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1.
iScience ; 23(3): 100952, 2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32179476

RESUMEN

It has been well documented that the ER responds to cellular stresses through the unfolded protein response (UPR), but it is unknown how the Golgi responds to similar stresses. In this study, we treated HeLa cells with ER stress inducers, thapsigargin (TG), tunicamycin (Tm), and dithiothreitol (DTT), and found that only TG treatment resulted in Golgi fragmentation. TG induced Golgi fragmentation at a low dose and short time when UPR was undetectable, indicating that Golgi fragmentation occurs independently of ER stress. Further experiments demonstrated that TG induces Golgi fragmentation through elevating intracellular Ca2+ and protein kinase Cα (PKCα) activity, which phosphorylates the Golgi stacking protein GRASP55. Significantly, activation of PKCα with other activating or inflammatory agents, including phorbol 12-myristate 13-acetate and histamine, modulates Golgi structure in a similar fashion. Hence, our study revealed a novel mechanism through which increased cytosolic Ca2+ modulates Golgi structure and function.

2.
Artículo en Inglés | MEDLINE | ID: mdl-32186840

RESUMEN

Fullerenes are known as highly efficient scavengers for reactive oxygen species (ROSs). In this study, a carnosine-modified fullerene derivative (C60-Car) was synthesized via a one-step nucleophilic addition reaction. C60-Car forms nanoparticles (NPs) readily in water at neutral pH and room temperature through self-assembly. The C60-Car NPs were found to possess good water solubility, biocompatibility, and excellent ROSs scavenging capability. The scavenging efficiency of ROSs is as high as 92.49% and significantly better than that of hydroxyfullerene (C60-OH NPs, 70.92%) and l-carnosine. Furthermore, C60-Car NPs showed strong cytoprotective ability against H2O2-induced damage to the normal human fetal hepatocyte cells (L-02) and human epidermal keratinocytes-adult (HEK-a) cells at a lower concentration of 2.5 µM. In contrast, C60-OH NPs showed a minor cytoprotective effect on cells at a high concentration of 10 µM. The excellent properties of such a fullerene derivative, C60-Car, can be attributed largely to the involvement of l-carnosine with biological activity and antioxidant property, which make it better for biomedicine, and it may provide a new strategy for mitigating acute oxidative stress based on fullerene materials.

3.
Zhen Ci Yan Jiu ; 45(3): 255-9, 2020 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-32202720

RESUMEN

The literature of experimental research on diet-induced obesity treated with acupuncture was retrieved. The aspects of epigenetics, neuroendocrine system, intestinal flora, inflammatory response, oxidative stress and substance metabolism of the mechanism of acupuncture in the treatment of diet-induced obesity were summarized. It is suggested that the potential mechanism of acupuncture in the treatment of diet-induced obesity should be discussed in the aspects of the interaction of Toll-like receptors on obesity-intestinal flora-immune function, the improvement of insulin resistance, epigenetics and antioxidant stress.

4.
Eur J Radiol ; 126: 108968, 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-32203827

RESUMEN

PURPOSE: Carbon monoxide (CO) intoxication causes gray matter (GM) changes and headache symptom in patients with CO intoxication, but the headache-associated GM changes are not well understood. The purpose of this study was to perform a voxel-based morphometry (VBM) analysis to investigate longitudinal GM changes of brain pain matrix in patients with CO intoxication. METHODS: This prospective study enrolled 24 patients with CO intoxication and 20 healthy controls. Whole brain high-resolution T1-weighted images were acquired in both groups and were repeated in patients at 1 week, and 1, 3, and 9 months after CO exposure. VBM was performed to detect global GM changes in patients with CO intoxication, and the automated anatomical labeling template was utilized to estimate the distribution of significant GM clusters in the brain. RESULTS: GM volumes were significantly decreased mainly in the frontal and occipital lobes, including several pain-matrix regions 1 week after CO intoxication. The regions with significant GM changes further involved the central GM structures and the periaqueductal gray (pain-modulating center) at 1 and 3 months after CO intoxication, but the alterations were partially normalized in the frontal lobe and cerebellum 9 months after CO intoxication. Significant negative correlations were revealed between GM volume and duration of coma in the pain matrix regions. Moreover, five patients exhibited delayed neuropsychiatric sequelae (DNS) and had greater GM volume changes than non-DNS patients. CONCLUSION: VBM analysis is helpful to understand the longitudinal GM changes of the pain matrix in patients with CO intoxication.

6.
J Hazard Mater ; 393: 122365, 2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-32120211

RESUMEN

In the present work, a pulse-modulated high-frequency (HF) dielectric barrier discharge (DBD) plasma has been employed and utilized to evaluate the feasibility of toluene degradation in a multistage rod-type reactor at room temperature. Experimental result indicates that the energy consumption is significantly reduced and heating effect can be effectively suppressed when the DBD plasma is ignited in pulse-modulated mode instead of continuous mode. The response surface methodology (RSM) based on central composite design (CCD) model has been proposed to evaluate the contribution of key operating parameters including duty cycle and modulation frequency. The proposed model offers a good fit for actal data. The contribution of the modulation frequency is observed to be more dominant compared to the duty cycle for both the degradation efficiency and the energy yield. According to the results provided by the proposed model, the toluene degradation efficiency of 62.9 % and the energy yield of 0.90 g/kWh are obtained under the optimal conditions of 400 Hz modulation frequency and 56 % duty cycle. The effect of initial toluene concentration and gas flow rate have also been investigated. Increasing toluene initial concentration and gas flow rate are found to be unfavorable for the degradation of toluene, however, which are of benefit to the energy yield. A long-time experiment to assess the stability of pulse-modulated DBD has been successful performed. The possible pathways in plasma degradation of toluene is proposed based on the intermediates identification using GC-MS and FTIR.

7.
Environ Pollut ; 262: 114188, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32126435

RESUMEN

Frequent heavy aerosol pollution occurs during the winter heating season in northern China. Here, we characterized the airborne bacterial community structure and concentration, during typical pollution episodes that occurred during the winter heating season of 2017-2018 in Jinan and Weihai. During this heating season, five and four heavy pollution episodes were observed in Jinan and Weihai, respectively. Compared with December and January, pollution episodes in March were significantly affected by sand dust events. Higher Bacillales were identified in the March samples from Jinan, indicating that sand dust influences bacterial communities. During similar pollution episodes, air pollution in the coastal city of Weihai was lower than the inland city of Jinan. The predominant bacteria included Staphylococcus, Cyanobacteria, Lactobacillus, Deinococcus, Enbydrobacter, Ralstonia, Bacillus, Comamonas, and Sphingomonas. These predominant bacteria are mainly from Proteobacteria, Firmicutes, Cyanobacteria, Actinobacteria, and Bacteroidetes phyla. Bacterial concentration showed significant variation with increased airborne pollutants. The highest concentration appeared during moderate pollution (up to 106 cells/m3), whereas bacterial concentration decreased during heavy and severe pollution (105 cells/m3), which may be related to toxic effects of high pollutant concentrations during heavy or severe pollution. Community structure variation indicated that Cyanobacterial genera were dominant in clean or slight pollution. With increased PM2.5, Staphylococcus increased and became the most abundant bacteria in moderate pollution (up to 40%). During heavy or severe pollution, bacteria that are adaptable to harsh or extreme environments predominate, such as Deinococcus and Bacillus. In the assessment of health risks from air pollution, the bioaerosols risks must consider. Additionally, although most microbial genera are similar between the two cities, there are important differences associated with pollution level. During air pollution regulation in different regions with varied geographical and climatic conditions, bioaerosol pollution difference is an unignored factor.

8.
J Hazard Mater ; 393: 122398, 2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32131037

RESUMEN

The simultaneously efficient removal of cationic and anionic radionuclides is an important and challenging topic for nuclear waste remediation as well as environmental protection. Herein, monoclinic ZIF-8 nanosheets modified with ethyleneimine polymer (denoted as ZIF-8/PEI) was achieved and used to determine the capture behaviors of both U(VI) oxycations and Re(VII) oxyanions from aqueous solution. ZIF-8/PEI assemblies showed a maximum U(VI) and Re(VII) uptake capacity of 665.3 (pH 5.0) and 358.2 mg/g (pH 3.5), respectively. Experimental, spectroscopic and theoretical calculation results directly unraveled that U(VI) adsorption onto ZIF-8/PEI assemblies was mainly ascribed to the coordination with abundant amino groups and weakly due to the Zn terminal hydroxyl groups, while anion exchange mechanism contributed predominantly to the Re(VII) sequestration. This work not only sheds light on the interaction mechanisms of simultaneous capture of U(VI) and Re(VII) but also highlights the versatile material design of cationic and anionic radionuclide immobilization in radioactive wastewater remediation.

9.
Stroke ; 51(4): 1248-1256, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32151234

RESUMEN

Background and Purpose- The observation that smokers with stroke could have better outcome than nonsmokers led to the term "smoking paradox." The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods- Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994-2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results- A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions- "The more you smoke, the earlier you stroke, and the longer sufferings you have to cope." Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.

10.
Psychiatry Res ; 287: 112907, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32179210

RESUMEN

New methods for using ketamine in patients with propofol-electroconvulsive therapy-resistant depression (ECT-RD) are needed in the clinic. This study aimed to investigate the therapeutic efficacy of ketamine plus ECT in ECT-RD patients, along with the treatment-induced brain alterations. A total of 28 ECT-RD patients were intravenously injected with ketamine six times and treated with propofol-ECT six times alternately within two weeks. The Hamilton Depression Scale was used to assess the treatment effect. Global functional connectivity density (gFCD) and functional connectivity strength (FCS) were used to evaluate functional brain alterations. As compared with the propofol-ECT treatment group, the addition of ketamine could improve the therapeutic outcomes in patients with ECT-RD. The treatment increased gFCD in the left temporal and subgenual anterior cingulated cortex. Simultaneously, the treatment decreased FCS within the default mode network. Although increased functional connectivity could be sustained for 10 days, the clinical effect was only sustained 7 days, indicating that the clinical effect and functional brain alterations were disjointed. Ketamine plus propofol-ECT can obviously improve the effects of propofol-ECT in ECT-RD patients. However, the effect is limited in 7 days, suggesting the benefit is short-term.

11.
Arthritis Res Ther ; 22(1): 57, 2020 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32209130

RESUMEN

Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear "start point" for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

12.
Cell Rep ; 30(12): 4152-4164.e6, 2020 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32209475

RESUMEN

Histone methyl groups can be removed by demethylases. Although LSD1 and JmjC domain-containing proteins have been identified as histone demethylases, enzymes for many histone methylation states or sites are still unknown. Here, we perform a screening of a cDNA library containing 2,500 nuclear proteins and identify hHR23A as a histone H4K20 demethylase. Overexpression of hHR23A reduces the levels of H4K20me1/2/3 in cells. In vitro, hHR23A specifically demethylates H4K20me1/2/3 and generates formaldehyde. The enzymatic activity requires Fe(II) and α-ketoglutarate as cofactors and the UBA domains of hHR23A. hHR23B, a protein homologous to hHR23A, also demethylates H4K20me1/2/3 in vitro and in vivo. We further demonstrate that hHR23A/B activate the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3. Nuclear magnetic resonance (NMR) analyses demonstrate that an HxxxE motif in the UBA1 domain is crucial for iron binding and demethylase activity. Thus, we identify two hHR23 proteins as histone demethylases.

13.
Sci Rep ; 10(1): 5297, 2020 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32210249

RESUMEN

Removal of hexavalent chromium [Cr(VI)] from soils and water has been widely studied for its high toxicity. Although leaching method is viewed as an effective approach to eliminate Cr(VI) and some studies attempted to enhance leaching performance via the external electric field, there is little knowledge about the influential factor in electro-leaching system on Cr(VI) removal performance. In this study, an electro-leaching technology was developed for removing Cr(VI) from groundwater aquifer to comprehensively discuss the correlation between the operational parameters and Cr(VI) removal efficiency. When the applied voltage was 20 V and the initial Cr(VI) concentration was 40 mg/kg, Cr(VI) removal efficiency achieved 99.9% in 120 min in the electro-leaching system, 15% higher than the system without the electric field. Cr(VI) removal efficiencies increased with the voltage demonstrating the significant enhancement of the electro-leaching method in removing Cr(VI). When Cr(VI) concentration climbed to 120 mg/kg, Cr(VI) removal efficiency remained above 85%. The effects of different voltages, Cr(VI) concentrations, pollutant distribution and salt content of leaching solution on the leaching effect were also investigated. Meanwhile, the relationship between the current intensity change and the amount of removed Cr(VI) during the electro-leaching process was first investigated, and the relevant model was fitted. There is a quadratic linear correlation between the amount of current change and the amount of removed Cr(VI). This novel electro-enhanced leaching method can effectively remove Cr(VI) from contaminated groundwater aquifer by enhancing the migration of charged contaminant ions during the leaching process, and it is worthy of further study of heavy metal remediation.

14.
Int J Med Sci ; 17(5): 577-590, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32210707

RESUMEN

Confocal Raman microspectral imaging was adopted to elucidate the cellular drug responses of osteosarcoma cells (OC) to N-[N-(3, 5-difluorophenyl acetyl)-L-alanyl]-sphenylglycine butyl ester (DAPT), a γ-secretase inhibitor, by identifying the drug induced subcellular compositional and structural changes. Methods: Spectral information were acquired from cultured osteosarcoma cells treated with 0 (Untreated Group, UT), 10 (10 µM DAPT treated, 10T), 20 µM (20 µM DAPT treated, 20T) DAPT for 24 hours. A one-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple test were sequentially applied to address spectral features among three groups. Multivariate algorithms such as K-means clustering analysis (KCA) and Principal component analysis (PCA) were used to highlight the structural and compositional differences, while, univariate imaging was applied to illustrate the distribution pattern of certain cellular components after drug treatment. Results: Major biochemical changes in DAPT-induced apoptosis came from changes in the content and structure of proteins, lipids, and nucleic acids. By adopted multivariate algorithms, the drug induced cellular changes was identified by the morphology and spectral characteristics between untreated cells and treated cells, testified that DAPT mainly acted in the nuclear region. With the increase of the drug concentration, the content of main subcellular compositions, such nucleic acid, protein, and lipid decreased. In an addition, DAPT-induced nuclear fragmentation and apoptosis was depicted by the univariate Raman image of major cellular components (nucleic acids, proteins and lipids). Conclusions: The achieved Raman spectral and imaging results illustrated detailed DAPT-induced subcellular compositional and structural variations as a function of drug dose. Such observations can not only explain drug therapeutic mechanisms of OC DAPT treatment, and also provide new insights for accessing the medicine curative efficacy and predicting prognosis.

15.
Medicine (Baltimore) ; 99(11): e19479, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176080

RESUMEN

OBJECTIVE: To systematically review the effect of recombinant human brain natriuretic peptide (rhBNP) on the cardiac function in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: PubMed, Web of Science, the Cochrane Library, Chinese Biomedical Database (CBD), and China National Knowledge Infrastructure (CNKI) were electronically searched to collect randomized controlled trials (RCTs) of traditional exercise for patients with AMI undergoing PCI from the beginning of the database inception to January 2019. Two reviewers independently screened the literature, extracted data, and evaluated the quality of included studies. Then, meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 16 RCTs and 1551 patients were included. The results of the meta-analysis showed that, compared with the control-treated patients, rhBNP-treated patients with AMI had an increased left ventricular ejection fraction (LVEF) of 3.34% ([MD = 3.34, 95% CI (0.39,6.29), P = .03]) 1 week postoperatively, 6.22% ([MD = 6.22, 95% CI (4.15,8.28), P < .00001]) 4 weeks postoperatively, 7.34% ([mean difference (MD) = 7.34, 95% CI (4.52, 10.16), P < .00001]) 12 weeks postoperatively, and 5.32% ([MD = 5.32, 95% CI (3.05, 7.59), P < .00001]) 24 weeks postoperatively. Moreover, the heart failure (HF) recurrence of rhBNP-treated patients with AMI 12 weeks postoperatively was 0.24 times that of the control-treated patients ([risk ratio (RR) = 0.24, 95% CI (0.06, 0.92), P = .04]), and the difference was statistically significant. At the same time, rhBNP-treated patients had decreased N-terminal pro-brain natriuretic peptide (NT-proBNP) (24 hours, 48 hours, 72 hours) and aldosterone (Ald) (24 hours, 72 hours, 168 hours) levels in comparison with the control-treated patients. CONCLUSION: Current evidence shows that the application of rhBNP presents a greater clinical benefit to patients with AMI undergoing PCI. Due to the methodological bias in the included studies and small sample size, more high-quality studies are required to verify the study findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42019126727).


Asunto(s)
Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Péptido Natriurético Encefálico/uso terapéutico , Intervención Coronaria Percutánea , Proteínas Recombinantes/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Sci Rep ; 10(1): 4783, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32179848

RESUMEN

Epigallocatechin-3-gallate (EGCG), a main active catechin in green tea, was reported to attenuate renal injury and hypertension. However, its effects on salt-induced hypertension and renal injury remain unclear. In the present study, we explored its effects on hypertension and renal damage in Dahl rats with salt-sensitive hypertension. We found that EGCG could lower blood pressure after 6 weeks of oral administration, reduce 24 h urine protein levels and decrease creatinine clearance, and attenuate renal fibrosis, indicating that it could attenuate hypertension by protecting against renal damage. Furthermore, we studied the renal protective mechanisms of EGCG, revealing that it could lower malondialdehyde levels, reduce the numbers of infiltrated macrophages and T cells, and induce the apoptosis of NRK-49F cells. Considering that the 67 kD laminin receptor (67LR) binds to EGCG, its role in EGCG-induced fibroblast apoptosis was also investigated. The results showed that an anti-67LR antibody partially abrogated the apoptosis-inducing effects of EGCG on NRK-49F cells. In summary, EGCG may attenuate renal damage and salt-sensitive hypertension via exerting anti-oxidant, anti-inflammatory, and apoptosis-inducing effects on fibroblasts; the last effect is partially mediated by 67LR, suggesting that EGCG represents a potential strategy for treating salt-sensitive hypertension.

17.
BMC Surg ; 20(1): 50, 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32183778

RESUMEN

BACKGROUND: Many options exist for the management of cholelithiasis and secondary choledocholithiasis. Among them, laparoscopic common bile duct exploration (LCBDE) with choledocotomy followed by laparoscopic cholecystectomy has gained popularity. However, efforts should be made to ensure minimally invasive or noninvasive management of the common bile duct (CBD). The purpose of this study was to explore the clinical experience of non-invasive surgical modality, i.e., laparoscopic transcystic dilation of the cystic duct confluence in CBD exploration (LTD-CBDE), including feasibility, safety, adverse events, and incidence. METHODS: In this retrospective analysis, 68 patients were offered the LTD-CBDE technique from December 2015 to April 2018 based on patient's own intention. During the surgery, the cystic duct confluence was dilated with separation forceps and/or a columnar dilation balloon. Subsequently, CBD exploration and stone extraction were performed with a choledochoscope. The entrance of the CBD was covered with a cystic duct stump wall and was subjected to primary closure at the end of surgery. RESULTS: Forty-nine females and 19 males with cholelithiasis and secondary choledocholithiasis were included. The mean age was 53 years old (18 to 72 year). Of these patients, 62 (91.2%) were successfully treated with the LTD-CBDE technique, and bile leakage was observed in 3 patients (4.4%). The mean operation time was 106 min, and the mean hospital stay was 5.9 days. Among the other 6 patients, 3 were converted to open cholecystectomy due to severe fibrosis, unclear anatomical structure at Calot's triangle (n = 2) or Mirizze syndrome (n = 1); LCBDE was performed in 3 patients due to cystic duct atresia (n = 2) and low level of flow from the gallbladder duct into the CBD (n = 1). These patients had a smooth postoperative course. In total, 43/68 of the patients presented no radiological evidence of retained CBD stones at the postoperative follow-up (40 patients treated with LTD-CBDE) 1 year later. CONCLUSIONS: The current work suggests that LTD-CBDE for the management of cholelithiasis and secondary choledocholithiasis is a feasible, safe and effective technique with a low complication rate. LTD-CBDE offers another alternative for surgeons to treat patients in similar scenarios. However, additional randomized, controlled studies are needed to demonstrate its efficacy, safety, and impact on CBD stenosis.

18.
Med Sci Monit ; 26: e920520, 2020 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-32188838

RESUMEN

BACKGROUND Freshly isolated mouse embryonic fibroblasts (MEFs) have great proliferation capacity but quickly enter senescent state after several rounds of cell cycle, a process called premature senescence. Cellular senescence can be induced by various stresses such as telomere erosion, DNA damage, and oncogenic signaling. But the contribution of other molecules, such as growth factors, to cellular senescence is incompletely understood. This study aimed to compare the gene expression difference between non-senescent and senescent MEFs to identify the key molecule(s) involved in the spontaneous senescence of MEFs. MATERIAL AND METHODS Primary MEFs were isolated from E12.5 pregnant C57/BL6 mice. The cells were continuously cultured in Dulbecco's Modified Eagle Medium for 9 passages. SA-ß-Gal staining was used as an indicator of cell senescence. The supernatant from primary MEFs (P1 medium) or Passage 6 MEFs (P6 medium) were used to culture freshly isolated MEFs to observe the effects on cell senescence state. Gene expression profiles of primary and senescent MEFs were investigated by RNA-Seq to find the key genes involved in cell senescence. Adipocyte differentiation assay was used to evaluate the stemness of MEFs cultured in FGF2-stimulated medium. RESULTS The senescence of MEFs cultured in the P1 medium was alleviated when compared to the P6 medium. Downregulation of FGF2 expression was revealed by RNA-Seq and further confirmed by real-time quantitative polymerase chain reaction and western blot. FGF2-stimulated medium also had anti-senescence function and could maintain the differentiation ability of MEFs. CONCLUSIONS The premature senescence of MEFs was at least partially caused by FGF2 deficiency. Exogenous FGF2 could alleviate the senescent phenotype.


Asunto(s)
Senescencia Celular/fisiología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/metabolismo , Animales , Diferenciación Celular , Proliferación Celular , Daño del ADN , Embrión de Mamíferos/metabolismo , Femenino , Perfilación de la Expresión Génica , Ratones , Ratones Endogámicos C57BL , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal
19.
J Affect Disord ; 268: 88-94, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32158011

RESUMEN

BACKGROUND: Few studies have explored the underlying mechanism between physical frailty and cognitive function. The aim of this study is to explore the mediating role of psychological distress (PD) for the association between cognitive function and physical frailty among the elderly in rural China. METHODS: A total of 3,242 rural older adults were included in the analysis. Logistic regression and Bootstrap analyses were employed to explore the association between cognitive function, PD and frailty, and the mediating role of PD. RESULTS: This study found that the prevalence of frailty and cognitive impairment among the elderly in rural China was 18.0%, 22.4%. After adjusted for controlling variables, cognitive function was significantly associated with high level of PD, and elderly with higher level of PD had a higher probability of suffering from frailty. PD played a partially mediating effect in cognitive function and frailty and the mediating effect of PD can explain the 11.0% of the total effect of cognitive function on frailty. LIMITATIONS: The data were cross-sectional, thus the causal relationship between variables could not be determined. The main variables in this study were measured by self-report information, which might result in recall bias. CONCLUSIONS: This study provide evidence that the effect of cognitive function on physical frailty was partially mediated by PD among the elderly in rural China. Primary health care should strengthen the screening of PD characterized by depression and anxiety, and strive to improve the physical and psychological well-being of rural elderly in China.

20.
Prog Neurobiol ; : 101790, 2020 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-32200043

RESUMEN

Pain symptoms can be transmitted across generations, but the mechanisms underlying these outcomes remain poorly understood. Here, we identified an essential role for primary somatosensory cortical (S1) glutamate neuronal DNA methyl-CpG binding protein 2 (MeCP2) in the transgenerational transmission of pain. In a female mouse chronic pain model, the offspring displayed significant pain sensitization. In these mice, MeCP2 expression was increased in S1 glutamate (GluS1) neurons, correlating with increased neuronal activity. Downregulation of GluS1 neuronal MeCP2 in maternal mice with pain abolished offspring pain sensitization, whereas overexpression of MeCP2 in naïve maternal mice induced pain sensitization in offspring. Notably, single-cell sequencing and chromatin immunoprecipitation analysis showed that the expression of a wide range of genes was changed in offspring and maternal GluS1 neurons, some of which were regulated by MeCP2. These results collectively demonstrate the putative importance of MeCP2 as a key regulator in pain transgenerational transmission through actions on GluS1 neuronal maladaptation.

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