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Current Molecular Medicine

L Chen, Y Wei, W Chi, D Fang, X Jiang, S Zhang
PURPOSE: Pathologic myopia is a leading cause of visual impairment in East Asia. The aim of this study was to investigate the potential mutations in Chinese pathologic myopic patients and to analyze the correlations between genotype and clinical phenotype. METHODS: One hundred and three patients with pathologic myopia and one hundred and nine unrelated healthy controls were recruited from Zhongshan Ophthalmic Center. Detailed clinical data, including ultra-widefield retinal images, measurements of best-corrected visual acuity, axial length, refractive error and ophthalmic examination results, were obtained...
February 11, 2019: Current Molecular Medicine
Pradipta Jana, Md Mobidullah Khan, Subrata Kumar De, Asru K Sinha, Santanu Guha, Gausal A Khan, Smarajit Maiti
BACKGROUND: An increase in the level of cytokines like TNF-α and IL-6 causes the inflammatory surge in acute ischemic heart disease (AIHD). OBJECTIVE: A high-level dermcidin isoform-2 (DCN-2) occurrence in AIHD was subjected to determine a possible regulation on cytokines expression.Effect of estrogen to counteract the inflammatory response was determined. METHODS: Blood was collected from AIHD patients and normal volunteers with consent nitric oxide (NO) was done with methemoglobin method...
February 7, 2019: Current Molecular Medicine
Aaron M Williams, Wei He, Yongqing Li, Umar F Bhatti, Vahagn C Nikolian, Panpan Chang, Zhigang Chang, Ihab Halaweish, Baoling Liu, Xin Cheng, Hasan B Alam
Cardiac reperfusion injury can have devastating consequences. Histone deacetylase (HDAC) inhibitors are potent cytoprotective agents, but their role in the prevention of cardiac injury remains ill-defined. We sought to determine the therapeutic potential of HDAC inhibitors in an in vitro model of cardiomyocyte hypoxia-reoxygenation (H/R). H9c2 cardiomyocytes were subjected to H/R and treated with various class-specific and pan-HDAC inhibitors in equal concentrations (5μM). Biologic activity of inhibitors was determined, as a proxy for concentration adequacy, by Western blot for acetylated histone H3 and α-tubulin...
February 7, 2019: Current Molecular Medicine
Zeng Wang, Junbo Ge, Aijun Sun, Huairui Shi, Huan Zhao, Zhen Dong, Buchang Zhao, Xinyu Weng, Rongle Liu, Xiao Li, Kai Hu, Yunzeng Zou
BACKGROUNDS: We recently reported that Naoxintong (NXT), a China Food and Drug Administration (FDA)-approved cardiac medicine, could reduce the plaque size, but the underlying mechanism remains elusive now. OBJECTIVE: In this study, we investigated the effects of NXT on foam cell accumulation both in vivo and in vitro and explored related mechanisms. METHOD: THP-1 cells and bone marrow derived macrophages were incubated with oxidized low density lipoprotein (ox-LDL) with/without Naoxintong...
February 7, 2019: Current Molecular Medicine
Victor Yu Glanz, Alexander N Orekhov, Alexey V Deykin
Advances in genetic engineering and genomic studies facilitated development of animal models of human diseases. To date, numerous models based on different animal species are available for the most socially significant human diseases, such as cardiovascular disorders, cancer, neurodegenerative and metabolic disorders. Modern genetic methods allow creating animals with certain genes up- or down-regulated, as well as bearing specific mutations. However, this precision is not easy to translate into clinical practice: animal models still have their limitations, including both physiological and genetic differences between humans and animals and complexity of disease conditions that are difficult to reproduce...
February 6, 2019: Current Molecular Medicine
Chenjun Zhang, Ying Wang, Zhiru Ge, Jie Lin, Jiwen Liu, Xiaofei Yuan, Zijun Lin
BACKGROUND: Growth differentiation factor 11 (GDF11) decreases with age, and increased C-C motif chemokine 11 (CCL11) is involved in aging. However, it is unclear about effects of GDF11 on Angiotensin II (ANG II)-induced hypertrophic cardiomyopathy and expression of markers for volume overload and hypertrophy such as ANP, BNP and beta-MHC, as well as the relationship between GDF11 and CCL11 in hypertrophhic cardiomyopathy. Therefore, the current study aimed to examine effects of GDF11 on ANG II-induced hypertrophic cardiomyopathy and expression of ANP, BNP and beta-MHC in mice, and explore possible molecular mechanisms...
February 3, 2019: Current Molecular Medicine
Shirin Mahmoodi, Navid Alexis Nezafat, Manica Negahdaripour, Younes Ghasemi
Cancer stem cells (CSCs) are a rare population of tumor cells, which play an important role in tumor initiation, progression, and maintenance. The concept that cancer cells arise from stem cells was presented about 150 years ago. Nowadays, because of the heterogeneity of tumor cells, this hypothesis has been renewed. CSCs are resistant to chemo-and radio-therapy; therefore, targeting CSCs could be a novel and effective strategy to struggle with tumor cells. <p> Objective: In this mini review article, we highlight that different immunotherapeutic approaches, which can be used to target cancer cells and to eradicate different tumor cells, one of the most important targets are specific markers like CD44, CD133, aldehyde dehydrogenase (ALDH), and SOX family members that have been recognized on the CSCs surface as CSC antigens...
February 3, 2019: Current Molecular Medicine
Samuel Garcia-Arellano, Luis Alexis Hernandez-Palma, Richard Bucala, Jorge Hernandez-Bello, Ulises De la Cruz-Mosso, Trinidad Garcia-Iglesias, Sergio Cerpa-Cruz, Jorge Ramon Padilla-Gutierrez, Yeminia Valle, Jose Guadalupe Sonanez-Organis, Isela Parra-Rojas, Ana Laura Pereira-Suarez, Jose Francisco Munoz-Valle
BACKGROUND: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL-17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS)...
January 29, 2019: Current Molecular Medicine
He Jin, Liangping Liu, Hui Ding, Miao He, Chi Zhang, Xingwu Zhong
BACKGROUND: Gamma-ray irradiation could significantly induce widespread apoptosis in corneas and reduced the allogenicity of donor cornea. And the X-rays may have the similar biological effects. The feasibility and effects of X-ray-irradiated corneal lamellae has not been assessed yet. METHODS: Different doses (10 gray unit (Gy), 20 Gy, 50 Gy, 100 Gy) of X-ray irradiated corneal lamellae which were collected from SMILE surgery. These corneal lamellae were assessed by physical characterization, hematoxylin and eosin (H-E) staining, Masson's staining, TdT-mediated dUTP nick end labeling (TUNEL), cell viability assay and transmission electron microscopy (TEM)...
January 29, 2019: Current Molecular Medicine
Xiao Hu, Lauren P Schewitz-Bowers, Philippa J P Lait, David A Copland, Madeleine L Stimpson, Jing Jing Li, Yizhi Liu, Andrew D Dick, Richard W J Lee, Lai Wei
BACKGROUND: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity...
January 25, 2019: Current Molecular Medicine
Xiaodong Gong, Qian Nie, Yuan Xiao, Jia-Wen Xiang, Ling Wang, Fangyuan Liu, Jia-Ling Fu, Yunfei Liu, Lan Yang, Yuwen Gan, Huimin Chen, Zhongwen Luo, Ruili Qi, Zhigang Chen, Xiangcheng Tang, David Wan-Cheng
It is well established now that protein sumoylation acts as an important regulatory mechanism mediating control of ocular development through regulation of multiple transcription factors. Yet the functional mechanisms of each factor modulated remains to be further explored using the available in vitro systems. In this regard, various ocular cell lines including HLE, FHL124, αTN4-1, N/N1003A and ARPE-19 have been demonstrated to be useful for biochemical and molecular analyses of normal physiology and pathogenesis...
January 12, 2019: Current Molecular Medicine
Qian Nie, Jie Xie, Xiaodong Gong, Zhongwen Luo, Ling Wang, Fangyuan Liu, Jia-Wen Xiang, Yuan Xiao, Jia-Ling Fu, Yunfei Liu, Zhigang Chen, Lan Yang, Huimin Chen, Yuwen Gan, David Wan-Cheng Li
Protein sumoylation is a well established regulatory mechanism to control many cellular processes such as chromatin structure dynamics, transcriptional regulation of gene expression, cell proliferation and differentiation, cell transformation and carcinogenesis, autophagy and senescence. In the vertebrate vision system, we and others have revealed that sumoylation plays important roles in regulating differentiation of several ocular tissues during eye development. To further elucidate the functional mechanisms of sumoylation, in vitro assay systems are needed...
January 12, 2019: Current Molecular Medicine
Yunfei Liu, Fangyuan Liu, Ling Wang, Jia-Ling Fu, Zhong-Wen Luo, Qian Nie, Xiao-Dong Gong, Jia-Wen Xiang, Yuan Xiao, David Wan-Cheng Li
It is now well established that protein sumoylation acts as an important regulator mechanism modulating functions over three thousand proteins. In the vision system, protein conjugation with SUMO peptides can regulate differentiation of multiple ocular tissues. Such regulation is often explored through analysis of biochemical and physiological changes with various cell lines in vitro. We have recently analyzed the expression levels of both mRNAs and proteins for seven de-sumoylation enzymes (SENPs) in five major ocular cell lines...
January 12, 2019: Current Molecular Medicine
Ying Chen, Zilin Chen, Wai Po Chong, Sihan Wu, Weiwei Wang, Hongyan Zhou, Jun Chen
Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in human, among which B10.RIII and C57BL/6 are the frequently used strains in mice, but to day no study has been reported to compare EAU disease between the two strains. Here we compared the differences in morphology, pathology, visual function of the retinal inflammation and Th1/Th17 immune responses in the EAU models induced by the interphotoreceptor retinoid binding protein (IRBP) between the B10.RIII and C57BL/6 strains, using fundus and histological examinations, optical coherence tomography, electroretinography and immunoassays...
January 12, 2019: Current Molecular Medicine
Jia-Wen Xiang, Lan Zhang, Xiangcheng Tang, Yuan Xiao, Yunfei Liu, Ling Wang, Fangyuan Liu, Xiao-Dong Gong, Jia-Ling Fu, Lan Yang, Zhongwen Luo, David Wan-Cheng Li
Protein Sumoylation is one of the most important and prevalent posttranscriptional modification. Increasing evidence have shown that the SENPs (sentrin/SUMO-specific proteases) are critical for steady-state levels of SUMO modification of target proteins, and protein de-sumoylation modulates a great diversity of biological processes including transcription, development, differentiation, neuroprotection, as well as pathogenesis. In the vertebrate eye, we and others have previously shown that sumoylation participated in the differentiation of major ocular tissues including retina and lens...
January 12, 2019: Current Molecular Medicine
Qian Nie, Xiaodong Gong, Lili Gong, Lan Zhang, Xiangcheng Tang, Ling Wang, Fangyuan Liu, Jia-Ling Fu, Jia-Wen Xiang, Yuan Xiao, Zhongwen Luo, Ruili Qi, Zhigang Chen, Yunfei Liu, Qian Sun, Wenjie Qing, Lan Yang, Jie Xie, Ming Zou, Yuwen Gan, Huimin Chen, David Wan-Cheng Li
Protein sumoylation is a highly dynamic and reversible post-translational modification, involving covalently conjugation of the small ubiquitin-like modifier (SUMO) to the lysine residue of the target protein. Similar to ubiquitination, sumoylation is catalyzed by E1, E2 and several E3 ligases. However, sumoylation usually does not cause protein degradation but alter the target function through diverse mechanisms. Increasing evidences have shown that sumoylation plays pivotal roles in the pathogenesis of human diseases, including neuron degeneration, cancer and heart disease, etc...
January 11, 2019: Current Molecular Medicine
Xiangcheng Tang, Zhigang Chen, Mi Deng, Ling Wang, Qian Nie, Jiawen Xiang, Yuan Xiao, Lan Yang, Yizhi Liu, David Wan-Cheng Li
The tumor suppressor p53 is a master regulator of apoptosis and also plays a key role in cell cycle checking. In our previous studies, we demonstrated that p53 directly regulates Bak in mouse JB6 cells (Qin et al. 2008. Cancer Research. 68(11):4150) and that p53-Bak signaling axis plays an important role in mediating EGCG-induced apoptosis. Furthermore, we have recently demonstrate that the same p53-Bak apoptotic signaling axis executes an essential role in regulating lens cell differentiation (Deng et al., 2012...
January 11, 2019: Current Molecular Medicine
Fangyuan Liu, Ling Wang, Jia-Ling Fu, Yuan Xiao, Xiaodong Gong, Yunfei Liu, Qian Nie, Jia-Wen Xiang, Lan Yang, Zhigang Chen, Yizhi Liu, David Wan-Cheng Li
Pax-6 is a master regulator for eye and brain development. Previous studies including ours have shown that Pax-6 exists in 4 major isoforms. According to their sizes, they are named p48, p46, p43 and p32 with the corresponding molecular weight of 48, 46, 43 and 32 kd, respectively. While p48 and p46 is derived from alternative splicing, p32 Pax-6 is generated through an internal translation initiation site. As for 43 kd Pax-6, two resources have been reported. In bird, it was found that an alternative splicing can generate a p43 Pax-6...
January 11, 2019: Current Molecular Medicine
Qian Nie, Ling Wang, Xiaodong Gong, Jia-Wen Xiang, Yuan Xiao, Jie Xie, Lan Yang, Huimin Chen, Yuwen Gan, Zhigang Chen, David Wan-Cheng Li
Protein sumoylation is a well established regulatory mechanism that regulate chromatin structure and dynamics, cell proliferation and differentiation, stress response and cell apoptosis. In the vertebrate eye, we and others have shown that sumoylation plays an indispensable role in regulating eye development. During stress induction and aging process, the ocular tissues gradually loss their normality and develop major ocular diseases such as cataract and aging-related macular degeneration. We have recently demonstrated that sumoylation actively regulates differentiation of lens cells, whether this process is implicated in lens pathogenesis remains to be investigated...
January 11, 2019: Current Molecular Medicine
M Jin, H Dai, X Zhang, Y Wang, M Han, H Zhang, Y Liu, Z Wang, X Gao, L Li, X Wen, Y Liu, L Wei, Y Chen
BACKGROUND: Anti-VEGF agent ranibizumab has been extensively used as a standard treatment for wet AMD. We investigated whether traditional Chinese medicine could serve as a complimentary therapy for this disease. METHODS: 144 patients with neovascular age-related macular degeneration received either intravitreal ranibizumab treatment as needed plus placebo or intravitreal ranibizumab treatment as needed plus a Chinese FDA approved traditional Chinese patent medicine named ZQMT...
January 7, 2019: Current Molecular Medicine
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