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Current Molecular Medicine

Y Ni, Y Qin, Z Fang, Z Zhang
PURPOSE: Dysfunction or death of retinal pigment epithelial (RPE) cells is a common pathogenesis of various types of retinal degenerative diseases. Recent reports indicated that ROCK pathway inhibitors regulate cell proliferation or apoptosis in a cell-type-dependent manner. Here, we aim to investigate the effect of ROCK inhibitor Y-27632 on the human retinal pigment epithelium (RPE) in vitro. METHODS: Cell proliferation and apoptosis were analyzed by CCK-8 and flow cytometry respectively...
March 16, 2018: Current Molecular Medicine
J Zhang, Y F Wang, B Wu, Z X Zhong, K X Wang, L Q Yang, Y Q Wang, Y Q Li, J Gao, Z S Li
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are one of the major participants in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of interaction between TILs and tumors is complex and remains unclear. OBJECTIVE: To evaluate the state of immunoreactions in PDAC tissues, and explore the prognostic value of these markers in a large sample, to provide a new theoretical basis for PDAC immunotherapy. METHOD: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a tissue microarray (TMA) of 143 cases of PDAC...
March 7, 2018: Current Molecular Medicine
F Chen, W Yuan, X Mo, J Zhuang, Y Wang, J Chen, Z Jiang, X Zhu, Q Zeng, Y Wan, F Li, Y Shi, L Cao, X Fan, S Luo, X Ye, Y Chen, G Dai, J Gao, X Wang, H Xie, P Zhu, Y Li, X Wu
Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. Zebrafish Fhl1A is the homologue of human FHL1. In the present study, we showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK...
March 7, 2018: Current Molecular Medicine
I De, N Dogra, S Singh
Mitochondria are the sole semiautonomous organelle of human cell and plays very important role in not only energy production but also in apoptosis, metabolism and cell signaling. It is also known to be major producer of ROS and RNS free radicals during ATP production. These free radicals in excessive amounts may damage the mitochondrial DNA as well as proteome resulting in accumulation of misfolded proteins which may prove deleterious to its functioning and is known to be involved in disease pathology. To maintain healthy proteome, mitochondria has developed as quality control machinery in semiautonomous manner, where cellular proteins such as proteases and heat shock proteins are used for quality control...
March 7, 2018: Current Molecular Medicine
A R Ramirez, O L Acosta, M B Maya, M El-Hafidi
In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment...
March 7, 2018: Current Molecular Medicine
B Lan, S Chai, P Wang, K Wang
VCP/p97/Cdc48, a member of the ATPases associated with diverse cellular activities (AAA) family, is necessary for the endoplasmic-reticulum-associated protein degradation (ERAD) pathway to maintain protein homeostasis. Overwhelming proteotoxic stress drove cancer cells to enhance VCP/p97/Cdc48-associated ERAD to maintain protein homeostasis for survival, demonstrating that VCP/p97/Cdc48 expression was positively correlated with cancer prognosis. More studies revealed that targeting VCP/p97/Cdc48 could be a potential target in cancer therapy...
March 7, 2018: Current Molecular Medicine
M Duran, A C M Luzo, J G de Souza, W J Favaro, P Garcia, N Duran
Graphene and graphene oxide topography have an effect on the fate of stem cells such as adhesion, differentiation, and proliferation. This overview clearly shows that a new design and manipulation of associated graphene oxide stem cell culture platforms are of paramount importance as a focus in stem cell to tissue engineering applications. This overview also proposes that a film of graphene oxide is an efficient platform to modulate structure and function of multipotent mesenchymal stem/stromal cells (MSCs) and in special human adipose tissue derived mesenchymal stromal/stem cells (AT-MSCs)...
March 7, 2018: Current Molecular Medicine
J Taneera, B Mussa, M Saber-Ayad, S Dhaiban, H Aljaibeji, N Sulaiman
Today, there are more than 32 million patients with diabetes in the Middle East (ME), the number is expected to double by 2040. In contrast to Europe and North America and despite the high prevalence of diabetes in MENA, epidemiological data about incident and types of diabetes in the region is very limited. Maturity-onset diabetes of the young (MODY) is a subtype of monogenic diabetes representing 2-5% of all diabetes patients. The disease is autosomal dominant mode of inheritance characterized by β-cell malfunction below the age of 35...
February 22, 2018: Current Molecular Medicine
N M Phani, M Vohra, P Adhikari, S K Nagri, U Shashikiran, S C D'Souza, P R R Kalluri, K Satyamoorthy, P S Rai
BACKGROUND: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology. OBJECTIVE: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas. METHOD: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited...
February 22, 2018: Current Molecular Medicine
L Xin, W Junhua, L Long, Y Jun, Y Xiaosu
The protective mechanism of exogenous hydrogen sulfide (H2S) on oxygen glucose deprivation/reoxygenation (OGD/R) at physiological doses in SH-SY5Y cells were investigated in this study. Comparing with the normal control group, the expressions of ERK3, p38MAPK and Nrf2 mRNA in other three groups were downregulated at the beginning of 24h. After 24h, the expressions of ERK3, p38MAPK and Nrf2 were upregulated significantly compared with the normal control group. When the cells were pretreated with 200μM NaHS at the beginning of 24h, the expressions of ERK3, p38MAPK and Nrf2 were decreased much more significantly than OGD/R and NaHS groups...
February 22, 2018: Current Molecular Medicine
Z Wu, Z Wang, P Xu, M Zhang, L Cheng, B Gong
BACKGROUND: The pathogenesis of acute aortic dissection (AAD) complicated with acute lung injury (ALI) is still not well defined. OBJECTIVE: We aim to investigate the roles of macrophages-derived matrix metalloproteinase 9 (MMP9) in the pathogenesis of AAD complicated with ALI and factors involves in the recruitment of macrophages. METHOD: This study included three parts: (i) determination of serum MMPs , AngII and MCP-1 in AAD complicated with/without ALI patients, nonruptured chronic aortic aneurysm patients or healthy volunteers using ELISA method...
February 22, 2018: Current Molecular Medicine
Z Hu, X Wang, Y Cui, C Li, S Wang
The growing evidence shows that LIM and SH3 Domain Protein 1 (LASP1) is a multi-functional protein that plays important role in forming cytoskeleton and prognostic marker in different cancers. LASP1 expression is correlated with the grade, size, and the metastasis of tumor in clinical samples. And the upregulation of LASP1 facilitates tumor cells proliferation, migration, and invasion perhaps through the interaction with cytoskeleton and increased nuclear translocation. The underlying mechanism of LASP1 on tumor is still in the initial stage; therefore, the signaling pathways in various tumors are specifically summarized to deepen the biological understanding of LASP1...
February 21, 2018: Current Molecular Medicine
M Ilie, J Benzaquen, V Hofman, S Lassalle, N Yazbeck, S Leroy, S Heeke, C Bence, B Mograbi, N Glaichenhaus, C H Marquette, P Hofman
Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC)...
February 21, 2018: Current Molecular Medicine
Y Li, F Zhang, W Lu, X Li
BACKGROUND: Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal neuronal cells is unknown. OBJECTIVE: To determine the effect of Jam-c on adult mouse eyes, particularly, on retinal structure, vasculature and photoreceptor cells, in order to explore potential important target molecules for ocular diseases...
February 12, 2018: Current Molecular Medicine
Q Zeng, Y Wan, P Zhu, M Zhao, F Jiang, J Chen, M Tang, X Zhu, Y Li, H Zha, Y Wang, M Hu, X Mo, Y Zhang, Y Deng, Y Chen, X Fan, Y Chen, X Ye, R Bodmer, K Ocorr, Z Jiang, J Zhuang, W Yuan, X Wu
The basic helix-loop-helix (bHLH) protein families are a large class of transcription factors, which are associated with cell proliferation, tissue differentiation, and other important development process. We reported that the Nuclear localized protein-1 (Nulp1) might act as a novel bHLH transcriptional factor to mediate cellular functions. However, its role in development in vivo remains unknown. Here we show that Drosophila Nulp1 (dNulp1) mutants, generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal, are partially homozygous lethal and the rare escapers have bent femurs, which are similar to the major manifestation of congenital bent-bone dysplasia in human Stuve-Weidemann syndrome...
February 12, 2018: Current Molecular Medicine
Z Wang, X Liu, Z Wang, Z Bao, W Zhang, C Zhang, T Jiang
BACKGROUND: Isocitrate dehydrogenase (IDH) mutation is the initiating event that defines major clinical and prognostic classes of gliomas, but the potential mechanisms have not been well interpreted yet. The main objective of the current study was to better understand the underlying biology of IDH mutant gliomas as captured by gene expression profiles. METHODS: RNA sequencing data of WHO grade II-IV gliomas from the Chinese Glioma Genome Atlas (CGGA, N=325) were used to assess differentially expressed genes between IDH mutant and wild type gliomas and to construct a gene expression-based classifier to detect IDH mutant samples with high sensitivity and specificity...
February 12, 2018: Current Molecular Medicine
L Dong, X Chen, H Shao, L Bai, X Li, X Zhang
PURPOSE: We have previously reported that MSCs inhibited experimental autoimmune uveitis (EAU) in rodent models induced by either uveitogenic antigens or antigen-specific T cells. In this study, we explored the inhibitory mechanisms of MSCs on dendritic cells (DCs) in EAU. METHODS: We collected the DCs from the lymph nodes of MSC treated or untreated EAU rats, as well as bone marrow derived DCs cultured in vitro with or without MSC treatment. The levels of costimulatory molecules of CD80, CD86, CD40, OX40L and suppressors of cytokine signaling (SOCS1, SOCS2, and SOCS3) on these DCs were analyzed by flow Cytometry...
February 7, 2018: Current Molecular Medicine
X F Huang, W Chi, D Lin, M L Dai, Y L Wang, Y M Yang, Z B Jin, Y Wang
AAU (acute anterior uveitis) is the most common entity of uveitis characterized by acute vision loss and violent sore eyes. IL-33 and IL-1RacP have been found to play crucial roles in the innate immune system. In the present study, we investigated the association of IL33 and IL1RAP genes with AAU. A total of 549 AAU patients and 1080 unrelated healthy controls were recruited for this study. Ten single nucleotide polymorphisms (SNPs) were genotyped using Sequenom Mass ARRAY technology. Our findings demonstrated that IL1RAP-rs3773978 significantly associated with AAU and could serve as a genetic risk marker in Chinese AAU patients...
February 7, 2018: Current Molecular Medicine
P Yang, L Du, Z Ye
During the past nine years, our center has grown into the largest uveitis referral center in China. To deal with this increasing stream of patients we have developed a management system to coordinate communication with our patients, their referring ophthalmologists, consultations with other medical specialties and world-renowned foreign uveitis specialists. Tools have been developed to deal with patient records, which include a patient database allowing continuous analysis of clinical features and response to treatment of patients with various uveitis entities as well as the evaluation of the relevance of various ancillary tests performed in this patient group...
February 7, 2018: Current Molecular Medicine
B Zhao, S Zhang, W Chen, R Zhang, R Jiang, R Zhang, L Chen
BACKGROUND & OBJECTIVE: Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS: 15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016...
February 7, 2018: Current Molecular Medicine
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