraperitoneal injections of lipopolysaccharide (LPS), followed by three subcutaneous injections of methylprednisolone (MPS). Each injection was conducted on working day, with an interval of 24 h. Six cycles of injections were conducted. Additional twelve mice (age- and gender-matched) were used as normal controls. At 2 and 6 weeks after completing induction, bilateral femora and bilateral tibiae were collected for histological examination, micro-CT scanning, and bulk RNA sequencing. All mice were alive until sacrificed at the indicated time points. The typical SAON lesion was identified by histological evaluation at week 2 and week 6 with increased lacunae and TUNEL+ osteocytes. Micro-CT showed significant bone degeneration at week 6 in SAON model. Histology and histomorphometry showed significantly lower Runx2+ area, mineralizing surface (MS/BS), mineral apposition rate (MAR), bone formation rate (BFR/BS), type H vessels, Ki67+ (proliferating) cells, and higher marrow fat fraction, osteoclast number and TNFα+ areas in SAON group. Bulk RNA-seq revealed changed canonical signaling pathways regulating cell cycle, angiogenesis, osteogenesis, and osteoclastogenesis in the SAON group. The present study successfully established SAON in mice with a combination treatment of LPS and MPS, which could be considered a reliable and reproducible animal model to study the pathophysiology and molecular mechanism of early-stage SAON and to develop potential therapeutic approaches for the prevention and treatment of SAON.


Assuntos
Lipopolissacarídeos , Osteonecrose , Masculino , Camundongos , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Osteonecrose/tratamento farmacológico , Esteroides , Osteogênese , Metilprednisolona/uso terapêutico
14.
Front Bioeng Biotechnol ; 12: 1352023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766649

RESUMO

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

15.
Arch Pathol Lab Med ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390749

RESUMO

CONTEXT.­: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes. OBJECTIVE.­: To address the concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC. DESIGN.­: Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities. RESULTS.­: We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen. CONCLUSIONS.­: We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.

16.
J Clin Invest ; 134(10)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512413

RESUMO

Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remain unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. The primary effect of glucocorticoids on osteogenic differentiation was not inhibitory; instead, they cooperated with macrophages to facilitate osteogenesis. Impaired local nutrient status - notably, obstructed fatty acid transportation - was a key factor contributing to glucocorticoid-induced impairment of bone turnover in vivo. Furthermore, fatty acid oxidation in macrophages fueled the ability of glucocorticoid-liganded receptors to enter the nucleus and then promoted the expression of BMP2, a key cytokine that facilitates osteogenesis. Metabolic reprogramming by localized fatty acid delivery partly rescued glucocorticoid-induced pathology by restoring a healthier immune-metabolic milieu. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders, thus suggesting possible therapeutic avenues.


Assuntos
Remodelação Óssea , Glucocorticoides , Osteogênese , Animais , Camundongos , Glucocorticoides/farmacologia , Osteogênese/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Ácidos Graxos/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/imunologia , Microambiente Celular/efeitos dos fármacos
17.
Mil Med Res ; 11(1): 33, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816888

RESUMO

Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.


Assuntos
Análise de Sequência de RNA , Análise de Célula Única , Humanos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Doenças Ósseas/terapia , Doenças Ósseas/fisiopatologia , Osso e Ossos , Biologia Computacional/métodos
18.
J Biol Chem ; 287(31): 26200-12, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22654119

RESUMO

To search for factors promoting bone fracture repair, we investigated the effects of extracorporeal shock wave (ESW) on the adhesion, spreading, and migration of osteoblasts and its specific underlying cellular mechanisms. After a single period of stimulation by 10 kV (500 impulses) of shock wave (SW), the adhesion rate was increased as compared with the vehicle control. The data from both wound healing and transwell tests confirmed an acceleration in the migration of osteoblasts by SW treatment. RT-PCR, flow cytometry, and Western blotting showed that SW rapidly increased the surface expression of α5 and ß1 subunit integrins, indicating that integrin ß1 acted as an early signal for ESW-induced osteoblast adhesion and migration. It has also been found that a significant elevation occurred in the expression of phosphorylated ß-catenin and focal adhesion kinase (FAK) at the site of tyrosine 397 in response to SW stimulation after the increasing expression of the integrin ß1 molecule. When siRNAs of integrin α5 and ß1 subunit were added, the level of FAK phosphorylation elevated by SW declined. Interestingly, the adhesion and migration of osteoblasts were decreased when these siRNA reagents as well as the ERK1/2 signaling pathway inhibitors, U0126 and PD98059, were present. Further studies demonstrated that U0126 could inhibit the downstream integrin-dependent signaling pathways, such as the FAK signaling pathway, whereas it had no influence on the synthesis of integrin ß1 molecule. In conclusion, these data suggest that ESW promotes the adhesion and migration of osteoblasts via integrin ß1-mediated expression of phosphorylated FAK at the Tyr-397 site; in addition, ERK1/2 are also important for osteoblast adhesion, spreading, migration, and integrin expression.


Assuntos
Adesão Celular/efeitos da radiação , Movimento Celular/efeitos da radiação , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Ondas de Choque de Alta Energia , Integrina beta1/metabolismo , Osteoblastos/fisiologia , Animais , Células Cultivadas , Feminino , Proteína-Tirosina Quinases de Adesão Focal/genética , Expressão Gênica , Integrina alfa5/genética , Integrina alfa5/metabolismo , Integrina beta1/genética , Sistema de Sinalização das MAP Quinases , Masculino , Osteoblastos/metabolismo , Osteoblastos/efeitos da radiação , Fosforilação , Cultura Primária de Células , Processamento de Proteína Pós-Traducional/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Crânio/citologia , Via de Sinalização Wnt , beta Catenina/metabolismo
19.
J Colloid Interface Sci ; 640: 199-210, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863177

RESUMO

HYPOTHESIS: Cement augmentation has been widely applied to promote osteoporotic fracture healing, whereas the existing calcium-based products suffer from the excessively slow degradation, which may impede bone regeneration. Magnesium oxychloride cement (MOC) shows promising biodegradation tendency and bioactivity, which is expected to be a potential alternative to the classic calcium-based cement for hard-tissue-engineering applications. EXPERIMENTS: Here, a hierarchical porous MOC foam (MOCF)-derived scaffold with favorable bio-resorption kinetic and superior bioactivity is fabricated through Pickering foaming technique. Then, a systematic characterization in terms of material properties and in vitro biological performance have been conducted to evaluate the feasibility of the as-prepared MOCF scaffold to be a bone-augmenting material for treating osteoporotic defects. FINDINGS: The developed MOCF shows excellent handling performance in the paste state, while exhibiting sufficient load-bearing capacity after solidification. In comparison with the traditional bone cement, calcium deficient hydroxyapatite (CDHA), our porous MOCF scaffold demonstrates a much higher biodegradation tendency and better cell recruitment ability. Additionally, the eluted bioactive ions by MOCF commits to a biologically inductive microenvironment, where the in vitro osteogenesis is significantly enhanced. It is anticipated that this advanced MOCF scaffold will be competitive for clinical therapies to augment osteoporotic bone regeneration.


Assuntos
Cimentos Ósseos , Magnésio , Cimentos Ósseos/farmacologia , Cimentos Ósseos/uso terapêutico , Magnésio/farmacologia , Cálcio , Durapatita/farmacologia , Osteogênese , Regeneração Óssea , Alicerces Teciduais
20.
RSC Adv ; 13(14): 9448-9456, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36968043

RESUMO

In this work, a hybrid Cu-ZnO/g-C3N4 nanocomposite was synthesized and introduced to fabricate photocatalytic cement mortars by internal mixing. The bactericidal properties of the photocatalytic mortars were explored by using E. coli, S. aureus and P. aeruginosa as a bacteria test strain. The results showed that the Cu-ZnO/g-C3N4 nanocomposite had an enhanced harvesting of visible light energy and exhibited excellent stability during the photocatalytic process, which favored a long-term usage performance. The sterilizing efficiency of the photocatalytic cement mortars improved with an increasing content of Cu-ZnO/g-C3N4 nanocomposites. A possible bactericidal mechanism was proposed based on the active species trapping experiments, verifying that the photogenerated holes (h+) and ˙O2 - radicals were the main active species.

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