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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28209631/hdpscs-fabricate-a-vascularised-woven-bone-tissue-a-new-tool-in-bone-tissue-engineering
#1
Francesca Paino, Marcella La Noce, Alessandra Giuliani, Alfredo De Rosa, Serena Mazzoni, Luigi Laino, Evzen Amler, Gianpaolo Papaccio, Vincenzo Desiderio, Virginia Tirino
Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells successfully used in human bone tissue engineering. To better establish if these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim to obtain a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers and cultured. Growth curves, expression of bone-related markers, calcification, angiogenesis as well as in vivo transplantation assay were performed...
February 16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28202686/simvastatin-pre-treatment-improves-survival-and-mitochondrial-function-in-a-three-day-fluid-resuscitated-rat-model-of-sepsis
#2
Jerome Morel, Iain Hargreaves, David Brealey, Viruna Neergheen, Janne T Backman, Sandro Lindig, Marcus Bläss, Michael Bauer, Daniel F McAuley, Mervyn Singer
Statins may offer protective effects in sepsis through anti-inflammatory, mitochondrial protection and other actions. We thus evaluated the effects of simvastatin on survival, organ and mitochondrial function, tissue and plasma ubiquinone levels and liver transcriptomics in a 3-day rat model of sepsis. Comparisons of rat plasma simvastatin and ubiquinone levels were made against levels sampled in blood from patients with acute lung injury (ALI) enrolled into a trial of statin therapy. Animals received simvastatin by gavage either pre- or post-induction of faecal peritonitis...
February 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28196857/deletion-of-hypoxia-inducible-factor-1%C3%AE-in-myeloid-lineage-exaggerates-angiotensin-ii-induced-formation-of-abdominal-aortic-aneurysm
#3
Yusuke Takahara, Tomotake Tokunou, Hiroshi Kojima, Yoshitaka Hirooka, Toshihiro Ichiki
Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodeling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient mice...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28196856/vardenafil-reduces-macrophage-pro-inflammatory-overresponses-in-cystic-fibrosis-through-pde5-and-cftr-dependent-mechanisms
#4
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Chronic inflammation that progressively disrupts the lung tissue is a hallmark of Cystic Fibrosis (CF). In mice, vardenafil, an inhibitor of phosphodiesterase type 5 (PDE5), restores transepithelial ion transport and corrects mislocalization of the most common CF mutation, F508del-CFTR. It also reduces lung pro-inflammatory responses in mice and in patients with CF. To test the hypothesis that macrophages are target effector cells of the immunomodulatory effect of vardenafil, we isolated lung macrophages from mice homozygous for the F508del mutation or invalidated for the cftr gene and from their corresponding wild-type littermates...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#5
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28188237/first-identification-of-kr%C3%A3-ppel-like-factor-2-mutation-in-heritable-pulmonary-arterial-hypertension
#6
Christina A Eichstaedt, Jie Song, Rebecca Rodríguez Viales, Zixuan Pan, Nicola Benjamin, Christine Fischer, Marius Hoeper, Silvia Ulrich, Katrin Hinderhofer, Ekkehard Grünig
Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the bone morphogenic protein receptor 2 gene and/or genes of its signalling pathway in about 85% of patients. We clinically and genetically analysed a HPAH family without mutations in previously described PAH genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterisation in case of suspected disease...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28183811/annexin-ii-binding-immunoglobulins-in-patients-with-lupus-nephritis-and-their-correlation-with-disease-manifestations
#7
Kwok Fan Cheung, Susan Yung, Mel Km Chau, Desmond Yh Yap, Kwok Wah Chan, Cheuk Kwong Lee, Colin So Tang, Tak Mao Chan
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in NZBWF1/J mice. Annexin II-binding immunoglobulins in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy...
February 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143892/activation-of-trpv4-by-dietary-apigenin-antagonizes-renal-fibrosis-in-deoxycorticosterone-acetate-doca-salt-induced-hypertension
#8
Xing Wei, Peng Gao, Yunfei Pu, Qiang Li, Tao Yang, Hexuan Zhang, Shiqiang Xiong, Yuanting Cui, Li Li, Xin Ma, Daoyan Liu, Zhiming Zhu
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remain elusive. In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143891/genome-wide-methylation-profiles-in-coronary-artery-ectasia
#9
Tzu-Pin Lu, Nai-Chen Chuang, Chin-Yu Cheng, Cheng-An Hsu, Yi-Chih Wang, Yen-Hong Lin, Jen-Kuang Lee, Cho-Kai Wu, Juey-Jen Hwang, Lian-Yu Lin, Shih-Fan Sherri Yeh, Kuo-Liang Chien, Jyh-Ming Jimmy Juang
Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies showed that risk factors for CAE are related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays (Illumina HumanMethylation450)...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28130436/oxytocin-its-role-in-the-benign-prostatic-hyperplasia-bph-via-the-erk-pathway
#10
Huan Xu, Shi Fu, Yanbo Chen, Qi Chen, Meng Gu, Chong Liu, Zhiguang Qiao, Juan Zhou, Zhong Wang
AIMS: To evaluate the oxytocin and benign prostatic hyperplasia (BPH) and study the cell signaling mechanism. METHODS: Investigation was performed in patients about the correlation between oxytocin level and BPH. Mice were injected with oxytocin or oxytocin antagonist for two weeks and the prostate morphology was studied after sacrifice. Furthermore, in-vitro experiments were performed to evaluate the oxytocin effect through MEK-ERK-RSK pathway. RESULTS: Oxytocin was significantly elevated in the serum and prostate tissue of BPH patients and a positive correlation with the prostate volume was indicated...
January 27, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28115681/allergic-environment-enhances-airway-epithelial-pro-inflammatory-responses-to-rhinovirus-infection
#11
Cristan Herbert, Kimchi Do, Vincent Chiu, Linda Garthwaite, Yifan Chen, Paul M Young, Daniela Traini, Rakesh K Kumar
Airway epithelial cells (AEC) exhibit a pro-inflammatory phenotype in patients with allergic asthma. We examined the effect of an allergic cytokine environment on the response of AEC to rhinovirus, the most common trigger of acute exacerbations of asthma. Calu-3 cells, a well-differentiated human AEC line, were cultured with or without the T-helper type 2 cytokines IL-4 and IL-13, then stimulated with a toll-like receptor (TLR) 3 agonist (poly I:C, dsRNA) or a TLR7 agonist (imiquimod), or infected with rhinovirus 16...
January 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28096316/bay-11-7082-inhibits-the-nf-kb-and-nlrp3-inflammasome-pathways-and-protects-against-imq-induced-psoriasis
#12
Natasha Irrera, Mario Vaccaro, Alessandra Bitto, Giovanni Pallio, Gabriele Pizzino, Maria Lentini, Vincenzo Arcoraci, Letteria Minutoli, Michele Scuruchi, Giuseppina Cutroneo, Giuseppe Pio Anastasi, Roberta Ettari, Francesco Squadrito, Domenica Altavilla
BAY 11-7082 antagonizes I-κB kinase-β preventing nuclear translocation of NF-κB; it also inhibits NLRP3 inflammasome activation.NF-κB is involved in psoriasis, while the role of NLRP3 is controversial. We investigated BAY 11-7082 effects in an experimental model of psoriasis-like dermatitis. Psoriasis-like lesions were induced by a topical application of imiquimod cream (IMQ; 62.5 mg/day) on the shaved back skin of C57BL/6 and NLRP3 knock-out mice for 7 consecutive days. Sham psoriasis animals were challenged with vaseline cream...
January 17, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28093453/interactions-between-microsatellite-instability-and-human-gut-colonization-by-escherichia-coli-in-colorectal-cancer
#13
Johan Gagnière, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, Nancy Uhrhammer, Pierre Sauvanet, Pierre Déchelotte, Nicolas Barnich, Richard Bonnet, Denis Pezet, Mathilde Bonnet
Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli (E. coli) could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway which leads to microsatellite instability (MSI). This work, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells...
16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28082516/hmgb1-induced-autophagy-a-new-pathway-to-maintain-treg-cell-function-during-chronic-hepatitis-b-virus-infection
#14
Li-Sha Cheng, Jing Li, Yun Liu, Fu-Ping Wang, Si-Qi Wang, Wei-Min She, Sheng-di Wu, Xiao-Long Qi, Yong-Ping Zhou, Wei Jiang
High-mobility group box-1 protein (HMGB1), as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly-conserved self-digestive process in response to environmental stress. Recent mouse studies indicate autophagy is highly active in regulatory T cells (Treg). Here, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles with transmission electron microscope...
January 12, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28053239/microrna-378-reduces-mesangial-hypertrophy-and-kidney-tubular-fibrosis-via-mapk-signaling
#15
Bo Wang, Kevin Yao, Andrea F Wise, Ricky Lau, Hsin-Hui Shen, Greg H Tesch, Sharon D Ricardo
AIMS: To determine the regulatory role of a novel miRNA, miR-378, in the development of fibrosis through repression of the MAPK1 (ERK2) pathway. METHODS: miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E, and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor...
January 4, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28049736/glp-1-analogue-induced-weight-loss-does-not-improve-obesity-induced-at-dysfunction
#16
Emilie Pastel, Laura J McCulloch, Rebecca Ward, Shivam Joshi, Kim M Gooding, Angela C Shore, Katarina Kos
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss which improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT which expresses GLP-1 receptors. This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8)...
January 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28007970/dual-effects-of-fructose-on-chrebp-and-foxo1-3%C3%AE-are-responsible-for-aldob-upregulation-and-vascular-remodeling
#17
Wei Cao, Tuanjie Chang, Xiao-Qiang Li, Rui Wang, Lingyun Wu
Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodeling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced upregulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms have been unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively...
December 22, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27923881/the-ligands-of-translocator-protein-inhibit-human-th1-responses-and-the-rejection-of-murine-skin-allografts
#18
Yannan Zhang, Sifei Yu, Xiaomin Li, Binyan Yang, Changyou Wu
The translocator protein (TSPO) ligands impacted inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the current study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose- dependent manner by purified human CD4(+) T cells from PBMCs after stimulation. TSPO ligands inhibited the production of IFN-γ by memory CD4(+) T cells and the differentiation of naïve CD4(+) T cells into Th1 cells via  suppressing the activity of the corresponding transcription factors as indicated by reduced expression of T-bet and downregulation of STAT1, STAT4 and STAT5 phosphorylation...
December 6, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28213611/transthyretin-amyloidosis-an-under-recognized-neuropathy-and-cardiomyopathy
#19
REVIEW
Natalie J Galant, Per Westermark, Jeffrey N Higaki, Avijit Chakrabartty
Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is an underdiagnosed and important type of cardiomyopathy and/or polyneuropathy that requires increased awareness within the medical community. Raising awareness among clinicians about this type of neuropathy and lethal form of heart disease is critical for improving earlier diagnosis and the identification of patients for treatment. The following review summarizes current criteria used to diagnose both hereditary and wild-type ATTR (ATTRwt) amyloidosis, tools available to clinicians to improve diagnostic accuracy, available and newly developing therapeutics, as well as a brief biochemical and biophysical background of TTR amyloidogenesis...
March 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28202749/endothelial-cell-oligodendrocyte-interactions-in-small-vessel-disease-and-aging
#20
REVIEW
Rikesh M Rajani, Anna Williams
Cerebral small vessel disease (SVD) is a prevalent, neurological disease that significantly increases the risk of stroke and dementia. The main pathological changes are vascular, in the form of lipohyalinosis and arteriosclerosis, and in the white matter (WM), in the form of WM lesions. Despite this, it is unclear to what extent the key cell types involved-the endothelial cells (ECs) of the vasculature and the oligodendrocytes of the WM-interact. Here, we describe the work that has so far been carried out suggesting an interaction between ECs and oligodendrocytes in SVD...
March 1, 2017: Clinical Science (1979-)
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