27 results on '"Qian, Sun"'
Search Results
2. Long-Term Effect of Elevated CO2 on the Development and Nutrition Contents of the Pea Aphid (Acyrthosiphon pisum)
- Author
-
Chunchun Li, Qian Sun, Yuping Gou, Kexin Zhang, Qiangyan Zhang, Jing-Jiang Zhou, and Changzhong Liu
- Subjects
Acyrthosiphon pisum ,elevated CO2 ,generation ,development ,nutrition ,Physiology ,QP1-981 - Abstract
It is predicted that the current atmospheric CO2 level will be doubled by the end of this century. Here, we investigate the impacts of elevated CO2 (550 and 750 μL/L) on the development and nutrition status of the green pea aphid for six generations, which is longer than previous studies. All seven examined physiological parameters were not affected over six generations under the ambient CO2 level (380 μL/L). However, the elevated CO2 levels (550 and 750 μL/L) prolonged nymph duration, decreased adult longevity, female fecundity and protein content, and increased the contents of total lipid, soluble sugar and glycogen. There was a significant interaction between the effect of CO2 levels and the effect of generations on nymph duration, female fecundity and adult longevity. The elevated CO2 had immediate effects on the female fecundity and the contents of total protein, total lipid and soluble sugar, starting within F0 generation. The adult longevity decreased, and the glycogen content increased from the F1 generation. However, the significant effect on the nymph development was only observed after three generations. Our study indicates that the elevated CO2 levels first influence the reproduction, the nutrition and the energy supply, then initiate aphid emergency responses by shortening lifespan and increasing glucose metabolism, and finally result in the slow development under further persistent elevated CO2 conditions after three generations, possibly leading to population decline under elevated CO2 conditions. Our results will guide further field experiments under climate change conditions to evaluate the effects of elevated CO2 on the development of the pea aphids and other insects, and to predict the population dynamics of the green pea aphid.
- Published
- 2021
- Full Text
- View/download PDF
3. Chronic Unpredictable Mild Stress in Rats Induces Colonic Inflammation
- Author
-
Lina Wei, Ye Li, Wenjun Tang, Qian Sun, Lixin Chen, Xia Wang, Qingyi Liu, Siqi Yu, Shuyan Yu, Chuanyong Liu, and Xuelian Ma
- Subjects
chronic unpredictable mild stress ,microbiota ,depression ,intestinal barrier ,colonic inflammation ,Physiology ,QP1-981 - Abstract
Chronic psychological stress is associated with an increased risk for relapse of inflammatory bowel diseases (IBD) and impedes the treatment of this condition. However, the impact of stress on the risk of IBD onset remains unclear. The goal of the present study was to examine whether chronic unpredictable mild stress (CUMS) could initiate or aggravate the onset of colon inflammation in rats which, in turn, would be capable of triggering bowel disease. We found that CUMS exposure increased infiltration of CD-45 positive cells and MPO activity, as well as augmented the expression of the inflammatory cytokines, IFN-γ and IL-6 within the colon of these rats. In addition, CUMS treatment changed the composition and diversity of gut microbiota and enhanced intestinal epithelial permeability, indicating the presence of a defect in the intestinal barrier. This CUMS-induced disruption of mucosal barrier integrity was associated with a reduction in expression of the tight junction protein, occludin 1, and an inhibition in mucosal layer functioning via reductions in goblet cells. Results from bacterial cultures revealed an increased presence of bacterial invasion after CUMS treatment as compared with that observed in controls. Thus, our data indicate that CUMS treatment induces alterations of the fecal microbiome and intestinal barrier defects, which facilitates bacterial invasion into colonic mucosa and further exacerbates inflammatory reactions within the colon. Accordingly, chronic stress may predispose patients to gastrointestinal infection and increase the risk of inflammation-related gut diseases.
- Published
- 2019
- Full Text
- View/download PDF
4. miR‐21‐regulated M2 polarization of macrophage is involved in arsenicosis‐induced hepatic fibrosis through the activation of hepatic stellate cells
- Author
-
Xiangyu Dai, Zhonglan Zou, Ming Shi, Jing Sun, Junchao Xue, Qizhan Liu, Huanwen Tang, Qian Sun, Haibo Xia, Aihua Zhang, Lu Wu, Tian Xiao, Shaofeng Wei, and Junjie Li
- Subjects
Liver Cirrhosis ,0301 basic medicine ,Arsenites ,Physiology ,Clinical Biochemistry ,Down-Regulation ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Fibrosis ,Hepatic Stellate Cells ,medicine ,Animals ,Humans ,PTEN ,Tensin ,ARG1 ,biology ,Chemistry ,Macrophages ,TOR Serine-Threonine Kinases ,Cell Biology ,medicine.disease ,Arginase ,MicroRNAs ,030104 developmental biology ,Liver ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Hepatic stellate cell ,Hepatic fibrosis ,Signal Transduction - Abstract
Arsenicosis induced by chronic exposure to arsenic is recognized as one of the main damaging effects on public health. Exposure to arsenic can cause hepatic fibrosis, but the molecular mechanisms by which this occurs are complex and elusive. It is not known if miRNAs are involved in arsenic-induced liver fibrosis. We found that in the livers of mice exposed to arsenite, there were elevated levels of microRNA-21 (miR-21), phosphorylated mammalian target of rapamycin (p-mTOR), and arginase 1 (Arg1); low levels of phosphatase and tensin homolog (PTEN); and more extensive liver fibrosis. For cultured cells, arsenite-induced miR-21, p-mTOR, and Arg1; decreased PTEN; and promoted M2 polarization of macrophages derived from THP-1 monocytes (THP-M), which caused secretion of fibrogenic cytokines, including transforming growth factor-β1. Coculture of arsenite-treated, THP-M with LX-2 cells induced α-SMA and collagen I in the LX-2 cells and resulted in the activation of these cells. Downregulation of miR-21 in THP-M inhibited arsenite-induced M2 polarization and activation of LX-2 cells, but cotransfection with PTEN siRNA or a miR-21 inhibitor reversed this inhibition. Moreover, knockout of miR-21 in mice attenuated liver fibrosis and M2 polarization compared with WT mice exposed to arsenite. Additionally, LN, PCIII, and HA levels were higher in patients with higher hair arsenic levels, and levels of miR-21 were higher than controls and positively correlated with PCIII, LN, and HA levels. Thus, arsenite induces the M2 polarization of macrophages via miR-21 regulation of PTEN, which is involved in the activation of hepatic stellate cells and hepatic fibrosis. The results establish a previously unknown mechanism for arsenicosis-induced fibrosis.
- Published
- 2021
5. The role of HDAC11 in obesity‐related metabolic disorders: A critical review
- Author
-
Saeed Muhammad, Chao Sun, Hong Yang, Lingling Chen, Fangyao Yao, and Qian Sun
- Subjects
0301 basic medicine ,Metabolic inflammation ,Physiology ,Clinical Biochemistry ,Metabolic homeostasis ,Bioinformatics ,Histone Deacetylases ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Obesity ,Cell Proliferation ,Inflammation ,Cell growth ,HDAC11 ,business.industry ,Cell Biology ,medicine.disease ,Structure and function ,Histone Deacetylase Inhibitors ,030104 developmental biology ,030220 oncology & carcinogenesis ,business - Abstract
At present, metabolic diseases, such as obesity and diabetes, have become the world's top health threats. These diseases are closely related to the abnormal development and function of adipocytes and metabolic inflammation associated with obesity. Histone deacetylase 11 (HDAC11), with a relatively unique structure and function in the HDAC family, plays a vital role in regulating cell growth, migration, and cell death. Currently, research on new key regulatory functions of HDAC11 in metabolic homeostasis is receiving more and more attention, and HDAC11 has also become a potential therapeutic target in the treatment of obesity and obesity-related diseases. Here, we summarized the latest literature on the role of HDAC11 in regulating the progress of obesity-related metabolic disorders.
- Published
- 2021
6. Differential Responses of NHX1 and SOS1 Gene Expressions to Salinity in two Miscanthus sinensis Anderss. Accessions with Different Salt Tolerance
- Author
-
Qian Sun, Toshihiko Yamada, Tetsuo Takano, and Yulai Han
- Subjects
chemistry.chemical_classification ,biology ,Physiology ,Chemistry ,Salt (chemistry) ,Miscanthus sinensis ,Plant Science ,biology.organism_classification ,Biochemistry ,Salinity ,Botany ,SOS1 ,Gene ,Differential (mathematics) - Published
- 2021
7. Adult Stress Promotes Purinergic Signaling to Induce Visceral Pain in Rats with Neonatal Maternal Deprivation
- Author
-
Guang-Yin Xu, Wan-Jie Du, Jian Song, Xin Li, Qian Sun, Ji-Tian Xu, Shufen Hu, and Ping-An Zhang
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Population ,Stress ,Irritable Bowel Syndrome ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Dorsal root ganglion ,Stress, Physiological ,Ganglia, Spinal ,Internal medicine ,medicine ,Animals ,Receptor ,education ,Visceral hypersensitivity ,Maternal deprivation ,education.field_of_study ,business.industry ,Maternal Deprivation ,General Neuroscience ,Antagonist ,P2X3 receptor ,Visceral pain ,Visceral Pain ,General Medicine ,Purinergic signalling ,β2 adrenergic receptor ,Rats ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Original Article ,medicine.symptom ,business ,Receptors, Purinergic P2X3 ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Chronic visceral pain is one of the primary symptoms of patients with irritable bowel syndrome (IBS), which affects up to 15% of the population world-wide. The detailed mechanisms of visceral pain remain largely unclear. Our previous studies have shown that neonatal maternal deprivation (NMD) followed by adult multiple stress (AMS) advances the occurrence of visceral pain, likely due to enhanced norepinephrine (NE)-β2 adrenergic signaling. This study was designed to explore the roles of P2X3 receptors (P2X3Rs) in the chronic visceral pain induced by combined stress. Here, we showed that P2X3Rs were co-expressed in β2 adrenergic receptor (β2-AR)-positive dorsal root ganglion neurons and that NE significantly enhanced ATP-induced Ca2+ signals. NMD and AMS not only significantly increased the protein expression of P2X3Rs, but also greatly enhanced the ATP-evoked current density, number of action potentials, and intracellular Ca2+ concentration of colon-related DRG neurons. Intrathecal injection of the P2X3R inhibitor A317491 greatly attenuated the visceral pain and the ATP-induced Ca2+ signals in NMD and AMS rats. Furthermore, the β2-AR antagonist butoxamine significantly reversed the expression of P2X3Rs, the ATP-induced current density, and the number of action potentials of DRG neurons. Overall, our data demonstrate that NMD followed by AMS leads to P2X3R activation, which is most likely mediated by upregulation of β2 adrenergic signaling in primary sensory neurons, thus contributing to visceral hypersensitivity.
- Published
- 2020
8. Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes
- Author
-
Yong-Chang Li, Rui-Xia Weng, Guang-Yin Xu, Qian Sun, Rui Wu, Hong-Hong Zhang, and Ping-An Zhang
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,endocrine system diseases ,Physiology ,DNA damage ,Hippocampus ,Morris water navigation task ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,Type 2 diabetes mellitus ,medicine ,Memory impairment ,Animals ,Receptor ,P2X4 receptors ,Microglia ,business.industry ,General Neuroscience ,Purinergic receptor ,nutritional and metabolic diseases ,General Medicine ,Rats ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Diabetes Mellitus, Type 2 ,Original Article ,business ,Cognition Disorders ,Receptors, Purinergic P2X4 ,030217 neurology & neurosurgery - Abstract
Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment. Electronic supplementary material The online version of this article (10.1007/s12264-020-00478-7) contains supplementary material, which is available to authorized users.
- Published
- 2020
9. Positive effects of selenium supplementation in women with newly diagnosed Hashimoto's thyroiditis in an area with low selenium status
- Author
-
Jadwiga Kryczyk-Kozioł, Anna Błażewska-Gruszczyk, Marian Słowiaczek, Ewelina Prochownik, Mirosław Bartyzel, Lutz Schomburg, Qian Sun, Paweł Zagrodzki, and Ewa Ochab
- Subjects
endocrine system ,endocrine system diseases ,chemistry.chemical_element ,Physiology ,Hashimoto Disease ,Thyroiditis ,Selenium ,Hypothyroidism ,medicine ,Humans ,Subclinical infection ,medicine.diagnostic_test ,business.industry ,Thyroid disease ,Thyroid ,General Medicine ,medicine.disease ,Anti-thyroid autoantibodies ,medicine.anatomical_structure ,chemistry ,Dietary Supplements ,Female ,Thyroid function ,business ,Lipid profile - Abstract
Objective Autoimmune thyroid diseases, including Hashimoto's thyroiditis, are the most common ones among autoimmune diseases. The reported effects of selenium supplementation on the course of Hashimoto's thyroiditis are not consistent. It is therefore important to continue this line of research. Design The participants received selenium in the form of sodium selenite(IV) at a dose of 100 µg/day for 6 months. Patients Newly diagnosed and previously untreated Hashimoto's thyroiditis with euthyroidism or subclinical hypothyroidism. A total of 36 patients (aged 20 to 52 years) qualified for this study, of whom 29 women were successfully enrolled and completed the intervention. Measurements Both before and after supplementation the following parameters in serum were tested: anti-thyroid peroxidase antibodies, thyroid function indicators, selenium as well as antioxidant status parameters and other biochemical parameters (lipid profile, glucose). Iodine supply and subjective assessment of physical and psychological health were also monitored. Results Selenium supplementation decreased significantly level of anti-thyroid peroxidase antibodies what might have had a stabilizing effect on thyroid function, as values of thyroid parameters were within normal range before and at the end of the study. Mean level of selenium among patients was not different to healthy people in Poland. Median of ioduria was within normal range. Conclusions The study shows a potential way of protective effect of selenium in limiting development of overt hypothyroidism. The increase in the concentrations of Se and SELENOP in the serum of patients verifies successful supplementation and good compliance, but did not affect the antioxidant status parameters measured.
- Published
- 2021
10. Topographic heterogeneity of intrinsic excitability in mouse hippocampal CA3 pyramidal neurons
- Author
-
Qian Sun, Yu-Qiu Jiang, and Melissa C Lu
- Subjects
Male ,Physiology ,General Neuroscience ,Pyramidal Cells ,Hippocampus ,Action Potentials ,Hippocampal formation ,Biology ,Hippocampal region ,Spatial memory ,CA3 Region, Hippocampal ,Mice, Inbred C57BL ,Mice ,nervous system ,Homogeneous ,Marked heterogeneity ,Animals ,Female ,Neuroscience ,Episodic memory ,Input resistance ,Research Article - Abstract
Area CA3 in the hippocampus is traditionally thought to act as a homogeneous neural circuit that is vital for spatial navigation and episodic memories. However, recent studies have revealed that CA3 pyramidal neurons in dorsal hippocampus display marked anatomic and functional heterogeneity along the proximodistal (transverse) axis. The hippocampus is also known to be functionally segregated along the dorsoventral (longitudinal) axis, with dorsal hippocampus strongly involved in spatial navigation and ventral hippocampus associated with emotion and anxiety. Surprisingly, however, relatively little is known about CA3 functional heterogeneity along the dorsoventral axis. Here, we carried out mouse-brain-slice patch-clamp recordings and morphological analyses to examine the heterogeneity of CA3 cellular properties along both proximodistal and dorsoventral axes. We find that CA3 pyramidal neurons exhibit considerable heterogeneity of somatodendritic morphology and intrinsic membrane properties, with ventral CA3 (vCA3) displaying more elaborate somatodendritic morphology, lower intrinsic excitability, smaller input resistance, greater cell capacitance, and more prominent hyperpolarization‐activated current than dorsal CA3 (dCA3). Furthermore, although both dCA3 and vCA3 exhibit proximal-to-distal gradients in intrinsic properties and neuronal morphology, these proximal-to-distal gradients in vCA3 are more moderate than those in dCA3. Taken together, our results extend previous findings on the proximodistal heterogeneity of dCA3 function and uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that extends to multiple anatomic dimensions and may contribute to its in vivo functional diversity. NEW & NOTEWORTHY Area CA3 is a major hippocampal region that is classically thought to act as a homogeneous neural network vital for spatial navigation and episodic memories. Here, we report that CA3 pyramidal neurons exhibit marked heterogeneity of somatodendritic morphology and cellular electrical properties along both proximodistal and dorsoventral axes. These new results uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that may contribute to its in vivo functional diversity.
- Published
- 2020
11. Urine metabolomics of rats with chronic atrophic gastritis
- Author
-
Liang-Kun Zhang, Jian Chen, Xi-Jian Liu, Ling Li, Keyun Sun, Tao Han, Qian-Qian Sun, Hailiang Huang, and Guoxiu Zu
- Subjects
Male ,Physiology ,Methylnitronitrosoguanidine ,Atrophic gastritis ,Nitrogen Metabolism ,Urine ,Biochemistry ,Mass Spectrometry ,Analytical Chemistry ,Pathogenesis ,chemistry.chemical_compound ,Spectrum Analysis Techniques ,Medicine and Health Sciences ,Metabolites ,Medicine ,Amino Acids ,Purine metabolism ,Liquid Chromatography ,Multidisciplinary ,Organic Compounds ,Chromatographic Techniques ,Body Fluids ,Chemistry ,Physical Sciences ,Purine Metabolism ,Metabolic Pathways ,Anatomy ,Basic Amino Acids ,Metabolic Networks and Pathways ,Research Article ,Gastritis, Atrophic ,medicine.medical_specialty ,Liquid Chromatography-Mass Spectrometry ,Science ,Research and Analysis Methods ,Metabolomics ,Internal medicine ,Animals ,Histidine ,Rats, Wistar ,business.industry ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Metabolism ,medicine.disease ,Rats ,Amino Acid Metabolism ,Disease Models, Animal ,Metabolic pathway ,Endocrinology ,chemistry ,business ,Biomarkers - Abstract
Background/aim To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). Materials and methods Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. Results Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. Conclusion By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.
- Published
- 2020
12. Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals
- Author
-
Likhona Masika, Livia Avallone, Yesim Ozarda, Brian Stolze, Toral Parikh, Kerry J. Welsh, Qian Sun, Steven J. Soldin, Katherine A Araque, and Jacqueline Jonklaas
- Subjects
lcsh:RC648-665 ,business.industry ,Endocrinology, Diabetes and Metabolism ,Thyroid ,Diurnal temperature variation ,Physiology ,030209 endocrinology & metabolism ,reference interval ,diurnal variation ,Mass spectrometric ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,thyroid hormone ,Reference intervals ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Thyroid hormones ,Medicine ,business ,Hormone ,Original Research ,mass spectrometry - Abstract
Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 ( p Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.
- Published
- 2019
13. cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING
- Author
-
Timothy R. Billiar, Melanie J. Scott, Zhao Lei, John E. Griepentrog, Patricia Loughran, Meihong Deng, Qian Sun, Feizhou Huang, Richard A. Shapiro, Hongbo Xu, Zhongjie Yi, Hai Huang, and Tunliang Li
- Subjects
0301 basic medicine ,Interferon Inducers ,Physiology ,Ischemia ,Apoptosis ,Pharmacology ,Protective Agents ,Mice ,03 medical and health sciences ,Physiology (medical) ,Autophagy ,medicine ,Animals ,Hepatology ,business.industry ,Gastroenterology ,Membrane Proteins ,Hypoxia (medical) ,medicine.disease ,Nucleotidyltransferases ,eye diseases ,Mice, Inbred C57BL ,Sting ,030104 developmental biology ,Liver ,Reperfusion Injury ,DNA Nucleotidyltransferases ,Interferon Type I ,Nucleotides, Cyclic ,medicine.symptom ,business ,Reperfusion injury ,Research Article ,Signal Transduction - Abstract
Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS−/−), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS−/− mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS−/− mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS−/− hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.
- Published
- 2018
14. Chronic Unpredictable Mild Stress in Rats Induces Colonic Inflammation
- Author
-
Qingyi Liu, Shuyan Yu, Chuanyong Liu, Xuelian Ma, Lixin Chen, Lina Wei, Xia Wang, Qian Sun, Ye Li, Wenjun Tang, and Siqi Yu
- Subjects
0301 basic medicine ,Physiology ,Inflammation ,Gut flora ,Occludin ,lcsh:Physiology ,colonic inflammation ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,microbiota ,Medicine ,Chronic stress ,Microbiome ,Original Research ,lcsh:QP1-981 ,Tight junction ,biology ,business.industry ,medicine.disease ,biology.organism_classification ,intestinal barrier ,030104 developmental biology ,depression ,Immunology ,chronic unpredictable mild stress ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Infiltration (medical) - Abstract
Chronic psychological stress is associated with an increased risk for relapse of inflammatory bowel diseases (IBD) and impedes the treatment of this condition. However, the impact of stress on the risk of IBD onset remains unclear. The goal of the present study was to examine whether chronic unpredictable mild stress (CUMS) could initiate or aggravate the onset of colon inflammation in rats which, in turn, would be capable of triggering bowel disease. We found that CUMS exposure increased infiltration of CD-45 positive cells and MPO activity, as well as augmented the expression of the inflammatory cytokines, IFN-γ and IL-6 within the colon of these rats. In addition, CUMS treatment changed the composition and diversity of gut microbiota and enhanced intestinal epithelial permeability, indicating the presence of a defect in the intestinal barrier. This CUMS-induced disruption of mucosal barrier integrity was associated with a reduction in expression of the tight junction protein, occludin 1, and an inhibition in mucosal layer functioning via reductions in goblet cells. Results from bacterial cultures revealed an increased presence of bacterial invasion after CUMS treatment as compared with that observed in controls. Thus, our data indicate that CUMS treatment induces alterations of the fecal microbiome and intestinal barrier defects, which facilitates bacterial invasion into colonic mucosa and further exacerbates inflammatory reactions within the colon. Accordingly, chronic stress may predispose patients to gastrointestinal infection and increase the risk of inflammation-related gut diseases.
- Published
- 2019
15. Brassica yellows virus P0 protein impairs the antiviral activity of NbRAF2 in Nicotiana benthamiana
- Author
-
Yuan-Yuan Li, Xian-Bing Wang, Zong-Ying Zhang, Yongliang Zhang, Jialin Yu, Qian Sun, Ying Wang, Hang-Hai Zhao, Chenggui Han, Dawei Li, and Tian-Yu Zhao
- Subjects
0301 basic medicine ,food.ingredient ,NbRAF2 ,Physiology ,viruses ,Cell ,Nicotiana benthamiana ,Plant Science ,stromules ,Biology ,Antiviral Agents ,Virus ,Polerovirus ,Viral Proteins ,03 medical and health sciences ,food ,Ubiquitin ,Brassica yellows virus ,Tobacco ,medicine ,Gene silencing ,nuclear localization ,Plant Proteins ,Potato leafroll virus ,fungi ,food and beverages ,P0 ,biology.organism_classification ,Research Papers ,Cell biology ,Luteoviridae ,030104 developmental biology ,medicine.anatomical_structure ,Plant—Environment Interactions ,Tobacco rattle virus ,biology.protein - Abstract
The Brassica yellows virus genotype A P0 protein interacts with Rubisco assembly factor 2 in tobacco, affecting its nuclear accumulation and promoting viral infection., In interactions between poleroviruses and their hosts, few cellular proteins have been identified that directly interact with the multifunctional virus P0 protein. To help explore the functions of P0, we identified a Brassica yellows virus genotype A (BrYV-A) P0BrA-interacting protein from Nicotiana benthamiana, Rubisco assembly factor 2 (NbRAF2), which localizes in the nucleus, cell periphery, chloroplasts, and stromules. We found that its C-terminal domain (amino acids 183–211) is required for self-interaction. A split ubiquitin membrane-bound yeast two-hybrid system and co-immunoprecipitation assays showed that NbRAF2 interacted with P0BrA, and co-localized in the nucleus and at the cell periphery. Interestingly, the nuclear pool of NbRAF2 decreased in the presence of P0BrA and during BrYV-A infection, and the P0BrA-mediated reduction of nuclear NbRAF2 required dual localization of NbRAF2 in the chloroplasts and nucleus. Tobacco rattle virus-based virus-induced gene silencing of NbRAF2 promoted BrYV-A infection in N. benthamiana, and the overexpression of nuclear NbRAF2 inhibited BrYV-A accumulation. Potato leafroll virus P0PL also interacted with NbRAF2 and decreased its nuclear accumulation, indicating that NbRAF2 may be a common target of poleroviruses. These results suggest that nuclear NbRAF2 possesses antiviral activity against BrYV-A infection, and that BrYV-A P0BrA interacts with NbRAF2 and alters its localization pattern to facilitate virus infection.
- Published
- 2018
16. Expression quantitative trait loci analysis of the Rubisco activase gene in maize
- Author
-
Qian Sun, Z. L. Zhang, Zhitong Yin, B. Chen, Yu Zhang, Xin Kan, Min Cui, H. B. Shi, Dexiang Deng, and B. Jia
- Subjects
0106 biological sciences ,0301 basic medicine ,Genetics ,medicine.medical_specialty ,education.field_of_study ,Physiology ,Population ,Plant Science ,Biology ,Quantitative trait locus ,01 natural sciences ,03 medical and health sciences ,030104 developmental biology ,Chromosome 4 ,Gene mapping ,Genetic marker ,Molecular genetics ,Expression quantitative trait loci ,medicine ,education ,Gene ,010606 plant biology & botany - Abstract
Expression quantitative trait loci (eQTL) analyses were applied in order to identify genetic factors that are relevant to the expression of a β-isoform Rubisco activase gene in maize, namely ZmRCAβ, in this study. During two years, a maize recombinant inbred line population was measured for ZmRCAβ expression levels at the grain filling stage. Based on a genetic map containing 916 molecular markers, we detected five eQTLs, namely qRCA2.1 on chromosome 2, and qRCA4.1, qRCA4.2, qRCA4.3, and qRCA4.4 on chromosome 4. These eQTLs explained the phenotypic variation ranging from 6.14% to 7.50% with the logarithm of the odd values ranging from 3.11 to 4.96. Based on the position of the eQTLs and ZmRCAβ on the chromosome, qRCA4.2 was inferred as a cis-eQTL and the remaining as a trans-eQTL, suggesting that a combination of both cis- and trans-acting elements might control ZmRCAβ expression. qRCA4.2, qRCA4.3, and qRCA4.4 were repeatedly detected during two years.
- Published
- 2017
17. Cross-sectional analysis of trace element status in thyroid disease
- Author
-
Christian L. Görlich, Kostja Renko, Julian Hackler, Tanja Schwerdtle, Jens Mittag, Qian Sun, Sebastian Mehl, Lutz Schomburg, and Johannes F. Kopp
- Subjects
Male ,chemistry.chemical_element ,Physiology ,010501 environmental sciences ,Iodine ,01 natural sciences ,Biochemistry ,Thyroiditis ,Inorganic Chemistry ,Cohort Studies ,03 medical and health sciences ,Selenium ,0302 clinical medicine ,Selenium deficiency ,Medicine ,Humans ,0105 earth and related environmental sciences ,business.industry ,Thyroid disease ,Thyroid ,Middle Aged ,medicine.disease ,Micronutrient ,Thyroid Diseases ,Trace Elements ,Thyroxine ,Zinc ,medicine.anatomical_structure ,Cross-Sectional Studies ,chemistry ,Case-Control Studies ,Molecular Medicine ,Female ,business ,030217 neurology & neurosurgery ,Biomarkers ,Copper ,Hormone - Abstract
The synthesis of thyroid hormone depends on a set of trace elements, most importantly selenium and iodine. The dietary supply with certain micronutrients is limited in many areas of the world, including central Europe and large parts of Asia and Africa. Moreover, both thyroid disease risk and therapy effects are modulated by trace element supply and status.Assessment of trace element status in thyroid patients in a European metropolis.Adult patients visiting a medical praxis in Berlin, Germany, were enrolled into a cross-sectional analysis, and serum samples were obtained from thyroid patients (n = 323) with different conditions including goitre, hypothyroidism, malignancy or autoimmune thyroid disease. Trace elements (iodine, selenium, copper and zinc) were assessed by ICP-MS/MS or total reflection X-ray analysis, along with two protein biomarkers of selenium status (selenoprotein P, glutathione peroxidase), and compared to the clinical phenotype.The patients displayed relatively low serum zinc and selenium concentrations as compared to a set (n = 200) of healthy subjects (zinc; 1025+/-233 vs. 1068+/-230 μg/L, p 0.01, selenium; 76.9+/18.8 vs. 85.1+/-17.4 μg/L, p 0.0001). A high fraction of patients (37.5%) was classified as selenium-deficient (serum selenium concentrations70 μg/L), in particular the patients with thyroid malignancy (59%). Serum copper was not different between the groups, and total serum iodine concentrations were unrelated to thyroid disease. Explorative statistical analyses yielded no significant interactions between the trace elements and disease parameters, except for free thyroxine inversely correlating to the copper/selenium ratio.In adult thyroid patients, there is no relation of circulating copper, iodine, selenium or zinc concentrations to thyroid hormone. However, a large fraction of German thyroid patients displays a considerable selenium deficit, known to constitute a disease risk potentially impairing convalescence and aggravating autoimmune disease processes. It appears advisable to testing thyroid patients for selenium deficiency, and once diagnosed, an increased supply via dietary counselling or active supplementation should be considered.
- Published
- 2019
18. SYP22 and VAMP727 regulate BRI1 plasma membrane targeting to control plant growth in Arabidopsis
- Author
-
Qian Sun, Yu Xi Duan, Yang Liu, Tian Ya Li, Lijie Chen, Yuan Hu Xuan, Jin Hee Jung, Liang Zhang, and Xiaofeng Zhu
- Subjects
Plant growth ,biology ,Physiology ,Chemistry ,Arabidopsis Proteins ,Qa-SNARE Proteins ,Cell Membrane ,Arabidopsis ,Plant Development ,Plant Science ,biology.organism_classification ,Cell biology ,Membrane ,Brassinosteroids ,Mutation ,Protein Kinases ,Protein Binding - Published
- 2019
19. Defect of mitochondrial respiratory chain is a mechanism of ROS overproduction in a rat model of alcoholic liver disease: role of zinc deficiency
- Author
-
Wei Zhong, Zhanxiang Zhou, Qian Sun, and Wenliang Zhang
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Mitochondrial DNA ,Physiology ,Liver and Biliary Tract Physiology/Pathophysiology ,Mitochondria, Liver ,Oxidative phosphorylation ,Biology ,Mitochondrion ,Oxidative Phosphorylation ,Electron Transport ,03 medical and health sciences ,Adenosine Triphosphate ,Cell Line, Tumor ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,NRF1 ,Rats, Wistar ,Liver Diseases, Alcoholic ,Membrane Potential, Mitochondrial ,Hepatology ,Gastroenterology ,TFAM ,Lipid Metabolism ,Immunohistochemistry ,Rats ,Oxidative Stress ,Zinc ,030104 developmental biology ,Endocrinology ,Mitochondrial respiratory chain ,Liver ,Mitochondrial biogenesis ,Reactive Oxygen Species ,Mitochondrial DNA replication - Abstract
Morphological and functional alterations of hepatic mitochondria have been documented in patients with alcoholic liver disease (ALD). Our recent study demonstrated that zinc level was decreased in whole liver and mitochondria by chronic alcohol feeding. The present study was undertaken to determine whether zinc deficiency mediates alcohol-induced mitochondrial electron transport chain (ETC) defect and whether defective ETC function may lead to generation of reactive oxygen species (ROS). Male Wistar rats were pair fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure increased hepatic triglyceride, free fatty acid, and 4-hydroxynonenal (4HNE) levels; meanwhile hepatic mitochondrial 4HNE level was also increased. Moreover, hepatic mitochondrial respiratory complexes I, III, IV, and V and hepatic ATP production were decreased by chronic alcohol exposure. Chronic alcohol feeding decreased peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial DNA. HepG2 cells were treated with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) for 6 h. Zinc deficiency significantly decreased mitochondrial respiratory complexes I, III, and IV. In addition, PGC1α, NRF1, and TFAM levels as well as mitochondrial DNA were significantly decreased by TPEN treatment. Knockdown of mitochondrial respiratory complexes I, III, or IV by shRNA caused a decrease in mitochondrial membrane potential and an increase in ROS production. These results suggest that alcohol-induced hepatic zinc deficiency could inactivate mitochondrial biogenesis pathway and decrease mitochondrial DNA replication, which, in turn, decreases mitochondrial complex protein expression. The defect of mitochondrial respiratory complexes may worsen alcohol-induced ROS production.
- Published
- 2016
20. MALAT1 via microRNA-17 regulation of insulin transcription is involved in the dysfunction of pancreatic β-cells induced by cigarette smoke extract
- Author
-
Hui Xu, Chao Chen, Jiachun Lu, Aohan Han, Qianlei Yang, Quanyong Xiang, Qizhan Liu, Qian Sun, Qingyun Tu, Ping Yang, Xiaohua Gao, and Junchao Xue
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Small interfering RNA ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Adenocarcinoma of Lung ,Apoptosis ,Cigarette Smoking ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Downregulation and upregulation ,Internal medicine ,Diabetes mellitus ,Insulin-Secreting Cells ,microRNA ,medicine ,Diabetes Mellitus ,Humans ,Insulin ,Glycated Hemoglobin ,business.industry ,Cell Biology ,Tobacco Products ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Homeostatic model assessment ,RNA, Long Noncoding ,Insulin Resistance ,business ,Carrier Proteins ,TXNIP ,Signal Transduction - Abstract
Cigarettes contain various chemicals with the potential to influence metabolic health. Exposure to cigarette smoke causes a dysfunction in pancreatic β-cells and impairs insulin production. However, the mechanisms for cigarette smoke-induced reduction of insulin remain largely unclear. Data from 558 patients with diabetes showed that, with smoking pack-years, homeostatic model assessment (HOMA)-β (a method for assessing β-cell function) decreased and that HOMA of insulin resistance increased. For β-cells (MIN6), cigarette smoke extract (CSE) increased the levels of thioredoxin-interacting protein (TXNIP) and the long noncoding (lnc)RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and downregulated the levels of the transcription factor, mafA, and microRNA (miR)-17. MALAT1, one of four lncRNAs predicted to regulate miR-17, was knocked down by small interfering RNA (siRNA). For these cells, an miR-17 mimic inhibited TXNIP and enhanced the production of insulin. Knockdown of MALAT1 induced an increase in miR-17, which suppressed TXNIP and promoted the production of insulin. In the sera of patients with diabetes who smoked, there were higher MALAT1 levels and lower miR-17 levels than in the sera of nonsmokers. Thus, CSE inhibits insulin production by upregulating TXNIP via MALAT1-mediated downregulation of miR-17, which provides an understanding of the processes involved in the reduced β-cells function caused by cigarette smoke.
- Published
- 2017
21. [Research on rat models of acute liver injury with syndrome of liver depression and spleen deficiency]
- Author
-
Xiao-Qian Sun, Rong Sun, Qian Yang, Nana Huang, and Xiaoyu Li
- Subjects
medicine.medical_treatment ,Intraperitoneal injection ,Physiology ,Adipose tissue ,Spleen ,Traditional Chinese medicine ,Pathogenesis ,chemistry.chemical_compound ,medicine ,Animals ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Medicine, Chinese Traditional ,Depression (differential diagnoses) ,business.industry ,Cholesterol ,Liver Diseases ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,Liver ,Hepatocytes ,business ,TBIL - Abstract
This paper aimed to establish animal models which are suitable for the activity found, efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism. Xiaoyao pill and silibin meglumine tablets were used as drug counter evidence for models in accordence with the principle of consistence of prescription and syndrome. Rats model were fed with high-lipid and low-protein fodder of different proportion and induced by intraperitoneal injection with pig serum, intragastric administration with edible alcohol once a day for 7 days. Daily record of body weight, daily food intake and daily water intake were conducted day after day in experimental session. Symptoms were also observed and evaluated by score at the same time. The contents of ALT, AST, PA, TBIL and TBA in serum were detected and histopathological changes of liver were checked at the ending of experiment. Obvious acute liver injury occurred to all rats in model groups at 1 week following model induction. Both main symptoms and secondary symptoms were consistent with syndrome manifestation of liver depression and spleen deficiency. Compared with normal control group, the activity of ALT,AST and contents of TBIL,TBA in serum increased and the content of PA decreased. Liver tissue pathological morphology showed inflammatory cells infiltration, eosinophilic or eosinophilic adipose change in hepatocytes of rats in model groups. All the above lesions manifestation could be improved by drug counterevidence. By the disproof of medicine, rat models of acute liver injury with syndrome of liver depression and spleen deficiency could be induced by fed with high-lipid and low-protein fodder which contained 89.5% cornstarch, 10% lard and 0.5% cholesterol, intraperitoneal injected with pig serum, intragastric administrated with edible alcohol for 7 days. The rat models with a low mortality could be induced in a short time and animal status were similar to syndrome performance of patients. So the rats models are suitable for the activity found, efficacy evaluation and drug discovery of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency, and also can be used in the research of correlation between prescription and syndrome and its mechanism.
- Published
- 2016
22. Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways
- Author
-
Xinguo Sun, Xiuhua Sun, Wei Zhong, Zhanxiang Zhou, Wenliang Zhang, Qiong Li, Daoyin Dong, Xiaobing Tan, and Qian Sun
- Subjects
Male ,Alcoholic liver disease ,Programmed cell death ,Time Factors ,Physiology ,Eukaryotic Initiation Factor-2 ,Caspase 3 ,Apoptosis ,Mitochondria, Liver ,Mitochondrion ,Activating Transcription Factor 4 ,Biology ,medicine.disease_cause ,Endoplasmic Reticulum ,Antioxidants ,Physiology (medical) ,Cell Line, Tumor ,medicine ,Animals ,Phosphorylation ,Rats, Wistar ,Cation Transport Proteins ,Liver Diseases, Alcoholic ,Chelating Agents ,Hepatology ,Ethanol ,Gastroenterology ,Membrane Transport Proteins ,medicine.disease ,Cell biology ,Disease Models, Animal ,Oxidative Stress ,Zinc ,Liver and Biliary Tract ,Liver ,Cancer research ,Zinc deficiency ,Carrier Proteins ,Deficiency Diseases ,Reactive Oxygen Species ,Oxidative stress ,Transcription Factor CHOP - Abstract
Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 μM N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 μM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment.
- Published
- 2014
23. NFATc1 phosphorylation by DYRK1A increases its protein stability
- Author
-
Long Chen, Ketao Wang, Heng Liu, Qian Sun, Xiulian Sun, Yuankai Zhang, and Shuai Chen
- Subjects
0301 basic medicine ,Cytoplasm ,DYRK1A ,Physiology ,Amino Acid Motifs ,lcsh:Medicine ,Biochemistry ,Ligases ,Database and Informatics Methods ,Ubiquitin ,Immune Physiology ,Serine ,Medicine and Health Sciences ,Post-Translational Modification ,Phosphorylation ,Amino Acids ,lcsh:Science ,Immune System Proteins ,Multidisciplinary ,integumentary system ,biology ,Organic Compounds ,Protein Stability ,Chemistry ,Kinase ,Protein-Tyrosine Kinases ,Precipitation Techniques ,Enzymes ,Cell biology ,Physical Sciences ,Cellular Structures and Organelles ,Sequence Analysis ,Research Article ,Proteasome Endopeptidase Complex ,NFATC2 ,Bioinformatics ,Immunoprecipitation ,Immunology ,Protein Serine-Threonine Kinases ,Research and Analysis Methods ,Antibodies ,03 medical and health sciences ,Sequence Motif Analysis ,Hydroxyl Amino Acids ,Humans ,Transcription factor ,NFATC Transcription Factors ,030102 biochemistry & molecular biology ,Organic Chemistry ,lcsh:R ,Ubiquitination ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Cell Biology ,Monoclonal Antibodies ,HEK293 Cells ,030104 developmental biology ,Tumor progression ,Proteolysis ,Enzymology ,biology.protein ,lcsh:Q - Abstract
NFATs are transcription factors involved in immune activation and tumor progression. Previous reports showed that DYRK1A suppressed NFATc2 transcriptional activity through phosphorylation. Nonetheless, our results showed that DYRK1A increased NFATc1/αA protein level and subsequent transcriptional activity. DYRK1A phosphorylation of NFATc1/αA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation. Our results imply that DYRK1A is a positive kinase in regulation of NFATc1.
- Published
- 2017
24. Heterochromatin protects retinal pigment epithelium cells from oxidative damage by silencing p53 target genes.
- Author
-
Lili Gong, Fangyuan Liu, Zhen Xiong, Ruili Qi, Zhongwen Luo, Xiaodong Gong, Qian Nie, Qian Sun, Yun-Fei Liu, Wenjie Qing, Ling Wang, Lan Zhang, Xiangcheng Tang, Shan Huang, Gen Li, Hong Ouyang, Mengqing Xiang, Quan Dong Nguyen, Yizhi Liu, and David Wan-Cheng Li
- Subjects
HETEROCHROMATIN ,RHODOPSIN ,EPITHELIUM ,P53 antioncogene regulation ,GENE silencing ,OXIDATIVE stress ,PHYSIOLOGY - Abstract
Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Heterochromatin, a compact and transcriptional inert chromatin structure, has been recently shown to be dynamically regulated in response to stress stimuli. The functional mechanism of heterochromatin on OS exposure is unclear, however. Here we show that OS increases heterochromatin formation both in vivo and in vitro, which is essential for protecting RPE cells from oxidative damage. Mechanistically, OS-induced heterochromatin selectively accumulates at p53-regulated proapoptotic target promoters and inhibits their transcription. Furthermore, OS-induced desumoylation of p53 promotes p53-heterochromatin interaction and regulates p53 promoter selection, resulting in the locus-specific recruitment of heterochromatin and transcription repression. Together, our findings demonstrate a protective function of OS-induced heterochromatin formation in which p53 desumoylation-guided promoter selection and subsequent heterochromatin recruitment play a critical role. We propose that targeting heterochromatin provides a plausible therapeutic strategy for the treatment of AMD. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
25. Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways.
- Author
-
Qian Sun, Wei Zhong, Wenliang Zhang, Qiong Li, Xiuhua Sun, Xiaobing Tan, Xinguo Sun, Daoyin Dong, and Zhanxiang Zhou
- Subjects
- *
ALCOHOLIC liver diseases , *APOPTOSIS , *ZINC deficiency diseases , *MITOCHONDRIAL physiology , *ENDOPLASMIC reticulum , *PHYSIOLOGICAL effects of alcohol , *LIVER cells , *LABORATORY rats , *PHYSIOLOGY - Abstract
Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 μM N,N,N'=,N'=-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 μM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
26. Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane.
- Author
-
Benveniste, Helene, Hedok Lee, Fengfei Ding, Qian Sun, Al-Bizri, Ehab, Makaryus, Rany, Probst, Stephen, Nedergaard, Maiken, Stein, Elliot A., Hanbing Lu, Lee, Hedok, Ding, Fengfei, Sun, Qian, and Lu, Hanbing
- Subjects
- *
ANIMAL experimentation , *BIOLOGICAL transport , *CELLULAR signal transduction , *CEREBRAL circulation , *COMBINATION drug therapy , *COMPARATIVE studies , *DOSE-effect relationship in pharmacology , *HIPPOCAMPUS (Brain) , *IMIDAZOLES , *ISOENZYMES , *ISOFLURANE , *LACTATE dehydrogenase , *MAGNETIC resonance imaging , *RESEARCH methodology , *MEDICAL cooperation , *PEPTIDES , *RATS , *RESEARCH , *RESEARCH funding , *EVALUATION research , *CONTRAST media , *INHALATION anesthetics , *PHYSIOLOGY - Abstract
Background: The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not.Methods: Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats.Results: Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats.Conclusions: We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
27. Synergistic Effect of Trehalose and Saccharose Pretreatment on Maintenance of Lyophilized Human Red Blood Cell Quality.
- Author
-
Yan-Qiong Li, Rui Hu, Li-Hui Zhong, Qian Sun, and You-Ping Yan
- Subjects
- *
ERYTHROCYTES , *TREHALOSE , *SUCROSE , *FREEZE-drying , *SUPEROXIDE dismutase , *ADENOSINE triphosphatase , *GLUCOSE-6-phosphate dehydrogenase , *PHYSIOLOGY , *THERAPEUTICS - Abstract
Purpose: To investigate the synergistic effect of trehalose and saccharose pretreatment on maintenance of lyophilized human red blood cell (RBC) quality. Methods: RBCs were pre-treated with trehalose and saccharose, and then lyophilized and re-hydrated. Prior to lyophilization and after re-hydration, RBC parameters, RBC counts, total hemoglobin concentration, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), comprehensive deformation index, hemolysis ratio and phosphatidylserine (PS) expression, were determined using a hematology analyzer, an RBC deformation instrument, a spectrophotometer and a flow cytometer, respectively. Superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G-6-PD), and adenosine triphosphatase (ATPase) activities were determined using kits for SOD, ATPase, and G-6- PD assay, respectively. Results: After lyophilization-rehydration, RBC counts and total hemoglobin recovery rates, deformability, and RBC SOD, ATPase, and G-6-PD activities were significantly decreased by 47.24 - 74.65% (p < 0.01), compared with the normal group. RBC osmotic fragility and PS expression on the outer surface of the RBC membrane were significantly increased by 168.53 and 629.30% (p < 0.01), respectively, compared with the normal group. RBC MCH and MCV values were not significantly affected by lyophilization-rehydration (p > 0.05). Trehalose and saccharose pretreatment significantly reversed the effects of lyophilization-rehydration on these RBC parameters by approximately 13.16 - 211.11% (p < 0.01), compared with the control group. The combined effects were synergistic. Conclusion: Trehalose and saccharose pretreatment synergistically enhances maintenance of lyophilized RBC quality. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.