Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.781
Filtrar
1.
Nutrients ; 13(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805289

RESUMO

Probiotics are reported to improve gastrointestinal (GI) function via regulating gut microbiota (GM). However, exactly how probiotics influence GM and GI function in elders is poorly characterized. Therefore, in this study, we assessed the effect of the probiotic Lacticaseibacillus paracasei PS23 (LPPS23) on the GM and GI function of aged mice. There were four groups of senescence-accelerated mouse prone-8 (SAMP8) mice (n = 4): a non-treated control group, a saline control group, a low dose LPPS23 group (1 × 108 colony-forming unit (CFU)/mouse/day), and a high dose LPPS23 group (1 × 109 CFU/mouse/day). Non-treated mice were euthanized at 16 weeks old, and others were euthanized at 28 weeks old. The next-generation sequencing results revealed that LPPS23 enriched Lactobacillus and Candidatus_Saccharimonas, while the abundance of Lachnospiraceae_UCG_001 decreased in aged mice given LPPS23. The abundance of Lactobacillus negatively correlated with the abundance of Erysipelotrichaceae. Moreover, LPPS23 improved the GI function of aged mice due to the longer intestine length, lower intestinal permeability, and higher phagocytosis in LPPS23-treated mice. The ELISA results showed that LPPS23 attenuated the alterations of pro-inflammatory factors and immunoglobulins. The abundance of LPPS23-enriched Lactobacillus was positively correlated with healthy GI function, while Lachnospiraceae_UCG_001, which was repressed by LPPS23, was negatively correlated with a healthy GI function in the aged mice according to Spearman's correlation analysis. Taken together, LPPS23 can effectively modulate GM composition and improve GI function in aged SAMP8 mice.

2.
Eur J Pharmacol ; : 174077, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798601

RESUMO

This study investigated the hemodynamic effect of Bay 60-7550, a phosphodiesterase type 2 (PDE2) inhibitor, in healthy rat hearts both in vivo and ex vivo and its underlying mechanisms. In vivo rat left ventricular pressure-volume loop, Langendorff isolated rat heart, Ca2+ transient of left ventricular myocyte and western blot experiments were used in this study. The results demonstrated that Bay 60-7550 (1.5 mg/kg, i.p.) increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-diastolic volume, heart rate, and ejection fraction. The simultaneous aortic pressure recording indicated that the systolic blood pressure was increased and diastolic blood pressure was decreased by Bay 60-7550. Also, the arterial elastance which is proportional to the peripheral vessel resistance was significantly decreased. Bay 60-7550 (0.001, 0.01, 0.1, 1 µmol/l) also enhanced the left ventricular development pressure in non-paced and paced modes with a decrease of heart rate in non-paced model. Bay 60-7550 (1 µmol/l) increased SERCA2a activity and SR Ca2+ content and reduced SR Ca2+ leak rate. Furthermore, Bay 60-7550 (0.1 µmol/l) increased the phosphorylation of phospholamban at 16-serine without significantly changing the phosphorylation levels of phospholamban at 17-threonine and RyR2. Bay 60-7550 increased the rat heart contractility and reduced peripheral arterial resistance may be mediated by increasing the phosphorylation of phospholamban and dilating peripheral vessels. PDE2 inhibitors which result in a positive inotropic effect and a decrease in peripheral resistance might serve as a target for developing agents for the treatment of heart failure in clinical settings.

3.
Nanomaterials (Basel) ; 11(3)2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33799398

RESUMO

The zoom metalens has been a research hotspot for metasurfaces in recent years. There are currently a variety of zoom methods, including dual metalenses, micro-electromechanical system metalenses, polydimethylsiloxane metalenses and Alvarez metalenses. However, for most metalenses, zooming is achieved by manipulating the relative displacement of two or more metasurfaces. Therefore, these methods seem inadequate when faced with more precise zooming requirements, and the precise control of the phase distribution cannot be achieved. In this paper, we innovatively propose an electrically-driven zoom metalens (EZM) of one-dimensional based on dynamically controlling barium titanate (BaTiO3, BTO) antennas. Using the electro-optic effect of BTO crystals, we can apply a voltage to change the refractive index of BTO nanopillars (n = 2.4-3.6), thereby accurately controlling the phase distribution of column antennas. The proposed EZM can achieve 5× zoom (f = 10-50 µm), with advantages, such as high-speed optical amplitude modulation, ultra-compactness, flexibility and replicability. It can be applied in fields that require ultra-compact beam focusing, zoom imaging, and microscopic measuring.

4.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803943

RESUMO

Acute heart failure (AHF) commonly arises from decompensated chronic heart failure or sudden structural and functional breakdown causing a decrease in cardiac contractility and consequently fluid accumulation and systemic congestion. Current treatment for AHF aims at reducing fluid overload and improving hemodynamic which results in quick symptom relief but still poor prognostic outcome. This study utilizes a zebrafish AHF model induced by aristolochic acid (AA) to look for natural products that could attenuate the progression of AHF. The project started off by testing nearly seventy herbal crude extracts. Two of the positive extracts were from Chinese water chestnuts and are further studied in this report. After several rounds of chromatographical chemical fractionation and biological tests, a near pure fraction, named A2-4-2-4, with several hydrophilic compounds was found to attenuate the AA-induced AHF. A2-4-2-4 appeared to inhibit inflammation and cardiac hypertrophy by reducing MAPK signaling activity. Chemical analyses revealed that the major compound in A2-4-2-4 is actually lactate. Pure sodium lactate showed attenuation of the AA-induced AHF and inflammation and cardiac hypertrophy suppression as well, suggesting that the AHF attenuation ability in A2-4-2-4 is attributable to lactate. Our studies identify lactate as a cardiac protectant and a new therapeutic agent for AHF.

5.
Sensors (Basel) ; 21(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799850

RESUMO

Sleep staging is important in sleep research since it is the basis for sleep evaluation and disease diagnosis. Related works have acquired many desirable outcomes. However, most of current studies focus on time-domain or frequency-domain measures as classification features using single or very few channels, which only obtain the local features but ignore the global information exchanging between different brain regions. Meanwhile, brain functional connectivity is considered to be closely related to brain activity and can be used to study the interaction relationship between brain areas. To explore the electroencephalography (EEG)-based brain mechanisms of sleep stages through functional connectivity, especially from different frequency bands, we applied phase-locked value (PLV) to build the functional connectivity network and analyze the brain interaction during sleep stages for different frequency bands. Then, we performed the feature-level, decision-level and hybrid fusion methods to discuss the performance of different frequency bands for sleep stages. The results show that (1) PLV increases in the lower frequency band (delta and alpha bands) and vice versa during different stages of non-rapid eye movement (NREM); (2) alpha band shows a better discriminative ability for sleeping stages; (3) the classification accuracy of feature-level fusion (six frequency bands) reaches 96.91% and 96.14% for intra-subject and inter-subjects respectively, which outperforms decision-level and hybrid fusion methods.

6.
Sensors (Basel) ; 21(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800839

RESUMO

Among aquatic biota, corals provide shelter with sufficient nutrition to a wide variety of underwater life. However, a severe decline in the coral resources can be noted in the last decades due to global environmental changes causing marine pollution. Hence, it is of paramount importance to develop and deploy swift coral monitoring system to alleviate the destruction of corals. Performing semantic segmentation on underwater images is one of the most efficient methods for automatic investigation of corals. Firstly, to design a coral investigation system, RGB and spectral images of various types of corals in natural and artificial aquatic sites are collected. Based on single-channel images, a convolutional neural network (CNN) model, named DeeperLabC, is employed for the semantic segmentation of corals, which is a concise and modified deeperlab model with encoder-decoder architecture. Using ResNet34 as a skeleton network, the proposed model extracts coral features in the images and performs semantic segmentation. DeeperLabC achieved state-of-the-art coral segmentation with an overall mean intersection over union (IoU) value of 93.90%, and maximum F1-score of 97.10% which surpassed other existing benchmark neural networks for semantic segmentation. The class activation map (CAM) module also proved the excellent performance of the DeeperLabC model in binary classification among coral and non-coral bodies.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33824414

RESUMO

BACKGROUND: The prevalence of preterm birth in Bangladesh is estimated to be 19.1%, the highest in the world. Although prenatal exposure to several metals has been linked with preterm birth, fewer prospective studies have investigated the socioeconomic factors that affect metal exposure, leading to preterm birth risk. OBJECTIVE: We aim to identify novel metal biomarkers and their critical exposure windows, as well as the upstream socioeconomic risk factors for preterm birth in rural Bangladeshi, to shed light for future interventional strategies. METHODS: This study included data from 780 mother-offspring pairs, who were recruited to participate in a prospective birth cohort in Bangladesh (2008-2011). Serum concentrations of 19 metals were measured in the first and second trimesters using inductively coupled plasma mass spectrometry. Mediation analysis was performed to explore the upstream socioeconomic factors that affect the risk of preterm birth mediated via metal exposure concentrations. RESULTS: Early pregnancy exposure to serum zinc, arsenic, and strontium and mid-pregnancy exposure to barium were significantly associated with risk of preterm birth. Furthermore, younger marriage age was associated with an exponential increase in the risk of preterm birth, and women who married after 18 years old had a considerably lower risk of preterm birth. Mediation analysis indicated that these four elements mediated 30.2% of the effect of marriage age on preterm birth. CONCLUSION: This study indicated that maternal serum metal exposure mediates the impact of child marriage on the increased risk of preterm birth via metal exposures. The findings shed light on the mechanisms underlying such association and provide insights into future interventional strategies.

8.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809404

RESUMO

Dynamic remodeling of the actin cytoskeleton plays a central role in the elongation of cotton fibers, which are the most important natural fibers in the global textile industry. Here, a high-resolution mapping approach combined with comparative sequencing and a transgenic method revealed that a G65V substitution in the cotton actin Gh_D04G0865 (GhACT17D in the wild-type) is responsible for the Gossypium hirsutum Ligon lintless-1 (Li1) mutant (GhACT17DM). In the mutant GhACT17DM from Li1 plant, Gly65 is substituted with valine on the lip of the nucleotide-binding domain of GhACT17D, which probably affects the polymerization of F-actin. Over-expression of GhACT17DM, but not GhACT17D, driven by either a CaMV35 promoter or a fiber-specific promoter in cotton produced a Li1-like phenotype. Compared with the wild-type control, actin filaments in Li1 fibers showed higher growth and shrinkage rates, decreased filament skewness and parallelness, and increased filament density. Taken together, our results indicate that the incorporation of GhACT17DM during actin polymerization disrupts the establishment and dynamics of the actin cytoskeleton, resulting in defective fiber elongation and the overall dwarf and twisted phenotype of the Li1 mutant.

9.
PLoS One ; 16(4): e0248290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793599

RESUMO

CD40 expressed on stimulatory dendritic cells (DC) provides an important accessory signal for induction of effector T cell responses. It is also expressed at lower levels on regulatory DC (DCreg), but there is little evidence that CD40 signaling contributes to the tolerogenic activity of these cells. Indeed, CD40 silencing within DCreg has been reported to induce T cell tolerance in multiple disease models, suggesting that CD40 is superfluous to DC-induced tolerance. We critically assessed whether CD40 does have a role in tolerance induced by IL-10-differentiated DC (DC10) by using DC10 generating from the bone marrow of wild-type (w.t.) or CD40-/- donor mice, or IL-10-complemented CD40-/- DC10 to treat asthmatic mice. Wild-type DC10 ablated the OVA-asthma phenotype via induction of Foxp3+ Treg responses, but CD40-/- DC10 had no discernible effects on primary facets of the phenotype (e.g., IL-5, IL-9, IL-13 levels, IgE & IgG1 antibodies; p>0.05) and were ≤40% effective in reversal of others. Foxp3+ T cells from the lungs of CD40-/- DC10-treated mice expressed reduced levels of a panel of six Treg-specific activation markers relative to Treg from w.t. DC10-treated mice. Coculture with effector T cells from asthmatic mice induced a marked upregulation of cell surface CD40 on w.t. DC10. While untreated CD40-/- and w.t. DC10 secreted equally low levels of IL-10, stimulation of w.t. DC10 with anti-CD40 for 72 h increased their expression of IL-10 by ≈250%, with no parallel induction of IL-12. Complementing IL-10 expression in CD40-/- DC10 by IL-10 mRNA transfection fully restored the cells' abilities to suppress the asthma phenotype. In summary, CD40 signaling in DC10 contributes importantly to their expression of IL-10 and to a robust induction of tolerance, including activation of induced Treg.

10.
Asia Pac J Clin Nutr ; 30(1): 140-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787050

RESUMO

BACKGROUND AND OBJECTIVES: Although fish consumption or omega-3 intake is associated with cardio- cerebrovascular disease including stroke, their correlation is still controversial. Therefore, this meta-analysis is to identify the relationship between the risk of stroke and fish consumption or omega-3 intake. METHODS AND STUDY DESIGN: We searched the PubMed, EMBASE and Cochrane Library databases as of May 2019. Multivariateadjusted risk ratios (RRs) with 95% confidence interval (CI) for stroke in different level intake of fish or Longchain omega-3 polyunsaturated fatty acids (LC ω3-PUFAs) were pooled using a random-effects meta-analysis. A dose-response analysis was conducted with the 2-stage generalized least-squares trend program. RESULTS: Our meta-analysis identified a total of 17 prospective cohort studies including 14986 strokes events in 672711 individuals. Meta-analysis revealed that the higher fish consumption was significantly associated with lower risk of stroke (RR=0.871, 95% CI: 0.779-0.975, p=0.016), especially with ischemic stroke (RR=0.808, 95% CI: 0.696- 0.937, p=0.005). Meantime, the combined RR of total stroke was 0.859 (95% CI: 0.769-0.959, p=0.007) for the highest versus lowest intake of LC ω3-PUFAs, and stratification analysis showed that higher LC ω3-PUFAs intake was associated with reduced stroke risk in women (RR=0.793, 95% CI: 0.706-0.891, p=0.000) but not in men. In addition, the dose-response analysis showed fish consumption with 1000g per month and LC ω3-PUFAs intake with 0.5g per month was associated with 17.3% (RR=0.927, 95% CI: 0.83-0.98) and 14% (RR=0.86, 95% CI: 0.78-0.95) lower risk of stroke, respectively. CONCLUSIONS: Both fish consumption and LC ω3-PUFAs intake were negatively associated with the risk of stroke, especially in women, which suggest that increased intake of fishery products and LC ω3-PUFAs may benefit primary prevention of stroke.

11.
Zhongguo Zhen Jiu ; 41(2): 133-6, 2021 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-33788459

RESUMO

OBJECTIVE: To compare the therapeutic effect between long-snake moxibustion combined with western medication and simple medication on diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: A total of 60 patients with IBS-D of spleen and kidney yang deficiency were randomized into an observation group and a control group, 30 cases in each one. In the control group, loperamide hydrochloride capsule (2.0 mg each time, 3 times a day) and bacillus licheniformis live capsule (0.5 mg each time, 3 times a day) were given orally. In the observation group, long-snake moxibustion was added on the basis of the treatment in the control group, ginger-partitioned moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) of governor vessel, once a week. The treatment was given for 8 weeks in both groups. The scores of main symptom and IBS quality of life questionnaire (IBS-QOL) were observed before and after treatment, and the therapeutic effect was evaluated in both groups. RESULTS: Compared before treatment, the symptom scores of abdominal pain, defecation frequency, mucous stool and appetite reduction were decreased (P<0.05), the scores of daily social intercourse, daily activity, diet, work, emotion, sleep quality, mental state and energy change were increased in both groups (P<0.05). After treatment, each sub-item score of main symptom in the observation group was lower than the control group (P<0.05), each sub-item score of IBS-QOL was higher than the control group (P<0.05). The total effective rate was 96.7% (29/30) in the observation group, which was superior to 73.3% (22/30) in the control group (P<0.05). CONCLUSION: Long-snake moxibustion combined with western medication can effectively treat the IBS-D of spleen and kidney yang deficiency, relieve the clinical symptoms and improve the quality of life, the effect is superior to the simple treatment of oral western medication.


Assuntos
Síndrome do Intestino Irritável , Moxibustão , Pontos de Acupuntura , Animais , Diarreia/tratamento farmacológico , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Rim , Qualidade de Vida , Serpentes , Baço , Deficiência da Energia Yang/tratamento farmacológico
12.
Artigo em Inglês | MEDLINE | ID: mdl-33754433

RESUMO

Carbon dots (CDs) have attracted extensive attention in white light-emitting diodes (LEDs) research due to their inherent optical advantages, such as emission wavelength tunability, high quantum yield (QY) and low photobleaching properties. However, their wide emission spectrum and the electron transfer between CDs make the fabrication of their light-emitting devices very complicated and difficult. Here, we show the fabrication of the CDs with green and orange emissions from PTCDA (perylene-3,4,9,10-tetracarboxylic dianhydride). Using these CDs as emitters, the orange (or green) CDs LEDs were fabricated, which show electroluminescence (EL) spectra centered at 560 nm (or 498 nm) with an external quantum efficiency (EQE) of 1.98% (1.76%) adhering a luminescence of 626 cd/m2 (or 519 cd/m2). We successfully constructed the machine learning model to predict PL CCT value. With the model, we achieve white photoluminescence (PL) emission with adjustable correlated color temperature (CCT) from 3093 to 11018 K via combining blue, green and orange CDs. We obtain the warm white CDs LEDs with CCT of 3107, 4071 and 4548 K, and cold white CDs LEDs with CCT of 5632 (CIE coordinates of (0.33, 0.33), EQE: 1.18%, luminescence: 598 cd/m2) and 6034 K accurately.

13.
Gut ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692094

RESUMO

OBJECTIVE: Solid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC). DESIGN: Anti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses. RESULTS: A negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades. CONCLUSIONS: CAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.

14.
Int Immunopharmacol ; 95: 107533, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33752080

RESUMO

Doxorubicin (DOX) is a potent chemotherapeutic drug but the clinical use was limited by its dose-dependent cardiotoxicity. Pinocembrin (PCB), a flavonoid originally isolated from honeybee propolis and rhizomes of Boesenbergia pandurate displays diverse biological activities. However, the role of PCB in DOX-induced cardiac injury and its underlying molecular mechanism are not fully elucidated. The present study was designed to evaluate the protective role of PCB in a DOX-induced cardiotoxicity in vivo and in vitro. Our results revealed that PCB administration greatly improved cardiac function and reduced cardiac fibrosis manifested by LVEF, LVFS, LVIDd, LVIDs, and myocardial fibrotic area which were impaired by DOX treatment. The cardiac injury evidenced by LDH and CK-MB activities were reduced while the levels of IL-1ß and IL-18 were decreased following PCB treatment compared to DOX-treated mice. Mechanically, our present results showed that PCB significantly inhibited DOX-induced cardiomyocyte pyroptosis via activating Nrf2/Sirt3 signal pathway. Furthermore, the inhibition of Nrf2 in H9c2 cells abolished the protective role of PCB against DOX-induced cell toxicity, which was at least partly via upregulation of NLRP3-mediated pyroptosis. In conclusion, our study clearly demonstrated that PCB reduced cardiomyocyte pyroptosis to protect hearts from DOX-induced cardiotoxicity through activation of Nrf2/Sirt3 signal pathway.

15.
Biochem Biophys Res Commun ; 550: 197-203, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33713857

RESUMO

Alcoholic fatty liver disease (AFLD) is induced by alcohol consumption and may progress to more severe liver diseases such as alcoholic steatohepatitis, fibrosis and cirrhosis, and even hepatocellular carcinoma. Mesencephalic astrocyte-derived neurotrophic factor (MANF) participates in maintaining lipid homeostasis. However, the role of MANF in the pathogenesis of AFLD remains unclear. We established an AFLD mouse model following the US National Institute on Alcohol Abuse and Alcoholism procedure. Both mRNA and protein levels of MANF were significantly increased in the chronic binge alcohol feeding model. Liver-specific knockout of MANF aggravated hepatic lipid accumulation. Similarly, liver-specific overexpression of MANF alleviated AFLD in mouse livers. MANF affected hepatic lipid metabolism by modulating autophagy. The levels of LC3-II and Atg5-Atg12 were decreased in mouse livers with MANF liver-specific knockout and increased with MANF liver-specific overexpression. Furthermore, MANF changed the phosphorylation of Stat3 and its nuclear localization. MANF may have a protective role in the development of AFLD.

16.
J Chin Med Assoc ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33742989

RESUMO

BACKGROUND: Direct-acting antivirals (DAA) improve sustained virological response (SVR) rates with normalization of liver enzymes in patients with hepatitis C. However, liver inflammation may persist despite virus eradication. We aimed to investigate the rate and risk factors for persistent elevated aminotransferase levels in patients with advanced fibrosis after DAA-induced SVR. METHODS: From January 2017 to April 2018, chronic hepatitis C patients with advanced fibrosis and SVR after DAA treatment at the Taipei Veterans General Hospital were prospectively enrolled. Persistent liver inflammation after SVR was defined as an increase in levels of alanine aminotransferase (ALT) (>40 U/L) at SVR12. RESULTS: A total of 461 patients were included (57.9% female, mean age 64 years, 69.6% genotype 1b, 46.4% cirrhosis). At SVR12, there was a decline in ALT levels (90.5 ± 80.8 U/L to 25.3 ± 26.5 U/L) from baseline levels. Persistent liver inflammation at SVR12 was detected in 45 patients (9.8%). The presence of cirrhosis, markers of impaired liver functions, history of interferon-based therapy, steatosis, and elevated ALT levels at baseline were associated with persistent liver inflammation after SVR12. Results of multivariate analysis indicated that levels of baseline serum total bilirubin (OR: 2.605, 95% CI: 1.158-5.858), INR (OR: 14.389, 95% CI: 1.754-118.049), ALT (OR: 1.006, 95% CI: 1.003-1.009), and the presence of steatosis (OR: 3.635, 95% CI: 1.716-7.698) were independent predictors of persistent liver inflammation at SVR12. CONCLUSION: Persistent liver inflammation is not uncommon in chronic hepatitis C patients with advanced fibrosis after DAA-induced SVR. It is associated with impaired baseline liver function and steatosis. Long-term follow-up is required to assess the implication of liver inflammation on disease progression.

17.
Res Nurs Health ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763879

RESUMO

Sleep disturbance is highly prevalent among shift-working nurses. We aimed to evaluate whether aerobic exercise (i.e., walking combined with jogging) improves objective sleep parameters among female nurses who met eligibility criterion as poor sleepers at the end of an 8-week exercise program and 4 weeks after study completion. This single-blinded, parallel-design, randomized controlled trial was conducted in a classroom of a hospital in northern Taiwan. Sixty eligible female nurses were randomly assigned to either the aerobic exercise (n = 30) or usual activity status (n = 30) group. A moderate-intensity aerobic exercise program was administered over 5 days (60 min per day) a week for 8 weeks after the nurses' day shifts. Objective sleep outcomes including total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were retrieved using an actigraph device. A generalized estimating equation model was used for data analysis. The aerobic exercise group exhibited improvements in TST and SE at 4 and 8 weeks compared with the baseline evaluation (TST: B = 70.49 and 55.96; SE: B = 5.21 and 3.98). Between-group differences were observed in SOL and WASO at 4 weeks but not 8 weeks compared with the baseline evaluation (SOL: B = -7.18; WASO: B = -11.38). Positive lasting effects for TST were observed only until the 4-week follow-up. To improve sleep quality and quantity, we encourage female nurses who sleep poorly to regularly perform moderate-intensity aerobic exercise.

18.
J Clin Invest ; 131(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720048

RESUMO

Chronic HIV-1 infection is generally characterized by progressive CD4+ T cell depletion due to direct and bystander death that is closely associated with persistent HIV-1 replication and an inflammatory environment in vivo. The mechanisms underlying the loss of CD4+ T cells in patients with chronic HIV-1 infection are incompletely understood. In this study, we simultaneously monitored caspase-1 and caspase-3 activation in circulating CD4+ T cells, which revealed that pyroptotic and apoptotic CD4+ T cells are distinct cell populations with different phenotypic characteristics. Levels of pyroptosis and apoptosis in CD4+ T cells were significantly elevated during chronic HIV-1 infection, and decreased following effective antiretroviral therapy. Notably, the occurrence of pyroptosis was further confirmed by elevated gasdermin D activation in lymph nodes of HIV-1-infected individuals. Mechanistically, caspase-1 activation closely correlated with the inflammatory marker expression and was shown to occur through NLRP3 inflammasome activation driven by virus-dependent and/or -independent ROS production, while caspase-3 activation in CD4+ T cells was more closely related to T cell activation status. Hence, our findings show that NLRP3-dependent pyroptosis plays an essential role in CD4+ T cell loss in HIV-1-infected patients and implicate pyroptosis signaling as a target for anti-HIV-1 treatment.

19.
Sci Rep ; 11(1): 6551, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753806

RESUMO

Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.

20.
Malar J ; 20(1): 124, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653360

RESUMO

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.


Assuntos
Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Epitopos , Guiné Equatorial/epidemiologia , Frequência do Gene , Variação Genética , Haplótipos , Humanos , Vacinas Antimaláricas , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Polimorfismo Genético , Proteínas de Protozoários/química , Proteínas de Protozoários/imunologia , Seleção Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...