bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein–Barr virus and thyroid cancer: The role of viral expressed proteins
Authors: Moghoofei Mohsen , Mostafaei Shayan , Nesaei Abolfazl , Etemadi Ashkan , Sadri Nahand Javid , Mirzaei Hamed , Rashidi Bahman , Babaei Farhad , Khodabandehlou Niloofar 
Published: October 2018

Background: Thyroid cancer is a common endocrine malignancy whose incidence has increased in recent years. Several internal and external risk factors are involved in the development of this cancer, such as infectious agents. Evidence supporting the role of viral infection as an etiology for the invasiveness of thyroid cancer is increasing. The aim of this study was to determine the presence of the Epstein–Barr virus (EBV) and the association between viral gene products and thyroid tumor development.Methods: Fifty‐seven thyroid cancer specimens were collected from the same number of patients as well as 18 samples from healthy controls. The presence of the EBV genome and the genotyping was examined by polymerase chain reaction (PCR). Also, an enzyme‐linked immunosorbent assay and real‐time PCR were used to measure the expression levels of viral and cellular genes.Results: The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor.Conclusion: Our results demonstrated that EBV infection may play a role in the development of thyroid tumor.
Downregulation of microRNA‐143‐5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen‐activated protein kinases 14‐dependent p38 mitogen‐activated protein kinases signaling pathway
Authors: Wang Bao‐Liang , Wang Zhi , Nan Xi , Zhang Qing‐Cai , Liu Wei 
Published: October 2018

AbstractMicroRNAs (miRNAs) play critical roles in various biological processes including cell differentiation. Some researchers suggested that the p38 mitogen‐activated protein kinases (MAPK) signaling pathway had an effect on regulating the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). This study focuses on the effects of miR‐143‐5p on hDPSCs by regulating the p38 MAPK signaling pathway. The targeting relationship of MAPK14 and miR‐143‐5p targets were verified by TargetScan and dual‐luciferase reporter gene assay. Through overexpression of miR‐143‐5p or silencing of miR‐143‐5p, expressions of miR‐143‐5p, MAPK14, Ras, MAPK kinase (MKK) 3/6, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteocalcin (OCN) were detected by reverse transcription quantitative polymerase chain reaction. Protein expressions of MAPK14, Ras, and MKK3/6 were determined by western blot analysis. ALP and alizarin red S staining were used to detect mineralization. Initially, MAPK14 was found to be negatively regulated by miR‐143‐5p. Meanwhile, the upregulated miR‐143‐5p decreased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. On the contrary, the downregulated miR‐143‐5p increased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. Furthermore, ALP activity and mineralized nodules increased after downregulation of miR‐143‐5p, and after its upregulation, ALP activity and mineralized nodules decreased. Our data suggest that poor expression of miR‐143‐5p promotes hDPSCs odontoblastic differentiation through the activation of the p38 MAPK signaling pathway by upregulating MAPK14.
Melanoma: Where we are and where we go
Authors: Mohammadpour Ali , Derakhshan Maryam , Darabi Hassan , Hedayat Pegah , Momeni Mohammad 
Published: October 2018

AbstractMelanoma is known as an aggressive tumor which shows an increasing incidence and poor prognosis in the metastatic phase. Hence, it seems that diagnosis and effective management (including early diagnosis, choosing of the effective therapeutic platform, caring, and training of patients for early detection) are major aspects of melanoma therapy. Early detection of melanoma is a key point for melanoma therapy. There are various diagnosis options such as assessing of biopsy, imaging techniques, and biomarkers (i.e., several proteins, polymorphism, and liquid biopsy). Among the various biomarkers, assessing circulating tumor cells, cell‐free DNAs, cell‐free RNAs, and microRNAs (miRNAs) have emerged as powerful diagnosis tools for melanoma patients. Deregulations of these molecules are associated with melanoma pathogenesis. After detection of melanoma, choosing of effective therapeutic regimen is a key step for recovery of melanoma patients. Several studies indicated that various therapeutic approaches including surgery, immunotherapy, systematic therapy, radiation therapy and antibodies therapy could be used as potential therapeutic candidates for melanoma therapy. Caring for melanoma patients is one of the important components of melanoma therapy. Caring and training for melanoma patients could contribute to better monitoring of patients in response to various therapeutic options. Here, we summarized various diagnosis approaches such as assessing biopsy, imaging techniques, and utilization of various biomarkers (i.e., proteins, CTCs, cfDNAs, and miRNAs) as a diagnostic biomarker for detection and monitoring patients with melanoma. Moreover, we highlighted various therapeutic options and caring aspects in patients with melanoma.
Osteochondral tissue cultures: Between limits and sparks, the next step for advanced in vitro models
Authors: Maglio Melania , Tschon Matilde , Sicuro Laura , Lolli Roberta , Fini Milena 
Published: October 2018

AbstractThe increasing demand for reliable preclinical models and to reduce, refine and, if possible, replace animal studies have brought forth the development of complex tissue cultures in different research areas, including the musculoskeletal field. In this paper, we review the literature within last 10 years on the state of progress for in vitro models of osteochondral tissue cultures, taking into account the clinical relevance of the management and treatment of osteochondral lesions. According to the selected research criteria, 35 works, 27 of which with animal tissues and 8 with human tissues, resulted to be relevant for the purposes of this review. Data analyzed revealed a great heterogeneity among the proposed tissue culture models. The anatomical harvesting sites resulted to be mainly the knee stifle joint, both for animal (prevalently bovines) and human tissues derived from joint replacement surgery, and significant heterogeneity among culture conditions and media were found. To date, very few papers have focused on the set up of a reproducible in vitro model, applicable to a variety of studies, thus suggesting a relevant gap to fill in the development of advanced three‐dimensional osteochondral culture models.
Dysregulation of microRNA‐657 influences inflammatory response via targeting interleukin‐37 in gestational diabetes mellitus
Authors: Wang Pingping , Wang Haidong , Li Cuihong , Zhang Xiaozhen , Xiu Xia , Teng Ping , Wang Zengfang 
Published: October 2018

AbstractA number of studies have implicated that microRNAs (miRNAs) play a critical role in the development of gestational diabetes mellitus (GDM). However, the role of miR‐657 in GDM remains vague up to date. We aim to investigate the modifying effect of miR‐657 on GDM, which will provide new insight into the pathogenesis of GDM and may help to identify new diagnostic or therapeutic targets for GDM. Increased expression of miR‐657 but decreased expression of interleukin‐37 (IL‐37) was observed in patients with GDM. Besides, negative association between miR‐657 and IL‐37 was demonstrated in this study. miR‐657 could targetedly regulate IL‐37 and enhance the proliferation of mononuclear macrophages. Moreover, miR‐657 promoted the generation of inflammatory cytokines (IL‐6 and tumor necrosis factor‐α [TNF‐α]) and activation of nuclear factor κB (NF‐κB) in lipopolysaccharide‐induced mononuclear macrophages, while its effect was significantly inhibited when exogenous recombinant IL‐37 was administrated into cells. Accordingly, dysregulation of miR‐657 contributes to the pathogenesis of GDM via IL‐37/NF‐κB signaling axis.
Dental pulp stem cells senescence and regenerative potential relationship
Authors: Iezzi Iolanda , Cerqueni Giorgia , Licini Caterina , Lucarini Guendalina , Mattioli Belmonte Monica 
Published: October 2018

AbstractUncomplicated treatments for pulpitis and periodontitis continues to be challenging and regenerative approaches could meet this contingency. Dental pulp stem cells (DPSCs) represent a good candidate for oral recovering therapies. Here, we investigated changes in morphology, proliferation, and in vitro differentiation toward mesenchymal and neuronal phenotypes of human DPSCs harvested from differently aged donors. Aging is a physiologic phenomenon occurring with time that hamper body’s capability to maintain homeostasis also affecting the functional reserve. Cytofluorimetric, immunohistochemical, quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), and western blot analyses were performed to gain insight for successful regenerative strategies in elderly. We observed a decline in DPSCs proliferation and differentiation potential with age. Interestingly, these cells behaved differently under osteogenic or odontogenic stimuli, showing different age‐related mineralization capabilities. Similarly, neurogenic differentiation decreased with age. In conclusion, our observations represent a valid tool for the development of tailored regenerative strategies in an aging society.
Pre‐cold acclimation improves the immune function of trachea and resistance to cold stress in broilers
Authors: Su Yingying , Wei Haidong , Bi Yanju , Wang Yanan , Zhao Peng , Zhang Runxiang , Li Xiang , Li Jianhong , Bao Jun 
Published: October 2018

AbstractAcclimation can alleviate the damage caused by adverse environmental factors. To investigate the effects of cold stimulation on immunity in tracheal of broilers, 360 one‐day‐old chicks were raised at normal temperatures during 1–7 days. From 8 day, G1 (control) continued to be raised at normal temperatures, whereas G2 and G3 (treatment groups) were cold‐stimulated at 3°C and 12°C below the temperature of G1, respectively. At 42 day, all the groups were subjected to a 24‐hr acute cold stress, designated as S1, S2, and S3. Tracheal tissues were collected to detect gene levels of immunoglobulins, antimicrobial peptides, Hsps, and cytokines, and oxidative stress‐related indicators at 14 day, 42 day, and 43 day, and protein levels of Hsps and proinflammatory cytokines as well as morphology changes at 42 day and 43 day. The results showed that, compared with 42G1, tracheal structure of 42G2 was basically intact, and gene levels of immunoglobulins and antimicrobial peptides increased (p < 0.05), whereas tracheal structure of 42G3 was destroyed, with decreased levels of immunoglobulins (
p < 0.05), and increased levels of Hsps and proinflammatory cytokines (
p < 0.05). At 43 day, tracheal damage was visible and gene levels of immunoglobulins and antimicrobial peptides decreased in S1 (
p < 0.05). Tracheal structure was relatively intact and gene levels of antimicrobial peptides increased in S2 (
p < 0.05). Compared with S1 and S3, immune‐related gene levels in S2 were higher, and Hsps and proinflammatory cytokines levels were lower. The results demonstrate that cold stimulation of lower 3°C from 8 to 42 day led to cold acclimation, which improved immunity of tracheal mucosa and resistance to cold stress in broilers.
Albumin induces CD44 expression in glomerular parietal epithelial cells by activating extracellular signal‐regulated kinase 1/2 pathway
Authors: Zhao Xueying , Chen Xiaoming , Chima Ashmeer , Zhang Yuanyuan , George Jasmine , Cobbs Alyssa , Emmett Nerimiah 
Published: October 2018

AbstractDe novo expression of CD44 in glomerular parietal epithelial cells (PECs) leads to a prosclerotic and migratory PEC phenotype in glomerulosclerosis. However, the regulatory mechanisms underlying CD44 expression by activated PECs remain largely unknown. This study was performed to examine the mediators responsible for CD44 induction in glomerular PECs in association with diabetes. CD44 expression and localization were evaluated in the glomeruli of Zucker diabetic rat kidneys and primary cultured PECs upon albumin stimulation. Real‐time polymerase chain reaction confirmed an albuminuria‐associated upregulation of the CD44 gene in the glomeruli of diabetic rats. Immunostaining analysis of diabetic kidneys further revealed an increase in CD44 in hypertrophic PECs, which often contain albumin‐positive vesicles. Losartan treatment significantly attenuated albuminuria and lowered CD44 protein levels in the diabetic kidneys. In primary cultured rat PECs, rat serum albumin (0.25–1 mg/ml) caused a dose‐dependent upregulation of CD44, claudin‐1, and megalin protein expression, which was accompanied by an activation of extracellular signal‐regulated kinase1/2 (ERK1/2) signaling. Albumin‐induced CD44 and claudin‐1 expression were greatly suppressed in the presence of the ERK1/2 inhibitor, U0126. In addition, knockdown of megalin by small interfering RNA interference in PECs resulted in a significant reduction of albumin‐induced CD44 and claudin‐1 proteins. Taken together, our results demonstrate that albumin induces CD44 expression by PECs via the activation of the ERK signaling pathway, which is partially mediated by endocytic receptor megalin.
Mesenchymal stem cells overexpressing heme oxygenase‐1 ameliorate lipopolysaccharide‐induced acute lung injury in rats
Authors: Chen Xuxin , Wu Shanshan , Tang Lu , Ma Lei , Wang Fan , Feng Huasong , Meng Jiguang , Han Zhihai 
Published: October 2018

AbstractAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and potentially lethal clinical syndromes characterized by acute respiratory failure resulting from excessive pulmonary inflammation, noncardiogenic pulmonary edema, and alveolar–capillary barrier disruption. At present, there is no effective and specific therapy for ALI/ARDS. Mesenchymal stem cells (MSCs) have well‐known therapeutic potential in patients with ALI/ARDS. Heme oxygenase‐1 (HO‐1), a cytoprotective enzyme, possesses antioxidative, anti‐inflammatory, and antiapoptotic effects. Thus, a combination of MSC transplantation with HO‐1 delivery may have an additional protective effect against ALI/ARDS. This study investigated the effect of HO‐1‐modified bone‐marrow–derived MSCs (MSCs‐HO‐1) on lipopolysaccharide (LPS)‐induced ALI and its underlying mechanisms. We established MSCs‐HO‐1 through lentiviral transduction. The ALI rat model was established by successive LPS inhalations following injection with MSCs‐HO‐1. The survival rate, histological changes in the lungs, total protein concentration and neutrophil counts in bronchoalveolar lavage fluid, lung wet/dry weight ratio, cytokine levels in serum and lungs, nuclear transcription factor‐κB activity, and protein expression of Toll‐like receptor 4 signaling adaptors were examined. Furthermore, the cell viability, apoptosis, and paracrine activity of MSCs‐HO‐1 were examined under inflammatory stimuli in vitro. MSCs‐HO‐1 injection improved these parameters compared with primary unmodified MSCs. Moreover, MSCs‐HO‐1 had superior prosurvival and antiapoptotic properties and enhanced paracrine functions in vitro. Therefore, MSCs‐HO‐1 exert an enhanced protective effect to alleviate LPS‐induced ALI in rats, and the mechanisms may be partially associated with superior prosurvival, antiapoptosis, and enhanced paracrine functions of MSCs‐HO‐1. These findings provide a novel insight into MSC‐based therapeutic strategies for treating ALI/ARDS.
Hypoxia‐induced tRNA‐derived fragments, novel regulatory factor for doxorubicin resistance in triple‐negative breast cancer
Authors: Cui Yangyang , Huang Yue , Wu Xiaowei , Zheng Mingjie , Xia Yiqin , Fu Ziyi , Ge Han , Wang Shui , Xie Hui 
Published: October 2018

AbstractTriple‐negative breast cancer (TNBC) is an aggressive subtype of epithelial breast malignancy, and chemoresistance is the major obstacle for cancer therapy. TNBC is associated with a hypoxic phenotype, and hypoxia contributes to the chemoresistance in breast cancer. Transfer RNA‐derived fragments (tDRs) represent a new class of small noncoding RNAs that can be induced specifically by hypoxia. Here, we conducted a comparative analysis of the aberrant expression of tDRs in hypoxia‐treated TNBC cell lines through the use of high‐throughput sequencing technique. Quantitative real‐time polymerase chain reaction was used to validate the differently expressed tDRs between two samples. The results showed that tDR‐0009 [derived from transfer RNA (tRNA)Gly‐GCC‐1‐1] and tDR‐7336 (derived from tRNA
Gly‐GCC‐1–2) were significantly upregulated when the SUM‐1315 cell lines were stimulated by hypoxia. Gene ontology (GO) and pathway analysis indicated that these two upregulated tDRs were mainly involved in maintenance of stem cell population and cellular response to interleukin (IL)‐6, which may be the underlying mechanism of hypoxia‐induced tDRs that facilitate the doxorubicin resistance in TNBC. The protein–protein interaction network for predicted target genes established by the STRING database manifested that tDR‐0009 (tDR‐7336) might be involved in the chemoresistance of TNBC via regulation of the activation of phosphorylation of STAT3. In summary, our study provided a comprehensive analysis of the deviant expression profiling of tDRs in hypoxia‐treated TNBC cell lines. Specific tDRs may be a new class of regulatory factors involved in the hypoxia‐induced chemoresistance in TNBC, and they could serve as potential biomarkers and intervention targets.
High fat diet reduces the expression of miRNA‐29b in heart and increases susceptibility of myocardium to ischemia/reperfusion injury
Authors: Guedes Elaine Castilho , da Silva Ivson Bezerra , Lima Vanessa Morais , Miranda Juliane B. , Albuquerque Rudá P. , Ferreira Julio C. B. , Barreto‐Chaves Maria Luiza M. , Diniz Gabriela Placoná 
Published: October 2018

AbstractSeveral studies have shown the role of microRNAs (miRNAs) in myocardial dysfunction in response to ischemia/reperfusion (I/R). In this study, we investigated the impact of high fat (HF) diet in the myocardial susceptibility to I/R injury, as well as in the expression of miRNA‐29b. Isolated heart experiments using the ex vivo Langendorff perfusion model were used to induce cardiac I/R injury. HF diet‐induced cardiac hypertrophy and impaired cardiac functional recovery after I/R. miRNA‐29b, which targets Col1, was reduced in the heart of HF diet‐fed mice, whereas the cardiac expression of Col1 was increased. In addition, hypoxia–reoxygenation (H/R) reduced the expression of miRNA‐29b in cardiomyoblasts cultures. However, the overexpression of miRNA‐29b in cardiomyoblasts reduced p53 mRNA levels and H/R injury, suggesting that downregulation of miRNA‐29b may be involved in I/R injury. Together, our findings suggest that the reduced expression of miRNA‐29b may be involved in the deteriorated cardiac functional recovery following I/R in obese mice.
microRNA modified tumor‐derived exosomes as novel tools for maturation of dendritic cells
Authors: Taghikhani Adeleh , Hassan Zuhair Mohammad , Ebrahimi Marzieh , Moazzeni Seyyed‐Mohammad 
Published: October 2018

AbstractTumor‐derived exosomes (TEX) are known by their immune suppression effects as well as initiation mediators in cancer progression and metastasis. Meanwhile, they are appropriate sources to induce immunity against tumor cells, as consist of tumor specific and associated antigens. The aim of the current study is modifying TEX with microRNA miR‐155, miR‐142, and let‐7i, to enhance their immune stimulation ability and induce potent dendritic cells (DC). For this, exosomes were isolated from mouse mammalian breast cancer cell line; 4T1, and subjected to miR‐155, miR‐142, and let‐7i by electroporation. Immature DCs were generated from mouse bone marrow in the presence of interleukin‐4 (IL‐4) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). To mature DCs, lipopolysaccharide (LPS), TEX, and modified TEX were used. The expression level of miRNAs and their target genes (IL‐6, IL‐17, IL‐1b, TGFβ, SOCS1, KLRK1, IFNγ, and TLR4) was determined. TEX were nanovesicles with spheroid morphology which expressed CD81, CD63, and TSG101, as exosome markers, at protein level. MHCII, CD80, and CD40 as maturation markers were assessed by flow cytometry. Overexpression of miRNAs were confirmed in exosomes and mDCs. Up and downregulation of target genes confirmed the gene network in DC maturation. We found that Let‐7i could efficiently induce the DC maturation, as well as miR‐142 and miR‐155 have enhancing effects. These findings reveal that the modified TEX would be a hopeful cell‐free vaccine for the cancer treatment.
Effects of macrophages and CXCR2 on adipogenic differentiation of bone marrow mesenchymal stem cells
Authors: Cao Dingding , Ma Feifei , Ouyang Shengrong , Liu Zhuo , Li Yuanyuan , Wu Jianxin 
Published: October 2018

AbstractMacrophages and many chemokines are closely associated with the adipogenic differentiation of bone marrow mesenchymal stem cells (MSCs), but their roles in adipogenesis and the underlying mechanisms are not fully understood. Here, we first investigated the influence of macrophages on the differentiation of MSCs in vitro. We found that RAW246.7 macrophages cocultured with MSCs strongly blocked the differentiation progress and inhibited the expression of C‐X‐C motif chemokine ligand 1 (CXCL1) during adipogenesis. Coculture with MSCs mainly induced macrophages toward M2 polarization. In addition, the expression of CXCL1 and its receptor, C‐X‐C chemokine receptor type 2, CXCR2 are high during adipogenic differentiation of MSCs and not in mature adipocytes. Although CXCL1 had no effect on adipogenesis, treatment with a specific CXCR2 inhibitor, SB225002, hampered the adipogenic differentiation of MSCs. Blocking CXCR2 decreased p38 and Elk1 phosphorylation but increased the extracellular signal–regulated kinase (ERK) phosphorylation at the initial stage of adipogenesis, which suppressed the phosphorylation of p38/ERK‐Elk1 at the late stage. Inhibition of ERK had similar effects on adipogenesis and Elk1 phosphorylation. Our data suggest that MSCs interact with macrophages during adipogenic differentiation. CXCR2 regulates the adipogenic differentiation of MSCs by altering the activation of the p38/ERK‐Elk1 signaling pathway.