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https://www.readbyqxmd.com/read/27920529/synthetic-high-density-lipoproteins-for-delivery-of-10-hydroxycamptothecin
#1
Yue Yuan, Jian Wen, Jie Tang, Qiming Kan, Rose Ackermann, Karl Olsen, Anna Schwendeman
The purpose of this study was to develop a novel synthetic high-density lipoprotein (sHDL) nanoparticle delivery system for 10-hydroxycamptothecin (HCPT) for treatment of colon carcinoma. HDL is recognized by scavenger receptor B-I (SR-BI) over-expressed in colon carcinomas 5- to 35-fold relative to the human fibroblasts. The sHDL nanoparticles were composed of apolipoprotein A-I mimic peptide (5A) and contained 0.5%-1.5% (w/w) of HCPT. An optimized HCPT-sHDL formulation exhibited 0.7% HCPT loading with 70% efficiency with an average size of 10-12 nm...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920257/pkr-mediates-inflammatory-response-induced-by-hyperosmotic-stress
#2
Kenneth T Farabaugh, Mithu Majumder, Bo-Jhih Guan, Raul Jobava, Jing Wu, Dawid Krokowski, Xing-Huang Gao, Andrew Schuster, Michelle Longworth, Edward D Chan, Massimiliano Bianchi, Madhusudan Dey, Antonis E Koromilas, Parameswaran Ramakrishnan, Maria Hatzoglou
High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA binding domain. In turn, PKR stimulated nuclear accumulation of nuclear factor-κB (NF-κB) p65 species phosphorylated at serine-536, which was paralleled by the induction of a subset of inflammatory NF-κB p65- responsive genes including inducible nitric oxide synthase (iNOS), IL-6, and IL-1β. The PKR mediated-hyperinduction of iNOS decreased cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and post-translational modification of proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27918096/back-cover-story-eur-j-immunol-12-16
#3
(no author information available yet)
Our back cover features an H&E stained biopsy section from a patient with eosinophilic myocarditis. Countless heart-infiltrating eosinophils with bright pink granules and bi-lobed nuclei are visible between large, striated cardiomyocytes. In addition, T cells and macrophages are infiltrating the heart. This image relates to the article by Diny et al. (pp. 2749-2760), in which the authors analyze the pathway required for eosinophil trafficking to the heart by examining heart biopsies from myocarditis patients and a murine myocarditis model...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27914813/normal-human-gingival-fibroblasts-undergo-cytostasis-and-apoptosis-after-long-term-exposure-to-butyric-acid
#4
Michihiro Shirasugi, Keisuke Nishioka, Toshiro Yamamoto, Takaaki Nakaya, Narisato Kanamura
The causes of periodontal disease are complex. Butyric acid, a metabolite of periodontopathic bacteria such as Porphyromonas gingivalis, acts as a histone deacetylase inhibitor that has a direct effect on mRNA expression. Butyric acid produced by Clostridium butyricum in the intestinal tract induces differentiation of regulatory T cells, thereby suppressing inflammation in the gut. Mice lacking Clostridium butyricum in the intestinal tract suffer from colitis. By contrast, butyric acid in the oral cavity worsens periodontal disease...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914707/adiponectin-alters-renal-calcium-and-phosphate-excretion-through-regulation-of-klotho-expression
#5
Joseph M Rutkowski, Johanne Pastor, Kai Sun, Sun K Park, I Alexandru Bobulescu, Christopher T Chen, Orson W Moe, Philipp E Scherer
The kidney controls systemic calcium and phosphate levels and disturbances of its control mechanisms can lead to a variety of diseases. The insulin-sensitizing adipokine adiponectin is renoprotective and accelerates functional recovery following renal injury. However, unlike other adipokines, adiponectin is reduced in obesity. High adiponectin levels are also correlated with bone loss, suggestive of an additional action in mineral metabolism. Using knockout, wild-type, and adiponectin-overexpressing transgenic mice, we sought to identify the mechanistic basis for adiponectin's ability to regulate calcium and phosphate balance at the level of the kidney...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27912044/mutations-in-prosc-disrupt-cellular-pyridoxal-phosphate-homeostasis-and-cause-vitamin-b6-dependent-epilepsy
#6
Niklas Darin, Emma Reid, Laurence Prunetti, Lena Samuelsson, Ralf A Husain, Matthew Wilson, Basma El Yacoubi, Emma Footitt, W K Chong, Louise C Wilson, Helen Prunty, Simon Pope, Simon Heales, Karine Lascelles, Mike Champion, Evangeline Wassmer, Pierangelo Veggiotti, Valérie de Crécy-Lagard, Philippa B Mills, Peter T Clayton
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms that are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain can be caused by inborn errors affecting B6 vitamer metabolism or by inactivation of PLP, which can occur when compounds accumulate as a result of inborn errors of other pathways or when small molecules are ingested...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27907202/a-reproducible-method-for-isolation-and-in-vitro-culture-of-functional-human-lymphoid-stromal-cells-from-tonsils
#7
Yotam E Bar-Ephraim, Tanja Konijn, Mehmet Gönültas, Reina E Mebius, Rogier M Reijmers
The stromal compartment of secondary lymphoid organs is classicaly known for providing a mechanical scaffold for the complex interactions between hematopoietic cells during immune activation as well as for providing a niche which is favorable for survival of lymphocytes. In recent years, it became increasingly clear that these cells also play an active role during such a response. Currently, knowledge of the interactions between human lymphoid stroma and hematopoietic cells is still lacking and most insight is based on murine systems...
2016: PloS One
https://www.readbyqxmd.com/read/27906035/extracellular-vesicles-in-the-pathogenesis-of-rheumatoid-arthritis-and-osteoarthritis
#8
REVIEW
Joseph Withrow, Cameron Murphy, Yutao Liu, Monte Hunter, Sadanand Fulzele, Mark W Hamrick
Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity in the US population. Extracellular vesicles (EVs), including exosomes and microvesicles, are now recognized to play important roles in cell-to-cell communication by transporting various proteins, microRNAs (miRNAs), and mRNAs. EV-derived proteins and miRNAs impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of both OA and RA. Some of the processes by which these membrane-bound vesicles can alter joint tissue include extracellular matrix degradation, cell-to-cell communication, modulation of inflammation, angiogenesis, and antigen presentation...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27905037/involvement-of-jak1-jak2-and-jak3-in-stimulation-of-functional-activity-of-mesenchymal-progenitor-cells-by-fibroblast-growth-factor
#9
G N Zyuz'kov, V V Zhdanov, E V Udut, L A Miroshnichenko, E V Simanina, T Yu Polyakova, L A Stavrova, V V Udut, M Yu Minakova, A M Dygai
We studied the involvement of individual JAK kinases in the realization of the growth potential of mesenchymal precursors under the effect of fibroblast growth factor. The important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells and participation of JAK1 in this process under conditions of cytokine stimulation of progenitor cells were demonstrated. Specific inhibitors of these kinases reduced the yield of fibroblast CFU and the rate of their division. Moreover, blockade of JAK1, JAK2, and JAK3 under the effect of fibroblast growth factor was accompanied by an increase in the intensity of progenitor cell differentiation...
December 1, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27903619/interleukin-10-mediated-regenerative-postnatal-tissue-repair-is-dependent-on-regulation-of-hyaluronan-metabolism-via-fibroblast-specific-stat3-signaling
#10
Swathi Balaji, Xinyi Wang, Alice King, Louis D Le, Sukanta S Bhattacharya, Chad M Moles, Manish J Butte, Vinicio A de Jesus Perez, Kenneth W Liechty, Thomas N Wight, Timothy M Crombleholme, Paul L Bollyky, Sundeep G Keswani
The cytokine IL-10 has potent antifibrotic effects in models of adult fibrosis, but the mechanisms of action are unclear. Here, we report a novel finding that IL-10 triggers a signal transducer and activator of transcription 3 (STAT3)-dependent signaling pathway that regulates hyaluronan (HA) metabolism and drives adult fibroblasts to synthesize an HA-rich pericellular matrix, which mimics the fetal regenerative wound healing phenotype with reduced fibrosis. By using cre-lox-mediated novel, inducible, fibroblast-, keratinocyte-, and wound-specific STAT3 knockdown postnatal mice-plus syngeneic fibroblast cell-transplant models-we demonstrate that the regenerative effects of IL-10 in postnatal wounds are dependent on HA synthesis and fibroblast-specific STAT3-dependent signaling...
November 30, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895816/clinical-impact-of-chemotherapy-to-improve-tumor-microenvironment-of-pancreatic-cancer
#11
REVIEW
Takahiro Tsuchikawa, Shintaro Takeuchi, Toru Nakamura, Toshiaki Shichinohe, Satoshi Hirano
A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells...
November 15, 2016: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/27895174/human-lung-fibroblasts-present-bacterial-antigens-to-autologous-lung-th-cells
#12
Andrew J Hutton, Marta E Polak, C Mirella Spalluto, Joshua C Wallington, Chris Pickard, Karl J Staples, Jane A Warner, Tom M A Wilkinson
Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4(+) Th cells. During severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating Th cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4(+) T cell Ag-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to IFN-γ...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894386/-study-of-the-correlation-between-the-expression-of-angiotensin-%C3%A2-and-its-receptors-and-collagen-deposition-in-human-keloid
#13
J J Chen, X J Wu, Z Y Zhang, Z X Chen, Y Cen
Objective: To study the correlation between the expression of angiotensin Ⅱ, angiotensin Ⅱ type 1 receptor (AT1R), angiotensin Ⅱ type 2 receptor (AT2R) and collagen deposition in human keloid. Methods: The keloid from 19 keloid patients and normal skin from 13 patients performed with free skin transplantation hospitalized in our unit from May 2014 to January 2015 were obtained. The expressions of angiotensin Ⅱ, AT1R, and AT2R were detected by immunohistochemical staining, and the results were semi-quantitatively analyzed by immunohistochemical scoring...
November 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27893716/hic-5-remodeling-of-the-stromal-matrix-promotes-breast-tumor-progression
#14
G J Goreczny, J L Ouderkirk-Pecone, E C Olson, M Krendel, C E Turner
The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5(-/-) mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5(-/-);PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5(+/-);PyMT mice...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893433/regulation-of-brachyury-by-fibroblast-growth-factor-receptor-1-in-lung-cancer
#15
Yunping Hu, Xin Feng, Akiva Mintz, W Jeffrey Petty, Wesley Hsu
Recent evidence suggests that T-box transcription factor brachyury plays an important role in lung cancer development and progression. However, the mechanisms underlying brachyury-driven cellular processes remain unclear. Here we found that fibroblast growth factor receptor 1/mitogen-activated protein kinase (FGFR1/MAPK) signaling regulated brachyury in lung cancer. Analysis of FGFR1-4 and brachyury expression in human lung tumor tissue and cell lines found that only expression of FGFR1 was positively correlated with brachyury expression...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890637/antiplasmodial-activity-of-heinsia-crinita-rubiaceae-and-identification-of-new-iridoids
#16
P Tshisekedi Tshibangu, P Mutwale Kapepula, M J Kabongo Kapinga, A Tujibikila Mukuta, Dibungi T Kalenda, Alembert T Tchinda, Ange A Mouithys-Mickalad, O Jansen, E Cieckiewicz, M Tits, L Angenot, M Frédérich
ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. MATERIALS AND METHODS: Different plant parts were extracted with methanol, ethanol and dichloromethane...
November 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27890241/distinct-fibroblasts-in-the-papillary-and-reticular-dermis-implications-for-wound-healing
#17
REVIEW
David T Woodley
Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct lineages of cells that have distinct cell markers and, more importantly, distinct functional abilities. Human skin wound healing largely involves the dermal fibroblast lineage from the reticular dermis and not the papillary dermis. If scientists could find a way to stimulate the dermal fibroblast lineages from the papillary dermis in early wound healing, perhaps human skin wounds could heal without scarring and with skin appendages...
January 2017: Dermatologic Clinics
https://www.readbyqxmd.com/read/27889201/expression-of-fibroblast-activating-protein-and-correlation-with-histological-grade-mitotic-index-and-ki67-expression-in-canine-mast-cell-tumours
#18
A Giuliano, R Dos Santos Horta, F Costantino-Casas, T Hoather, J Dobson
Fibroblast activating protein (FAP) is a membrane serine protease expressed by activated fibroblasts, particularly tumour associated fibroblasts (TAFs). FAP expression has not been reported in canine mast cell tumours (MCTs). The objective of this study was to evaluate the expression of FAP in TAFs and its correlation with histological grade, mitotic index and Ki67 expression in canine MCTs. FAP expression was evaluated by immunohistochemistry (IHC) in 30 canine MCTs. Twenty-eight (90%) of the MCTs expressed FAP in the stroma, 16 cases showed low to intermediate FAP score and 14 cases had a high FAP score...
November 24, 2016: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/27888897/treating-scars-on-the-oral-mucosa
#19
REVIEW
Erik William Evans
Mucosal wounds tend to heal more rapidly than skin wounds and with minimal to no scar formation and hence have a minimal impact on function or aesthetics. This is likely due to differences in the magnitude and timing of the various factors that contribute to wound healing. Some examples of these differences are fibroblast proliferation, transforming growth factor-β, macrophages, neutrophils, and T cells. Other factors, such as the moist environment, contribute to the favorable wound-healing characteristics of mucosa...
February 2017: Facial Plastic Surgery Clinics of North America
https://www.readbyqxmd.com/read/27881983/high-endothelial-venules-and-lymphatic-vessels-in-tertiary-lymphoid-organs-characteristics-functions-and-regulation
#20
REVIEW
Nancy H Ruddle
High endothelial venules (HEVs) and lymphatic vessels (LVs) are essential for the function of the immune system, by providing communication between the body and lymph nodes (LNs), specialized sites of antigen presentation and recognition. HEVs bring in naïve and central memory cells and LVs transport antigen, antigen-presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs (TLOs) are accumulations of lymphoid and stromal cells that arise and organize at ectopic sites in response to chronic inflammation in autoimmunity, microbial infection, graft rejection, and cancer...
2016: Frontiers in Immunology
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