bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines
Authors: Naghizadeh Sanaz , Mansoori Behzad , Mohammadi Ali , Kafil Hossein Samadi , Mousavi Zohreh , Sakhinia Ebrahim , Baradaran Behzad 
Published: October 2018

AbstractBackgroundAlthough there are multiple treatments for lung cancer, the death rate of this cancer remains high because of metastasis in earlier stages. So a novel treatment for overcoming metastasis is urgently needed. Overexpression of high‐mobility group AT‐hook 2 (HMGA2), a nonhistone chromosomal protein has been observed in metastatic cancers. So, we suggested that HMGA2 upregulation may play a critical role in treating lung cancer.MethodsThe A549 cells were transfected with specific HMGA2 small interfering RNA (siRNA) using transfection reagent. Relative HMGA2 and matrix metallopeptidase 1 (MMP1), C‐X‐C chemokine receptor type 4 (CXCR4), vimentin, and E‐cadherin messenger RNA expression levels were measured by quantitative real‐time polymerase chain reaction. To diagnose cytotoxic effect of HMGA2 siRNA and other components of transfection process, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was applied. The migration capacity after transfection with HMGA2 siRNA was detected by wound‐healing assay.ResultsHMGA2 siRNA significantly reduced HMGA2 expression in a dose‐dependent manner 48 hours after transfection. Expression levels of MMP1, vimentin, and CXCR4 were reduced, but E‐cadherin level was not changed meaningfully. HMGA2 knockdown significantly reduced cell survival rate and also led to the inhibition of cell migration.ConclusionsOur results indicated that RNA interference by downregulation of HMGA2 gene expression and affecting downstream genes led to the inhibition of cell migration and proliferation. Therefore, HMGA2 siRNA might be an alternative treatment option for metastatic lung cancer.
Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo
Authors: Wei Gejin , Liang Tihong , Wei Chengming , Nong Xiaolian , Lu Qiteng , Zhao Jinmin 
Published: October 2018

AbstractWear particle–induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle–induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle–induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti‐inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle–induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle–induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow–derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast‐related signaling pathways. The results showed that arctigenin inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose‐dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF‐κB) ligand–induced NF‐κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast‐related osteolytic diseases caused by excessive osteoclast formation.
The relationship between homeobox B7 expression and the clinical characteristics of patient with prostate cancer
Authors: Song Zhangxing , Liao Zhaolin , Cui Yingdong , Yang Chao 
Published: October 2018

AbstractBackgroundThe prognosis of patients with prostate cancer (PCa) remains poor.MethodsGSE16560, GSE32448, GSE79957, GSE17951, and TCGA‐PRAD were reanalyzed to evaluate the expression of homeobox B7 (HOXB7) between PCa tissues and normal prostate tissues and to characterize the correlation between the expression of HOXB7 and the clinicopathological features of patients with PCa. Gene set enrichment analysis was conducted to investigate the mechanisms.ResultsHOXB7 was upregulated in PCa tissues (P = 0.0005). Both the univariate and multivariate analyses demonstrated that the expression of HOXB7 was correlated with the Gleason score and TNM staging of patients with PCa. The Gleason score and TNM staging were higher in the HOXB7 high expression group. The overall survival (hazard ratio [HR] = 0.632; 95% confidence interval [CI]: 0.4773‐0.8369;
P = 0.0014) and progression‐free survival (HR = 0.544; 95% CI: 0.3157‐0.9373;
P = 0.0283) favored patients with PCa in HOXB7 low expression group over those in HOXB7 high expression group. PCa samples in HOXB7 low expression group were enriched in gene sets associated with the epithelial mesenchymal transition, apical junction, angiogenesis, ultraviolet response, and hypoxia.ConclusionsHOXB7 might be an independent prognostic factor of patients with PCa.
SEMA3B‐AS1‐inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis
Authors: Zhang Chen , Zhu Yun , Liu Yugang , Zhang Xiguang , Yue Qiaoning , Li Li , Chen Yatang , Lu Sheng , Teng Zhaowei 
Published: October 2018

AbstractHuman mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair‐related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B‐AS1 regulating hMSCs osteogenesis. SEMA3B‐AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B‐AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B‐AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix–receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B‐AS1 is a target for controlling osteogenesis of hMSCs.
Identification of a crucial amino acid responsible for the loss of specifying FGFR1–KLB affinity of the iodinated FGF21
Authors: Luo Wu , Lin Xiao‐Mian , Wang Tian‐Xiang , Cai Jia‐Long , Zeng Xiang‐Feng , Zhu Cai‐Rong , Li Rong‐Zhen , Wang Heng , Wu Xiao‐Ping 
Published: October 2018

AbstractPrevious studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor‐1 (FGFR1) and the coreceptor beta‐Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1–KLB after iodination with Na125I and chloramine T, whereas human FGF19 retained its affinity for FGFR1–KLB even after iodination. The molecular mechanisms underlying these differences remained elusive. In this study, we first demonstrated that an intramolecular disulfide bond was formed between cysteine‐102 and cysteine‐121 in FGF21, implying that the oxidation of the cysteine to cysteic acid, which may interfere with the active conformation of FGF21, did not occur during the iodination procedures, and thus ruled out the possibility of the two conserved cysteine residues mediating the loss of FGF21 binding affinity to FGFR1–KLB upon iodination. Site‐directed mutagenesis and molecular modeling were further applied to determine the residue(s) responsible for the loss of FGFR1–KLB affinity. The results showed that mutation of a single tyrosine‐207, but not the other five tyrosine residues in FGF21, to a phenylalanine retained the FGFR1–KLB affinity of FGF21 even after iodination, whereas replacing the corresponding phenylalanine residue with tyrosine in FGF19 did not alter its binding affinity to FGFR1–KLB, but decreased the receptor binding ability of the iodinated protein, suggesting that tyrosine‐207 is the crucial amino acid responsible for the loss of specifying FGFR1–KLB affinity of the iodinated FGF21.
MiR‐208b regulates cell cycle and promotes skeletal muscle cell proliferation by targeting CDKN1A
Authors: Wang Jian , Song Chengchuang , Cao Xiukai , Li Hui , Cai Hanfang , Ma Yilei , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Ma Yun , Bai Yueyu , Lin Fengpeng , Chen Hong 
Published: October 2018

AbstractSkeletal muscle is the most abundant tissue in the body. The development of skeletal muscle cell is complex and affected by many factors. A sea of microRNAs (miRNAs) have been identified as critical regulators of myogenesis. MiR‐208b, a muscle‐specific miRNA, was reported to have a connection with fiber type determination. However, whether miR‐208b has effect on proliferation of muscle cell was under ascertained. In our study, cyclin‐dependent kinase inhibitor 1A (CDKN1A), which participates in cell cycle regulation, was predicted and then validated as one target gene of miR‐208b. We found that overexpression of miR‐208b increased the expression of cyclin D1, cyclin E1, and cyclin‐dependent kinase 2 at the levels of messenger RNA and protein in cattle primary myoblasts in vivo and in vitro. Flow cytometry showed that forced expression of miR‐208b increased the percentage of cells at the S phase and decreased the percentage of cells at the G0/G1 phase. These results indicated that miR‐208b participates in the cell cycle regulation of cattle primary myoblast cells. 5‐Ethynyl‐20‐deoxyuridine and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays showed that overexpression of miR‐208b promoted the proliferation of cattle primary myoblasts. Therefore, we conclude that miR‐208b participates in the cell cycle and proliferation regulation of cattle primary skeletal muscle cell through the posttranscriptional downregulation of CDKN1A.
Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet’s disease
Authors: Ahmadi Majid , Yousefi Mehdi , Abbaspour‐Aghdam Sanaz , Dolati Sanam , Aghebati-Maleki Leili , Eghbal‐Fard Shadi , Khabbazi Alireza , Rostamzadeh Davood , Alipour Shahriar , Shabani Mahdi , Nouri Mohammad , Babaloo Zohreh 
Published: October 2018

AbstractImpaired inflammatory immune cells have been implicated in the pathogenesis of Behcet’s disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real‐time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme‐linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)‐10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL‐17, IL‐23, and retinoic acid‐related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17‐associated cytokines in the supernatant was found to be elevated in BD patients. T‐cell‐associated miRNA expression levels, miR‐25, miR‐106b, miR‐326, and miR‐93 were significantly upregulated, while miR‐146a and miR‐155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD.
Cinnamaldehyde regulates H2O2‐induced skeletal muscle atrophy by ameliorating the proteolytic and antioxidant defense systems
Authors: Kaur Nirmaljeet , Gupta Prachi , Saini Vikram , Sherawat Sandeep , Gupta Sanjeev , Dua Anita , Kumar Vinod , Injeti Elisha , Mittal Ashwani 
Published: October 2018

AbstractSkeletal muscle atrophy/wasting is associated with impaired protein metabolism in diverse physiological and pathophysiological conditions. Elevated levels of reactive oxygen species (ROS), disturbed redox status, and weakened antioxidant defense system are the major contributing factors toward atrophy. Regulation of protein metabolism by controlling ROS levels and its associated catabolic pathways may help in treating atrophy and related clinical conditions. Although cinnamaldehyde (CNA) enjoys the established status of antioxidant and its role in ROS management is reported, impact of CNA on skeletal muscle atrophy and related pathways is still unexplored. In the current study, the impact of CNA on C2C12 myotubes and the possible protection of cultured cells from H
2O
2‐induced atrophy is examined. Myotubes were treated with H
2O
2 in the presence and absence of CNA and the changes in the antioxidative, proteolytic systems, and mitochondrial functions were scored. Morphological analysis showed significant protective effects of CNA on length, diameter, and nuclei fusion index of myotubes. The evaluation of biochemical markers of atrophy; creatine kinase, lactate dehydrogenase, succinate dehydrogenase along with the study of muscle‐specific structural protein (i.e., myosin heavy chain‐fast [MHCf] type) showed significant protection of proteins by CNA. CNA pretreatment not only checked the activation of proteolytic systems (ubiquitin‐proteasome E3‐ligases [MuRF1/Atrogin1]), autophagy [Beclin1/LC3B], cathepsin L, calpain, caspase), but also prevented any alteration in the activities of antioxidative defense enzymes (catalase, glutathione‐
S‐transferase, glutathione‐peroxidase, superoxide dismutase, glutathione reductase). The results suggest that CNA protects myotubes from H
2O
2‐induced atrophy by inhibiting/resisting the amendments in proteolytic systems and maintains cellular redox‐balance.
The mechanisms of DIRAS family members in role of tumor suppressor
Authors: Li Xueli , Liu Shuiping , Fang Xiao , He Chao , Hu Xiaotong 
Published: October 2018

AbstractDIRAS family is a group of GTPases belonging to the RAS superfamily and shares homology with the pro‐oncogenic Ras GTPases. Currently, accumulating evidence show that DIRAS family members could be identified as putative tumor suppressors in various cancers. The either lost or reduced expression of DIRAS proteins play an important role in cancer development, including cell growth, migration, apoptosis, autophagic cell death, and tumor dormancy. This review focuses on the latest research regarding the roles and mechanisms of the DIRAS family members in regulating Ras function, cancer development, assessing potential challenges, and providing insights into the possibility of targeting them for therapeutic use.
Tyrosine phosphorylation of HDAC3 by Src kinase mediates proliferation of HER2‐positive breast cancer cells
Authors: Seo Jaesung , Guk Garam , Park Seung‐Ho , Jeong Mi‐Hyeon , Jeong Ji‐Hoon , Yoon Ho‐Geun , Choi Kyung‐Chul 
Published: October 2018

AbstractThe role of histone deacetylase 3 (HDAC3) is to repress the expression of various genes by eliminating acetyl group from histone. Thus, the regulation of HDAC3 activity is essential to maintain cellular homeostasis. In this study, we found that HDAC3 interacts with c‐Src kinase. However, the interaction between HDAC3 and c‐Src was previously reported, it has still been ambiguous whether c‐Src phosphorylates HDAC3 and affects the function of HDAC3. First, we confirmed that HDAC3 directly binds to c‐Src, and c‐Src identified to interact with C‐terminal domain (277–428 a.a.) of HDAC3. c‐Src also phosphorylated three tyrosine sites of HDAC3 at tyrosine 325, 328, and 331. Importantly, wild‐type c‐Src increases HDAC3 activity, but not mutant c‐SrcK298M (kinase inactive form). When these tyrosine residues are all substituted for alanine residues, the deacetylase activity of mutant HDAC3 was abolished. In addition, a proliferation of HER2‐positive breast cancer cells expressing phosphorylation deficient mutant HDAC3 is decreased in comparison with control cells. Thus, our findings suggested that phosphorylation of HDAC3 by c‐Src kinase regulates the HDAC3 activity and the proliferation of breast cancer cells.
Differentiation of microfluidic‐encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats
Authors: Barati Ghasem , Nadri Samad , Hajian Ramin , Rahmani Ali , Mostafavi Hossein , Mortazavi Yousef , Taromchi Amir Hossein 
Published: October 2018

AbstractTissue and stem cell encapsulation andtransplantation were considered as promising tools in the treatment of patients with diabetes mellitus. The aim of this study was to evaluate the effect of microfluidic encapsulation on the differentiation of trabecular meshwork mesenchymal stem cells (TM‐MSC), into insulin‐producing cells (IPCs) both in vitro and in vivo. The presence of differentiated cells in microfibers (three dimensional [3D]) and tissue culture plates (TCPS; two dimensional [2D]) culture was evaluated by detecting mRNA and protein expression of pancreatic islet‐specific markers as well as measuring insulin release of cells in response to glucose challenges. Finally, semi‐differentiated cells in microfibers (3D) and 2D cultures were used to control the glucose level in diabetic rats. The results of this study showed that MSCs differentiated in alginate microfibers (fabricated by microfluidic device) express more Pdx‐1 mRNA (1.938‐fold, p‐value: 0.0425) and Insulin mRNA (2.841‐fold,
p‐value: 0.0001) compared with those cultured on TCPS. Furthermore, cell encapsulation in microfluidic derived microfibers decreased the level of blood glucose in diabetic rats. The approach used in this study showed the possibility of alginate microfibers as a matrix for differentiation of TM‐MSCs (as a new source) into IPCs. In addition, it could minimize different steps in stem cell differentiation, handling, and encapsulation, which lead to loss of an unlimited number of cells.
Glucose intolerance in monosodium glutamate obesity is linked to hyperglucagonemia and insulin resistance in α cells
Authors: Araujo Thiago R. , da Silva Joel A. , Vettorazzi Jean F. , Freitas Israelle N. , Lubaczeuski Camila , Magalhães Emily A. , Silva Juliana N. , Ribeiro Elane S. , Boschero Antonio C. , Carneiro Everardo M. , Bonfleur Maria L. , Ribeiro Rosane Aparecida 
Published: October 2018

AbstractObesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β‐cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)‐obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1.25 mg/g BW). At 90 days of age, MSG‐obese mice were hyperglycemic, hyperinsulinemic, and hyperglucagonemic and had lost the capacity to increase their insulin/glucagon ratio when transitioning from the fasting to fed state, exacerbating hepatic glucose output. Furthermore, hepatic protein expressions of phosphorylated (p)‐protein kinase A (PKA) and cAMP response element‐binding protein (pCREB), and of phosphoenolpyruvate carboxykinase (PEPCK) enzyme were higher in fed MSG, before and after glucagon stimulation. Increased pPKA and phosphorylated hormone‐sensitive lipase content were also observed in white fat of MSG. MSG islets hypersecreted glucagon in response to 11.1 and 0.5 mmol/L glucose, a phenomenon that persisted in the presence of insulin. Additionally, MSG α cells were hypertrophic displaying increased α‐cell mass and immunoreactivity to phosphorylated mammalian target of rapamycin (pmTOR) protein. Therefore, severe glucose intolerance in MSG‐obese mice was associated with increased hepatic glucose output, in association with hyperglucagonemia, caused by the refractory actions of glucose and insulin in α cells and via an effect that may be due to enhanced mTOR activation.
DGCR5 attenuates neuropathic pain through sponging miR‐330‐3p and regulating PDCD4 in CCI rat models
Authors: Peng Chengwei , Zhang Chuanqing , Su Zhe , Lin Dongyang 
Published: October 2018

AbstractNeuropathic pain caused by somatosensory nervous system dysfunction is a serious public health problem. Some long noncoding RNAs (lncRNAs) can participate in physiological processes involved in neuropathic pain. However, the effects of lncRNA DGCR5 in neuropathic pain have not been explored. Therefore, in our current study, we concentrated on the biological roles of DGCR5 in neuropathic pain. Here, it was observed that DGCR5 was significantly decreased in chronic sciatic nerve injury (CCI) rat models. DGCR5 overexpression was able to alleviate neuropathic pain development including mechanical and thermal hyperalgesia. In addition, the current understanding of miR‐330‐3p function in neuropathic pain remains largely incomplete. Here, we found that miR‐330‐3p was greatly increased in CCI rats and DGCR5 can modulate miR‐330‐3p expression negatively. Upregulation of DGCR5 repressed inflammation‐correlated biomarkers including interleukin 6 (IL‐6), tumor necrosis factor α, and IL‐1β in CCI rats by sponging miR‐330‐3p. The negative correlation between DGCR5 and miR‐330‐3p was confirmed in our current study. Inhibition of miR‐330‐3p suppressed neuropathic pain progression by restraining neuroinflammation in vivo. In addition, PDCD4 was predicted as a downstream target of miR‐330‐3p. Furthermore, PDCD4 was significantly increased in CCI rats and DGCR5 regulated PDCD4 expression through sponging miR‐330‐3p in CCI rat models. Taken these together, it was implied that DGCR5/miR‐330‐3p/PDCD4 axis participated in neuropathic pain treatment.