Publications by authors named "Shuo Zhu"

17 Publications

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The Maturation of Tumor Suppressor miR-497 in Hepatocellular Carcinoma is Inhibited by Oncogenic circRNA SCARB1.

Cancer Manag Res 2021 16;13:5751-5759. Epub 2021 Jul 16.

Department of Hepatobiliary Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu Province, 221000, People's Republic of China.

Introduction: Circular RNA (CircRNA) SCARB1 plays an oncogenic role in renal cell carcinoma, while its role in other cancers is unclear. The aim of this study was to explore the role of circRNA SCARB1 in hepatocellular carcinoma (HCC).

Methods: The expression of circRNA SCARB1, mature miR-497 and miR-497 precursor in HCC and paired non-tumor tissues from 64 HCC patients were analyzed by RT-qPCR. CircRNA SCARB1 was overexpressed in HCC cells, followed by the measurement of the expression levels of both mature miR-497 and miR-497 precursor to evaluate the effects of overexpression of circRNA SCARB1 on the maturation of miR-497. The effects of circRNA SCARB1 and miR-497 on the proliferation and migration of HCC cells were assessed by CCK-8 assay and Transwell assay, respectively.

Results: We found that circRNA SCARB1 was upregulated in HCC. In addition, mature miR-497 and miR-497 were downregulated in HCC. Correlation analysis showed that circRNA SCARB1 was inversely correlated with mature miR-497 but not miR-497 precursor. Consistently, in HCC cells, downregulated mature miR-497, but not miR-497 precursor, was observed in HCC cells transfected with circRNA SCARB1 expression vector. Analysis of cellular behaviors showed that overexpression of circRNA SCARB1 increased the proliferation and migration of HCC cells, while overexpression of miR-497 decreased cell proliferation and migration. Moreover, overexpression of miR-497 reduced the effects of overexpression of circRNA SCARB1.

Discussion: Therefore, circRNA SCARB1 is upregulated in HCC and promotes HCC cell proliferation and migration by suppressing the maturation of miR-497.
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http://dx.doi.org/10.2147/CMAR.S304125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292958PMC
July 2021

Multifactorial Mechanisms of Tolerance to Ketoconazole in Candida albicans.

Microbiol Spectr 2021 Jun 23:e0032121. Epub 2021 Jun 23.

Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Candida albicans is a prevalent opportunistic human fungal pathogen for which treatment is limited to only four main classes of antifungal drugs, with the azole and echinocandin classes being used most frequently. Drug tolerance, the ability of some cells to grow slowly in supra-MIC drug concentrations, decreases the number of available treatment options. Here, we investigated factors affecting tolerance and resistance to ketoconazole in C. albicans. We found both temperature and the composition of growth medium significantly affected tolerance with little effect on resistance. In deletion analysis of known efflux pump genes, was partially required for azole tolerance, while and were dispensable. Tolerance also required Hsp90 and calcineurin components; , which encodes a transcription factor downstream of calcineurin, was required only partially. Deletion of , which encodes a vacuolar ATPase subunit, and concanamycin A, a V-ATPase inhibitor, abolished tolerance, indicating the importance of vacuolar energy transactions in tolerance. Thus, tolerance to ketoconazole is regulated by multiple factors, including physiological and genetic mechanisms. Due to the ever-expanding range of invasive medical procedures and treatments, invasive fungal infections now pose a serious global threat to many people living in an immunocompromised status. Like humans, fungi are eukaryotic, which significantly limits the number of unique antifungal targets; the current arsenal of antifungal agents is limited to just three frontline drug classes. Additional treatment complexities result from the development of drug tolerance and resistance, which further narrows therapeutic options; however, the difference between tolerance and resistance remains largely unknown. This study demonstrates that tolerance and resistance are regulated by multiple genetic and physiological factors. It is prudent to note that some factors affect tolerance only, while other factors affect both tolerance and resistance. The complex underlying mechanisms of these drug responses are highlighted by the fact that there are both shared and distinct mechanisms that regulate tolerance and resistance.
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http://dx.doi.org/10.1128/Spectrum.00321-21DOI Listing
June 2021

Hepatobiliary phase images of gadoxetic acid-enhanced MRI may improve accuracy of predicting the size of hepatocellular carcinoma at pathology.

Acta Radiol 2021 May 8:2841851211014194. Epub 2021 May 8.

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, PR China.

Background: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size.

Purpose: To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference.

Material And Methods: A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland-Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC).

Results: Correlation between the MR images and pathology was high for both readers (0.899-0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, ≤0.012; reader 2, ≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971-0.997).

Conclusion: The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.
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http://dx.doi.org/10.1177/02841851211014194DOI Listing
May 2021

Locating and Imaging through Scattering Medium in a Large Depth.

Sensors (Basel) 2020 Dec 25;21(1). Epub 2020 Dec 25.

Jiangsu Key Laboratory of Spectral Imaging and Intelligent Sense, Nanjing University of Science and Technology, Nanjing 210094, China.

Scattering medium brings great difficulties to locate and reconstruct objects especially when the objects are distributed in different positions. In this paper, a novel physics and learning-heuristic method is presented to locate and image the object through a strong scattering medium. A novel physics-informed framework, named DINet, is constructed to predict the depth and the image of the hidden object from the captured speckle pattern. With the phase-space constraint and the efficient network structure, the proposed method enables to locate the object with a depth mean error less than 0.05 mm, and image the object with an average peak signal-to-noise ratio (PSNR) above 24 dB, ranging from 350 mm to 1150 mm. The constructed DINet firstly solves the problem of quantitative locating and imaging via a single speckle pattern in a large depth. Comparing with the traditional methods, it paves the way to the practical applications requiring multi-physics through scattering media.
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http://dx.doi.org/10.3390/s21010090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796240PMC
December 2020

Relevance of EGFR Between Serum VEGF and MMP-9 in Primary Hepatocellular Carcinoma Patients with Transarterial Chemoembolization.

Onco Targets Ther 2020 23;13:9407-9417. Epub 2020 Sep 23.

Department of Clinical laboratory, Xuzhou Cancer Hospital, Xuzhou, Jiangsu 221005, People's Republic of China.

Objective: The aim of this study was to estimate the relevance of the epidermal growth factor receptor (EGFR) between serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) in primary hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE).

Methods: The pre-treatment and post-treatment concentrations of the serum VEGF and MMP‑9 were detected with Luminex assay in 80 EGFR-negative patients and 59 EGFR-positive patients who received TACE therapy with different chemotherapeutic drugs.

Results: The serum concentration of MMP-9 in the EGFR-positive patients with primary HCC was significantly higher than that in the EGFR-negative patients ( < 0.05). In EGFR-positive patients with primary HCC, differences in stage, metastasis, and differentiation were significant ( < 0.05). Serum VEGF level significantly decreased at the second course of treatment in the EGFR-negative patients from the P group ( < 0.05), while serum MMP-9 level significantly decreased at the second course of treatment in the EGFR-negative patients from the E group ( < 0.05). Serum VEGF level in the EGFR-positive patients among three groups slightly decreased at the first, second and third courses of treatments; however, the differences were not significant ( > 0.05). Serum MMP-9 level in the EGFR-positive patients among three groups showed mild decrease at the first and second courses of treatments; however, the decreases at the third course of treatment were significant ( < 0.05).

Conclusion: Serum VEGF and MMP-9 are potential biomarkers for the treatment monitoring of EGFR-positive and -negative patients after TACE therapy with different chemotherapeutic drugs.
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http://dx.doi.org/10.2147/OTT.S257271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520140PMC
September 2020

Magnetic resonance morphologic features predict progression of incidental pancreatic cystic lesions during follow-up.

Diagn Interv Radiol 2020 Sep;26(5):396-402

Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.

Purpose: We aimed to evaluate which morphologic features on magnetic resonance imaging (MRI) could predict the progression of pancreatic cystic lesions (PCLs) that are suitable for follow-up.

Methods: A total of 2176 MRI findings of PCLs were retrospectively reviewed between January 2009 and December 2016. The study population was composed of 223 patients. Clinical data and morphologic features of PCLs were recorded. We divided the individuals into two sub-groups according to the final features on MRI. Univariable and multivariable regression analyses were performed to identify independent risk factors for progression of PCLs.

Results: A total of 84 PCLs (37.7%) progressed during follow-up, while 139 PCLs (62.3%) were stable. Age (odds ratio [OR], 1.042; P = 0.017), number of lesions (OR, 0.491; P = 0.048), communication to pancreatic duct (PD) (OR, 2.425; P = 0.007) and presence of septa (OR, 6.105; P < 0.001) were significant independent factors for progression of PCLs. Among 84 lesions that progressed, 23 lesions (27.4%) increased to ≥ 30 mm in diameter or showed worrisome imaging features at the end of follow-up that needed clinical intervention. The initial size and communication to PD were independent factors for progression of PCLs necessitating clinical intervention (P < 0.001 and P = 0.011, respectively).

Conclusion: Age, number of the lesions, communication to PD and presence of septa were independent risk factors for the progression of PCLs, and the initial size and communication to PD could potentially predict PCLs needing clinical interventions.
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http://dx.doi.org/10.5152/dir.2020.19362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490034PMC
September 2020

Learning-based method to reconstruct complex targets through scattering medium beyond the memory effect.

Opt Express 2020 Jan;28(2):2433-2446

Strong scattering medium brings great difficulties to image objects. Optical memory effect makes it possible to image through strong random scattering medium in a limited angle field-of-view (FOV). The limitation of FOV results in a limited optical memory effect range, which prevents the optical memory effect to be applied to real imaging applications. In this paper, a kind of practical convolutional neural network called PDSNet (Pragmatic De-scatter ConvNet) is constructed to image objects hidden behind different scattering media. The proposed method can expand at least 40 times of the optical memory effect range with a average PSNR above 24dB, and enable to image complex objects in real time, even for objects with untrained scales. The provided experiments can verify its accurateness and efficiency.
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http://dx.doi.org/10.1364/OE.383911DOI Listing
January 2020

Recurrence After Curative Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: Diagnostic Algorithms on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

Liver Transpl 2020 06 21;26(6):751-763. Epub 2020 Apr 21.

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Small recurrent hepatocellular carcinoma (HCC) can show atypical imaging patterns, and a specific diagnostic algorithm for HCC is lacking. This study aimed to better characterize postoperative recurrent HCCs <20 mm in size with gadoxetic acid-enhanced magnetic resonance imaging (MRI). We evaluated 373 newly developed nodules after hepatectomy in 204 HCC patients with chronic hepatitis B virus infection. The diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) version 2018 was calculated with gadoxetic acid-enhanced MRI to characterize recurrent HCC. Modified diagnostic algorithms were proposed by combining significant imaging biomarkers related to subcentimeter and 10-19 mm recurrence, and the algorithms were then compared with the LI-RADS system. A total of 256 recurrent HCCs (108 recurrent HCCs <10 mm in size; 148 recurrent HCCs 10-19 mm in size) were confirmed via histology or follow-up imaging. Nonrim arterial phase hyperenhancement (APHE) and 3 LI-RADS ancillary features (AFs; hepatobiliary phase hypointensity, mild-moderate T hyperintensity, and restricted diffusion) were significantly related to recurrent HCCs <20 mm in size according to a multivariate analysis. For subcentimeter recurrence, combining at least 2 of the 3 AFs only achieved better specificity (sensitivity, 83.3%; specificity, 87.7%) than the LR-4 category (sensitivity, 88.9%, P = 0.21; specificity, 70.8%, P = 0.006). For 10-19 mm recurrences, combining nonrim APHE and at least 1 of the 3 AFs achieved only a significantly enhanced sensitivity of 85.1% but a lower specificity of 86.5% compared with the LR-5 category (sensitivity: 63.5%, P < 0.001; specificity: 94.2%, P = 0.13). In conclusion, the diagnostic algorithms for subcentimeter and 10-19 mm recurrent HCCs should be stratified. Combining at least 2 AFs demonstrated comparable sensitivity with significantly enhanced specificity compared with the LR-4 category for characterizing subcentimeter recurrence.
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http://dx.doi.org/10.1002/lt.25713DOI Listing
June 2020

Pharmacodynamics Of Linezolid-Plus-Fosfomycin Against Vancomycin-Susceptible And -Resistant Enterococci In Vitro And In Vivo Of A Larval Infection Model.

Infect Drug Resist 2019 12;12:3497-3505. Epub 2019 Nov 12.

Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People's Republic of China.

Objectives: To explore the in vitro and in vivo antibacterial activity of linezolid/fosfomycin combination against vancomycin-susceptible and -resistant enterococci (VSE and VRE), and provide a theoretical basis for the treatment of VRE.

Methods: The checkerboard method and time-kill curve study were used to evaluate the efficacy of linezolid combined with fosfomycin against VSE and VRE. The transmission electron microscopy (TEM) was employed to observe the cell morphology of bacteria treated with each drug alone or in combination, which further elucidate the mechanism of action of antibiotic combination therapy. The infection model was constructed to demonstrate the in vivo efficacy of linezolid plus fosfomycin for VSE and VRE infection.

Results: The fractional inhibitory concentration index (FICI) values of all strains suggested that linezolid showed synergy or additivity in combination with fosfomycin against five of the six strains. Time-kill experiments demonstrated that the combination of linezolid-fosfomycin at 1×MIC or 2×MIC led to higher degree of bacterial killing without regrowth for all isolates tested than each monotherapy. TEM images showed that the combination treatment damaged the bacterial cell morphology more obviously than each drug alone. In the infection model, the enhanced survival rate of the combination treatment compared with linezolid monotherapy (P<0.05) was revealed.

Conclusion: Our data manifested that the combination of linezolid and fosfomycin was a potential therapeutic regimen for VRE infection. The combination displayed excellent bacterial killing and inhibited amplification of fosfomycin-resistant subpopulations.
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http://dx.doi.org/10.2147/IDR.S219117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858807PMC
November 2019

Difference analysis in prevalence of incidental pancreatic cystic lesions between computed tomography and magnetic resonance imaging.

BMC Med Imaging 2019 05 24;19(1):43. Epub 2019 May 24.

Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, 180 Fenglin Rd., Shanghai, 200032, China.

Background: The purpose was to investigate the difference of detection rate of incidental pancreatic cystic lesions (PCLs) with computed tomography (CT) and magnetic resonance imaging (MRI) and to compare the difference between CT and MRI and to explore the effect of this difference on surgical resection.

Methods: We reviewed the diagnostic reports for incidental PCLs between 2013 and 2016. Images of PCLs would be re-evaluated. Clinical and imaging data were recorded. The chi-square and independent t-test were conducted for categorical and continuous variables.

Results: The prevalence of PCLs was 1.91% (1038/54210) and 3.36% (1282/38099) on CT and MRI respectively, and increased with increasing age (P < 0.001). No significant differences were found in the annual prevalence of PCLs on CT (P = 0.796) and MRI (P = 0.213) from 2013 to 2016 while the number of examinations was increasing every year. The annual detection rate of MRI for small PCLs (< 20 mm) was significantly higher than CT (P < 0.001), but was not significantly different for large PCLs (≥20 mm). The rate of surgical resection of PCLs (≥20 mm) in MRI group was higher than CT (55.2% vs. 37.0%, P < 0.001).

Conclusions: The detection rate of PCLs on CT and MRI tended to be stable despite increasing scan volumes. Female had a slightly more frequency of PCLs than male. MRI detected more small PCLs(< 20 mm) and had higher impact on surgical resection of large PCL(≥20 mm) compared with CT.
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http://dx.doi.org/10.1186/s12880-019-0341-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534824PMC
May 2019

Manufacturing and Analysis of High-Performance Refractory High-Entropy Alloy via Selective Laser Melting (SLM).

Materials (Basel) 2019 Mar 1;12(5). Epub 2019 Mar 1.

School of Mechanical Engineering, Xi'an Jiao Tong University, State Key Laboratory of Manufacturing System Engineering, Xi'an 710049, China.

Refractory high-entropy alloys (HEAs) have excellent mechanical properties, which could make them the substitutes of some superalloys. However, the high melting point of refractory HEAs leads to processing problems when using traditional processing techniques. In this study, a single BCC solid solution of NbMoTaW alloy was formed by selective laser melting (SLM) with a linear energy density of up to 2.83 J/mm. The composition distribution was analyzed, and the element with a lower melting point and lower density showed a negative deviation (no more than 5%) of the molar ratio in the formed alloy. The HEA shows an excellent microstructure, microhardness, and corrosion resistance performance compared with traditional superalloys, making it a new substitute metal with great application prospects in aerospace and energy fields.
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http://dx.doi.org/10.3390/ma12050720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427779PMC
March 2019

Selenium Attenuates Staphylococcus aureus Mastitis in Mice by Inhibiting the Activation of the NALP3 Inflammasome and NF-κB/MAPK Pathway.

Biol Trace Elem Res 2019 Sep 7;191(1):159-166. Epub 2018 Dec 7.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Mastitis is one of the most important diseases affecting the dairy industry in the world, and it also poses a great threat to human food safety. In this study, we explored whether selenium can inhibit the activation of the NALP3 inflammasome and NF-κB/MAPK pathway to achieve anti-inflammatory effects. Sixty BALB/c female mice were randomly divided into three groups according to diets of different selenium concentrations (high, normal, and low). After 90 days, mice fed the same selenium concentration were randomly divided into two smaller groups, one of which was inoculated with Staphylococcus aureus and the other injected with saline as a control. Through histopathologic examination staining, western blot, qPCR, and ELISA, the results showed that with increasing selenium concentrations, the expression levels of IL-1β, TNF-α, NALP3, caspase-1, and ASC were decreased in mouse mammary tissue. Therefore, this study revealed that selenium can attenuate S. aureus mastitis by inhibiting the activation of the NALP3 inflammasome and NF-κB/MAPK pathway.
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http://dx.doi.org/10.1007/s12011-018-1591-8DOI Listing
September 2019

T mapping on gadoxetic acid-enhanced MR imaging predicts recurrence of hepatocellular carcinoma after hepatectomy.

Eur J Radiol 2018 Jun 28;103:25-31. Epub 2018 Mar 28.

Department of Radiology, Zhongshan Hospital, Fudan University, and Shanghai Medical Imaging Institute, Shanghai, China. Electronic address:

Purpose: Our purpose was to demonstrate the prognostic significance of T mapping on gadoxetic acid-enhanced MR imaging in prediction of recurrence of single HCC after hepatectomy.

Materials And Methods: One hundred and seven patients with single nodular HCC (≤3 cm) who underwent preoperative gadoxetic acid-enhanced MRI were included in the study. T mapping with syngo MapIt was obtained on a 1.5 T scanner. Radiological features and reduction rate of T relaxation time (Δ%) of tumors were assessed by two radiologists. Cumulative recurrence rates were compared between groups of low and high reduction rate of T relaxation time. A further classified cumulative recurrence rate of the overall cohort was based on the numbers of independent predictive factors.

Results: Reduction rate of T relaxation time (P = 0.001) and non-hypervascular hypointense nodules (P = 0.042) in preoperative gadoxetic acid-enhanced MRI were independently related to recurrence of HCC after hepatectomy. Patients of lower reduction rates group had higher cumulative recurrence rates (P < 0.0001) than patients of higher reduction rates group. A combination of the two risk factors in patients with single HCC had significantly higher recurrence rates compared to those with either or none of the two risk factors.

Conclusions: Reduction rate of T relaxation time combined with non-hypervascular hypointense nodules can be reliable biomarkers in the preoperative prediction of recurrence of HCC after hepatectomy.
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http://dx.doi.org/10.1016/j.ejrad.2018.03.027DOI Listing
June 2018

[Left ventricle segmentation in echocardiography based on adaptive mean shift].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2018 04;35(2):273-279

Guizhou Medcial University, Guiyang 550025, P.R.China.

The use of echocardiography ventricle segmentation can obtain ventricular volume parameters, and it is helpful to evaluate cardiac function. However, the ultrasound images have the characteristics of high noise and difficulty in segmentation, bringing huge workload to segment the object region manually. Meanwhile, the automatic segmentation technology cannot guarantee the segmentation accuracy. In order to solve this problem, a novel algorithm framework is proposed to segment the ventricle. Firstly, faster region-based convolutional neural network is used to locate the object to get the region of interest. Secondly, -means is used to pre-segment the image; then a mean shift with adaptive bandwidth of kernel function is proposed to segment the region of interest. Finally, the region growing algorithm is used to get the object region. By this framework, ventricle is obtained automatically without manual localization. Experiments prove that this framework can segment the object accurately, and the algorithm of adaptive mean shift is more stable and accurate than the mean shift with fixed bandwidth on quantitative evaluation. These results show that the method in this paper is helpful for automatic segmentation of left ventricle in echocardiography.
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http://dx.doi.org/10.7507/1001-5515.201702037DOI Listing
April 2018

microRNA-452 exerts growth-suppressive activity against T-cell acute lymphoblastic leukemia.

J Investig Med 2018 04 10;66(4):773-779. Epub 2018 Jan 10.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored. It was found that miR-452 expression levels were significantly lower in T-ALL specimens than in normal lymph node biopsies (P=0.0079). T-ALL specimens had a significantly higher methylation level in the promoter of miR-452 than normal lymph node tissues (P=0.0014). Consistently, miR-452 was downregulated in Jurkat and Molt-4 T-ALL cells, whose expression was restored after treatment with a demethylation agent 5-aza-2'-deoxycytidine. Ectopic expression of miR-452 inhibited the proliferation of Jurkat and Molt-4 cells and induced a G0/G1 cell cycle arrest. Overexpression of miR-452 suppressed the protein expression of BMI1 in T-ALL cells. Rescue experiments revealed that overexpression of BMI1 partially reversed the growth-suppressive effect of miR-452 on T-ALL cells. Xenograft tumor studies confirmed that overexpression of miR-452 suppressed tumor growth in nude mice and reduced the expression of BMI1. Collectively, miR-452 is epigenetically silenced and targets BMI1 to exert a growth suppressive activity in T-ALL. Restoration of miR-452 expression may represent a promising therapeutic strategy for this malignancy.
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http://dx.doi.org/10.1136/jim-2017-000591DOI Listing
April 2018

Characterization of a novel anti-lipopolysaccharide factor isoform (SpALF5) in mud crab, Scylla paramamosain.

Mol Immunol 2015 Apr 30;64(2):262-75. Epub 2014 Dec 30.

Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou 515063, China; Marine Biology Institute, Shantou University, Shantou 515063, China. Electronic address:

Anti-lipopolysaccharide factors (ALFs), the potential antimicrobial peptides that bind and neutralize lipopolysaccharide (LPS), are common effectors of innate immunity in crustaceans. In this study, a novel isoform of ALFs (SpALF5) was isolated from the hemocytes of mud crab Scylla paramamosain. The full-length 975bp SpALF5 contains a 375bp open reading frame (ORF) encoding 125 amino acids. Although SpALF5 exhibits a low degree of nucleotide homology with other reported ALFs, it contains the conserved amino acid sequence with a signal peptide and a LPS-binding domain including two conservative cysteine residues. The genomic organization of SpALF5 consists of four exons and three introns, with each intron containing one or more tandem repeats. Unlike most of ALFs mainly distributed in crab hemocytes, SpALF5 transcript was predominantly observed in the brain, muscle and skin, while barely detected in the hemocytes in our study. In situ hybridization assay also showed that SpALF5 mRNA was localized in brain, muscle and skin tissues of mud crab. Further, SpALF5 transcript was significantly up-regulated after challenge with LPS, polyinosinic polycytidylic acid (PolyI:C) (with the except of that in brain), Vibrio parahemolyticus or white spot syndrome virus (WSSV). The recombinant SpALF5 protein showed a varying degree of binding activity towards bacteria and fungus. Moreover, in vitro, the recombinant SpALF5 revealed a strong antimicrobial activity against Gram-negative bacteria (V. parahemolyticus, Vibrio alginolyticus, Escherichia coli, Aeromonas hydrophila) and fungus (Sacchromyces cerevisiae), but could only inhibited the growth of some Gram-positive bacteria like Staphylococcus aureus. The results suggest that SpALF5 is a potent immune protector and plays an important role in immune defense against invading pathogens in S. paramamosain.
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http://dx.doi.org/10.1016/j.molimm.2014.12.006DOI Listing
April 2015

Characterization of microRNAs in mud crab Scylla paramamosain under Vibrio parahaemolyticus infection.

PLoS One 2013 30;8(8):e73392. Epub 2013 Aug 30.

Guangdong Provincial Key Laboratory of Marine Biology, Marine Biology Institute, Shantou University, Shantou, China.

Background: Infection of bacterial Vibrio parahaemolyticus is common in mud crab farms. However, the mechanisms of the crab's response to pathogenic V. parahaemolyticus infection are not fully understood. MicroRNAs (miRNAs) are a class of small noncoding RNAs that function as regulators of gene expression and play essential roles in various biological processes. To understand the underlying mechanisms of the molecular immune response of the crab to the pathogens, high-throughput Illumina/Solexa deep sequencing technology was used to investigate the expression profiles of miRNAs in S. paramamosain under V. parahaemolyticus infection.

Methodology/principal Findings: Two mixed RNA pools of 7 tissues (intestine, heart, liver, gill, brain, muscle and blood) were obtained from V. parahaemolyticus infected crabs and the control groups, respectively. By aligning the sequencing data with known miRNAs, we characterized 421 miRNA families, and 133 conserved miRNA families in mud crab S. paramamosain were either identical or very similar to existing miRNAs in miRBase. Stem-loop qRT-PCRs were used to scan the expression levels of four randomly chosen differentially expressed miRNAs and tissue distribution. Eight novel potential miRNAs were confirmed by qRT-PCR analysis and the precursors of these novel miRNAs were verified by PCR amplification, cloning and sequencing in S. paramamosain. 161 miRNAs (106 of which up-regulated and 55 down-regulated) were significantly differentially expressed during the challenge and the potential targets of these differentially expressed miRNAs were predicted. Furthermore, we demonstrated evolutionary conservation of mud crab miRNAs in the animal evolution process.

Conclusions/significance: In this study, a large number of miRNAs were identified in S. paramamosain when challenged with V. parahaemolyticus, some of which were differentially expressed. The results show that miRNAs might play some important roles in regulating gene expression in mud crab under V. parahaemolyticus infection, providing a basis for further investigation of miRNA-modulating networks in innate immunity of mud crab.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073392PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758354PMC
April 2014
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