140 results on '"Hong Sun"'
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2. Protein production from HEK293 cell line-derived stable pools with high protein quality and quantity to support discovery research.
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Hong Sun, Songyu Wang, Mei Lu, Christine E Tinberg, and Benjamin M Alba
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Medicine ,Science - Abstract
Antibody-based therapeutics and recombinant protein reagents are often produced in mammalian expression systems, which provide human-like post-translational modifications. Among the available mammalian cell lines used for recombinant protein expression, Chinese hamster ovary (CHO)-derived suspension cells are generally utilized because they are easy to culture and tend to produce proteins in high yield. However, some proteins purified from CHO cell overexpression suffer from clipping and display undesired non-human post translational modifications (PTMs). In addition, CHO cell lines are often not suitable for producing proteins with many glycosylation motifs for structural biology studies, as N-linked glycosylation of proteins poses challenges for structure determination by X-ray crystallography. Hence, alternative and complementary cell lines are required to address these issues. Here, we present a robust method for expressing proteins in human embryonic kidney 293 (HEK293)-derived stable pools, leading to recombinant protein products with much less clipped species compared to those expressed in CHO cells and with higher yield compared to those expressed in transiently-transfected HEK293 cells. Importantly, the stable pool generation protocol is also applicable to HEK293S GnTI- (N-acetylglucosaminyltransferase I-negative) and Expi293F GnTI- suspension cells, facilitating production of high yields of proteins with less complex glycans for use in structural biology projects. Compared to HEK293S GnTI- stable pools, Expi293F GnTI- stable pools consistently produce proteins with similar or higher expression levels. HEK293-derived stable pools can lead to a significant cost reduction and greatly promote the production of high-quality proteins for diverse research projects.
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- 2023
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3. Direct detection of polioviruses using a recombinant poliovirus receptor
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Nancy Gerloff, Mark Mandelbaum, Hong Pang, Nikail Collins, Brittani Brown, Hong Sun, Chelsea Harrington, Jessica Hecker, Chadi Agha, Cara C. Burns, and Everardo Vega
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Medicine ,Science - Abstract
Polioviruses are positive-sense, single-stranded RNA picornaviruses and the principal cause of poliomyelitis. Global poliovirus surveillance has relied on poliovirus isolation in cells, which may take a minimum of 10 days, involves maintaining two cell lines, and propagates virus in high titers. With eradication underway, a major objective of the Global Polio Eradication Initiative (GPEI) is to develop culture-independent detection of polioviruses as an alternative method to complement the current virus isolation technique. A culture-independent method on poliovirus-positive stool suspensions was assessed with commercially available recombinant soluble poliovirus receptor (PVR) coupled to Histidine (His) tags. Viral RNA was screened by quantitative real-time reverse transcription PCR using the poliovirus intratypic differentiation kit. Poliovirus recovery was optimized with PVR-His–tagged protein and buffers supplemented with polyethylene glycol. To validate the poliovirus-PVR–His tag purification assay, 182 poliovirus-positive stools of programmatic importance were parallel tested against the GPLN-accepted virus isolation method. The PVR-His tag enrichment method detected poliovirus in 164 of 171 poliovirus-positive stools, whereas the virus isolation method misidentified 38 stools as poliovirus-negative (McNemar χ2p
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- 2021
4. Validation of a redesigned pan-poliovirus assay and real-time PCR platforms for the global poliovirus laboratory network.
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Hong Sun, Chelsea Harrington, Nancy Gerloff, Mark Mandelbaum, Stacey Jeffries-Miles, Lea Necitas G Apostol, Ma Anne-Lesley D Valencia, Shahzad Shaukat, Mehar Angez, Deepa K Sharma, Uma P Nalavade, Shailesh D Pawar, Elisabeth Pukuta Simbu, Seta Andriamamonjy, Richter Razafindratsimandresy, and Everardo Vega
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Medicine ,Science - Abstract
Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key to the surveillance workflow, where viruses are screened after cell culture isolation before a subset are verified by sequencing. The ITD kit is a series of real-time RT-PCR assays that screens cytopathic effect (CPE)-positive cell cultures using the standard WHO method for virus isolation. Because ITD screening is a critical procedure in the poliovirus identification workflow, validation of performance of real-time PCR platforms is a core requirement for the detection of poliovirus using the ITD kit. In addition, the continual update and improvement of the ITD assays to simplify interpretation in all platforms is necessary to ensure that all real-time machines are capable of detecting positive real-time signals. Four platforms (ABI7500 real-time systems, Bio-Rad CFX96, Stratagene MX3000P, and the Qiagen Rotor-Gene Q) were validated with the ITD kit and a redesigned poliovirus probe. The poliovirus probe in the real-time RT-PCR pan-poliovirus (PanPV) assay was re-designed with a double-quencher (Zen™) to reduce background fluorescence and potential false negatives. The updated PanPV probe was evaluated with a panel consisting of 184 polioviruses and non-polio enteroviruses. To further validate the updated PanPV probe, the new assay was pilot tested in five Global Polio Laboratory Network (GPLN) laboratories (Madagascar, India, Philippines, Pakistan, and Democratic Republic of Congo). The updated PanPV probe performance was shown to reduce background fluorescence and decrease the number of false positives compared to the standard PanPV probe.
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- 2021
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5. Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.
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Sung-Hyun Park, Yuting Lu, Yongzhao Shao, Colette Prophete, Lori Horton, Maureen Sisco, Hyun-Wook Lee, Thomas Kluz, Hong Sun, Max Costa, Judith Zelikoff, Lung-Chi Chen, and Mitchell D Cohen
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Medicine ,Science - Abstract
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.
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- 2021
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6. Optimal fertigation for high yield and fruit quality of greenhouse strawberry.
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Yong Wu, Li Li, Minzan Li, Man Zhang, Hong Sun, and Nikolaos Sigrimis
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Medicine ,Science - Abstract
Nitrogen (N), phosphorus (P), potassium (K), and water are four crucial factors that have significant effects on strawberry yield and fruit quality. We used a 11 that involved 36 treatments with five levels of each of the four variables (N, P, and K fertilizers and water) to optimize fertilization and water combination for high yield and quality. Moreover, we used the SSC/TA ratio (the ratio of soluble solid content to titratable acid) as index of quality. Results showed that N fertilizer was the most important factor, followed by water and P fertilizer, and the N fertilizer had significant effect on yield and SSC/TA ratio. By contrast, the K fertilizer had significant effect only on yield. N×K fertilizer interacted significantly on yield, whereas the other interactions among the four factors had no significant effects on yield or SSC/TA ratio. The effects of the four factors on yield and SSC/TA ratio were ranked as N fertilizer > water > K fertilizer > P fertilizer and N fertilizer > P fertilizer > water > K fertilizer, respectively. The yield and SSC/TA ratio increased when NPK fertilizer and water increased, but then decreased when excessive NPK fertilizer and water were applied. The optimal fertilizer and water combination were 22.28-24.61 g plant-1 Ca (NO3)2·4H2O, 1.75-2.03 g plant-1 NaH2PO4, 12.41-13.91 g plant-1 K2SO4, and 12.00-13.05 L water plant-1 for yields of more than 110 g plant-1 and optimal SSC/TA ratio of 8.5-14.
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- 2020
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7. A four-stage DEA-based efficiency evaluation of public hospitals in China after the implementation of new medical reforms.
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Wanhui Zheng, Hong Sun, Peilin Zhang, Guojiang Zhou, Quanyu Jin, and Xiaoqin Lu
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Medicine ,Science - Abstract
This study applied the non-parametric four-stage data envelopment analysis method (Four-Stage DEA) to measure the relative efficiencies of Chinese public hospitals from 2010 to 2016, and to determine how efficiencies were affected by eight factors. A sample of public hospitals (n = 84) was selected from Chongqing, China, including general hospitals and traditional Chinese medicine hospitals graded level 2 or above. The Four-Stage-DEA method was chosen since it enables the control of the impact of environment factors on efficiency evaluation results. Data on the number of staff, government financial subsidies, the number of beds and fixed assets were used as input whereas the number of out-patients and emergency department patients and visits, the number of discharged patients, medical and health service income and hospital bed utilization rate were chosen as study outputs. As relevant environmental variables, we selected GDP per capita, permanent population, population density, number of hospitals and number of available sickbeds in local medical institutions. The relative efficiencies (i.e. technical, pure technical, scale) of sample hospitals were also calculated to analyze the change between the first stage and fourth stage every year. The study found that Four-Stage-DEA can effectively filter the impact of environmental factors on evaluation results, which sets it apart from other models commonly used in existing studies.
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- 2018
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8. Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.
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Ashley Jordan, Xiaoru Zhang, Jinquan Li, Freda Laulicht-Glick, Hong Sun, and Max Costa
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Medicine ,Science - Abstract
Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds' carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel's effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.
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- 2017
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9. Depletion of NEAT1 lncRNA attenuates nucleolar stress by releasing sequestered P54nrb and PSF to facilitate c-Myc translation.
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Wen Shen, Xue-Hai Liang, Hong Sun, Cheryl L De Hoyos, and Stanley T Crooke
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Medicine ,Science - Abstract
Altered expression of NEAT1, the architectural long non-coding RNA (lncRNA) of nuclear paraspeckles, has been reported during tumorigenesis, as well as under various cellular stress conditions. Here we report that the depletion of NEAT1 lncRNA alleviates nucleolar stress during RNAP I inhibition through releasing sequestered P54nrb and PSF to facilitate the IRES-dependent translation of c-Myc. RNAP I inhibitor CX5461 disrupts the SL1-rDNA interaction and induces nucleolar disruption, demonstrated by the accumulation of fibrillarin-containing nucleoplasmic foci and nucleolar clearance of ribosomal proteins in HeLa cells. Antisense oligonucleotide-mediated depletion of NEAT1 lncRNA significantly attenuated the RNAP I inhibition and its related nucleolar disruption. Interestingly, induction in the levels of c-Myc protein was observed in NEAT1-depeleted cells under RNAP I inhibition. NEAT1-associated paraspeckle proteins P54nrb and PSF have been reported as positive regulators of c-Myc translation through interaction with c-Myc IRES. Indeed, an increased association of P54nrb and PSF with c-Myc mRNA was observed in NEAT1-depleted cells. Moreover, apoptosis was observed in HeLa cells depleted of P54nrb and PSF, further confirming the positive involvement of P54nrb and PSF in cell proliferation. Together, our results suggest that NEAT1 depletion rescues CX5461-induced nucleolar stress through facilitating c-Myc translation by relocating P54nrb/PSF from nuclear paraspeckles to c-Myc mRNAs.
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- 2017
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10. The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.
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Rongyuan Zhuang, Song Li, Qian Li, Xi Guo, Feng Shen, Hong Sun, and Tianshu Liu
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Medicine ,Science - Abstract
KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information independently. Review Manager 5.3 software was used to perform the statistical analysis. Thirty studies were included in the present meta-analysis. Our analysis showed that KRAS mutation in cfDNA was associated with a poorer survival in cancer patients for overall survival (OS, HR 2.02, 95% CI 1.63-2.51, P
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- 2017
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11. Up-Regulation of CYP2C19 Expression by BuChang NaoXinTong via PXR Activation in HepG2 Cells.
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Hong Sun, Xiao-Ya Lou, Xiao-Ying Wu, Huan Wang, Qiang Qu, Shen-Lan Tan, Jun-Shan Ruan, Jian Qu, and Hui Chen
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Medicine ,Science - Abstract
Cytochrome P450 2C19 (CYP2C19) is an important drug-metabolizing enzyme (DME), which is responsible for the biotransformation of several kinds of drugs such as proton pump inhibitors, platelet aggregation inhibitors and antidepressants. Previous studies showed that Buchang NaoXinTong capsules (NXT) increased the CYP2C19 metabolic activity in vitro and enhanced the antiplatelet effect of clopidogrel in vivo. However, the underlying molecular mechanism remained unclear. In the present study, we examined whether Pregnane X receptor (PXR) plays a role in NXT-mediated regulation of CYP2C19 expression.We applied luciferase assays, real-time quantitative PCR (qPCR), Western blotting and cell-based analysis of metabolic activity experiments to investigate the NXT regulatory effects on the CYP2C19 promoter activity, the mRNA/ protein expression and the metabolic activity.Our results demonstrated that NXT significantly increased the CYP2C19 promoter activity when co-transfected with PXR in HepG2 cells. Mutations in PXR responsive element abolished the NXT inductive effects on the CYP2C19 promoter transcription. Additionally, NXT incubation (150 and 250μg/mL) also markedly up-regulated endogenous CYP2C19 mRNA and protein levels in PXR-transfected HepG2 cells. Correspondingly, NXT leaded to a significant enhancement of the CYP2C19 catalytic activity in PXR-transfected HepG2 cells.In summary, this is the first study to suggest that NXT could induce CYP2C19 expression via PXR activation.
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- 2016
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12. Solar Simulated Ultraviolet Radiation Induces Global Histone Hypoacetylation in Human Keratinocytes.
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Xiaoru Zhang, Thomas Kluz, Lisa Gesumaria, Mary S Matsui, Max Costa, and Hong Sun
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Medicine ,Science - Abstract
Ultraviolet radiation (UVR) from sunlight is the primary effector of skin DNA damage. Chromatin remodeling and histone post-translational modification (PTM) are critical factors in repairing DNA damage and maintaining genomic integrity, however, the dynamic changes of histone marks in response to solar UVR are not well characterized. Here we report global changes in histone PTMs induced by solar simulated UVR (ssUVR). A decrease in lysine acetylation of histones H3 and H4, particularly at positions of H3 lysine 9, lysine 56, H4 lysine 5, and lysine 16, was found in human keratinocytes exposed to ssUVR. These acetylation changes were highly associated with ssUVR in a dose-dependent and time-specific manner. Interestingly, H4K16ac, a mark that is crucial for higher order chromatin structure, exhibited a persistent reduction by ssUVR that was transmitted through multiple cell divisions. In addition, the enzymatic activities of histone acetyltransferases were significantly reduced in irradiated cells, which may account for decreased global acetylation. Moreover, depletion of histone deacetylase SIRT1 in keratinocytes rescued ssUVR-induced H4K16 hypoacetylation. These results indicate that ssUVR affects both HDAC and HAT activities, leading to reduced histone acetylation.
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- 2016
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13. Hexavalent Chromium (Cr(VI)) Down-Regulates Acetylation of Histone H4 at Lysine 16 through Induction of Stressor Protein Nupr1.
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Danqi Chen, Thomas Kluz, Lei Fang, Xiaoru Zhang, Hong Sun, Chunyuan Jin, and Max Costa
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Medicine ,Science - Abstract
The environmental and occupational carcinogen Hexavalent Chromium (Cr(VI)) has been shown to cause lung cancer in humans when inhaled. In spite of a considerable research effort, the mechanisms of Cr(VI)-induced carcinogenesis remain largely unknown. Nupr1 (nuclear protein 1) is a small, highly basic, and unfolded protein with molecular weight of 8,800 daltons and is induced by a variety of stressors. Studies in animal models have suggested that Nupr1 is a key factor in the development of lung and pancreatic cancers, with little known about the underlying molecular mechanisms. Here we report that the level of Nupr1 is significantly increased in human bronchial epithelial BEAS2B cells following exposure to Cr(VI) through epigenetic mechanisms. Interestingly, Cr(VI) exposure also results in the loss of acetylation at histone H4K16, which is considered a 'hallmark' of human cancer. Cr(VI)-induced reduction of H4K16 acetylation appears to be caused by the induction of Nupr1, since (a) overexpression of Nupr1 decreased the levels of both H4K16 acetylation and the histone acetyltransferase MOF (male absent on the first; also known as Kat8, Myst 1), which specifically acetylates H4K16; (b) the loss of acetylation of H4K16 upon Cr(VI) exposure is greatly compromised by knockdown of Nupr1. Moreover, Nupr1-induced reduction of H4K16 acetylation correlates with the transcriptional down-regulation at several genomic loci. Notably, overexpression of Nupr1 induces anchorage-independent cell growth and knockdown of Nupr1 expression prevents Cr(VI)-induced cell transformation. We propose that Cr(VI) induces Nupr1 and rapidly perturbs gene expression by downregulating H4K16 acetylation, thereby contributing to Cr(VI)-induced carcinogenesis.
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- 2016
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14. Low Goiter Rate Associated with Small Average Thyroid Volume in Schoolchildren after the Elimination of Iodine Deficiency Disorders.
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Peihua Wang, Hong Sun, Li Shang, Qinglan Zhang, Yingxia He, Zhigao Chen, Yonglin Zhou, Jingjing Zhang, Qingqing Wang, Jinkou Zhao, and Hongbing Shen
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Medicine ,Science - Abstract
After the implementation of the universal salt iodization (USI) program in 1996, seven cross-sectional school-based surveys have been conducted to monitor iodine deficiency disorders (IDD) among children in eastern China.This study aimed to examine the correlation of total goiter rate (TGR) with average thyroid volume (Tvol) and urinary iodine concentration (UIC) in Jiangsu province after IDD elimination.Probability-proportional-to-size sampling was applied to select 1,200 children aged 8-10 years old in 30 clusters for each survey in 1995, 1997, 1999, 2001, 2002, 2005, 2009 and 2011. We measured Tvol using ultrasonography in 8,314 children and measured UIC (4,767 subjects) and salt iodine (10,184 samples) using methods recommended by the World Health Organization. Tvol was used to calculate TGR based on the reference criteria specified for sex and body surface area (BSA).TGR decreased from 55.2% in 1997 to 1.0% in 2009, and geometric means of Tvol decreased from 3.63 mL to 1.33 mL, along with the UIC increasing from 83 μg/L in 1995 to 407 μg/L in 1999, then decreasing to 243 μg/L in 2005, and then increasing to 345 μg/L in 2011. In the low goiter population (TGR < 3.9%), TGR was positively associated with average Tvol (r = 0.99); UIC showed a non-linear association with average Tvol, and UIC > 300 μg/L was associated with a smaller average Tvol in children.After IDD elimination in Jiangsu province in 2001, lower TGR was associated with smaller average Tvol. Average Tvol was more sensitive than TGR in detecting the fluctuation of UIC. A UIC of 300 μg/L may be defined as a critical value for population level iodine status monitoring.
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- 2015
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15. Role of hydrogen sulfide in early blood-brain barrier disruption following transient focal cerebral ischemia.
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Zheng Jiang, Chun Li, Morganne L Manuel, Shuai Yuan, Christopher G Kevil, Kimberly D McCarter, Wei Lu, and Hong Sun
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Medicine ,Science - Abstract
We determined the role of endogenous hydrogen sulfide (H2S) in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Regional vascular response and cerebral blood flow (CBF) during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE)) and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST)), but not O-(Carboxymethyl)hydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS)), abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/-) reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn't further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S) production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia.
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- 2015
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16. Chinese herbal therapy and Western drug use, belief and adherence for hypertension management in the rural areas of Heilongjiang province, China.
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Xia Li, Mingkai Peng, Yuan Li, Zheng Kang, Yanhua Hao, Hong Sun, Lijun Gao, Mingli Jiao, Qunhong Wu, and Hude Quan
- Subjects
Medicine ,Science - Abstract
Traditional Chinese medicine (TCM) including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users). When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.
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- 2015
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17. Physical Violence against General Practitioners and Nurses in Chinese Township Hospitals: A Cross-Sectional Survey.
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Kai Xing, Mingli Jiao, Hongkun Ma, Hong Qiao, Yanhua Hao, Ye Li, Lijun Gao, Hong Sun, Zheng Kang, Libo Liang, and Qunhong Wu
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Medicine ,Science - Abstract
The purpose of this study is to identify risk factors of physical violence in Chinese township hospitals.A cross-sectional survey was used in a sample of 442 general practitioners and 398 general nurses from 90 township hospitals located in Heilongjiang province, China (response rate = 84.8%).A total of 106 of the 840 (12.6%) respondents reported being physically attacked in their workplace in the previous 12 months. Most perpetrators were the patients' relatives (62.3%), followed by the patient (22.6%); 73.6% of perpetrators were aged between 20 and 40 years. Of the physical violence incidents, about 56.6% (n = 60) resulted in a physical injury, and 45.4% of respondents took two or three days of sick leave. Reporting workplace violence in hospitals to superiors or authorities was low (9.4%). Most respondents (62.8%) did not receive training on how to avoid workplace violence. Logistic regression analyses indicated that general nurses, aged 35 years or younger, and with a higher-level professional title were more likely to experience physical violence. Healthcare workers with direct physical contact (washing, turning, lifting) with patients had a higher risk of physical violence compared to other health care workers. Procedures for reporting workplace violence were a protective factor for physical violence; when in place, reporting after psychological violence (verbal abuse, bullying/mobbing, harassment, and threats) was more protective than waiting until an instance of physical violence (beating, kicking, slapping, stabbing, etc.).Physical violence in Chinese township hospitals is an occupational hazard of rural public health concern. Policies, procedures, and intervention strategies should be undertaken to manage this issue.
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- 2015
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18. PIK3CA and TP53 gene mutations in human breast cancer tumors frequently detected by ion torrent DNA sequencing.
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Xusheng Bai, Enke Zhang, Hua Ye, Vijayalakshmi Nandakumar, Zhuo Wang, Lihong Chen, Chuanning Tang, Jianhui Li, Huijin Li, Wei Zhang, Wei Han, Feng Lou, Dandan Zhang, Hong Sun, Haichao Dong, Guangchun Zhang, Zhiyuan Liu, Zhishou Dong, Baishuai Guo, He Yan, Chaowei Yan, Lu Wang, Ziyi Su, Yangyang Li, Lindsey Jones, Xue F Huang, Si-Yi Chen, and Jinglong Gao
- Subjects
Medicine ,Science - Abstract
Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5-10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
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- 2014
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19. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.
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Zhi Xu, Xinying Huo, Hua Ye, Chuanning Tang, Vijayalakshmi Nandakumar, Feng Lou, Dandan Zhang, Haichao Dong, Hong Sun, Shouwen Jiang, Guangchun Zhang, Zhiyuan Liu, Zhishou Dong, Baishuai Guo, Yan He, Chaowei Yan, Lu Wang, Ziyi Su, Yangyang Li, Dongying Gu, Xiaojing Zhang, Xiaomin Wu, Xiaowei Wei, Lingzhi Hong, Yangmei Zhang, Jinsong Yang, Yonglin Gong, Cuiju Tang, Lindsey Jones, Xue F Huang, Si-Yi Chen, and Jinfei Chen
- Subjects
Medicine ,Science - Abstract
Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7%) in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.
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- 2014
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20. Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.
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Xin Cai, Jianhui Sheng, Chuanning Tang, Vijayalakshmi Nandakumar, Hua Ye, Hong Ji, Haiying Tang, Yu Qin, Hongwei Guan, Feng Lou, Dandan Zhang, Hong Sun, Haichao Dong, Guangchun Zhang, Zhiyuan Liu, Zhishou Dong, Baishuai Guo, He Yan, Chaowei Yan, Lu Wang, Ziyi Su, Yangyang Li, Lindsey Jones, Xue F Huang, Si-Yi Chen, Taihua Wu, and Hongli Lin
- Subjects
Medicine ,Science - Abstract
Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
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- 2014
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21. Quantitative dynamic modelling of the gene regulatory network controlling adipogenesis.
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Yin Wang, Rudong Li, Chunguang Ji, Shuliang Shi, Yufan Cheng, Hong Sun, and Yixue Li
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Medicine ,Science - Abstract
Gene regulatory networks (GRNs) coherently coordinate the expressions of genes and control the behaviors of cellular systems. The complexity in modeling a quantitative GRN usually results from inaccurate parameter estimation, which is mostly due to small sample sizes. For better modeling of GRNs, we have designed a small-sample iterative optimization algorithm (SSIO) to quantitatively model GRNs with nonlinear regulatory relationships. The algorithm utilizes gene expression data as the primary input and it can be applied in case of small-sized samples. Using SSIO, we have quantitatively constructed the dynamic models for the GRNs controlling human and mouse adipogenesis. Compared with two other commonly-used methods, SSIO shows better performance with relatively lower residual errors, and it generates rational predictions on the adipocyte responses to external signals and steady-states. Sensitivity analysis further indicates the validity of our method. Several differences are observed between the GRNs of human and mouse adipocyte differentiations, suggesting the differences in regulatory efficiencies of the transcription factors between the two species. In addition, we use SSIO to quantitatively determine the strengths of the regulatory interactions as well as to optimize regulatory models. The results indicate that SSIO facilitates better investigation and understanding of gene regulatory processes.
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- 2014
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22. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.
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Zheng Jiang, Chun Li, Denise M Arrick, Shu Yang, Alexandra E Baluna, and Hong Sun
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Medicine ,Science - Abstract
The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.
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- 2014
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23. Germinal center B cell depletion diminishes CD4+ follicular T helper cells in autoimmune mice.
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Isharat Yusuf, Jessica Stern, Tom M McCaughtry, Sandra Gallagher, Hong Sun, Changshou Gao, Thomas Tedder, Gianluca Carlesso, Laura Carter, Ronald Herbst, and Yue Wang
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Medicine ,Science - Abstract
BACKGROUND: Continuous support from follicular CD4(+) T helper (Tfh) cells drives germinal center (GC) responses, which last for several weeks to produce high affinity memory B cells and plasma cells. In autoimmune Sle1 and NZB/W F1 mice, elevated numbers of Tfh cells persist, promoting the expansion of self-reactive B cells. Expansion of circulating Tfh like cells have also been described in several autoimmune diseases. Although, the signals required for Tfh differentiation have now been well described, the mechanisms that sustain the maintenance of fully differentiated Tfh are less understood. Recent data demonstrate a role for GC B cells for Tfh maintenance after protein immunization. METHODS AND FINDING: Given the pathogenic role Tfh play in autoimmune disease, we explored whether B cells are required for maintenance of autoreactive Tfh. Our data suggest that the number of mature autoreactive Tfh cells is controlled by GC B cells. Depletion of B cells in Sle1 autoimmune mice leads to a dramatic reduction in Tfh cells. In NZB/W F1 autoimmune mice, similar to the SRBC immunization model, GC B cells support the maintenance of mature Tfh, which is dependent mainly on ICOS. The CD28-associated pathway is dispensable for Tfh maintenance in SRBC immunized mice, but is required in the spontaneous NZB/W F1 model. CONCLUSION: These data suggest that mature Tfh cells require signals from GC B cells to sustain their optimal numbers and function in both autoimmune and immunization models. Thus, immunotherapies targeting B cells in autoimmune disease may affect pathogenic Tfh cells.
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- 2014
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24. Substrate specificity provides insights into the sugar donor recognition mechanism of O-GlcNAc transferase (OGT).
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Xiaofeng Ma, Pi Liu, Hui Yan, Hong Sun, Xiaoyan Liu, Feng Zhou, Lei Li, Yi Chen, Musleh M Muthana, Xi Chen, Peng G Wang, and Lianwen Zhang
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Medicine ,Science - Abstract
O-Linked β-N-acetylglucosaminyl transferase (OGT) plays an important role in the glycosylation of proteins, which is involved in various cellular events. In human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and nucleocytoplasmic OGT [ncOGT]) share the same catalytic domain, implying that they might adopt a similar catalytic mechanism, including sugar donor recognition. In this work, the sugar-nucleotide tolerance of sOGT was investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) analogs tested using the casein kinase II (CKII) peptide as the sugar acceptor, four compounds could be used by sOGT, including UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. Determined values of Km showed that the substitution of the N-acyl group, deoxy modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc decreased its affinity to sOGT. A molecular docking study combined with site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl group of GlcNPr, as well as the hydrophobic environment near Met501, were responsible for the selective binding of UDP-GlcNPr. These findings illustrate the interaction of OGT and sugar nucleotide donor, providing insights into the OGT catalytic mechanism.
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- 2013
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25. GSTM1 and GSTT1 null polymorphisms and childhood acute leukemia risk: evidence from 26 case-control studies.
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Qiuqin Tang, Jing Li, Simin Zhang, Beilei Yuan, Hong Sun, Di Wu, Chuncheng Lu, Wei Wu, Yankai Xia, Hongjuan Ding, Lingqing Hu, Daozhen Chen, Jiahao Sha, and Xinru Wang
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Medicine ,Science - Abstract
Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) null polymorphisms and childhood acute leukemia; however, the conclusions remain controversial. We performed an extensive meta-analysis on 26 published case-control studies with a total of 3252 cases and 5024 controls. Crude odds ratios (ORs) with 95% confidence interval were used to assess the strength of association between childhood acute leukemia risk and polymorphisms of GSTM1 and GSTT1. With respect to GSTM1 polymorphism, significantly increased risk of childhood acute leukemia was observed in the overall analysis (OR = 1.30; 95%CI, 1.11-1.51). Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism are associated with childhood acute leukemia in group of Asians (OR = 1.94; 95%CI, 1.53-2.46), Blacks (OR = 1.76; 95%CI, 1.07-2.91), ALL (OR = 1.33; 95%CI, 1.13-1.58), '< 100 cases and
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- 2013
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26. miR-141 contributes to fetal growth restriction by regulating PLAG1 expression.
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Qiuqin Tang, Wei Wu, Xia Xu, Lu Huang, Qiong Gao, Huijuan Chen, Hong Sun, Yankai Xia, Jiahao Sha, Xinru Wang, Daozhen Chen, and Qian Xu
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Fetal growth restriction (FGR) is an important but poorly understood condition of pregnancy, which results in significant fetal, neonatal and long-term morbidity and mortality. Novel research has suggested that altered miRNA expression in the plasma and placenta is associated with adverse pregnancy. We hypothesized that aberrant expression of microRNA-141 (miR-141) in the placenta is associated with FGR. Additionally, expression levels of predicted target genes of miR-141 were also analyzed in placental tissues of FGR and normal controls. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative real time PCR, we analyzed the expression level of miR-141 and its target genes in placentas of FGR pregnancies (n = 21) and normal controls (n = 34). Western blot was used to detect the protein expression level of the target genes of miR-141. MiR-141 showed significant up regulation in FGR and significant down regulation of its targets, i.e. E2F transcription factor 3 (E2F3) protein, pleiomorphic adenoma gene 1 (PLAG1) mRNA and protein. Moreover, a positive correlation was found between PLAG1 and insulin-like growth factor 2 (IGF2) expression levels (Spearman r = 0.56, p
- Published
- 2013
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27. ERK/PP1a/PLB/SERCA2a and JNK pathways are involved in luteolin-mediated protection of rat hearts and cardiomyocytes following ischemia/reperfusion.
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Xin Wu, Tongda Xu, Dongye Li, Shasha Zhu, Qiuping Chen, Wenjing Hu, Defeng Pan, Hong Zhu, and Hong Sun
- Subjects
Medicine ,Science - Abstract
Luteolin has long been used in traditional Chinese medicine for treatment of various diseases. Recent studies have suggested that administration of luteolin yields cardioprotective effects during ischemia/reperfusion (I/R) in rats. However, the precise mechanisms of this action remain unclear. The aim of this study is to confirm that luteolin-mediated extracellular signal regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways are responsible for their cardioprotective effects during I/R. Wistar rats were divided into the following groups: (i) DMSO group (DMSO); (ii) I/R group (I/R); (iii) luteolin+I/R group (Lut+I/R); (iv) ERK1/2 inhibitor PD98059+I/R group (PD+I/R); (v) PD98059+luteolin+I/R group (PD+Lut+I/R); and (vi) JNK inhibitor SP600125+I/R group (SP+I/R). The following properties were measured: contractile function of isolated heart and cardiomyocytes; infarct size; the release of lactate dehydrogenase (LDH); the percentage of apoptotic cells; the expression levels of Bcl-2 and Bax; and phosphorylation status of ERK1/2, JNK, type 1 protein phosphatase (PP1a), phospholamban (PLB) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Our data showed that pretreatment with luteolin or SP600125 significantly improved the contraction of the isolated heart and cardiomyocytes, reduced infarct size and LDH activity, decreased the rate of apoptosis and increased the Bcl-2/Bax ratio. However, pretreatment with PD98059 alone before I/R had no effect on the above indexes. Further, these consequences of luteolin pretreatment were abrogated by co-administration of PD98059. We also found that pretreatment with PD98059 caused a significant increase in JNK expression, and SP600125 could cause ERK1/2 activation during I/R. In addition, we are the first to demonstrate that luteolin affects PP1a expression, which results in the up-regulation of the PLB, thereby relieving its inhibition of SERCA2a. These results showed that luteolin improves cardiomyocyte contractile function after I/R injury by an ERK1/2-PP1a-PLB-SERCA2a-mediated mechanism independent of JNK signaling pathway.
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- 2013
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28. Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing.
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Hongjiang Wu, Hong Sun, Xuehai Liang, Walt F Lima, and Stanley T Crooke
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Medicine ,Science - Abstract
Mammalian RNase H1 has been implicated in mitochondrial DNA replication and RNA processing and is required for embryonic development. We identified the mitochondrial protein P32 that binds specifically to human RNase H1, but not human RNase H2. P32 binds human RNase H1 via the hybrid-binding domain of the enzyme at an approximately 1∶1 ratio. P32 enhanced the cleavage activity of RNase H1 by reducing the affinity of the enzyme for the heteroduplex substrate and enhancing turnover, but had no effect on the cleavage pattern. RNase H1 and P32 were partially co-localized in mitochondria and reduction of P32 or RNase H1 levels resulted in accumulation of mitochondrial pre ribosomal RNA [12S/16S] in HeLa cells. P32 also co-immunoprecipitated with MRPP1, a mitochondrial RNase P protein required for mitochondrial pre-rRNA processing. The P32-RNase H1 complex was shown to physically interact with mitochondrial DNA and pre-rRNA. These results expand the potential roles for RNase H1 to include assuring proper transcription and processing of guanosine-cytosine rich pre-ribosomal RNA in mitochondria. Further, the results identify P32 as a member of the 'RNase H1 degradosome' and the key P32 enhances the enzymatic efficiency of human RNase H1.
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- 2013
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29. Chronic activation of the G protein-coupled receptor 30 with agonist G-1 attenuates heart failure.
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Shoulei Kang, Ying Liu, Di Sun, Chunle Zhou, Aiying Liu, Chuanying Xu, Yanling Hao, Dongye Li, Changdong Yan, and Hong Sun
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Medicine ,Science - Abstract
G protein-coupled receptor (GPR) 30 is a novel estrogen receptor. Recent studies suggest that activation of the GPR30 confers rapid cardioprotection in isolated rat heart. It is unknown whether chronic activation of GPR30 is beneficial or not for heart failure. In this study we investigated the cardiac effect of sustained activation or inhibition of GPR30. Female Sprague-Dawley rats were divided into 7 groups #2Q1: sham surgery (Sham), bilateral ovariectomy (OVX), OVX+estrogen (E(2)), OVX+isoproterenol (ISO), OVX+ISO+G-1, OVX+ISO+E(2)+G15, OVX+ISO+E(2). ISO (85 mg/kg×17 day, sc) was given to make the heart failure models. G-1(120 µg/kg·d×14 day) was used to activate GPR30 and G15 (190 µg/kg·d×14 day) was used to inhibit GPR30. Concentration of brain natriuretic peptide in serum, masson staining in isolated heart, contractile function and the expression of β(1) and β(2)- adrenergic receptor (AR) of ventricular myocytes were also determined. Our data showed that ISO treatment led to heart failure in OVX rats. G-1 or E(2) treatment decreased concentration of brain natriuretic peptide, reduced cardiac fibrosis, and enhanced contraction of the heart. Combined treatment with β(1) (CGP20712A) and β(2)-AR (ICI118551) antagonist abolished the improvement of myocardial function induced by G-1. We also found that chronic treatment with G-1 normalized the expression of β(1)-AR and increased the expression of β(2)-AR. Our results indicate that chronic activation of the GPR30 with its agonist G-1 attenuates heart failure by normalizing the expression of β(1)-AR and increasing the expression of β(2)-AR.
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- 2012
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30. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.
- Author
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Yongsoon Kim and Hong Sun
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Medicine ,Science - Abstract
In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.
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- 2012
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31. Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ.
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Hong Sun, Wanfen Xiong, Denise M Arrick, and William G Mayhan
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Medicine ,Science - Abstract
We examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγ antagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662.Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ.
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- 2012
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32. Comparison of gene expression profiles in chromate transformed BEAS-2B cells.
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Hong Sun, Harriet A Clancy, Thomas Kluz, Jiri Zavadil, and Max Costa
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Medicine ,Science - Abstract
Hexavalent chromium [Cr(VI)] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated.We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI) followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated) that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI) transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI) transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated in all Cr(VI) transformed cells, while genes associated with the interaction between cells and their extracellular matrices were down-regulated. Additionally, expression of genes involved in cell proliferation and apoptosis were also changed.This study is the first to report gene expression profiling of Cr(VI) transformed cells. The gene expression changes across individual chromate exposed clones were remarkably similar to each other but differed significantly from the gene expression found in anchorage-independent clones that arose spontaneously. Our analysis identified many novel gene expression changes that may contribute to chromate induced cell transformation, and collectively this type of information will provide a better understanding of the mechanism underlying chromate carcinogenicity.
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- 2011
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33. Liprin-α4 is required for nickel induced receptor protein tyrosine phosphatase-leukocyte antigen related receptor F (RPTP-LAR) activity.
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Kathrin Kiok, Hong Sun, Hailey Clancy, Sutapa Bose, Thomas Kluz, Fen Wu, and Max Costa
- Subjects
Medicine ,Science - Abstract
Liprin-α4 was strongly induced following nickel (II) chloride exposure in a variety of cell types including BEAS-2B, A549, BEP2D and BL41 cells. Liprin-α4, a member of the Liprin alpha family, has seven isoforms but only three of these variants were detected in BEAS-2B cells (004, 201 and 202). The level of Liprin-α4 variants 201 and 004 were highly increased in BEAS-2B cells in response to nickel. We showed that Liprin-α4 bound directly to the cytoplasmic region of RPTP-LAR (receptor protein tyrosine phosphatase-leukocyte antigen-related receptor F). The cytoplasmic region of RPTP-LAR contains two phosphatase domains but only the first domain shows activity. The second domain interacts with other proteins. The phosphatase activity was increased both following nickel treatment and also in the presence of nickel ions in cell extracts. Liprin-α4 knock-down lines with decreased expression of Liprin-α4 variants 004 and 201 exhibited greater nickel toxicity compared to controls. The RPTP-LAR phosphatase activity was only slightly increased in a Liprin-α4 knock-down line. Liprin-α4 appeared necessary for the nickel induced tyrosine phosphatase activity. The presence of Liprin-α4 and nickel increased tyrosine phosphatase activity that reduced the global levels of tyrosine phosphorylation in the cell.
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- 2011
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34. Thyroid disruption by Di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) in Xenopus laevis.
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Ouxi Shen, Wei Wu, Guizhen Du, Renping Liu, Lugang Yu, Hong Sun, Xiumei Han, Yi Jiang, Wei Shi, Wei Hu, Ling Song, Yankai Xia, Shoulin Wang, and Xinru Wang
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Di-n-butyl phthalate (DBP), a chemical widely used in many consumer products, is estrogenic and capable of producing seriously reproductive and developmental effects in laboratory animals. However, recent in vitro studies have shown that DBP and mono-n-butyl phthalate (MBP), the major metabolite of DBP, possessed thyroid hormone receptor (TR) antagonist activity. It is therefore important to consider DBP and MBP that may interfere with thyroid hormone system. METHODOLOGY/PRINCIPAL FINDINGS: Nieuwkoop and Faber stage 51 Xenopus laevis were exposed to DBP and MBP (2, 10 or 15 mg/L) separately for 21 days. The two test chemicals decelerated spontaneous metamorphosis in X. laevis at concentrations of 10 and 15 mg/L. Moreover, MBP seemed to possess stronger activity. The effects of DBP and MBP on inducing changes of expression of selected thyroid hormone response genes: thyroid hormone receptor-beta (TRβ), retinoid X receptor gamma (RXRγ), alpha and beta subunits of thyroid-stimulating hormone (TSHα and TSHβ) were detected by qPCR at all concentrations of the compounds. Using mammalian two-hybrid assay in vitro, we found that DBP and MBP enhanced the interactions between co-repressor SMRT (silencing mediator for retinoid and thyroid hormone receptors) and TR in a dose-dependent manner, and MBP displayed more markedly. In addition, MBP at low concentrations (2 and 10 mg/L) caused aberrant methylation of TRβ in head tissue. CONCLUSIONS: The current findings highlight potential disruption of thyroid signalling by DBP and MBP and provide data for human risk assessment.
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- 2011
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35. Mechanisms of c-myc degradation by nickel compounds and hypoxia.
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Qin Li, Thomas Kluz, Hong Sun, and Max Costa
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Medicine ,Science - Abstract
Nickel (Ni) compounds have been found to cause cancer in humans and animal models and to transform cells in culture. At least part of this effect is mediated by stabilization of hypoxia inducible factor (HIF1a) and activating its downstream signaling. Recent studies reported that hypoxia signaling might either antagonize or enhance c-myc activity depending on cell context. We investigated the effect of nickel on c-myc levels, and demonstrated that nickel, hypoxia, and other hypoxia mimetics degraded c-myc protein in a number of cancer cells (A549, MCF-7, MDA-453, and BT-474). The degradation of the c-Myc protein was mediated by the 26S proteosome. Interestingly, knockdown of both HIF-1alpha and HIF-2alpha attenuated c-Myc degradation induced by Nickel and hypoxia, suggesting the functional HIF-1alpha and HIF-2alpha was required for c-myc degradation. Further studies revealed two potential pathways mediated nickel and hypoxia induced c-myc degradation. Phosphorylation of c-myc at T58 was significantly increased in cells exposed to nickel or hypoxia, leading to increased ubiquitination through Fbw7 ubiquitin ligase. In addition, nickel and hypoxia exposure decreased USP28, a c-myc de-ubiquitinating enzyme, contributing to a higher steady state level of c-myc ubiquitination and promoting c-myc degradation. Furthermore, the reduction of USP28 protein by hypoxia signaling is due to both protein degradation and transcriptional repression. Nickel and hypoxia exposure significantly increased the levels of dimethylated H3 lysine 9 at the USP28 promoter and repressed its expression. Our study demonstrated that Nickel and hypoxia exposure increased c-myc T58 phosphorylation and decreased USP28 protein levels in cancer cells, which both lead to enhanced c-myc ubiquitination and proteasomal degradation.
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- 2009
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36. Structural relationships between highly conserved elements and genes in vertebrate genomes.
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Hong Sun, Geir Skogerbø, Zhen Wang, Wei Liu, and Yixue Li
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Medicine ,Science - Abstract
Large numbers of sequence elements have been identified to be highly conserved among vertebrate genomes. These highly conserved elements (HCEs) are often located in or around genes that are involved in transcription regulation and early development. They have been shown to be involved in cis-regulatory activities through both in vivo and additional computational studies. We have investigated the structural relationships between such elements and genes in six vertebrate genomes human, mouse, rat, chicken, zebrafish and tetraodon and detected several thousand cases of conserved HCE-gene associations, and also cases of HCEs with no common target genes. A few examples underscore the potential significance of our findings about several individual genes. We found that the conserved association between HCE/HCEs and gene/genes are not restricted to elements by their absolute distance on the genome. Notably, long-range associations were identified and the molecular functions of the associated genes do not show any particular overrepresentation of the functional categories previously reported. HCEs in close proximity are found to be linked with different set of gene/genes. The results reflect the highly complex correlation between HCEs and their putative target genes.
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- 2008
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37. Rotenone causes mitochondrial dysfunction and prevents maturation in porcine oocytes
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Geun Heo, Ming-Hong Sun, Wen-Jie Jiang, Xiao-Han Li, Song-Hee Lee, Jing Guo, Dongjie Zhou, and Xiang-Shun Cui
- Subjects
Multidisciplinary ,Cumulus Cells ,Swine ,Rotenone ,Oocytes ,Animals ,Female ,Reactive Oxygen Species ,Mitochondria - Abstract
Rotenone is a commonly used insecticidal chemical in agriculture and it is an inhibitor of mitochondrial complex Ⅰ. Previous studies have found that rotenone induces the production of reactive oxygen species (ROS) by inhibiting electron transport in the mitochondria of somatic and germ cells. However, there is little precise information on the effects of rotenone exposure in porcine oocytes during in vitro maturation, and the mechanisms underlying these effects have not been determined. The Cumulus-oocyte complexes were supplemented with different concentrations of rotenone to elucidate the effects of rotenone exposure on the meiotic maturation of porcine oocytes during in vitro maturation for about 48 hours. First, we found that the maturation rate and expansion of cumulus cells were significantly reduced in the 3 and 5 μM rotenone-treated groups. Subsequently, the concentration of rotenone was determined to be 3 μM. Also, immunofluorescence, western blotting, and image quantification analyses were performed to test the rotenone exposure on the meiotic maturation, total and mitochondrial ROS, mitochondrial function and biogenesis, mitophagy and apoptosis in porcine oocytes. Further experiments showed that rotenone treatment induced mitochondrial dysfunction and failure of mitochondrial biogenesis by repressing the level of SIRT1 during in vitro maturation of porcine oocytes. In addition, rotenone treatment reduced the ratio of active mitochondria to total mitochondria, increased ROS production, and decreased ATP production. The levels of LC3 and active-caspase 3 were significantly increased by rotenone treatment, indicating that mitochondrial dysfunction induced by rotenone increased mitophagy but eventually led to apoptosis. Collectively, these results suggest that rotenone interferes with porcine oocyte maturation by inhibiting mitochondrial function.
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- 2022
38. Direct detection of polioviruses using a recombinant poliovirus receptor
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Nikail Collins, Chadi Agha, Nancy Gerloff, Hong Sun, Everardo Vega, Brittani Brown, Jessica Wielgus Hecker, Mark Mandelbaum, Hong Pang, Chelsea Harrington, and Cara C. Burns
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RNA viruses ,Viral Diseases ,Hydrolases ,viruses ,Artificial Gene Amplification and Extension ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Polymerase Chain Reaction ,Biochemistry ,law.invention ,Enteroviruses ,Feces ,Medical Conditions ,law ,Medicine and Health Sciences ,RNA structure ,Multidisciplinary ,Poliovirus ,Recombinant Proteins ,Enzymes ,Reverse transcription polymerase chain reaction ,Nucleic acids ,Titer ,Infectious Diseases ,Medical Microbiology ,Viral Pathogens ,Viruses ,Recombinant DNA ,Medicine ,RNA extraction ,Pathogens ,Poliovirus Receptor ,Research Article ,Nucleases ,Science ,Biology ,complex mixtures ,Microbiology ,Virus ,Extraction techniques ,DNA-binding proteins ,medicine ,RNA folding ,Molecular Biology Techniques ,Microbial Pathogens ,Molecular Biology ,Biology and life sciences ,Organisms ,RNA ,Proteins ,Reverse Transcriptase-Polymerase Chain Reaction ,Virology ,Research and analysis methods ,Macromolecular structure analysis ,Enzymology ,Poliomyelitis - Abstract
Polioviruses are positive-sense, single-stranded RNA picornaviruses and the principal cause of poliomyelitis. Global poliovirus surveillance has relied on poliovirus isolation in cells, which may take a minimum of 10 days, involves maintaining two cell lines, and propagates virus in high titers. With eradication underway, a major objective of the Global Polio Eradication Initiative (GPEI) is to develop culture-independent detection of polioviruses as an alternative method to complement the current virus isolation technique. A culture-independent method on poliovirus-positive stool suspensions was assessed with commercially available recombinant soluble poliovirus receptor (PVR) coupled to Histidine (His) tags. Viral RNA was screened by quantitative real-time reverse transcription PCR using the poliovirus intratypic differentiation kit. Poliovirus recovery was optimized with PVR-His–tagged protein and buffers supplemented with polyethylene glycol. To validate the poliovirus-PVR–His tag purification assay, 182 poliovirus-positive stools of programmatic importance were parallel tested against the GPLN-accepted virus isolation method. The PVR-His tag enrichment method detected poliovirus in 164 of 171 poliovirus-positive stools, whereas the virus isolation method misidentified 38 stools as poliovirus-negative (McNemar χ2 p
- Published
- 2021
39. Validation of a redesigned pan-poliovirus assay and real-time PCR platforms for the global poliovirus laboratory network
- Author
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Shailesh D. Pawar, Deepa Sharma, Everardo Vega, Ma. Anne-Lesley D. Valencia, Mehar Angez, Richter Razafindratsimandresy, Seta Andriamamonjy, Mark Mandelbaum, Uma P. Nalavade, Stacey Jeffries-Miles, Chelsea Harrington, Elisabeth Pukuta Simbu, Nancy Gerloff, S. Shahid Shaukat, Hong Sun, and Lea Necitas G. Apostol
- Subjects
RNA viruses ,Background fluorescence ,Viral Diseases ,Research Facilities ,Computer science ,Artificial Gene Amplification and Extension ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Polymerase Chain Reaction ,Enteroviruses ,Geographical Locations ,Feces ,Medical Conditions ,Medicine and Health Sciences ,False positive paradox ,Multidisciplinary ,Sewage ,Poliovirus ,WHO method ,Infectious Diseases ,Real-time polymerase chain reaction ,Medical Microbiology ,Viral Pathogens ,Viruses ,Medicine ,Biological Cultures ,Pathogens ,Research Laboratories ,Research Article ,Asia ,Virus isolation ,Science ,Nucleotide sequencing ,Computational biology ,Real-Time Polymerase Chain Reaction ,Research and Analysis Methods ,Microbiology ,medicine ,Molecular Biology Techniques ,Microbial Pathogens ,Molecular Biology ,Biology and life sciences ,Organisms ,Reverse Transcriptase-Polymerase Chain Reaction ,Cell Cultures ,People and Places ,Laboratories ,Poliomyelitis ,Government Laboratories - Abstract
Surveillance and detection of polioviruses (PV) remain crucial to monitoring eradication progress. Intratypic differentiation (ITD) using the real-time RT-PCR kit is key to the surveillance workflow, where viruses are screened after cell culture isolation before a subset are verified by sequencing. The ITD kit is a series of real-time RT-PCR assays that screens cytopathic effect (CPE)-positive cell cultures using the standard WHO method for virus isolation. Because ITD screening is a critical procedure in the poliovirus identification workflow, validation of performance of real-time PCR platforms is a core requirement for the detection of poliovirus using the ITD kit. In addition, the continual update and improvement of the ITD assays to simplify interpretation in all platforms is necessary to ensure that all real-time machines are capable of detecting positive real-time signals. Four platforms (ABI7500 real-time systems, Bio-Rad CFX96, Stratagene MX3000P, and the Qiagen Rotor-Gene Q) were validated with the ITD kit and a redesigned poliovirus probe. The poliovirus probe in the real-time RT-PCR pan-poliovirus (PanPV) assay was re-designed with a double-quencher (Zen™) to reduce background fluorescence and potential false negatives. The updated PanPV probe was evaluated with a panel consisting of 184 polioviruses and non-polio enteroviruses. To further validate the updated PanPV probe, the new assay was pilot tested in five Global Polio Laboratory Network (GPLN) laboratories (Madagascar, India, Philippines, Pakistan, and Democratic Republic of Congo). The updated PanPV probe performance was shown to reduce background fluorescence and decrease the number of false positives compared to the standard PanPV probe.
- Published
- 2021
40. Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane
- Author
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Colette Prophete, Mitchell D. Cohen, Yuting Lu, Hong Sun, Lori Horton, Sung-Hyun Park, Lung Chi Chen, Max Costa, Maureen Sisco, Judith T. Zelikoff, Hyun-Wook Lee, Yongzhao Shao, and Thomas Kluz
- Subjects
Male ,Gene Expression ,Mathematical and Statistical Techniques ,Rats, Inbred SHR ,Gene expression ,Medicine and Health Sciences ,Immune Response ,Regulation of gene expression ,Principal Component Analysis ,Inhalation Exposure ,Multidisciplinary ,Inhalation ,Isoflurane ,Statistics ,Drugs ,Heart ,Geology ,Circadian Rhythms ,Physical Sciences ,Anesthetics, Inhalation ,Medicine ,Volcanoes ,Anatomy ,medicine.drug ,Extracellular matrix organization ,Research Article ,medicine.medical_specialty ,Science ,Immunology ,Volcanology ,Research and Analysis Methods ,Internal medicine ,medicine ,Genetics ,Pain Management ,Animals ,Gene Regulation ,Circadian rhythm ,Statistical Methods ,Anesthetics ,Pharmacology ,business.industry ,Biology and Life Sciences ,medicine.disease ,Rats ,Endocrinology ,Heart failure ,Anesthetic ,Multivariate Analysis ,Cardiovascular Anatomy ,Earth Sciences ,business ,Transcriptome ,Chronobiology ,Mathematics - Abstract
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.
- Published
- 2021
41. 99mTc-MIBI uptake as a marker of mitochondrial membrane potential in cancer cells and effects of MDR1 and verapamil
- Author
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Park, Jin Won, primary, Hong, Sun-pyo, additional, Lee, Jin Hee, additional, Moon, Seung Hwan, additional, Cho, Young Seok, additional, Jung, Kyung-Ho, additional, Lee, Jeeyun, additional, and Lee, Kyung-Han, additional
- Published
- 2020
- Full Text
- View/download PDF
42. Multivariate analysis reveals phenotypic diversity of Euscaphis japonica population
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Shuang Quan Zou, Xueyan Yuan, Wei-Hong Sun, Wen Chieh Tsai, Si-Ren Lan, and Zhong-Jian Liu
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0106 biological sciences ,0301 basic medicine ,Leaves ,Heredity ,Plant Science ,01 natural sciences ,Japonica ,Trees ,Cluster Analysis ,education.field_of_study ,Principal Component Analysis ,Multidisciplinary ,biology ,Ecology ,Altitude ,Plant Anatomy ,food and beverages ,Eukaryota ,Plants ,Phenotypes ,Deciduous ,Phenotype ,Seeds ,Medicine ,Research Article ,China ,Ecological Metrics ,Science ,Population ,Zoology ,Fruits ,03 medical and health sciences ,Magnoliopsida ,Genetic variation ,Genetics ,education ,Ecosystem ,Genetic diversity ,Evolutionary Biology ,Population Biology ,Quantitative Traits ,fungi ,Ecology and Environmental Sciences ,Organisms ,Genetic Variation ,Biology and Life Sciences ,Species Diversity ,Phenotypic trait ,Evergreen ,biology.organism_classification ,Plant Leaves ,030104 developmental biology ,Biological Variation, Population ,Fruit ,Multivariate Analysis ,Genetic Polymorphism ,Biological dispersal ,Population Genetics ,010606 plant biology & botany - Abstract
Fruit traits affect population genetic diversity by affecting seed protection and dispersal strategies, thereby comprising important components of phenotypic variation. Understanding of the phenotypic variation is an indispensable first step for developing breeding strategies. However, little information is known about the genetic variation in E. japonica-a monotypic species with abundant phenotypes that is mainly distributed in southern China. In this study, we evaluated the phenotypic diversity of 67 E. japonica using 23 phenotypic traits. Our results showed that the Shannon-Wiener (I) index of qualitative traits ranged from 0.55 to 1.26, and the color traits had a relatively high I. The average coefficient of variation of compound leaf traits (14.74%) was higher than that of fruit and seed traits (12.77% and 11.47%, respectively). Principal component analysis also showed that compound leaf and fruit traits were important components of total variation. Furthermore, correlation analysis revealed a significant difference in elevation and fruit color, irregular ribs, leaf margin and texture. The F value within populations was smaller than among populations, indicating the variation in phenotypic traits among populations was much greater than within populations. Dehua and Zunyi populations had the highest coefficients of variation, whereas Wenzhou population had the smallest-which may be attributed to habitat destruction. According to Q-type clustering, 67 samples clustered into four groups, with those having similar phenotypes clustering into the same group. In general, leaf and fruit traits had abundant phenotypic diversity, representing the main sources of phenotypic variation. Combined with clustering results and field surveys, this study suggests that the phenotypes of E. japonica are classified into two main categories: The deciduous E. japonica present at high altitudes; and the evergreen E. japonica present at low altitudes. Excavating E. japonica variations provides a theoretical reference for its classification and diversity, and is of great significance for planning genetic resources and establishing conservation strategies.
- Published
- 2019
43. Whole-genome sequencing reveals origin and evolution of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018
- Author
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Han-Ju Zhang, Yong Shao, Adeniyi C. Adeola, Xiaonan Zhao, Yao-Yao Chen, Yan-Hong Sun, Xiaoqing Fu, Duo Li, Jie-Nan Zhou, and Mei-Ling Zhang
- Subjects
RNA viruses ,0301 basic medicine ,Viral Diseases ,Influenza Viruses ,DNA Mutational Analysis ,Hemagglutinin Glycoproteins, Influenza Virus ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Biochemistry ,Epitopes ,Influenza A Virus, H1N1 Subtype ,Medicine and Health Sciences ,Influenza A virus ,Amino Acids ,Phylogeny ,Data Management ,Genetics ,Vaccines ,Multidisciplinary ,biology ,Phylogenetic tree ,Organic Compounds ,Microbial Mutation ,Phylogenetic Analysis ,Subclade ,Phylogenetics ,Chemistry ,Treatment Outcome ,Infectious Diseases ,Influenza Vaccines ,Medical Microbiology ,Viral Pathogens ,Viruses ,Physical Sciences ,Medicine ,Pathogens ,Research Article ,China ,Computer and Information Sciences ,Substitution Mutation ,Infectious Disease Control ,Science ,030106 microbiology ,Neuraminidase ,Hemagglutinin (influenza) ,Microbiology ,Evolution, Molecular ,03 medical and health sciences ,medicine ,Humans ,Evolutionary Systematics ,Amino Acid Sequence ,Microbial Pathogens ,Demography ,Taxonomy ,Whole genome sequencing ,Evolutionary Biology ,Whole Genome Sequencing ,Biology and life sciences ,Organic Chemistry ,Organisms ,Chemical Compounds ,Proteins ,Vaccine efficacy ,Influenza ,030104 developmental biology ,Amino Acid Substitution ,Mutation ,biology.protein ,Orthomyxoviruses - Abstract
The continuous variation of the seasonal influenza viruses, particularly A(H1N1)pdm09, persistently threatens human life and health around the world. In local areas of southwest china, the large time-scale genomic research on A(H1N1)pdm09 is still insufficient. Here, we sequenced 45 whole-genome sequences of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018, by next-generation sequencing technology to characterize molecular mechanisms of their origin and evolution. Our phylogenetic analyses suggest that the A(H1N1)pdm09 strains circulating in Lincang belong to clade 6B and the subclade 6B.1A predominates in 2018. Further, the strains in 2018 possess elevated evolutionary rate as compared to strains in other years. Several newly emerged mutations for HA (hemagglutinin) in 2018 are revealed (i.e., S183P and R221K). Intriguingly, the substitution R221K falls into the RBS (receptor binding site) of HA protein, which could affect antigenic properties of influenza A(H1N1)pdm09 viruses, and another substitution S183P near to RBS with a high covering frequency (11/14 strains) in 2018 is exactly located at the epitope B. Notably, the NA (neuraminidase) protein harbors a new mutation I23T, potentially involved in N-glycosylation. Based on the background with a higher evolutionary rate in 2018 strains, we deeply evaluate the potential vaccine efficacy against Lincang strains and discover a substantive decline of the vaccine efficacy in 2018. Our analyses reaffirm that the real-time molecular surveillance and timely updated vaccine strains for prevention and control of influenza A(H1N1)pdm09 are crucial in the future.
- Published
- 2020
44. A four-stage DEA-based efficiency evaluation of public hospitals in China after the implementation of new medical reforms
- Author
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Peilin Zhang, Xiaoqin Lu, Wanhui Zheng, Guojiang Zhou, Quanyu Jin, and Hong Sun
- Subjects
Critical Care and Emergency Medicine ,Hospital bed ,Economics ,Health Care Providers ,Social Sciences ,Nurses ,lcsh:Medicine ,Efficiency, Organizational ,0302 clinical medicine ,Cognition ,Sociology ,Per capita ,Medicine and Health Sciences ,Psychology ,030212 general & internal medicine ,Medical Personnel ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,030503 health policy & services ,Hospitals ,Professions ,Scale (social sciences) ,0305 other medical science ,Research Article ,China ,Population ,Decision Making ,Sample (statistics) ,Hospitals, General ,Education ,03 medical and health sciences ,Health Economics ,Population Metrics ,Data envelopment analysis ,Humans ,Operations management ,education ,Population Density ,Population Biology ,Hospitals, Public ,lcsh:R ,Cognitive Psychology ,Biology and Life Sciences ,Health Care ,Medical Education ,Health Care Facilities ,People and Places ,Fixed asset ,Cognitive Science ,Population Groupings ,lcsh:Q ,Business ,Utilization rate ,Medical Humanities ,Finance ,Neuroscience - Abstract
This study applied the non-parametric four-stage data envelopment analysis method (Four-Stage DEA) to measure the relative efficiencies of Chinese public hospitals from 2010 to 2016, and to determine how efficiencies were affected by eight factors. A sample of public hospitals (n = 84) was selected from Chongqing, China, including general hospitals and traditional Chinese medicine hospitals graded level 2 or above. The Four-Stage-DEA method was chosen since it enables the control of the impact of environment factors on efficiency evaluation results. Data on the number of staff, government financial subsidies, the number of beds and fixed assets were used as input whereas the number of out-patients and emergency department patients and visits, the number of discharged patients, medical and health service income and hospital bed utilization rate were chosen as study outputs. As relevant environmental variables, we selected GDP per capita, permanent population, population density, number of hospitals and number of available sickbeds in local medical institutions. The relative efficiencies (i.e. technical, pure technical, scale) of sample hospitals were also calculated to analyze the change between the first stage and fourth stage every year. The study found that Four-Stage-DEA can effectively filter the impact of environmental factors on evaluation results, which sets it apart from other models commonly used in existing studies.
- Published
- 2018
45. Effects of plant population density and root-induced cytokinin on the corn compensatory growth during post-drought rewatering
- Author
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Run-Hong Sun, Lin Qi, Rong-Rong Qin, Jiang Shi, Xiao-Gai Hou, and Xiao-Ling Wang
- Subjects
0106 biological sciences ,Drought stress ,Leaves ,Cytokinins ,lcsh:Medicine ,Plant Science ,01 natural sciences ,Biochemistry ,Plant Roots ,chemistry.chemical_compound ,Natural Resources ,Compensatory growth (organism) ,Plant Hormones ,Photosynthesis ,lcsh:Science ,Multidisciplinary ,Dehydration ,Plant Biochemistry ,Organic Compounds ,Plant Anatomy ,Eukaryota ,food and beverages ,04 agricultural and veterinary sciences ,Plants ,Plant population ,Horticulture ,Chemistry ,Experimental Organism Systems ,Plant Physiology ,Cytokinin ,Physical Sciences ,Water Resources ,Vascular Bundles ,Research Article ,Carbohydrates ,chemical and pharmacologic phenomena ,Biology ,Research and Analysis Methods ,Zea mays ,complex mixtures ,Intraspecific competition ,Zeatin riboside ,Model Organisms ,Plant and Algal Models ,Xylem ,Grasses ,Ecology and Environmental Sciences ,Organic Chemistry ,fungi ,lcsh:R ,Organisms ,Chemical Compounds ,Biology and Life Sciences ,Hormones ,Maize ,respiratory tract diseases ,chemistry ,Seedlings ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,lcsh:Q ,010606 plant biology & botany - Abstract
The effect of plant population density (PPD) and root-induced leaf cytokinin on the compensatory growth of potted corn seedlings during post-drought rewatering was investigated. The study design comprised four treatments: (1) wetness with low PPD, (2) wetness with high PPD, (3) rewatering with low PPD, and (4) rewatering with high PPD. Results showed that drought stress restrained the growth of corns. By contrast, rewatering enhanced the net photosynthetic rate and growth of corns. During the 8 days of rewatering, compensatory growth during post-drought rewatering occurred in corns with high PPD; however, such compensatory growth did not occur in corns with low PPD. Zeatin riboside concentrations in leaves and xylem saps were significantly higher under rewatering treatment than those under wet treatment. High leaf cytokinin concentration accelerated corn growth. The coefficients of variation and Gini-coefficient of wet treatment were significantly higher than those of rewatering treatment under high PPD, demonstrating that intense intraspecific competition occurred in the wet treatment. Extreme intraspecific competition negatively affected net photosynthetic rate. In brief, the interactions between root-induced leaf cytokinin and weak intraspecific competition promoted the compensatory growth under high PPD.
- Published
- 2018
46. Non-targeted metabolomics unravels a media-dependent prodiginines production pathway in Streptomyces coelicolor A3(2)
- Author
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Lim, Yonghwan, primary, Jung, Eun Sung, additional, Lee, Je Hyeon, additional, Kim, Eun Joo, additional, Hong, Sun Joo, additional, Lee, Yeon Hee, additional, and Lee, Choong Hwan, additional
- Published
- 2018
- Full Text
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47. The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis
- Author
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Xi Guo, Qian Li, Song Li, Tianshu Liu, Rongyuan Zhuang, Hong Sun, and Feng Shen
- Subjects
0301 basic medicine ,Oncology ,Colorectal cancer ,Physiology ,DNA Mutational Analysis ,Gene Identification and Analysis ,lcsh:Medicine ,Cochrane Library ,Biochemistry ,Lung and Intrathoracic Tumors ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Neoplasms ,Medicine and Health Sciences ,lcsh:Science ,Multidisciplinary ,DNA, Neoplasm ,Prognosis ,Body Fluids ,Blood ,Cell-free fetal DNA ,030220 oncology & carcinogenesis ,Meta-analysis ,Mutation (genetic algorithm) ,Physical Sciences ,Anatomy ,Statistics (Mathematics) ,Research Article ,medicine.medical_specialty ,Research and Analysis Methods ,Blood Plasma ,Disease-Free Survival ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Pancreatic Cancer ,Internal medicine ,Pancreatic cancer ,Gastrointestinal Tumors ,medicine ,Genetics ,Biomarkers, Tumor ,Humans ,Statistical Methods ,Mutation Detection ,Colorectal Cancer ,business.industry ,lcsh:R ,Cancer ,Biology and Life Sciences ,Cancers and Neoplasms ,medicine.disease ,Non-Small Cell Lung Cancer ,030104 developmental biology ,Mutation ,lcsh:Q ,business ,Kras mutation ,Mathematics ,Biomarkers ,Meta-Analysis - Abstract
KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information independently. Review Manager 5.3 software was used to perform the statistical analysis. Thirty studies were included in the present meta-analysis. Our analysis showed that KRAS mutation in cfDNA was associated with a poorer survival in cancer patients for overall survival (OS, HR 2.02, 95% CI 1.63-2.51, P
- Published
- 2017
48. Prognostic implications of preoperative anemia in urothelial carcinoma: A meta-analysis
- Author
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Zhi-Hua Zhang, Ya-Shen Wang, Yan-Hui Su, Fei Luo, Jian Li, and Hong-Hong Sun
- Subjects
Oncology ,Male ,Lymphovascular invasion ,030232 urology & nephrology ,Cancer Treatment ,lcsh:Medicine ,Nephrectomy ,Database and Informatics Methods ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Recurrence ,Medicine and Health Sciences ,Database Searching ,lcsh:Science ,Multidisciplinary ,Hazard ratio ,Anemia ,Hematology ,Prognosis ,Treatment Outcome ,030220 oncology & carcinogenesis ,Preoperative Period ,Physical Sciences ,Female ,Anatomy ,Statistics (Mathematics) ,Research Article ,medicine.medical_specialty ,Urologic Neoplasms ,Bladder ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Cystectomy ,Urinary System Procedures ,03 medical and health sciences ,Diagnostic Medicine ,Internal medicine ,medicine ,Carcinoma ,Humans ,Statistical Methods ,Survival analysis ,Radical Surgery ,Carcinoma, Transitional Cell ,Surgical Excision ,business.industry ,Carcinoma in situ ,lcsh:R ,Biology and Life Sciences ,Renal System ,medicine.disease ,Survival Analysis ,Confidence interval ,Concomitant ,T-stage ,lcsh:Q ,business ,Mathematics ,Meta-Analysis - Abstract
The prognostic significance of preoperative anemia (PA) has been identified in various malignancies. However, its predictive role in urothelial carcinoma (UC) remains controversial. The aim of this study was to investigate the prognostic value of PA in UC patients. We performed a meta-analysis of the association between PA and survival outcome in UC patients. Electronic databases were searched up to June 30, 2016. Study characteristics and prognostic data were extracted from each included study. Cancer-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS) were pooled using hazard ratio (HR) with corresponding 95% confidence intervals (CI). Herein, 12 studies comprising 3815 patients were included in the meta-analysis. There were 1593 (41.76%) patients in the PA group and 2222 (58.24%) in the control group. The overall pooled HRs of PA for CSS, RFS, and OS were significant at 2.21, (95% CI: 1.83-2.65, Pheterogeneity = 0.49, I2 = 0%), 1.87 (95% CI: 1.59-2.20, Pheterogeneity = 0.22, I2 = 28%), and 2.04(95% CI: 1.76-2.37, Pheterogeneity = 0.36, I2 = 9%) respectively. Stratified analyses indicated that PA was a predictor of poor prognosis based on ethnicity, sample size, tumor T stage, G grade, lymphovascular invasion (LVI), concomitant carcinoma in situ (CIS), and follow-up values. Our findings show that PA has negative prognostic effects on the survival outcome (CSS, RFS, and OS) in UC patients and can serve as a useful and cost-effective marker to aid prognosis prediction.
- Published
- 2017
49. 99mTc-MIBI uptake as a marker of mitochondrial membrane potential in cancer cells and effects of MDR1 and verapamil.
- Author
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Park, Jin Won, Hong, Sun-pyo, Lee, Jin Hee, Moon, Seung Hwan, Cho, Young Seok, Jung, Kyung-Ho, Lee, Jeeyun, and Lee, Kyung-Han
- Subjects
- *
MEMBRANE potential , *MITOCHONDRIAL membranes , *CANCER cells , *CELL membranes , *PLASMA potentials - Abstract
We investigated the relation of 99mTc-MIBI uptake to mitochondrial membrane potential (MMP) in cancer cell lines and patient-derived tumor cells (PDCs). In T47D and HT29 cells with low MDR1 expression, FCCP dose-dependently reduced MMP and 99mTc-MIBI accumulation in similar patterns with nearly perfect linear relationships. T47D and HT29 cells with high MDR1 expression had low 99mTc-MIBI accumulation that was minimally affected by FCCP dose. In these cells, verapamil markedly increased 99mTc-MIBI accumulation to magnitudes that were excessive compared to MMP increase. Decreased plasma membrane potential by verapamil and its recovery by FCCP suggested that enhanced 99mTc-MIBI transport through modified plasma membranes contributed to the excess accumulation. Evaluation of three different colon cancer PDCs with low to modest MDR1 expression verified that FCCP significantly suppressed MMP and similarly reduced 99mTc-MIBI accumulation. Verapamil partially recovered both MMP and 99mTc-MIBI accumulation that was lowered by FCCP. Importantly, a high linear correlation was found (r = 0.865) between 99mTc-MIBI accumulation and MMP in these cells. These findings indicate that low baseline 99mTc-MIBI uptake that is markedly increased by verapamil represents cancer cells with high levels of MDR1 expression. However, in cancer cells with low or modest levels of MDR1 expression that do not markedly increase 99mTc-MIBI uptake by verapamil, the magnitude of uptake is largely dependent on cellular MMP. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
50. Hexavalent Chromium (Cr(VI)) Down-Regulates Acetylation of Histone H4 at Lysine 16 through Induction of Stressor Protein Nupr1
- Author
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Lei Fang, Danqi Chen, Thomas Kluz, Max Costa, Xiaoru Zhang, Hong Sun, and Chunyuan Jin
- Subjects
0301 basic medicine ,Chromium ,Lung Neoplasms ,lcsh:Medicine ,medicine.disease_cause ,Cell Transformation ,Biochemistry ,Lung and Intrathoracic Tumors ,Epigenesis, Genetic ,Histones ,0302 clinical medicine ,Medicine and Health Sciences ,Basic Helix-Loop-Helix Transcription Factors ,Small interfering RNAs ,Nuclear protein ,Post-Translational Modification ,lcsh:Science ,Lung ,Gene knockdown ,Multidisciplinary ,DNA methylation ,biology ,Chemical Reactions ,Acetylation ,Chromatin ,3. Good health ,Neoplasm Proteins ,Up-Regulation ,Nucleic acids ,Chemistry ,Histone ,Cell Transformation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Physical Sciences ,Hyperexpression Techniques ,Epigenetics ,DNA modification ,Chromatin modification ,Research Article ,Chromosome biology ,Cell biology ,Cell Physiology ,Research and Analysis Methods ,Cell Line ,Histone H4 ,03 medical and health sciences ,DNA-binding proteins ,medicine ,Genetics ,Gene Expression and Vector Techniques ,Humans ,Molecular Biology Techniques ,Non-coding RNA ,Molecular Biology ,Molecular Biology Assays and Analysis Techniques ,Biology and life sciences ,Lysine ,lcsh:R ,Proteins ,Cancers and Neoplasms ,Histone acetyltransferase ,DNA ,Molecular biology ,Carcinogens, Environmental ,Gene regulation ,030104 developmental biology ,biology.protein ,RNA ,lcsh:Q ,Gene expression ,Carcinogenesis - Abstract
The environmental and occupational carcinogen Hexavalent Chromium (Cr(VI)) has been shown to cause lung cancer in humans when inhaled. In spite of a considerable research effort, the mechanisms of Cr(VI)-induced carcinogenesis remain largely unknown. Nupr1 (nuclear protein 1) is a small, highly basic, and unfolded protein with molecular weight of 8,800 daltons and is induced by a variety of stressors. Studies in animal models have suggested that Nupr1 is a key factor in the development of lung and pancreatic cancers, with little known about the underlying molecular mechanisms. Here we report that the level of Nupr1 is significantly increased in human bronchial epithelial BEAS2B cells following exposure to Cr(VI) through epigenetic mechanisms. Interestingly, Cr(VI) exposure also results in the loss of acetylation at histone H4K16, which is considered a 'hallmark' of human cancer. Cr(VI)-induced reduction of H4K16 acetylation appears to be caused by the induction of Nupr1, since (a) overexpression of Nupr1 decreased the levels of both H4K16 acetylation and the histone acetyltransferase MOF (male absent on the first; also known as Kat8, Myst 1), which specifically acetylates H4K16; (b) the loss of acetylation of H4K16 upon Cr(VI) exposure is greatly compromised by knockdown of Nupr1. Moreover, Nupr1-induced reduction of H4K16 acetylation correlates with the transcriptional down-regulation at several genomic loci. Notably, overexpression of Nupr1 induces anchorage-independent cell growth and knockdown of Nupr1 expression prevents Cr(VI)-induced cell transformation. We propose that Cr(VI) induces Nupr1 and rapidly perturbs gene expression by downregulating H4K16 acetylation, thereby contributing to Cr(VI)-induced carcinogenesis.
- Published
- 2016
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