bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin‐1β, in human immune cells
Authors: Martin Tamara J. , Maise JaQuel , Gabure Sahra , Whalen Margaret M. 
Published: March 2019

AbstractPentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 μm for PCP and 260 nm for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin (IL)‐1β is a proinflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL‐1β are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL‐1β. This study shows that the increased secretion of IL‐1β seen with both contaminants is due to compound‐induced increases in the production of this cytokine. Increased production began within 6 hours of exposure to PCP and continued to increase up to 24 hours. DDT‐induced stimulation of IL‐1β appeared to be maximal after 6 hours of exposure and then diminished by 24 hours. The increases seen in IL‐1β production stimulated by PCP appear to be at least partially due to compound‐induced increases in IL‐1β mRNA. Although DDT caused increased production of IL‐1β, it did not appear to cause consistent increases in its mRNA. PCP‐ and DDT‐induced increases in IL‐1β production were dependent primarily on the p38 mitogen‐activated protein kinase pathway. These results indicate that both PCP and DDT are able to increase IL‐1β production in a p38 mitogen‐activated protein kinase‐dependent manner, which may have the potential to influence chronic inflammation.
Structural bioinformatics insights into the CARD‐CARD interaction mediated by the mitochondrial antiviral‐signaling protein of black carp
Authors: Rout Ajaya K. , Udgata Sheela R. , Dehury Budheswar , Pradhan Smruti P. , Swain Himanshu S. , Behera Bijay K. , Das Basanta K. 
Published: March 2019

AbstractThe innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen‐associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral‐signaling (MAVS) protein, are crucial for RLR‐triggered interferon (IFN) antiviral immunity. Recent studies have shown that the N‐terminal caspase recruitment domain (CARD) and transmembrane domain play a pivotal role in oligomerization of black carp MAVS (BcMAVS), crucial for the host innate immune response against viral invasion. In this study, we have used molecular modeling, docking, and molecular dynamics (MD) simulation approaches to shed molecular insights into the oligomerization mechanism of BcMAVSCARD. MD simulation and interaction analysis portrayed that the type‐I surface patches of BcMAVS
CARD make the major contribution to the interaction. Moreover, the evidence from surface patches and critical residues involved in the said interaction is found to be similar to that of the human counterpart and requires further investigation for legitimacy. Altogether, our study provided crucial information on oligomerization of BcMAVS CARDs and might be helpful for clarifying the innate immune response against pathogens and downstream signaling in fishes.
The effect of decitabine on the expression and methylation of the PPP1CA, BTG2, and PTEN in association with changes in miR‐125b, miR‐17, and miR‐181b in NALM6 cell line
Authors: Vafadar Asma , Mokaram Pooneh , Erfani Mehran , Yousefi Zahra , Farhadi Ali , Elham Shirazi Tehrani , Tamaddon Gholamhossein 
Published: March 2019

AbstractPrecursor B‐cell acute lymphoblastic leukemia (B‐ALL) is the most prevalent pediatric cancer. DNA methylation and changes in the microRNAs (miRNAs) expression are known to be important causes of B‐ALL. Decitabine as a DNA methyltransferase inhibitor agent is able to induce hypomethylation in several tumor suppressor genes. Much evidence has proven BTG2, PPP1CA, and PTEN act as tumor suppressor genes in many malignancies. In this case control study, the messenger RNA (mRNA) expression of PPP1CA, BTG2, and PTEN genes using quantitative real‐time polymerase chain reaction (rRT‐PCR) in Nalm6 cell line and five patients suffer from ALL with mean age 5.6 years were determined in compare with seven normal healthy donors age and sex matched. qRT‐PCR analysis revealed that the expression levels of PPP1CA, BTG2, and PTEN genes were significantly decreased in Nalm6 ([FC] = 0.46, [FC] = 0.046, [FC] = 0.54) and according to the Methylation‐specific PCR (MSP) analysis, these genes were hypermethylated in Nalm6. In next step, the effects of decitabine treatment on the methylation and expression of these genes in association with changes in miR‐125b, miR‐17, and miR‐181b expression levels were evaluated in optimal concentration 2.5 µM of decitabine. Our data showed that decitabine is able to restore the expression levels of aforementioned genes and downregulate expression levels of oncomiRs; including miR‐125b, miR‐17, and miR‐181b in Nalm6 cell line. Therefore, it seems that decitabine can be used as a potential drug for the first line treatment of patients with B‐ALL, but further in vivo investigation is necessary.
microRNA‐448 inhibits the progression of non‐small–cell lung cancer through regulating IRS2
Authors: Gao Jie , Feng Xiaojing , Wang Fang , Wang Junlan , Wang Hongmei , Li Hua , Zhang Weiwei , Hao Lijun , Shi Zhiming 
Published: March 2019

AbstractRecently, microRNA‐448 (miR‐448) has been reported to be a tumor‐associated miRNA in many human cancers. In this study, we investigated the function of miR‐448 in non‐small–cell lung cancer (NSCLC) progression and confirmed the relationship between miR‐448 and insulin receptor substrates 2 (IRS2). First, downregulation of miR‐448 and upregulation of IRS2 were detected in NSCLC using the quantitative real‐time polymerase chain reaction (qRT‐PCR) assay. Furthermore, the MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) assay showed that miR‐448 inhibited cell viability in NSCLC. Transwell and Western blot assays indicated that the upregulation of miR‐448 inhibited cell metastasis and epithelial‐to‐mesenchymal transition (EMT) in NSCLC. And it was found that overexpression of miR‐448 reduced the adhesion of A549 cells to HUVEC cells using the adhesion assay. Furthermore, the dual luciferase assay indicated that miR‐448 directly targeted IRS2 in NSCLC. In addition, it was found that IRS2 silencing had an inhibitory effect on the progression of NSCLC, and the upregulation of IRS2 partially impaired the inhibitory effect of miR‐448 in NSCLC. Briefly, overexpression of miR‐448 inhibited cell proliferation, metastasis, and EMT by suppressing IRS2 expression in NSCLC.
Regulation of signaling pathways by β‐elemene in cancer progression and metastasis
Authors: Qureshi Muhammad Z. , Attar Rukset , Romero Mirna A. , Sabitaliyevich Uteuliyev Y. , Nurmurzayevich Sadykov B. , Ozturk Ozlem , Wakim Lara H. , Lin Xiukun , Ozbey Ulku , Yelekenova Armida Bakhytbekovna , Farooqi Ammad A. 
Published: March 2019

AbstractEntry of β‐elemene into various phases of clinical trials advocates its significance as a premium candidate likely to gain access to mainstream medicine. Based on the insights gleaned from decades of research, it seems increasingly transparent that β‐elemene has shown significant ability to modulate multiple cell signaling pathways in different cancers. We partition this multicomponent review into how β‐elemene strategically modulates various signal transduction cascades. We have individually summarized regulation of tumor necrosis factor related apoptosis‐inducing ligand, signal transducers and activators of transcription, transforming growth factor/SMAD, NOTCH, and mammalian target of rapamycin pathways by β‐elemene. Last, we will discuss the results of clinical trials of β‐elemene and how effectively we can use these findings to stratify patients who can benefit most from β‐elemene.
Long noncoding RNA SOX21‐AS1 promotes cervical cancer progression by competitively sponging miR‐7/VDAC1
Authors: Zhang Xiaoyan , Zhao Xianlan , Li Yan , Zhou Yan , Zhang Zhenyu 
Published: March 2019

AbstractGrowing evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in cervical cancer. Dy000sregulation of lncRNA SOX21 antisense RNA 1 (SOX21‐AS1) has been reported in several tumors. However, its expression pattern and potential biological function in cervical cancer (CC) have not been investigated. In this study, we first reported that SOX21‐AS1 expression was significantly upregulated in both CC tissues and cell lines. High expression of SOX21‐AS1 was found to be significantly correlated with Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and depth of cervical invasion. Further clinical assay confirmed that high SOX21‐AS1 expression was associated with shorter overall survival and could be used as a potential prognostic biomarker for CC patients. Functional investigation showed that knockdown of SOX21‐AS1 suppressed CC cells proliferation, migration, and invasion, as well as epithelial to mesenchymal transition progress. Furthermore, our data showed that microRNA‐7 (miR‐7) interacted with SOX21‐AS1 by directly targeting the miRNA‐binding site in the SOX21‐AS1 sequence, and quantitative real‐time polymerase chain reaction results showed overexpression of SOX21‐AS1 decreased the levels of miR‐7 in CC cells. Moreover, we confirmed that miR‐7 directly targeted the 3′‐untranslated region of voltage dependent anion channel 1 (VDAC1). Final in vitro assay suggested that in CC cells with SOX21‐AS1, VDAC1 overexpression resulted in an increase of cell proliferation, migration, and invasion. Overall, our findings illuminate how SOX21‐AS1 formed a regulatory network to confer an oncogenic function in CC and SOX21‐AS1 could be regarded as an efficient therapeutic target and potential biomarker for CC patients.
Importance of probiotics in the prevention and treatment of colorectal cancer
Authors: Eslami Majid , Yousefi Bahman , Kokhaei Parviz , Hemati Maral , Nejad Zahra Rasouli , Arabkari Vahid , Namdar Afshin 
Published: March 2019

AbstractColorectal cancer (CRC) remains one of the most common and deadly cancers. Intestinal gut microflora is important to maintain and contributes to several intestinal functions, including the development of the mucosal immune system, absorption of complex macromolecules, synthesis of amino acids/vitamins and the protection against pathogenic microorganisms. It is well known that the gut microbiota changes or dysbiosis may have an essential impact in the initiation and promotion of chronic inflammatory pathways and also have a profound different genetic and epigenetic alterations leading to dysplasia, clonal expansion, and malignant transformation. Probiotic bacteria has antitumor activity with various mechanisms such as nonspecific physiological and immunological mechanisms. This review evaluates the effects of microbiota and probiotics in clinical trials, in vitro and animal model studies that have explored how probiotic against cancer development and also discusses the possible immunomodulatory mechanisms. Several mechanisms alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; antiproliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase; reduces the enteropathogenic complications before and after colon cancer surgery and improve diarrhea and it's have been able to create the integrity of gut mucosal and have stimulatory effects on the systemic immune system and prevent the CRC metastasis. Research in clinical trials encouraging findings that support a role of probiotics in CRC prevention and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.
Silencing of a novel lncRNA LOC105369748 suppresses the progression of hepatocellular carcinoma by sponging miR‐5095 from MBD2
Authors: E Changyong , Li Chunsheng , Li Hang , Yang Jinghui 
Published: March 2019

AbstractA growing number of studies have suggested that long noncoding RNAs (lncRNAs) play critical roles in human malignant cancers, including hepatocellular carcinoma (HCC). However, the functions of most lncRNAs have not been elucidated in HCC. In the present study, we explored the potential functions of a novel lncRNA LOC105369748 in the HCC progression. We identified that LOC105369748 expression was significantly elevated in HCC tissues compared with normal tissues based on bioinformatics analysis, quantitative reverse transcription polymerase chain reaction (qRT‐PCR) analysis and in situ hybridization (ISH) examination. Moreover, we found that the LOC105369748 overexpression was associated with poor prognosis in patients with HCC. Then we measured the effects of LOC105369748 on HCC cell proliferation, migration, invasion, and epithelial‐to‐mesenchymal transition (EMT). And our results demonstrated that LOC105369748 exerted oncogenic roles. In terms of mechanism, LOC105369748 was shown to promote MBD2 expression through competitively binding to microRNA(miR)‐5095 in HCC. In conclusion, our findings elucidate that the LOC105369748/miR‐5095/MBD2 signaling axis regulates the HCC progression and may be a novel therapeutic avenue.
Novel therapeutic approaches in utilizing platelet lysate in regenerative medicine: Are we ready for clinical use?
Authors: Zamani Majid , Yaghoubi Yoda , Movassaghpour Aliakbar , Shakouri Kazem , Mehdizadeh Amir , Pishgahi Alireza , Yousefi Mehdi 
Published: March 2019

AbstractHemoderivative materials are used to treat different diseases. These derivatives include platelet‐rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet‐derived growth factor, fibroblast growth factor, insulin‐like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL‐derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials.
Hydrogen sulfide attenuates homocysteine‐induced osteoblast dysfunction by inhibiting mitochondrial toxicity
Authors: Zhai Yuankun , Behera Jyotirmaya , Tyagi Suresh C. , Tyagi Neetu 
Published: March 2019

AbstractHomocysteine (Hcy) is detrimental to bone health in a mouse model of diet‐induced hyperhomocysteinemia (HHcy). However, little is known about Hcy‐mediated osteoblast dysfunction via mitochondrial oxidative damage. Hydrogen sulfide (H2S) has potent antioxidant, anti‐inflammatory, and antiapoptotic effects. In this study, we hypothesized that the H2S mediated recovery of osteoblast dysfunction by maintaining mitochondrial biogenesis in Hcy‐treated osteoblast cultures in vitro. MC3T3‐E1 osteoblastic cells were exposed to Hcy treatment in the presence or absence of an H2S donor (NaHS). Cell viability, osteogenic differentiation, reactive oxygen species (ROS) production were determined. Mitochondrial DNA copy number, adenosine triphosphate (ATP) production, and oxygen consumption were also measured. Our results demonstrated that administration of Hcy increases the intracellular Hcy level and decreases intracellular H2S level and expression of the cystathionine β‐synthase/Cystathionine γ‐lyase system, thereby inhibiting osteogenic differentiation. Pretreatment with NaHS attenuated Hcy‐induced mitochondrial toxicity (production of total ROS and mito‐ROS, ratio of mitochondrial fission (DRP‐1)/fusion (Mfn‐2)) and restored ATP production and mitochondrial DNA copy numbers as well as oxygen consumption in the osteoblast as compared with the control, indicating its protective effects against Hcy‐induced mitochondrial toxicity. In addition, NaHS also decreased the release of cytochrome c from the mitochondria to the cytosol, which induces cell apoptosis. Finally, flow cytometry confirmed that NaHS can rescue cells from apoptosis induced by Hcy. Our studies strongly suggest that NaHS has beneficial effects on mitochondrial toxicity, and could be developed as a potential therapeutic agent against HHcy‐induced mitochondrial dysfunction in cultured osteoblasts in vitro.
NF‐κB targeting for overcoming tumor resistance and normal tissues toxicity
Authors: Mortezaee Keywan , Najafi Masoud , Farhood Bagher , Ahmadi Amirhossein , Shabeeb Dheyauldeen , Musa Ahmed E. 
Published: March 2019

AbstractRadiotherapy and chemotherapy are two famous modalities in tumor‐targeted therapy that lead to systemic and local toxicities for normal tissues. Moreover, several studies have confirmed that exposure of the tumor to radiation or chemotherapy drugs stimulate some signaling pathways in the tumor microenvironment (TME), leading to resistance of cancer cells to apoptosis, as well as promoting angiogenesis and tumor growth. Nuclear factor kappa B (NF‐κB) plays a central role in the regulation of inflammatory responses in both normal tissues and tumors via the release of several cytokines, regulation of prostaglandins, reduction/oxidation (redox) reactions, angiogenesis, and cell death. Upregulation of NF‐κB in normal tissues causes an appearance of inflammatory reactions and oxidative stress, whereas it regulates angiogenesis and suppresses apoptosis, leading to resistance to subsequent doses of radiation or chemotherapy. Selective inhibition of NF‐κB in experimental studies has shown promising results for tumor sensitization via apoptosis induction, inhibition of angiogenesis, and increasing delay of tumor growth. The use of some agents for NF‐κB inhibition has been shown to alleviate radiation/chemotherapy toxicities in normal cells/ tissues. In this current review, we explained the pivotal role of NF‐κB in both normal tissue toxicity and tumor resistance. We also discussed the promising strategies for overcoming these problems with regard to chemotherapy and radiotherapy.
Gene expression, protein profiling, and chemotactic activity of infrapatellar fat pad mesenchymal stem cells in pathologies of the knee joint
Authors: Bravo Beatriz , Guisasola Maria Concepcion , Vaquero Javier , Tirado Irene , Gortazar Arancha R. , Forriol Francisco 
Published: March 2019

AbstractThe infrapatellar fat pad (IPFP) is a periarticular adipose knee tissue. This tissue contains a large number of mesenchymal stem cells (MSCs). In the present work, we wanted to study the IPFP MSCs and their relationship and differences in two groups, anterior cruciate ligament (ACL) ruptures knees and ostheoarthrosis (OA). The IPFP of 42 patients with OA or ACL rupture were analyzed. Isolation, primary culture, and a genetic and proteomic study of MSCs from IPFP were performed. Gene expression of IL‐6, tumor necrosis factor (TNF), IL‐8, HSPA1A (Hsp70), CXCL10, RANTES, MMP1, MMP3, TIMP1, and BMP7 was analyzed by real‐time quantitative polymerase chain reaction (RT‐qPCR). We analyzed MSCs from from 12 diferents patients in two cellular pools (6 from AO disease and 6 from ALC rupture to form two cell pool), for the iTRAQ Proteomic Assay. The conditional media were used in quantitative analysis of MSC soluble factors by Luminex and for de migration assay. A higher gene expression of IL‐6, TNF, CXCL10, RANTES, and MMP1 and OPG in MSCs from OA versus ACL (p < 0.05) was observed. Conversely HSPA1A, TIMP1, and RANKL showed a significant lower expression in OA‐MSCs (p < 0.05). In the secretome analysis, adipsin and visfantin levels in the supernatants from OA‐MSCs were lower (p < 0.05) respect to ACL‐MSCs. Also, the monocytic cells migrated two‐folds in the presence of conditioned media from OA‐MSCs patients versus patients with ACL‐MSC. The infrapatellar pad should be considered as an adipose tissue capable of producing and excreting inflammatory mediators directly in the knee joint, influencing the development and progression of knee joint pathologies.
Radiochemical and radiopharmacological characterization of a 64Cu‐labeled α‐MSH analog conjugated with different chelators
Authors: Gao Feng , Sihver Wiebke , Bergmann Ralf , Walther Martin , Stephan Holger , Belter Birgit , Neuber Christin , Haase‐Kohn Cathleen , Bolzati Cristina , Pietzsch Jens , Pietzsch Hans‐Jürgen 
Published: March 2019

Radiolabeled α‐melanocyte‐stimulating hormone (α‐MSH) derivatives have a high potential for diagnosis and treatment of melanoma, because of high specificity and binding affinity to the melanocortin‐1 receptor (MC1R). Hence, the α‐MSH‐derived peptide NAP‐NS1 with a β‐Ala linker (ε‐Ahx‐β‐Ala‐Nle‐Asp‐His‐D‐Phe‐Arg‐Trp‐Gly‐NH2) was conjugated to different chelators: either to NOTA (p‐SCN‐Bn‐1,4,7‐triazacyclononane‐1,4,7‐triacetic acid), to a hexadentate bispidine carbonate derivative (dimethyl‐9‐(((4‐nitrophenoxy)carbonyl)oxy)‐2,4‐di(pyridin‐2‐yl)‐3,7‐bis(pyridin‐2‐ylmethyl)‐3,7‐diazabicyclo[3.3.1]nonane‐1,5‐dicarboxylate), or to DMPTACN (p‐SCN‐Ph‐bis(2‐pyridyl‐methyl)‐1,4,7‐triaza‐cyclononane), labeled with 64Cu, and investigated in terms of radiochemical and radiopharmacological properties. For the three 64Cu‐labeled conjugates negligible transchelation, suitable buffer and serum stability, as well as appropriate water solubility, was determined. The three conjugates exhibited high binding affinity (low nanomolar range) in murine B16F10, human MeWo, and human TXM13 cells. The Bmax values of [64Cu]Cu‐bispidine‐NAP‐NS1 ([64Cu]Cu‐2) and [64Cu]Cu‐DMPTACN‐NAP‐NS1 ([64Cu]Cu‐3) were higher than those of [64Cu]Cu‐NOTA‐NAP‐NS1 ([64Cu]Cu‐1), implying that different charged chelate units might have an impact on binding capacity. Preliminary in vivo biodistribution studies suggested the main excretion pathway of [64Cu]Cu‐1 and [64Cu]Cu‐3 to be renal, while that of [64Cu]Cu‐2 seemed to be both renal and hepatobiliary. An initial moderate uptake in the kidney decreased clearly after 60 minutes. All three 64Cu‐labeled conjugates should be considered for further in vivo investigations using a suitable xenograft mouse model.