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Current Molecular Medicine

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https://www.readbyqxmd.com/read/30421677/the-inhibition-of-digitoxin-on-store-operated-calcium-entry-is-dependent-on-the-phosphorylation-sites-and-pore-region-of-orai1
#1
Lijuan Zhou, Xiangxiang Chi, Yaping Zhu, Tian Zhang, Jindou Liu, Guolin Ma, Lian He, Shuce Zhang, Ping Gao, Yubin Zhou, Jin Liu, Youjun Wang
BACKGROUND: Mostly mediated by STIM1 and Orai1, Store-operated Ca2+ entry (SOCE) is a major Ca2+ influx pathway that has been linked with many types of diseases like myopathy, epilepsy, immune deficient diseases, and cancer. Currently many details about SOCE process have been revealed. However, the dissection of the molecular mechanisms underlying SOCE activation and the development possible treatments of SOCE related diseases are hindered, partly due to the lack of more specific pharmacological tools and poor understandings of currently available SOCE modifiers, including the a newly identified SOCE inhibitor, digitoxin...
November 12, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30421676/establishment-of-retinal-degeneration-model-in-rat-and-monkey-by-intravitreal-injection-of-sodium-iodate
#2
Qingjian Ou, Tong Zhu, Peng Li, Zongyi Li, Li Wang, Chunpin Lian, Hua Xu, Caixia Jin, Furong Gao, Jing-Ying Xu, Juan Wang, Jieping Zhang, Weiye Li, Haibin Tian, Lixia Lu, Guo-Tong Xu
BACKGROUND: Animal models play critical roles in studying etiology and therapy of retinal degeneration (RD). OBJECTIVE: To establish a RD model in monkey without severe systemic side-effects. METHODS: Cynomolgus monkeys and Sprague-Dawley rats were treated with intravenous and intravitreal sodium iodate (SI). The ERG, FFA, OCT and retinal morphology were examined to evaluate the retinal function and structure. ARPE19 cells were treated with SI for cell viability and morphology examinations...
November 12, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30421675/enhanced-resistance-of-triploid-crucian-carp-to-cadmium-induced-oxidative-and-endoplasmic-reticulum-stresses
#3
W-B Liu, Y-H Wen, M-M Wang, S-Y Gui, X-C Li, Y-P Fan, X Yan, Y-Q Lin, Y-Y Sun, J-H Liu, L-Y Peng, S-J Liu, D W-C Li, Y-M Xiao
Cadmium (Cd) is highly toxic to aquatic organisms. In this study, we found a new variety of triploid crucian carp with strong Cd resistance. Under Cd stress, the mortality and abnormality rates in triploid crucian carp were lower than those of diploid strains. To explore the molecular mechanisms underlying Cd stress, the liver transcriptomes of triploid crucian carp were obtained. The expression of 5,797 unigenes in Cd-treated triploid crucian carp differed significantly from those of control group. These differential expression genes mainly involved in endoplasmic reticulum (ER) associated ubiquitin-dependent proteins, membrane proteins of ER and mitochondria...
November 12, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30411685/role-of-hif-1-in-cancer-progression-novel-insights-a-review
#4
Pezzuto Aldo, Carico Elisabetta
Hypoxia is a condition always present in tumor environment owing to the fast growth of tumor cells not supported by adequate blood supply. There is increasing evidence that hypoxia plays an important role in cancer dormancy and cancer metabolism, increasing stemness activity and bringing about cancer initiation and progression . This condition may influence the production of hypoxia inducible factor (HIF) a helix transcription factor which is involved in carcinogenesis and tumor growth through the regulation of genes involved in angiogenesis, glycolytic metabolism and other biological mechanisms...
November 9, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30411684/research-of-gene-delivery-mediated-by-ultrasound-microbubble-and-folate-modified-chitosan-nanoparticles
#5
Yue Li, Yan Lin, Chun Liu Fu, Jiawei Tu, Chaopin Yang, Zhi Yi Chen
Objective-To study transfection efficiency of folate-modified chitosan (FA-CS) nanoparticles as a non-viral vector delivering pEGFP-C3plasmid (FA-CS/P) to 293T cells with or without the combination of ultrasound and microbubble. Method-pEGFP-C3 was used as reporter gene and FA-CS nanoparticles, which prepared by complex coagulation method were used as biological carriers. Transfection efficiency to 293T cells mediated by FA-CS/P nanoparticles, ultrasound (US) and microbubble (MB) was assessed by fluorescence microscopy and flow cytometry...
November 9, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30411683/comparison-of-small-incision-femtosecond-laser-assisted-intrastromal-keratoplasty-and-lamellar-keratoplasty-in-rhesus-monkeys-using-xenogenic-corneal-lamellae
#6
He Jin, Miao He, Wei Wang, Hongshan Liu, Xiaoying Zhong, Liangping Liu, Hui Ding, Xingwu Zhong
BACKGROUND: In our previous study, both allogeneic and xenogeneic small-incision femtosecond laser-assisted intrastromal keratoplasty were demonstrated to be safe and effective surgeries. Glycerol-dehydrated corneal lamellae could serve as alternative xenogeneic inlay grafts. However, these xenogeneic lamellae have not been explored in lamellar keratoplasty (LK). The immunoreactivity differences between corneal intrastromal xenotransplantation and xenogeneic LK have not been assessed...
November 9, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30360737/mutation-analysis-of-pre-mrna-splicing-genes-in-chinese-families-with-autosomal-dominant-retinitis-pigmentosa
#7
Zehua Wu, Min Zhong, Min Li, Hui Huang, Jian Liao, Aiping Li, Ketai Guo, Nengjun Ma, Jiansuo Lin, Juan Duan, Luhong Liu, Fan Xu, Zilin Zhong, Jianjun Chen
BACKGROUND: To screen variants in pre-mRNA Splicing genes in 95 Chinese autosomal dominant retinitis pigmentosa (adRP) families. METHODS: Clinical examination and pedigree analysis were performed. Targeted exome sequencing (TES) and / or Sanger sequencing were performed to detect the variants in genes of Splicing factors and do intra-familiar segregation analysis with DNA available. In silico analysis was performed to predict pathogenicity of variants in protein level and in vitro splicing assays were performed to compare splicing variants with their corresponding wildtype about their splicing effect...
October 24, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30360736/excessive-oxidative-stress-in-the-synergistic-effects-of-shikonin-on-the-hyperthermia-induced-apoptosis
#8
J-L Piao, Y-J Jin, M-L Li, S A Zakki, L Sun, Q -W Feng, D Zhou, T Kondo, Z-G Cui, H Inadera
BACKGROUND: Hyperthermia (HT) has been used widely for cancer therapy, and the development of modern devices has made it more efficient. Shikonin (SHK) is a natural naphthoquinone derivative from a Chinese herb. Although the anti-cancer properties of SHK are evident, the underlying molecular mechanisms are not fully understood. OBJECTIVE: In this study, the effects of combining low doses of SHK with mild HT were investigated in the U937 cell line. METHODS: The cells were subjected to HT at 44°C for 10 min with or without SHK pretreatment, and parameters reflecting apoptosis, ROS generation and intracellular calcium elevation were evaluated by using DNA fragmentation, flow cytometry, and western blot analyses...
October 24, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30295190/utilization-of-analytical-omics-tools-in-the-molecular-diagnostics-of-multiple-myeloma
#9
Zsuzsanna Kovacs, Andras Guttman
Multiple myeloma (MM) is characterized as the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and genetic factors have apparent roles in the process. Accurate diagnosis is important to properly identify and stratify the disease, however, MM identification steps are time-consuming and expensive...
October 8, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289073/vegfr2-and-vegf-c-suppresses-the-epithelial-mesenchymal-transition-via-yap-in-retinal-pigment-epi%C3%A2-thelial-cells
#10
Y Du, Q Chen, L Huang, S Wang, X Yin, L Zhou, Z Ye, X Ren, Y Cai, X Ding, H Ouyang, X Li, R Ju
BACKGROUND: Whereas retinal pigment epithelial (RPE) cells are known to secrete VEGF-A and VEGFR2, the functions of the autocrine VEGF signaling remain unclear. Meanwhile, anti-VEGF therapies have been applied routinely to treat ocular vascular diseases. OBJECTIVE: The aim of this study was to determine the functions of the VEGF signaling in RPE cells and evaluate the consequences of its interruption. METHODS: The genes involved in the VEGF and Hippo signal pathways were knocked down with siRNAs in both ARPE-19 cell line and human primary RPE cells via transient transfection whereas overexpression of VEGFR2 was mediated via adenovirus transduction...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289072/probable-mechanisms-involved-in-immunotoxin-mediated-capillary-leak-syndrome-cls-and-recently-developed-countering-strategies
#11
B Darvishi, L Farahmand, N Jalili, K Majidzadeh-A
Antibody-toxin fused agents or immunotoxins, are a newly engineered class of cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either to a monoclonal antibody or a specific growth factor. Nevertheless, acquiring a full potency in clinic is mostly restricted due to the Capillary leak syndrome (CLS), a serious immune provoked, life-threatening side effect, subsequent to the endothelial damage, resulting in fluid escape from the bloodstream into tissues including lungs, muscle and brain, developing organ failure and eventually death...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289071/mir-19b-functions-as-a-potential-protector-in-experimental-autoimmune-encephalomyelitis
#12
B Hu, Z Hu, Q Zeng, B Xiao, H Yang
MicroRNA-19b (miR-19b) is essential in determining oligodendroglia proliferation. Phosphatase and tensin homologue (PTEN) on chromosome 10 is considered the target of miR-19b and participates in oligodendrocyte differentiation and proliferation. We found that the expression of miR-19b is significantly reduced in an experimental autoimmune encephalomyelitis (EAE) mouse model. This downregulation, which is associated with the neurological scores, can be dramatically ameliorated by agomiR-19b. Our results show that agomiR-19b increases the expression of myelin basic protein (MBP) and cyclic nucleotide phosphodiesterase (CNP), which are regularly utilized as molecular markers of oligodendrocytes...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289070/genetic-modifiers-of-fetal-haemoglobin-hbf-and-phenotypic-severity-in-%C3%AE-thalassemia-patients
#13
S A A Razak, N A A Murad, F Masra, D L S Chong, N Abdullah, N Jalil, H Alauddin, R Z A R Sabudin, A Ithnin, H Alias, L C Khai, N A Aziz, Z Muda, H Ibrahim, R Jamal, Z A Latif
The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly in the HBB cluster, BCL11A (B-cell CLL/lymphoma 11A) and HBS1L-MYB (HBS1-like translational GTPase-MYB proto-oncogene, transcription factor) with regards to clinical severity. A total of 149 patients were included in the study...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289069/coding-and-non-coding-molecular-portrait-of-gist-and-its-clinical-implication
#14
I Bure, F Haller, D V Zaletaev
Gastrointestinal stromal tumours are the most common mesenchymal tumours of the gastrointestinal tract. Despite similar mutation pattern of activating mutations in KIT or PDGFRA receptors in 85% of cases, they demonstrate significantly heterogeneous clinical behaviour and pathological characteristics. This heterogeneity opens the question of the role of other factors and mechanisms of regulation in the development of GIST. Additional mutations in downstream effectors of GIST related signalling pathways or aberrant expression of non-coding RNAs may be additional contributing factors, the latter being increasingly recognized in carcinogenesis in general...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289068/co-existence-of-novel-pde6a-mutations-and-a-recurrent-rpgr-mutation-a-potential-explanation-for-phenotypic-diversity-in-female-rpgr-mutation-carriers
#15
X Chen, X Sheng, G Liu, Y Liu, H Li, P Xie, Q Liu, B Yan, C Zhao
BACKGROUND: To report the co-existence of novel biallelic PDE6A mutations and heterozygous RPGR mutation in a Chinese female patient with retinitis pigmentosa (RP), and to analyze the intrafamilial phenotypic diversity. METHODS: Three patients with retinopathy and four healthy family members were included for genetic and clinical analyses. Personal medical records were obtained from another four unaffected female family members who refused blood donation. Family history was carefully recorded...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30289067/bone-minimodeling-a-special-modeling-pattern-and-potential-as-therapeutic-target-for-osteoporosis
#16
X Li, J Zhang, X Wang
The concept of minimodeling is defined as a kind of focal bone formation that features the absence of preceding bone absorption by osteoclasts. In the process of minimodeling, osteogenetic and osteoclastic activities are decoupled. Linear boundary between old bone and new bone can be discovered. Frost et al. presumed that minimodeling in trabeculae can continue throughout life. The concept of minimodeling is not new, however its function and nature are still imperfectly understood. Our review will focus on minimodeling-based formation in 5 aspects below: 1...
October 4, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30259816/role-of-mammalian-target-of-rapamycin-in-atherosclerosis
#17
Z Cai, Y He, Y Chen
The mammalian target of rapamycin (mTOR) regulates multiple pathophysiological processes, such as cell development, angiogenesis, autophagy, as well as innate-adaptive immune responses. Numerous studies have demonstrated that mTOR signaling plays an important role in the process of atherosclerosis (AS) itself or AS-related diseases. The activation of mTOR signaling contributes to the endothelium dysfunction and the formation of foam cells via enhancing the process from monocyte to macrophage in the initial stage of atherosclerosis...
September 26, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30259815/interferon-%C3%AE-3-as-a-predictor-of-survival-in-hemodialysis-patients
#18
A E Grzegorzewska, M K Swiderska, W Warchol
BACKGROUND: IFNL4 polymorphisms are associated with circulating IFN-λ3, and higher plasma IFN-λ3 are associated with higher production of antibodies to HBV surface antigen (anti-HBs). The IFNL4 rs8099917 T allele and anti-HBs development in response to HBV vaccine are associated with better survival in hemodialysis (HD) patients. OBJECTIVE: To show whether plasma IFN-λ3 is also a predictor of survival in HD patients. METHOD: Plasma IFN-λ3 was measured in 135 HD patients who were followed-up for 2...
September 26, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30259814/imidazoline-receptors-agonists-for-managing-hypertension-may-hold-promise-for-treatment-of-intracerebral-hemorrhage
#19
J Mahmoudi, A Majdi, S Lattanzi, M Di Napoli, E M Bershad, C M P Rodrigues, A A Divani
Intracerebral hemorrhage (ICH), which accounts for 10-15% of all strokes, leads to higher morbidity and mortality compared with other stroke subtypes. Hypertension has been recognized as a major risk factor for ICH. Current antihypertensive options have not been fully effective for either prevention of ICH or ameliorating its complications. Therefore, attempts should be made to use novel antihypertensive medications for more effective management of blood pressure (BP) in the acute phase of ICH. Imidazoline receptors (IR) agonists can potentially be effective agents for BP control with the adjunctive ability to attenuate post-ICH brain injury...
September 26, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30259813/hypoxia-induced-caveolin-1-expression-promotes-migration-and-invasion-of-tumor-cells
#20
J Castillo Bennett, P Silva, S Martinez, V A Torres, A F G Quest
The exacerbated proliferation of cancer cells in nascent tumors leads to the genesis of a hypoxic microenvironment, which is associated with poor patient prognosis because these stress conditions enhance migratory, invasive and metastatic capacities of tumor cells. These changes are associated with the induction of the hypoxia-inducible factors (HIFs, mainly HIF1α) and increased expression of target genes, including Caveolin-1 (CAV1). Results from our group have shown that CAV1 expression in metastatic cancer cells promotes cell migration/invasion in vitro and metastasis in vivo in a manner dependent on tyrosine-14 phosphorylation by Src family kinases...
September 26, 2018: Current Molecular Medicine
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