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1.
Sci Rep ; 10(1): 16225, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004823

RESUMO

Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, α2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T > G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS.

2.
Mol Oncol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037696

RESUMO

Oncolytic viruses are potent anticancer agents that replicate within and kill cancer cells rather than normal cells and their selectivity is largely determined by oncogenic mutations. M1, a novel oncolytic virus strain, has been shown to target cancer cells, but the relationship between its cancer selectivity and oncogenic signaling pathways is poorly understood. Here, we report that RAS mutation promotes the replication and oncolytic effect of M1 in cancer, and we further provide evidence that the inhibition of the RAS/RAF/MEK signaling axis suppresses M1 infection and the subsequent cytopathic effects. Transcriptome analysis revealed that the inhibition of RAS signaling upregulates the type I interferon antiviral response, and further RNA interference screen identified CDKN1A as a key downstream factor that inhibits viral infection. Gain- and loss-of-function experiments confirmed that CDKN1A inhibited the replication and oncolytic effect of M1 virus. Subsequent TCGA data mining and tissue microarray (TMA) analysis revealed that CDKN1A is commonly deficient in human cancers, suggesting extensive clinical application prospects for M1. Our report indicates that viro-therapy is feasible for treating undruggable RAS-driven cancers and provides reliable biomarkers for personalized cancer therapy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33047970

RESUMO

To explore which TLIF techniques are advantageous in reducing the risk of complications and conducive to bone fusion under the vibration. The L1-L5 finite element lumbar model was modified to simulate three different TLIF techniques (a unilateral standard cage, a crescent-shaped cage, and bilateral standard cages). The results showed that the crescent-shaped cage may reduce the risk of subsidence and provide a more stable and suitable environment for vertebral cell growth under the vibration compared to the other TLIF techniques. Unilateral cage may increase the risk of adjacent segment disease and cage failure including fatigue failure under vibration.

4.
Int J Numer Method Biomed Eng ; : e3402, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33021071

RESUMO

Lumbar vertebrae osteoporosis is the most common challenge for lumbar interbody fusion, and this challenge has been widely concerned by scholars for many years. However, under whole-body vibration, osteoporosis how to affect the vibration characteristics of the fusion lumbar spine, complications, and fusion outcomes is urgent to know. The L1-L5 finite element model of lumbar spine was modified to simulate the transforaminal lumbar interbody fusion model with the bilateral pedicle screw fixator at L4-L5 level. A 5 Hz, 40 N sinusoidal vertical load supplemented with a 400 N preload was used to simulate the vertical vibration of human body. The results showed that under whole-body vibration, osteoporosis of fused vertebrae may cause the adjacent segments more unstable and increase the risk of adjacent segment diseases, subsidence, cage failure, rod failure, and lumbar instability. Osteoporosis of the fused vertebrae may cause the vertebral cells an unstable, inhibited growth and lead to poorer fusion outcomes. The findings may assist us in understanding the effect of osteoporosis on the vibration characteristics of lumbar spine fusion and provide references to clinical treatments for lumbar interbody fusion and lumbar vertebrae osteoporosis.

5.
Cell Stem Cell ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33010822

RESUMO

Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.

6.
Neurobiol Dis ; : 105139, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065280

RESUMO

The blossoming field of epitranscriptomics has recently garnered attention across many fields by findings that chemical modifications on RNA have immense biological consequences. Methylation of nucleotides in RNA, including N6-methyladenosine (m6A), 2-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), and 5-methylcytosine (m5C) and isomerization of uracil to pseudouridine (Ψ), have the potential to alter RNA processing events and contribute to developmental processes and different diseases. Though the abundance and roles of some RNA modifications remain contentious, the epitranscriptome is thought to be especially relevant in stem cell biology and neurobiology. In particular, m6A occurs at the highest levels in the brain and plays major roles in embryonic stem cell differentiation, brain development, and neurodevelopmental disorders. However, studies in these areas have reported conflicting results on epitranscriptomic regulation of stem cell pluripotency and mechanisms in neural development. In this review we provide an overview of the current understanding of several RNA modifications and disentangle the various findings on epitranscriptomic regulation of stem cell biology and neural development.

7.
J Hazard Mater ; 398: 122869, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33027880

RESUMO

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33048598

RESUMO

Here, we report a chromosome-level genome assembly of Talaromyces rugulosus (Syn. Penicillium rugulosum) strain W13939 (6 chromosomes; contig N50: 5.90Mb), generated using a combination of PacBio long-read and Illumina paired end data. T. rugulosus is not only a potent enzyme producer, but also a mycoparasite of Aspergillus flavus which is a notorious plant pathogen and mycotoxin producer, making it a promising bio-control agent. T. rugulosus genome is rich in genes encoding proteases, carbohydrate-active enzymes, fungal cell wall degrading enzymes, lectin and secondary metabolite biosynthetic enzymes, reflecting its mycoparasitic life style and mycotoxingenic capability. This high-quality assembly of the T. rugulosus genome will be a valuable resource to assist us in the understanding of molecular basis of mycoparasitism and facilitate the agricultural and biotechnological applications of Talaromyces.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1625-1630, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067964

RESUMO

OBJECTIVE: To investigate the expression level and the clinical significance of serum interleukin-6(IL-6) , IL-10, tumor necrosis factor α(TNF-α) and ß2-microglobulin(ß2-MG) in multiple myeloma(MM) patients with different blood separation results. METHODS: The clinical data of 124 newly diagnosed MM patients (76 cases of IgG type, 48 cases of IgA type) treated in our hospital from October 2015 to October 2019 were enrolled and analyzed. The blood samples were divided into control group (the order from top to bottom is serum, separator gel and red blood cells) and abnormal group (the order from top to bottom is serum, red blood cells, separator gel and red blood cells) according to the blood separation result. The differences of expression level in serum IL-6, IL-10, TNF-α and ß2-MG were compared between the two groups, and the changes of blood separation result and different indexes were analyzed after treatment. RESULTS: Abnormal separation results were found in 21 cases (16.94%), including 13 cases of IgG type and 8 cases of IgA type. The levels of serum IL-6, IL-10, TNF-α and ß2-MG in abnormal group were significantly higher than those in control group (P<0.05) . After treatment, 85 patients in control group (103 cases) achieved complete remission (CR) or very good partial remission (VGPR) and partial remission(PR). The results of blood separation showed no change. 18 patients achieved less than PR, and the separation result in 5 patients changed from normal to abnormal separation. The blood separation of 9 patients with CR and VGPR in abnormal group (21 cases) were changed from abnormal to normal. 8 patients achieved PR, and the separation result in 6 patients were changed from abnormal to normal and 2 cases showed no change, while the blood separation showed no changes in 4 cases MM patients who achieved less than PR in abnormal group. The expression levels of IL-6, IL-10, TNF-α and ß2-MG of patients in control group transformed to abnormal blood separation result after treatment showed significantly higher than those before treatment (P<0.05) , and the levels of IL-6 and ß2-MG were significantly lower in the patients with out change in blood separation results than those before treatment (P<0.05). The serum levels of IL-6, IL-10, TNF-α and ß2-MG of patients in abnormal group transformed to normal blood separation after treatment were significantly lower than those before treatment (P<0.05), and the serum levels of IL-6, IL-10, TNF-α and ß2-MG in abnormal group with no changes in blood separation results showed not significantly different from those before treatment (P>0.05). CONCLUSION: Abnormal separation phenomenon can be found after centrifugation in patients with multiple myeloma. The expression levels of serum IL-6, IL-10, TNF-α and ß2-MG in MM patients with different blood separation results are different, which suggesting different degrees of tumor burden. The changes of blood separation result and levels of IL-6, IL-10, TNF-α and ß2-MG after treatment can predict the therapeutic effect, and also provide the experimental basis for the evaluation of disease condition and prognosis of patients with different blood separation results.

10.
Front Immunol ; 11: 575818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072119

RESUMO

Pigs have anatomical and physiological characteristics comparable to those in humans and, therefore, are a favorable model for immune function research. Interferons (IFNs) and inflammasomes have essential roles in the innate immune system. Here, we report that G10, a human-specific agonist of stimulator of interferon genes (STING), activates both type I IFN and the canonical NLRP3 inflammasome in a STING-dependent manner in porcine cells. Without a priming signal, G10 alone transcriptionally stimulated Sp1-dependent p65 expression, thus triggering activation of the nuclear factor-κB (NF-κB) signaling pathway and thereby priming inflammasome activation. G10 was also found to induce potassium efflux- and NLRP3/ASC/Caspase-1-dependent secretion of IL-1ß and IL-18. Pharmacological and genetic inhibition of NLRP3 inflammasomes increased G10-induced type I IFN expression, thereby preventing virus infection, suggesting negative regulation of the NLRP3 inflammasome in the IFN response in the context of STING-mediated innate immune activation. Overall, our findings reveal a new mechanism through which G10 activates the NLRP3 inflammasome in porcine cells and provide new insights into STING-mediated innate immunity in pigs compared with humans.

11.
Quant Biol ; : 1-7, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32923014

RESUMO

Background: Various models have been applied to predict the trend of the epidemic since the outbreak of COVID-19. Methods: In this study, we designed a dynamic graph model, not for precisely predicting the number of infected cases, but for a glance of the dynamics under a public epidemic emergency situation and of different contributing factors. Results: We demonstrated the impact of asymptomatic transmission in this outbreak and showed the effectiveness of city lockdown to halt virus spread within a city. We further illustrated that sudden emergence of a large number of cases could overwhelm the city medical system, and external medical aids are critical to not only containing the further spread of the virus but also reducing fatality. Conclusion: Our model simulation showed that highly populated modern cities are particularly vulnerable and lessons learned in China could facilitate other countries to plan the proactive and decisive actions. We shall pay close attention to the asymptomatic transmission being suggested by rapidly accumulating evidence as dramatic changes in quarantine protocol are required to contain SARS-CoV-2 from spreading globally. Supplementary Materials: The supplementary materials can be found online with this article at 10.1007/s40484-020-0215-4.

12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(4): 474-479, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32985161

RESUMO

OBJECTIVE: To investigate the psychological and behavior status of minor children of medical staff in Hubei province during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: A cross-sectional questionnaire survey was conducted through WeChat from March 13 to 15, 2020, which included a general data questionnaire and Conners parental assessment questionnaire (PSQ). The questionnaires received from outside of Hubei province were excluded through IP address, and the questionnaires with answer time <150 s were also excluded. The influence of parental work status on the psychological behavior was analyzed in children of different age groups. RESULTS: A total of 391 valid questionnaires were collected, there were 207 males (52.9%) and 184 females (47.1%); 91 (23.3%) aged 3 to 6, 183 (46.8%) aged 6 to 10, and 117 (29.9%) aged 10 to 16. Both parents were medical staff in 87 participants(22.3%), one parent was medical staff in 139(35.5%) participants, and no parents were medical staff in 165 (42.2%) participants. In 3-<6 years group, there was no significant difference in the PSQ scores of the children in each factor level (all P>0.05) between children with parents as medical staff and those without. In 6-<10 years group, children with both parents as medical staff had higher hyperactivity-impulse factor score, learning problem factor score and total score than those without parents as medical staff (all P<0.05), while they had higher learning problem factor score than those with one parent as medical staff (P<0.05); the anxiety score of children with one or both parents as medical staff was higher than that of those without parents as medical staff (all P<0.05). In 10 to 16 years group, the behavior problems, learning problems, hyperactivity-impulse, more dynamic index and the total score in children with one parent as medical staff were lower than those with both parents as medical staff or without parents as medical staff (P<0.05 or P<0.01); while there were no significant differences in psychosomatic problems, anxiety factor scores between children with one parent as medical staff and other two groups (all P>0.05). CONCLUSIONS: s During COVID-19 epidemic period, the psychological and behavior status of minor children of Hubei medical staff with different ages shows differences with those without parents as medical staff, particularly in 6-<10 years and 10 to 16 year groups. It is necessary to pay attention to the psychological and behavioral status of children of medical staff in these age groups.


Assuntos
Infecções por Coronavirus , Coronavirus , Corpo Clínico , Saúde Mental , Pandemias , Pneumonia Viral , Adolescente , Betacoronavirus , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Corpo Clínico/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Inquéritos e Questionários
13.
BMC Psychiatry ; 20(1): 472, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993575

RESUMO

BACKGROUND: Since the 1990s, families from the ecologically hostile mountainous southern areas of Ningxia Province, China, have been migrating to the northern areas of the province. This study compared the prevalence of behavioral problems among migrant adolescents to those among host adolescents (adolescents from the northern areas) and adolescents in the region of origin (adolescents from the southern areas), to determine whether ecological migration is related to adolescent behavioral problems, and possible changes in such problems over time. METHODS: We used the Children and Adolescents Ecological Migration Survey on Mental Health, administered to 4805 students aged 12-16 years and their parents between 2012 and 2014 (W1), of whom 1753 students and their parents completed the follow-up between 2014 and 2017 (W2). Parents answered questions related to adolescent behavioral problems, main source of family income, parents' desire to reverse migrate, improved standard of living, and parents' educational attainment, while children completed the Eysenck Personality Questionnaire and a classroom environment questionnaire. RESULTS: The prevalence of behavioral problems among the migrant adolescents (28.04%) was significantly higher than among host adolescents (21.59%) or adolescents in the region of origin (24.37%; p < 0.001) at W1. After adjusting for gender and age, parents' work outside the home was the main source of family income (OR = 1.42, 95% CI = 1.13-1.78), and adolescents' learning burden (OR = 1.04, 95% CI = 1.01-1.06) in school negatively influenced behavioral problems. Strong student-teacher relationships (OR = 0.97,95% CI = 0.94-0.99) and parents who had no intention to move back to the original residence (OR = 0.70, 95% CI = 0.52-0.94) exerted a protective effect at W1; at W2, a protective effect was associated with improved living conditions (OR = 0.39-0.55, 95% CI = 0.25-0.84). The extent of behavioral problems among migrant adolescents significantly decreased after two years. CONCLUSION: Ecological migration will increase children's behavioral problems in the early stage, with various factors influencing the extent of these problems.

14.
Surg Innov ; : 1553350620958265, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909910

RESUMO

Objective. To compare the clinical efficacies of mediastinoscope-assisted and thoracoscope-assisted esophagectomy. Materials and Methods. Seventy-six patients with esophageal cancer who underwent minimally invasive esophagectomy at the General Hospital of Ningxia Medical University between June 2015 and January 2019 were retrospectively evaluated. Among them, 28 patients underwent mediastinoscope-assisted transhiatal esophagectomy (MATHE), and 48 received thoracoscope-assisted transthoracic esophagectomy (TATTE). The perioperative clinical data and follow-up data of the 2 groups were compared. Results. All operations were successful in both groups. MATHE was favorable in terms of operation time, intraoperative blood loss, drainage volume 3 days after surgery, postoperative hospital stay, and hypoproteinemia (P < .05). Lymph node dissections were less than those in the TATTE (P < .05). No significant differences in long-term postoperative complications and survival rate were found between the 2 groups (P > .05). Conclusion. MATHE has the advantages of minimal trauma, shorter operation time, less intraoperative blood loss, and faster recovery. More adequate tumor clearance in terms of lymph node dissection can be achieved with TATTE. However, the comparison of survival rates between the 2 groups is similar.

15.
Brain Behav ; : e01824, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902155

RESUMO

INTRODUCTION: Parkinson's disease (PD) is a common degenerative disease of the central nervous system (CNS). The main pathological change is the apoptosis of dopaminergic neurons in the substantia nigra pars compacta (SNPc), thereby leading to dopamine reduction in nigral striatum. 6-Hydroxydopamine (6-OHDA), a neurotoxic substance, mediates apoptosis of dopaminergic neurons and causes Parkinson-like symptoms in mice. METHODS: Our team previously found that Antrodia camphorata polysaccharide (ACP) exerted a good behavioral improvement effect on the PD mouse model established by 6-OHDA; however, the mechanism remains unknown. Therefore, in this study, we focused on ROS-NLRP3 signal to investigate the mechanism of 6-OHDA-induced apoptosis of dopaminergic neurons MES23.5 and the protective effects of ACP on dopaminergic neurons. RESULT: 6-OHDA could further activate the expression of inflammasome NLRP3 by inducing ROS, thereby resulting in apoptosis of MES23.5 cells. ACP could inhibit the expression of ROS-NLRP3 induced by 6-OHDA, exerting a protective role in MES23.5 cells. Animal experiments also confirmed that ACP intervention could reduce the activation level of ROS-NLRP3 in the substantia nigra-striatum and improve the exercise capacity of PD mice. CONCLUSION: Our study validated that 6-OHDA could induce apoptosis of dopaminergic neurons via ROS-NLRP3 activation. ACP could inhibit this signal and protect dopaminergic neurons, which might be promising in research of PD therapeutics.

16.
J Sci Food Agric ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894778

RESUMO

BACKGROUND: The fruiting body of Pleurotus tuoliensis deteriorates rapidly after harvest, causing a decline in its commercial value and a great reduction in its shelf life. According to the present research, carbohydrate-active enzymes (CAZymes) may cause the softening, liquefaction and autolysis of mature mushrooms after harvest. To further understand the in vivo molecular mechanism of CAZymes affecting the postharvest quality of P. tuoliensis fruiting bodies, a tandem mass tags labelling combined liquid chromatography-tandem mass spectrometry (TMT-MS/MS) proteomic analysis was performed on P. tuoliensis fruiting bodies during storage at 25 °C. RESULTS: A total of 4737 proteins were identified, which had at least one unique peptide and had a confidence level above 95%. Consequently, 1307 differentially expressed proteins (DEPs) were recruited using the criteria of abundance fold change (FC) >1.5 or < 0.67 and P < 0.05. The identified proteins were annotated by dbCAN2, a meta server for automated CAZymes annotation. Subsequently, 222 CAZymes were obtained. Several CAZymes participating in the cell wall degradation process, including ß-glucosidase, glucan 1,3-ß-glucosidase, endo-1,3(4)-ß-glucanase and chitinases, were significantly upregulated during storage. The protein expression level of CAZymes, such as xylanase, amylase and glucoamylase, were upregulated significantly, which may participate in the P. tuoliensis polysaccharide degradation. CONCLUSIONS: The identified CAZymes degraded the polysaccharides and lignin, destroying the cell wall structure, preventing cell wall remodeling, causing a loss of nutrients and the browning phenomenon, accelerating the deterioration of P. tuoliensis fruiting body. © 2020 Society of Chemical Industry.

17.
Biomed Pharmacother ; 131: 110724, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920518

RESUMO

Stachydrine is a main active component of Leonurus japonicus (Chinese motherwort), which has traditionally been used to promote postpartum recovery and alleviate myocardial and cerebral ischemic injuries due to its pro-angiogenic effect. Our prior study demonstrated that stachydrine increased angiogenesis in zebrafish embryos, but its pro-angiogenic effect and underlying mechanisms on human umbilical vein endothelial cells (HUVECs) remain largely unknown. In the present study, we further investigated the role of stachydrine in sunitinib-injured HUVECs and its potential molecular mechanisms. The results showed that stachydrine exhibited a protective effect on sunitinib-injured HUVECs and significantly promoted their proliferation, migration, and tube formation, all central events of angiogenesis. In addition, stachydrine inhibited apoptosis and ROS production in sunitinib-injured HUVECs. Furthermore, our findings illustrated for the first time that stachydrine's molecular mechanisms for promoting angiogenesis might correlate with activation of the VEGFR2/MEK/ERK and inhibition of the mitochondrial-mediated apoptosis signaling pathway.

19.
Oxid Med Cell Longev ; 2020: 6092715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908633

RESUMO

To explore whether epigallocatechin-3-gallate (EGCG) improves renal damage in diabetic db/db mice and high-glucose- (HG-) induced injury in HK-2 cells by regulating the level of Klotho gene promoter methylation. Western blotting was used to detect the protein expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, DNMT3b, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Klotho. The methylation level of the Klotho gene promoter was detected by pyrosequencing. Chromatin immunoprecipitation was used to detect the binding of the Klotho gene promoter to DNMT1 and DNMT3a. The expression of oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)) in kidney homogenates was also measured using ELISA. Klotho and DNMT3b protein expression was upregulated, while DNMT1, DNMT3a, TGF-ß1, and α-SMA protein expression was downregulated after EGCG treatment. EGCG treatment also reduced the methylation level of the Klotho gene promoter as well as the binding of DNMT3a to the Klotho gene promoter. In addition, EGCG treatment significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1ß, IL-6, and TNF-α and increased the levels of CAT and SOD. Under HG conditions, EGCG regulated Klotho gene promoter methylation via DNMT3a and decreased the methylation level of the Klotho gene promoter, thereby upregulating the expression of the Klotho protein to exert its protective effect.

20.
Med Biol Eng Comput ; 58(11): 2725-2736, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32880092

RESUMO

Clinical studies have extensively shown that burst fractures can cause severe and long-term neurological deficits. However, the mechanism of burst fracture is not clear, and the influence of different spinal postures on burst fracture is still unidentified. The study aimed at investigating the influence of different postures under vertical impact load on thoracolumbar burst fracture. A detailed nonlinear finite element model of T12-L2 segment was developed to investigate these problems. In this work, a rigid ball was used to vertically impact the finite element spinal segment, which emulated the process of burst fracture as in experimental condition. During the process, amounting to 9 different postures (normal, flexion, extension, right/left lateral bending of 8°, right/left axial rotation of 4° and 8°) were studied. Totally five failure modes were observed. Six different parameters, including vertebral height, vertebral bulge, interpedicular widening, vertebral kyphotic angle, posterior vertebral body angle, and joint facet contact force, were observed to evaluate the corresponding severity of burst fracture. Burst fracture in extension was the severest, and the loss of vertebral height in flexion was the most. The different postures in these simulations changed the morphology of intervertebral disc and facet joints force, resulting in different types of fracture.

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