bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral infiltrating lymphocytes correlate with improved survival in colorectal cancer patients: Independent of oncogenetic features
Authors: Nazemalhosseini‐Mojarad Ehsan , Mohammadpour Somayeh , Torshizi Esafahani Amir , Gharib Ehsan , Larki Pegah , Moradi Afshin , Amin Porhoseingholi Mohammad , Asadzade Aghdaei Hamid , Kuppen Peter J. K. , Zali Mohammad Reza 
Published: October 2018

AbstractBackgroundThe clinical relevance and prognostic value of tumor‐infiltrating lymphocytes (TILs) as an interplay between malignant cells and immune function has been known for decades. On contrary, this potential may be different by T lymphocytes subsets endowed with a different function. Colorectal cancer (CRC) is a heterogeneous disease with different suggested prognostic biomarkers. So, this study was conducted to examine the prognostic value of CD8+ TILs on the survival rate of CRC as an independent factor of oncogenetic tumor features.MethodsWith respect to this, 281 formalin‐fixed, paraffin‐embedded tissue samples of Iranian CRC patients were evaluated for clinical features including tumor location, tumor stage, differentiation grade, and mucinous characteristics. Then, using the standard immunohistochemical technique, tumor sections were examined, and CD8+ TILs were counted and identified in two regions of the tumor, including intratumoral (ITCIL TILs) and stromal (S TILs). The prognostic value of CD8+ TILs was determined by comparing with parameters, such as diagnostic age, tumor stage, adjuvant therapy, microsatellite instability (MSI) status, KRAS and BRAF mutations, family history, and survival.ResultsThe presence of intratumoral tumor cell‐infiltrating lymphocytes (ITCIL) CD8+ lymphocytes are significantly associated with differentiation (p = 0.004), tumor, node, and metastases (TNM) stage (p = 0.001), and MSI (p = 0.001). Meanwhile, based on the level of stromal infiltrating lymphocytes (SIL) infiltration, analysis of CRC patients was statistically associated with a location (p = 0.002), TNM stage (p < 0.001), metastasis (p < 0.001), and KRAS mutation (p = 0.031). Also, tumors with severe ITCIL CD8+ lymphocytes have a good prognosis compared with tumors with poor or moderate ITCIL CD8+ lymphocytes.ConclusionsThese results suggest that intratumor cell‐infiltrating CD8− T lymphocytes as an independent prognostic factor that have an antitumor activity as judged by their favorable effect on patients’ survival and could potentially be exploited in the treatment of CRC.
Knockdown of MAML1 inhibits proliferation and induces apoptosis of T‐cell acute lymphoblastic leukemia cells through SP1‐dependent inactivation of TRIM59
Authors: Cheng Hui , Chen Li , Hu Xiaoxia , Qiu Huiying , Xu Xiaoqian , Gao Lei , Tang Gusheng , Zhang Weiping , Wang Jianmin , Yang Jianmin , Huang Chongmei 
Published: October 2018

AbstractNotch exerts important functions in cell proliferation, survival, and differentiation, which plays a critical role in tumor development when aberrantly activated. Mastermind‐like protein 1 (MAML1) has been functioning as crucial coactivators of Notch receptors and is required for stable formation of Notch transcriptional complexes. However, the mechanism whereby MAML1 induces T‐cell acute lymphoblastic leukemia (T‐ALL) tumorigenesis is largely unknown. The CCK‐8 and flow cytometry assay were performed to examine the effect of MAML1 knockdown on T‐ALL cell proliferation, apoptosis, and cell cycle. The expression of MAML1, cell cycle, and apoptosis‐related gene, as well as TRIM family members and specific protein 1 (SP1) was measured by western blot analysis and qPCR. Our results showed that MAML1 knockdown significantly inhibited cell proliferation and induced G0/G1 cell cycle arrest and apoptosis in Jurkat and MOLT‐4 cells. Cell cycle and apoptosis‐related gene expression, including CDK2, Bcl‐2, Bax, and Bad, was modified by the MAML1 knockdown. MAML1 knockdown obviously inhibited the CDK2 and Bcl‐2 expression and increased the Bax, p53, and Bad expression. Moreover, the TRIM family members, including TRIM13, TRIM32, TRIM44, and TRIM59, were significantly decreased by the MAML1 knockdown, with the highest decrease detected in TRIM59 expression. Interesting, overexpression of SP1 not only increased the expression of MAML1 and TRIM59, but also promoted the promoter activation of TRIM59. Taken together, knockdown of MAML1 inhibits proliferation and induces apoptosis of T‐ALL cells through SP1‐dependent inactivation of TRIM59, and therefore suggest that MAML1‐SP1‐TRIM59 axis may serve as potentially interesting therapeutic targets for treatment of T‐ALL.
Curcumin nanofibers for the purpose of wound healing
Authors: Fereydouni Narges , Darroudi Majid , Movaffagh Jebrail , Shahroodi Azadeh , Butler Alexandra E. , Ganjali Shiva , Sahebkar Amirhossein 
Published: October 2018

AbstractPoor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti‐inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.
Regulating ferroportin‐1 and transferrin receptor‐1 expression: A novel function of hydrogen sulfide
Authors: Zhang Meng‐Wan , Yang Guang , Zhou Yu‐Fu , Qian Christopher , Mu Ming‐Dao , Ke Ya , Qian Zhong‐Ming 
Published: October 2018

AbstractHydrogen sulfide (H2S) has a significant effect on the regulation of interleukin‐6 (IL‐6) and signal transducer and activator of transcription 3 (STAT3) activities, while IL‐6 directly regulates hepcidin expression via STAT3. We therefore hypothesized that H
2S has a role in body iron homeostasis by regulating the expression of iron transport proteins via the IL‐6/STAT3/Hepcidin pathway. Here, we investigated the effects of two H
2S donors sodium hydrosulfide and GYY4137 on the expression of ferroportin‐1 (Fpn1), transferrin receptor‐1 (TfR1), hepcidin, IL‐6 and pSTAT3 in the spleen of mice in vivo and peritoneal macrophage in vitro. We also examined the effects of H
2S on serum iron, transferrin saturation, and ferritin light chain contents in the spleen, and on nitrite content, nuclear factor erythroid 2‐related factor‐2 (Nrf2) and iron regulatory protein 1 (IRP1) in the macrophages. We demonstrated that H
2S regulates the expression of TfR1 and Fpn1 in the spleen in vivo and in peritoneal macrophages in vitro predominantly via the IL‐6/pSTAT3/hepcidin pathway, under the conditions of inflammation induced by lipopolysaccharides. We also provide evidence that under uninflamed conditions, the regulation of Fpn1 and TfR1 expression by H
2S, both in vivo and in vitro, are mediated by the nitric oxide (NO)/Nrf2 and iron regulatory protein/iron responsive element pathways, respectively, which are independent of IL‐6/pSTAT3/hepcidin signals. These findings show that H
2S is a key player in iron homeostasis under not only the inflamed conditions but also uninflamed conditions.
Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta‐analysis
Authors: Guo Yu , Long Jianhong , Lei Shaorong 
Published: October 2018

AbstractMelanoma is one of the most common skin cancer that is characterized by rapid growth, early metastasis, high malignant, and mortality. Accumulating evidence demonstrated that promoter methylation of tumor‐suppressor genes is implicated in the pathogenesis of melanoma. In the current study, we performed a meta‐analysis to identify promising methylation biomarkers in the diagnosis of melanoma. We carried out a systematic literature search using Pubmed, Embase, and ISI web knowledge database and found that gene promoter methylation of 50 genes was reported to be associated with the risk of melanoma. Meta‐analysis revealed that hypermethylation of claudin 11 (CLDN11; odds ratio [OR], 16.82; 95% confidence interval [CI], 1.97–143.29; p = 0.010), O‐6‐methylguanine‐DNA methyltransferase (MGMT; OR, 5.59; 95% CI, 2.51–12.47; p < 0.0001), cyclin‐dependent kinase inhibitor 2A (p16; OR, 6.57; 95% CI, 2.19–19.75; p = 0.0008), retinoic acid receptor β (RAR‐β2; OR, 24.31; 95% CI, 4.58–129.01; p = 0.0002), and Ras association domain family member (RASSF1A; OR, 9.35; 95% CI, 4.73–18.45; p < 0.00001) was significantly higher in melanoma patients compared with controls. CLDN11 (OR, 14.52; 95% CI, 1.84–114.55; p = 0.01), MGMT (OR, 8.08; 95% CI, 1.84–35.46; p = 0.006), p16 (OR, 9.44; 95% CI, 2.68–33.29; p = 0.0005), and RASSF1A (OR, 7.72; 95% CI, 1.05–56.50; p = 0.04) hypermethylation was significantly increased in primary melanoma compared with controls. Methylation frequency of CLDN11 (OR, 25.56; 95% CI, 2.32–281.66; p = 0.008), MGMT (OR, 4.64; 95% CI, 1.98–10.90; p = 0.0004), p16 (OR, 4.31; 95% CI, 1.33–13.96; p = 0.01), and RASSF1A (OR, 10.10; 95% CI, 2.87–35.54; p = 0.0003) was significantly higher in metastasis melanoma compared with controls. These findings indicated that CLDN11, MGMT, p16, RAR‐β2, and RASSF1A hypermethylation is a risk factor and a potential biomarker for melanoma. CLDN11, MGMT, p16, and RASSF1A promoter methylation may take part in the development of melanoma and become useful biomarkers in the early diagnosis of the disease.
Molecular insights into development of Trichoderma interfusants for multistress tolerance enhancing antagonism against Sclerotium rolfsii Sacc
Authors: Hirpara Darshna G. , Gajera H. P. , Patel Abha K. , Katakpara Zinkal A. , Golakiya B. A. 
Published: October 2018

AbstractThe current study aimed at developing diverse Trichoderma fusants for fungicides, drought, and salt tolerance with enhanced antagonistic activity against Sclerotium rolfsii Sacc. Trichoderma virens NBAII Tvs12 (mycoparasitic) and Trichoderma koningii MTCC796 (multistress tolerant) were used as parental strains for development of interspecific protoplast fusants. A total of 36 stable fusants were used for mycoparasitism, fungicides, and abiotic stresses (drought and salt) tolerance. The results revealed 20 homozygous progenies showing characteristics of either one parental strain and 14 heterozygous mutants depicting traits of both parental strains. A novel concept of inhibition coefficient was established using growth‐related key parameters that represent the pathogen biology and the biocontrol‐related biophysics of Trichoderma fusants. The results indicated a differential inhibition coefficient of the test pathogen and the highest (92.88%) inhibition coefficient of S. rolfsii was observed by interstable fusant Fu21. It also grew better under fungicides and abiotic stress (drought and salt) conditions. The molecular characterization and heterozygosity analysis evidenced the highest observed heterozygosity (0.5441) and gene flow (0.3872) in stable heterozygous Fu21. Principal coordinates analysis exhibited 62.7% of total variability. The ecofriendly heterozygous Trichoderma fusant (Fu21) might be useful for biocontrol of stem rot disease under adverse conditions or as a part of integrated disease management.
OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway
Authors: Zhaolin Zeng , Jiaojiao Chen , Peng Wu , Yami Liu , Tingting Zhang , Jun Tao , Shiyuan Wu , Jinyan Xiao , Dangheng Wei , Zhisheng Jiang , Zuo Wang 
Published: October 2018

AbstractPyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR‐125a‐5p increases in hyperlipidemic–hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR‐125a‐5p may be implicated in oxidized low‐density lipoprotein (oxLDL)‐induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR‐125a‐5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor‐κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)‐1β and IL‐18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL‐induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR‐125a‐5p and TET2 in VECs. Modulation of their expression levels may serve as a potential target for therapeutic strategies of As.
Multiomics analysis on DNA methylation and the expression of both messenger RNA and microRNA in lung adenocarcinoma
Authors: Yang Zhaoyang , Liu Bao , Lin Tie , Zhang Yingli , Zhang Limin , Wang Meng 
Published: October 2018

AbstractLung adenocarcinoma (LUAD) poses a significant threat to public health worldwide, while the genetic and epigenetic abnormalities involved in the oncogenesis of LUAD remains unknown. This study aimed to identify and validate key genes during the development and progression of LUAD by multiomics analysis. First, Empirical Analysis of Digital Gene Expression Data in R (EdgeR) was used to identify differentially regulated genes between normal samples and LUAD samples. Then significance analysis of microarrays (SAM) was used to identify differentially methylated genes and regulated microRNAs (miRNAs) between normal samples and LUAD samples. Following that, Kyoto Encyclopedia of Genes and Genomes (KEGG)‐enrichment analysis was used to analyze the function that these genes enriched in. A total of 4,816 genes, 419 miRNAs, and 4,476 methylated genes that were significantly differentially expressed corresponding to the normal tissues in LUAD were obtained, and some of the pathways these genes enriched in were the same. Moreover, 255 genes differentially methylated and expressed at the same time were also found, and these 255 genes were the target genes of the miRNAs differentially expressed in LUAD. Finally, nine genes (BRCA1, COL1A1, ESR1, FGFR2, HNF4A, IGFBP3, MET, MMP3, and PAK1) network analysis, and two of which were found to be related to the survival of LUAD patients. In summary, a total of nine genes that may play important roles in the development of LUAD were identified, and two (PAK1 and FGFR2) of them can be served as prognostic biomarkers for LUAD patients. The genes found in this study played different roles in the tumor progression of LUAD, indicating these genes may be considered as potential target genes for LUAD treatment.
HDAC6 inhibition induces the failure of mouse early embryonic development
Authors: Wang Hui , Ling Li , Ai Limei , Bai Liping 
Published: October 2018

AbstractHistone deacetylases (HDACs) have been implicated in numerous biological events. However, to date, the role of HDAC6 in early embryos remains unknown. In the current study, Tubastatin A (TubA), a potent HDAC6 inhibitor, was used to block HDAC6 activity in mouse embryos. We found that TubA exposure significantly reduced the blastocyst formation of early embryos. Confocal microscopy revealed the markedly increased chromosomal congression failure in the mouse embryos treated with the HDAC6 inhibitor. Moreover, the HDAC6 inhibition resulted in the overproduction of reactive oxygen species (ROS) in embryos. In addition, we observed the accumulation of phosphorylated γH2AX in TubA‐treated embryos, indicative of the increased DNA damage. In line with this, cell apoptosis of blastocysts was frequently detected in HDAC6‐deficient embryos compared with their controls. Altogether, our data indicate that HDAC6 may serve as an important regulator of chromatin structure and mitochondrial function, determining the developmental potential of the early embryos of mouse.
Retracted: Effects of IGFBP3 gene silencing mediated inhibition of ERK/MAPK signaling pathway on proliferation, apoptosis, autophagy, and cell senescence in rats nucleus pulposus cells
Authors: Chen Gang , Zhou Xiaopeng , Xu Zhengkuan 
Published: October 2018

AbstractObjectiveDisc degeneration is the common life‐threatening disease characterized by flank pain. The gene expression of insulin‐like growth factor binding protein 3 (IGFBP3) is increased in patients with disc degeneration, however, its mechanism is still unknown. This study aimed to investigate the influence of IGFBP3 gene silencing mediated inhibition of extracellular signal‐related kinase (ERK)/mitogen‐activated protein kinase (MAPK) signaling on proliferation, apoptosis, autophagy, and cell senescence in rats nucleus pulposus (NP) cells.MethodsThe expression of IGFBP3 in disc NP of patients was assessed by real‐time PCR (RT‐PCR) and western blot. RT‐PCR, transwell assay, immunohistochemical staining, SA‐β‐Gal staining, and western blot were performed to explore the molecular mechanism of IGFBP3 in NP cell migration and invasion.ResultsIn this study, IGFBP3 was highly expressed in disc NP of patients. With RT‐PCR, transwell assay, immunohistochemical staining, SA‐β‐Gal staining, and western blot, downregulated IGFBP3 could inhibit NP cells' migration and invasion by targeting the ERK/MAPK signaling pathway.ConclusionOur findings revealed that the inhibition of the ERK/MAPK pathway was mediated by IGFBP3 silencing that had effects on proliferation, apoptosis, autophagy, and cell senescence. Furthermore, our findings suggested the underlying mechanism of disc degeneration.
Gymnemic acid I triggers mechanistic target of rapamycin‐mediated β cells cytoprotection through the promotion of autophagy under high glucose stress
Authors: Wu Yanyang , Hu Yongquan , Yuan Yuju , Luo Yushuang , lai Dengni , Zhou Haiyan , Tong Zhongyi , Liu Dongbo 
Published: October 2018

AbstractGymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3‐I (LC3‐I)/LC3‐II in MIN‐6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β‐1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase‐3 under the high glucose stress. The inhibition of apoptosis and caspase‐3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet β cells MIN‐6. Our data suggested that GA I‐induced autophagy protected MIN‐6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR.
Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival
Authors: Liu Yuan , Zheng Qijun , He Guangbin , Zhang Mei , Yan Xianchun , Yang Ziyan , Zhang Peiran , Wang Lili , Liu Jiankang , Liang Liang , Han Hua 
Published: October 2018

AbstractSprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5′‐rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two‐pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription‐polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.
Evidence for calpains in cancer metastasis
Authors: Chen Jiaxin , Wu Yizheng , Zhang Lumin , Fang Xiao , Hu Xiaotong 
Published: October 2018

AbstractMetastatic dissemination represents the final stage of tumor progression as well as the principal cause of cancer‐associated deaths. Calpains are a conserved family of calcium‐dependent cysteine proteinases with ubiquitous or tissue‐specific expression. Accumulating evidence indicates a central role for calpains in tumor migration and invasion via participating in several key processes, including focal adhesion dynamics, cytoskeletal remodeling, epithelial‐to‐mesenchymal transition, and apoptosis. Activated after the increased intracellular calcium concentration () induced by membrane channels and extracellular or intracellular stimuli, calpains induce the limited cleavage or functional modulation of various substrates that serve as metastatic mediators. This review covers established literature to summarize the mechanisms and underlying signaling pathways of calpains in cancer metastasis, making calpains attractive targets for aggressive tumor therapies.