ABSTRACT
Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Subject(s)
Creatine/metabolism , Extracellular Vesicles , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Regeneration , Connexins/metabolismABSTRACT
Ménière's disease （MD） is an inner ear disease characterized by vertigo， tinnitus， hearing loss， and ear stuffiness. Modern therapies such as drugs， surgery， and vestibular function rehabilitation have limited effects in relieving the symptoms and reducing the recurrence. Traditional Chinese medicine （TCM） can alleviate the symptoms of MD with simple operation and mild adverse reactions while emphasizing psychological adjustment. The TCM treatment of MD is individualized depending on different stages and pathogenic factors. The internal treatment mainly targets phlegm， dampness， water， wind， fire， deficiency， and blood stasis. External interventions include acupuncture and moxibustion. This paper reviewed the published articles about the treatment of MD with TCM. In recent five years， the published studies were mainly clinical trials and experience discussion （or case reports）， and few reports of fundamental research were published. In these studies， the Western medicine diagnosis of MD mostly refers to the Diagnostic Basis and Efficacy Evaluation of Ménière's Disease （Guiyang， 2006） and the Guidelines for Diagnosis and Treatment of Ménière's Disease （2017）， while the TCM diagnosis mostly refers to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine issued by the National Administration of TCM in 1994. The efficacy was mostly evaluated based on clinical efficacy， scales， syndrome scores， pure tone audiometry， etc.， while caboratory indexes were rarely used. The available clinical studies about the treatment of MD with TCM generally have low quality of evidence and single intervention means. In the future， the research on the treatment of MD with TCM can be improved by standardizing the research program， improving the quality of evidence， exploring more intervention methods， and strengthening basic research.
ABSTRACT
Posterior cortical atrophy (PCA) is a kind of neurodegenerative dementia. The core feature of the PCA includes progressive decline in visual processing and other posterior parietal-occipital cortex-related cognitive functions. Recently, neuroimaging features of PCA from magnetic resonance imaging/single photon emission computed tomography/ 18F-deoxyglucose positron emission tomography-computer tomography studies represent the typical characteristics of cortical atrophy, hypoperfusion, and hypometabolism in the posterior parietal-occipital cortex. The most common neuropathological changes of PCA are amyloid plaques deposition and neurofibrillary tangles in posterior cortex, while the molecular biomarkers are decreased amyloid β-protein 1-42 together with increased T-tau and/or P-tau in cerebral spinal fluid. From this point, PCA is also considered as an atypical form of Alzheimer′s disease (AD). However, individuals fulfilling the criteria for the core clinico-radiological PCA syndrome, can also fulfill the core clinical criteria for any other neurodegenerative syndrome, and represent negative AD-related pathophysiological biomarkers. Heterogeneity within the PCA syndrome and pathophysiological biomarkers prompt the PCA working group to establish a new consensus on PCA classification and diagnostic criteria, which is proposed for use in a number of different research contexts and the research of AD, atypical AD and related syndromes. This paper gives a brief introduction and interpretation of the newly proposed classification and diagnostic criteria of PCA.
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In recent years,magnetic resonance imaging (MRI) has been widely used in the early diagnosis as well as long-term follow-up study of Alzheimer's disease (AD).The studies were reviewed which applied the structural MRI and arterial spin labeling MRI (ASL-MRI) in AD over the past 20 years,and found more gray matter volume loss in multiple brain structures in individuals with AD spectrum.Among them,medial temporal lobe atrophy and posterior cortical atrophy are the most diagnostic.Meanwhile,cerebral blood flow changes in various brain regions with the progression of the AD.More investigations combining the changes of gray matter volume and cerebral blood flow to explore pathophysiological mechanisms underlying cognitive decline in AD spectrum are necessary in the future.
ABSTRACT
Military flying labor hygiene is a discipline that focuses on influences of special flight environment and labor condition on human body and related prevent measures,with the core of flight fatigue.Health information and technique training can help flight surgeons to enhance professional competency and improve the prevention and recovery of military flying fatigue.The course construction of teaching system in this study included survey of demand,arrangement of content,identification of strategy,determination of evaluation,and feedback of results.Meanwhile,the textbook compilation,cultivation of teaching team and construction of laboratory were also needed.After a 4-year practice,a formal teaching system has been established and its teaching effectiveness has basically fulfilled the professional requirement for flight surgeons.
ABSTRACT
OBJECTIVE： To study the improving effects of echinacoside （ECH） on spatial cognitive function in mice under hypobaric hypoxia environment and its mechanism. METHODS： Totally 60 mice were randomly divided into blank group （normal saline）， model group （normal saline）， positive group （Ginkgo leaf extract tablet，100 mg/kg） and ECH low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 10 mice in each group. Except for blank group， other groups were cultured in hypobaric oxygen chamber to simulate hypobaric hypoxia； they were given relevant medicine intragastrically once a day， for consecutive 7 d （Placing into hypobaric oxygen chamber immediately after medication）. Using the times of horizontal and vertical activities of mice in 2 min as index， negative emotions and spatial cognitive function were evaluated. Histopathological changes of hippocampus in mice were observed by microscopy after HE staining. The levels of SOD， CAT， GSH-Px and MDA in hippocampal tissue of mice were detected. RESULTS： Compared with blank group， the times of horizontal activities， MDA level were increased significantly in model group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were decreased significantly （P＜0.05）； the pyramidal cells in the CA1 area of the hippocampal tissue were arranged loosely， and many pyramidal cells were compressed and stained deeply. Compared with model group， the times of horizontal activities and MDA level were decreased significantly in positive group and ECH high-dose group （P＜0.05）， while the times of vertical activities， the levels of SOD， CAT and GSH-Px were increased significantly （P＜0.05）； the pyramidal cells in the CA1 region of the hippocampal tissue were abundant and closely arranged， and a few of them are constricted and deeply stained. CONCLUSIONS： ECH can improve spatial cognitive impairment of mice under hypobaric hypoxia environment， the mechanism of which may be associated with up-regulation of SOD， CAT and GSH-Px， down-regulation of MDA in the hippocampal tissue.
ABSTRACT
Military flying labor hygiene is a discipline that focuses on influences of special flight environment and labor condition on human body and related prevent measures, with the core of flight fatigue. Health information and technique training can help flight surgeons to enhance professional competency and improve the prevention and recovery of military flying fatigue. The course construction of teaching system in this study included survey of demand, arrangement of content, identification of strategy, determination of evaluation, and feedback of results. Meanwhile, the textbook compilation, cultivation of teaching team and construction of laboratory were also needed. After a 4-year practice, a formal teaching system has been established and its teaching effectiveness has basically fulfilled the professional requirement for flight surgeons.
ABSTRACT
Objective:To investigate the changes of gene or protein expression and activity of matrix metalloprotein9 (MMP9) and tissue inhibitor ofmetalloproteinasel (TIMP1) in the carotid artery (CA) of 4 wk hindlimb unweighted rat.Methods:A 4 weeks(wk) hindlimb unweighted (HU) rat model was used to simulate the effect of weightlessness on the cardiovascular system.Transmission electron microscopy was used to detect the content of ECM.Reverse transcriptase polymerase chain reaction(RT-PCR) was conducted to measure the mRNA content MMP and TIMP1.Immunohistochemistry and Western blot technique were used to measure the protein abundance.Gelatin zymography was carried out to detect the activity of MMP9.Results:Compared to the control group (CON),the area of ECM was enhanced (P＜0.05) and the content of collage fiber was increased (P＜0.05) in the CA of HU rats;moreover,HU did not affect the mRNA expression of MMP9,but significantly reduced the protein content (P＜0.05) or enzymatic activity (P＜0.05).Accordingly,the mRNA or protein expression of TIMP1 in the CA was significantly increased by HU (P＜0.05).Conclusion:Simulated weightlessness caused imbalance between MMP and TIMP1 expression,which might contribute to the ECM aggregation and stiffness of CA.
ABSTRACT
<p><b>OBJECTIVE</b>This study aims to detect the expression level of interleukin-23 (IL-23) in tongue squamous cell carcinoma tissues and its relationship with clinical prognosis, as well as explore the anti-apoptotic and drug resistance of the tongue squamous cell line-SCC9 before and after treatment with IL-23.</p><p><b>METHODS</b>The expression of IL-23 in tumor tissues from 28 tongue cancer patients was analyzed by immunohistochemistry assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of Wingless-related integration site (Wnt)1 and c-myc in SCC9 cells treated with different IL-23 concentrations. After interferencing the β-catenin with small interfering RNA (siRNA), the expression of β-catenin, B-cell lymphoma-2 (Bcl-2), ATP-binding cassette sub-family G member 2 (ABCG2), and permeability-glycoprotein (P-gp) in SCC9 was measured by Western blot analysis. The effect of IL-23 on the apoptotic resistance of SCC9 to cisplatin was examined by methyl thiazolyl tetrazolium test.</p><p><b>RESULTS</b>The expression of IL-23 in tongue cancer tissues was correlated with lymphatic metastasis, nerve invasion, and the recurrence after therapy (P<0.05). After dealing with IL-23, SCC9 showed the upregulation effect of Bcl-2, ABCG2 and P-gp expressions. IL-23 was closely related to the activation level of the Wnt pathway and significantly strengthened the resistance to cisplatin (P<0.01).</p><p><b>CONCLUSION</b>IL-23 activates the Wnt pathway in tongue squamous cell carcinoma, thereby enhancing its resistance to apoptosis and drug.</p>