bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio–temporal patterns of cognitive control revealed with simultaneous electroencephalography and functional magnetic resonance imaging
Authors: Hinault Thomas , Larcher Kevin , Zazubovits Natalja , Gotman Jean , Dagher Alain
Published: September 2018

Optimal performance depends in part on the ability to inhibit the automatic processing of irrelevant information and also on the adjusting the level of control from one trial to the next. In this study, we investigated the spatio–temporal neural correlates of cognitive control using simultaneous functional magnetic resonance imaging and electroencephalography, while 22 participants (10 women) performed a numerical Stroop task. We investigated the spatial and temporal dynamic of the conflict adaptation effects (i.e., reduced interference on items that follow an incongruent stimulus compared to after a congruent stimulus). Joint independent component analysis linked the N200 component to activation of anterior cingulate cortex (ACC) and the conflict slow potential to widespread activations within the fronto–parietal executive control network. Connectivity analyses with psychophysiological interactions and dynamic causal modeling demonstrated coordinated engagement of the cognitive control network after the processing of an incongruent item, and this was correlated with better behavioral performance. Our results combined high spatial and temporal resolution to propose the following network of conflict adaptation effect and specify the time course of activation within this model: first, the anterior insula and inferior frontal gyrus are activated when incongruence is detected. These regions then signal the need for higher control to the ACC, which in turn activates the fronto–parietal executive control network to improve the performance on the next trial.
The temporal dynamics of structure and content in sentence comprehension: Evidence from fMRI‐constrained MEG
Authors: Matchin William , Brodbeck Christian , Hammerly Christopher , Lau Ellen
Published: September 2018

Humans have a striking capacity to combine words into sentences that express new meanings. Previous research has identified key brain regions involved in this capacity, but little is known about the time course of activity in these regions, as hemodynamic methods such as fMRI provide little insight into temporal dynamics of neural activation. We performed an MEG experiment to elucidate the temporal dynamics of structure and content processing within four brain regions implicated by fMRI data from the same experiment: the temporo‐parietal junction (TPJ), the posterior temporal lobe (PTL), the anterior temporal lobe (ATL), and the anterior inferior frontal gyrus (IFG). The TPJ showed increased activity for both structure and content near the end of the sentence, consistent with a role in incremental interpretation of event semantics. The PTL, a region not often associated with core aspects of syntax, showed a strong early effect of structure, consistent with predictive parsing models, and both structural and semantic context effects on function words. These results provide converging evidence that the PTL plays an important role in lexicalized syntactic processing. The ATL and IFG, regions traditionally associated with syntax, showed minimal effects of sentence structure. The ATL, PTL and IFG all showed effects of semantic content: increased activation for real words relative to nonwords. Our fMRI‐guided MEG investigation therefore helps identify syntactic and semantic aspects of sentence comprehension in the brain in both spatial and temporal dimensions.
Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Elbel Erin E. , Lavine Joel E. , Downes Michael , Van Natta Mark , Yu Ruth , Schwimmer Jeffrey B. , Behling Cynthia , Brunt Elizabeth M. , Tonascia James , Evans Ronald
Published: September 2018

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials. Liver messenger RNA was isolated from 40 children (10‐19 years) undergoing end‐of‐treatment biopsy in the Treatment of NAFLD in Children (TONIC) trial. High‐throughput quantitative polymerase chain reaction assayed NR messenger RNA. Cluster analysis was used to group 36 NRs, and NR levels were related to histologic measures of specific NAFLD features. Cluster analysis determined five groupings of NRs. Significant (P < 0.05) differential expressions of specific NRs associated with histologic measures include farnesoid X receptor alpha and retinoic acid receptor (RARβ and RARβ) for steatosis; estrogen receptor alpha (ERα) and peroxisome proliferator‐activated receptor gamma 3 (PPARγ3) for hepatocellular ballooning; ER and PPARγ2 for lobular inflammation; PPARα/δ/γ1/γ2, ERα, constitutive androstane receptor, chicken ovalbumin upstream promoter transcription factor 1, RARα, RARβ1, retinoid X receptor, pregnane X receptor, thyroid hormone receptors α and β, and nuclear receptor related‐1 for fibrosis; and ERα and RARβ/β1/α for diagnosis of NASH. Conclusion: Differential expression of specific NRs correlates with histologic severity of specific NAFLD features. These NRs are pleiotropic transactivators regulating basal metabolic functions and inflammatory responses. Derangement of activity of these receptors in NAFLD provides a rationale for exploiting their ability with receptor‐specific ligands to ameliorate NASH and its consequences.
Prospective intervention opportunities regarding device ownership and the reduction of damage to handheld ruggedized devices with shift workers
Authors: Burch Reuben F. , Strawderman Lesley , Cannon Angela B. , Vander Linde Rebecca
Published: September 2018

Industrial equipment such as ruggedized handheld computers, scanners, and label printers used within asset tracking environments are expensive to purchase and costly to repair. For organizations that use this equipment, there is value in understanding when and why damage occurs and how much of those costs are potentially associated with the employees’ own sense of psychological ownership and organizational pride. Given the connection between psychological ownership and pride, the purpose of this study was to analyze employee surveys to determine what methods, tools, or programs could reduce repair and replacement while developing a stronger sense of ownership for ruggedized devices used in material‐handling industries by shift workers. Unstructured interviews about device repair with management from a large industrial company were utilized to create a multiple‐choice, anonymous online survey (n = 353). Of the six interventions proposed, assigning the same device to the same employee every shift appeared to have the most consistent and positive response. Destruction rates and costs should be posted for employee viewing and managers of workgroups with consistently high destruction rates should receive additional training. An incentive‐based program for employees responsible for the least amount of device damage as well as an individual‐assignment of devices to employees may be considered. Applications for this student include providing a tool with which organizations can use to gauge employee ownership of equipment as well as to identify interventions that may aid in mitigating expenses associated with industrially rugged equipment.
Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV‐infected patient
Authors: Caccuri Francesca , Muraro Elena , Gloghini Annunziata , Turriziani Ombretta , Riminucci Mara , Giagulli Cinzia , Mastorci Katy , Fae' Damiana Antonia , Fiorentini Simona , Caruso Antonino , Carbone Arnaldo , Dolcetti Riccardo
Published: September 2018

Despite antiretroviral therapy, HIV+ individuals still have increased risk to develop lymphomas, including marginal zone lymphomas, suggesting that factors other than HIV‐related immunosuppression are probably acting as lymphomagenic factors in the HIV setting. The possible pathogenic involvement of HIV p17 protein variants was investigated in a particularly informative case of HIV‐related splenic marginal zone lymphoma, which was negative for oncogenic virus infections, thus allowing us to assess the possible direct contribution of these HIV‐encoded proteins to lymphomagenesis. The presence of p17 protein was analyzed by immunohistochemistry in lymphoma tissue. Recombinant p17 protein derived from the dominant sequence detected in plasma and lymphoma biopsy was characterized for B‐cell proliferation, clonogenicity in soft agar, in vitro tube formation and wound healing. Intracellular signaling was investigated by immunoblotting. HIV p17 protein was detected in reactive lymphoid follicles but not within lymphoma cells. An identical dominant variant p17 sequence, p17‐Lyrm, carrying a 117 to 118 Ala‐Ala insertion was detected in both plasma and lymphoma tissue. Recombinant p17‐Lyrm enhanced B‐cell proliferation and clonogenicity promoted the formation of capillary‐like structures and enhanced endothelial cell migration. Unlike reference p17, the p17‐Lyrm variant enhanced the activation of Akt and ERK, critical kinases in lymphomagenesis. p17‐Lyrm clonogenic activity was dependent on the activation of Akt but not of ERK1/2. These results indicated that HIV p17 variants with distinct molecular signatures and functional properties may accumulate in lymphoid tissues of HIV‐infected individuals where they may act as a local stimulus promoting the development of lymphomas.
Changes in inpatients' distribution and benefits under institution level–based quota payment for specific diseases in rural China: An interrupted time‐series analysis
Authors: Li Hao‐Miao , Chen Ying‐Chun , Gao Hong‐Xia , Zhang Yan , Su Dai , Chang Jing‐Jing , Jiang Di , Hu Xiao‐Mei , Lei Shi‐Han
Published: September 2018

The distribution of patients is increasingly disordered in China, which leads to the waste of medical resources, increase in inpatients' economic burden, and decrease in benefits from health insurance. Institution level–based quota payment for specific diseases represents a typical payment‐system reform mode in rural China that rationalizes the distribution of rural inpatients. The aim of this study is to evaluate the effectiveness of this mode by estimating rural inpatients' distribution among hospitals at different levels, per capita cost of hospitalization, and actual compensation ratio and then to provide suggestions to advance this mode. Interrupted time‐series analysis was applied to evaluate the effect of the reform mode in the study, and Weiyuan County, Gansu Province, was selected as our sample. Institution level–based quota payment for specific diseases in Weiyuan County has rationalized the distribution of rural inpatients and improved their benefit levels. Further research should be conducted to evaluate the appropriateness of medical services, the health outcomes of rural inpatients, and the sustainability and replicability of the policy.
Using voluntary agreements to exclude stock from waterways: An evaluation of project success and persistence
Authors: Moore Harriet Elizabeth , Rutherfurd Ian D
Published: September 2018

Agriculture is one of the major drivers of ecological degradation in river basins. Excluding stock (cows and sheep) from grazing riverbanks and accessing rivers is one of the most common river restoration activities. To be effective, stock exclusion must be maintained indefinitely. In Australia, and elsewhere, stock exclusion projects are most commonly implemented by establishing voluntary agreements between landholders and government agencies. This study examined the extent to which landholders in 3 catchment management authority (CMA) regions in southeast Australia maintain stock exclusion from waterways, whether vegetation on riverbanks recovered, and the effectiveness of assessment methods. It was found that nearly half of landholders continue to graze stock on the riverbank. There has been some success with improving the condition of riparian vegetation. Sites with full stock exclusion contain the pre-European abundance of juvenile trees, and sites with continued grazing contain significantly lower abundance of juvenile trees. Establishing the effectiveness of management was made more difficult by the inconsistent methods used by the different CMAs. Stock exclusion projects implemented with voluntary agreements have the potential to succeed if oversight is improved between government agencies and CMAs and between CMAs and landholders. Projects will be easier to assess if regional authorities use consistent methods of assessment. Voluntary agreements are only suitable for environmental management if projects are monitored, maintained, and assessed appropriately. Integr Environ Assess Manag 2019;15:237–247. © 2018 SETAC
Potentially functional genetic variants in the complement‐related immunity gene‐set are associated with non‐small cell lung cancer survival
Authors: Qian Danwen , Liu Hongliang , Wang Xiaomeng , Ge Jie , Luo Sheng , Patz Edward F. , Moorman Patricia G. , Su Li , Shen Sipeng , Christiani David C. , Wei Qingyi
Published: September 2018

The complement system plays an important role in the innate and adaptive immunity, complement components mediate tumor cytolysis of antibody‐based immunotherapy, and complement activation in the tumor microenvironment may promote tumor progression or inhibition, depending on the mechanism of action. In the present study, we conducted a two‐phase analysis of two independently published genome‐wide association studies (GWASs) for associations between genetic variants in a complement‐related immunity gene‐set and overall survival of non‐small cell lung cancer (NSCLC). The GWAS dataset from Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was used as the discovery, and multivariate Cox proportional hazards regression with false‐positive report probability for multiple test corrections were performed to evaluate associations between 14,699 single‐nucleotide polymorphisms (SNPs) in 111 genes and survival of 1,185 NSCLC patients. The identified significant SNPs in a single‐locus analysis were further validated with 984 NSCLC patients in the GWAS dataset from the Harvard Lung Cancer Susceptibility (HLCS) Study. The results showed that two independent, potentially functional SNPs in two genes (VWF rs73049469 and ITGB2 rs3788142) were significantly associated with NSCLC survival, with a combined hazards ratio (HR) of 1.22 [95% confidence interval (CI) = 1.07–1.40, P = 0.002] and 1.16 (1.07–1.27, 6.45 × 10−4), respectively. Finally, we performed expression quantitative trait loci (eQTL) analysis and found that survival‐associated genotypes of VWF rs73049469 were also significantly associated with mRNA expression levels of the gene. These results indicated that genetic variants of the complement‐related immunity genes might be predictors of NSCLC survival, particularly for the short‐term survival, possibly by modulating the expression of genes involved in the host immunity.
Mitigating Myside Bias in Argumentation
Authors: Christensen‐Branum Lezlie , Strong Ashley , Jones Cindy D'On
Published: September 2018

The ubiquity of written argument in academic contexts has underscored the importance of effective argument evaluation and writing pedagogies. Teachers can improve students’ argumentation proficiency by intentionally addressing myside bias, the propensity to support arguments with which one preemptively agrees while selectively ignoring contradictory claims and evidence. In this article, the authors identify three themes detected in a review of the literature on myside bias and offer instructional implications and strategies to address myside bias in secondary and postsecondary classrooms. Such strategies that promote critical reflection and balanced argument have implications for academic achievement and critical thinking skills beyond the classroom.
Ionic cobalt but not metal particles induces ROS generation in immune cells in vitro
Authors: Chamaon Kathrin , Schönfeld Peter , Awiszus Friedemann , Bertrand Jessica , Lohmann Christoph H.
Published: September 2018

Total joint replacement is one of the most successful procedures in orthopedic surgery today. However, metal implant materials undergo wear and corrosion processes. Generated particles and ions can cause a variety of cellular reactions. Cobalt‐containing alloys are used frequently in implant materials. Some studies suggest that cobalt exhibits potential cytotoxic effects, for example, via generation of reactive oxygen species (ROS). To further elucidate the effects of cobalt on human cells, we determined cell viability and cytosolic and mitochondrial superoxide formation after incubation of either ions or particles with different cells. MM‐6 and Jurkat cell lines were treated for 24, 48 and 72 h with either CoCrMo particles or cobalt ions (supplied as CoCl2). A total of 24 h exposure of both forms of cobalt did not induce cell death using terminal deoxynucleotidyl transferase (TUNEL) and trypan blue assay. Interestingly, the formation of superoxide (O2.−) is evoked mainly by ionic CoCl2 but not cobalt particles. Cobalt alloy particles are likely to even suppress O2.− formation in mitochondria in both used cell lines. Furthermore, we did not observe any effect of cobalt particles on O2.− formation in peripheral blood mononuclear cells (PBMCs) from healthy donors. We also found that the O2− formation by CoCl2 within mitochondria is a generalized effect for all cell types used, while the formation of superoxide in cytosolic compartment is cell‐type dependent. In summary, our data suggest that cobalt ions specifically induce the formation of O2.−, whereas the cobalt particles were better tolerated. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1246–1253, 2019.
Sodium butyrate ameliorates lipopolysaccharide‐induced cow mammary epithelial cells from oxidative stress damage and apoptosis
Authors: Li Lin , Wang Huan‐Huan , Nie Xin‐Tian , Jiang Wan‐Ru , Zhang Yuan‐Shu
Published: September 2018

This study investigated the molecular mechanism by which sodium butyrate (NaB) causes oxidative stress damage induced by lipopolysaccharide (LPS) on cow mammary epithelial cells (MAC‐T). We found that NaB significantly increased the activities of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, catalase, peroxidase, and total antioxidant capacity and decreased the reactive oxygen species production in LPS‐induced MAC‐T cells. NaB attenuated protein damage and reduced apoptosis in LPS‐induced MAC‐T cells. The messenger RNA (mRNA) levels of caspase‐3, caspase‐9, and Bax decreased, while the Bcl‐2 mRNA level increased in LPS‐induced MAC‐T cells treated with NaB. Our results showed that NaB treatment increased the phosphoinositide 3‐kinase (PI3K) and phospho‐AKT (P‐AKT) protein levels, whereas it decreased the Bax, caspase‐3, and caspase‐9 protein levels in LPS‐induced MAC‐T cells. However, the increase in PI3K and P‐AKT protein levels and the decrease in Bax, caspase‐3, and caspase‐9 protein levels induced by NaB treatment were reversed when the cells were pretreated with LY294002 (PI3K inhibitor). These results indicate that NaB ameliorates LPS‐induced oxidative damage by increasing antioxidative enzyme activities and ameliorating protein damage in MAC‐T cells. In addition, NaB decreased apoptosis by inhibiting caspase‐3, caspase‐9, and Bax protein levels, and this action was mainly achieved via activation of the PI3K/AKT signaling pathways in LPS‐induced MAC‐T cells. These results provide substantial information for NaB as a chemical supplement to treat oxidative stress and its related diseases in ruminants.
MicroRNA‐140 attenuates myocardial ischemia‐reperfusion injury through suppressing mitochondria‐mediated apoptosis by targeting YES1
Authors: Yang Shuguo , Li Haide , Chen Lianghua
Published: September 2018

Myocardial ischemia‐reperfusion (I/R) injury is thought to have its detrimental role in coronary heart disease (CHD), which is considered as the foremost cause of death all over the world. However, molecular mechanism in the progression of myocardial I/R injury is still unclear. The goal of this study was to investigate the expression and function of microRNA‐140 (miR‐140) in the process of myocardial I/R injury. The miR‐140 expression level was analyzed in the myocardium with I/R injury and control myocardium using quantitative real‐time polymerase chain reaction. Then the relation between the level of miR‐140 and YES proto‐oncogene 1 (YES1) was also investigated via luciferase reporter assay. Assessment of myocardial infarct size measurement of serum myocardial enzymes and electron microscopy analysis were used for analyzing the effect of miR‐140 on myocardial I/R injury. We also used Western blot analysis to examine the expression levels of the mitochondrial fission–related proteins, Drp1 and Fis1. miR‐140 is downregulated, and YES1 is upregulated after myocardial I/R injury. Overexpression of miR‐140 could reduce the increase related to myocardial I/R injury in infarct size and myocardial enzymes, and it also could inhibit the expression of proteins related to mitochondrial morphology and myocardial I/R‐induced mitochondrial apoptosis by targeting YES1. Taken together, these findings may provide a novel insight into the molecular mechanism of miR‐140 and YES1 in the progression of myocardial I/R injury. MiR‐140 might become a promising therapeutic target for treating myocardial I/R injury.
Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury
Authors: Çakır Murat , Tekin Suat , Taşlıdere Aslı , Çakan Pınar , Düzova Halil , Gül Cemile Ceren
Published: September 2018

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia‐reperfusion injury (IRI). It was determined that transient receptor potential melastatin‐2 (TRPM2) channels and phospholipase A2 (PLA
2) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of
N‐(
p‐amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA
2 enzyme inhibitor on renal IRI. A total of 36 male Sprague‐Dawley rats were divided into four groups: control, ischemia‐reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule‐1 (KIM‐1), neutrophil gelatinase‐associated lipocalin (NGAL), and interleukin‐18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase‐3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM‐1, NGAL, interleukin‐18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase‐3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.
Investigation of follicular helper T cells, as a novel player, in preeclampsia
Authors: Heydarlou Hanieh , Eghabl‐Fard Shadi , Ahmadi Majid , Aghebati‐Maleki Leili , Dolati Sanam , Movassaghpour Ali Akbar , Jadidi‐Niaragh Farhad , Danaei Shahla , Mahmoudilafout Farzaneh , Talebi Mehdi , Rahimifar Shahrzad , Yousefi Mehdi
Published: September 2018

Preeclampsia (PE) is characterized by hypertension and proteinuria. It occurs in an around 3% to 5% of all pregnancies worldwide. The fetus is kind of semiallograft to the maternal host; immune system components encounter fetal antigens and develop adverse immune responses. Recently, it has been observed that the immune system plays an important role in PE. In the current study, we have tried to investigate the role of follicular helper T (Tfh) cells in the pathogenesis of PE. Blood samples of 49 PE women and 50 healthy controls were collected. Peripheral blood mononuclear cells were isolated, cells were cultured, and then RNA was extracted. Autoantibody and secretory cytokine levels were analyzed by ELISA. Tfh frequency and transcription levels of the related molecules and cytokine were assessed by flow cytometry and real‐time PCR, respectively. The frequency of circulating Tfh cell in PE women was significantly higher compared with the healthy pregnant woman (Tfh cells with CD4+ICOS
+,
P = 0.0064 and Tfh cells with CD4
+CXCR5
+,
P = 0.029). Moreover, mRNA expression levels of CXCR5, BCL6, IL‐21, and IL‐6 (
P = 0.0006,
P = 0.008,
P = 0.0063, and
P = 0.027, respectively) were upregulated in PE patients. Furthermore, IL‐6 (
P = 0.0014) and IL‐21 (
P = 0.0059) levels in both group were assayed and the results showed increased in patient group. We also measured autoantibody levels including antiphospholipid antibodies (
P = 0.0001), anticardiolipin antibodies (
P = 0.0004), anti‐TPO (
P = 0.0008), anti‐TG (
P = 0.001) in circulation of PE group, which were higher than the control group. This study provided insights into the involvement of Tfh cells in etiology and pathogenesis of PE, probably by developing autoantibodies.
Hydrogen gas reduces chronic intermittent hypoxia‐induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation
Authors: Guan Peng , Lin Xiao‐Meng , Yang Sheng‐Chang , Guo Ya‐Jing , Li Wen‐Ya , Zhao Ya‐Shuo , Yu Fu‐Yang , Sun Zhi‐Min , An Ji‐Ren , Ji En‐Sheng
Published: September 2018

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H
2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H
2 gas significantly improved CIH‐induced abnormal vascular relaxation. Nevertheless, inhalation of H
2 gas alone did not cause such changes. Moreover, H
2 gas‐treated rats exposed to CIH showed a significant reduction in 8‐hydroxy‐2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H
2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H
2.
Simulated microgravity reduces intracellular‐free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts
Authors: Sun Zhongyang , Li Ying , Zhou Hua , Cai Min , Liu Jing , Gao Shanshan , Yang Junsheng , Tong Liangcheng , Wang Jianling , Zhou Sheng , Hu Zebing , Wang Yixuan , Wang Ke , Zhang Lijun , Wang Han , Zhang Lianchang , Shi Fei , Cao Xinsheng , Zhang Shu , Ji Yongzhang , Zhao Jianning
Published: September 2018

Calcium homeostasis in osteoblasts plays fundamental roles in the physiology and pathology of bone tissue. Various types of mechanical stimuli promote osteogenesis and increase bone formation elicit increases in intracellular‐free calcium concentration in osteoblasts. However, whether microgravity, a condition of mechanical unloading, exerts an influence on intracellular‐free calcium concentration in osteoblasts or what mechanisms may underlie such an effect are unclear. Herein, we show that simulated microgravity reduces intracellular‐free calcium concentration in primary mouse osteoblasts. In addition, simulated microgravity substantially suppresses the activities of L‐type voltage‐sensitive calcium channels, which selectively allow calcium to cross the plasma membrane from the extracellular space. Moreover, the functional expression of ryanodine receptors and inositol 1,4,5‐trisphosphate receptors, which mediate the release of calcium from intracellular storage, decreased under simulated microgravity conditions. These results suggest that simulated microgravity substantially reduces intracellular‐free calcium concentration through inhibition of calcium channels in primary mouse osteoblasts. Our study may provide a novel mechanism for microgravity‐induced detrimental effects in osteoblasts, offering a new avenue to further investigate bone loss induced by mechanical unloading.
MiR‐130b increases fibrosis of HMC cells by regulating the TGF‐β1 pathway in diabetic nephropathy
Authors: Ma Yujin , Shi Jingxia , Wang Feifei , Li Shipeng , Wang Jie , Zhu Chaoxia , Li Liping , Lu Haibo , Li Chun , Yan Junqiang , Zhang Xin , Jiang Hongwei
Published: September 2018

Basement membrane thickening, glomerular hypertrophy, and deposition of multiple extracellular matrix characterize the pathological basis of diabetic nephropathy (DN), a condition which ultimately leads to glomerular and renal interstitial fibrosis. Here, we identified a novel microRNA, miR‐130b, and investigated its role and therapeutic efficacy in alleviating DN. Introduction of miR‐130b dramatically increased cell growth and fibrosis in DN cells. We found that transforming growth factor (TGF)‐β1 was a functional target of miR‐130b in human glomerular mesangial cells (HMCs) and overexpression of miR‐130b increased expressions of the downstream signaling molecules of TGF‐β1, t‐Smad2/3, p‐Smad2/3, and SMAD4. An ectopic application of miR‐130b increased messenger RNA and protein expressions of collagen type I (colI), colIV, and fibronectin, whose expression levels were correlated with the expression of miR‐130b. Taken together, the findings of this study reveal that miR‐130b in HMC cells plays an important role in fibrosis regulation and may thus be involved with the pathogenesis of DN. Therefore, miR‐130b may serve as a novel therapeutic target for the prevention and the treatment of DN.
Individual or combination treatments with lapatinib and paclitaxel cause potential bone loss and bone marrow adiposity in rats
Authors: Lee Alice M. C. , Bowen Joanne M. , Su Yu‐Wen , Plews Erin , Chung Rosa , Keefe Dorothy M. K. , Xian Cory J.
Published: September 2018

Cancer treatments with cytotoxic drugs have been shown to cause bone loss. However, effects on bone are less clear for ErbB‐targeting tyrosine kinase inhibitors or their combination use with cytotoxic drugs. This study examined the effects of individual or combination treatments with breast cancer drugs lapatinib (a dual ErbB1/ErbB2 inhibitor) and paclitaxel (a microtubule‐stabilizing cytotoxic agent) on bone and bone marrow of rats. Wistar rats received lapatinib (240 mg/kg) daily, paclitaxel (12 mg/kg) weekly, or their combination for 4 weeks, and effects on bone/bone marrow were examined at the end of week 4. Microcomputed tomographical structural analyses showed a reduction in trabecular bone volume in tibia following the lapatinib, paclitaxel or their combination treatments (
P < 0.05). Histomorphometry analyses revealed marked increases in bone marrow adipocyte contents in all treatment groups. Reverse transcription polymerase chain reaction gene expression studies with bone samples and cell culture studies with isolated bone marrow stromal cells showed that the all treatment groups displayed significantly reduced levels of osterix expression and osteogenic differentiation potential but increased expression levels of adipogenesis transcription factor peroxisome proliferator‐activated receptor γ. In addition, these treatments suppressed the expression of Wnt10b and/or increased expression of Wnt antagonists (secreted frizzled‐related protein 1, Dickkopf‐related protein 1 and/or sclerostin). Furthermore, all treatment groups showed increased numbers of bone‐resorbing osteoclasts on trabecular bone surfaces, although only the lapatinib group displayed increased levels of osteoclastogenic signal (receptor activator of nuclear factor κΒ ligand/osteoclastogenesis inhibitor osteoprotegrin expression ratio) in the bones. Thus, inhibiting ErbB1 and ErbB2 by lapatinib or blocking cell division by paclitaxel or their combination causes significant trabecular bone loss and bone marrow adiposity involving a switch in osteogenesis/adipogenesis potential, altered expression of some major molecules of the Wnt/β‐catenin signalling pathway, and increased recruitment of bone‐resorbing osteoclasts.
Continuous exposure of nicotine and cotinine retards human primary pterygium cell proliferation and migration
Authors: Yang Qichen , Jhanji Vishal , Tan Sze Qin , Chan Kwok Ping , Cao Di , Chu Wai Kit , Zhang Mingzhi , Pang Chi Pui , Ng Tsz Kin
Published: September 2018

Pterygium is a triangular‐shaped hyperplastic growth, characterized by conjunctivalization, inflammation, and connective tissue remodeling. Our previous meta‐analysis found that cigarette smoking is associated with a reduced risk of pterygium. Yet, the biological effect of cigarette smoke components on pterygium has not been studied. Here we reported the proliferation and migration properties of human primary pterygium cells with continuous exposure to nicotine and cotinine. Human primary pterygium cells predominantly expressed the α5, β1, and γ subunits of the nicotinic acetylcholine receptor. Continuous exposure to the mixture of 0.15 μM nicotine and 2 μM cotinine retarded pterygium cell proliferation by 16.04% (P = 0.009) and hindered their migration by 11.93% (
P = 0.039), without affecting cell apoptosis. SNAIL and α‐smooth muscle actin protein expression was significantly downregulated in pterygium cells treated with 0.15 μM nicotine‐2 μM cotinine mixture by 1.33‐ (
P = 0.036) and 1.31‐fold (
P = 0.001), respectively. Besides, the 0.15 μM nicotine‐2 μM cotinine mixture also reduced matrix metalloproteinase (MMP)‐1 and MMP‐9 expressions in pterygium cells by 1.56‐ (
P = 0.043) and 1.27‐fold (
P = 0.012), respectively. In summary, this study revealed that continuous exposure of nicotine and cotinine inhibited human primary pterygium cell proliferation and migration in vitro by reducing epithelial‐to‐mesenchymal transition and MMP protein expression, partially explaining the lower incidence of pterygium in cigarette smokers.
Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF‐κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy
Authors: Wen Yi , Pan Ming‐Ming , Lv Lin‐Li , Tang Tao‐Tao , Zhou Le‐Ting , Wang Bin , Liu Hong , Wang Feng‐Mei , Ma Kun‐Ling , Tang Ri‐Ning , Liu Bi‐Cheng
Published: September 2018

Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune‐regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg
−1·d
−1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II‐induced injury of the human kidney 2 (HK‐2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF‐κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF‐κB in Ang II‐treated HK‐2 cells, while BAY11‐7082 (an inhibitor of NF‐κB) significantly inhibited Ang II‐induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF‐κB/NLRP3 signaling pathway.
Localization and characterization of a putative cysteine desulfurase in Chlamydia psittaci
Authors: Wen Yating , Chen Yanbo , Li Li , Xu Man , Tan Yuan , Li Yumeng , Wang Chuan , Chen Qian , Kuang Xingxing , Wu Yimou
Published: September 2018

Chlamydia psittaci is an obligate intracellular pathogen with a biphasic developmental life cycle. It is auxotrophic for a variety of essential metabolites and obtains amino acids from eukaryotic host cells. Chlamydia can develop inside host cells within chlamydial inclusions. A pathway secreting proteins from inclusions into the host cellular cytoplasm is the type III secretion system (T3SS). The T3SS is universal among several Gram‐negative bacteria. Here, we show that CPSIT_0959 of C. psittaci is expressed midcycle and secreted into the infected cellular cytoplasm via the T3SS. Recombinant CPSIT_0959 possesses cysteine desulfurase and PLP‐binding activity, which removes sulfur from cysteine to produce alanine, and helps chlamydial replication. Our study shows that CPSIT_0959 improve the infectivity of offspring elementary bodies and seems to promote the replication by its product. This phenomenon has inhibited by the PLP‐dependent enzymes inhibitor. Moreover, CPSIT_0959 increased expression of Bim and tBid, and decreased the mitochondrial membrane potential of host mitochondria to induce apoptosis in the latecycle for release of offspring. These results demonstrate that CPSIT_0959 has cysteine desulfurase and PLP‐binding activity and is likely to contribute to apoptosis of the infected cells via a mitochondria‐mediated pathway to improve the infectivity of progeny.
The inhibitory effects of ginsenoside Rd on the human glioma U251 cells and its underlying mechanisms
Authors: Gu Biao , Wang Jipeng , Song Yaqi , Wang Qi , Wu Qingquan
Published: September 2018

Objective

The current study was designed to investigate the inhibitory effects of ginsenoside Rd (Gs‐Rd) on human glioma U251 cells in vitro and its possible underlying mechanisms.

Methods

The groups included blank control group, low concentration Gs‐Rd treatment group (20 μM), mid concentration Gs‐Rd treatment group (40 μM), and high concentration Gs‐Rd treatment group (80 μM). The proliferative activity of human glioma U251 cells was detected by the MTT assay. Flow cytometry was performed to measure cell apoptosis of human glioma U251 cells. In addition, the ELISA assay was used to measure the telomerase activities in different groups on 24 hours, 48 hours, and 72 hours. Furthermore, real‐time quantitative polymerase chain reaction (RT‐PCR) and Western blot analysis were performed to measure the expression of Bcl‐2, human telomerase catalytic subunit (hTERT), and caspase‐3 in different groups on 48 hours at both messenger RNA (mRNA) and protein levels.

Results

The proliferation of U251 cells was inhibited by Gs‐Rd with different concentrations in the dose‐ and time‐dependent manners. In addition, Gs‐Rd promoted U251 cell apoptosis rate in a dose‐dependent manner. Gs‐Rd with different concentrations (20 μM, 40 μM, and 80 μM) significantly enhanced the expression of teleomerase on 24 hours and 48 hours. In addition, Gs‐Rd with different concentrations significantly increased caspase‐3 and decreased Bcl‐2 and hTERT expressions at both mRNA and protein levels.

Conclusion

The Gs‐Rd can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to inhibiting telomerase activity, downregulating expression of Bcl‐2 and hTERT, and upregulating expression of caspase‐3 of human glioma U251 cells.
Quantitative differences in TAD border strength underly the TAD hierarchy in Drosophila chromosomes
Authors: Luzhin Artem V. , Flyamer Ilya M. , Khrameeva Ekaterina E. , Ulianov Sergey V. , Razin Sergey V. , Gavrilov Alexey A.
Published: September 2018

Chromosomes in many organisms, including Drosophila and mammals, are folded into topologically associating domains (TADs). Increasing evidence suggests that TAD folding is hierarchical, wherein subdomains combine to form larger superdomains, instead of a sequence of nonoverlapping domains. Here, we studied the hierarchical structure of TADs in Drosophila. We show that the boundaries of TADs of different hierarchical levels are characterized by the presence of different portions of active chromatin, but do not vary in the binding of architectural proteins, such as CCCTC binding factor or cohesin. The apparent hierarchy of TADs in Drosophila chromosomes is not likely to have functional importance but rather reflects various options of long‐range chromatin folding directed by the distribution of active and inactive chromatin segments and may represent population average.
Oleuropein induces apoptosis via abrogating NF‐κB activation cascade in estrogen receptor–negative breast cancer cells
Authors: Liu Lian , Ahn Kwang Seok , Shanmugam Muthu K , Wang Hong , Shen Hongyuan , Arfuso Frank , Chinnathambi Arunachalam , Alharbi Sulaiman Ali , Chang Yung , Sethi Gautam , Tang Feng Ru
Published: September 2018

Oleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)‐negative breast cancer is not fully understood.

This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER‐negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye‐uptake assay, apoptosis by flow cytometric analysis, nuclear factor‐κB (NF‐κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA‐MB‐231 as compared with MCF‐7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF‐κB was abrogated as demonstrated by Western blot analysis, NF‐κB‐DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF‐κB activation cascade in breast cancer cells.
In silico evidence of direct interaction between statins and β‐amyloid
Authors: Shakour Neda , Bianconi Vanessa , Pirro Matteo , Barreto George E. , Hadizadeh Farzin , Sahebkar Amirhossein
Published: September 2018

Introduction

Aggregation of amyloid‐β (Aβ) peptides represents a crucial step in the pathogenesis of Alzheimer disease (AD). Compelling evidence from preclinical studies has established that statins may reduce amyloidogenesis and Aβ‐mediated neurodegeneration, supporting a potential role of statin treatment in the prevention of AD. Different statins have been shown to interfere indirectly with Aβ production and clearance through either cholesterol‐dependent or cholesterol‐independent mechanisms. However, whether there may be a direct interaction between statins and Aβ metabolism is still unclear.

Materials and methods

To test the possible direct interaction between statins and Aβ, we performed an in silico study by testing the orientation of different ligands, including statins and sulindac (the standard ligand of Aβ), in the Aβ active site using molecular operating environment (MOE) software.

Results

Docking experiments showed that all the tested statins could directly interact with Aβ protofibrils. Among statins, pitavastatin had the strongest interaction with Aβ (pki = 7.66), followed by atorvastatin (pk
i = 7.63), rosuvastatin (pk
i = 6.99), fluvastatin (pk
i = 6.96), pravastatin (pk
i = 6.46), lovastatin (pk
i = 6.37), and simvastatin (pk
i = 5.90). According to the above‐mentioned results, pitavastatin, atorvastatin, rosuvastatin, and fluvastatin had a stronger binding to Aβ compared with the standard ligand sulindac (pk
i = 6.62).

Conclusion

This study showed a direct interaction between statins and Aβ protofibrils, which may underlie the protective role of this widely used class of drugs against amyloidogenesis and Aβ‐mediated neurodegeneration.
A study on correlation between oxidative stress parameters and inflammatory markers in type 2 diabetic patients with kidney dysfunction in north Indian population
Authors: Neelofar Km , Arif Zarina , Arafat Mir Yasir , Alam Khursheed , Ahmad Jamal
Published: September 2018

Background

Research reports support the statement that oxidative stress and inflammation are well‐known risk factors for chronic kidney disease (CKD) in patients with diabetes. This study was designed to ascertain the associated role of oxidative stress parameters and inflammatory markers in diabetes and related CKD among the north Indian population.

Methods

The study was divided into three groups as healthy subjects (group 1), patients with diabetes without complication (group 2), and with CKD (group 3). Serum levels of malondialdehyde (MDA) and nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) content were estimated in all individuals. Inflammatory cytokines interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α)‐α were determined by enzyme‐linked immuno‐sorbent assay.

Results

MDA, protein carbonyl, and NO were significantly elevated in patients with type 2 diabetes as compared with healthy subjects (P ≤ 0.05). Total thiols content were found to be significantly decreased in patients with diabetes with CKD. The activity of antioxidant enzymes SOD, CAT, and GR showed a significant suppression in patients with type 2 diabetes with or without CKD as compared with healthy subjects. Nevertheless, the levels of proinflammatory cytokines IL‐6 and TNF‐α were significantly upregulated (
P ≤ 0.05) as compared with healthy subjects.

Conclusion

Determination of antioxidant defense parameters and inflammatory markers contributes to understand the relationship between oxidative stress and inflammation on the development and prevention of chronic kidney disease in Indian patients with diabetes.