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1.
J Ethnopharmacol ; 264: 113226, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32829054

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingganjiuwei powder (QGJWS) is a well-known traditional drug containing nine kinds of medicinal materials. This drug is commonly used in the Inner Mongolia region and exerts remarkable clinical effects on hepatic protection. AIM OF THE STUDY: To investigate whether QGJWS inhibits liver fibrosis in rats and to reveal its potential mechanisms. METHODS: Liver fibrosis model was induced by CCl4 for 8 weeks in SD rats. Next, rats were intragastrically administered quantum satis doses of QGJWS (0.525, 1.575, 4.725 g/kg per day) or Silymarin (SIL; 120 mg/kg per day) for 8 weeks. Afterwards, the rats were sacrificed, and serum aminotransferase (ALT and AST) levels, histopathological changes as well as the mRNA and protein expression of matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase1 (TIMP1), collagen type Ⅰ(COL1), α-smooth muscle actin (α-SMA), combined with phosphorylation levels of extracellular signal-regulated kinase (ERK), C-Jun amino-terminal kinases (JNKs) and stress-activated protein kinase-2 (p38) protein in liver tissues were measured in each groups, respectively. RESULTS: The symptoms and signs of the model rats were consistent with the diagnostic criteria of liver fibrosis. By contrast, treatment with QGJWS clearly improved the general condition of rats. Also, the morphology and structure of liver can be ameliorated, there are fewer hepatocyte necrosis and lymphocytic infiltration and pseudolobuli in QGJWS treatment groups as demonstrated by histopathological analysis, thus helping bring about lower METAVIR scores. QGJWS administration also dramatically decreased serum ALT and AST levels. Further immunohistochemistry, western blotting and Real-Time PCR analysis revealed that QGJWS significantly enhanced the mRNA and protein expression of MMP2, MMP9, and downregulated the expression levels of COL1, TIMP1 and α-SMA. Furthermore, QGJWS reduced the activities of mitogen-activated protein kinases (MAPKs) pathway in liver by inhibited the phosphorylation of ERK, JNKs and p38 proteins. CONCLUSIONS: QGJWS offers notable protection against CCl4-induced liver fibrosis in rats, which may be due to its ability to inhibited the MAPKs signaling pathway.

2.
Front Endocrinol (Lausanne) ; 11: 598948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193111

RESUMO

Purpose: Cardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility. Methods: In this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy. Results: Preoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3rd postoperative month and persisted until the 12th month. The interventricular septum was initially thickened in the 3rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels. Conclusion: Our findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility.

3.
Genome Med ; 12(1): 105, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239103

RESUMO

BACKGROUND: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. METHODS: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. RESULTS: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7). CONCLUSIONS: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

4.
Transbound Emerg Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155433

RESUMO

In this study, we introduce a vulnerability index to measure the regional ASF epidemic and present the ASF severity ratings of the 31 provinces of mainland China. The index is defined based on the data from the investigation, national statistical yearbook and reports. The data to be used include pig breeding, financial resources, human resources, epidemic information of ASF and price fluctuation from the 31 provinces. Then, we use the data envelopment analysis (DEA) method to define the vulnerability index, the relative severity value for each region, which quantitatively reflects the damage degree caused by the epidemic of ASF. The method allows us to provide a systematic classification for the regional vulnerability level of ASF in China. Using this index, we find that the vulnerability of the whole country is at a high level, and there is no regional aggregation phenomenon. The vulnerability level of the 31 provinces is quite different and the provinces with high vulnerability level are dispersive geographically. For the five major prevention and control zones for ASF in China, the northern region has the highest vulnerability level, while the eastern zoon level is the lowest.

5.
BMC Complement Med Ther ; 20(1): 369, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246450

RESUMO

BACKGROUND: Liquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine. In the previous study we found the anti-breast cancer effect of triterpenoid in Liquidambaris Fructus. This study is a further investigation of the triterpenoids in Liquidambaris Fructus and aims to identify their anti-breast cancer targets, meanwhile, to estimate the rationality of the traditional applications of Liquidambaris Fructus. METHODS: Triterpenoids in Liquidambaris Fructus were isolated and their structures were identified by NMR spectrums. Potential targets of these triterpenoids were predicted using a reverse pharmacophore mapping strategy. Associations between these targets and the therapeutic targets of breast cancer were analyzed by constructing protein-protein interaction network, and targets played important roles in the network were identified using Molecular Complex Detection method. Binding affinity between the targets and triterpenoids was studied using molecular docking method. Gene ontology enrichment analysis was conducted to reveal the biological process and signaling pathways that the identified targets were involved in. RESULTS: Thirteen triterpenoids were identified and 6 of them were the first time isolated from Liquidambaris Fructus. Predicted ADME properties revealed a good druggability of these triterpenoids. We identified 18 protein targets which were closely related to breast cancer progression, especially triple-negative, basal-like or advanced stage breast cancers. The triterpenoids could bind with these targets as their inhibitors: hydrophobic skeleton is a favorable factor for them to stabilize at binding site and polar C17- or C3- substituent was necessary for binding. GO enrichment analysis indicated that inhibition of protein tyrosine kinases autophosphorylation might be the primary mechanism for the anti-breast cancer effect of the triterpenoids, and ErbB4 and EGFR were the most relevant targets. CONCLUSIONS: The study revealed that triterpenoids from Liquidambaris Fructus might exert anti-breast cancer effect by directly inhibit multiple protein targets and signaling pathways, especially ErbB4 and EGFR and related pathways. This study also brings up another hint that the traditional applications of Liquidambaris Fructus on hypogalactia should be reassessed systematically because it might suppress rather than promote lactation by inhibiting the activity of ErbB4.

6.
Biomed Pharmacother ; 131: 110796, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152952

RESUMO

The acoustic radiation forces produced by ultrasonic stimulation induce shear stress on objects in the acoustic field. Piezo1, a mechanosensitive ion channel protein that is expressed on the plasma membranes of vertebrate cells, can sense shear stress and transduce it into downstream signaling. In this study, we examined the sensitivity of Piezo1 to ultrasonic stimulation and assessed its downstream biological functions in human umbilical vein endothelial cells (HUVECs). Ultrasonic stimulation using a stimulation power of 0.2 W and a frequency of 1 MHz for 10 s did not induce cell damage. However, ultrasonic stimulation induced an influx of calcium ions, which increased with an increase in the stimulation duration. Knockdown of Piezo1 protein decreased the influx of calcium ions during ultrasonic stimulation, which demonstrated that Piezo1 may be activated by the shear stress produced by ultrasonic stimulation. The influx of calcium ions in response to ultrasonic stimulation could be modulated by the Piezo1 protein level. Additionally, ultrasonic stimulation reduced the levels of downstream factors such as MLCK and ATP, which are involved in the Ca2+/CaM/MLCK pathway, by suppressing Piezo1. As the Ca2+/CaM/MLCK pathway influences the permeability of the cell membrane, the internalization of FITC-Dextran into cells under ultrasonic stimulation was validated. Ultrasonic stimulation was demonstrated to promote the increase in cell permeability, and the suppression of Piezo1 was shown to induce the decrease in cell permeability. Therefore, this study shows that ultrasonic stimulation may modulate the permeability of the membrane of HUVECs by modulating the expression of Piezo1 protein.

7.
FASEB J ; 34(12): 16243-16261, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070362

RESUMO

Our previous research revealed that steroid receptor coactivators (Src)-1 and -2 serve a critical cooperative role in production of parturition signals, surfactant protein A and platelet-activating factor, by the developing mouse fetal lung (MFL). To identify the global landscape of genes in MFL affected by Src-1/-2 double-deficiency, we conducted RNA-seq analysis of lungs from 18.5 days post-coitum (dpc) Src-1-/- /-2-/- (dKO) vs. WT fetuses. One of the genes most highly downregulated (~4.8 fold) in Src-1/-2 dKO fetal lungs encodes 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which catalyzes conversion of inactive 11-dehydrocorticosterone to the glucocorticoid receptor (GR) ligand, corticosterone. Glucocorticoids were reported to upregulate 11ß-HSD1 expression in various cell types via induction of C/EBP transcription factors. We observed that C/ebpα and C/ebpß mRNA and protein were markedly reduced in Src-1/-2 double-deficient (Src-1/-2d/d ) fetal lungs, compared to WT. Moreover, glucocorticoid induction of 11ß-hsd1, C/ebpα and C/ebpß in cultured MFL epithelial cells was prevented by the SRC family inhibitor, SI-2. Cytokines also contribute to the induction of 11ß-HSD1. Expression of IL-1ß and TNFα, which dramatically increased toward term in lungs of WT fetuses, was markedly reduced in Src-1/-2d/d fetal lungs. Our collective findings suggest that impaired lung development and surfactant synthesis in Src-1/-2d/d fetuses are likely caused, in part, by decreased GR and cytokine induction of C/EBP and NF-κB transcription factors. This results in reduced 11ß-HSD1 expression and glucocorticoid signaling within the fetal lung, causing a break in the glucocorticoid-induced positive feedforward loop.

8.
Sci Adv ; 6(42)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33055157

RESUMO

We uncover a cycling and NF-κB-driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two κB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbα is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbα (a known dual NF-κB/Nlrp3 repressor) to inactivate NF-κB signaling and Nlrp3 inflammasome in macrophages. Furthermore, Lnc-UC ablation sensitizes mice to experimental colitis and abolishes the diurnal rhythmicity in disease severity. Mechanistically, Lnc-UC physically interacts with Cbx1 protein to reduce its gene silencing activity via H3K9me3, thereby enhancing Rev-erbα transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbα expression and restrain inflammations.

9.
Disaster Med Public Health Prep ; : 1-16, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33100249

RESUMO

Based on the public data from the health departments of Tianjin and Shenzhen, we conducted a comparative analysis of the corona virus disease 2019 (COVID-19) epidemic situation between these two cities. The aim of this study was to evaluate the role of public data in epidemic prevention and control of COVID-19, providing a scientific advice for the subsequent mitigation and containment of COVID-19 prevalence.

10.
Eur J Endocrinol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112282

RESUMO

BACKGROUND: Facial abnormality is the most significant feature in acromegaly patients. However, it is unclear whether and how patient facial appearance improves after treatment. This study aimed to identify 3D facial changes in acromegaly patients after surgical treatment. METHODS: This study included 30 acromegaly patients who underwent resection of a pituitary GH adenoma. The location and extent of facial changes were identified by comparing baseline and 2-year follow-up 3D images of the face. Relationships between facial changes and GH and IGF-1 were evaluated with simple or multivariable linear regression models. RESULTS: Significant soft tissue improvements were observed in acromegaly patients with complete remission, especially in the nose and lip region. Significant reductions in nasal width (3.46 mm, p < 0.001), tip protrusion (1.18 mm, p=0.003), face curve length (3.89 mm, p=0.004) and vermilion area (1.42 cm3, p=0.001) were observed at the 2-year follow-up. Further, changes in nasal width were associated with decreases in GH (ß=4.440, p=0.017), the GH nadir (ß=4.393, p=0.011) and IGF-1 (ß=5.263, p=0.002). The associations were maintained after adjusting for confounders. CONCLUSIONS: Acromegaly patients achieved considerable facial improvements after surgical treatment. The change in nose width was associated with GH and IGF-1 decreases. Better control of patient hormone levels after surgery improves patient facial recovery.

11.
Nat Prod Res ; : 1-8, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043693

RESUMO

Four new triterpene glucosides (1-4) were isolated from the 90% ethanol extract of Salacia cochinchinensis, together with five known compounds (5-9). The structures of the new compounds were elucidated by comprehensive spectroscopic analysis including HRESIMS, IR, 1 D and 2 D NMR analysis. All isolates were assayed for their α-glucosidase inhibitory activity. Compound 9 showed remarkable α-glucosidase inhibitory activity with an IC50 value of 0.31 µM, and the triterpene glycosides (1-5) exhibited moderate α-glucosidase inhibitory activity.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33031533

RESUMO

CONTEXT: The accumulation of aberrant lipids and abnormal lipid metabolism in silent corticotroph adenomas (SCAs) could contribute to changes in clinical phenotypes, especially sphenoid sinus invasion. OBJECTIVE: To systematically investigate lipidomic and transcriptomic alterations associated with invasiveness and their potential molecular mechanisms in SCAs and to provide candidate biomarkers for predicting invasiveness and novel treatment options for invasive SCAs by targeting lipids. METHODS: Fifty-four SCAs (34 invasive/20 noninvasive) were subjected to lipidomic analysis based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), and 42 clinically nonfunctioning pituitary adenomas (23 invasive/19 noninvasive) were subjected to transcriptomic analysis. Differential analysis was performed to determine differential lipids and genes between invasive and noninvasive tumors. A functionally connected network was constructed with the molecular pathways as cores. Multiple machine learning methods were applied to identify the most critical lipids, which were further used to construct a lipidomic signature to predict invasive SCAs by multivariate logistic regression, and its performance was evaluated by receiver operating characteristic analysis. RESULTS: Twenty-eight differential lipids were identified, and a functionally connected network was constructed with 2 lipids, 17 genes, and 4 molecular pathways. Connectivity Map (CMap) analysis further revealed 32 potential drugs targeting 4 genes and related pathways. Then, the four most critical lipids were identified as risk factors contributing to the invasive phenotype. A lipidomic signature was constructed and showed excellent performance in discriminating invasive and noninvasive SCAs. CONCLUSIONS: The lipidomic signature could serve as a promising predictor for the invasive SCA phenotype and provide potential therapeutic targets for SCAs.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33079177

RESUMO

CONTEXT: Quality of life (QoL) continues to be impaired in acromegaly after treatment. OBJECTIVE: We conducted the first nationwide survey assessing QoL status among Chinese patients with treated acromegaly and explored correlations with clinical parameters, treatment modalities and outcomes. DESIGN: Cross-sectional study. SETTING: Survey via Chinese Association of Patients with Acromegaly (CAPA) online platform. PATIENTS: Treated patients from CAPA. MAIN OUTCOME MEASURES: QoL was assessed using acromegaly QoL questionnaire (AcroQoL), five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), and 12-item short-form health survey questionnaire (SF-12). RESULTS: Complete, valid questionnaires from 327 patients (mean age: 39.2 years, 61.5% females) at a mean of 10 years after treatment were included. Biochemical control was satisfied in 52.9% of these patients. The controlled patients had significantly better QoL than the uncontrolled patients in all AcroQoL dimensions, most SF-12 dimensions, and pain/discomfort and anxiety/depression dimensions of the EQ-5D-5L. Patients with either controlled or uncontrolled acromegaly had significantly worse QoL than the age- and sex-adjusted population reference in most SF-12 dimensions except for physical functioning. More acromegaly-associated symptoms and comorbidities at follow-up were independent risk factors for decreased QoL across all questionnaires. Medical treatment, especially with somatostatin analogs (SSAs), and radiotherapy were predictors of worse QoL. Female patients had lower scores of physical-related QoL than male patients. CONCLUSIONS: Our study suggests that biochemical control improved but did not normalize QoL in acromegaly. Numbers of symptoms and comorbidities at follow-up, sex, radiotherapy, and medical treatment with SSAs were factors determining QoL of patients with treated acromegaly.

14.
Aging (Albany NY) ; 12(18): 18297-18321, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957084

RESUMO

Glioblastoma (GBM) is the most common and lethal primary brain tumor. In this study, we aimed to investigate the differentiation states of GBM cells and their clinical relevance. Integrated single-cell RNA-sequencing (scRNA-seq) data and bulk RNA-seq data from GBM samples were used for analysis. Two subsets of GBM cells in distinct differentiation states were characterized, and 498 GBM cell differentiation-related genes (GDRGs) were identified. GDRGs were significantly correlated with immune regulation and metabolic pathways. We classified the GBM patients into two groups based on the expression of GDRGs in tumors and found that the cell differentiation-based classification successfully predicted patient overall survival (OS), immune checkpoint expression and likelihood of immunotherapy response in GBMs. FN1, APOE, RPL7A and GSTM2 were the 4 most significant survival-predicting GDRGs, and patients with different expression levels of each of these genes had distinct survival outcomes. Finally, a nomogram composed of the GDRG signature, age, pharmacotherapy, radiotherapy, IDH mutations and MGMT promoter methylation was generated and validated in two large GBM cohorts to predict GBM prognosis. This study highlights the significant roles of cell differentiation in predicting the clinical outcomes of GBM patients and their potential response to immunotherapy, suggesting promising therapeutic targets for GBM.

15.
Int J Nanomedicine ; 15: 6327-6338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922004

RESUMO

Purpose: To construct a three-dimensional (3D) culture model of adenovirus in vitro using the nanoself-assembling peptide RADA16-I as a 3D cell culture scaffold combined with virology experimental technology to provide a novel research method for virus isolation and culture, pathogenesis research, antiviral drug screening and vaccine preparation. Methods: The nanoself-assembling peptide RADA16-I was used as a 3D scaffold material for 293T cell culture, and adenovirus was cultured in the cells. The growth, morphological characteristics and pathological effects of 3D-cultured 293T cells after adenovirus infection were observed with an inverted microscope and MTS. The proliferation of adenovirus in 293T cells was observed by TEM and detected by qPCR. The levels of TNF-α and IL-8 secreted by adenovirus-infected 293T cells in the RADA16-I 3D culture system were detected by ELISA. Results: The 293T cells grew well in the RADA16-I 3D culture system for a prolonged period of time. The adenovirus infection persisted for a long time with multiple proliferation peaks, which closely resembled those of in vivo infections. The adenovirus virions amplified in the 3D system remained infectious. There were multiple secretion peaks of TNF-α and IL-8 secretion levels in adenovirus-infected 293T cells cultured in 3D culture systems. Conclusion: The nanoself-assembling peptide RADA16-I can be used as a 3D scaffold for adenovirus isolation, culture and research. The 3D culture system shows more realistic in vivo effects than two-dimensional (2D) culture.


Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/fisiologia , Técnicas de Cultura de Células/métodos , Nanopartículas/química , Peptídeos/química , Adenoviridae/crescimento & desenvolvimento , Adenoviridae/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células HEK293 , Humanos , Vírion/ultraestrutura
16.
Antiviral Res ; 183: 104933, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32949635

RESUMO

Stimulator of interferon genes (STING), as a signaling hub in innate immunity, plays a central role for the effective initiation of host defense mechanisms against microbial infections. Upon binding of its ligand cyclic dinucleotides (CDNs) produced by the cyclic GMP-AMP synthase (cGAS) or invading bacteria, STING is activated, leading to the induction of both type I interferon responses and autophagy, which are critical for the control of certain microbial infections. RNA viruses, such as Parainfluenza virus (PIV) and Rhinovirus (HRV), are among the leading causes of respiratory infections that affect human health without effective treatments. Activation of STING pathway may provide a new therapeutic approach fighting against these viruses. However, the role of STING in the control of RNA virus infection remains largely unexplored. In this study, using dimeric amidobenzimidazole (diABZI), a newly discovered synthetic small molecule STING receptor agonist with much higher potency than CDNs, we found that activation of STING elicits potent antiviral effects against parainfluenza virus type 3 (PIV3) and human rhinovirus 16 (HRV16), two representative respiratory viral pathogens. Notably, while anti-PIV3 activity was depend on the induction of type I interferon responses through TANK-binding kinase 1 (TBK1), anti-HRV16 activity required the induction of autophagy-related gene 5 (ATG5)-dependent autophagy, indicating that two distinct antiviral mechanisms are engaged upon STING activation. Antiviral activity and individual specific pathway was further confirmed in infected primary bronchial epithelial cells. Our findings thus demonstrate the distinct antiviral mechanisms triggered by STING agonist and uncover the potential of therapeutic effect against different viruses.

17.
J Adv Nurs ; 76(12): 3623-3630, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32951241

RESUMO

AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.

18.
Pestic Biochem Physiol ; 170: 104700, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980067

RESUMO

Argonautes (Ago) are important core proteins in RNA interference (RNAi) pathways of eukaryotic cells. Generally, it is thought that Ago1, Ago2 and Ago3 are involved in the miRNA (microRNA), siRNA (small interfering RNA) and piRNA (Piwi-interacting RNA)-mediated RNAi pathways, respectively. As a main component of the RNA-induced silencing complex (RISC), Ago2 plays an indispensable role in using siRNA to recognize and cut target messenger RNAs resulting in suppression of transcript levels, but the contributions of Ago1 and Ago3 to the siRNA-mediated RNAi pathway remain to be explored in many insect species. In this study, we investigated the contributions of four Ago genes (named LmAgo1, LmAgo2a and LmAgo2b and LmAgo3) to RNAi efficiency in Locusta migratoria by using both in vivo and in vitro experiments. Our results showed that suppression of each of the Ago genes significantly impaired RNAi efficiency when targeting Lmß-tubulin transcripts, resulting in recovery of 48, 43.3, 61.4 or 26% of Lmß-tubulin transcripts following RNAi-mediated suppression of LmAgo1, LmAgo2a, LmAgo2b, and LmAgo3, respectively. Furthermore, overexpression of LmAgo1, LmAgo2a, LmAgo2b, or LmAgo3 in a PAc5.1-V5/HisB vector and co-transfection with psicheck2 fluorescence vector in S2 cells reduced luciferase fluorescence by 38.3, 58.9, 53.3 or 55.6%, respectively. Taken together, our results showed that LmAgo1, LmAgo2a, LmAgo2b, and LmAgo3 each make significant contributions to RNAi efficiency in L. migratoria and suggest that the involvement of all four enzymes could be one of the major factors supporting robust RNAi responses observed in this species.


Assuntos
Locusta migratoria/genética , MicroRNAs/genética , Animais , Proteínas Argonauta/genética , Interferência de RNA , RNA de Cadeia Dupla/genética , RNA Interferente Pequeno/genética
19.
Aging (Albany NY) ; 12(17): 17038-17061, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32857727

RESUMO

The hypoxic tumor microenvironment (TME) was reported to promote the aggressive phenotype, progression, recurrence, and chemoresistance of glioblastoma (GBM). We developed and validated a hypoxia gene signature for individualized prognostic prediction in GBM patients. In total, 259 GBM-specific hypoxia-related genes (HRGs) were obtained in hypoxic cultured GBM cells compared with normoxic cells. By applying the k-means algorithm, TCGA GBM patients were divided into two subgroups, and the patients in Cluster 1 exhibited high HRG expression patterns, older age, and poor prognosis, which was validated in the CGGA cohort. Cox regression analyses were performed to generate an HRG-based risk score model consisting of five HRGs, which could reliably discriminate the overall survival (OS) and progression-free survival (PFS) of high- and low-risk patients in both the TCGA training and CGGA validation cohorts. Then, nomograms with the hypoxia signature for OS and PFS prediction were constructed for individualized survival prediction, better treatment decision-making, and follow-up scheduling. Finally, functional enrichment, immune infiltration, immunotherapy response prediction and chemotherapy resistance analyses demonstrated the vital roles of the hypoxic TME in the development, progression, multitherpy resistance of GBM. The hypoxia gene signature could serve as a promising prognostic predictor and potential therapeutic target to combat chemoresistant GBM.

20.
Br J Nutr ; : 1-14, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32792039

RESUMO

To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows' diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows' diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1-PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.

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