Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells

IL-2 gene expression in activated T-cells is initiated by chromatin remodeling at the IL-2 proximal promoter and conversion of a transcriptional repressor into a potent transcriptional activator. A purine-box regulator complex was purified from activated Jurkat T-cell nuclei based on sequence-specific DNA binding to the antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target DNA sequence in the proximal IL-2 promoter. ARRE DNA-binding subunits were identified as NF90, NF45 and systemic lupus erythematosis autoantigens, Ku80 and Ku70. Monoclonal antibodies to Ku80, Ku70 and NF90 specifically inhibit constitutive and inducible ARRE DNA-binding activity in Jurkat T-cells. Ku80, Ku70 and NF90 bind specifically to the IL-2 gene promoter in vivo, as demonstrated by chromatin immunoprecipitation. Activation of Jurkat T-cells and mouse primary spleen cells induces binding of Ku80 and NF90 to the IL-2 promoter in vivo, and decreases binding of Ku70 to the IL-2 promoter in vivo, and these dynamic changes are inhibited by immunosuppressants cyclosporin A and triptolide. Dynamic changes in binding of Ku80, Ku70 and NF90 to the IL-2 proximal promoter in vivo correlate with chromatin remodeling and transcriptional initiation in activated T-cells

Effect of Aerobic Exercise on Inflammatory Markers in Healthy Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Chronic inflammation plays a significant role in accelerating the aging process and is closely associated with the initiation and progression of a broad range of age-related diseases. Physical exercise is considered beneficial in alleviating these conditions, but the effects of aerobic exercise on inflammatory markers in a healthy population should be furtherly clarified.Objective: The purpose of this systematic review and meta-analysis was to evaluate the effect of aerobic exercise on inflammatory markers in middle-aged and older adults.Methods: The literature search was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library from their inception through April 2018, and the reference lists were screened to identify appropriate studies. Only randomized controlled trials that investigated the effect of aerobic exercise on inflammatory markers in middle-aged and older adults were eligible for this review.Results: Eleven studies involving 1,250 participants were retrieved from the databases for analysis. The pooled results showed that aerobic exercise significantly reduced inflammatory markers (C-reactive protein (CRP): SMD = 0.53, 95% CI 0.26–0.11, p = 0.0002; tumor necrosis factor-alpha (TNF-α): SMD = 0.75, 95% CI 0.31–1.19, p = 0.0007; interleukin 6 (IL-6): SMD = 0.75, 95% CI 0.31–1.19, p = 0.0007). No significant improvement was found in relation to interleukin 4 (IL-4).Conclusions: Aerobic exercise may have a positive effect on reduction of CRP, TNF-α, and IL-6 in middle-aged and older adults. Further randomized controlled trials (RCTs) need to be conducted to determine the effect of aerobic exercise on additional inflammatory markers in the population of middle-aged and older adults

Primary prevention for risk factors of ischemic stroke with Baduanjin exercise intervention in the community elder population: study protocol for a randomized controlled trial

BACKGROUND: Stroke is a major cause of death and disability in the world, and the prevalence of stroke tends to increase with age. Despite advances in acute care and secondary preventive strategies, primary prevention should play the most significant role in the reduction of the burden of stroke. As an important component of traditional Chinese Qigong, Baduanjin exercise is a simple, safe exercise, especially suitable for older adults. However, current evidence is insufficient to inform the use of Baduanjin exercise in the prevention of stroke. The aim of this trail is to systematically evaluate the prevention effect of Baduanjin exercise on ischemic stroke in the community elder population with high risk factors. METHODS: A total of 170 eligible participants from the community elder population will be randomly allocated into the Baduanjin exercise group and usual physical activity control group in a 1:1 ratio. Besides usual physical activity, participants in the Baduanjin exercise group will accept a 12-week Baduanjin exercise training with a frequency of five days a week and 40 minutes a day. Primary and secondary outcomes will be measured at baseline, 13 weeks (at end of intervention) and 25 weeks (after additional 12-week follow-up period). DISCUSSION: This study will be the randomized trial to evaluate the effectiveness of Baduanjin exercise for primary prevention of stroke in community elder population with high risk factors of stroke. The results of this trial will help to establish the optimal approach for primary prevention of stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003588. Registration date: 24 July, 2013

Stiffness of Substrate Influences the Distribution but not the Synthesis of Autophagosomes in Human Liver (LO2) Cells

Extracellular matrix (ECM) often becomes stiffer during tumor development, which not only gives the tumor's hardness feel but also actively contributes to the tumor formation. A good example is hepatocellular carcinoma (HCC) that usually develops within chronically stiffened liver tissues due to fibrosis and cirrhosis. On the other hand, HCC cells exhibit reduced autophagy in a malignancy dependent manner, suggesting autophagy is suppressed during tumor development. However, it is not known whether ECM stiffness would influence autophagy during tumor development. To investigate this issue, We cultured the human liver (LO2) cells that stably expressed autophagosome indicator LC3 on polydimethylsiloxane (PDMS) gels with stiffness varying from 11 to 1220 kPa. and on plastic cell culture dish as controls for up to 48h. We found that the total protein level of LC3-II in LO2 cells was not affected by the substrate stiffness. However the autophagosomes in LO2 cells cultured on the soft substrate (11 kPa PDMS gel) were localized and accumulated around the nucleus, while those on the stiff substrate (1220 kPa PDMS gel or plastic dish surface) were dispersed throughout the cytoplasmic space. Therefore, our data suggest that ECM stiffness may not directly synthesize nascent autophagosomes, but instead influence the location/translocation and ultimately distribution of autophagosomes in the cells

Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial

BackgroundOxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process.MethodA total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention.ResultAfter 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p < 0.001) and the decreased EFS scores (1.94 ± 0.20 points, p = 0.012) in the Baduanjin group were significantly higher than those in the control group. Serum antioxidant SOD levels were increased by 10.03 ± 4.73 U/mL (p < 0.001), and the prooxidative MDA and 8-iso-PGF2α levels were decreased by −1.08 ± 0.80 nmol/mL (p = 0.030) and −86.61 ± 15.03 ng/L (p < 0.001) in the Baduanjin training group; while inflammatory cytokines IFN-γ, IL-2 and IL-4 levels were increased (1.08 ± 0.33 pg./mL, p = 0.034, 2.74 ± 0.75 pg./mL, p = 0.04 and 1.48 ± 0.35 pg./mL, p = 0.042). In addition, a mediation effect that Baduanjin training improved cognitive ability mediated by an increase of circulating IFN-γ and IL-2 levels were observed in this study.ConclusionRegular Baduanjin exercise training could improve the cognitive frailty of the community-dwelling older adults with CF, and modulate oxidative stress and inflammatory processes by reducing circulating pro-oxidative MDA and 8-iso-PGF2α levels and increasing anti-oxidative SOD levels, as well as impacting inflammatory cytokines IFN-γ, IL-2, and IL-4 levels. Nevertheless, the mechanism of Baduanjin exercise mediating oxidative stress and inflammatory processes should be cautious to be explained.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, ChiCTR1800020341

Biodegradable and water resistant poly(vinyl) alcohol (PVA)/starch (ST)/glycerol (GL)/halloysite nanotube (HNT) nanocomposite films for sustainable food packaging

As a novel biodegradable material, poly (vinyl) alcohol (PVA)/starch (ST)/ glycerol (GL)/halloysite nanotube (HNT) nanocomposite films were prepared by solution casting at the HNT contents of 0.25, 0.5, 1, 3, and 5 wt%. Water absorption capacity and water solubility of nanocomposite films were decreased remarkably by 44.24 and 48.05%, respectively, with increasing the HNT content from 0 to 5 wt% when compared with those of biopolymer matrices. Moreover, the water contact angle of nanocomposite films increased by 21.36◦ with the incorporation of HNTs. The presence of HNTs appeared to reduce the overall migration rates for PVA/ST/GL/HNT nanocomposite films when interacting with either hydrophilic or lipophilic food simulants. However, the migration rates of HNTs alone were enhanced with increasing the HNT content in hydrophilic, lipophilic, and acidic food simulants. On the other hand, the biodegradation rate and light transmittance of nanocomposite films were reduced linearly by 18.56 and 26.90% with increasing the HNT content from 0 to 5 wt%. Overall, novel PVA/ST/GL/HNT nanocomposite films in this study offer highly competitive materials with excellent water resistance, good biodegradability, and acceptable transparency to be potentially used for sustainable food packaging particularly targeting lipophilic and acidic foodstuffs

Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures

BackgroundLow temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear.MethodsThis study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed.ResultsExperimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze−thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability.ConclusionOur studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment