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1.
Sci Rep ; 10(1): 1939, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029883

RESUMO

The exploration of advanced water treatment technologies e.g. heterogeneous photocatalysis is the most promising way to address organic pollution issues. Semiconductors based bimetallic photocatalysis with wide bandgap, have displayed splendid degradation performance in the UV light region, but their extension to the visible light/near infra-red region is still a matter of great concern. CuO, Co(OH)2, CoO and Co(OH)2/CuO nanocomposites were synthesized via simple co-precipitation method and further practiced for Rhodamine B (RhB) decomposition by introducing per-sulfate (PS) as a sacrificial agent. Results revealed that Co(OH)2/CuO catalyst had shown robust catalytic activity for RhB photodegradation (degradation time 8 min, k = 0.864 min-1) under light illumination, significantly less (12-60 times) than the other reported bimetallic catalysts. Catalyst also have verified excellent performance for a broader pH range (5-9) with excellent stability. Main reactive species responsible for the photocatalytic reaction were sulfate (SO4•-) and superoxide (O2•) radicals, duly verified by ESR and by using radical scavengers. With outstanding recycling abilities, this is probably the fewer successful attempt for RhB decolorization and can be highly favorable for effluent treatment by using the synergic effect of absorption and photodegradation.

2.
Cardiovasc Diabetol ; 19(1): 15, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041617

RESUMO

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). CONCLUSIONS: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

3.
Bioorg Chem ; 96: 103638, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062448

RESUMO

The dried fruits of Amomum tsao-ko are well-known dietary spices and traditional Chinese medicines. The random screen revealed that 50% ethanol-water extract of A. tsao-ko demonstrated significant α-glucosidase inhibitory activity with an IC50 value of 38.6 µg/mL. Bioactivity-guided isolation on the active fraction afforded 13 new 2,6-epoxy diarylheptanoids, tsaokopyranols A-M (1-13), and four known ones (14-17). Their structures featuring a 2,6-epoxy pyran ring were established by extensively spectroscopic analyses (HRESIMS, IR, UV, 1D and 2D NMR) and ECD calculations. Seven new (4-6, 8-11) and one known (16) compounds showed obvious α-glucosidase inhibitory activity with IC50 values ranging from 59.4 to 116.5 µM, higher than acarbose (IC50: 219.0 µM). An enzyme kinetic analysis indicated that compounds 12 and 13 were noncompetitive-type inhibitors of α-glucosidase with Ki values of 539.6 and 385.2 µM. This result provided new insights for the usage of A. tsao-ko, and 2,6-epoxydiarylheptanoids as new anti-diabetic candidates.

4.
Neuropharmacology ; : 108012, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32067988

RESUMO

Although the lateral habenula (LHb) is involved in the regulation of multiple brain functions and this region expresses abundant M-type potassium channel (M-channel) subunits Kv7.2 and Kv7.3, the role of M-channels in regulating working memory is unclear, particularly in Parkinson's disease (PD). Here we tested the effects of activation and blockade of LHb M-channels on working memory by the T-maze rewarded alternation test in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra compacta (SNc). The SNc lesion induced working memory impairment, increased the firing rate of LHb neurons, decreased dopamine (DA) level in the ventral medial prefrontal cortex (vmPFC) and reduced the expression of Kv7.2 subunit in the LHb. Intra-LHb injection of M-channel activator retigabine induced enhancement of working memory in SNc sham-lesioned and SNc-lesioned rats; conversely, the injection of M-channel blocker XE-991 impaired working memory in the two groups of rats. However, doses producing significant effects in SNc-lesioned rats were higher than those in SNc sham-lesioned rats. Further, intra-LHb injection of retigabine decreased the firing rate of LHb neurons and increased release of DA and serotonin (5-HT) in the vmPFC, while XE-991 increased the firing rate and decreased DA and 5-HT release in the two groups of rats. Compared with SNc sham-lesioned rats, the duration of M-channel activation and blockade action on the firing rate of the neurons and release of DA and 5-HT was significantly shortened in SNc-lesioned rats, which was consistent with reduced expression of Kv7.2 subunit in the LHb after lesioning the SNc. Collectively, these findings suggest involvement of LHb Kv7.2 subunit-containing M-channels in working memory impairment in SNc-lesioned rats, and that enhanced or impaired working memory after activation or blockade of M-channels in the LHb is related to the changes in the firing activity of LHb neurons and DA and 5-HT release in the vmPFC.

5.
J Am Heart Assoc ; 9(3): e014581, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013705

RESUMO

Background Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (PCI), previous observations have somewhat been limited by either small sample size or short-term follow-up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long-term outcomes in a large cohort of stable coronary artery disease patients after PCI. Methods and Results In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing PCI from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of <15 (low), 15 to 30 (medium), and ≥30 mg/dL (high). All patients were followed up for occurrence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average of 4.9 years of follow-up, 315 (7.7%) cardiovascular events occurred. The events group had significantly higher lipoprotein(a) levels than the nonevents group. Compared with the low lipoprotein(a) group, Kaplan-Meier analysis showed that the high lipoprotein(a) group had a significantly lower cumulative event-free survival rate, and multivariate Cox regression analysis further revealed that the high lipoprotein(a) group had significantly increased cardiovascular events risk. Moreover, adding continuous or categorical lipoprotein(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. Conclusions With a large sample size and long-term follow-up, our data confirmed that high lipoprotein(a) levels could be associated with a poor prognosis after PCI in stable coronary artery disease patients, suggesting that lipoprotein(a) measurements may be useful for patient risk stratification before selective PCI.

6.
Theranostics ; 10(1): 74-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903107

RESUMO

Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia.

7.
Neuropsychobiology ; : 1-10, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940619

RESUMO

BACKGROUND: Depression is one of the most common neuropsychiatric disturbances in Parkinson's disease (PD), but its pathophysiology is not definite. Lines of evidence have indicated that the hippocampus and serotonin 1A (5-HT1A) receptors are related to the regulation of depression. OBJECTIVE: The purpose of the present study was to observe the effect of 5-HT1A receptors in the dorsal hippocampus (dHIP) on PD-related depression in rats. METHODS: Unilateral 6-hydroxydopamine lesioning of the medial forebrain bundle (MFB) was used to establish the hemiparkinsonian rat model. The effects of intra-dHIP injection of the 5-HT1A receptor -agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) or antagonist WAY-100635 on depressive-like behaviors were observed in sucrose preference and forced swim tests in control and lesioned rats. Monoamine levels including dopamine (DA), 5-HT, and noradrenaline (NA) in depression-related brain regions were determined by a neurochemical method in all groups. RESULTS: Behavioral results showed that MFB lesions induced depressive-like behaviors. Intra-dHIP injection of 8-OH-DPAT produced antidepressant effects, while WAY-100635 induced or increased the depressive-like behaviors in both control and the lesioned rats. Neurochemical results found that intra-dHIP injection of 8-OH-DPAT significantly increased DA and 5-HT levels in the medial prefrontal cortex (mPFC), lateral habenula (LHb), ventral hippocampus and amygdala in the lesioned group and decreased NA levels in the mPFC and LHb in the control group. Moreover, after injection of WAY-100635, NA levels in all these regions of the lesioned group were significantly increased. CONCLUSIONS: These findings suggest that hippocampal 5-HT1A receptors regulate depression and PD-related depression by neurochemical mechanisms.

8.
Org Lett ; 22(2): 709-713, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31909628

RESUMO

Herein, we describe an efficient, practical photocatalytic deoxygenation/defluorination protocol for the synthesis of γ,γ-difluoroallylic ketones from commercially available aromatic carboxylic acids, triphenylphosphine, and α-trifluoromethyl alkenes. The protocol has good functional group tolerance and a broad substrate scope. Using this method, we accomplished the late-stage functionalization of several bioactive molecules.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31905317

RESUMO

Background: Lipid disorder was one of the major risk factors for coronary artery disease (CAD), especially in postmenopausal women, whose lipid profile significantly changed during the transition period to menopause. The aim of the present study was to examine whether plasma lipoprotein(a) [Lp(a)] was a biomarker for predicting the presence and severity of CAD in postmenopausal women. Methods: A total of 783 postmenopausal women who had their first angina-like chest pain were enrolled and classified into two groups according to the results of coronary angiography: CAD group (n = 309) and age-matched non-CAD group (n = 309). Patients with CAD were further divided into the three groups based on Gensini score (GS). The relationships of plasma Lp(a) levels to the presence and severity of CAD were evaluated, and the predictive value of Lp(a) for CAD was also examined. Results: CAD group had higher Lp(a) levels when compared to non-CAD ones (p < 0.001). The multivariate logistic regression analysis suggested that Lp(a) was an independent predictor for the presence of CAD (p < 0.001). Plasma levels of Lp(a) were significantly related to GS (p < 0.001). In addition, plasma Lp(a) level was significantly elevated according to the tertiles of GS (p = 0.001) and was independently associated with high GS (p < 0.001). In receiver-operating characteristic analysis for predicting the presence of CAD in postmenopausal women, Lp(a) was found to have the area under the curve of 0.703, with an optimal cutoff value of 255.69 mg/L. Conclusions: Lp(a) is an independent risk factor for predicting the presence and the severity of new-onset CAD in postmenopausal women, suggesting that Lp(a) may be a lipid target for prevention and treatment in such patients.

10.
BMC Plant Biol ; 20(1): 8, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906856

RESUMO

BACKGROUND: Photoperiod and/or thermo-sensitive male sterility is an effective pollination control system in crop two-line hybrid breeding. We previously discovered the spontaneous mutation of a partially male sterile plant and developed a thermo-sensitive genic male sterile (TGMS) line 373S in Brassica napus L. The present study characterized this TGMS line through cytological observation, photoperiod/ temperature treatments, and genetic investigation. RESULTS: Microscopic observation revealed that the condensed cytoplasm and irregular exine of microspores and the abnormal degradation of tapetum are related to pollen abortion. Different temperature and photoperiod treatments in field and growth cabinet conditions indicated that the fertility alteration of 373S was mainly caused by temperature changes. The effects of photoperiod and interaction between temperature and photoperiod were insignificant. The critical temperature leading to fertility alteration ranged from 10 °C (15 °C/5 °C) to 12 °C (17 °C/7 °C), and the temperature-responding stage was coincident with anther development from pollen mother cell formation to meiosis stages. Genetic analysis indicated that the TGMS trait in 373S was controlled by one pair of genes, with male sterility as the recessive. Multiplex PCR analysis revealed that the cytoplasm of 373S is pol type. CONCLUSIONS: Our study suggested that the 373S line in B. napus has a novel thermo-sensitive gene Bnmst1 in Pol CMS cytoplasm background, and its fertility alteration is mainly caused by temperature changes. Our results will broaden the TGMS resources and lay the foundation for two-line hybrid breeding in B. napus.

12.
J Cell Mol Med ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31930700

RESUMO

CTRP9 has been reported to regulate lipid metabolism and exert cardioprotective effects, yet its role in high-fat diet (HFD)-induced cardiac lipotoxicity and the underlying mechanisms remain unclear. In the current study, we established HFD-induced obesity model in wild-type (WT) or CTRP9 knockout (CTRP9-KO) mice and palmitate-induced lipotoxicity model in neonatal rat cardiac myocytes (NRCMs) to investigate the effects of CTRP9 on cardiac lipotoxicity. Our results demonstrated that the HFD-fed CTRP9-KO mice accentuated cardiac hypertrophy, fibrosis, endoplasmic reticulum (ER) stress-initiated apoptosis and oxidative stress compared with the HFD-fed WT mice. In vitro, CTRP9 treatment markedly alleviated palmitate-induced oxidative stress and ER stress-induced apoptosis in NRCMs in a dose-dependent manner. Phosphorylated AMPK at Thr172 was reduced, and phosphorylated mammalian target of rapamycin (mTOR) was strengthened in the heart of the HFD-fed CTRP9-KO mice compared with the HFD-fed control mice. In vitro, AMPK inhibitor compound C significantly abolished the effects of CTRP9 on the inhibition of the apoptotic pathway in palmitate-treated NRCMs. In a further mechanistic study, CTRP9 enhanced expression of phosphorylated LKB1 at Ser428 and promoted LKB1 cytoplasmic localization. Besides, silencing of LKB1 gene by lentivirus significantly prohibited activation of AMPK by CTRP9 and partially eliminated the protective effect of CTRP9 on the cardiac lipotoxicity. These results indicate that CTRP9 exerted anti-myocardial lipotoxicity properties and inhibited cardiac hypertrophy probably through the LKB1/AMPK signalling pathway.

13.
Cell Death Dis ; 11(1): 9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907363

RESUMO

Blood-brain barrier damage is a critical pathological feature of ischemic stroke. Oligodendrocyte precursor cells are involved in maintaining blood-brain barrier integrity during the development. However, whether oligodendrocyte precursor cell could sustain blood-brain barrier permeability during ischemic brain injury is unknown. Here, we investigate whether oligodendrocyte precursor cell transplantation protects blood-brain barrier integrity and promotes ischemic stroke recovery. Adult male ICR mice (n = 68) underwent 90 min transient middle cerebral artery occlusion. After ischemic assault, these mice received stereotactic injection of oligodendrocyte precursor cells (6 × 105). Oligodendrocyte precursor cells transplantation alleviated edema and infarct volume, and promoted neurological recovery after ischemic stroke. Oligodendrocyte precursor cells reduced blood-brain barrier leakage via increasing claudin-5, occludin and ß-catenin expression. Administration of ß-catenin inhibitor blocked the beneficial effects of oligodendrocyte precursor cells. Wnt7a protein treatment increased ß-catenin and claudin-5 expression in endothelial cells after oxygen-glucose deprivation, which was similar to the results of the conditioned medium treatment of oligodendrocyte precursor cells on endothelial cells. We demonstrated that oligodendrocyte precursor cells transplantation protected blood-brain barrier in the acute phase of ischemic stroke via activating Wnt/ß-catenin pathway. Our results indicated that oligodendrocyte precursor cells transplantation was a novel approach to the ischemic stroke therapy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31992509

RESUMO

BACKGROUND: An objective and accurate evaluation of liver grafts is required to improve the prognosis of liver transplant recipients and to increase the number of available liver grafts. AIM: To compare outcomes using FibroScan with that of pathology in liver grafts from brain-dead donors (DBD). METHODS: Liver grafts from 52 DBD were examined using ultrasound (US), FibroScan before liver transplantation (LT). Blood tested before LT and a biopsy was performed pre- or intra-operation to determine pathology. The diagnostic accuracy of the FibroScan results was compared with the pathology results, which is the gold standard for evaluating liver grafts. The donors enrolled were grouped by the stage of liver fibrosis (F0-F4) and steatosis (S0-S3), based on Kleiner's scoring system of nonalcoholic fatty liver disease, respectively. RESULTS: The liver stiffness (LS) value in group F1 was significantly increased compared with group F0 (8.74±1.32kPa and 5.93±1.64kPa, respectively, P<0.01). The LS value had a significant positive correlation with the liver graft fibrosis stage (r=0.73, P<0.01). The area under receiver operating characteristic curves (AUROC) for F1 stage fibrosis was 0.93 (P<0.01). Significant differences in the controlled attenuation parameter (CAP) were found among groups S0, S1, and S2 (173.30±38.36dB/m, 230.29±23.27dB/m, 250.00±57.01dB/m, respectively; F=12.41, P<0.01). The CAP was associated with the liver graft steatosis stage (r=0.64, P<0.01). The AUROC for S1 and S2 stage steatosis in liver grafts was 0.89 (P=0.002) and 0.83 (P=0.007), respectively. CONCLUSIONS: Transient elastography quantifies fibrosis and steatosis in liver grafts from 52 DBD with a high diagnostic accuracy and provides further imaging evidence for use in assessing liver grafts.

15.
Biomed Pharmacother ; 123: 109718, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918208

RESUMO

Tumor cell-induced platelet aggregation (TCIPA) is the core mechanism potentiating high viability for circulatory tumor cells,which is the rate-limiting factor for metastasis.Additionally,as supported by the successful application of aspirin,the pro-malignant effects during tumor-platelets interaction can be largely neutralized by pharmacological deactivation of platelets.Caulis Spatholobi is widely used as an anti-coagulation herb in traditional Chinese medicine,indicating its potential against TCIPA.In our study,three fractions of Caulis Spatholobi extracts were firstly prepared.In colorectal cancer(CRC) model,the anti-metastatic potential was evaluated both in vitro and in vivo followed by the detection of their platlet regulatory effects.Results showed that all three extracts significantly suppressed the invasion and metastasis of CRC.Mechanistically,by blocking platelet-derived PDGF-B releasing,they reversed the enhanced epithelial mesenchymal transition during MC38-platelets interation.Further,ethyl acetate fraction shows the most promising efficacy for the future application in treatment.Overall,our study have for the first time proved CaulisSpatholobi extracts,especially the ethyl acetate fraction,as a potent TCIPA inhibitor during metastatic progression,which provided a novel candidate for pharmacologically blockage of metastasis in CRC.

16.
Stroke ; 51(2): 619-627, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31822249

RESUMO

Background and Purpose- Blood-brain barrier (BBB) disruption is a critical pathological feature after stroke. MicroRNA-126 (miR-126) maintains BBB integrity by regulating endothelial cell function during development. However, the role of miR-126-3p and -5p in BBB integrity after stroke is unclear. Here, we investigated whether miR-126-3p and -5p overexpression regulates BBB integrity after cerebral ischemia. Methods- A lentivirus carrying genes encoding miR-126-3p or -5p was stereotactically injected into adult male Institute of Cancer Research mouse brains (n=36). Permanent middle cerebral artery occlusion was performed 2 weeks after virus injection. Brain infarct volume, edema volume, and modified neurological severity score were assessed at 1 and 3 days after ischemia. Immunostaining of ZO-1 (zonula occludens-1) and occludin was used to evaluate BBB integrity. IL-1ß (interleukin-1ß), TNF-α (tumor necrosis factor-α), VCAM-1 (vascular cell adhesion molecule-1), and E-selectin expression levels were determined by real-time polymerase chain reaction and Western blot analysis. Results- The expression of miR-126-3p and -5p decreased at 1 and 3 days after ischemia (P<0.05). Injection of lentiviral miR-126-3p or -5p reduced brain infarct volume and edema volume (P<0.05) and attenuated the decrease in ZO-1/occludin protein levels and IgG leakage at 3 days after stroke (P<0.05). Injection of lentiviral miR-126-5p improved behavioral outcomes at 3 days after stroke (P<0.05). miR-126-3p and -5p overexpression downregulated the expression of proinflammatory cytokines IL-1ß and TNF-α and adhesion molecules VCAM-1 and E-selectin, as well as decreased MPO+ (myeloperoxidase positive) cell numbers at 3 days after ischemia (P<0.05). Conclusions- miR-126-3p and -5p overexpression reduced the expression of proinflammatory cytokines and adhesion molecules, and attenuated BBB disruption after ischemic stroke, suggesting that miR-126-3p and -5p are new therapeutic targets in the acute stage of stroke.

17.
Biochem Biophys Res Commun ; 521(3): 652-659, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677789

RESUMO

WW domain containing E3 Ub-protein ligase 2 (WWP2) plays an important role in tumor progression as an E3 ligase of PTEN. Here, we investigated the role of WWP2 in gastric cancer (GC). We found that WWP2 is overexpressed in GC tissues, which is closely related to poor prognosis of GC patients. Using a WWP2-shRNA lentivirus expressing system, we established WWP2 stable-knockdown GC cell lines and found that knockdown of WWP2 inhibits the proliferation of GC cells both in vitro and in vivo. Also, WWP2 silencing induced the up-regulation of PTEN protein level and down-regulation of AKT phosphorylation level. We further investigated the role of PTEN in this regulating process by performing rescue assay and found that PTEN is essential for WWP2-mediated regulation of GC cells proliferation. Taken together, our results demonstrated that WWP2 promotes proliferation of GC cells by downregulating PTEN, which may provide new therapeutic targets for GC.

18.
Per Med ; 17(1): 67-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31686591

RESUMO

Aim: The aim of the present study was to examine the predictive value of lipoprotein(a) (Lp[a]) levels for coronary collateral circulation (CCC) in patients with acute myocardial infarction (AMI). Method & methods: A total of 409 consecutive patients with AMI were enrolled for this study. Patients were divided into two groups according to rentrop grades assessed by coronary angiography: bad (n = 277) and good CCC group (n = 132). Result: Patients with bad CCC had a higher level of Lp(a) than that with good CCC (median Lp[a] 219.1 vs 122.0 mg/l). The area under the receiver-operating characteristic curves of Lp(a) in predicting bad CCC was 0.647 (95% CI: 0.592-0.702) with the cut-off value of 199.0 mg/l. Conclusion: Our data firstly suggested that Lp(a) might be a useful marker for CCC after AMI.

19.
Water Res ; 169: 115193, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670083

RESUMO

The positive roles of N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS) in aerobic granular sludge (AGS) have been widely acknowledged. However, it is not feasible to manipulate granulation via direct addition of AHL chemicals or AHL-producing strains. Here, several strains with high AHL-producing capacity were successfully isolated from AGS. These QS strains were cultivated, mixed as a consortium, and then divided into two groups: AHLs supernatant and bacterial cells encapsulated in sodium alginate (CEBs). The potential of QS regulation, via doses of AHLs supernatant and CEBs, in accelerating granulation was evaluated. Results clearly indicated that short-term (days 21-70) addition of AHLs supernatant led to a rapid specific growth rate (0.08 d-1), compact structure without filamentous bacteria overgrowth, excellent settlement performance (SVI10 37.2 mL/g), and a high integrity coefficient (4.4%) of the granules. Sustainable release of AHLs (mainly C6- and C8-HSL) was induced by exogenous AHLs, possibly attributed to the enrichment of the genera Aeromonas and Pseudomonas. Further, tryptophan and aromatic protein substances were produced to maintain structural stability, suggesting that short-term QS regulation had long-term positive effects on the characteristics of AGS. By comparison, the addition of CEBs posed negligible or negative impact on the granulation, as evidenced by the rupture of smaller aggregates and poor characteristics of AGS. Overall, augmentation of the signaling content via addition of AHLs supernatant from QS strains is an economical and feasible regulation strategy to accelerate granulation and sustain long-term structural stability.


Assuntos
4-Butirolactona , Percepção de Quorum , 4-Butirolactona/análogos & derivados , Acil-Butirolactonas , Bactérias , Esgotos
20.
J Magn Reson Imaging ; 51(2): 635-643, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31301201

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) in MRI plays an increasingly important role in diagnostic applications and developing imaging biomarkers. Automated whole-breast segmentation is an important yet challenging step for quantitative breast imaging analysis. While methods have been developed on dynamic contrast-enhanced (DCE) MRI, automatic whole-breast segmentation in breast DWI MRI is still underdeveloped. PURPOSE: To develop a deep/transfer learning-based segmentation approach for DWI MRI scans and conduct an extensive study assessment on four imaging datasets from both internal and external sources. STUDY TYPE: Retrospective. SUBJECTS: In all, 98 patients (144 MRI scans; 11,035 slices) of four different breast MRI datasets from two different institutions. FIELD STRENGTH/SEQUENCES: 1.5T scanners with DCE sequence (Dataset 1 and Dataset 2) and DWI sequence. A 3.0T scanner with one external DWI sequence. ASSESSMENT: Deep learning models (UNet and SegNet) and transfer learning were used as segmentation approaches. The main DCE Dataset (4,251 2D slices from 39 patients) was used for pre-training and internal validation, and an unseen DCE Dataset (431 2D slices from 20 patients) was used as an independent test dataset for evaluating the pre-trained DCE models. The main DWI Dataset (6,343 2D slices from 75 MRI scans of 29 patients) was used for transfer learning and internal validation, and an unseen DWI Dataset (10 2D slices from 10 patients) was used for independent evaluation to the fine-tuned models for DWI segmentation. Manual segmentations by three radiologists (>10-year experience) were used to establish the ground truth for assessment. The segmentation performance was measured using the Dice Coefficient (DC) for the agreement between manual expert radiologist's segmentation and algorithm-generated segmentation. STATISTICAL TESTS: The mean value and standard deviation of the DCs were calculated to compare segmentation results from different deep learning models. RESULTS: For the segmentation on the DCE MRI, the average DC of the UNet was 0.92 (cross-validation on the main DCE dataset) and 0.87 (external evaluation on the unseen DCE dataset), both higher than the performance of the SegNet. When segmenting the DWI images by the fine-tuned models, the average DC of the UNet was 0.85 (cross-validation on the main DWI dataset) and 0.72 (external evaluation on the unseen DWI dataset), both outperforming the SegNet on the same datasets. DATA CONCLUSION: The internal and independent tests show that the deep/transfer learning models can achieve promising segmentation effects validated on DWI data from different institutions and scanner types. Our proposed approach may provide an automated toolkit to help computer-aided quantitative analyses of breast DWI images. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:635-643.

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