The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.
BackgroundOsteosarcoma is a high malignant neoplasm, and conflicting findings have been reported on the survival and function recovery of osteosarcoma patients experiencing limb salvage or amputation. In the present study, we compared limb salvage surgery (LSS) with amputation in clinical outcomes of osteosarcoma patients by a meta-analysis.MethodsThe survival rate of osteosarcoma patients was collected from research reports from CNKI, MEDLINE, EMBASE, the Cochrane Database, and Google Scholar till April 30, 2016. The quality of including articles was evaluated by two independent reviewers. Differences between patients undergoing limb salvage surgery and amputation were analyzed based on postoperative survival rates.ResultsTen articles were included according to selection criteria. There were 1343 patients in total from these studies. Our results showed that there was no significant difference between limb salvage surgery and amputation according to local recurrence; however, patients with limb salvage surgery had a higher 5-year overall survival.ConclusionsLSS results in higher 5-year survival rates and better survival, while not increasing the risk of local recurrence. This study provided more evidences to support limb salvage surgery as a considerable treatment of osteosarcoma patients.
Abstract. Eosinophilic pancreatitis (EP) is a rare form of chronic pancreatitis characterized by localized or diffuse eosinophilic infiltration of the pancreas and elevated serum immunoglobulin E levels. EP is difficult to distinguish from pancreatic cancer on the basis of clinical symptoms and the results of auxiliary examination alone. A retrospective analysis of the clinicopathological characteristics and laboratory, imaging, and pathology results of 3 patients with EP, who were initially diagnosed with pancreatic malignancy, was performed. EP is an allergic disease with non-specific clinical manifestations that is difficult to distinguish from pancreatic cancer based exclusively on clinical symptoms and auxiliary examination, resulting in the need for invasive procedures to confirm the diagnosis. An increase in the eosinophil count in the peripheral blood and pathological examination are essential for the diagnosis of EP.
L. Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-1-mediated renal fibrosis and dysfunction. Am J Physiol Endocrinol Metab 295: E1234 -E1242, 2008. First published September 16, 2008 doi:10.1152/ajpendo.90672.2008.-Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl--D-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10 Ϫ8 mol/l UII for 48 h caused a significant increase of TGF-1, but not ANG II, production that was GPR14-and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF-1 by UII. Furthermore, exposure of NRK-52E cells to TGF-1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-1-mediated renal fibrosis and dysfunction. diabetic nephropathy; G protein-coupled receptor 14; renal extracellular matrix accumulation; streptozotocin diabetic rats; angiotensin II; transforming growth factor-1 DIABETIC NEPHROPATHY (DN) is one of the major microvascular complications and also the leading cause of the end-stage renal disease (ESRD). Therefore, to develop an effective approach to delay or halt the pathogenic progression toward ESRD in patients with overt DN is urgent (8,17,19). To understand the mechanisms responsible for the initiation and development of the diabetes-induced renal pathogenesis will help us to develop the effectively preventive or therapeutic approaches for DN (19). Many factors play roles in the pathogenesis of DN; for instance, both transforming growth factor 1 (TGF-1) and ANG II are important factors to promote the development of DN (10,17,19,27).Urotensin II (UII), an 11-amino acid vasoactive peptide, was identified as the ligand for a novel G protein-coupled receptor, GPR14 (also named as urotensin receptor) (13). UII was found to be a powerful vasoconstrictor with potency gre...
Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and an increase in mucous glands, which may lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we observed substantially thickened lung tissue with extensive fibrosis in ovalbumin-sensitized mice, which was interrelated with transforming growth factor-β1 (TGF-β1) expression in bronchoalveolar lavage fluid. In vitro experiments further demonstrated that TGF-β1 resulted in epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, which was characterized by the expected decrease in E-cadherin expression and the increase in vimentin and α-smooth muscle actin expression, as well as the associated increase in Snail expression at mRNA and protein levels. Furthermore, the downregulation of Snail by small interfering RNA (siRNA) attenuated the TGF-β1‑induced EMT-like phenotype. Of note, a significantly increased synthesis of fibronectin was observed following TGF-β1 treatment, which further supported the hypothesis that EMT is a pivotal factor in peribronchial fibrosis. In combination, the results indicated that myofibroblasts deriving from bronchial epithelial cells via EMT may contribute to peribronchial fibrosis and that Snail may be an important factor in this phenomenon.
Context: Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease (STD) and 5-nitroimidazole drugs are used for the treatment. However, a growing number of T. vaginalis isolates are resistant to these drugs, which make it becomes an urgent issue. Objective: The current study was designed to evaluate the anti-T. vaginalis activity of the essential oil from A. tsao-ko used in traditional Chinese medicine and as a spice and its main component, geraniol. Materials and methods:The anti-T. vaginalis activities of A. tsao-ko essential oil and geraniol were evaluated by the minimum lethal concentration (MLC) and 50% inhibitory concentration (IC 50 ) in vitro. The morphological changes of T. vaginalis were observed by transmission electron microscopy (TEM). Additionally, sub-MLC concentration treatment with sub-MLC A. tsao-ko essential oil and geraniol was also performed. Results: This study shows that MLC/IC 50 of A. tsao-ko essential oil was 44.97 mg/ml/22.49 mg/ml for T. vaginalis isolate Tv1, and 89.93 mg/ml/44.97 mg/ml for T. vaginalis isolate Tv2. Those of geraniol were 342.96 mg/ml/171.48 mg/ml, respectively. After A. tsao-ko essential oil or geraniol treatment, obvious similar morphological changes of T. vaginalis were observed by TEM: the nuclear membrane was damaged, nuclei were dissolved, and the chromatin was accumulated; in the cytoplasm, numerous vacuoles appeared, rough endoplasmic reticulum dilated, the number of ribosomes were reduced, organelles disintegrated, the cell membrane was partially damaged, with cytoplasmic leakage, and cell disintegration was observed. The action time did not increase the effect of A. tsao-ko essential oil or geraniol against T. vaginalis, as no significant difference was observed after sub-MLC concentration treatment for 1, 3, and 5 h with A. tsao-ko essential oil and geraniol. Discussion and conclusion: The study describes the first report on the activity and morphological changes of A. tsao-ko essential oil and geraniol against T. vaginalis. The results obtained herein presented new opportunities for antitrichomonal drugs.
Enhanced PDT and siRNA transfection effect of siRNA@CpMBs were successfully achieved by in situ conversion of MBs to NPs.
Background: Osteosarcoma is a rare type of bone tumor, and this study aimed to assess the clinicopathologic features and prognoses of osteosarcoma patients. Methods: Clinicopathologic and survival data of 1025 patients between 2010 and 2016, 230 between 2008 and 2009 were downloaded and analyzed from the SEER database. Patients’ survival was analyzed using the Kaplan-Meier analysis; prognostic factors were assessed using the Cox regression hazards model. The 1-, 3-, and 5-year survival rates were estimated with nomogram. Competitive risk models were used to identify prognostic risk factors related to endpoint events of osteosarcoma patients. Results: Overall, 722 samples were obtained from the extremities, 134 from the axial bones, and 119 from the cranial and mandible in SEER (2010-2016 cohort). After the preliminary diagnosis, the median survival time of patients with osteosarcoma was 39 months, and the 1-, 3-, and 5-year survival rates were 87.3%, 67.2%, and 58.0%, respectively (P < 0.001). The competitive risk model revealed no competitive risks of the endpoint event. Conclusion: Our study found out the prognostic factors in patients with Osteosarcoma by Cox regression hazards model, after that, nomogram was established to predict the 1-, 3-, and 5-year survival rates, which may help oncologists to understand the highly malignant tumor.
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