156 results on '"Sun GC"'
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2. Psychological effects of yi ren medical qigong and progressive resistance training in adults with type 2 diabetes mellitus: a randomized controlled pilot study.
- Author
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Putiri AL, Lovejoy JC, Gillham S, Sasagawa M, Bradley R, and Sun GC
- Abstract
Background Previous studies suggest that qigong therapy has physiological benefits for adults with type 2 diabetes; however, information about the psychological benefits of qigong therapy in this population is limited. Objective The objective of this research project was to identify psychological responses to qigong vs control interventions in adults with type 2 diabetes. Design The research team designed a randomized, controlled, three-arm clinical trial comparing 12 weeks of Yi Ren Medical Qigong (YRMQ), progressive resistance training (PRT), and standard care. Setting The study was performed at Bastyr University Research Institute, Kenmore, Washington. Participants Participants were 13 men and 19 women (N=32) with diagnosed type 2 diabetes, a mean age of 56.3±8.1 (standard deviation) years, glycated hemoglobin>7.5%, and fasting blood glucose>7 mmol/dL (126 mg/dL). Intervention For 12 weeks, participants in the YRMQ and PRT group attended a 1-hour weekly group session that a certified instructor led and were instructed to practice at least twice a week for 30 minutes. Primary Outcome Measures The research team used the Perceived Stress Scale and the Beck Depression Inventory scores to analyze the data. Results YRMQ decreased perceived-stress scores by 29.3% (P<.05) and depression scores by 14.3% (not significant [NS]). The active control group, PRT, also decreased stress scores by 18.6% (NS) and decreased depression scores by 50% (P<.03). Stress and depression measures remained unchanged in the standard care group. Conclusion YRMQ and PRT may be beneficial in reducing perceived stress and improving depression in patients with type 2 diabetes, although verification of the clinical significance of these findings requires a longer study with a larger sample size. (Altern Ther Health Med. 2012;18(1)30-34.). [ABSTRACT FROM AUTHOR] more...
- Published
- 2012
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3. Targeting acetylated high mobility group box 1 protein (HMGB1) and toll-like receptor (TLR4) interaction to alleviate hypertension and neuroinflammation in fructose-fed rats.
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Lin YT, Ho CY, Sun GC, Wong TY, Hsiao M, Tseng CJ, and Cheng PW
- Abstract
Background and Purpose: Our previous study reported that fructose intake increased systemic blood pressure and reduced nitric oxide (NO) in the nucleus tractus solitarius (NTS) due to oxidative stress and neuroinflammation. However, it remains unclear how reactive oxygen species (ROS) reduce NO and how this process impacts neuroinflammation in the NTS. This study aimed at investigating the effect of ROS on acetylation of high mobility group box 1 protein (HMGB1) in the NTS of fructose-induced hypertensive rats., Experimental Approach: Male Wistar-Kyoto (WKY) rats were fed with 10% fructose water to elevate blood pressure. Thereafter, CLI-095 and glycyrrhizic acid (GA) treatments were delivered for up to 2 weeks (1 mg·12 μL
-1 ·day-1 , by intracerebroventricular injection) to reduce the negative effects of toll-like receptor 4 (TLR4) and HMGB1 activation., Key Results: Two weeks of CLI-095 and GA treatment reduced systemic blood pressure and significantly preserved neuronal and endothelial nitric oxide synthase (nNOS and eNOS) availability against the inflammatory insults of fructose consumption. Both CLI-095 and GA halted the interaction of acetylated HMGB1 and TLR4. Two weeks of CLI-095 and GA treatment markedly reduced NTS inflammation (pro-inflammatory cytokines and microglial activation) and lowered serum norepinephrine levels., Conclusion and Implications: Our data reveal novel pharmacological properties for CLI-095 and GA, which improved blood pressure and inflammatory conditions by decreasing the interaction of acetylated HMGB1 with TLR4. These findings challenge the commonly accepted dogma that essential hypertension is specifically mediated by neuroinflammation due to acetylated HMGB1 coupling to TLR4., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.) more...- Published
- 2024
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4. Induction of Ca 2+ signaling and cytotoxic responses of human lung fibroblasts upon an antihistamine drug oxatomide treatment and evaluating the protective effects of Ca 2+ chelating.
- Author
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Liang WZ, Hsieh KW, Yang ZD, and Sun GC
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- Humans, Cell Line, Calcium Chelating Agents pharmacology, Type C Phospholipases metabolism, Protein Kinase C metabolism, Histamine Antagonists pharmacology, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum metabolism, Thapsigargin pharmacology, Egtazic Acid analogs & derivatives, Egtazic Acid pharmacology, Estrenes pharmacology, Pyrrolidinones, Calcium Signaling drug effects, Fibroblasts drug effects, Fibroblasts metabolism, Cell Survival drug effects, Lung drug effects, Lung metabolism, Calcium metabolism
- Abstract
Background: Oxatomide, an antihistamine drug of the diphenylmethylpiperazine family, has anti-inflammatory effects in airway disease. Because oxatomide was shown to cause diverse physiological responses in several cell models, the impact of oxatomide on Ca
2+ signaling and its related physiological effects has not been explored in IMR-90 human fetal lung fibroblasts., Objectives: This study assessed the effect of oxatomide on cell viability and intracellular free Ca2+ concentrations ([Ca2+ ]i ) and examined whether oxatomide-induced cytotoxicity through Ca2+ signaling in IMR-90 cells., Methods: Cell viability was measured by the cell proliferation reagent (WST-1). [Ca2+ ]i was measured by the Ca2+ -sensitive fluorescent dye fura-2., Results: Oxatomide (10-40 μM) concentration dependently reduced cell viability and induced [Ca2+ ]i rises in IMR-90 cells. This cytotoxic effect was reversed by chelation of cytosolic Ca2+ with BAPTA-AM. In terms of Ca2+ signaling, oxatomide-caused Ca2+ entry was inhibited by modulators of store-operated Ca2+ channels (2-APB and SKF96365) and protein kinase C (PKC) inhibitor (GF109203X). Furthermore, oxatomide-induced Ca2+ influx was confirmed by Mn2+ -induced quench of fura-2 fluorescence. In a Ca2+ -free medium, preincubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited oxatomide-evoked [Ca2+ ]i rises. Conversely, treatment with oxatomide abolished thapsigargin-induced [Ca2+ ]i rises. Inhibition of phospholipase C (PLC) with U73122 also inhibited oxatomide-caused [Ca2+ ]i rises., Conclusion: In IMR-90 cells, oxatomide-induced cytotoxicity by preceding [Ca2+ ]i rises involving PKC-sensitive store-operated Ca2+ entry and PLC-dependent Ca2+ release from the endoplasmic reticulum. BAPTA-AM, with its Ca2+ chelating effects, may be a potential compound for preventing oxatomide-induced cytotoxicity., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.) more...- Published
- 2025
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5. High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer.
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Si LH, Sun GC, Liu ZW, Gu SY, Yan CH, Xu JY, and Jia Y
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- Female, Humans, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Apoptosis genetics, Cell Proliferation genetics, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Ovarian Neoplasms genetics, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology
- Abstract
Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy., (© 2024. The Author(s).) more...
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- 2024
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6. Exploration of beauvericin's toxic effects and mechanisms in human astrocytes and N-acetylcysteine's protective role.
- Author
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Liang WZ, Chia YY, Sun HJ, and Sun GC
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- Humans, Cell Line, Antioxidants pharmacology, Acetylcysteine pharmacology, Astrocytes drug effects, Oxidative Stress drug effects, Depsipeptides toxicity, Reactive Oxygen Species metabolism, Apoptosis drug effects
- Abstract
Beauvericin (BEA) is a newly identified mycotoxin produced by various Fusarium species, and its contamination in food and animal feed is widespread globally. This mycotoxin demonstrates cytotoxic effects by inducing oxidative stress in multiple models. Furthermore, evidence indicates that BEA possesses diverse toxic activities, making it a promising candidate for toxicological research. Recent studies have highlighted the ability of BEA to traverse the blood-brain barrier, suggesting its potential neurotoxicity. However, limited information is available regarding the neurotoxic effects of BEA on human astrocytes. Therefore, this study aimed to assess the neurotoxic effects of BEA on the Gibco® Human Astrocyte (GHA) cell line and elucidate the underlying mechanisms. Additionally, the study aimed to investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against BEA-induced toxicity. The data show that exposure to BEA within the 2.5-15 μM concentration range resulted in concentration-dependent cytotoxicity. BEA-treated cells exhibited significantly increased levels of reactive oxygen species (ROS), while intracellular glutathione (GSH) content was significantly reduced. Western blot analysis of cells treated with BEA revealed altered protein levels of Bax, cleaved caspase-9, and caspase-3, along with an increased Bax/Bcl-2 ratio, indicating the induction of apoptosis. Additionally, BEA exposure triggered antioxidant responses, as evidenced by increased protein expression of Nrf2, HO-1, and NQO1. Significantly, pretreatment with NAC partially attenuated the significant toxic effects of BEA. In conclusion, our findings suggest that BEA-induced cytotoxicity in GHA cells involves oxidative stress-associated apoptosis. Furthermore, NAC demonstrates potential as a protective agent against BEA-induced oxidative damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...
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- 2024
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7. Dapagliflozin prevents ERK activation and SGLT2-dependent endoglin upregulation in a mechanically provoked cardiac injury model.
- Author
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Yeh TC, Wu YC, Wong TY, Sun GC, Tseng CJ, and Cheng PW
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- Humans, Animals, Endoglin metabolism, Up-Regulation, Sodium-Glucose Transporter 2 metabolism, Troponin I metabolism, Stroke Volume, Myocytes, Cardiac metabolism, Heart Failure metabolism, Myocardial Infarction, Benzhydryl Compounds, Glucosides
- Abstract
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are rapidly gaining ground in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and acute myocardial infarction (AMI) by an unknown mechanism. Upregulation of Na
+ /H+ exchanger 1 (NHE1), SGLT1, and Ca2+ /calmodulin-dependent protein kinase II (CaMKII) in the diseased hearts was found to be attenuated by prolonged SGLT2i treatment. Unfortunately, dapagliflozin is not well understood as to how Na+ /Ca2+ homeostasis is affected in cardiomyocytes. In this study, we aimed to investigate whether mechanical stretch in cardiomyocytes upregulate SGLT2, resulted to loss of Na+ /Ca2+ homeostasis via ERK and eNOS signaling. AMI (+) and AMI (-) serum levels were estimated using ELISA assays of TGFβ-1 or endoglin (CD105). Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. Immunofluorescence assays were used to estimate troponin I, CD105, SGLT1/2, eNOSS633 , and ERK1/2T202/Y204 levels was performed for 5% (mild), and 25% elongation for 24 h. AMI (+) serum showed increased TGFβ1 and CD105 compared to AMI (-) patients. In consistent, troponin I, CD105, SGLT1/2, eNOSS633 and ERK1/2T202/Y204 were upregulated after 25% of 24 h cyclic stretch. Dapagliflozin addition caused SGLT2 inhibition, which significantly decreased troponin I, CD105, SGLT1/2, eNOSS633 , and ERK1/2T202/Y204 under 25% cyclic stretching. In summary, SGLT2 may have sensed mechanical stretch in a way similar to cardiac overloading as in vivo. By blocking SGLT2 in stretched cardiomyocytes, the AMI biomarkers (CD105, troponin I and P-ERK) were decreased, potentially to rescue eNOS production to maintain normal cellular function. This discovery of CD105 and SGLT2 increase in mechanically stretched cardiomyocytes suggests that SGLT2 may conceive a novel role in direct or indirect sensing of mechanical stretch, prompting the possibility of an in vitro cardiac overloaded cell model, an alternative to animal heart model., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.) more...- Published
- 2024
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8. Risk factors for surgical site infection after closed proximal humerus fractures.
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Li M, Sun GC, Cui J, and Lou QL
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- Humans, Male, Female, Risk Factors, Retrospective Studies, Middle Aged, Aged, Adult, Aged, 80 and over, Incidence, Fractures, Closed surgery, Surgical Wound Infection epidemiology, Surgical Wound Infection etiology, Shoulder Fractures surgery, Fracture Fixation, Internal adverse effects, Fracture Fixation, Internal methods
- Abstract
Proximal humerus fractures are common in clinical practice, and there are relatively a few studies on postoperative incision infections of such fractures. The purpose of this study was to explore the risk factors for surgical site infection (SSI) after internal fixation in patients with closed proximal humerus fractures. Patients with closed proximal humerus fractures who underwent surgery from January 2016 to January 2022 were retrospectively analysed. Cases with superficial or deep infections within 3 months after surgery were in the infection group and the remaining cases were in the non-infection group. The types of pathogenic bacteria in the infection group were analysed. The potential risk factors for SSI in all patients were recorded: (1) patient-related factors: gender, age, body mass index (BMI), smoking, comorbidities; (2) trauma-related factors: mechanism of injury, Injury Severity Score, visual analogue scale, fracture type, soft tissue condition and combined dislocation; (3) laboratory-related indexes: haemoglobin, albumin; (4) surgery-related factors: time from injury to surgery, American Society of Anesthesiologists anaesthesia classification, surgical time, fixation mode, intraoperative blood loss, suture method, bone graft and postoperative drainage. The risk factors for the occurrence of SSI were analysed using univariate analysis and multivariate logistic regression. The incidence of SSI was 15.7%. The most common bacterium in the infection group was Staphylococcus aureus. High BMI (p = 0.033), smoking (p = 0.030), an increase in mean time from injury to definitive surgery (p = 0.013), and prolonged surgical time (p = 0.044) were independent risk factors for the development of SSI after closed proximal humeral fractures. In patients with closed proximal humerus fractures, weight loss, perioperative smoking cessation, avoidance of delayed surgery, and shorter surgical time may be beneficial in reducing the incidence of SSI., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.) more...
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- 2024
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9. Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori -infected patients.
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Wang LH, Su BB, Wang SS, Sun GC, Lv KM, Li Y, Shi H, and Chen QQ
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- Humans, Immunoglobulin G, Food Intolerance complications, Retrospective Studies, Esophagitis, Peptic pathology, Helicobacter pylori, Metabolic Syndrome epidemiology, Metabolic Syndrome complications, Helicobacter Infections complications, Helicobacter Infections epidemiology, Helicobacter Infections diagnosis
- Abstract
Background: Reflux esophagitis has an increasing prevalence and complex and diverse symptoms. Identifying its risk factors is crucial to understanding the etiology, prevention, and management of the disease. The occurrence of reflux esophagitis may be associated with food reactions, Helicobacter pylori ( H. pylori ) infection, and metabolic syndromes., Aim: To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin (Ig) G-mediated food intolerance, H. pylori infection, and metabolic syndrome on reflux esophagitis., Methods: Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled. The patients' basic information, test results, gastroscopy results, H. pylori test results, and IgG-mediated food intolerance results were collected. Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis. Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H. pylori infection affecting reflux esophagitis., Results: A total of 7954 outpatients were included; the prevalence of reflux esophagitis, IgG-mediated food intolerance, H. pylori infection, and metabolic syndrome were 20.84%, 61.77%, 35.91%, and 60.15%, respectively. Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance (OR = 1.688, 95%CI: 1.497-1.903, P < 0.00001) and metabolic syndrome (OR = 1.165, 95%CI: 1.030-1.317, P = 0.01484), and the independent protective factor for reflux esophagitis was H. pylori infection (OR = 0.400, 95%CI: 0.351-0.456, P < 0.00001). IgG-mediated food intolerance had a partially positive mediating effect on H. pylori infection as it was associated with reduced occurrence of reflux esophagitis ( P = 0.0200). Metabolic syndrome had a partially negative mediating effect on H. pylori infection and reduced the occurrence of reflux esophagitis ( P = 0.0220)., Conclusion: Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis, while patients with H. pylori infection were at lower risk. IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H. pylori infection; however, metabolic syndrome increased the risk of patients with H. pylori infection developing reflux esophagitis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.) more...
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- 2024
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10. Microglial activation and toll-like receptor 4-Dependent regulation of angiotensin II type I receptor-mu-opioid receptor 1 heterodimerization and hypertension in fructose-fed rats.
- Author
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Ho CY, Sun GC, Lin YT, Wong TY, Hsiao M, Tseng CJ, and Cheng PW
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- Rats, Animals, Microglia metabolism, Toll-Like Receptor 4 metabolism, Nitric Oxide metabolism, Receptors, Opioid metabolism, Fructose, Neuroinflammatory Diseases, Blood Pressure, Receptor, Angiotensin, Type 1 metabolism, Polyesters, Solitary Nucleus, Angiotensin II pharmacology, Hypertension
- Abstract
Our previous study reported that the heterodimer of Angiotensin II Type I Receptor (AT1R) and Mu-Opioid Receptor 1 (MOR1) involves Nitric Oxide (NO) reduction which leads to elevation of blood pressure. Secondly, we showed that Toll-like Receptor 4 (TLR4) may be involved in the heterodimerization of AT1R and MOR1 in the brainstem Nucleus Tractus Solitarii (NTS), which regulates systemic blood pressure and gastric nitric oxide through the insulin pathway. Here, we investigated the role of microglial activation and TLR4 in the heterodimerization of AT1R and MOR1. Hypertensive rats were established after four weeks of fructose consumption. SBP of rats was measured using non-invasive blood pressure method. PLA technique was utilized to determine protein-protein interaction in the nucleus tractus solitarii. Results showed that the level of MOR-1 and AT1R was induced significantly in the fructose group compared with control. PLA signal potentially showed that AT1R and MOR1 were formed in the nucleus tractus solitarii after fructose consumption. Meanwhile, the innate immune cell in the CNS microglia was observed in the nucleus tractus solitarii using biomarkers and was activated. TLR4 inhibitor CLI-095, was administered to animals to suppress the neuroinflammation and microglial activation. CLI-095 treatment reduced the heterodimer formation of AT1R and MOR1 and restored nitric oxide production in the nucleus tractus solitarii. These findings imply that TLR4-primed neuroinflammation involves formation of heterodimers AT1R and MOR1 in the nucleus tractus solitarii which leads to increase in systemic blood pressure., Competing Interests: Declaration of competing interest The authors hereby declare that they have no competing interests pertaining to the publication of this research. This encompasses financial, professional, or personal interests that might have influenced the performance or presentation of the work described in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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11. [Surgical progress of anterior cruciate ligament injury].
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Ouyang YL and Sun GC
- Subjects
- Humans, Knee Joint surgery, Anterior Cruciate Ligament surgery, Anterior Cruciate Ligament Injuries surgery
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- 2023
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12. Attenuation of epithelial-mesenchymal transition via SGLT2 inhibition and diabetic cataract suppression by dapagliflozin nanoparticles treatment.
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Chen YY, Chen CK, Wu TT, Ho CY, Yeh TC, Sun GC, Tseng CJ, and Cheng PW
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- Animals, Rats, Cadherins metabolism, Diabetes Mellitus metabolism, Lens, Crystalline metabolism, Rats, Sprague-Dawley, Sodium-Glucose Transporter 2 metabolism, Cataract drug therapy, Cataract metabolism, Diabetes Complications drug therapy, Diabetes Complications metabolism, Epithelial-Mesenchymal Transition, Sodium-Glucose Transporter 2 Inhibitors pharmacology
- Abstract
Aims: Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects., Main Methods: SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats., Key Findings: In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution., Significance: Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts., Competing Interests: Declaration of competing interest The authors declared no competing financial interest., (Copyright © 2023. Published by Elsevier Inc.) more...
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- 2023
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13. Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors.
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Ou SY, Lee YJ, Chou YM, Sun GC, and Chia YY
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- Humans, Lactic Acid, Survivors, Hyperlactatemia epidemiology, Hyperlactatemia complications, Brain Ischemia complications, Stroke complications, Sepsis complications, Sepsis epidemiology, Myocardial Infarction complications, Kidney Failure, Chronic complications, Ischemic Stroke complications
- Abstract
Introduction: Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors., Methods: In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease., Results: After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups., Conclusion: We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses. more...
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- 2023
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14. [Long-term outcomes of lateral femoral notch after early anterior cruciate ligament reconstruction].
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Li M, Cao W, Cui J, Lou QL, and Sun GC
- Subjects
- Male, Female, Humans, Young Adult, Adult, Adolescent, Middle Aged, Retrospective Studies, Magnetic Resonance Imaging, Femur surgery, Treatment Outcome, Knee Joint diagnostic imaging, Knee Joint surgery, Anterior Cruciate Ligament Injuries surgery, Anterior Cruciate Ligament Reconstruction
- Abstract
Objective: To investigate the outcome of lateral femoral notch (LFN) after early anterior cruciate ligament (ACL) reconstruction and evaluate the recovery of knee joint function after the operation., Methods: The clinical data of 32 patients who underwent early ACL reconstruction from December 2015 to December 2019 were retrospectively analyzed. The study included 18 males and 14 females, aged 16 to 54 years old, with an average age of (25.39±2.82) years. The body mass index (BMI) of the patients ranged from 20 to 30 kg/cm2, with an average of (26.15±3.09) kg/cm
2 . Among them, 6 cases were caused by traffic accidents, 19 by exercise, and 7 by the crush of heavy objects. MRI of all patients showed LFN depth was more than 1.5 mm after injury, and no intervention for LFN was performed during surgery. Preoperative and postoperative depth, area, and volume of LFN defects were observed by MRI data. International Cartilage Repair Society (ICRS) score, Lysholm score, Tegner activity levels, and knee injury and osteoarthritis outcome score (KOOS) were analyzed before and after the operation., Results: All patients were followed up from 2 to 6 years with an average of (3.28±1.12) years. There was no significant difference in the defect depth of LFN from (2.31±0.67) mm before the operation to (2.53±0.50) mm at follow-up ( P =0.136). The defect area of LFN was decreased from (207.55±81.01)mm2 to (171.36±52.69)mm2 ( P =0.038), and the defect volume of LFN was decreased from (426.32±176.54) mm3 to (340.86±151.54)mm3 ( P =0.042). The ICRS score increased from (1.51±0.34) to (2.92±0.33) ( P <0.001), the Lysholm score increased from (35.37±10.54) to (94.46±8.45) ( P <0.001), and the Tegner motor score increased from (3.45±0.94) to (7.56±1.28), which was significantly higher than that of the preoperative data ( P <0.001). The KOOS score of the final follow-up was 90.42±16.35., Conclusion: With the increase of recovery time after anterior cruciate ligament reconstruction, the defect area and volume of LFN decreased gradually, but the defect depth remained unchanged. The knee joint function of the patients significantly improved. The cartilage of the LFN defect improved, but the repair effect was not good. more...- Published
- 2023
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15. The transfrontal isthmus approach for insular glioma surgery.
- Author
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Sun GC, Shu XJ, Zheng XQ, Ma XD, Cheng G, Liu JL, Chen L, and Zhang JN
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- Male, Humans, Female, Adult, Treatment Outcome, Cerebral Cortex diagnostic imaging, Cerebral Cortex surgery, Cerebral Cortex pathology, Neurosurgical Procedures methods, Middle Cerebral Artery, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Brain Neoplasms pathology, Glioma diagnostic imaging, Glioma surgery, Glioma pathology
- Abstract
Objective: The classic transopercular or transsylvian approach to insular gliomas removes the tumor laterally through the insular cortex. This study describes a new anteroposterior approach through the frontal isthmus for insular glioma surgery., Methods: The authors detailed the surgical techniques for resection of insular gliomas through the transfrontal isthmus approach. Fifty-nine insular gliomas with at least Berger-Sanai zone I involvement were removed with the new approach, and extent of resection and postoperative neurological outcomes were assessed., Results: Fifty-nine patients were enrolled in the study, including 35 men and 24 women, with a mean (range) age 44.3 (19-75) years. According to the Berger-Sanai classification system, the most common tumor was a giant glioma (67.8%), followed by involvement of zones I and IV (18.6%). Twenty-two cases were Yaşargil type 3A/B, and 37 cases were Yaşargil type 5A/B. The average angle between the lateral plane of the putamen and sagittal line was 33.53°, and the average width of the isthmus near the anterior insular point was 33.33 mm. The average angle between the lateral plane of the putamen and the sagittal line was positively correlated with the width of the isthmus near the anterior insular point (r = 0.935, p < 0.0001). The median (interquartile range [IQR]) preoperative tumor volume was 67.82 (57.64-92.19) cm3. Of 39 low-grade gliomas, 26 (66.67%) were totally resected; of 20 high-grade gliomas, 19 (95%) were totally resected. The median (IQR) extent of resection of the whole group was 100% (73.7%-100%). Intraoperative diffusion-weighted imaging showed no cases of middle cerebral artery- or lenticulostriate artery-related stroke. Extent of insular tumor resection was positively correlated with the angle of the lateral plane of the putamen and sagittal line (r = -0.329, p = 0.011) and the width of the isthmus near the anterior insular point (r = -0.267, p = 0.041). At 3 months postoperatively, muscle strength grade exceeded 4 in all cases, and all patients exhibited essentially normal speech. The median (IQR) Karnofsky performance score at 3 months after surgery was 90 (80-90)., Conclusions: The transfrontal isthmus approach changes the working angle from lateral-medial to anterior-posterior, allowing for maximal safe removal of insular gliomas. more...
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- 2022
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16. Reading beyond quantitative electroencephalography-based indices: a case of erroneously high entropy values during ophthalmic surgery.
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Wu YS, Chen PN, Sun GC, Cheng KI, and Wu ZF
- Subjects
- Entropy, Humans, Electroencephalography, Reading
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- 2022
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17. The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea .
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Li L, Yu MX, Guo J, Hao ZN, Zhang Z, Lu ZQ, Wang JY, Zhu XM, Wang YL, Chen J, Sun GC, and Lin FC
- Abstract
Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea . The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δ bcpex8 , Δ bcpex10 , and Δ bcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δ bcpex8 , Δ bcpex10 , and Δ bcpex12 strains. The mycelial growth rates of Δ bcpex8 , Δ bcpex10 , and Δ bcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δ bcpex8 , Δ bcpex10 , and Δ bcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8 , BcPEX10 , and BcPEX12 are indispensable for the development and pathogenicity of B . cinerea ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yu, Guo, Hao, Zhang, Lu, Wang, Zhu, Wang, Chen, Sun and Lin.) more...
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- 2022
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18. Deep Learning model-based approach for preoperative prediction of Ki67 labeling index status in a noninvasive way using magnetic resonance images: A single-center study.
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Shu XJ, Chang H, Wang Q, Chen WG, Zhao K, Li BY, Sun GC, Chen SB, and Xu BN
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- Humans, Ki-67 Antigen, Magnetic Resonance Imaging methods, Retrospective Studies, Adenoma pathology, Deep Learning, Pituitary Neoplasms diagnostic imaging, Pituitary Neoplasms pathology, Pituitary Neoplasms surgery
- Abstract
Objectives: Ki67 is an important biomarker of pituitary adenoma (PA) aggressiveness. In this study, PA invasion of surrounding structures is investigated and deep learning (DL) models are established for preoperative prediction of Ki67 labeling index (Ki67LI) status using conventional magnetic resonance (MR) images., Methods: We reviewed 362 consecutive patients with PAs who underwent endoscopic transsphenoidal surgery, of which 246 patients with primary PA are selected for PA invasion analysis. MRI data from 234 of these PA patients are collected to develop DL models to predict Ki67LI status, and DL models were tested on 27 PA patients in the clinical setting., Results: PA invasion is observed in 46.8% of cases in the Ki67 ≥ 3% group and 33.3% of cases in the Ki67 < 3% group. Three deep-learning models are developed using contrast-enhanced T1-weighted images (ceT1WI), T2-weighted images (T2WI), and multimodal images (ceT1WI+T2WI), respectively. On the validation dataset, the prediction accuracy of the ceT1WI model, T2WI model, and multimodal model were 87.4%, 89.4%, and 89.2%, respectively. In the clinical test, 27 MR slices with the largest tumors from 27 PA patients were tested using the ceT1WI model, T2WI model, and multimodal model, the average accuracy of Ki67LI status prediction was 63%, 77.8%, and 70.4%, respectively., Conclusion: Preoperative prediction of PA Ki67LI status in a noninvasive way was realized with the DL model by using MRI. T2WI model outperformed the ceT1WI model and multimodal model. This end-to-end model-based approach only requires a single slice of T2WI to predict Ki67LI status and provides a new tool to help clinicians make better PA treatment decisions., (Copyright © 2022 Elsevier B.V. All rights reserved.) more...
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- 2022
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19. Blocking of SGLT2 to Eliminate NADPH-Induced Oxidative Stress in Lenses of Animals with Fructose-Induced Diabetes Mellitus.
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Chen YY, Wu TT, Ho CY, Yeh TC, Sun GC, Tseng CJ, and Cheng PW
- Subjects
- Animals, Fructose adverse effects, NADP metabolism, NADPH Oxidases metabolism, Oxidative Stress, Reactive Oxygen Species metabolism, Receptor for Advanced Glycation End Products metabolism, Resveratrol pharmacology, Sodium-Glucose Transporter 2 metabolism, Cataract, Diabetes Mellitus, Metformin pharmacology
- Abstract
Chronic hyperglycemia triggers an abnormal rise in reactive oxygen species (ROS) that leads to blindness in patients with diabetes mellitus (DM) and cataracts. In this study, the effects of dapagliflozin, metformin and resveratrol on ROS production were investigated in lens epithelial cells (LECs) of animals with fructose-induced DM. LECs were isolated from patients without DM, or with DM devoid of diabetic retinopathy. Animals were treated with 10% fructose for 8 weeks to induce DM, which was verified by monitoring blood pressure and serum parameters. For drug treatments, 1.2 mg/day of dapagliflozin was given for 2 weeks, 500 mg/kg/day of metformin was given, and 10 mg/kg/day of resveratrol was given. Dihydroethidium was used to stain endogenous O
2 ˙- production in vivo of the LECs. Superoxide production was expressed in the cataract of DM, or patients without DM. Sodium-glucose cotransporter 2 (SGLT2), glucose transporter 1 (GLUT1), GLUT5, the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47/p67-phox, NOX4 and RAGE were significantly increased in LECs with DM. In addition, the dapagliflozin treatment reduced GLUT5, p47/p67-phox, NADPH oxidase 4 (NOX4) and receptor for advanced glycation end products (RAGE) expressions. On the contrary, metformin or resveratrol inhibited p47-phox, GLUT5, and SGLT2 expressions, but not nuclear factor erythroid 2-related factor 2 (NRF2). In summary, dapagliflozin, metformin or resveratrol down-regulated p47-phox expression through SGLT2 inactivation and ROS reduction. These important findings imply that SGLT2 can be blocked to ameliorate oxidative stress in the cataracts of DM patients. more...- Published
- 2022
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20. Resection of Insular Glioma Through the Transfrontal Limiting Sulcus Approach.
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Sun GC, Zhao K, Shu XJ, Liu RY, Dong MX, Chen XL, and Xu BN
- Subjects
- Cerebral Cortex surgery, Humans, Neurosurgical Procedures methods, Treatment Outcome, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Brain Neoplasms surgery, Glioma pathology, Glioma surgery
- Abstract
Background: The current transsylvian or transopercular approaches make access difficult because of the limited exposure of insular tumors. Hence, maximal and safe removal of insular gliomas is challenging. In this article, a new approach to resect insular gliomas is presented., Objective: To determine whether the new transfrontal limiting sulcus approach is helpful for maximal and safe removal of insular gliomas., Methods: The authors reported surgical techniques for insular gliomas resected through the transfrontal limiting sulcus approach. The authors evaluated the surgical resections of 69 insular gliomas performed through the new approach in their department. The extents of resection and postoperative neurological outcomes were analyzed to determine the value of this new approach., Results: Based on the Berger-Sanai classification, most insular gliomas were giant tumors (59.42%), followed by zone I + IV tumors (24.64%). The median (interquartile range) extent of resection of all patients was 100% (91%, 100%). The total resection rate for all gliomas was (55 of 69, 79.7%), and the total resection rate for low-grade gliomas was (28 of 40, 70%), which was significantly lower than that for high-grade gliomas (27 of 29, 93.1%) (P = .019). All patients had muscle strength greater than grade 4 3 months after surgery. Only 1 patient had a speech disorder 3 months after surgery. The median Karnofsky Performance Status score at the time of the 3-month follow-up was 90., Conclusion: The transfrontal limiting sulcus approach can help to achieve maximal and safe removal of insular gliomas., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.) more...
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- 2022
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21. [Feasibility study on local infiltration anesthesia for postoperative analgesia in patients with hallux valgus].
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Kong DH, Zhao YJ, Guan GF, Deng MM, Yin G, and Sun GC
- Subjects
- Adult, Aged, Aged, 80 and over, Anesthesia, Local, Feasibility Studies, Female, Humans, Male, Middle Aged, Pain, Postoperative drug therapy, Young Adult, Analgesia, Bunion, Hallux Valgus surgery
- Abstract
Objective: To evaluate the clinical efficacy of local infiltration anesthesia of ropivacaine combined with compound betamethasone for postoperative analgesia in patients with hallux valgus., Methods: From September 2019 to December 2020, 48 patients with hallux valgus were treated surgically. According to different postoperative analgesia methods, the patients were divided into combined local infiltration group and intravenous analgesia pump group. There were 24 cases, in the combined local infiltration group including 2 males and 22 females;the age ranged from 21 to 78 years old, with an average of (58.3±7.7) years old;soft tissue release and chevron osteotomy were performed in 15 cases and metatarsophalangeal joint fusion in 9 cases;immediately after operation, 20 ml of ropivacaine combined with compound betamethasone mixed diluent was used for local infiltration anesthesia once. There were 24 patients in intravenous analgesia pump group, including 3 males and 21 females;the age ranged from 23 to 81 years old, with an average of(56.8±8.3) years old;soft tissue release and Chevron osteotomy were performed in 17 cases and metatarsophalangeal joint fusion in 7 cases;immediately after operation, intravenous analgesia pump was used for analgesia. The basic flow was 2 ml / h;the self control dose was 0.5 ml;and the locking time was 15 min. Visual analogue scale (VAS) was recorded at 12, 24, 48 and 72 hours after operation;and the VAS was recorded at 24 hours after operation. The occurrence of adverse drug reactions at 0 to 12 hours, 12 to 24 hours and 24 to 48 hours after operation were recorded;and the healing of incision was recorded., Results: All patients were followed up, and the duration ranged from 14 to 17 days, with a mean of (14.60±0.92) days. There was significantdifference in VAS at 12, 24 and 48 hours between the combined local infiltration group and the intravenous analgesia pump group( P <0.05). There was no significant difference in VAS between the two groups 72 hours after operation ( P >0.05). There was no significant difference in the number of adverse drug reactions between the two groups at 0 to 12 hours after operation ( P >0.05);there was significant difference in the number of adverse drug reactions 12 to 24 hours after operation ( P <0.05). No adverse drug reactions occurred in both groups 24 to 48 hours after operation. There was no significant difference in the grade of knife edge healing between the two groups after suture removal ( P >0.05)., Conclusion: Compared with intravenous analgesia pump group, ropivacaine combined with compound betamethasone can significantly reduce postoperative wound pain without increasing adverse drug reactions, and does not increase wound infection. more...
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- 2021
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22. Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction.
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Cheng PW, Wu YC, Wong TY, Sun GC, and Tseng CJ
- Abstract
Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)
S9 /p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3βS9 was directly bound to p-TauS396 . In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect. more...- Published
- 2021
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23. μ-Opioid Receptor-Mediated AT1R-TLR4 Crosstalk Promotes Microglial Activation to Modulate Blood Pressure Control in the Central Nervous System.
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Sun GC, Tse J, Hsu YH, Ho CY, Tseng CJ, and Cheng PW
- Abstract
Opioids, a kind of peptide hormone involved in the development of hypertension, cause systemic and cerebral inflammation, and affects regions of the brain that are important for blood pressure (BP) control. A cause-and-effect relationship exists between hypertension and inflammation; however, the role of blood pressure in cerebral inflammation is not clear. Evidence showed that AT1R and μOR heterodimers' formation in the NTS might lead to the progression of hypertension. In this study, we investigated the formation of the μOR/AT1R heterodimer, determined its correlation with μORs level in the NTS, and explored the role of TLR4-dependent inflammation in the development of hypertension. Results showed that Ang II increased superoxide and Iba-1 (microgliosis marker: ionized calcium-binding adaptor molecule (1) levels in the NTS of spontaneously hypertensive rats (SHRs). The AT1R II inhibitor, losartan, significantly decreased BP and abolished superoxide, Iba-1, TLR4 expression induced by Ang II. Furthermore, losartan significantly increased nNsOS
S1416 phosphorylation. Administration of a μOR agonist or antagonist in the NTS of WKY and SHRs increased endogenous μ-opioids, triggered the formation of μOR/AT1R heterodimers and the TLR4-dependent inflammatory pathway, and attenuated the effect of depressor nitric oxide (NO). These results imply an important link between neurotoxicity and superoxides wherein abnormal increases in NTS endogenous μ-opioids promote the interaction between Ang II and μOR, the binding of Ang II to AT1R, and the activation of microglia. In addition, the interaction between Ang II and μOR enhanced the formation of the AT1R and μOR heterodimers, and inactivated nNOS-derived NO, leading to the development of progressive hypertension. more...- Published
- 2021
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24. Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition.
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Li JJ, Liang Q, and Sun GC
- Subjects
- Epithelial-Mesenchymal Transition, Humans, Medicine, Chinese Traditional, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Epithelial-mesenchymal transition (EMT), which endows epithelial cells with mesenchymal properties, plays an important role in the early stages of metastasis. Conventional cancer therapies have promising effects, but issues remain, such as high rates of metastasis and drug resistance. Thus, exploring and evaluating new therapies is an urgent need. Traditional Chinese medicines (TCMs) have been acknowledged for their multi-target and coordinated intervention effects against HCC. Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC. However, studies on the effects of TCM on EMT in HCC are scarce. In this review, we summarized recent developments in anti-EMT TCMs and formulae, focusing on their underlying pharmacological mechanisms, to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2021
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25. MAT Loci Play Crucial Roles in Sexual Development but Are Dispensable for Asexual Reproduction and Pathogenicity in Rice Blast Fungus Magnaporthe oryzae .
- Author
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Wang JY, Wang SZ, Zhang Z, Hao ZN, Shi XX, Li L, Zhu XM, Qiu HP, Chai RY, Wang YL, Li L, Liu XH, Feng XX, Sun GC, and Lin FC
- Abstract
Magnaporthe oryzae , a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae . Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1 , MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus. more...
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- 2021
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26. Exercise prevents the impairment of learning and memory in prenatally phthalate-exposed male rats by improving the expression of plasticity-related proteins.
- Author
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Sun GC, Lee YJ, Lee YC, Yu HF, and Wang DC
- Subjects
- Age Factors, Animals, Cognitive Dysfunction metabolism, Cognitive Dysfunction physiopathology, Female, Male, Pregnancy, Prenatal Exposure Delayed Effects metabolism, Prenatal Exposure Delayed Effects physiopathology, Rats, Rats, Sprague-Dawley, Spatial Learning physiology, Spatial Memory physiology, Behavior, Animal physiology, Cognitive Dysfunction chemically induced, Cognitive Dysfunction prevention & control, Endocrine Disruptors adverse effects, Neuronal Plasticity physiology, Phthalic Acids adverse effects, Physical Conditioning, Animal physiology, Prenatal Exposure Delayed Effects chemically induced, Prenatal Exposure Delayed Effects prevention & control
- Abstract
Regular exercise has been identified to facilitate neuroplasticity that maximize functional outcome after brain injuries. Brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity after exercise. The activity-regulated cytoskeleton associated protein (Arc) is induced by BDNF and N-methyl-d-aspartic acid receptor (NMDAR), contributing to functional modification of neuroplasticity in the hippocampus. Meanwhile, early-life exposure to neuroendocrine disruptor di-(2-ethylhexyl)-phthalate (DEHP) is a risk factor for behavioral deficits, but the mechanisms responsible for DEHP-induced neurotoxicity are not well understood. The purpose of this study is to investigate whether hippocampal Arc expression is impaired by DEHP exposure and to examine the protective role of exercise in the prenatally DEHP-exposed male rats. Sprague Dawley dams were fed with vehicle or DEHP during gestation. The male offspring were trained to treadmill running for 5 weeks followed by examination of behavioral and biochemical outcomes. The results showed that DEHP-exposed rats exhibited impairment of spatial learning and memory as well as down-regulations of BDNF, NMDAR, Arc, and synaptophysin. Importantly, aerobic exercise during childhood-adolescence prevented the impairment of learning and memory by recovering the expressions of BDNF, NMDAR, Arc, and synaptophysin. These findings suggest that exercise may provide beneficial effects on ameliorating the impairment of neuroplasticity in the prenatally DEHP-exposed male rats at late adolescence., (Copyright © 2021 Elsevier B.V. All rights reserved.) more...
- Published
- 2021
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27. [ANXA8 Regulates Proliferation of Human Non-Small Lung Cancer Cells A549 via EGFR-AKT-mTOR Signaling Pathway].
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Zhou GZ, Sun YH, Shi YY, Zhang Q, Zhang L, Cui LQ, and Sun GC
- Subjects
- A549 Cells, Annexins genetics, Annexins metabolism, Cell Proliferation genetics, ErbB Receptors genetics, Humans, Signal Transduction, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Annexins physiology, Lung Neoplasms genetics, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Annexin A8 (ANXA8) is a member of the annexin family, which had been reported to regulate multiple cancer cellular processes including proliferation, metastasis and inflammation. However, the specific role of ANXA8 in lung cancer cell biology remains unknown. Our previous transcriptome study revealed that ANXA8 mRNA was downregulated in curcumin analog (MHMD) -treated human non-small lung cancer cells (A549 cell line). Here, we continued to study the ANXA8 expression in A549 cells using reverse transcription-quantitative PCR and Western blotting, compared with that in human normal bronchial epithelium cells (BE-AS-2B cell line). Overexpression of ANXA8 via transfection of pEGFP-ANXA8 recombinant vector contributed to the proliferation and migration of A549 cells. Moreover, the cell cycle protein cyclin E1 was upregulated in ANXA8-transfected A549 cells. Knockdown of ANXA8 using an RNA interference technique decreased A549 cell viability and restrained their migration in vitro. The expression levels of multiple cellular factors, including EGFR, PI3K, Akt, mTOR, p70S6K and 4EBP1, in the epidermal growth factor receptor (EGFR) signaling pathway were also altered by ANXA8 knockdown or overexpression in A549 cells, which confirmed the activation of the EGFR/Akt/mTOR signaling pathway by ANXA8. The present results provided evidence to support further investigation of the functional identification of ANXA8 in lung cancer cells in the future. more...
- Published
- 2021
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28. 3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus.
- Author
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Wu TT, Chen YY, Ho CY, Yeh TC, Sun GC, Tseng CJ, and Cheng PW
- Abstract
Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPK
T172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPKT172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM. more...- Published
- 2021
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29. Identification of risk factors for poor language outcome in surgical resection of glioma involving the arcuate fasciculus: an observational study.
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Li FY, Liu HY, Zhang J, Sun ZH, Zhang JS, Sun GC, Yu XG, Chen XL, and Xu BN
- Abstract
The arcuate fasciculus is a critical component of the neural substrate of human language function. Surgical resection of glioma adjacent to the arcuate fasciculus likely damages this region. In this study, we evaluated the outcome of surgical resection of glioma adjacent to the arcuate fasciculus under the guidance of magnetic resonance imaging and diffusion tensor imaging, and we aimed to identify the risk factors for postoperative linguistic deficit. In total, 54 patients with primary glioma adjacent to the arcuate fasciculus were included in this observational study. These patients comprised 38 men and 16 women (aged 43 ± 11 years). All patients underwent surgical resenction of glioma under the guidance of magnetic resonance imaging and diffusion tensor imaging. Intraoperative images were updated when necessary for further resection. The gross total resection rate of the 54 patients increased from 38.9% to 70.4% by intraoperative magnetic resonance imaging. Preoperative language function and glioma-to-arcuate fasciculus distance were associated with poor language outcome. Multivariable logistic regression analyses showed that glioma-to-arcuate fasciculus distance was the major independent risk factor for poor outcome. The cutoff point of glioma-to-arcuate fasciculus distance for poor outcome was 3.2 mm. These findings suggest that intraoperative magnetic resonance imaging combined with diffusion tensor imaging of the arcuate fasciculus can help optimize tumor resection and result in the least damage to the arcuate fasciculus. Notably, glioma-to-arcuate fasciculus distance is a key independent risk factor for poor postoperative language outcome. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. S2014-096-01) on October 11, 2014., Competing Interests: None more...
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- 2021
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30. [Role of systematic integration teaching reform at the basic medicine teaching stage in Chinese medical education system].
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Zhu L, Sun GC, and Guan YF
- Subjects
- Asian People, China, Curriculum, Humans, Education, Medical, Medicine
- Abstract
Systematic integration teaching is a curriculum system focusing on organs and systems, which is an important direction of medical education reform in China. Based on the practice of integrated curriculum teaching in Dalian Medical University for more than 10 years, combined with the experience in 15 medical colleges and universities in China, this paper analyzed the modes of systematic integrated teaching at the basic medicine teaching stage for medical higher education, and specified the purpose and significance of this teaching reform. The results showed that: (1) The systematic integrated teaching is a well-accepted and widely used teaching mode in domestic medical colleges and universities, which mainly includes three types of methodologies, i.e., integration of basic medicine courses, integration of clinical medicine courses and integration of basic and clinical medicine courses. The systematic integrated teaching is carried out by reforming various teaching methods including problem-based learning (PBL), case-based learning (CBL) and team-based learning (TBL). (2) The systematic integration teaching at the basic medicine teaching stage can significantly optimize the transition between basic and clinical courses, promote the cooperation and exchange between basic and clinical teachers, and improve the medical students' knowledge construction and critical thinking, and teachers' teaching ability as well. (3) The systematic integration teaching concept of "Six focuses" and "Five combinations" effectively guides the design and implementation of the integrated curriculum at the basic medical teaching stage of Dalian Medical University. With the deepening and development of medical education system reform in China, giving full play to the respective advantages of the systematic integrated teaching and traditional single-subject teaching at the basic medicine stage, and strengthening the integration of basic and clinical courses will play an important role in optimizing medical education curriculum system with Chinese characteristics. more...
- Published
- 2020
31. TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression.
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Zhang LH, Yin YH, Chen HZ, Feng SY, Liu JL, Chen L, Fu WL, Sun GC, Yu XG, and Xu DG
- Subjects
- Carrier Proteins, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Neoplastic Stem Cells, SOXB1 Transcription Factors genetics, Brain Neoplasms genetics, Glioblastoma genetics
- Abstract
Background: Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of tripartite motif-containing 24 (TRIM24) in GSCs., Methods: Immunofluorescence, flow cytometry, and western blot analyses were used to evaluate TRIM24 and cluster of differentiation (CD)133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients' tumors, as measured by both immunohistochemistry and western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion, and xenograft immunohistochemistry were conducted to determine GBM cell invasion., Results: We identified that TRIM24 was coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2 weighted image abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, western blot, and immunohistochemistry demonstrated that TRIM24 activated the expression of the pluripotency transcription factor sex determining region Y-box 2 (Sox2) to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and Sox2 was validated by testing samples enrolled in our study and exploring external databases., Conclusions: Our findings uncover essential roles of the TRIM24-Sox2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...
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- 2020
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32. Antiproliferative effect and autophagy induction of curcumin derivative ZYX02-Na on the human lung cancer cells A549.
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Zhou GZ, Guo SS, Liu DX, Zhang L, and Sun GC
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- A549 Cells, Cell Survival drug effects, Humans, Antineoplastic Agents pharmacology, Autophagy drug effects, Cell Proliferation drug effects
- Abstract
At present, a large number of curcumin derivatives had been produced and identified aiming to replace the curcumin in view of its low bioavailability and stability. Here, a novel curcumin derivative ZYX02-Na was first used to reduce the cell viability of human non-small cell lung cells A549, which was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and Western blot analysis showed that ZYX02-Na could lead to cell cycle arrest in G0/G1 phase, which demonstrated that ZYX02-Na inhibited the proliferation of A549 cells. Furthermore, the AMPK/mTOR/4E-BP1 signaling pathway was activated in ZYX02-Na-treated A549 cells. Besides, wounding healing and transwell experiments showed that ZYX02-Na could also inhibited the migration ability of A549 cells. Moreover, we also found that ZYX02-Na could induce autophagy of A549 cells by acridine orange staining, GFP-LC3 subcellular localization observation and Western blotting analysis, respectively. In short, our current studies indicated that ZYX02-Na possessed the antiproliferation effect and autophagy induction on A549 cells, while in vivo anticancer study of ZYX02-Na needs to be done in future., (© 2020 Wiley Periodicals LLC.) more...
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- 2020
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33. Mechanism of a methylxanthine drug theophylline-induced Ca 2+ signaling and cytotoxicity in AML12 mouse hepatocytes.
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Sun GC and Liang WZ
- Abstract
Theophylline is a methylxanthine drug used in therapy for respiratory diseases. However, the impact of theophylline on Ca
2+ signaling has not been explored in liver cells. This study examined whether theophylline affected Ca2+ homeostasis and its related cytotoxicity in AML12 mouse hepatocytes. Cell viability was measured by the cell viability reagent (WST-1). Cytosolic Ca2+ concentration ([Ca2+ ]i ) was measured by the Ca2+ -sensitive fluorescent dye fura-2. Theophylline (25-125 μM) induced [Ca2+ ]i rises and cause cytotoxicity in AML12 cells. This cytotoxic response was reversed by chelation of cytosolic Ca2+ with BAPTA/AM. In Ca2+ -free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished theophylline-induced [Ca2+ ]i rises. Conversely, treatment with theophylline also abolished thapsigargin-induced [Ca2+ ]i rises. However, inhibition of PLC failed to alter theophylline-evoked [Ca2+ ]i rises. In Ca2+ -containing medium, modulators of store-operated Ca2+ channels inhibited 30% of the [Ca2+ ]i rises, whereas the PKC modulators had no effect. Furthermore, theophylline-induced Ca2+ influx was confirmed by Mn2+ -induced quench of fura-2 fluorescence. Together, in AML12 cells, theophylline caused Ca2+ -associated cytotoxicity and induced Ca2+ entry through PLC-independent Ca2+ release from the endoplasmic reticulum and PKC-insensitive store-operated Ca2+ channels. BAPTA-AM with its protective effects may be a potential compound for prevention of theophylline-induced cytotoxicity., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) more...- Published
- 2020
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34. Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) promotes glioblastoma multiforme progression via regulating miR-1301-3p/TMBIM6 axis.
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Jin Z, Piao LH, Sun GC, Lv CX, Jing Y, and Jin RH
- Subjects
- Animals, Apoptosis Regulatory Proteins genetics, Cell Line, Central Nervous System Neoplasms pathology, Glioblastoma pathology, Humans, Male, Membrane Proteins genetics, Mice, Mice, Nude, MicroRNAs genetics, Neoplasms, Experimental metabolism, Neoplasms, Experimental pathology, RNA, Long Noncoding genetics, Apoptosis Regulatory Proteins metabolism, Central Nervous System Neoplasms metabolism, Glioblastoma metabolism, Membrane Proteins metabolism, MicroRNAs metabolism, RNA, Long Noncoding metabolism
- Abstract
Objective: To explore whether plasmacytoma variant translocation 1 (PVT1) could regulate glioblastoma multiforme (GBM) progression via microRNA-1301-3p (miR-1301-3p) and transmembrane BAX inhibitor motif containing 6 (TMBIM6) axis., Materials and Methods: Expression patterns of PVT1 and RMBIM6 in GBM patients were analyzed using GEPIA, an online gene expression analysis tool. Levels of PVT1 in GBM cells and normal cells were analyzed with quantitative real-time PCR method. Cell Counting Kit-8 (CCK-8), transwell invasion assay, and flow cytometry assay were applied to detect cell viability and apoptosis. Connections of PVT1 or TMBIM6 with miR-1301-3p were validated with bioinformatic tool and luciferase activity reporter assay., Results: PVT1 was significantly expressed in GBM tissues and cells. PVT1 promotes GBM cell proliferation and invasion but inhibits apoptosis in vitro. TMBIM6 was significantly expressed in GBM tissues. The knockdown of TMBIM6 reversed the stimulation effects of PVT1 on GBM cell malignancy behaviors with miR-1301-3p as a bridge., Conclusions: Collectively, we showed PVT1 elevated TMBIM6 expression mediated by miR-1301-3p and thus to promote GBM progression. more...
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- 2020
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35. High-Throughput Metabolomics Method for Discovering Metabolic Biomarkers and Pathways to Reveal Effects and Molecular Mechanism of Ethanol Extract From Epimedium Against Osteoporosis.
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Zhao JF, Xu JY, Xu YE, Chen SL, Guo YX, Gao QY, and Sun GC
- Abstract
Metabolomics is an effective strategy to explore the molecular mechanism of herbal medicine. Epimedium, a traditional Chinese herb from the Epimedium brevicornu Maxim., has a therapeutic effect on osteoporosis (OP), however the molecular mechanism of the anti-OP effect is uncle\ar. Therefore, we investigated the pharmacological effect and action mechanism of ethanol extract of epimedium (Ext-epi) onOP rat model. The serum of OP rats was analyzed utilized UPLC-Q-TOF/MS metabolomics, and the potential biomarkers were screened and identified using multivariate data analysis systems and network databases. To further appraise the influence of Ext-epi on biological markers and metabolic pathways, and reveal the potential mechanism of Ext-epi on OP treatment. The results showed that 46 potential biomarkers were screened out and after intervention with Ext-epi extracts solution, 16 potential biomarkers were significantly recalled. Further pathway experiments showed that key pathway analysis include sarachidonic acid metabolism, glycerolphospholipid metabolism as potential targets which is related with the efficacy of Ext-epi protect against OP. These results explain the correlation between metabolites and molecular mechanisms, which is of great significance for understanding the intervention of Ext-epi on OP. In short, based on UPLC-Q-TOF/MS metabolomics may provide effective strategies for understanding the pathogenesis of diseases and evaluating the intervention effect of natural products., (Copyright © 2020 Zhao, Xu, Xu, Chen, Guo, Gao and Sun.) more...
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- 2020
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36. CX3CR1-microglia mediates neuroinflammation and blood pressure regulation in the nucleus tractus solitarii of fructose-induced hypertensive rats.
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Ho CY, Lin YT, Chen HH, Ho WY, Sun GC, Hsiao M, Lu PJ, Cheng PW, and Tseng CJ
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- Animals, Blood Pressure, Cytokines metabolism, Fructose toxicity, Hypertension chemically induced, Hypertension complications, Inflammation etiology, Rats, Rats, Inbred WKY, Solitary Nucleus metabolism, CX3C Chemokine Receptor 1 metabolism, Hypertension metabolism, Inflammation metabolism, Microglia metabolism, Solitary Nucleus pathology
- Abstract
Background: Inflammation is a common pathophysiological trait found in both hypertension and cardiac vascular disease. Recent evidence indicates that fractalkine (FKN) and its receptor CX3CR1 have been linked to inflammatory response in the brain of hypertensive animal models. Here, we investigated the role of CX3CR1-microglia in nitric oxide (NO) generation during chronic inflammation and systemic blood pressure recovery in the nucleus tractus solitarii (NTS)., Methods: The hypertensive rat model was used to study the role of CX3CR1-microglia in NTS inflammation following hypertension induction by oral administration of 10% fructose water. The systolic blood pressure was measured by tail-cuff method of non-invasive blood pressure. The CX3CR1 inhibitor AZD8797 was administered intracerebroventricularly (ICV) in the fructose-induced hypertensive rat. Using immunoblotting, we studied the nitric oxide synthase signaling pathway, NO concentration, and the levels of FKN and CX3CR1, and pro-inflammatory cytokines were analyzed by immunohistochemistry staining., Results: The level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, FKN, and CX3CR1 were elevated two weeks after fructose feeding. AZD8797 inhibited CX3CR1-microglia, which improved the regulation of systemic blood pressure and NO generation in the NTS. We also found that IL-1β, IL-6, and TNF-α levels were recovered by AZD8797 addition., Conclusion: We conclude that CX3CR1-microglia represses the nNOS signaling pathway and promotes chronic inflammation in fructose-induced hypertension. Collectively, our results reveal the role of chemokines such as IL-1β, IL-6, and TNF-α in NTS neuroinflammation with the involvement of FKN and CX3CR1. more...
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- 2020
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37. Vitamin D Attenuates Loss of Endothelial Biomarker Expression in Cardio-Endothelial Cells.
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Lai CC, Juang WC, Sun GC, Tseng YK, Jhong RC, Tseng CJ, Wong TY, and Cheng PW
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- Animals, Biomarkers analysis, Cardiovascular Diseases pathology, Cell Line, Disease Models, Animal, Endothelium pathology, Fibrosis, Humans, Male, Rats, Rats, Inbred WKY, Cardiovascular Diseases drug therapy, Endothelium drug effects, Heart drug effects, Myocardium pathology, Vitamin D therapeutic use, Vitamins therapeutic use
- Abstract
Vitamin D is associated with cardiovascular health through activating the vitamin D receptor that targets genes related to cardiovascular disease (CVD). The human cardiac microvascular endothelial cells (HCMECs) were used to develop mechanically and TGF-β1-induced fibrosis models, and the rat was used as the isoproterenol (ISO)-induced fibrosis model. The rats were injected with ISO for the first five days, followed by vitamin D injection for the consecutive three weeks before being sacrificed on the fourth week. Results showed that mechanical stretching reduced endothelial cell marker CD31 and VE-cadherin protein expressions, as well as increased α-smooth muscle actin (α-SMA) and fibronectin (FN). The transforming growth factor-β1 (TGF-β1) reduced CD31, and increased α-SMA and FN protein expression levels. Vitamin D presence led to higher protein expression of CD31, and lower protein expressions of α-SMA and FN compared to the control in the TGF-β1-induced fibrosis model. Additionally, protein expression of VE-cadherin was increased and fibroblast-specific protein-1 (FSP1) was decreased after vitamin D treatment in the ISO-induced fibrosis rat. In conclusion, vitamin D slightly inhibited fibrosis development in cell and animal models. Based on this study, the beneficial effect of vitamin D may be insignificant; however, further investigation of vitamin D's effect in the long-term is required in the future. more...
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- 2020
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38. Exploring the impact of a naturally occurring sapogenin diosgenin on underlying mechanisms of Ca 2+ movement and cytotoxicity in human prostate cancer cells.
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Sun GC, Jan CR, and Liang WZ
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- Cell Line, Tumor, Cell Survival drug effects, Humans, Male, PC-3 Cells, Sapogenins pharmacology, Type C Phospholipases antagonists & inhibitors, Antineoplastic Agents pharmacology, Calcium metabolism, Diosgenin pharmacology, Prostatic Neoplasms metabolism
- Abstract
Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca
>2+ concentration ([Ca 2+ ]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250-1000 μM) caused [Ca2+ ]i rises which was reduced by Ca2+ removal. Treatment with thapsigargin eliminated diosgenin-induced [Ca2+ ]i increases. In contrast, incubation with diosgeninabolished thapsigargin-caused [Ca2+ ]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin-caused [Ca2+ ]i increases. Diosgenin evoked Mn2+ influx suggesting that diosgenin induced Ca2+ entry. Diosgenin-induced Ca2+ influx was suppressed by PMA, GF109203X, and nifedipine, econazole, or SKF96365. Diosgenin (250-600 μM) concentration-dependently decreased cell viability. However, diosgenin-induced cytotoxicity was not reversed by chelation of cytosolic Ca2+ with BAPTA/AM. Together, diosgenin evoked [Ca2+ ]i increases via Ca2+ release and Ca2+ influx, and caused Ca2+ -non-associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer., (© 2019 Wiley Periodicals, Inc.) more...- Published
- 2020
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39. Correction: A handy method to remove bacterial contamination from fungal cultures.
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Shi XX, Qiu HP, Wang JY, Zhang Z, Wang YL, and Sun GC
- Abstract
[This corrects the article DOI: 10.1371/journal.pone.0224635.].
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- 2020
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40. Mechanisms underlying the effect of an oral antihyperglycaemic agent glyburide on calcium ion (Ca 2+ ) movement and its related cytotoxicity in prostate cancer cells.
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Sun GC, Liang WZ, and Jan CR
- Subjects
- Cell Death drug effects, Cell Line, Tumor, Cell Survival drug effects, Diabetes Mellitus, Type 2 metabolism, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum metabolism, Humans, Male, PC-3 Cells, Prostatic Neoplasms metabolism, Protein Kinase C metabolism, Calcium metabolism, Calcium Signaling drug effects, Glyburide pharmacology, Hypoglycemic Agents pharmacology, Prostatic Neoplasms drug therapy
- Abstract
Glyburide is an agent commonly used to treat type 2 diabetes and also affects various physiological responses in different models. However, the effect of glyburide on Ca
2+> movement and its related cytotoxicity in prostate cancer cells is unclear. This study examined whether glyburide altered Ca 2+ signalling and viability in PC3 human prostate cancer cells and investigated those underlying mechanisms. Intracellular Ca2+ concentrations ([Ca2+ ]i ) in suspended cells were measured by using the fluorescent Ca2+ -sensitive dye fura-2. Cell viability was examined by WST-1 assay. Glyburide at concentrations of 100-1000 μM induced [Ca2+ ]i rises. Ca2+ removal reduced the signal by approximately 60%. In Ca2+ -containing medium, glyburide-induced Ca2+ entry was inhibited by 60% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and inhibitor (GF109203X), and modulators of store-operated Ca2+ channels (nifedipine, econazole and SKF96365). Furthermore, glyburide induced Mn2+ influx suggesting of Ca2+ entry. In Ca2+ -free medium, inhibition of phospholipase C (PLC) with U73122 significantly inhibited glyburide-induced [Ca2+ ]i rises. Treatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished glyburide-evoked [Ca2+ ]i rises. Conversely, treatment with glyburide abolished BHQ-evoked [Ca2+ ]i rises. Glyburide at 100-500 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, glyburide induced [Ca2+ ]i rises by Ca2+ entry via PKC-sensitive store-operated Ca2+ channels and Ca2+ release from the ER in a PLC-dependent manner. Glyburide also caused Ca2+ -independent cell death. This study suggests that glyburide could serve as a potential agent for treatment of prostate cancer., (© 2019 John Wiley & Sons Australia, Ltd.) more...- Published
- 2020
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41. Angiotensin II inhibits DDAH1-nNOS signaling via AT1R and μOR dimerization to modulate blood pressure control in the central nervous system.
- Author
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Sun GC, Wong TY, Chen HH, Ho CY, Yeh TC, Ho WY, Tseng CJ, and Cheng PW
- Subjects
- Amidohydrolases, Angiotensin II Type 1 Receptor Blockers pharmacology, Animals, Dimerization, Extracellular Signal-Regulated MAP Kinases, Hypertension physiopathology, Losartan pharmacology, Male, Nitric Oxide metabolism, Oligopeptides metabolism, Rats, Inbred SHR, Rats, Inbred WKY, Receptor, Angiotensin, Type 1, Receptors, Opioid, mu agonists, Signal Transduction, Solitary Nucleus enzymology, Angiotensin II metabolism, Blood Pressure drug effects, Nitric Oxide Synthase Type I metabolism, Solitary Nucleus drug effects
- Abstract
G protein-coupled receptors (GPCRs) are important drug targets. Blocking angiotensin II (Ang II) type 1 receptor signaling alleviates hypertension and improves outcomes in patients with heart failure. Changes in structure and trafficking of GPCR, and desensitization of GPCR signaling induce pathophysiological processes. We investigated whether Ang II, via induction of AT1R and μ-opioid receptor (μOR) dimerization in the nucleus tractus solitarius (NTS), leads to progressive hypertension. Ang II signaling increased μOR and adrenergic receptor α2A (α2A-AR) heterodimer levels and decreased expression of extracellular signal-regulated kinases 1/2T202/Y204, ribosomal protein S6 kinaseT359/S363, and nNOSS1416 phosphorylation. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression was abolished in the NTS of adult spontaneously hypertensive rats (SHRs). Endomorphin-2 was overexpressed in NTS of adult SHRs compared with that in 6-week-old Wistar-Kyoto rats (WKY). Administration of μOR agonist into the NTS of WKY increased blood pressure (BP), decreased nitric oxide (NO) production, and decreased DDAH1 activity. μOR agonist significantly reduced the activity of DDAH1 and decreased neuronal NO synthase (nNOS) phosphorylation. The AT1R II inhibitor, losartan, significantly decreased BP and abolished AT1R-induced formation of AT1R and μOR, and α2A-AR and μOR, heterodimers. Losartan also significantly increased the levels of nNOSS1416 phosphorylation and DDAH1 expression. These results show that Ang II may induce expression of endomorphin-2 and abolished DDAH1 activity by enhancing the formation of AT1R and μOR heterodimers in the NTS, leading to progressive hypertension., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) more...
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- 2019
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42. Pex13 and Pex14, the key components of the peroxisomal docking complex, are required for peroxisome formation, host infection and pathogenicity-related morphogenesis in Magnaporthe oryzae.
- Author
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Wang JY, Li L, Chai RY, Qiu HP, Zhang Z, Wang YL, Liu XH, Lin FC, and Sun GC
- Subjects
- Amino Acid Sequence, Fungal Proteins metabolism, Hordeum microbiology, Oryza microbiology, Peroxisomes metabolism, Plant Diseases microbiology, Virulence, Fungal Proteins genetics, Host-Pathogen Interactions, Magnaporthe genetics, Magnaporthe pathogenicity, Peroxisomes genetics
- Abstract
Peroxisomes are ubiquitous organelles in eukaryotic cells that fulfill multiple important metabolisms. Pex13 and Pex14 are key components of the peroxisomal docking complex in yeasts and mammals. In the present work, we functionally characterized the homologues of Pex13 and Pex14 (Mopex13 and Mopex14) in the rice blast fungus Magnaporthe oryzae. Mopex13 and Mopex14 were peroxisomal membrane distributed and were both essential for the maintenance of Mopex14/17 on the peroxisomal membrane. Mopex13 and Mopex14 interacted with each other, and with Mopex14/17 and peroxisomal matrix protein receptors. Disruption of Mopex13 and Mopex14 resulted in a cytoplasmic distribution of peroxisomal matrix proteins and the Woronin body protein Hex1. In the ultrastructure of Δmopex13 and Δmopex14 cells, peroxisomes were detected on fewer occasions, and the Woronin bodies and related structures were dramatically affected. The Δmopex13 and Δmopex14 mutants were reduced in vegetative growth, conidial generation and mycelial melanization, in addition, Δmopex13 showed reduced conidial germination and appressorial formation and abnomal appressorial morphology. Both Δmopex13 and Δmopex14 were deficient in appressorial turgor and nonpathogenic to their hosts. The infection failures in Δmopex13 and Δmopex14 were also due to their reduced ability to degrade fatty acids and to endure reactive oxygen species and cell wall-disrupting compounds. Additionally, Mopex13 and Mopex14 were required for the sexual reproduction of the fungus. These data indicate that Mopex13 and Mopex14, as key components of the peroxisomal docking complex, are indispensable for peroxisomal biogenesis, fungal development and pathogenicity in the rice blast fungus. more...
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- 2019
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43. A handy method to remove bacterial contamination from fungal cultures.
- Author
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Shi XX, Qiu HP, Wang JY, Zhang Z, Wang YL, and Sun GC
- Subjects
- Cell Culture Techniques instrumentation, Culture Media, Feasibility Studies, Hyphae, Microbiological Techniques instrumentation, Bacteria, Cell Culture Techniques methods, Fungi, Microbiological Techniques methods
- Abstract
Contamination control and removal are very important technical aspects of microbiological research. Bacterial contamination is very common in fungal cultures. Currently, the commonly used approach for inhibiting bacteria is antibiotic treatment; however, there are drawbacks to using antibiotics, including incomplete removal, limited antibacterial spectra, tendency toward recontamination, effects to fungal strains, and potential risks to the environment. Therefore, in the present work, we developed a new method for bacterial removal from fungi cultured on solid medium, the Cabin-Sequestering (CS) method, based on the different culture characteristics between fungi and bacteria. First, 3-5 mm round or square holes (the "cabin") are excavated on a solid medium plate. The fungal strain containing possible bacterial contamination is inoculated into the cabin. The cabin is then covered with a sterilized coverslip, followed by incubation at the appropriate temperature. After 7-10 days of culturing, fungal hyphae grow out along the edge of the coverslip; however, the contaminating bacteria cannot pass through the space formed between the medium and the coverslip and, thus, remain in the cabin. The newly grown fungal hyphae around the coverslip are re-inoculated into fresh culture plates, where they form bacteria-free fungal colonies. The CS method is easy handling, with a short experimental cycle and rare recontamination. When necessary, it can also be used in combination with antibiotics in bacterial removal operations., Competing Interests: The authors have declared that no competing interests exist. more...
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- 2019
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44. Dapagliflozin Prevents NOX- and SGLT2-Dependent Oxidative Stress in Lens Cells Exposed to Fructose-Induced Diabetes Mellitus.
- Author
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Chen YY, Wu TT, Ho CY, Yeh TC, Sun GC, Kung YH, Wong TY, Tseng CJ, and Cheng PW
- Subjects
- Aged, Animals, Diabetes Mellitus etiology, Diabetes Mellitus metabolism, Diabetes Mellitus pathology, Disease Models, Animal, Female, Fructose adverse effects, Humans, Male, Middle Aged, NADPH Oxidases metabolism, Rats, Reactive Oxygen Species metabolism, Sodium-Glucose Transporter 2 metabolism, Lens, Crystalline cytology, Lens, Crystalline metabolism, NADPH Oxidases genetics, Oxidative Stress genetics, Sodium-Glucose Transporter 2 genetics
- Abstract
Purpose: Cataracts in patients with diabetes mellitus (DM) are a major cause of blindness in developed and developing countries. This study aims to examine whether the generation of reactive oxygen species (ROS) via the increased expression of glucose transporters (GLUTs) and the receptor for advanced glycation end products (RAGE) influences the cataract development in DM., Methods: Lens epithelial cells (LECs) were isolated during cataract surgery from patients without DM or with DM, but without diabetic retinopathy. In a rat model, fructose (10% fructose, 8 or 12 weeks) with or without dapagliflozin (1.2 mg/day, 2 weeks) treatment did induce DM, as verified by blood pressure and serum parameter measurements. Immunofluorescence stainings and immunoblottings were used to quantify the protein levels. Endogenous O
2 ˙¯ production in the LECs was determined in vivo with dihydroethidium stainings., Results: We investigated that GLUT levels in LECs differed significantly, thus leading to the direct enhancement of RAGE-associated superoxide generation in DM patients with cataracts. Superoxide production was significantly higher in LECs from rats with fructose-induced type 2 DM, whereas treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin prevented this effect in fructose-fed rats. Protein expression levels of the sodium/glucose cotransporter 2 (SGLT2), GLUT1, GLUT5, the nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase subunit p67-phox, NOX2/4 and RAGE were upregulated in fructose-fed animals, whereas dapagliflozin treatment reversed these effects., Conclusions: In rats with fructose-induced DM, dapagliflozin downregulates RAGE-induced NADPH oxidase expression in LECs via the inactivation of GLUTs and a reduction in ROS generation. These novel findings suggest that the SGLT2 inhibitor dapagliflozin may be a candidate for the pharmacological prevention of cataracts in patients with DM. more...- Published
- 2019
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45. Closer to Nature Through Dynamic Culture Systems.
- Author
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Wong TY, Chang SN, Jhong RC, Tseng CJ, Sun GC, and Cheng PW
- Subjects
- Animals, Cell Differentiation, Cell Proliferation, Humans, Mechanotransduction, Cellular
- Abstract
Mechanics in the human body are required for normal cell function at a molecular level. It is now clear that mechanical stimulations play significant roles in cell growth, differentiation, and migration in normal and diseased cells. Recent studies have led to the discovery that normal and cancer cells have different mechanosensing properties. Here, we discuss the application and the physiological and pathological meaning of mechanical stimulations. To reveal the optimal conditions for mimicking an in vivo microenvironment, we must, therefore, discern the mechanotransduction occurring in cells. more...
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- 2019
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46. Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma.
- Author
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Liu J, Qiu WC, Shen XY, and Sun GC
- Subjects
- Base Sequence, Biomarkers, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular metabolism, Cell Line, Tumor, Cell Proliferation, Cell Survival, Disease Progression, Humans, Liver Neoplasms metabolism, Neovascularization, Pathologic, Prognosis, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, Carcinoma, Hepatocellular drug therapy, Computational Biology, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Liver Neoplasms drug therapy, Sorafenib pharmacology
- Abstract
Hepatocellular carcinoma (HCC) is increasingly known as a serious, worldwide public health concern. Sorafenib resistance is the main challenge faced by many advanced HCC patients. The specific mechanisms of sorafenib resistance remind unclear. In the current study, GEO2R was conducted to identify differentially expressed genes (DEGs) between sorafenib-resistant samples and the control group by using RNA-sequence analysis and analyzing dataset GSE109211. Next, protein-protein interaction (PPI) network was built to explore key targets proteins in sorafenib-resistant HCC. Furthermore, gene ontology (GO) analysis was used to research the underlying roles of key proteins. Moreover, the Kaplan-Meier survival analysis was performed to display the effect of key proteins on overall survival in HCC. Western blotting was performed to detected resistance-related proteins and CCK-8 assay was employed to measured cell viability. In the present research, 164 sorafenib resistance-related DEGs in HCC were identified by using RNA-sequence analysis and analyzing the dataset GSE109211. GO analysis revealed DEGs were involved in regulating multiple biological processes and molecular functions. DYNLL2, H2AFJ, SHANK2, ZWILCH, CDC14A, IFT20, MTA3, SERPINA1 and TCF4 were confirmed as key genes in this process. Moreover, our study showed Akt signaling was aberrantly activated and inhibition of Akt signaling enhanced anti-tumor capacity of sorafenib in sorafenib-resistant HCC cells. Identification of the DEGs in sorafenib resistant HCC cells may further provide the new insights of underlying sorafenib-resistant mechanisms and offer latent targets for early diagnosis and new therapies to improve clinical efficacy for sorafenib-resistant HCC patients. more...
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- 2019
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47. Exploration of the effect of the alkaloid colchicine on Ca 2+ handling and its related physiology in human oral cancer cells.
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Sun GC, Chen HH, Liang WZ, and Jan CR
- Subjects
- Alkaloids, Apoptosis, Calcium, Calcium Signaling, Cell Line, Tumor, Cell Survival, Colchicine, Humans, Mouth Neoplasms
- Abstract
Objective: Colchicine, extracted from plants of the genus Colchicum, is a commonly prescribed drug for inflammatory diseases. It has been shown that colchicine affected various physiological responses in different models. However, the effect of colchicine on cytosolic free Ca
2+ levels ([Ca2+ ]i ) and its related physiology in human oral cancer cells is unknown. This study examined whether colchicine altered Ca2+ homeostasis and caused cytotoxicity in OC2 human oral cancer cells., Methods: The Ca2+ -sensitive fluorescent dye fura-2 was used to measure [Ca2+ ]i . Cell viability was measured by the fluorescent reagent 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay., Results: Colchicine at concentrations of 250-650 μM induced [Ca2+ ]i rises concentration-dependently. The response was reduced by approximately 40% by removing extracellular Ca2+ . In Ca2+ -free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited colchicine-evoked [Ca2+ ]i rises. Conversely, treatment with colchicine inhibited thapsigargin-evoked [Ca2+ ]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished colchicine-induced Ca2+ release. In Ca2+ -containing medium, colchicine-induced Ca2+ entry was supported by Mn2+ -caused quenching of fura-2 fluorescence and the entry was partly inhibited by protein kinase C (PKC) modulators (phorbol 12-myristate 13 acetate, PMA; and GF109203X) and by three modulators of store-operated Ca2+ channels (nifedipine, econazole and SKF96365). Colchicine at 250-650 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM)., Conclusions: In OC2 cells, colchicine induced [Ca2+ ]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Furthermore, colchicine caused cell death that was not triggered by preceding [Ca2+ ]i rises., (Copyright © 2019 Elsevier Ltd. All rights reserved.) more...- Published
- 2019
- Full Text
- View/download PDF
48. Autophagy induction and antiproliferative effect of a novel curcumin derivative MOMI-1 on the human lung cancer cells A549.
- Author
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Zhou GZ, Shi YY, Wei LL, and Sun GC
- Subjects
- 3T3 Cells, A549 Cells, Animals, G1 Phase drug effects, Humans, Lung Neoplasms pathology, Mice, Resting Phase, Cell Cycle drug effects, Wound Healing drug effects, Antineoplastic Agents pharmacology, Autophagy drug effects, Cell Proliferation drug effects, Curcumin analogs & derivatives, Curcumin pharmacology
- Abstract
To date, there are some chemically synthesized curcumin derivatives which were produced and identified to evade the disadvantages of physiochemical stability and solubility of curcumin. Here, one novel curcumin derivative, (2-(3-{(1E)-{(E)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxocyclohexylidene)methyl)-1H-indol-1-yl)acetic acid}, (abbreviated as MOMI-1) was first used to detect the antiproliferation activity with MTT assays in different cancer cells including A549 lung cancer cells, MCF-7, and HEPG2 cell lines, and exhibited its wide inhibition spectrum. Next, we found that MOMI-1 could induce autophagic genesis of A549 cells by acridine orange or monodansylcadaverine (MDC) staining and green fluorescent protein-light chain 3 (GFP-LC3) recombinant plasmid transfection analysis, respectively. Western blot analysis confirmed the LC3-I/II conversion, beclin-1 increase and p62 reduction of A549 cells after exposure of MOMI-1, which suggested the typical autophagy induction. The following cell cycle test showed that MOMI-1 could block A549 cells in G0/G1 phase. Furthermore, wounding healing experiment and transwell assays demonstrated that MOMI-1 also possessed the antimigration ability of A549 cells. Our current results confirmed that MOMI-1 could inhibit the proliferation and induce autophagy of A549 cells, which provide a new potential chemical candidate of antigrowth of A549 lung cancer cells. Future work needs to focus on the mechanism of autophagy pathway of A549 cells., (© 2018 Wiley Periodicals, Inc.) more...
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- 2019
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49. Antihypertensive Potential of Coenzyme Q10 via Free Radical Scavenging and Enhanced Akt-nNOS Signaling in the Nucleus Tractus Solitarii in Rats.
- Author
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Chen HH, Yeh TC, Cheng PW, Ho WY, Ho CY, Lai CC, Sun GC, and Tseng CJ
- Subjects
- Animals, Fructose adverse effects, Glucose Transporter Type 1 metabolism, Hypertension chemically induced, Hypertension drug therapy, Hypertension metabolism, Insulin metabolism, Male, NADPH Oxidases metabolism, Proto-Oncogene Proteins c-akt metabolism, Rats, Wistar, Solitary Nucleus metabolism, Superoxide Dismutase metabolism, Ubiquinone pharmacology, Uric Acid blood, Antihypertensive Agents pharmacology, Free Radical Scavengers pharmacology, Nitric Oxide Synthase Type I metabolism, Solitary Nucleus drug effects, Ubiquinone analogs & derivatives
- Abstract
Scope: In the Natural Medicines database, coenzyme Q10 (CoQ10) is classified as possibly effective for the treatment of hypertension. Patients with hypertension frequently have a significant deficiency of the antioxidant CoQ10. Furthermore, reactive oxygen species are overproduced in the nucleus tractus solitarii (NTS) during the cardiovascular regulation of hypertension in vivo. However, the molecular mechanisms by which CoQ10 modulates cardiovascular functions in the NTS are unclear. In this study, the effects of CoQ10 on superoxide generation, downstream NO signaling in the NTS, and blood pressure were evaluated in rats with fructose-induced hypertension., Methods and Results: Treatment with oral CoQ10 for 4 weeks abolished nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) activation, decreased p38 phosphorylation, and increased superoxide dismutase 2 production in the NTS of fructose-fed rats. The serum levels of uric acid decrease in response to CoQ10 treatment in fructose-fed rats. Oral CoQ10 reduced blood pressure by inducing Akt and nNOS phosphorylation in NTS of fructose-induced hypertensive rats., Conclusion: Oral CoQ10 decreases blood pressure by negatively regulating fructose-induced NADPH oxidase levels, abolishing ROS generation, reducing p38 phosphorylation, and enhancing the Akt-nNOS pathway in the NTS. These results support the beneficial effects of CoQ10 in oxidative stressassociated hypertension., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.) more...
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- 2019
- Full Text
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50. One novel curcumin derivative ZYX01 induces autophagy of human non-small lung cancer cells A549 through AMPK/ULK1/Beclin-1 signaling pathway.
- Author
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Zhou GZ, Wang QQ, Wang PB, Wang ZC, and Sun GC
- Subjects
- A549 Cells, Carcinoma, Non-Small-Cell Lung enzymology, Cell Movement drug effects, Cell Proliferation drug effects, Curcumin chemistry, Cytoplasmic Vesicles drug effects, Cytoplasmic Vesicles metabolism, Humans, Lung Neoplasms enzymology, Microtubule-Associated Proteins metabolism, Adenylate Kinase metabolism, Autophagy drug effects, Autophagy-Related Protein-1 Homolog metabolism, Beclin-1 metabolism, Carcinoma, Non-Small-Cell Lung pathology, Curcumin pharmacology, Intracellular Signaling Peptides and Proteins metabolism, Lung Neoplasms pathology, Signal Transduction
- Abstract
Presently, curcumin derivatives had been paid more attention in view of their high bioavailability or water solubility, which herein possibly replaced the curcumin for their functional applications in future. Here, one novel chemically synthesized curcumin derivative, ZYX01, was used to identify anti-proliferation activity of human non-small lung cancer cells A549 and its anti-proliferative mechanism. Our study showed that ZYX01 could induce autophagic death of A549 cells by morphological observation, MTT assay, acridine orange staining and MDC assay, which possess a dose-and time-dependent manner. ZYX01-treated A549 cells possessed an increase in LC3-II/LC3-I ratio, upregulation of beclin-1 and downregulation of p62 expression. We further confirmed the cellular AMPK/ULK1/Beclin-1 signaling pathway in A549 cells after ZYX01 treatment. The anti-migration effect of ZYX01 in A549 cells was also explored by wound healing assay and transwell experiment. Current results had confirmed that ZYX01 induced A549 cells autophagy through AMPK/ULK1/Beclin-1 pathway and shed light on the future study on the anti-cancer molecular mechanism. more...
- Published
- 2019
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