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1.
J Immunol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046503

RESUMO

Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.

2.
NPJ Biofilms Microbiomes ; 6(1): 39, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046723

RESUMO

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. To define the HPV-associated microbial community among a high vaccination coverage population, we carried out a cross-sectional study with 345 young Swedish women. The microbial composition and its association with HPV infection, including 27 HPV types, were analyzed. Microbial alpha-diversity was found significantly higher in the HPV-infected group (especially with oncogenic HPV types and multiple HPV types), compared with the HPV negative group. The vaginal microbiota among HPV-infected women was characterized by a larger number of bacterial vaginosis-associated bacteria (BVAB), Sneathia, Prevotella, and Megasphaera. In addition, the correlation analysis demonstrated that twice as many women with non-Lactobacillus-dominant vaginal microbiota were infected with oncogenic HPV types, compared with L. crispatus-dominated vaginal microbiota. The data suggest that HPV infection, especially oncogenic HPV types, is strongly associated with a non-Lactobacillus-dominant vaginal microbiota, regardless of age and vaccination status.

3.
J Card Surg ; 35(10): 2559-2566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043654

RESUMO

BACKGROUND: Few data are available on the association between postoperative serum uric acid (SUA) level and poor survival in patients undergoing coronary artery bypass grafting (CABG). We evaluated the relationship between postoperative SUA and major adverse cardiac and cerebrovascular events (MACCE) among patients undergoing CABG. METHODS: This study used data from 1614 consecutive patients undergoing CAGB at Fuwai Hospital (Beijing, China) from 2011 to 2015. Patients were stratified into statistical quartiles of postoperative SUA (between 6 and 18 hours after cardiac surgery): less than 203.7, 203.7 to 254.1, 254.1 to 316.6, and ≥316.6 µmol/L. The association of postoperative SUA with MACCE (ie, death, myocardial infarction [MI], stroke, or repeat revascularization) and the composite endpoint of mortality/MI were assessed. RESULTS: Patients had a mean age of 60.3 ± 8.4 years, and 79.3% were male. During mean follow-up of 2.5 ± 0.7 years, MACCE occurred in 201 (12.5%) patients. In separate multivariable regression models, postoperative SUA level was positively associated with in-hospital MACCE (highest vs lowest SUA quartile: odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.29, 4.48; P = .006) and in-hospital composite endpoint of mortality/MI (OR: 2.88; 95% CI: 1.45, 5.72; P = .003), respectively. And elevated postoperative SUA level was independently associated with MACCE (Hazard ratio [HR]: 1.70; 95% CI: 1.12, 2.57; P = .01) and the composite endpoint of mortality/MI (HR: 2.42; 95% CI: 1.32, 4.43; P = .004) respectively within 3 years after CABG. CONCLUSIONS: Elevated postoperative SUA level is associated with poor clinical outcomes after CABG. Patients with high postoperative SUA levels after CABG might require to be closely monitored.

4.
Euro Surveill ; 25(40)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33034281

RESUMO

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

5.
Bioresour Technol ; 318: 124202, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035945

RESUMO

Pilot-scale saturated vertical flow constructed wetlands (VF-CWs) were established to identify whether T. tubifex has the similar performance in saturated VF-CWs to that in surface flow CWs in improving pollutant removal efficiency (RE). The saturated VF-CWs with T. tubifex achieved REs of 67.3% total nitrogen (TN) and 39.8% chemical oxygen demand (COD), which were significantly higher than treatments without T. tubifex (42.2% TN and 31.4% COD). There existed significant interactions between macrophytes and T. tubifex. T. tubifex greatly improved the dissolved oxygen by increasing the connectivity between layers, and enhanced dehydrogenase activity and fluorescein diacetate. Adding T. tubifex improved the bacterial diversity and relative abundance of both N-cycle bacteria and fermentation bacteria in the biofilms. The improvements of ammonia oxidation and anammox were the main pathways for the increased nitrogen removal by T. tubifex. Therefore, T. tubifex is a useful tool for improving pollutant REs in saturated VF-CWs.

6.
Stem Cell Res Ther ; 11(1): 434, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032649

RESUMO

BACKGROUND: The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE: To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS: Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS: Treatment BMSCs with 50 µM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3ß. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS: The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

7.
Asian J Androl ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33037173

RESUMO

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

8.
J Magn Reson Imaging ; : e27390, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037745

RESUMO

BACKGROUND: Treatment regimens and prognoses of gastrointestinal stromal tumors (GIST) are quite different for tumors in different risk categories. Accurate preoperative grading of tumors is important for avoiding under- or overtreatment. PURPOSE: To develop and validate an MRI texture-based model to predict the mitotic index and its risk classification. STUDY TYPE: Retrospective. POPULATION: Ninety-one patients with histologically-confirmed GIST; 64 patients in a training cohort, and 27 patients in a test cohort. FIELD STRENGTH/SEQUENCE: T2 -weighted imaging (T2 WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced three-dimensional volumetric interpolated breath-hold examination (3D-VIBE) at 1.5T. ASSESSMENT: GIST images were manually segmented by two independent radiologists using ITK-SNAP software and MRI features were extracted using Pyradiomics. Two pathologists reviewed the tissue specimens of the tumors to identify the mitotic index and risk classification in consensus. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. A logistic regression model was established based on the radiomic score (radscore), tumor location, and maximum diameter to predict tumor classification and develop a nomogram. Receiver operator characteristic (ROC) curves were used to evaluate the ability of the nomogram to distinguish between two tumors with different risk classifications, and a calibration curve was used to evaluate the consistency between the predicted risk and the actual risk. RESULTS: The texture signature achieved high efficacy in predicting the mitotic index area under the curve ([AUC], 0.906; 95% confidence interval [CI]: 0.813, 0.961). A nomogram for prediction of the risk classification of GIST, which incorporated this texture signature together with maximum tumor diameter and location, allowed good discrimination in the training cohort (AUC, 0.878; 95% CI: 0.769, 0.960) and the validation cohort (AUC, 0.903; 95% CI: 0.732, 0.922). DATA CONCLUSION: The texture-based model can be used to predict GIST mitotic index and risk classification preoperatively. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3.

9.
Parkinsonism Relat Disord ; 80: 65-72, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32961396

RESUMO

INTRODUCTION: Genetic inheritance plays key roles in patients with ataxia and/or spastic paraplegia in consanguineous families. This study aims to clarify the genetic spectrum of patients with autosomal recessive hereditary ataxia and spastic paraplegias (AR-HA/HSPs) in consanguineous families. METHODS: A total of 36 AR-HA/HSPs consanguineous pedigrees from China were recruited into this study. Next generation sequencing (NGS), guided by homozygosity mapping (HM), was applied to identify the pathogenic variants in known genes or novel candidate genes. RESULTS: We totally made molecular diagnosis in 47.2% (17/36) of AR-HA/HSPs families. Among them, 13 AR-HAs carried pathogenic variants in SETX (n = 4), SACS (n = 2), STUB1, HSD17B4, NEU1, ADCK3, TPP1, PLA2G6 and MTCL1, while four AR-HSPs carried pathogenic variants in SPG11, ZFYVE26, ATP13A2 and ABCD1. One homozygous nonsense mutation in MRPS27 was identified in an AR-HA family, which was potentially a novel candidate gene of AR-HA. CONCLUSION: HM and NGS can serve as an efficient molecular diagnostic tool for AR-HA/HSPs in consanguineous families. Our findings provide a better understanding of genetic architecture of AR-HA/HSPs in consanguinity and broaden the clinical-genetic spectrum of the disease.

10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 491-496, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895101

RESUMO

Objective To investigate the value of head and neck CT angiography(CTA)in the evaluation of intraoperative hemorrhage of carotid body tumours. Methods Head and neck CTA images of 36 patients with carotid body tumours confirmed by pathology were retrospectively analyzed.Patients were divided into two groups based on the intraoperative bleeding volume:<500 ml and≥500 ml groups.The patient's age,sex,Shamblin classification,size of the lesion,number of blood supply arteries,course of the disease,plain scan,and enhanced CT value between two groups were compared and analyzed.Logistics regression equation was established based on the CTA parameters with significant differences between the two intraoperative bleeding volume groups,and combined parameter was acquired.The receiver operating characteristic curve was established based on CTA single and combined parameters. Results The bleeding volume during the operation of carotid body tumors was significantly correlated with the age of patients(P=0.019),the maximum diameter of tumours on axial images(P=0.003),the maximum upper and lower diameters(P=0.004),Shamblin classification(P=0.012),and number of blood supply arteries(P<0.001).The area under the receiver operating characteristic curve of the number of feeding arteries,the maximum diameter of axial images,maximum upper and lower diameters,Shamblin classification,and combined parameters were 0.865,0.781,0.806,0.766,and 0.927,respectively.When the optimal critical value was 0.408,the Youden index was 0.794,and the corresponding accuracy,sensitivity,and specificity were 0.919,0.909,and 0.923,respectively. Conclusions Preoperative head and neck CTA can be used to evaluate the intraoperative blood loss.Combined parameters has the best diagnostic performance compared with single parameters.


Assuntos
Tumor do Corpo Carotídeo , Angiografia por Tomografia Computadorizada , Tumor do Corpo Carotídeo/diagnóstico por imagem , Cabeça , Humanos , Pescoço , Estudos Retrospectivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-32918671

RESUMO

The impact of atrial fibrillation (AF) on outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is controversial, and with a paucity of evidence base. This study aimed to investigate the potential association between AF and outcomes after MT in AIS patients. A post-hoc analysis of a multi-center prospective clinical trial was conducted. Before and after propensity score matching (PSM), the clinical features were compared between patients with and without AF. Multivariable logistic regression and mediation analyses were performed to assess the relationship between AF and ICH. Of the total 245 patients, 123 patients were included in the AF group. After PSM, the AF group showed more retrieval attempts (P = 0.004), comparable favorable outcome (P = 0.493), and mortality (P = 0.362) at 90 days. Multivariate analysis revealed that AF was significantly associated with increased risk for ICH (OR 2.198; 95%CI 1.099-4.395; P = 0.026). INR and retrieval attempts were found to act as partial mediations. In the subgroup with lower INR, AF still had a significant association with ICH (OR 2.496; 95%CI 1.331-4.679; P = 0.004). In AIS patients undergoing MT, AF was associated with more retrieval attempts and higher risk of any ICH. Of note, the effect of AF on the increased risk of ICH was partly attributable to the adjusted anticoagulation status and more retrieval attempts. It is crucial to elaborately prevent ICH after thrombectomy for stroke patients with AF.

12.
Biomed Res Int ; 2020: 7838924, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908912

RESUMO

We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.

13.
Cell Commun Signal ; 18(1): 138, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867798

RESUMO

BACKGROUND: Polycystin-2 (TRPP2) is a Ca2+ permeable nonselective cationic channel essential for maintaining physiological function in live cells. Stromal interaction molecule 1 (STIM1) is an important Ca2+ sensor in store-operated Ca2+ entry (SOCE). Both TRPP2 and STIM1 are expressed in endoplasmic reticular membrane and participate in Ca2+ signaling, suggesting a physical interaction and functional synergism. METHODS: We performed co-localization, co-immunoprecipitation, and fluorescence resonance energy transfer assay to identify the interactions of TRPP2 and STIM1 in transfected HEK293 cells and native vascular smooth muscle cells (VSMCs). The function of the TRPP2-STIM1 complex in thapsigargin (TG) or adenosine triphosphate (ATP)-induced SOCE was explored using specific small interfering RNA (siRNA). Further, we created TRPP2 conditional knockout (CKO) mouse to investigate the functional role of TRPP2 in agonist-induced vessel contraction. RESULTS: TRPP2 and STIM1 form a complex in transfected HEK293 cells and native VSMCs. Genetic manipulations with TRPP2 siRNA, dominant negative TRPP2 or STIM1 siRNA significantly suppressed ATP and TG-induced intracellular Ca2+ release and SOCE in HEK293 cells. Inositol triphosphate receptor inhibitor 2-aminoethyl diphenylborinate (2APB) abolished ATP-induced Ca2+ release and SOCE in HEK293 cells. In addition, TRPP2 and STIM1 knockdown significantly inhibited ATP- and TG-induced STIM1 puncta formation and SOCE in VSMCs. Importantly, knockdown of TRPP2 and STIM1 or conditional knockout TRPP2 markedly suppressed agonist-induced mouse aorta contraction. CONCLUSIONS: Our data indicate that TRPP2 and STIM1 are physically associated and form a functional complex to regulate agonist-induced intracellular Ca2+ mobilization, SOCE and blood vessel tone. Video abstract.

14.
Cancer Med ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32881351

RESUMO

BACKGROUND: Autologous stem cell transplantation (ASCT) has been recommended as a standard approach for young multiple myeloma (MM) patients for decades, even in the era of novel agents. Gain of chromosome 1q21 is a common cytogenetic abnormality in MM, while its clinical prognostic value is still controversial. METHODS: In this multicenter study, we retrospectively analyzed 1q21 gain in 446 newly diagnosed MM patients who received at least one ASCT from three large myeloma centers in China. RESULTS: Of the all 446 patients, 1q21 gain was an adverse predictor of progression-free survival (PFS) (34 vs 56 months, P = .005) and overall survival (OS) (69 vs 100 months, P = .002). Gain of 1q21 was more likely to coexist with t(4;14), t(14;16), and del(13q). Nevertheless, isolated 1q21 gain still exhibited unfavorable effects on PFS (35 vs 66 months, P = .045) and OS (61 vs 100 months, P = .026). The coexistence of 1q21 gain and high-risk cytogenetics (HRCs) [del(17p), t(4;14),and/or t(14;16)] showed poor prognosis on both PFS and OS, while no additional adverse effect could be identified when compared with HRCs alone. Moreover, when coexisting with t(11;14), patients with 1q21 gain showed a comparable survival to those without 1q21 gain. For patients treated with novel induction regimens followed by ASCT, 1q21 gain also conferred an inferior prognosis. Multivariate analysis further confirmed 1q21 gain could independently predict shorter PFS and OS. CONCLUSION: In conclusion, 1q21 gain is an adverse prognostic factor for MM patients received ASCT.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1104-1107, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924111

RESUMO

OBJECTIVE: To determine the carrier rate of Fragile X mental retardation 1 gene (FMR1) mutants in women with a history of adverse pregnancy or childbirth, and to provide prenatal diagnosis for the carriers. METHODS: Peripheral blood samples were collected from women with a history of adverse pregnancy or childbirth, and the FMR1 gene cytosine-guanine-guanine repeat number (CGG)n was determined by triple-repeat primer polymerase chain reaction (TP-PCR) combined with capillary electrophoresis. Prenatal diagnosis was provided for the carriers during pregnancy. RESULTS: Among 819 samples, 9 gray zone repeats carriers and 10 premutation carriers were detected, which gave a prevalence of 1 in 91 and 1 in 82, respectively, with a total prevalence of 1 in 43. Prenatal diagnosis was provided during 7 pregnancies for 6 carriers. A female fetus with premutation (n = 30/57) and an affected male fetus with full mutation (n = 336) were detected. CONCLUSION: FMR1 gene testing in women with a history of adverse pregnancy or childbirth can facilitate genetic counseling and reproductive guidance for carriers of gray zone repeats and premutations. Prenatal diagnosis for carriers of premutation can facilitate reduction of the birth of children with fragile X syndrome.

16.
Oral Dis ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32989880

RESUMO

OBJECTIVES: To explore how various methylation mechanisms function and affect macrophages in periodontitis, with an aim of getting a comprehensive understanding of pathogenesis of the disease. SUBJECT: Alterations in DNA methylation are associated with different periodontitis susceptible factors and disrupt immunity homeostasis. The host's immune response to stimulus plays a vital role in the progression of periodontitis. Macrophages are key immune cells of immune system. They act as critical regulators in maintaining issue homeostasis with their nature of high plasticity. The altered methylation status of genes may cause abnormal expression of proteins in the progress of periodontitis, thus, exert potential influence on macrophages. RESULTS: Certain genes are selectively activated or silenced due to the changes in the methylation status, which causes the alteration of the expression level of cytokines/chemokines, signal molecules, extracellular matrix molecules, leads to the change in local microenvironment, affects activation states of immune cells including macrophages, thus influences the host immune response during periodontitis.. This results in differential susceptibility and therapeutic outcome. CONCLUSION: DNA methylation alteration may cause aberrant expression level of genes associated with periodontal diseases, thus results in deregulation of macrophages, which supports the prospect of using DNA methylation-related parameter as a new biomarker for the diagnosis and treatment of periodontitis.

18.
J Biol Chem ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963106

RESUMO

Hypoxia-inducible factors are heterodimeric transcription factors that play a crucial role in a cell's ability to adapt to low oxygen. The von-Hippel Lindau tumor suppressor (pVHL), acts as a master regulator of HIF activity, and its targeting of prolyl hydroxylated HIF-α for proteasomal degradation under normoxia is thought to be a major mechanism for pVHL tumor suppression and cellular response to oxygen. Whether pVHL regulates other targets through a similar mechanism is largely unknown. Here, we identify TET2/3 as novel targets of pVHL. pVHL induces proteasomal degradation of TET2/3, resulting in reduced global 5-hydroxymethylcytosine levels. Conserved proline residues within the LAP/LAP-like motifs of these two proteins are hydroxylated by the prolyl hydroxylase enzymes (PHD2/EGLN1 and PHD3/EGLN3), which is prerequisite for pVHL-mediated degradation. Using zebrafish as a model, we determined that global 5-hydroxymethylcytosine levels are enhanced in vhl-null, egln1a/b-double null and egln3-null embryos. Therefore, we reveal a novel function for the PHD-pVHL pathway in regulating TET protein stability and activity. These data extend our understanding of how TET proteins are regulated and provide new insight into the mechanisms of pVHL in tumor suppression.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32894445

RESUMO

The regeneration of EDTA-FeII is a key step in electrobiofilm reduction-integrated systems for NOx removal from industrial boiler flue gas. The current and carbon sources are proposed to be the two crucial electron donors for EDTA-FeII regeneration. These parameters strongly influence the reactivity of EDTA-FeII-generated products in the system. Therefore, their effects on EDTA-FeII-NO and EDTA-FeIII reduction and the EDTA-FeII generation mechanism were studied. The results showed that the electrobiofilm method has obvious advantages over biological or electrochemical methods used alone for EDTA-FeII regeneration. Under the optimal conditions at a current of 22.9A m-3 net cathode chamber, the rate of EDTA-FeII regeneration reached 98.35%. The glucose concentration is the primary factor influencing the reduction of both EDTA-FeII-NO and EDTA-FeIII, while the current significantly promotes both processes. Comparison of the Km values of the two substrates indicated that microbial activity was crucial to the reduction of EDTA-FeII-NO, but the biological reduction of EDTA-FeIII had a competitive influence on EDTA-FeII-NO reduction, which limited the abundance and effectiveness of the bacteria responsible for EDTA-FeII-NO reduction in the electrobiofilm system.

20.
Plant Cell ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883711

RESUMO

Pectins are abundant in the cell walls of dicotyledonous plants, but how they interact with other wall polymers and influence wall integrity and cell growth has remained mysterious. Here, we verified that QUASIMODO2 (QUA2) is a pectin methyltransferase and determined that QUA2 is required for normal pectin biosynthesis. To gain further insight into how pectin affects wall assembly and integrity maintenance, we investigated cellulose biosynthesis, cellulose organization, cortical microtubules, and wall integrity signaling in two mutant alleles of Arabidopsis thaliana QUA2, qua2 and tsd2. In both mutants, crystalline cellulose content is reduced, cellulose synthase particles move more slowly, and cellulose organization is aberrant. NMR analysis shows higher mobility of cellulose and matrix polysaccharides in the mutants. Microtubules in mutant hypocotyls have aberrant organization, and depolymerize more readily upon treatment with oryzalin or external force. The expression of genes related to wall integrity, wall biosynthesis, and microtubule stability is dis-regulated in both mutants. These data provide insights into how homogalacturonan is methylesterified upon its synthesis, the mechanisms by which pectin functionally interacts with cellulose, and how these interactions are translated into intracellular regulation to maintain the structural integrity of the cell wall during plant growth and development.

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