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1.
Heliyon ; 10(6): e26995, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38560683

RESUMO

There have been many research reports on the reinforcement of small-sized square columns with a cross-section of 200mm-300mm using prestressed carbon fiber-reinforced polymer (CFRP) materials, while there are few studies on piers in bridge and tower columns in cable-stayed bridges with a cross-section of several meters or even tens of meters. The horizontal prestressed steel tendons in the anchorage zone of tower columns in cable-stayed bridge replaced by prestressed CFRP sheets can not only facilitate construction and maintenance, but also have good fatigue resistance. The prestressed CFRP plate is used to reinforce the large-sized tower columns by using a specific device to tension the CFRP plate wrapped around the surface of the members. The tensioning device and test pedestal based on WSGG (wave-shaped-gear-grip) anchor clamping of CFRP plate have been developed in this paper, and the CFRP plate circumferential tensioning tests on the pedestal have been conducted. The test results are as follows: (1) the developed device can achieve circumferential tensioning of single-layer CFRP plate to 0.5ftk of the material, reaching a tensile force of 60kN, and generate effective restraint pressure on a 2-m long composite compression component; (2)The calculation formula for the constraint pressure generated by the circumferential prestressed CFRP sheet on the component has been derived and verified, and the maximum error between the calculated value and the experimental value is within 5%; (3) When iron sheet serves as the interface medium between CFRP plate and compression components, the prestress loss of the CFRP plate tensioned at one end is about 84% and 58%-60% when tensioned at both ends. It can be seen that the effective prestress of the CFRP plate with iron sheet as the interface medium is relatively small. Meanwhile, based on the distribution of compressive stress in the components and the effective pre tension value of CFRP plate, it can be seen that two end tensioning is better than one end tensioning; (4) The tensile stress of CFRP plate along the member is a cubic function when the tension force is 60kN, so it is deduced that the constrained compressive stress generated by CFRP plate on the member is a quadratic function distribution.

2.
Biomol Biomed ; 24(2): 401-410, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37897663

RESUMO

This study focused on the development and validation of a diagnostic model to differentiate between spinal tuberculosis (STB) and pyogenic spondylitis (PS). We analyzed a total of 387 confirmed cases, out of which 241 were diagnosed with STB and 146 were diagnosed with PS. These cases were randomly divided into a training group (n = 271) and a validation group (n = 116). Within the training group, four machine learning (ML) algorithms (least absolute shrinkage and selection operator [LASSO], logistic regression analysis, random forest, and support vector machine recursive feature elimination [SVM-RFE]) were employed to identify distinctive variables. These specific variables were then utilized to construct a diagnostic model. The model's performance was subsequently assessed using the receiver operating characteristic (ROC) curves and the calibration curves. Finally, internal validation of the model was undertaken in the validation group. Our findings indicate that PS patients had an average platelet-to-neutrophil ratio (PNR) of 277.86, which was significantly higher than the STB patients' average of 69.88. The average age of PS patients was 54.71 years, older than the 48 years recorded for STB patients. Notably, the neutrophil-to-lymphocyte ratio (NLR) was higher in PS patients at 6.15, compared to the 3.46 NLR in STB patients. Additionally, the platelet volume distribution width (PDW) in PS patients was 0.2, compared to 0.15 in STB patients. Conversely, the mean platelet volume (MPV) was lower in PS patients at an average of 4.41, whereas STB patients averaged 8.31. Hemoglobin (HGB) levels were lower in PS patients at an average of 113.31 compared to STB patients' average of 121.64. Furthermore, the average red blood cell (RBC) count was 4.26 in PS patients, which was less than the 4.58 average observed in STB patients. After evaluation, seven key factors were identified using the four ML algorithms, forming the basis of our diagnostic model. The training and validation groups yielded area under the curve (AUC) values of 0.841 and 0.83, respectively. The calibration curves demonstrated a high alignment between the nomogram-predicted values and the actual measurements. The decision curve indicated optimal model performance with a threshold set between 2% and 88%. In conclusion, our model offers healthcare practitioners a reliable tool to efficiently and precisely differentiate between STB and PS, thereby facilitating swift and accurate diagnoses.


Assuntos
Espondilartrite , Espondilite , Tuberculose da Coluna Vertebral , Humanos , Pessoa de Meia-Idade , Algoritmos , Aprendizado de Máquina
3.
J Cardiovasc Pharmacol ; 83(2): 193-204, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030139

RESUMO

ABSTRACT: Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice. On day 14 after surgery, echocardiography showed that left ventricle mass (LV mass), interventricular septum, left ventricle posterior wall diastole, and left ventricular posterior wall systole were significantly increased, and ejection fraction was decreased compared with control mice. Masson and Wheat Germ Agglutinin staining indicated enhanced myocardial fibrosis and cell morphology compared with control mice. Importantly, these effects were inhibited by DAPA treatment in ISO-induced mice. In H9c2 cells and neonatal rat cardiomyocytes, we found that mitochondrial fragmentation and mitochondrial oxidative stress were significantly augmented in the ISO-induced group. However, DAPA rescued the cardiac hypertrophy in ISO-induced H9c2 cells and neonatal rat cardiomyocytes. Mechanistically, we found that DAPA restored the PIM1 activity in ISO-induced H9c2 cells and subsequent increase in dynamin-associated protein 1 (Drp1) phosphorylation at S616 and decrease in Drp1 phosphorylation at S637 in ISO-induced cells. We found that DAPA mitigated ISO-induced cardiac hypertrophy by suppressing Drp1-mediated mitochondrial fission in a PIM1-dependent fashion.


Assuntos
Compostos Benzidrílicos , Cardiomegalia , Glucosídeos , Dinâmica Mitocondrial , Ratos , Camundongos , Masculino , Animais , Isoproterenol/farmacologia , Camundongos Endogâmicos C57BL , Cardiomegalia/metabolismo , Miócitos Cardíacos
4.
J Org Chem ; 88(23): 16497-16510, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982674

RESUMO

The first organocatalytic diastereoselective (4 + 1) cycloaddition of o-hydroxyphenyl-substituted secondary phosphine oxides (SPOs) has been established, which makes use of o-hydroxyphenyl substituted SPOs as suitable four-atom phosphorus-containing 1,4-dinucleophiles and 3-indolylformaldehydes as competent 1,1-dielectrophiles under BroÌ·nsted acid catalysis. The reaction mechanism was suggested to involve the formation of 3-indolylmethanol intermediates and vinyliminium intermediates, which played an important role in controlling the reactivity and diastereoselectivity of the (4 + 1) cycloaddition under BroÌ·nsted acid catalysis. By this approach, a series of benzo oxaphospholes bearing P- and C-stereocenters were synthesized in moderate to good yields (50%-95% yields) with excellent diastereoselectivities (all >95:5 dr). This reaction not only represents the first organocatalytic diastereoselective (4 + 1) cycloaddition of o-hydroxyphenyl-substituted SPOs but also provides an efficient and diastereoselective method for the construction of phosphorus-containing benzo five-membered heterocyclic skeletons bearing both P-stereocenter and C-stereocenter.

5.
Front Psychol ; 14: 1233809, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809305
6.
Mol Med Rep ; 28(3)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37539751

RESUMO

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2A on p. 8311, portraying the results of immunostaining experiments for osterix, the 'GIOP' and 'GIOP+TMP (20)' data panels contained overlapping data, such that these images were derived from apparently the same original source, where they were intended to show the results from differently performed experiments. Moreover, in Fig. 3A on p. 8312 showing the results from ALP staining and Alizarin Red S staining experiments, two pairs of apparently overlapping data panels were identified in the Dex 106 M / TMP 50 µM, 100 µM and 200 µM data panels. After having re­examined their original data, the authors have realized that the data featured in Figs. 2A and 3A were assembled incorrectly in these figures. Revised versions of Fig. 2 and 3, now containing replacement data for the experiments shown in Figs. 2A and 3A, are shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 16: 8307­8314, 2017; DOI: 10.3892/mmr.2017.7610].

7.
World Neurosurg ; 169: e51-e58, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252906

RESUMO

OBJECTIVE: To compare the clinical efficacy of the minimally invasive technique and the open method in the treatment of irreducible unilateral subaxial cervical facet joint dislocation (SCFD). METHODS: From March 2015 to September 2018, 62 patients with unilateral SCFD were studied. The cases were divided into 2 groups based on different surgery strategies. Thirty-one patients were enrolled in the minimally invasive surgery (MIS) group, and 31 patients were enrolled in the open surgery group. The duration of prone position operation, blood loss, and total hospitalization costs were recorded. The clinical effects were evaluated using visual analogue scale scores, the Oswestry Disability Index, and Japanese Orthopedic Association scores at each follow-up. In addition, the segmental Cobb angle and intervertebral height were recorded and compared. RESULTS: The amount of intraoperative blood loss, prone position operation duration, and total hospital costs in the MIS group were significantly lower than in the open surgery group. The visual analogue scale, Oswestry Disability Index, and Japanese Orthopedic Association scores of the 2 groups significantly improved after the operation. A satisfactory fusion rate was obtained in both groups, and the segmental Cobb angle and intervertebral height scores in both groups improved significantly. CONCLUSIONS: Minimally invasive reduction had equal clinical efficacy to posterior open surgery. However, MIS was less invasive and had lower costs. Therefore, it is a potential option in the treatment of SCFD.


Assuntos
Luxações Articulares , Fusão Vertebral , Articulação Zigapofisária , Humanos , Fusão Vertebral/métodos , Resultado do Tratamento , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/cirurgia , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Vértebras Lombares/cirurgia , Estudos Retrospectivos
8.
BMC Nurs ; 21(1): 352, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36503477

RESUMO

BACKGROUND: Fatigue is a symptom characterized by an elevated prevalence in patients undergoing hemodialysis, which may cause extreme mental and muscular debilitation, significantly influencing social interaction, life quality and well-being. However, the significance of fatigue to patients undergoing hemodialysis has not been recognized yet, and prevention and management of fatigue in this population have not been thoroughly investigated. Additionally, previous studies mainly focused on muscular fatigue, while mental fatigue has been seldom discussed. This study aims to investigate the interaction between nurses and multidisciplinary of nonpharmacological integrated care interventions (NICIs) and assess the impact of fatigue on patients undergoing hemodialysis. METHODS: The integrative nonpharmacological care interventions in this study included walking, motivational interviewing (MI) and health education regarding behavioral self-management. A single-center randomized controlled trial was conducted in the dialysis center of the nephrological department in a tertiary affiliated hospital of medical university from January to June 2019. A total of 118 patients were selected and randomly divided into the intervention group (IG) and the control group (CG). Four patients dropped out during the study, and 114 patients were enrolled for the eventual analysis. The 60 patients in the IG received routine nursing combined with integrated care interventions, while the 54 patients in the CG received routine nursing only. This study lasted for six months. RESULTS: The experimental group exhibited significant reductions of overall fatigue (2.26 vs. 0.48), mental fatigue (1.41 vs. 0.54), muscular fatigue (2.13 vs. 0.75), and some biochemical indicators (e.g., serum urea) (P<0.05), compared with the CG. CONCLUSIONS: Nurses and multidisciplinary teams have been demonstrated to play a key role and interplay function in chronic disease management. Hence, the nurse-led multidisciplinary NICIs significantly alleviated total fatigue (muscular fatigue and mental fatigue) and improved other parameters. TRIAL REGISTRATION: ChiCTR-IOR-16008621 (March 18, 2016).

9.
Comput Math Methods Med ; 2022: 1047959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299678

RESUMO

This study was designed to investigate the effects of nonpharmacological integrated care protocols on fatigue in patients with hemodialysis. This parallel randomized controlled trial was conducted on patients undergoing hemodialysis from May to October 2020 at the Dialysis Center of the Fifth Affiliated Hospital of Zunyi Medical University. The patients were randomized into an intervention group (accepting nonpharmacological integrated care protocols and standard care) or a control group (accepting standard care only) using a computer-generated random number. The nonpharmacological holistic care intervention used in this study involved a well-rounded multidisciplinary team that worked together to improve dietary compliance, medication adherence, and self-management to improve patients' care and promote self-management. From the 120 evaluated patients, 116 cases were eligible and analyzed. The results showed that patients from the intervention group had obviously reduced overall fatigue, mental fatigue, and muscular fatigue relative to the control group. The nonpharmacological integrated care protocols were interactive and promotive to each other. Meanwhile, the role and function of nurses in the management of chronic disease were demonstrated to be crucial.


Assuntos
Prestação Integrada de Cuidados de Saúde , Fadiga , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Fadiga/prevenção & controle
10.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4256-4260, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046916

RESUMO

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Prescrições , Controle de Qualidade , Síndrome
11.
Bone ; 163: 116508, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35907616

RESUMO

Diagnosis of rare skeletal diseases is based primarily on clinical phenotype and radiographic analysis. Genetic etiology of these heterogeneous diseases remains largely unknown. Here, we report the identification of two genomic mutations using exome sequencing from patients with multiple epiphyseal dysplasia (MED) of an unusual family in autosomal dominant and X-linked inheritance. A dominant mutation (c.2224G > A; p.Gly687Ser) in the known causal COL2A1 gene was identified in three patients with MED, deformed femoral heads and vertebral dysplasia. Furthermore, a hemizygous mutation (c.2830G > A; p.Ala944Thr) in the USP9X gene was identified in the fourth patient with short stature, MED, deformed femoral head, thoracic and lumbar platyspondyly, right ankle condyle dysplasia, and subchondral sclerosis. This is the first identification of an X-linked candidate causative gene in a patient with MED, suggesting a new clinical entity. Our findings shed a new light on the role of USP9X in MED-associated disorders.


Assuntos
Osteocondrodisplasias , Colágeno Tipo II , Exoma , Humanos , Mutação , Linhagem , Ubiquitina Tiolesterase , Sequenciamento do Exoma
12.
J Cardiovasc Pharmacol ; 79(6): 925-934, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234738

RESUMO

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.


Assuntos
Sulfeto de Hidrogênio , Dinâmica Mitocondrial , Células Cultivadas , Fibroblastos/metabolismo , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
13.
Neuropharmacology ; 207: 108963, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35065082

RESUMO

Microglia-mediated neuroinflammation and mitochondrial dysfunction play critical role in the pathogenic process of Parkinson's disease (PD). Mitophagy plays central role in mitochondrial quality control. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia-mediated neurodegeneration and neuroinflammation. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA). Several preclinical studies have reported the beneficial effects of UA on age-related conditions by increasing mitophagy and blunting excessive inflammatory responses. However, the specific role of UA in pathology of PD remains unknown. In this study, we showed that treatment with UA reduced the loss of dopaminergic neurons, ameliorated behavioral deficits and neuroinflammation in MPTP mouse model of PD. Further study revealed that UA promotes mitophagy, restores mitochondrial function and attenuate proinflammatory response in BV2 microglial cells exposed to LPS. Moreover, UA also reduced NLRP3 inflammasome activation both in vitro and in vivo. Importantly, disruption of microglial mitophagy with pharmacological or genetic approach partly blunted the neuroprotective effects of UA in MPTP mouse model of PD. Collectively, these results provide strong evidence that UA protects against dopaminergic neurodegeneration and neuroinflammation. The mechanism may be related with its inhibition of NLRP3 inflammasome activation via promoting mitophagy in microglia.


Assuntos
Cumarínicos/farmacologia , Inflamassomos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Mitofagia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Doenças Neuroinflamatórias/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Intoxicação por MPTP/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
14.
Food Funct ; 13(1): 375-385, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34905594

RESUMO

Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Therapeutic strategies targeting mitochondrial dysfunction hold considerable promise for the treatment of PD. Recent reports have highlighted the protective role of urolithin A (UA), a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries and walnuts, in several neurological disorders including Alzheimer's disease and ischemic stroke. However, the potential role of UA in PD has not been characterized. In this study, we investigated the underlying mechanisms for role of UA in 6-OHDA-induced neurotoxicity in cell cultures and mice model of PD. Our results revealed that UA protected against 6-OHDA cytotoxicity and apoptosis in PC12 cells. Meanwhile, administration of UA to 6-OHDA lesioned mice ameliorated both motor deficits and nigral-striatal dopaminergic neurotoxicity. More important, UA treatment significantly attenuated 6-OHDA-induced mitochondrial dysfunction in PC12 cells accompanied by enhanced mitochondrial biogenesis. Mechanistically, we demonstrated that UA exerts neuroprotective effects by promoting mitochondrial biogenesis via SIRT1-PGC-1α signaling pathway. Taken together, these data provide new insights into the novel role of UA in regulating mitochondrial dysfunction and suggest that UA may have potential therapeutic applications for PD.


Assuntos
Cumarínicos/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Células PC12 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
15.
Exp Ther Med ; 22(6): 1405, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34675998

RESUMO

Radix isatidis (R. isatidis) is a commonly used traditional Chinese herbal medicine, which has been used for thousands of years in China and is believed to have the pharmacological properties of heat-clearing and detoxification. Heat-clearing and detoxification are theories of traditional Chinese medicine meaning that R. isatidis could treat febrile disease by clearing heat and reducing swelling. Polysaccharides isolated from R. isatidis by water extraction and alcohol precipitation have exhibited numerous biological activities, including antiviral and immunomodulatory effects. The present study was performed to investigate the immunomodulatory effects of water-soluble R. isatidis polysaccharides (RIPs) on RAW264.7 macrophages and murine splenocytes, and attempt to preliminarily identify the mechanism of immunomodulation. In vitro, RIPs had a low cytotoxicity, as shown by CellTiter 96® AQueous One Solution Cell Proliferation Assay. RAW264.7 cells treated with different concentrations of RIP displayed different morphological changes, from a round shape and aggregation to polygonal shape and dispersion in a dose-dependent manner. In the 5 mg/ml RIP-treated group, the changes of morphology were as same as the lipopolysaccharide-treated group. RIP also significantly enhanced the release of nitric oxide as shown by Griess method, and the secretion of TNF-α and IL-6 in RAW264.7 cells was confirmed by ELISA assay. Western blotting revealed a significant increase of toll-like receptor-4 (TLR-4) in RIP-treated RAW264.7, suggesting that TLR-4 may be associated with the immunomodulatory mechanism of RIP. Animal experiments also demonstrated through ELISA assays a significant increase in IFN-γ and IL-10 levels after the splenocytes of RIP-immunized mice were stimulated by inactivated herpes simplex virus type 2. The immune function of RIP-immunized mice was improved. The present study suggested that RIP could be potentially used as a novel immunomodulator.

16.
Life Sci ; 265: 118778, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33217442

RESUMO

AIMS: The intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD. MAIN METHODS: Human AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry. KEY FINDINGS: Here, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects. SIGNIFICANCE: These results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.


Assuntos
Anel Fibroso/metabolismo , Movimento Celular/fisiologia , Endotélio/citologia , Exossomos/metabolismo , Inflamação/fisiopatologia , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/irrigação sanguínea , Adolescente , Adulto , Idoso , Anel Fibroso/fisiologia , Apoptose , Western Blotting , Endotélio/metabolismo , Endotélio/fisiologia , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana , Humanos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/fisiopatologia , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Escoliose/metabolismo , Escoliose/fisiopatologia , Adulto Jovem
17.
World Neurosurg ; 145: e224-e232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059078

RESUMO

OBJECTIVE: An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. METHODS: In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. RESULTS: There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. CONCLUSIONS: The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Escoliose/cirurgia , Adolescente , Estudos de Coortes , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
18.
Mol Ther Nucleic Acids ; 22: 1092-1106, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33294295

RESUMO

Angiogenesis is a pathological signature of intervertebral disc degeneration (IDD). Accumulating evidence has shown that notochordal cells (NCs) play an essential role in maintaining intervertebral disc development and homeostasis with inhibitive effect on blood vessel in-growth. However, the anti-angiogenesis mechanism of NCs is still unclear. In the current study, we, for the first time, isolated NC-derived exosomes (NC-exos) and showed their increased concentration following compressive load cultures. We further found that NC-exos from 0.5 MPa compressive load cultures (0.5 MPa/NC-exos) inhibit angiogenesis via transferring high expressed microRNA (miR)-140-5p to endothelial cells and regulating the downstream Wnt/ß-catenin pathway. Clinical evidence showed that exosomal miR-140-5p expression of the nucleus pulposus is negatively correlated with angiogenesis in IDD. Finally, 0.5 MPa/NC-exos were demonstrated to have a therapeutical impact on the degenerated disc with an anti-angiogenesis effect in an IDD model. Consequently, our present findings provide insights into the anti-angiogenesis mechanism of NC-exos, indicating their therapeutic potential for IDD.

19.
Sci Rep ; 10(1): 17127, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033312

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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