Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.899
Filtrar
1.
Mol Med Rep ; 22(5): 4173-4182, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000260

RESUMO

Pulmonary hypertension (PH) in newborns and adults is a disease that can lead to right heart failure and result in a shorter lifespan. PH was induced by maintaining pregnant rats in a hypoxic chamber for 4 h twice a day, from days 7­21 of pregnancy. Hypoxia was confirmed by a decrease in the partial pressure of oxygen (PaO2) and the oxygen saturation (SaO2) of arterial blood in the aorta. The body weight of newborns from hypoxic rats was ~20% decreased compared with the control newborns of normoxic rats. The vascular wall thickness/vascular diameter values of hypoxia treated pubs were increased compared with that of control newborns 7 days after birth; however, it decreased to similar levels than in the control group after 3 months, and then further decreased to significantly lower levels than in the control group at 6 months after birth. At birth, the lung tissues of newborns from hypoxic rats exhibited an increase in the levels of mRNA and proteins associated with PH such as HIF­1α, HIF­2α, V2R, TGF­ß, TNF­α, Ang­2 and α­SMA. At 3 and 6 months after birth, the levels of both V2R mRNA and protein in offspring from hypoxic rats were at least 2­fold higher, whereas the expression of all other factors decreased compared with the control offspring. By contrast, HIF­2α and Ang­2 expression levels were significantly increased in the 6­month­old control offspring from normoxic rats. V2R overexpression in pups induced by hypoxia in maternal rats was sustained until their adulthood. V2R may be a marker for detecting PH.

2.
J Nat Prod ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33035058

RESUMO

Eight new germacranolides, minusolides A-H (1-8), along with two known analogues, 9 and 10, were isolated from the whole plant of Carpesium minus. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2, and 6 and 9 are two pairs of rare epimers with opposite configurations at C-2 of the 2-methylbutyryloxy group. The absolute configurations were determined by X-ray diffraction studies. Compound 7 exhibited cytotoxic activities against MDA-MB-231, A549, and HCT-116 cells with IC50 values of 6.1 ± 0.2, 8.4 ± 0.6, and 3.7 ± 0.6 µM, respectively. Compound 7 induced the apoptosis of HCT-116 cells via suppression of PARP and promoting cleavage of PARP.

3.
Clin Immunol ; : 108611, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068796

RESUMO

Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (≥28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-α (TNF-α), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.

4.
Animals (Basel) ; 10(10)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081100

RESUMO

miRNA is a small non-coding RNA, which plays an important role in diverse biological processes. In the present study, we explore the effect of ssc-miR-451 on porcine adipose development and meat quality. We observed that ssc-miR-451 was downregulated during porcine primary adipocyte differentiation. Overexpression of ssc-miR-451 inhibited adipogenic differentiation, while inhibition of ssc-miR-451 promoted adipogenic differentiation. The dual luciferase reporter system indicated Acetyl-CoA carboxylase alpha (ACACA) as a target gene of ssc-miR-451. Correlation analysis negatively correlated miR-451 expression with intramuscular fat content (IMF) and positively correlated ACACA expression with IMF. Further analysis of fatty acid composition revealed that pigs with high expression of ssc-miR-451 had higher monounsaturated fatty acid (MUFA) and lower polyunsaturated fatty acid (PUFA). Taken together, our study suggests that ssc-miR-451 regulates lipid deposition and fatty acid composition by targeting ACACA, and ssc-miR-451 may serve as a potential genetic marker to improve pork quality.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33085819

RESUMO

We report a carbon-boron clathrate with composition 2La@B 6 C 6 (LaB 3 C 3 ). Like recently reported SrB 3 C 3 , [1] single-crystal X-ray diffraction and computational modelling indicate that the isostructural La member crystallizes in the cubic bipartite sodalite structure (Type-VII clathrate) with La atoms encapsulated within truncated octahedral cages comprised of alternating carbon and boron atoms. The covalent nature of B-C bonding results in a hard, incompressible framework, and due to the balanced electron count, La 3+ [B 3 C 3 ] 3- exhibits markedly improved pressure stability and is a semiconductor with an indirect band gap predicted near 1.3 eV. A variety of different guest atoms may potentially be substituted within Type-VII clathrate cages, presenting opportunities for a large family of boron-stabilized, carbon-based clathrates with ranging physical properties.

6.
Oral Dis ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031609

RESUMO

OBJECTIVE: Experiments were performed to evaluate CYLD expression in human gingival tissue samples and to examine the effects of CYLD on inflammatory responses in lipopolysaccharide (LPS)- or TNF-α-stimulated human gingival fibroblasts (HGFs). METHODS: Immunohistochemistry for CYLD and p65 expression was performed with healthy and inflamed gingival tissue samples. siRNA was used to knock down the expression of CYLD in HGFs. Upon LPS or TNF-α stimulation, NF-κB activation was detected in control and CYLD-knockdown HGFs. RT-PCR was applied to determine gene expression. Western blot analyses were employed to assess protein expression. Immunofluorescence staining was carried out to evaluate the nuclear translocation of p65. RESULTS: Immunohistochemical staining showed the expression of CYLD in human gingival tissues. In addition, CYLD protein expression was reduced in inflamed gingival tissue samples compared with healthy tissue samples. CYLD knockdown greatly enhanced the mRNA expression of proinflammatory cytokines in LPS- or TNF-α-stimulated HGFs. Furthermore, knocking down CYLD expression increased LPS-stimulated NF-κB activation in HGFs. Unexpectedly, CYLD knockdown did not affect TNF-α-induced NF-κB activation. CONCLUSIONS: Our results suggest that CYLD participates in periodontal inflammatory responses by negatively regulating LPS-induced NF-κB signalling.

7.
Plant Dis ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021907

RESUMO

Osmanthus fragrans Lour. is widely distributed in China, Japan, Thailand and India (Zang et al., 2003) and one of the top 10 most well-known flowering plants in China. Since February, 2017, a foliar disease, with a disease incidence of ~60%, occurred on O. fragrans in a community park in Luzhai, Guangxi, China. Symptoms began as round or irregular small yellow spots and became pale brown to gray-brown with time. Small leaf tissues (3 to 4 mm2) cut from lesion margins were surface-sterilized in 75% ethanol for 30 s and 1% NaClO for 90 s before they were rinsed in ddH2O and dried on sterilized filter paper. After drying, the sterilized tissues were plated on potato dextrose agar (PDA) and incubated at 25°C in the dark for 5 days. Five single-spore isolates were obtained and a representative isolate (GH3) was selected and deposited in the China's Forestry Culture Collection Center. The colony on PDA was white with concentric zonation and white aerial mycelia, but the reverse was yellow. Black pycnidia developed on alfalfa extract + Czapek at 25°C with a 14/10 h light/dark cycle after 17 days. Conidiophores were hyaline, branched, septate, straight to sinuous, 12.4-24 × 1.9-2.5 µm (n = 20). The conidia were fusoid, hyaline, smooth, mostly 2-guttules and measured 7.2 ± 0.7 × 2.3 ± 0.2 µm (n = 50). The morphological characters of pycnidia, conidiophores and conidia of all five isolates matched those of Diaporthe spp. (Gomes et al. 2013). DNA of isolates GH3, GH7 and GH8 was extracted and the internal transcribed spacer region (ITS), partial sequences of elongation factor 1-alpha (EF1-α), calmodulin (CAL), beta-tubulin (ß-tub) and histone H3 (HIS) genes were amplified with primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R and CAL228F/CAL737R (Carbone et al. 1999), ßt2a/ßt2b and CYLH3F/H3-1b (Glass and Donaldson 1995, Crous et al. 2004), respectively. The sequences of GH3, GH7 and GH8 were deposited in GenBank (GH3: Accession nos. MT499213 for ITS, MT506473 to MT506476 for EF1-α, ß-tub, HIS, and CAL; GH7: MT856374 and MT860397 to MT860400; GH8: MT856375 and MT860401 to MT860404). BLAST results showed that the ITS, EF1-α, ß-tub, HIS, and CAL sequences of GH3 were highly similar with sequences of Phomopsis sp. [LC168784 (ITS), Identities = 506/506(100%)], Diaporthe fusicola [MK654863 (EF1-α), Identities = 274/275(99%)], D. amygdali [MK570513 (ß-tub), Identities = 461/461(100%)], D. fusicola [MK726253 (HIS), Identities = 403/403(100%)] and D. amygdali [KC343263 (CAL), Identities = 428/428(100%)], respectively. A maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed isolates GH3, GH7 and GH8 in the D. fusicola cluster and separated them from D. eres and D. osmanthi, which were previously reported from Osmanthus spp. (Gomes et al., 2013; Long et al., 2019). Based on the multi-gene phylogeny and morphology, all three isolates were identified as D. fusicola. The pathogenicity of GH3 was tested on 1-yr-old seedlings of O. fragrans. Healthy leaves were wounded with a sterile needle and then inoculated with either 5-mm mycelial plugs cut from the edge of a 5-day-old culture of GH3 or 10 µL of conidial suspensions (106 conidia/mL). Control leaves were treated with PDA plugs or ddH2O. Three plants were used for each treatment. The plants were covered with a plastic bag after inoculation and sterilized H2O was sprayed into the bags twice/day to maintain humidity and kept in a greenhouse at the day/night temperatures at 25 ± 2°C/16 ± 2°C. Lesions appeared 3 days later. No lesions were observed on control leaves. The same fungus was re-isolated from lesions. This is the first report of D. fusicola causing leaf blotch on O. fragrans. These results form the basis for developing effective strategies for monitoring and managing this potential high-risk disease.

8.
Bioengineered ; 11(1): 1084-1098, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33054494

RESUMO

The relationship between Cyclin-Dependent Kinase Inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) variants rs1333049 G/C and rs4977574 A/G and the risk of coronary heart disease is unclear. We conducted an update analysis incorporating odds ratios and 95% confidence intervals to assess the correlation. Furthermore, we used in silico analysis to investigate the genes and proteins that interact with CDKN2B. Fifty case-control studies with a sample size of 35,915 cases and 48,873 controls were involved. We revealed that the rs1333049 C allele could increase the risk of coronary heart disease in the overall analysis (allele comparison, OR = 1.13, 95%CI = 1.05-1.21, P = 0.001; homozygous contrast, OR = 1.29, 95%CI = 1.11-1.49, P = 0.001; dominant comparison, OR = 1.14, 95%CI = 1.03-1.27, P = 0.011; recessive comparison, OR = 1.21, 95%CI = 1.10-1.34, P < 0.001). In subgroup analysis, positive correlations were detected in studies involving West and East Asians and in population-based control studies. The rs4977574 G allele was also a risk factor for coronary heart disease (allelic comparison, P = 0.001; heterozygous comparison, P = 0.003; homozygous comparison, P < 0.001; dominant comparison, P = 0.001). These results indicate correlation of CDKN2B-AS1 rs1333049 G/C and rs4977574 A/G variants may be correlated with the risk of coronary heart disease. Abbreviations CDK: Cyclin Dependent Kinase; CCND: G1/S-specific cyclin-D; CDKN: Cyclin Dependent Kinase Inhibitor; GWAS: Genome-wide association study; CDKN2B-AS1: Cyclin-Dependent Kinase Inhibitors 2B Antisense RNA 1; CHD: Coronary heart disease; MAF: minor allele frequencies; HWE: Hardy-Weinberg equilibrium of controls; CI: confidence interval; COL8A2: Collagen type VIII alpha 2 chain; HB: Hospital-based; ORs: odds ratios; ITGA11: Integrin subunit alpha 11; LTBP: Latent transforming factor beta binding protein; PB: Population-based; IBC: Itmat Broad Care; NA: Not applicable; PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism; MI: Myocardial Infarction; SNP: single nucleotide polymorphism; SMAD: Mothers against decapentaplegic homolog; RT-PCR: Real-time polymerase chain reaction; UK: United Kingdom.

9.
J Med Virol ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064304

RESUMO

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections and there are currently no safer or more effective drugs available. It is important to find novel medications for RSV infection. A series of steroidal pyridines was synthesized for screening and evaluation of their antiviral activity, and investigation of their antiviral mechanism of action. Compound 3l had the highest antiviral activity, with a half maximal effective concentration (EC50 ) of 3.13 µM. 3l was explored for its effects in vitro on RSV 2 hours before infection (pretreatment), at the time of infection (competition), and 2 hours after infection (postinfection). Toll-like receptor (TLR)-3, retinoic acid-inducible gene (RIG)-I, interleukin (IL)-6 and interferon (IFN)-ß were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by 3l. Decreased expression of TLR-3, RIG-I, IL-6, IFN-ß and IL-10 was also found in vivo. The results indicated that compound 3l exerted its antiviral effects mainly through inhibition of viral replication and downregulation of inflammatory factors. This article is protected by copyright. All rights reserved.

10.
Pharmacotherapy ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064889

RESUMO

BACKGROUND: Cirrhotic patients are at a high risk of fungal infections. Voriconazole is widely used as prophylaxis and in the treatment of invasive fungal disease. However, the safety, pharmacokinetics and optimal regimens of voriconazole are currently not well defined in cirrhotic patients. DESIGN: Retrospective pharmacokinetics study SETTING: Two large, academic, tertiary-care medical center. PATIENTS: Two hundred and nineteen plasma trough concentrations (Cmin ) from 120 cirrhotic patients and 83 plasma concentrations from 11 non-cirrhotic patients were included. METHODS: Data pertaining to voriconazole were collected retrospectively. A population pharmacokinetics analysis was performed and model-based simulation was used to optimize voriconazole dosage regimens. RESULTS: Voriconazole-related adverse events (AEs) developed in 29 cirrhotic patients, and the threshold Cmin for AE was 5.12 mg/L. A two-compartment model with first-order elimination adequately described the data. The Child-Pugh class and body-weight were the significant covariates in the final model. Voriconazole clearance in non-cirrhotic, Child-Pugh class A and B cirrhotic (CP-A/B) and Child-Pugh class C cirrhotic (CP-C) patients was 7.59 L/h, 1.86 L/h and 0.93 L/h, respectively. The central distribution volume and peripheral distribution volume was 100.8 L and 55.2 L, respectively. The oral bioavailability was 91.6%. Model-based simulations showed that a loading dose regimen of 200 mg/12 h intravenously or orally led to 65.0% - 75.7% of voriconazole Cmin in therapeutic range on day 1, and the appropriate maintenance dosage regimens were 75 mg/12 h and 150 mg/24 h intravenously or orally for CP-A/B patients, and 50 mg/12 h and 100 mg/24 h intravenously or orally for CP-C patients. The predicted probability of achieving the therapeutic target concentration for optimized regimens at steady-state was 66.8% - 72.3% for CP-A/B patients and 70.3% - 74.0% for CP-C patients. CONCLULSIONS: These results recommended that the halved loading dose regimens should be used, and voriconazole maintenance doses in cirrhotic patients should be reduced to one-fourth for CP-C patients and to one-third for CP-A/B patients compared to that for patients with normal liver function.

11.
J Ethnopharmacol ; : 113473, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068649

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Metastasis is the main cause of death in lung cancer patients. Circulating tumor cells (CTCs) may be an important target of metastasis intervention. Previous studies have shown that Jinfukang could prevent the recurrence and metastasis of lung cancer, and we have established a circulating lung tumor cell line CTC-TJH-01. However, whether Jinfukang inhibition of lung cancer metastasis is related to CTCs is still unknown. AIM OF THE STUDY: To further explore the mechanism of Jinfukang in anti-metastasis of lung cancer from the perspective of intervention of CTCs. MATERIALS AND METHODS: CTC-TJH-01 and H1975 cells were treated with Jinfukang. Cell viability was detected by CCK8, and the cell apoptosis was detected by flow cytometry. Transwell was used to detected cell migration and invasion. Cell anoikis was detected by anoikis detection kit. Protein expression was analysis by western blot. RESULTS: Jinfukang could inhibit the proliferation, migration and invasion of CTC-TJH-01 and H1975 cells. Besides, Jinfukang could also induce anoikis in CTC-TJH-01 and H1975 cells. Analysis of the mRNA expression profile showed ECM-receptor interaction and focal adhesion were regulated by Jinfukang. Moreover, it was also find that Jinfukang significantly inhibited integrin/Src pathway in CTC-TJH-01 and H1975 cells. When suppress the expression of integrin with ATN-161, it could promote Jinfukang to inhibit migration and induce anoikis in CTC-TJH-01 and H1975 cells. CONCLUSIONS: Our results indicate that the migration and invasion of CTCs are inhibited by Jinfukang, and the mechanism may involve the suppression of integrin/Src axis to induce anoikis. These data suggest that Jinfukang exerts anti-metastatic effects in lung cancer may through anoikis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33052846

RESUMO

Accumulating efforts have been made to discover effective solutions for fatigue recovery with the ultimate aim of reducing adverse consequences of mental fatigue in real life. The previously-reported behavioral benefits of physical exercise on mental fatigue recovery prompted us to investigate the restorative effect and reveal the underlying neural mechanisms. Specifically, we introduced an empirical method to investigate the beneficial effect of physical exercise on the reorganization of EEG functional connectivity (FC) in a two-session experiment where one session including a successive 30-min psychomotor vigilance task (PVT) (No-intervention session) compared to an insertion of a mid-task 15-min cycling exercise (Intervention session). EEG FC was obtained from 21 participants and quantitatively assessed via graph theoretical analysis and a classification framework. The findings demonstrated the effectiveness of exercise intervention on behavioral performance as shown in improved reaction time and response accuracy. Although we found significantly altered network alterations towards the end of experiment in both sessions, no significant differences between the two sessions and no interaction between session and time were found in EEG network topology. Further interrogation of functional connectivity through classification analysis showed decreased FC in distributed brain areas, which may lead to the significant reduction of network efficiency in both sessions. Moreover, we showed distinct patterns of FC alterations between the two sessions, indicating different information processing strategies adopted in the intervention session. In sum, these results provide some of the first quantitative insights into the complex neural mechanism of exercise intervention for fatigue recovery and lead a new direction for further application research in real-world situations.

13.
J Neural Eng ; 17(5): 056021, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052888

RESUMO

OBJECTIVE: The data scarcity problem in emotion recognition from electroencephalography (EEG) leads to difficulty in building an affective model with high accuracy using machine learning algorithms or deep neural networks. Inspired by emerging deep generative models, we propose three methods for augmenting EEG training data to enhance the performance of emotion recognition models. APPROACH: Our proposed methods are based on two deep generative models, variational autoencoder (VAE) and generative adversarial network (GAN), and two data augmentation ways, full and partial usage strategies. For the full usage strategy, all of the generated data are augmented to the training dataset without judging the quality of the generated data, while for the partial usage, only high-quality data are selected and appended to the training dataset. These three methods are called conditional Wasserstein GAN (cWGAN), selective VAE (sVAE), and selective WGAN (sWGAN). MAIN RESULTS: To evaluate the effectiveness of these proposed methods, we perform a systematic experimental study on two public EEG datasets for emotion recognition, namely, SEED and DEAP. We first generate realistic-like EEG training data in two forms: power spectral density and differential entropy. Then, we augment the original training datasets with a different number of generated realistic-like EEG data. Finally, we train support vector machines and deep neural networks with shortcut layers to build affective models using the original and augmented training datasets. The experimental results demonstrate that our proposed data augmentation methods based on generative models outperform the existing data augmentation approaches such as conditional VAE, Gaussian noise, and rotational data augmentation. We also observe that the number of generated data should be less than 10 times of the original training dataset to achieve the best performance. SIGNIFICANCE: The augmented training datasets produced by our proposed sWGAN method significantly enhance the performance of EEG-based emotion recognition models.

14.
Adv Mater ; : e2002085, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015871

RESUMO

The highly immunosuppressive tumor microenvironment (TME) in solid tumors often dampens the efficacy of immunotherapy. In this study, bacterial outer membrane vesicles (OMVs) are demonstrated as powerful immunostimulants for TME reprogramming. To overcome the obstacles of antibody-dependent clearance and high toxicity induced by OMVs upon intravenous injection (a classic clinically relevant delivery mode), calcium phosphate (CaP) shells are employed to cover the surface of OMVs, which enables potent OMV-based TME reprograming without side effects. Meanwhile, the pH-sensitive CaP shells facilitate the neutralization of acidic TME, leading to highly beneficial M2-to-M1 polarization of macrophages for improved antitumor effect. Moreover, the outer shells can be integrated with functional components like folic acid or photosensitizer agents, which facilitates the use of the OMV-based platform in combination therapies for a synergic therapeutic effect.

15.
Phys Rev Lett ; 125(12): 127601, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33016718

RESUMO

Using first-principles calculations, we predict a lightweight room-temperature ferroelectric carbon-boron framework in a host-guest clathrate structure. This ferroelectric clathrate, with composition ScB_{3}C_{3}, exhibits high polarization density and low mass density compared with widely used commercial ferroelectrics. Molecular dynamics simulations show spontaneous polarization with a moderate above-room-temperature T_{c} of ∼370 K, which implies large susceptibility and possibly large electrocaloric and piezoelectric constants at room temperature. Our findings open the possibility for a new class of ferroelectric materials with potential across a broad range of applications.

16.
Inorg Chem ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33095003

RESUMO

Two DyIII complexes, [Dy(bbpen-F)X] [X = Cl (1), Br (2); H2bbpen-F = N,N'-bis(2-hydroxybenzyl)-N,N'-bis(5-fluoro-2-methylpyridyl)ethylenediamine], have been synthesized that show remarkable single-molecule-magnet behavior with effective barriers of magnetic reversal of 837.7 K for 1 and 1149.7 K for 2 under zero direct-current field and hysteresis loops up to 20 K for 1 and 30 K for 2, as confirmed by magnetic properties and ab initio calculations.

17.
Immun Inflamm Dis ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098626

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is one of the most common chronic immune joint diseases, mainly involving blood vessels and small joints. The complex pathogenesis of RA greatly increases the difficulty of treatment. At present, the common hormone and immunosuppressive therapy are not effective, while low-dose interleukin-2 (IL-2) recently has been found to possess some advantages for immunotherapy. However, its related signal pathway remains to be elucidated. METHODS: We fabricated the model of arthritis in mice, and then low-dose IL-2 was injected at a fixed time point to observe the changes of related vascular and organ pathology, inflammatory factors, and signal pathway proteins, which were verified by statistical analysis. RESULTS: Low dose IL-2 can reduce the severity of vascular and bone lesions in collagen-induced arthritis immune model, and inhibit osteoclast formation in vitro by phosphorylation of nuclear factor-κB (NF-κB), which inhibits the receptor activator of NF-κB ligand effect through c-Jun N-terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK. CONCLUSION: It is the first time for us to prove that low dose IL-2 can inhibit osteoclast formation in collagen-induced arthritis through the JNK dependent pathway, which will provide the angle and theoretical basis for future immunotherapy of IL-2.

18.
Toxicol Lett ; 334: 94-101, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010382

RESUMO

Silica dust mainly attacks alveolar macrophages (AMs). The apoptosis of AMs is correlated with the progress of silicosis. Our previous study showed that autophagic degradation was blocked in AMs from silicosis patients. However, the effects of nicotine on AM autophagy and apoptosis in silicosis are unknown. In this study, we collected AMs from twenty male workers exposed to silica and divided them into observer and silicosis patient groups, according to the tuberous pathological changes observed by X-ray. The AMs from both groups were exposed to nicotine. We found increased levels of LC3, p62, and cleaved caspase-3, decreased levels of LAMP2, and damaged lysosomes after nicotine stimulation of the AMs from both groups. We also found that the autophagy inhibitor 3-methyladenine (3MA) inhibited nicotine-induced apoptosis in the AMs. Furthermore, 3MA reversed both the nicotine-induced decrease in Bcl-2 and the increase in Bax in both groups. These results suggest that nicotine may induce apoptosis by blocking AM autophagic degradation in human silicosis.

19.
Biochemistry ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074652

RESUMO

Calcium binding to troponin C (TnC) activates striated muscle contraction by removing TnI (troponin I) from its inhibitory site on actin. Troponin T (TnT) links TnI with tropomyosin, causing tropomyosin to move from an inhibitory position on actin to an activating position. Positive charges within the C-terminal region of human cardiac TnT limit Ca2+ activation. We now show that the positively charged region of TnT has an even larger impact on skeletal muscle regulation. We prepared one variant of human skeletal TnT that had the C-terminal 16 residues truncated (Δ16) and another with an added C-terminal Cys residue and Ala substituted for the last 6 basic residues (251C-HAHA). Both mutants reduced (based on S1 binding kinetics) or eliminated (based on acrylodan-tropomyosin fluorescence) the first inactive state of actin at <10 nM free Ca2+. 251C-HAHA-TnT and Δ16-TnT mutants greatly increased ATPase activation at 0.2 mM Ca2+, even without high-affinity cross-bridge binding. They also shifted the force-pCa curve of muscle fibers to lower Ca2+ by 0.8-1.2 pCa units (the larger shift for 251C-HAHA-TnT). Shifts in force-pCa were maintained in the presence of para-aminoblebbistatin. The effects of modification of the C-terminal region of TnT on the kinetics of S1 binding to actin were somewhat different from those observed earlier with the cardiac analogue. In general, the C-terminal region of human skeletal TnT is critical to regulation, just as it is in the cardiac system, and is a potential target for modulating activity.

20.
Int J Mol Sci ; 21(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008068

RESUMO

With the successful completion of genomic sequencing for Brassica napus, identification of novel genes, determination of functions performed by genes, and exploring the molecular mechanisms underlying important agronomic traits were challenged. Mutagenesis-based functional genomics techniques including chemical, physical, and insertional mutagenesis have been used successfully in the functional characterization of genes. However, these techniques had their disadvantages and inherent limitations for allopolyploid Brassica napus, which contained a large number of homologous and redundant genes. Long intron-spliced hairpin RNA (ihpRNA) constructs which contained inverted repeats of the target gene separated by an intron, had been shown to be very effective in triggering RNAi in plants. In the present study, the genome-wide long ihpRNA library of B. napus was constructed with the rolling circle amplification (RCA)-mediated technology. Using the phytoene desaturase (PDS) gene as a target control, it was shown that the RCA-mediated long ihpRNA construct was significantly effective in triggering gene silence in B. napus. Subsequently, the resultant long ihpRNA library was transformed into B. napus to produce corresponding RNAi mutants. Among the obtained transgenic ihpRNA population of B. napus, five ihpRNA lines with observable mutant phenotypes were acquired including alterations in the floral model and the stamen development. The target genes could be quickly identified using specific primers. These results showed that the RCA-mediated ihpRNA construction method was effective for the genome-wide long ihpRNA library of B. napus, therefore providing a platform for study of functional genomics in allopolyploid B. napus.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA