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Fang Wang, Zhi-Fen Zhang, Yi-Ran He, Hong-Yan Wu, Shuang-Shuang Wei
AIM: Examine the effects of dipeptidyl peptidase-4 (DPP4) inhibitor Sitagliptin on the transforming growth factor-β1 (TGF-β1) signal transduction pathway in polycystic ovary syndrome (PCOS) rats with ovarian fibrosis. METHODS: Thirty rats were divided randomly into the PCOS model group, Sitagliptin treatment group and blank control group. Dehydroepiandrosterone was administered to the model group and treatment group to establish the models. Then, the phenotype of rats was recorded, and the serum sex hormone levels were measured...
December 4, 2018: Journal of Obstetrics and Gynaecology Research
Jun Shi, Yanting Wu, Siyi Guo, Huidi Zhang, Guitian Chen, Xiaoqi Xu
The aim of this study was to investigate the efficacy of anti-VEGF antibody-modified Paeonol liposome gels (PAE-BEV-lip gels) in the prevention and treatment of Hypertrophic Scars (HSs). Systematic optimization of the encapsulation process of anti-VEGF antibody-modified Paeonol liposomes (PAE-BEV-lips) was performed using Box-Behnken design with the optimized parameters as follows: SPC concentration of 7.36 mg·mL-1 ; SPC-Chol-PAE:pNP-PEG3000 -DOPE:BVE-PEG3000 -DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydration temperature of 41 °C; stripping using pH 7...
December 4, 2018: Drug Development and Industrial Pharmacy
Mingyu He, Luyao Sun, Xiaoling Fu, Sean P McDonough, Chih-Chang Chu
The objective of this study is to design a new family of biodegradable synthetic polymeric biomaterials for providing a tunable inhibition of macrophage's nitric oxide synthase (NOS) pathway. L-Arginine (Arg) is the common substrate for NOS and arginase. Both two metabolic pathways participate in the wound healing process. An impaired wound healing, such as diabetic or other chronic wounds is usually associated with an overproduction of NO by macrophages via the NOS pathway. In this study, a new family of L-nitroarginine (NOArg) based polyester amide (NOArg-PEA) and NOArg-Arg PEA copolymers (co-PEA) were designed and synthesized with different composition ratios...
November 30, 2018: Acta Biomaterialia
Junmou Hong, Zhipeng Hu, Qi Wu, Chaoliang Tang, Junxia Hu, Ruoshi Chen, Bowen Li, Zhiwei Wang
BACKGROUND:  Micro-array analysis of clinical aortic samples suggested a potential role for STIM1 in the modulation of aortic medial degeneration (AMD), despite the uncertainty about STIM1 in normal aortic smooth muscle cells (ASMCs). Here, we aimed to explore changes in STIM1 expression in AMD, and the possible mechanisms. Methods: An AMD model was established using auto-delivery of angiotensin II into ApoE-/- mice. We assessed the effects of SKF96365, a STIM1 inhibitor, in AMD model and i n vitro  cultured ASMCs...
November 30, 2018: Bioscience Reports
Fabio Castiglione, Petter Hedlund, Emanuel Weyne, Lukman Hakim, Francesco Montorsi, Trinity J Bivalacqua, Dirk De Ridder, Uros Milenkovic, David Ralph, Giulio Garaffa, Asif Muneer, Steven Joniau, Maarten Albersen
INTRODUCTION: Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronie's disease (PD) prevents the development of fibrosis. AIM: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD. METHODS: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction...
November 29, 2018: Sexual Medicine
Ting Du, Nakita Buenbrazo, Laura Kell, Sadia Rahmani, Lyann Sim, Stephen G Withers, Shawn DeFrees, Warren Wakarchuk
We have developed an Escherichia coli strain for the in vivo production of O-glycosylated proteins. This was achieved using a dual plasmid approach: one encoding a therapeutic protein target, and a second encoding the enzymatic machinery required for O-glycosylation. The latter plasmid encodes human polypeptide N-acetylgalactosaminyl transferase as well as a β1,3-galactosyl transferase and UDP-Glc(NAc)-4-epimerase, both from Campylobacter jejuni, and a disulfide bond isomerase of bacterial or human origin...
November 2, 2018: Cell Chemical Biology
Chandraiah Godugu, Preeti Kumari, Amit Khurana
AIM: The present study was designed to probe the cardioprotective effects of nanoyttria (NY). MATERIALS & METHODS: NY was characterized using various techniques. Isoproterenol (ISO)-induced cardiotoxicity challenged mice were treated with NY for 28 days at two doses (0.4 and 4 mg/kg, intraperitoneally). RESULTS: NY demonstrated free radical scavenging activity as shown by a 2,2-diphenyl-1-picrylhydrazyl assay. NY treatment showed alleviation of ISO-induced cardiotoxicity as evident from the reduction in biochemical parameters...
December 3, 2018: Nanomedicine
Jolanta Weresa, Anna Pędzińska-Betiuk, Rafał Kossakowski, Barbara Malinowska
BACKGROUND: Drugs targeting CB1 and CB2 receptors have been suggested to possess therapeutic benefit in cardiovascular disorders associated with elevated sympathetic tone. Limited data suggest cannabinoid ligands interact with postsynaptic β-adrenoceptors. The aim of this study was to examine the effects of CB1 and CB2 antagonists, AM251 and AM630, respectively, at functional cardiac β-adrenoceptors. METHODS: Experiments were carried out in isolated spontaneously beating right atria and paced left atria where inotropic and chronotropic increases were induced by isoprenaline and selective agonists of β1 and β2 -adrenergic receptors...
September 17, 2018: Pharmacological Reports: PR
Sajjad Mohammadi, Seeram Ramakrishna, Sophie Laurent, Mohammad Ali Shokrgozar, Dariush Semnani, Davoud Sadeghi, Shahin Bonakdar, Mohsen Akbari
Providing affinity sites on alginate (ALG) matrix enables specific binding of growth factors to the polymer backbone and allows their release in a controlled fashion. In this study, we used a blend of alginate sulfate (ALG-S) and polyvinyl alcohol (PVA) to fabricate electrospun scaffolds capable of delivering a heparin-like growth factor, transforming growth factor-beta1 (TGF-β1). The alginate was sulfated with different degrees of sulfation (DS, from 0.8, 3.4 to 12.4%) by a simple process. The success of sulfation was determined by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), elemental analysis, ultraviolet (UV) spectroscopy and staining with dimethylmethylene blue...
November 28, 2018: Journal of Biomedical Materials Research. Part A
Patrick Sieber, Anny Schäfer, Raphael Lieberherr, François Le Goff, Manuel Stritt, Richard W D Welford, John Gatfield, Oliver Peter, Oliver Nayler, Urs Lüthi
Pathological features of pulmonary fibrosis include accumulation of myofibroblasts and increased extracellular matrix (ECM) deposition in lung tissue. Contractile α-smooth muscle actin (α-SMA)-expressing myofibroblasts that produce and secrete ECM are key effector cells of the disease and therefore represent a viable target for potential novel anti-fibrotic treatments. We used primary normal human lung fibroblasts (NHLF) in two novel high-throughput screening assays to discover molecules that inhibit or revert fibroblast-to-myofibroblast differentiation...
2018: PloS One
Silvia Bona, Graziella Rodrigues, Andrea J Moreira, Fábio C Di Naso, Alexandre S Dias, Thêmis R Da Silveira, Claudio A Marroni, Norma P Marroni
Background and Aim: Liver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4 ) in rats. Methods: Twenty male Wistar rats (230-250 g) were divided into four groups...
August 2018: JGH open: an open access journal of gastroenterology and hepatology
Paramananda Saikia, Shanmugapriya Thangavadivel, Carla S Medeiros, Luciana Lassance, Rodrigo Carlos de Oliveira, Steven E Wilson
Purpose: To determine whether (1) the in vitro expression of epithelial basement membrane components nidogen-1, nidogen-2, and perlecan by keratocytes, corneal fibroblasts, and myofibroblasts is modulated by cytokines/growth factors, and (2) perlecan protein is produced by stromal cells after photorefractive keratectomy. Methods: Marker-verified rabbit keratocytes, corneal fibroblasts, myofibroblasts were stimulated with TGF-β1, IL-1α, IL-1β, TGF-β3, platelet-derived growth factor (PDGF)-AA, or PDGF-AB...
November 1, 2018: Investigative Ophthalmology & Visual Science
Mai A Zaafan, Ahmed R Haridy, Amr M Abdelhamid
Amitriptyline is a tricyclic antidepressant that was suggested to have antifibrotic potential. The current study aimed to investigate the modulatory effects of amitriptyline on bleomycin-induced pulmonary fibrosis in rats. Rats were randomly assigned into 4 groups: normal control, bleomycin control, amitriptyline+bleomycin, and amitriptyline only treated group. Lung injury was evaluated through the histological examination and immunohistochemical detection of α-smooth muscle actin (α-SMA) in lung tissue, in addition to the biochemical assessment of pulmonary contents of hydroxyproline and transforming growth factor beta-1 (TGF-β1)...
November 24, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Guozhen Yuan, Anbang Han, Jing Wu, Yingdong Lu, Dandan Zhang, Yuxiu Sun, Jian Zhang, Mingjing Zhao, Bingbing Zhang, Xiangning Cui
Chronic heart failure (CHF) leads to pulmonary structural remodeling, which may be a key factor for poor clinical outcomes in patients with end-stage heart failure, and few effective therapeutic options are presently available. The aim of the current study was to explore the mechanism of action and pulmonary-protective effects of treatment with Bao Yuan decoction combined with Tao Hong Si Wu decoction (BYTH) on lung structural remodeling in rats with ischemic heart failure. In a model of myocardial infarction (MI) induced by ligation of the left anterior descending (LAD) artery, rats were treated with BYTH...
2018: Bioscience Trends
Jin Sug Kim, Kyung Sook Cho, Seon Hwa Park, Sang Ho Lee, Ji Hwan Lee, Kyung Hwan Jeong, Tae Won Lee
BACKGROUND: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis...
November 23, 2018: American Journal of Nephrology
Tjing-Tjing Hu, Marc Vanhove, Michaël Porcu, Inge Van Hove, Tine Van Bergen, Bart Jonckx Bart, Philippe Barbeaux, Elke Vermassen, Jean H M Feyen
Integrins are associated with various eye diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) and implicated in main pathologic disease hallmarks like neovascularization, inflammation, fibrosis and vascular leakage. Targeting integrins has the potential to attenuate these vision-threatening processes, independent of anti-vascular endothelial growth factor (VEGF) responsiveness. The current investigation characterized THR-687 as a novel pan RGD (arginylglycylaspartic acid) integrin receptor antagonist able to compete for binding with the natural ligand with nanomolar potency (e...
November 22, 2018: Experimental Eye Research
Yu-Dong Liu, Xin Sun, Yao Zhang, Hua-Jie Wu, Hao Wang, Rui Yang
Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is a major metabolite of anthocyanins and was reported to possess anti-allergic response. However, the effects of PCA on airway smooth muscle cells (ASMCs) proliferation and migration remain unclear. Therefore, this study aims to investigate the effects of PCA on proliferation and migration of ASMCs. ASMCs were pre-incubated with various concentrations of PCA for 30 min before stimulation with transforming growth factor-β1 (TGF-β1) for different times...
November 5, 2018: Journal of Pharmacological Sciences
Daisuke Momma, Tomohiro Onodera, Kentaro Homan, Shinji Matsubara, Fumio Sasazawa, Junichi Furukawa, Masatake Matsuoka, Tadashi Yamashita, Norimasa Iwasaki
OBJECTIVE: Gangliosides, ubiquitously existing membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions, are key molecules of inflammatory and neurological disorders. However, the functions of gangliosides in the cartilage degradation process remain unclear. We investigated the functional role of gangliosides in cartilage metabolism related to osteoarthritis (OA) pathogenesis. DESIGN: We generated knockout (KO) mice by targeting the β1, 4-N-acetylgalactosaminyltransferase (GalNAcT) gene, which encodes an enzyme of major gangliosides synthesis, and the GD3 synthase (GD3S) gene, which encodes an enzyme of partial gangliosides synthesis...
November 21, 2018: Osteoarthritis and Cartilage
Asha Kumari, D K Singh, D Dash, Rashmi Singh
OBJECTIVE: Bacterial infections can exacerbate asthmatic inflammation depending on lipopolysaccharide (LPS) composition, the outermost component of cell wall, its exposure timings as well as host's immune status. In present study, Balb/c mice were exposed to antigen (ovalbumin) and LPS simultaneously to establish an asthmatic model. Curcumin (diferuloylmethane), well known for its anti-inflammatory potential, was administered through intranasal route 1 h before LPS and OVA (ovalbumin) exposure to evaluate its efficacy against airway structural changes...
November 23, 2018: Inflammopharmacology
Peter J Wermuth, Fabian A Mendoza, Sergio A Jimenez
Excessive connective tissue deposition in skin and various internal organs is characteristic of systemic sclerosis (SSc). The profibrotic growth factor TGF-β plays a crucial role in SSc pathogenesis. The expression of NADPH oxidase 4 (NOX4), a critical mediator of oxidative stress, is potently stimulated by TGF-β. Here, we evaluated the effect of NOX4 on the development of TGF-β-induced tissue fibrosis. C57BL6/J control mice and Nox4 knockout mice were implanted subcutaneously with osmotic pumps containing either saline or 2...
November 23, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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