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1.
J Immunol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732528

RESUMO

Humoral autoimmunity is central to the development of systemic lupus erythematosus (SLE). Complement receptor type 2 (CR2)/CD21 plays a key role in the development of high-affinity Abs and long-lasting memory to foreign Ags. When CR2 is bound by its primary C3 activation fragment-derived ligand, designated C3d, it coassociates with CD19 on B cells to amplify BCR signaling. C3d and CR2 also mediate immune complex binding to follicular dendritic cells. As the development of SLE involves subversion of normal B cell tolerance checkpoints, one might expect that CR2 ligation by C3d-bound immune complexes would promote development of SLE. However, prior studies in murine models of SLE using gene-targeted Cr2-/- mice, which lack both CR2 and complement receptor 1 (CR1), have demonstrated contradictory results. As a new approach, we developed a highly specific mouse anti-mouse C3d mAb that blocks its interaction with CR2. With this novel tool, we show that disruption of the critical C3d-CR2 ligand-receptor binding step alone substantially ameliorates autoimmunity and renal disease in the MRL/lpr model of SLE.

2.
Int J Biol Macromol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669275

RESUMO

Polysaccharide has been considered as an important bioactive compound in Codonopsis lanceolata. High fat/high sucrose (HFHS) diet-induced insulin resistance is implicated in multiple metabolic diseases, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), these metabolic diseases has become epidemic health issue worldwide. In this study, the effect of C. lanceolata polysaccharide (CLPS) on improving insulin sensitivity in chronic HFHS diet-fed mice was investigated. Our data indicates that CLPS significantly reduced fasting blood glucose (FBG), fasting serum insulin (FINS) and insulin resistance index, in parallel with improved glucose and insulin tolerance impaired by HFHS diet. Impaired phosphorylation of PKB/Akt and hyperphosphorylation of IRS-1 at Ser307 were observed in the mice fed with HFHS diet, and those defects were also rescued by CLPS administration. In addition, CLPS caused a significant decrease in the level of malondialdehyde (MDA), and an increase in reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio; concurrent with enhanced expression of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), and activated Nrf2 signaling. In summary, these findings suggest that CLPS ameliorates HFHS diet-induced insulin resistance through activating anti-oxidative signaling pathway, providing new insights into the protective effects of C. lanceolata polysaccharide in metabolic disease.

3.
Orthop Surg ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773895

RESUMO

OBJECTIVE: To determine the value of Böhler's angle (BA) in a group of Chinese people, analyze possible factors that influence it, and compare BA with that in previous literature. METHODS: A total of 143 cases, aged from 4 to 79 years, were enrolled in the study, including 64 males and 79 females (79 left feet and 64 right feet). Radiographs were independently measured by six observers. Age, sex, body side, subtalar joint congruity (STJC), and X-beam obliquity (TT) were recorded. The database was assessed based on intraobserver agreement, data distribution, the randomness of case selection, and the ratio equality of binomial variables. Then, the normal value of BA was established, as well as the correlation between BA and other parameters. RESULTS: In the present study, the interobserver reliability of BA, STJC, and TT was excellent. The BA data revealed a normal distribution, and the randomness of case selection was verified for age, sex, and body side. The ratio of sex and body side was equal. Homogeneity of variance was observed when comparing the value of BA between different groups. The value of BA was 31.6° ± 5.19° (range, 20.08°-47.19°), which was not related to age, sex, body side, and minor X-ray beam obliquity. BA application was not suitable for individuals younger than 10 years. The mean value of BA in this study was not identical with those in previous reports. This demonstrated that BA varies for different races. CONCLUSION: For Chinese people, 30° to 33° is recommended as the target value of BA for calcaneal fracture reduction, except in children under 10 years of age.

4.
Proc Natl Acad Sci U S A ; 116(44): 22331-22340, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31604827

RESUMO

It is highly intriguing how bacterial pathogens can quickly shut down energy-costly infection machinery once successful infection is established. This study depicts that mutation of repressor SghR increases the expression of hydrolase SghA in Agrobacterium tumefaciens, which releases plant defense signal salicylic acid (SA) from its storage form SA ß-glucoside (SAG). Addition of SA substantially reduces gene expression of bacterial virulence. Bacterial vir genes and sghA are differentially transcribed at early and later infection stages, respectively. Plant metabolite sucrose is a signal ligand that inactivates SghR and consequently induces sghA expression. Disruption of sghA leads to increased vir expression in planta and enhances tumor formation whereas mutation of sghR decreases vir expression and tumor formation. These results depict a remarkable mechanism by which A. tumefaciens taps on the reserved pool of plant signal SA to reprogram its virulence upon establishment of infection.

5.
Sci Total Environ ; 693: 133490, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31635006

RESUMO

Lead is among the most common toxic heavy metals and its contamination is of great public concern. Bacillus coagulans is the probiotic which can be considered as the lead absorption sorbent to apply in the lead contaminant water directly or indirectly. A better understanding of the lead resistance and tolerance mechanisms of B. coagulans would help further its development and utilization. Wild-type Bacillus coagulans strain R11 isolated from a lead mine, was acclimated to lead-containing culture media over 85 passages, producing two lead-adapted strains, and the two strains shown higher lead intracellular accumulation ability (38.56-fold and 19.36-fold) and reducing ability (6.94-fold and 7.44-fold) than that of wild type. Whole genome sequencing, genome resequencing, and comparative transcriptomics identified lead resistance and tolerance process significantly involved in these genes which regulated glutathione and sulfur metabolism, flagellar formation and metal ion transport pathways in the lead-adapted strains, elucidating the relationships among the mechanisms regulating lead deposition, deoxidation, and motility and the evolved tolerance to lead. In addition, the B. coagulans mutants tended to form flagellar and chemotaxis systems to avoid lead ions rather than export it, suggesting a new resistance strategy. Based on the present results, the optimum lead concentration in environment should be considered when employed B. coagulans as the lead sorbent, due to the bacteria growth ability decreased in high lead concentration and physiology morphology changed could reduce the lead removal effectiveness. The identified deoxidization and compound secretion genes and pathways in B. coagulans R11 also are potential genetic engineering candidates for synthesizing glutathione, cysteine, methionine, and selenocompounds.


Assuntos
Bacillus coagulans/fisiologia , Chumbo , Probióticos , Estresse Fisiológico
6.
Curr Med Sci ; 39(5): 694-701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612385

RESUMO

Long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be highly expressed in many kinds of cancers. This meta-analysis summarized its potential prognostic value in digestive system malignancies. A meta-analysis was performed through a comprehensive search in PubMed, EMBASE, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27, 2019. Pooled hazard ratios (HRs) with 95% confidence interval (95%CI) were calculated to summarize the effect. Sixteen studies were included in the study, with a total of 1504 patients. A significant association was observed between UCA1 abundance and poor overall survival (OS), and shorter disease-free survival (DFS) for patients with digestive system malignancies, with pooled HR of 2.07 (95%CI: 1.74-2.47), and of 2.50 (95%CI: 1.62-3.86). Subgroup analysis and sensitivity analysis suggested the reliability of our findings. It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.

8.
J Autism Dev Disord ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31583625

RESUMO

Existing literature regarding social communication outcomes of interventions in autism spectrum disorder (ASD) depends upon human raters, with limited generalizability to real world settings. Technological innovation, particularly virtual reality (VR) and collaborative virtual environments (CVE), could offer a replicable, low cost measurement platform when endowed with intelligent agent technology and peer-based interactions. We developed and piloted a novel collaborative virtual environment and intelligent agent (CRETA) for the assessment of social communication and collaboration within system and peer interactions. The system classified user statements with moderate to high accuracies. We found moderate to high agreement in displayed communication and collaboration skills between human-human and human-agent interactions. CRETA offers a promising avenue for future development of autonomous measurement systems for ASD research.

9.
Small ; 15(47): e1904245, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31617305

RESUMO

Perforated ultrathin Pd nanosheets with crystalline/amorphous heterostructures are rationally synthesized to offer a large electrochemically active surface area of 172.6 m2 g-1 and deliver a 5.6 times higher apparent reaction rate in comparison to commercial Pd/C, thus offering a facile confined growth method to generate superior catalysts.

10.
Cell Microbiol ; : e13114, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487436

RESUMO

Nuclear import of proteins relies on nuclear import receptors called importins/karyopherins (Kaps), whose functions were reported in yeasts, fungi, plants, and animal cells, including cell cycle control, morphogenesis, stress sensing/response, and also fungal pathogenecity. However, limited is known about the physiological function and regulatory mechanism of protein import in the rice-blast fungus Magnaporthe oryzae. Here, we identified an ortholog of ß-importin in M. oryzae encoded by an ortholog of KAP119 gene. Functional characterisation of this gene via reverse genetics revealed that it is required for vegetative growth, conidiation, melanin pigmentation, and pathogenicity of M. oryzae. The mokap119Δ mutant was also defective in formation of appressorium-like structure from hyphal tips. By affinity assay and liquid chromatography-tandem mass spectrometry, we identified potential MoKap119-interacting proteins and further verified that MoKap119 interacts with the cyclin-dependent kinase subunit MoCks1 and mediates its nuclear import. Transcriptional profiling indicated that MoKap119 may regulate transcription of infection-related genes via MoCks1 regulation of MoSom1. Overall, our findings provide a novel insight into the regulatory mechanism of M. oryzae pathogenesis likely by MoKap119-mediated nuclear import of the cyclin-dependent kinase subunit MoCks1.

11.
BMC Infect Dis ; 19(1): 812, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533652

RESUMO

BACKGROUND: Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known. METHODS: This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged < 3 months of age in southern mainland China between January 2013 and June 2016. Genes for antibiotic resistance to tetracycline, erythromycin, and clindamycin were also examined. RESULTS: From a total of 93 GBS isolates taken from 34 early-onset disease (EOD, 0-6 days after birth) and 59 late-onset disease (LOD, 7-89 days after birth) cases, four serotypes were identified: serotypes III (79.6%), Ib (12.9%), Ia (4.3%), and V (3.2%). Serotype III accounted for 73.5% of EOD and 83.1% of LOD and was responsible for 75.5% of cases involving meningitis. Fifteen STs were found, with the majority being ST17 (61.3%), ST12 (7.5%), ST19 (7.5%), and others (23.7%). 96.8% of STs belonged to only five clonal complexes (CCs): CC17 (64.5%), CC10 (12.9%), CC19 (9.7%), CC23 (6.5%), and CC1 (3.2%). The hvgA gene was detected in 66.7% of GBS isolates and 95% of CC17 isolates, all of which were serotype III except one serotype Ib/CC17 isolate. A large proportion of GBS isolates were found to be resistant to tetracycline (93.5%), clindamycin (65.5%), and erythromycin (60.2%). Genes of tetO (74.7%) and tetM (46.0%) were found in tetracycline resistant isolates, linB (24.6%) in clindamycin resistant isolates, and ermB (87.5%) and mefA (3.6%) in erythromycin resistant isolates. CONCLUSION: Our results reveal higher prevalence of serotype III, ST17, CC17, hvgA expressing, and antibiotic resistant GBS isolates than previously reported in southern mainland China. This study provides guidance for appropriate measures of prevention and control to be taken in the future.


Assuntos
Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Adesinas Bacterianas/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Tipagem de Sequências Multilocus , Prevalência , Estudos Retrospectivos , Sorogrupo , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/genética
12.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
13.
Int J Hyperthermia ; 36(1): 926-931, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466485

RESUMO

Objective: To evaluate the outcomes of subsequent pregnancies in patients with a history of cesarean scar pregnancy (CSP) treated with high intensity focused ultrasound (HIFU) followed by ultrasound-guided dilation and curettage (USg-D&C). Methods: A retrospective analysis was performed on data collected from 154 patients with CSP who were treated by HIFU followed by USg-D&C in Suining Central Hospital between January 2015 and January 2018. Among them, 28 patients wanted to conceive following treatment. Baseline characteristics, treatment results, intraoperative hemorrhages during USg-D&C, post-curettage serum beta human chorionic gonadotropin (ß-hCG) levels and vaginal bleeding were investigated. Subsequent pregnancy outcomes, including intervals between pregnancy and treatment of CSP, complications during pregnancy, and outcomes of newborns were evaluated. Results: All patients with CSP were successfully treated by HIFU combined with USg-D&C. Of the 28 CSP patients who intended to conceive after the treatment, 23 patients (82.14%) successfully conceived. The average interval between conception and HIFU treatment was 18.38 ± 10.04 months. Eighteen patients (78.26%) had an intrauterine pregnancy, in which 12 had delivery by cesarean section, 1 had an ongoing pregnancy, and 5 had an abortion in the first trimester. Among the other 5 women, 3 had tubal ectopic pregnancy and 2 had recurrent CSP. These five patients underwent laparoscopy within the first trimester. Conclusion: HIFU followed by USg-D&C is an effective and safe treatment for patients with CSP who wish to conceive. Prospective multi-center studies with larger sample sizes and longer follow-up periods are needed to compare this treatment with others.

14.
World J Gastroenterol ; 25(24): 3044-3055, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31293340

RESUMO

BACKGROUND: The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells (HSCs) and the imbalance of extracellular matrix (ECM) production and degradation. The treatment of liver fibrosis mainly includes removing the cause, inhibiting the activation of HSCs, and inhibiting inflammation. NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5/NOD27/CLR16.1 (NLRC5) is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB (NF-κB) signaling. It has been found that NLRC5 plays an important role in liver fibrosis, but its specific effect and possible mechanism remain to be fully elucidated. AIM: To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-ß (TGF-ß) and MDI, and to explore its relationship with liver fibrosis. METHODS: A total of 24 male C57BL/6 mice were randomly divided into three groups, including normal, fibrosis, and recovery groups. Twenty-four hours after a liver fibrosis and spontaneous reversion model was established, the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group. LX-2 cells were cultured in vitro and treated with TGF-ß1 and MDI. Real-time quantitative PCR (qPCR) and Western blot were used to analyze the expression levels of NLRC5, α-smooth muscle actin (α-SMA), and collagen type I alpha1 (Col1a1) in each group. The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected. RESULTS: Compared with the normal mice, the expression level of NLRC5 increased significantly (P < 0.01) in the fibrosis group, but decreased significantly in the recovery group (P < 0.01). In in vitro experiments, the content of NLRC5 was enhanced after TGF-ß1 stimulation and decreased to a lower level when treated with MDI (P < 0.01). The expression of α-SMA and Col1a1 proteins and mRNAs in TGF-ß1-mediated cells was suppressed by transfection with NLRC5-siRNA (P < 0.01). Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα (p-IκBα) was increased in the liver of mice in the fibrosis group but decreased in the recovery group (P < 0.01), and the protein level of nuclear p65 and p-IκBα was significantly increased after treatment with NLRC5-siRNA (P < 0.01). CONCLUSION: NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31174699

RESUMO

Sepsis is a life-threatening condition that may develop to multiple organ failure and septic shock. Autophagy is considered to play an important role in the regulation of inflammation. The present study aims to investigate the protective role of mTORC1 inhibitor, rapamycin, on septic death using cecal ligation and puncture (CLP) mice model. Here, results showed that pretreatment with rapamycin reduced the pyroptosis of peritoneal macrophages stimulated by cecal contents and the release of inflammatory factors such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α); In septic mice, rapamycin treatment decreased the activation of inflammasome in lung, and alleviated the pathological injuries in lung, liver and spleen tissues during acute stage of sepsis. Treatment of rapamycin rescued animals from septic death significantly. Our results indicated that activation of autophagy is a potential strategy to regulate the excessive inflammation in acute stage of sepsis.


Assuntos
Autofagia/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Sepse/tratamento farmacológico , Sirolimo/uso terapêutico , Animais , Ceco , Citocinas/imunologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Ligadura , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
16.
J Colloid Interface Sci ; 552: 633-638, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170616

RESUMO

Integrating nanoscale active materials on conductive holey reduced graphene oxide (RGO) framework is an effective strategy to synthesize composite electrode materials for advanced lithium-ion batteries. Herein, a composite of γ-Fe2O3 nanoparticles stabilized by the engineered holes on RGO was successfully synthesized by using a facile in-situ etching route, which exhibited high lithium storage performance. The fundamental insight of its enhancement mechanism was discussed. This work offers a newly route to synthesize the composite of holey RGO confined metal oxide nanoparticles for the applications in lithium ion batteries and beyond.

17.
Annu Rev Microbiol ; 73: 559-578, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31226024

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that causes a variety of acute and chronic infections. Usually a commensal on the host body, P. aeruginosa is capable of transforming into a virulent pathogen upon sensing favorable changes in the host immune system or stress cues. P. aeruginosa infections are hard to eradicate, because this pathogen has developed strong resistance to most conventional antibiotics; in addition, in chronic infections it commonly forms a biofilm matrix, which provides bacterial cells a protected environment to withstand various stresses including antibiotics. Given its importance as a human pathogen and its notorious antimicrobial tolerance, P. aeruginosa has been the subject of intensive investigations internationally. Research progress over the last two decades has unveiled a range of chemical communication systems in this pathogen. These diversified chemical communication systems endow P. aeruginosa a superb ability and remarkable flexibility to coordinate and modulate accordingly the transcriptional expression of various sets of genes associated with virulence and other physiologic activities in response to environmental changes. A fair understanding of the chemical signaling mechanisms with which P. aeruginosa governs virulence gene expression may hold the key to developing alternative therapeutic interventions that control and prevent bacterial infections.

18.
Cell Microbiol ; 21(10): e13076, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254473

RESUMO

Pseudomonas aeruginosa, an opportunistic life-threatening human bacterial pathogen, employs quorum-sensing (QS) signal molecules to modulate virulence gene expression. 2-(2-hydroxyphenyl)-thiazole-4-carbaldehyde (IQS) is a recently identified QS signal that integrates the canonical lasR-type QS of P. aeruginosa and host phosphate stress response to fine-tune its virulence production for a successful infection. To address the role of IQS in pathogen-host interaction, we here present that IQS inhibits host cell growth and stimulates apoptosis in a dosage-dependent manner. By downregulating the telomere-protecting protein POT1 in host cells, IQS activates CHK1, CHK2, and p53 in an Ataxia telangiectasia mutated (ATM)/ATM and RAD3-related (ATR)-dependent manner and induces DNA damage response. Overexpression of POT1 in host cells presents a resistance to IQS treatment. These results suggest a pivotal role of IQS in host apoptosis, highlighting the complexity of pathogenesis mechanisms developed by P. aeruginosa during infection.

19.
J Appl Clin Med Phys ; 20(7): 142-150, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31124276

RESUMO

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS. METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares. RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016). CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.

20.
Huan Jing Ke Xue ; 40(5): 2143-2151, 2019 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087850

RESUMO

To investigate the major ionic characteristics, seasonal variation, and controlling factors of karst groundwater at Xiangshui, Chongzuo, 210 groundwater samples were collected and measured in wet season, dry season, and flat season in 2016. The controlling factors of karst groundwater were analyzed by using multivariate statistical analysis method. The results showed that the groundwater samples were weakly alkaline fresh water and rich in Ca2+ and HCO3-, which accounted for more than 75% and 70% of total ion concentration. The average concentrations of K+, Na+, Cl-, and NO3- decreased in the order of wet season > flat season > dry season. None of the concentrations of Ca2+, Mg2+, HCO3-, SO42-, pH, TDS, TZ+, and TZ- showed significant seasonal variation. The hydrochemical characteristics were found to be of HCO3-Ca type and mainly determined by carbonate rock dissolution. Only a small proportion of them were of HCO3·Cl-Ca and HCO3·SO4-Ca type in wet season and flat season, Cl·NO3-Ca type appeared in flat season, and HCO3-Ca·Mg type appeared in dry season, reflecting the influence of dolomite and ferric mudstone dissolution in the stratum, and of NO3- and Cl- input from anthropogenic activities. Groundwater Ca2+ and HCO3- mainly came from limestone dissolution; Na+, Cl-, K+, and NO3- came from atmospheric precipitation and human activities; while Mg2+ and SO42- came from dolomite and ferric mudstone dissolution. The chemical composition of groundwater was controlled by water-rock interaction, the groundwater in the carbonate aquifer was controlled by carbonate rocks dissolution, and the groundwater in villages and densely populated areas was affected by atmospheric precipitation and human activity.

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