bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Living Dead: Mitochondria and Metabolic Arrest
Authors: Hadj‐Moussa Hanane , Green Stuart R. , Storey Kenneth B. 
Published: September 2018

AbstractMitochondria are not just the powerhouses of the cell; these ‘end of function’ organelles are crucial components of cellular physiology and influence many central metabolic and signaling pathways that support complex multicellular life. Not surprisingly, these organelles play vital roles in adaptations for extreme survival strategies including hibernation and freeze tolerance, both of which are united by requirements for a strong reduction and reprioritization of metabolic processes. To facilitate metabolic rate depression, adaptations of all aspects of mitochondrial function are required, including; energetics, physiology, abundance, gene regulation, and enzymatic controls. This review discusses these factors with a focus on the stress‐specific nature of mitochondrial genes and transcriptional regulators, and processes including apoptosis and chaperone protein responses. We also analyze the regulation of glutamate dehydrogenase and pyruvate dehydrogenase, central mitochondrial enzymes involved in coordinating the shifts in metabolic fuel use associated with extreme survival strategies. Finally, an emphasis is given to the novel mitochondrial research areas of microRNAs, peptides, epigenetics, and gaseous mediators and their potential roles in facilitating hypometabolism. © 2018 IUBMB Life, 70(12):1260–1266, 2018
Sirtuin 6 inhibits myofibroblast differentiation via inactivating transforming growth factor‐β1/Smad2 and nuclear factor‐κB signaling pathways in human fetal lung fibroblasts
Authors: Zhang Qian , Tu Wei , Tian Kunming , Han Lianyong , Wang Qin , Chen Panpan , Zhou Xue 
Published: September 2018

AbstractFibroblast‐to‐myofibroblast differentiation, which is characterized by increased expression of α‐smooth muscle actin, is known to be involved in the pathogenesis of idiopathic pulmonary fibrosis. Sirtuin 6 (SIRT6), a member of the sirtuin family, has been proved to inhibit epithelial‐to‐mesenchymal transition during idiopathic pulmonary fibrosis. However, the function of SIRT6 in lung myofibroblast differentiation is still obscure. Transforming growth factor‐β1 (TGF‐β1) is one of the main factors that can powerfully promote myofibroblast differentiation. In the current study, we aimed to explore the role of SIRT6 in the cellular model of fibroblast‐to‐myofibroblast differentiation induced by TGF‐β1 using human fetal lung fibroblasts (HFL1). We demonstrated that the SIRT6 protein level is upregulated by TGF‐β1 in HFL1 cells. Overexpression of SIRT6 significantly suppresses TGF‐β1‐induced myofibroblast differentiation in HFL1 cells. Mechanistically, SIRT6 decreases phosphorylation and nuclear translocation of Smad2 under TGF‐β1 stimulation. Nevertheless, mutant SIRT6 (H133Y) without histone deacetylase activity fails to inhibit phosphorylation and nuclear translocation of Smad2. Meanwhile, SIRT6 interacts with the nuclear factor‐κB (NF‐κB) subunit p65 and represses TGF‐β1‐induced NF‐κB‐dependent transcriptional activity, which is also dependent on its deacetylase activity. Overexpression of wild‐type SIRT6 but not the H133Y mutant inhibits the expression of NF‐κB‐dependent genes including interleukin (IL)‐1β, IL‐6 and matrix metalloproteinase‐9 (MMP‐9) induced by TGF‐β1, all of which have been demonstrated to promote myofibroblast differentiation. Collectively, our study reveals that SIRT6 prevents TGF‐β1‐induced lung myofibroblast differentiation through inhibiting TGF‐β1/Smad2 and NF‐κB signaling pathways.
MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women
Authors: Darooei Mina , Khan Fazal , Rehan Mohd , Zubeda Syeda , Jeyashanker Erukambattu , Annapurna Srirambhatla , Shah Ashwin , Maddali Srinivas , Hasan Qurratulain 
Published: September 2018

AbstractFibroadenoma is the most common type of benign breast tumor, accounting for 90% of benign lesions in India. Somatic mutations in the mediator complex subunit 12 (MED12) gene play a critical role in fibroepithelial tumorigenesis. The current study evaluated the hotspot region encompassing exon 2 of the
MED12 gene, in benign and malignant breast tumor tissue from women who presented for breast lump evaluation. A total of 100 (80 fibroadenoma and 20 breast cancer) samples were analyzed by polymerase chain reaction‐Sanger sequencing. Sequence variant analysis showed that 68.75% of nucleotide changes were found in exon 2 and the remaining in the adjacent intron 1. Codon 44 was implicated as a hotspot mutation in benign tumors, and 86.36% of the identified mutations involved this codon. An in silico functional analysis of missense mutations using consensus scoring sorting intolerant from tolerant (SIFT), SIFT seq, Polyphen2, Mutation Assessor, SIFT transFIC, Polyphen2 transFIC, Mutation Assesor transFIC, I‐Mutant, DUET, PON‐PS, SNAP2, and protein variation effect analyzer] revealed that apart from variants involving codon 44 (G44S; G44H), others like V41A and E55D were also predicted to be deleterious. Most of the missense mutations appeared in the loop region of the MED12 protein, which is expected to affect its functional interaction with cyclin C–CDK8/CDK19, causing loss of mediator‐associated cyclin depended kinase (CDK) activity. These results suggest a key role of
MED12 somatic variations in the pathogenesis of fibroadenoma. For the first time, it was demonstrated that
MED12 sequence variations are present in benign breast tumors in the south Indian population.
Identification specific miRNA in t(4;14) multiple myeloma based on miRNA‐mRNA expressing profile correlation analysis
Authors: Liu Huimin , Wang Guihua , Huang Ying , Zhao Chunmei , Chen Jing , Wang Xudong 
Published: September 2018

AbstractBackgroundMultiple myeloma (MM) is a common malignancy belonging to the hematological system. The translocation t(4;14)(p16.3;q32.3) is a critical cytogenetic change of MM, which is presenting a poor prognosis. The specific microRNAs (miRNAs) that are involved in t(4;14) myeloma are still unknown. Thus, the main purpose of this research was to identify specific miRNAs in t(4;14) positive myeloma.MethodsThe expression profiles of miRNA and messenger RNA (mRNA) in t(4; 14) positive and negative samples were obtained from the gene expression omnibus data series. The miRNA‐mRNA regulatory network was constructed based on two self‐defined regulation models. Subsequently, we performed the topology analysis for mining the hub genes, and Pearson’s correlation coefficient analysis was used to calculate the relevance of the hub genes and specific miRNAs.ResultsThirteen differentially expressed miRNAs and 206 differential mRNAs were extracted between t(4;14) positive group and negative group. The network consisted of 8 miRNAs and 154 mRNAs in 2 reverse regulated models, which showed a total of 485 interactions, including 376 cis‐regulated and 109
trans‐regulated relationships. The miR‐125a‐3p, miR‐125a‐5p, miR‐99b‐5p, and let‐7e were powerful miRNAs correlating with the FGFR3, MAP1B, MYRIP, and CDC42BPA under the relevance analysis in the subnetwork.ConclusionIn our study, a distinctive correlation analysis of miRNA‐mRNA was established to excavate specific miRNAs and hub target mRNAs in patients with t(4;14), but it was only a matter of theoretical principles. The further experimental explorations are needed to confirm valuable diagnostic and therapeutic symbols specific associated with t(4;14) in the future.
Physical exercise prevents alterations in purinergic system and oxidative status in lipopolysaccharide‐induced sepsis in rats
Authors: Miron Vanessa Valéria , Bottari Nathieli Bianchin , Assmann Charles Elias , Stefanello Naiara , da Costa Pauline , Pelinson Luana Paula , Reichert Karine Paula , da Silva Anielen Dutra , Lopes Thauan Faccin , da Cruz Ivana Beatrice Mânica , Sévigny Jean , Morsch Vera Maria , Schetinger Maria Rosa Chitolina , Cardoso Andréia Machado 
Published: September 2018

AbstractSepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti‐inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)‐induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis, and after 24 hours, lungs and blood samples were collected for analysis. The results showed that the exercise protocol used was able to prevent, in septic animals: (1) the increase in body temperature; (2) the increase of lipid peroxidation and reactive species levels in the lung, (3) the increase in adenosine triphosphate levels in serum; (4) the change in the activity of the enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the density of purinergic enzymes and receptors in the lung, and (6) the increase of IL‐6 and IL‐1β gene expression. Our results revealed the involvement of purinergic signaling and oxidative damage in the mechanisms by which exercise prevents sepsis aggravations. Therefore, the regular practice of physical exercise is encouraged as a better way to prepare the body against sepsis complications.
Long noncoding RNA HEIH promotes the proliferation and metastasis of non–small cell lung cancer
Authors: Jia Kegang , Chen Fan , Xu Lian 
Published: September 2018

AbstractObjectivesThis study is aimed to explore the functions of long noncoding RNA (lncRNA) HEIH on the proliferation as well as metastasis of non–small cell lung cancer (NSCLC).MethodsHEIH was shown to be increased in NSCLC by a microarray study on lncRNA profiling. We detected the expression of HEIH in different human NSCLC lines and tissues by quantitative real‐time PCR. After gain‐ and loss‐of‐function approaches in A549 and Calu‐1 cells, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays and a colony formation assay were applied to test the proliferative activity of cells, and the apoptosis of cells was measured by flow cytometry. Western blot analysis was used to evaluate the protein expression, and the effects of lncRNA HEIH on cell migratory and invasive abilities of A549 and Calu‐1 cells were evaluated using wound healing and transwell assays.ResultsIn our study, we confirmed the elevated expression of HEIH in NSCLC tissues and cell lines compared with the normal ones. After constructing A549 and Calu‐1 cells with altered HEIH expression by transient transfection, cell viability was found to be positively regulated by the HEIH level. Moreover, overexpression of HEIH accelerated the cell migrating rate and increased the invasive cell number according to the results of a wound healing assay and transwell assay.ConclusionsHEIH could accelerate the proliferation and metastasis of NSCLC, providing a novel therapeutic target for clinical treatment.
Oridonin‐induced mitochondria‐dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways
Authors: Jiang Jin‐Huan , Pi Jiang , Jin Hua , Cai Ji‐Ye 
Published: September 2018

AbstractOridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial‐mediated apoptosis in KYSE‐30, KYSE‐150, and EC9706 cells with dose‐dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle‐related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl‐2, as well as the increased expression of cleaved caspase‐3, ‐8, and ‐9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.
Social and community program approaches to participants: Exploring best practices
Authors: Minas Maria , Ribeiro Maria Teresa , Anglin James P. 
Published: September 2018

AbstractThis article presents the results of a deepened study of the best practices and outcomes of 15 programs (across 9 countries) that work with socioeconomically disadvantagedd communities. Using thematic analysis, we identified best practices that participants, community leaders, and professionals recognized as key. Data collection involved in loco observation and semistructured interviews with participants and professionals, and focus groups with professionals. Associated with best practices, programs adopted two central perspectives on approaching participants: approaching participants as users and approaching participants as contributors. Such approaches were crossed with best practices and outcomes identified througout the analysis. For programs that approached participants as users, the best practices were valuing, facilitating the access to resources, showing availability, and promoting competencies and openness, and the main outcome was participants’ improved self‐confidence. For programs that approached participants as contributors, the best practices were contributing, encouraging participation, valuing participants, becoming masters, and reciprocity, and the main outcome was participants having an impact.
A critical role of the transient receptor potential melastatin 2 channel in a positive feedback mechanism for reactive oxygen species‐induced delayed cell death
Authors: Li Xin , Jiang Lin‐Hua 
Published: September 2018

AbstractTransient receptor potential melastatin 2 (TRPM2) channel activation by reactive oxygen species (ROS) plays a critical role in delayed neuronal cell death, responsible for postischemia brain damage via altering intracellular Zn2+ homeostasis, but a mechanistic understanding is still lacking. Here, we showed that H2O2 induced neuroblastoma SH‐SY5Y cell death with a significant delay, dependently of the TRPM2 channel and increased [Zn2+]i, and therefore used this cell model to investigate the mechanisms underlying ROS‐induced TRPM2‐mediated delayed cell death. H2O2 increased concentration‐dependently the [Zn2+]i and caused lysosomal dysfunction and Zn2+ loss and, furthermore, mitochondrial Zn2+ accumulation, fragmentation, and ROS generation. Such effects were suppressed by preventing poly(adenosine diphosphate ribose, ADPR) polymerase‐1‐dependent TRPM2 channel activation with PJ34 and 3,3′,5,5′‐tetra‐tert‐butyldiphenoquinone, inhibiting the TRPM2 channel with 2‐aminoethoxydiphenyl borate (2‐APB) and N‐(p‐amylcinnamoyl)anthranilic acid, or chelating Zn2+ with N,N,N,N‐tetrakis(2‐pyridylmethyl)‐ethylenediamine (TPEN). Bafilomycin‐induced lysosomal dysfunction also resulted in mitochondrial Zn2+ accumulation, fragmentation, and ROS generation that were inhibited by PJ34 or 2‐APB, suggesting that these mitochondrial events are TRPM2 dependent and sequela of lysosomal dysfunction. Mitochondrial TRPM2 expression was detected and exposure to ADPR‐induced Zn2+ uptake in isolated mitochondria, which was prevented by TPEN. H2O2‐induced delayed cell death was inhibited by apocynin and diphenyleneiodonium, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase (NOX) inhibitors, GKT137831, an NOX1/4‐specific inhibitor, or Gö6983, a protein kinase C (PKC) inhibitor. Moreover, inhibition of PKC/NOX prevented H2O2‐induced ROS generation, lysosomal dysfunction and Zn2+ release, and mitochondrial Zn2+ accumulation, fragmentation and ROS generation. Collectively, these results support a critical role for the TRPM2 channel in coupling PKC/NOX‐mediated ROS generation, lysosomal Zn2+ release, and mitochondrial Zn2+ accumulation, and ROS generation to form a vicious positive feedback signaling mechanism for ROS‐induced delayed cell death.
Association of the genetic polymorphisms in immunoinflammatory microRNAs with risk of ischemic stroke and subtypes in an Iranian population
Authors: Darabi Hassan , Salmaninejad Arash , Jaripour Mohamad Ehsan , Azarpazhooh Mahmoud reza , Mojarrad Majid , Sadr‐Nabavi Ariane 
Published: September 2018

AbstractStroke is one of the most common type of cerebrovascular disease threatening human health and life with high mortality, disability, and morbidity. Ischemic stroke (IS) is determined to be a complex disease containing a group of heterogeneous disorders with various environmental and genetic risk factors. This study evaluated the polymorphisms of microRNAs involved in inflammatory routes leading to stroke in an Iranian population. This study evaluated the associations of hsa‐mir‐608 C/G rs4919510, hsa‐mir‐499 A/G rs3746444, and hsa‐mir‐145 C/T rs190323149 polymorphisms in precursor miRNAs with the risk of IS. These microRNA polymorphisms were analyzed in 470 patients with IS and 489 control subjects. The TOAST criteria was applied for IS subtypes classification. The frequency of the allele G of hsa‐mir‐499/rs3746444 A/G revealed significant association with IS in comparison with controls (
p < 0.0001, OR = 1.838, 95% CI = 1.406–2.401). Increased IS risks were associated with hsa‐mir‐499/ rs3746444 A/G genotypes in diverse genetic model (homozygote comparison:
p = 0.004, OR = 2.136, 95% CI = 1.269–3.597; heterozygote comparison:
p = 0.029, OR = 1.373, 95% CI = 1.033–1.825). Statistical analysis in IS subtypes showed that cardio‐embolic patients compared with other subtypes (large artery atherosclerosis and lacunar) had higher frequency of G allele (LAA vs. CEI,
p = 0.017; LAC vs. CEI,
p = 0.009), AG genotype (LAA vs. CEI,
p = 0.016; LAC vs. CEI,
p = 0.013). Nevertheless, this study did not find any association between the alleles and genotypes of mir‐608 C/G rs4919510 SNP and IS, respectively (
p > 0.05). The current investigation provided verification that hsa‐mir‐499 rs3746444 A/G polymorphism may be associated with a significantly increased risk of IS in an Iranian population.
Pyruvate dehydrogenase kinase 1 contributes to cisplatin resistance of ovarian cancer through EGFR activation
Authors: Zhang Meng , Cong Qing , Zhang Xiao‐Yan , Zhang Ming‐Xing , Lu Ying‐Ying , Xu Cong‐Jian 
Published: September 2018

AbstractPatients with ovarian cancer frequently develop acquired drug resistance after the long‐term chemotherapy, leading to disease progression. Enhanced epithelial–mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated. PDK1 was upregulated in cisplatin‐resistant ovarian cancer cells. PDK1 knockdown in resistant cells led to increased sensitivity to cisplatin‐induced cell death and apoptosis. PDK1 downregulation also reversed the EMT and cell motility in cisplatin‐resistant cells. In a mouse xenograft model, tumors derived from PDK1‐silenced ovarian cancer cells exhibited decreased tumor growth and EMT compared with control after the cisplatin treatment. Mechanistically, PDK1 overexpression led to increased phosphorylation of EGFR, and blocking EGFR kinase activity by erlotinib reversed cisplatin resistance induced by PDK1 overexpression. Furthermore, in patients with ovarian cancer, higher PDK1 and p‐EGFR levels were associated with chemoresistance. These results supported that PDK1 contributes to chemoresistance of ovarian cancer by activating EGFR. Therefore, PDK1 may serve as a promising target to combat chemoresistance of ovarian cancer.
Melatonin and pancreatic cancer: Current knowledge and future perspectives
Authors: Tamtaji Omid Reza , Mirhosseini Naghmeh , Reiter Russel J. , Behnamfar Morteza , Asemi Zatollah 
Published: September 2018

AbstractPancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio‐ and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine produced in the pineal gland mediated and receptor‐independent action is the pancreas and other where has both receptors. Melatonin is a potent antioxidant and tissue protector against inflammation and oxidative stress. In vivo and in vitro studies have shown that melatonin supplementation is an appropriate therapeutic approach for pancreatic cancer. Melatonin may be an effective apoptosis inducer in cancer cells through regulation of a large number of molecular pathways including oxidative stress, heat shock proteins, and vascular endothelial growth factor. Limited clinical studies, however, have evaluated the role of melatonin in pancreatic cancer. This review summarizes what is known regarding the effects of melatonin on pancreatic cancer and the mechanisms involved.
Retracted: LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR‐203/BCAT1 axis
Authors: Ji Degang , Jiang Chengwei , Zhang Lirong , Liang Na , Jiang Tiechao , Yang Bin , Liang Haiying 
Published: September 2018

AbstractObjectiveTo investigate the impact of long noncodingRNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) on hepatocellular cancer (HCC) cell propagation, invasion, and migration by mediating miR‐203/
BCAT1 axis.MethodsMicroarray analysis was based on 25 pairs of HCC cancerous tissues and adjacent tissues. The expression levels of CRNDE, miR‐203, and BCAT1 in HCC tissues were analyzed by quantitative real‐time polymerase chain reaction (qRT‐PCR). The liver cell line L‐02 and HCC cell lines HepG2 and Huh‐7 were utilized to assess the regulatory eﬀects of CRNDE and miR‐203 on HCC progression in vitro. Western blot was used to qualify BCAT1 protein expression level. Cell proliferation and apoptosis were evaluated using CCK‐8 and flow cytometry analysis, whereas cell invasion and migration assay were performed by the Transwell assay. The relationship among CRNDE, miR‐203, and
BCAT1 was validated by dual luciferase assay. Tumor Xenograft study was established to verify the pathological effect of CRNDE on HCC development in vivo.ResultsThe expression levels of the CRNDE and BCAT1 were upregulated in HCC tissues and cells, whereas miR‐203 was downregulated in HCC. Knockdown of CRNDE or miR‐203 overexpression would inhibit HCC cell propagation and metastasis, and induced cell apoptosis. Moreover, miR‐203 was negatively correlated with CRNDE, the same as miR‐203 with
BCAT1. Dual luciferase assay showed that miR‐203 was an inhibitory target of CRNDE, and
BCAT1 was directly targeted by miR‐203 as well.ConclusionLncRNA CRNDE could enhance HCC tumorgenesis by sponging miR‐203 and mediating BCAT1. LncRNA CRNDE might facilitate HCC cell propagation, invasiveness, and migration through regulating miR‐203/
BCAT1 axis.