bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic potency of oncolytic virotherapy–induced cancer stem cells targeting in brain tumors, current status, and perspectives
Authors: Bahreyni Amirhossein , Ghorbani Elnaz , Fuji Hamid , Ryzhikov Mikhail , Khazaei Majid , Erfani Marjan , Avan Amir , Hassanian Seyed M. , Azadmanesh Kayhan 
Published: October 2018

AbstractBrain tumors are the most common form of solid tumors in children and is presently a serious therapeutic challenge worldwide. Traditional treatment with chemotherapy and radiotherapy was shown to be unsuccessful in targeting brain tumor cancer stem cells (CSCs), leading to recurrent, treatment‐resistant secondary malignancies. Oncolytic virotherapy (OV) is an effective antitumor therapeutic strategy which offers a novel, targeted approach for eradicating pediatric brain tumor CSCs by utilizing mechanisms of cell killing that differ from conventional therapies. A number of studies and some clinical trials have therefore investigated the effects of combined therapy of radiations or chemotherapies with oncolytic viruses which provide new insights regarding the effectiveness and improvement of treatment responses for brain cancer patients. This review summarizes the current knowledge of the therapeutic potency of OVs‐induced CSCs targeting in the treatment of brain tumors for a better understanding and hence a better management of this disease.
Extracellular matrix (ECM) stiffness and degradation as cancer drivers
Authors: Najafi Masoud , Farhood Bagher , Mortezaee Keywan 
Published: October 2018

AbstractAlteration in the density and composition of extracellular matrix (ECM) occurs in tumors. The alterations toward both stiffness and degradation are contributed to tumor growth and progression. Cancer‐associated fibroblasts (CAFs) are the main contributors to ECM stiffness and degradation. The cells interact with almost all cells within the tumor microenvironment (TME) that could enable them to modulate ECM components for tumorigenic purposes. Cross‐talks between CAFs with cancer cells and macrophage type 2 (M2) cells are pivotal for ECM stiffness and degradation. CAFs induce hypoxia within the TME, which is one of the key inducers of both stiffness and degradation. Cancer cell modulatory roles in integrin receptors are key for adjusting ECM constituents to either fates. Cancer cell proliferation, migration, and invasion as well as angiogenesis are consequences of ECM stiffness and degradation. ECM stiffness in a transforming growth factor‐β (TGF‐β) related pathway could make a bridge in the basement membrane, and ECM degradation in a matrix metalloproteinase (MMP)‐related pathway could make a path in the TME, both of which contribute to cancer cell invasion. ECM stiffness is also obstructive for drug penetration to the tumor site. Therefore, it would be a promising strategy to make a homeostasis in ECM for easy penetration of chemotherapeutic drugs and increasing the efficacy of antitumor approaches. MMP and TGF‐β inhibitors, CAF and M2 reprogramming toward their normal counterparts, reduction of TME hypoxia and hampering integrin signaling are among the promising approaches for the modulation of ECM in favor of tumor regression.
Effect of rapamycin on the level of autophagy in rats with early heart failure
Authors: Zhang Chunxiao , Liu Aifen , Su Guohai , Chen Yudong 
Published: October 2018

AbstractObjectivesHeart failure (HF) progression can be prevented by an inhibitor of the mammalian target of rapamycin and an autophagy enhancer rapamycin. This current study aimed to investigate the effect of rapamycin on HF progression and myocardial cells apoptosis.MethodsHF rats were injected with low‐, middle‐, and high‐dose rapamycin. Echocardiography, hematoxylin‐eosin staining, plasma brain natriuretic peptide, myocardial cells apoptosis, and Akt activation in rapamycin‐treated rats were detected.ResultsHF rats showed reduced cardiac functions, destructive pathological changes in the myocardium, enhanced Akt activation and myocardial cells apoptosis. However, rapamycin reversed all the changes in a dose‐dependent manner. Cardiac functions were enhanced by rapamycin. Myocardial cells apoptotic percentage, Akt expression, and pathological changes of the myocardium in HF rats were inhibited by rapamycin administration.ConclusionsRapamycin protected against myocardial hypertrophy and myocardial cells apoptosis in HF rats in a dose‐dependent manner.
Transactive response DNA binding protein of 43/histone deacetylase 6 axis alleviates H2O2‐induced retinal ganglion cells injury through inhibiting apoptosis and autophagy
Authors: Yi En‐Hui , Xu Feng , Li Peng , Guo Jian‐Qiang 
Published: October 2018

AbstractOxidative damage is believed to contribute to the pathogenesis of diabetic retinopathy (DR). The current study aimed to detect the effects of transactive response DNA binding protein of 43 (TDP‐43) on cell damage induced by hydrogen peroxide (H2O2) in retinal ganglion cells (RGCs) and to investigate the molecular mechanisms involved in this process. We observed that TDP‐43 was highly expressed in RGC‐5 cells induced by H2O2, and that repression of TDP‐43 obviously ameliorated H2O2‐induced RGC‐5 cell injury. In addition, loss of TDP‐43 profoundly mitigated H2O2‐triggered oxidative stress by decreasing the production of intracellular reactive oxygen species and the activity of oxidative stress indicator malondialdehyde, as well as enhancing the content of antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase to restore the antioxidant defense system. Moreover, suppression of TDP‐43 obviously obstructed H2O2‐induced apoptosis. Meanwhile, knockdown of TDP‐43 attenuated the expression of the proapoptotic proteins Bax and Cytochrome c, elevated the anti‐apoptotic protein Bcl‐2, and suppressed the activation of caspase 3 in H2O2‐induced RGC‐5 cells. Moreover, elimination of TDP‐43 inhibited H2O2‐triggered autophagy, which appeared as decreased expression of LC3II/I and Beclin‐1, along with p62 degradation. Importantly, silencing of TDP‐43 diminished the expression of histone deacetylase 6 (HDAC6), and HDAC6 also abolished the inhibitory effect of TDP‐43 inhibition on H2O2‐induced apoptosis and autophagy. Collectively, our findings demonstrated that depletion of TDP‐43 may protect RGC‐5 cells against oxidative stress‐mediated apoptosis and autophagy by suppressing its target HDAC6. Thus, the TDP‐43/HDAC6 axis might be a promising strategy for the treatment of DR.
Rapamycin combined with MCC950 to treat multiple sclerosis in experimental autoimmune encephalomyelitis
Authors: Xu Ling , Zhang Cuili , Jiang Nan , He Dan , Bai Ying , Xin Yi 
Published: October 2018

AbstractMultiple sclerosis (MS) is a highly disabling demyelinating disease, which mainly affects young adults and is difficult to cure. Activated microglia may be involved in the process of neuronal cell damage and release inflammatory cytokines to injure neurons. Rapamycin (RAPA), an immunosuppressant, can induce autophagy in microglia to delay the process of the disease. As an inhibitor of NLRP3, MCC950 (CP‐456773) can regulate the activation of inflammasome. An experimental autoimmune encephalomyelitis model, a disease model of MS, was established to detect the role of activated microglia in the dynamic evolution of MS. Our research showed that RAPA and MCC950 could reduce both the clinical symptom and the release of cytokines in immune cells. MCC950 reduced interleukin‐1β (IL‐1β) production in vivo and enhanced the effect of RAPA. We hypothesized that inflammation and demyelination in the central nervous system can be reduced by inhibiting the immune response mediated by microglia. This study provides theoretical support to the therapeutic evaluation of RAPA and MCC950 to make the mammalian targets of RAPA and NLRP3 the therapeutic targets of MS.
Triad1 regulates the expression and distribution of EHD1 contributing to the neurite outgrowth of neurons after spinal cord injury
Authors: Wu Chunshuai , Bao Guofeng , Xu Guanhua , Sun Yuyu , Wang Lingling , Chen Jiajia , Zhang Jinlong , Chen Chu , Zhu Qiancheng , Cui Zhiming 
Published: October 2018

AbstractTraumatic spinal cord injury is a common and severe complication after an accident. As we all know that neurite outgrowth of neurons is difficult after a spinal cord injury. Endosome system is associated with cargoes transportation and contributes in promoting the neuronal capability for neurite outgrowth. EH domain‐containing protein 1 (EHD1) transports proteins through the endosome system, especially in the recycling endosomes and regulating the neurite outgrowth. In mammalian cells, the involvement of the ubiquitin‐proteasome system in endosomal sorting has been well established. Two RING ﬁngers and a DRIL (double RING ﬁnger‐linked) 1 (Triad1) plays an important role in membrane trafficking and its mutant results in the wrong accumulation of receptors in endosomes and plasma membrane. In this current study, we reasonably integrated the results of the above research and investigated the regulating function of Triad1 to EHD1 following the spinal cord injury. We characterized the upregulated expression and distribution of Triad1 and EHD1 in the neurons after SCI and declared the interaction between Triad1 with EHD1 both in vitro and in vivo. Triad1 regulated the interaction between itself and the full‐length or EH domain of EHD1, which influenced the neurite outgrowth of PC12 cells. Our data delineate a novel interaction between Triad1 and EHD1 that may contribute to the regulation of neurite outgrowth for neurons after the spinal cord injury.
1H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae
Authors: Rona Germana B , Almeida Natalia P , Santos Gilson C , Fidalgo Tatiana KS , Almeida Fabio CL , Eleutherio Elis CA , Pinheiro Anderson S 
Published: October 2018

AbstractNSD3s, the proline‐tryptophan‐tryptophan‐proline (PWWP) domain‐containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein‐dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.
Interactome analysis of the human Cap‐specific mRNA (nucleoside‐2′‐O‐)‐methyltransferase 1 (hMTr1) protein
Authors: Simabuco Fernando Moreira , Pavan Isadora Carolina Betim , Pestana Nathalie Fortes , Carvalho Paulo Costa , Basei Fernanda Luisa , Campos Granato Daniela , Paes Leme Adriana Franco , Zanchin Nilson Ivo Tonin 
Published: October 2018

AbstractIn a previous study, we have shown that the gene promoter of a protein termed KIAA0082 is regulated by interferon and that this protein interacts with the RNA polymerase II. It has been subsequently shown that KIAA0082 is the human cap‐specific messenger RNA (mRNA) (nucleoside‐2′‐O‐)‐methyltransferase 1 (hMTr1), which catalyzes methylation of the 2′‐O
‐ribose of the first nucleotide of capped mRNAs. Pre‐mRNAs are cotranscriptionally processed, requiring coordinate interactions or dissociations of hundreds of proteins. hMTr1 potentially binds to the 5′‐end of the whole cellular pre‐mRNA pool. Besides, it contains a WW protein interaction domain and thus is expected to be associated with several proteins. In this current study, we determined the composition of complexes isolated by hMTr1 immunoprecipitation from HEK293 cellular extracts. Consistently, a large set of proteins that function in pre‐mRNA maturation was identified, including splicing factors, spliceosome‐associated proteins, RNA helicases, heterogeneous nuclear ribonucleoproteins (HNRNPs), RNA‐binding proteins and proteins involved in mRNA 5′‐ and 3′‐end processing, forming an extensive interaction network. In total, 137 proteins were identified in two independent experiments, and some of them were validated by immunoblotting and immunofluorescence. Besides, we further characterized the nature of several hMTr1 interactions, showing that some are RNA dependent, including PARP1, ILF2, XRCC6, eIF2α, and NCL, and others are RNA independent, including FXR1, NPM1, PPM1B, and PRMT5. The data presented here are consistent with the important role played by hMTr1 in pre‐mRNA synthesis.
Beneficial effects of metformin on muscle atrophy induced by obesity in rats
Authors: Hasan Mai M. , Shalaby Sally M. , El‐Gendy Jehan , Abdelghany Eman M. A. 
Published: October 2018

AbstractAimA growing interest to understand the signaling pathways mediating obesity‐induced muscle atrophy is given. Metformin (Met) was reported to possess positive effects on preventing muscle damage and promoting muscle mass maintenance. The aim of the present study to investigate pathways involved in Met effect on obesity induced muscle atrophy.MethodsThirty adult male albino rats were assigned into two groups: normal chew diet fed group as control group (C; n = 10) and high‐fat‐diet (HFD) fed group (
n = 20). After 16 weeks, the HFD‐fed animals were subdivided into two groups; HFD group (
n = 10) and HFD fed treated with oral Met (320 mg/day) treatment (Met,
n = 10) for 4 weeks. At the end of the experiment; final body weight, visceral fat weight, fasting blood glucose, insulin, lactate, total cholesterol, triglycerides were measured and calculated homeostatic model assessment insulin resistant (HOMA‐IR) for all groups. Soleus muscle weight, histopathlogical examination and expression of peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), forkhead box O3 (FoxO3), atrogin‐1/MAFbx, and muscle RING finger 1 (MuRF‐1) were performed.ResultsHFD‐fed animals showed significant increase in final body weight, visceral fat mass, fasting blood glucose, insulin, calculated HOMA‐IR, lactate, total cholesterol and triglycerides with significant decrease in soleus muscle weight, PGC‐1α and significant increase in FoxO3, atrogin‐1/MAFbx, and MuRF‐1 expression. Also, there was significant decrease in fiber diameter, myosin heavy chain (MHC) I content while collagen content and myosin heavy chain IIa were increased compared with control group. Met‐treated group showed a significant decrease in the measured parameters compared with the HFD group. It also restored the gene expression, morphometric measures and MHC composition toward normal.ConclusionThe current study is the first to provide evidence that Met could ameliorate muscle atrophy in high‐fat diet induced obesity and this effect may be in part due to regulation of PGC‐1α‐FoxO3 pathway.
Does proliferation capacity of lymphocytes depend on human blood types?
Authors: Viswanathan Sribala , Kanagaraj Karthik , Raavi Venkateswarlu , Dhanasekaran Shanmugapriya , Panicker Vinod Kumar , R Krishnamoorthy , S. Balajee Adayabalam , Perumal Venkatachalam 
Published: October 2018

AbstractIn vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual’s blood type may potentially modulate in vitro proliferation response. These factors have to be carefully evaluated to release reliable test report in routine cytogenetic evaluation for various genetic conditions, radiation biodosimetry, etc. With this objective, the current study was focused on analyzing the proliferation response of lymphocytes drawn from 90 individuals (21‐29 years) with different blood types. The proliferation response was assessed in the cultured lymphocytes by cell cycle, mitotic index (MI), and nuclear division index (NDI) after stimulation with phytohaemagglutinin (PHA). To investigate the toxic effect on proliferation, MI was calculated in representative samples of each blood type were X‐irradiated. The results showed that there was no significant difference among the cell cycle phases of lymphocytes in different blood types (P > 0.05). Similarly, both MI and NDI of lymphocytes derived from different blood types also did not show significant difference (
P > 0.05). The extensive interindividual variation within and among the blood types is likely responsible for the lack of significant difference in lymphocyte proliferation. Although spontaneous proliferation efficiency of lymphocytes of different blood types after PHA stimulation was grossly similar, the MI observed after radiation exposure showed a significant difference (
P < 0.05) indicating a differential proliferation response among the blood types. Our results suggest that the blood types did not have any impact on PHA‐induced proliferation; however, a specific differential lymphocyte proliferation observed after radiation exposure needs to be considered.
Identification of B‐ and T‐cell epitopes on HtrA protein of Orientia tsutsugamushi
Authors: Sankar Sathish , Saravanan Nithiyanandan , Rajendiran Prashanth , Ramamurthy Mageshbabu , Nandagopal Balaji , Sridharan Gopalan 
Published: October 2018

AbstractOrientia tsutsugamushi, a cause of scrub typhus is emerging as an important pathogen in several parts of the tropics. The control of this infection relies on rapid diagnosis, specific treatment, and prevention through vector control. Development of a vaccine for human use would be very important as a public health measure. Antibody and T‐cell response have been found to be important in the protection against scrub typhus. This study was undertaken to predict the peptide vaccine that elicits both B‐ and T‐cell immunity. The outer‐membrane protein, 47‐kDa high‐temperature requirement A was used as the target protein for the identification of protective antigen(s). Using BepiPred2 program, the potential B‐cell epitope PNSSWGRYGLKMGLR with high conservation among
O. tsutsugamushi and the maximum surface exposed residues was identified. Using IEDB, NetMHCpan, and NetCTL programs, T‐cell epitopes MLNELTPEL and VTNGIISSK were identified. These peptides were found to have promiscuous class‐I major histocompatibility complex (MHC) binding affinity to MHC supertypes and high proteasomal cleavage, transporter associated with antigen processing prediction, and antigenicity scores. In the I‐TASSER generated model, the C‐score was −0.69 and the estimated TM‐score was 0.63 ± 0.14. The location of the epitope in the 3D model was external. Therefore, an antibody to this outer‐membrane protein epitope could opsonize the bacterium for clearance by the reticuloendothelial system. The T‐cell epitopes would generate T‐helper function. The B‐cell epitope(s) identified could be evaluated as antigen(s) in immunodiagnostic assays. This cocktail of three peptides would elicit both B‐ and T‐cell immune response with a suitable adjuvant and serve as a vaccine candidate.
The role of IL‐3 in bone
Authors: Soysa Niroshani Surangika , Alles Neil 
Published: October 2018

AbstractIn the recent past, there has been a burgeoning interest in targeting cytokines such as IL‐3 for specific disease conditions of bone such as rheumatoid arthritis and multiple myeloma. Unlike other cytokines, IL‐3 is a cytokine with a multilineage potential and broad spectrum of target cells and it plays a vital role in hematopoiesis. Due to its common receptor subunit, the action of IL‐3 shows functional redundancy with other cytokines such as the granulocyte‐macrophage colony‐stimulating factor and IL‐5. IL‐3 has been successfully used in ameliorating radiation‐induced bone marrow aplasia and similar conditions. However, the role of IL‐3 in bone cells has not been fully unraveled yet; therefore, the aim of this overview is to present the effects of IL‐3 in bone with a special emphasis on osteoclasts and osteoblasts in a concise manner.
CD62P and P10 as predictive markers for assessing the efficacy of hemodialysis in treating end‐stage renal disease
Authors: Yu Ji‐Rong , Wang Feng‐Mei , Xu Sheng‐Chun , Gao Min 
Published: October 2018

BackgroundCD62P is a platelet α‐granule membrane protein, and P10 is a platelet membrane glycoprotein thrombospondin. To better understand the effects of hemodialysis (HD), we have conducted this study to investigate CD62P and P10 in assessing the efficacy of HD in treating patients with end‐stage renal disease (ESRD).MethodsThe case group consisted of 111 patients suffering ESRD treated with regular HD and the control group enrolled 117 healthy subjects. Before and after HD treatment, a series of parameters were observed, based on which, CD62P and P10 levels were detected in the patients in two groups before and after HD therapy. The correlation analysis analyzed the correlations of CD62P and P10 markers with serum creatinine (Scr), blood urea nitrogen (BUN), and subjective score; and logistic regression analysis was performed to reveal factors affecting the efficacy of HD.ResultsBUN, Scr, serum phosphorus, intact parathyroid hormone (iPTH), fibrinogen, and β2‐microglobulin (β2‐MG) decreased while hemoglobin, albumin, and activated partial thromboplastin time increased in the patients suffering ESRD; patients presented with improvements in subjective symptoms and an increase in dry weight. CD62P and P10 levels were lower in post‐treatment patients. CD62P and P10 positively correlated with Scr, BUN and subjective score; post‐treatment CD62P and P10 levels, BUN, hemoglobin, albumin, triglyceride, iPTH, β2‐MG, and fibrinogen were correlated with the efficacy of HD.ConclusionCD62P and P10 might be correlated to the efficacy of HD in treating ESRD, in turn providing predictive markers for assessing the ability of HD in treating ESRD.
Queering Black activism: Exploring the relationship between racial identity and Black activist orientation among Black LGBTQ youth
Authors: Pender Kristen N. , Hope Elan C. , Riddick Kristen N. 
Published: October 2018

AbstractLinked fate, or connection to the Black community, may be a pathway to engagement in social justice action for Black liberation. The purpose of this study is to understand the role of racial identity on Black queer youths’ orientation toward Black activism. We used hierarchical linear regression to examine relationships between dimensions of racial identity and Black activism orientation among 142 queer‐identified youth. We found that racial centrality and racial ideologies predicted high‐risk activism orientation. Additionally, assimilationist ideology moderated the relationship between racial centrality and high‐risk activism orientation. The degree to which Black queer youth feel race is central to their self‐concept relates with their intent to engage in Black activism. These findings demonstrate that racial ideologies matter distinctively to activism orientation and offer that perception of risk nuances linked fate as a pathway to activism for Black queer youth.