bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eriodictyol inhibits high glucose‐induced oxidative stress and inflammation in retinal ganglial cells
Authors: Lv Peilin , Yu Jingni , Xu Xiayu , Lu Tianjian , Xu Feng 
Published: October 2018

AbstractDiabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and is considered as a leading cause of blindness. Oxidative stress and inflammation are significant drivers for the development of DR. Eriodictyol, a flavonoid compound, was proved to possess anti‐inflammatory, antioxidative, and antidiabetic activities. However, the role of eriodictyol in DR has not been unveiled. In the current study, we explored the protective effects of eriodictyol on high glucose (HG)‐induced rat retinal ganglial cells (RGCs). The results suggested that eriodictyol improved cell viability of HG‐induced rat RGC‐5 cells in a dose‐dependent manner. Eriodictyol reduced the reactive oxygen species production and increased the activities of superoxide dismutase, glutathione peroxidase and catalase in rat RGC‐5 cells in response to HG stimulation. The production of proinflammatory cytokines including tumor necrosis factor alpha and interleukin‐8 was diminished after eriodictyol treatment. Eriodictyol also suppressed cell apoptosis induced HG in rat RGC‐5 cells. Furthermore, eriodictyol enhanced the nuclear translocation of nuclear factor erythroid‐2 (E2)‐related factor 2 (Nrf2) and elevated the expression of antioxidant enzyme heme‐oxygenase‐1 (HO‐1). These findings suggested that eriodictyol protects the RGC‐5 cells from HG‐induced oxidative stress, inflammation, and cell apoptosis through regulating the activation of Nrf2/HO‐1 pathway.
Retracted: MicroRNA‐105 promotes epithelial‐mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl‐1
Authors: Jin Xiangfeng , Yu Yi , Zou Qiang , Wang Mingzhao , Cui Yaojie , Xie Jing , Wang Zizong 
Published: October 2018

AbstractBackgroundA growing number of microRNAs have been proved to play significant roles in limiting tumor growth and the epithelial‐mesenchymal transition (EMT) process of nonsmall cell lung cancer (NSCLC). Present work aims to study the function of microRNA (miR)‐105 in EMT of NSCLC cells, which is unrevealed yet.MethodsTwo NSCLC cell lines A549 and Calu‐3 were transfected with miR‐105 mimic, inhibitor, or scrambled control. And then the effects of miR‐105 were evaluated by performing trypan blue staining, transwell assay, ANNEXIN‐FITC/propidium iodide (PI) double staining and Western blot analysis. The expression levels of myeloid cell leukemia‐1 (Mcl‐1) after transfection were tested by real‐time quantitative polymerase chain reaction and Western blot analysis. Whether Mcl‐1 was a downstream effector of miR‐105, and the involvement of mammalian target of Rapamycin (mTOR) and p38 mitogen‐activated protein kinase (p38MAPK) signaling pathways were assessed.ResultsThe overexpression of miR‐105 significantly increased the viability and migration of A549 and Calu‐3, but had no impacts on cell apoptosis. Meanwhile, E‐cadherin was remarkably downregulated, and N‐cadherin, Vimentin, ZEB1, and Snail were upregulated by miR‐105 overexpression. Mcl‐1 was positively regulated by miR‐105, and the effects of miR‐105 overexpression on A549 and Calu‐3 cells viability, migration and EMT were all flattened by Mcl‐1 silence. Both mTOR and p38MAPK pathways were activated in miR‐105‐overexpressing and Mcl‐1‐overexpressing cells. Besides, inhibition of mTOR and p38MAPK pathways by using Rapamycin and VX‐702 abolished the regulatory effects of Mcl‐1 on EMT.ConclusionOur study underlines the importance of miR‐105 in modulating NSCLC cells EMT. miR‐105 promoted the EMT of NSCLC cells possibly via upregulation of Mcl‐1 and thereby activation of mTOR and p38MAPK signaling.
Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner
Authors: Huo Jun‐Feng , Chen Xiao‐Bing 
Published: October 2018

AbstractMalignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest‐specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy‐related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin‐inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5‐mediated depression in cisplatin‐evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5‐increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.
Retracted: Downregulated microRNA‐224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF‐β/Smad pathway
Authors: Xu Hai‐Ming , Sui Feng‐Hua , Sun Mei‐Hua , Guo Gong‐Liang 
Published: October 2018

AbstractRecent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR‐224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF‐β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR‐224 inhibitor was prepared for investigating the effect of downregulated miR‐224 on the contents of nitric oxide (NO) and endothelin‐1 (ET‐1), blood lipid levels and inflammatory factor levels in serum as well as the TGF‐β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high‐density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET‐1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM‐1 and MMP‐2 protein expression, TGF‐β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF‐β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR‐224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF‐β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.
Alteration of cellular and immune‐related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes
Authors: Jafarzadeh Nazli , Safari Zohreh , Pornour Majid , Amirizadeh Naser , Forouzandeh Moghadam Mehdi , Sadeghizadeh Majid 
Published: October 2018

AbstractLeukemic cells can impact the bone marrow niche to create a tumor‐favorable microenvironment using their secreted factors. Little knowledge is available about immunosuppressive and tumor‐promoting properties of chronic myeloid leukemia derived exosomes in bone marrow stromal components. We report here that K562‐derived exosomes can affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of bone marrow mesenchymal stem cells (BM‐MSCs) and macrophages. Human BM‐MSCs and mouse macrophages were treated with K562‐derived exosomes. Our results demonstrated that the expression of the genes involved in hematopoietic developmental pathways and immune responses, including C‐X‐C motif chemokine 12 (Cxcl12), Dickkopf‐related protein 1 (DKK1), wnt5a, interleukin 6 (IL‐6), transforming growth factor‐beta, and tumor necrosis factor‐alpha (TNF‐alpha), changed with respect to time and exosome concentration in BM‐MSCs. The TNF‐alpha level was higher in exosome‐treated BM‐MSCs compared with the control. Exosome treatment of BM‐MSCs led to an increased production of NO and a decreased production of reactive oxygen species (ROS) in a time‐ and concentration‐dependent manner. We have shown that K562‐derived exosomes induce overexpression of IL‐10 and TNF‐alpha and downregulation of iNOS transcript levels in macrophages. The enzyme‐linked immunosorbent assay results showed that TNF‐alpha and IL‐10 secretions increased in macrophages. Treatment of macrophages with purified exosomes led to reduced NO and ROS levels. These results suggest that K562‐derived exosomes may alter the local bone marrow niche toward a leukemia‐reinforcing microenvironment. They can modulate the inflammatory molecules (TNF‐alpha and NO) and the redox potential of BM‐MSCs and macrophages and direct the polarization of macrophages toward tumor‐associated macrophages.
Induction of apoptotic but not autophagic cell death by Cinnamomum cassia extracts on human oral cancer cells
Authors: Yu Ching‐Han , Chu Shu‐Chen , Yang Shun‐Fa , Hsieh Yih‐Shou , Lee Chih‐Yi , Chen Pei‐Ni 
Published: October 2018

AbstractCinnamomum cassia has been widely studied in different fields to reveal its antidiabetic, antidepressive, antiviral, anti‐inflammatory, antiosteoporotic, and anticancer effects. Its antimalignant activities have been explored in lung cancer, breast cancer, colorectal cancer, and even oral cancer, but the detailed signaling mechanism and effects of this plant on animal models need to be clarified. In the current study,
C. cassia extract (CCE) was used to investigate the antitumorigenesis mechanism in vitro and in vivo. The major constituents of CCE used in this study were coumarin, cinnamic acid, and cinnamic aldehyde. CCE reduced the viability, number, and colony formation of human oral cancer cells, and induced their apoptosis. Caspase‐3 activation, Bcl‐2 reduction, and phosphatidylserine inversion were involved in CCE‐stimulated apoptosis. CCE also enhanced the expression of autophagic markers, including acidic vesicular organelle, microtubule‐associated protein 1 light chain 3‐I, autophagy‐related protein 14, rubicon, and p62. The combined treatment of CCE and caspase inhibitor significantly restored mitochondrial membrane potential (Δ
ψ
m) and cell viability. However, the combined treatment of CCE and autophagy inhibitor further reduced the cell viability indicating that autophagy might be a survival pathway of CCE‐treated SASVO3 cells. In contrast, CCE treatment for 12 days did not adversely affect SASVO3 tumor‐bearing nude mice. CCE also elicited dose‐dependent effects on the decrease in tumor volume, tumor weight, and Ki‐67 expression. These results suggested that CCE showed the potential for the complementary treatment of oral caner.
Interferon‐stimulated gene 15 enters posttranslational modifications of p53
Authors: Wang Yang , Ding Qi , Lu Yu‐Chen , Cao Shi‐Yang , Liu Qing‐Xue , Zhang Lei 
Published: October 2018

AbstractThe tumor suppressor protein p53 is a central governor of various cellular signals. It is well accepted that ubiquitination as well as ubiquitin‐like (UBL) modifications of p53 protein is critical in the control of its activity. Interferon‐stimulated gene 15 (ISG15) is a well‐known UBL protein with pleiotropic functions, serving both as a free intracellular molecule and as a modifier by conjugating to target proteins. Initially, attentions have historically focused on the antiviral effects of ISG15 pathway. Remarkably, a significant role in the processes of autophagy, DNA repair, and protein translation provided considerable insight into the new functions of ISG15 pathway. Despite the deterministic revelation of the relation between ISG15 and p53, the functional consequence of p53 ISGylation appears somewhat confused. More important, more recent studies have hinted p53 ubiquitination or other UBL modifications that might interconnect with its ISGylation. Here, we aim to summarize the current knowledge of p53 ISGylation and the differences in other significant modifications, which would be beneficial for the development of p53‐based cancer therapy.
Melatonin defends mouse oocyte quality from benzo[ghi]perylene‐induced deterioration
Authors: Li Wei‐Dong , Yu Shuai , Luo Shi‐Ming , Shen Wei , Yin Shen , Sun Qing‐Yuan 
Published: October 2018

AbstractBenzo[ghi]perylene (B[ghi]P) is a polycyclic aromatic hydrocarbon widely found in haze. Long‐term exposure to humans or animals can cause serious damage to the respiratory system. Melatonin is an endogenous natural hormone synthesized and released by the pineal gland. In this study, we investigated the effects of melatonin on in vitro cultured B[ghi]P‐exposed mouse oocytes and the protective roles of melatonin. Our data indicate that B[ghi]P exposure leads to meiotic maturation arrest and reduced ability of sperm binding and parthenogenetic activation. Also, B[ghi]P exposure disrupts actin filament dynamics, spindle assembly, and kinetochore–microtubule attachment stability, which results in oocyte aneuploidy. Simultaneously, B[ghi]P exposure disturbs the distribution of mitochondria, increases the level of oxidative stress, and induces apoptosis of oocytes. Whereas all of these toxic effects of B[ghi]P can be restored after melatonin supplement. In conclusion, our findings validate that melatonin has a certain protective effect on preventing the reduced oocyte quality caused by B[ghi]P exposure during meiotic maturation in mouse oocytes.
LINC01433 promotes hepatocellular carcinoma progression via modulating the miR‐1301/STAT3 axis
Authors: Huang Haijin , Bu Yan‐Zhi , Zhang Xiao‐Yu , Liu Juan , Zhu Li‐Yao , Fang Yong 
Published: October 2018

AbstractLong noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR‐1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull‐down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR‐1301, and it was shown that miR‐1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR‐1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR‐1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.
Snake venoms promote stress‐induced senescence in human fibroblasts
Authors: Lewinska Anna , Bocian Aleksandra , Petrilla Vladimir , Adamczyk‐Grochala Jagoda , Szymura Karolina , Hendzel Wiktoria , Kaleniuk Edyta , Hus Konrad K. , Petrillova Monika , Wnuk Maciej 
Published: October 2018

AbstractSnake venoms are widely studied in terms of their systemic toxicity and proteolytic, hemotoxic, neurotoxic, and cytotoxic activities. However, little is known about snake‐venom‐mediated effects when used at low, noncytotoxic concentrations. In the current study, two human fibroblast cell lines of different origin, namely WI‐38 fetal lung fibroblasts and BJ foreskin fibroblasts were used to investigate snake‐venom‐induced adaptive response at a relatively noncytotoxic concentration (0.01 µg/ml). The venoms of Indochinese spitting cobra (
Naja siamensis), western green mamba (
Dendroaspis viridis), forest cobra (
Naja melanoleuca), and southern copperhead (
Agkistrodon contortrix) were considered. Snake venoms promoted FOXO3a‐mediated oxidative stress response and to a lesser extent DNA damage response, which lead to changes in cell cycle regulators both at messenger RNA and protein levels, limited cell proliferation and migration, and induced cellular senescence. Taken together, we have shown for the first time that selected snake venoms may also exert adverse effects when used at relatively noncytotoxic concentrations.
Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility
Authors: Nishiyama Kazuhiro , Aono Kimiya , Fujimoto Yasuyuki , Kuwamura Mitsuru , Okada Toshiya , Tokumoto Hayato , Izawa Takeshi , Okano Ryoichi , Nakajima Hidemitsu , Takeuchi Tadayoshi , Azuma Yasu‐Taka 
Published: October 2018

AbstractOrgan–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor‐α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.
Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer
Authors: Huang Liang , Lin Hongcheng , Kang Liang , Huang Pinzhu , Huang Jun , Cai Jinlin , Xian Zhenyu , Zhu Peixuan , Huang Meijin , Wang Liping , Xian Cory J. , Wang Jianping , Dong Jianghui 
Published: October 2018

AbstractLong noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT‐PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc‐small‐nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc‐SNHG15 was significantly associated with lymph‐node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA‐SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA‐SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc‐SNHG15 overexpression was significantly associated with CLM and high‐expression of lnc‐SNHG15 in CRC was an independent predictor of poor survival.
A pH‐sensitive luminal His‐cluster promotes interaction of PAM with V‐ATPase along the secretory and endocytic pathways of peptidergic cells
Authors: Rao Vishwanatha K. , Zavala Gerardo , Deb Roy Abhijit , Mains Richard E. , Eipper Betty A. 
Published: October 2018

AbstractThe biosynthetic and endocytic pathways of secretory cells are characterized by progressive luminal acidification, a process which is crucial for posttranslational modifications and membrane trafficking. This progressive fall in luminal pH is mainly achieved by the vacuolar‐type‐H+ ATPase (V‐ATPase). V‐ATPases are large, evolutionarily ancient rotary proton pumps that consist of a peripheral V1 complex, which hydrolyzes ATP, and an integral membrane V0 complex, which transports protons from the cytosol into the lumen. Upon sensing the desired luminal pH, V‐ATPase activity is regulated by reversible dissociation of the complex into its V1 and V0 components. Molecular details of how intraluminal pH is sensed and transmitted to the cytosol are not fully understood. Peptidylglycine α‐amidating mono‐oxygenase (PAM; EC 1.14.17.3), a secretory pathway membrane enzyme which shares similar topology with two V‐ATPase accessory proteins (Ac45 and prorenin receptor), has a pH‐sensitive luminal linker region. Immunofluorescence and sucrose gradient analysis of peptidergic cells (AtT‐20) identified distinct subcellular compartments exhibiting spatial co‐occurrence of PAM and V‐ATPase. In vitro binding assays demonstrated direct binding of the cytosolic domain of PAM to V1H. Blue native PAGE identified heterogeneous high‐molecular weight complexes of PAM and V‐ATPase. A PAM‐1 mutant (PAM‐1/H3A) with altered pH sensitivity had diminished ability to form high‐molecular weight complexes. In addition, V‐ATPase assembly status was altered in PAM‐1/H3A expressing cells. Our analysis of the secretory and endocytic pathways of peptidergic cells supports the hypothesis that PAM serves as a luminal pH‐sensor, regulating V‐ATPase action by altering its assembly status.