bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of protein kinase R protects against palmitic acid–induced inflammation, oxidative stress, and apoptosis through the JNK/NF‐kB/NLRP3 pathway in cultured H9C2 cardiomyocytes
Authors: Mangali Sureshbabu , Bhat Audesh , Udumula Mary Priyanka , Dhar Indu , Sriram Dharmarajan , Dhar Arti 
Published: September 2018

AbstractBackground and PurposeDouble‐stranded RNA‐dependent protein kinase (PKR) is a critical regulator of apoptosis, oxidative stress, and inflammation under hyperlipidemic and insulin resistance conditions. Saturated free fatty acids, such as palmitic acid (PA), are known inducers of apoptosis in numerous cell types. However, the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of PA on cultured rat H9C2 cardiac myocytes cells and to investigate the PKR mediated harmful effects of PA in vitro in cultured cardiomyocytes.Experimental ApproachPKR expression was determined by immunofluorescence and immunoblotting. Oxidative stress and apoptosis were determined by flow cytometry and assay kits. The expression of different gene markers of apoptosis, oxidative stress, and inflammation were measured by Western blot analysis and reverse transcription polymerase chain reaction.Key ResultsPKR expression, reactive oxygen species levels as well as apoptosis were increased in PA‐treated cultured H9C2 cardiomyocytes. The harmful effects of PA were attenuated by a selective PKR inhibitor, C16. Moreover, we observed that upregulation of c‐Jun N‐terminal kinase (JNK), nuclear factor‐kB (NF‐kB) and NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) pathways is associated with increased expression of interleukin 6 and tumor necrosis factor‐α in PA‐treated cardiomyocytes and attenuation by a selective PKR inhibitor.Conclusion and ImplicationsOur study reports, for the first time, that PKR‐mediated harmful effects of PA in cultured cardiomyocytes via activation of JNK, NF‐kB, and NLRP3 pathways. Inhibition of PKR is one of the possible mechanistic approaches to inhibit inflammation, oxidative stress, and apoptosis in lipotoxicity‐induced cardiomyocyte damage.
Pingchuanning decoction attenuates airway inflammation by suppressing autophagy via phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin signaling pathway in rat models of asthma
Authors: Wang Xinheng , Gao Yating , Yang Qinjun , Fang Xiangming , Li Zegeng 
Published: September 2018

AbstractBackgroundPingchuanning decoction is a well‐known traditional Chinese medicine for the treatment of airway inflammatory diseases, including asthma. However, the potential mechanism by which Pingchuanning decoction contributes to the amelioration of airway inflammation remains unknown.MethodsA rat model of asthma was well established by inducing ovalbumin. Lipopolysaccharide‐stimulated rat tracheal epithelial (RTE) cells were used as cellular model. Lung histopathology and goblet cell hyperplasia were assessed by hematoxylin‐eosin (HE) and periodic acid Schiff staining, respectively. Total inflammatory cells count and RTE cell apoptosis were analyzed by flow cytometry. The autophagic activities were evaluated by immunohistochemical and immunofluorescence analysis and Western blot analysis of autophagy‐related proteins. We also detected the effects of Pingchuanning decoction on phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and high‐mobility group box 1 (HMGB1)‐mediated toll‐like receptor 4 (TLR4)/NF‐κB pathways‐related proteins and inflammatory cytokines using the Western blot analysis and enzyme‐linked immunosorbent assay.ResultsPingchuanning decoction effectively attenuated pulmonary pathology and autophagy. Treatment with Pingchuanning decoction activated PI3K/Akt/mTOR pathway and inhibited HMGB1/TLR4/NF‐κB pathway, which could be overturned by LY294002, a PI3K antagonist, or rapamycin (Rapa), an autophagy inducer.ConclusionPingchuanning decoction exerted a therapeutic effect on asthma by inhibiting autophagy via PI3K/Akt /mTOR signaling pathway.
Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress
Authors: Yang Qining , Zhou Yongwei , Wang Jinhua , Fu Weicong , Li Xiaofei 
Published: September 2018

AbstractObjectiveThe aim of the study was to explore the mechanism of excessive apoptosis of nucleus pulposus cells induced by short hairpin RNA (shRNA) Piezo type mechanosensitive ion channel component 1 (Piezo1) under abnormal mechanical stretch stress.MethodsIn vitro mechanical stretch stress model of nucleus pulposus cells in vitro was established, in which the expression of Piezo1 was interfered by transfection of shRNA‐Piezo1 interfering vector. Both messenger RNA and protein level of Piezo1 were measured by reverse‐transcription polymerase chain reaction and Western blot analysis, respectively. Cytoplasmic Ca2+ was detected by Fluo3‐AM kit, and changes of mitochondrial membrane potential in cells were detected using Cell Meter Assay kit. Finally, the apoptosis was evaluated with annexin V‐fluorescein isothiocyanate kit.ResultsThe highest transfection efficiency of lentivirus titer was 1 × 10 TU/mL and the nucleus pulposus cells were transfected with plural multiplicity of infection = 50. Homo‐3201 sequence exhibited the most effective silencing effect and was used in subsequent experiments as the default sequence of shRNA‐Piezo1. The calcium content in the cytoplasm of the tension stress group increased significantly compared with that in the blank control group (
q = 3.773;
P < 0.05). The level of cytosolic calcium in shRNA‐interference group was significantly lower than that in stretch stress group (
q = 5.159;
P < 0.05). Stretch stress treatment resulted in an elevated ratio of mitochondrial membrane potential turnover as opposed to blank control group (
q = 4.332;
P < 0.05), while shRNA‐interference group showed smaller ratio of mitochondrial membrane potential turnover than that in stretch stress group (
q = 4.974;
P < 0.05). Similar results were also observed in apoptosis rate analysis (
q = 3.175;
P < 0.05).ConclusionShRNA‐Piezo1 can protect cells by reducing the level of intracellular Ca2+ and the change of mitochondrial membrane potential.
Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide‐induced hypocampal neuroinflammation in rats
Authors: Garcia Israel José Pereira , Kinoshita Paula Fernanda , Silva Lílian Nara David e , De Souza Busch Mileane , Atella Georgia Correa , Scavone Cristoforo , Cortes Vanessa Faria , Barbosa Leandro Augusto , De Lima Santos Hérica 
Published: September 2018

AbstractOur study aimed to analyze the effect of ouabain (OUA) administration on lipopolysaccharide (LPS)‐induced changes in hippocampus of rats. Oxidative parameters were analyzed in Wistar rats after intraperitoneal injection of OUA (1.8 µg/kg), LPS (200 µg/kg), or OUA plus LPS or saline. To reach our goal, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), in addition to levels of reduced glutathione (GSH), protein carbonyl (PCO) and lipid peroxidation (LPO) were evaluated. We also analyzed the membrane lipid profile and some important lipids for the nervous system, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidic acid and sphingomyelin. The group that received only LPS showed increased oxidative stress, as evidenced by an increase in LPO (about twice), PCO (about three times) levels, and CAT activity (80%). Conversely, administration of LPS decreased GSH levels (55%), and GPx activity (30%), besides a reduction in the amount of PI (60%) and PC (45%). By other side, OUA alone increased the amount of PI (45%), PE (85%), and PC (70%). All harmful effects recorded were attenuated by OUA, suggesting a protective effect against LPS‐induced oxidative stress. The relevance of our results extends beyond changes in oxidative parameters induced by LPS, because nanomolar doses of OUA may be useful in neurodegenerative models. Other studies on other cardenolides and substances related issues, as well as the development of new molecules derived from OUA, could also be useful in general oxidative and/or cellular stress, a condition favoring the appearance of neuronal pathologies.
The AP2M1 gene expression is a promising biomarker for predicting survival of patients with hepatocellular carcinoma
Authors: Cho Sung Hwan , Pak Kyoungjune , Jeong Dae Cheon , Han Myoung‐Eun , Oh Sae‐Ock , Kim Yun Hak 
Published: September 2018

AbstractThere is a growing need for the discovery of new prognostic factors for cases where the scoring and staging system of hepatocellular carcinoma (HCC) does not result in a clear definition. We analyzed whether AP‐2 complex subunit mu (AP2M1) expression could be a new prognostic marker for HCC based on the roles of AP2M1 in influencing hepatocyte growth factor (HGF) promoter regulation and hepatitis C virus (HCV) assembly. Patient data were extracted from cohorts of the Gene Expression Omnibus (GSE10186), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential expression value between matched cancer and normal liver was identified using ICGC cohort. Subsequently, we compared AP2M1 expression as a prognostic gene with other well‐known prognostic genes for HCC, using the time‐dependent area under the curve (AUC) of the Uno's C‐index, the AUC value of the receiver operating characteristics at 5 years, Kaplan‐Meier survival curve, and multivariate analysis. Particularly, TCGA and GSE10186 patients were divided into subgroups based on alcohol intake, hepatitis B, and C viral infections, and analyzed in the same methods. The AP2M1 expression values in patients with cancer were much higher than matched normal liver. The AP2M1 level showed excellent prognosis predictions in comparison with existing markers in the three independent cohorts (n = 647). In particular, it was more predictive of prognosis than other markers in alcohol intake and HCV infections. In conclusion, we were confident that AP2M1 provides sufficient value as a new prognostic marker for HCC especially patients with HCV infection and/or alcohol intake.
Itraconazole inhibits proliferation of pancreatic cancer cells through activation of Bak‐1
Authors: Jiang Fan , Xing Hong‐S. , Chen Wei‐Y. , Du Jie , Ruan Yue‐l. , Lin An‐Y. , Zhou Chi‐Z. 
Published: September 2018

AbstractItraconazole is an FDA‐approved antifungal agent, which has been reported to possess promising anticancer activities in recent years. This study investigates the antiproliferative effects of itraconazole on pancreatic cancer cells and the molecular mechanism of its apoptosis‐inducing effects. In this study, our results showed that itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization. A Bak‐1 activation dependent apoptosis was identified in CFPAC‐1 cells. These data suggested that itraconazole exhibited antiproliferative effects in pancreatic cancer cells by inducing apoptosis through Bak‐1 activation.
From an increase in the number of tandem repeats through the decrease of sialylation to the downregulation of MUC1 expression level
Authors: Syrkina Marina , Viushkov Vladimir , Potashnikova Daria , Veiko Vladimir , Vassetzky Yegor , Rubtsov Mikhail 
Published: September 2018

AbstractEnhanced glucose uptake by cancer cells was demonstrated in many studies in vitro and in vivo. Glycolysis is one of the main ways of obtaining energy in hypoxia conditions. However, in addition to energy exchange, carbohydrates are also necessary for the posttranslational modification of the protein molecules. Cancer cells are often characterized by an enhanced expression of different glycoproteides. Correct glycosylation defines the structure and activity of such molecules. We demonstrated that under the same cultivation conditions, the intensity of glycosylation does not depend on the total number of potential O‐glycosylation sites in one molecule. As a model for the investigation, the tandem repeat region (region with variable number of tandem repeats) of the human mucin MUC1, in which each of the repeats carries four potential
O‐glycosylation sites, was used. An increase of the tandem repeat number in the recombinant protein did not lead to a proportional increase in the level of sLea glycosides. A consequence of this was a reduction in the number of recombinant proteins associated with the cytoplasmic membrane at an overall high expression level. Prolongation of the cultivation duration led to a reduction in the expression level of the recombinant proteins by up to 30% of the initial level, and the intensity of this reduction was in a direct ratio to the number of tandem repeats in the protein molecule.
microRNA‐211 promotes proliferation, migration, and invasion ability of oral squamous cell carcinoma cells via targeting the bridging integrator 1 protein
Authors: Zheng Jiabao , Wang Jiali , Jia Yunlong , Liu Tianxu , Duan Yuqing , Liang Xing , Liu Lihua 
Published: September 2018

AbstractOral squamous cell carcinoma (OSCC), the most common pathological type of oral cancer, is still a frequent malignancy with unsatisfactory prognosis. Accumulating studies have proven some microRNAs (miRNAs) can function as oncogenes in OSCC by targeting tumor suppressors. In this study, we first investigated the expression and role of tumor suppressor bridging integrator‐1 (BIN1) in OSCC tissues and cells. Our results indicated that BIN1 was low expressed in the OSCC tissues and cell lines (SCC6, SCC9, SCC25, HN4, and HN6) along with miR‐211 was highly expressed in OSCC tissues and cell lines, and BIN1 overexpression could evidently inhibit their proliferation, migration, and invasion abilities. Next, we used bioinformation algorithms to predict the potential miRNA targeting BIN1 and chose miR‐211 for further study. miR‐211, a highly expressed miRNA in OSCC cells, could specifically bind with the 3′‐untranslated region (3′‐UTR) of BIN1 to trigger its degradation. Addition of miR‐211 inhibitor could evidently suppress the malignant behaviors of OSCC cells by upregulating BIN1 expression and inhibit the activation of the EGFR/MAPK pathway. Taken together the findings of the study indicated that miR‐211 mediated BIN1 downregulation had crucial significances in OSCC, suggesting the miR‐211 might be a novel potential therapeutic target for the OSCC treatment.
MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma
Authors: Sotoudeh Masoud , Shirvani Seyed Iman , Merat Shahin , Ahmadbeigi Naser , Naderi Mahmood 
Published: September 2018

AbstractGastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody‐based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody‐based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on‐target and off‐tumor toxicities owing to their higher sensitivity to low‐level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off‐tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.
20(S)‐protopanaxadiol induces apoptosis in human umbilical vein endothelial cells by activating the PERK‐eIF2alpha‐ATF4 signaling pathway
Authors: Wang Xue , Xia Hua‐Ying , Qin Hong‐You , Kang Xiang‐Ping , Hu Hai‐Yan , Zheng Jing , Jiang Jia‐Ye , Yao Ling‐Ai , Xu Yan‐Wu , Zhang Tong , Zhang Xue‐Li 
Published: September 2018

Abstract20(S)‐protopanaxadiol (PPD)‐type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti‐cancer activity. Anti‐angiogenesis is a promising therapeutic approach for controlling angiogenesis‐related diseases such as malignant tumors, age‐related macular degeneration, and atherosclerosis. Studies showed that 20(S)‐PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)‐PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)‐PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)‐PPD induces apoptosis in HUVECs for the first time. We found that caspase‐9 and its downstream caspase, caspase‐3, were cleaved into their active forms after 20(S)‐PPD treatment. Treatment with 20(S)‐PPD decreased the level of Bcl‐2 expression but did not change the level of Bax expression. 20(S)‐PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R‐like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP‐homologous protein (CHOP) expression increased after treatment with 20(S)‐PPD. Furthermore, siRNA‐mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)‐PPD‐induced apoptosis. Collectively, our findings show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)‐PPD could be used to treat angiogenesis‐related diseases.
Uniform decompositions of complete multigraphs into cycles
Authors: Berry Duncan , Bryant Darryn , Dean Matthew , Maenhaut Barbara 
Published: September 2018

AbstractThe notion of uniformity, as in uniform ‐factorisations, extends naturally to graph decompositions generally. The existence of uniform decompositions of complete multigraphs into cycles is investigated and some connections with families of classical designs are established. We show that if there exists a uniform decomposition of into ‐cycles then (A) and , or (B) and , or (C) , and or (D) and . For case A, there are only a few small values of and to consider, and we exhibit all uniform decompositions up to isomorphism for each such and . In each of cases B and C, we construct examples of uniform decompositions for infinitely many values of , and we investigate the isomorphism classes of our examples for each such . We have no examples of uniform decompositions in case D, but we rule out the smallest example, namely and , and we prove that if such decompositions exist, then so do large quasiresidual designs that are not residual.
Mosaic trisomy 22 in a 4‐year‐old boy with congenital heart disease and general hypotrophy: A case report
Authors: Kalayinia Samira , Shahani Tina , Biglari Alireza , Maleki Majid , Rokni‐Zadeh Hassan , Razavi Zahra , Mahdieh Nejat 
Published: September 2018

BackgroundTrisomy 22 mosaicism is a rare autosomal anomaly with survival compatibility. Recognition of the complete trisomy 22 which is incompatible with life from the mosaic form is critical for genetic counseling. Affected mosaic cases have prevalent clinical presentations such as webbed neck, developmental delay, abnormal ears, cardiac disorders, and microcephaly. Phenotype of these patients is milder than full chromosomal aneuploidy, and the severity of the phenotype depends on the count of trisomic cells. We describe a 4‐year‐old boy with mosaic trisomy 22 from healthy parents and no family history of any genetic disorders in the pedigree.Method and ResultsThe patient had determined dysmorphic clinical features including facial asymmetry, cleft palate, gastroenteritis, hydronephrosis, developmental delay, genital anomalies, dysplastic toenails, flattened nasal bridge, congenital heart defect, hearing loss, cryptorchidism, and hypotonic muscle. He is the first reported with hypothyroidism and larynx wall thickness in worldwide and the first with atrial septal defect (ASD) from Iran. Chromosomal analyses using G‐banding indicated a de novo Mos 47,XY,+22(6)/46,XY(44) karyotype with no other chromosomal structural changes.ConclusionsOur observations confirm the importance of cytogenetic analyses for determining the cause of congenital anomalies and provide a useful genetic counseling. In addition, due to the fact that some of mosaic trisomy 22 features are unavoidable such asCHDand general hypotrophy, we suggest including echocardiography test for early diagnosis during the clinical assessment.
Elevation of serum oxLDL/β2‐GPI complexes was correlated with diabetic microvascular complications in Type 2 diabetes mellitus patients
Authors: Xie Lianzhi , Lin Hui , Wang Caihong 
Published: September 2018

BackgroundHigh levels of oxLDL/β2‐GPI complexes might be a consequence of LDL atherogenic modification mediated by oxidative stress. We aimed to determine whether the levels of serum oxLDL/β2‐GPI complexes were correlated with diabetic microvascular complications in type 2 diabetes mellitus (T2DM) patients.MethodsLevels of oxLDL/β2‐GPI complexes, oxLDL, routine lipid/lipoprotein parameters were measured in 100 healthy controls, 128 T2DM patients without any microvascular complications, and 172 T2DM patients with microvascular complications. Spearman's correlation, multivariable linear regression logistic regression analysis, and receiver operating characteristic (ROC) curve were performed.ResultsLevels of serum oxLDL/β2‐GPI complexes and oxLDL were significantly higher in T2DM patients with microvascular complications (oxLDL/β2‐GPI complexes: 1.10 ± 0.18 U/mL; oxLDL: 48.12 ± 7.24 mmol/L) than those in T2DM patients without microvascular complications (oxLDL/β2‐GPI complexes: 0.98 ± 0.16 U/mL; oxLDL: 41.45 ± 6.81 mmol/L) and controls (oxLDL/β2‐GPI complexes: 0.79 ± 0.15 U/mL; oxLDL: 27.85 ± 5.32 mmol/L). Variables that remained significantly associated with oxLDL/β2‐GPI complexes were oxLDL (β = 0.568, P < 0.001), TC (β = 0.312, P = 0.013) and microvascular complications (β = 0.205, P = 0.027), which accounted for 58.3% of the variation of the level of oxLDL/β2‐GPI complexes in T2DM patients (R2 = 0.583). Logistic regression analysis demonstrated that elevation of oxLDL/β2‐GPI complexes (OR = 3.14, 95% CI: 1.04‐9.46, P = 0.042) and oxLDL levels (OR = 3.02, 95% CI: 1.16‐7.83, P = 0.023) were independently associated with occurrence of microvascular complications. Cutoff value of oxLDL/β2‐GPI for the presence of microvascular complications was 1.05 U/mL, and AUC area of ROC curve was 0.783 (95%CI: 0.713‐0.853), yielding a sensitivity of 86.8% and specificity of 64.9%.ConclusionsElevation of serum oxLDL/β2‐GPI complexes was associated with microvascular complications in T2DM patients.