Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 315
Filtrar
1.
Food Funct ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595580

RESUMO

As a functional bowel disorder, irritable bowel syndrome (IBS), especially IBS-diarrhea (IBS-D), affects approximately 9-20% of the population worldwide. Classical treatments for IBS usually result in some side effects and intestinal microbial disorders, which inhibit the clinical effects. Natural edible medicines with beneficial effects and few side effects have received more attention in recent years. Puerarin is the main active ingredient in pueraria and has been used in China to treat splenasthenic diarrhea and as a natural food in folk medicine for hundreds of years. However, there have been no reports of using puerarin in the treatment of IBS-D, and the underlying mechanism is also still unclear. In this study, a comprehensive model that could reflect the symptoms of IBS-D was established by combining neonatal maternal separation (NMS) and adult colonic acetic acid stimulation (ACAAS) in rats. The results showed that puerarin could reverse the abdominal pain and diarrhea in IBS-D rats. The therapeutic effect was realized by regulating the richness of the gut microbiota to maintain the stabilization of the intestinal micro-ecology. Furthermore, the possible mechanism might be related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis by the suppressed expression of corticotropin-releasing hormone receptor (CRF) 1. At the same time, intestinal function was improved by enhancing the proliferation of colonic epithelial cells by upregulating the expression of p-ERK/ERK and by repairing the colonic mucus barrier by upregulating occludin expression. All these results suggest that puerarin could exert excellent therapeutic effects on IBS-D.

2.
Virol Sin ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534085

RESUMO

Our recent study reported that ATP1B3 inhibits hepatitis B virus (HBV) replication via inducing NF-κB activation. However, ATP1B3 mutants which were defective in NF-κB activation still maintained the moderate degree of suppression on HBV replication, suggesting that another uncharacterized mechanism is also responsible for ATP1B3-mediated HBV suppression. Here, we demonstrated that ATP1B3 reduced the expression of HBV envelope proteins LHBs, MHBs and SHBs, but had no effect on intracellular HBV DNA, RNA levels as well as HBV promoter activities. Further investigation showed that proteasome inhibitor MG132 rescued ATP1B3-mediated envelope proteins degradation, demonstrating that proteasome-dependent pathway is involved in ATP1B3-induced degradation of envelope proteins. Co-IP showed that ATP1B3 interacts with LHBs and MHBs and induces LHBs and MHBs polyubiquitination. Immunofluorescence co-localization analysis confirmed LHBs and MHBs colocalized with ATP1B3 together. Our work provides important information for targeting ATP1B3 as a potential therapeutic molecule for HBV infection.

3.
Inorg Chem ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591741

RESUMO

A bifunctional ligand strategy for modification of the functional pores is of great significance in the structural design of metal-organic frameworks (MOFs). Herein, a new 2-fold interpenetrated "pillared-layer" 3D Co-MOF, {[Co(HL)(4,4'-bipy)]·DMF·2H2O}n (1), was successfully synthesized by using two kinds of ligands, imidazolecarboxylic acid and pyridine. The metal-carboxylic layers are pillared by the 4,4'-bipy ligand, displaying a 3D framework with rectangular 3D channels (high BET surface of 190.9 m2 g-1 and maximum aperture of 3.9 Å) that are decorated with abundant uncoordinated N and O atoms. 1 shows good water stability and thermal stability (320 °C). The proper pores and active sites endowed 1 with a selective adsorption of Congo red in aqueous solution. In addition, a high CO2 adsorption capacity and an excellent CO2 chemical conversion were observed.

4.
Sci Adv ; 7(4)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523945

RESUMO

Genetic diversity and phylogenetic diversity reflect the evolutionary potential and history of species, respectively. However, the levels and spatial patterns of genetic and phylogenetic diversity of wildlife at the regional scale have largely remained unclear. Here, we performed meta-analyses of genetic diversity in Chinese terrestrial vertebrates based on three genetic markers and investigated their phylogenetic diversity based on a dated phylogenetic tree of 2461 species. We detected strong positive spatial correlations among mitochondrial DNA-based genetic diversity, phylogenetic diversity, and species richness. Moreover, the terrestrial vertebrates harbored higher genetic and phylogenetic diversity in South China and Southwest China than in other regions. Last, climatic factors (precipitation and temperature) had significant positive effects while altitude and human population density had significant negative impacts on levels of mitochondrial DNA-based genetic diversity in most cases. Our findings will help guide national-level genetic diversity conservation plans and a post-2020 biodiversity conservation framework.

5.
Ann Hematol ; 100(3): 715-723, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33389024

RESUMO

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

6.
Ann Nucl Med ; 35(2): 139-147, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33460010

RESUMO

Alzheimer's disease (AD) is on the rise all over the world, and brings with it great challenges to medical care and heavy burdens to family and society. Accurate diagnosis and differential diagnosis are of great importance. Tau positron emission tomography (PET) might offer novel insights and be of great assistance in monitoring disease progression and supporting the differential diagnosis. 18F-AV-1451, as the first Tau PET imaging agent approved by the Food and Drug Administration (FDA), has been of great potential in clinical trials. Here, we reviewed the synthesis and characteristics of 18F-AV-1451 and its role in monitoring AD progression and supporting the differential diagnosis.

7.
J Inflamm Res ; 13: 961-968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262632

RESUMO

Sepsis is life-threatening organ dysfunction caused by an imbalance in the body's response to infection and acute lung injury (ALI) related to sepsis is a common complication. The rapid morbidity and high mortality associated with sepsis is a significant clinical problem facing critical care medicine. Inflammation plays a vital role in the occurrence of sepsis. Notably, the body produces different immune cells and pro-inflammatory factors to clear pathogens. However, excessive inflammation can damage multiple tissues and organs when it fails to resolve in time. Additionally, lymphatic vessels could effectively transfer inflammatory cells and factors away from tissues and into blood circulation, thereby reducing damage, and promoting the resolution of inflammation. Therefore, any dysfunction and/or destruction of the lymphatic system may result in lymphedema followed by inflammatory storms and eventual sepsis. Consequently, the present study aimed to review and highlight the role of lymphatic vessels in related body tissues and organs during sepsis and other associated diseases.

8.
Opt Lett ; 45(22): 6226-6229, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186956

RESUMO

Usually, the pump light in lasers should perform fast light owing to operating in the absorption band. In this study, we observe and demonstrate anomalous slowdown of the pump light in a Raman fiber laser. Experiments show that the pump light can be slowed down to sub-nanoseconds at a repetition rate of 50-500 MHz. Theoretical analysis shows that the hole-burning effect is formed at the Raman gain spectrum in the saturation regime, which imposes on the pump light by normal dispersion. Consequently, the pump light experiences an unusual slow light effect rather than the fast light effect after absorption. We believe it has promising potentials in the improvement of ultrashort pulse generation, and may have significant influence on improving the conversion efficiency in pulse-pumped laser systems.

9.
Phys Rev Lett ; 125(16): 163901, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33124849

RESUMO

We study theoretically and experimentally the subharmonic entrainment (SHE) breather soliton in mode-locked lasers for the first time, in which the ratio of the breather period to the round-trip time is an integer. We build a non-Hermitian degeneracy map of breather soliton, and illustrate that SHE arises between the two exceptional points (EPs). We obtain SHE at the ratio of 20, observe the evolution of breather soliton when tuning the gain and/or cavity loss, and prove that this phenomenon can improve the stability of breather soliton. Our research brings insight into the EP physics of ultrafast lasers and makes the mode-locked laser a powerful test bed for non-Hermitian degeneracy, which may open a new course in ultrafast laser research.

10.
Chin J Integr Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000415

RESUMO

OBJECTIVE: To observe the effects and safety of Tongyan Spray () on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia. METHODS: Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment. RESULTS: Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P<0.05). There were no obvious adverse reactions observed in oral mucosa in both groups during the whole study. CONCLUSION: Tongyan Spray was an effective and safe medicine for improving swallowing function in patients with ischemic post-stroke dysphagia.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33029166

RESUMO

Objective: To observe the influence of the catgut-embedding method in Du Meridian acupoint on the mental and psychological state of patients with gastroesophageal reflux disease (GERD) and analyze its possible mechanism. Methods: According to the random number table, 60 patients with GERD were randomly divided into groups of acupoint catgut embedding and Western medicine, 30 cases in each group. The acupoint group was given catgut embedment in the positive reaction points along the Du Meridian, while the Western medicine group received lansoprazole tablet. They were both treated for six weeks. Scores of Gastroesophageal Reflux Disease Questionnaire (GerdQ), Zung's Self-Rating Anxiety Scale (SAS), Zung's Self-Rating Depression Scale (SDS), and Health-Related Quality of Life Scale for GERD (GERD-HRQL) were measured before and after treatment to analyze and evaluate the differences of symptom scores and mental and psychological conditions between the two groups. Results: (1) The scores of GerdQ, GERD-HRQL, SAS, and SDS in the two groups both significantly decreased after treatment (P < 0.05), and those of the acupoint group were much lower than the Western medicine group (P < 0.05). (2) The total effective rate was 90.00% in the acupoint group and 53.33% in the Western medicine group, with a statistically significant difference (P < 0.05). (3) The correlation coefficients r between the GerdQ score and scores of SAS and SDS were 0.563 and 0.322, respectively, and those between the GERD-HRQL score and scores of SAS and SDS were, respectively, 0.506 and 0.435. Conclusion: (1) The main symptoms of GERD patients, such as acid reflux and heartburn, mental and psychological condition, and quality of life, were all improved in the two groups, but the efficacy in the acupoint group is superior to that of the Western medicine group. (2) The clinical symptoms and scores of patients' quality of life are positively correlated with the degree of their anxiety and depression. (3) The acupoint catgut-embedding method can effectively regulate the anxiety and depressive symptoms of patients, which complements the efficacy of proton-pump inhibitors and benefits a wider range of population.

12.
Int J Mol Sci ; 21(19)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992529

RESUMO

Novel H7N9 influenza virus transmitted from birds to human and, since March 2013, it has caused five epidemic waves in China. Although the evolution of H7N9 viruses has been investigated, the evolutionary changes associated with codon usage are still unclear. Herein, the codon usage pattern of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), was studied to understand the evolutionary changes in relation to host, epidemic wave, and pathogenicity. Both genes displayed a low codon usage bias, with HA higher than NA. The codon usage was driven by mutation pressure and natural selection, although the main contributing factor was natural selection. Additionally, the codon adaptation index (CAI) and deoptimization (RCDI) illustrated the strong adaptability of H7N9 to Gallus gallus. Similarity index (SiD) analysis showed that Homo sapiens posed a stronger selection pressure than Gallus gallus. Thus, we assume that this may be related to the gradual adaptability of the virus to human. In addition, the host strong selection pressure was validated based on CpG dinucleotide content. In conclusion, this study analyzed the usage of codons of two genes of H7N9 and expanded our understanding of H7N9 host specificity. This aids into the development of control measures against H7N9 influenza virus.

13.
Transbound Emerg Dis ; 67(6): 2901-2910, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32946195

RESUMO

Astroviruses (AstVs) are major causative agents of gastroenteritis in children and have been reported in many species. Canine astrovirus (CaAstV), as an enteric pathogen, has been widely detected worldwide, but little is known about their genetic diversity and evolution, partly owing to a lack of genomic data. Here, we sequenced 12 nearly full-length CaAstV genomes to address the gap in knowledge. We found 14 (13.2%) and 7 (3.35%) CaAstV-positive samples from pet dogs with and without diarrhoea, respectively. Co-infections were with co-infection with Torque teno canis virus (TTCaV) reported for the first time. Phylogenetic analysis of the ORF2 gene revealed four major lineages. In particular, lineage 4 might have evolved from a recombinant virus from lineage 2 and lineage 3. The strains sequenced here clustered with lineages 2, 3 and 4 in contrast with other Chinese strains identified previously that clustered with lineages 2 and 4. Amino acid sequence alignment within lineage revealed intralineage amino acid diversity and that the type of epidemic strains within lineages changes over time. Three amino acids substitutions located in predicted B-cell epitopes, which might be involved escape of host immunity. Moreover, frequent inter-clade ORF2 gene recombinants were identified. The identification of individual recombination events and a recombinant lineage indicated that recombination plays a crucial role in CaAstV genetic evolution and diversity by generating divergent viruses. Moreover, phylogenetic analysis of ORF1b, the most conserved gene of astrovirus, revealed a close relationship between CaAstV and California sea lion astroviruses. Overall, we report detailed information on the genetic evolution and diversity of CaAstV, which indicates that CaAstV may pose challenges for diagnostics and future control strategies.

14.
Sci Total Environ ; 738: 140269, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32806366

RESUMO

The niche divergence and potential climate change-induced loss of evolutionarily significant units (ESUs) of flagship amphibian species in China, the Chinese giant salamander clade, were investigated. We tested niche-related ecological hypotheses and identified suitable habitats that are essential for the conservation of ESUs in response to future climate change according to ecological niche models (ENMs). We predicted the localized habitat loss crisis of ESUs induced by global climate heating using the predicted climate derived from two representative concentration pathway (RCP) scenarios 2.6 and 8.5, respectively. In our study, a niche conservatism pattern was found between the two distinctive northern and southern ESUs with sufficient distributional records, but their niches were not equivalent. Furthermore, there was neither abrupt environmental change in nor remarkable biogeographic barriers between the suitable habitats of the species, as indicated by random linear, blob and ribbon range-breaking tests. Under the low-emission scenario RCP2.6, the northern ESU had a moderate loss of suitable range, while the southern ESU had range expansion in the 2070s. The climatic velocities were low in the ranges of both ESUs. However, under the high-emission scenario RCP8.5, the climatic velocities were found to become larger in the suitable ranges of both ESUs. Moreover, the northern ESU had severe habitat loss, bringing it to the edge of extinction, while the southern ESU also had intensified range loss. Considering this, climatic velocity can be an effective indicator of range loss. We argued conclusively that conservation prioritization of ESUs should effectively take into account the underlying geographic and ecological mechanisms driving the speciation process. The conservation of ESUs should consider the conservation of both evolutionary potential and ecological adaptation capacity of each lineage. The present study provided practical guidelines for repopulation programs for endangered species and the conservation of evolutionary diversity.


Assuntos
Anfíbios , Ecossistema , Animais , China , Mudança Climática , Espécies em Perigo de Extinção
15.
J Virol ; 94(21)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796072

RESUMO

Guanylate binding protein 5 (GBP5) belongs to the GTPase subfamily, which is mainly induced by interferon gamma (IFN-γ) and is involved in many important cellular processes, including inflammasome activation and innate immunity against a wide variety of microbial pathogens. However, it is unknown whether GBP5 inhibits respiratory syncytial virus (RSV) infection. In this study, we identified GBP5 as an effector of the anti-RSV activity of IFN-γ and found that in children, the weaker immune response, especially the weaker IFN-γ response and the decreased GBP5 expression, leads to RSV susceptibility. Furthermore, we revealed that GBP5 reduced the cell-associated levels of the RSV small hydrophobic (SH) protein, which was identified as a viroporin. In contrast, overexpression of the SH protein rescued RSV replication in the presence of GBP5. The GBP5-induced decrease in intracellular SH protein levels is because GBP5 promotes the release of the SH protein into the cell culture. Moreover, the GBP5 C583A mutants with changes at the C terminus or the GBP5 ΔC mutant lacking the C-terminal region, which impairs GBP5 localization in the Golgi, could not inhibit RSV infection, whereas the GTPase-defective GBP5 maintained RSV inhibition, suggesting that Golgi localization but not the GTPase activity of GBP5 is required for RSV inhibition. Interestingly, we found that RSV infection or RSV G protein downregulates GBP5 expression by upregulating DZIP3, an E3 ligase, which induces GBP5 degradation through the K48 ubiquitination and proteasomal pathways. Thus, this study reveals a complicated interplay between host restrictive factor GBP5 and RSV infection and provides important information for understanding the pathogenesis of RSV.IMPORTANCE RSV is a highly contagious virus that causes multiple infections in infants within their first year of life. It can also easily cause infection in elderly or immunocompromised individuals, suggesting that individual differences in immunity play an important role in RSV infection. Therefore, exploring the pathogenic mechanisms of RSV and identifying essential genes which inhibit RSV infection are necessary to develop an effective strategy to control RSV infection. Here, we report that the IFN-inducible gene GBP5 potently inhibits RSV replication by reducing the cell-associated levels of the RSV small hydrophobic (SH) protein, which is a viroporin. In contrast, the RSV G protein was shown to upregulate the expression of the DZIP3 protein, an E3 ligase that degrades GBP5 through the proteasomal pathway. Our study provides important information for the understanding of the pathogenic mechanisms of RSV and host immunity as well as the complicated interplay between the virus and host.

16.
Int J Immunopathol Pharmacol ; 34: 2058738420941756, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32664812

RESUMO

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK + ALCL) is most frequent in youth and possesses a broad morphologic spectrum. However, involvement in central nervous system (CNS) is definitely rare. The case we presented was a 12-year-old Chinese male who presented with headache and emesis for a couple of days. The neoplastic component was smaller cells resembling starry-sky growth pattern and immunohistochemical stained positively for CD30, ALK1, and CD56. Monoclonal T-cell receptor (TCRγ) gene rearrangement and gene translocation involving ALK identified by fluorescence in situ hybridization (FISH) using ALK break apart probe supported the diagnosis of ALK + ALCL. This case showed ALK + ALCL occur in a rare site with an abnormal CD56 expression. Awareness of this entity is important to distinguish it from other intracranial lymphoma.

17.
Materials (Basel) ; 13(11)2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32512830

RESUMO

This paper presents the results of an experimental investigation on the material properties and self-healing ability of a blended cement mortar incorporating blast furnace slag (BFS). The effect of different types and Blaine fineness of BFS on the material properties and self-healing was investigated. Thirteen cement mixtures with BFS of different types and degrees of Blaine fineness are tested to evaluate the mechanical properties, namely compressive strength, bending strength, freeze-thaw, and accelerated carbonation. The pore structure is examined by means of mercury intrusion porosimetry. Seven blended mortar mixtures incorporating BFS for cement are used to evaluate the mechanical properties after applying freeze-thaw cycles until the relative dynamic modulus of elasticity reached 60%. The experimental results reveal that incorporating BFS improves the mechanical properties and self-healing ability. In the investigation of self-healing, smaller particle and high replacement ratios of BFS contribute to increasing the relative dynamic modulus of elasticity and decreasing the carbonation coefficient in the mortar after re-water curing. Moreover, BFS's larger particles and high replacement ratio are found to provide better self-healing ability. A regression equation is created to predict the relative dynamic modulus of elasticity in mortar considering the Blaine fineness, BFS replacement ratio, and curing conditions.

18.
Sci Rep ; 10(1): 10333, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587295

RESUMO

Limited biomarkers have been identified as prognostic predictors for stage III colon cancer. To combat this shortfall, we developed a computer-aided approach which combing convolutional neural network with machine classifier to predict the prognosis of stage III colon cancer from routinely haematoxylin and eosin (H&E) stained tissue slides. We trained the model by using 101 cancers from West China Hospital (WCH). The predictive effectivity of the model was validated by using 67 cancers from WCH and 47 cancers from The Cancer Genome Atlas Colon Adenocarcinoma database. The selected model (Gradient Boosting-Colon) provided a hazard ratio (HR) for high- vs. low-risk recurrence of 8.976 (95% confidence interval (CI), 2.824-28.528; P, 0.000), and 10.273 (95% CI, 2.177-48.472; P, 0.003) in the two test groups, from the multivariate Cox proportional hazards analysis. It gave a HR value of 10.687(95% CI, 2.908-39.272; P, 0.001) and 5.033 (95% CI,1.792-14.132; P, 0.002) for the poor vs. good prognosis groups. Gradient Boosting-Colon is an independent machine prognostic predictor which allows stratification of stage III colon cancer into high- and low-risk recurrence groups, and poor and good prognosis groups directly from the H&E tissue slides. Our findings could provide crucial information to aid treatment planning during stage III colon cancer.

19.
Mol Cell Probes ; 53: 101618, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32534013

RESUMO

Viral canine diarrhea has high morbidity and mortality and is prevalent worldwide, resulting in severe economic and spiritual losses to pet owners. However, diarrhea pathogens have similar clinical symptoms and are difficult to diagnose clinically. Thus, fast and accurate diagnostic methods are of great significance for prevention and accurate treatment. In this study, we developed a one-step multiplex TaqMan probe-based real-time PCR for the differential diagnosis of four viruses causing canine diarrhea including, CPV (Canine Parvovirus), CCoV (Canine Coronavirus), CAstV (Canine Astrovirus), and CaKoV (Canine Kobuviruses). The limit of detection was up to 102 copies/µL and performed well with high sensitivity and specificity. This assay was optimized and used to identify possible antagonistic relationships between viruses. From this, artificial pre-experiments were performed for mixed infections, and a total of 82 canine diarrhea field samples were collected from different animal hospitals in Zhejiang, China to assess the method. The virus prevalence was significantly higher than what previously reported based on RT-PCR (Reverse Transcription-Polymerase Chain Reaction). Taken together, these results suggest that the method can be used as a preferred tool for monitoring laboratory epidemics, timely prevention, and effective monitoring of disease progression.


Assuntos
Sondas de DNA , Diarreia/veterinária , Doenças do Cão/virologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Animais , Avastrovirus , Coronavirus Canino , Diarreia/diagnóstico , Diarreia/virologia , Doenças do Cão/diagnóstico , Cães , Kobuvirus , Parvovirus Canino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32581100

RESUMO

NF-κB-interacting long noncoding RNA (NKILA) was recently identified as a negative regulator of NF-κB signaling and plays an important role in the development of various cancers. It is well known that NF-κB-mediated activation of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven gene expression is required for HIV-1 transcription and reactivation of latency. However, whether NKILA plays essential roles in HIV-1 replication and latency is unclear. Here, by ectopic expression and silencing experiments, we demonstrate that NKILA potently inhibits HIV-1 replication in an NF-κB-dependent manner by suppressing HIV-1 LTR promoter activity. Moreover, NKILA showed broad-spectrum inhibition on the replication of HIV-1 clones with different coreceptor tropisms as well as on LTR activity of various HIV-1 clinical subtypes. Chromatin immunoprecipitation (ChIP) assays revealed that NKILA expression abolishes the recruitment of p65 to the duplicated κB binding sites in the HIV-1 LTR. NKILA mutants disrupting NF-κB inhibition also lost the ability to inhibit HIV-1 replication. Notably, HIV-1 infection or reactivation significantly downregulated NKILA expression in T cells in order to facilitate viral replication. Downregulated NKILA was mainly due to reduced acetylation of histone K27 on the promoter of NKILA by HIV-1 infection, which blocks NKILA expression. Knockdown of NKILA promoted the reactivation of latent HIV-1 upon phorbol myristate acetate (PMA) stimulation, while ectopic NKILA suppressed the reactivation in a well-established clinical model of withdrawal of azidothymidine (AZT) in vitro These findings improve our understanding of the functional suppression of HIV-1 replication and latency by NKILA through NF-κB signaling.IMPORTANCE The NF-κB pathway plays key roles in HIV-1 replication and reactivation of HIV-1 latency. A regulator inhibiting NF-κB activation may be a promising therapeutic strategy against HIV-1. Recently, NF-κB-interacting long noncoding RNA (NKILA) was identified to suppress the development of different human cancers by inhibiting IκB kinase (IKK)-induced IκB phosphorylation and NF-κB pathway activation, whereas the relationship between NKILA and HIV-1 replication is still unknown. Here, our results show that NKILA inhibits HIV-1 replication and reactivation by suppressing HIV-1 long terminal repeat (LTR)-driven transcription initiation. Moreover, NKILA inhibited the replication of HIV-1 clones with different coreceptor tropisms. This project may reveal a target for the development of novel anti-HIV drugs.


Assuntos
HIV-1/fisiologia , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Latência Viral/fisiologia , Replicação Viral/fisiologia , Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos/virologia , Imunoprecipitação da Cromatina , Regulação Viral da Expressão Gênica , Células HEK293 , Infecções por HIV/virologia , Repetição Terminal Longa de HIV/fisiologia , HIV-1/genética , Humanos , Fosforilação , RNA Longo não Codificante/genética , RNA Longo não Codificante/farmacologia , Transdução de Sinais/efeitos dos fármacos , Latência Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA