bluuebunny/crossref_metadata_2025_split huggingface dataset:
The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer
Authors: Samavarchi Tehrani Sadra , Mahmoodzadeh Hosseini Hamideh , Yousefi Tooba , Abolghasemi Maryam , Qujeq Durdi , Maniati Mahmood , Amani Jafar 
Published: October 2018

AbstractDNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell‐cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.
Retracted: Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo
Authors: Wei Gejin , Liang Tihong , Wei Chengming , Nong Xiaolian , Lu Qiteng , Zhao Jinmin 
Published: October 2018

AbstractOsteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone‐protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti‐cancer, anti‐cholesterol, and anti‐angiocardiopathy, promoting osteoblasts differentiation, and even anti‐osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor‐kB ligand (RANKL)‐induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite‐resorbing activity of mature osteoclasts by inhibiting RANKL‐induced NF‐kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c‐Fos), tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide‐induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL‐induced osteoclastogenesis through suppressing NF‐ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases.
Therapeutic potential of targeting the Wnt/β‐catenin pathway in the treatment of pancreatic cancer
Authors: Javadinia Seyed Alireza , Shahidsales Soodabeh , Fanipakdel Azar , Joudi‐Mashhad Mona , Mehramiz Mehrane , Talebian Sahar , Maftouh Mona , Mardani Ramin , Hassanian Seyed Mahdi , Khazaei Majid , Ferns Gordon A. , Avan Amir 
Published: October 2018

AbstractThe Wnt/β‐catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the
CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β‐catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.
Downregulation of miR‐20b‐5p facilitates Mycobacterium tuberculosis survival in RAW 264.7 macrophages via attenuating the cell apoptosis by Mcl‐1 upregulation
Authors: Zhang Defeng , Yi Zhengjun , Fu Yurong 
Published: October 2018

AbstractTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). The interaction between Mtb and macrophages, which is regulated by microRNAs, determines the development of TB. However, the function of microRNA‐20b‐5p (miR‐20b‐5p) in RAW 264.7 macrophages against Mtb remains unknown. In this study, we analyzed the expression level of miR‐20b‐5p in macrophage responses to Mtb infection and exosomes derived from macrophages after Mtb infection. MiR‐20b‐5p mimics and inhibitor were, respectively, transfected to evaluate the effect of miR‐20b‐5p on Mtb and macrophages. In addition, the targets of miR‐20b‐5p were predicted by a bioinformatics analysis. The macrophages were respectively transfected with miR‐20b‐5p mimics and inhibitor to determine the messenger RNA expression levels of the targets by reverse transcription‐polymerase chain reaction assay. The results revealed that the miR‐20b‐5p expression level was decreased in the infected macrophages at different times. MiR‐20b‐5p was shown in the exosomes released from macrophages infected with Mtb. Upregulation of the miR‐20b‐5p level suppressed the survival of Mtb in macrophages, while downregulation of the miR‐20b‐5p level enhanced the survival of Mtb in macrophages. Overexpression of miR‐20b‐5p decreased the cell viability and induced apoptosis in Mtb‐infected macrophages, while underexpression of miR‐20b‐5p increased the cell vitality and attenuated apoptosis in Mtb‐infected macrophages. The bioinformatics analysis revealed that Mcl‐1 was a target of miR‐20b‐5p. MiR‐20b‐5p negatively regulated the expression of Mcl‐1. Overall, this study is the first to demonstrate the effect of miR‐20b‐5p on Mtb infection and present miR‐20b‐5p and exosomes as the potential therapeutic targets of TB.
Novel association of oral squamous cell carcinoma with GSTP1 Arg187Trp gene polymorphism
Authors: Rajesh Deepa , Balakrishna Sharath , Azeem Mohiyuddin S. M. , Suryanarayana Ravishankar , Kutty A. V. Moideen 
Published: October 2018

AbstractAimsGlutathione S‐transferase subtype pi 1 (GSTP1) is an enzyme that is involved in the detoxification of carcinogenic substances. Arg187Trp is a functional polymorphism in the corresponding GSTP1 gene that reduces the enzymatic activity by 45%. We evaluated, for the first time, the association of Arg187Trp with the risk of oral squamous cell carcinoma and compared it with other established
GSTP1 polymorphisms viz, Ile105Val and Ala114Val.Materials and MethodsWe carried out a 1:2 case‐control study by recruiting 100 patients with oral squamous cell carcinoma and 200 age and gender‐matched healthy individuals. Ile105Val, Ala114Val, and Arg187Trp polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method and their distribution in the study groups was compared by chi‐squared test (Fisher’s exact).ResultsThe minor allele of Ala114Val and Arg187Trp were more common in patients than in controls. In contrast, the distribution of Ile105Val minor allele was similar in the two groups. The differential distribution was also significant at the level of genotypes.ConclusionsThese results indicate that GSTP1 Arg187Trp is associated with the risk of developing oral squamous cell carcinoma. Our study underlines the importance of detoxification pathway in the risk of carcinogenesis.
Heme oxygenase‐1 attenuates the inhibitory effect of bortezomib against the APRIL‐NF‐κB‐CCL3 signaling pathways in multiple myeloma cells: Corelated with bortezomib tolerance in multiple myeloma
Authors: He Zheng C. , Li Xin Y. , Guo Yong L. , Ma Dan , Fang Qin , Ren Ling L. , Zhang Zhao Y. , Wang Weili , Yu Zheng Y. , Zhao Peng , Wang Ji S. 
Published: October 2018

AbstractOsteoclasts (OCs) play an essential role in bone destruction in patients with multiple myeloma (MM). Bortezomib can ameliorate bone destruction in patients with MM, but advanced MM often resists bortezomib. We studied the molecular mechanisms of bortezomib tolerance in MM. The expression of the MM‐related genes in newly diagnosed patients with MM and normal donors were studied. C‐C motif chemokine ligand 3 (CCL3) is a cytokine involved in the differentiation of OCs, and its expression is closely related to APRIL (a proliferation‐inducing ligand). We found that bortezomib treatment inhibited APRIL and CCL3. But the heme oxygenase‐1 (HO‐1) activator hemin attenuated the inhibitory effects of bortezomib on APRIL and CCL3. We induced mononuclear cells to differentiate into OCs, and the enzyme‐linked immunosorbent assay showed that the more OCs differentiated, the higher the levels CCL3 secretions detected. Animal experiments showed that hemin promoted MM cell infiltration in mice. The weight and survival rate of tumor mice were associated with HO‐1 expression. Immunohistochemical staining showed that HO‐1, APRIL, and CCL3 staining were positively stained in the tumor infiltrating sites. Then, MM cells were transfected with L‐HO‐1/si‐HO‐1 expression vectors and cultured with an nuclear factor (NF)‐kappa B (κB) pathway inhibitor, QNZ. The results showed that HO‐1 was the upstream gene of APRIL, NF‐κB, and CCL3. We showed that HO‐1 could attenuate the inhibitory effect of bortezomib against the APRIL‐NF‐κB‐CCL3 signaling pathways in MM cells, and the tolerance of MM cells to bortezomib and the promotion of bone destruction are related to HO‐1.
Endoplasmic reticulum stress, autophagic and apoptotic cell death, and immune activation by a natural triterpenoid in human prostate cancer cells
Authors: Johnson Benjamin M. , Radwan Faisal F. Y. , Hossain Azim , Doonan Bently P. , Hathaway‐Schrader Jessica D. , God Jason M. , Voelkel‐Johnson Christina V. , Banik Narendra L. , Reddy Sakamuri V. , Haque Azizul 
Published: October 2018

AbstractThough the current therapies are effective at clearing an early stage prostate cancer, they often fail to treat late‐stage metastatic disease. We aimed to investigate the molecular mechanisms underlying the anticancer effects of a natural triterpenoid, ganoderic acid DM (GA‐DM), on two human prostate cancer cell lines: the androgen‐independent prostate carcinoma (PC‐3), and androgen‐sensitive prostate adenocarcinoma (LNCaP). Cell viability assay showed that GA‐DM was relatively more toxic to LNCaP cells than to PC‐3 cells (IC50s ranged 45‐55 µM for PC‐3, and 20‐25 µM for LNCaP), which may have occurred due to differential expression of p53. Hoechst DNA staining confirmed detectable nuclear fragmentation in both cell lines irrespective of the p53 status. GA‐DM treatment decreased Bcl‐2 proteins while it upregulated apoptotic Bax and autophagic Beclin‐1, Atg5, and LC‐3 molecules, and caused an induction of both early and late events of apoptotic cell death. Biochemical analyses of GA‐DM‐treated prostate cancer cells demonstrated that caspase‐3 cleavage was notable in GA‐DM‐treated PC‐3 cells. Interestingly, GA‐DM treatment altered cell cycle progression in the S phase with a significant growth arrest in the G2 checkpoint and enhanced CD4
+ T cell recognition of prostate tumor cells. Mechanistic study of GA‐DM‐treated prostate cancer cells further demonstrated that calpain activation and endoplasmic reticulum stress contributed to cell death. These findings suggest that GA‐DM is a candidate for future drug design for prostate cancer as it activates multiple pathways of cell death and immune recognition.
PKM2 promotes glucose metabolism through a let‐7a‐5p/Stat3/hnRNP‐A1 regulatory feedback loop in breast cancer cells
Authors: Yao Ao , Xiang Yuan , Si Yu‐Rui , Fan Li‐Juan , Li Jia‐Peng , Li Hui , Guo Wei , He Hui‐Xin , Liang Xing‐Jie , Tan Yao , Bao Le‐Yuan , Liao Xing‐Hua 
Published: October 2018

AbstractTumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than normal cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let‐7a‐5p/Stat3/hnRNP‐A1/PKM2 signaling in breast cancer cell glucose metabolism. PKM2 depletion via small interfering RNA (siRNA) inhibits cell proliferation and aerobic glycolysis in breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) promotes upregulation of heterogeneous nuclear ribonucleoprotein (hnRNP)‐A1 expression, hnRNP‐A1 binding to pyruvate kinase isoenzyme (PKM) pre messenger RNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let‐7a‐5p, which functionally targets Stat3, whereas hnRNP‐A1 blocks the biogenesis of let‐7a‐5p to counteract its ability to downregulate the Stat3/hnRNP‐A1/PKM2 signaling pathway. The downregulation of Stat3/hnRNP‐A1/PKM2 by let‐7a‐5p is verified using a breast cancer. These results suggest that let‐7a‐5p, Stat3, and hnRNP‐A1 form a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of breast cancer cells. These findings elucidate a new pathway mediating aerobic glycolysis in breast cancers and provide an attractive potential target for breast cancer therapeutic intervention.
Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels
Authors: Yan Jing‐Ya , Li Zhi‐Qin , Yu Zu‐Jiang , Kan Quan‐Chen 
Published: October 2018

AbstractNo consensus exists with respect to positive hepatitis B virus (HBV) DNA results and persistent normal or mildly elevated alanine aminotransferase (ALT). The aim of this study is to investigate the appropriate management and prognosis of these populations with chronic hepatitis B (CHB). A total of 235 subjects with positive HBV DNA results and persistent normal or mildly elevated ALT were enrolled in this study. Liver biopsy and liver stiffness measurements (LSM) were performed in all participants at baseline. Antiviral therapy was initiated in patients with significant hepatic inflammation (G ≥ 2) and/or fibrosis (S ≥ 2). The patients were divided into entecavir and adefovir groups based on HBV DNA load (>2000 IU/mL vs <2000 IU/mL). The liver biopsies were repeated at 72 weeks for the patients received antiviral therapy. We found that 112 subjects were hepatitis B e antigen (HBeAg) positive, and 123 subjects were negative. The corresponding median ALTs were 46 (39.5‐52.5) and 48 (41.5‐57.0) U/mL, respectively. G ≥ 2 and/or S ≥ 2 diseases were present in 48.8% (82/168) of the HBeAg‐positive and 51.2% (86/168) of HBeAg‐negative patients, respectively. In addition, 96 HBeAg‐positive and 72 HBeAg‐negative patients were divided into entecavir and adefovir groups. Meanwhile, liver biopsies had greater diagnostic accuracy for determining cirrhosis than LSM (0.711 vs 1.0, P < 0.0001). At the end of the study period, undetectable HBV DNA levels and normal ALT levels were observed in CHB‐infected patients. Furthermore, the patients showed histologic improvement at 72 weeks compared with baseline measurements (G, 1.72 ± 1.00 vs 0.73 ± 0.88, P = 0.0002; S, 1.484 ± 0.90 vs 0.99 ± 1.13, P < 0.0001). Collectively, liver biopsy enhanced diagnostic accuracy for CHB‐infected individuals with persistent normal or mildly elevated aminotransferase levels. Moreover, antiviral therapy can improve or regress the hepatic fibrosis and cirrhosis.
Downregulation of miR‐33b promotes non‐small cell lung cancer cell growth through reprogramming glucose metabolism miR‐33b regulates non‐small cell lung cancer cell growth
Authors: Zhai Shengping , Zhao Lingyan , Lin Tiantian , Wang Wei 
Published: October 2018

AbstractGlucose metabolism is a common target for cancer regulation and microRNAs (miRNAs) are important regulators of this process. Here we aim to investigate a tumor‐suppressing miRNA, miR‐33b, in regulating the glucose metabolism of non‐small cell lung cancer (NSCLC). In our study, quantitative real‐time polymerase chain reaction (qRT‐PCR) showed that miR‐33b was downregulated in NSCLC tissues and cell lines, which was correlated with increased cell proliferation and colony formation. Overexpression of miR‐33b through miR‐33b mimics transfection suppressed NSCLC proliferation, colony formation, and induced cell‐cycle arrest and apoptosis. Meanwhile, miR‐33b overexpression inhibited glucose metabolism in NSCLC cells. Luciferase reporter assay confirmed that miR‐33b directly binds to the 3′‐untranslated region of lactate dehydrogenase A (LDHA). qRT‐PCR and Western blot analysis showed that miR‐33b downregulated the expression of LDHA. Moreover, introducing LDHA mRNA into cells over‐expressing miR‐33b attenuated the inhibitory effect of miR‐33b on the growth and glucose metabolism in NSCLC cells. Taken together, these results confirm that miR‐33b is an anti‐oncogenic miRNA, which inhibits NSCLC cell growth by targeting LDHA through reprogramming glucose metabolism.
Tissue differences revealed by gene expression profiles of various cell lines
Authors: Chen Lei , Pan Xiaoyong , Zhang Yu‐Hang , Kong Xiangyin , Huang Tao , Cai Yu‐Dong 
Published: October 2018

AbstractMechanisms through which tissues are formed and maintained remain unknown but are fundamental aspects in biology. Tissue‐specific gene expression is a valuable tool to study such mechanisms. But in many biomedical studies, cell lines, rather than human body tissues, are used to investigate biological mechanisms Whether or not cell lines maintain their tissue‐specific characteristics after they are isolated and cultured outside the human body remains to be explored. In this study, we applied a novel computational method to identify core genes that contribute to the differentiation of cell lines from various tissues. Several advanced computational techniques, such as Monte Carlo feature selection method, incremental feature selection method, and support vector machine (SVM) algorithm, were incorporated in the proposed method, which extensively analyzed the gene expression profiles of cell lines from different tissues. As a result, we extracted a group of functional genes that can indicate the differences of cell lines in different tissues and built an optimal SVM classifier for identifying cell lines in different tissues. In addition, a set of rules for classifying cell lines were also reported, which can give a clearer picture of cell lines in different issues although its performance was not better than the optimal SVM classifier. Finally, we compared such genes with the tissue‐specific genes identified by the Genotype‐tissue Expression project. Results showed that most expression patterns between tissues remained in the derived cell lines despite some uniqueness that some genes show tissue specificity.
Mitochondrial impairment following neonatal overfeeding: A comparison between normal and ischemic‐reperfused hearts
Authors: de Moura Freitas Cristiane , Nascimento Luciana Caroline Paulino do , Braz Glauber Rudá Feitoza , Andrade‐Silva Severina Cassia , Lima‐Junior Nelson C. , de Araujo Silva Tercya , Fernandes Mariana Pinheiro , Ferreira Diorginis José Soares , Lagranha Claudia Jacques 
Published: October 2018

AbstractOverweight and obesity are established factors underpin several metabolic impairments, including the cardiovascular. Although the diversity of factors involved in overweight/obesity‐induced cardiovascular diseases, mitochondria has been highlighted due to its role in cardiac metabolism. As obesity can be originated in early postnatal life, the current study evaluates the effects of neonatal overfeeding on the cardiac mitochondrial bioenergetics and oxidative balance in rats that underwent an ischemia‐reperfusion insult. Seventy‐two hours after delivery, Wistar rat litters were randomly assigned into the control (C; nine pups per mother) and the Overfed (OF; three pups per mother) groups throughout the lactation period. At weaning, male offspring were fed with laboratory chow ad libitum until sacrifice at 30 and 60 days of life. Mitochondrial heart bioenergetics and oxidative balance showed to be deeply affected by neonatal overfeeding at both ages. Interestingly, after ischemia‐reperfusion insult I/R (Langendorff or mineral oil incubation), most parameters evaluated in OF animals were not influenced by additional ischemic‐reperfusion injury. Our findings demonstrated that suckling overfeeding deregulates cardiac mitochondrial alike to ischemia‐reperfusion insult by disengaging electrical mitochondrial coupling and potentiate oxidative stress, wherein the neonatal overfeeding shows to be so detrimental as I/R. Our findings support the concept that nutritional insults in the critical development periods increase the risk for cardiovascular disease and mitochondria impairments throughout life while oxidative damage change between molecular targets.
Antihepatotoxic benefits of Poria cocos polysaccharides on acetaminophen‐lesioned livers in vivo and in vitro
Authors: Wu Ka , Guo Chao , Yang Bin , Wu Xinmou , Wang Weimin 
Published: October 2018

AbstractIn our previous study, preliminary data indicates that Poria cocos polysaccharides (PCP) shows beneficial hepatoprotection against acetaminophen (APAP)‐induced liver injury in mice. However, biological molecular mechanism warrants to be further discussed. In current study, a number of biochemical tests and immunoassays were subjected to respective PCP‐dosed mice in vivo and liver cells in vitro. As a result, PCP‐treated mice showed reduced contents of inflammatory cytokines (tumor necrosis factor [TNF]‐β and TNFsR‐I), enzymological molecules (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase [LDL]), and heat shock protein 90 (Hsp90) after APAP exposure. Additionally, immunostaining assays exhibited that lowered‐positive cells of cleaved‐caspase‐3, cleaved‐poly ADP ribose polymerase, and Hsp90‐labeled cells in PCP‐treated livers were observed, and increased cluster of differentiation 29 (CD29), CD73‐positive cells in the spleen were detected. Further, PCP‐treated mouse liver cells resulted in increased cell growth, reduced LDL level. Increased proliferating cell nuclear antigen (PCNA), P38 mitogen‐activated protein kinase (MAPK)‐labeled cells and decreased Hsp90‐positive cells in APAP‐exposed liver cells were observed dose‐dependently after PCP cotreatments. Collectively, our present experimental findings elucidate that PCP beneficially play hepatoprotective effects against APAP‐lesioned liver cells in vivo and in vitro, potentially through the molecular mechanisms of suppressing cell death, reducing hepatocellular inflammatory stress and Hsp90 bioactivity.