50 results on '"Shuanglian Wang"'
Search Results
2. Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice
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Shuang Li, Yao Shi, Jianchun Zhu, Jingxin Li, Shuanglian Wang, and Chuanyong Liu
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vincristine ,oxytocin ,gastrointestinal motility ,myenteric neurons ,oxidative stress ,MAPK pathways ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Aims: Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism.Methods: Mice were injected either with saline or VCR (0.1 mg/kg/d, i. p.) for 14 days, and OT (0.1 mg/kg/d, i.p.) was applied 1 h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot.Results: VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment.Conclusion: Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.
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- 2024
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3. Procyanidin improves experimental colitis by regulating macrophage polarization
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Yao Shi, Haojie Zhang, Shuang Li, Danqing Xin, Shiyang Li, Bing Yan, Shuanglian Wang, and Chuanyong Liu
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Procyanidin ,Inflammatory bowel disease ,Proinflammatory macrophages ,STAT3/NF-κB pathways ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. Purpose: Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. Methods: In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. Results: The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. Conclusions: This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases.
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- 2023
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4. Automated retinal boundary segmentation of optical coherence tomography images using an improved Canny operator
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Jian Liu, Shixin Yan, Nan Lu, Dongni Yang, Hongyu Lv, Shuanglian Wang, Xin Zhu, Yuqian Zhao, Yi Wang, Zhenhe Ma, and Yao Yu
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Medicine ,Science - Abstract
Abstract Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2–6 microns (1–2 pixels) for healthy subjects and 3–10 microns (1–3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.
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- 2022
- Full Text
- View/download PDF
5. Automatic segmentation of foveal avascular zone based on adaptive watershed algorithm in retinal optical coherence tomography angiography images
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Jian Liu, Shixin Yan, Nan Lu, Dongni Yang, Chunhui Fan, Hongyu Lv, Shuanglian Wang, Xin Zhu, Yuqian Zhao, Yi Wang, Zhenhe Ma, and Yao Yu
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foveal avascular zone ,optical coherence tomography angiography ,watershed algorithm ,diabetic retinopathy ,Technology ,Optics. Light ,QC350-467 - Abstract
The size and shape of the foveal avascular zone (FAZ) have a strong positive correlation with several vision-threatening retinovascular diseases. The identification, segmentation and analysis of FAZ are of great significance to clinical diagnosis and treatment. We presented an adaptive watershed algorithm to automatically extract FAZ from retinal optical coherence tomography angiography (OCTA) images. For the traditional watershed algorithm, “over-segmentation” is the most common problem. FAZ is often incorrectly divided into multiple regions by redundant “dams”. This paper analyzed the relationship between the “dams” length and the maximum inscribed circle radius of FAZ, and proposed an adaptive watershed algorithm to solve the problem of “over-segmentation”. Here, 132 healthy retinal images and 50 diabetic retinopathy (DR) images were used to verify the accuracy and stability of the algorithm. Three ophthalmologists were invited to make quantitative and qualitative evaluations on the segmentation results of this algorithm. The quantitative evaluation results show that the correlation coefficients between the automatic and manual segmentation results are 0.945 (in healthy subjects) and 0.927 (in DR patients), respectively. For qualitative evaluation, the percentages of “perfect segmentation” (score of 3) and “good segmentation” (score of 2) are 99.4% (in healthy subjects) and 98.7% (in DR patients), respectively. This work promotes the application of watershed algorithm in FAZ segmentation, making it a useful tool for analyzing and diagnosing eye diseases.
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- 2022
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6. Establishment of Personalized Finite Element Model of Crystalline Lens Based on Sweep-Source Optical Coherence Tomography
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Guangheng Liu, Ang Li, Jian Liu, Yuqian Zhao, Keliang Zhu, Zhen Li, Yang Lin, Shixin Yan, Hongyu Lv, Shuanglian Wang, Yao Yu, Yi Wang, Jingmin Luan, and Zhenhe Ma
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sweep-source optical coherence tomography ,finite element modeling ,lens accommodation ,accommodative response ,Applied optics. Photonics ,TA1501-1820 - Abstract
The virtual lens model has important value in ophthalmic research, clinical diagnosis, and treatment. However, the establishment of personalized lens models and the verification of accommodation accuracy have not been paid much attention. We proposed a personalized lens model establishment and the accommodation accuracy evaluation method based on sweep-source optical coherence tomography (SS-OCT). Firstly, SS-OCT is used to obtain a single lens image in the maximum accommodation state. After refraction correction, boundary detection, and curve fitting, the central curvature radius, thickness, and lens nucleus contour of the anterior and posterior surfaces of the lens were obtained. Secondly, a personalized finite element model improved from Burd’s model was established using these individual parameters, and the adaptation process of the lens model was simulated by pulling the suspensory ligament. Finally, the shape and refractive power changes of the real human lens under different accommodation stimuli were collected and compared with the accommodation process of the finite element model. The results show that the accommodation process of the finite element model is highly consistent with that of the real lens. From the un-accommodation state to the maximum-accommodation state, the difference rate of all geometric and refractive parameters between the two is less than 5%. Thus, the personalized lens finite element model obtained by the calibration and correction of the existing model can accurately simulate the regulation process of a specific human lens. This work helps to provide a valuable theoretical basis and research ideas for the study of clinical diagnosis and treatment of related diseases.
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- 2022
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7. Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers
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Yiting Chen, Jieling Ning, Wenjie Cao, Shuanglian Wang, Tao Du, Jiahui Jiang, Xueping Feng, and Bin Zhang
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TXNIP (thioredoxin interacting protein) ,cancer ,oxidative stress ,research progress ,clinical significance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.
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- 2020
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8. GABA coordinates with insulin in regulating secretory function in pancreatic INS-1 β-cells.
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Paul Bansal, Shuanglian Wang, Shenghao Liu, Yun-Yan Xiang, Wei-Yang Lu, and Qinghua Wang
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Medicine ,Science - Abstract
Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABA(A)Rs). We and others recently reported that islet β-cells also express GABA(A)Rs and that activation of GABA(A)Rs increases insulin release. Here we investigate the effects of insulin on the GABA-GABA(A)R system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 µM) suppressed the GABA-induced current (I(GABA)) by 43%. Zinc-free insulin also suppressed I(GABA) to the same extent of inhibition by regular insulin. The inhibition of I(GABA) occurs within 30 seconds after application of insulin. The insulin-induced inhibition of I(GABA) persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that insulin suppresses GABA(A)Rs through a mechanism that involves ERK activation. Radioimmunoassay revealed that the secretion of C-peptide was enhanced by GABA, which was blocked by pre-incubating the cells with picrotoxin (50 µM, p
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- 2011
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9. Gasdermin C sensitizes tumor cells to PARP inhibitor therapy in cancer models.
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Shuanglian Wang, Chiung-Wen Chang, Juan Huang, Shan Zeng, Xin Zhang, Mien-Chie Hung, and Junwei Hou
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Several poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved by FDA to treat cancer with BRCA mutations. BRCA mutations are considered to fuel a PARPi killing effect by inducing apoptosis. However, resistance to PARPi is frequently observed in the clinic due to an incomplete understanding on the molecular basis of PARPi function and a lack of good markers, beyond BRCA mutations, to predict response. Here, we show that gasdermin C (GSDMC) sensitized tumor cells to PARPi in vitro and in immunocompetent mice and caused durable tumor regression in an immune-dependent manner. A high expression level of GSDMC predicted better response to PARPi treatment in patients with triple-negative breast cancer (TNBC). PARPi treatment triggered GSDMC/caspase-8-mediated cancer cell pyroptosis (CCP) that enhanced PARPi killing of tumor cells. GSDMC-mediated CCP increased memory CD8+ T cell population in lymph node (LN), spleen, and tumor and, thus, promoted cytotoxic CD8+ T cell infiltration in the tumor microenvironment. T cell-derived granzyme B (GZMB) activated caspase-6, which subsequently cleaved GSDMC to induce pyroptosis. Interestingly, IFN-γ induced GSDMC expression, which, in turn, enhanced the cytotoxicity of PARPi and T cells. Importantly, GSDMC promoted tumor clearance independent of BRCA deficiency in multiple cancer types with PARPi treatment. This study identifies a general marker and target for PARPi therapy and offers insights into the mechanism of PARPi function. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Radiosensitization of Nasopharyngeal Carcinoma by Graphene Oxide Nanosheets to Reduce Bcl-2 Level
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Qi Zhou, Yadong Li, Liya Li, Nianzhe Sun, Hanghao Zhang, Jiahui Jiang, Tao Du, Yan Mo, Alaa Aldeen, Runsha Xiao, Yiting Chen, Shuanglian Wang, Mian Liu, Chengmin Li, and Xueping Feng
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Electrochemistry ,General Materials Science ,Surfaces and Interfaces ,Condensed Matter Physics ,Spectroscopy - Published
- 2023
11. Chronic GPER activation prompted the proliferation of ileal stem cell in ovariectomized mice depending on Paneth cell–derived Wnt3
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Jianbo Liu, Kaixuan Liu, Shiquan Chai, Runze Xu, Ying Wang, Yundi Zhang, Shuanglian Wang, Chuanyong Liu, and Bing Xue
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Paneth Cells ,Stem Cells ,Estrogens ,General Medicine ,Wnt3 Protein ,Mice ,Ileum ,Animals ,Female ,Cyclin D1 ,Intestinal Mucosa ,Wnt Signaling Pathway ,beta Catenin ,Cell Proliferation - Abstract
Menopausal women often face long-term estrogen treatment. G protein-coupled estrogen receptor (GPER) expressed in intestinal crypt was activated by estrogen therapy, but it was unclear whether chronic GPER activation during menopause had an effect on intestinal stem cells (ISCs). We tested the effect of chronic GPER activation on ISCs of ovariectomized (OVX) mice by injection of the selective GPER agonist G-1 for 28 days, or G-1 stimulation of organoids derived from crypts of OVX mice. G-1 up-regulated crypt depth, the number of Ki67+, bromodeoxyuridine+ cells and Olfm4+ ISCs, and the expression of ISCs marker genes (Lgr5, Olfm4 and Axin2). G-1 administration promoted organoid growth, increased the number of EdU+ cells per organoid and protein expression of Cyclin D1 and cyclin B1 in organoids. After G-1 treatment in vivo or in vitro, Paneth cell–derived Wnt3, Wnt3 effector β-catenin and Wnt target genes c-Myc and Cyclin D1 increased in ileum or organoids. Once blocking the secretion of Wnt3 from Paneth cells, the effects of G-1 on organoids growth, ISCs marker genes and Wnt/β-catenin signaling were abolished. G-1 did not affect the number of Paneth cells in ex vivo organoids, while activated Mmp7/cryptdin program in Paneth cells, promoted their maturation, and increased the expression of lysozyme protein. G-1 pretreatment in OVX mice inhibited radiation-induced ISCs proliferation injury and enhanced the resistance of mice to intestinal injury. In conclusion, chronic GPER activation prompted the Wnt3 synthesis in Paneth cells, thus increased the proliferation of ISCs via activation of Wnt3/β-catenin signaling in OVX mice.
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- 2023
12. Detection of Gasdermin C-Mediated Cancer Cell Pyroptosis
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Junwei Hou, Shuanglian Wang, Rui Miao, Xin Zhang, and Mien-Chie Hung
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- 2023
13. Label-Free Quantification based Proteomic Analysis of Serum Obtained from Henoch–Schönlein Purpura Patients before and after Zhenbao Pill Treatment
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Wuritunashun Wuritunashun, Burenbatu Burenbatu, Narenqiqige Narenqiqige, Jiuguniang Jiuguniang, Eerdunduleng Eerdunduleng, Shuanglian Wang, Cuiqin Gong, Hashengaowa Hashengaowa, Huizhi Jin, Baiwurihan Baiwurihan, and Chunhaizi Chunhaizi
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Animal Science and Zoology - Published
- 2023
14. Radiosensitizer EXO-miR-197-3p Inhibits Nasopharyngeal Carcinoma Progression and Radioresistance by Regulating the AKT/mTOR Axis and HSPA5-mediated Autophagy
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Jiahui, Jiang, Qiao, Tang, Jiaoe, Gong, WeiHong, Jiang, Yiting, Chen, Qi, Zhou, Alaa, Aldeen, Shuanglian, Wang, Chengmin, Li, Wuwu, Lv, Tao, Du, Xingwei, Wang, Xueying, Long, and Xueping, Feng
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Radiation-Sensitizing Agents ,Nasopharyngeal Carcinoma ,TOR Serine-Threonine Kinases ,Nasopharyngeal Neoplasms ,Cell Biology ,Applied Microbiology and Biotechnology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Line, Tumor ,Autophagy ,Humans ,Proto-Oncogene Proteins c-akt ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Cell Proliferation ,Developmental Biology - Abstract
The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression
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- 2022
15. Automated retinal boundary segmentation of optical coherence tomography images using an improved Canny operator
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Shuanglian Wang, Shixin Yan, Dongni Yang, Xin Zhu, Jian Liu, Hongyu Lv, Yi Wang, Yao Yu, Nan Lu, Yuqian Zhao, and Zhenhe Ma
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genetic structures ,Computer science ,Science ,Boundary (topology) ,Article ,Retina ,chemistry.chemical_compound ,Macular Degeneration ,Optical coherence tomography ,Image processing ,medicine ,Humans ,Computer vision ,Segmentation ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Operator (physics) ,Retinal ,Middle Aged ,eye diseases ,chemistry ,Medicine ,Female ,Artificial intelligence ,business ,Artifacts ,Biomedical engineering ,Algorithms ,Tomography, Optical Coherence - Abstract
Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2-6 microns (1~2 pixels) for healthy subjects and 3-10 microns (1~3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.
- Published
- 2022
16. Automatic segmentation of foveal avascular zone based on adaptive watershed algorithm in retinal optical coherence tomography angiography images
- Author
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Shuanglian Wang, Dongni Yang, Hongyu Lv, Xin Zhu, Jian Liu, Yi Wang, Shixin Yan, Yuqian Zhao, Zhenhe Ma, Yao Yu, Chunhui Fan, and Nan Lu
- Subjects
Technology ,Watershed ,Computer science ,Biomedical Engineering ,Medicine (miscellaneous) ,foveal avascular zone ,watershed algorithm ,optical coherence tomography angiography ,Positive correlation ,chemistry.chemical_compound ,medicine ,Segmentation ,Computer vision ,business.industry ,Retinal ,QC350-467 ,Foveal avascular zone ,Optical coherence tomography angiography ,Diabetic retinopathy ,Optics. Light ,medicine.disease ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,diabetic retinopathy ,chemistry ,Automatic segmentation ,Artificial intelligence ,business - Abstract
The size and shape of the foveal avascular zone (FAZ) have a strong positive correlation with several vision-threatening retinovascular diseases. The identification, segmentation and analysis of FAZ are of great significance to clinical diagnosis and treatment. We presented an adaptive watershed algorithm to automatically extract FAZ from retinal optical coherence tomography angiography (OCTA) images. For the traditional watershed algorithm, “over-segmentation” is the most common problem. FAZ is often incorrectly divided into multiple regions by redundant “dams”. This paper analyzed the relationship between the “dams” length and the maximum inscribed circle radius of FAZ, and proposed an adaptive watershed algorithm to solve the problem of “over-segmentation”. Here, 132 healthy retinal images and 50 diabetic retinopathy (DR) images were used to verify the accuracy and stability of the algorithm. Three ophthalmologists were invited to make quantitative and qualitative evaluations on the segmentation results of this algorithm. The quantitative evaluation results show that the correlation coefficients between the automatic and manual segmentation results are 0.945 (in healthy subjects) and 0.927 (in DR patients), respectively. For qualitative evaluation, the percentages of “perfect segmentation” (score of 3) and “good segmentation” (score of 2) are 99.4% (in healthy subjects) and 98.7% (in DR patients), respectively. This work promotes the application of watershed algorithm in FAZ segmentation, making it a useful tool for analyzing and diagnosing eye diseases.
- Published
- 2021
17. Long-Term Tracking of Cancer Cell Nucleus and Identification of Colorectal Cancer with an Aggregation-Induced Emission-Based Fluorescent Probe
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Mian Liu, Jing Hou, Wenbin Zeng, Xueping Feng, Zhikang Chen, Shuanglian Wang, Tang Gao, Jiu Yang, Wuwu Lv, Tao Du, and Zihua Chen
- Subjects
Cell Nucleus ,Fluorescence-lifetime imaging microscopy ,Chemistry ,Colorectal cancer ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Cancer ,Bioengineering ,medicine.disease ,Fluorescence ,Cell nucleus ,chemistry.chemical_compound ,medicine.anatomical_structure ,Cancer cell ,medicine ,Nucleic acid ,Cancer research ,Humans ,General Materials Science ,DAPI ,Colorectal Neoplasms ,Fluorescent Dyes - Abstract
In clinical diagnosis and treatment, it is very important to distinguish cancer cells from normal cells. Nuclear-selective fluorescent probe that specifically target tumors can not only make the difference in assessing tumor margins during surgery and then facilitating accurate resection of the tumor, but also can provide crucial biomedical information of tumor progress if it can be used for long-term dynamic visualization of nucleus in cancer. Herein, a novel fluorescent probe 3 was designed and characterized to be of low-toxicity and water-solubility. The biological evaluation indicated that probe 3 prefers nucleic acids rather than accumulation in non-neuclear sites while superior to the commercial available agent DAPI (4',6-diamidino-2-phenylindole), in terms of its character of aggregation-induced emission (AIE), large Stokes shift (175 nm) and light stability. Further experiments demonstrated that probe 3 can not only differentiate SW480 and SW620 (cancer cells) from GES-1 (normal cells) with high contrast (dyed in nuclear of cancer cells and not in nuclear of normal cells), but also used for tracking cancer cell nuclear for long time. Furthermore, 3D reconstruction fluorescence imaging proved that probe 3 was able for identifying colorectal cancer tissues from para-carcinoma tissues by a strong contrast. Therefore, in precise surgery of colorectal cancer, probe 3 may be a promising-agent for guiding of intraoperation.
- Published
- 2019
18. L-Cysteine Provides Neuroprotection of Hypoxia-Ischemia Injury in Neonatal Mice via a PI3K/Akt-Dependent Mechanism
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Dexiang Liu, Yijing Zhao, Jiangbing Li, Shuanglian Wang, Tingting Li, Hongfei Ke, Zhen Wang, and Tong tong Li
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0301 basic medicine ,Morpholines ,Pharmaceutical Science ,Pharmacology ,Neuroprotection ,neuroinflammation ,03 medical and health sciences ,Mice ,Structure-Activity Relationship ,0302 clinical medicine ,Drug Discovery ,PTEN ,Tensin ,Animals ,Cysteine ,Phosphorylation ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Original Research ,Drug Design, Development and Therapy ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Akt/PKB signaling pathway ,H2S ,Akt ,Mice, Inbred C57BL ,hypoxia-ischemia ,Disease Models, Animal ,030104 developmental biology ,Neuroprotective Agents ,Chromones ,030220 oncology & carcinogenesis ,Hypoxia-Ischemia, Brain ,biology.protein ,Female ,Signal transduction ,Phosphatidylinositol 3-Kinase ,Cell activation ,Proto-Oncogene Proteins c-akt - Abstract
Tingting Li,1,* Jiangbing Li,1,2,* Tong Li,3,* Yijing Zhao,1 Hongfei Ke,1 Shuanglian Wang,1 Dexiang Liu,4 Zhen Wang1 1Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery Surgery, Qingdao Municipal Hospital, Shandong Province, People’s Republic of China; 4Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dexiang LiuDepartment of Medical Psychology and Ethics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail liudexiang@sdu.edu.cnZhen WangDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, 250012, People’s Republic of ChinaEmail wangzhen@sdu.edu.cnBackground: Previous work within our laboratory has revealed that hydrogen sulfide (H2S) can serve as neuroprotectant against brain damage caused by hypoxia-ischemia (HI) exposure in neonatal mice. After HI insult, activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has been shown to be implicated in neuro-restoration processes. The goal of the current study was to determine whether the neuroprotective effects of H2S were mediated by the PI3K/Akt signaling pathway.Methods: The mouse HI model was built at postnatal day 7 (P7), and the effects of L-Cysteine treatment on acute brain damage (72 h post-HI) and long-term neurological responses (28 days post-HI) were evaluated. Nissl staining and Transmission electron microscopy were used to evaluate the neuronal loss and apoptosis. Immunofluorescence imaging and dihydroethidium staining were utilized to determine glial cell activation and ROS content, respectively.Results: Quantitative results revealed that L-Cysteine treatment significantly prevented the acute effects of HI on apoptosis, glial cell activation and oxidative injury as well as the long-term effects upon memory impairment in neonatal mice. This protective effect of L-Cysteine was found to be associated with the phosphorylation of Akt and phosphatase and a tensin homolog deletion on chromosome 10 (PTEN). Following treatment with the PI3K inhibitor, LY294002, the neuroprotective effects of L-Cysteine were attenuated.Conclusion: PTEN/PI3K/Akt signaling was involved in mediating the neuroprotective effects of exogenous H2S against HI exposure in neonatal mice.Keywords: Akt, H2S, hypoxia-ischemia, neuroinflammation
- Published
- 2021
19. Down-regulating GRP78 reverses pirarubicin resistance of triple negative breast cancer by miR-495-3p mimics and involves the p-AKT/mTOR pathway
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Mian Liu, Jiu Yang, Wuwu Lv, Shuanglian Wang, Tao Du, Kejing Zhang, Yuhui Wu, and Xueping Feng
- Subjects
GRP78 ,Biophysics ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,p-AKT ,Biochemistry ,Cell Movement ,Cell Line, Tumor ,Humans ,Neoplasm Invasiveness ,Triple negative breast cancer ,Phosphorylation ,Molecular Biology ,Endoplasmic Reticulum Chaperone BiP ,Diagnostics & Biomarkers ,Research Articles ,Cell Proliferation ,Cancer ,Gene Expression & Regulation ,TOR Serine-Threonine Kinases ,Cell Biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Doxorubicin ,Drug Resistance, Neoplasm ,Female ,Pirarubicin chemoresistance ,Proto-Oncogene Proteins c-akt ,Chemoresistance ,miR-495-3p mimics ,Signal Transduction - Abstract
Due to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC.
- Published
- 2021
20. Author response for 'iTRAQ‐based quantitative proteomic analysis of immune thrombocytopenia patients before and after Qishunbaolier treatment'
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Eerdunduleng Eerdunduleng, Wuritunashun Wuritunashun, Cuiqin Gong, Risu Na, Shuanglian Wang, Guihua Guihua, Sarula Sarula, Hashengaowa Hashengaowa, Burenbatu Burenbatu, Haihua Bai, and Yanbo Wang
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business.industry ,Immunology ,Medicine ,business ,Qishunbaolier ,Immune thrombocytopenia - Published
- 2020
21. Hydrogen-Rich Saline Regulates Microglial Phagocytosis and Restores Behavioral Deficits Following Hypoxia-Ischemia Injury in Neonatal Mice via the Akt Pathway
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Shuanglian Wang, Danqing Xin, Min Han, Zhen Wang, Dexiang Liu, Tingting Li, Hongfei Ke, and Xili Chu
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0301 basic medicine ,Phagocytosis ,Pharmaceutical Science ,microglia ,Apoptosis ,Brain damage ,Pharmacology ,Neuroprotection ,03 medical and health sciences ,Mice ,HS ,0302 clinical medicine ,Pregnancy ,Drug Discovery ,Medicine ,Animals ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Original Research ,Drug Design, Development and Therapy ,Microglia ,business.industry ,Akt/PKB signaling pathway ,Akt ,phagocytosis ,Mice, Inbred C57BL ,Disease Models, Animal ,hypoxia-ischemia ,030104 developmental biology ,medicine.anatomical_structure ,Neuroprotective Agents ,Animals, Newborn ,030220 oncology & carcinogenesis ,Hypoxia-Ischemia, Brain ,Female ,Saline Solution ,medicine.symptom ,business ,Proto-Oncogene Proteins c-akt ,Injections, Intraperitoneal ,Hydrogen ,Signal Transduction - Abstract
Hongfei Ke1 ,* Dexiang Liu2 ,* Tingting Li,1 Xili Chu,1 Danqing Xin,1 Min Han,1 Shuanglian Wang,1 Zhen Wang1 1Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen WangDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of ChinaEmail wangzhen@sdu.edu.cnIntroduction: We have reported previously that hydrogen-rich saline (HS) plays a neuroprotective role in hypoxia-ischemia (HI) brain damage in newborn mice. However, the mechanisms for this neuroprotection resulting from HS remain unknown. In this study, we examined the potential for HS to exert effects upon microglial phagocytosis via involvement of the Akt signaling pathway as one of the neuroprotective mechanisms in response to neonatal HI.Methods: The HI brain injury model was performed on postnatal day (PND) 7 (modified Vannucci model). The acute brain damage was detected at 3 days after HI exposure. The behavioral and functional screening of the pups at PND11 and PND13 and their long-term outcomes (PND35, 28-days post-HI) were evaluated sensorimotor performance and cognitive functions, respectively.Results: The result showed that HS administration alleviated HI-induced edema, infract volume and cellular apoptosis within the cortex of neonatal mice. Accompanying these indices of neuroprotection from HS were reductions in HI-induced phagocytosis in microglia as demonstrated in vivo and in vitro, effects that were associated with increasing levels of Akt phosphorylation and improvements in neurobehavioral responses. These beneficial effects of HS were abolished in mice treated with an Akt inhibitor.Discussion: These results demonstrate that HS treatment attenuates neurobehavioral deficits and apoptosis resulting from HI, effects which were associated with reductions in phagocytosis and appear to involve the Akt signaling pathway.Keywords: microglia, phagocytosis, hypoxia-ischemia, HS, Akt
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- 2020
22. miR-495 enhances the efficacy of radiotherapy by targeting GRP78 to regulate EMT in nasopharyngeal carcinoma cells
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Wuwu Lv, Qian He, Shuanglian Wang, and Xueping Feng
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0301 basic medicine ,Male ,Cancer Research ,Cell ,Apoptosis ,Radiation Tolerance ,miR-495 ,0302 clinical medicine ,Tumor Cells, Cultured ,glucose-regulated protein 78 ,Child ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,Aged, 80 and over ,Nasopharyngeal Carcinoma ,General Medicine ,Articles ,Cell cycle ,Middle Aged ,Prognosis ,radioresistance ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Adult ,Epithelial-Mesenchymal Transition ,Adolescent ,Biology ,03 medical and health sciences ,Young Adult ,Radioresistance ,microRNA ,medicine ,Biomarkers, Tumor ,Humans ,Aged ,Cell Proliferation ,Oncogene ,Carcinoma ,Cancer ,Computational Biology ,Nasopharyngeal Neoplasms ,medicine.disease ,Molecular medicine ,MicroRNAs ,030104 developmental biology ,Nasopharyngeal carcinoma ,Case-Control Studies ,Cancer research ,Follow-Up Studies - Abstract
Glucose-regulated protein 78 (GRP78) was revealed to be associated with the radioresistance of nasopharyngeal carcinoma (NPC) in our previous study. GRP78 is a highly expressed cell surface protein, and holds great promise as a cancer specific target. Its expression may be impacted by the regulation of miRNAs, which may be involved in the radioresistance of NPC. A better understanding of the mechanisms of radioresistance may generate new targets of therapy for NPC patients. The present study was designed to investigate the effect of microRNA targeting GRP78 on the radiosensitivity of NPC. First, we used miRWalk software to predict miRNAs that may interact with GRP78. Subsequently, analysis of miR-495 and GRP78 expression was performed in the primary tissues of 92 NPC tissues and cell lines by immunohistochemistry and real-time PCR and the results revealed that miR-495 expression was lower in radioresistant NPC tissues in comparison to chronic rhinitis tissues, and also lower in radioresistant 5-8F cells (5-8F-IR) in comparison to its parental 5-8F cells. Notably, we observed an inverse association between the expression miR-495 and GRP78. Our bioinformatics analysis led to the identification of miR-495 as the optimal miRNA interacting with GRP78 mRNA. Furthermore, miR-495 targeting the 3′untranslated region (UTR) of GRP78 was detected by a Dual-Glo Luciferase Assay system. Finally, we observed that miR-495 inhibition led to a significant increase in the radioresistance of 5-8F cells and higher GRP78 expression, which may be involved in epithelial-mesenchymal transition (EMT) phenotype. miR-495 targeted the 3′UTR of GRP78 and contributed to the efficacy of radiation therapy in NPC.
- Published
- 2018
23. A self-assembled nanoprobe for long-term cancer cell nucleus-specific staining and two-photon breast cancer imaging
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Shuanglian Wang, Wuwu Lv, Jie Dong, Wenbin Zeng, Hongliang Zeng, Zhu Chen, Ziping Wu, Tang Gao, Xueping Feng, and Mian Liu
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Light ,Nucleolus ,Contrast Media ,Nanoprobe ,Breast Neoplasms ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Fluorescence ,Catalysis ,Self assembled ,Breast cancer ,Two-photon excitation microscopy ,Cell Line, Tumor ,Materials Chemistry ,medicine ,Humans ,Fluorescent Dyes ,business.industry ,Metals and Alloys ,General Chemistry ,021001 nanoscience & nanotechnology ,medicine.disease ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,medicine.anatomical_structure ,Cell Tracking ,Cell culture ,Cancer cell ,Ceramics and Composites ,Cancer research ,Nanoparticles ,Female ,0210 nano-technology ,business ,Nucleus ,Cell Nucleolus - Abstract
Herein, a novel self-assembled nanoprobe for the long-term tracking of the nucleoli of cancer cells and for differentiating between clinical breast cancer tissues and para-carcinoma tissues has been developed.
- Published
- 2018
24. Deep learning based label-free small extracellular vesicles analyzer with light-sheet illumination differentiates normal and cancer liver cells
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Zhuo Wang, Shuanglian Wang, Gao Chen, and Xuantao Su
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Spectrum analyzer ,Materials science ,Liver cell ,Metals and Alloys ,Nanoparticle ,Cancer ,Condensed Matter Physics ,medicine.disease ,Extracellular vesicles ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Materials Chemistry ,Biophysics ,medicine ,Particle ,Particle size ,Electrical and Electronic Engineering ,Instrumentation ,Label free - Abstract
Small extracellular vesicles (sEVs) are considered as potential markers for tumor detection and vehicles for tumor treatment. Here we develop a deep learning based nanoparticle analyzer that can measure label-free sEVs. Light sheet technology is adopted to illuminate single nanoparticles on chip that suppresses the background noise. A deep learning method for nanoscale particle tracking is demonstrated, which accurately obtains the particle size distribution of polystyrene beads as small as 41 nm in diameter. Small extracellular vesicles from normal and cancerous liver cell linage cells, and from sorafenib drug treated cancerous cells, are analyzed label-freely. It is shown that the three types of sEVs can be well differentiated by their particle size distributions. Our deep learning based small extracellular vesicles analyzer (DeepEVAnalyzer) not only provides a new technique for sEV-like nanoparticle analysis, but also demonstrates the potential of using sEVs as label-free marker for cancer diagnosis.
- Published
- 2021
25. Noise-induced chaotic motions in Hamiltonian systems with slow-varying parameters
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Shuanglian, Wang, Yimu, Guo, and Chunbiao, Gan
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- 2001
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26. Down-regulating GRP78 reverses pirarubicin resistance of triple negative breast cancer by miR-495-3p mimics and involves the p-AKT/mTOR pathway.
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Mian Liu, Jiu Yang, Wuwu Lv, Shuanglian Wang, Tao Du, Kejing Zhang, Yuhui Wu, and Xueping Feng
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TRIPLE-negative breast cancer ,CANCER cells ,DRUG therapy - Abstract
Due to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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27. Highly selective discrimination of cysteine from glutathione and homo-cysteine with a novel AIE-ESIPT fluorescent probe
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Xueping Feng, Liu Huang, Shuai Huang, Yi Liu, Jiaxin Wu, Bin Feng, Min Liu, Tao Du, Wenbin Zeng, Shuanglian Wang, and Xueyan Huang
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Stereochemistry ,High selectivity ,Metals and Alloys ,02 engineering and technology ,Glutathione ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Highly selective ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,Cascade reaction ,chemistry ,Intramolecular force ,Materials Chemistry ,Michael reaction ,Electrical and Electronic Engineering ,0210 nano-technology ,Instrumentation ,Cysteine - Abstract
Biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play pivotal roles in numerous physiological events, however, due to the similar structures and reactivities, differentiation of these biothiols remains a challenging task. Herein, we reported a maleimide-appended fluorescent probe ABTT-MA capable of specific sensing of Cys over other structure-alike biothiols with an ultralow detection limit (9.4 nM). Via a series of investigations into the mechanism, the high selectivity toward Cys is ascribed to a Michael addition/S,N-intramolecular rearrangement cascade reaction, in which the involvement of the mercapto and the adjacent amino groups is necessary to proceed the sensing process. Given this presupposition, Cys could be kinetically discriminated from Hcy and GSH. Upon the addition of Cys, a strong fluorescence appeared and the intensity at 503 nm was correlated with Cys concentration linearly over a wide range (0–10 μM). Thanks to the aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) activity, the selective detection of Cys was realized not only in aqueous media but in the paper-based point-of-care test (POCT). Significantly, the practicability of ABTT-MA in exogenous and endogenous Cys imaging in living cells was elucidated as well.
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- 2020
28. Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential
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Song Liu, Hansen Liu, Tong Li, Fuwu Wang, Aijun Hao, Zhen Wang, Qun Zhang, Xueer Wang, Lin Yuan, Shuanglian Wang, and Dexiang Liu
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Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,transplants ,hydrogen sulfide ,Apoptosis ,chemistry.chemical_compound ,0302 clinical medicine ,Ischemia ,Neurotrophic factors ,Hypoxia ,Ischemic Preconditioning ,bcl-2-Associated X Protein ,Membrane Potential, Mitochondrial ,Neurons ,Brain Diseases ,vascular endothelial growth factor ,hemic and immune systems ,Vascular endothelial growth factor ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,Mitochondrial Membranes ,medicine.symptom ,Research Paper ,medicine.medical_specialty ,Cell Survival ,MAP Kinase Signaling System ,Mesenchymal Stem Cell Transplantation ,03 medical and health sciences ,stomatognathic system ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Rats, Wistar ,Protein kinase B ,Brain-derived neurotrophic factor ,business.industry ,Brain-Derived Neurotrophic Factor ,bone marrow mesenchymal stem cells ,Mesenchymal Stem Cells ,Hypoxia (medical) ,Rats ,Surgery ,Transplantation ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Cancer research ,business ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery - Abstract
// Qun Zhang 1 , Song Liu 1 , Tong Li 1 , Lin Yuan 1 , Hansen Liu 2 , Xueer Wang 1 , Fuwu Wang 3 , Shuanglian Wang 1 , Aijun Hao 3 , Dexiang Liu 2 , Zhen Wang 1, 3 1 Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China 2 Department of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China 3 Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China Correspondence to: Dexiang Liu, email: Liudexiang@sdu.edu.cn Zhen Wang, email: wangzhen@sdu.edu.cn Keywords: hydrogen sulfide, bone marrow mesenchymal stem cells, transplants, brain-derived neurotrophic factor, vascular endothelial growth factor Received: February 08, 2016 Accepted: July 27, 2016 Published: August 09, 2016 ABSTRACT Bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great promises for treating various brain diseases. However, poor viability of transplanted BMSCs in injured brain has limited the therapeutic efficiency. Hypoxia-ischemic injury is one of major mechanisms underlying the survival of transplanted BMSCs. We investigated the mechanism of preconditioning of BMSCs with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury. In this study, we demonstrated that preconditioning of NaHS, a H2S donor, effectively suppressed hypoxia-ischemic-induced apoptosis whereby the rise in Bax/Bcl-2 ratio. Further analyses revealed Akt and ERK1/2 pathways were involved in the protective effects of NaHS. In addition, NaHS preconditioning increased secretion of BDNF and VEGF in BMSCs. Consistent with in vitro data, transplantation of NaHS preconditioned BMSCs in vivo further enhanced the therapeutic effects of BMSCs on neuronal injury and neurological recovery, associated with increased vessel density and upregulation of BDNF and VEGF in the ischemic tissue. These findings suggest that H2S could enhance the therapeutic effects of BMSCs. The underlying mechanisms might be due to enhanced capacity of BMSCs and upregulation of protective cytokines in the hypoxia tissue.
- Published
- 2016
29. Up-Regulation of GABAergic Signal Events in Bone Marrow Lymphocytes in Childhood Acute Lymphoblastic Leukemia
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Mei Feng, Xupeng Yang, Tao Li, Yanli Liu, Hongmei Wang, Chuanfei Wei, Chuanyong Liu, Shuanglian Wang, Shuang Cui, Fan Yi, and Mengjun Qian
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Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Lymphocyte ,Blotting, Western ,Glutamate decarboxylase ,Bone Marrow Cells ,Lymphocyte proliferation ,Biology ,gamma-Aminobutyric acid ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Lymphocytes ,Child ,gamma-Aminobutyric Acid ,Cellular localization ,Glutamate Decarboxylase ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Receptors, GABA-A ,Up-Regulation ,Isoenzymes ,Blot ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Case-Control Studies ,Child, Preschool ,030220 oncology & carcinogenesis ,GABAergic ,Female ,Bone marrow ,Signal Transduction ,medicine.drug - Abstract
Gamma-aminobutyric acid (GABA) is involved in the proliferation, differentiation, and migration of several cell types including cancer cells. Whether GABA may be involved with acute lymphoblastic leukemia (ALL) is unclear. Therefore, the goal of this report was to examine if GABAergic signaling expression is altered in bone marrow lymphocytes of ALL children. RT-PCR and western blot analysis were used to examine the expression of the GABA synthetizing enzyme glutamic acid decarboxylase (GAD) isoforms (GAD65 and GAD67), and type-A GABA receptor (GABAAR) subunits [α(1-6), β(1-3), γ(1-3), δ, ε, θ, π, and ρ(1-3)] in bone marrow lymphocytes of 19 ALL children before chemotherapy. The data obtained were compared with those in 13 age-matched non-ALL children. Immunofluorescent staining was used to examine the cellular localization of GAD. We found that GAD and GABAAR subunits were expressed in bone marrow lymphocytes of ALL children. Moreover, RT-PCR and western blot showed that GAD and several GABAAR subunits were significantly increased in ALL children as compared with the data of non-ALL children. Our present study reveals up-regulation of GABAergic signaling events in bone marrow lymphocytes in ALL children. However, the role of this signaling system in lymphocyte proliferation and invasion as related to the progression of ALL requires further investigation.
- Published
- 2016
30. Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment
- Author
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Hasengaowa, Yangjian Liu, Jie Yang, Narisu Narisu, Xiaohui Sun, Eerdunduleng, Ming Li, Burenbatu, Mandula Borjigin, Xuemei Zhang, Cuiqin Gong, Longmei, Guiping Zhang, Wenyan Huo, Shuanglian Wang, and Haihua Bai
- Subjects
Genetic Markers ,Male ,medicine.medical_treatment ,Splenectomy ,Pathogenesis ,immune system diseases ,hemic and lymphatic diseases ,microRNA ,medicine ,Humans ,Platelet ,Pharmacology ,Autoimmune disease ,Purpura, Thrombocytopenic, Idiopathic ,Plant Extracts ,Platelet Count ,business.industry ,Gene Expression Profiling ,Case-control study ,General Medicine ,medicine.disease ,Thrombocytopenic purpura ,MicroRNAs ,Treatment Outcome ,Gene Expression Regulation ,Case-Control Studies ,Immunology ,Female ,Plant Preparations ,business ,Glucocorticoid ,Drugs, Chinese Herbal ,medicine.drug - Abstract
Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy.
- Published
- 2015
31. Protective roles of hepatic GABA signaling in liver injury
- Author
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Shuanglian, Wang, Lu, Zhang, Chuanyong, Liu, and Wei-Yang, Lu
- Subjects
Original Article - Abstract
In addition to functioning as a neurotransmitter, γ-aminobutyric acid (GABA) generates signals, via its type A or type B receptors (GABAARs or GABABRs), in various types of cells. Studies, including ours, show that GABAAR-mediated auto- and paracrine GABAergic signaling occurs in rodent hepatocytes and cholangiocytes, protecting the liver against toxic injuries. This short article briefly introduces the GABA signaling system in rodent livers and discusses potential mechanisms by which the hepatic GABA signaling protects the liver function.
- Published
- 2017
32. iTRAQ-based quantitative proteomics analysis of immune thrombocytopenia patients before and after Qishunbaolier treatment.
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Burenbatu, Yanbo Wang, Shuanglian Wang, Narisu, Wuritunashun, Cuiqin Gong, Hashengaowa, Eerdunduleng, Sarula, Guihua, and Haihua Bai
- Subjects
PROTEOMICS ,THROMBOPOIETIN receptors ,IDIOPATHIC thrombocytopenic purpura ,TANDEM mass spectrometry ,WESTERN immunoblotting ,POLYMERASE chain reaction ,QUANTITATIVE research - Abstract
Rationale: Treatment of immune thrombocytopenia (ITP) usually involves long-term use of immunosuppressive corticosteroids and splenectomy. However, these treatments often have side effects in patients. The Mongolian medicine Qishunbaolier (QSBLE) has a high curative effect, reduces the chances of relapse, and has no obvious side effects. This study was designed to identify potential therapeutic targets of QSBLE for treating ITP. Methods: To reveal differences in protein expression between ITP patients (ITPs) before and after QSBLE treatment, comparative proteomics studies were performed using isobaric tags for relative and absolute quantification (iTRAQ). The analysis used nanospray liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) in positive ion electrospray ionization mode. Key proteins relevant to ITP were revealed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and other bioinformatics tools. Real-time polymerase chain reaction (RT-PCR) analysis was carried out for confirmation of differentially expressed proteins. Results: A total of 982 differentially expressed proteins were identified in ITPs compared with the controls. Compared with the pre-QSBLE treatment group, 61 differentially expressed proteins were identified in the post-QSBLE treatment group, with 48 proteins being significantly upregulated and 13 downregulated. Twenty-nine pathways were significantly enriched. Q6N030 and other proteins were the key players in the protein-pathway network. Twenty proteins that may play important roles in the treatment of ITP were further filtered. RT-PCR and Western blot analyses further confirmed that MIF, PGK1 and IGHM were upregulated in ITPs after QSBLE treatment, in accordance with the proteomics data. Conclusions: It is believed that the identified proteins and the results of bioinformatics analysis will provide a potential therapeutic target site for QSBLE for ITP therapy and biomarkers. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic β-cells
- Author
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Shuanglian Wang, Roy Nofech-Mozes, Fan Yi, Wei-Yang Lu, Allen L. Feng, Changhui Wang, Xupeng Yang, Ziwei Li, Yan Luo, Chuanyong Liu, Tao Li, and Meng Yu
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Biology ,Carbohydrate metabolism ,Toxicology ,gamma-Aminobutyric acid ,Cell Line ,Membrane Potentials ,Mice ,Insulin-Secreting Cells ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Insulin ,Glucose homeostasis ,GABA-A Receptor Agonists ,GABA-A Receptor Antagonists ,Autocrine signalling ,gamma-Aminobutyric Acid ,geography ,geography.geographical_feature_category ,Ethanol ,Receptors, GABA-A ,Islet ,Rats ,Endocrinology ,GABAergic ,Signal transduction ,Signal Transduction ,medicine.drug - Abstract
Alcohol overindulgence is a risk factor of type 2 diabetes mellitus. However, the mechanisms by which alcohol overindulgence damages glucose metabolism remain unclear. Pancreatic islet β-cells are endowed with type-A γ-aminobutyric acid receptor (GABAAR) mediated autocrine signaling mechanism, which regulates insulin secretion and fine-tunes glucose metabolism. In neurons GABAAR is one of the major targets for alcohol. This study investigated whether ethanol alters glucose metabolism by affecting GABAAR signaling in pancreatic β-cells. Blood glucose level of test mice was measured using a blood glucose meter. Insulin secretion by the pancreatic β-cell line INS-1 cells was examined using a specific insulin ELISA kit. Whole-cell patch-clamp recording was used to evaluate GABA-elicited current in INS-1 cells. Western blot and immunostaining were used to measure the expression of GABAAR subunits in mouse pancreatic tissues or in INS-1 cells. Intraperitoneal (i.p.) administration of ethanol (3.0g/kg body weight) to mice altered glucose metabolism, which was associated with decreased expression of GABAAR α1- and δ- subunits on the surface of pancreatic β-cells. Acute treatment of cultured INS-1cells with ethanol (60mM) decreased the GABA-induced current and reduced insulin secretion. In contrast, treating INS-1 cells with GABA (100μM) largely prevented the ethanol-induced reduction of insulin release. Importantly, pre-treating mice with GABA (i.p., 1.5mg/kg body weight) partially reversed ethanol-induced impairment of glucose homeostasis in mice. Our data suggest a novel role of pancreatic GABA signaling in protecting pancreatic islet β-cells from ethanol-induced dysfunction.
- Published
- 2014
34. Immunofluorescently labeling glutamic acid decarboxylase 65 coupled with confocal imaging for identifying GABAergic somata in the rat dentate gyrus—A comparison with labeling glutamic acid decarboxylase 67
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Xueying Song, Shuanglian Wang, Xiaochen Wang, Jianchun Zhu, Enpu Guo, Fei Gao, and Ren-Zhi Zhan
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Male ,endocrine system ,endocrine system diseases ,Glutamate decarboxylase ,Fluorescent Antibody Technique ,Hippocampal formation ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Interneurons ,medicine ,Animals ,GABAergic Neurons ,Microscopy, Confocal ,biology ,Glutamate Decarboxylase ,Dentate gyrus ,nutritional and metabolic diseases ,Granule cell ,Molecular biology ,Rats ,medicine.anatomical_structure ,nervous system ,Biochemistry ,Dentate Gyrus ,Axoplasmic transport ,biology.protein ,GABAergic ,Calretinin ,Parvalbumin - Abstract
As γ-aminobutyric acid (GABA) is synthesized by two isoforms of glutamic acid decarboxylase (GAD), namely, GAD65 and GAD67, immunohistochemically targeting either isoform of GAD is theoretically useful for identifying GABAergic cell bodies. In practice, targeting GAD67 remains to be a popular choice. However, identifying GABAergic cell bodies with GAD67 immunoreactivity in the hippocampal dentate gyrus, especially in the hilus, is not without pitfalls. In the present study, we compared the characteristics of GAD65 immunoreactivity to GAD67 immunoreactivity in the rat dentate gyrus and examined perikaryal expression of GAD65 in four neurochemically prevalent subgroups of interneurons in the hilus. Experiments were done in normal adult Sprague-Dawley rats and GAD67-GFP knock-in mice. Horizontal hippocampal slices cut from the ventral portion of hippocampi were immunofluorescently stained and scanned using a confocal microscope. Immunoreactivity for both GAD67 and GAD65 was visible throughout the dentate gyrus. Perikaryal GAD67 immunoreactivity was denser but variable in terms of distribution pattern and intensity among cells whereas perikaryal GAD65 immunoreactivity displayed similar distribution pattern and staining intensity. Among different layers of the dentate gyrus, GAD67 immunoreactivity was densest in the hilus despite GAD65 immunoreactivity being more intense in the granule cell layer. Co-localization experiments showed that GAD65, but not GAD67, was expressed in all hilar calretinin (CR)-, neuronal nitric oxide synthase (nNOS)-, parvalbumin (PV)- or somatostatin (SOM)-positive somata. Labeling CR, nNOS, PV, and SOM in sections obtained from GAD67-GFP knock-in mice revealed that a large portion of SOM-positive cells had weak GFP expression. In addition, double labeling of GAD65/GABA and GAD67/GABA showed that nearly all of GABA-immunoreactive cells had perikaryal GAD65 expression whereas more than one-tenth of GABA-immunoreactive cells lacked perikaryal GAD67 immunoreactivity. Inhibition of axonal transport with colchicine dramatically improved perikaryal GAD65 immunoreactivity in GABAergic cells without significant augmentation to be seen in granule cells. Double labeling GAD65 and GAD67 in the sections obtained from colchicine-pretreated animals confirmed that a portion of GAD65-immunoreactive cells had weak or even no GAD67 immunoreactivity. We conclude that for confocal imaging, immunofluorescently labeling GAD65 for identifying GABAergic somata in the hilus of the dentate gyrus has advantages over labeling GAD67 in terms of easier recognition of perikaryal labeling and more consistent expression in GABAergic somata. Inhibition of axonal transport with colchicine further improves perikaryal GAD65 labeling, making GABAergic cells more distinguishable.
- Published
- 2014
35. Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury
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Cheng Peng, Shuanglian Wang, Wei-Yang Lu, Zhiyan Liu, Dan Luo, Chuanyong Liu, Shaofeng Sui, Xinhuan Fan, and Jia Liu
- Subjects
0301 basic medicine ,Adult ,Male ,Alcoholic liver disease ,medicine.medical_specialty ,Apoptosis ,Biology ,Protein Serine-Threonine Kinases ,Toxicology ,MAP Kinase Kinase Kinase 5 ,gamma-Aminobutyric acid ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,GABA receptor ,Internal medicine ,Endoribonucleases ,medicine ,Animals ,Humans ,GABA-A Receptor Agonists ,GABA-A Receptor Antagonists ,Liver Diseases, Alcoholic ,gamma-Aminobutyric Acid ,Liver injury ,Ethanol ,GABAA receptor ,Glutamate Decarboxylase ,JNK Mitogen-Activated Protein Kinases ,Bicuculline ,Middle Aged ,medicine.disease ,Endoplasmic Reticulum Stress ,Receptors, GABA-A ,3. Good health ,Up-Regulation ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,nervous system ,Muscimol ,chemistry ,Liver ,Acute Disease ,Liver function ,Chemical and Drug Induced Liver Injury ,medicine.drug ,Signal Transduction - Abstract
Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A GABA receptor (GABAA R) subunits was upregulated in ethanol-treated mice compared with saline-treated controls. Remarkably, pretreatment of mice with GABA (1.5 mg kg-1 body weight, intraperitoneal injection [i.p.]) or with the GABAA R agonist muscimol (1.2 mg kg-1 body weight, i.p.) protected the liver against ethanol toxicity and improved liver function, whereas pretreatment of mice with the GABAA R antagonist bicuculline (2.0 mg kg-1 body weight, i.p.) worsened the liver function. Further analyses suggest that GABAA R-mediated signaling protects the liver from ethanol injury by, at least partially, inhibiting the IRE1α-ASK1-JNK pro-apoptotic pathway in hepatocytes in the process of ethanol-induced endoplasmic reticulum stress response.
- Published
- 2017
36. Hydrogen sulfide attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation
- Author
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Aijun Hao, Qingrui Zhang, Zhen Wang, Qun Zhang, Lin Yuan, Jianmei Wang, Shuanglian Wang, Yanfen Gong, Dexiang Liu, and Hongda Liu
- Subjects
MAPK/ERK pathway ,Cell Survival ,p38 mitogen-activated protein kinases ,Sodium hydrosulfide ,Pharmacology ,Nitric Oxide ,Neuroprotection ,Mice ,chemistry.chemical_compound ,In vivo ,medicine ,Animals ,Hydrogen Sulfide ,Hypoxia ,Neurons ,Mice, Inbred BALB C ,Microglia ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,NF-kappa B ,Neurotoxicity ,Macrophage Activation ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Immunology ,Mitogen-Activated Protein Kinases ,Neuron death - Abstract
Endogenously produced hydrogen sulfide (H2S) may have multiple functions in the brain including potent anti-inflammatory effects. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to hypoxic injuries in the developing brain. The aim of this study is to investigate the potential role of H2S in altering hypoxia-induced neurotoxicity via its anti-inflammatory actions as examined in vitro and in vivo models. Using the BV-2 microglial cell line, we found that sodium hydrosulfide (NaHS), a H2S donor, significantly inhibited hypoxia-induced microglial activation and suppressed subsequent pro-inflammatory factor release. In addition, treating murine primary cortical neurons with conditioned medium (CM) from hypoxia-stimulated microglia induced neuronal apoptosis, an effect that was reversed by CM treated with NaHS. Further, NaHS inhibited phosphorylation of the p65 subunit of NF-κB, phosphorylation of ERK and p38 but not JNK MAPK in these hypoxia-induced microglia. When administered in vivo to neonatal mice subjected to hypoxia, NaHS was found to attenuate neuron death, an effect that was associated with suppressed microglial activation, pro-inflammatory cytokines and NO levels. Taken together, H2S exerts neuroprotection against hypoxia-induced neurotoxicity through its anti-inflammatory effect in microglia. This effect appears to be attributable to inhibition of iNOS, NF-κB, ERK and p38 MAPK signaling pathways. Our results suggest a potential therapeutic application of H2S releasing drugs in hypoxic brain damage treatment.
- Published
- 2014
37. Curcumin ameliorates ethanol-induced memory deficits and enhanced brain nitric oxide synthase activity in mice
- Author
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Lin Zhang, Shuanglian Wang, Junxia Luo, Rui Gao, Hong Jiang, and Shu Yan Yu
- Subjects
Male ,Curcumin ,Hippocampus ,Mice, Inbred Strains ,Pharmacology ,Nitric Oxide ,Amygdala ,Nitric oxide ,Mice ,chemistry.chemical_compound ,Escape Reaction ,Reaction Time ,medicine ,Animals ,Enzyme Inhibitors ,Prefrontal cortex ,Biological Psychiatry ,Memory Disorders ,Ethanol ,biology ,Brain ,Central Nervous System Depressants ,Recognition, Psychology ,Nitric oxide synthase ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Toxicity ,Exploratory Behavior ,biology.protein ,Nitric Oxide Synthase - Abstract
Ethanol consumption has well-known deleterious effects on memory. However, the mechanism by which ethanol exerts its effects on memory has received little attention, which has retarded the identification and development of effective therapeutic strategies against ethanol toxicity. The aim of this study was to explore the neuronal mechanisms underlying the protective action of curcumin, a natural polyphenolic compound of Curcuma longa, against ethanol-induced memory deficits. Adult mice were pretreated with curcumin (40 mg/kg, i.p.) before administration of ethanol (1 g/kg, i.p.) for the memory acquisition measurement, or were sacrificed 30 min later for evaluation of regional brain differences in the nitric oxide synthase (NOS) activity and nitric oxide (NO) concentration. The results showed that pretreatment with curcumin significantly ameliorated the memory deficits resulting from acute ethanol administration to mice in the novel object recognition and inhibitory avoidance tasks. Furthermore, acute ethanol treatment increased the NOS activity and NO production in brain regions associated with memory including prefrontal cortex (PFC), amygdala and hippocampus, while this enhancement was suppressed by pretreatment with curcumin. Taken together, these results suggest that the protective effects of curcumin on acute ethanol-induced memory deficits are mediated, at least in part, by suppressing NOS activity in the brain of mice. Thus, manipulation of the NOS/NO signaling pathway might be beneficial for the prevention of ethanol toxicity.
- Published
- 2013
38. Protective roles of hepatic GABA signaling in acute liver injury of rats
- Author
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Fan Yi, Wei-Yang Lu, Yun-Yan Xiang, Shuanglian Wang, Chuanyong Liu, Jingxin Li, and Jianchun Zhu
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Baclofen ,Physiology ,Galactosamine ,Biology ,Cholangiocyte ,Rats, Sprague-Dawley ,03 medical and health sciences ,Paracrine signalling ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,GABA-A Receptor Agonists ,gamma-Aminobutyric Acid ,Acute liver injury ,Hepatology ,Muscimol ,Gastroenterology ,Hep G2 Cells ,Receptors, GABA-A ,3. Good health ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Liver ,Hepatocyte ,GABA-B Receptor Agonists ,Hepatocytes ,GABAergic ,Liver function ,Chemical and Drug Induced Liver Injury - Abstract
γ-Aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes. The function of hepatic GABA signaling system in rats was examined using models of d-galactosamine (GalN)-induced acute hepatocytic injury in vivo and in vitro. The expression of GAD increased whereas GABAAR subunits decreased in the liver of GalN-treated rats. Remarkably, treating rats with GABA or the GABAAR agonist muscimol, but not the GABABR agonist baclofen, protected hepatocytes against GalN toxicity and improved liver function. In addition, muscimol treatment decreased the formation of pseudobile ductules and the enlargement of hepatocytic canaliculi in GalN-treated rats. Our results revealed that a complex GABA signaling system exists in the rat liver. Activation of this intrahepatic GABAergic system protected the liver against toxic injury.NEW & NOTEWORTHY Auto- and paracrine GABAergic signaling systems exist in the rat hepatocytes and cholangiocytes. Activation of GABA signaling protects liver function from d-galactosamine injury by reducing toxic impairment of hepatocytes and by decreasing cholangiocyte proliferation.
- Published
- 2016
39. Ethanol impedes embryo transport and impairs oviduct epithelium
- Author
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Shuanglian Wang, Tonghui Xu, Chuanyong Liu, Wenfu Wang, Jingxin Li, Ruoxi Liu, and Qiuhong Yang
- Subjects
Adult ,medicine.medical_specialty ,animal structures ,Alcohol Drinking ,Alcohol abuse ,Embryonic Development ,Oviducts ,Toxicology ,Epithelium ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,030219 obstetrics & reproductive medicine ,Ethanol ,biology ,Embryogenesis ,Embryo ,Middle Aged ,medicine.disease ,Nitric oxide synthase ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,NG-Nitroarginine Methyl Ester ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Microscopy, Electron, Scanning ,Oviduct ,Female - Abstract
Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50 ± 6 mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy.
- Published
- 2016
40. The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration
- Author
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Qingrui Zhang, Shuanglian Wang, Liwei Liu, Xudong Yang, Dexiang Liu, Gang Li, Lin Yuan, and Zhen Wang
- Subjects
Lipopolysaccharides ,Male ,Sucrose ,Curcumin ,Lipopolysaccharide ,medicine.medical_treatment ,Interleukin-1beta ,Nitric Oxide Synthase Type II ,Mice, Inbred Strains ,Pharmacology ,Motor Activity ,Statistics, Nonparametric ,Proinflammatory cytokine ,Behavioral Neuroscience ,chemistry.chemical_compound ,Food Preferences ,Mice ,medicine ,Animals ,RNA, Messenger ,Swimming ,biology ,Chemistry ,Depression ,Tumor Necrosis Factor-alpha ,Brain ,Tail suspension test ,Antidepressive Agents ,Nitric oxide synthase ,Disease Models, Animal ,Cytokine ,Gene Expression Regulation ,Hindlimb Suspension ,Cyclooxygenase 2 ,Immunology ,biology.protein ,Tumor necrosis factor alpha ,Behavioural despair test - Abstract
Current evidence supports that inflammation and increased cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. Curcumin has anti-inflammatory, antioxidant and anti-depressant-like properties. Here, we examined the effects of curcumin on lipopolysaccharide (LPS)-induced depressive-like behavior and inflammation in male mice. A single administration of LPS (0.83mg/kg, i.p.) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), reduced sucrose consumption without affecting spontaneous locomotor activity. Pretreatment with curcumin (50mg/kg, i.p.) for 7 consecutive days reversed LPS-induced alterations in the FST, TST, and sucrose preference test. Moreover, pre-treatment with curcumin attenuated LPS-induced microglial activation and overproduction of pro-inflammatory cytokine (interleukin-1β and tumor necrosis factor-α), as well as the levels of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in the hippocampus and prefrontal cortex (PFC). In addition, curcumin ameliorated LPS-induced NF-κB activation in the hippocampus and PFC. The results demonstrate that curcumin may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude.
- Published
- 2014
41. Isoflurane regulates atypical type-A γ-aminobutyric acid receptors in alveolar type II epithelial cells
- Author
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Xuanmao Chen, Jingxin Li, James C. Hogg, Shuanglian Wang, Yun-Yan Xiang, Beverley A. Orser, Wei-Yang Lu, Gil Faclier, and John F. MacDonald
- Subjects
Patch-Clamp Techniques ,Blotting, Western ,Fluorescent Antibody Technique ,Pharmacology ,Bicuculline ,Aminobutyric acid ,gamma-Aminobutyric acid ,Article ,GABAA-rho receptor ,GABA Antagonists ,Mice ,medicine ,Animals ,Humans ,Receptor ,Coloring Agents ,GABA Agonists ,A549 cell ,Lung ,Microscopy, Confocal ,biology ,Isoflurane ,GABAA receptor ,Muscimol ,Epithelial Cells ,Trypan Blue ,respiratory system ,Receptors, GABA-A ,Cell biology ,Pulmonary Alveoli ,Solutions ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Cyclooxygenase 2 ,Anesthetics, Inhalation ,biology.protein ,Cyclooxygenase ,medicine.drug - Abstract
Background: Volatile anesthetics act primarily through upregulating the activity of γ-aminobutyric acid type A (GABAA) receptors. They also exhibit antiinflammatory actions in the lung. Rodent alveolar type II (ATII) epithelial cells express GABAA receptors and the inflammatory factor cyclooxygenase-2 (COX-2). The goal of this study was to determine whether human ATII cells also express GABAA receptors and whether volatile anesthetics upregulate GABAA receptor activity, thereby reducing the expression of COX-2 in ATII cells. Methods: The expression of GABAA receptor subunits and COX-2 in ATII cells of human lung tissue and in the human ATII cell line A549 was studied with immunostaining and immunoblot analyses. Patch clamp recordings were used to study the functional and pharmacological properties of GABAA receptors in cultured A549 cells. Results: ATII cells in human lungs and cultured A549 cells expressed GABAA receptor subunits and COX-2. GABA induced currents in A549 cells, with half-maximal effective concentration of 2.5 µm. Isoflurane (0.1–250 µm) enhanced the GABA currents, which were partially inhibited by bicuculline. Treating A549 cells with muscimol or with isoflurane (250 µm) reduced the expression of COX-2, an effect that was attenuated by cotreatment with bicuculline. Conclusions: GABAA receptors expressed by human ATII cells differ pharmacologically from those in neurons, exhibiting a higher affinity for GABA and lower sensitivity to bicuculline. Clinically relevant concentrations of isoflurane increased the activity of GABAA receptors and reduced the expression of COX-2 in ATII cells. These findings reveal a novel mechanism that could contribute to the antiinflammatory effect of isoflurane in the human lung.
- Published
- 2013
42. An autocrine γ-aminobutyric acid signaling system exists in pancreatic β-cell progenitors of fetal and postnatal mice
- Author
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Mary M, Feng, Yun-Yan, Xiang, Shuanglian, Wang, and Wei-Yang, Lu
- Subjects
endocrine system ,Original Article - Abstract
Gamma-aminobutyric acid (GABA) is produced and secreted by adult pancreatic β-cells, which also express GABA receptors mediating autocrine signaling and regulating β-cell proliferation. However, whether the autocrine GABA signaling involves in β-cell progenitor development or maturation remains uncertain. By means of immunohistochemistry we analyzed the expression profiles of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the α1-subunit of type-A GABA receptor (GABAARα1) in the pancreas of mice at embryonic day 15.5 (E15.5), E18.5, postnatal day 1 (P1) and P7. Our data showed that at E15.5 the pancreatic and duodenum homeobox-1 (Pdx1) was expressed in the majority of cells in the developing pancreata. Notably, insulin immunoreactivity was identified in a subpopulation of pancreatic cells with a high level of Pdx1 expression. About 80% of the high-level Pdx-1 expressing cells in the pancreas expressed GAD and GABAARα1 at all pancreatic developmental stages. In contrast, only about 30% of the high-level Pdx-1 expressing cells in the E15.5 pancreas expressed insulin; i.e., a large number of GAD/GABAARα1-expressing cells did not express insulin at this early developmental stage. The expression level of GAD and GABAARα1 increased steadily, and progressively more GAD/GABAARα1-expressing cells expressed insulin in the course of pancreatic development. These results suggest that 1) GABA signaling proteins appear in β-cell progenitors prior to insulin expression; and 2) the increased expression of GABA signaling proteins may be involved in β-cell progenitor maturation.
- Published
- 2013
43. Ethanol upregulates iNOS expression in colon through activation of nuclear factor-kappa B in rats
- Author
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Xuelian Ma, Junfang Qin, Shuanglian Wang, Yinglian Lv, Chao Wang, and Chuanyong Liu
- Subjects
Male ,Contraction (grammar) ,Colon ,Cell ,Medicine (miscellaneous) ,Motility ,Nitric Oxide Synthase Type II ,Biology ,Toxicology ,Gene Expression Regulation, Enzymologic ,chemistry.chemical_compound ,Downregulation and upregulation ,Western blot ,Pyrrolidine dithiocarbamate ,medicine ,Animals ,Rats, Wistar ,Myenteric plexus ,medicine.diagnostic_test ,Ethanol ,NF-kappa B ,Molecular biology ,Rats ,Up-Regulation ,Nitric oxide synthase ,Psychiatry and Mental health ,medicine.anatomical_structure ,Biochemistry ,chemistry ,biology.protein - Abstract
Background: Alcohol inhibits colonic motility but the mechanism is unknown. The goal of this study was to test the possibility that nuclear factor-kappa B (NF-κB) is involved in the upregulation of inducible nitric oxide synthase (iNOS) expression induced by ethanol in colon. Methods: The isometric contraction of longitudinal muscle strips of proximal colon (LP) was monitored by polygraph. Western blot analysis was used to measure the amount of iNOS and I-κB in the cytoplasm and P65 in the nucleus. Immunohistochemistry was applied to locate iNOS in colon. Results: Ethanol (87mM) inhibited the contraction of LP. Pretreatment of S-methylisothioure (SMT) (1 mM), a specific iNOS inhibitor, Pyrrolidine dithiocarbamate (PDTC) (10 mM) and BAY11-7082(10 mM), specific inhibitors of NF-κB significantly reversed the inhibitory effect of ethanol on LP contraction. Ethanol increased the amount of iNOS and content of NO in colon, and these effects were attenuated by pretreatment of PDTC. Following ethanol administration, the amount of I-κB in the cytoplasm decreased, but that of P65, the subunit of NF-κB in the nucleus, increased. The iNOS was located in the cell body of myenteric plexus in colon. Conclusion: Ethanol inhibited the contraction of LP in colon mainly through activation of NF-κB, the subsequent upregulation of iNOS expression and increase of NO release in myenteric plexus.
- Published
- 2009
44. Estradiol upregulates the expression of oxytocin receptor in colon in rats
- Author
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Jun Fang Qin, Paulus S. Wang, Chuanyong Liu, Chao Wang, Mei Feng, Yanfang Ye, Shuanglian Wang, and Dong Ping Xie
- Subjects
medicine.medical_specialty ,17β-oestradiol ,Physiology ,medicine.drug_class ,Colon ,Endocrinology, Diabetes and Metabolism ,Ovariectomy ,Blotting, Western ,Motility ,Estrous Cycle ,Biology ,In Vitro Techniques ,Oxytocin ,Ovarian hormone ,Random Allocation ,Hormone Antagonists ,Vasotocin ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Dose-Response Relationship, Drug ,Estradiol ,Reverse Transcriptase Polymerase Chain Reaction ,Oxytocin receptor ,Immunohistochemistry ,Rats ,Up-Regulation ,Endocrinology ,Estrogen ,Receptors, Oxytocin ,Excitatory postsynaptic potential ,Ovariectomized rat ,Female ,Gastrointestinal Motility ,medicine.drug ,Muscle Contraction - Abstract
The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E2). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4–100 μg/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.
- Published
- 2009
45. Nitric oxide mediates the inhibitory effect of ethanol on the motility of isolated longitudinal muscle of proximal colon in rats
- Author
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Chuanyong Liu, K J Liu, Shuanglian Wang, M Feng, D P Xie, Wolfgang Kunze, and J F Qin
- Subjects
Male ,Nitroprusside ,medicine.medical_specialty ,Physiology ,Colon ,Motility ,Tetrodotoxin ,Nitric Oxide ,Poisons ,Nitric oxide ,chemistry.chemical_compound ,Organ Culture Techniques ,Sex Factors ,Internal medicine ,Mole ,medicine ,Animals ,Nitric Oxide Donors ,Enzyme Inhibitors ,Ethanol ,Dose-Response Relationship, Drug ,Endocrine and Autonomic Systems ,Gastroenterology ,Central Nervous System Depressants ,Muscle, Smooth ,In vitro ,Rats ,Dose–response relationship ,Endocrinology ,chemistry ,Female ,Sodium nitroprusside ,Gastrointestinal Motility ,medicine.drug - Abstract
The aim of the present study was to investigate the effect of ethanol on colon motility in rats and to test the possibility that nitric oxide (NO) mediates this effect. Proximal colon longitudinal muscle strips (LM) (8 x 3 mm) cut parallel to the longitudinal muscle fibres of the colon were isolated and mounted in an organ bath. Ethanol (0.57, 0.87 and 1.30 mmol L(-1)) dose-dependently inhibited the motility of LM. Longitudinal muscle strips from female rats were more sensitive to the inhibitory effect of ethanol than that from male rats. L-NAME (N-nitro-L-arginine methyl ester) (100 micromol L(-1)), AG (aminoguanidine) (10 micromol L(-1)), ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) (10 micromol L(-1)) and PTIO (2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide) (200 micromol L(-1)) partly blocked the inhibitory effect of ethanol on LM. Pretreatment with L-NAME, AG, ODQ and PTIO abolished the sex difference of the inhibitory effect of ethanol on LM. Tetrodotoxin (TTX) (10 micromol L(-1)) partly blocked the inhibitory effect but did not influence the sex difference. The relaxation of LM induced by SNP (sodium nitroprusside) (0.1-10 micromol L(-1)) in female rats was greater than that in male rats. In conclusion, ethanol inhibited the colon motility in vitro. This inhibitory effect on LM was mediated by NO through the iNOS - NO - cGMP pathway.
- Published
- 2007
46. Protective roles of hepatic GABA signaling in acute liver injury of rats.
- Author
-
Shuanglian Wang, Yun-Yan Xiang, Jianchun Zhu, Fan Yi, Jingxin Li, Chuanyong Liu, and Wei-Yang Lu
- Subjects
- *
GABA , *LIVER injuries - Abstract
γ-Aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes. The function of hepatic GABA signaling system in rats was examined using models of D-galactosamine (GalN)-induced acute hepatocytic injury in vivo and in vitro. The expression of GAD increased whereas GABAAR subunits decreased in the liver of GalN-treated rats. Remarkably, treating rats with GABA or the GABAAR) agonist muscimol, but not the GABABR agonist baclofen, protected hepatocytes against GalN toxicity and improved liver function. In addition, muscimol treatment decreased the formation of pseudobile ductules and the enlargement of hepatocytic canaliculi in GalN-treated rats. Our results revealed that a complex GABA signaling system exists in the rat liver. Activation of this intrahepatic GABAergic system protected the liver against toxic injury. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
47. GABA Coordinates with Insulin in Regulating Secretory Function in Pancreatic INS-1 β-Cells
- Author
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Wei-Yang Lu, Paul Bansal, Qinghua Wang, Shenghao Liu, Shuanglian Wang, and Yun-Yan Xiang
- Subjects
medicine.medical_treatment ,lcsh:Medicine ,Biochemistry ,Ion Channels ,chemistry.chemical_compound ,Endocrinology ,0302 clinical medicine ,Insulin-Secreting Cells ,Molecular Cell Biology ,Insulin ,lcsh:Science ,gamma-Aminobutyric Acid ,0303 health sciences ,Multidisciplinary ,C-Peptide ,biology ,C-peptide ,GABAA receptor ,Glucagon secretion ,Insulin oscillation ,Medicine ,Metabolic Pathways ,Research Article ,Signal Transduction ,medicine.drug ,medicine.medical_specialty ,gamma-Aminobutyric acid ,03 medical and health sciences ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Protein Interactions ,Biology ,030304 developmental biology ,Diabetic Endocrinology ,Endocrine Physiology ,lcsh:R ,Proteins ,Biological Transport ,Receptors, GABA-A ,Rats ,Insulin receptor ,Metabolism ,nervous system ,chemistry ,Metabolic Disorders ,biology.protein ,Regular insulin ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABA(A)Rs). We and others recently reported that islet β-cells also express GABA(A)Rs and that activation of GABA(A)Rs increases insulin release. Here we investigate the effects of insulin on the GABA-GABA(A)R system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 µM) suppressed the GABA-induced current (I(GABA)) by 43%. Zinc-free insulin also suppressed I(GABA) to the same extent of inhibition by regular insulin. The inhibition of I(GABA) occurs within 30 seconds after application of insulin. The insulin-induced inhibition of I(GABA) persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that insulin suppresses GABA(A)Rs through a mechanism that involves ERK activation. Radioimmunoassay revealed that the secretion of C-peptide was enhanced by GABA, which was blocked by pre-incubating the cells with picrotoxin (50 µM, p
- Published
- 2011
48. GABA Coordinates with Insulin in Regulating Secretory Function in Pancreatic INS-1 β-Cells.
- Author
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Bansal, Paul, Shuanglian Wang, Shenghao Liu, Yun-Yan Xiang, Wei-Yang Lu, and Qinghua Wang
- Subjects
- *
GABA , *INSULIN , *AMINOBUTYRIC acid , *HYPOGLYCEMIC agents , *SECRETION - Abstract
Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABAARs). We and others recently reported that islet β-cells also express GABAARs and that activation of GABAARs increases insulin release. Here we investigate the effects of insulin on the GABA-GABAAR system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 μM) suppressed the GABA-induced current (IA) by 43%. Zinc-free insulin also suppressed IGABA to the same extent of inhibition by regular insulin. The inhibition of IGABA occurs within 30 seconds after application of insulin. The insulin-induced inhibition of IGABA persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that insulin suppresses GABAARs through a mechanism that involves ERK activation. Radioimmunoassay revealed that the secretion of C-peptide was enhanced by GABA, which was blocked by pre-incubating the cells with picrotoxin (50 μM, p<0.01) and insulin (1 μM, p<0.01), respectively. Together, these data suggest that autocrine GABA, via activation of GABAARs, depolarizes the pancreatic β-cells and enhances insulin secretion. On the other hand, insulin down-regulates GABA-GABAAR signaling presenting a feedback mechanism for fine-tuning β-cell secretion. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
49. Ethanol Upregulates iNOS Expression in Colon Through Activation of Nuclear Factor-kappa B in Rats.
- Author
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Chao Wang, Shuanglian Wang, Junfang Qin, Yinglian Lv, Xuelian Ma, and Chuanyong Liu
- Subjects
- *
ALCOHOL , *NITRIC oxide , *IMMUNOHISTOCHEMISTRY , *CYTOPLASM , *PROTOPLASM - Abstract
Background: Alcohol inhibits colonic motility but the mechanism is unknown. The goal of this study was to test the possibility that nuclear factor-kappa B (NF-κB) is involved in the upregulation of inducible nitric oxide synthase (iNOS) expression induced by ethanol in colon. Methods: The isometric contraction of longitudinal muscle strips of proximal colon (LP) was monitored by polygraph. Western blot analysis was used to measure the amount of iNOS and I-κB in the cytoplasm and P65 in the nucleus. Immunohistochemistry was applied to locate iNOS in colon. Results: Ethanol (87mM) inhibited the contraction of LP. Pretreatment of S-methylisothioure (SMT) (1 mM), a specific iNOS inhibitor, Pyrrolidine dithiocarbamate (PDTC) (10 mM) and BAY11-7082(10 mM), specific inhibitors of NF-κB significantly reversed the inhibitory effect of ethanol on LP contraction. Ethanol increased the amount of iNOS and content of NO in colon, and these effects were attenuated by pretreatment of PDTC. Following ethanol administration, the amount of I-κB in the cytoplasm decreased, but that of P65, the subunit of NF-κB in the nucleus, increased. The iNOS was located in the cell body of myenteric plexus in colon. Conclusion: Ethanol inhibited the contraction of LP in colon mainly through activation of NF-κB, the subsequent upregulation of iNOS expression and increase of NO release in myenteric plexus. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
50. Estradiol upregulates the expression of oxytocin receptor in colon in rats.
- Author
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Mei Feng, Junfang Qin, Chao Wang, Yanfang Ye, Shuanglian Wang, Dongping Xie, Wang, Pautus S., and Chuanyong Liu
- Subjects
OXYTOCIN ,IMMUNOHISTOCHEMISTRY ,OLIGOPEPTIDES ,PITUITARY hormones ,COLON (Anatomy) ,LABORATORY rats - Abstract
The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E
2 ). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4-100 μg/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus. [ABSTRACT FROM AUTHOR]- Published
- 2009
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