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Hadi Hezaveh, Steffen Cosson, Ellen A Otte, Guannan Su, Benjamin D Fairbanks, Justin J Cooper-White
Capturing cell-secreted extracellular matrix (ECM) proteins through cooperative binding with high specificity and affinity is an important function of native tissue matrices during both tissue homeostasis and repair. However, whilst synthetic hydrogels, such as those based on polyethylene glycol (PEG), are often proposed as ideal materials to deliver human mesenchymal stem cells (hMSCs) to sites of injury to enable tissue repair, they do not have this capability, a capability that would enable cells to actively remodel their local extracellular microenvironment and potentially provide the required feedback control for more effective tissue genesis...
February 13, 2018: Biomacromolecules
Yu Yan, Hua Qian, Hongda Jiang, Haiyang Yu, Liyao Sun, Xi Wei, Yunduan Sun, Hongyan Ge, Haizhou Zhou, Xiaoguang Li, Takashi Hashimoto, Xianling Tang, Ping Liu
Cataracts are the most common eye disease to cause blindness in patients. The abnormal deposition of laminins (LMs) in the lens capsule and the disruption of capsular epithelium contribute to cataract development, although the mechanism by which this occurs is currently unclear. The present study aimed to reproduce HLE B‑3 basement membranes (BMs) using HLE B‑3 cells and to analyze the similarities of LM expression between HLE B‑3 BMs and human anterior lens capsule (ALC). Immunohistochemistry (IHC), ELISA, western blot analysis and immunoprecipitation (IP)‑western blot analysis were used to detect total LMs, LM trimers and 11 LM subunits in HLE B‑3 cells, HLE B‑3 BMs and human ALCs...
February 8, 2018: Molecular Medicine Reports
Alexandra N Tsoras, Julie A Champion
Peptide subunit vaccines are desirable because they increase control over the immune response and safety of the vaccine by reducing the risk of off-target responses to molecules other than the target antigen. The immunogenicity of most peptides, however, is low. Peptide nanoclusters (PNC) are proposed as a subunit peptide vaccine delivery system made completely of cross-linked peptide antigen that could improve the immunogenicity of a peptide vaccine. Proof of concept is demonstrated with oncofetal antigen (OFA), an immature laminin receptor protein expressed by many hematologic cancer cells but not by healthy cells...
February 13, 2018: Bioconjugate Chemistry
Yong Wang, Yahui Liu, Jianshuai Jiang, Hanbin Cui
The existence of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) is regarded as the cause of tumor formation and recurrence. Matrine has been reported to exhibit antitumor effects in cancer cells. In the present study, a preliminary study was performed on the mechanisms of matrine on hepatocellular carcinoma (HCC) stem-like cells. The HCC SMMC-7721 cell line was cultured in tumor stem cell-specific medium to form spheres, and different concentrations (1, 2 and 5 mg/kg) of cisplatin were then used in order to purify the most drug-resistant cells, which were used as CSLCs...
February 2018: Oncology Letters
Zhi-Xue Yang, Bo Zhang, Jinrong Wei, Guo-Qin Jiang, Yan-Lin Wu, Bing-Jing Leng, Chun-Gen Xing
Background: Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4. Methods: Western blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC...
2018: Cancer Cell International
Severin Mühleder, Karoline Pill, Mira Schaupper, Krystyna Labuda, Eleni Priglinger, Pablo Hofbauer, Verena Charwat, Uwe Marx, Heinz Redl, Wolfgang Holnthoner
BACKGROUND: Co-cultures of endothelial cells with mesenchymal stem cells currently represent one of the most promising approaches in providing oxygen and nutrient supply for microvascular tissue engineering. Still, to translate this model into clinics several in vitro parameters including growth medium and scaffold degradation need to be fine-tuned. METHODS: We recently described the co-culture of adipose-derived stem cells with endothelial cells in fibrin, resulting in capillary formation in vitro as well as their perfusion in vivo...
February 12, 2018: Stem Cell Research & Therapy
Michio Nagata
PURPOSE OF REVIEW: Earlier works of the glomerulogenesis described morphological steps and protein expression during in-vivo and in-vitro kidney development. Recent technologies using cell-specific or conditional knock-out mice for several factors provide important knowledge about cross-talk signaling among resident cells as local events. Based on the recent advancement, this review revisits comprehensive morphological development of the glomerulus. RECENT FINDINGS: Interactions of presumptive podocyte vascular endothelial growth factor with vascular endothelial growth factor-2 on angioblasts initiate glomerular vascularization...
February 9, 2018: Current Opinion in Nephrology and Hypertension
Michael James McClure, David Josh Cohen, Allison N Ramey, Caroline B Bivens, Satya Mallu, Jonathan E Isaacs, Emily Imming, Yen-Chen Huang, MoonHae Sunwoo, Zvi Schwartz, Barbara Boyan
Current strategies to treat volumetric muscle loss use primarily pedicle or free muscle transfers, but these grafts fail to adequately regenerate functional tissue. Decellularized soft tissue grafts possess physical and chemical cues to promote muscle regeneration, suggesting their potential for use in large muscle defects. In this study, we developed a decellularized muscle matrix (DMM) graft using rat gastrocnemius. Anisotropy and chemical components of the extracellular matrix were retained, including laminin, fibronectin, and collagen...
February 12, 2018: Tissue Engineering. Part A
Young-Yoon Kim, Hailan Li, Yu Seok Song, Hyo-Soon Jeong, Hye-Young Yun, Kwang Jin Baek, Nyoun Soo Kwon, Yong Kyoo Shin, Kyoung-Chan Park, Dong-Seok Kim
Since the use of animal experimentation is restricted with regard to cosmetic materials, alternative in vitro models such as skin equivalents (SEs) are needed. Laminin is one of the major non-collagenous glycoproteins. The pentapeptide YIGSR (Tyr-Ile-Gly-Ser-Arg) is a functional motif of laminin that binds to the laminin receptor. In the present study, we examined whether YIGSR could improve the reconstruction of SEs. YIGSR has no effects on monolayer cell proliferation of CCD25-Sk fibroblasts or HaCaT keratinocytes...
February 7, 2018: Journal of Tissue Viability
Seung-Nam Jung, Hyun Sil Lim, Lihua Liu, Jae Won Chang, Young Chang Lim, Ki Sang Rha, Bon Seok Koo
Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, a protein of the extracellular matrix secreted by cultured human keratinocytes. While LAMB3 is involved in the invasive and metastatic abilities of several tumor types, including those found in the colon, pancreas, lung, cervix, stomach, and prostate, its mechanism of action in thyroid cancer has not been investigated previously. Our results show that LAMB3 is up-regulated in papillary thyroid cancer, and that its suppression reduces cell migration/invasion via down-regulation of epithelial‒mesenchymal transition-associated proteins (N-cadherin, vimentin, slug) and inhibition of matrix metalloproteinase 9...
February 9, 2018: Scientific Reports
Upasana Sridharan, Preethi Ragunathan, Barbara Spellerberg, Karthe Ponnuraj
Metal binding receptors are one of the extracellular components of ATP-binding cassette transporters that are essential for regulation of metal homeostasis in bacteria. Laminin binding adhesin (Lmb) of Streptococcus agalactiae falls under this class of solute binding proteins. It binds to zinc with a high affinity. Crystal structure of Lmb solved previously by our group reveals that the zinc is tetrahedrally coordinated by three histidines and a glutamate at the interdomain cleft. Lmb contains a long disordered loop close to the metal binding site whose precise function is unknown...
February 8, 2018: Journal of Biomolecular Structure & Dynamics
Tong Wu, Jiajia Xue, Haoxuan Li, Chunlei Zhu, Xiumei Mo, Younan Xia
Scaffolds functionalized with circular gradients of active proteins are attractive for tissue regeneration due to their enhanced capability to accelerate cell migration and/or promote neurite extension in a radial fashion. Here we report a general method for generating circular gradients of active proteins on scaffolds comprised of radially aligned nanofibers. In a typical process, the scaffold, with its central portion raised using a copper wire to take a cone shape, was placed in a container (upright or up-side-down), followed by dropwise addition of a bovine serum albumin (BSA) solution into the container...
February 8, 2018: ACS Applied Materials & Interfaces
Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Jer-Wei Chang, Kelly Su, Han-Shui Hsu, Shih-Chieh Hung
Epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis and tumorigenesis in lung cancer stem-like cells (CSCs). However, the exact mechanism underlying this is not clear. We used microarray analysis to identify candidate genes responsible for EMT in spheroid and monolayer cultures of lung cancer cells. We found increased expression of a variety of adhesion molecules in CSCs. One of these molecules, Collagen XVII (Col XVII), was demonstrated to be required for maintenance of EMT phenotypes and metastasis ability in lung CSCs...
January 5, 2018: Oncotarget
Mirela Maier, Cindy Baldwin, Lamine Aoudjit, Tomoko Takano
Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called "podocytes" within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1...
February 6, 2018: International Journal of Molecular Sciences
Thais Gonçalves Ferreira, Camilla Nunes Dos Reis Trindade, Petra Bell, André Teixeira-Ferreira, Jonas E Perales, Rossiane C Vommaro, Regina Maria Cavalcanti Pilotto Domingues, Eliane de Oliveira Ferreira
BACKGROUND: Members of the Bacteroides fragilis group are the most important components of the normal human gut microbiome, but are also major opportunistic pathogens that are responsible for significant mortality, especially in the case of bacteraemia and other severe infections, such as intra-abdominal abscesses. Up to now, several virulence factors have been described that might explain the involvement of B. fragilis in these infections. The secretion of extracellular membrane vesicles (EMVs) has been proposed to play a role in pathogenesis and symbiosis in gram-negative bacteria, by releasing soluble proteins and other molecules...
March 2018: Memórias do Instituto Oswaldo Cruz
Beatrice Sandner, Radhika Puttagunta, Melanie Motsch, Frank Bradke, Jörg Ruschel, Armin Blesch, Norbert Weidner
Following a spinal cord injury (SCI) a growth aversive environment forms, consisting of a fibroglial scar and inhibitory factors, further restricting the already low intrinsic growth potential of injured adult central nervous system (CNS) neurons. Previous studies have shown that local administration of the microtubule-stabilizing drug paclitaxel or epothilone B (Epo B) reduce fibrotic scar formation and axonal dieback as well as induce axonal growth/sprouting after SCI. Likewise, systemic administration of Epo B promoted functional recovery...
February 1, 2018: Experimental Neurology
Karen K McKee, Maya Aleksandrova, Peter D Yurchenco
Laminin polymerization is a key step of basement membrane self-assembly that depends on the binding of the three different N-terminal globular LN domains. Several mutations in the LN domains cause LAMA2-deficient muscular dystrophy and LAMB2-deficient Pierson syndrome. These mutations may affect polymerization. A novel approach to identify the amino acid residues required for polymerization has been applied to an analysis of these and other laminin LN mutations. The approach utilizes laminin-nidogen chimeric fusion proteins that bind to recombinant non-polymerizing laminins to provide a missing functional LN domain...
February 2, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Uwe Rauch, Eva Bengtsson, Isabel Gonçalves, Anna Hultgårdh-Nilsson
The clinical consequences of arterial atherosclerotic lesions depend, apart from their size, on their composition of cellular and extracellular components. While an intact endothelium at the interface of atherosclerotic plaques towards the blood can prevent its erosion, underlying smooth muscle cells within the plaque can reduce the risk of plaque ruptures, due to the deposition of stabilizing extracellular matrix. Basement membranes underlay and support the function of endothelial cells, and embed smooth muscle cells in the media, the source of most smooth muscle cells within atherosclerotic plaques...
February 6, 2018: Histology and Histopathology
Kazuo Takayama, Naoki Akita, Natsumi Mimura, Rina Akahira, Yukimasa Taniguchi, Makoto Ikeda, Fuminori Sakurai, Osamu Ohara, Tomohiro Morio, Kiyotoshi Sekiguchi, Hiroyuki Mizuguchi
Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS-HLCs for hepatocyte transplantation. First, human iPS-HLCs were generated from a human leukocyte antigen-homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder-free condition using human recombinant laminin 111, laminin 511, and type IV collagen...
December 2017: Hepatology Communications
Maria José Menal, Ignasi Jorba, Marta Torres, Josep M Montserrat, David Gozal, Anna Colell, Gerard Piñol-Ripoll, Daniel Navajas, Isaac Almendros, Ramon Farré
Background: Evidence from patients and animal models suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD) and that AD is associated with reduced brain tissue stiffness. Aim: To investigate whether intermittent hypoxia (IH) alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA. Methods: Six-eight month old (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) AD mutant mice and wild-type (WT) littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day) or normoxia for 8 weeks...
2018: Frontiers in Neurology
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