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1.
Mult Scler Relat Disord ; 37: 101432, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32172999

RESUMO

Neuromyelitis optica (NMO) is a disease characterised by severe relapses of optic neuritis and longitudinally extensive transverse myelitis and it has a strong female predilection. Pain is one of the most typical symptom in NMO. However, few studies have been conducted to examine the neuropathic pain mechanism of NMO patients or gender-specific effects using magnetic resonance imaging technique. A total of 38 female patients with NMO, 28 with pain (NMOWP) and 10 without pain (NMOWoP), were classified using the Brief Pain Inventory (BPI); 22 healthy females were also recruited. We used the FSL Image Registration and Segmentation Toolbox (FIRST) for subcortical region volumes quantifications, and voxel-based morphometry analysis for cortical gray matter (GM) volume, to examine the brain morphology in NMOWP patients. In addition, correlation test between structural measurements of NMO patients and clinical indexes was also performed. The results showed: 1) no significant differences in cortical GM density between the NMOWP and NMOWoP groups; 2) significantly smaller hippocampus and pallidum volumes in the NMOWP group compared with the NMOWoP group; 3) significant negative correlation between the average BPI and volumes of the accumbens nucleus and thalamus in NMO patients. These results revealed that structural abnormality exists in NMO female patients who have pain, with significant implications for our understanding of the brain morphology in NMO patients with pain.

2.
Mult Scler Relat Disord ; 37: 101438, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32173002

RESUMO

BACKGROUND: X chromosome-linked interleukin-1 receptor-associated kinase (IRAK1) polymorphisms have been demonstrated to be associated with the risks of several autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and autoimmune thyroid diseases. However, no studies have investigated the association of IRAK1 polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). This case-control study was performed to determine the correlation between IRAK1 polymorphisms and the risk of NMOSD. METHODS: Two single nucleotide polymorphisms (SNPs) rs1059703G>A and rs3027898C>A of IRAK1 were selected and genotyped using SNPscan in a Chinese cohort, including 332 patients with NMOSD and 520 healthy controls. Chi-square tests and logistic regression analyses were used to determine the associations between IRAK1 polymorphisms and the risk of NMOSD. RESULTS: Patients with NMOSD showed a lower frequency of the minor allele A of rs1059703 than did controls (Odds ratio [OR] = 0.68; 95% confidence intervals [CI], 0.52-0.88; Pcorr = 0.007). Compared with wild genotype GG of rs1059703, homozygous mutation AA and heterozygous mutation GA were significantly associated with the decreased risk of NMOSD after adjusting for sex and age (adjusted OR = 0.64; 95%CI, 0.49-0.84; Pcorr = 0.002). Similar associations were also observed for IRAK1 rs3027898C>A. Stratification analysis according to sex revealed that the significantly different allele distributions of the two SNPs were mainly found in females. However, IRAK1 polymorphisms were not correlated with aquaporin-4-IgG, onset symptoms, or age at onset. CONCLUSIONS: This study is first to demonstrate that X-chromosome-linked IRAK1 polymorphisms are associated with the risk of NMOSD and provide novel insights into the underlying mechanisms of this disease. Further studies are needed to elucidate the function of IRAK1 variants in the pathogenesis of NMOSD and the underlying molecular mechanisms.

3.
Sci Total Environ ; 723: 138050, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32217391

RESUMO

Health concerns of silver nanoparticles (AgNPs) emerged with the increase of their industrial and biomedical application and thus human exposure. The highly dynamic properties of AgNPs lead to coexposure to nanoparticulate and ionic silver, and the combined effects of different Ag species might alter their individual toxicity. Herein, the toxicity of AgNPs combined with ionic Ag+ toward the rat was investigated after intravenous (i.v.) exposure to either AgNPs (5 mg/kg), Ag+ (5 mg/kg), or a mixture of Ag+ and AgNPs (5 mg/kg for both). Comparable results by histopathological and biochemical studies revealed that the exposure to individual AgNPs causes no apparent toxicity in rats, while Ag+ ions at the same dose induced marked acute toxicity. More importantly, while there was a negligible combined effect on the Ag accumulation, the less toxic AgNPs ameliorated Ag+ induced toxicity to rat organs after coexposure to the mixture of Ag+ and AgNPs, which might result from the complexation of Ag+ with the thiols like metallothioneins. Therefore, the combined toxicity of particulate and ionic Ag was complicated by their individual toxicities and also their interaction with intracellular detoxification biomolecules, regardless of differences in Ag accumulation. Although further investigations are still needed for the potential toxic mechanisms of the coexposed AgNPs and Ag+, considerations of the combined toxicity of different Ag species will reflect more accurate assessments of their health impacts.

4.
Antimicrob Resist Infect Control ; 9(1): 23, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005246

RESUMO

BACKGROUND: Studies on risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) infection have provided inconsistent results, partly due to the choice of the control group. We conducted a systematic review and meta-analysis to assess the risk factors for CRKP infection by comparing CRKP-infected patients with two types of controls: patients infected with carbapenem-susceptible Klebsiella pneumoniae (comparison 1) or patients not infected with CRKP (comparison 2). METHODS: Data on potentially relevant risk factors for CRKP infection were extracted from studies indexed in PubMed, EMBASE, Web of Science or EBSCO databases from January 1996 to April 2019, and meta-analyzed based on the outcomes for each type of comparison. RESULTS: The meta-analysis included 18 studies for comparison 1 and 14 studies for comparison 2. The following eight risk factors were common to both comparisons: admission to intensive care unit (ICU; odds ratio, ORcomparison 1 = 3.20, ORcomparison 2 = 4.44), central venous catheter use (2.62, 3.85), mechanical ventilation (2.70, 4.78), tracheostomy (2.11, 8.48), urinary catheter use (1.99, 0.27), prior use of antibiotic (6.07, 1.61), exposure to carbapenems (4.16, 3.84) and exposure to aminoglycosides (1.85, 1.80). Another 10 risk factors were unique to comparison 1: longer length of hospital stay (OR = 15.28); prior hospitalization (within the previous 6 months) (OR = 1.91); renal dysfunction (OR = 2.17); neurological disorders (OR = 1.52); nasogastric tube use (OR = 2.62); dialysis (OR = 3.56); and exposure to quinolones (OR = 2.11), fluoroquinolones (OR = 2.03), glycopeptides (OR = 3.70) and vancomycin (OR = 2.82). CONCLUSIONS: Eighteen factors may increase the risk of carbapenem resistance in K. pneumoniae infection; eight factors may be associated with both K. pneumoniae infections in general and CRKP in particular. The eight shared factors are likely to be 'true' risk factors for CRKP infection. Evaluation of risk factors in different situations may be helpful for empirical treatment and prevention of CRKP infections.

5.
Sci Rep ; 10(1): 2529, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054899

RESUMO

Scalp nerve block with ropivacaine has been shown to provide perioperative analgesia. However, the best concentration of ropivacaine is still unknown for optimal analgesic effects. We performed a prospective study to evaluate the effects of scalp nerve block with varied concentration of ropivacaine on postoperative pain and intraoperative hemodynamic variables in patients undergoing craniotomy under general anesthesia. Eighty-five patients were randomly assigned to receive scalp block with either 0.2% ropivacaine, 0.33% ropivacaine, 0.5% ropivacaine, or normal saline. Intraoperative hemodynamics and post-operative pain scores at 2, 4, 6, 24 hours postoperatively were recorded. We found that scalp blockage with 0.2% and 0.33% ropivacaine provided adequate postoperative pain relief up to 2 h, while administration of 0.5% ropivacaine had a longer duration of action (up to 4 hour after craniotomy). Scalp nerve block with varied concentration of ropivacaine blunted the increase of mean arterial pressure in response to noxious stimuli during incision, drilling, and sawing skull bone. 0.2% and 0.5% ropivacaine decreased heart rate response to incision and drilling. We concluded that scalp block using 0.5% ropivacaine obtain preferable postoperative analgesia compared to lower concentrations. And scalp block with ropivacaine also reduced hemodynamic fluctuations in craniotomy operations.

6.
J Mol Neurosci ; 70(4): 610-617, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31925706

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that preferentially affects central nerve system. Herein, we evaluated changes of CD40L and CD40 mRNA expressions in NMOSD and controls to explore their potential roles in development of NMOSD. The expressions of CD40L and CD40 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with NMOSD and healthy controls were detected by quantitative real-time PCR (qPCR). Kruskal-Wallis tests were used to compare expression levels of CD40L and CD40 mRNA between groups, and Spearman correlation analysis was performed to evaluate correlation between mRNA expression levels and annual relapse rate (ARR) of NMOSD. A total of 71 patients with NMOSD and 42 gender- and age-matched healthy volunteers were recruited in our study. Compared with healthy controls, expression of CD40L mRNA was significantly decreased in untreated patients with NMOSD, and similar trends were observed also in CD40 mRNA expression although the difference was not significant. Other than that, immunosuppressants not only successfully increased CD40L and CD40 mRNA levels during remission of NMOSD, but also corrected the negative correlation between CD40L mRNA expression and annual relapse rate (ARR) of patients NMOSD. These results favored the long-term prognosis of NMOSD patients. Our results suggest that decreased expressions of CD40L mRNA may be involved in developing of NMOSD and the proper CD40L mRNA levels benefit to prevent attacks of NMOSD. Nevertheless, the relationship between protein and mRNA expressions of CD40L and their underlying roles in the pathogenesis of NMOSD remains to be further studied.

7.
J Neuroimmunol ; 338: 577093, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31726377

RESUMO

BACKGROUND: Sexual dysfunction (SD) is a common but poorly understood symptom in patients with neuromyelitis optica spectrum disorder (NMOSD). The study was designed to compare SD between NMOSD patients and healthy controls (HCs), and to investigate factors that influenced SD in NMOSD patients. METHODS: The study enrolled 102 sexually active NMOSD patients and 110 HCs. SD was investigated with the Female Sexual Function Inventory (FSFI), the abridged International Index of Erectile Function-5 (IIEF-5) and the Chinese Index of Premature Ejaculation-5 (CIPE-5). Disability, lower urinary tract dysfunction (LUTD), fatigue, depression and anxiety were also evaluated. RESULTS: The prevalence of SD, including female sexual dysfunction (FSD), erectile dysfunction (ED), and premature ejaculation (PE), was significantly higher in NMOSD patients than in HCs (P < .01). The FSFI, IIEF-5 and CIPE-5 scores were all significantly lower in NMOSD patients than in HCs (P < .01). Correlation analysis showed that SD was strongly correlated with age, age at onset, disability, LUTD, fatigue, depression and anxiety (P < .05). Regression analysis further revealed that age at onset (OR = 1.057, P = .036), disability (OR = 1.591, P = .011), and depression (OR = 1.111, P = .041) were independent predictors of FSD in NMOSD patients. CONCLUSIONS: This study provided evidence that SD is a common problem in NMOSD patients and that age at onset, disability, and depression are independent predictors of FSD. More attention should be paid to SD in patients with NMOSD.

8.
J Neuroimmunol ; 339: 577126, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31841737

RESUMO

BACKGROUND: Accumulating evidence points to an association of alternations in the gut microbiota with health and disease, including the development of neurological diseases. However, there are relatively scarce studies of the role of the gut microbiota in neuromyelitis optica spectrum disorders (NMOSD). Therefore, the aim of the present study was to evaluate the differences in the intestinal microbiota composition between patients with NMOSD and healthy control subjects. METHODS: This was a cross-sectional study. Stool samples were obtained from 20 patients with NMOSD and 20 healthy family members of the patients as controls (HC). The bacterial 16S rRNA gene amplification sequencing (V3-V4 region) was used to detect the composition and structure of the intestinal microbiota community in the two groups. RESULTS: The gut microbiota compositions clearly differed between the NMOSD and HC groups, although there was no significant difference in the overall microbial community structure. In detail, patients with NMOSD had an increased abundance of the pathogenic genera Flavonifractor (P = .004) and Streptococcus (P = .007) compared with the HC. In addition, several intestinal commensal bacteria were detected at significantly lower abundance in the NMOSD patients compared to the controls, including Faecalibacterium, Lachnospiracea_incertae_sedis, Prevotella, Blautia, Roseburia, Romboutsia, Coprococcus, and Fusicatenibacter (all P < .05). ROC curve analysis suggested that gut microbiota genera had potential to distinguish NMOSD from controls. Functional analysis further indicated that the gut microbiome of NMOSD patients was associated with three significantly downregulated metabolic pathways: "Photosynthesis" (P < .001), "Photosynthesis proteins" (P < .001), and "Thiamine metabolism" (P = .007). These differences remained significant even after correction for multiple comparisons (all PFDR < 0.05). CONCLUSION: Our results reveal the dysbiosis of intestinal bacteria and regarding metabolic abnormalities in patients with NMOSD. Further studies are warranted to elucidate the potential mechanism by which dysbiosis of microbiota contributes to the onset and progression of NMOSD.

9.
ACS Nano ; 14(1): 289-302, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31869202

RESUMO

Nanoparticle structural parameters, such as size, surface chemistry, and shape, are well-recognized parameters that affect biological activities of nanoparticles. However, whether the core material of a nanoparticle also plays a role remains unknown. To answer this long-standing question, we synthesized and investigated a comprehensive library of 36 nanoparticles with all combinations of three types of core materials (Au, Pt, and Pd), two sizes (6 and 26 nm), and each conjugated with one of six surface ligands of different hydrophobicity. Using this systematic approach, we were able to identify cellular perturbation specifically attributed to core, size, or surface ligand. We discovered that core materials exhibited a comparable regulatory ability as surface ligand on cellular ROS generation and cytotoxicity. Pt nanoparticles were much more hydrophilic and showed much less cell uptake compared to Au and Pd nanoparticles with identical size, shape, and surface ligands. Furthermore, diverse core materials also regulated levels of cellular redox activities, resulting in different cytotoxicity. Specifically, Pd nanoparticles significantly reduced cellular H2O2 and promoted cell survival, while Au nanoparticles with identical size, shape, and surface ligand induced higher cellular oxidative stress and cytotoxicity. Our results demonstrate that nanoparticle core material is as important as other structural parameters in nanoparticle-cell interactions, making it also a necessary consideration when designing nanomedicines.

10.
Cancer Med ; 9(3): 988-998, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846222

RESUMO

OBJECTIVE: Stage I-II uterine papillary serous carcinoma (UPSC) has aggressive biological behavior and leads to poor prognosis. However, clinicopathologic risk factors to predict cancer-specific survival of patients with stage I-II UPSC were still unclear. This study was undertaken to develop a prediction model of survival in patients with early-stage UPSC. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) database, 964 patients were identified with International Federation of Gynecology and Obstetrics (FIGO) stage I-II UPSC who underwent at least hysterectomy between 2004 and 2015. By considering competing risk events for survival outcomes, we used proportional subdistribution hazards regression to compare cancer-specific death (CSD) for all patients. Based on the results of univariate and multivariate analysis, the variables were selected to construct a predictive model; and the prediction results of the model were visualized using a nomogram to predict the cancer-specific survival and the response to adjuvant chemotherapy and radiotherapy of stage I-II UPSC patients. RESULTS: The median age of the cohort was 67 years. One hundred and sixty five patients (17.1%) died of UPSC (CSD), while 8.6% of the patients died from other causes (non-CSD). On multivariate analysis, age ≥ 67 (HR = 1.45, P = .021), tumor size ≥ 2 cm (HR = 1.81, P = .014) and >10 regional nodes removed (HR = 0.52, P = .002) were significantly associated with cumulative incidence of CSD. In the age ≥67 cohort, FIGO stage IB-II was a risk factor for CSD (HR = 1.83, P = .036), and >10 lymph nodes removed was a protective factor (HR = 0.50, P = .01). Both adjuvant chemotherapy combined with radiotherapy and adjuvant chemotherapy alone decreased CSD of patients with stage I-II UPSC older than 67 years (HR = 0.47, P = .022; HR = 0.52, P = .024, respectively). The prediction model had great risk stratification ability as the high-risk group had higher cumulative incidence of CSD than the low-risk group (P < .001). In the high-risk group, patients with post-operative adjuvant chemoradiotherapy had improved CSD compared with patients who did not receive radiotherapy nor chemotherapy (P = .037). However, there was no such benefit in the low-risk group. CONCLUSION: Our prediction model of CSD based on proportional subdistribution hazards regression showed a good performance in predicting the cancer-specific survival of early-stage UPSC patients and contributed to guide clinical treatment decision, helping oncologists and patients with early-stage UPSC to decide whether to choose adjuvant therapy or not.

11.
J Neurol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776721

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune demyelinating disease of the CNS, often leads to severe visual and/or motor disability. This study aimed to evaluate the long-term effects of the first-line immunotherapies on relapse and disability, and identify the prognostic predictors in NMOSD. METHODS: In this prospective cohort study, we enrolled patients with NMOSD from Southwest China and performed a long-term follow-up. We compared no immunotherapies (NIT) versus treatment of mycophenolate mofetil (MMF), azathioprine (AZA), or only corticosteroid (CS). Cox proportional-hazards model was used to explore the prognostic predictors in NMOSD. RESULTS: Ultimately, 281 patients were enrolled during 2009 to 2017. The proportions of relapse, motor disability, and mortality were significantly lower in treatments of MMF and AZA than in NIT (all P < 0.001), while no significant difference was found between the CS and NIT groups. The multivariate Cox analyses indicated that onset with optic neuritis and increased age at onset were risk predictors of visual disability and motor disability, respectively. Comparing with NIT, MMF and AZA were remarkably reduced risk of relapse and motor disability but not visual disability. Additionally, median time to first relapse and motor disability was significantly longer in treatments of MMF and AZA than in NIT (both P < 0.001). Furthermore, we estimated the risk of relapse and disability for AQP4-Abs positive NMOSD in 1-5 years based on prognostic predictors identified above. CONCLUSIONS: Our study revealed the potential predictors of relapse and disability, and strengthened evidence that early immunosuppressive treatments, such as MMF and AZA, could effectively reduce the risk of relapse and disability, and delayed progression of NMOSD.

12.
Medicine (Baltimore) ; 98(41): e17547, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593135

RESUMO

RATIONALE: Leakage of bone cement from femoral medullary cavity is a rare complication after hip arthroplasty, and there is no report on the leaked bone cement entering into iliac vessels. PATIENT CONCERNS: An 89-year-old woman presented with a fracture in the right femoral neck. She had well-fixed right femoral head replacement after careful preoperative examinations, and no adverse reactions appeared. She was able to get off bed to walk at the 2nd day after surgery. DIAGNOSES: Postoperative radiograph showed leakage of bone cement into the joint through femoral medullary cavity entering into iliac vessels, but the patient complained no discomforts. She received a treatment with low-molecular weight heparin and rivaroxaban. OUTCOMES: The patient was able to walk with normal gait, without swelling in both lower extremities and discomfort in the hip. There was no other complication concerning intravascular foreign bodies. LESSONS: This case calls into the phenomenon of leakage of injected bone cement in femoral head replacement regardless of complete and nonfractured femur, which may be into the lower limb and pelvic veins, given that, dangerous consequences will not occur.


Assuntos
Artroplastia de Quadril/efeitos adversos , Cimentos para Ossos/efeitos adversos , Cabeça do Fêmur/cirurgia , Veia Ilíaca/patologia , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Veia Ilíaca/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Radiografia/métodos , Rivaroxabana/uso terapêutico , Resultado do Tratamento
13.
Biol Open ; 8(11)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31649118

RESUMO

Tumor protein D52 (TPD52) is an oncogene amplified and overexpressed in various cancers. Tumor-suppressive microRNA-449a and microRNA-34a (miR-449a/34a) were recently reported to inhibit breast cancer cell migration and invasion via targeting TPD52. However, the upstream events are not clearly defined. Star-PAP is a non-canonical poly (A) polymerase which could regulate the expression of many miRNAs and mRNAs, but its biological functions are not well elucidated. The present study aimed to explore the regulative roles of Star-PAP in miR-449a/34a and TPD52 expression in breast cancer. We observed a negative correlation between the expression of TPD52 and Star-PAP in breast cancer. Overexpression of Star-PAP inhibited TPD52 expression, while endogenous Star-PAP knockdown led to increased TPD52. Furthermore, RNA immunoprecipitation assay suggested that Star-PAP could not bind to TPD52, independent of the 3'-end processing. RNA pull-down assay showed that Star-PAP could bind to 3'region of miR-449a. In line with these results, blunted cell proliferation or cell apoptosis caused by Star-PAP was rescued by overexpression of TPD52 or downregulation of miR-449a/34a. Our findings identified that Star-PAP regulates TPD52 by modulating miR-449a/34a, which may be an important molecular mechanism underlying the tumorigenesis of breast cancer and provide a rational therapeutic target for breast cancer treatment.

14.
J Chem Phys ; 151(14): 144112, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615261

RESUMO

Molecular dynamics simulations contain detailed kinetic information related to the functional states of proteins and macromolecules, but this information is obscured by the high dimensionality of configurational space. Markov state models and transition network models are widely applied to extract kinetic descriptors from equilibrium molecular dynamics simulations. In this study, we developed the Directed Kinetic Transition Network (DKTN)-a graph representation of a master equation which is appropriate for describing nonequilibrium kinetics. DKTN models the transition rate matrix among different states under detailed balance. Adopting the mixing time from the Markov chain, we use the half mixing time as the criterion to identify critical state transition regarding the protein conformational change. The similarity between the master equation and the Kolmogorov equation suggests that the DKTN model can be reformulated into the continuous-time Markov chain model, which is a general case of the Markov chain without a specific lag time. We selected a photo-sensitive protein, vivid, as a model system to illustrate the usage of the DKTN model. Overall, the DKTN model provides a graph representation of the master equation based on chemical kinetics to model the protein conformational change without the underlying assumption of the Markovian property.

15.
Recent Pat Nanotechnol ; 13(3): 202-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553297

RESUMO

BACKGROUND: Natural latex has been widely used in medical gloves, gas masks and nipples characterized by high elasticity, good film-forming performance and flexible film, but it is seldom used in nanomaterials. Electrospinning is an effective technology for manufacturing microfibrous or nanofibrous membranes. Latex-based nanofibers can be fabricated by electrospinning. Few relevant patents to the topic have been reviewed and cited. METHODS: The natural rubber latex and PVA solution were prepared for electrospinning in this study. RESULTS: When the rubber tends to nano scales, the flexibility of natural rubber gets enhanced. Additionally, the latex fluid can be used as an additive to improve mechanical property of nanofibers. CONCLUSION: The electrospinning rubber nanofibers shed a new light on rubber industry.

16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(7): 767-774, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31413214

RESUMO

OBJECTIVE: To explore the changes of serum miR-375 and its target genes in patients with allergic rhinitis (AR) before and after treatment and its significance.
 Methods: A total of 120 AR patients treated in Wuhan Fourth Hospital were selected as an observation group (AR group), and 120 healthy volunteers served as a control group. Real-time quantitative polymerase chain reaction was used to detect the expression changes of miR-375 and its predicted target genes, such as 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT1), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3), as well as inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) in the AR group before and after treatment. According to the relative expression levels of miR-375 and target genes, the AR patients were also subdivided into a high expression group and a low expression group for comparative analysis.
 Results: Before treatment, the level of miR-375 in the serum in the AR group was higher than that in the control group (P<0.01); the expressions of PDK1, AKT1, JAK2 and STAT3 in the plasma in the AR group were lower than those in the control group (all P<0.01); the plasma levels of TNF-α, IL-6, IL-10, and IL-13 in the AR group were higher than those in the control group (all P<0.05). After treatment, compared with the control group, the level of miR-375 in the serum was down-regulated (P<0.01), while the levels of target genes (PDK1, AKT1, JAK2 and STAT3) were up-regulated (all P<0.05), and the levels of TNF-α, IL-6, IL-10, and IL-13 were down-regulated in the AR group (all P<0.05). The total effective rate, total nasal symptom score (TNSS), symptom improvement time, and incidence of adverse reactions in the AR groups with high expression of miR-375 and low expression of target genes before treatment were better than those in the correspending groups with low expression of miR-375 and high expression of target genes (all P<0.05).
 Conclusion: MiR-375 might be a potential predictor of treatment response for AR patient, which might be related to the plasma levels of its target genes and inflammatory factors.


Assuntos
Rinite Alérgica , Humanos , Interleucina-6 , MicroRNAs , Fator de Transcrição STAT3 , Fator de Necrose Tumoral alfa
17.
J Cancer ; 10(18): 4217-4225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413740

RESUMO

Background: To develop and validate a radiomic nomogram incorporating radiomic features with clinical variables for individual local recurrence risk assessment in nasopharyngeal carcinoma (NPC) patients before initial treatment. Methods: One hundred and forty patients were randomly divided into a training cohort (n = 80) and a validation cohort (n = 60). A total of 970 radiomic features were extracted from pretreatment magnetic resonance (MR) images of NPC patients from May 2007 to December 2013. Univariate and multivariate analyses were used for selecting radiomic features associated with local recurrence, and multivariate analyses was used for building radiomic nomogram. Results: Eight contrast-enhanced T1-weighted (CET1-w) image features and seven T2-weighted (T2-w) image features were selected to build a Cox proportional hazard model in the training cohort, respectively. The radiomic nomogram, which combined radiomic features and multiple clinical variables, had a good evaluation ability (C-index: 0.74 [95% CI: 0.58, 0.85]) in the validation cohort. The radiomic nomogram successfully categorized those patients into low- and high-risk groups with significant differences in the rate of local recurrence-free survival (P <0.05). Conclusions: This study demonstrates that MR imaging-based radiomics can be used as an aid tool for the evaluation of local recurrence, in order to develop tailored treatment targeting specific characteristics of individual patients.

18.
Mol Phys ; 117(9-12): 1334-1343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354173

RESUMO

Protein allostery is ubiquitous phenomena that are important for cellular signaling processes. Despite extensive methodology development, a quantitative model is still needed to accurately measure protein allosteric response upon external perturbation. Here, we introduced the relative entropy concept from information theory as a quantitative metric to develop a method for measurement of the population shift with regard to protein structure during allosteric transition. This method is referred to as relative entropy-based dynamical allosteric network (REDAN) model. Using this method, protein allostery could be evaluated at three mutually dependent structural levels: allosteric residues, allosteric pathways, and allosteric communities. All three levels are carried out using rigorous searching algorithms based on relative entropy. Application of the REDAN model on the second PDZ domain (PDZ2) in the human PTP1E protein provided metric-based insight into its allostery upon peptide binding.

19.
Front Mol Biosci ; 6: 47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355207

RESUMO

TEM family of enzymes is one of the most commonly encountered ß-lactamases groups with different catalytic capabilities against various antibiotics. Despite the studies investigating the catalytic mechanism of TEM ß-lactamases, the binding modes of these enzymes against ligands in different functional catalytic states have been largely overlooked. But the binding modes may play a critical role in the function and even the evolution of these proteins. In this work, a newly developed machine learning analysis approach to the recognition of protein dynamics states was applied to compare the binding modes of TEM-1 ß-lactamase with regard to penicillin in different catalytic states. While conventional analysis methods, including principal components analysis (PCA), could not differentiate TEM-1 in different binding modes, the application of a machine learning method led to excellent classification models differentiating these states. It was also revealed that both reactant/product states and apo/product states are more differentiable than the apo/reactant states. The feature importance generated by the training procedure of the machine learning model was utilized to evaluate the contribution from residues at active sites and in different secondary structures. Key active site residues, Ser70 and Ser130, play a critical role in differentiating reactant/product states, while other active site residues are more important for differentiating apo/product states. Overall, this study provides new insights into the different dynamical function states of TEM-1 and may open a new venue for ß-lactamases functional and evolutional studies in general.

20.
Cell Chem Biol ; 26(8): 1122-1132.e6, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31130519

RESUMO

Natural killer (NK) cells play a crucial role in the surveillance of malignant cells. The engagement of NK group 2 member D (NKG2D) receptor with its ligands on target cells represents a promising therapeutic strategy against cancers. Here, we report that parvifoline AA (PAA), a natural ent-kaurane diterpenoid, markedly stimulates the expression of NKG2D ligands on hepatocellular carcinoma (HCC) cells, considerably enhancing their recognition and lysis by NK cells. We determined that PAA covalently binds to the conserved cysteine site of peroxiredoxins I/II (Prxs-I/II) and inhibits their catalytic activity, subsequently activating the ROS/ERK axis and the immunogenicity of HCC toward NK cells. Robust tumor growth inhibition by PAA dependent on NK cell activation was detected in vivo. Our data suggest Prxs-I/II as a promising cancer immune therapeutic target and provide a compelling rationale for further development of the inhibitor PAA as a sensitizer agent for NK cell-mediated HCC immunotherapy.

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