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Current Molecular Medicine

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https://www.readbyqxmd.com/read/28828972/endothelium-and-oxidative-stress-the-pandora-s-box-of-cerebral-and-non-only-small-vessel-disease
#1
M Maccarrone, L Ulivi, N Giannini, V Montano, L Ghiadoni, R M Bruno, U Bonuccelli, M Mancuso
Common cerebral small vessel disease (cSVD) abnormalities are a common neuroradiological finding, especially in the elderly. They are associated with a wide clinical spectrum that leads to an increasing disability, impaired global function outcome and a reduced quality of life. A strong association is demonstrated with age and hypertension and other common vascular risk factors, including diabetes mellitus, dyslipoproteinemia, smoking, low vitamin B12 level, and hyperomocysteinemia. Although these epidemiological associations suggest a systemic involvement, etiopathogenetic mechanisms remain unclear...
August 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28828971/molecular-biomarkers-of-anaplastic-thyroid-carcinoma
#2
F Bozorg-Ghalati, M Hedayati
Anaplastic thyroid carcinoma is the rarest but extremely aggressive thyroid cancer subtype. This neoplasia is composed of undifferentiated tumor cells with poor prognosis and resistant to common thyroid cancer therapy. Early stage identification of this cancer for prompt treatment is very vital. Presently, cytological evaluation of fine needle aspiration biopsy (FNAB) which is known as invasive recognition assay, is the standard diagnostic method for the diagnosis of malignant thyroid tumors. Frequent studies have suggested that using the molecular biomarkers of thyroid cancer tissue alongside cytological examination, increase the accuracy of diagnostic tests...
August 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28782485/a-low-concentration-of-tacrolimus-semifluorinated-alkane-sfa-eyedrop-suppresses-intraocular-inflammation-in-experimental-models-of-uveitis
#3
S De Majumdar, M Subinya, J Korward, A Pettigrew, D Scherer, H Xu
PURPOSE: Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration. The aim of this study was to evaluate the therapeutic potential of 0.03% tacrolimus eyedrop in mouse models of uveitis. METHODS: 0.03% tacrolimus in perfluorobutylpentane (F4H5) (0...
August 7, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28782484/gene-expression-meta-analysis-of-potential-metastatic-breast-cancer-markers
#4
R Bell, R Barraclough, O Vasieva
Breast cancer metastasis is a highly prevalent cause of death for European females. DNA microarray analysis has established that primary tumors, which remain localized, differ in gene expression from those that metastasize. The aim of the project was to validate suggested prognostic and therapeutic markers using meta-analysis of data on gene expression in metastatic and primary breast cancer tumors combined from 12 studies available from the Genevestigator database. Our analysis suggested that transcriptional expression of the COX2 gene is significantly downregulated in metastatic tissue compared to normal breast tissue, but is not downregulated in primary tumors compared with normal breast tissue and may be used as a differential marker in metastatic breast cancer diagnostics...
August 7, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28782483/arrdc3-inhibits-the-progression-of-human-prostate-cancer-through-arrdc3-itg%C3%AE-4-pathway
#5
Y Zheng, Z-Y Lin, J-J Xie, F-N Jiang, C-J Chen, J-X Li, X Zhou, W-D Zhong
Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian α-arrestins family, which has been identified as a tumor suppressor gene in human breast cancer, but its functions are still not clear in human prostate cancer (PCa). The purpose of the present study was to investigate clinical significance, biological functions and underlying mechanisms of ARRDC3 deregulation in PCa. Microarray analysis found that ARRDC3 low expression was significantly associated with high Gleason score in TMA, and the expression level of ARRDC3 was negatively correlated with Gleason score, metastasis and biochemical recurrence in online Taylor Dataset...
August 7, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28730965/efficient-non-invasive-plasmid-dna-administration-into-tibialis-cranialis-muscle-of-little-mice
#6
C R Cecchi, E Higuti, E R Lima, D P Vieira, P L Squair, C N Peroni, P Bartolini
An alternative treatment for growth hormone deficiency based on hGH-DNA administration, followed by electro gene transfer, was investigated by injecting the plasmid into surgically exposed or non-exposed quadriceps or tibialis muscle of immunodeficient "little" mice. Previously optimized electrotransfer conditions were also improved via a new combination of high/low voltage pulses: after 3 days, serum hGH was determined. Both groups exhibited similar results: 5.0 ± 2.2 (SD) and 3.5 ± 0.9 ng hGH/ml (P>0...
July 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28721806/l-tetrahydropalmatine-induces-apoptosis-in-eu-4-leukemia-cells-by-down-regulating-x-linked-inhibitor-of-apoptosis-protein-and-increases-the-sensitivity-towards-doxorubicin
#7
S Li, D Chen, Renzhi Pei, Y Lu, P Zhang, J Ma, X Liu, X Du, K Sha, L Chen, J Cao, X Zhuang, J Wu, L Li, Z Fan, P Ye, S Tang, B Zhang, X Shi, K Li
BACKGROUND: L-Tetrahydropalmatine (L-THP) is a tetra-hydro protoberberine isoquinoline alkaloid. The phyto-compounds bearing isoquinoline alkaloids have been reported to show a potential effect against a number of human cancers cell lines including leukemia. We hypothesized that L-THP, being an isoquinoline alkaloid, could be a potential molecule against acute lymphoblastic leukemia (ALL), in this study, we evaluate L-THP against p53 deficient leukemia EU-4 cell lines in vitro. METHODS: For the study, p53 null leukemia EU-4 cells were used and treated with L-THP...
July 18, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#8
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429673/hydroxytyrosol-attenuates-lps-induced-acute-lung-injury-in-mice-by-regulating-autophagy-and-sirtuin-expression
#9
X Yang, T Jing, Y Li, Y He, B Wang, W Zhang, Y Xiao, W Wang, J Zhang, J Wei, R Lin
BACKGROUND: Recently, the effects of hydroxytyrosol on autophagy during acute lung injury (ALI) have drawn increasing attention. OBJECTIVE: We explored the underlying molecular mechanisms by which hydroxytyrosol exerts its anti-inflammatory effects in a murine model of ALI by up-regulating autophagy. METHODS: Male BALB/c mice, challenged with intranasal instillations of LPS, were treated with or without hydroxytyrosol (HT, 100 mg/kg, intragastrically) 1 h prior to LPS exposure...
April 21, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#10
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429671/ethanolamine-metabolism-in-the-mammalian-gastrointestinal-tract-mechanisms-patterns-and-importance
#11
J Zhou, X Xiong, K Wang, L Zou, D Lv, Y Yin
Nutritional exchanges and cooperation between bacteria in the gastrointestinal tract and the mammalian host play an important role in health and disease. Ethanolamine is an essential dietary lipid nutrient for animals and is abundant in both intestinal and bacterial cell membranes. Ethanolamine can be utilized by intestinal eukaryotic cells via the cytidine phosphoethanolamine pathway for de novo synthesis of phosphatidylethanolamine, and certain bacteria are able to catabolize it as a major carbon and/or nitrogen source with the help of ethanolamine utilization proteins...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429670/expression-of-dominant-negative-k6w-ubiquitin-in-the-lens-epithelium-via-an-adenoviral-vector-delays-posterior-capsule-opacification-in-a-rabbit-model
#12
Xuan Bao, Min Hou, Ruiping Peng, Furong Luo, Mingxing Wu
PURPOSE: Ubiquitin is involved in cell proliferation and differentiation, and the objective of this study is to investigate the potential of dominant negative Ubiquitin (Ub) with a lysine to tryptophan mutation at the 6 position (K6W) through an adenoviral expression vector in the prevention of posterior capsule opacification (PCO) in a rabbit PCO model. METHODS: Recombinant dominant negative K6W-Ub adenovirus (RAd-K6W-Ub) with green fluorescent protein (RAd-K6W-Ub/GFP) and RAd-GFP viruses (control) were generated with QBI-HEK 293A cells...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429669/what-can-pharmacological-models-of-retinal-degeneration-tell-us
#13
M H Reisenhofer, J Balmer, V Enzmann
Animal models with pharmacologically induced retinal degeneration including sodium iodate (NaIO3) and N-methyl-N-nitrosourea (MNU) have been extensively used in ophthalmic research to investigate retinal degeneration. NaIO3 induces degeneration of the retinal pigment epithelium (RPE) followed by photoreceptor (PRC) cell death, mimicking features of age-related macular degeneration. In contrast, MNU leads to rapid destruction of the PRCs only, enabling the use of the MNU model to investigate degeneration induced in retinitis pigmentosa...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28429668/the-role-of-mitochondria-associated-reactive-oxygen-species-in-the-amyloid-%C3%AE-induced-production-of-angiogenic-factors-by-arpe-19-cells
#14
L Wu, X Tan, L Liang, H Yu, C Wang, D Zhang, A Kijlstra, P Yang
OBJECTIVE: This study aimed to investigate the mechanisms whereby Amyloid-beta (Aβ) induces the production of angiogenic factors by a human retinal pigment epithelial cell line (ARPE-19) cells. METHODS: ARPE-19 cells obtained from the American Type Culture Collection (ATCC) were utilized in this study. The expression level of vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and complement activation fragments C3a and C5a were measured by Real-time quantitative PCR (RT-PCR) and Enzyme-linked immunosorbent assay (ELISA)...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28266275/molecular-basis-of-human-diseases-and-targeted-therapy-based-on-small-molecule-inhibitors-of-er-stress-induced-signaling-pathways
#15
W Rozpędek, A Nowak, D Pytel, J Alan Diehl, I Majsterek
The Endoplasmic Reticulum (ER) provides a conserved protein quality control system and plays a fundamental role in cell growth and homeostasis. Disturbances in the ER homeostasis may originate especially from hypoxia, glucose deficiency, presence of mutant proteins, that directly impair protein folding capacity and after deposition of unfolded and misfolded proteins within ER lumen trigger ER stress conditions. That subsequently activates the Unfolded Protein Response (UPR) branches, which has a dual pro-adaptive or pro-apoptotic role dependently on severity and time of duration of ER stress conditions...
March 6, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28260505/copy-number-variations-with-isolated-fetal-ventriculomegaly
#16
P Hu, Y Wang, R Sun, L Cao, X Chen, C Liu, C Luo, D Ma, W Wang, X Fu, W Shi, S Yi, K Zhang, H Liu, Z Xu
BACKGROUND: Copy Number Variations (CNVs) are an important genetic cause of a number of neurodevelopmental disorders (NDs). However, the association between CNVs and the development and prognosis of isolated fetal ventriculomegaly (IMV) is unclear. OBJECTIVES: To investigate possible associations between CNVs and the development of fetal IMV. METHODS: This retrospective study recruited 154 subjects with ultrasound-confirmed fetal IMV and 190 subjects in a control cohort who underwent a high-risk prenatal serum screening program...
March 3, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28231755/the-immune-function-of-ly6chi-inflammatory-monocytes-during-infection-and-inflammation
#17
L Liu, Y Wei, X Wei
Monocytes originate from progenitors in bone marrow and circulate through blood vessels and patrol the vascular endothelium or differentiate into mononuclear phagocytes and infiltrate via the bloodstream to peripheral tissues during infection and other inflammatory conditions. Recruitment of inflammatory monocytes is essential for effectively clearance of bacteria, control of Toxoplasma gondii infections and limiting tissue damage. Unexpectedly, Ly6Chiinflammatory monocytes acquire the inflammatory regulatory capacity dual phenotypes during acute infection and inflammation...
February 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28231754/survival-and-immunosuppression-induced-by-hepatocyte-growth-factor-in-chronic-lymphocytic-leukemia
#18
P Giannoni, G Cutrona, D de Totero
Chronic lymphocytic leukemia (CLL), the most common leukemia among adults in the western world, is characterized by a progressive accumulation of relatively mature CD5+ B cells in peripheral blood, lymph nodes and bone marrow. Despite much recent advancement in therapy, CLL is still incurable. Lymph nodes and bone marrow represent sanctuary sites preserving leukemic cells from spontaneous or drug-induced apoptosis, and infiltration of leukemic cells in these districts correlates with clinical stages and prognosis...
February 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28231753/prion-function-and-pathophysiology-in-non-mammalian-models
#19
N Guerrero, M M Meynard, J Borgonovo, K Palma, M L Concha, C Hetz
More than thirty years have passed since the discovery of the prion protein (PrP) and its causative role in transmissible spongiform encephalopathy. Since a combination of both gain- and loss-of-function mechanisms may underlay prion pathogenesis, understanding its physiological role may give important clues about disease mechanisms. Historically, the primary strategy for prion research has involved the use of human tissue, cell cultures and mammalian animal models. Nevertheless, experimental difficulties of in vivo studies and some controversial observations obtained in these systems have triggered the search for alternative animal models...
February 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28231752/decreased-hoxd10-expression-promotes-a-proliferative-and-aggressive-phenotype-in-prostate-cancer
#20
R-J Mo, J-M Lu, Y-P Wan, W Hua, Y-X Liang, Y-J Zhuo, Q-W Kuang, Y-L Liu, H-C He, W-D Zhong
HoxD10 gene plays a critical role in cell proliferation in the process of tumor development. However, the protein expression level and the function of HoxD10 in prostate cancer remain unknown. Using tissue microarray, we demonstrate that the protein expression of HoxD10 is commonly decreased in prostate cancer tissues (n = 92) compared to adjacent benign prostate tissues (n = 77). Functionally, knockdown of HoxD10 resulted in significant promotion of prostate cancer cell proliferation. Moreover, knockdown of HoxD10 strikingly stimulated prostate tumor growth in a mouse xenograft model...
February 19, 2017: Current Molecular Medicine
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