ABSTRACT
BACKGROUND: Previous studies of left ventricular diastolic function (LVDF) have focused on the decrease in active and passive diastolic function due to ischemic factors but have not investigated if the decrease in compliance of the coronary arteries that bypass the surface of the heart and travel between the myocardium could cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis. METHODS AND RESULTS: 581 patients diagnosed with coronary heart disease (CHD) were divided into A group (patients are the control group), B group (patients with less than 50% coronary artery stenosis), C group (patients with coronary artery stenosis between 50 and 75%), D group (patients with coronary artery stenosis greater than 75%) according to the degree of coronary stenosis. The diastolic function of the ventricle is reflected by applying the relaxation time constant T value, which refers to the time between peak dp/dt and end-diastolic pressure in the left ventricle. It was concluded that there was a statistical difference in Gensini scores between patients in groups B, C and D (P < 0.001). And multiple linear regression analysis showed that T was correlated with Gensini score and C-dp/dtmax (R = 0.711, P < 0.001). Grouping according to the site of stent implantation and the number of stents implanted, it was found out that the changes in T values before and after left anterior descending artery (LAD) stent implantation were greater than left circumflex artery (LCX) and right coronary artery (RCA) (P < 0.001). And multiple linear regression revealed a correlation between T values and stent length, ventricular stiffness, and C-dp/dtmax (P = 0.001). CONCLUSIONS: The decrease in compliance of the coronary arteries bypassing the surface of the heart and travelling between the myocardium would cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis.
Subject(s)
Coronary Stenosis , Coronary Vessels , Diastole , Fibrosis , Heart Ventricles , HumansABSTRACT
OBJECTIVE: To investigate the clinical value of urinary antigen detection of Legionella, and to describe the clinical characteristics of Legionella pneumonia. METHODS: Patients with suspected Legionella pneumonia were enrolled from the Respiratory departments of 3 tertiary hospitals in Shenyang during May 2011 to November 2013. Urinary Legionella antigen was detected for all the enrolled patients. Bacterial culture, polymerase chain reaction (PCR) for Legionella, and double Legionella antibody detection in sera were performed for each patient whose urinary antigen was positive. Patients confirmed to have Legionella pneumonia were pooled and analyzed. RESULTS: Totally 13 cases presenting with pneumonia were positive for Legionella by the urinary antigen method, and in one of them Legionella strain was isolated from the secretion of lower respiratory tract. PCR detection was performed in 8 patients, and 4 of them were positive. Legionella antibody detection was performed in 12 patients, and 7 of them were positive. Nine patients had a history of exposure to Legionella high-risk environments. The characteristics of the cases with Legionella pneumonia were as follows: characteristic orange sputum in 4 patients, digestive symptoms in 6, neurologic disorders in 8, hyponatremia in 10, hypoxia with oxygenation index < 300 mmHg (1 mmHg = 0.133 kPa) in 11, and severe pneumonia with PSI of grade V (PSI score > 130) in 8 patients . Chest CT scan showed bilateral involvement in 6, ground-glass opacity combined with consolidation in 11, and moderate pleural effusion in 11 patients. Cavity and reversed halo sign were found in one case, respectively. All of the patients received fluoroquinolone treatment, and 11 patients recovered completely while 2 died of multiple organ dysfunction syndrome, one of them was complicated with secondary infection. CONCLUSION: Detection of urinary antigen of Legionella is very useful in the diagnosis of Legionella pneumonia. Attention should be paid to exposure history to the high-risk environments and multiple organ impairment when Legionella infection is suspected. Orange sputum may be characteristic for Legionella pneumonia and therefore a clue for diagnosis. In critical cases, secondary infection and additional lung injuries induced by high concentration oxygen therapy may occur.
Subject(s)
Antigens, Bacterial/urine , Legionella/isolation & purification , Legionnaires' Disease/diagnosis , Antibodies, Bacterial , Fluoroquinolones , Humans , Legionnaires' Disease/urine , Pleural Effusion , Pneumonia/diagnosis , Pneumonia/urineABSTRACT
A series of novel quinoline-docetaxel analogues (6a-6g, 13a-13g) were designed and synthesized by introducing bioactive quinoline scaffold to C2'-OH of docetaxel. The anticancer activities of these novel analogues were investigated against different human cancer cell lines including Hela, A549, A2780, MCF-7 and two resistant strains A2780-MDR and MCF-7-MDR. The data showed these analogues possessed similar to better cytotoxicity than docetaxel. Compound 6c was found to be the most potent one, and its IC50 value against MCF-7-MDR was 8.8 nM (IC50 of docetaxel was 180 nM). The work indicated that the introduction of quinolyl group in docetaxel could enhance cytotoxicity and reduce drug-resistance.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Quinolines/pharmacology , Taxoids/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Docetaxel , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , MCF-7 Cells , Molecular Structure , Quinolines/chemistry , Structure-Activity Relationship , Taxoids/chemistryABSTRACT
OBJECTIVE: To observe effect of subclinical hypothyroidism (SCH) on serum lipid level and expression of toll-like receptor 4 (TLR4) in rats' peripheral blood mononuclear cells (PBMC). METHODS: Fifty Wistar female rats were divided into three groups: normal control (NC group; n=10), sham group (n=10), and L-T-4 (L-thyroxine) group (n=30, with thyroidectomy, fed with rich-calcium water after operation. 5 weeks later, abdominal subcutaneous injection of L-T-4: 0.95 µg/100g/d). 8 weeks later, the rats were killed then the peripheral blood was collected to determine the levels of serum thyroid-stimulating hormone (TSH), total thyroid hormone (TT4), total cholesterol (TC) and low density lipoprotein cholesterin (LDL-C). Rats in L-T-4 group were divided into normal lipid (NL) group) and high lipid (HL) group) according to lipid value of NC group. Monocytes were separated from blood to determine TLR4 expression by flow cytometry. RESULTS: In NL and HL groups TSH were higher than in NC and Sham groups (p<0.05). TT4 have no significant differences (p>0.05). TLR4, TLR4 mRNA, NF-κB (p65) were increased (p<0.05). TNF-α, IL-6 and IL-1ß were higher than in NC and sham groups (p<0.01). There were no significant differences of TLR4, TLR4 mRNA, NF-κB (p65), TNF-α, IL-6 and IL-1ß expression between NL and HL groups (p>0.05). CONCLUSION: TLR4, TLR4 mRNA, NF-κB (p65) of PBMC and TNF-α, IL-6, IL-1ß expression in serum were all increased in SCH rats, which was not related to serum dyslipidemia.
Subject(s)
Hypothyroidism/immunology , Hypothyroidism/pathology , Monocytes/immunology , Monocytes/metabolism , Toll-Like Receptor 4/biosynthesis , Toll-Like Receptor 4/blood , Animals , Cholesterol/biosynthesis , Cholesterol/blood , Cholesterol, LDL/biosynthesis , Cholesterol, LDL/blood , Cytokines/biosynthesis , Cytokines/blood , Disease Models, Animal , Female , Flow Cytometry , Hypothyroidism/blood , Monocytes/pathology , RNA, Messenger/biosynthesis , RNA, Messenger/blood , Rats , Rats, Wistar , Thyroid Hormones/biosynthesis , Thyroid Hormones/blood , Thyrotropin/biosynthesis , Thyrotropin/blood , Thyroxine/administration & dosage , Thyroxine/biosynthesis , Thyroxine/blood , Thyroxine/toxicityABSTRACT
Recently, angiotensin-converting enzyme inhibitor (ACEI) has gained increasing attention for its anti-atherosclerosis activity, but the underlying mechanism is unknown. In our study, we used rabbits fed with high-fat forage, as an atherosclerosis model to investigate the effect of fosinopril, which is an ACEI. Animals which received both high-fat forage and fosinopril, were maintained as the drug-treated group. Ultrasonography and Sudan III staining were used to determine the process of atherosclerosis. The expression of TLR4 and activity NF-κB were determined using western blot, RT-PCR and ELISA. The results showed that the atherosclerotic plaque was visible at sixteen weeks. More importantly, the atherosclerotic plaque was significantly decreased after fosinopril treatment. In the atherosclerosis model, the levels of TLR4 and NF-κB were increased, but this increased expression was inhibited in the fosinopril treated group. Our results demonstrated that TLR4 could be used as a potential biomarker for atherosclerosis and ACEI has the potential to be a new anti-atherosclerotic drug.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Atherosclerosis/drug therapy , Fosinopril/therapeutic use , NF-kappa B/metabolism , Plaque, Atherosclerotic/drug therapy , Toll-Like Receptor 4/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Atherosclerosis/immunology , Biomarkers , Diet, High-Fat , Fosinopril/pharmacology , Rabbits , Toll-Like Receptor 4/immunologyABSTRACT
OBJECTIVE: To evaluate the effect of the fosinoprilat on lipopolysacharides (LPS) induced inflammation in monocytes in vitro. METHODS: Human mononuclear THP1 cells were cultured in complete medium, treated with or without LPS and different concentrations (0,0.25,0.5,1,5,and 10µmol/L) of fosinoprilat. Toll-like receptor (TLR4) mRNA expression was detected by real-time RT-PCR and TLR4 protein level on the surface of monocyte was determined by flow cytometry. Nuclear factor-kappa B (NF-κB) protein level was detected by Western blotting. Cultured supernatant of the THP1 cells in different groups were analyzed by ELISA to detect the levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF-α). RESULTS: Both the mRNA and surface protein level of the TLR4 in the THP1 cells were enhanced by the LPS treatment and down-regulated by pretreatment of the fosinoprilat. Accordingly, LPS-induced NF-κB protein was decreased by the fosinoprilat treatment. The increasing secretion of IL-1ß, IL-6 and TNF-α induced by LPS could also be attenuated by the fosinoprilat treatment. CONCLUSION: The inhibitory effect of the fosinoprilat on the TRL4/NF-κB signaling pathway reveals a potential anti-inflammatory and anti-atherosclerosis target.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Fosinopril/analogs & derivatives , Inflammation/drug therapy , NF-kappa B/antagonists & inhibitors , Toll-Like Receptor 4/antagonists & inhibitors , Blotting, Western , Cell Line , Flow Cytometry , Fosinopril/pharmacology , Humans , Inflammation/immunology , Inflammation/metabolism , Interleukin-1beta/immunology , Interleukin-6/immunology , Monocytes , NF-kappa B/genetics , NF-kappa B/immunology , RNA, Messenger/chemistry , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/immunology , Tumor Necrosis Factor-alpha/immunologyABSTRACT
The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.
Subject(s)
Caspase 3/genetics , Interleukin-6/genetics , Ischemic Preconditioning , Myocardial Reperfusion Injury/genetics , Myocardium/pathology , Suppressor of Cytokine Signaling Proteins/genetics , Tumor Necrosis Factor-alpha/genetics , Animals , Apoptosis/genetics , Caspase 3/metabolism , Creatine Kinase/blood , Gene Expression Regulation , HSP27 Heat-Shock Proteins/metabolism , L-Lactate Dehydrogenase/blood , Male , Malondialdehyde/blood , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/diagnostic imaging , Myocardial Reperfusion Injury/enzymology , Myocardium/enzymology , Nitric Oxide/blood , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins/metabolism , Ultrasonography , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
In the molecule of the the title compound, [Fe(C5H5)(C28H22F6N2PS)], the absolute configuration is R C ,SFe . The dihedral angle between the trifluoro-methyl-substituted phenyl ring and the thio-urea plane is 41.8â (9)°. The iron atom is bound to the cyclo-penta-dienyl rings in the typical η(5)-manner in a close to eclipsed conformation. The crystal structure features N-Hâ¯S hydrogen bonds, with the S atom as an acceptor for both N-H groups, forming a layered arrangement parallel to (1-10). The two -CF3 groups are each disordered over two positions with refined occupancy rates for the major components of 0.66â (7) and 0.55â (5). The crystal was grown from mixed solvents (n-hexane and ethyl acetate). These solvents are disordered in the crystal and the resulting electron density was found to be uninterpretable. The solvent contribution to the structure factors was taken into account by back-Fourier transformation of all density found in the disordered solvent area using the SQUEEZE routine in PLATON [Spek (2009 â¶). Acta Cryst. D65, 148-155]. The formula mass and density do not take account of the solvent.
ABSTRACT
OBJECTIVE: To investigate the differences of clinical features, pulmonary function tests, chest imaging and prognosis between patients with idiopathic pulmonary fibrosis (IPF) combined with emphysema and without emphysema. METHODS: Of the 117 patients diagnosed as IPF for the first time in the First Affiliated Hospital of China Medical University from January 2002 to January 2007, 23 cases met the diagnostic criteria for combined pulmonary fibrosis and emphysema (CPFE). Thirty-three cases with isolated IPF from 2002 to 2003 were selected as the control group. Clinical characteristics, pulmonary function indexes, PaO2, bronchoalveolar lavage fluid (BALF) results and survival time were retrospectively analyzed and compared between the 2 groups. RESULTS: The smoking indexes (pack-years)were significantly higher in the CPFE group (28 ± 18) compared with the IPF group (18 ± 16), t = 2.10, P < 0.05. No significant difference was observed between the 2 groups in terms of age, gender and the percentage of smokers. The CPFE group showed significantly lower FEV1/FVC% [(77 ± 7)%, (83 ± 8)%, t = 3.55, P < 0.05] and D(L)CO% pred [(44 ± 12)%, (54 ± 16)%, t = 2.48, P < 0.05] compared to those of the IPF group, while TLC%pred was significantly higher in the CPFE group [(77 ± 11)%, (64 ± 12)%, t = 3.93, P < 0.05]. VC% pred and PaO2 showed no significant difference between the 2 groups. The total cell count, the percentages of macrophages, neutrophils, lymphocytes and eosinophils in BALF showed no significant difference between the 2 groups. There was no significant difference in median survival time between the 2 groups. CONCLUSION: Smoking was an important risk factor for IPF combined with emphysema. The pulmonary function of IPF combined with emphysema is characterized by a mild abnormality in the lung volume but a significant decrease in the diffusing capacity. Combined emphysema has no influence on the survival time of patients with IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis/complications , Pulmonary Emphysema/complications , Smoking/adverse effects , Aged , Case-Control Studies , Female , Humans , Idiopathic Pulmonary Fibrosis/mortality , Idiopathic Pulmonary Fibrosis/physiopathology , Leukocyte Count , Lung/pathology , Lung/physiopathology , Male , Middle Aged , Prognosis , Pulmonary Emphysema/mortality , Pulmonary Emphysema/physiopathology , Respiratory Function Tests , Retrospective Studies , Risk Factors , Survival Rate , Vital CapacityABSTRACT
The role of kynurenic acid (KynA) in neurological and mental diseases has been widely studied. Emerging studies disclosed that KynA has a protective effect on tissues including heart, kidney, and retina. However, the role of KynA in osteoporosis has not been reported so far. To elucidate the role of KynA in age-related osteoporosis, both control and osteoporosis mice were administrated KynA for three consecutive months, and micro-computed tomography (µCT) analysis was then performed. In addition, primary bone marrow mesenchymal stem cells (BMSCs) were isolated for osteogenic differentiation induction and treated with KynA in vitro. Our data suggested that KynA administration rescued age-related bone loss in vivo, and KynA treatment promotes BMSC osteogenic differentiation in vitro. Moreover, KynA activated the Wnt/ß-catenin signaling during BMSC osteogenic differentiation. Wnt inhibitor MSAB inhibited KynA-induced osteogenic differentiation. Further data demonstrated that KynA exerted its effect on BMSC osteogenic differentiation and Wnt/ß-catenin signaling activation via G protein-coupled receptor 35 (GPR35). In conclusion, the protective effect of KynA on age-related osteoporosis was disclosed. Additionally, the promoting effect of KynA on osteoblastic differentiation via Wnt/ß-catenin signaling was verified and the effect dependent on GPR35. These data suggest that KynA administration potentially contributes to the treatment of age-related osteoporosis.
Subject(s)
Osteoporosis , Mice , Animals , Osteogenesis , beta Catenin/metabolism , Kynurenic Acid/pharmacology , X-Ray Microtomography , Cell Differentiation , Osteoporosis/drug therapy , Wnt Signaling Pathway , Cells, Cultured , Receptors, G-Protein-CoupledABSTRACT
Sarcoidosis is a systemic granulomatous disease of the lungs that commonly involves intrathoracic lymph nodes. Here, we report the case of a 68-year-old woman who complained of shortness of breath and had suffered from the enlargement of intrathoracic lymph nodes for 12 years, swelling of the right middle finger for 7 years, and nasal obstruction for 2 years. The damage to the phalange was aggravated continuously and a malignant lesion could not be excluded, thus leading to amputation of the right middle finger. Pathological data indicated chronic inflammatory granulomatous disease and anti-acid staining was negative. Examination of the paranasal sinuses indicated destruction of the sinonasal bone and the swollen mucosa. Combined with the elevated ratio of CD4+/CD8+ T cells in bronchoalveolar lavage fluid and other results, the patient was finally diagnosed with sarcoidosis and received corticosteroid therapy. The shortness of breath and abnormality of the nose were significantly improved after treatment. Our case demonstrated the process of differential diagnosis for systemic granulomatous diseases, indicating the necessity of corticosteroid therapy for systematic sarcoidosis.
ABSTRACT
Here, we report a surface etching strategy for the controllable synthesis of metal-organic framework (MOF)-derived ZnCo2O4@ZnO/Co3O4 oxides. Different from previous studies, ZnCo-glycolate (ZnCo-gly) spheres acted as sacrificial templates to provide Zn2+ and Co2+ ions, which coordinated with 2-MeIm to form Zeolitic Imidazolate Frameworks (ZIFs) on the surface of ZnCo-gly. A series of characterizations were employed to clarify the evolution of the surface etching strategy. Interestingly, the ZIF thickness of the ZnCo-gly surface could be controlled by adjusting the reaction time. After calcination, p-n heterojunctions were formed between the MOF-derived ZnO and Co3O4, which made it show excellent selectivity to methanal gas.
ABSTRACT
Rationale: The diagnostic yield of traditional ultrasound-guided pleural biopsy remains unsatisfactory, particularly when the pleural thickness is ⩽5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography (UE) has a better diagnostic yield than traditional ultrasound for malignant pleural effusion (MPE). However, studies on UE-guided pleural biopsies are lacking. Objectives: To evaluate the feasibility and safety of UE-guided pleural biopsy. Methods: In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness was ⩽5 mm with no pleural nodules were enrolled between July 2019 and August 2021. The diagnostic yield of UE-guided pleural biopsy for pleural effusion and its sensitivity for detecting MPE were evaluated. Results: Ninety-eight patients (mean age, 62.4 ± 13.2 yr; 65 men) were prospectively enrolled. The diagnostic yield of UE-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and its sensitivity for MPE was 88.7% (55/62). In addition, its sensitivity for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax. Conclusions: UE-guided pleural biopsy is a novel technique for diagnosing MPE with good diagnostic yield and sensitivity. Clinical trial registered with https://www.chictr.org.cn (ChiCTR2000033572).
Subject(s)
Elasticity Imaging Techniques , Pleural Effusion, Malignant , Pleural Effusion , Male , Humans , Middle Aged , Aged , Prospective Studies , Ultrasonics , Pleural Effusion/diagnostic imaging , Pleural Effusion, Malignant/diagnostic imaging , Image-Guided Biopsy/methods , Diagnostic Tests, RoutineABSTRACT
Brief episodes of myocardial ischemia-reperfusion (IR) employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR)-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA) level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.
Subject(s)
Ischemic Postconditioning , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Animals , Ca(2+) Mg(2+)-ATPase/metabolism , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Heart/physiopathology , L-Lactate Dehydrogenase/blood , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardium/pathology , Oxidative Stress , Rats , Rats, Wistar , Sodium-Potassium-Exchanging ATPase/metabolism , Superoxide Dismutase/metabolismABSTRACT
Osteoporosis occurs frequently in women after menopause and old age, and it is very easy to cause osteoporotic fractures, resulting in disability and death. In osteoporosis patients, the potential of bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts gradually is inhibited, leading to decreased new bone formation. In the current study, the potential effect of G-protein-coupled receptor 124 (GPR124) on the osteoblastic differentiation of BMSCs was determined. BMSCs were isolated and cultured in osteogenic media to induced osteogenic differentiation. Then, osteogenic differentiation was evaluated by Alizarin Red staining and ALP activity. The expression of osteogenic differentiation biomarkers, and Wnt/ß-catenin signaling were determined by qRT-PCR and Western blotting. The results indicated that the expression of GPR124 was significantly increased during osteogenic differentiation of BMSCs. Moreover, GPR124 knockdown significantly inhibited osteoblastic differentiation and GPR124 overexpression promoted osteoblastic differentiation of BMSCs. GPR124 knockdown suppressed the activation of Wnt/ß-catenin signaling pathway. What's more, the increased osteogenic differentiation induced by GPR124 overexpression was abolished by the inhibitor of Wnt/ß-catenin pathway and Wnt7a knockdown. Taken together, GPR124 promotes osteogenic differentiation of BMSCs through the Wnt/ß-catenin pathway and may serve as a potential target for enhancing osteogenesis of osteoporosis patients.
Subject(s)
Mesenchymal Stem Cells , Osteoporosis , Animals , Biomarkers/metabolism , Cell Differentiation/genetics , Cells, Cultured , Female , Humans , Osteogenesis/genetics , Osteoporosis/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Wnt Signaling Pathway/genetics , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
Background: Cytology remains the gold standard for the detection of malignant cells in pleural effusion. However, its sensitivity is limited. The aim of this study was to establish a novel panel of cancer-specific methylated genes for the differential diagnosis of malignant pleural effusion (MPE). Methods: A cohort of 100 cancer patients (68 lung cancer, 32 other malignant tumors) and 48 patients with benign disease presenting with pleural effusion was prospectively enrolled. Pleural effusion was evaluated by means of cytopathological investigation and DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation-specific real-time PCR (MS-PCR). Cytopathological and DNA methylation results were evaluated with regard to the final clinical diagnosis. Results: The LungMe® SHOX2 and RASSF1A Assay (Tellgen Corporation, China) has been reported to be highly sensitive and specific for lung cancer using bronchial aspirates. As expected, LungMe® detected metastases of lung cancer (sensitivity: 76.5%) as well as metastases of other malignant tumors (sensitivity: 68.8%). OncoMe, a novel combination of SHOX2, RASSF1A, SEPTIN9 and HOXA9 methylation, led to an additional 11% increase in the detection rate of MPE, resulting in a sensitivity of 85% and a specificity of 96%. Overall, OncoMe showed a higher positive detection rate in SCLC (100%), LUAC (87%), OC (100%), BC (92.9%), GC (80.0%), and MESO (80%) than in LUSC (50%). Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe® and OncoMe. Conclusion: OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.
ABSTRACT
The present study was undertaken to evaluate the protection potential of ethanol extract of Salvia miltiorrhiza (SMEE) against oxidative injury in the ischemia-reperfusion (I/R) model of rats in vivo. Rats were divided into six groups of 10 rats each. Group I/R model and sham were fed with a standard rat chow, groups SMEE I and SMEE II were fed with a standard rat chow and 400 or 800 mg/kg b.w. ethanol extract for 12 days before the beginning of I/R studies. Positive control group was fed with a standard rat chow and salvianolic acid B (55 mg/kg b.w.) or tanshinone II-A (55 mg/kg b.w.) for 12 days before the beginning of I/R studies. To produce I/R, the left anterior descending artery (LAD) was occluded in anesthetized rats for 15 min, followed by 120 min reperfusion. Infarct sizes were found significantly decreased in SMEE-treated and positive control groups compared to I/R model group. Serum AST, LDH and CK-MB activities were significantly reduced and myocardium Na+-K+ ATPase, Ca2+-Mg2+ ATPase activities and antioxidant enzyme activities (SOD, CAT, GSH-Px) were markedly increased in SMEE-treated and salvianolic acid B or tanshinone II-A positive control groups compared to the I/R model group. Pretreatment of S. miltiorrhiza ethanol extract and salvianolic acid B or tanshinone II-A dose-dependently reduced significantly myocardium MDA level, ROS and NOS activities and enhanced myocardium GSH level in I/R rats compared to I/R rats model. In conclusion, we clearly demonstrated that S. miltiorrhiza ethanol extract pretreatment can decrease oxidative injury in rats subjected to myocardial I/R.
Subject(s)
Antioxidants/metabolism , Ethanol/chemistry , Plant Extracts/therapeutic use , Reperfusion Injury/drug therapy , Salvia miltiorrhiza/chemistry , Animals , Aspartate Aminotransferases/blood , Ca(2+) Mg(2+)-ATPase , Catalase/metabolism , Creatine Kinase/blood , Disease Models, Animal , Electrocardiography , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , L-Lactate Dehydrogenase/blood , Malondialdehyde/metabolism , Myocardium/enzymology , Myocardium/pathology , Organ Size/drug effects , Phytotherapy , Plant Extracts/pharmacology , Rats , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Reperfusion Injury/blood , Reperfusion Injury/physiopathology , Sodium-Potassium-Exchanging ATPase/metabolism , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Atherosclerosis (AS) is a multifocal, smoldering immune inflammatory disease of medium and large arteries driven by lipids. The aim of this study is to discuss the mechanism of microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B α (IKBα) signal axis in plaque formation of AS mice. METHODS: ApoE-/- mice were fed with high-fat feed for 12 weeks to establish AS mice model. The expression of miR-146a-3p, KLF5, HDAC1 and IKBα in aortic wall tissues of AS mice was tested. The targeting relationship between miR-146a-3p and HDAC1 was verified. AS mice were injected with miR-146a-3p antagomir or HDAC1 overexpression to verify the impacts of miR-146a-3p and HDAC1 on blood lipids and inflammatory factors in serum, aortic wall apoptotic cells, antioxidant stress capacity and the plaque area in AS mice. VECs proliferation and apoptosis were also measured in vitro. RESULTS: miR-146a-3p and KLF5 were increased while HDAC1 and IKBα were reduced in aortic wall tissues of AS mice. miR-146a-3p directly targeted to HDAC1. Depletion of miR-146a-3p or restoration of HDAC1 was correlated to lower plasma lipid level, reduced inflammatory factors in serum, attenuated aortic wall apoptosis, increased antioxidant stress capacity and improved the stability of pathological plaque of AS mice. miR-146a-3p down-regulation or HDAC1 up-regulation promoted VECs proliferation and inhibited apoptosis. CONCLUSION: Functional studies show that depleted miR-146a-3p advances HDAC1 and IKBα expression as well as inhibits KLF5 expression to facilitate the stability of pathological plaques in AS mice.
Subject(s)
Atherosclerosis/genetics , Histone Deacetylase 1/metabolism , Kruppel-Like Transcription Factors/metabolism , MicroRNAs/metabolism , NF-KappaB Inhibitor alpha/metabolism , Plaque, Atherosclerotic/genetics , Signal Transduction , Animals , Antioxidants/metabolism , Apoptosis/genetics , Atherosclerosis/blood , Atherosclerosis/pathology , Base Sequence , Cell Proliferation/genetics , Down-Regulation/genetics , Endothelial Cells/metabolism , Endothelial Cells/pathology , Histone Deacetylase 1/genetics , Inflammation/blood , Inflammation/pathology , Kruppel-Like Transcription Factors/genetics , Lipids/blood , Male , Mice, Inbred C57BL , MicroRNAs/genetics , Plaque, Atherosclerotic/blood , Signal Transduction/genetics , Up-Regulation/geneticsABSTRACT
Borderline ovarian tumor (BOT) refers to a distinct tumor of the ovary of epithelial origin and typically has a favorable prognosis. However, these tumors are not exempt from risks of recurrence and malignant transformation, which can arise from the remaining ovarian tissue, peritoneal implants, or distant localization. Here, we report a case of a mucinous BOT with multiple pulmonary cystic nodules without evidence of pulmonary metastasis even after two fine needle biopsies. Staging surgery was performed, and no evidence of peritoneal implants or invasion to adjacent organs found. At the end of the 7-year monitored follow-up after surgery, the pulmonary lesions were found to be increased in size. The transbronchial lung biopsy and pleural biopsy confirmed transformation into malignant mucinous adenocarcinoma with pleural metastasis. In the current case, we observed potential pulmonary metastasis of the BOT with malignant transformation and a latency as long as 7 years, which reminds us that multiple pulmonary cystic changes in patients with BOTs should be screened carefully to evaluate the pulmonary involvement of BOTs and potentially false-negative results after fine needle biopsy. Thus, a thorough check-up for complete staging of the disease and a close long-term follow-up to monitor potential recurrence and malignant transformation are advised.
ABSTRACT
Graphitic carbon nitride (g-C3N4, CN) with nitrogen vacancies was synthesized by a controlled thermal etching method in a semi-closed air-conditioning system. The defect-modified g-C3N4 shows an excellent photocatalytic performance demonstrated by water splitting under visible light irradiation. With proper heat-treatment durations such as 2 h (CN2) and 4 h (CN4) at 550 °C, the hydrogen production rates significantly increase to 100 µmol h-1 and 72 µmol h-1, which are 11 times and 8 times the rate of the pristine CN (8.8 µmol h-1) respectively. The excellent hydrogen production performance of nitrogen defect modified CN2 is due to the synergy effect of the decreased band gap, enlarged specific surface area and increased separation/migration efficiency of photoinduced charge carriers. This simple defect engineering method provides a good paradigm to improve the photocatalytic performance by tailoring the electronic and physical structures of g-C3N4.