bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA and exosome: Key players in rheumatoid arthritis
Authors: Zakeri Zahra , Salmaninejad Arash , Hosseini Nayyerehalsadat , Shahbakhsh Yas , Fadaee Elyas , Shahrzad Mohammad Karim , Fadaei Sara 
Published: March 2019

AbstractRheumatoid arthritis (RA) is known as one of important autoimmune disorders which can lead to joint pain and damage throughout body. Given that internal (ie, genetic and epigenetic alterations) and external factors (ie, lifestyle changes, age, hormones, smoking, stress, and obesity) involved in RA pathogenesis. Increasing evidence indicated that cellular and molecular alterations play critical roles in the initiation and progression of RA. Among various targets and molecular signaling pathways, microRNAs (miRNAs) and their regulatory networks have key roles in the RA pathogenesis. It has been showed that deregulation of many miRNAs involved in different stages of RA. Hence, identification of miRNAs and their signaling pathways in RA, could contribute to new knowledge which help to better treatment of patients with RA. Besides miRNAs, exosomes have been emerged as key messengers in RA pathogenesis. Exsosomes are nanocarriers which could be released from various cells and lead to changing of behaviors recipient cells via targeting their cargos (eg, proteins, messenger RNAs, miRNAs, long noncoding RNAs, DNAs). Here, we summarized several miRNAs involved in RA pathogenesis. Moreover, we highlighted the roles of exosomes in RA pathogenesis.
miR‐224‐5p inhibits proliferation, migration, and invasion by targeting PIK3R3/AKT3 in uveal melanoma
Authors: Li Jianchang , Liu Xiuming , Li Chaopeng , Wang Wenqi 
Published: March 2019

AbstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults. Accumulating investigations have identified the aberrant expression of miRNAs (microRNAs) in UM, such as miR‐181, miR‐20a, miR‐144, miR‐146a. The purpose of this study is to investigate the biological function of miR‐224‐5p in UM. The expression of miR‐224‐5p, PIK3R3, and AKT3 in 30 tumor tissues and paired adjacent noncancerous tissues were analyzed using Western blot analysis and quantitative real‐time polymerase chain reaction (qRT‐PCR) assays. Cell proliferation assay, transwell assay, and wound healing assay were used to measure the effects of miR‐224‐5p on the motility of UM in vitro. Western blot analysis and luciferase assays were used to detect the expression of PIK3R3 and AKT3 as miR‐224‐5p downstream targets. The results of Western blot analysis and qRT‐PCR assays indicated that the expression of miR‐224‐5p was lower in UM tissues compared to normal tissue, while the expression of PIK3R3 and AKT3 were simultaneously increased. Upregulation of miR‐224‐5p significantly inhibited capacities of proliferation, invasion, and migration of OCM‐1A cells and decreased expression of PIK3R3 and AKT3. Luciferase assay demonstrated PIK3R3 and AKT3 as downstream targets of miR‐224‐5p. Moreover, upregulating PIK3R3 and AKT3 restrained miR‐224‐5p‐induced inhibition of the motility of OCM‐1A cells. Thus, our study proved that miR‐224‐5p was involved in proliferation, invasion, and migration of UM cells via regulation the expression of PIK3R3 and AKT3. And the results also established a miR‐224‐5p/PIK3R3/PI3K/AKT axis in the regulation of UM progression, providing an experimental basis for further exploring the miR‐224‐5p as a therapeutic and diagnosis target for patients with UM.
Expression profiling of long noncoding RNAs associated with vasculogenic mimicry in osteosarcoma
Authors: Ren Ke , Ni Yicheng , Li Xingjia , Wang Chen , Chang Qing , Li Yonggang , Gao Zengxin , Wu Sujia , Shi Xin , Song Jie , Yao Nan , Zhou Jing 
Published: March 2019

AbstractOsteosarcoma (OS) is the most common highly malignant bone tumor in teens. Vasculogenic mimicry (VM) is defined as de novo extracellular matrix‐rich vascular‐like networks formed by highly aggressive tumor cells. We previously reported the presence of VM and it is an unfavorable prognostic factor in OS patients. Long noncoding RNAs (lncRNAs) are aberrantly expressed in OS and involved in cancer cell VM. However, lncRNAs in VM formation of OS have not been investigated. We, therefore, profiled the expression of lncRNAs in highly aggressive OS cell line 143B compared with its parental poorly aggressive cell line HOS. The differentially expressed (DE) lncRNAs and messenger RNA (mRNAs) were subjected to constructed lncRNA‐mRNA coexpressed network. The top‐ranked hub gene lncRNA n340532 knockdown 143B cells were used for in vitro and in vivo VM assays. The annotation of DE lncRNAs was performed according to the coexpressed mRNAs by Gene Ontology and pathway analysis. A total of 1360 DE lncRNAs and 1353 DE mRNAs were screened out. lncRNA MALAT1 and FTX, which have known functions related to VM formation and tumorigenesis were identified in our data. The coexpression network composed of 226 lncRNAs and 118 mRNAs in which lncRNA n340532 had the highest degree number. lncRNA n340532 knockdown reduced VM formation in vitro. The suppression of n340532 also exhibited potent anti‐VM and antimetastasis effect in vivo, suggesting its potential role in OS VM and metastasis. Furthermore, n340532 coexpressed with 10 upregulation mRNAs and 3 downregulation mRNAs. The enriched transforming growth factor‐β signaling pathway, angiogenesis and so forth were targeted by those coexpressed mRNAs, implying n340532 may facilitate VM formation in OS through these pathways and gene functions. Our findings provide evidence for the potential role of lncRNAs in VM formation of OS that could be used in the clinic for anti‐VM therapy in OS.
Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis
Authors: Zeng Fanfan , Liu Hongbo , Lu Di , Liu Qianqian , Chen Huoying , Zheng Fang 
Published: March 2019

AbstractPsoriasis is a common inflammatory skin disease mediated by cells and molecules in both the innate and adaptive immune systems. Recently, gene expression profile analysis revealed a large set of immune‐related differentially expressed genes (DEGs) in psoriasis. However, the associations between these DEGs and their transcriptional regulation mechanisms have not been completely elucidated. In this study, several psoriasis Gene Expression Omnibus data sets were systematically analyzed using bioinformatics tools to uncover important transcription factors (TFs) that regulate the expression of immune‐related DEGs and further enhance our understanding of psoriasis pathogenesis. Common DEGs encoding chemokines, cytokines, antimicrobial peptides, and keratins were identified in psoriasis, and extensive correlations existed among these DEGs. Several common TFs that bind the promoters of the DEGs, including the well‐known signal transducer and activator of transcription 1 (STAT1), STAT3, and nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) as well as ETS homologous factor (EHF), Fos‐like antigen 1 (FOSL1), and Forkhead box C1 (FOXC1), which are rarely studied in psoriasis, were also identified. STAT1, EHF, FOSL1, STAT3, and NFKB1 were positively correlated with these DEGs in psoriasis lesions, whereas FOXC1 was negatively correlated with most DEGs. The decreased expression of the DEGs was accompanied by the downregulation of STAT1, EHF, FOSL1, STAT3, and NFKB1 and the upregulation of FOXC1 upon blocking interleukin 17 (IL‐17) or tumor necrosis factor α signaling in psoriasis. Additionally, the downregulation of IL37 in psoriasis was negatively correlated with STAT1 and CXCL10, which are associated with Th1 responses. These results suggest that TFs play an important role in the pathogenesis of psoriasis, and interfering with the activity of key TFs may be a promising therapeutic strategy for psoriasis.
Docosahexaenoic acid enhances M2 macrophage polarization via the p38 signaling pathway and autophagy
Authors: Kawano Aki , Ariyoshi Wataru , Yoshioka Yoshie , Hikiji Hisako , Nishihara Tatsuji , Okinaga Toshinori 
Published: March 2019

AbstractMacrophages, critical modulators of the immune response, polarize into various phenotypes, including M1 and M2. M1 macrophages are typically activated by lipopolysaccharide and produce proinflammatory cytokines. Conversely, M2 macrophages are activated by stimulation with interleukin 4 (IL)−4 and promote tissue remodeling and anti‐inflammatory reactions. Recently, polyunsaturated fatty acids (PUFAs) have been shown to play important roles in the regulation of inflammation. Docosahexaenoic acid (DHA), a PUFA, has anti‐inflammatory effects on chronic inflammatory disease, but its role in macrophage polarization remains unclear. In this study, we clarified the effects of DHA on macrophage polarization using U937 cells. Treatment with DHA resulted in upregulation of M2 macrophage markers and increased secretion of anti‐inflammatory cytokines by U937 cells. IL‐4, but not DHA, triggered phosphorylation of signal transducer and activator of transcription 6 (STAT6). DHA enhanced the expression of krüppel‐like factor‐4 (KLF4), a transcription factor involved in the regulation of macrophage polarization and increased the phosphorylation of p38 mitogen‐activated protein kinase (MAPK). A selective inhibitor of p38 MAPK downregulated the expression of CD206 in DHA‐treated U937 cells. Moreover, inhibitors of autophagy suppressed the phosphorylation of p38 MAPK and the expression of CD206 in DHA‐treated U937 cells. Expression of microtubule‐associated protein light chain 3‐II, which is involved in autophagosome formation, was enhanced in DHA‐treated U937 cells. Taken together, these results indicated that DHA enhanced the expression of M2 macrophage markers through the p38 MAPK signaling pathway and autophagy, suggesting that DHA regulates M2 macrophage polarization and plays an important role in innate immunity.
c‐Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T‐cell lymphoma
Authors: Zhu Linan , Zhang Xudong , Fu Xiaorui , Li Zhaoming , Sun Zhenchang , Wu Jingjing , Wang Xinhua , Wang Feng , Li Xiangke , Niu Songtao , Ding Mengjie , Yang Zhenzhen , Yang Wanqiu , Yin Meifeng , Zhang Lei , Zhang Mingzhi 
Published: March 2019

AbstractNasal‐type natural killer/T‐cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c‐Myc and SNHG12 expression was upregulated in NKTCL cell lines. c‐Myc‐ and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T‐cell lymphoma cell line YTS cells, and c‐Myc and SNHG12‐downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK‐6 cells. Moreover, c‐Myc‐ and SNHG12 overexpression increased Ki67 and P‐gp expression in YTS cells, whereas c‐Myc and SNHG12‐downregulation reduced the Ki67 and P‐gp expression in SNK‐6 cells. Correlational analyses revealed that c‐Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c‐Myc and c‐Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c‐Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c‐Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL.
Angiotensin‐converting enzyme inhibitors attenuated advanced glycation end products‐induced renal tubular hypertrophy via enhancing nitric oxide signaling
Authors: Hwang Jean‐Yu , Kan Wei‐Chih , Liu Yao‐Bin , Chuang Lea‐Yea , Guh Jinn‐Yuh , Yang Yu‐Lin , Huang Jau‐Shyang 
Published: March 2019

AbstractAdvanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin‐converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE‐induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3′,5′‐cyclic monophosphate (cGMP) synthesis, and cGMP‐dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP), and the PKG activator 8‐para‐chlorophenylthio‐cGMPs (8‐pCPT‐cGMPs). In addition, AGE‐enhanced activation of extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK), and p38 mitogen‐activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8‐pCPT‐cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE‐induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8‐pCPT‐cGMPs decreased protein levels of fibronectin, p21
Waf1/Cip1, and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE‐increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway.
Small regulatory polypeptide of amino acid response negatively relates to poor prognosis and controls hepatocellular carcinoma progression via regulating microRNA‐5581‐3p/human cardiolipin synthase 1
Authors: Yin Jian , Liu Qian , Chen Chao , Liu Wenxiang 
Published: March 2019

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies with extremely high rates of occurrence and death. Long noncoding RNAs (lncRNAs) have been increasingly revealed to participate in tumorigenesis and development of multiple human cancers, including HCC. LINC00961 is a novel lncRNA which has been uncovered as a tumor suppressor in lung cancer and glioma. However, the role of LINC00961 in HCC has never been probed yet. Herein, we revealed a marked downregulation of LINC00961 in HCC tissues and cell lines. Correlation of low LINC00961 expression with poor outcomes in patients with HCC suggested LINC00961 as an independent predictor for HCC prognosis. Functionally, LINC00961 overexpression obviously inhibited cell proliferation, migration, and invasion in HCC cells. Mechanistically, LINC00961 regulated cardiolipin synthase 1 (CRLS1) expression via sponging miR‐5581‐3p. Importantly, both miR‐5581‐3p upregulation and CRLS1 inhibition led to an acceleration in cellular processes in HCC cells. At length, the rescue assays suggested that LINC00961 functioned in HCC through the miR‐5581‐3p/CRLS1 axis. On the whole, our findings disclosed that LINC00961 played a suppressive role in HCC progression via modulating miR‐5581‐3p/CRLS1, thus providing a potentially effective target for the prognosis and treatment of patients with HCC.
Long‐chain noncoding RNA GAS5 mediates oxidative stress in cardiac microvascular endothelial cells injury
Authors: Diao Liwei , Bai Long , Jiang Xingpei , Li Jianjun , Zhang Qinghua 
Published: March 2019

AbstractThis study is performed to figure out the role of long‐chain noncoding RNA growth‐arrest specific transcript 5 (GAS5) in homocysteine (HCY)‐induced cardiac microvascular endothelial cells (CMECs) injury. CMECs were cultured and the model of CMECs injury was established by coincubation with HCY. To construct stable overexpression of GAS5 cells, the expression of GAS5, microRNA‐33a‐5p (miR‐33a‐5p) and ATP‐binding cassette transporter A1 (ABCA1), and biological characteristics of cells were determined. The messenger RNA (mRNA) level and secretion of vascular endothelial growth factor (VEGF), activity of reactive oxygen species (ROS) and superoxide dismutase (SOD), and the content of malondialdehyde (MDA) were measured. The binding site between GAS5 and miR‐33a‐5p and between miR‐33a‐5p and ABCA1 was verified. CMECs were successfully cultured. Reduction of GAS5 expression and ABCA1 expression together with increased expression of miR‐33a‐5p was found in CMECs induced by HCY. After overexpression of GAS5, there showed increased proliferative activity, decreased cell apoptosis rate and apoptosis index, enhanced cell migration ability, increased number of lumen formation, increased mRNA expression of VEGF in cells and the secretion in the supernatant, decreased activity of ROS and SOD in cells, and decreased content of ROS in cells. miR‐33a‐5p could promote the enrichment of GAS5 and ABCA1 was the direct target gene of miR‐33a‐5p. Our study suggests that the low expression of GAS5 was observed in HCY‐induced CMECs injury, and the upregulation of GAS5 could attenuate HCY‐induced CMECs injury by mediating oxidative stress, and its mechanism is related to the upregulation of ABCA1 expression by competitively binding with miR‐33a‐5p.
Characterization of metabolic profiles and lipopolysaccharide effects on porcine vascular wall mesenchymal stem cells
Authors: Nesci Salvatore , Bernardini Chiara , Salaroli Roberta , Zannoni Augusta , Trombetti Fabiana , Ventrella Vittoria , Pagliarani Alessandra , Forni Monica 
Published: March 2019

AbstractThe link between metabolic remodeling and stem cell fate is still unclear. To explore this topic, the metabolic profile of porcine vascular wall mesenchymal stem cells (pVW‐MSCs) was investigated. At the first and second cell passages, pVW‐MSCs exploit both glycolysis and cellular respiration to synthesize adenosine triphosphate (ATP), but in the subsequent (third to eighth) passages they do not show any mitochondrial ATP turnover. Interestingly, when the first passage pVW‐MSCs are exposed to 0.1 or 10 μg/ml lipopolysaccharides (LPSs) for 4 hr, even if ATP synthesis is prevented, the spare respiratory capacity is retained and the glycolytic capacity is unaffected. In contrast, the exposure of pVW‐MSCs at the fifth passage to 10 μg/ml LPS stimulates mitochondrial ATP synthesis. Flow cytometry rules out any reactive oxygen species (ROS) involvement in the LPS effects, thus suggesting that the pVW‐MSC metabolic pattern is modulated by culture conditions via ROS‐independent mechanisms.
Histone demethylase KDM6B regulates 1,25‐dihydroxyvitamin D3‐induced senescence in glioma cells
Authors: Sui Aixia , Xu Yongbing , Pan Baogen , Guo Tao , Wu Jiang , Shen Yongqing , Yang Junjie , Guo Xiaoqiang 
Published: March 2019

AbstractVitamin D is a fat‐soluble vitamin and plays an important role in calcium absorption and bone development, whose lack can cause a variety of diseases, including cancer. Human epidemiological studies suggested that vitamin D3 deficiency might increase glioma incidence, but molecular mechanism is less understood. In this study, we show that 1,25‐dihydroxyvitamin D3 (the active form of vitamin D3) induces senescence of glioma cells and increases the expression of senescence markers, INK4A and cyclin‐dependent kinase inhibitor 1A (CDKN1A). 1,25‐Dihydroxyvitamin D3 also upregulates the expression of histone demethylase, KDM6B. Knockdown of KDM6B attenuates 1,25‐dihydroxyvitamin D3‐induced senescence and upregulation of INK4A and CDKN1A. KDM6B promotes the transcription of INK4A by eliminating the trimethylation of repressive marker H3K27me3 near its promoter. This study reveals a new regulatory mechanism involved in vitamin D3 inhibition on gliomas, which is beneficial to prevention and adjuvant therapy of glioma.
Influence of mandibular third molar surgical extraction on the periodontal status of adjacent second molars
Authors: Passarelli Pier Carmine , Lajolo Carlo , Pasquantonio Guido , D'Amato Giuseppe , Docimo Raffaella , Verdugo Fernando , D'Addona Antonio 
Published: March 2019

AbstractBackgroundThe periodontal health distal of second molars (M2) is often compromised because of third molar (M3) impactions. The aim of this study was to evaluate healing and periodontal status of mandibular M2 after M3 surgical extraction.MethodsEighty‐nine consecutive patients with 89 asymptomatic M3 who needed surgical extraction of one fully‐ or semi‐impacted M3 entered this study. Clinical measurements, probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), gingival index (GI), and bleeding on probing (BOP), were compared for M2 at baseline (T0) and 6‐months (T1) postsurgical extraction. Multiple logistic regression analysis assessed different risk factors for postoperative changes of periodontal parameters.ResultsSix‐month M2 PPD improved at disto‐vestibular (T0‐5.2/T1‐3.0 mm) and disto‐lingual (T0‐5.4/T1‐3.2 mm) sites. The average attachment gains at T1 were 1.9 and 2 mm, respectively (P < 0.05). BOP, PI, and GI showed significant clinical improvements after extractions. Fifty‐three out of 72 (73.6%) M2 presenting a PPD ≥ 4mm at baseline healed at 6 months recall without periodontal pockets. Older age (mean 55 years, SD 16.7; range 26 to 81) and mean distal PPD at baseline of 7 mm was more likely to be associated with PPD ≥ 4 mm 6 months postextraction (P < 0.05). Past history of periodontitis patients were 41 times more likely to present PPD ≥ 4 mm after healing (OR = 41.4; 95% CI = 10.9 to 156.5, P < 0.05).ConclusionMandibular M3 extractions seem to improve overall periodontal health distal of M2. History of periodontitis, preoperative deep pockets and older age are independent risk factors for poorer healing and residual pockets after M3 surgical extraction.
Dealing with an insufficient future liver remnant: Portal vein embolization and two‐stage hepatectomy
Authors: Kawaguchi Yoshikuni , Lillemoe Heather A. , Vauthey Jean‐Nicolas 
Published: March 2019

AbstractColorectal liver metastases (CLM) are not always resectable at the time of diagnosis. An insufficient future liver remnant is a factor excluding patients from curative intent resection. To deal with this issue, two‐stage hepatectomy was introduced approximately 20 years ago. It is a sequential treatment strategy for bilateral CLM, which consists of preoperative chemotherapy, portal vein embolization, and planned first and second liver resections. This study reviews current evidence supporting use of two‐stage hepatectomy.
“Green cannibalism” or an “organic inside job”? Empirical insights into the rivalry of ethical grocery types
Authors: Frank Phillip , Brock Christian 
Published: March 2019

AbstractDespite having favorable purchase intentions toward organic groceries, the respective purchase behavior falls often short. This so‐called intention–behavior gap is investigated by exploring the impact of competing ethical products fulfilling green consumption motives (“green fit”) as well or lacking credibility of organic groceries on organic purchase behavior. The first two studies (n
1 = 225;
n
2 = 321) assessing actual and reported purchase behavior are testing the impact of perceived substitutability of local and fair trade alternatives compared with organic groceries. A third study (
n
3 = 145) examines the impact of food miles and packaging on perceived product quality and credibility as possible reasons for a lacking “green fit” of organic groceries in terms of an experimental design. Local (fair trade) and organic groceries are perceived as substitute (complementary) alternatives. Additionally, local (organic) “green fit” impedes (enhances) the transformation from organic intentions into a respective purchase behavior. Wrapped organic produces with high food miles are linked to lower quality and credibility perceptions, reducing organic sales rates in favor of local groceries.