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1.
Am J Pathol ; 194(3): 430-446, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38101566

RESUMEN

Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.


Asunto(s)
Osificación Heterotópica , Osteogénesis , Animales , Ratones , Factor I del Crecimiento Similar a la Insulina , Péptidos Similares a la Insulina , Mamíferos , Osificación Heterotópica/etiología , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Receptor IGF Tipo 1 , Serina-Treonina Quinasas TOR , Microtomografía por Rayos X
2.
BMC Plant Biol ; 24(1): 159, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38429715

RESUMEN

BACKGROUND: Flower buds of Anthurium andraeanum frequently cease to grow and abort during the early flowering stage, resulting in prolonged planting times and increased commercialization costs. Nevertheless, limited knowledge exists of the mechanism of flower development after initiation in A. andraeanum. RESULTS: In this study, the measurement of carbohydrate flow and intensity between leaves and flowers during different growth stages showed that tender leaves are strong sinks and their concomitant flowers are weak ones. This suggested that the tender leaves compete with their concomitant flower buds for carbohydrates during the early growth stages, potentially causing the abortion of the flower buds. The analysis of transcriptomic differentially expressed genes suggested that genes related to sucrose metabolism and auxin response play an important role during flower bud development. Particularly, co-expression network analysis found that AaSPL12 is a hub gene engaged in flower development by collaborating carbohydrate and auxin signals. Yeast Two Hybrid assays revealed that AaSPL12 can interact with AaARP, a protein that serves as an indicator of dormancy. Additionally, the application of exogenous IAA and sucrose can suppress the expression of AaARP, augment the transcriptional abundance of AaSPL12, and consequently expedite flower development in Anthurium andraeanum. CONCLUSIONS: Collectively, our findings indicated that the combination of auxin and sugar signals could potentially suppress the repression of AaARP protein to AaSPL12, thus advancing the development of flower buds in Anthurium andraeanum.


Asunto(s)
Araceae , Reproducción , Femenino , Embarazo , Humanos , Sacarosa , Araceae/genética , Flores/genética , Ácidos Indolacéticos
3.
Phytother Res ; 38(1): 156-173, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37846877

RESUMEN

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is the main complication secondary to long-term or excessive use of glucocorticoids (GCs). Taxifolin (TAX) is a natural antioxidant with various pharmacological effects, such as antioxidative stress and antiapoptotic properties. The purpose of this study was to explore whether TAX could regulate oxidative stress and apoptosis in GIONFH by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. We conducted qRT-PCR, Western blotting, TUNEL assays, flow cytometry, and other experiments in vitro. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were performed to determine the therapeutic effect of TAX in vivo. TAX mitigated the overexpression of ROS and NOX gene expression induced by DEX, effectively reducing oxidative stress. Additionally, TAX could alleviate DEX-induced osteoblast apoptosis, as evidenced by qRT-PCR, Western blotting, and other experimental techniques. Our in vivo studies further demonstrated that TAX mitigates the progression of GIONFH in rats by combating oxidative stress and apoptosis. Mechanistic exploration revealed that TAX thwarts the progression of GIONFH through the activation of the Nrf2 pathway. Overall, our research herein reports that TAX-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of GIONFH.


Asunto(s)
Glucocorticoides , Osteonecrosis , Quercetina/análogos & derivados , Ratas , Animales , Glucocorticoides/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal , Cabeza Femoral/metabolismo , Microtomografía por Rayos X , Estrés Oxidativo , Osteonecrosis/inducido químicamente , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/metabolismo , Apoptosis
4.
J Hand Surg Am ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39001768

RESUMEN

PURPOSE: This study compared the biomechanical stability of transosseous repair and transosseous combined with capsular repair techniques to reattach the triangular fibrocartilage complex (TFCC) for distal radioulnar joint instability. METHODS: Eight adult cadaveric upper-extremity specimens were studied. Each underwent peripheral ulnar-sided detachment of the deep and superficial TFCC fibers and repair. Four groups were prepared sequentially: intact TFCC, disrupted TFCC, transosseous repair, and combined transosseous with capsular repair. Forearm rotational torque was measured in three wrist positions: 60° flexion, neutral position, and 60° extension. Maximum dorsal and palmar ulnar translations in response to a 20-N traction load were measured at nine wrist positions after stabilizing the humerus and radius. Measurements were taken before and after TFCC disruption and following repair. RESULTS: Clear instability of the radius relative to the ulna was observed after sectioning the deep and superficial fibers of the TFCC, and stability was markedly improved after reconstruction in all positions. Compared with the normal group, rotational torque was similar between the two repair methods. In the pronation palmar flexion and supination dorsal extension positions, dorsal-palmar translation was smaller in the combined transosseous with capsular repair group than in the transosseous repair-alone group. CONCLUSIONS: Triangular fibrocartilage complex deep fibers are the primary stabilizing structure of the distal radioulnar joint. In this cadaveric study, the combined transosseous with capsular repair technique demonstrated less dorsal-palmar translation compared with the transosseous-alone repair technique. CLINICAL RELEVANCE: Combined transosseous with capsular repair is expected to provide improved postoperative stability for patients with peripheral TFCC tears and distal radioulnar joint instability.

5.
Nano Lett ; 23(15): 6937-6943, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37486358

RESUMEN

We demonstrate enhanced electronic transport through dimer molecular junctions, which self-assemble between two gold electrodes in π-π stabilized binding configurations. Single molecule junction conductance measurements show that benzimidazole molecules assemble into dimer junctions with a per-molecule conductance that is higher than that in monomer junctions. Density functional theory calculations reveal that parallel stacking of two benzimidazoles between electrodes is the most energetically favorable due to the large π system. Imidazole is smaller and has greater conformational freedom to access different stacking angles. Transport calculations confirm that the conductance enhancement of benzimidazole dimers results from the changed binding geometry of dimers on gold, which is stabilized and made energetically accessible by intermolecular π stacking. We engineer imidazole derivatives with higher monomer conductance than benzimidazole and large intermolecular interaction that promote cooperative in situ assembly of more transparent dimer junctions and suggest at the potential of molecular devices based on self-assembled molecular layers.

6.
New Phytol ; 239(4): 1464-1474, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37292017

RESUMEN

The ecological and evolutionary processes shaping community structure and functions of microbial symbionts are known to be scale-dependent. Nonetheless, understanding how the relative importance of these processes changes across spatial scales, and deciphering the hierarchical metacommunity structure of fungal endophytes has proven challenging. We investigated metacommunities of endophytic fungi within leaves of an invasive plant (Alternanthera philoxeroides) across wide latitudinal transects both in its native (Argentina) and introduced (China) ranges to test whether metacommunities of fungal endophytes were structured by different drivers at different spatial scales. We found Clementsian structures with seven discrete compartments (distinctive groups of fungal species with coincident distribution ranges), which coincided with the distribution of major watersheds. Metacommunity compartments were explicitly demarcated at three spatial scales, that is, the between-continent, between-compartment, and within-compartment scales. At larger spatial scales, local environmental conditions (climate, soil, and host plant traits) were replaced by other geographical factors as principal determinants of metacommunity structure of fungal endophytes and community diversity-function relationships. Our results reveal novel insights into the scale dependency of diversity and functions of fungal endophytes, which are likely similar for plant symbionts. These findings can potentially improve our understanding of the global patterns of fungal diversity.


Asunto(s)
Endófitos , Plantas , Plantas/microbiología , Evolución Biológica , China , Hongos , Biodiversidad
7.
J Nanobiotechnology ; 21(1): 486, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38105181

RESUMEN

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.


Asunto(s)
Condrocitos , Exosomas , Células Madre Mesenquimatosas , MicroARNs , Osteoartritis , Animales , Ratas , Condrocitos/metabolismo , Exosomas/metabolismo , MicroARNs/metabolismo , Osteoartritis/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Factor 6 Asociado a Receptor de TNF/farmacología
8.
BMC Musculoskelet Disord ; 24(1): 935, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38042803

RESUMEN

BACKGROUND: Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. METHODS: Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. RESULTS: All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. CONCLUSION: Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.


Asunto(s)
Síndrome del Túnel Carpiano , Gota , Humanos , Dedos , Muñeca , Gota/complicaciones , Gota/cirugía , Tendones/cirugía , Tendones/fisiología
9.
Br J Neurosurg ; 37(5): 1292-1296, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33325256

RESUMEN

BACKGROUND: Upper limb spasticity leads to different degrees of disabilities in cerebral palsy, which seriously affects the life of patients. Contralateral C7 nerve transfer has been shown to improve function and reduce spasticity in the affected upper limb with post-stroke hemiplegia. However, reports about the efficacy of this procedure in treating upper limb spasticity caused by hemiplegic cerebral palsy were limited. CASE DESCRIPTION: We reported two cases (a 23-year-old male and a 18-year-old female) who suffered from hemiplegic cerebral palsy with unilateral sustained upper limb spasticity and underwent contralateral C7 nerve transfer in adulthood. The scores of Fugel-Meyer and ROM of the affected upper limbs were observed before and after surgery. Compared with the preoperative, scores of the latest follow-up both were significantly improved. The muscle tension of the upper limbs decreased, and the symptoms of spasm were alleviated. CONCLUSIONS: Considering contralateral C7 nerve transfer could effectively relieve spasticity and improve upper limb activity, it can be recommended as one of the reliable methods to manage spasticity and dystonia of upper limbs in patients with hemiplegic cerebral palsy.


Asunto(s)
Parálisis Cerebral , Transferencia de Nervios , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Parálisis Cerebral/complicaciones , Parálisis Cerebral/cirugía , Transferencia de Nervios/métodos , Hemiplejía/etiología , Hemiplejía/cirugía , Espasticidad Muscular/cirugía , Espasticidad Muscular/complicaciones , Extremidad Superior/cirugía
10.
J Chem Phys ; 157(23): 234201, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36550043

RESUMEN

We demonstrate single molecule conductance as a sensitive and atomically precise probe of binding configurations of adenine and its biologically relevant variants on gold. By combining experimental measurements and density functional theory (DFT) calculations of single molecule-metal junction structures in aqueous conditions, we determine for the first time that robust binding of adenine occurs in neutral or basic pH when the molecule is deprotonated at the imidazole moiety. The molecule binds through the donation of the electron lone pairs from the imidazole nitrogen atoms, N7 and N9, to the gold electrodes. In addition, the pyrimidine ring nitrogen, N3, can bind concurrently and strengthen the overall metal-molecule interaction. The amine does not participate in binding to gold in contrast to most other amine-terminated molecular wires due to the planar geometry of the nucleobase. DFT calculations reveal the importance of interface charge transfer in stabilizing the experimentally observed binding configurations. We demonstrate that biologically relevant variants of adenine, 6-methyladenine and 2'-deoxyadenosine, have distinct conductance signatures. These results lay the foundation for biosensing on gold using single molecule conductance readout.


Asunto(s)
Aminas , Oro , Oro/química , Conformación Molecular , Adenina/química , Nitrógeno
11.
Int Orthop ; 46(10): 2283-2289, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35882639

RESUMEN

PURPOSE: This study aimed to investigate the optimal tension for the reconstruction of the distal radioulnar ligaments (DRULs) in the treatment of the distal radioulnar joint (DRUJ) instability. METHODS: A total of eight human cadaver upper extremities were used. First, the Tekscan sensor film system was used to measure the contact characteristics of the intact DRUJ. Following this, the DRULs were resected, and the measurement was repeated. The DRULs were then reconstructed according to Adams' procedure, and the contact forces under different initial tension were compared with that of the intact group to obtain the optimal tension. At that point, the contact force of the DRUJ was close to normal. The reliability of the obtained tension was verified by translational testing, which reflected the stability of the DRUJ. RESULTS: In the neutral position, the contact force, area, and pressure inside DRUJ were 0.51 ± 0.10 N, 64.08 ± 11.58 mm2, and 8.33 ± 2.42 kPa, respectively. After the DRULs were resected, they were 0.19 ± 0.02 N, 41.75 ± 5.01 mm2, and 4.86 ± 1.06 kPa, respectively. The relationship between the tension and contact force was linear regression (Y = 0.0496x + 0.229, R2 = 0.9575, P < 0.0001). According to the equation, when the tension was 3.64-7.68 N, the contact force was close to normal. There was no statistical difference in the stability of the reconstructed DRUJ under this tension compared with the intact group (P = 0.08). CONCLUSION: By comparing the contact forces under different reconstruction tensions with the normal value, we obtained the optimal tension, which can provide the theoretical basis for the clinical treatment of chronic DRUJ instability.


Asunto(s)
Inestabilidad de la Articulación , Cúbito , Fenómenos Biomecánicos , Cadáver , Humanos , Inestabilidad de la Articulación/cirugía , Ligamentos , Radio (Anatomía)/cirugía , Reproducibilidad de los Resultados , Cúbito/cirugía , Articulación de la Muñeca/cirugía
12.
Arch Orthop Trauma Surg ; 142(8): 2111-2120, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35397657

RESUMEN

INTRODUCTION: In the reconstruction of distal radioulnar ligaments (DRULs), interference screws can be used for antegrade or retrograde fixation of grafts to the ulna. However, the biomechanics of interference screw fixation are currently unknown. This study aimed to determine the biomechanical effects of these two fixations on the distal radioulnar joint (DRUJ) in a cadaveric model and to investigate the appropriate initial tension. MATERIALS AND METHODS: A total of 30 human cadaver upper extremities were used, and the DRULs were reconstructed according to Adams' procedure. First, eight specimens were randomly divided into two groups: antegrade and retrograde, followed by translational testing and load testing. Then, the other eight specimens were divided into the two groups above, and the contact mechanics, including forces, areas, and pressures, were measured. Finally, to investigate the appropriate initial tension, the remaining 14 specimens were fixed with interference screws under different tensions in an antegrade way, and the translational testing was repeated as before. RESULTS: In the neutral position, antegrade fixation exhibited less translation than retrograde fixation (7.21 ± 0.17 mm versus 10.77 ± 1.68 mm, respectively). The maximum failure load was 70.45 ± 6.20 N in antegrade fixation, while that in retrograde fixation was 35.17 ± 2.95 N (P < 0.0001). Antegrade fixation exhibited a larger increase in contact force than retrograde fixation (99.72% ± 23.88% versus 28.18% ± 10.43%) (P = 0.001). The relationship between tension and displacement was nonlinear (Y = - 1.877 ln(x) + 7.94, R2 = 0.868, P < 0.0001). CONCLUSIONS: Compared with retrograde fixation, the antegrade fixation of interference screws may be a more reliable surgical technique, as it shows a higher failure load and stability. In addition, to avoid the risk of potential arthritis caused by anterograde fixation, we propose an equation to determine the appropriate initial tension in DRUL reconstruction.


Asunto(s)
Cúbito , Articulación de la Muñeca , Fenómenos Biomecánicos , Tornillos Óseos , Cadáver , Humanos , Ligamentos , Articulación de la Muñeca/cirugía
13.
Int Wound J ; 19(7): 1637-1649, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35077000

RESUMEN

The study aimed to establish a machine learning-based scoring nomogram for early recognition of likely pressure injuries in an intensive care unit (ICU) using large-scale clinical data. A retrospective cohort study design was employed to develop and validate a top-performing clinical feature panel accessibly in the electronic medical records (EMRs), which was in the mode of a quantifiable nomogram. Clinical factors regarding demographics, admission cause, clinical laboratory index, medical history and nursing scales were extracted as risk candidates. The performance improvement was based on the application of the machine learning technique, comprising logistic regression, decision tree and random forest algorithm with five-fold cross-validation (CV) technique. The comprehensive assessment of sensitivity, specificity and the area under the receiver operating characteristic curve (AUROC) was considered in the evaluation of predictive performance. The receiver operating characteristic curves revealed the top performance for the logistic regression model in respect to machine learning improvement, achieving the highest sensitivity and AUC among three types of classifiers. Compared against the 23-point Braden scale routinely recorded online, an incorporated nomogram of logistic regression model and Braden scale achieved the best performance with an AUC of 0.87 ± 0.07 and 0.84 ± 0.05 in training and test cohort, respectively. Our findings suggest that the machine learning technique potentiated the limited predictive validity of routinely recorded clinical data on pressure injury development during ICU hospitalisation. Easily accessible electronic records held the potentials to substitute the traditional Braden score in the prediction of pressure injury in intensive care unit. Preoperative prediction of pressure injury facilitates the exemption from the severe consequences.


Asunto(s)
Unidades de Cuidados Intensivos , Aprendizaje Automático , Úlcera por Presión , Humanos , Algoritmos , Registros Electrónicos de Salud , Estudios Retrospectivos
14.
J Cell Mol Med ; 25(16): 7734-7745, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34160894

RESUMEN

MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. The role of miR-206 and E74-like factor 3 (Elf3) has been identified in osteoarthritis (OA), while the effect of exosomal miR-206 from bone marrow mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to explore the role of exosomal miR-206 from BMSCs in OA with the involvement of Elf3. BMSCs and BMSC-derived exosomes (BMSC-exos) were obtained and identified. OA mouse models were constructed by anterior cruciate ligament transection and then treated with BMSC-exos or BMSC-exos containing miR-206 mimic/inhibitor. The expression of miR-206, Elf3, inflammatory factors, osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The pathological changes in mouse femur tissues were observed. The mouse osteoblasts were identified and treated with untransfected or transfected BMSC-exos, and then, the expression of miR-206, Elf3, OCN and BMP2 was determined. The alkaline phosphatase (ALP) activity, calcium deposition level, OCN secretion, proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. MiR-206 was down-regulated while Elf3 was up-regulated in OA animal and cellular models. Exosomal miR-206 ameliorated inflammation and increased expression of OCN and BMP2 in mouse femoral tissues. Moreover, exosomal miR-206 promoted ALP activity, calcium deposition level, OCN secretion and proliferation and inhibited apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR-206 up-regulation-induced effects on OA osteoblasts. BMSC-derived exosomal miR-206 promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. Our research may provide novel targets for OA treatment.


Asunto(s)
Proteínas de Unión al ADN/antagonistas & inhibidores , Exosomas/genética , Células Madre Mesenquimatosas/citología , MicroARNs/farmacología , Osteoartritis/prevención & control , Osteoblastos/citología , Factores de Transcripción/antagonistas & inhibidores , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , MicroARNs/genética , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoblastos/metabolismo , Factores de Transcripción/metabolismo
15.
J Cell Mol Med ; 25(7): 3573-3584, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33751809

RESUMEN

Osteoarthritis (OA) is a common chronic degenerative condition in the elderly, in which inflammation plays a key role in disease pathology. Lycopene (Lye), a member of the carotenoid family, has been reported to have anti-inflammatory effects. The purpose of this study was to investigate the effect of Lye on the inflammation of chondrocytes and the mouse OA model. Chondrocytes were treated with interleukin (IL)-1ß, and the mouse OA model was induced by the surgical destabilization of the medial meniscus (DMM). The results showed that Lye could inhibit the expression of inflammatory factors and alleviate the degradation of extracellular matrix (ECM). Additionally, Lye could activate the Nrf2/HO-1 pathway and reverse the activations of NF-κB and STAT3 signal pathway induced by IL-1ß, suggesting that its anti-inflammatory effect may be mediated via these pathways. The animal experiments showed that Lye could decrease the Osteoarthritis Research Society International (OARSI) scores of the knee, indicating that it could inhibit the occurrence and development of OA in mouse. Overall, our results indicated that Lye might be used as a novel drug for OA treatment.


Asunto(s)
Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Matriz Extracelular/metabolismo , Inflamación/metabolismo , Licopeno/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Osteoartritis/metabolismo , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Interleucina-1beta , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal
16.
J Cell Physiol ; 236(6): 4369-4386, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33164235

RESUMEN

The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1ß-induced chondrocytes were identified. Our data revealed decreased H2 S expression in both human degenerative OA cartilage tissue and IL-1ß-induced chondrocytes. Pretreatment with the H2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1ß-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1ß-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1ß-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2 S may antagonize IL-1ß-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.


Asunto(s)
Antirreumáticos/farmacología , Apoptosis/efectos de los fármacos , Condrocitos/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/toxicidad , Articulaciones/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Sulfuros/farmacología , Anciano , Animales , Antirreumáticos/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Condrocitos/inmunología , Condrocitos/metabolismo , Condrocitos/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Sulfuro de Hidrógeno/metabolismo , Articulaciones/inmunología , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Mitocondrias/inmunología , Mitocondrias/metabolismo , Mitocondrias/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Osteoartritis/inmunología , Osteoartritis/metabolismo , Osteoartritis/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sulfuros/metabolismo
17.
New Phytol ; 230(2): 845-856, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33454953

RESUMEN

Re-establishment of heritable latitudinal clines in growth-related traits has been recognised as evidence for adaptive evolution in invasive plants. However, less information is known about latitudinal clines in defence and joint clinal evolution of growth and defence in invasive plants. We planted 14 native Argentinean populations and 14 introduced Chinese populations of Alternanthera philoxeroides in replicate common gardens in China. We investigated the latitudinal clines of traits related to growth and defence, and plasticity of these traits in relation to experiment site and soil nitrogen. We found that chemical defence decreased with latitude in introduced populations but increased with latitude in native populations. For growth rate, latitudinal clines were positive in introduced populations but nonexistent in native populations. There were also parallel positive latitudinal clines in total/shoot biomass and specific leaf area. Experiment site affected the occurrence or magnitude of latitudinal clines in growth rate, branch intensity and triterpenoid saponins concentration. Introduced populations were more plastic to experiment site and soil nitrogen than native populations. We provide evidence for rapid evolution of clines in growth and defence in an invasive plant. Altered herbivory gradients and trade-off between growth and defence may explain nonparallel clines between the native and introduced ranges.


Asunto(s)
Amaranthaceae , Malezas , China , Herbivoria , Especies Introducidas , Malezas/genética
18.
BMC Musculoskelet Disord ; 22(1): 41, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33413272

RESUMEN

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare, benign, proliferative neoplastic process that commonly affects synovial-lined anatomic spaces. The diffuse type (DPVNS) is characterized by invasion of the entire joint synovium, while the localized type (LPVNS) is characterized by a relatively normal synovial appearance. This report describes a unique case of massive intraarticular LPVNS with an extraarticular extension through the lateral patellar retinaculum. No similar cases have been found in the literature. CASE PRESENTATION: A 58-year-old woman had a history of hyperuricemia and knee trauma and presented with unilateral knee acute swelling and pain symptoms with sudden onset. Recent expansion of the LPVNS caused the development of a tender palpable soft tissue mass in the anterolateral aspect of the knee and acute reduced mobility. Preoperative magnetic resonance imaging of the knee revealed the presence of only the soft tissue mass and mild degenerative changes. Open synovectomy was performed successfully to excise the mass. Intraoperatively, macroscopic features of the bright brown inflamed synovium suggested LPVNS, which was confirmed histopathologically. Postoperatively, the symptoms of limited mobility and pain were appreciably relieved. Recurrence was not observed during the clinical follow-up at 1, 6 or 18 months after surgery. CONCLUSIONS: Here, we report the unique case of localized pigmented villonodular synovitis of the knee in a misdiagnosed patient with intra- and extraarticular lesion, which might be attributed to the history of knee trauma and the focal defect of the lateral patellar retinaculum. Open synovectomy effectively relieved the symptoms of limited mobility and pain and no recurrence was observed prior to 18 months postoperatively. To reduce misdiagnosis, MRI examinations are recommended for all patients suspected of having PVNS, including those who have a history of hyperuricemia.


Asunto(s)
Sinovitis Pigmentada Vellonodular , Artroscopía , Femenino , Humanos , Rodilla , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Sinovectomía , Sinovitis Pigmentada Vellonodular/diagnóstico por imagen , Sinovitis Pigmentada Vellonodular/cirugía
19.
Knee Surg Sports Traumatol Arthrosc ; 29(12): 3997-4003, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34417658

RESUMEN

PURPOSE: The optimal technique for arthroscopic rotator cuff repair is still controversial. The aim of this study was to compare modified arthroscopic double-pulley suture-bridge (DPSB) technique with medial knot tying to those without tying, considering clinical and radiological outcomes. METHODS: This study included 292 patients with large full-thickness rotator cuff tears treated with modified DPSB technique. The patients were divided into 158 cases with medial knot tying (knot-tying group) and 134 without tying (knotless group). At follow-up, clinical outcome was assessed by the Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Shoulder Rating Scale of the University of California at Los Angeles (UCLA) score. The assessment of tendon healing was performed with magnetic resonance imaging (MRI) at a minimum of 12 months postoperatively. RESULTS: The Constant score, ASES score and UCLA score in the knot-tying and knotless groups all improved significantly from before surgery to 12 months postoperatively (P < 0.05, respectively). No significant differences were observed between groups for each phase evaluated (n.s.). Tendon healing was categorised according to Sugaya's classification. The retearing rate was 27/158 (17.0%) in the knot-tying group and 20/134 (14.9%) in the knotless group, with no statistically significant difference between groups (n.s.). Additionally, the retear was classified using the Cho's classification. When comparing the retear rates of different types independently, no statistically significant differences were found between groups (n.s.). CONCLUSIONS: The knotless modified DPSB technique showed comparable short-term functional outcomes to those of the knot tying method in large full-thickness rotator cuff tears. Additionally, no significant differences in repair integrity were observed between the two methods. Both techniques can be considered effective treatments for patients with large-sized full-thickness rotator cuff tears. LEVEL OF EVIDENCE: III.


Asunto(s)
Lesiones del Manguito de los Rotadores , Manguito de los Rotadores , Artroscopía , Humanos , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/cirugía , Técnicas de Sutura , Suturas
20.
Nano Lett ; 20(6): 4687-4692, 2020 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-32364746

RESUMEN

We identify imidazole as a pH-activated linker for forming stable single molecule-gold junctions with several distinct configurations and reproducible electrical characteristics. Using a scanning tunneling microscope break junction (STMBJ) technique, we find multiple robust conductance signatures at integer multiples of 1.9 × 10-2G0 and 1.2 × 10-4G0 and determine that this molecule bridges the electrodes in its deprotonated form through the nitrogen atoms in basic conditions only, with several molecules able to bind in parallel and in series. The elongation these junctions can sustain is longer than the length of the molecule, suggesting that plastic deformation of gold electrodes occurs during stretching. Density functional theory calculations confirm that the imidazolate-linked junctions exhibit bond strengths of ∼2 eV, which can allow for plastic extraction of gold atoms. On the basis of these results, we hypothesize that lower conductance peaks correspond to chains of repeating molecule-gold units that we form and measure in situ.

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