bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: Role of CXCL12–CXCR4 axis in ovarian cancer metastasis and CXCL12–CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro
Authors: Liu Yan , Ren Chen‐Chen , Yang Li , Xu Yi‐Ming , Chen Yan‐Nan 
Published: September 2018

AbstractOvarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to the head. CXCL12 and its receptor chemokine receptor 4 (
CXCR4) have been found to be highly expressed in OC and contribute to the disease progression by affecting tumor cell proliferation and invasion. Here, in this study, we aim to explore whether the blockade of CXCL12–CXCR4 axis with AMD3100 (a selective CXCR4 antagonist) has effects on the progression of OC. On the basis of the gene expression omnibus database of OC gene expression chips, the OC differentially expressed genes were screened by microarray analysis. OC (nonmetastatic and metastatic) and normal ovarian tissues were collected to determine the expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and pCNS‐CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was assessed. Cell viability, apoptosis, migration, and invasion were all evaluated. The microarray analysis screened out the differential expression of CXCL12–CXCR4 in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was observed to have a critical role in inhibiting cell proliferation, migration, and invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed CXCR4 brought significantly promoting effects on the proliferation and invasiveness of OC cells. These results reinforce that the blockade of CXCL12–CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of the inhibition of CXCL12–CXCR4 axis offers a preclinical validation of CXCL12–CXCR4 axis as a therapeutic target in OC.
Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment
Authors: Kain Vasundhara , Halade Ganesh V. 
Published: September 2018

AbstractBioactive lipid mediators derived from n‐3 and
n‐6 fatty acids are known to modulate leukocytes. Metabolic transformation of essential fatty acids to endogenous bioactive molecules plays a major role in human health. Here we tested the potential of substrates; linoleic acid (LA) and docosahexaenoic acid (DHA) and their bioactive products; resolvin D1 (RvD1) and 12‐
S‐hydroxyeicosatetraenoic acids (HETE) to modulate macrophage plasticity and cardiac fibroblast phenotype in presence or absence of lipid metabolizing enzyme 12/15‐lipoxygenase (LOX). Peritoneal macrophages and cardiac fibroblasts were isolated from wild‐type (C57BL/6J) and 12/15LOX
−/− mice and treated with DHA, LA, 12(S)‐HETE, and RvD1 for 4, 8, 12, and 24 hr. LA, DHA, 12(S)‐HETE, and RvD1 elicited mRNA expression of proinflammatory markers; tumor necrosis factor‐α (
Tnf‐α), interleukin 6 (
IL‐6), chemokine (C–C motif) ligand 2
(Ccl2), and
IL‐1β in wild type (WT) and in 12/15LOX
−/− macrophages at early time point (4 hr). Bioactive immunoresolvent RvD1 lowered the levels of
Tnf‐α, IL‐6, and
IL‐1β at 24 hr time point. Both DHA and RvD1 stimulated the proresolving markers such as arginase 1 (
Arg‐1), chitinase‐like protein 3 (
Ym‐1), and mannose receptor C‐type 1 in WT macrophage. RvD1 induced proresolving phenotype
Arg‐1 expression in both WT 12/15LOX
−/− macrophages even in presence of 12(S)‐HETE. RvD1 peaked 5LOX expression in both WT and 12/15LOX
−/− at 24 hr time point compared with DHA. RvD1 diminished cyclooxygenase‐2 but upregulated 5LOX expression in fibroblast compared with DHA. In summary, the feed‐forward enzymatic interaction with fatty acids substrates and direct mediators (RvD1 and 12(S)‐HETE) are responsive in determining macrophages phenotype and cardiac fibroblast plasticity. Particularly, macrophages and fibroblast phenotypes are responsive to milieu and RvD1 governs the milieu‐dependent chemokine signaling in presence or absence of 12/15LOX enzyme to resolve inflammation.
Heme oxygenase 1 regulates apoptosis induced by heat stress in bovine ovarian granulosa cells via the ERK1/2 pathway
Authors: Wang Yi‐Ru , Chen Kun‐Lin , Li Cheng‐Min , Li Lian , Wang Gen‐Lin 
Published: September 2018

AbstractHeat stress can inhibit follicular development in dairy cows, and thus can affect their reproductive performance. Follicular granulosa cells can synthesize estrogen, that affects the development and differentiation of follicles by apoptosis. Heme oxygenase 1 (HO‐1/heat shock protein 32) plays an antiapoptotic and cytoprotective role in various cells during stress‐induced apoptosis, but little is known about its definitive function in bovine (ovarian) granulosa cells (bGCs). In our study, the roles and mechanism of HO‐1 on the heat stress‐induced apoptosis of bGCs were studied. Our results show that the expression of HO‐1 was significantly increased under heat stress. Moreover, HO‐1 silencing increased apoptosis, whereas its overexpression dampened apoptosis by regulating the expression of Bax/Bcl‐2 and the levels of cleaved caspase‐3. In addition, HO‐1 can also play a cytoprotective role by affecting estrogen levels and decomposing heme to produce biologically active metabolite carbon monoxide (CO). Meanwhile, CO significantly increased the level of HO‐1, decreased Bax/Bcl‐2 levels, and inhibited the activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) signaling pathway. The apoptosis of ovarian GCs can affect the secretion of estrogen and lead to disorder of the ovarian microenvironment, thus affecting the normal function of the ovary. Our results indicate that HO‐1 acts as a cytoprotective enzyme and plays a protective role in heat‐induced apoptosis of bGCs. In conclusion, HO‐1 and its metabolite CO inhibit the apoptosis of bGCs induced by heat stress through the ERK1/2 pathway. The results of this study provide a valuable clue for improving the fertility of heat stressed cows in summer.
PD‐1/PD‐L1 immune checkpoint: Potential target for cancer therapy
Authors: Dermani Fatemeh K. , Samadi Pouria , Rahmani Golebagh , Kohlan Alisa K. , Najafi Rezvan 
Published: September 2018

AbstractRecent studies show that cancer cells are sometimes able to evade the host immunity in the tumor microenvironment. Cancer cells can express high levels of immune inhibitory signaling proteins. One of the most critical checkpoint pathways in this system is a tumor‐induced immune suppression (immune checkpoint) mediated by the programmed cell death protein 1 (PD‐1) and its ligand, programmed death ligand 1 (PD‐L1). PD‐1 is highly expressed by activated T cells, B cells, dendritic cells, and natural killer cells, whereas PD‐L1 is expressed on several types of tumor cells. Many studies have shown that blocking the interaction between PD‐1 and PD‐L1 enhances the T‐cell response and mediates antitumor activity. In this review, we highlight a brief overview of the molecular and biochemical events that are regulated by the PD‐1 and PD‐L1 interaction in various cancers.
Phosphorylation of nucleolin is indispensable to upregulate miR‐21 and inhibit apoptosis in cardiomyocytes
Authors: Tong Zhongyi , Tang Yuting , Jiang Bimei , Wu Yanyang , Liu Yanjuan , Li Yuanbin , Xiao Xianzhong 
Published: September 2018

AbstractNucleolin is a multifunctional phosphoprotein and is involved in protecting from myocardial ischemia/reperfusion (I/R) injury. The function of nucleolin is regulated by posttranslational modifications, including phosphorylation and glycosylation. To study whether phosphorylation of nucleolin (P‐nucleolin) was involved in the protection from myocardial I/R injury. We investigated the expression pattern of P‐nucleolin (Thr‐76 and 84) in hearts subjected to I/R injury, or rat cardiac myoblast cells (H9C2) subjected to hydrogen peroxide (H
2O
2). The results showed that the expression of P‐nucleolin and the ratio of P‐nucleolin/nucleolin were significantly increased both in vivo and in vitro. Mutant nucleolin was obtained by site directed mutagenesis in vitro: threonine at 76 and 84 was replaced by alanine, and we found that the protective effect of nucleolin on apoptosis induced by oxidative stress was dependent on its phosphorylation at 76 and 84 in H9C2 cells. Furthermore, the cardio‐protective roles of P‐nucleolin (Thr‐76 and 84) in H9C2 cardiomyocytes, were attributable to the upregulation of microRNA (miR)‐21. Further analysis found that P‐nucleolin (Thr‐76 and 84) could bind to miR‐21, and P‐nucleolin colocalized with argonaute 2 (Ago2) in cytoplasm and could interact with Ago2 in a RNA‐independent manner under cell oxidative stress. The current study revealed that P‐nucleolin (Thr‐76 and 84) increased in I/R injury myocardium, P‐nucleolin was indispensable to upregulate miR‐21 and inhibited apoptosis induced by H
2O
2 in H9C2 cardiomyocytes. These findings provided new insight into the molecular mechanisms of nucleolin in myocardial I/R injury and oxidative stress cells.
Hepatocyte growth factor promotes the proliferation of human embryonic stem cell derived retinal pigment epithelial cells
Authors: Karamali Fereshteh , Esfahani Mohammad‐Hossein Nasr , Hajian Mehdi , Ejeian Fatemeh , Satarian Leila , Baharvand Hossein 
Published: September 2018

AbstractResearch that pertains to the molecular mechanisms involved in retinal pigment epithelial (RPE) development can significantly contribute to cell therapy studies. The effects of periocular mesenchymal cells on the expansion of RPE cells remain elusive. We have examined the possible proliferative role of hepatocyte growth factor (HGF) as a mesenchymal cell secretory factor against human embryonic stem cell derived RPE (hESC‐RPE). We found that the conditioned medium of human mesenchymal stem cells from apical papilla and/or exogenous HGF promoted proliferation of the hESC‐RPE cells as single cells and cell sheets, in addition to rabbit RPE sheets in vitro. Blockage of HGF signaling by HGF receptor inhibitor, PHA‐665752, inhibited proliferation of hESC‐RPE cells. However, differentiation of hESCs and human‐induced pluripotent stem cells to a rostral fate and eye‐field specification was unaffected by HGF. Our in vivo analysis showed HGF expression in periocular mesenchymal cells after optic cup formation in chicken embryos. Administration of HGF receptor inhibitor at this developmental stage in chicken embryos led to reduced eye size and disorganization of the RPE sheet. These findings suggested that HGF administration could be beneficial for obtaining higher numbers of hESC‐RPE cells in human preclinical and clinical trials.
The role of microRNAs in 5‐FU resistance of colorectal cancer: Possible mechanisms
Authors: Marjaneh Reyhaneh Moradi , Khazaei Majid , Ferns Gordon A. , Avan Amir , Aghaee‐Bakhtiari Seyed Hamid 
Published: September 2018

AbstractColorectal cancer (CRC) is one of the most common cancers globally. Despite recent advances in therapeutic approaches, this cancer continues to have a poor prognosis, particularly when diagnosed late. 5‐Fluorouracil (5‐FU) has been commonly prescribed for patients with CRC, but resistance to 5‐FU is one of the main reasons for failure in the treatment of this condition. Recently, microRNAs (miRNAs) have been established as a means of modifying the signaling pathways involved in initiation and progression of CRC and their role as oncogene or tumor suppressor have been investigated in various studies. Moreover, miRNAs through various mechanisms play an important role in inducing tumor resistance or sensitivity to anticancer drugs. Detecting and targeting these mechanisms may be a new therapeutic approach. This review summarizes the current knowledge about the potential roles of miRNAs in 5‐FU resistance, with particular emphasis on molecular mechanism involved.
Arsenic induces fibrogenic changes in human kidney epithelial cells potentially through epigenetic alterations in DNA methylation
Authors: Chang Yu‐Wei , Singh Kamaleshwar P. 
Published: September 2018

AbstractArsenic contamination is a significant public health issue, and kidney is one of the target organ for arsenic‐induced adverse effects. Renal fibrosis is a well‐known pathological stage frequently observed in progressive chronic kidney disease (CKD). Epidemiological studies implicate arsenic exposure to CKD, but the role of arsenic in kidney fibrosis and the underlying mechanism is still unclear. It is in this context that the current study evaluated the effects of long‐term arsenic exposure on the cellular response in morphology, and marker genes expression with respect to fibrosis using human kidney 2 (HK‐2) epithelial cells. Results of this study revealed that in addition to increased growth, HK‐2 cells underwent phenotypic, biochemical and molecular changes indicative of epithelial–mesenchymal transition (EMT) in response to the exposure to arsenic. Most importantly, the arsenic‐exposed cells acquired the pathogenic features of fibrosis as supported by increased expression of markers for fibrosis, such as Collagen I, Fibronectin, transforming growth factor β, and α‐smooth muscle actin. Upregulation of fibrosis associated signaling molecules such as tissue inhibitor of metalloproteinases‐3 and matrix metalloproteinase‐2 as well as activation of AKT was also observed. Additionally, the expression of epigenetic genes (DNA methyltransferases 3a and 3b; methyl‐CpG binding domain 4) was increased in arsenic‐exposed cells. Treatment with DNA methylation inhibitor 5‐Aza‐2′‐dC reversed the EMT properties and restored the level of phospho‐AKT. Together, these data for the first time suggest that long‐term exposure to arsenic can increase the risk of kidney fibrosis. Additionally, our data suggest that the arsenic‐induced fibrotic changes are, at least in part, mediated by DNA methylation and therefore potentially can be reversed by epigenetic therapeutics.
Therapeutic potency of pharmacological adenosine receptors agonist/antagonist on cancer cell apoptosis in tumor microenvironment, current status, and perspectives
Authors: Soleimani Anvar , Bahreyni Amirhossein , Roshan Mostafa K. , Soltani Arash , Ryzhikov Mikhail , Shafiee Mojtaba , Soukhtanloo Mohammad , Jaafari Mahmoud R. , Mashkani Baratali , Hassanian Seyed M. 
Published: September 2018

AbstractThe hypoxic niche of tumor leads to a tremendous increase in the extracellular adenosine concentration through alteration of adenosine metabolism in the tumor microenvironment (TME). This consequently affects cancer progression, local immune responses, and apoptosis of tumor cells. Regulatory effect of adenosine on apoptosis in TME depends on the cancer cell type, pharmacological characteristics of adenosine receptor subtypes, and the adenosine concentration in the tumor niche. Exploiting specific pharmacological adenosine receptor agonist and antagonist inducing apoptosis in cancer cells can be considered as a proper procedure to control cancer progression. This review summarizes the regulatory role of adenosine in cancer cell apoptosis for a better understanding, and hence better management of the disease.
Luteolin attenuates glucocorticoid‐induced osteoporosis by regulating ERK/Lrp‐5/GSK‐3β signaling pathway in vivo and in vitro
Authors: Jing Zheng , Wang Changyuan , Yang Qining , Wei Xuelian , Jin Yue , Meng Qiang , Liu Qi , Liu Zhihao , Ma Xiaodong , Liu Kexin , Sun Huijun , Liu Mozhen 
Published: September 2018

AbstractGlucocorticoid‐induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO. Meanwhile, LUT decreased caspase‐3, caspase‐9, and Bax protein expressions and increased Bcl‐2 protein expression in GIO. LUT increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor‐κB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels of osteogenic markers, including runt‐related transcription factor 2, osterix, collagen type I, and osteocalcin. LUT also enhanced the extracellular signal‐regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3β (GSK‐3β) phosphorylation, mRNA expression levels of lipoprotein‐receptor‐related protein 5 (Lrp‐5) and β‐catenin. Further study revealed that Lrp‐5 small interfering RNA (siRNA )and ERK‐siRNA reduced the effects of LUT on GSK‐3β phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL mRNA expression. Moreover, ERK‐siRNA decreased Lrp‐5 mRNA expression in vitro. These results indicated that LUT promoted proliferation by attenuating oxidative stress and promoted osteoblastic differentiation by regulating the ERK/Lrp‐5/GSK‐3β pathway in GIO. This study may bring to light the possible mechanisms involved in the action of LUT in GIO treatment, and benefit for further research on GIO.
Adjuvant chemotherapy with melatonin for targeting human cancers: A review
Authors: Najafi Masoud , Salehi Eniseh , Farhood Bagher , Nashtaei Maryam Shabani , Hashemi Goradel Nasser , Khanlarkhani Neda , Namjoo Zeinab , Mortezaee Keywan 
Published: September 2018

AbstractMelatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re‐establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer‐specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.
Inhibition of glycolysis alleviates lipopolysaccharide‐induced acute lung injury in a mouse model
Authors: Zhong Wen‐Jing , Yang Hui‐Hui , Guan Xin‐Xin , Xiong Jian‐Bing , Sun Chen‐Chen , Zhang Chen‐Yu , Luo Xiao‐Qin , Zhang Yan‐Feng , Zhang Jun , Duan Jia‐Xi , Zhou Yong , Guan Cha‐Xiang 
Published: September 2018

AbstractGluconic metabolic reprogramming, immune response, and inflammation are intimately linked. Glycolysis involves in the pathologic progress in acute and chronic inflammatory diseases. However, the involvement of glycolysis in the acute lung injury (ALI) is still unclear. This study investigated the role of glycolysis in an animal model of ALI. First, we found that lactate content in serum was remarkably increased in ALI patients and a murine model induced by intratracheal administration of lipopolysaccharide (LPS). The key proteins involving in glycolysis were robustly elevated, including HK2,
PKM2, and
HIF‐1α. Intriguingly, inhibition of glycolysis by 2‐deoxyglucose (2‐DG) pronouncedly attenuated the lung tissue pathological injury, accumulation of neutrophil, oxidative stress, expression of proinflammatory factors in the lung of ALI mice induced by LPS. The 2‐DG treatment also strongly suppressed the activation of the NOD‐like receptor (NLR) family and pyrin domain‐containing protein 3 (NLRP3) inflammasome. Furthermore, we investigated the role of glycolysis in the inflammatory response of primary murine macrophages activated by LPS in vitro. We found that the 2‐DG treatment remarkably reduced the expression of proinflammatory factors induced by LPS, including tumor necrosis factor‐α messenger RNA (mRNA), pro‐interleukin (IL)‐1β mRNA, pro‐IL‐18 mRNA, NLRP3 mRNA, caspase‐1 mRNA, and IL‐1β protein. Altogether, these data provide a novel link between gluconic metabolism reprogramming and uncontrolled inflammatory response in ALI. This study suggests glycolytic inhibition as an effective anti‐inflammatory strategy in treating ALI.
PI3k/AKT signaling pathway: Erythropoiesis and beyond
Authors: Jafari Mahjoobeh , Ghadami Elham , Dadkhah Tahereh , Akhavan‐Niaki Haleh 
Published: September 2018

AbstractErythropoiesis is a multi‐step process that involves the differentiation of hematopoietic stem cells into mature red blood cells (RBCs). This process is regulated by several signaling pathways, transcription factors and microRNAs (miRNAs). Many studies have shown that dysregulation of this process can lead to hematologic disorders. PI3K/AKT is one of the most important pathways that control many cellular processes including, cell division, autophagy, survival, and differentiation. In this review, we focus on the role of PI3K/AKT pathway in erythropoiesis and discuss the function of some of the most important genes, transcription factors, and miRNAs that regulate different stages of erythropoiesis which play roles in differentiation and maturation of RBCs, prevention of apoptosis, and autophagy induction. Understanding the role of the PI3K pathway in erythropoiesis may provide new insights into diagnosing erythrocyte disorders.
The immunomodulatory role of probiotics in allergy therapy
Authors: Hajavi Jafar , Esmaeili Seyed‐Alireza , Varasteh Abdol‐Reza , Vazini Hossein , Atabati Hadi , Mardani Fatemeh , Momtazi‐Borojeni Amir A. , Hashemi Maryam , Sankian Mojtaba , Sahebkar Amirhossein 
Published: September 2018

AbstractThe increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of speciﬁc allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro‐T‐helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.