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Roel C Op 't Veld, Onno I van den Boomen, Ditte M S Lundvig, Ewald M Bronkhorst, Paul H J Kouwer, John A Jansen, Esther Middelkoop, Johannes W Von den Hoff, Alan E Rowan, Frank A D T G Wagener
Changing wound dressings inflicts pain and may disrupt wound repair. Novel synthetic thermosensitive hydrogels based on polyisocyanopeptide (PIC) offer a solution. These gels are liquid below 16 °C and form gels beyond room temperature. The architecture and mechanical properties of PIC gels closely resemble collagen and fibrin, and include the characteristic stiffening response at high strains. Considering the reversible thermo-responsive behavior, we postulate that PIC gels are easy to apply and remove, and facilitate healing without eliciting foreign body responses or excessive inflammation...
July 30, 2018: Biomaterials
Zun-En Xia, Juan-Li Xi, Lei Shi
3,3'-Diindolylmethane (DIM), a natural acid condensation extracted from cruciferous plants, exhibits anti-fibrotic effects in hepatic and cardiac fibrosis models. The effects of DIM on renal fibrosis, however, are unclear. This study aimed to explore the protective effects of DIM on renal fibrosis. Unilateral ureteral obstruction (UUO) and transforming growth factor (TGF)-β1-stimulated normal rat kidney (NRK)-49F fibroblast cell mouse models were established. The models were then treated with DIM for the assessment of its anti-fibrotic effects and mechanisms...
November 2018: Renal Failure
Marta Michalik, Katarzyna Wójcik-Pszczoła, Milena Paw, Dawid Wnuk, Paulina Koczurkiewicz, Marek Sanak, Elżbieta Pękala, Zbigniew Madeja
Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins...
August 12, 2018: Cellular and Molecular Life Sciences: CMLS
Wei Wei, Hai-Yang Zhang, Xin-Kou Gong, Zhuo Dong, Zhi-Yuan Chen, Rui Wang, Jun-Xuan Yi, Yan-Nan Shen, Shun-Zi Jin
OBJECTIVE: To investigate the regulatory mechanism of MEN1 gene in radiation-induced lung fibrosis in mice and provide a new theoretical basis for the clinical treatment of radiation pulmonary fibrosis. METHODS: First, 80 C57BL/6 mice aged 8 weeks and weighing 18-22 g were selected, half of them were male and the other half were female. The mice were divided into control group and irradiation group (40 mice in each group) according to the method of the random number table...
August 9, 2018: Gene
Walison N Silva, Caroline Leonel, Pedro H D M Prazeres, Isadora F G Sena, Daniel A P Guerra, Debora Heller, Ivana M A Diniz, Vitor Fortuna, Akiva Mintz, Alexander Birbrair
Dermal wound healing is the process of repairing and remodeling skin following injury. Delayed or aberrant cutaneous healing pose a challenge for the health-care system. The lack of detailed understanding of cellular and molecular mechanisms involved in this process hamper the development of effective targeted treatments. In a recent study, Parfejevs and colleagues, by using state-of-the-art technologies, including in vivo sophisticated Cre/loxP techniques in combination with a mouse model of excisional cutaneous wounding, reveal that Schwann cells induce adult dermal wound healing...
August 11, 2018: Wound Repair and Regeneration
Carla S Medeiros, Gustavo K Marino, Marcony R Santhiago, Steven E Wilson
Purpose: The purpose of this review was to provide detailed insights into the pathophysiology of myofibroblast-mediated fibrosis (scarring or late haze) after corneal injury, surgery, or infection. Method: Literature review. Results: The epithelium and epithelial basement membrane (EBM) and/or endothelium and Descemet's basement membrane (BM) are commonly disrupted after corneal injuries, surgeries, and infections. Regeneration of these critical regulatory structures relies on the coordinated production of BM components, including laminins, nidogens, perlecan, and collagen type IV by epithelial, endothelial, and keratocyte cells...
August 1, 2018: Investigative Ophthalmology & Visual Science
Siu Chiu Chan, Ying Zhang, Annie Shao, Svetlana Avdulov, Jeremy Herrera, Karam Aboudehen, Marco Pontoglio, Peter Igarashi
BACKGROUND: Mutation of HNF1B , the gene encoding transcription factor HNF-1 β , is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in renal function. HNF-1 β has also been implicated in epithelial-mesenchymal transition (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not known. METHODS: To explore the mechanism of fibrosis, we created HNF-1 β -deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal differentially expressed genes in wild-type and HNF-1 β -deficient mIMCD3 cells, and performed cell lineage analysis in HNF-1 β mutant mice...
August 10, 2018: Journal of the American Society of Nephrology: JASN
Richard Conway, Lorraine O'Neill, Geraldine M McCarthy, Conor C Murphy, Aurelie Fabre, Susan Kennedy, Douglas J Veale, Sarah M Wade, Ursula Fearon, Eamonn S Molloy
OBJECTIVES: The pathogenesis of giant cell arteritis (GCA) remains unclear. TH 1 and TH 17 pathways are implicated, but the proximal initiators and effector cytokines are unknown. Our aim was to assess the role of interleukin 12 (IL-12) and interleukin 23 (IL-23) in GCA pathogenesis. METHODS: IL-12 and IL-23 expression were quantified by immunohistochemistry in temporal artery biopsies (TABs). Temporal artery (TA) explant, peripheral blood mononuclear cell (PBMC) and myofibroblast outgrowth culture models were established...
August 10, 2018: Annals of the Rheumatic Diseases
Euphrasie Kawila Mafanda, Rajani Kandhi, Diwakar Bobbala, Md Gulam Musawwir Khan, Madhuparna Nandi, Alfredo Menendez, Sheela Ramanathan, Subburaj Ilangumaran
The hepatic fibrogenic response is a protective mechanism activated by hepatocyte damage and is resolved upon elimination of the cause. However, persistent injuries cause liver fibrosis (LF) to evolve into cirrhosis, which promotes the development of hepatocellular carcinoma (HCC). Development of efficient treatments for LF requires better understanding the underlying molecular pathogenic mechanisms. The loss of suppressor of cytokine signaling 1 (SOCS1) expression promotes LF and HCC in human and mice, but the underlying mechanisms remain unclear...
August 7, 2018: Cytokine
Wei Liu, Yanhua Wu, Feng Yu, Wenxue Hu, Xiaowu Fang, Wenke Hao
AIM: This study was purposed to figure out the contribution of Numb-induced Notch signaling to the development of diabetic nephropathy (DN). METHODS: Two hundred and twenty six DN patients were included, and human glomerular endothelial cells (RGEC) were cultured. MSCV-Numb-IRES-GFP, MSCV-Notch1-IRES-GFP and MSCV-Hes1-IRES-GFP were transfected to construct the recombinant retroviral vectors. RESULT: The over-expressed Numb and Notch1, as well as the under-expressed Hes-1 were correlated with the undesirable prognosis of DN patients (P < 0...
July 10, 2018: Journal of Diabetes and its Complications
Xiaohe Li, Cheng Lu, Shuangwei Liu, Shuaishuai Liu, Chengcheng Su, Ting Xiao, Zhun Bi, Pengzhen Sheng, Mengying Huang, Xinhua Liu, Yujiao Wei, Lin Zhao, Shengxiang Miao, Jiahe Mao, Kai Huang, Shaoyan Gao, Ning Liu, Min Qi, Tongtong Liu, Shuanglin Qin, Luqing Wei, Tao Sun, Wen Ning, Guang Yang, Honggang Zhou, Cheng Yang
In this study, anti-IPF lead compounds 42 and 44, derived from natural sesquiterpene lactones Isoalantolactone and alantolactone, were discovered by screening from a high-throughput TGF-β1 reporter luciferase assay. Notably, they could reduce the myofibroblast activation and extracellular matrix deposition both in vitro and in vivo. Additionally, compounds 42 and 44 could significantly attenuate bleomycin-induced pulmonary fibrosis in mice. Further validation of pharmacokinetics study and toxicity evaluation indicated that compound 44 might be a promising anti-IPF drug candidate...
August 3, 2018: European Journal of Medicinal Chemistry
Rosaria Santoro, Denis Scaini, Luisa Ulloa Severino, Francesco Amadeo, Silvia Ferrari, Giacomo Bernava, Gloria Garoffolo, Marco Agrifoglio, Loredana Casalis, Maurizio Pesce
Differentiation of valve interstitial cells (VICs) into pro-calcific cells is one of the central events in calcific aortic valve (AoV) disease (CAVD). While the paracrine pathways and the responsivity of VICs to mechanical compliance of the surrounding environment are well characterized, the molecular programming related to variations in local stiffness, and its link to cytoskeleton dynamics, is less consolidated. By using a simple method to produce 2D poly-acrylamide gels with stiffness controlled with atomic force microscopy (AFM), we manufactured adhesion substrates onto which human VICs from stenotic valves were plated, and subsequently investigated for cytoskeleton dynamics and activation of the mechanosensing-related transcription factor YAP...
July 31, 2018: Biomaterials
Xijin Mao, Hairong Liu, Jing Du, Ning Yu, Liang Chen, Lin Zhang
RATIONALE: Inflammatory myofibroblastic tumors (IMTs), particularly breast IMTs, are rare neoplastic lesions typically associated with a favorable prognosis. Breast IMTs are easily misdiagnosed as other types of malignant lesions, and therefore there is a significant unmet need for a better preoperational differential diagnosis based on imaging manifestations. Here, we report the imaging findings of a breast IMT and compare our findings with previously published features of breast IMTs...
August 2018: Medicine (Baltimore)
Yan Zhang, Feng Gao, Yuan Tang, Jinwen Xiao, Chuanchuan Li, Yu Ouyang, Yuemei Hou
Myocardial fibrosis (MF) plays an important part in cardiovascular diseases. The main cytological characteristics of MF is the increased number of myofibroblasts, which have multiple sources such as EMT, EndMT, myeloid progenitors, monocytes, and fibrocytes. Recent data showed that pericytes may represent a major source of myofibroblasts in kidney fibrosis. Valproic acid (VPA) is a kind of short-chain fatty acid. It was reported in recent studies that VPA regulates gene expression and influences various signal pathways...
2018: American Journal of Translational Research
Kazuki Nakagawa, Haruhiko Yamada, Hidetsugu Mori, Keiko Toyama, Kanji Takahashi
This study aimed to investigate the differences between images obtained by optical coherence tomography angiography (OCTA) with those from immunohistochemical labeling of laser-induced choroidal neovascularization (CNV) in a mouse model. CNV was induced by laser photocoagulation (GYC-2000, NIDEK; wavelength 532 nm) in the left eyes of 10 female C57BL/6J mice aged 6 weeks. The laser parameters included a 100-μm spot, 100-ms pulse duration and 200-mW incident power to rupture Bruch's membrane. OCT and OCTA CNV images were obtained using the RS-3000 Advance (NIDEK) 5 days post-laser photocoagulation...
2018: PloS One
Joselyn Allen, Jingtao Zhang, Michael D Quickel, Mary Kennett, Andrew D Patterson, Pamela A Hankey-Giblin
Liver fibrosis is commonly observed in the terminal stages of non-alcoholic steatohepatitis (NASH) and with no specific and effective anti-fibrotic therapies available, this disease is a major global health burden. The MSP/Ron receptor axis has been shown to have anti-inflammatory properties in a number of mouse models, due at least in part, to its ability to limit pro-inflammatory responses in tissue-resident macrophages and hepatocytes. In this study, we established the role of the Ron receptor in steatohepatitis-induced hepatic fibrosis using Ron ligand domain knockout mice on an apolipoprotein E knockout background (DKO)...
August 9, 2018: Journal of Proteome Research
Sinead M Walsh, Julie C Worrell, Aurelie Fabre, Boris Hinz, Rosemary Kane, Michael P Keane
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia that is characterized by excessive fibroproliferation. Key effector cells in IPF are myofibroblasts that are recruited from three potential sources: resident fibroblasts, fibrocytes and epithelial cells. We hypothesized that IPF myofibroblasts from different sources of origin displayed unique genetic profiles and distinct functional characteristics. Primary human pulmonary fibroblasts (normal and IPF), fibrocytes and epithelial cells were activated into myofibroblasts using the pro fibrotic factors TGF β and TNF α...
August 9, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ximeng Lian, Xiaowei Chen, Jingping Sun, Guoliang An, Xiaoli Li, Yan Wang, Piye Niu, Zhonghui Zhu, Lin Tian
Silicosis is pathologically characterized by diffused pulmonary fibrosis and abundant deposition of extracellular matrix (ECM) components. The ECM is mainly secreted by myofibroblasts which are the activated state of fibroblasts. MicroRNA-29b (miR-29b) is one of the well-known microRNAs involved in fibrosis, but its roles in silicosis have not been specified. In this study, we hypothesized that miR-29b might play a protective role in the progression of silicosis. MTT assay, qRT-PCR, immunofluorescence and western blotting were applied...
November 1, 2017: Toxicology Research
Kumari A Lata, Vaishali Upadhyay, Shashi S Pawar
Inflammatory myofibroblastic tumor (IMT) of the central nervous system is a rare entity of unknown etiology and a diagnostic dilemma for radiologists. We report a case of meningeal IMT occurring in a 15-year-old boy. Magnetic resonance imaging showed a large homogeneously enhancing extra-axial mass in left parietal region. Mass was resected en bloc and histopathological examination revealed the lesion to be composed of plasma cells, lymphocytes admixed with histiocytes, and spindle cells without any atypical cells, characteristic of IMT...
April 2018: Journal of Pediatric Neurosciences
Santosh Kumar, Sriharsha Ajjur Shankaregowda, Abhishek Chandna
Inflammatory pseudotumor is a rare benign condition of unknown cause. A 19-year-old female presented with gross hematuria and storage symptoms to the emergency. Contrast-enhanced computed tomography scan revealed a mass of 5 cm × 6 cm involving the dome and anterior wall of the bladder. Urachal carcinoma was kept as a possibility and transurethral biopsy of the aforementioned lesion was performed. The histopathology revealed inflammatory myofibroblastic tumor (IMT) of the bladder. A laparoscopic partial cystectomy was undertaken with adequate resection margins and the histopathology of the lesion confirmed IMT...
July 2018: Urology Annals
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