bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell type‐dependent functions of microRNA‐92a
Authors: Kohram Fatemeh , Fallah Parviz , Shamsara Mehdi , Bolandi Zohreh , Rassoulzadegan Minoo , Soleimani Masoud , Ghanbarian Hossein 
Published: March 2018

AbstractThe role of miR‐17/92 family in development and progression of various cancers has been established. The members of this miRNA family have been shown to be over expressed and target various genes within proliferation, metastasis and angiogenesis pathways. Although all members might be overexpressed in a certain cancer type, only certain members of the family may have roles in progression of that cancer. In this study, we have chosen miR‐92a, a member of the miR‐17/92 family to compare its function in three different cancer cell lines. HL60, MCF7, and Jurkat cell lines were transduced with miR‐92a and proliferation and apoptosis was measured in these cells by cell count, MTT, and caspase assays. Although in comparison to pre‐miR‐17/92, the level of miR‐92a is higher in Jurkat cells compared to MCF7 and HL60 cells, here we have shown that increasing miR‐92a levels results in apoptosis in Jurkat cells and proliferation in MCF7 and HL60 cells. miR‐92a was also microinjected into mice fertilized eggs and after dissection, apoptosis was only observed in white pulp of spleen that is mainly made up of white blood cells. Our results show that miR‐92a possesses a cell‐type dependent function.
MicroRNA‐190b regulates lipid metabolism and insulin sensitivity by targeting IGF‐1 and ADAMTS9 in non‐alcoholic fatty liver disease
Authors: Xu Min , Zheng Xi‐Ming , Jiang Fang , Qiu Wei‐qiang 
Published: March 2018

AbstractNonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation and insulin resistance, yet the underlying molecular mechanisms are poorly understood. MiR‐190b is thought to play a role in hepatocellular carcinoma by modulating insulin resistance; however, its role in NAFLD remains unknown. Here, we found that miR‐190b expression was significantly increased in the liver tissues of patients with NAFLD, compared to normal tissues. Moreover, miR‐190b was upregulated in a high‐fat diet NAFLD mouse model and a free fatty acid‐induced NAFLD cellular model. Knockdown of miR‐190b decreased aspartate transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3‐hydroxy‐3‐methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro. Furthermore, we confirmed that miR‐190b directly targeted IGF‐1 and ADAMTS9. MiR‐190b overexpression suppressed expression of IGF‐1 and ADAMTS9, which were increased by miR‐190b inhibition. Expression of IGF‐1 and ADAMTS9 was inversely correlated with miR‐190b in liver tissues of patients with NAFLD, respectively. We also found that IGF‐1 or ADAMTS9 inhibition partially reversed the effects of miR‐190b on lipid metabolism and insulin signaling in vitro. Taken together, the data reveal that miR‐190b inhibition suppressed lipid accumulation and improved insulin sensitivity by targeting IGF‐1 and ADAMTS9, suggesting that miR‐190b inhibition may be a therapeutic strategy against NAFLD.
Expression profiling of planarians shed light on a dual role of programmed cell death during the regeneration
Authors: Yuan Junsong , Wang Zhihong , Zou Di , Peng Quekun , Peng Rui , Zou Fangdong 
Published: March 2018

AbstractMost animals hold the ability to regenerate damaged cells, tissues, and even any lost part of their bodies. To date, there is little known about the precise regulatory mechanism of regeneration and many fundamental questions remain unanswered. To further understand the precise regulatory mechanism of regeneration, we used planarian Dugesia japonica as a model and sequenced the transcriptomes of their regenerated tissues at different regeneration stages. Through de novo assembly and expression profiling, we found that Heat shock protein and MAPK pathway were involved into early response of regeneration in D. japonica. In addition, immune response, cell proliferation, and migration were activated during regeneration. Of notes, our results revealed a specific functional role of programmed cell death (PCD) in regeneration of D. japonica. PCD may not only remove the damaged and superfluous tissues for further patterning with regenerated tissues, but also provide signals to trigger neoblasts proliferation and differentiation directly. Together, our results revealed Heat shock protein and MAPK pathway mediated early response of regeneration and found a dual role of PCD in regeneration D. japonica. Meanwhile, we constructed regulatory networks of apoptosis, autophagy, and related signaling pathways and proposed a schematic model, which provided a global landscape of regeneration.
Novel organometallic chloroquine derivative inhibits tumor growth
Authors: Hall Elizabeth A. , Ramsey Jon E. , Peng Zhihua , Hayrapetyan Davit , Shkepu Viacheslav , O'Rourke Bruce , Geiger William , Lam Kevin , Verschraegen Claire F. 
Published: March 2018

AbstractAutophagy has emerged as a mechanism critical to both tumorigenesis and development of resistance to multiple lines of anti‐cancer therapy. Therefore, targeting autophagy and alternative cell death pathways has arisen as a viable strategy for refractory tumors. The anti‐malarial 4‐aminoquinoline compounds chloroquine and hydroxychloroquine are currently being considered for re‐purposing as anti‐cancer therapies intended to sensitize different tumors by targeting the lysosomal cell death pathway. Here, we describe a novel organometallic chloroquine derivative, cymanquine, that exhibits enhanced bioactivity compared to chloroquine in both normal, and reduced pH tumor microenvironments, thus overcoming a defined limitation of traditional 4‐aminoquinolines. In vitro, cymanquine exhibits greater potency than CQ in a diverse panel of human cancer cell lines, including melanoma, in both normal pH and in reduced pH conditions that mimic the tumor microenvironment. Cymanquine treatment results in greater lysosomal accumulation than chloroquine and induces lysosomal dysfunction leading to autophagy blockade. Using a mouse model of vemurafenib‐resistant melanoma, cymanquine slowed tumor growth greater than hydroxychloroquine, and when used in combination with vemurafenib, cymanquine partially restored sensitivity to vemurafenib. Overall, we show that cymanquine exhibits superior lysosomal accumulation and autophagy blockade than either chloroquine or hydroxychloroquine in vitro; and in addition to its high level of tolerability in mice, exhibits superior in vivo efficacy in a model of human melanoma.
The power of precise bioinformatics prediction of miRNA:mRNA interactions:miR‐4699 as a potential inducer of Wnt signaling pathway
Authors: Hosseini Vahedeh , Mohammadi‐Yeganeh Samira , Ghanbarian Hossein , Hashemi Seyed Mahmoud , Khojasteh Arash 
Published: March 2018

AbstractmicroRNAs have attracted interest because of their regulatory effects on gene expression. Experimental detection of potential targets of miRNAs is a laborious task. Considering the expensive techniques of detection, computational approaches for miRNA target prediction can be used as the first step in miRNA research. A large number of tools and algorithms have been developed during the last two decades, led to problems such as confusion in selecting an appropriate tool and false positive or negative results. Therefore, one of the most frequent problems and critical issues of miRNA research is finding a reliable miRNA target prediction tool. In this study, we have proposed a research direction and introduced user‐friendly and current databases and tools with the highest accuracy. To verify whether our proposed research direction is practical, we have provided a case example of predicting a miRNA which can target negative regulators of osteogenesis and experimentally evaluated the accuracy of the prediction results by Real‐Time PCR and Luciferase assay. The results of RT‐qPCR and Luciferase assay indicated a significant decline in expression of Dickkopf‐related protein 1 (DKK1) and tumor necrosis factor ligand superfamily member 11 (TNFSF11) as the key negative regulators of osteogenesis upon overexpression of miR‐4699‐3p. The results emphasize the validity and importance of accurate in silico investigation as the first step in experimental studies. This is the first report detailing the prediction and validation of miR‐4699‐3p target genes. We suggest hsa‐miR‐4699 for further investigation as an osteogenic miRNA for therapeutics purposes.
Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress
Authors: Torre‐Villalvazo Ivan , Bunt Ana E. , Alemán Gabriela , Marquez‐Mota Claudia C. , Diaz‐Villaseñor Andrea , Noriega Lilia G. , Estrada Isabela , Figueroa‐Juárez Elizabeth , Tovar‐Palacio Claudia , Rodriguez‐López Leonardo A. , López‐Romero Patricia , Torres Nimbe , Tovar Armando R. 
Published: March 2018

AbstractSubcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may be involved in SAT dysfunction during obesity. The objectives of this study were to assess UPR activation and adiponectin synthesis in: 1) SAT and VAT from mice exposed to acute pharmacologic or chronic obesity‐induced ER stress and in 2) cultured mice primary mature adipocytes or adipocytes differentiated in vitro from SAT and VAT exposed to tunicamycin or thapsigargin. Mice fed a high‐fat diet developed obesity, increased FFA and lower circulating adiponectin in association with lower adiponectin synthesis and increased UPR markers in SAT. Mice subjected to acute ER stress by pioglitazone administration and a low‐dose tunicamycin injection presented a maladaptive UPR activation in SAT along with reduced adiponectin synthesis and secretion and increased lipolysis with respect to VAT, associated with lipid accumulation in skeletal muscle and liver. Primary adipocytes and adipocytes differentiated from SAT exposed to pharmacologic ER stress also developed maladaptive UPR, along with reduced adiponectin synthesis and increased lipolysis with respect to those from VAT. Our results indicate that compared to VAT, SAT is more susceptible to ER stress, leading to increased lipolysis and reduced adiponectin synthesis and secretion.
The overexpression of TcAP1 endonuclease confers resistance to infective Trypanosoma cruzi trypomastigotes against oxidative DNA damage
Authors: Valenzuela Lucía , Sepúlveda Soía , Ponce Iván , Galanti Norbel , Cabrera Gonzalo 
Published: March 2018

AbstractTrypanosoma cruzi, the causative agent of Chagas’ disease survives to DNA damage generated by ROS/RNS inside to their different hosts. In recent eukaryotes, oxidative DNA damage is repaired mainly by the Base Excision Repair (BER) pathway, being essential the apurinic/apyrimidinic endonuclease activity. Using a pTREX‐gfp vector, the nucleotide sequence that encodes T. cruzi AP endonuclease TcAP1 (orthologue of human APE1) and a putative TcAP1 dominant negative (TcAP1DN), were transfectedand expressed in T. cruzi epimastigotes. TcAP1‐GFP and TcAP1DN‐GFP were expressed in those modified epimastigotes and found in the parasite nucleus. The endonucleases were purified under native conditions and the AP endonuclease activity was evaluated. While TcAP1 presents the expected AP endonuclease activity TcAP1DN does not. Moreover, TcAP1DN partially inhibits in vitro TcAP1 enzymatic activity. Transfected epimastigotes expressing TcAP1‐GFP and TcAP1DN‐GFP were differentiated to infective trypomastigotes. The infective parasites maintained both proteins (TcAP1‐GFP and TcAP1DN‐GFP) in the nucleus. The overexpression of TcAP1‐GFP in epimastigotes and trypomastigotes increases the viability of both parasite forms when exposed to oxidative stress while the expression of TcAP1DN‐GFP did not show any in vivo inhibitory effect, suggesting that endogenous TcAP1 constitutive expression overcomes the TcAP1DN inhibitory activity. Our results show that TcAP1 is important for trypomastigote survival under oxidative conditions similar to those found in infected mammalian cells, then increasing its permanence in the infected cells and the possibility of development of Chagas disease.
High expression of glutamate‐ammonia ligase is associated with unfavorable prognosis in patients with ovarian cancer
Authors: Fan Shaohua , Wang Yanyan , Zhang Zifeng , Lu Jun , Wu Zhiyong , Shan Qun , Sun Chunhui , Wu Dongmei , Li Mengqiu , Sheng Ning , Xie Ying , Zheng Yuanlin 
Published: March 2018

AbstractGlutamate‐ammonia ligase (GLUL), which is also called GS (glutamine synthetase), is the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP‐dependent reaction. Here, we found higher expression of GLUL in the ovarian cancer patients was associated with worse disease‐free survival (DFS) and overall survival (OS). In addition, GLUL was heterogeneously expressed in various ovarian cancer cells. The mRNA and protein expression levels of GLUL in NIH:OVCAR‐3 and ES‐2 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of GLUL in NIH:OVCAR‐3 or ES‐2 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK signaling pathway in NIH:OVCAR‐3 or ES‐2 cells. Our findings suggest that decreasing expression of GLUL may be a new approach that can be used for ovarian cancer treatment.
Glucocorticoids inhibit notch target gene expression in osteoblasts
Authors: Zanotti Stefano , Yu Jungeun , Adhikari Suyash , Canalis Ernesto 
Published: March 2018

AbstractGlucocorticoids in excess suppress osteoblast function and cause osteoporosis. We demonstrated that cortisol induces the expression of selected Notch receptors in osteoblasts, revealing a potential mechanism for the skeletal effects of glucocorticoids. However, it remains to be determined whether increased expression of Notch receptors results into enhanced signaling. Following activation of Notch, its intracellular domain (NICD) binds to the DNA‐associated protein recombination signal binding protein for immunoglobulin kappa‐J region (RBPJ) and induces the expression of target genes such as Hey1, Hey2, and HeyL. To determine whether glucocorticoids modulate Notch signaling in the skeleton, 1 month old wild‐type mice were administered prednisolone or placebo and sacrificed after 72 h, and gene expression was analyzed in femoral bone. Prednisolone induced Tsc22d3, a glucocorticoid target gene, and suppressed Hey1 and HeyL expression, which is indicative of inhibited Notch receptor activity or direct Hey downregulation. To determine the mechanisms of Hey suppression, wild‐type osteoblast‐enriched cells were seeded on the Notch cognate ligand Delta‐like (DLL)1 or transfected with constructs expressing the NOTCH1 NICD fragment and exposed to either cortisol or vehicle. Cortisol opposed the induction of mRNA and heterogeneous nuclear RNA for Hey1, Hey2, and HeyL by DLL1, but had no effect on mRNA stability, indicating that glucocorticoids inhibit Hey expression by transcriptional mechanisms. Transactivation studies and electrophoretic mobility shift assays revealed that cortisol did not oppose RBPJ‐mediated transcription or RBPJ/DNA interactions, respectively. In conclusion, glucocorticoids suppress expression of Hey1, Hey2, and HeyL in osteoblasts by RBPJ‐independent transcriptional mechanisms.
The effects of transient receptor potential channel (TRPC) on airway smooth muscle cell isolated from asthma model mice
Authors: Zhang Xiaoyu , Zhao Zhixin , Ma Lijun , Guo Yali , Li Xiaosu , Zhao Limin , Tian Cuijie , Tang Xueyi , Cheng Dongjun , Chen Zhuochang , Zhang Luoxian 
Published: March 2018

AbstractThis study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non‐ asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca2+ concentration and significantly induced the viability of ASMCs; whereas TRPC1 or TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of TRPC1 and TRPC3 also exerted different effects on the protein expression of growth‐related proteins p‐p38, p‐JNK, cleaved caspase‐3 and Bcl‐2, as well as on cell cycle. Finally, we found Ca2+ chelator EGTA or BAPTA‐AM significantly diminished the effects of si‐TRPC1 and si‐TRPC3 on the cell viability, cell cycle, and the protein expression of p‐p38, p‐JNK, cleaved caspase‐3, and Bcl‐2 in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially, through regulating Ca2+ influx.
LncRNA FLVCR1‐AS1 acts as miR‐513c sponge to modulate cancer cell proliferation, migration, and invasion in hepatocellular carcinoma
Authors: Zhang Kunsong , Zhao Zhenxian , Yu Junfeng , Chen Wei , Xu Qiongcong , Chen Liuhua 
Published: March 2018

AbstractIn the present study, we aimed to search for dysregulated lnRNAs in Hepatocellular carcinoma (HCC) tissues, and analyze the relationship of its expression level with the clinicopathological feature and patient prognosis. The biological function of FLVCR1‐AS1, the identified lncRNA, in the process of HCC development, and progression was investigated in vitro and in vivo. The underlying molecular mechanism was further explored. We determined FLVCR1‐AS1 expression in HCC tissues and peri‐tumor tissues by bioinformatic analysis, qRT‐PCR, Northern blot and in situ hybridization. The relationship between FLVCR1‐AS1 expression level and prognosis was determined by analyzing clinical samples. The effects of FLVCR1‐AS1 knockdown on HCC cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, FACS, and tanswell assay, respectively. Tumor xenograft model was used to determine the influence of down‐regulated FLVCR1‐AS1 on tumor growth and metastasis. lncRNA FLVCR1‐AS1 was extremely up‐regulated in HCC tissues and cell lines. FLVCR1‐AS1 expression level was positively correlated with tumor severity. FLVCR1‐AS1 knockdown remarkably inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo while induced cell apoptosis. In mechanism, FLVCR1‐AS1 acted as a competitive endogenous RNAs to sponge miR‐513c which targeted the mRNA of MET for degradation. By directly sponging miR‐513c, FLVCR1‐AS1 increased MET expression in HCC, and then promoted HCC progression. It was demonstrated that FLVCR1‐AS1 played a positive role in HCC development and progression according to the study in its mechanism, function and clinical manifestation, so that it could be expected to become a new target in HCC prevention and treatment.
DMC is not better than TMZ on intracranial anti‐glioma effects
Authors: Shi Lei , Sun Guan 
Published: March 2018

AbstractPrevious studies showed Demethoxycurcumin (DMC) has stronger anti‐glioma and anti‐GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower toxicity than TMZ on nude mice. However, this conclusion was confirmed to be wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected with U87MG‐luc cells in the caudate nucleus of the brain and treated with DMC (30 mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection. Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Western blot was used to detect the expression of p‐Akt, cleaved‐caspase‐3 and Bax. The average value of BLI showed TMZ determined a significant tumor regression while DMC had a mild regression effect on tumor growth compared with control group. Immunohistochemistry for Ki67, proliferating cell nuclear antigen (PCNA), and TUNEL demonstrated that TMZ more effectively inhibited the expression of Ki67 and PCNA, and increased the ratio of TUNEL‐positive cells in in situ tumor tissue. Western blot analysis also indicated that TMZ but not DMC more significantly decreased p‐Akt and increased cleaved‐caspase‐3 and Bax expression.These findings suggested a fact that TMZ appear to be more effective in controlling the growth of glioblastoma than DMC in an orthotopic glioblastoma xenograft model.
Crocin improves renal function by declining Nox‐4, IL‐18, and p53 expression levels in an experimental model of diabetic nephropathy
Authors: Yaribeygi Habib , Mohammadi Mohammad T. , Rezaee Ramin , Sahebkar Amirhossein 
Published: March 2018

AbstractOxidative damage, inflammation and apoptosis play significant roles in diabetic nephropathy. Previous studies demonstrated anti‐inflammatory and anti‐oxidative effects of crocin, but there is no evidence about its effects on IL‐18, NOX‐4, and p53 expression in diabetic kidneys. The aim of this study was to evaluate possible effects of crocin on improving main mechanisms underlying diabetic nephropathy. Male Wistar rats were randomly divided into four separate groups as normal (C), normal treated (CC), diabetic (D), and diabetic treated (DC) (n = 6). Diabetes was induced by a single dose of streptozotocin (40 mg/kg/intravenous). Treated groups received crocin (40 mg/kg, intraperitoneal) for 8 weeks. At the end of the 8th week of the study, all rats were sacrificed and urine, blood and tissue were collected. Levels of urea, uric acid, creatinine and glucose were determined collected sera, and proteinuria was measured in urine samples. Moreover, the contents of malondialdehyde (MDA), nitrate, and glutathione (GLT) as well as catalase (CAT) and superoxide dismutase (SOD) enzymes activities were measured. The expression of NOX‐4, IL‐18, and p53 at both mRNA and protein levels were also assessed. Hyperglycemia significantly increased proteinuria in diabetic rats (D). Also, depressed antioxidant defense system potency, but increased NOX‐4 expression and free radicals production resulting in oxidative stress, were observed. Moreover, expressions of IL‐18 (as a marker of inflammation) and p53 (as a marker of apoptosis) were increased. These outcomes were accompanied by enhanced histological damages and renal failure but, treatment with crocin improved these deteriorations, and ameliorated renal function. It potentiated renal cells antioxidant defense system and declined inflammation. Also, crocin lowered apoptosis and improved histological damages in renal cells. Oxidative stress, inflammation and apoptosis are considered three main mechanisms underlying diabetic nephropathy. Treatment with crocin prevented these deleterious effects and improved renal function under diabetic conditions.