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1.
Appl Clin Inform ; 12(4): 816-825, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496418

RESUMO

BACKGROUND: Clinical trials are the gold standard for generating robust medical evidence, but clinical trial results often raise generalizability concerns, which can be attributed to the lack of population representativeness. The electronic health records (EHRs) data are useful for estimating the population representativeness of clinical trial study population. OBJECTIVES: This research aims to estimate the population representativeness of clinical trials systematically using EHR data during the early design stage. METHODS: We present an end-to-end analytical framework for transforming free-text clinical trial eligibility criteria into executable database queries conformant with the Observational Medical Outcomes Partnership Common Data Model and for systematically quantifying the population representativeness for each clinical trial. RESULTS: We calculated the population representativeness of 782 novel coronavirus disease 2019 (COVID-19) trials and 3,827 type 2 diabetes mellitus (T2DM) trials in the United States respectively using this framework. With the use of overly restrictive eligibility criteria, 85.7% of the COVID-19 trials and 30.1% of T2DM trials had poor population representativeness. CONCLUSION: This research demonstrates the potential of using the EHR data to assess the clinical trials population representativeness, providing data-driven metrics to inform the selection and optimization of eligibility criteria.

2.
Neuroscience ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508847

RESUMO

Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is a protein highly expressed in neurons that may play important roles in the ubiquitin proteasome pathway in neurons, axonal integrity, and motor function after traumatic brain injury (TBI). Binding of reactive lipid species to cysteine 152 of UCHL1 results in unfolding, aggregation, and inactivation of the enzyme. To test the role of this mechanism in TBI, mice bearing a cysteine to alanine mutation at site 152 (C152A mice) that renders UCHL1 resistant to inactivation by reactive lipids were subjected to the controlled cortical impact model (CCI) of TBI and compared to wild type (WT) controls. Alterations in protein ubiquitination and activation of autophagy pathway markers in traumatized brain were detected by immunoblotting. Cell death and axonal injury were determined by histological assessment and anti-amyloid precursor protein (APP) immunohistochemistry. Behavioral outcomes were determined using the beam balance and Morris water maze tests. C152A mice had reduced accumulation of ubiquitinated proteins, decreased activation of the autophagy markers Beclin-1 and LC3B, a decreased number of abnormal axons, decreased CA1 cell death, and improved motor and cognitive function compared to WT controls after CCI; no significant change in spared tissue volume was observed. These results suggest that binding of lipid substrates to cysteine 152 of UCHL1 is important in the pathogenesis of injury and recovery after TBI and may be a novel target for future therapeutic approaches.

3.
Macromol Rapid Commun ; : e2100499, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480782

RESUMO

Stimulus-responsive hydrogels are of great significance in soft robotics, wearable electronic devices, and sensors. Near-infrared (NIR) light is considered an ideal stimulus as it can trigger the response behavior remotely and precisely. In this work, a smart flexible stimuli-responsive hydrogel with excellent photothermal property and decent conductivity are prepared by incorporating MXene nanosheets into the physically cross-linked poly(N-isopropyl acrylamide) hydrogel matrix. Because of outstanding photothermal effect and dispersion of MXene, the composite hydrogel exhibits rapid photothermal responsiveness and excellent photothermal stability under the NIR irradiation. Furthermore, the anisotropic bilayer hydrogel actuator shows fast and controllable light-driven bending behavior, which can be used as a light-controlled soft manipulator. Meanwhile, the hydrogel sensor exhibits cycling stability and good durability in detecting various deformation and real-time human activities. Therefore, the present study involving the fabrication of MXene nanocomposite hydrogels for potential applications in remotely controlled actuator and wearable electronic device provides a new method for the development of photothermal responsive conductive hydrogels.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34500402

RESUMO

Due to global outbreak of rice false smut disease, ustiloxin A (UA) was detected in rice. However, accurate methods for monitoring UA in human body fluids were lacking. In this context, a UPLC-MS/MS method based on two-step SPE was constructed for measuring UA in urine. The limits of UA quantification in human and mice urine were 58.3 and 108.7 ng/L, respectively. The proposed method was applied to detect UA in urine samples collected from human and mice. After dietary exposure, the contents of UA in mice urine were from 6.03 to 16.76 µg/g of creatine, accounting for approximate 14% of daily intake dose. Furthermore, due to the trace residues in rice (78-109 ng/kg), no detectable UA was observed in the urine of 20 volunteers. To the best of our knowledge, it is the first time to report the occurrence of UA in mammal urine.

5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(9): 1161-1166, 2021 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-34523282

RESUMO

Objective: To compare the refracture risk between sandwich vertebrae and ordinary adjacent vertebrae, and to explore the risk factors related to refracture. Methods: Retrospective analysis was performed on the data of patients who received percutaneous vertebral augmentation (PVA) and formed sandwich vertebrae between April 2015 and October 2019. Of them, 115 patients were enrolled in the study. There were 27 males and 88 females with an average age of 73.9 years (range, 53-89 years). Univariate analysis was performed to analyzed the patients' general data, vertebral augmentation related indexes, and sandwich vertebrae related indexes. Survival analysis was performed for all untreated vertebrae at T 4-L 5 of the included patients at the vertebra-specific level, and risk curves of refracture probability of untreated vertebrae between sandwich vertebrae and ordinary adjacent vertebrae were compared. Cox's proportional hazards regression model was used to analyze risk factors for refracture. Results: The 115 patients were followed up 12.6-65.9 months (mean, 36.2 months). Thirty-seven refractures involving 51 vertebral bodies occurred in 31 patients. The refracture rate of 27.0% (31/115) in patients with sandwich vertebrae was significantly higher than that of 15.2% (187/1228) in all patients who received PVA during the same period ( χ 2=10.638, P=0.001). Univariate analysis results showed that there was a significant difference in the number of augmented vertebrae between patients with and without refractures ( Z=0.870, P=0.004). However, there was no significant difference in gender, age, body mass index, whether had clear causes of fracture, whether had dual energy X-ray absorptiometry testing, whether the sandwich vertebra generated through the same PVA, puncture method, method of PVA, number of PVA procedures, number of vertebrae with old fracture, whether complicated with spinal deformity, bone cement distribution, and kyphosis angle of sandwich vertebral area ( P>0.05). Among the 1 293 untreated vertebrae, there were 136 sandwich vertebrae and 286 ordinary adjacent vertebrae. The refracture rate of sandwich vertebrae was 11.3% which was higher than that of ordinary adjacent vertebrae (6.3%)( χ 2=4.668, P=0.031). The 1- and 5-year fracture-free probabilities were 0.90 and 0.87 for the sandwich vertebrae, and 0.95 and 0.93 for the ordinary adjacent vertebrae, respectively. There was a significant difference between the two risk curves of refracture ( χ 2=4.823, P=0.028). Cox's proportional hazards regression model analysis results showed that the sandwich vertebrae, thoracolumbar location, the number of the augmented vertebrae, and the unilateral puncture were significant risk factors for refracture ( P<0.05). Conclusion: The sandwich vertebrae has a higher risk of refracture when compared with the ordinary adjacent vertebrae, and its 1- and 5-year fracture-free probabilities are lower than those of the ordinary adjacent vertebrae. However, the 5-year fracture-free probability of sandwich vertebrae is still 0.87, so prophylactic enhancement is not recommended for all sandwich vertebrae. In addition, the sandwich vertebrae, thoracolumbar location, the number of the augmented vertebrae, and the unilateral puncture were important risk factors for refracture.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Cimentos Ósseos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Coluna Vertebral
6.
Sci Rep ; 11(1): 18263, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521930

RESUMO

Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1ß while showing less toxicity to the liver and kidney.

7.
Front Cell Infect Microbiol ; 11: 701820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532298

RESUMO

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.

8.
Eur J Cancer ; 157: 114-123, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508993

RESUMO

AIM: CD73 overexpression has been reported in several malignancies and is considered to be a novel immune checkpoint. However, the role and significance of CD73 in gastric cancer (GC) still remain obscure. We aim to investigate the role of CD73 expression in predicting prognosis, shaping immune contexture and guiding therapeutic strategy in GC. METHODS: The study enrolled four independent cohorts with a total of 902 patients with GC. CD73 expression and immune contexture were examined by immunohistochemistry, single-sample gene set enrichment analysis and flow cytometry. Clinical outcomes of patient subgroups were evaluated using the Kaplan-Meier curves and Cox proportional hazard analysis. All statistical tests were two-sided. RESULTS: CD73 was identified as an independent adverse prognostic factor for survival in GC. CD73high tumours showed a specific microenvironment with more CD8+ T cell infiltration, but these CD8+ T cells displayed a dysfunctional phenotype. Furthermore, the CD73 (NT5E) mRNA level was associated with the Cancer Genome Atlas molecular subtypes, and NT5E high tumours showed significant fibroblast growth factor receptor 2 activation and vascular endothelial growth factor and receptor enrichment. In addition, CD73high tumours indicated better chemotherapeutic responsiveness to fluorouracil yet a worse objective response rate to pembrolizumab in GC. CONCLUSIONS: High CD73 expression indicated an immunoevasive contexture with CD8+ T cell dysfunction and represented an independent predictor for adverse clinical outcomes. As a potential immunotherapeutic target, CD73 could potentially be a novel biomarker for adjuvant chemotherapy, targeted therapies and immunotherapy. The crucial role of CD73 in the therapeutic landscape of GC needs further validation retrospectively and prospectively.

9.
BMC Musculoskelet Disord ; 22(1): 777, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511102

RESUMO

BACKGROUND: Biomechanical studies have demonstrated that uncovertebral joint contributes to segment mobility and stability to a certain extent. Simultaneously, osteophytes arising from the uncinate process are a common cause of cervical spondylotic radiculopathy (CSR). For such patients, partial uncinatectomy (UT) may be required. However, the clinical efficacy and sagittal alignment of partial UT during anterior cervical discectomy and fusion (ACDF) have not been fully elucidated. METHODS: A total of 87 patients who had undergone single level ACDF using a zero-profile device from July 2014 to December 2018 were included. Based on whether the foraminal part of the uncovertebral joint was resected or preserved, the patients were divided into the ACDF with UT group (n = 37) and the ACDF without UT group (n = 50). Perioperative data, radiographic parameters, clinical outcomes, and complications were compared between the two groups. RESULTS: The mean follow-up was 16.86 ± 5.63 and 18.36 ± 7.51 months in the ACDF with UT group and ACDF without UT group, respectively (p > 0.05). The average preoperative VAS arm score was 5.89 ± 1.00 in the ACDF with UT group and 5.18 ± 1.21 in the ACDF without UT group (p = 0.038). However, the average VAS arm score was 4.22 ± 0.64, 4.06 ± 1.13 and 1.68 ± 0.71, 1.60 ± 0.70 at 1 week post operation and at final follow up, respectively, (p > 0.05). We also found that the C2-7 SVA and St-SVA at the last follow-up and their change (last follow-up value - preoperative value) in the ACDF with UT group were significantly higher than ACDF without UT group (p < 0.05). No marked differences in the other cervical sagittal parameters, fusion rate or complications, including dysphagia, ASD, and subsidence, were observed. CONCLUSIONS: Our result indicates that ACDF using a zero-p implant with or without partial UT both provide satisfactory clinical efficacy and acceptable safety. However, additional partial UT may has a negative effect on cervical sagittal alignment.


Assuntos
Radiculopatia , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Seguimentos , Humanos , Radiculopatia/diagnóstico por imagem , Radiculopatia/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
10.
Redox Biol ; : 102129, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34526248

RESUMO

Hepatotoxicity caused by an overdose of acetaminophen (APAP) is the leading reason for acute drug-related liver failure. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein that helps to regulate redox homeostasis and coordinate stress responses via binding to the Kelch-like ECH-associated protein 1 (Keap1). Targeting the Keap1-Nrf2 interaction has recently emerged as a potential strategy to alleviate liver injury caused by APAP. Here, we designed and synthesized a number of iridium (III) and rhodium (III) complexes bearing ligands with reported activity against oxidative stress, which is associated with Nrf2 transcriptional activation. The iridium (III) complex 1 bearing a bioactive ligand 2,9-dimethyl-1,10-phenanthroline and 4-chloro-2-phenylquinoline, a derivative of the bioactive ligand 2-phenylquinoline, was identified as a direct small-molecule inhibitor of the Keap1-Nrf2 protein-protein interaction. 1 could stabilize Keap1 protein, upregulate HO-1 and NQO1, and promote Nrf2 nuclear translocation in normal liver cells. Moreover, 1 reversed APAP-induced liver damage by disrupting Keap1-Nrf2 interaction and without inducing organ damage and immunotoxicity in mice. Our study demonstrates the identification of a selective and efficacious antagonist of Keap1-Nrf2 interaction possessed good cellular permeability in cellulo and ideal pharmacokinetic parameters in vivo, and, more importantly, validates the feasibility of conjugating metal complexes with bioactive ligands to generate metal-based drug leads as non-toxic Keap1-Nrf2 interaction inhibitors for treating APAP-induced acute liver injury.

11.
Front Cell Infect Microbiol ; 11: 704100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513727

RESUMO

Objective: To investigate variation in gut microbiome in female patients with invasive mole (IM) and choriocarcinoma (CC) and compare it with healthy controls. Methods: Fecal microbiome of 12 female patients with IM, 9 female patients with CC, and 24 healthy females were analyzed based on 16s rDNA sequencing. Alpha (α) diversity was evaluated using Shannon diversity index and Pielou evenness index, while beta (ß) diversity was assessed using principle coordinate analysis (PCoA) of unweighted Unifrac distances. The potential functional changes of microbiomes were predicted using Tax4Fun. The relative abundance of microbial taxa was compared using Welch's t test. The role of varied gut microbiota was analyzed via receiver operating characteristic (ROC) curve. Results: The α diversity and ß diversity were significantly different between IM patients and controls, but not between CC patients and controls. In addition, the abundance of cancer-related genes was significantly increased in IM and CC patients. Notably, a total of 19 families and 39 genera were found to have significant differences in bacterial abundance. ROC analysis indicated that Prevotella_7 may be a potential biomarker among IM, CC, and controls. Conclusion: Our study demonstrated that the diversity and composition of gut microbiota among IM patients, CC patients, and healthy females were significantly different, which provides rationale for using gut microbiota as diagnostic markers and treatment targets, as well as for further study of gut microbiota in gestational trophoblastic neoplasia (GTN).

12.
Artigo em Inglês | MEDLINE | ID: mdl-34519919

RESUMO

Lactic acid can synthesize high value-added chemicals such as poly lactic acid. In order to further minimize the cost of lactic acid production, some effective strategies (e.g., effective mutagenesis and metabolic engineering) have been applied to increase productive capacity of lactic acid bacteria. In addition, low-cost cheap raw materials (e.g., cheap carbon source and cheap nitrogen source) are also used to reduce the cost of lactic acid production. In this review, we summarized the recent developments in lactic acid production, including efficient strain modification technology (high-efficiency mutagenesis means, adaptive laboratory evolution, and metabolic engineering), the use of low-cost cheap raw materials, and also discussed the future prospects of this field, which could promote the development of lactic acid industry.

13.
Front Public Health ; 9: 691669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490182

RESUMO

Objective: Explore the correlation and predictive power of health physical fitness on health-promoting lifestyle of adolescents to provide an important reference for reform in middle school physical education classroom teaching. Methods: Taking some junior and senior high school students in Nanchong City of Sichuan Province as survey objects, a stratified random sampling method was used to carry out a health/fitness test and conduct a questionnaire survey. SPSS17.0, amos 21.0, and other statistical analysis software were used to process the relevant data. Results: (1) Male adolescents had 14.4% predictive power for their overall health-promoting lifestyle through the combined effects of cardiopulmonary endurance, muscle strength, and explosive strength, while female adolescents had 16.8% predictive power for their overall health-promoting lifestyle through the combined effects of cardiopulmonary endurance, flexibility, and body mass index (BMI). (2) Ten percent of the variation in the health-promoting lifestyle of men under 14 years old was caused by the combined effects of muscle endurance and muscle strength, while 14.4% of the variation in the health-promoting lifestyle of female adolescents was caused by the combined effects of muscle endurance, muscle strength, flexibility, and cardiopulmonary endurance. (3) Some 10.9 and 17.6% of the variation in health-promoting lifestyle of male and female adolescents aged between 14 and 17 was caused by the combined effects of cardiopulmonary endurance, muscle strength, and flexibility, respectively. (4) Some 20.7% of the variation in health promoting lifestyle of male adolescents aged 17 years or above was caused by cardiopulmonary endurance, explosive force, and muscle endurance, while 16.8% of the variation in health-promoting lifestyle of female adolescents was caused by the combined effect of cardiopulmonary endurance, BMI, and muscle endurance. Conclusion: Health and physical fitness of adolescents can significantly predict their health-promoting lifestyle, and the predictive power and typical correlation between them are affected by demographic factors.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34491715

RESUMO

The fabrication of a single polymer network that exhibits a good reversible two-way shape memory effect (2W-SME), can be formed into arbitrarily complex three-dimensional (3D) shapes, and is recyclable remains a challenge. Herein, we design and fabricate poly(thiourethane) (PTU) networks with an excellent thermadapt reversible 2W-SME, arbitrary reconfigurability, and good recyclability via the synergistic effects of multiple dynamic covalent bonds (i.e., ester, urethane, and thiourethane bonds). The PTU samples with good mechanical performance simultaneously demonstrate a maximum tensile stress of 29.7 ± 1.1 MPa and a high strain of 474.8 ± 7.5%. In addition, the fraction of reversible strain of the PTU with 20 wt % hard segment reaches 22.4% during the reversible 2W-SME, where the fraction of reversible strain is enhanced by self-nucleated crystallization of the PTU. A sample with arbitrarily complex permanent 3D shapes can be realized via the solid-state plasticity, and that sample also exhibits excellent reversible 2W-SME. A smart light-responsive actuator with a double control switch is fabricated using a reversible two-way shape memory PTU/MXene film. In addition, the PTU networks are de-cross-linked by alcohol solvolysis, enabling the recovery of monomers and the realization of recyclability. Therefore, the present study involving the design and fabrication of a PTU network for potential applications in intelligent actuators and multifunctional shape-shifting devices provides a new strategy for the development of thermadapt reversible two-way shape memory polymers.

15.
Langmuir ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493039

RESUMO

Giant surfactants with different numbers of aryl-trifluorovinyl ether-functionalized polyhedral oligomeric silsesquioxane (FVPOSS) heads and one poly(ethylene oxide) (PEO) tail, (FVPOSS)n-PEO227, are precisely synthesized. The phase behaviors of (FVPOSS)n-PEO227 at the air-water interface were investigated through surface pressure measurements (isotherm and hysteresis experiments) and the Brewster angle microscopy. Upon increasing the number of FVPOSS heads, the interfacial behaviors of these giant surfactants greatly change. More phase transitions occur during the compression as the number of FVPOSS heads increased from one to two and three. The evolution of morphologies of Langmuir films and compression-expansion hysteresis curves further illustrate phase transitions at the air-water interface. Furthermore, molecular mechanisms to describe phase transitions of (FVPOSS)n-PEO227 at the interface are put forward. This study deepens the understanding of interfacial phase behaviors of special giant surfactants and provides knowledge of nanostructure design and construction at the interface.

16.
J Mater Chem B ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494067

RESUMO

1T-phase niobium telluride (NbTe2) nanosheets are becoming increasingly important in emerging fields, such as spintronics, sensors and magneto-optoelectronics, due to their excellent physical and chemical properties. However, exploration on their biomedical applications are limited. Herein, ultrathin 1T-phase NbTe2 single-crystalline nanosheets with excellent photothermal performance, high drug-loading rate, near-infrared (NIR) light/acidic pH-triggered drug release, and low toxicity were developed for potentiated photothermal therapy. Importantly, they showed excellent biocompatibility in vivo and in vitro. NbTe2 nanosheets loaded with integrated stress response inhibitors (ISRIB) could achieve chemo-photothermal therapy of tumors through the ATF4-ASNS signaling axis. Ultrathin 1T-phase NbTe2 single-crystalline nanosheets with unique photothermal properties, drug loading rate and safety provide dramatic possibilities in biomedical applications, such as tissue imaging, photothermal therapeutics and pharmaceutics.

17.
Cell Tissue Bank ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494222

RESUMO

Neural progenitor cells (NPCs) transplantation is known as a potential strategy for treating spinal cord injury (SCI). This study aimed to investigate effects of insulin growth factor-1 (IGF-I) on NPCs proliferation and clarify associated mechanisms. NPCs isolated from T8-T10 segmental spinal cord tissues of rats were cultured and identification. Then, lentivirus packing plasmids containing IGF-I was constructed and used for NPCs infection. Cell proliferation was evaluated by detecting 5-Bromodeoxyuridine (BrdU) expression in NPCs, cell differentiation was detected using double-labeling immunofluorescence staining while cell apoptosis was detected using TUNEL assay. In addition, the signal expression of Akt/mTOR/p70S6K in NPCs cells were investigated using immunofluorescence staining and western blot assay. The experimental group was defined as pCMV-IGF-I group, while the negative control group was defined as pCMV-LacZ group. Cells infected with pCMV-IGF-I lentivirus followed by addition of 100 mg/ml rapamycin were defined as pCMV-IGF-I + Rapa group. NPCs were successfully isolated, identified and cultured. IGF-I overexpression significantly inhibited cell apoptosis and enhanced cell migration. Akt/mTOR/ p70S6K signaling cascade was proved to be present in NPCs, IGF-I overexpression significantly activated Akt/mTOR/p70S6K signaling cascade, while rapamycin addition inhibited its expression. Also, the activated Akt/mTOR/p70S6K signal cascade induced by IGF-I significantly enhanced BrdU expression and inhibited cell apoptosis, and promoted the differentiation of NPC into the neuronal system. However, the rapamycin addition inhibited the cell response induced by IGF-I overexpression. IGF-I overexpression could enhance cell proliferation, inhibit cell apoptosis and promote their differentiation into neuronal systems by activating Akt/mTOR/p70S6K signaling cascade in vitro, indicating that the Akt/mTOR/p70S6K signaling cascade may be the potentially mechanism for the endogenous repair and remodeling of spinal cord after injury.

18.
Zhongguo Zhen Jiu ; 41(9): 999-1002, 2021 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-34491649

RESUMO

OBJECTIVE: To explore the therapeutic effect on rheumatoid arthritis treated with Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" and the relevant effect mechanism. METHODS: A total of 104 patients with rheumatoid arthritis were randomized into and an observation group (52 cases, 1 case dropped off) and a control group (52 cases, 3 cases dropped off). In the control group, methotrexate tablets were prescribed for oral administration, 5 mg each time, once a week. In the observation group, on the base of the treatment as the control group, Bo's abdominal acupuncture was combined. The acupoints included Zhongwan (CV 12), Xiawan (CV 10), Guanyuan (CV 4), Qihai (CV 6), Huaroumen (ST 24), Wailing (ST 26), etc. The treatment was given once every two days, 3 times weekly. Totally 12 weeks were required in the two groups. Before and after treatment, the score of TCM symptoms (including joint pain, the range of motion, joint swelling and morning stiffness), and the levels of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and C-reactive protein (CRP) were observed and the clinical therapeutic effect was assessed in the two groups. RESULTS: After treatment, the total effective rate was 88.2% (45/51) in the observation group, higher than 73.5% (36/49) in the control group (P<0.05). The score of each TCM symptom and the total scores after treatment were all lower than those before treatment in the two groups (P<0.05), and these scores in the observation group were lower than the control group (P<0.05). After treatment, the levels of ESR, RF and CRP were all lower than those before treatment in the two groups (P<0.05), while the levels of those indexes in the observation group were lower than the control group (P<0.05). CONCLUSION: Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" as the adjunctive therapy effectively relieves the clinical symptoms in the patients with rheumatoid arthritis, which is related to the reduction of ESR, RF and CRP in mechanism.


Assuntos
Terapia por Acupuntura , Artrite Reumatoide , Abdome , Pontos de Acupuntura , Artrite Reumatoide/terapia , Sedimentação Sanguínea , Humanos , Fator Reumatoide , Resultado do Tratamento
19.
Environ Microbiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472183

RESUMO

Colletotrichum higginsianum is an important fungal pathogen causing anthracnose disease of cruciferous plants. In this study, we characterized a putative ortholog of yeast SPE1 in C. higginsianum, named ChODC. Deletion mutants of ChODC were defective in hyphal and conidial development. Importantly, deletion of ChODC significantly affected appressorium-mediated penetration in C. higginsianum. However, polyamines partially restore appressorium function and virulence indicating that loss of ChODC caused significantly decreased virulence by the crosstalk between polyamines and other metabolic pathways. Subsequently, transcriptomic and metabolomic analyses demonstrated that ChODC played an important role in metabolism of various carbon and nitrogen compounds including amino acids, carbohydrates and lipids. Along with these clues, we found deletion of ChODC affected glycogen and lipid metabolism, which were important for conidial storage utilization and functional appressorium formation. Loss of ChODC affected the mTOR signaling pathway via modulation of autophagy. Interestingly, cAMP treatment restored functional appressoria to the ΔChODC mutant, and rapamycin treatment also stimulated formation of functional appressoria in the ΔChODC mutant. Overall, ChODC was associated with the polyamine biosynthesis pathway, as a mediator of cAMP and mTOR signaling pathways to regulate appressorium function. Our study provides evidence of a link between ChODC and the cAMP signaling pathway and defines a novel mechanism by which ChODC regulates infection-associated autophagy and plant infection by fungi. This article is protected by copyright. All rights reserved.

20.
Histol Histopathol ; : 18370, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472621

RESUMO

The increasing demand for bone grafts and the scarcity of donors worldwide are promoting researchers to seek alternatives. The extracellular matrix (ECM) has been reported to enhance properties of osteoconduction and osteoinduction by simulating the molecular structure of bone and facilitating cell infiltration for bone repair. As one of several novel biomaterials, ECM has many desirable properties, including biocompatibility, bioactivity, and biosafety. Thus, we evaluated whether ECM is a promising scaffold biomaterial for bone repair. In this review, we explore ECM composition, the sources and fabrication methods, especially the decellularization technique, of ECM scaffolds. Furthermore, we highlight recent progress in the use of ECM as a scaffold biomaterial for bone repair. Generally, ECM is used in 1) three-dimensional (3D) cell cultures to promote osteogenic differentiation, 2) combinations with other biomaterials to increase their osteogenic effects, 3) 3D printing to produce customized or patient-tailored scaffolds for bone repair, and 4) hydrogels derived from ECM used for bone repair. In addition, we focus on future prospects for application of ECM as a scaffold material used for bone repair. From this review, we expect to have a perfect understanding of ECM-based scaffold materials in the hope that this leads to further research of the production of ECM biomaterials to meet the clinical needs for bone repair.

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