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1.
J Orthop Translat ; 47: 63-73, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39007034

ABSTRACT

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/ß-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords "Wnt*", "bone*" and "muscle*". A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/ß-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/ß-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

3.
Sci Rep ; 14(1): 10119, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698057

ABSTRACT

The production plan of an open-pit mine depends on the block model, so it's crucial to determine the appropriate method and size for partitioning it. This study proposes a new method based on a closed shell three-dimensional geological model for determining block model size in open-pit mines. Instead of using regular block models, the shell model is directly cut, and the discrete geological body is referred to as the "mining model." Mining parameters and the shovel-truck's performance are integrated into the method. Bench height determines the Z-axis size, bench slope angle determines the inclination angle, and shovel width determines the X-axis size of the block model. The operation efficiency of the shovel-truck considers the probability distribution of simultaneous operations, allowing the determination of the Y-axis size of block models for different types of shovels. The developed "Mining Model" module in the software "Life Cycle Mining System" is used for practical implementation. By comparing the results with traditional block models, the superiority of the proposed method is demonstrated. This study provides a more accurate model for optimizing the production plan of open-pit mines throughout their life cycle.

4.
J Orthop Translat ; 46: 91-102, 2024 May.
Article in English | MEDLINE | ID: mdl-38817243

ABSTRACT

The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies. Moreover, there is still lack of strong consensus on the specific effects of exercise on improving the morphology and function of the ageing NMJ. Consequently, the purpose of this study was to conduct a systematic review to elucidate the effects of exercise training on NMJ compartments in the elderly. We conducted a systematic review using PubMed, Embase, and Web of Science databases, employing relevant keywords. Two independent reviewers selected studies that detailed NMJ changes during exercise in ageing, written in English, and available in full text. In total, 20 papers were included. We examined the altered adaptation of the NMJ to exercise, focusing on presynaptic and postsynaptic structures and myofibers in older animals or humans. Our findings indicated that aged NMJs exhibited different adaptive responses to physical exercise compared to younger counterparts. Endurance training, compared with resistance and voluntary exercise regimens, was found to have a more pronounced effect on NMJ structural remodeling, particularly in fast twitch muscle fibers. Physical exercise was observed to promote the formation and maintenance of acetylcholine receptor (AChR) clusters by increasing the recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). These insights suggest that research on exercise-related therapies could potentially attenuate the progression of neuromuscular degeneration. Translational potential of this article: This systematic review provides a detailed overview of the effects of different types of physical exercise on improving NMJ in the elderly, providing scientific support for the timely intervention of muscle degeneration in the elderly by physical exercise, and providing help for the development of new therapeutic interventions in the future.

5.
J Orthop Translat ; 45: 247-255, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38601198

ABSTRACT

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

6.
Aging Cell ; 23(7): e14156, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38532712

ABSTRACT

Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low-magnitude high-frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia. We first compared morphological differences of NMJ between sarcopenic and non-sarcopenic subjects, as well as young and old C57BL/6 mice. We then systematically characterized the age-related degeneration of NMJ in SAMP8 against its control strain, SAMR1 mice, from 3 to 12 months old. We also investigated effects of LMHFV in SAMP8 on the maintenance of NMJ during the onset of sarcopenia with respect to the Agrin-LRP4-MuSK-Dok7 pathway and investigated the mechanism related to ERK1/2 signaling. We observed sarcopenic/old NMJ presented increased acetylcholine receptors (AChRs) cluster fragmentation and discontinuity than non-sarcopenic/young NMJ. In SAMP8, NMJ degeneration (morphologically at 6 months and functionally at 8 months) was observed associated with the sarcopenia onset (10 months). SAMR1 showed improved NMJ morphology and function compared with SAMP8 at 10 months. Skeletal muscle performance was improved at Month 4 post-LMHFV treatment. Vibration group presented improved NMJ function at Months 2 and 6 posttreatment, accompanied with alleviated morphological degeneration at Month 4 posttreatment. LMHFV increased Dok7 expression at Month 4 posttreatment. In vitro, LMHFV could promote AChRs clustering in myotubes by increasing Dok7 expression through suppressing ERK1/2 phosphorylation. In conclusion, NMJ degeneration was observed associated with the sarcopenia onset in SAMP8. LMHFV may attenuate NMJ degeneration and sarcopenia progression by increasing Dok7 expression through suppressing ERK1/2 phosphorylation.


Subject(s)
Mice, Inbred C57BL , Neuromuscular Junction , Sarcopenia , Vibration , Sarcopenia/pathology , Sarcopenia/metabolism , Animals , Vibration/therapeutic use , Neuromuscular Junction/metabolism , Neuromuscular Junction/pathology , Mice , Male , Humans , Aging , Female
7.
J Orthop Surg Res ; 19(1): 84, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254120

ABSTRACT

BACKGROUND: Deep vein thrombosis (DVT) has been one of the most dangerous complications in total hip arthroplasty (THA). If a patient's pre-surgical DVT is overlooked, it can easily be mistaken for a post-operative thrombus and lead to an increased risk of DVT during and after surgery. This retrospective study was to explore the incidence and associated risk factors of deep vein thrombosis (DVT) in non-fracture patients before total hip arthroplasty (THA). METHODS: From September 2015 to September 2020, 1242 patients admitted for THA were enrolled with 1120 patients (90.2%) for primary THA and 122 patients (9.8%) for revision THA. An experienced sonographer performed a bedside ultrasound to detect DVT in bilateral lower limbs preoperatively. Univariate and logistic regression analysis was performed to identify the independent risk factors. RESULTS: 38 patients (3.1%) were detected with preoperative DVT. Univariate analysis showed that age (P < 0.001), D-dimer level (P = 0.002), female patients (P = 0.016), revision THA (P < 0.001), Barthel Index score (P = 0.010) were significantly associated with preoperative DVT. In subgroup comparison, the incidence of DVT increased with age significantly (P < 0.001) and D-dimer level (P < 0.001). In logistic regression analysis, age ≥ 75 years old (odds ratio [OR] 3.678, 95% CI [2.197-18.721], P < 0.001), gender (OR 2.709, 95% CI [1.244-5.896], P = 0.012), higher D-dimer ≥ 0.5 mg/l (OR 6.841, 95% CI [2.197-18.721], P < 0.001) and revision THA (OR 2.240, 95% CI [1.143-5.372], P = 0.05) were confirmed as the independent risk factors. CONCLUSIONS: The incidence of preoperative DVT in non-fracture patients was 3.1%, with 2.4% in primary THA and 9.0% in revision THA. Age ≥ 75 years old, female, D-dimer ≥ 0.5 mg/l, and revision THA were independent risk factors. When evaluating the risk factors associated with thrombus formation preoperatively, it is important to take these into account before surgery.


Subject(s)
Arthroplasty, Replacement, Hip , Thrombosis , Venous Thrombosis , Humans , Female , Aged , Arthroplasty, Replacement, Hip/adverse effects , Prevalence , Retrospective Studies , Risk Factors , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
8.
Front Bioeng Biotechnol ; 11: 1281503, 2023.
Article in English | MEDLINE | ID: mdl-38026856

ABSTRACT

Background: Deep Vein Thrombosis (DVT) is a common disease, frequently afflicting the lower limb veins of bedridden patients. Intermittent Pneumatic Compression (IPC) is often employed as an effective solution for this problem. In our study, a random selection of 264 patients underwent IPC treatment for either one or 8 hours daily. The rate of severe venous thrombosis was substantially reduced in the IPC-treated group compared to the control group. However, real-time monitoring of blood flow during IPC operation periods remains a challenge, leading to rare awareness of IPC working mechanism on thrombosis prevention. Methods: Here, microfluidic chip methodology is used to create an in vitro vein-mimicking platform integrating venous valves in a deformable channel. Whole blood of patients after knee surgery was perfused into the venous channel at a controlled flow rate obtained from patients with IPC treatment clinically. Results: According to the numerical simulations results, both of an increase in compressive pressure and a decrease in time interval of IPC device can accelarete blood flow rate and the shear stress within the vein. The vein chip experiments also reveal that the fibrin accumulation can be greatly lowered in IPC treated group, indicating less thrombosis formation in future. A time interval of 24 seconds and a maximum contraction pressure of 40 mmHg were proved to be the most effective parameters for the IPC device adopted in our clinical trail. Conclusion: This vein chip presents a novel method for observing the functional mechanisms of IPC device for DVT prevention. It provides crucial data for further standardization and optimization of IPC devices in clinical usage.

9.
PLoS One ; 18(8): e0290117, 2023.
Article in English | MEDLINE | ID: mdl-37566618

ABSTRACT

This paper proposes a novel hybrid algorithm, named Multi-Strategy Hybrid Harris Hawks Tunicate Swarm Optimization Algorithm (MSHHOTSA). The primary objective of MSHHOTSA is to address the limitations of the tunicate swarm algorithm, which include slow optimization speed, low accuracy, and premature convergence when dealing with complex problems. Firstly, inspired by the idea of the neighborhood and thermal distribution map, the hyperbolic tangent domain is introduced to modify the position of new tunicate individuals, which can not only effectively enhance the convergence performance of the algorithm but also ensure that the data generated between the unknown parameters and the old parameters have a similar distribution. Secondly, the nonlinear convergence factor is constructed to replace the original random factor c1 to coordinate the algorithm's local exploitation and global exploration performance, which effectively improves the ability of the algorithm to escape extreme values and fast convergence. Finally, the swarm update mechanism of the HHO algorithm is introduced into the position update of the TSA algorithm, which further balances the local exploitation and global exploration performance of the MSHHOTSA. The proposed algorithm was evaluated on eight standard benchmark functions, CEC2019 benchmark functions, four engineering design problems, and a PID parameter optimization problem. It was compared with seven recently proposed metaheuristic algorithms, including HHO and TSA. The results were analyzed and discussed using statistical indicators such as mean, standard deviation, Wilcoxon's rank sum test, and average running time. Experimental results demonstrate that the improved algorithm (MSHHOTSA) exhibits higher local convergence, global exploration, robustness, and universality than BOA, GWO, MVO, HHO, TSA, ASO, and WOA algorithms under the same experimental conditions.


Subject(s)
Algorithms , Urochordata , Animals , Benchmarking , Birds , Engineering
10.
Sci Rep ; 13(1): 8676, 2023 May 29.
Article in English | MEDLINE | ID: mdl-37248405

ABSTRACT

Reasonable production capacity is related to the economic benefits of an open-pit coal mine. This study analyzes the relationship between the working face length, the annual advancing speed and the production capacity. It constructs a production capacity function relationship model. Take the Baorixile open-pit coal mine as an example. The remaining unmined parts are divided into four regions, and the range of production capacity in each region is analyzed by the established model and the determined respectively. On this basis, three mining district division plans are proposed. By analyzing and comparing the stripping ratio, mining life of the district, fault influence, difficulty of transition connection in the mining districts, the convenience of transportation system layout and other indexes of each plan, Plan 3 is determined to be the optimal plan. The production capacity planning results of each mining district in this plan are as follows: the production capacity of the 3rd mining district is 30-35 Mt/a; the production capacity of the 4th mining district in Region 1 is 20-31 Mt/a, and the production capacity in Region 2 is 24-33 Mt/a; the production capacity of the 5th mining district is 20-27 Mt/a.

11.
BMC Musculoskelet Disord ; 23(1): 435, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35538467

ABSTRACT

OBJECTIVES: To analyze the changes of lower limb hemodynamics parameters before and after wearing graduated compression stockings (GCS) during ankle pump exercise in patients preparing for arthroplastic surgery. METHOD: The leg veins of 16 patients awaiting arthroplasty were analyzed using a Sonosite M-Turbo ultrasound system during ankle pump exercise with or without GCS. The age of them was 70 ± 7 years (mean ± SD) (range 56-82 years) and body mass index was 25.8 ± 3.0 kg/m2 (range 18.0-30.5 kg/m2). Measured data including the cross-sectional area (CSA), anteroposterior (AP) diameter and lateromedial (LM) diameter of the soleus vein (SV), posterior tibial vein (PTV) and great saphenous vein (GSV). Additionally, the peak velocities of femoral vein (FV) were also measured. RESULTS: GCS could significantly decrease the cross-sectional area of SV, PTV and GSV in supine position at rest and maximum ankle plantar flexion. But the compression effect of GCS to SV and GSV was not observed during maximum ankle dorsiflexion. It was found that GCS application reduced the peak flow velocity of the femoral vein from 61.85 cm/s (95% CI = 50.94-72.75 cm/s) to 38.01 cm/s (95% CI = 28.42-47.59 cm/s) (P < 0.001) during ankle plantar flexion and decreased the femoral vein in these patients from 80.65 cm/s (95% CI = 70.37-90.92 cm/s) to 51.15 cm/s (95% CI = 42.58-59.73 cm/s) (P < 0.001) during ankle dorsiflexion. But this effect was not significant in supine position at rest. CONCLUSIONS: GCS could significantly reduce the peak flow velocity of the femoral vein during ankle pump exercise in the patients preparing for arthroplastic surgery.


Subject(s)
Femoral Vein , Stockings, Compression , Aged , Aged, 80 and over , Ankle/diagnostic imaging , Ankle Joint , Exercise Therapy , Femoral Vein/diagnostic imaging , Femoral Vein/surgery , Humans , Middle Aged
12.
Front Bioeng Biotechnol ; 10: 875363, 2022.
Article in English | MEDLINE | ID: mdl-35402421

ABSTRACT

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), bone marrow mesenchymal stem cells (BMSCs), and bone morphogenetic protein 2 (BMP2), we created a photo-crosslinked composite bioactive scaffold. The composite scaffolds had appropriate mechanical properties for stem cells adhesion and proliferation, as well as good biocompatibility and the ability to stimulate BMSCs osteogenic differentiation in vitro. The synergistic effect of BMSCs and BMP2 enabled the composite bioactive scaffold to exhibit higher osteogenic potential in vivo than scaffolds loaded alone with BMSCs or BMP2, according to imaging and histology studies. In conclusion, by promoting the osteogenic differentiation of BMSCs, the composite bioactive scaffold based on BMSCs-BMP2-GelMA has demonstrated remarkable application potential in bone regeneration and bone defects repair.

13.
Bioact Mater ; 7: 478-490, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34466747

ABSTRACT

Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.

14.
Carbohydr Polym ; 270: 118342, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34364595

ABSTRACT

The naturally tight entanglement of fibers in bacterial cellulose (BC) results in low printability when BC is used as a bioink for printing scaffolds. In this study, neat BC was treated by TEMPO-mediated oxidation (TO-BC) and maleic acid (MA-BC) to prepare homogeneous BC dispersions to fabricate scaffolds for bone regeneration. Results showed that the treatments released individual fibrils in the corresponding uniform dispersions without impairing inherent crystalline properties. Compared with TO-BC, MA-BC hybridized with gelatin could endow the gel with improved rheological properties and compression modulus for 3D printing. Both TO-BC and MA-BC dispersions showed good osteoblast viability. However, MA-BC possessed more pronounced ability to express osteogenic marker genes and formation of mineralized nodules in vitro. Compared with TO-BC-based gelatin scaffolds, MA-BC-based gelatin scaffolds showed a better ability to stimulate the regeneration of rat calvaria, demonstrating a higher bone mineral density of newly formed bone and trabecular thickness in vivo.


Subject(s)
Bone Regeneration , Cellulose/chemistry , Gelatin/chemistry , Polysaccharides, Bacterial/chemistry , Printing, Three-Dimensional , Tissue Scaffolds/chemistry , Animals , Cyclic N-Oxides/chemistry , Hydrogels/chemistry , Hydrolysis , Maleates/chemistry , Mice , Nanofibers/chemistry , Osteoblasts/metabolism , Osteogenesis , Oxidation-Reduction , Rats , Skull/metabolism , Tissue Engineering/methods
15.
Int J Biol Macromol ; 165(Pt B): 1634-1645, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33049237

ABSTRACT

In this work, the biological polysaccharide-based antioxidant polyglucose-sorbitol-carboxymethyl ether (PSC) was used as the precursor to synthesize Fe2O3@PSC nanoparticles, which are expected to scavenge excess reactive oxygen species (ROS) to inhibit osteogenesis and promote osteoclast differentiation in iron accumulation (IA)-related osteoporosis. The Fe2O3@PSC nanoparticles obtained were of a uniform particle size of 7.3 nm with elemental O/Fe/Cl/C at a ratio of 190:7:2:88. In addition, the Fe2O3@PSC nanoparticles showed the ability to supply equivalent amounts of iron as the typical iron agent ferric ammonium citrate (FAC) in vitro and in vivo. Importantly, the Fe2O3@PSC nanoparticles not only induced antioxidative MC3T3-E1 and Raw 264.7 cells to scavenge ROS but also promoted osteogenic differentiation by activating Akt-GSK-3ß-ß-catenin and inhibiting osteoclast differentiation by inhibiting the MAPK and NF-κB pathways in vitro. In vivo, no IA-related osteoporosis was induced in a mouse model when enough iron was supplied by the Fe2O3@PSC nanoparticles. Overall, the biological polysaccharide-based antioxidant PSC can supply iron and prevent IA-related osteoporosis, indicating that it is a promising novel iron agent for applications to treat iron deficiency diseases.


Subject(s)
Free Radical Scavengers/pharmacology , Iron/metabolism , Magnetic Iron Oxide Nanoparticles/chemistry , Osteoporosis/pathology , Osteoporosis/prevention & control , Polysaccharides/chemistry , Reactive Oxygen Species/metabolism , Animals , Antioxidants/pharmacology , Bone and Bones/diagnostic imaging , Bone and Bones/drug effects , Cell Differentiation/drug effects , Cell Line , Disease Models, Animal , Ferric Compounds/pharmacology , Glucans/chemistry , Magnetic Iron Oxide Nanoparticles/ultrastructure , Mice, Inbred ICR , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteogenesis/drug effects , Phosphorylation/drug effects , Quaternary Ammonium Compounds/pharmacology , X-Ray Microtomography
16.
Physiol Res ; 67(2): 293-305, 2018 05 04.
Article in English | MEDLINE | ID: mdl-29303602

ABSTRACT

The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px), in the medulla oblongata were examined through spectrophotometer. Reactive oxygen species (ROS) were detected in the hypoglossal nucleus, cuneate nucleus, Botzinger complex, dorsal vagal complex, and airway through dihydroethidium fluorescence. Hematoxylin-eosin (HE) staining and substance P expression via immunohistochemistry revealed the inflammatory levels in the airway. TRPM2 was observed in the medulla oblongata through immunofluorescence and Western blot. The ultrastructure of the blood-brain barrier and neuronal mitochondria was determined by using a transmission electron microscope. Our study suggests that melatonin treatment decreased PM2.5-induced oxidative stress level in the brains and lungs and relieved airway inflammation and chronic cough. TRPM2 might participate in oxidative stress in the cough center by regulating cough.


Subject(s)
Air Pollutants/adverse effects , Antioxidants/therapeutic use , Cough/drug therapy , Melatonin/therapeutic use , Oxidative Stress/drug effects , Particulate Matter/adverse effects , TRPM Cation Channels/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/pathology , Brain Chemistry/drug effects , Cough/chemically induced , Cough/pathology , Guinea Pigs , Lung/drug effects , Male , Medulla Oblongata/drug effects , Medulla Oblongata/metabolism , Particle Size
17.
Life Sci ; 151: 157-166, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-26926080

ABSTRACT

AIMS: The mechanism of cough hypersensitivity induced by particulate matter 2.5 (PM2.5) remains elusive. The current study was designed to explore the effect of transient receptor potential vanilloid-1 (TRPV1) on cough hypersensitivity in airway and central nervous system. MAIN METHODS: The PM2.5-induced chronic cough model of guinea pig was established by exposure to different doses of PM2.5 for three weeks. After exposure, the animals were microinjected with TRPV1 agonist capsaicine, antagonist capsazepine in the dorsal vagal complex respectively. Cough sensitivity was measured by determining the provocative concentration of citric acid inducing 5 or more coughs (C5). Airway inflammation was detected by hematoxylin eosin (HE) staining and Evans blue fluorescence, and substance P (SP) and TRPV1 expressions in airway were observed by immunohistochemical staining. TRPV1 expressions in the dorsal vagal complex were observed by immunofluorescence. Retrograde tracing by pseudorabies virus-Bartha (PRV-Bartha) was conducted to confirm the regulatory pathway between airway and central nervous system. KEY FINDINGS: PM2.5 induced TRPV1 expressions in both of airway and dorsal vagal complex and airway neurogenic inflammation. Airway vascular permeability increased after being exposed to PM2.5. The expressions of SP in the airway and airway inflammation was increased after microinjecting TRPV1 agonist, and decreased after microinjecting TRPV1 antagonist. PRV infected neurons in medulla oblongata mainly located in the dorsal vagal complex. SIGNIFICANCE: These findings show that TRPV1 in the dorsal vagal complex could promote airway neurogenic inflammation and cough reflex sensitivity through neural pathways of vagal complex-airways, which indicate the therapeutic potential of specific inhibition of TRPV1 for chronic cough induced by PM2.5.


Subject(s)
Central Nervous System Diseases/genetics , Cough/genetics , Hypersensitivity/genetics , Respiratory Hypersensitivity/genetics , TRPV Cation Channels/metabolism , Animals , Capillary Permeability/drug effects , Capsaicin/analogs & derivatives , Capsaicin/antagonists & inhibitors , Capsaicin/pharmacology , Central Nervous System Diseases/physiopathology , Cough/chemically induced , Cough/physiopathology , Guinea Pigs , Herpesvirus 1, Suid/genetics , Hypersensitivity/physiopathology , Male , Particulate Matter/toxicity , Respiratory Hypersensitivity/physiopathology , Signal Transduction/genetics , Substance P/biosynthesis , TRPV Cation Channels/drug effects , Vagus Nerve/drug effects
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