bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications
Authors: Pereira Isabel , Fraga Sónia , Silva Susana , Teixeira João Paulo , Gama Miguel 
Published: November 2018

AbstractHydrogels are three‐dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a low‐molecular‐weight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrin‐based hydrogel (HG). The HG and its components were tested for cyto‐ and genotoxicity according to the International Standard ISO 10993‐3 on the biological evaluation of medical devices. To assess genotoxicity, a battery of in vitro genotoxicity tests employing both eukaryotic and prokaryotic models was performed: comet assay, cytokinesis‐block micronucleus assay and Ames test. Our data revealed that the HG (IC50 = 2.8 mg/mL) and oxidized dextrin by itself (IC50 = 1.2 mg/mL) caused a concentration‐dependent decrease in cellular viability of human lymphoblastoid TK6 cells after 24 hours of exposure to the test agents. However, these concentrations are unlikely to be reached in vivo. In addition, no significant increase in the DNA and chromosomal damage of TK6 cells exposed to non‐cytotoxic concentrations of the HG and its isolated components was detected. Furthermore, neither the HG nor its metabolites exerted a mutagenic effect in different of Salmonella typhimurium strains and in an Escherichia coli mix. Our data demonstrated the genocompatibility of the HG (up to 3.5 mg/mL) for biomedical applications. To our best acknowledge, this is the first report with a detailed genotoxicity assessment of an aldehyde‐modified polysaccharide/adipic acid dihydrazide hydrogel.
LncRNA MALAT1 promotes oxidized low‐density lipoprotein‐induced autophagy in HUVECs by inhibiting the PI3K/AKT pathway
Authors: Li Shu , Pan Xudong , Yang Shaonan , Ma Aijun , Yin Shuangshuang , Dong Yi , Pei Haotian , Bi Xinran , Li Wei 
Published: November 2018

AbstractEmerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in many biological processes, such as cell growth, differentiation, apoptosis, and autophagy. Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), highly expressed in endothelial cells, is well conserved and implicated in endothelial cell migration and proliferation. However, whether MALAT1 participates in oxidized low‐density lipoprotein (ox‐LDL)‐induced autophagy regulation in human umbilical vein endothelial cells (HUVECs) remains unknown. In this study, we observed that autophagy was upregulated and MALAT1 expression was markedly increased in HUVECs treated with ox‐LDL. The ox‐LDL‐induced autophagy of HUVECs is significantly associated with the PI3K/AKT pathway. Furthermore, we found that MALAT1 overexpression inhibited PI3K, Akt and p70S6K phosphorylation and downregulated RHEB expression, simultaneously increasing ox‐LDL‐induced autophagy. MALAT1 silencing caused higher phosphorylated PI3K, Akt and p70S6K levels, upregulated RHEB expression and markedly suppressed autophagy. These results indicated that lncRNA MALAT1 promotes ox‐LDL‐induced autophagy in HUVECs partly through the PI3K/AKT signaling pathway.
LincRNA‐p21 enhances the sensitivity of radiotherapy for gastric cancer by targeting the β‐catenin signaling pathway
Authors: Chen Lijun , Yuan Dongfang , Yang Yichen , Ren Minzhu 
Published: November 2018

AbstractLong noncoding RNAs (lncRNAs) are a large and diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that modulate the gene expression at the posttranscriptional or transcriptional level. LncRNAs played crucial roles in many biological processes, such as cell proliferation, metastasis, and migraton. In this study, we evaluated the role of lincRNA‐p21 in the gastric cancer (GC). We demonstrated that the expression level of lincRNA‐p21 was downregulated in the GC tissues and cell lines. Moreover, ectopic expression of lincRNA‐p21 suppressed the GC cell growth, cell cycle, and migration. Furthermore, we demonstrated that the X‐ray increased the expression level of lincRNA‐p21 in both the HCG‐27 and SGC7901 cells and elevated expression of lincRNA‐p21 increased the radiotherapy sensitivity of the GC cell. In addition, we showed that ectopic expression of lincRNA‐p21 suppressed the β‐catenin and c‐myc expression. Overexpression of lincRNA‐p21 inhibited the GC cell proliferation and increased the radiosensitivity of GC cells by regulating the β‐catenin signaling pathway. These data suggested that lincRNA‐p21 acted as a tumor suppressor gene in the development of GC.
miR‐203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes
Authors: Li Yang , Liu Xiping , Du Aolin , Zhu Xiaolong , Yu Bo 
Published: November 2018

AbstractMyocarditis is an inflammatory disease of the myocardium. MicroRNA‐203 (miR‐203) is involved in various physiological and pathological processes. In this work, we aimed to explore the roles and potential mechanisms of miR‐203 in myocarditis in vitro. Cardiomyocyte H9c2 was subjected to 10 μg/mL lipopolysaccharide (LPS) for 24 hours. Real‐time polymerase chain reaction analysis revealed that LPS upregulated miR‐203 expression in H9c2 cells. Cell counting kit‐8 (CCK‐8) and lactate dehydrogenase (LDH) assays demonstrated that inhibition of miR‐203 reduced cell injury induced by LPS. The cell apoptosis rate, caspase 3 activity, caspase 3/7 activities, and the expression of cleaved‐caspase 3 (c‐caspase 3) were declined upon miR‐203 depletion. In addition, miR‐203 silencing attenuated the expression and production of inflammatory cytokines (tumor necrosis factor‐α, interleukin [IL]‐6, and IL‐8). On the contrary, overexpression of miR‐203 showed the opposite trend in cell apoptosis and inflammation. Luciferase reporter assay confirmed that miR‐203 could bind with the nuclear factor interleukin‐3 (NFIL3) 3′‐untranslated regions (3′‐UTR), and miR‐203 regulated the expression of NFIL3 negatively. Moreover, NFIL3 silencing partly abolished the myocardial protective functions of miR‐203 inhibitor. Herein, we suggest that miR‐203 promoted cell apoptosis and inflammation induced by LPS via targeting NFIL3.
Pyrazinamide resistance and mutations L19R, R140H, and E144K in Pyrazinamidase of Mycobacterium tuberculosis
Authors: Khan Muhammad Tahir , Junaid Muhammad , Mao Xueying , Wang Yanjie , Hussain Abid , Malik Shaukat Iqbal , Wei Dong‐Qing 
Published: November 2018

AbstractPyrazinamide (PZA) is an important component of first‐line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid. Mutations in the
pncA gene have been recognized as the major cause of PZA resistance. We detected some novel mutations, Leucine19Arginine (L19R), Arginine140Histidine (R140H), and Glutamic acid144 Lysine (E144K), in the
pncA gene of PZA‐resistant isolates in our wet lab PZA drug susceptibility testing and sequencing. As the molecular mechanism of resistance of these variants has not been reported earlier, we have performed multiple analyses to unveil different mechanisms of resistance because of PZase mutations L19R, R140H, and E144K. The mutants and native PZase structures were subjected to comprehensive computational molecular dynamics (MD) simulations at 100 nanoseconds in apo and drug‐bound form. Mutants and native PZase binding pocket were compared to observe the consequence of mutations on the binding pocket size. Hydrogen bonding, Gibbs free energy, and natural ligand Fe
+2 effect were also analyzed between native and mutants. A significant variation between native and mutant PZase structure activity was observed. The native PZase protein docking score was found to be the maximum, showing strong binding affinity in comparison with mutants. MD simulations explored the effect of the variants on the biological function of PZase. Hydrogen bonding, metal ion Fe
+2 deviation, and fluctuation also seemed to be affected because of the mutations L19R, R140H, and E144K. The variants L19R, R140H, and E144K play a significant role in PZA resistance, altering the overall activity of native PZase, including metal ion Fe
+2 displacement and free energy. This study offers valuable evidence for better management of drug‐resistant tuberculosis.
USP28 contributes to the proliferation and metastasis of gastric cancer
Authors: Zhao Li‐Juan , Zhang Ting , Feng Xue‐Jian , Chang Jiao , Suo Feng‐Zhi , Ma Jin‐Lian , Liu Ying‐Jun , Liu Ying , Zheng Yi‐Chao , Liu Hong‐Min 
Published: November 2018

AbstractUSP28, a member of the deubiquitinating enzymes family, plays a vital role in the physiological process of cell proliferation, differentiation and apoptosis, DNA repair, immune response, and stress response. USP28 has been reported to be overexpressed in bladder cancer, colon cancer, breast carcinomas, and so on. Nevertheless, the role of USP28 in gastric cancer has not yet been investigated. In our study, we examined the USP28 expression in 87 paired samples of gastric cancer and normal gastric tissues. We found that USP28 was overexpressed in gastric cancer compared with normal gastric tissues (P < 0.01), and its overexpression was related to the degree of differentiation and metastases. Inhibiting USP28 expression in vitro suppressed the proliferation and invasion of gastric cancer cells by downregulating lysine specific demethylase 1. On the basis of our data, it can be concluded that USP28 may be a novel therapeutic target for gastric cancer.
Resveratrol improves ex vivo expansion of CB‐CD34+ cells via downregulating intracellular reactive oxygen species level
Authors: Tang Chaochun , Zhang Weiwei , Cai Haibo , Ye Zhaoyang , Zhang Xu , Tan Wensong 
Published: November 2018

AbstractIntracellular reactive oxygen species (ROS) play important roles in the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). In this study, the effects of resveratrol (RES), on the ex vivo expansion of HSPCs were investigated by analyzing CD34+ cells expansion and biological functions, with the objective to optimize ex vivo culture conditions for CD34
+ cells. Among the five tested doses (0, 0.1, 1, 10, 20, and 50 μM), 10 μM RES was demonstrated to be the most favorable for ex vivo CD34
+ cells expansion. In the primary cultures, 10 μM RES favored higher expansion folds of CD34
+ cells, CD34
+CD38
− cells, and colony‐forming units (CFUs) (
P < 0.05). It was found that the percentages of primitive HSPCs (CD34
+CD38
−CD45R
−CD49f
+CD90
+ cells) in 10 μM RES cultures were higher than those without RES. Further, in the secondary cultures, expanded CD34
+ cells derived from primary cultures with 10 μM RES exhibited significantly higher total cells and CD34
+ cells expansion (
P < 0.05). In the semisolid cultures, the frequency of CFU‐GM and total CFUs of 10 μM RES group were both higher than those of without RES group, demonstrating that CD34
+ cells expanded with 10 μM RES possessed better biological function. Furthermore, the addition of 10 μM RES downregulated the intracellular ROS level via strengthening the scavenging capability of ROS, and meanwhile reducing the percentages of apoptotic cells in cultures. Collectively, RES could stimulate the ex vivo expansion of CD34
+ cells, preserved more primitive HSPCs and maintain better biological function by alleviating intracellular ROS level and cell apoptosis in cultures.
KDM4B promotes gastric cancer metastasis by regulating miR‐125b‐mediated activation of Wnt signaling
Authors: Jing Jia‐Chen , Feng Zhen , Chen Zhong‐Hua , Ji Bei‐Na , Hong Jing , Tang Nan , Yu Jin Ling , Wang Shao‐Ying 
Published: November 2018

AbstractEmerging evidence has demonstrated that the aberrant expression of histone‐modifying enzymes such as histone demethylases contributes to gastric carcinogenesis and progression. The role of KDM4B in cancer progression has been gradually revealed. However, the underlying mechanisms regulating gastric cancer metastasis of KDM4B remain unclear. In the present study we determined KDM4B expression in gastric cancer and its biologic function in vitro and in vivo. We found that KDM4B expression was significantly increased in most gastric cancer tissues compared with the adjacent normal tissues. Upregulated expression of KDM4B in human gastric cancer was correlated with poor prognosis. In vitro, KDM4B overexpression in AGS cells promoted cell invasion, whereas knockdown of KDM4B inhibited cell invasion. Furthermore, KDM4B overexpression also promoted tumor metastasis in vivo. Mechanistically, KDM4B upregulated miR‐125b expression and activated Wnt signaling pathway. More important, miR‐125b partially mediated KDM4B‐induced activation of Wnt signaling. Finally, we demonstrated that KDM4B promoted gastric cancer cell invasion in vitro and cancer metastasis in vivo, at least in part, by upregulating miR‐125b expression. These data provided novel insights on the role of KDM4B‐driven gastric cancer metastasis and indicated that KDM4B may be served as a potential target for gastric cancer.
Silencing of long noncoding RNA MEG3 enhances cerebral protection of dexmedetomidine against hypoxic‐ischemic brain damage in neonatal mice by binding to miR‐129‐5p
Authors: Zhou Xiu‐Min , Liu Jie , Wang Ying , Zhang Man‐He 
Published: November 2018

AbstractHypoxic‐ischemic brain damage (HIBD) is a leading cause of neonatal acute mortality and chronic nervous system injury. Recently, it has been found that long noncoding RNAs (lncRNAs) play a significant role in the neurodevelopment and etiopathogenesis of HIBD. Here, the researchers aimed to determine the role of lncRNA maternally expressed gene (MEG3) in the therapeutic effect of dexmedetomidine (DEX) in neonatal mice with HIBD through the regulation of microRNA‐129‐5p (miR‐129‐5p). HIBD models were established in C57/BL6 neonatal mice. Subsequently, the target relationship between MEG3 and miR‐129‐5p was predicted and verified. The neonatal mice were injected with DEX, ad‐shMEG3, and mimics and inhibitors of miR‐129‐5p to identify roles of MEG3 and miR‐129‐5p in therapeutic effects of DEX on neuronal apoptosis and injury, cerebral atrophy, and learning and memory ability of neonatal mice with HIBD. MEG3 directly targeted and inhibited the expression of miR‐129‐5p. Silencing of MEG3 or upregulation of miR‐129‐5p effectively promoted the therapeutic effect of DEX on neonatal mice with HIBD. Silencing of MEG3 or upregulation of miR‐129‐5p reduced the neuronal apoptosis rate and degree of cerebral atrophy, and also enhanced the learning and memory ability of HIBD neonatal mice. Collectively, the key findings obtained from the present study support the notion that MEG3 silencing enhances the therapeutic effect of DEX on neonatal mice with HIBD by binding to miR‐129‐5p.
Overexpression of miR‐98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models
Authors: Zhong Liang , Fu Kui , Xiao Weimin , Wang Fang , Shen Lu‐Lu 
Published: November 2018

AbstractMicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR‐98 has been reported to be involved in various diseases. However, little is known about the role of miR‐98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR‐98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR‐98 was downregulated in CCI rat models. Overexpression of miR‐9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR‐98 and the direct correlation was confirmed. Then, miR‐98 was overexpressed in CCI rats and it was found that miR‐98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL‐6), IL‐1β, and tumor necrosis factor‐α (TNF‐α) expression was obviously induced in CCI rats, while miR‐98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR‐98 on neuropathic pain development. Taken these together, we reported that overexpression of miR‐98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.
MicroRNA‐9 inhibits retinal neovascularization in rats with diabetic retinopathy by targeting vascular endothelial growth factor A
Authors: Liu Wen‐Lan 
Published: November 2018

AbstractDiabetic retinopathy (DR) is a leading cause of adult visual impairment and loss. This study aims to explore the effects of microRNA‐9 (miR‐9) on retinal neovascularization during DR by targeting the vascular endothelial growth factor A (VEGFA). DR rat models were successfully established. Retinal microvascular endothelial cells (RMECs) of DR rats were isolated and treated with miR‐9 mimic, miR‐9 inhibitor or small interfering RNA (siRNA)‐VEGFA. The expressions of miR‐9, VEGFA, and cluster of differentiation 31 (CD31) of the rats’ tissues and cells were examined. The targeting relationship between miR‐9 and VEGFA was testified. The tubule formation, the cell proliferation and the periodic distribution and apoptosis were evaluated after transfection. In the retinal tissues of DR rats, miR‐9 expression decreased while the expression of VEGFA and CD31 increased. Notably, miR‐9 targeted and inhibited VEGFA expression. In response to the treatment of miR‐9 mimic and siRNA‐VEGFA, a reduction was identified in CD31 expression, tubule formation, and proliferation of RMECs and cell ratio in the S phase, but an increase was observed in apoptosis rate of RMECs. The treatment of miR‐9 inhibitor reversed the manifestations. Our study demonstrated that miR‐9 could inhibit retinal neovascularization of DR and tubule formation, and promote apoptosis in RMECs by targeting VEGFA.
Role of toll‐like receptors 2 and 4 in the neuroprotective effects of bone marrow–derived mesenchymal stem cells in an experimental model of ischemic stroke
Authors: Nejati Majid , Tameh Abolfazl Azami , Atlasi Mohammad Ali 
Published: November 2018

AbstractObjectiveIschemic stroke is a major cause of death and prolonged disability worldwide. Inflammation plays an important role in post‐ischemic injury. Mesenchymal stem cells (MSCs) have protective effects in stroke treatment due to their anti‐inflammatory properties. Toll‐like receptors (TLRs) 2 and 4 are two innate immune receptors that trigger inflammatory processes. Here, we investigated the association of these receptors with the protective effect of MSCs after middle cerebral artery occlusion (MCAO) in rats.MethodsMSCs were isolated from the bone marrow of young rats and expanded in vitro. A model of ischemic stroke was performed by transient MCAO with 24 or 72 hours of reperfusion. Two hours after ischemia/reperfusion (I/R), the rats received MSCs or saline via tail vein and the sham group underwent surgery without MCAO. The relative gene expressions of TLR2, TLR4, and MyD88 were evaluated in the ischemic penumbra by the real‐time PCR technique. Active astrocyte and microglia and TLR‐expressing cells were detected by immunohistochemistry (IHC).ResultsMSCs significantly decreased the genes expression of TLR2 (P = 0.006
), TLR4 (P = 0.038
), and MyD88 (P = 0.009
) after their upregulation by I/R. Moreover, the IHC results indicated that glial fibrillary acidic protein (GFAP) and ionized calcium‐binding adapter molecule 1 (Iba‐1) positive cells were significantly increased by I/R (
P < 0.001), and MSCs significantly decreased the number of GFAP (
P = 0.003), Iba‐1 (
P = 0.001), TLR2 (
P = 0.004), and TLR4 (
P = 0.007) positive cells 72 hours after I/R.ConclusionThe neuroprotective effect of MSCs in brain ischemic injury is associated with its anti‐inflammatory effects and modulation of the activity of immune cells. Inhibition of TLR2 and TLR4 expression is one of the possible mechanisms of this protective effect.
Long noncoding RNA LINC00339 promotes laryngeal squamous cell carcinoma cell proliferation and invasion via sponging miR‐145
Authors: Liu Shouzhou , Duan Wenchao 
Published: November 2018

AbstractLaryngeal squamous cell carcinoma (LSCC) is a very common neoplasm of the head and neck in the world. Long noncoding RNAs play key roles in cell infiltration, fate, apoptosis, and invasion. However, the functional role and expression of LINC00339 remains unclear in LSCC. In this study, we showed that the expression level of LINC00339 was upregulated in LSCC tissues and cell lines. LINC00339 silencing suppressed the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) progression of LSCC cells. In addition, we showed that LINC00339 acted as a sponge of miR‐145, and LINC00339 silencing promoted the expression of miR‐145 in Hep2 cell. Furthermore, the expression of miR‐145 was lower in LSCC tissues than in their paired normal samples and the miR‐145 expression level was negatively correlated with LINC00339 expression in LSCC tissues. The knockdown of miR‐145 promoted the proliferation, invasion, and EMT progression of LSCC cells. Finally, we indicated that LINC00339 silencing inhibited the proliferation, invasion, and EMT progression of LSCC cells by suppressing the miR‐145 expression. These data suggested that LINC00339 acted as an oncogene in the development of LSCC, partly by regulating the miR‐145 expression.
Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population
Authors: Shahba Sara , Jafari Shakib Reza , Jamshidi Ahmadreza , Vojdanian Mahdi , Akhtari Maryam , Aslani Saeed , Poursani Shiva , Nikokar Iraj , Mahmoudi Mahdi 
Published: November 2018

AbstractBackgroundCopy number variation (CNV) of DNA segments has been considered as an important component of genetic variation, affecting the quality and quantity of gene expression. Bone morphogenic protein 8A (BMP8A) has been reported to function in bone formation. With respect to the bone and joint complications in ankylosing spondylitis (AS), this investigation aimed to study the role of BMP8A gene CNV in impressing the gene expression as well as the disease risk.MethodsA total of 900 individuals, including 450 patients with AS and 450 healthy controls were enrolled. The copy numbers of BMP8A gene were detected by TaqMan real‐time polymerase chain reaction (PCR) method. BMP8A messenger RNA (mRNA) transcript level in peripheral blood mononuclear cells (PBMCs) was also measured by SYBR Green real‐time gene expression PCR method.ResultsNo significant association of BMP8A copy number was detected with the risk of AS. BMP8A mRNA expression level was significantly downregulated in patients compared with controls. mRNA expression level of BMP8A in both AS patients with and without syndesmophyte was significantly lower than the healthy control group. There was no correlation between the mRNA expression level of BMP8A and both demographic and clinical data of the patients.ConclusionsAlthough BMP8A gene expression was downregulated in patients with AS, its copy number could not affect the transcript level of BMP8A gene in PBMCs and was not associated with susceptibility to AS in Iranian population. BMP8a may take into account as an indicator of bone formation process in AS, but it seems that mechanisms other than CNV may regulate this protein.