230 results on '"Hong, Xu"'
Search Results
2. Huoxin Pill Reduces Myocardial Ischemia Reperfusion Injury in Rats via TLR4/NFκB/NLRP3 Signaling Pathway.
- Author
-
Cao, Ce, Qi, Yu-tong, Wang, Ao-ao, Wang, Zi-yan, Liu, Zi-xin, Meng, Hong-xu, Li, Lei, and Liu, Jian-xun
- Subjects
INTERLEUKINS ,BIOMARKERS ,HERBAL medicine ,ANIMAL experimentation ,WESTERN immunoblotting ,CELL receptors ,SIGNAL peptides ,NF-kappa B ,CREATINE kinase ,SUPEROXIDE dismutase ,MYOCARDIAL reperfusion complications ,CELLULAR signal transduction ,RATS ,ISOENZYMES ,MALONDIALDEHYDE ,BIOINFORMATICS ,GENE expression ,LACTATE dehydrogenase ,COMPUTER-assisted molecular modeling ,EXTRACELLULAR space ,CHINESE medicine ,TOLL-like receptors ,DRUG administration ,DRUG dosage - Abstract
Objective: To explore the protective effect of Huoxin Pill (HXP) on acute myocardial ischemia-reperfusion (MIRI) injury in rats. Methods: Seventy-five adult SD rats were divided into the sham-operated group, model group, positive drug group (diltiazem hydrochloride, DH), high dose group (24 mg/kg, HXP-H) and low dose group (12 mg/kg, HXP-L) of Huoxin Pill (n=15 for every group) according to the complete randomization method. After 1 week of intragastric administration, the left anterior descending coronary artery of the rat's heart was ligated for 45 min and reperfused for 3 h. Serum was separated and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), hypersensitive C-reactive protein (hs-CRP) and interleukin-1β (IL-1β) were measured. Myocardial ischemia rate, myocardial infarction rate and myocardial no-reflow rate were determined by staining with Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC). Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN) databases were used to screen for possible active compounds of HXP and their potential therapeutic targets; the results of anti-inflammatory genes associated with MIRI were obtained from GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Datebase (TTD) databases was performed; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the intersected targets; molecular docking was performed using AutoDock Tools. Western blot was used to detect the protein expression of Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NFκB)/NOD-like receptor protein 3 (NLRP3). Results: Compared with the model group, all doses of HXP significantly reduced the levels of LDH, CK and CK-MB (P<0.05, P<0.01); HXP significantly increased serum activity of SOD (P<0.05, P<0.01); all doses of HXP significantly reduced the levels of hs-CRP and IL-1β (P<0.05, P<0.01) and the myocardial infarction rate and myocardial no-reflow rate (P<0.01). GO enrichment analysis mainly involved positive regulation of gene expression, extracellular space and identical protein binding, KEGG pathway enrichment mainly involved PI3K-Akt signaling pathway and lipid and atherosclerosis. Molecular docking results showed that kaempferol and luteolin had a better affinity with TLR4, NFκB and NLRP3 molecules. The protein expressions of TLR4, NFκB and NLRP3 were reduced in the HXP group (P<0.01). Conclusions: HXP has a significant protective effect on myocardial ischemia-reperfusion injury in rats, and its effect may be related to the inhibition of redox response and reduction of the inflammatory response by inhibiting the TLR4NFκB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. Minute Cellular Nodules as Early Lesions in Rats with Silica Exposure via Inhalation
- Author
-
Yaqian Li, Fuyu Jin, Tian Li, Xinyu Yang, Wenchen Cai, Shifeng Li, Xuemin Gao, Na Mao, Heliang Liu, Hong Xu, and Fang Yang
- Subjects
rats ,silicosis ,macrophage alveolitis ,cellular nodules ,fibrotic cellular nodules ,Veterinary medicine ,SF600-1100 - Abstract
Mechanisms of silicosis have yet to be clarified, and pathological conditions are inaccurately described in some experimental studies on silicosis. This study was aimed at describing initial lesions in silicosis, as observed in rats with silica exposure via inhalation, and major histopathologic alterations. Male Wistar rats were exposed to silica for 24 weeks. Hematoxylin and eosin staining indicated the presence of “cellular nodule+ macrophage alveolitis” in rats exposed to silica from the 2–16 weeks time points and “fibrotic cellular + cellular nodule” in rats exposed to silica via inhalation for 24 weeks. By immunohistochemistry, the following were noted: a continual increase in the positive expression of CD68 in macrophages in the lungs of rats exposed to silica; hyperplasia in alveolar type II cells (AT2); loss of original phenotypes in fibrotic cellular nodules, macrophages, and AT2 cells; loss of endothelial cells in silicotic nodules; and positive expression of α-smooth muscle actin in macrophages. Typical pathological changes in silicosis were also summarized. Among these changes were macrophage alveolitis, cellular nodules, and fibrotic cellular nodules, including an increase in minute cellular nodules in the early stages and the formation of fibrotic cellular nodules in the late stages.
- Published
- 2022
- Full Text
- View/download PDF
4. LncRNA MALAT1 Regulates USP22 Expression Through EZH2-Mediated H3K27me3 Modification to Accentuate Sepsis-Induced Myocardial Dysfunction
- Author
-
Hong, Xu, Wei, Ye, and Baochang, Shi
- Subjects
Heart Diseases ,Apoptosis ,Toxicology ,Rats ,Histones ,MicroRNAs ,Sepsis ,Animals ,Enhancer of Zeste Homolog 2 Protein ,Myocytes, Cardiac ,RNA, Long Noncoding ,Ubiquitin-Specific Proteases ,Cardiology and Cardiovascular Medicine ,Molecular Biology - Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), has been confirmed to recruit enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) to regulate cardiomyocyte apoptosis in diabetic cardiomyopathy. However, whether the similar regulatory axis exists in sepsis-induced myocardial dysfunction (SIMD) has not been clearly established. The current study sought to define the mechanism governing MALAT1-mediated EZH2 in SIMD. MALAT1 was significantly upregulated in lipopolysaccharide-induced cardiomyocytes. Depletion of MALAT1 by caudal vein injection of small interfering RNA targeting MALAT1 alleviated myocardial injury in SIMD rats, restored cardiac function, reduced oxidative stress production and fibrosis, and inhibited inflammatory factors and apoptosis in myocardial tissues. Moreover, MALAT1 bound to EZH2 and promoted EZH2 activity in the nucleus of cardiomyocytes. EZH2 repressed ubiquitin-specific peptidase 22 (USP22) expression through H3K27me3 modification. EZH2 elevation aggravated the cardiac injury in SIMD rats, while USP22 upregulation inhibited the effect of EZH2, which reduced the cardiac injury in SIMD rats. Taken together, MALAT1 decreased USP22 expression by interacting with EZH2, thereby worsening SIMD, highlighting an attractive therapeutic strategy for SIMD.
- Published
- 2022
5. c(RGDyk)-modified nanoparticles encapsulating quantum dots as a stable fluorescence probe for imaging-guided surgical resection of glioma under the auxiliary UTMD
- Author
-
Ying-Zheng Zhao, Qing-Hua Lan, Cui-Tao Lu, He-Lin Xu, Bin Chen, Ming-Ling Fang, Qi-Long Wu, Hui Li, Cui Xiong, Jing-Hong Xu, Jin-Hua Cai, Fang-Yi Tao, and Shu-Ting Zhu
- Subjects
Surgical resection ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Nanoparticle ,Poloxamer ,macromolecular substances ,02 engineering and technology ,Peptides, Cyclic ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Cell Line, Tumor ,Glioma ,Quantum Dots ,medicine ,Animals ,Humans ,Fluorescent Dyes ,Microbubbles ,Chemistry ,business.industry ,General Medicine ,021001 nanoscience & nanotechnology ,medicine.disease ,Fluorescence ,Rats ,nervous system diseases ,Disease Models, Animal ,Surgery, Computer-Assisted ,Ultrasonic Waves ,Quantum dot ,030220 oncology & carcinogenesis ,Nanoparticles ,Administration, Intravenous ,0210 nano-technology ,Nuclear medicine ,business ,Biotechnology ,Glioblastoma - Abstract
Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of –10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.
- Published
- 2023
- Full Text
- View/download PDF
6. Mussel-inspired adhesive gelatin–polyacrylamide hydrogel wound dressing loaded with tetracycline hydrochloride to enhance complete skin regeneration
- Author
-
Yamei Wang, Dongdong Xiao, Lin Quan, Hongbin Chai, Xiaofeng Sui, Bijia Wang, Hong Xu, and Zhiping Mao
- Subjects
Wound Healing ,Adhesives ,Acrylic Resins ,Animals ,Gelatin ,Hydrogels ,General Chemistry ,Tetracycline ,Condensed Matter Physics ,Bandages ,Anti-Bacterial Agents ,Rats - Abstract
Even though the global wound care market size was valued at USD 19.83 billion in 2020, it is still a challenge to develop a hydrogel-based wound dressing with a good mechanical property, adhesiveness and antibacterial property. This study established and validated a mussel-inspired adhesive hydrogel wound dressing with antibacterial activity by dispersing tetracycline hydrochloride into hydrogel based polydopamine, gelatin and polyacrylamide. A tough hydrogel with a fracture stress of 0.42 MPa was prepared by changing the contents of the gelatin and polyacrylamide. With the addition of polydopamine and tetracycline hydrochloride, the hydrogel was endowed with an adhesive property (with a tissue adhesive strength of 4.13 kPa) and antibacterial activity against both
- Published
- 2022
7. The protective effect of manganese superoxide dismutase from thermophilic bacterium HB27 on hydrochloric acid-induced chemical cystitis in rats
- Author
-
Shi-Hui Liu, Jing Jin, Wen-Hua Xie, Xiao-Qin Zhang, Jianwei Lv, Yi-Fang Cao, Hai-Long Li, Yi He, Ling-Feng Wu, Hong Xu, Fan-Guo Meng, Jin-Lai Gao, Naiwen Chen, and Wei Chen
- Subjects
Urology ,medicine.medical_treatment ,Urinary Bladder ,Sodium hyaluronate ,Inflammation ,Pharmacology ,medicine.disease_cause ,Rats, Sprague-Dawley ,Superoxide dismutase ,chemistry.chemical_compound ,Bacterial Proteins ,Cystitis ,Threshold of pain ,medicine ,Animals ,Bladder Pain ,Saline ,biology ,Superoxide Dismutase ,business.industry ,medicine.disease ,Rats ,chemistry ,Nephrology ,biology.protein ,Hydrochloric Acid ,medicine.symptom ,business ,Infiltration (medical) ,Oxidative stress - Abstract
Purpose To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. Methods Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. Results Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. Conclusions Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.
- Published
- 2021
8. Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
- Author
-
Fuyu, Jin, Yaqian, Li, Tian, Li, Xinyu, Yang, Wenchen, Cai, Shifeng, Li, Xuemin, Gao, Fang, Yang, Hong, Xu, and Heliang, Liu
- Subjects
Adult ,Inhalation Exposure ,General Immunology and Microbiology ,Occupational Exposure ,General Chemical Engineering ,General Neuroscience ,Silicosis ,Humans ,Animals ,Quartz ,Silicon Dioxide ,General Biochemistry, Genetics and Molecular Biology ,Rats - Abstract
The major cause of silicosis is the inhalation of silica in the occupational environment. Despite some anatomical and physiological differences, rodent models continue to be an essential tool for studying human silicosis. For silicosis, the classic pathological process needs to be inducible via the inhalation of freshly generated quartz particles, which means specifically inducing human occupational disease. This study described a technique to establish a silicosis rat model with inhalation of silica via the whole body in an inhalation chamber, which is simple, easy to operate, and effectively mimics the pathological dynamic evolution process of silicosis. Further, the technique had good repeatability with no surgery involved. The inhalation exposure system was fabricated, validated, and used for toxicology studies on respirable particle inhalation. The critical components were as follows: (1) bulk dry SiO2 powder generator adjusted with an air-flow controller; (2) 0.3 m
- Published
- 2022
9. Evaluation of differential serum expression of three factors and pulmonary function in patients with silicosis
- Author
-
Xia Yu Duan, Liang He Liu, Feng Shi Li, Kui Sheng Zhang, Ying Zhu, Yun Qi Cheng, Xin Jing Yao, Hong Xu, Xiang Ju Yuan, and Fang Yang
- Subjects
medicine.medical_specialty ,Silicosis ,Vital Capacity ,ptpn2 ,Protein tyrosine phosphatase ,Complement factor B ,Gastroenterology ,Pulmonary function testing ,Forced Expiratory Volume ,Internal medicine ,Animals ,Humans ,Medicine ,In patient ,Occupational lung disease ,Lung ,Protein Tyrosine Phosphatase, Non-Receptor Type 2 ,medicine.diagnostic_test ,business.industry ,Kinase ,pulmonary function ,Public Health, Environmental and Occupational Health ,General Medicine ,medicine.disease ,Rats ,Respiratory Function Tests ,Bronchoalveolar lavage ,factor b ,roc ,business ,early diagnosis - Abstract
Objectives Silicosis is a chronic occupational lung disease. As was previously found by the authors, some proteins increased in the lung tissue of activated rats, and protein tyrosine phosphatase non-receptor type 2 (PTPN2), factor B, and vaccinia-related kinase 1 (VRK1) showed highly differential expressions. Material and Methods In this study, serum and bronchoalveolar lavage fluid samples were collected from patients with silicosis and healthy people to verify the expression of PTPN2, factor B, and VRK1. The diagnostic value of differentially expressed proteins for silicosis was judged. Results The expression levels of serum PTPN2, VRK1, and factor B in patients with silicosis were significantly higher than those in the control group (p < 0.01). Higher serum PTPN2 and factor B concentrations significantly and negatively correlated with the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV 1 /FVC), maximum vital capacity (VC max ), FEV 1 , and FVC, suggesting that the high expression of PTPN2 and factor B is associated with decreased pulmonary ventilation function and restrictive ventilatory impairment in patients with silicosis. All area under curve (AUC) measurements generated from single detection events were >0.744, with PTPN2 reaching the highest value (0.858). The AUC, sensitivity, and specificity for the combined diagnosis using factor B and PTPN2 were 0.907, 86.91% and 85.07%, respectively, for factor B and PTPN2. The 3 differentially expressed proteins are potential classes of predictive biomarkers for silicosis. Conclusions Regarding the economy and test practicality, the best diagnostic combination is factor B and PTPN2 for the analysis of AUC, sensitivity and specificity. Int J Occup Med Environ Health. 2021;34(4):527–40
- Published
- 2021
10. Schwann-like cell conditioned medium promotes angiogenesis and nerve regeneration
- Author
-
Yusheng Wei, Jiahong Yu, Tianyan Chen, Jiqin Zhou, Jiabo Hu, Bin Tang, Lei Zhang, Wei Ni, Hong Xu, Jing Li, and Kai Ye
- Subjects
Angiogenesis ,Biomedical Engineering ,Rats, Sprague-Dawley ,Biomaterials ,Myelin ,Peripheral Nerve Injuries ,medicine ,Animals ,Tube formation ,Transplantation ,Chemistry ,Regeneration (biology) ,Endothelial Cells ,Cell Biology ,Sciatic Nerve ,Neural stem cell ,Nerve Regeneration ,Rats ,respiratory tract diseases ,Cell biology ,Endothelial stem cell ,medicine.anatomical_structure ,nervous system ,Culture Media, Conditioned ,Peripheral nerve injury ,Schwann Cells ,Sciatic nerve - Abstract
Vascular network reconstruction plays a pivotal role in the axonal regeneration and nerve function recovery after peripheral nerve injury. Increasing evidence indicates that Schwann cells (SCs) can promote nerve function repair, and the beneficial effects attributed to SCs therapy may exert their therapeutic effects through paracrine mechanisms. Recently, the previous research of our group demonstrated the promising neuroregenerative capacity of Schwann-like cells (SCLCs) derived from differentiated human embryonic stem cell-derived neural stem cells (hESC-NSCs) in vitro. Herein, the effects of SC-like cell conditioned medium (SCLC-CM) on angiogenesis and nerve regeneration were further explored. The assays were performed to show the pro-angiogenic effects of SCLC-CM, such as promoted endothelial cell proliferation, migration and tube formation in vitro. In addition, Sprague-Dawley rats were treated with SCLC-CM after sciatic nerve crush injury, SCLC-CM was conducive for the recovery of sciatic nerve function, which was mainly manifested in the SFI increase, the wet weight ratio of gastrocnemius muscle, as well as the number and thickness of myelin. The SCLC-CM treatment reduced the Evans blue leakage and increased the expression of CD34 microvessels. Furthermore, SCLC-CM upregulated the expressions of p-Akt and p-mTOR in endothelial cells. In conclusion, SCLC-CM promotes angiogenesis and nerve regeneration, it is expected to become a new treatment strategy for peripheral nerve injury.
- Published
- 2021
11. A keratin/chitosan sponge with excellent hemostatic performance for uncontrolled bleeding
- Author
-
Rong-Rong Yan, Dai Xue, Chang Su, Yan Xu, Jin-Song Gong, Yan-Ling Liu, Min Jiang, Yan Geng, Guo-Zhong Lv, Zheng-Hong Xu, and Jin-Song Shi
- Subjects
Chitosan ,Hemostasis ,Biocompatible Materials ,Hemorrhage ,Surfaces and Interfaces ,General Medicine ,Bandages ,Hemostatics ,Rats ,Colloid and Surface Chemistry ,Animals ,Gelatin ,Keratins ,Physical and Theoretical Chemistry ,Biotechnology - Abstract
Uncontrolled bleeding leads to a higher fatality rate in the situation of surgery, traffic accidents and warfare. Traditional hemostatic materials such as bandages are not ideal for uncontrolled or incompressible bleeding. Therefore, it is of great significance to develop a new medical biomaterial with excellent rapid hemostatic effect. Keratin is a natural, biocompatible and biodegradable protein which contains amino acid sequences that induce cell adhesion. As a potential biomedical material, keratin has been developed and paid attention in tissue engineering fields such as promoting wound healing and nerve repair. Herein, a keratin/chitosan (K/C) sponge was prepared to achieve rapid hemostasis. The characterizations of K/C sponge were investigated, including SEM, TGA, liquid absorption and porosity, showing that the high porosity up to 90.12 ± 2.17 % resulted in an excellent blood absorption. The cytotoxicity test and implantation experiment proved that the K/C sponge was biocompatible and biodegradable. Moreover, the prepared K/C sponge showed better hemostatic performance than chitosan sponge (CS) and the commercially available gelatin sponge in both rat tail amputation and liver trauma bleeding models. Further experiments showed that K/C sponge plays a hemostatic role through the endogenous coagulation pathway, thus shortening the activated partial thromboplastin time (APTT) effectively. Therefore, this study provided a K/C sponge which can be served as a promising biomedical hemostatic material.
- Published
- 2022
12. Effects of icariin on the fracture healing in young and old rats and its mechanism
- Author
-
Chi Zhang, Feng Chen, Xuan Zhang, Tian Xia, Jie Han, Zhang Xiaoyun, Can-Hong Xu, Shi-Lei Song, and Yue-Ping Chen
- Subjects
Male ,Cell Survival ,Osteocalcin ,Pharmaceutical Science ,epimedium ,Bone healing ,RM1-950 ,Pharmacology ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Rats, Wistar ,Cells, Cultured ,rat bone mesenchymal stem cells ,Epimedium ,Flavonoids ,Fracture Healing ,bmp-2/smad5/runx2 pathway ,biology ,Dose-Response Relationship, Drug ,Chemistry ,Mechanism (biology) ,Age Factors ,Mesenchymal Stem Cells ,General Medicine ,biology.organism_classification ,Rats ,Tibial Fractures ,Complementary and alternative medicine ,Molecular Medicine ,Alkaline phosphatase ,Female ,Therapeutics. Pharmacology ,Icariin ,alkaline phosphatase ,Research Article - Abstract
Context Icariin has attracted increasing attention because of its wide variety of pharmacological effects. Objective This study investigates whether icariin could promote fracture healing in young and old rats and its mechanisms. Materials and methods A Wistar rat model for the tibia fracture in relatively young and old rats, respectively, was established. The rats were divided into four groups: model group, L-icariin (50 mg/kg icariin), M-icariin (100 mg/kg icariin) and H-icariin (200 mg/kg icariin), and intragastric administration of icariin was performed for 10 days or 20 days. In addition, isolated and cultured rat bone mesenchymal stem cells (rBMSCs) from young and old rats were cultured with 5% and 20% of icariin-containing serum, respectively, then cell viability and alkaline phosphatase (ALP) activity were measured. Results Icariin administration induced the expression of Runx2, Osterix, BMP-2, p-Smad5 and osteocalcin secretion (young rats: model: 2.50 ± 0.71; L-icariin: 10.10 ± 1.55; M-icariin: 24.95 ± 2.19; H-icariin: 36.80 ± 2.26; old rats: model: 1.55 ± 0.49; L-icariin:6.55 ± 0.50; M-icariin: 15.00 ± 0.85; H-icariin:20.50 ± 2.27) at the fracture site, and increased the levels of bone formation markers (OC, BAP, NTX-1 and CTX-1) in a dose-dependent manner. In vitro, icariin treatment promoted rBMSC viability, increased ALP activity and the expression of BMP-2/Smad5/Runx2 pathway proteins. Discussion and conclusions Icariin may accelerate fracture healing by activating the BMP-2/Smad5/Runx2 pathway in relatively young and old rats. The research on the mechanism of icariin to promote fracture healing can provide a theoretical basis for the clinical application and promotion of icariin.
- Published
- 2021
13. Phyllanthin Averts Oxidative Stress and Neuroinflammation in Cerebral Ischemic-Reperfusion Injury through Modulation of the NF-κB and AMPK/Nrf2 Pathways
- Author
-
Haitao Yuan, Sankareswaran Muruganantham, Hong Xu, Qin Yang, Bo Yang, Omaima Nasif, and Jing Chen
- Subjects
Health, Toxicology and Mutagenesis ,Inflammation ,Pharmacology ,Toxicology ,medicine.disease_cause ,Neuroprotection ,Antioxidants ,Lignans ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,Cerebral edema ,Neuroblastoma ,chemistry.chemical_compound ,Cell Line, Tumor ,Animals ,Medicine ,Rats, Wistar ,Neuroinflammation ,business.industry ,AMPK ,NF-κB ,General Medicine ,medicine.disease ,Rats ,Neuroprotective Agents ,chemistry ,Reperfusion Injury ,medicine.symptom ,business ,Oxidative stress - Abstract
Cerebral ischemia-reperfusion (CIR) is a common feature of ischemic stroke and is a major cause of disability and death among stroke patients worldwide. Phyllanthin, a lignin polyphenol, is known for its varied biological properties, although its protective effects against CIR have not been reported. We evaluated the neuroprotective property of phyllanthin against CIR as well as the involvement of the AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways. Experimental animals were divided into five groups: controls (sham-operated), CIR-induced by middle cerebral artery occlusion (MCAO), and CIR-induced and administered phyllanthin at 2.5, 5, and 10 mg/kg, respectively. We investigated neurological functions, various signaling genes, and inflammatory clues. The results of in vitro assays demonstrated that phyllanthin assertively improved cellular functions through abrogation of the Nrf2 pathway. In vivo, CIR rats demonstrated neurological function deficits, while ischemic severity was evidenced by the activation of neuroinflammatory cytokines and tissue oxidative stress. Moreover, the expression of apoptosis markers such as Bax, B-cell lymphoma (Bcl-2), caspase-3, COX-2, PGE2, and LOX-1 abruptly increased. Phyllanthin prevented brain dysfunction and cerebral edema, and protected brain integrity. Conversely, it improved antioxidative enzyme activity, abrogated inflammatory cytokines, and increased IL-10 in chemokines. Also, phyllanthin significantly reduced Nrf2 and AMPK levels, with reduced expression of NF-κB indicating that cross-talk between the NF-kB and Nrf2 pathways is activated in CIR. Phyllanthin rescues the ischemic brain by regulating cellular signaling, which supports its use for complications like CIR and associated injury.
- Published
- 2021
14. Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development
- Author
-
Zhen Qin, Ye Liu, Yong Liu, Dan Su, Dexu Xu, Yuan Zhao, Hao Peng, Lusong Luo, Bo Ren, Fan Wang, Changxin Huo, Min Wei, Yingcai Feng, Huibin Yan, Qiu Ming, Yin Guo, Kuang Xianzhao, Wenfeng Gong, Zhiwei Wang, Hong Xu, Xuebing Sun, Yajuan Gao, Xuesong Liu, Ruipeng Qi, Lai Wang, Beibei Jiang, Changyou Zhou, Yiyuan Wu, Fenglong Yu, Yutong Zhu, Hexiang Wang, Lei Lv, Xing Wang, and Tristin Tang
- Subjects
Indoles ,DNA repair ,Poly ADP ribose polymerase ,Carbazoles ,Poly(ADP-ribose) Polymerase Inhibitors ,01 natural sciences ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,Dogs ,Microsomes ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Structure–activity relationship ,IC50 ,Polymerase ,Cell Proliferation ,030304 developmental biology ,chemistry.chemical_classification ,Fluorenes ,0303 health sciences ,Binding Sites ,biology ,Xenograft Model Antitumor Assays ,Rats ,0104 chemical sciences ,Isoenzymes ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Enzyme ,chemistry ,PARP inhibitor ,biology.protein ,Cancer research ,Molecular Medicine ,Female ,Poly(ADP-ribose) Polymerases ,Drug metabolism ,Half-Life - Abstract
Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.
- Published
- 2020
15. Preparation and characterization of carboxymethylated cotton fabrics as hemostatic wound dressing
- Author
-
Bijia Wang, Yujun Liu, Yi Zhong, Xueling Feng, Xiaofeng Sui, Hong Xu, Wang Yamei, Zhize Chen, Dongdong Xiao, Linping Zhang, and Zhiping Mao
- Subjects
Biocompatibility ,Rat model ,Biocompatible Materials ,02 engineering and technology ,Biochemistry ,Hemostatics ,Rats, Sprague-Dawley ,03 medical and health sciences ,Crystallinity ,Structural Biology ,Animals ,Cotton Fiber ,Food science ,Molecular Biology ,030304 developmental biology ,Hemostasis ,Wound Healing ,0303 health sciences ,Viscosity ,Chemistry ,Liver Diseases ,technology, industry, and agriculture ,General Medicine ,021001 nanoscience & nanotechnology ,Bandages ,Rats ,Disease Models, Animal ,Wound dressing ,0210 nano-technology - Abstract
Uncontrolled hemorrhage is a large cause of death in the global scope, thus leading to an urgent demand to develop efficient hemostatic materials. In this study, a series of modified cotton fabrics (MCFs) with different carboxymethyl group contents were prepared from cotton fabric (CF) by a carboxymethylation process to choose the appropriate one with the best hemostatic performance. The carboxymethyl group contents of MCFs rose up as the dosages of ClCH2COOH increased. The crystallinity of CF decreased after carboxymethylation, and MCFs can dissolve slightly with the phenomenon that there were vague boundaries between fibers after being treated with water. Furthermore, the MCF with the carboxymethyl group content at 0.77 mmol/g (MCF-0.77) could absorb the blood quickly, achieve dense distribution of blood cells and have high viscosity of leaching liquor. In addition, the MCF-0.77 with good biocompatibility accelerated the hemostasis time to 46.6 ± 8.4 s compared with the CF (88.8 ± 31.5 s) in a rat model of liver injury. In summary, the prepared MCF-0.77 is a potential hemostatic wound dressing for clinical use since every second counts for pre-hospital care.
- Published
- 2020
16. The influence of mosapride on gut microbiota of carbon tetrachloride-induced cirrhosis rats based on 16S rRNA gene sequencing
- Author
-
Dongya Chen, Jingfang Xiong, Hui Feng, Yihui Liu, Jianjun Xu, and Hong Xu
- Subjects
Liver Cirrhosis ,Male ,Bacteria ,Morpholines ,Medicine (miscellaneous) ,Genes, rRNA ,General Biochemistry, Genetics and Molecular Biology ,Gastrointestinal Microbiome ,Rats ,Rats, Sprague-Dawley ,RNA, Ribosomal, 16S ,Reviews and References (medical) ,Benzamides ,Internal Medicine ,Animals ,Pharmacology (medical) ,Carbon Tetrachloride ,Genetics (clinical) - Abstract
Mosapride significantly improves intestinal motility in liver cirrhosis, ultimately leading to the reduction in plasma endotoxin levels and bacterial translocation.To investigate the effects of mosapride on intestinal microecology in cirrhotic rats and its potential mechanisms.Forty-five healthy male Sprague-Dawley rats that were pathogen-free (weight 200-220 g) were randomly divided into a control group (n = 15), model group (n = 15) and mosapride group (n = 15). Then, the pathological changes in the liver and intestine were determined through tissue staining and using transmission electron microscope (TEM). Bacterial translocation was examined. High throughput 16S rRNA sequencing was performed to determine the changes of gut microbiota in each group.Compared with the model group, mosapride treatment induced no attenuation in hepatic morphology and pathology changes. The TEM indicated no differences in intestinal structure in both groups. There was a significant decline in the rate of gut microbiota translocation in the mosapride group compared with the model group. There were intestinal microbiota changes in the mosapride group compared with that of the model group, including Bacteroidetes, Prevotellaceae, Alloprevotella, Ruminiclostridium, Negativicutes, Selenomonadales, Veillonellaceae, Anaerovibrio, Campylobacterales, Epsilonbacteraeota, Helicobacter, Oscillibacter, Verrucomicrobiales, Akkermansia, Intestinimonas, Eubacterium, Clostridiaceae, Clostridium, Bacteroides, Tyzzerella, Actinobacteria, and Bifidobacteriales. Among these bacteria, Alloprevotella showed a strong correlation with the other bacteria.Taken together, we concluded that mosapride may reduce intestinal bacterial translocation through regulating the gut microbiota in rats with hepatic cirrhosis.
- Published
- 2022
- Full Text
- View/download PDF
17. Tanshinone IIA Ameliorates Progression of CAD Through Regulating Cardiac H9c2 Cells Proliferation and Apoptosis by miR-133a-3p/EGFR Axis
- Author
-
Hong, Xu, Haiqing, Li, Pengxiong, Zhu, Yun, Liu, Mi, Zhou, and Anqing, Chen
- Subjects
Drug Design, Development and Therapy ,Cell Survival ,EGFR ,Anti-Inflammatory Agents, Non-Steroidal ,Apoptosis ,Salvia miltiorrhiza ,Hydrogen Peroxide ,tanshinone IIA ,Rats ,ErbB Receptors ,miR-133a-3p ,MicroRNAs ,Abietanes ,Animals ,Humans ,Cells, Cultured ,coronary artery disease ,Cell Proliferation ,Original Research - Abstract
Hong Xu,* Haiqing Li,* Pengxiong Zhu, Yun Liu, Mi Zhou, Anqing Chen Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Anqing ChenDepartment of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, People’s Republic of ChinaEmail chenanqing08@hotmail.comBackground: Coronary artery disease (CAD) leads to the highest mortality worldwide, seriously threatening human health. Tanshinone IIA (Tan IIA), which could be extracted from Danshen, is applied in the treatment of cardiovascular and cerebrovascular diseases. MicroRNAs (miRNAs, miRs) play pivotal roles in cell proliferation and cell apoptosis of the cardiovascular system. The aim of the present study was to explore the role of Tan IIA in CAD in vitro and the underlying molecular mechanism.Methods: Real-time polymerase chain reaction (RT-PCR) and Western blot were used for the detection of miRNA/mRNA and protein, respectively. Target genes of miR-133a-3p were searched in TargetScan, and the targeting relationship was verified by dual-luciferase reporter assay. Cell proliferation was determined using a Cell Counting Kit-8 (CCK-8) and EdU labeling. Cell apoptosis was detected by flow cytometry and TUNEL staining.Results: In the present study, lower miR-133a-3p level and higher epidermal growth factor receptor (EGFR; the target of miR-133a-3p) level were found in H2O2-induced H9c2 cells. In addition, Tan IIA upregulated miR-133a-3p and downregulated EGFR expression. Moreover, Tan IIA promoted cell proliferation and suppressed apoptosis and enhanced G0/G1, which was reversed by miR-133a-3p inhibitor, while siRNA-EGFR abolished the effects induced by miR-133a-3p in H2O2-induced H9c2 cells.Conclusion: Tan IIA reversed H2O2-induced cell proliferation reduction, cell apoptosis induction, and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis. The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD.Keywords: tanshinone IIA, coronary artery disease, miR-133a-3p, EGFR
- Published
- 2020
18. Durable and Effective Antibacterial Cotton Fabric Collaborated with Polypropylene Tissue Mesh for Abdominal Wall Defect Repair
- Author
-
Xiaofeng Sui, Gu Yan, Xueling Feng, Mujun Lu, Dongdong Xiao, Zhiping Mao, Liduo Rong, Dongchao Yang, Bijia Wang, and Hong Xu
- Subjects
Staphylococcus aureus ,Materials science ,Biocompatibility ,0206 medical engineering ,Biomedical Engineering ,Two layer ,02 engineering and technology ,Polypropylenes ,Biomaterials ,chemistry.chemical_compound ,Escherichia coli ,medicine ,Animals ,Polypropylene ,Abdominal wall defect ,Composite mesh ,Abdominal Wall ,Surgical Mesh ,021001 nanoscience & nanotechnology ,medicine.disease ,020601 biomedical engineering ,Anti-Bacterial Agents ,Rats ,Polypropylene mesh ,chemistry ,0210 nano-technology ,Biomedical engineering - Abstract
A feasible, efficient antibacterial and anti-infective mesh for clinical abdominal wall defect repair is significant, but challenging due to the complexity of the postoperative wound environment. Herein, a simple strategy was provided to construct woven cotton fabric modified with gentamicin (Gem) via the enamine bonds. The obtained cotton fabric possessed favorable antibacterial properties against E. coli and S. aureus with the bactericidal rate of over 99.99% and could be combined with a commercial polypropylene (PP) mesh to serve as a two-layer composite mesh for abdominal wall defect repair. The antibacterial cotton layer was systematically characterized by FTIR, XPS, SEM, EDS, and mechanical measurements. The C2C12 cells and human fibroblasts were employed to assess the cytocompatibility of the composite mesh in vitro. Furthermore, the rat abdominal wall defect model was used to evaluate the efficacy of antibacterial and anti-infection properties. It was demonstrated that the two-layer composite mesh possessed favorable biocompatibility and satisfactory anti-infection properties involved in abdominal wall defect repair. Therefore, this synergetic two-layer composite mesh would out-perform surgical PP meshes in preventing infectious complications.
- Published
- 2020
19. Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex
- Author
-
Na Mao, Ying Zhu, Gengxu Li, Zhongqiu Wei, Xuemin Gao, Fang Yang, Dingjie Xu, Wenchen Cai, Shifeng Li, Qiaodan Zhang, Siyu Niu, Hong Xu, Guizhen Zhang, Xue Yi, Si Chen, and Dan Li
- Subjects
Male ,0301 basic medicine ,Silicosis ,Kinesins ,Medicine (miscellaneous) ,fibroblast ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Primary cilia ,Zinc Finger Protein Gli3 ,GLI3 ,medicine ,Animals ,Humans ,Hedgehog Proteins ,KIF3A ,Cilia ,Sonic hedgehog ,Myofibroblasts ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,biology ,Oncogene ,Chemistry ,Cilium ,Cell Differentiation ,Fibroblasts ,Silicon Dioxide ,medicine.disease ,Glioma-associated oncogene homolog 3 ,Actins ,Rats ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Kinesin family member 3A ,sense organs ,ACTA2 ,Myofibroblast ,Research Paper ,Signal Transduction ,Transcription Factors - Abstract
The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2. Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.
- Published
- 2020
20. Identification and characterization of the Cucurbitacins, a novel class of small-molecule inhibitors of Tropomyosin receptor kinase a
- Author
-
Li-Mei Li, Xu Gaojie, Xuemiao Zhang, Yi Zhong, Tai Yang, Minhui Li, Jin Liu, Zhong Yueling, Ting Zeng, and Hong Xu
- Subjects
Kinase ,animal structures ,Momordica charantia ,Amino Acid Motifs ,Bitter gourd ,Tropomyosin receptor kinase A ,PC12 Cells ,03 medical and health sciences ,0302 clinical medicine ,Cucumis melo ,Nerve Growth Factor ,Animals ,Humans ,Enzyme Inhibitors ,Phosphorylation ,Receptor, trkA ,Kinase activity ,Tyrosine ,Protein kinase B ,030304 developmental biology ,0303 health sciences ,Plant Extracts ,Chemistry ,TrkA ,Inhibitors ,Pruritus ,General Medicine ,Cucurbitacins ,lcsh:Other systems of medicine ,lcsh:RZ201-999 ,Rats ,Kinetics ,Complementary and alternative medicine ,Biochemistry ,nervous system ,Cell culture ,Fruit ,030220 oncology & carcinogenesis ,Research Article - Abstract
Background NGF-TrkA is well known to play a key role in propagating and sustaining pruritogenic signals, which form the pathology of chronic pruritus. Inhibition of NGF-TrkA is a known strategy for the treatment of pruritus. In the present paper, we describe the identification, in vitro characterization, structure–activity analysis, and inhibitory evaluation of a novel TrkA inhibitory scaffold exemplified by Cucurbitacins (Cus). Methods Cus were identified as TrkA inhibitors in a large-scale kinase library screen. To obtain structural models of Cus as TrkA inhibitors, AutoDock was used to explore their binding to TrkA. Furthermore, PC12 cell culture systems have been used to study the effects of Cus and traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) extracts on the kinase activity of TrkA. Results Cus block the phosphorylation of TrkA on several tyrosine sites, including Tyr490, Tyr674/675, and Tyr785, and inhibit downstream Akt and MAPK phosphorylation in response to NGF in PC12 cell model systems. Furthermore, traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) containing Cu extracts were shown to inhibit the phosphorylation of TrkA and Akt. These data reveal mechanisms, at least partly, of the anti-pruritus bioactivity of Cus. Conclusion Taken together, with the recent discovery of the important role of TrkA as a therapeutic target, Cus could be the basis for the design of improved TrkA kinase inhibitors, which could someday help treat pruritus.
- Published
- 2019
21. Effect of thermophilic bacterium HB27 manganese superoxide dismutase in a rat model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
- Author
-
Xue-Cheng Wei, Yu-Xiang Cheng, Hong Xu, Jin-Lai Gao, Ling-Feng Wu, Naiwen Chen, Yi He, Wen-Hua Xie, and Jing Jin
- Subjects
Male ,medicine.medical_specialty ,Urology ,Aspartate transaminase ,Prostatitis ,medicine.disease_cause ,Pelvic Pain ,Superoxide dismutase ,Rats, Sprague-Dawley ,Chronic prostatitis/chronic pelvic pain syndrome ,Internal medicine ,medicine ,Animals ,Humans ,chemistry.chemical_classification ,Inflammation ,Reactive oxygen species ,biology ,Superoxide Dismutase ,Glutathione peroxidase ,NF-kappa B ,General Medicine ,Syndrome ,medicine.disease ,Fibrosis ,Rats ,Endocrinology ,chemistry ,Alanine transaminase ,biology.protein ,Cytokines ,Chronic Pain ,Oxidative stress - Abstract
We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS.
- Published
- 2021
22. Glycolytic Reprogramming in Silica-Induced Lung Macrophages and Silicosis Reversed by Ac-SDKP Treatment
- Author
-
Na Mao, Yaqian Li, Ying Sun, Honghao Yang, Fuyu Jin, Heliang Liu, Xinyu Yang, Jie Yin, Tian Li, Hong Xu, and Fang Yang
- Subjects
Male ,QH301-705.5 ,Pulmonary Fibrosis ,Silicosis ,Inflammation ,PKM2 ,Catalysis ,Article ,Inorganic Chemistry ,Mice ,Western blot ,N-acetyl-seryl-aspartyl-lysyl-proline ,Pulmonary fibrosis ,Macrophages, Alveolar ,medicine ,Macrophage ,Animals ,Glycolysis ,Biology (General) ,Physical and Theoretical Chemistry ,RNA, Small Interfering ,Rats, Wistar ,QD1-999 ,Molecular Biology ,Lung ,Spectroscopy ,medicine.diagnostic_test ,Chemistry ,Macrophages ,Organic Chemistry ,General Medicine ,glycolysis ,Fibroblasts ,medicine.disease ,Silicon Dioxide ,Computer Science Applications ,Cell biology ,Rats ,Mice, Inbred C57BL ,medicine.symptom ,Reprogramming ,Oligopeptides - Abstract
Glycolytic reprogramming is an important metabolic feature in the development of pulmonary fibrosis. However, the specific mechanism of glycolysis in silicosis is still not clear. In this study, silicotic models and silica-induced macrophage were used to elucidate the mechanism of glycolysis induced by silica. Expression levels of the key enzymes in glycolysis and macrophage activation indicators were analyzed by Western blot, qRT-PCR, IHC, and IF analyses, and by using a lactate assay kit. We found that silica promotes the expression of the key glycolysis enzymes HK2, PKM2, LDHA, and macrophage activation factors iNOS, TNF-α, Arg-1, IL-10, and MCP1 in silicotic rats and silica-induced NR8383 macrophages. The enhancement of glycolysis and macrophage activation induced by silica was reduced by Ac-SDKP or siRNA-Ldha treatment. This study suggests that Ac-SDKP treatment can inhibit glycolytic reprogramming in silica-induced lung macrophages and silicosis.
- Published
- 2021
23. The regulatory effect of pulmonary lymphatic drainage on silicosis fibrosis
- Author
-
Jie, Cui, Hailan, He, Hong, Xu, Ziying, Chen, Jingsi, Wang, Yi, Liu, Xiaohui, Hao, Lingli, Guo, Heliang, Liu, and Hongli, Wang
- Subjects
Inflammation ,Phosphatidylinositol 3-Kinases ,Health, Toxicology and Mutagenesis ,Silicosis ,Public Health, Environmental and Occupational Health ,Animals ,General Medicine ,Silicon Dioxide ,Fibrosis ,Pollution ,Lymphatic Vessels ,Rats - Abstract
Silicosis is a fibrotic disease caused by long-term inhalation of SiO
- Published
- 2022
24. Interaction of N ‐acetyl‐seryl‐aspartyl‐lysyl‐proline with the angiotensin‐converting enzyme 2–angiotensin‐(1–7)–Mas axis attenuates pulmonary fibrosis in silicotic rats
- Author
-
Fuyu Jin, Fang Yang, Yalou Liu, Hui Zhang, Shifeng Li, Dingjie Xu, Bonan Zhang, Xiaohui Hao, Shumin Li, Dan Li, Zhongqiu Wei, Heliang Liu, Xuemin Gao, Hong Xu, Lijuan Zhang, Guizhen Zhang, Tao Tao, Wenchen Cai, and Na Mao
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Pulmonary Fibrosis ,Silicosis ,Peptidyl-Dipeptidase A ,030204 cardiovascular system & hematology ,Proto-Oncogene Mas ,Collagen Type I ,Receptors, G-Protein-Coupled ,Renin-Angiotensin System ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Proto-Oncogene Proteins ,Physiology (medical) ,Internal medicine ,Pulmonary fibrosis ,Renin–angiotensin system ,medicine ,Animals ,Humans ,Rats, Wistar ,Receptor ,Cells, Cultured ,Nutrition and Dietetics ,Chemistry ,Angiotensin II ,Cell Differentiation ,General Medicine ,Fibroblasts ,medicine.disease ,Actins ,Peptide Fragments ,Rats ,Endocrinology ,Angiotensin-converting enzyme 2 ,Collagen ,Angiotensin I ,Oligopeptides ,Myofibroblast ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery - Abstract
New findings What is the central question of this study? What are the effects of the antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas axis during the occurrence and progression of silicosis? What is the main finding and its importance? Ac-SDKP inhibited lung fibrosis in rats exposed to silica by activation of the ACE2-angiotensin-(1-7)-Mas axis. Angiotensin-(1-7) potentially promotes Ac-SDKP by increasing the level of meprin α, the major synthetase of Ac-SDKP. Thus, the interaction Ac-SDKP and angiotesin-(1-7) in silicosis could provide a new therapeutic strategy. Abstract The central role of angiotensin-converting enzyme (ACE) in the occurrence and progression of silicosis has been established. The antifibrotic peptide acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) can be degraded by ACE. The ACE2-angiotensin-(1-7)-Mas axis is protective and acts to counterbalance the detrimental effects of ACE-angiotensin II (Ang II)-Ang II type 1 receptor and exerts antifibrotic effects. Here, we demonstrate an interaction between Ac-SDKP and Ang-(1-7) in the inhibition of collagen deposition and myofibroblast differentiation in rats exposed to silica. Treatment with Ac-SDKP increased the level of ACE2-Ang-(1-7)-Mas in rats or in cultured fibroblasts and decreased the levels of collagen type I and α-smooth muscle actin. Furthermore, exogenous Ang-(1-7) had similar antifibrotic effects and increased the level of meprin α, a major Ac-SDKP synthetase, both in vivo and in vitro. Compared with non-silicotic patients exposed to silica, the level of serum ACE was increased in patients with silicosis phase III; the levels of Ang II and Ang-(1-7) were high in patients with silicosis phase II; and the level of Ac-SDKP was high in the silicosis phase III group. These data imply that Ac-SDKP and Ang-(1-7) have an interactive effect as regulatory peptides of the renin-angiotensin system and exert antifibrotic effects.
- Published
- 2019
25. Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats
- Author
-
Xin Zhang, Xuemin Gao, Hui Zhang, Bonan Zhang, Hong Xu, Guizhen Zhang, and Fang Yang
- Subjects
medicine.medical_specialty ,Captopril ,Primary Cell Culture ,Silicosis ,Peptidyl-Dipeptidase A ,Biochemistry ,Collagen Type I ,Receptor, Angiotensin, Type 1 ,Renin-Angiotensin System ,Pathogenesis ,Fibrosis ,Internal medicine ,Genetics ,medicine ,Van Gieson's stain ,Animals ,Humans ,Rats, Wistar ,Lung ,Angiotensin II receptor type 1 ,Chemistry ,Angiotensin II ,Fibroblasts ,Silicon Dioxide ,medicine.disease ,Actins ,Rats ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,Angiotensin-Converting Enzyme 2 ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
The dynamic variation of renin-angiotensin system (RAS) in silicosis remains unclear. Seventy Wistar rats were divided into 7 groups including control group, silicosis groups (inhaling SiO2 for 2, 4, 8, 16 and 24 weeks, respectively) and Captopril (Cap) group. Rat lung primary fibroblasts were divided into control group, SiO2-stimulated group (0, 0.5, 1, 3, 6, 12, 24 and 48 h) and Cap group. The silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) staining. Cap relieved the lung fibrosis and collagen deposition. Immunohistochemistry indicated the positive expression of α-smooth muscle actin (α-SMA) was increased gradually in silicotic rat lung tissue. Western blotting revealed the expression of collagen type I (Col I) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by SiO2. Cap decreased the expression of Col I and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by SiO2. Western blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) was increased, and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by SiO2. ELISA showed the serum levels of ACE and angiotensin II (Ang II) were also increased and ACE2 and Ang (1-7) were decreased in the silicosis group. Treatment with Cap decreased the expression levels of ACE, Ang II and AT1, and increased the expression levels of ACE2, Ang (1-7) and Mas. These findings suggested that an imbalance between ACE-Ang II-AT1 axis and ACE2-Ang (1-7)-Mas axis may participate in the development of silicosis.
- Published
- 2019
26. Proteomic profile of TGF-β1 treated lung fibroblasts identifies novel markers of activated fibroblasts in the silica exposed rat lung
- Author
-
Bonan Zhang, Dan Li, Shumin Li, Gao Xuemin, Ruimin Wang, Guizhen Zhang, Dingjie Xu, Hui Zhang, Jin Wang, Lijuan Zhang, Yang Fang, Fuyu Jin, Mao Na, Cai Wenchen, Hong Xu, Shifeng Li, Dominic Sales, Ying Zhu, Wei Zhongqiu, and Ross Summer
- Subjects
Male ,0301 basic medicine ,Silicosis ,Cell ,Very Low-Density Lipoprotein Receptor ,Biology ,Proteomics ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Pulmonary fibrosis ,medicine ,Animals ,Rats, Wistar ,Fibroblast ,Cells, Cultured ,Gene knockdown ,Chemistry ,Cell Biology ,Fibroblasts ,respiratory system ,medicine.disease ,Molecular biology ,Transmembrane protein ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, LDL ,030220 oncology & carcinogenesis ,Collagen ,Syndecan-2 ,Transcriptome ,Myofibroblast ,Transforming growth factor - Abstract
We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-β1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-β1 treatment and 196 proteins were expressed at ≥ 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-β1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-β1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-β1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.HighlightsWe identified 196 proteins differentially expressed between control and TGF-β1 treated fibroblastsby LC-MS/MS.Several proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2Knockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.
- Published
- 2019
27. Oral Delivery of Honokiol Microparticles for Nonrapid Eye Movement Sleep
- Author
-
Yang Yang, Changyou Zhan, Tian-Xiao Wang, Jun Qian, Zhi-Li Huang, Juan Guan, Xiaoqin Liu, Wei-Min Qu, Juan Wang, Junyi Chen, and Xin-Hong Xu
- Subjects
Honokiol ,animal structures ,Eye Movements ,medicine.drug_class ,Cmax ,Administration, Oral ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Sleep, Slow-Wave ,030226 pharmacology & pharmacy ,Non-rapid eye movement sleep ,Lignans ,Rats, Sprague-Dawley ,Benzodiazepines ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Oral administration ,Drug Discovery ,Animals ,Medicine ,Drug Carriers ,Benzodiazepine ,biology ,business.industry ,GABAA receptor ,Biphenyl Compounds ,Electroencephalography ,Receptors, GABA-A ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Rats ,Bioavailability ,Magnolia officinalis ,chemistry ,embryonic structures ,Molecular Medicine ,Female ,0210 nano-technology ,business - Abstract
Honokiol (HNK) is a small-molecule lignin extracted from Magnolia Officinalis, demonstrating high potency in promoting nonrapid eye movement (NREM) sleep by modulating the benzodiazepine site of the GABAA receptor. However, the clinical use of HNK in the treatment of insomnia is restricted by its extremely low oral bioavailability. In the present work, enhanced oral bioavailability of HNK was achieved by loading it into poly lactide–glycolide acid microparticles (HNK-MP). After oral administration, HNK-MP demonstrated 15-fold increase of AUC0–12 h in comparison to free HNK. The maximum blood concentration (Cmax) of HNK in HNK-MP-treated rats was 3.6 μg/mL at 2 h after oral administration, which was 6.5-fold of that in free HNK-treated rats. Oral administration of HNK-MP (20 mg/kg) efficiently increased NREM sleep by 60% by enhancing the transition from wakefulness to NREM sleep in rats. The biosafety of HNK-MP was assessed in vivo, and no damage occurred in the gastrointestinal tract. The present study pr...
- Published
- 2019
28. Noncoding transcribed ultraconserved region (T‐UCR) UC.48+ is a novel regulator of high‐fat diet induced myocardial ischemia/reperfusion injury
- Author
-
Jiani Zhao, Lu Ding, Rumeng Wang, Shenqiang Rao, Tao Li, Shuo Wang, Shanping Peng, Wen Xiao, Xingzi Liu, Hong Xu, Yuanyuan Liu, Chengxin Gong, Shangdong Liang, and Chaopeng Xiong
- Subjects
Male ,0301 basic medicine ,Physiology ,Clinical Biochemistry ,Regulator ,Apoptosis ,Myocardial Reperfusion Injury ,Diet, High-Fat ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pyrrolidine dithiocarbamate ,Downregulation and upregulation ,medicine ,Animals ,Gene silencing ,Myocytes, Cardiac ,RNA, Messenger ,RNA, Small Interfering ,Sp1 transcription factor ,Purinergic receptor ,Cell Biology ,Transfection ,medicine.disease ,Molecular biology ,Rats ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,030220 oncology & carcinogenesis ,RNA, Long Noncoding ,Receptors, Purinergic P2X7 ,Reperfusion injury - Abstract
Increasing evidence has suggested high-fat diet (HFD) is an independent risk factor for myocardial ischemia/reperfusion (MI/R) injury. Long noncoding RNAs (lncRNAs) recently attracted much attraction in the study of MI/R injury. However, the functional questions of specific lncRNAs in HFD-induced MI/R injury have not been well elucidated. Uc.48+ is a lncRNA from a transcribed ultraconserved region (T-UCR) of human, mouse, and rat genomes. Here, we explored the aggravating role of uc.48+and identified purinergic P2X7 receptor (P2X7R) as a downstream regulator of uc.48+ in HFD-induced MI/R vulnerability. We demonstrated uc.48+ expression was upregulated, accompanied by the corresponding upregulation of P2X7R in HFD I/R myocardium and HFD-induced MI/R vulnerability. Overexpression of uc.48+enhanced, whereas silencing of uc.48 + decreased the expression of P2X7R, cardiomyocyte apoptosis, and MI/R injury. The functional relevance of uc.48+ regulated P2X7R expression and the subsequent NF-κB signaling to promote cardiomyocyte apoptosis was supported by inhibition of P2X7R with its specific antagonist (A438079) as well as the inhibitor of NF-κB signaling (pyrrolidine dithiocarbamate, PDTC) in H9c2 hypoxia/reoxygenation (H/R) cells transfected with pcDNA3.0-uc.48 + plasmid, and RNA immunoprecipitation (RIP) suggested uc.48+ could interact with transcription factor Sp1. Importantly, Sp1 inhibitor (mithramycin, MIT) was found to suppress uc.48+ -induced P2X7R expression and the NF-κB signaling and cardiomyocyte apoptosis. Our findings provide a potential novel mechanism through which uc.48+ boosts cardiomyocyte apoptosis and MI/R vulnerability to HFD. Thus, uc.48+ is a novel regulator of HFD-induced MI/R injury; targeting uc.48+ may be a novel therapeutic approach of MI/R vulnerability to HFD.
- Published
- 2018
29. Bone marrow mesenchymal stem cells stimulated with low‐intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury
- Author
-
Hong Xu, Guangzhi Ning, Ru‐Sen Zhu, Ji‐Qing Li, Shibo Zhu, Shiqing Feng, Yu Wu, Zhigang Qu, Qiu-Li Wu, Wen-Ye Song, and Man Wang
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Ultrasonic Therapy ,Low-intensity pulsed ultrasound ,Mesenchymal Stem Cell Transplantation ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Neurotrophic factors ,Physiology (medical) ,Animals ,Medicine ,Pharmacology (medical) ,Rats, Wistar ,Spinal cord injury ,Cells, Cultured ,Spinal Cord Injuries ,Bone Marrow Transplantation ,Pharmacology ,biology ,business.industry ,hemic and immune systems ,Original Articles ,Spinal cord ,medicine.disease ,Rats ,Transplantation ,Psychiatry and Mental health ,Treatment Outcome ,030104 developmental biology ,Nerve growth factor ,medicine.anatomical_structure ,Ultrasonic Waves ,biology.protein ,Female ,Stem cell ,business ,030217 neurology & neurosurgery ,Neurotrophin - Abstract
Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low‐intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS‐BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS‐BMSCs postinjury, locomotor function was significantly improved in LIPUS‐BMSCs transplantation group with higher level of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS‐BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS‐BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.
- Published
- 2018
30. Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water
- Author
-
Fei Ran, Run-Chun Xu, Junzhi Lin, Bi Feng, Li Han, Min Qiu, Bo Cao, Jiao Song, Ding-Kun Zhang, and Hong Xu
- Subjects
Male ,Linoleic acid ,Analgesic ,Mammary Gland Tissue ,Anti-Inflammatory Agents ,Administration, Oral ,Pain ,Traditional Chinese medicine ,Pharmacology ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Oral administration ,Drug Discovery ,medicine ,Animals, Outbred Strains ,Animals ,Metabolomics ,Medicine, Chinese Traditional ,030304 developmental biology ,Inflammation ,0303 health sciences ,Analgesics ,Hyperplasia ,business.industry ,Alcoholic Beverages ,Water ,Drug Synergism ,Oryza ,medicine.disease ,Rats ,Disease Models, Animal ,chemistry ,030220 oncology & carcinogenesis ,Pharmacodynamics ,Female ,Animal studies ,business ,Drugs, Chinese Herbal - Abstract
Ethnopharmacological relevance Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was “taking orally after soaked with Chinese Baijiu”, the modern method was changed to “taking orally with water” in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. Aim of the study To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). Materials and methods COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200–220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. Results The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. Conclusion In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.
- Published
- 2021
31. Anti-allergic Inflammatory Components from the Leaves of Piper crocatum RuizPav
- Author
-
Yue, Gong, Hong Xu, Li, Rui Hong, Guo, Wahyu, Widowati, Young Ho, Kim, Seo Young, Yang, and Young Ran, Kim
- Subjects
Plant Leaves ,Mice ,RAW 264.7 Cells ,Plant Extracts ,Cell Line, Tumor ,Methanol ,Anti-Allergic Agents ,Anti-Inflammatory Agents ,Drug Evaluation, Preclinical ,Animals ,Piper ,Rats - Abstract
Piper crocatum RuizPav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and β-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased β-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.
- Published
- 2021
32. Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high‐resolution tandem mass spectrometry
- Author
-
Ming-Hua Ma, Hua Nian, Xiao-Hong Xu, Xue-Mei Hu, Yi-Jun Zhang, and Qiang-Guo Ji
- Subjects
Male ,Electrospray ionization ,Glucuronidation ,Hydroxylation ,Mass spectrometry ,Tandem mass spectrometry ,01 natural sciences ,Analytical Chemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,Stilbenes ,Animals ,Bile ,Chromatography, High Pressure Liquid ,Spectroscopy ,Chromatography ,Molecular Structure ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Glutathione ,Rats ,0104 chemical sciences ,Metabolic pathway ,Hepatocytes ,Glucuronide - Abstract
Rationale Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti-oxidant and anti-inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. Methods The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high-resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. Results A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3'-hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. Conclusions The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.
- Published
- 2021
33. OC-STAMP Overexpression Drives Lung Alveolar Epithelial Cell Type II Senescence in Silicosis
- Author
-
Fuyu Jin, Yi-Bing Gao, Yaqian Li, Fang Yang, Wenchen Cai, Zhongqiu Wei, Shifeng Li, Hong Xu, Ying Sun, Dingjie Xu, Tian Li, Xinyu Yang, Zi-Yi Gao, Shu-Peng Liu, Heliang Liu, Xuemin Gao, and Na Mao
- Subjects
Senescence ,Aging ,Article Subject ,Silicosis ,Biochemistry ,Cell Line ,Myosin ,Animals ,Rats, Wistar ,Osteoclast stimulatory transmembrane protein ,Cellular Senescence ,Gene knockdown ,QH573-671 ,Chemistry ,Endoplasmic reticulum ,Membrane Proteins ,Cell Biology ,General Medicine ,Transfection ,In vitro ,Cell biology ,Rats ,Disease Models, Animal ,Gene Expression Regulation ,Alveolar Epithelial Cells ,Unfolded protein response ,Cytology ,Research Article - Abstract
Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.
- Published
- 2021
34. Nicotine withdrawal induces hyperalgesia via downregulation of descending serotonergic pathway in the nucleus raphe magnus
- Author
-
Liang Zhao, Kai Wei, Hai-Bo Qiu, Cheng-Jian Li, Hui-hong Xu, Zhi-Jie Lu, Ling Shen, and Cheng-Cheng Zhu
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Nicotine ,Serotonin ,Injections, Subcutaneous ,Methysergide ,Down-Regulation ,Serotonergic ,Nucleus Raphe Magnus ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Injections, Spinal ,Pharmacology ,Nucleus raphe magnus ,TPH2 ,business.industry ,medicine.disease ,Rats ,Substance Withdrawal Syndrome ,030104 developmental biology ,Nicotine withdrawal ,Endocrinology ,Hyperalgesia ,Receptors, Serotonin ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug ,Serotonergic Neurons - Abstract
Patients deprived of cigarettes exhibit increased pain sensitivity during perioperative periods, yet the underlying neuroanatomical and molecular bases of this hypersensitivity are unclear. The present study showed that both the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were significantly decreased in a rat model of nicotine withdrawal. These rats showed less tryptophan hydroxylase 2 (TPH2) positive neurons and reduced TPH2 expression in the nucleus raphe magnus (NRM), and thus resulted in decreased 5-hydroxytryptamine (5-HT) levels in cerebrospinal fluid. Intrathecal injection of 5-HT or NRM microinjection of TPH-overexpression adeno-associated virus alleviated nicotine withdrawal-induced hyperalgesia, whereas 5-HT receptor pharmacological blockade by methysergide (a 5-HT receptor antagonist) exacerbated hypersensitivity and diminished the difference between the two groups. Together, these data indicate that hyperalgesia after nicotine withdrawal is mediated by declined descending serotonergic pathways in the NRM. This provides a new perspective to improve the postoperative pain management of patients, especially the smokers.
- Published
- 2020
35. Discovery of new 2-phenyl-1H-benzo[d]imidazole core-based potent α-glucosidase inhibitors: Synthesis, kinetic study, molecular docking, and in vivo anti-hyperglycemic evaluation
- Author
-
Jin-He Zhang, Cheng-Shi Jiang, Zhi-Ling Song, Kai-Ming Wang, Kong-Kai Zhu, Yong-Xi Ge, Yue Li, Juan Zhang, and Hong-Xu Xie
- Subjects
Blood Glucose ,Stereochemistry ,Allosteric regulation ,Biochemistry ,Streptozocin ,Cell Line ,Diabetes Mellitus, Experimental ,Structure-Activity Relationship ,chemistry.chemical_compound ,Aniline ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Imidazole ,Glycoside Hydrolase Inhibitors ,Viability assay ,Molecular Biology ,Acarbose ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Imidazoles ,alpha-Glucosidases ,In vitro ,Rats ,Molecular Docking Simulation ,Kinetics ,Enzyme ,chemistry ,medicine.drug - Abstract
In the present study, a series of 2-phenyl-1H-benzo[d]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1H-benzo[d]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a, and the most promising inhibitors were found to be compounds 15o and 22d with IC50 values of 2.09 ± 0.04 and 0.71 ± 0.02 µM, respectively. Fluorescence quenching experiment confirmed the direct binding of compounds 15o and 22d with α-glucosidase. Kinetic study revealed that both compounds were non-competitive inhibitors, that was consistent with the result of molecular docking studies where they located at the allosteric site of the enzyme. Cell viability evaluation demonstrated the non-cytotoxicity of 15o and 22d against LO2 cells. Furthermore, the in vivo pharmacodynamic study revealed that compound 15o showed significant hypoglycemic activity and improved oral sucrose tolerance, comparable to the positive control acarbose.
- Published
- 2021
36. The involvement of ADAR1 in antidepressant action by regulating BDNF via miR-432
- Author
-
Yufei Li, Xiaonan Zhang, Wei Yan, Ziwei Zhao, Yi Wu, Hong Xu, Zhaoyang Xiao, Ying Xue, Xiuli Zhai, Lin Gui, Weizhi Yu, Deqin Yu, Jinying Li, Shengming Yin, and Ye Sun
- Subjects
Male ,medicine.medical_specialty ,Adenosine Deaminase ,PC12 Cells ,Epigenesis, Genetic ,03 medical and health sciences ,Behavioral Neuroscience ,Interferon-gamma ,Mice ,0302 clinical medicine ,Adenosine deaminase ,Neurotrophic factors ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Inducer ,Epigenetics ,030304 developmental biology ,Brain-derived neurotrophic factor ,0303 health sciences ,Messenger RNA ,Mice, Inbred BALB C ,biology ,Behavior, Animal ,Chemistry ,Depression ,Brain-Derived Neurotrophic Factor ,Rats ,Disease Models, Animal ,MicroRNAs ,Endocrinology ,Cell culture ,biology.protein ,Antidepressant ,030217 neurology & neurosurgery ,Stress, Psychological - Abstract
Brain-derived neurotrophic factor (BDNF) is a biomarker of depression. Recent studies have found adenosine deaminase acting on RNA1 (ADAR1) is a novel target being sensitive to stress at epigenetic level. The epigenetic regulation mechanism of stress-related depression is still unclear so far. To explore the potential regulating mechanism of ADAR1 on BDNF, over and low expression of ADAR1 in PC12 and SH-SY5Y cell lines are prepared. In the meanwhile, chronic unpredictable stress (CUS) mice are treated with ADAR1 inducer (interferon-γ, IFN-γ). ADAR1 regulates BDNF expression, which is proven by that over and low expressions of ADAR1 increase and decrease BDNF mRNA and protein respectively in vitro. Additionally, ADAR1 inducer alleviates the depressive-like behavior of CUS mice by recovering the decreased BDNF protein in brain and serum. Moreover, over and low expressions of ADAR1 reduce and enhance microRNA-432 (miR-432) expression respectively in vitro. Furtherly, over and low miR-432 expressions lead to decreased and increased BDNF and ADAR1 mRNA, protein and immunoreactivity respectively in vitro. The above results demonstrate that ADAR1 is involved in antidepressant action by regulating BDNF via miR-432. Those novel findings can provide a new idea for the study of epigenetic regulation mechanism, early diagnosis, and effective treatment of stress-related depression.
- Published
- 2020
37. A modified four vessel occlusion model of global cerebral ischemia in rats
- Author
-
Yue Geng, Xuesong Tian, Hong Xu, Yeting Chen, Wei Sun, Yongjie Zhang, Zean Zhang, Xiao-Hang Tang, and Runjie Guo
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Visual perception ,genetic structures ,Optic tract ,Carotid Artery, Common ,Ischemia ,Hippocampal formation ,Hippocampus ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine.artery ,medicine ,Hippocampus (mythology) ,Animals ,Common carotid artery ,Maze Learning ,Retina ,business.industry ,General Neuroscience ,Cerebral Infarction ,medicine.disease ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Cardiology ,Ligation ,business ,030217 neurology & neurosurgery - Abstract
Background To develop and evaluate a modified four vessel occlusion (4VO) model of global cerebral ischemia-reperfusion (GCI/R) in rats based on the Pulsinelli and Brierley's method. New methods Vertebral arteries (VAs) were isolated and then permanently ligated with 5-0 nylon surgical sutures under visual conditions. A total of 24 h later, GCI was induced by transient clipping of the bilateral common carotid artery for 20 min. Cognitive function and visual perception were then evaluated by behavioral and histopathological approaches. Results There was no significant difference in the survival rates between the groups. The modified 4VO group had a significantly lower body weight at each time point assessed. In the Y-maze test, the percentage of time spent and distance traveled in the III arm was significantly decreased on day 28, suggesting that cognitive function may have been impaired by the modified 4VO model. The modified 4VO procedure induced severe hippocampal damage but did not result in noticeable changes in visual perception, as indicated by the light-dark box test, and analysis of the optic tract and retinal structures. The modified 4VO procedure-induced cognitive deficits were thus likely the result of hippocampal damage, not visual perception. Comparison with existing methods The advantage of this model is the permanent ligation of the bilateral VAs under visual conditions rather than electrocoagulation, which is performed blind. Conclusions This modified 4VO model can mimic the GCI/R method of the Pulsinelli and Brierley and may serve as a valuable tool for studies on GCI/R.
- Published
- 2020
38. Electroacupuncture promotes axonal regrowth by attenuating the myelin-associated inhibitors-induced RhoA/ROCK pathway in cerebral ischemia/reperfusion rats
- Author
-
Yamin Zhang, Suhui Chen, Hong Xu, Huanyuan Wang, and Hua Sun
- Subjects
0301 basic medicine ,Male ,RHOA ,Neurite ,Electroacupuncture ,medicine.medical_treatment ,Neuronal Outgrowth ,Ischemia ,Pharmacology ,Rats, Sprague-Dawley ,03 medical and health sciences ,Myelin ,0302 clinical medicine ,medicine ,Animals ,Gap-43 protein ,Molecular Biology ,Stroke ,Myelin Sheath ,Pain Measurement ,rho-Associated Kinases ,biology ,business.industry ,General Neuroscience ,Fasudil ,Brain ,medicine.disease ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Reperfusion Injury ,biology.protein ,Neurology (clinical) ,business ,rhoA GTP-Binding Protein ,030217 neurology & neurosurgery ,Developmental Biology ,Signal Transduction - Abstract
The limited capacity of central nerve regeneration after cerebral ischemia has been the focus of attention in the field. Electroacupuncture (EA) is an effective therapy for functional rehabilitation after cerebral stroke. However, the underlying mechanism is still unclear. This study explored whether EA can improve the inhibitory microenvironment, attenuate RhoA/ROCK-mediated neurite regrowth inhibitory pathways, and promote the expression of neuroplasticity proteins, thus exerting a protective role in cerebral ischemia/reperfusion (I/R) injury. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 7 days of reperfusion, and they received EA or fasudil once daily for 7 days. The Garcia JH score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and transmission electron microscopy (TEM) were used to assess neural injury. The protein and mRNA levels of myelin-associated inhibitors (MAIs), RhoA/ROCK pathway-related molecules and neuroplasticity-related proteins were examined to explore the effect of EA on rats with cerebral I/R injury. We found that EA significantly decreased the infarct size and improved neurological function and hippocampal ultrastructure in the rats with cerebral ischemia/reperfusion (I/R) injury. EA ameliorates the inhibition of axonal regrowth and provides a protective role in functional rehabilitation after cerebral stroke by downregulating the MAI-induced RhoA/ROCK signaling pathway and by promoting the expression of GAP43 and BDNF to protect against cerebral I/R injury. Our findings provide a better understanding of the molecular mechanism underlying EA as an effective therapy for ischemic stroke.
- Published
- 2020
39. Photothermal Effect-based Cytotoxic Ability of Melanin from
- Author
-
Ya Mei, Liu, Wei Shuai, Ma, Yu Xi, Wei, and Yuan Hong, Xu
- Subjects
Melanins ,Rats, Sprague-Dawley ,Staphylococcus aureus ,Wound Healing ,Animal Shells ,Mytilus edulis ,Escherichia coli ,Animals ,Staphylococcal Infections ,Photochemical Processes ,Escherichia coli Infections ,Anti-Bacterial Agents ,Rats - Abstract
Owing to antibiotic abuse and the subsequent development of antibiotic resistance, bacterial infection has become one of the most persistent unresolved problems. New antibacterial agents, especially those that are environmental-friendly, are urgently needed.Melanin extracted by filtration centrifugation and acid and proteolytic hydrolysis was characterized using UV, FTIR, TEM, and XPS. Photothermal conversion was calculated, and the bacteriostatic effects,Natural melanin hydrolyzed by trypsin had good photothermal conversion effects, which resulted in superior bacteriostatic activities. The extracted melanin along with laser NIR irradiation at 808 nm promoted the healing of wounds infected by drug-resistant bacteriaThe present findings indicated a safe and efficient method of developing natural antibacterial agents.
- Published
- 2020
40. Icariin Accelerates Fracture Healing
- Author
-
Xiao-Yun, Zhang, Yue-Ping, Chen, Chi, Zhang, Xuan, Zhang, Tian, Xia, Jie, Han, Nan, Yang, Shi-Lei, Song, and Can-Hong, Xu
- Subjects
Flavonoids ,Fracture Healing ,Male ,Tibia ,Osteocalcin ,Cell Differentiation ,Mesenchymal Stem Cells ,Wnt1 Protein ,Alkaline Phosphatase ,Rats ,Disease Models, Animal ,Fractures, Bone ,Osteogenesis ,Animals ,Female ,Rats, Wistar ,Wnt Signaling Pathway ,Cells, Cultured ,beta Catenin - Abstract
Icariin has been shown to enhance bone formation.The present study aimed to investigate whether icariin also promotes bone fracture healing and its mechanisms.First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontaining serum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkaline phosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, we established a model of fracture healing in rats and performed gavage treatment for 20 days. Then, we detected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography, DR), and osteocalcin expression (immunohistochemistry).Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 and BMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen (NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing.Icariin can promote the levels of bone-formation markers, accelerate fracture healing, and activate the WNT1/β-catenin osteogenic signaling pathway.
- Published
- 2020
41. Protein Expression Profile in Rat Silicosis Model Reveals Upregulation of PTPN2 and Its Inhibitory Effect on Epithelial-Mesenchymal Transition by Dephosphorylation of STAT3
- Author
-
Ying Zhu, Hong Xu, Juxiang Yuan, Qiyun Cheng, Fang Yang, Jingxin Yao, Shumin Li, Heliang Liu, Xuemin Gao, and Yuxia Duan
- Subjects
Male ,STAT3 Transcription Factor ,Epithelial-Mesenchymal Transition ,Vimentin ,Protein tyrosine phosphatase ,Catalysis ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,STAT3 ,proteomics ,Downregulation and upregulation ,Silicosis ,silicosis ,medicine ,Gene silencing ,Animals ,Epithelial–mesenchymal transition ,Physical and Theoretical Chemistry ,Phosphorylation ,Rats, Wistar ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Gene knockdown ,Protein Tyrosine Phosphatase, Non-Receptor Type 2 ,biology ,Chemistry ,Organic Chemistry ,EMT ,General Medicine ,medicine.disease ,Molecular biology ,Computer Science Applications ,Rats ,Up-Regulation ,Disease Models, Animal ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,biomarker ,PTPN2 ,Transcriptome - Abstract
Silicosis is a chronic occupational lung disease caused by long-term inhalation ofcrystalline silica particulates. We created a rat model that closely approximates the exposure and development of silicosis in humans. Isobaric tags for relative and absolute quantitation (iTRAQ) technologies weused to identify proteins differentially expressed in activated rat lung tissue. We constructed three lentiviral knockdown vectorsand an overexpression vectorfor the protein tyrosine phosphatase non-receptor type 2 (PTPN2) geneto achieve stable long-term expression.A total of 471 proteins were differentially expressed in the silicosis group compared with controls. Twenty upregulated, and eight downregulated proteins exhibited a &ge, 1.5-fold change relative to controls. We next found that the PTPN2, Factor B, and VRK1 concentrations in silicotic rats silicosis and SiO2-stimulated MLE-12 cells were significantly higher than control groups.More importantly, we found that overexpression of PTPN2 simultaneously decreased the expression of phospho&ndash, signal transducer and activator of transcription 3 (p-STAT3) and Vimentin, while increasing E-cadherin expression. The opposite pattern was observed for PTPN2-gene silencing. We identified three proteins with substantially enhanced expression in silicosis. Our study also showed that PTPN2 can inhibit epithelial-mesenchymal transition by dephosphorylating STAT3 in silicosis fibrosis.
- Published
- 2020
- Full Text
- View/download PDF
42. MiR-411-3p alleviates Silica-induced pulmonary fibrosis by regulating Smurf2/TGF-β signaling
- Author
-
Fuyu Jin, Zhongqiu Wei, Na Mao, Fang Yang, Hong Xu, Shifeng Li, Shumin Li, Tian Li, Wenchen Cai, Heliang Liu, Xuemin Gao, Yaqian Li, Xue Yi, and Dingjie Xu
- Subjects
0301 basic medicine ,Male ,Pulmonary Fibrosis ,Ubiquitin-Protein Ligases ,Silicosis ,SMAD ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,Tgf β signaling ,Transforming Growth Factor beta ,Pulmonary fibrosis ,microRNA ,medicine ,Animals ,Rats, Wistar ,Lung ,Cell growth ,Cell Biology ,medicine.disease ,Silicon Dioxide ,Rats ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein - Abstract
Occupational exposure to silica dust particles was the major cause of pulmonary fibrosis, and many miRNAs have been demonstrated to regulate target mRNAs in silicosis. In the present study, we found that a decreasing level of miR-411-3p in silicosis rats and lung fibroblasts induced by TGF-β1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-β1 treatment and attenuate lung fibrosis in silicotic mice. In addition, a mechanistic study showed that miR-411-3p exert its inhibitory effect on Smad ubiquitination regulatory factor 2 (Smurf2) expression and decrease ubiquitination degradation of Smad7 regulated by smurf2, result in blocking of TGF-β/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-β/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.
- Published
- 2019
43. Effects of palmatine on rats with comorbidity of diabetic neuropathic pain and depression
- Author
-
Guilin Li, Changshui Xu, Hui Liu, Shangdong Liang, Shuangmei Liu, Yulin Shen, Hong Xu, Cancan Yin, Huixiang Ge, Guodong Li, Shu Guan, Yun Gao, Lingkun He, Lijuan Liu, and Wei Xiong
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,MAP Kinase Signaling System ,Berberine Alkaloids ,Hippocampus ,Rats, Sprague-Dawley ,Food Preferences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Diabetic Neuropathies ,Internal medicine ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Hippocampus (mythology) ,Phosphorylation ,Swimming ,Pain Measurement ,Analgesics ,Depression ,Tumor Necrosis Factor-alpha ,business.industry ,General Neuroscience ,Palmatine ,medicine.disease ,Comorbidity ,Rats ,Disease Models, Animal ,030104 developmental biology ,Allodynia ,Nociception ,Endocrinology ,Gene Expression Regulation ,chemistry ,Hyperalgesia ,Neuropathic pain ,Exploratory Behavior ,Receptors, Purinergic P2X7 ,medicine.symptom ,Food Deprivation ,business ,030217 neurology & neurosurgery ,Behavioural despair test - Abstract
Diabetic neuropathic pain (DNP) is one of the common complications of diabetes. Depression (DP) is also one of the common complications of diabetes. P2X7 receptors play an important role in the transmission of nociceptive signal and are associated with depressive illness. In the study, the hyperalgesia, allodynia and depressive behaviours of rats with comorbidity of DNP and DP were confirmed by the thermal withdrawal latency (TWL) test, mechanical withdrawal threshold (MWT) test, sucrose preference test (SPT), immobility time of forced swimming test (IMFST) and open-field test (OFT). The change in expression of the P2X7 receptor of the hippocampus was observed through RT-PCR, qPCR, Western blotting and immunohistochemical staining methods The results showed that palmatine treatment can alleviate the hyperalgesia, allodynia and depressive behaviours of rats with comorbidity of DNP and DP. Meanwhile, the expression of P2X7 receptors, GFAP, TNF-α and IL-1β in the hippocampus of the rats with comorbidity of DNP and DP was significantly increased compared with the control rats, and palmatine treatment could decrease the expression. Furthermore, the enhanced phosphorylation of ERK1/2 in the hippocampus of rats with DNP and DP was decreased noticeably by palmatine treatment. The results of this study suggest that palmatine can alleviate the comorbidity of DNP and DP by inhibiting the expression of P2X7 receptors in the hippocampus, and its action may be related to suppression of the phosphorylation of ERK1/2 and the release of TNF-α and IL-1β in the hippocampus.
- Published
- 2018
44. Puerarin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of inflammation
- Author
-
Shu-Hong Xu, Jingjing Liu, Chen Liang, Qing-Li Wang, Yan-Ling Mu, Jie Li, Xiao-Hui Sun, Yan Wang, Yi-Chi Zhang, Mao-Shan Yin, and Fu-Wen Wang
- Subjects
0301 basic medicine ,Antioxidant ,Diabetic Cardiomyopathies ,medicine.medical_treatment ,Pharmaceutical Science ,Inflammation ,Endogeny ,Pharmacology ,Cell Line ,Diabetes Mellitus, Experimental ,Analytical Chemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Puerarin ,Diabetic cardiomyopathy ,Drug Discovery ,Animals ,Medicine ,cardiovascular diseases ,Cells, Cultured ,chemistry.chemical_classification ,Molecular Structure ,business.industry ,Myocardium ,Organic Chemistry ,NF-kappa B ,General Medicine ,medicine.disease ,Isoflavones ,In vitro ,Rats ,Glucose ,030104 developmental biology ,Enzyme ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Molecular Medicine ,medicine.symptom ,business ,Myoblasts, Cardiac ,Signal Transduction - Abstract
Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus complications. Inflammation factors may be one reason for the damage from DM. The purpose of this research is to study the potential protective effects of puerarin on DM and the possible mechanisms of action related to NF-κB signal pathway. Following administration of puerarin to the disease model rat, several changes were observed including the changes of serum biochemical index, improved diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities, further NF-κB signaling activation. Puerarin showed cardio-protective effects on DCM by inhibiting inflammation, and it might be a potential candidate for the treatment of DCM.
- Published
- 2018
45. Design, synthesis and biological evaluation of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives as α-glucosidase inhibitors
- Author
-
Yue Li, Kong-Kai Zhu, Cheng-Shi Jiang, Jin-He Zhang, Juan Zhang, Hong-Xu Xie, Kai-Ming Wang, Lei Fang, and Zhi-Ling Song
- Subjects
Blood Glucose ,Sucrose ,medicine.drug_class ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,Thiophenes ,Biochemistry ,Cell Line ,Rats, Sprague-Dawley ,Structure-Activity Relationship ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Bioassay ,Glycoside Hydrolase Inhibitors ,Hydrazine (antidepressant) ,Cytotoxicity ,Molecular Biology ,IC50 ,Acarbose ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,alpha-Glucosidases ,In vitro ,Rats ,Hydrazines ,Drug Design ,Molecular Medicine ,medicine.drug - Abstract
In this present study, a series of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)hydrazine-1-carboxamide derivatives against α-glucosidase were designed and synthesized, and their biological activities were evaluated in vitro and in vivo. Most of the designed analogues exhibited better inhibitory activity than the marketed acarbose, especially the most potent compound 7 with an IC50 value of 9.26 ± 1.84 μM. The direct binding of 7 and 8 with α-glucosidase was confirmed by fluorescence quenching experiments, and the kinetic and molecular docking studies revealed that 7 and 8 inhibited α-glucosidase in a non-competitive manner. Cytotoxicity bioassay indicated compounds 7 and 8 were non-toxic towards LO2 and HepG2 at 100 μM. Furthermore, both compounds were demonstrated to have in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-treated rats.
- Published
- 2021
46. Effects of Electroacupuncture on the Cortical Extracellular Signal Regulated Kinase Pathway in Rats with Cerebral Ischaemia/Reperfusion
- Author
-
Xin Zhang, Chun Li, Lu Yang, Jing Chen, Qiushi Li, Zhulian Zhan, Chunxiao Wu, Guimei Jiang, Guoping Zhou, and Xiu-Hong Xu
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,medicine.medical_specialty ,Pathology ,MAP Kinase Signaling System ,Electroacupuncture ,medicine.medical_treatment ,Brain Ischemia ,Rats, Sprague-Dawley ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Extracellular Signal-Regulated MAP Kinases ,business.industry ,General Medicine ,Immunohistochemistry ,Rats ,Up-Regulation ,Cortex (botany) ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,Endocrinology ,Complementary and alternative medicine ,Cerebral cortex ,Apoptosis ,Reperfusion Injury ,Neurology (clinical) ,business ,Acupuncture Points ,030217 neurology & neurosurgery - Abstract
Objective To explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R). Methods 160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group. Eight rats from each group were sacrificed at the following time points: 2 hours, 6 hours, 1 day, 3 days and 1 week. Neurological function was assessed using neurological deficit scores, morphological examination was performed following haematoxylin-eosin staining of cortical tissues, and apoptotic indices were calculated after terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling. Cortical protein and mRNA expression of p-ERK and ERK were measured by immunohistochemistry and real-time quantitative PCR, respectively. Results Compared with the I/R group, neurological deficit scores and apoptotic indices were lower in the I/R+EA group at 1 and 3 days, whereas mRNA/protein expression of ERK/p-ERK was higher in the EA group at all time points studied. Conclusion Our results suggest that EA can alleviate neurological deficits and reduce cortical apoptosis in rats with I/R injury. These anti-apoptotic effects may be due to upregulation of p-ERK. Moreover, apoptosis appeared to peak at 1 day after I/R injury, which might therefore represent the optimal time point for targeting of EA.
- Published
- 2017
47. Changes in hydrogen sulfide in rats with hepatic cirrhosis in different stages
- Author
-
Li-hong Xu, Ning Zhang, Keshu Xu, Li-Xiu Song, Yong Zheng, Rui Li, and Wei-Gang Chen
- Subjects
Liver Cirrhosis ,0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,Cystathionine beta-Synthase ,Vena Cava, Inferior ,Biochemistry ,Inferior vena cava ,Vascular remodelling in the embryo ,03 medical and health sciences ,chemistry.chemical_compound ,Internal medicine ,parasitic diseases ,Genetics ,medicine ,Animals ,Humans ,Hydrogen Sulfide ,Carbon Tetrachloride ,Messenger RNA ,biology ,Portal Vein ,business.industry ,Cystathionine gamma-Lyase ,equipment and supplies ,medicine.disease ,Cystathionine beta synthase ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,medicine.vein ,Hyperdynamic circulation ,Carbon tetrachloride ,biology.protein ,Immunohistochemistry ,business - Abstract
This study aimed to observe changes in the hydrogen sulfide (H2S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15th, 30th, and 52nd day. The expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The results indicated that H2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mRNA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H2S protects vascular remodelling in the liver, and that CSE is indispensable in this process.
- Published
- 2017
48. The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia
- Author
-
Shenqiang Rao, Shuangmei Liu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Changshui Xu, Guilin Li, Hong Xu, Chunping Zhang, and Shangdong Liang
- Subjects
Male ,Pain Threshold ,0301 basic medicine ,Purinergic P2X Receptor Antagonists ,endocrine system diseases ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Diabetic Neuropathies ,Ganglia, Spinal ,Animals ,Humans ,Molecular Biology ,nutritional and metabolic diseases ,Cell Biology ,Rats ,body regions ,HEK293 Cells ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Morphinans ,Hyperalgesia ,Original Article ,Erratum ,Receptors, Purinergic P2X3 ,030217 neurology & neurosurgery - Abstract
Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with sinomenine were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and mRNA in T2DM rat DRG were higher compared with those of the control, while those in T2DM rats treated with sinomenine were significantly lower compared with those of the T2DM rats. Sinomenine significantly inhibited P2X3 agonist ATP-activated currents in HEK293 cells transfected with the P2X3 receptor. Sinomenine decreased the phosphorylation and activation of P38MAPK in T2DM DRG. Therefore, sinomenine treatment may suppress the up-regulated expression and activation of the P2X3 receptor and relieve the hyperalgesia potentiated by the activation of P38MAPK in T2DM rats.
- Published
- 2017
49. LncRNA NONRATT021972 siRNA rescued decreased heart rate variability in diabetic rats in superior cervical ganglia
- Author
-
Guodong Li, Lifang Zou, Bing Wu, Shouyu Wang, Guilin Li, Shanhong Zhao, Changle Liu, Shenqiang Rao, Hong Xu, Yun Xue, Tengling Zhang, Shanshan Sun, Shangdong Liang, Shuangmei Liu, Luling He, and Tianyu Jia
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Diabetic Cardiomyopathies ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,Random Allocation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Heart Rate ,Ganglia, Spinal ,Insulin receptor substrate ,Internal medicine ,Diabetic cardiomyopathy ,Diabetes mellitus ,medicine ,Animals ,Heart rate variability ,RNA, Small Interfering ,Tumor Necrosis Factor-alpha ,Endocrine and Autonomic Systems ,business.industry ,Arrhythmias, Cardiac ,medicine.disease ,Long non-coding RNA ,Rats ,IRS1 ,RNAi Therapeutics ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Cervical ganglia ,Cervical Vertebrae ,Insulin Receptor Substrate Proteins ,RNA, Long Noncoding ,Tumor necrosis factor alpha ,Neurology (clinical) ,business - Abstract
Diabetic cardiac autonomic neuropathy (DCAN) is a serious and common complication in diabetes mellitus (DM). Long noncoding RNAs (lncRNAs), an important class of regulatory molecules in diverse biological processes, have attracted considerable interest in DCAN. Our previous study has indicated a lncRNA, NONRATT021972 (NONCODE ID), was enhanced in sympathetic neuronal-like PC12 cells in the setting of high glucose (HG) and high FFAs (HF); its silence was found to significantly alleviate HGHF-induced tumor necrosis factor-α (TNF-α) release in PC12 cells. Here we further explore the effects of NONRATT021972 small interference RNA (siRNA) on heart rate variability (HRV) mediated by superior cervical ganglia (SCG) in diabetic rats and the possible mechanism underlying. We found an increment of NONRATT021972 in SCG of DM rats. Treatment of NONRATT021972 siRNA in DM rats decreased the elevated expression of TNF-α, blocked serine phosphorylation of insulin receptor substrate (IRS) 1 and increased the down-regulated expression of IRS1 in SCG. Meanwhile, NONRATT021972 siRNA rescued decreased HRV in DM rats. Therefore, inhibition of NONRATT021972 may serve as a novel therapeutic strategy for preventing the development of DCAN.
- Published
- 2016
50. Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway
- Author
-
Zheyi Zhou, Hong Xu, Junlei Lu, Linglu Dun, Changjun Lu, Yanyan Gan, Wei Bingxin, Xiumiao Lin, Zhongling Liao, Guocheng Liu, and An Hongwei
- Subjects
0301 basic medicine ,Nervous system ,Ketone ,Ischemia ,Xylenes ,Brain Ischemia ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Neural Stem Cells ,medicine ,Animals ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,chemistry.chemical_classification ,Musk ketone ,Akt/PKB signaling pathway ,General Neuroscience ,Cell Differentiation ,medicine.disease ,Neural stem cell ,In vitro ,Cell biology ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,chemistry ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Traditional Chinese medicine has been reported to influence the proliferation and differentiation of neural stem cells (NSCs) that may be protective against nervous system diseases. Recent evidence indicates the importance of musk ketone in nerve recovery and preventing secondary damage after cerebral ischemic injury. A middle cerebral artery occlusion (MCAO) rat model was established by a transient filament model, and rats were treated with musk ketone (0.9 or 1.8 μM). Next, an in vitro oxygen-glucose deprivation (OGD) cell model was established to study the effect of musk ketone on the proliferation and differentiation of NSCs. To determine the potential mechanisms of musk ketone involved in activities of NSCs, the effect of musk ketone on the PI3K/Akt signaling pathway activation was assessed. Furthermore, NSCs were treated with musk ketone in the presence of PI3K/Akt inhibitor Akti-1/2 to examine their roles on NSC proliferation and differentiation. Musk ketone reduced cerebral ischemic injury in a dose-dependent manner in rats. In addition, NSCs treated with musk ketone showed enhanced proliferation and differentiation along with increased PI3K/Akt signaling pathway activation. The effects of muck ketone were reversed by Akti-1/2. Altogether, musk ketone promoted NSC proliferation and differentiation and protected against cerebral ischemia by activating the PI3K/Akt signaling pathway, highlighting the potential of musk ketone as a physiologically validated approach for the treatment of cerebral ischemia.
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.