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OBJECTIVE: To promote research on knowledge extraction and knowledge graph construction of chest discomfort medical cases in Traditional Chinese Medicine (TCM), this paper focuses on their named entity recognition (NER). The recognition task includes six entity types: "syndrome", "symptom", "etiology and pathogenesis", "treatment method", "medication", and "prescription". METHODS: We annotated data in a BIO (B-begin, I-inside, O-outside) manner. For the characteristics of medical case texts, we proposed a custom dictionary method that can be dynamically updated for word segmentation. To compare the effect of the method on the experimental results, we applied the method in the BiLSTM-CRF model and IDCNN-CRF model, respectively. RESULTS: The models using custom dictionaries (BiLSTM-CRF-Loaded and IDCNN-CRF-Loaded) outperformed the models without custom dictionaries (BiLSTM-CRF and IDCNN-CRF) in accuracy, precision, recall, and F1 score. The BiLSTM-CRF-Loaded model yielded F1 scores of 92.59% and 93.23% on the test set and validation set, respectively, surpassing the BERT-BiLSTM-CRF model by 3.59% and 4.87%. Furthermore, when analyzing the results for the six entity categories separately, we found that the use of custom dictionaries has a marked impact, with the categories of "etiology and pathogenesis" and "syndrome" demonstrating the most noticeable improvements. By comparing the F1 scores, we observed that the entity category "medication" yielded the highest performance, reaching F1 scores of 96.04% and 96.48% on the test set and validation set, respectively. CONCLUSION: We propose a word segmentation method based on a dynamically updated custom dictionary. The method is combined with the BILSTM-CRF and the IDCNN-CRF models, which enhances the model to recognize domain-specific terms and new entities. It can be widely applied in dealing with complex text structures and texts containing domain-specific terms.
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Machine learning has great potential in predicting chemical information with greater precision than traditional methods. Graph neural networks (GNNs) have become increasingly popular in recent years, as they can automatically learn the features of the molecule from the graph, significantly reducing the time needed to find and build molecular descriptors. However, the application of machine learning to energetic materials property prediction is still in the initial stage due to insufficient data. In this work, we first curated a dataset of 12,072 compounds containing CHON elements, which are traditionally regarded as main composition elements of energetic materials, from the Cambridge Structural Database, then we implemented a refinement to our force field-inspired neural network (FFiNet), through the adoption of a Transformer encoder, resulting in force field-inspired Transformer network (FFiTrNet). After the improvement, our model outperforms other machine learning-based and GNNs-based models and shows its powerful predictive capabilities especially for high-density materials. Our model also shows its capability in predicting the crystal density of potential energetic materials dataset (i.e. Huang & Massa dataset), which will be helpful in practical high-throughput screening of energetic materials.
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Molecular representation learning is an essential component of many molecule-oriented tasks, such as molecular property prediction and molecule generation. In recent years, graph neural networks (GNNs) have shown great promise in this area, representing a molecule as a graph composed of nodes and edges. There are increasing studies showing that coarse-grained or multiview molecular graphs are important for molecular representation learning. Most of their models, however, are too complex and lack flexibility in learning different granular information for different tasks. Here, we proposed a flexible and simple graph transformation layer (i.e., LineEvo), a plug-and-use module for GNNs, which enables molecular representation learning from multiple perspectives. The LineEvo layer transforms fine-grained molecular graphs into coarse-grained ones based on the line graph transformation strategy. Especially, it treats the edges as nodes and generates the new connected edges, atom features, and atom positions. By stacking LineEvo layers, GNNs can learn multilevel information, from atom-level to triple-atoms level and coarser level. Experimental results show that the LineEvo layers can improve the performance of traditional GNNs on molecular property prediction benchmarks on average by 7%. Additionally, we show that the LineEvo layers can help GNNs have more expressive power than the Weisfeiler-Lehman graph isomorphism test.
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Benchmarking , Redes Neurales de la ComputaciónRESUMEN
To explore the research hotspots and frontier directions of pyroptosis in the field of traditional Chinese medicine(TCM), the authors searched CNKI and Web of Science for literature related to pyroptosis in TCM, screened literature according to the search strategy and inclusion criteria, and analyzed the publication trend of the included literature. VOSviewer was used to draw author cooperation and keyword co-occurrence network diagrams, and CiteSpace was employed for keyword clustering, emergence, and timeline view. Finally, 507 Chinese literature and 464 English literature were included, and it was found that the number of Chinese and English literature was increasing rapidly year by year. The co-occurrence of the authors showed that in terms of Chinese literature, there was a representative research team composed of DU Guan-hua, WANG Shou-bao and FANG Lian-hua, and for English literature, the representative research team was composed of XIAO Xiao-he, BAI Zhao-fang and XU Guang. The network visualization of Chinese and English keywords revealed that inflammation, apoptosis, oxidative stress, autophagy, organ damage, fibrosis, atherosclerosis, and ischemia-reperfusion injury were the primary research diseases and pathological processes in TCM; berberine, resveratrol, puerarin, na-ringenin, astragaloside â £, and baicalin were the representative active ingredients; NLRP3/caspase-1/GSDMD, TLR4/NF-κB/NLRP3, and p38/MAPK signaling pathways were the main research pathways. Keyword clustering, emergence, and timeline analysis indicated that the pyroptosis research in TCM focused on the mechanism of TCM monomers and compounds intervening in diseases and pathological processes. Pyroptosis is a research hotspot in the area of TCM, and the current discussion mainly focuses on the mechanism of the therapeutic effect of TCM.
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Medicina Tradicional China , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR , Reconocimiento de Normas Patrones Automatizadas , ApoptosisRESUMEN
Molecular representation learning is a crucial task to accelerate drug discovery and materials design. Graph neural networks (GNNs) have emerged as a promising approach to tackle this task. However, most of them do not fully consider the intramolecular interactions, i.e. bond stretching, angle bending, torsion, and nonbonded interactions, which are critical for determining molecular property. Recently, a growing number of 3D-aware GNNs have been proposed to cope with the issue, while these models usually need large datasets and accurate spatial information. In this work, we aim to design a GNN which is less dependent on the quantity and quality of datasets. To this end, we propose a force field-inspired neural network (FFiNet), which can include all the interactions by incorporating the functional form of the potential energy of molecules. Experiments show that FFiNet achieves state-of-the-art performance on various molecular property datasets including both small molecules and large protein-ligand complexes, even on those datasets which are relatively small and without accurate spatial information. Moreover, the visualization for FFiNet indicates that it automatically learns the relationship between property and structure, which can promote an in-depth understanding of molecular structure.
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In this study, evidence mapping was employed to sort out and summarise the evidence from clinical studies of Chinese patent medicines for hypertension and to understand the evidence distribution in related studies. Chinese patent medicines for hypertension were searched from Medicine Catalogue for National Basic Medical Insurance, Employment Injury Insurance, and Maternity Insu-rance(2021) and Chinese Pharmacopoeia(2020). Relevant articles(published from January 1, 2016 to February 14, 2022) were retrieved from Cochrane Library, PubMed, Web of Science, CNKI, Wanfang, VIP, and SinoMed. Then, the evidence distribution was analysed based on description, tables, and bubble charts. A total of 31 Chinese patent medicines were identified and 20 were finally included, involving 111 articles. The basic information of the 20 Chinese patent medicines, the number of related articles, the hypertension staging and traditional Chinese medicine(TCM) syndrome types of the subjects, sample size, interventions, and outcome indicators were compared. The results showed Chinese patent medicines with the function of pacifying liver and eliminating wind were frequently studied, and most of them were single-center, small-sample, short-period randomized controlled trials. They failed to highlight the key and advantages of TCM. A wide variety of outcome indicators were involved, and in addition to blood pressure, surrogate outcome indicators and composite outcome indicators were emphasized. However, health economic indicators, quality of life, and damage to target organs such as blood vessels and heart, were rarely used.
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Medicamentos Herbarios Chinos , Hipertensión , China , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Medicina Tradicional China , Medicamentos sin Prescripción , Embarazo , Calidad de VidaRESUMEN
The lack of accurate methods for predicting the viscosity of solvent materials, especially those with complex interactions, remains unresolved. Deep eutectic solvents (DESs), an emerging class of green solvents, have a severe lack of viscosity data, resulting in their application still staying at the stage of random trial and error, and it is difficult for them to be implemented on an industrial scale. In this work, we demonstrate the successful prediction of the viscosity of DESs based on the transition state theory-inspired neural network (TSTiNet). The TSTiNet adopts multilayer perceptron (MLP) for the transition state theory-inspired equation (TSTiEq) parameters calculation and verification using the most comprehensive DESs viscosity data set to date. For the energy parameters of the TSTiEq, the constant assumption and the fast iteration with the help of MLP can allow TSTiNet to achieve the best performance (the average absolute relative deviation on the test set of 6.84% and R 2 of 0.9805). Compared with the traditional machine learning methods, the TSTiNet has better generalization ability and dramatically reduces the maximum relative deviation of prediction under the constraints of the thermodynamic formulation. It requires only the structural information on DESs and is the most accurate and reliable model available for DESs viscosity prediction.
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Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.
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OBJECTIVE: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. METHODS: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded. RESULTS: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up. CONCLUSION: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.
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Traumatismos del Tobillo/cirugía , Arteria Femoral/trasplante , Colgajo Perforante/trasplante , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Muslo/irrigación sanguínea , Cicatrización de Heridas , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the clinical efficacy of free flap transplantation combined with Ilizarov bone transport in the treatment of severe composite tibial and soft tissue defects. METHODS: We retrospectively analyzed the clinical data of 40 patients with severe composite tibial and soft tissue defects who underwent free flap transplantation combined with Ilizarov bone transport. The clinical efficacy was evaluated according to the following criteria: success rate of wound repair by free flap transplantation, incidence or recurrence rate of deep infection, healing rate of bone defects and external fixation index, incidence of complications, and functional score of affected extremities. RESULTS: All infections were generally well controlled by radical debridement and negative-pressure therapy, and all 40 patients' wounds healed after repair and reconstruction of the tibia and soft tissues. Postoperative complications were alleviated by active treatment. The mean external fixation time was 12.83 ± 2.85 months, and the external fixation index was 1.55 m/cm. According to the Association for the Study and Application of Methods of Ilizarov (ASAMI) score, an excellent or good functional outcome was attained in 85% of patients. CONCLUSION: Free flap transplantation combined with Ilizarov bone transport is an effective treatment for severe composite tibial and soft tissue defects.
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Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Fracturas de la Tibia , Humanos , Estudios Retrospectivos , Tibia/cirugía , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Deep dead space may be thought as an independent risk factor of the poor infection control after flap reconstruction in complex limb wounds. But it can be easily neglected. The conventional skin flap and musculocutaneous flap are difficult to obliterate the deep dead space in irregular shape effectively. It was investigated that the clinical application of chimeric anterolateral thigh perforator flap in the treatment of complex wounds complicated with deep dead space of the extremities in the paper. METHODS: Fifty-six cases complicated with deep dead space wounds were registered in group. Following thorough debridement and treatment with VSD, the granulation tissues grew with well-controlled infection. And then the chimeric anterolateral thigh perforator flap was used to obliterate the deep dead space and repair the wounds. The postoperative flap survival and infection conditions were evaluated. RESULTS: Overall, the infection was effectively controlled, without persistent exudation or sinus tract formation after wound healing. While 5 cases lost to follow-up, the remaining 51 cases were followed up until 15 months on average. Generally, the affected extremities recovered satisfactorily with normal appearances and texture of the flaps, along with normal functions. Importantly, no recurrence of infection was observed. CONCLUSION: During the grafting of chimeric perforator flap pedicled with lateral thigh muscle flap, the muscle flap is recommended to obliterate the deep dead space while the skin flap is being used to cover the wound. The combination of these two technologies performed well in the repair and reconstruction of the complex wounds of the extremities, possessing potential for broader clinical application.
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Extremidades/lesiones , Extremidades/cirugía , Colgajos Tisulares Libres/trasplante , Colgajo Perforante/trasplante , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Muslo/cirugía , Recolección de Tejidos y Órganos/métodos , Adulto , Femenino , Arteria Femoral , Colgajos Tisulares Libres/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective was to explore the relative indications of free vascularized fibular graft (FVFG) and Ilizarov bone transport (IBT) in the treatment of infected bone defects of lower extremities via comparative analysis on the clinical characteristics and efficacies. METHODS: The clinical data of 66 cases with post-traumatic infected bone defects of the lower extremities who underwent FVFG (n = 23) or IBT (n = 43) from July 2014 to June 2018 were retrieved and retrospectively analyzed. Clinical characteristics, operation time, and intraoperative blood loss were statistically compared between two groups. Specifically, the clinical efficacies of two methods were statistically evaluated according to the external fixation time/index, recurrence rate of deep infection, incidence of complications, the times of reoperation, and final functional score of the affected extremities. RESULTS: Gender, age, cause of injury, Gustilo grade of initial injury, proportion of complicated injuries in other parts of the affected extremities, and numbers of femoral/tibial defect cases did not differ significantly between treatment groups, while infection site distribution after debridement (shaft/metaphysis) differed moderately, with metaphysis infection little more frequent in the FVFG group (P = 0.068). Femoral/tibial defect length was longer in the FVFG group (9.96 ± 2.27 vs. 8.74 ± 2.52 cm, P = 0.014). More patients in the FVFG group presented with moderate or complex wounds with soft-tissue defects. FVFG treatment required a longer surgical time (6.60 ± 1.34 vs. 3.12 ± 0.99 h) and resulted in greater intraoperative blood loss (873.91 ± 183.94 vs. 386.08 ± 131.98 ml; both P < 0.05) than the IBT group, while average follow-up time, recurrence rate of postoperative osteomyelitis, degree of bony union, and final functional scores did not differ between treatment groups. However, FVFG required a shorter external fixation time (7.04 ± 1.72 vs. 13.16 ± 2.92 months), yielded a lower external fixation index (0.73 ± 0.28 vs. 1.55 ± 0.28), and resulted in a lower incidence of postoperative complications (0.87 ± 0.76 vs. 2.21±1.78, times/case, P < 0.05). The times of reoperation in the two groups did not differ (0.78 ± 0.60 vs. 0.98 ± 0.99 times/case, P = 0.615). CONCLUSION: Both FVFG and IBT are effective methods for repairing and reconstructing infected bone defects of the lower extremities, with unique advantages and limitations. Generally, FVFG is recommended for patients with soft tissue defects, bone defects adjacent to joints, large bone defects (particularly monocortical defects), and those who can tolerate microsurgery.
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Trasplante Óseo/métodos , Fémur/cirugía , Peroné/irrigación sanguínea , Peroné/trasplante , Técnica de Ilizarov , Extremidad Inferior/cirugía , Osteomielitis/cirugía , Procedimientos de Cirugía Plástica/métodos , Tibia/cirugía , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Fémur/lesiones , Estudios de Seguimiento , Humanos , Extremidad Inferior/lesiones , Masculino , Persona de Mediana Edad , Tempo Operativo , Osteomielitis/etiología , Complicaciones Posoperatorias/epidemiología , Recurrencia , Reoperación , Estudios Retrospectivos , Tibia/lesiones , Adulto JovenRESUMEN
PURPOSE: Patients with type 1 diabetes (T1D) are associated with a high risk of multiple complications, so the development of T1D treatment is urgently needed. This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance. PATIENTS AND METHODS: Subcutaneous adipose tissues were collected from 68 T1D patients and 51 healthy controls. Insulin resistance model rats and cells were constructed and treated with metformin respectively. Western blot was used to detect p53 and RAP2A protein levels, and qPCR was utilized to measure p53 and RAP2A mRNA levels. SiRNA and RAP2A siRNA vectors were constructed to observe their effects on insulin resistance model cells. RESULTS: In T1D, p53 was up-regulated, while RAP2A was down-regulated. Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A. P53 induced insulin resistance and inflammatory response by inhibiting RAP2A and promoted apoptosis. CONCLUSION: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Metformina/farmacología , Proteína p53 Supresora de Tumor/biosíntesis , Proteínas de Unión al GTP rap/metabolismo , Células 3T3-L1 , Animales , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Placas Óseas/efectos adversos , Clavícula/lesiones , Fijación Interna de Fracturas/efectos adversos , Fracturas Óseas/cirugía , Dolor Postoperatorio/diagnóstico , Adulto , Clavícula/cirugía , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Resultado del TratamientoRESUMEN
Multiple pathways contribute to nonalcoholic fatty liver disease (NAFLD) in response to high fat diets (HFD). A homolog of mammalian JNK-interacting protein 3 (JIP3), also known as JSAP-1, activates different components in various signaling pathways to modulate cellular processes. The purpose of this study was to examine the role of JIP3 in obesity-related pathologies pathway. Wild-type (WT) C57BL/6 and JIP3-knockout (JIP3-/-) mice were randomized to chow or HFD. HFD-fed WT mice increased hepatic JIP3 expression. Mice lacking JIP3 exhibited reduced weight gain, hepatic steatosis, insulin resistance, lipid accumulation, oxidative stress and inflammatory response in mice fed a HFD, which were, importantly, dependent on various signaling pathways. Lipogenesis-linked pathway was inhibited in JIP3-/- mice after HFD, while PPARα/γ were increased. Additionally, JIP3-/- inhibited hepatic oxidative stress, evidenced by down-regulation of total reactive oxygen species (ROS), H2O2, O2.-, malondialdehyde (MDA), xanthine oxidase (XO), inducible nitric oxide synthase (iNOS), and up-regulation of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in mice after HFD feeding, which might be related to nuclear respiratory factor 2 (Nrf-2) pathway activation. Further, inflammatory response was blocked in JIP3-/- mice fed with HFD. The process might be attributed to the suppression of toll-like receptors (TLRs), p-nuclear factor kappa B (NF-κB) and p-c-Jun-N-terminal kinase (JNK). Thus, JIP3 absence is associated with decreased lipogenesis, oxidative stress and inflammation, supplying a new target for NAFLD treatment.
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Proteínas Adaptadoras Transductoras de Señales/genética , Dieta Alta en Grasa/efectos adversos , Hígado/patología , Proteínas del Tejido Nervioso/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Línea Celular , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Resistencia a la Insulina/genética , Lipogénesis , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Oxidativo , Transducción de SeñalRESUMEN
OBJECTIVE: The adaptation capacities of the mandibular condyle in response to mechanical stimuli might be different between juveniles and adults, but has not been compared. This study aimed to investigate whether abnormal molar occlusion and subsequent molar extraction could lead to different remodeling responses in the mandibular condyles of juvenile and adult rats. METHODS: Abnormal molar occlusion (AMO) was established in the 5- and 16-wk old rats by moving their maxillary left and mandibular right third molars distally. AMO was removed in the molar extraction group at 4 weeks but remained in the AMO group. All rats were sacrificed at 8 weeks. Micro-computed tomography, histomorphology, immunohistochemistry and real-time PCR were adopted to evaluate the remodeling of condylar subchondral bone. RESULTS: Condylar subchondral bone loss and increased osteoclastic activities were observed in both juvenile and adult AMO groups, while increased osteoblastic activities were only seen in the juvenile AMO group. Decreased bone mineral density, bone volume fraction and trabecular thickness, but increased trabecular separation, number and surface of osteoclasts and mRNA levels of TRAP, cathepsin-K, RANKL in the juvenile AMO group were all reversed after molar extraction (all P<0.05). However, these parameters showed no difference between adult AMO and extraction groups (all P>0.05). CONCLUSIONS: Abnormal molar occlusion led to degenerative remodeling in the mandibular condyles of both juvenile and adult rats, while exemption of abnormal occlusion caused significant rescue of the degenerative changes only in the juvenile rats.
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Remodelación Ósea/fisiología , Maloclusión/fisiopatología , Cóndilo Mandibular/fisiopatología , Animales , Femenino , Inmunohistoquímica , Osteoblastos/fisiología , Osteoclastos/fisiología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Microtomografía por Rayos XRESUMEN
This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and ß-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression, and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV, and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities.
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Condrocitos/metabolismo , Osteoartritis/patología , Receptores Adrenérgicos alfa 2/metabolismo , Transducción de Señal/efectos de los fármacos , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Agonistas Adrenérgicos/farmacología , Antagonistas Adrenérgicos/farmacología , Agrecanos/biosíntesis , Animales , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Femenino , Cóndilo Mandibular/fisiología , Metaloproteinasas de la Matriz/biosíntesis , Norepinefrina/farmacología , Ligando RANK/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta/biosíntesis , Articulación Temporomandibular/citologíaRESUMEN
The mouthpart of a honeybee is a natural well-designed micropump that uses a reciprocating glossa through a temporary tube comprising a pair of galeae and labial palpi for loading nectar. The shapes and sizes of mouthparts differ among castes of honeybees, but the diversities of the functional microstructures inside the mouthparts of honeybee workers and drones remain poorly understood. Through scanning electron microscopy, we found the dimensional difference of uniformly distributed microridges on the inner galeae walls of Apis mellifera ligustica workers and drones. Subsequently, we recorded the feeding process of live honeybees by using a specially designed high-speed camera system. Considering the microridges and kinematics of the glossa, we constructed a hydrodynamic model to calculate the friction coefficient of the mouthpart. In addition, we test the drag reduction through the dimensional variations of the microridges on the inner walls of mouthparts. Theoretical estimations of the friction coefficient with respect to dipping frequency show that inner microridges can reduce friction during the feeding process of honeybees. The effects of drag reduction regulated by specific microridges were then compared. The friction coefficients of the workers and drones were found to be 0.011±0.007 (mean±s.d.) and 0.045±0.010, respectively. These results indicate that the mouthparts of workers are more capable of drag reduction compared with those of drones. The difference was analyzed by comparing the foraging behavior of the workers and drones. Workers are equipped with well-developed hypopharyngeal, and their dipping frequency is higher than that of drones. Our research establishes a critical link between microridge dimensions and drag reduction capability during the nectar feeding of honeybees. Our results reveal that microridges inside the mouthparts of honeybee workers and drones reflect the caste-related life cycles of honeybees.
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Abejas/anatomía & histología , Ingestión de Alimentos/fisiología , Boca/anatomía & histología , Animales , Fenómenos Biomecánicos , Fricción , Hidrodinámica , Microscopía Electrónica de Rastreo , Modelos Teóricos , Boca/ultraestructura , Néctar de las Plantas , Grabación en VideoRESUMEN
The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of ß-adrenergic receptors (ß-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their ß-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and ß2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. ß-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while ß-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of ß2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of ß2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that ß2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.
Asunto(s)
Resorción Ósea/metabolismo , Huesos/metabolismo , Osteoartritis/metabolismo , Receptores Adrenérgicos beta/metabolismo , Transducción de Señal/fisiología , Articulación Temporomandibular/metabolismo , Adrenérgicos/farmacología , Animales , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Resorción Ósea/patología , Huesos/efectos de los fármacos , Huesos/patología , Femenino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Norepinefrina/farmacología , Osteoartritis/patología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Ligando RANK/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Articulación Temporomandibular/efectos de los fármacos , Articulación Temporomandibular/patologíaRESUMEN
OBJECTIVE: Investigate the expression and significance of eosinophils in brucellosis. METHODS: Retrospective analysis of clinical data for 151 brucellosis patients (BR group), complete blood count and blood bacterial culture etc.; in addition, 150 general bacterial infection patients (BI group) and 135 persons in healthy physical condition upon testing (NC group) are selected respectively as the control groups to comparatively study expression of white blood cells and eosinophils for brucellosis patients. Adopt t test to compare measurement data. RESULTS: In comparison with BI group, WBC, NE, EO, MO, NE% and EO% in BR group are reduced but LY, LY% and MO% are increased and such difference shows statistical significance (P<0.01). In comparison with NC group, difference of WBC and NE in BR group shows no statistical significance (P>0.05). NE%, EO and EO% are reduced but MO, LY% and MO% are increased and such difference shows statistical significance (P<0.01). LY is increased and the difference shows statistical significance (P<0.05). White blood cell count is normal or is reduced among most of Brucellosis patients, accounting for 90.73% (137/151); the patients whose eosinophils are reduced account for 75.50% (114/151) and those whose eosinophils disappear are about 18.54% (28/151). CONCLUSION: There is an incidence rate of eosinophils decrease or disappearance in Brucellosis and it shows the indication significance in the diagnosis of early disease.