Publications by authors named "Lihong Zheng"

26 Publications

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Artificial intelligence (AI) for medical imaging to combat coronavirus disease (COVID-19): a detailed review with direction for future research.

Artif Intell Rev 2021 Apr 15:1-31. Epub 2021 Apr 15.

Discipline of Business Analytics in Business School, The University of Sydney, Sydney, Australia.

Since early 2020, the whole world has been facing the deadly and highly contagious disease named coronavirus disease (COVID-19) and the World Health Organization declared the pandemic on 11 March 2020. Over 23 million positive cases of COVID-19 have been reported till late August 2020. Medical images such as chest X-rays and Computed Tomography scans are becoming one of the main leading clinical diagnosis tools in fighting against COVID-19, underpinned by Artificial Intelligence based techniques, resulting in rapid decision-making in saving lives. This article provides an extensive review of AI-based methods to assist medical practitioners with comprehensive knowledge of the efficient AI-based methods for efficient COVID-19 diagnosis. Nearly all the reported methods so far along with their pros and cons as well as recommendations for improvements are discussed, including image acquisition, segmentation, classification, and follow-up diagnosis phases developed between 2019 and 2020. AI and machine learning technologies have boosted the accuracy of Covid-19 diagnosis, and most of the widely used deep learning methods have been implemented and worked well with a small amount of data for COVID-19 diagnosis. This review presents a detailed mythological analysis for the evaluation of AI-based methods used in the process of detecting COVID-19 from medical images. However, due to the quick outbreak of Covid-19, there are not many ground-truth datasets available for the communities. It is necessary to combine clinical experts' observations and information from images to have a reliable and efficient COVID-19 diagnosis. This paper suggests that future research may focus on multi-modality based models as well as how to select the best model architecture where AI can introduce more intelligence to medical systems to capture the characteristics of diseases by learning from multi-modality data to obtain reliable results for COVID-19 diagnosis for timely treatment .
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http://dx.doi.org/10.1007/s10462-021-09985-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047522PMC
April 2021

Retracted: Dexmedetomidine Regulates Proliferation, Apoptosis, Migration, and Invasion in Ovarian Cancer Cells via MiR-155-HIF-1α Axis.

Med Sci Monit 2021 Jan 28;27:e931024. Epub 2021 Jan 28.

Department of Anesthesiology, Taixing People's Hospital, Taizhou, Jiangsu, China (mainland).

This paper is retracted at the author's request. Reference: 1. Lihong Zheng, Ruimei Jia, Juan Zhao: Dexmedetomidine Regulates Proliferation, Apoptosis, Migration, and Invasion in Ovarian Cancer Cells via MiR-155-HIF-1alpha Axis. Med Sci Monit, 2019; 25: 10164-10172. DOI: 10.12659/MSM.919112.
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http://dx.doi.org/10.12659/MSM.931024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852561PMC
January 2021

Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats.

J Mol Neurosci 2021 Jan 5. Epub 2021 Jan 5.

First Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 26, Heping Road, Xiangfang District, Harbin, 150040, China.

Baihui-penetrating-Qubin acupuncture is frequently used to treat intracerebral hemorrhage (ICH) in China. Acupuncture affects multiple microRNAs in diseases. MicroRNA-23a-3p (miR-23a-3p) has been demonstrated to be up-regulated in ICH patients. Herein, the effect of Baihui-penetrating-Qubin acupuncture on miR-23a-3p expression after ICH and the role of miR-23a-3p in ICH were discussed. A rat model of ICH was induced by infusing autologous blood into caudate nucleus. Acupuncture was performed after ICH once a day for 30 min. After 3 consecutive days of acupuncture, the neurobehavioral function, brain edema, neuronal cell death, inflammation, ferroptosis, nuclear factor E2-like 2 (NFE2L2) signaling and miR-23a-3p levels in brain tissues were analyzed. Additionally, antagomiR-23a-3p was injected into rats 3 days prior to ICH modeling to analyze the function of miR-23a-3p in neuronal cell death, inflammation, ferroptosis, and NFE2L2 signaling. Acupuncture relieved the ICH-induced neurological function deficits, increases in brain water content and Fluoro-Jade B (FJB)-positive cells and release of proinflammatory cytokines. Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. This study provides a potential mechanism underlying the Baihui-penetrating-Qubin acupuncture improving the early injury after ICH.
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http://dx.doi.org/10.1007/s12031-020-01770-xDOI Listing
January 2021

Effect of Dexmedetomidine on Perioperative Stress Response and Immune Function in Patients With Tumors.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820977542

Department of Anesthesiology, Northwest Women and Children's Hospital, Xian, Shanxi, China.

Objective: This study aims to investigate the effect of dexmedetomidine on perioperative stress response and immune function in patients with tumors.

Methods: Sixty patients who underwent selective radical gastrectomy for cancer were randomly divided into 3 groups: remifentanil group (group R), dexmedetomidine group (group D), and sufentanil group (group S). Remifentanil, dexmedetomidine, and sufentanil were used as general anesthetics. Endotracheal intubation and mechanical ventilation were performed after the spontaneous respiration disappeared. Then, the data were recorded, and blood samples were collected at all time points.

Results: The heart rate significantly increased ( < 0.05) at T1 in group S, and both heart rate and mean arterial pressure significantly increased ( < 0.05) in group R when compared to group D. The heart rate significantly increased ( < 0.05) at T2 in group S and group R. Furthermore, the heart rate significantly increased ( < 0.05) at T3 and T4 in group S and group R. Intra-group comparison: The heart rate at T1-T4 and mean arterial pressure at T1-T4 significantly increased ( < 0.05) in group S, and the heart rate at T1 and T4, and mean arterial pressure at T2-T4 significantly increased ( < 0.05) in group R when compared to T0. The serum IL-6, IFN-γ, and β-EP significantly increased ( < 0.05) at T0' in group S and group R when compared to group D. Blood glucose, and serum IL-10, IFN-γ, and β-EP significantly increased ( < 0.05), while IL-18 significantly decreased ( < 0.05) at T1' in group S and group R.

Conclusion: Continuous infusion of dexmedetomidine in combination with the inhalation of sevoflurane is superior to sevoflurane + remifentanil or sufentanil in patients undergoing tumor surgery.
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http://dx.doi.org/10.1177/1533033820977542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768568PMC
December 2020

Dexmedetomidine Regulates Proliferation, Apoptosis, Migration, and Invasion in Ovarian Cancer Cells via MiR-155-HIF-1α Axis.

Med Sci Monit 2019 Dec 30;25:10164-10172. Epub 2019 Dec 30.

Department of Anesthesiology, Taixing People's Hospital, Taizhou, Jiangsu, China (mainland).

BACKGROUND Dexmedetomidine (DMED) is widely used as an adjuvant anesthetic, but how DMED regulates biological behavior of OC cells remains an area of active research. This study investigated the mechanism by which DMED regulates the proliferation, apoptosis, migration, and invasion abilities of OC cells. MATERIAL AND METHODS We determined the optimal concentration of DMED for use in treating SKOV3 cells. The biological activities of DMED-treated SKOV3 cells following transfection with miR-155 inhibitor or si-HIF-1alpha were measured by CCK-8 assay, flow cytometry, wound healing assay, and Transwell assay. qRT-PCR and Western blot analysis were performed to assess the expression levels of apoptotic-related caspase-3 and Mcl-1. Luciferase reporter assay verified the targeting relationship of miR-155 and HIF-1alpha. RESULTS miR-155 was downregulated while HIF-1alpha was upregulated in SKOV3 cells. DMED dose-dependently reduced HIF-1alpha expression in SKOV3 cells, and upregulated the expression of miR-155. DMED inhibited the proliferation, migration and invasion abilities of OC cells, but also contributed to apoptosis of SKOV3 cells, while transfection of miR-155 inhibitor inhibited the effect of DMED on SKOV3 cells. In contrast, transfection with si-HIF-1alpha enhanced the effects of DMED on SKOV3 cells. HIF-1alpha was found to be a target gene of miR-155. CONCLUSIONS Our results suggest that DMED blocks cell proliferation, migration, and invasion and accelerates cell apoptosis in OC.
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http://dx.doi.org/10.12659/MSM.919112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951111PMC
December 2019

Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.

EBioMedicine 2019 May 8;43:201-210. Epub 2019 Apr 8.

John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address:

Background: Bromodomain and extra-terminal inhibitors (BETi) have shown efficacy for the treatment of aggressive triple negative breast cancer (TNBC). However, BETi are plagued by a narrow therapeutic window as manifested by severe toxicities at effective doses. Therefore, it is a limitation to their clinical implementation in patient care.

Methods: The impact of vitamin C on the efficacy of small compounds including BETi was assessed by high-throughput screening. Co-treatment of TNBC by BETi especially JQ1 and vitamin C was evaluated in vitro and in vivo.

Findings: High-throughput screening revealed that vitamin C improves the efficacy of a number of structurally-unrelated BETi including JQ1, I-BET762, I-BET151, and CPI-203 in treating TNBC cells. The synergy between BETi and vitamin C is due to suppressed histone acetylation (H3ac and H4ac), which is in turn caused by upregulated histone deacetylase 1 (HDAC1) expression upon vitamin C addition. Treatment with JQ1 at lower doses together with vitamin C induces apoptosis and inhibits the clonogenic ability of cultured TNBC cells. Oral vitamin C supplementation renders a sub-therapeutic dose of JQ1 able to inhibit human TNBC xenograft growth and metastasis in mice.

Interpretation: Vitamin C expands the therapeutic window of BETi by sensitizing TNBC to BETi. Using vitamin C as a co-treatment, lower doses of BETi could be used to achieve an increased therapeutic index in patients, which will translate to a reduced side effect profile. FUND: University of Miami Sylvester Comprehensive Cancer Center, Bankhead Coley Cancer Research program (7BC10), Flight Attendant Medical Research Institute, and NIH R21CA191668 (to GW) and 1R56AG061911 (to CW and CHV).
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http://dx.doi.org/10.1016/j.ebiom.2019.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557781PMC
May 2019

Etoposide-induced DNA damage affects multiple cellular pathways in addition to DNA damage response.

Oncotarget 2018 May 16;9(35):24122-24139. Epub 2018 Feb 16.

Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.

DNA damage response (DDR) coordinates lesion repair and checkpoint activation. DDR is intimately connected with transcription. However, the relationship between DDR and transcription has not been clearly established. We report here RNA-sequencing analyses of MCF7 cells containing double-strand breaks induced by etoposide. While etoposide does not apparently cause global changes in mRNA abundance, it altered some gene expression. At the setting of fold alteration ≥ 2 and false discovery rate (FDR) ≤ 0.001, FDR < 0.05, or < 0.05, etoposide upregulated 96, 268, or 860 genes and downregulated 41, 133, or 503 genes in MCF7 cells. Among these differentially expressed genes (DEGs), the processes of biogenesis, metabolism, cell motility, signal transduction, and others were affected; the pathways of Ras GTPase activity, RNA binding, cytokine-mediated signaling, kinase regulatory activity, protein binding, and translation were upregulated, and those pathways related to coated vesicle, calmodulin binding, and microtubule-based movement were downregulated. We further identified RABL6, RFTN2, FAS-AS1, and TCEB3CL as new DDR-affected genes in MCF7 and T47D cells. By metabolic labelling using 4-thiouridine, we observed dynamic alterations in the transcription of these genes in etoposide-treated MCF7 and T47D cells. During 0-2 hour etoposide treatment, RABL6 transcription was robustly increased at 0.5 and 1 hour in MCF7 cells and at 2 hours in T47D cells, while FAS-AS1 transcription was dramatically and steadily elevated in both cell lines. Taken together, we demonstrate dynamic alterations in transcription and that these changes affect multiple cellular processes in etoposide-induced DDR.
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http://dx.doi.org/10.18632/oncotarget.24517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963631PMC
May 2018

Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis.

Oncol Rep 2018 Jun 12;39(6):2807-2816. Epub 2018 Apr 12.

Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.

Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.
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http://dx.doi.org/10.3892/or.2018.6363DOI Listing
June 2018

An Effective Hybrid Routing Algorithm in WSN: Ant Colony Optimization in combination with Hop Count Minimization.

Sensors (Basel) 2018 Mar 29;18(4). Epub 2018 Mar 29.

School of Computing and Maths, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.

Low cost, high reliability and easy maintenance are key criteria in the design of routing protocols for wireless sensor networks (WSNs). This paper investigates the existing ant colony optimization (ACO)-based WSN routing algorithms and the minimum hop count WSN routing algorithms by reviewing their strengths and weaknesses. We also consider the critical factors of WSNs, such as energy constraint of sensor nodes, network load balancing and dynamic network topology. Then we propose a hybrid routing algorithm that integrates ACO and a minimum hop count scheme. The proposed algorithm is able to find the optimal routing path with minimal total energy consumption and balanced energy consumption on each node. The algorithm has unique superiority in terms of searching for the optimal path, balancing the network load and the network topology maintenance. The WSN model and the proposed algorithm have been implemented using C++. Extensive simulation experimental results have shown that our algorithm outperforms several other WSN routing algorithms on such aspects that include the rate of convergence, the success rate in searching for global optimal solution, and the network lifetime.
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http://dx.doi.org/10.3390/s18041020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948582PMC
March 2018

PDCD5 regulates cell proliferation, cell cycle progression and apoptosis.

Oncol Lett 2018 Jan 14;15(1):1177-1183. Epub 2017 Nov 14.

Department of Biogenetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.

Programmed cell death (PDCD)5 is cloned from human leukemia cell line TF-1. PDCD5 is one of the members of the programmed cell death protein family that is frequently involved in tumor growth and apoptosis. To investigate the molecular and cellular functions of PDCD5, the present study established a PDCD5 stably overexpressing A431 cell line and examined the role of PDCD5 in cell proliferation, cell cycle progression and apoptosis. The data demonstrated that overexpression of PDCD5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis in A431 cells. The expression profiles of certain key regulators of these cellular events were further investigated, including P53, B cell lymphoma (BCL)-2, BCL-2 associated X protein (BAX) and caspase (CASP)3. The data demonstrated that at the transcript and protein levels, P53, BAX and CASP3 were all upregulated in the PDCD5 stably overexpressing A431 cells whereas BCL-2 was downregulated, indicating that PDCD5 acts as an important upstream regulator of P53, BCL-2, BAX and CASP3. The data suggest that PDCD5 regulates cell proliferation, cell cycle progression and apoptosis in A431 cells. PDCD5 may be a novel tumor suppressor gene, and may be potentially used for cancer treatment in the future.
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http://dx.doi.org/10.3892/ol.2017.7401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780840PMC
January 2018

Specificity and Latent Correlation Learning for Action Recognition Using Synthetic Multi-View Data From Depth Maps.

IEEE Trans Image Process 2017 Dec 14;26(12):5560-5574. Epub 2017 Aug 14.

This paper presents a novel approach to action recognition using synthetic multi-view data from depth maps. Specifically, multiple views are first generated by rotating 3D point clouds from depth maps. A pyramid multi-view depth motion template is then adopted for multi-view action representation, characterizing the multi-scale motion and shape patterns in 3D. Empirically, despite the view-specific information, the latent information between multiple views often provides important cues for action recognition. Concentrating on this observation and motivated by the success of the dictionary learning framework, this paper proposes to explicitly learn a view-specific dictionary (called specificity) for each view, and simultaneously learn a latent dictionary (called latent correlation) across multiple views. Thus, a novel method, specificity and latent correlation learning, is put forward to learn the specificity that captures the most discriminative features of each view, and learn the latent correlation that contributes the inherent 3D information to multiple views. In this way, a compact and discriminative dictionary is constructed by specificity and latent correlation for feature representation of actions. The proposed method is evaluated on the MSR Action3D, the MSR Gesture3D, the MSR Action Pairs, and the ChaLearn multi-modal data sets, consistently achieving promising results compared with the state-of-the-art methods based on depth data.
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http://dx.doi.org/10.1109/TIP.2017.2740122DOI Listing
December 2017

Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis.

Oncotarget 2017 Jan;8(1):1628-1640

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications.
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http://dx.doi.org/10.18632/oncotarget.13703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352083PMC
January 2017

A promoter polymorphism in APJ gene is significantly associated with blood pressure changes and hypertension risk in Chinese women.

Oncotarget 2016 Dec;7(52):86257-86265

Department of Biochemistry, School of Basic Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang, China.

The aim of this study was to interrogate the gender-specific association of 5 well-defined polymorphisms in apelin/APJ system with both blood pressure changes and hypertension risk in a northeastern Chinese population. This is a population-based case-control study, including 650 hypertensive patients and 645 normotensive controls. Data were analyzed by STATA and Haplo.Stats. The genotype distributions of 5 study polymorphisms were in Hardy-Weinberg equilibrium in both genders. The rs7119375 and rs10501367 were completely linked. The genotypes (P = 0.001) and alleles (P < 0.001) of rs7119375 differed significantly between patients and controls in women. Carriers of rs7119375-AA genotype had significant higher systolic blood pressure (SBP) than carriers of rs7119375-GG genotype in both patients and controls of female gender (P < 0.01). Moreover, carriers of rs7119375-A allele were 1.80 times more likely to develop hypertension relative to carriers of rs7119375-GG genotype after adjusting for age, body mass index and glucose (odds ratio: 1.80; 95% confidence interval: 1.03-3.16; P= 0.040). Further allele combination analysis supported the leading contribution of rs7119375 to hypertension risk. Our findings demonstrated that the mutation of promoter polymorphism rs7119375 in APJ gene was significantly associated with elevated SBP and increased hypertension risk in Chinese women.
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http://dx.doi.org/10.18632/oncotarget.13370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349911PMC
December 2016

Antinociceptive activity of a polysaccharide from the roots of Sophora flavescens.

Int J Biol Macromol 2016 Dec 23;93(Pt A):501-505. Epub 2016 Aug 23.

The Anesthesiology Department of the Tumor Hospital Affiliated to Harbin Medical University, Harbin, 150081, PR China. Electronic address:

A polysaccharide (SFWP), with a molecular weight of 51kDa, was successfully purified from the roots of Sophora flavescens and the antinociceptive actions of SFWP were evaluated using acetic acid induced writhing, tail flick, and formalin tests in mice. GC-MS results showed that SFWP had a backbone composed of (1→2)-linked Glc, (1→2,6)-inkedGal and (1→3,6)-inked Man residues, which were terminated with (1→)-inked Xyl and (1→)-inked Ara at O-6 of (1→2,6)-inkedGal and (1→3,6)-inked Man along the main chain, in the ratio of 2.0: 1.02: 1.09: 1.10: 0.98. Data showed that SFWP (100, 200 and 400mg/kg) significantly reduced the number of writhings induced by acetic acid in a dose-dependent manner. However, SFWP did not produce analgesia in tail-flick test. Moreover SFWP strongly attenuated the formalin-induced flinching behaviour in the second phases but not in the first phase in a dose-dependent manner. These results revealed that SFWP could be used safely to attenuate both inflammatory and peripheral neuropathic pain.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.08.054DOI Listing
December 2016

The role of the androgen receptor in ovarian cancer carcinogenesis and its clinical implications.

Oncotarget 2017 Apr;8(17):29395-29405

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Ovarian cancer is the major cause of death in women with gynecologic malignancies. There is emerging evidence that Androgen/androgen receptor (AR) signaling plays a critical role in the etiology and progression of this disease. Androgen receptor is frequently expressed in various subtypes of ovarian cancers and androgen/AR signaling has been shown to promote proliferation, migration, and invasion of ovarian cancer cells. Furthermore, shorter AR CAG repeats length and increased AR activity are associated with increased ovarian cancer risk and may be a useful prognosticator under certain circumstances. Here, we summarize current findings regarding the role of the AR in ovarian cancer and discuss agents that target this pathway as potential therapeutics for ovarian cancer.
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http://dx.doi.org/10.18632/oncotarget.12561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438739PMC
April 2017

Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population.

J Cell Mol Med 2016 10 31;20(10):1966-73. Epub 2016 May 31.

Department of Biogenetics, Qiqihar Medical University, Qiqihar, Heilongjiang, China.

Breast cancer constitutes an enormous burden in China. A strong familial clustering of breast cancer suggests a genetic component in its carcinogenesis. To examine the genetic predisposition of high mobility group box-1/receptor for advanced glycation end products (HMGB1/RAGE) pathway to breast cancer, we genotyped six well-defined polymorphisms in this pathway among 524 breast cancer patients and 518 cancer-free controls from Heilongjiang province, China. There were no deviations from Hardy-Weinberg equilibrium for all polymorphisms. In single-locus analysis, the frequency of rs1800624 polymorphism mutant A allele in RAGE gene was significantly higher in patients than in controls (24.52% versus 19.50%, P = 0.006), with the carriers of rs1800624-A allele being 1.51 times more likely to develop breast cancer relative to those with rs1800624-GG genotype after adjustment (95% confidence interval or CI: 1.17-1.94, P = 0.001). In HMGB1 gene, haplotype analysis did not reveal any significance, while in RAGE gene, haplotypes C-T-A and C-A-G (alleles in order of rs1800625, rs18006024, rs2070600) were significantly associated with an increased risk of breast cancer (adjusted OR = 2.72 and 10.35; 95% CI: 1.20-6.18 and 1.58-67.80; P = 0.017 and 0.015 respectively). In further genetic score analysis, per unit and quartile increments of unfavourable alleles were significantly associated with an increased risk of breast cancer after adjustment (odds ratio or OR = 1.20 and 1.26; 95% CI: 1.09-1.32 and 1.12-1.42; P < 0.001 and <0.001 respectively). Our findings altogether demonstrate a significant association between RAGE gene rs1800624 polymorphism and breast cancer risk, and more importantly a cumulative impact of multiple risk associated polymorphisms in HMGB1/RAGE pathway on breast carcinogenesis.
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http://dx.doi.org/10.1111/jcmm.12888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020633PMC
October 2016

The Benefits and Side Effects of Bevacizumab for the Treatment of Recurrent Ovarian Cancer.

Curr Drug Targets 2017 ;18(10):1125-1131

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, China.

Background: Ovarian cancer is the leading cause of deaths attributable to gynecologic malignancies. Late diagnosis and a high tendency of metastasis and drug resistance often lead to recurrence and poor outcomes. Anti-angiogenesis is considered a promising therapeutic strategy for recurrent ovarian cancers. Anti-VEGF body, bevacizumab, is an angiogenesis inhibitor with demonstrated activity and tolerable toxicity.

Objective: To elucidate the benefits and side effects of bevacizumab for the therapy of recurrent ovarian cancer.

Methods: Reviewed the results of published clinical trials.

Results: Recent Phase II studies indicated that bevacizumab monotherapy or in combination with conventional or other anti-angiogenic chemotherapy reagents could be effective for recurrent (platinum- sensitive and -resistant) ovarian cancers. Additionally, two phase III randomized trials reached similar conclusions that in either platinum-sensitive or -resistant ovarian cancers, adding bevacizumab to chemotherapy can improve progression-free survival. Despite the general recognition of bevacizumab as a well-tolerated drug in recurrent ovarian cancer patients, oncologists have become aware of the significant risks associated with gastrointestinal perforation.

Conclusion: Bevacizumab used alone or combined with other chemotherapy reagents is efficacious and tolerable in the treatment of recurrent ovarian cancer.
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http://dx.doi.org/10.2174/1389450117666160502150237DOI Listing
April 2018

Advance on the bioactivity and potential applications of dietary fibre from grape pomace.

Food Chem 2015 Nov 15;186:207-12. Epub 2014 Jul 15.

College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066600, PR China. Electronic address:

The winemaking grape pomaces are rich in bioactive phytochemicals and dietary fibre (DF). DFs are phenolic-rich DF matrix and are dietary supplement with benefits on human health. As a result of the increased attention to sustainability of winemaking by-products, efforts have been made to use grape pomace in different bio-industries. In this review, we summarize the existing knowledge on the bioactivity and potential applications of DF from grape pomace, as well as the chemical compositions of DF. Furthermore, the biological activities of DF such as, anti-cancer activity, antibacterial activity, anti-inflammatory activity, antioxidant activity, improving gastrointestinal health activity, anti-apoptotic activity, preventing cardiovascular disease activity, anti-hypercholesterolemic activity, are discussed. Finally, the possible applications and future prospects of grape pomace DF in various fields are also summarised.
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http://dx.doi.org/10.1016/j.foodchem.2014.07.057DOI Listing
November 2015

Midazolam inhibits the apoptosis of astrocytes induced by oxygen glucose deprivation via targeting JAK2-STAT3 signaling pathway.

Cell Physiol Biochem 2015 2;35(1):126-36. Epub 2015 Jan 2.

Department of Anesthesiology, the Third Hospital of Harbin Medical University, Harbin, China.

Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition.

Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10 μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay.

Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ.

Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.
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http://dx.doi.org/10.1159/000369681DOI Listing
September 2015

Circulating soluble advanced glycation end product is inversely associated with the significant risk of developing cancer: evidence from a meta-analysis.

Tumour Biol 2014 Sep 30;35(9):8749-55. Epub 2014 May 30.

Basic Medical Science College, Qiqihar Medical University, Bukui North Street 333, Jianhua District, Qiqihar, 161006, Heilongjiang, China.

Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: -373.77 to -70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = -87.62; 95 % CI: -138.60 to -36.63; P = 0.001) with improved heterogeneity (I (2) = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = -231.34; 95 % CI: -450.10 to -12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: -67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function.
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http://dx.doi.org/10.1007/s13277-014-2122-7DOI Listing
September 2014

Karyotypic and molecular genetic changes associated with fetal cardiovascular abnormalities: results of a retrospective 4-year ultrasonic diagnosis study.

Int J Biol Sci 2013 9;9(5):463-71. Epub 2013 May 9.

Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

Objective: To investigate the incidence of aneuploidy in fetuses with congenital heart defects (CHDs) and to further identify submicroscopic changes and global DNA methylation levels as potential biomarkers in complex CHD cases.

Methods: Fetuses at high risk for birth defects or with obvious sonographic anomalies were recruited at the Prenatal Diagnosis Center and Ultrasonic Diagnosis Center. Elective fetal karyotyping and DNA copy number and promoter methylation analyses were carried out following parental consent. G-banded karyotyping was performed to detect fetal aneuploidy. Copy number variations (CNVs) were detected using the Affymetrix SNP Array 6.0 and validated by real time PCR. Global DNA methylation analyses were conducted using a Roche NimbleGen Human DNA Methylation 3x720K Array, and DNA methylation differences were assayed by a Sequenom MassARRAY EpiTYPER.

Results: Conventional karyotyping identified 30 cases with aneuploidy in 179 CHD fetuses. Various CNVs were found in two aneuploid fetuses and in five euploid CHD fetuses. Verified segmental deletion or duplications were not directly associated with cardiovascular malformations except in DAAM1 and GATA6. Verifiable aberrant DNA methylation could not be identified in three complex CHD fetuses.

Conclusions: In this study, Trisomy 18, Trisomy 21 and 45,XO were the most common aneuploidies identified in CHD fetuses. In the affected samples, only DAAM1 deletion and GATA6 amplification could be associated with cardiovascular biological processes.
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http://dx.doi.org/10.7150/ijbs.5404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654495PMC
December 2013

Matrix solid-phase dispersion extraction followed by HPLC-diode array detection method for the determination of major constituents in a traditional Chinese medicine Folium isatidis (Da-qing-ye).

J Sep Sci 2012 Sep;35(18):2453-9

Basic Medical Science College, Qiqihar Medical University, Qiqihar, PR China.

A simple and low-cost method based on matrix solid-phase dispersion (MSPD) extraction, HPLC separation, and diode array detection has been developed for the determination of indigo and indirubin in Folium isatidis. The experimental parameters that may affect the MSPD method, including dispersing sorbent, ratio of dispersing sorbent to sample, elution solvent, and volume of the elution solvent were examined and optimized. The optimized conditions were determined to be that C18 was used as dispersing sorbent, the ratio of C18 to sample mass was selected to be 4:1, and 10 mL of N,N-dimethyl formamide was used as elution solvent. The highest extraction yields of the two compounds were obtained under the optimized conditions. The method showed good linearity (r > 0.9995) and precision (RSD < 3.0%) for indigo and indirubin, with the limits of detection of 18 and 22.5 ng/mL, respectively. The recoveries were in the range of 90.33-100.74% with RSD values ranging from 1.7 to 3.6%. Comparing to ultrasonic and Soxhlet methods, the proposed MSPD procedure was more convenient and less time-consuming with reduced requirements on sample and solvent amounts. The proposed procedure was applied to analyzed three real samples that were collected from different localities.
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http://dx.doi.org/10.1002/jssc.201200422DOI Listing
September 2012

Supervised latent linear Gaussian process latent variable model for dimensionality reduction.

IEEE Trans Syst Man Cybern B Cybern 2012 Dec 17;42(6):1620-32. Epub 2012 May 17.

Intelligent and Distributed Computing Laboratory, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

The Gaussian process (GP) latent variable model (GPLVM) has the capability of learning low-dimensional manifold from highly nonlinear data of high dimensionality. As an unsupervised dimensionality reduction (DR) algorithm, the GPLVM has been successfully applied in many areas. However, in its current setting, GPLVM is unable to use label information, which is available for many tasks; therefore, researchers proposed many kinds of extensions to the GPLVM in order to utilize extra information, among which the supervised GPLVM (SGPLVM) has shown better performance compared with other SGPLVM extensions. However, the SGPLVM suffers in its high computational complexity. Bearing in mind the issues of the complexity and the need of incorporating additionally available information, in this paper, we propose a novel SGPLVM, called supervised latent linear GPLVM (SLLGPLVM). Our approach is motivated by both SGPLVM and supervised probabilistic principal component analysis (SPPCA). The proposed SLLGPLVM can be viewed as an appropriate compromise between the SGPLVM and the SPPCA. Furthermore, it is also appropriate to interpret the SLLGPLVM as a semiparametric regression model for supervised DR by making use of the GP to model the unknown smooth link function. Complexity analysis and experiments show that the developed SLLGPLVM outperforms the SGPLVM not only in the computational complexity but also in its accuracy. We also compared the SLLGPLVM with two classical supervised classifiers, i.e., a GP classifier and a support vector machine, to illustrate the advantages of the proposed model.
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http://dx.doi.org/10.1109/TSMCB.2012.2196995DOI Listing
December 2012

White-light LED clusters with high color rendering.

Opt Lett 2010 Sep;35(17):2955-7

Department of Applied Physics, Dong Hua University, 1882 Yan'an Road (W), Shanghai 200051, China.

We established a model for spectra of LEDs at different drive currents. The simulation program of color rendering of white-light LED clusters has been developed, according to the principle of additive color mixture. The experimental results show that white/red LED clusters can realize color temperature untunable white light with a high color rendering index and high luminous efficacy and that neutral-white/red/blue LED clusters can realize color temperature tunable white light with a high color rendering index and high luminous efficacy.
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http://dx.doi.org/10.1364/OL.35.002955DOI Listing
September 2010

Color temperature tunable white-light light-emitting diode clusters with high color rendering index.

Appl Opt 2010 Aug;49(24):4670-6

Department of Applied Physics, Dong Hua University, 1882 Yan'an Road (W), Shanghai 200051, China.

A model for LED spectra at different drive currents is established. The simulation program of color rendering of a white-light LED cluster is developed according to the principle of additive color mixtures. The program can predict not only the spectral power distribution, chromaticity coordinates, correlated color temperature (CCT), and color rendering index (CRI), but also the drive currents of LEDs, luminous flux, input power, and luminous efficacy of white-light LED clusters. Three types of CCT tunable white-light LED clusters [warm-white/red/green/blue (WW/R/G/B), neutral-white (NW)/R/G/B, and cool-white/R/amber/G clusters] with high CRI are found by simulation analysis and realized in our laboratory. The experimental results show that the WW/R/G/B cluster can realize CCT tunable white light with high CRIs (above 90) but lower luminous efficacies (below 65 lm/W), and that the NW/R/G/B cluster can realize CCT tunable white light with high CRIs (above 86), as well as high luminous efficacies (above 64 lm/W).
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http://dx.doi.org/10.1364/AO.49.004670DOI Listing
August 2010

Y chromosomal STR polymorphism in northern Chinese populations.

Biol Res 2009 29;42(4):497-504. Epub 2010 Jan 29.

Laboratory of Medical Genetics, Harbin Medical University, Harbin, 150081, China.

Y chromosomal STRs show sufficient variability among individduals in a population and a high degree of geographical differentiation, such that their polymorphic character makes them especially suited for population genetic studies. To investígate the polymorphism of a set of 17 Y-STR loci in northern China, we genotyped the 17 Y chromosomal STR loci in a population sample of 377 unrelated males from eight ethnic populations in northern China. We calculated the haplotype frequencies, Rst value and carried out the analysis of molecular variance (AMOVA). We then drew the multidimensional scaling analysis (MDS) plot and phylogenetic tree based on the Rst value. All populations showed a high level of haplotype diversity, with low inter-population variance as measured by an analysis of molecular variance. However, the genetic distances were significant when the eight populations were compared to other populations. By MDS and the phylogenetic tree, we found that the eight populations had a close relationship and Xibo had a northeast origination.
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http://dx.doi.org//S0716-97602009000400011DOI Listing
September 2010