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1.
Artículo en Inglés | MEDLINE | ID: mdl-33609809

RESUMEN

MiR-150 is a microRNA (miRNA) present in a number of teleost species, but its target and regulation mechanism are unknown. Similarly, lysosome membrane protein 2-like (LMP2L) is a gene identified in fish but with unknown function. In this study, we examined the regulation mechanism and function of flounder miR-150 (named pol-miR-150) and its target gene LMP2L (named PoLMP2L) in association with bacterial and viral infection. We found that pol-miR-150 expression was not only modulated by the bacterial pathogen Streptococcus iniae but also by the viral pathogen megalocytivirus. Pol-miR-150 targeted PoLMP2L by binding to the 3'-untranslated region (3'-UTR) of PoLMP2L and inhibited PoLMP2L expression in vitro and in vivo. PoLMP2L is a member of the CD36 superfamily of scavenger receptors and homologous to but phylogenetically distinct from lysosomal integral membrane protein type 2 (LIMP2). PoLMP2L was localized mainly in the lysosomes and expressed in multiple organs of flounder. In vivo knockdown and overexpression of PoLMP2L enhanced and suppressed, respectively, S. iniae dissemination in flounder tissues, whereas in vivo knockdown and overexpression of pol-miR-150 produced the opposite effects on S. iniae dissemination. In addition, pol-miR-150 knockdown also significantly inhibited the replication of megalocytivirus. The results of this study revealed the regulation mechanism and immune functions of fish miR-150 and LMP2L, and indicated that LMP2L and miR-150 play an important role in the antimicrobial immunity of fish.

2.
Mol Neurobiol ; 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33629272

RESUMEN

Alzheimer's disease (AD) is the most common neurodegenerative disease in the older adults. Although much effort has been made in the analyses of diagnostic biomarkers, such as amyloid-ß, tau, and neurofilament light chain, identifying peripheral blood-based biomarkers is in extremely urgent need for their minimal invasiveness and more convenience. Here we characterized the miRNA profile by RNA sequencing in human serum exosomes from AD patients and healthy controls (HC) to investigate its potential for AD diagnosis. Subsequently, Gene Ontology analysis and pathway analysis were performed for the targeted genes from the differentially expressed miRNAs. These basic functions were differentially enriched, including cell adhesion, regulation of transcription, and the ubiquitin system. Functional network analysis highlighted the pathways of proteoglycans in cancer, viral carcinogenesis, signaling pathways regulating pluripotency of stem cells, and cellular senescence in AD. A total of 24 miRNAs showed significantly differential expression between AD and HC with more than ± 2.0-fold change at p value < 0.05 and at least 50 reads for each sample. Logistic regression analysis established a model for AD prediction by serum exosomal miR-30b-5p, miR-22-3p, and miR-378a-3p. Sequencing results were validated using quantitative reverse transcription PCR. The data showed that miR-30b-5p, miR-22-3p, and miR-378a-3p were significantly deregulated in AD, with area under the curve (AUC) of 0.668, 0.637, and 0.718, respectively. The combination of the three miRs gained a better diagnostic capability with AUC of 0.880. This finding revealed a miR panel as potential biomarker in the peripheral blood to distinguish AD from HC.

3.
Ann Palliat Med ; 10(1): 495-500, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33545780

RESUMEN

BACKGROUND: The purpose of this study is to investigate the optimal surgical options for different kinds of advanced hip tuberculosis, which are still controversial. METHODS: We reviewed seven advanced hip tuberculosis patients received operations from November 2014 to September 2018. All patients received anti-tubercular chemotherapy at least 2 weeks preoperatively and twelve months postoperatively. One active case with sinus tract of seven patients underwent three-stage operations including two debridements/cement spacer implantations and one total hip arthroplasty, while the other six cases received one = stage arthroplasty surgery. All patients are followed up based on Harris score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and X-ray. RESULTS: The mean follow-up time was 41.6 months, while no reactivation was detected. The average Harris score increased from 40.0 preoperatively to 89.4 at the final follow-up. ESR of 3 active hip tubercular cases decreased from 143.7 mm/L at diagnosis time to 6.7 mm/L at the final follow-up. CRP of 3 active hip tubercular cases decreased from 80.01 mg/L (range, 37.34-136.92 mg/L) at diagnosis time to 1.91 mg/L (range, 1.05-2.57 mg/L) at the final follow-up. The ESR and CRP of all patients had returned to normal level at the final follow-up. No prosthesis dislocation, loosening and neurovascular injury was found. CONCLUSIONS: THA is an effective and safe option for hip tuberculosis. The essentials for good outcome include early diagnosis, regular perioperative anti-tubercular chemotherapy, radical debridement of inflamed tissue and necrotic bone, staged-operation if necessary.

4.
Biomed Res Int ; 2021: 8850256, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33575349

RESUMEN

Purpose: A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods: PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results: Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002). Conclusion: Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

5.
J Exp Med ; 218(4)2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33561195

RESUMEN

Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin αvß3 at a novel site. ProAgio induces apoptosis via the integrin. Cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in TNBC tumor express high levels of integrin αvß3. ProAgio effectively induces apoptosis in CAFs and aECs. The depletion of CAFs by ProAgio reduces intratumoral collagen and decreases growth factors released from CAFs in the tumor, resulting in decreased cancer cell proliferation and apoptotic resistance. ProAgio also eliminates leaky tumor angiogenic vessels, which consequently reduces tumor hypoxia and improves drug delivery. The depletion of CAFs and reduction in hypoxia by ProAgio decreases lysyl oxidase (LOX) secretion, which may play a role in the reduction of metastasis. ProAgio stand-alone or in combination with a chemotherapeutic agent provides survival benefit in TNBC murine models, highlighting the therapeutic potential of ProAgio as a treatment strategy.

6.
Asian J Surg ; 2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33581945

RESUMEN

BACKGROUND: In this study, we investigated the impact of concomitant coronary artery bypass grafting (CABG) on operative and midterm mortality in patients with acute type A aortic dissection (ATAAD) undergoing surgical repair. METHODS: From January 2012 to December 2014, among 489 patients (mean age: 47.6 ± 10.4 years, 77.1% male) with ATAAD who received surgical repair at our institute, 21 patients (4.3%) underwent concomitant CABG. Isolated aortic repair was performed in the remaining 468 cases (95.7%). Coronary dissection was indicated in 15 patients (Neri classification type B in 2, type C in 13), concomitant coronary artery disease in five and coronary artery compression in one. The follow-up time was 97.3% at 44.1 ± 13.9 months. RESULTS: A total of 44 patients (9%) died from surgery, and operative mortality in the concomitant CABG group was significantly higher than that in the isolated aortic repair group (47.6%, 10/21 vs. 7.3%, 34/468; P < 0.001). Among the 11 survivors in the concomitant CABG group, no deaths occurred during the follow-up. Cox regression indicated that concomitant CABG increased the operative mortality risk by 9.2 times (HR, 9.26; 95% CI, 4.31-19.89; P < 0.001). Although it predicted a 5.2-fold increase in overall mortality (HR, 5.20; 95% CI, 2.55-10.61; P < 0.001), concomitant CABG did not affect midterm death (P = 0.996). CONCLUSIONS: Concomitant CABG carries a significant operative risk in ATAAD patients undergoing surgical repair. However, survivors may benefit from concomitant CABG and had similar midterm mortality compared with the other cases.

7.
Int J Clin Pract ; : e14065, 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33533568

RESUMEN

OBJECTIVE: The rate of lung cancer in female patients is increasing, with different features from male patients being displayed. Hormonal factors could play a role. The association between the development of uterine myoma (UM) and female hormones has also been reported. The relationship between female lung cancer and UM may be due to the effect of female hormones. METHODS: Data from 50 711 Taiwanese women with UM were retrieved from the National Health Insurance Research Database between 2000 and 2012. They were propensity-score matched with 50 711 women without UM (control group). A multivariate Cox proportional hazard regression model was used to compare the incidence of lung cancer between groups and to determine the hazard ratio of lung cancer in the UM group. RESULTS: The risk of lung cancer was significantly higher in women with myoma (adjusted hazard ratio: 1.62, 95% confidence ratio = 1.24-2.12). Stratified analyses demonstrated that the significantly increased risk of lung cancer was more likely to be found in certain groups, such as women who (a) are of younger age, (b) have a mid-level income, (c) have the highest urbanisation level, (d) are office workers and (e) with a longer follow-up period of myoma. Furthermore, myomectomy did not affect the risk pattern. CONCLUSION: The results from this nationwide population-based cohort study suggested that UM is associated with a higher risk of developing lung cancer. However, the exact underlying mechanism accounted for this remains unclear, and our findings still need to be verified by further comprehensive studies elsewhere.

8.
Epilepsy Behav ; 117: 107814, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33611102

RESUMEN

PURPOSE: Lacosamide (LCM) was approved in China in 2018. However, the safety of LCM has not been established in pediatric patients. Therefore, the objective of this study was to investigate its safety, efficacy, and tolerability in pediatric patients living in Uygur, Northwest China. METHODS: This is a retrospective analysis of pediatric patients diagnosed with epilepsy and on LCM therapy at a medical center. The seizure frequencies at 3, 6, and 12 months after starting LCM therapy were recorded and compared with the baseline monthly frequency. The primary outcome variables were the 50% responder and seizure-free rates. The secondary outcome variables included the terminal 6-month seizure remission and percentages of discontinuation due to a lack of efficacy and tolerability. Safety variables included the incidence and type of adverse reactions. RESULTS: Seventy-two pediatric patients with epilepsy living in Uygur, China and receiving LCM treatment were included in the present study. Fifty (69%) children responded to LCM therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, at 14%, 19%, and 20% at 3, 6, and 12 months, respectively. The number of baseline anti-seizure medications (ASMs) and order of LCM introduction significantly impacted the likelihood of seizure remission during the 12-month follow-up period (p < 0.05). During the entire period of LCM treatment, twenty-two children (30.5%) experienced at least one adverse reaction. CONCLUSION: This retrospective study of 72 pediatric patients with epilepsy in Uygur, China, showed that LCM therapy is safe and effective for epilepsy in children, resulting in a reduction in the seizure rate.

9.
Environ Int ; 151: 106439, 2021 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-33626455

RESUMEN

This study focused on the effect of algae on the fouling potential and dynamic fouling variation of foulants in an innovative algal-sludge membrane bioreactor (AS-MBR). Filtration experiments revealed that the soluble extracellular polymeric substance (S-EPS) released by the algal-sludge flocs showed a slower diminishing rate of flux than that released by the sludge flocs. The intermediate blocking and cake filtration models demonstrated the major mechanisms, which implied a reduction in the driving force of pore blocking and fouling layer formation induced by the algal-bacterial S-EPS. Furthermore, the relative flux decrements of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) in the AS-MBR were lower than those of the control without algae, indicating a reduction in the fouling potential of the bound EPS (B-EPS) in the algal-sludge flocs compared to the control. This could be attributed to the reduction in the membrane intercepts for LB- and TB-EPS, respectively. Specifically, S-EPS and B-EPS released by algal-sludge flocs had a lower free energy of cohesion (ΔGcoh) than those released by sludge flocs (decreased of 19.14%, 45.93%, and 43.34% for the S-EPS, LB-EPS, and TB-EPS, respectively). Furthermore, these changes could contribute to the decrease in the relative abundance of adsorbed polysaccharide- and protein-like substances in the B-EPS (released by algal-sludge flocs) filtration membrane, leading to the formation of less rough peaks and valleys in the fouling layer in the AS-MBR. Accordingly, the lower fouling propensity and weaker cohesion energy of S-EPS and B-EPS tend to decrease the hydrophobicity and the free energy of the floc surface and further provide less driving force to adhere to the membrane, resulting in significant mitigation of membrane fouling in the AS-MBR. Therefore, the overall fouling behavior caused by S-EPS, B-EPS and flocs should be comprehensively considered to achieve an underlying understanding of the algal effect on membrane fouling control.

10.
BMC Anesthesiol ; 21(1): 33, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33530942

RESUMEN

BACKGROUND: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P <  0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P <  0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS: The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION: ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

11.
J Clin Lab Anal ; : e23709, 2021 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-33547838

RESUMEN

BACKGROUND: This study aimed to investigate the relationship of serum JNK pathway-associated phosphatase (JKAP) expression with rheumatoid arthritis (RA) risk and clinical features, also to explore the longitudinal change of JKAP during etanercept treatment and its relationship with etanercept treatment response in RA patients. METHODS: A total of 87 RA patients and 44 healthy controls (HCs) were enrolled; then, their JKAP expression in serum was determined by enzyme-linked immunosorbent assay (ELISA). Among 87 RA patients, 42 cases further received the 24-week etanercept treatment; then, their JKAP level in serum (detected by ELISA) and clinical response (evaluated by disease activity score in 28 joints (DAS28) score) were evaluated at week 4 (W4), week 12 (W12), and week 24 (W24) after initiation of etanercept treatment. RESULTS: JKAP expression was decreased in RA patients compared to HCs, which disclosed a good predictive value for RA risk. JKAP expression was negatively associated with tender joint count, swollen joint count, erythrocyte sedimentation rate, C-reactive protein, and DAS28 in RA patients, respectively. For RA patients who received 24-week etanercept treatment, their clinical response rate was 0.0%, 33.3%, 50.0%, and 69% at W0, W4, W12, and W24, respectively. Importantly, JKAP was gradually increased during etanercept treatment, whose longitudinal elevation positively related to etanercept treatment response in RA patients. CONCLUSION: Circulating JKAP links with decreased RA risk and mild disease activity, whose longitudinal elevation positively relates to etanercept treatment response.

12.
Endocrine ; 2021 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-33548014

RESUMEN

PURPOSE: To investigate the relationship between parathyroid hormone (PTH) levels and body weight, body mass index (BMI), lipid profiles, and fat distribution in subjects with primary hyperparathyroidism (PHPT) and controls. METHODS: This was a cross-sectional study in 192 patients with PHPT and 202 controls. Serum concentrations of calcium, 25-hydroxyvitamin D (25(OH)D), PTH, lipids profiles, and other hormones were quantified. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Fat distribution evaluation utilizing quantitative computed tomography was conducted in another 66 patients with PHPT and 155 controls. RESULTS: PHPT patients were older (P < 0.001) and had less body weight (P < 0.001), lower BMI (P = 0.019), lower serum concentrations of 25(OH)D (P < 0.001), total cholesterol (P = 0.036), low-density lipoprotein-cholesterol (P = 0.036), and higher circulating concentration of free fatty acid (FFA) (P = 0.047) as compared with controls. After adjusting multiple confounders, PTH was positively correlated with weight (r = 0.311, P < 0.001), BMI (r = 0.268, P < 0.01), and visceral adipose tissue area (VAA) (r = 0.191, P < 0.05) in the first tertile of PTH. However, these associations were not observed in the second tertile. While in the third tertile, PTH was negatively correlated with weight (r = -0.200, P < 0.05), BMI (r = -0.223, P < 0.05) and marginally with VAA (r = -0.306, P = 0.065), it showed positive association with FFA (r = 0.230, P < 0.05). CONCLUSIONS: The inverted U-shape relationship between PTH and body weight, BMI, VAA found in this study is helpful to explain the conflicting results among these parameters, and extend our understanding of the metabolic effects of PTH.

13.
Sci Total Environ ; 774: 144826, 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33610986

RESUMEN

Low temperatures, or a sudden decrease in operating temperature, can seriously inhibit anammox activity, it is, therefore, important to maintain anammox activities at a low temperature. In this study, the use of gel beads to enhance the resistance of anammox biomass to a low temperature was investigated. The performance of three reactors: R1 without gel beads; R2 with polyvinyl alcohol/chitosan (PVA/CS); R3 with PVA/CS/Fe, was studied and compared in a temperature transition from 35 to 8 °C. When the operating temperature was ≥25 °C, there was little difference in nitrogen removal among the three reactors. Decreasing the temperature to < 25 °C created obvious difference between R1 and R2/R3. R1 had a nitrogen removal efficiency (NRE) of 33.1 ± 25.3% at 10 °C, significantly lower than that of R2 (90.5 ± 2.5%) or R3 (87.7 ± 11.1%). Unclassified Candidatus Brocadiaceae was the dominant genus at 10 °C, with an abundance of 44.4, 56.5 and 58.7% in R1, R2 and R3, respectively. These differences were attributed to the use of gel beads, which promoted the granulation of both the non-immobilized sludge and the immobilized biomass, resulting in higher anammox activities in R2/R3. The non-immobilized sludge of R1 was dominated by small particles (<300 µm) at 10 °C, while in R2 and R3 large particles (1000-2000 µm) were the main components. Furthermore, the immobilized biomass on gel beads exhibited much higher anammox activity and maintained a relatively high level of nitrate reductase and nitrite reductase in response to the temperature decrease. The Fe2+/Fe3+ in the PVA/CS/Fe gel beads further promoted microbial aggregation and led to an improved performance in R3 compared to R2. The results of this study demonstrate an effective approach to increase anammox resistance at low operating temperatures.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 164-168, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33627212

RESUMEN

OBJECTIVE: To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens. METHODS: A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis. RESULTS: Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (P > 0.05). There were significant differences in the 5-year OS rate between the children with or without reoperation after recurrence and between the children with different recurrence sites (P < 0.05). The children with reoperation after recurrence had a significantly longer survival time than those without reoperation (P=0.007), and the risk of death in children undergoing reoperation after recurrence was 0.389 times (95% confidence interval:0.196-0.774) that in children who did not undergo such reoperation. CONCLUSIONS: As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.

15.
Genomics ; 113(3): 867-873, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33545268

RESUMEN

The efficacy of susceptible variants derived from genome-wide association studies (GWAs) optimizing discriminatory accuracy of colorectal cancer (CRC) in Chinese remains unclear. In the present validation study, we assessed 75 recently identified variants from GWAs. A risk predictive model combining 19 variants using the least absolute shrinkage and selection operator (LASSO) statistics offered certain clinical advantages. This model demonstrated an area under the receiver operating characteristic (AUC) of 0.61 during training analysis and yielded robust AUCs from 0.59 to 0.61 during validation analysis in three independent centers. The individuals carrying the highest quartile of risk score revealed over 2-fold risks of CRC (ranging from 2.12 to 2.90) compared with those who presented the lowest quartile of risk score. This genetic model offered the possibility of partitioning risk within the average risk population, which might serve as a first step toward developing individualized CRC prevention strategies in China.

16.
Microbiome ; 9(1): 34, 2021 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-33517890

RESUMEN

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota. RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice. CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.

17.
J Chem Phys ; 154(5): 054903, 2021 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-33557527

RESUMEN

The external voltage-driven polymer translocation through a conical pore (with a large opening at the entry and a small tip at the exit) is studied by using the Langevin dynamics simulation in this paper. The entire translocation process is divided into an approaching stage and a threading stage. First, the approaching stage starts from the polymer entering the large opening and ends up at a terminal monomer reaching the pore tip. In this stage, the polymer will undergo the conformation adjustment to fit the narrowed cross-sectional area of the pore, leading to three approaching modes: the non-stuck mode with a terminal monomer arriving at the pore tip smoothly, the weak-stuck mode for the polymer stuck inside the pore for a short duration with minor conformational adjustments, and the strong-stuck mode with major conformational changes and a long duration. The approaching times (the duration of the approaching stage) of the three approaching modes show different behavior as a function of the pore apex angle. Second, the threading stage describes that the polymer threads through the pore tip with a linear fashion. In this stage, an increase in the apex angle causes the reduction of the threading time (the duration of the threading stage) due to the increase in the driving force with the apex angle at the tip. Moreover, we also find that with the increase in the apex angle or the polymer length, the polymer threading dynamics will change from the quasi-equilibrium state to the non-equilibrium state.

18.
Dev Comp Immunol ; : 104037, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33545212

RESUMEN

Bacillus subtilis subsp. subtilis G7 was isolated from a deep-sea hydrothermal vent and is pathogenic to pathogenic to fish (Japanese flounder) and mice. G7 is able to survive in host sera and phagocytes. In this study, we investigated the underlying mechanism of G7 serum resistance. We found that (i) the remaining complement activity was very low in G7-incubated flounder serum but high in G7-incubated mouse serum; (ii) cleaved C3 and C5 components were detected on flounder serum-incubated G7 but not on mouse serum-incubated G7; (iii) abundant uncleaved C5 was localized in G7-incubated mouse, but not flounder, serum; (iv) G7-incubated flounder, but not mouse, serum exhibited strong chemotactic activity; (v) pre-treatment with low-dose lysozyme abolished the serum resistance of G7. Hence, G7 activates flounder complement but is protected from complement-mediated destruction by its cell wall structure, while G7 prevents the activation of mouse complement. These results indicate that G7 employs different mechanisms to avoid the complement killing of different hosts.

19.
Stem Cell Res Ther ; 12(1): 119, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579362

RESUMEN

BACKGROUND: Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. METHODS: Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. RESULTS: Targeted antigen showed a surface antigen expression pattern, and the 43-55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. CONCLUSIONS: ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7.

20.
Neurol Sci ; 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33598798

RESUMEN

BACKGROUNDS: Beta-2-microglobulin (ß2-MG) levels vary in many infectious and autoimmune diseases. We investigated plasma and cerebrospinal fluid (CSF) ß2-MG levels in patients with Guillain-Barré syndrome (GBS) and their correlations with clinical parameters. METHODS: CSF samples from 50 patients with GBS including 19 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 10 acute motor-sensory axonal neuropathy (AMSAN), 7 Miller-Fisher syndrome (MFS), and 8 unclassified patients were collected. Moreover, 23 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 42 enrolled patients and 29 healthy individuals were also collected. The ß2-MG levels were measured by immunoturbidimetry on automatic biochemical analyser. Besides, clinical data were extracted from electronic patient documentation system. RESULTS: CSF levels of ß2-MG, lactate dehydrogenase (LDH), and lactate were significantly increased in patients with GBS (p = 0.004, p = 0.041, p = 0.040, respectively), particularly in patients with AIDP (p < 0.001, p = 0.001, p = 0.015, respectively), whereas no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were positively correlated with Hughes functional score (r = 0.493, p = 0.032), LDH (r = 0.796, p < 0.001), and lactate (r = 0.481, p = 0.037) but not with protein (r = - 0.090, p = 0.713) in AIDP patients. CONCLUSIONS: CSF ß2-MG levels may help identify AIDP and indicate clinical severity. CSF LDH and lactate levels correlate with CSF ß2-MG levels; interaction among these biomarkers would need further investigation.

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