Publications by authors named "Man Sun"

53 Publications

Clinical value of MRI in evaluating and diagnosing of humeral lateral condyle fracture in children.

J Orthop Surg Res 2021 Oct 18;16(1):617. Epub 2021 Oct 18.

Department of Radiology, Tianjin Hospital, No. 406, Jiefang Nan Road, Hexi District, Tianjin, 300211, China.

Background: Humeral lateral condyle fractures (HLCFs) are common paediatric fractures. Radiographs are hard to accurately evaluate and diagnose the damage of articular epiphyseal cartilage in HLCFs.

Methods: 60 children who should be suspected to be HLCFs in clinical practice from Dec 2015 to Nov 2017 were continuously included as the first part patients. Subsequently, 35 HLCFs patients with complete follow-up information who had no obvious displacement on radiograph were the second part patients. The sensitivity and specificity of radiograph and MRI in diagnosing of HLCFs and their stability were calculated respectively. Calculated the sensitivity and specificity of each scan sequence of MRI in diagnosing of HLCFs osteochondral fractures. The degree of fracture displacement was measured respectively. Compared the ratio of surgical treatment, secondary fracture displacement and complications between the stable fracture group and the unstable fracture group on MRI in part 2 patients.

Results: Sensitivity of diagnosing HLCFs by MRI was significantly higher than radiograph (100.00% vs. 89.09%, P = 0.03). Sensitivity of diagnosing integrity of trochlear cartilage chain by MRI was 96.30%, which was significantly higher than that by radiograph (62.96%, P < 0.01). The sensitivity of cartilage sensitive sequence (3D-FS-FSPGR/3D-FSPGR) was different with FS-PDWI and FS-T2WI (P = 0.01 and P = 0.02, respectively). The degree of HLCFs displacement by MRI was higher than radiograph (P < 0.05). In the unstable fracture group, 5 cases (45.45%) had a fracture displacement of more than 2 mm on MRI, which was significantly higher than that in stable fracture group (0.00%, P < 0.01).

Conclusions: MRI is superior to the radiograph of elbow joint in evaluating and diagnosing children HLCFs and their stability. The coronal 3D-FS-FSPGR/3D-FSPGR sequence is a significant sequence for diagnosing osteochondral fractures in HLCFs. MRI can provide important clinical value for treatment decisions of HLCFs without significant displacement.
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http://dx.doi.org/10.1186/s13018-021-02726-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522220PMC
October 2021

Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis.

Front Oncol 2021 1;11:731318. Epub 2021 Oct 1.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.

Methods: We first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.

Results: Firstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan-Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).

Conclusions: Preoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.
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http://dx.doi.org/10.3389/fonc.2021.731318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519510PMC
October 2021

Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment.

Front Oncol 2021 19;11:633462. Epub 2021 Jul 19.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, =0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, =0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, =0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.
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http://dx.doi.org/10.3389/fonc.2021.633462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327774PMC
July 2021

Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney.

Front Oncol 2020 8;10:609839. Epub 2021 Jan 8.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.
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http://dx.doi.org/10.3389/fonc.2020.609839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873889PMC
January 2021

Directed Network Defects in Alzheimer's Disease Using Granger Causality and Graph Theory.

Curr Alzheimer Res 2020 ;17(10):939-947

School of Computer Science and Engineering, Central South University, Changsha, 410008 Hunan, China.

Background: Few works studied the directed whole-brain interaction between different brain regions of Alzheimer's disease (AD). Here, we investigated the whole-brain effective connectivity and studied the graph metrics associated with AD.

Methods: Large-scale Granger causality analysis was conducted to explore abnormal whole-brain effective connectivity of patients with AD. Moreover, graph-theoretical metrics including smallworldness, assortativity, and hierarchy, were computed from the effective connectivity network. Statistical analysis identified the aberrant network properties of AD subjects when compared against healthy controls.

Results: Decreased small-worldness, and increased characteristic path length, disassortativity, and hierarchy were found in AD subjects.

Conclusion: This work sheds insight into the underlying neuropathological mechanism of the brain network of AD individuals such as less efficient information transmission and reduced resilience to a random or targeted attack.
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http://dx.doi.org/10.2174/1567205017666201215140625DOI Listing
November 2021

Rates and Anticoagulation Treatment of Known Atrial Fibrillation in Patients with Acute Ischemic Stroke: A Real-World Study.

Adv Ther 2020 10 27;37(10):4370-4380. Epub 2020 Aug 27.

Atrial Fibrillation Centre and Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Introduction: Known atrial fibrillation (AF) rate and appropriate prescription of oral anticoagulants (OACs) in acute ischemic stroke (AIS) patients with AF in China are not as well known as in Western countries.

Methods: Known AF and unknown AF, rate and adequacy of OACs use of AIS patients with AF attending five hospitals from April 2018 to August 2019 in the northwest region of China were investigated.

Results: A total of 344 patients were enrolled. Of these, 237 (AF-known group; 237/344, 68.9%) and 107 patients (AF-unknown group; 107/344, 31.1%) were diagnosed with AF before and after AIS during this hospitalization, respectively. In the AF-known group with echocardiography results (178 patients, including 103 female and 75 male patients), 154 of overall, 88 of female and 66 of male patients, respectively, were indicated to be taking OACs. However, the actual OACs proportion was much lower [overall (30.5%, 47/154); female (31.8%, 28/88) and male (28.8%, 19/66) patients] than indicated. Only one female patient met the guideline-based criteria for OACs. As for patients diagnosed with massive cerebral infraction (MCI; 43.0%, 148/344), the known AF rate was 65.5% (97/148). Among the MCI patients in the AF-known group with echocardiography results (61 patients), 50 patients had an OACs indication. However, only 22.0% (11/50) of these patients took OACs, and none met the guideline-based criteria for OACs.

Conclusions: This study revealed a low known AF rate, low OACs use rate and low rate of meeting the guideline-based criteria for OACs in AIS patients with AF in the northwest region of China. These findings indicated the importance of AF as a public health problem in China.
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http://dx.doi.org/10.1007/s12325-020-01469-wDOI Listing
October 2020

The Alteration of Carnitine Metabolism in Second Trimester in GDM and a Nomogram for Predicting Macrosomia.

J Diabetes Res 2020 11;2020:4085757. Epub 2020 Aug 11.

Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China.

Objective: The metabolism of three major nutrients (sugar, lipid, and protein) will change during pregnancy, especially in the second trimester. The present study is aimed at evaluating carnitine alteration in fatty acid metabolism in the second trimester of pregnancy and the correlation between carnitine and GDM.

Methods: 450 pregnant women were recruited in the present prospective study. Metabolic profiling of 31 carnitines was detected by LC-MS/MS in these women. Correlation between carnitine metabolism and maternal and neonatal complication with GDM was analyzed.

Results: We found the levels of 7 carnitines increased in age > 35, BMI ≥ 30, weight gain > 20 kg, and ART pregnant groups, but the level of free carnitine (C0) decreased. Nine carnitines were specific metabolites of GDM. Prepregnancy BMI, weight gain, and carnitines (C0, C3, and C16) were independent risk factors associated with GDM and related macrosomia. C0 was negatively correlated with FBG, LDL, TG, and TC. A nomogram was developed for predicting macrosomia in GDM based on carnitine-related metabolic variables.

Conclusion: The carnitine metabolism in the second trimester is abnormal in GDM women. The dysfunction of carnitine metabolism is closely related to the abnormality of blood lipid and glucose in GDM. Carnitine metabolism abnormality could predict macrosomia complicated with GDM.
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http://dx.doi.org/10.1155/2020/4085757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439181PMC
July 2021

[Downregulation of SND1 Expression Accelerates Cell Senescence of Human Diploid Fibroblasts 2BS via Modulating the SASP].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 May;51(3):365-370

Department of Laboratory Medicine, Taihe Hospital, Shiyan 442000, China.

Objective: To investigate the effect of down-regulation of SND1 expression on senescence of human diploid fibroblasts.

Methods: Western blot and immunohistochemistry were used to detect the expression of SND1 in young or senescent 2BS cells and aged tissues. Immunofluorescence was conducted to detect the localization of SND1 in young 2BS cells. CCK8 and EDU were performed to detect the proliferation of 2BS. Colony formation analysis was used to evaluate the capacity of colony formation of 2BS. Expression chip and RT-qPCR analysis were performed to detect the change of SASP expression level. β-galactosidase staining was employed to indicate the senescent 2BS cells.

Results: The expression of SND1 in the senescent 2BS cells was significantly down-regulated compared with in the younger 2BS cells, and in human colon adenomas, its expression was also significantly down-regulated compared with in non-lesion colon tissues. In young 2BS, knockdown of 1 inhibited the proliferation and colony formation of 2BS, and led to stronger senescence-associated beta-galactosidase staining (SA-β-gal). Expression chip and RT-qPCR analysis indicated that knockdown of 1 up-regulated the expression of senescence-associated secretory phenotype components (SASP).

Conclusions: Our data indicated that down-regulation of SND1 regulated human diploid cell senescence by up-regulating the expression of SASP components.
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http://dx.doi.org/10.12182/20200560504DOI Listing
May 2020

The Safety and Efficiency of Tirofiban in Acute Ischemic Stroke Patients Treated with Mechanical Thrombectomy: A Multicenter Retrospective Cohort Study.

Biochem Res Int 2020 27;2020:5656173. Epub 2020 Apr 27.

Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.

Introduction: Limited comparative studies have reported the safety and efficacy of tirofiban in acute ischemic stroke (AIS) patients after mechanical thrombectomy (MT). Additionally, the available studies are inconsistent with each other, which makes application of tirofiban unclear in neuro-intervention. Here, we performed a comparative retrospective study to investigate whether tirofiban combined with MT improves short- and long-term prognosis in AIS patients and whether its use is associated with complications.

Method: Retrospective data were collected for AIS patients admitted between January 2013 and January 2019 at three stroke centers. According to whether tirofiban was used during the operation, patients were divided into tirofiban group and control group. Multivariate and COX regression analyses were performed to determine the association of tirofiban treatment with safety and efficiency in subjects treated with MT.

Result: A total of 174 patients were analyzed, of whom 89 (51.1%) were treated with tirofiban. There were no differences in the incidence of symptomatic intracerebral hemorrhage (10.2% 10.6%, =0.918), parenchymal hemorrhage type 2 (18.0% . 16.5%, =0.793), and reocclusion at 24 h (3.4% . 10.6%, =0.060) between the tirofiban group and control group. Multivariate regression showed that tirofiban was not associated with intracerebral hemorrhage, early neurological deterioration, neurological improvement at 7 days, functional independence at 3-month and 9-month follow-up, or death at 9-month follow-up (adjusted > 0.05 for all). However, AIS patients treated with MT + tirofiban showed a trend towards acquiring faster functional independence, with a median time to acquire functional independence of 4.0 months compared with 6.5 months in the control group (risk ratio = 1.49, 95% confidence interval 0.98-2.27; long rank =0.066).

Conclusion: Tirofiban may help AIS patients given MT to gain functional independence faster, without increasing the risk of complications.
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http://dx.doi.org/10.1155/2020/5656173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211241PMC
April 2020

Contrast-Induced Encephalopathy Resulting From Use of Ioversol and Iopromide.

Clin Neuropharmacol 2020 Jan/Feb;43(1):15-19

Department of Neurology, the Second Affiliated Hospital, Medical School, Xi'an Jiaotong University.

Background: Contrast-induced encephalopathy (CIE) is a rare disease, whose etiology and risk factors remain unclear and need investigation.

Methods: We collected 7 CIE cases from 2646 patients injected with ioversol and 5 CIE cases from 526 patients injected with iopromide, all of whom underwent neurointervention surgery in our regional centers. The incidence of CIE, its characteristics, and risks were analyzed in both groups.

Results: The overall incidence of CIE was 0.38%, specifically 0.95% and 0.26% in the iopromide and ioversol groups, respectively; the former incidence was significantly higher than the latter (P = 0.029). The risk of CIE with iopromide was 3.567 to 3.618 times higher than that with ioversol (single-factor analysis odds ratio [OR], 3.618; 95% confidence interval [CI], 1.144-11.443; P = 0.029; multifactor analysis OR, 3.567 (95% CI, 0.827-15.379); P = 0.088). Moreover, acute cerebral infarction was an independent risk factor for CIE (OR, 4.024; 95% CI, 1.137-14.236; P = 0.031). Contrast-induced encephalopathy could occur within 5 minutes after injecting contrast media. The CIE characteristics differed according to the medium. In the ioversol group, the most common characteristic was visual disorder (71.43%), whereas in the iopromide group, the most common characteristic was delirium (100%).

Conclusions: Compared with ioversol, iopromide appeared more likely to lead to CIE. Acute cerebral infarction was an independent risk factor for CIE. The earliest CIE onset was within 5 minutes after injecting contrast. The characteristics of CIE varied significantly for different contrast media.
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http://dx.doi.org/10.1097/WNF.0000000000000374DOI Listing
December 2020

Basi-parallel anatomic scanning (BPAS-MRI) compared with high-resolution MRI for the diagnosis of vertebrobasilar artery abnormalities.

Eur J Radiol 2020 Feb 18;123:108791. Epub 2019 Dec 18.

Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China. Electronic address:

Purpose: To investigate the utility of basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) for the diagnosis of vertebrobasilar artery lesions.

Method: From October 2017-November 2018, 105 consecutive patients with abnormal configuration of the vertebrobasilar artery on time-of-flight magnetic resonance angiography (TOF-MRA) were enrolled. Conventional high-resolution MRI combined with TOF-MRA were performed to diagnose lesions and were used as the standard for sensitivity and specificity determination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were calculated. The consistencies between the two methods were evaluated by kappa test.

Results: Of the 105 patients, 45 were diagnosed with arteriosclerosis, 46 with vertebral artery dysplasia, 11 with artery dissection or dissecting aneurysm, and 3 as simple dilatation. Results Compared with conventional high-resolution MRI combined with TOF-MRA, for vertebrobasilar arteriosclerosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were 95.6 %, 95.0 %, 93.5 %, 96.6 % and 95.2 %, respectively and kappa value was 0.903. For vertebral artery dysplasia, they were 100 %, 96.6 %, 95.8 %, 100 %, and 98.1 %, respectively and kappa value was 0.961. For vertebrobasilar artery dissection or dissection aneurysm, they were 81.8 %, 96.8 %, 97.8 %, 75.0 % and 95.2 %, respectively and kappa value was 0.756.

Conclusions: BPAS-MRI can show the outer contour of the vertebrobasilar artery system. Combined with TOF-MRA, it may be used to differentiate among vertebrobasilar artery abnormalities, and be used in hospitals where conventional high-resolution MRI is not feasible.
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http://dx.doi.org/10.1016/j.ejrad.2019.108791DOI Listing
February 2020

Bilirubin: a novel predictor of hemorrhagic transformation and symptomatic intracranial hemorrhage after mechanical thrombectomy.

Neurol Sci 2020 Apr 11;41(4):903-909. Epub 2019 Dec 11.

Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwulu, Xi'an, 710004, Shaanxi, China.

Background And Purpose: The role of bilirubin in patients treated with mechanical thrombectomy (MT) is unknown. We investigated the relationship between admission bilirubin levels and hemorrhagic complication in acute ischemic stroke (AIS) patients treated with MT and detailed the roles of direct bilirubin (DB), indirect bilirubin (IDB), and total bilirubin (TB).

Methods: Consecutive AIS patients treated with MT were enrolled from two stroke centers. Outcome measures included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 48 h. An independent association of bilirubin with outcomes was identified by multivariate logistic regression analysis. The accuracies of bilirubin in predicting outcome were evaluated using receiver operating characteristic curve analysis.

Results: Of the 153 enrolled patients, 64 (41.8%) were diagnosed with HT, of which 28 (18.3%) had sICH. In univariate analyses, DB, IDB, and TB were higher in patients with HT and sICH than in patients without. After adjustment for potential confounders, DB (odds ratio [OR], 1.364; 95% confidence interval [CI], 1.133-1.641; p = 0.001), IDB (OR, 1.143; 95% CI, 1.052-1.242; p = 0.002), and TB (OR, 1.106; 95% CI, 1.041-1.175; p = 0.001) were independently associated with HT. IDB (OR, 1.177; 95% CI, 1.064-1.303; p = 0.002) and TB (OR, 1.102; 95% CI, 1.027-1.182; p = 0.007) were independently associated with sICH. Receiver operating characteristic curve analysis showed no significant difference between the three indicators of predicting HT and sICH.

Conclusions: Elevated admission bilirubin is an independent predictor of HT and sICH in AIS patients treated with MT.
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http://dx.doi.org/10.1007/s10072-019-04182-xDOI Listing
April 2020

MicroRNA‑21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c‑Jun (AP‑1) signalling pathway.

Int J Oncol 2020 Jan 2;56(1):178-192. Epub 2019 Dec 2.

Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

Accumulating evidence has demonstrated that microRNAs are associated with malignant biological behaviour, including tumorigenesis, cancer progression and metastasis via the regulation of target gene expression. Our previous study demonstrated that programmed cell death protein 4 (PDCD4), which is a tumour suppressor gene, is a target of microRNA‑21 (miR‑21), which affects the proliferation and transformation capabilities of renal cell carcinoma (RCC) cells. However, the role of miR‑21 in the molecular mechanism underlying the migration, invasion and angiogenesis of RCC remains poorly understood. The effects of miR‑21 on the invasion, migration and angiogenesis of RCC cells was determined through meta‑analysis and regulation of miR‑21 expression in vitro. After searching several databases, 6 articles including a total of 473 patients met the eligibility criteria for this analysis. The combined results of the meta‑analysis revealed that increased miR‑21 expression was significantly associated with adverse prognosis in patients with RCC, with a pooled hazard ratio estimate of 1.740. In in vitro experiments, we demonstrated that a miR‑21 inhibitor decreased the number of migrating and invading A498 and 786‑O RCC cells, along with a decrease in PDCD4, c‑Jun, matrix metalloproteinase (MMP)2 and MMP9 expression. Additionally, inhibition of miR‑21 was revealed to reduce tube formation and tube junctions in the endothelial cell line HMEC‑1 by affecting the expression of angiotensin‑1 and vascular endothelial growth factor A, whereas PDCD4 small interfering RNA exerted opposite effects on the same cells. Overall, these findings, along with evidence‑based molecular biology, demonstrated that miR‑21 expression promoted the migration, invasion and angiogenic abilities of RCC cells by directly targeting the PDCD4/c‑Jun signalling pathway. The results may help elucidate the molecular mechanism underlying the development and progression of RCC and provide a promising target for microRNA‑based therapy.
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http://dx.doi.org/10.3892/ijo.2019.4928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910186PMC
January 2020

Sludge-based activated carbon catalyzed HO oxidation of reactive azo dyes.

Environ Technol 2021 Feb 22;42(5):682-693. Epub 2019 Jul 22.

School of Energy and Environment, Anhui University of Technology, Ma'anshan, People's Republic of China.

Sludge-based activated carbon (ZAC) was successfully employed as both adsorbent and catalyst for the oxidation process of reactive yellow 86 (RY86) and reactive black 5 (RB5). Physicochemical properties of the prepared sewage sludge-derived activated carbon were evaluated by N adsorption/desorption, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The effects of parameters such as initial pH, HO concentrations, ZAC dosages, dye concentrations and temperature on the removal of RY86 and RB5 were investigated. Kinetics results showed that the adsorption rates of RY86 and RB5 by ZAC can be approximated by the pseudo-first order model, and that the oxidation rates by Behnajady-Modirshahla-Ghanbery (BMG) model. Under the optimum conditions in the experiment, i.e. pH = 6.0,  = 303 K, [HO] = 49.5 mmol/L, [ZAC] = 4 g/L, [dyes] = 300 mg/L and  = 150 min, 99%, 88% and 84% of colour, COD and TOC were removed by Fenton -like oxidation for RY86, while for RB5, the three removal rates were 90%, 70% and 62%, respectively, indicating that sludge-based activated carbon can be used as an effective catalyst to oxidation of dyes by HO from coloured wastewater.
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http://dx.doi.org/10.1080/09593330.2019.1643409DOI Listing
February 2021

Microstructural White Matter Alterations in Mild Cognitive Impairment and Alzheimer's Disease : Study Based on Neurite Orientation Dispersion and Density Imaging (NODDI).

Clin Neuroradiol 2020 Sep 7;30(3):569-579. Epub 2019 Jun 7.

Department of Radiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, 300192, Tianjin, China.

Purpose: To investigate microstructural alterations in white matter in mild cognitive impairment (MCI) and Alzheimer's disease (AD) using neurite orientation dispersion and density imaging (NODDI) and to assess the potential diagnostic performance of NODDI-derived parameters.

Methods: In this study 14 MCI patients, 14 AD patients, and 14 healthy controls (HC) were recruited. The diffusion tensor imaging(DTI)-derived fractional anisotropy (FA) and NODDI-derived neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso) were calculated from the diffusion data. The tract-based spatial statistics (TBSS) method was used for statistical analysis with one-way ANOVA. The correlations between the parameter values and mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores were examined. A receiver operating characteristic (ROC) curve was conducted to assess the diagnostic performance of different parameters.

Results: Compared with the HC group, the NDI and ODI values decreased significantly and the Viso values were significantly increased in the MCI and AD groups (p < 0.01, threshold-free cluster enhancement (TFCE)-corrected); however, there were no significant differences in FA values in the MCI group. The NDI, ODI, and Viso values of multiple fibers were significantly correlated with MMSE and MoCA scores. For the diagnosis of AD, the area under the ROC curve (AUC) for the NDI value of the splenium of corpus callosum was larger than the FA value (AUC = 0.885, 0.714, p = 0.042). The AUC of the Viso value of the right cerebral peduncle was larger than FA value (AUC = 0.934, 0.531, p = 0.004).

Conclusion: The NDI is more sensitive to white matter microstructural changes than FA and NODDI could be superior to DTI in the diagnosis of AD.
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http://dx.doi.org/10.1007/s00062-019-00805-0DOI Listing
September 2020

Dynamic Effects of Ioversol on the Permeability of the Blood-Brain Barrier and the Expression of ZO-1/Occludin in Rats.

J Mol Neurosci 2019 Jun 7;68(2):295-303. Epub 2019 Apr 7.

Department of Neurology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, No.157 XiWuLu Street, Xi'an, 710004, Shaanxi, China.

Blood-brain barrier (BBB) dysfunction is involved in the pathogenesis of contrast-induced encephalopathy (CIE), which is a rare adverse event following angiography. In this study, we observed the dynamic effect and potential mechanism of ioversol on the BBB in rats. Eighty-one healthy rats were randomly divided into a normal control group (n = 9), ioversol group (n = 36), and 0.9% NaCl group (n = 36); the latter two groups were separately subdivided into four groups based on time points after treatment (0.5, 3, 6, and 24 h) (n = 9/group). Permeability of the BBB was measured by an Evans Blue (EB) assay. Levels of the tight junction (TJ) proteins ZO-1 and occludin were determined by western blot and immunofluorescence staining. EB content increased at 3 h after the administration of ioversol via the carotid artery and reached a peak at 6 h (P < 0.05), whereas it decreased to its normal level at 24 h. Western blot and immunofluorescence staining indicated that the expression of ZO-1 in brain tissues gradually decreased to its lowest level at 3 h, and then increased gradually, but was still lower than that of the normal control group at 24 h (P < 0.05). Occludin was similar, but its lowest expression appeared at 0.5 h. This study demonstrated that the permeability of BBB in rats increased first and then decreased after ioversol was injected into the carotid artery. The mechanism may be related to altered protein expression of TJs, which are important structures in BBB. Early intervention against TJ proteins may be an effective measure to prevent and treat CIE.
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http://dx.doi.org/10.1007/s12031-019-01305-zDOI Listing
June 2019

Measurement of morphological parameters of giant cell tumor of bone in the knee.

Oncol Lett 2019 Apr 21;17(4):3867-3873. Epub 2019 Feb 21.

Department of Bone Tumors, Tianjin Hospital, Tianjin 300211, P.R. China.

The aim of the present study was to characterize the morphological parameters of giant cell tumor of bone (GCTB) in the knee. The imaging data of 250 patients with GCTB in the knee were retrospectively reviewed, and the morphological parameters were analyzed. The study included 137 cases with GCTB in the distal femur and 113 cases with GCTB in the proximal tibia. The maximal longitudinal diameter of the tumor was 6.616±2.322 cm in the femur group and 5.738±2.278 cm in the tibia group (P=0.003). The maximal transverse diameter in the two groups was 4.865±1.525 and 4.313±1.309 cm, respectively (P=0.003). The shortest distance from the articular surface (SDAS) in the two groups was 0.381±0.404 and 0.280±0.328 cm, respectively (P=0.035), whereas the longest distance from the articular surface in the two groups was 6.924±2.135 and 5.878±1.825 cm, respectively (P=0.001). There were statistically significant differences between the two groups in terms of the range of SDAS (P=0.043). Additionally, the incidence of pathological fractures in the femur was higher compared with that in the tibia (P=0.001), and the incidence of pathological fractures in the two groups gradually increased with the increase in lesion diameter. GCTB in the distal femur was larger compared with that in the proximal tibia, whereas GCTB in the tibia was closer to the articular surface compared with that in the femur. Furthermore, the incidence of pathological fractures in the femur was higher compared with that in the tibia.
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http://dx.doi.org/10.3892/ol.2019.10064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425395PMC
April 2019

Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway.

Life Sci 2019 Mar 13;221:259-266. Epub 2019 Feb 13.

Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China. Electronic address:

Aims: Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro.

Main Methods: Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by Aβ. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed.

Key Findings: The results showed that apoptosis and reactive oxygen species levels significantly increased in Aβ-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40 μM. Aβ-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by Aβ, accompanied by decreases in SOD and HO-1 expression.

Significance: Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.
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http://dx.doi.org/10.1016/j.lfs.2019.02.025DOI Listing
March 2019

Overexpression of Collapsin Response Mediator Protein 1 Inhibits Human Trophoblast Cells Proliferation, Migration, and Invasion.

Reprod Sci 2019 07 22;26(7):954-960. Epub 2018 Nov 22.

Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No.36, Sanhao street, Shenyang, Liaoning Province, 110004, China.

Collapsin response mediator protein 1 (CRMP-1) is widely expressed in the nervous system and has tumor suppressive effects. Our previous studies have demonstrated that CRMP-1 was expressed in the trophoblasts of the whole stage of pregnancy with significantly increasing expression in the placenta of early-onset preeclampsia. Preeclampsia, especially early onset, is strongly associated with the dysfunction of trophoblast including proliferation, apoptosis, migration, and invasion. In this study, we found an inhibitory effect of CRMP-1 on proliferation, migration, invasion, and an enhanced effect on apoptosis in human trophoblast cell lines HTR-8/SVneo and JEG-3 by MTT assay, colony formation assay, cell viability assay, caspase 3/7 activity assay, scratch wound assay, and Matrigel Transwell assay. Overexpression of CRMP-1 in trophoblast cells led to downregulate expression of matrix metalloproteinase 2 and 9. The expression of CRMP-1 was detected by real-time quantitative polymerase chain reaction and Western blot analysis. Thus, we suggested that CRMP-1 might have implications for the pathogenesis of preeclampsia by regulating the biological behavior of trophoblast cells.
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http://dx.doi.org/10.1177/1933719118799214DOI Listing
July 2019

2-Thiophene ethylamine modified hyaluronic acid with its application on hepatocytes culture.

Mater Sci Eng C Mater Biol Appl 2018 Jul 20;88:157-165. Epub 2018 Mar 20.

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China. Electronic address:

Hyaluronic acid (HA) is a component of extracellular matrix, which is important for cell functions and tissue integrity. Biosynthesized HA, as well as its derivatives, is widely used in cosmetics industry, biochemical medicine and medical surgery. In this research, we report a new hyaluronic acid derivative synthesized by amidation of hyaluronic acid with 2-thiophene ethylamine (2TEA). 2-chloro-dimethoxy-1,3,5-triazine (CDMT) served as the activating agent of the carboxylic groups. Primary mouse hepatocytes cultured with this derivative HA-2TEA maintained their epithelial morphology and showed better hepatic functions. This result was confirmed by the higher expression levels of hepatic functional genes in primary hepatocyte cultured with HA-2TEA derivative. Moreover, the protein levels of several hepatic genes were further confirmed by immunofluorescence staining. Thus HA-2TEA(2-thiopheneethylamine) derivative demonstrated good capacity on hepatocytes culture, and maintained hepatocyte functions in vitro.
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http://dx.doi.org/10.1016/j.msec.2018.03.009DOI Listing
July 2018

YAP Is Decreased in Preeclampsia and Regulates Invasion and Apoptosis of HTR-8/SVneo.

Reprod Sci 2018 09 5;25(9):1382-1393. Epub 2018 Jan 5.

1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Preeclampsia (PE) is a gestational disorder with hypertension and proteinuria leading to maternal and fetal morbidity and mortality. Yes-associated protein (YAP), a transcription coactivator of Hippo pathway, was identified as an oncoprotein participated in tumorigenesis. However, the effect of YAP on trophoblast has not been investigated. In our study, YAP expression levels in first-trimester, full-term, and PE placentas were detected using quantitative real-time polymerase chain reaction (PCR), Western blot assays, and immunohistochemistry. Yes-associated protein expression was also detected in BeWo and HTR-8/SVneo. Overexpression plasmid and YAP small interfering RNA were introduced into trophoblast cells. Furthermore, we utilized a Transwell invasion assay, flow cytometry, and Cell Counting Kit-8 analysis to examine the role of YAP in the invasion, apoptosis, and proliferation of HTR-8/SVneo trophoblast cells. The result showed that both YAP messenger RNA (mRNA) and protein expression levels were less in preeclamptic placentas. Yes-associated protein mRNA and protein expression levels were more highly expressed in BeWo. Yes-associated protein enhanced cell invasion, reduced the cellular apoptotic response, and had no effect on proliferation. In addition, the overexpression of YAP activated the expression of caudal-related homeobox transcription factor 2 (CDX2), whereas reduced expression of YAP inhibited the expression of CDX2. Our results demonstrate that decreased YAP levels may contribute to the development of PE by regulating trophoblast invasion and apoptosis involving regulation of CDX2. Collectively, we proposed decreased YAP may contribute to trophoblast dysfunction, which suggests it might represent a prognostic biomarker and therapeutic target for PE.
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http://dx.doi.org/10.1177/1933719117746784DOI Listing
September 2018

Human lung epithelial cells A549 epithelial-mesenchymal transition induced by PVA/Collagen nanofiber.

Colloids Surf B Biointerfaces 2018 Feb 11;162:390-397. Epub 2017 Dec 11.

School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China. Electronic address:

Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell-cell contact to become mesenchymal stem cells, which is important on development and embryogenesis, wound healing, and cancer metastasis. This research aims to investigate the effect of topological cue as modulating factor on the EMT by tuning the diameter of electrospinning nanofiber. The cell-nanofiber interaction between human lung epithelial cell A549 and electrospinning nanofibers composed of polyvinyl alcohol (PVA) and type I collagen were investigated. The electrospinning of regenerated PVA/Collagen nanofibers were performed with water/acetic acid as a spinning solvent and glutaraldehyde as a chemical cross-linker. Parameterization on concentration, applied voltage and feeding rate was finalized to generate smooth nanofibers with good homogeneity. The scanning electron microscopy result demonstrated that A549 cell appropriately achieved extended morphology by the filopodia attaching to the surface of the nanofibrous mats. When the diameter changed from 90nm to 240nm, the A549 cell was correspondingly express varied EMT related genes. Gene expression analysis was conducted by qPCR using three typical markers for detecting EMT: N-cadherin (NCad), Vimentin (Vim), and Fibronectin (Fib). An increasing expression pattern was observed on cell culturing on 170nm sample with respect to cell cultured on 90nm and 240nm. This result indicated the 170nm PVA/Collagen nanofibers induce A549 cells to process epithelial-mesenchymal transition more seriously than those on 90nm or 240nm.
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http://dx.doi.org/10.1016/j.colsurfb.2017.12.010DOI Listing
February 2018

Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3β.

Cancer Lett 2018 01 25;412:289-296. Epub 2017 Oct 25.

Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, 471003, PR China. Electronic address:

The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3β) and subsequent decrease of active β-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC.
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http://dx.doi.org/10.1016/j.canlet.2017.10.018DOI Listing
January 2018

Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex.

Neoplasia 2017 Nov 19;19(11):868-884. Epub 2017 Sep 19.

Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China, 471003; Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China, 471003. Electronic address:

Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front-rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing that SET modulated DOCK7/RAC1 and cofilin signaling events. Moreover, a detailed analysis of the spatial distribution of RAC1 and cofilin allowed us to decipher the synergistical contributions of the two in coordinating the advancing dynamics by measuring architectures, polarities, and cytoskeletal organizations of the lamellipodia leading edges. In further investigations in vivo, we identified their unique role at multiple levels of the invasive cascade for SET cell and indicate the necessity for their functional balance to enable efficient invasion as well. Additionally, SET epigenetically repressed miR-30c expression by deacetylating histones H2B and H4 on its promoter, which was functionally important for the biological effects of SET in our cell-context. Finally, we corroborated our findings in vivo by evaluating the clinical relevance of SET signaling in the metastatic burden in mice and a large series of patients with ESCC at diagnosis, observing it's significance in predicting metastasis formation. Our findings uncovered a novel signaling network initiated by SET that epigenetically modulated ESCC properties and suggest that targeting the regulatory axis might be a promising strategy to inhibit migration and metastasis.
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http://dx.doi.org/10.1016/j.neo.2017.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608591PMC
November 2017

Different frequencies of Porphyromonas gingivalis infection in cancers of the upper digestive tract.

Cancer Lett 2017 09 11;404:1-7. Epub 2017 Jul 11.

Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, 471003, China; Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, 471003, China. Electronic address:

The high incidence rate of multiple carcinomas in the upper digestive tract is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers. We previously reported occurrence of Porphyromonas gingivalis (P. gingivalis) DNA in esophagus cancer. In this study, the presence of P. gingivalis in specimens of various types of cancer from the upper digestive tract was investigated. Here we report that P. gingivalis was preferentially and frequently present in specimens of esophageal cancer as well as in those from dysplasia of the esophagus but rarely in matched noncancerous portions and are quite low or absent in cancers from the cardia or stomach. Therefore, it led us to propose that, the microorganism does not survive in conditions of high acidity. We then investigate the pH dependence of survival of P. gingivalis as well as the acid tolerance of it. We found that, exposure to acidic buffers of a wide range of pH values led to a decline in colony forming units of P. gingivalis, thus, providing a possible explanation for variations in frequencies of P. gingivalis infection in this study.
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http://dx.doi.org/10.1016/j.canlet.2017.07.003DOI Listing
September 2017

PFKFB3-Driven Macrophage Glycolytic Metabolism Is a Crucial Component of Innate Antiviral Defense.

J Immunol 2016 10 26;197(7):2880-90. Epub 2016 Aug 26.

State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and

Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3). Using a genetic inactivation approach together with pharmacological perturbations in mouse cells, we show that PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages, via metabolically supporting the engulfment and removal of virus-infected cells. Furthermore, the antiviral function of PFKFB3, as well as some contribution of its action from the hematopoietic compartment, was confirmed in a mouse model of respiratory syncytial virus infection. Therefore, different from the long-standing perception of glycolysis as a proviral pathway, our findings establish an antiviral, immunometabolic aspect of glycolysis that may have therapeutic implications.
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http://dx.doi.org/10.4049/jimmunol.1600474DOI Listing
October 2016

Non-Gaussian diffusion alterations on diffusion kurtosis imaging in patients with early Alzheimer's disease.

Neurosci Lett 2016 Mar 18;616:11-8. Epub 2016 Jan 18.

Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China. Electronic address:

Objective: To evaluate non-Gaussian diffusion changes of the whole-brain and its correlation with cognitive performance in patients with early Alzheimer's disease (AD), using diffusion kurtosis imaging (DKI).

Methods: Twenty-six patients with early AD and twenty-six normal controls underwent diffusion imaging. Seven parametric maps were calculated from multiple b-value diffusion data, including mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). Voxel-based analyses were performed to evaluate the group difference between the AD patients and normal controls. Then correlation between the diffusion parameters (MK, FA and MD) and cognitive performance were analyzed in AD patients.

Results: For AD patients, increased MD, AxD and RD were found in white matter (WM), including the genu of corpus callosum, bilateral cingulate bundle, bilateral temporal and frontal WM, and were also found in gray matter (GM), including the bilateral temporal GM, parahippocampal gyrus, hippocampus, cingulate gyrus, thalamus, and amygdala. These regions were partially overlapped with those showing decreased FA, MK, AK and RK. However, only kurtosis indices could detect the significant differences in the lentiform nucleus between AD patients and health control. DKI indices in AD patients significantly correlated with the clinical scores in genu of CC, cingulate bundle, temporal and frontal lobe, while the voxel number showing significant correlation with MK was more than that with FA and MD.

Conclusions: Early AD patients already have microstructural changes in both WM and GM. DKI can provide supplementary information in reflecting these changes and may be sensitive in diagnosing early AD.
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http://dx.doi.org/10.1016/j.neulet.2016.01.021DOI Listing
March 2016

Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

Bioorg Med Chem Lett 2015 Dec 30;25(24):5729-31. Epub 2015 Oct 30.

State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China. Electronic address:

The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9μM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.
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http://dx.doi.org/10.1016/j.bmcl.2015.10.089DOI Listing
December 2015

Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters.

Atherosclerosis 2015 Sep 27;242(1):77-86. Epub 2015 Jun 27.

Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. Electronic address:

Objective: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet.

Methods And Results: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter.

Conclusion: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.046DOI Listing
September 2015

Functional annotation of cis-regulatory elements in human cells by dCas9/sgRNA.

Cell Res 2015 Jul 5;25(7):877-80. Epub 2015 Jun 5.

State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu 210061, China.

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http://dx.doi.org/10.1038/cr.2015.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493279PMC
July 2015
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