bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of microRNAs as potential markers of ovarian toxicity
Authors: Furlong Hayley C. , Stämpfli Martin R. , Gannon Anne M. , Foster Warren G. 
Published: January 2018

AbstractExposure to environmental toxicants has been associated with ovarian dysfunction yet sensitive biomarkers of adverse effect are lacking. We previously demonstrated that cigarette smoke exposure induced decreased relative ovarian weight, increased follicle loss and granulosa cell autophagy in mice. We postulate that cigarette smoke exposure will induce changes in the epigenome that can be used to reveal potential sensitive biomarkers of ovarian toxicity. Therefore, we evaluated differences in expression of 940 microRNAs (miRNAs), environmentally responsive small non‐coding genes that regulate expression of genes at the post‐transcriptional level, in ovarian tissue from 8‐week‐old female C57BL/6 mice exposed to room air or cigarette smoke 5 days per week for 8 weeks. A total of 152 miRNAs were dysregulated in expression, 17 of which were examined with quantitative polymerase chain reaction analysis. Using an online miRNA database tool, complete lists of predicted miRNA gene targets were generated, 12 of which were measured for their expression levels with quantitative polymerase chain reaction. An online bioinformatics resource database, DAVID generated functional classification lists of the target genes and their associated biological pathways. Results of the present pilot study suggest that miR‐379, miR‐15b, miR‐691, miR‐872 and miR‐1897‐5p are potentially useful markers of ovarian toxicity and dysfunction. Examination of the expression pattern of the target mRNA for these miRNA species demonstrated that cigarette smoke exposure induced significant changes that affect mitogen‐activated protein kinase signaling pathways. We therefore suggest that miRNAs could serve as sensitive markers of ovarian toxicity and elucidate affected pathways.
Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3‐E1 osteoblasts
Authors: Zhu Wen‐qing , Ming Pan‐pan , Qiu Jing , Shao Shui‐yi , Yu Ying‐juan , Chen Jia‐xi , Yang Jie , Xu Li‐na , Zhang Song‐mei , Tang Chun‐bo 
Published: January 2018

AbstractTitanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long‐term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion‐induced YAP activation was found to downregulate osteogenic differentiation of MC3T3‐E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri‐implantitis.
Mesoporous bioactive glass embedding propolis and cranberry antibiofilm compounds
Authors: Galarraga‐Vinueza Maria Elisa , Mesquita‐Guimarães Joana , Magini Ricardo S. , Souza Júlio C. M. , Fredel Marcio C. , Boccaccini Aldo R. 
Published: January 2018

AbstractThe aim of this study was to evaluate the chemical reactivity of 58S mesoporous bioactive glass (MBG) particles in as‐synthesized condition and after embedding propolis and cranberry antibiofilm compounds at different concentrations. MBG 58S was synthesized by alkali sol‐gel method with the addition of the triblock pluronic copolymer P123 as surfactant. Samples were characterized by physicochemical properties measurement, N2 adsorption/desorption analysis, and field emission gun scanning electron microscopy (FEGSEM) observations. MBG powders were immersed into 5 and 10 µg/mL propolis or cranberry solutions for 24 h. The chemical reactivity of the specimens was evaluated by FEGSEM, EDX, FTIR, Ca/P ratio, XRD, and sample weight gain analysis after being immersed in simulated body fluid (SBF) for 8, 24, and 72 h. MBG particles exhibited the expected chemical composition with a particle size distribution ranging from 1.44 to 955 µm, and a mean particle size of 154 µm. MBG particles exhibited a pore volume of 0.8 cc/g, pore radius of ∼2 nm, and surface area of 350.2 m2/g, according to BJH and BET analyses. A hydroxyl‐carbonate apatite (HCAp) layer was formed on all samples after SBF immersion for 72 h. Pure MBG showed the highest chemical reactivity after 72 h, with the resulting apatite layer exhibiting a Ca/P ratio of ∼1.6 in accordance to stoichiometric biological apatite. MBG embedding propolis and cranberry can be considered for future microbiological analysis since the presence of propolis or cranberry did not interfere with MBG's ability to develop a HCAp layer, which is an essential feature for bone regeneration applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1614–1625, 2018.
Retracted: microRNA‐129‐5p involved in the neuroprotective effect of dexmedetomidine on hypoxic‐ischemic brain injury by targeting COL3A1 through the Wnt/β‐catenin signaling pathway in neonatal rats
Authors: Zhou Xiu‐Min , Liu Jie , Wang Ying , Zhang Shu‐Li , Zhao Xin , Xu Xiang , Pei Jian , Zhang Man‐He 
Published: January 2018

AbstractOur study aims to elucidate the mechanisms how microRNA‐129‐5p (miR‐129‐5p) involved in the neuroprotective effect of dexmedetomidine (DEX) on hypoxic‐ischemic brain injury (HIBI) by targeting the type III procollagen gene (COL3A1) through the Wnt/β‐catenin signaling pathway in neonatal rats. A total of 120 rats were obtained, among which 15 rats were selected as sham group and rest rats as model, DEX, DEX + negative control (DEX + NC), DEX + miR‐129‐5p mimics, DEX + miR‐129‐5p inhibitors, DEX + XAV‐939, and DEX + miR‐129‐5p inhibitors + XAV‐939 groups. A dual‐luciferase reporter assay was performed for the target relationship between miR‐129‐5p and COL3A1. Weight rate and water content of cerebral hemisphere were detected. Quantitative real‐time polymerase chain reaction and Western blot analysis were conducted to detect miR‐129‐5p expression and expressions of COL3A1, E‐cadherin, T‐cell factor (TCF)− 4, and β‐catenin. The DEX, DEX + miR‐129‐5p mimics, DEX + XAV‐939 groups had increased weight rate of the cerebral hemisphere, but decreased water content of left cerebral hemisphere, levels of COL3A1, β‐catenin, TCF‐4, and E‐cadherin in the hippocampus compared with the model and DEX + miR‐129‐5p inhibitors groups. COL3A1 was verified as the target gene of the miR‐129‐5p. Compared with the DEX + NC and DEX + miR‐129‐5p inhibitors + XAV‐939 groups, the DEX + XAV‐939 and DEX + miR‐129‐5p mimics groups had elevated weight rate of the cerebral hemisphere, but reduced water content of left cerebral hemisphere, levels of COL3A1, β‐catenin, TCF‐4, and E‐cadherin in the hippocampus. Our findings demonstrate that miR‐129‐5p improves the neuroprotective role of DEX in HIBI by targeting COL3A1 through the Wnt/β‐catenin signaling pathway in neonatal rats.
LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF‐1α/VEGF signaling in ischemic stroke
Authors: Zhang Lin , Luo Xianliang , Chen Feng , Yuan Wei , Xiao Xinli , Zhang Xiaohua , Dong Yaru , Zhang Yuanxiao , Liu Yong 
Published: January 2018

AbstractStudies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro‐vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen‐glucose deprivation (OGD)‐cultured mice brain micro‐vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR‐18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase‐3 activity and cell apoptosis in OGD‐cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR‐18a, thereby regulating the de‐repression of its endogenous target HIF‐1α and promoting BMEC survival through HIF‐1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF‐1α/VEGF signaling through acting as a ceRNA for miR‐18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease.
The exosomes released from different cell types and their effects in wound healing
Authors: Golchin Ali , Hosseinzadeh Simzar , Ardeshirylajimi Abdolreza 
Published: January 2018

AbstractDespite important advances in regenerative medicine and tissue engineering, still, wound healing remains a challenging clinical problem. Cell therapy has opened a new viewpoint in medicine as well as wound management, although it has some limitations. On the other hand, there are some hopes for the eliminated of cellular therapies limitations by “exosomes.” The term “exosome” has been frequently used to describe all vesicles released by different cells into the extracellular environment and can influence tissue responses to injury, infection, immune system, and healing. Exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs that have been found in some body fluids and can be transferred between cells to mediating cell‐to‐cell communication and interactions. Recently, several studies have demonstrated that exosomes are one of the key secretory products of various cell type especially mesenchymal stem cells (MSCs) to regulate many biological processes such wound healing. Hence, understanding these exosomes effects may help to improve wound management and highlight a new therapeutic model for cell‐free therapies with decreased side effects for the wound repair.
Pretreatment of glial cell‐derived neurotrophic factor and geranylgeranylacetone ameliorates brain injury in Parkinson's disease by its anti‐apoptotic and anti‐oxidative property
Authors: Yue Peijian , Gao Lin , Wang Xuejing , Ding Xuebing , Teng Junfang 
Published: January 2018

AbstractThe aim of the present study was to determine the combined effects of glial cell‐derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of PD and cellular models of H2O2 and MPP+‐treated PC12 cells were established. Swimming, pole, and traction tests were used to detect behavioral impairment. Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis. MDA levels and activities of antioxidant enzymes were used to detect the oxidative damage. The PD model of mice received GDNF and GGA exhibited a significant recovery in their swim, pole, and traction scores. Moreover, the combined treatment significantly reduced the neuron apoptosis in the substantia nigra (SN) of PD mice or in H2O2 or MPP+‐induced PC12 cells compared with the single drug group. In addition, significant reduction of MDA levels and improvement of activities of CAT, SOD, and GSH‐px were observed after GDNF and GGA treatment in the PD model and H2O2 or MPP+‐induced PC12 cells. The combination of GDNF and GGA ameliorated neural apoptosis and oxidative damage in PD.
Glycosylated CD147 reduces myocardial collagen cross‐linking in cardiac hypertrophy
Authors: Ru Ning‐Yu , Cui Long‐Biao , Jiao Bo , Zhang Lin , Jiang Shuai , Yu Zhi‐Bin 
Published: January 2018

AbstractThe mechanism of transition from chronic pressure overload‐induced cardiac hypertrophy to heart failure is still unclear. Angiotensin II (Ang II) may be an important factor that mediates the transition in the end‐stage of cardiac hypertrophy. In the present study, Goldblatt two‐kidney one‐clip (2K1C) rat model was used to simulate Ang II‐induced hypertension. The elevated Ang II not only induced the concentric hypertrophy of left ventricle and cardiac fibrosis, but also increased the expression and glycosylation of CD147 in 2K1C rats. The left ventricular structure and function detected by echocardiogram showed a sign of the transition from cardiac hypertrophy to heart failure in 16 weeks of 2K1C rats. Ang II can activate N‐acetylglucosamine transferase V (GnT‐V), a key enzyme for CD147 glycosylation. Retinoic acid, an agonist of GnT‐V, further increased glycosylated CD147, and activated matrix metalloproteinase‐2/‐9 (MMP‐2 and MMP‐9) in the hypertrophied left ventricle of 2K1C rat. Meanwhile, collagen cross‐linking in the hypertrophied left ventricle significantly reduced in 2K1C rats. On the contrary, tunicamycin, an inhibitor of N‐glycan biosynthesis, inhibited glycosylation of CD147 and activity of MMP‐2 and MMP‐9, and then maintained a stable of collagen cross‐linking in the 2K1C rat hearts. The above results suggested that Ang II increased glycosylated CD147 which activated MMP‐2 and MMP‐9. Collagens were degraded by the activated MMPs and then reduced collagen cross‐linking. Finally, the hypertrophied left ventricle was progressively dilated in chronic pressure overload due to losing the limitation of collagen cross‐linking. Therefore, the compensated hypertrophy of left ventricle gradually transited to congestive heart failure.
The α1‐adrenergic receptor is involved in hepcidin upregulation induced by adrenaline and norepinephrine via the STAT3 pathway
Authors: Kong Wei‐Na , Cui Yanmei , Fu Yu‐Jian , Lei Yuhua , Ci Yunzhe , Bao Yongping , Zhao Shuqiang , Xie Lide , Chang Yan‐Zhong , Zhao Shu‐E 
Published: January 2018

AbstractElevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron‐regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1‐adrenergic receptor agonist), prazosin (PZ, α1‐adrenergic receptor antagonist), and/or propranolol (Pro, β‐adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin‐light (Ft‐L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft‐L protein and non‐heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1‐adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen.
Retracted: Ginsenoside Rh2 inhibits proliferation and migration of medulloblastoma Daoy by down‐regulation of microRNA‐31
Authors: Chen Yan , Shang Hong , Zhang Shunli , Zhang Xiaohong 
Published: January 2018

AbstractThis study aimed to investigate the effects of ginsenoside Rh2 on proliferation, apoptosis, and migration of the human medulloblastoma cell line Daoy, as well as to explore the potential mechanisms of the effects. The human medulloblastoma cell line Daoy was cultured in vitro and treated with or without ginsenoside Rh2. CCK‐8 assay was performed to investigate the effect of Rh2 on cell survival using a cell counting Kit‐8. Cell proliferation was assessed by BrdU assay. Cell apoptosis was determined using flow cytometry analysis. Cell migration was detected using a modified two‐chamber migration assay. MiR‐31 mimic and the NC control were transfected into Daoy cells and detected by qRT‐PCR. The expression of Wnt3a, Wnt5a, and β‐catein was detected by Western blot analysis. Rh2 efficiently suppressed the proliferation and migration, and promoted the apoptosis of Daoy cells. Additionally, Rh2 could down‐regulate miR‐31. miR‐31 overexpression reversed the effects of Rh2 on proliferation, apoptosis and migration of Daoy cells, and activated the Wnt/β‐catein signaling pathways in Daoy cells. Rh2 could inhibit the proliferation and migration, and induce apoptosis of Daoy medulloblastoma cells through down‐regulation of miR‐31 to inactivate the Wnt/β‐catein signaling pathway. Therefore, Rh2 may have a utility in clinical applications for the treatment of medulloblastoma.
ER stress mediated regulation of miR23a confer Hela cells better adaptability to utilize glycolytic pathway
Authors: Poyyakkara Aswini , Raji Grace R. , Kunhiraman Haritha , Edatt Lincy , Kumar Sameer V.B. 
Published: January 2018

AbstractCancer cells exhibit increased dependency on aerobic glycolysis, a phenomenon referred as the “Warburg effect” and therefore, blocking glycolysis by using non‐metabolizable analogues of glucose, like 2‐Deoxy glucose (2‐DG), has been proposed to be of huge therapeutic importance. One of the major drawbacks of using 2‐DG as a chemotherapeutic agent is that it can induce ER stress. ER stress is a hall mark in many solid tumors and the unfolded protein response (UPR) associated with it initiates many survival mechanisms in cancer cells. In the present study, we report a novel survival mechanism associated with ER stress, by which the cancer cells become more adapted to aerobic glycolysis. When ER stress was induced in Hela cells by treating them with 2‐DG or Thapsigargin (TG) the expression and activity of LDH was significantly up regulated, conferring the cells a greater glycolytic potential. A simultaneous decrease was observed in the expression of miR‐23a, which was predicted in silico to have target site on the 3′UTR of LDH A and B mRNAs. miRNA over expression studies and mRNA degradation assays suggest that miR‐23a could target LDH A and LDH B mRNAs. Further on the basis of our results and previous scientific reports, we propose that “c‐Myc,” which is over expressed during ER stress, repress the expression of miR‐23a, which in turn regulates the expression of its target genes viz., LDH A and LDH B, thereby making the cells more competent to survive in tumor microenvironment, which requires efficient use of aerobic glycolysis.
Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3
Authors: Kusama Kazuya , Bai Rulan , Imakawa Kazuhiko 
Published: January 2018

AbstractIn human trophoblast cells, cyclic AMP or its inducer forskolin (FSK) activates two downstream signaling molecules, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), both of which induce syncytialization, cell fusion, and the production of human chorionic gonadotropin (hCG) and progesterone. However, a transcription factor other than GCM1 and molecular mechanisms associated with these events have not been well characterized. To identify novel transcription factors involved in syncytialization of cAMP‐stimulated human choriocarcinoma BeWo cells, the microarray analysis was performed with RNAs extracted from PKA‐ or EPAC‐selective cAMP analog‐stimulated BeWo cells, from which two up‐regulated transcription factors, STAT5 and NR4A3, were found. The knockdown of STAT5B decreased FSK‐induced cell fusion and the expression of syncytialization markers, CGB, syncytin1, syncytin2, GCM1, and OVOL1, but NR4A3 knockdown increased FSK‐induced cell fusion and the expression of CGB and syncytin2. These findings indicated that cAMP‐PKA up‐regulated STAT5B, followed by increase in syncytin2 expression through GCM1 and OVOL1, resulting in cell fusion and hCG production, while cAMP‐PKA‐up‐regulated NR4A3 could decrease syncytin2 expression, and suggested that both positive and negative effects of STAT5B and NR4A3, respectively, are required to control the degree of syncytialization in human trophoblast cells.
Calbindin‐D28K mediates 25(OH)D3/VDR‐regulated bone formation through MMP13 and DMP1
Authors: Yang Li‐Ping , Dong Ya‐Ping , Luo Wen‐Ting , Zhu Tong , Li Qi‐Wei , Zhang Li‐Jun , Kong Juan , Yuan Zheng‐Wei , Zhao Qun 
Published: January 2018

AbstractCalcium binding protein calbindin‐D28K (CaBP28K) mediates the relationship between vitamin D and calcium, but its mechanism remains unclear during bone formation. The present study reports that maternal CaBP28K levels were positively correlated with paired umbilical cord CaBP28K levels. In addition, CaBP28K levels were positively correlated with the body length, and head and chest circumferences of neonates, but negatively correlated with maternal 25(OH)D3 levels. CaBP28K was also downregulated in MC3T3‐E1 osteoblasts when treated with 1,25(OH)2D or VDR overexpression, but was upregulated in the femur of 1α(OH)ase(−/−) mice. Furthermore, it was found CaBP28K may influence cell differentiation and matrix formation through the regulation of DMP1 and the interaction with MMP13 in osteoblasts. This suggests that CaBP28K could be a candidate for the negative role of 1,25(OH)2D/VDR in regulating bone mass.