bluuebunny/crossref_metadata_2025 huggingface dataset:
Sinonasal cancer in The Netherlands: Follow‐up of a population‐based study 1989‐2014 and incidence of occupation‐related adenocarcinoma
Authors: Kuijpens J. (Hans) L. P. , Louwman Marieke W. J. , Takes Robert , Slootweg Piet J. , Burdorf Alex , van Dijk Boukje A. C.
Published: October 2018

Background

Long‐term trends of sinonasal cancer in The Netherlands have been investigated with particular attention on adenocarcinoma for which wood or leather dust is a well‐known risk factor.

Methods

All 4345 patients (1989‐2014) registered in the Netherlands Cancer Registry were included. Standardized 3‐year moving incidence rates per 1 000 000/person‐years, and estimated annual percentage change (EAPC) were calculated.

Results

Forty‐seven percent of the patients had squamous cell carcinoma (SCC), 12% had lymphoma, and 12% had adenocarcinoma. Sixty‐one percent of the tumors were located in the nasal cavity, 22% in the maxillary, and 11% in the ethmoidal sinus. Male incidence decreased to 11.5/1 000 000 due to less SCC (EAPC −0.9%; 95% confidence interval [CI] −1.6 to 0.3) and adenocarcinoma (EAPC −4.3%; 95% CI −5.5 to 3.1). Female incidence increased to 7/1 000 000 (EAPC +2.0%; 95% CI +1.1 to +3.0) due to more SCC (EAPC +2.2%; 95% CI +1.0 to +3.5), whereas adenocarcinoma remained stable (0.6/1 000 000; EAPC +1.1%; 95% CI −6.0 to +8.7). Tumors of the nasal cavity increased in women (EAPC +3.3%; 95% CI +2.0 to 4.7).

Conclusion

The decrease of male sinonasal adenocarcinoma may be the result of preventive measures combined with less workers in high‐risk occupations.
FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice
Authors: Iracheta‐Vellve Arvin , Calenda Charles D. , Petrasek Jan , Ambade Aditya , Kodys Karen , Adorini Luciano , Szabo Gyongyi
Published: October 2018

Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein‐coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role. OCA, INT‐777, and INT‐767 are BA derivatives with selective agonist properties for FXR, TGR5, or both, respectively. These compounds were tested in two mouse models (3‐day binge model and prolonged Lieber DeCarli diet for 12 days) of early ALD. Serum alanine aminotransferase and liver histology were used to assess liver injury, Oil Red O staining of liver sections to assess steatosis, and real‐time polymerase chain reaction to assess changes in gene expression. In the ethanol binge model, treatment with OCA and INT‐777 decreased hepatic macrovesicular steatosis and protected from ethanol‐induced liver injury. After prolonged ethanol administration, mice treated with OCA, INT‐767, or INT‐777 showed decreased hepatic steatosis, associated with reduced liver fatty acid synthase protein expression, and protection from liver injury. Treatment with BA receptor agonists in both models of ethanol administration modulated lipogenic gene expression, and decreased liver interleukin‐1β mRNA expression associated with increased ubiquitination of NLRP3 inflammasome through cyclic adenosine monophosphate–induced activation of protein kinase A. Conclusion: OCA, INT‐767, or INT‐777 administration is effective in reducing acute and chronic ethanol‐induced steatosis and inflammation in mice, with varying degrees of efficacy depending on the duration of ethanol administration, indicating that both FXR and TGR5 activation can protect from liver injury in ALD models.
Interferon‐induced transmembrane protein 1‐mediated EGFR/SOX2 signaling axis is essential for progression of non‐small cell lung cancer
Authors: Yang Ying‐Gui , Koh Young Wha , Sari Ita Novita , Jun Nayoung , Lee Sanghyun , Phi Lan Thi Hanh , Kim Kwang Seock , Wijaya Yoseph Toni , Lee Sang Hun , Baek Moo‐Jun , Jeong Dongjun , Kwon Hyog Young
Published: October 2018

Emerging data indicate that interferon‐induced transmembrane protein 1 (IFITM1) plays an important role in many cancers. However, it remains unclear whether IFITM1 is functionally indispensable in nonsmall cell lung cancer (NSCLC). Here, using NSCLC cell lines and patient‐derived samples, we show that IFITM1 is essentially required for the progression of NSCLC in vitro and in vivo. Specifically, IFITM1 depletion resulted in a significant reduction in sphere formation, migration, and invasion of NSCLC cells in vitro; these events were inversely correlated with the ectopic expression of IFITM1. In addition, tumor development was significantly impaired in the absence of IFITM1 in vivo. Mechanistically, epidermal growth factor receptor/sex‐determining region Y‐box 2 (EGFR/SOX2) signaling axis was compromised in the absence of IFITM1, and the ectopic expression of SOX2 partially rescued the defects caused by IFITM1 depletion. More importantly, using 226 patient‐derived samples, we demonstrate that a high level of IFITM1 expression is associated with a poor overall survival (OS) rate in adenocarcinoma but not in squamous cell carcinoma. Collectively, these data suggest that IFITM1 is a poor prognostic marker of adenocarcinoma and an attractive target to develop novel therapeutics for NSCLC.
Circulating concentrations of B group vitamins and urothelial cell carcinoma
Authors: Bassett Julie K. , Brinkman Maree T. , Dugué Pierre‐Antoine , Ueland Per M. , Midttun Øivind , Ulvik Arve , Bolton Damien , Southey Melissa C. , English Dallas R. , Milne Roger L. , Hodge Allison M. , Giles Graham G.
Published: October 2018

B‐group vitamins, as components of the one carbon metabolism pathway, are involved in DNA synthesis, repair and methylation. Our aim was to investigate associations between circulating plasma levels of B vitamins and urothelial cell carcinoma (UCC). We conducted a nested case–control study of UCC within the Melbourne Collaborative Cohort Study. B vitamins were measured in pre‐diagnostic plasma samples. Conditional logistic regression was used to estimate odds ratios (OR) for UCC risk associated with circulating B vitamins in 363 matched cases and controls. In a case‐only analysis (N = 390), hazard ratios (HR) for overall survival associated with plasma B vitamins were estimated using Cox regression. There were no strong associations between UCC risk and pre‐diagnostic levels of plasma B vitamins. No heterogeneity in UCC risk was observed by subtype (invasive or superficial), sex, smoking status or alcohol intake. There was no heterogeneity by country of birth for most B vitamins, except for folate (p‐homogeneity = 0.03). In UCC cases, there were no strong associations between plasma B vitamins and overall survival. We found no associations between pre‐diagnostic plasma concentrations of B‐group vitamins and UCC risk or survival.
Space shift keying modulation under spectrum sharing over Nakagami‐m fading
Authors: Sahu Hemanta K. , Sahu Pravas R.
Published: October 2018

In this letter, we analyze the performance of the space shift keying (SSK) modulation scheme for underlay spectrum‐sharing environments. For underlay spectrum‐sharing transmission, the transmit power condition of the proposed spectrum‐sharing system is considered by the interference temperature limit on the primary network and the maximum transmission power at the secondary network. Closed‐form expression for the average bit error probability (ABEP) is derived for Nakagami‐m fading channels. The obtained expression contains a hypergeometric function. Numerical and simulation results are presented to illustrate the impact of the fading parameters on the system performance.
P53‐dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride‐induced liver fibrosis and hepatic stellate cell activation
Authors: Wang Ling , Zhang Zili , Li Mengmeng , Wang Feixia , Jia Yan , Zhang Feng , Shao Jiangjuan , Chen Anping , Zheng Shizhong
Published: October 2018

Ferroptosis is recently reported as a new mode of regulated cell death. Its essential characteristics are disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. However, the role of ferroptosis in liver fibrosis remains poorly understood. In this study, we attempted to investigate the effect of artemether (ART) on ferroptosis in hepatic fibrosis and to further clarify the possible mechanisms. Our data showed that ART treatment markedly attenuated liver injury and reduced fibrotic scar formation in the mouse model of liver fibrosis. Moreover, experiments in vitro also confirmed that ART treatment significantly decreased expression of hepatic stellate cell (HSC) activation markers. Interestingly, HSCs treated by ART presented morphological features of ferroptosis. Furthermore, ART remarkably triggered ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas inhibition of ferroptosis by specific inhibitor ferrostatin‐1 (Fer‐1) completely abolished ART‐induced antifibrosis effect. More importantly, our discovery determined that tumor suppressor P53 was an upstream molecule in the facilitation of ART‐induced HSC ferroptosis. Conversely, knockdown of P53 by siRNA evidently blocked ART‐induced HSC ferroptosis in turn exacerbated liver fibrosis. Overall, our findings revealed that P53‐dependent induction of ferroptosis is necessary for ART to ameliorate CCl4‐induced hepatic fibrosis and inhibit HSC activation. © 2018 IUBMB Life, 71(1):45–56, 2019
Urinary N‐Telopeptide as Predictor of Onset of Menopause‐Related Bone Loss in Pre‐ and Perimenopausal Women
Authors: Shieh Albert , Greendale Gail A , Cauley Jane A , Karvonen‐Gutierrez Carrie , Lo Joan , Karlamangla Arun S
Published: October 2018

The menopause transition (MT) is a period of rapid bone loss and has been proposed to be a time‐limited window for early intervention to prevent permanent microarchitectural damage and reduce the risk of subsequent fracture. To intervene early, however, we first need to be able to determine whether menopause‐related bone loss is about to begin, in advance of substantial bone loss. The objective of this study was, therefore, to assess whether urinary N‐telopeptide (U‐NTX) in pre‐ or early perimenopause can predict the onset of menopause‐related bone loss. Repeated U‐NTX measurements were obtained during pre‐ and early perimenopause in 1243 participants from the Study of Women's Health Across the Nation (SWAN). We examined the ability of U‐NTX to predict the onset of significant menopause‐related bone loss (categorical outcome, yes versus no) at the lumbar spine (LS) and femoral neck (FN), defined as annualized bone mineral density (BMD) decline at a rate faster than the smallest detectable change in BMD over the 3 to 4 years from the time of U‐NTX measurement. Adjusting for age, race/ethnicity, body mass index, urine collection time, starting BMD, and study site in multivariable, modified Poisson regression, every standard deviation increment in U‐NTX, measured at baseline in early perimenopausal women, was associated with an 18% and 22% greater risk of significant bone loss at the LS (p = 0.003) and FN (p = 0.003), respectively. The area under the receiver‐operator curve for predicting LS and FN bone loss was 0.72 and 0.72, respectively. In mixed‐effects analysis of all repeated measures of early perimenopausal U‐NTX over follow‐up, U‐NTX predicted onset of bone loss at the LS (p = 0.002) but not at the FN. We conclude that U‐NTX can be used early in the MT to determine if a woman is about to experience significant LS bone loss before there has been substantial skeletal deterioration. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action
Authors: Ovadia Caroline , Lövgren‐Sandblom Anita , Edwards Lindsey A. , Langedijk Jacqueline , Geenes Victoria , Chambers Jenny , Cheng Floria , Clarke Louise , Begum Shahina , Noori Muna , Pusey Charles , Padmagirison Radhika , Agarwal Sangita , Peerless James , Cheesman Kate , Heneghan Michael , Oude Elferink Ronald , Patel Vishal C. , Marschall Hanns‐Ulrich , Williamson Catherine
Published: October 2018

Introduction

Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments.

Methods

Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC‐MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests.

Results

Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P = .03 and P = .04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines.

Conclusions

Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.
Clinical presentation in thrombotic thrombocytopenic purpura: Real‐world data from two Mexican institutions
Authors: Bugarin‐Estrada Emmanuel , Gómez‐De León Andrés , López‐García Yadith Karina , Díaz‐Chuc Erik Alejandro , Priesca‐Marín José Manuel , Ruiz‐Argüelles Guillermo J. , Jaime‐Pérez José Carlos , Gómez‐Almaguer David
Published: October 2018

Background

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease that can be fatal if not treated early. We aimed to describe the clinical characteristics of Mexican patients with idiopathic TTP.

Study design and methods

We conducted a retrospective study, including all adult patients diagnosed with idiopathic TTP from 2011 to 2017 in two Mexican centers. We further compared our results with the published literature.

Results

Twenty patients were included; 70% were female, with a median age of 38.5 years at diagnosis (range 16‐63). The median time from onset of symptoms to hospital admission was 1.5 days (range 0‐16). Most patients (85%) presented with at least one systemic manifestation at admission (including fever) and 90% had neurological symptoms, most of them major (70%) including loss of consciousness, transient focal abnormalities, headache, and confusion. Only one patient (5%) had the classical pentad at the time of admission. Kidney failure was present in 25% of patients and hemorrhagic symptoms in 60%. Digestive and cardiorespiratory symptoms were less common (45% and 15%, respectively). Median platelet count and lactate dehydrogenase were 10 500/μL and 1319 IU/L, respectively. Eighty percent of patients achieved remission following treatment. Patients admitted within the first 48 hours (after the onset of symptoms) tended to have better overall survival.

Conclusion

Clinical presentation in Mexican TTP patients is similar to that in other countries. Early admission and a high suspicion for the disease will avoid delays in the initial work‐up and initiation of therapy, further improving prognosis.
Differentiation expression of toll‐like receptor4 (TLR4) caused by the dysregulation of microRNA‐140‐5p is responsible for the development of postoperation infection
Authors: Zheng Ge , Li Zhishu , Xiang Wenna , Huang Yumao , Pan Minli
Published: October 2018

Background

Toll‐like receptor4 (TLR4) has proven to be an important factor that's responsible for the development of postoperation infection. MicroRNAs (miRNAs) are widely regarded as key mediators of gene expression. The objectives of our study were to identify miRNA(s) and the target genes differentially expressed in monocytes in the individuals with postoperation infection.

Methods

MiRNA microarrays were performed to identify and compare miRNA expression in monocytes from those with or without postoperative infection. In‐silico analysis was used to further investigate the target miRNAs and finally, luciferase assay and real‐time polymerase chain reaction (PCR) were performed to confirm the target miRNA identified. Enzyme‐linked immunosorbent assay, real‐time PCR and Western‐blot were performed to explore the role of miR‐140 involved in postoperation infection.

Results

MiRNA microarray results showed that ten miRNAs were upregulated in the postoperation infection group, while six miRNAs were downregulated, compared with those in the postoperation group without infection. Computational analysis was further performed to reveal that four miRNAs (miR‐140, miR‐7, miR‐448, and miR‐217) targeted the 3′‐untranslated region (UTR) of TLR4 mRNA. The luciferase assay showed that only miR‐140 inhibited luciferase activity of wild‐type TLR4 3′‐UTR and the luciferase activity of the cells cotransfected with miR‐7, miR‐448 or miR‐217 and wild‐type or mutant TLR4 3′‐UTR was comparable with the control. Furthermore, only miR‐140 levels were significantly lower in the postoperation infection group, while levels of miR‐217, miR‐7, and miR‐448 showed no obvious difference between the postoperation infection and postoperation without infection groups. TLR4, tumor necrosis factor‐α (TNF‐α), and IL‐6 levels were much higher in the postoperation infection group. In comparison with the control group, TLR4, TNF‐α and Interleukin 6 (IL‐6) levels in cells were decreased following transfection with miR‐140 mimics and TLR4 small interfering RNA. However, the cells treated with lipopolysaccharides increased TLR4, TNF‐α, and IL‐6 levels.

Conclusion

This study demonstrates that miR‐140 is differentially expressed in monocytes collected from patients diagnosed with postoperation infection. The downregulation of miR‐140 cause upregulation of toll‐like receptor4 (TLR4), a proinflammatory factor, and is associated with infection risk in patients received surgery.
The protective effect exerted by ascorbic acid on DNA fragmentation of human leukocytes induced by Lachesis muta muta venom
Authors: Cardoso Trento Marcus Vinícius , de Faria Eleutério Mateus William , Silva Abreu Tatiane , Andrade Machado Gustavo Henrique , Cesar Pedro Henrique Souza , Assaid Simão Anderson , Marcussi Silvana
Published: October 2018

The objective of this study was to evaluate the genotoxic and mutagenic effects of the toxins present in Lachesis muta muta's venom on human peripheral blood leukocytes and the protective potential of ascorbic acid on DNA fragmentation. The venom of
L. muta muta was incubated in different concentrations (1, 2.5, 5, 7.5, 10, 15, 20, 30, 40, 50, 60, and 120 µg/mL) with human blood to evaluate DNA fragmentation using the comet, agarose gel electrophoresis, and micronucleus assays. In these concentrations evaluated, the venom of
L. muta muta induced genotoxicity (comet assay and agarose gel electrophoresis) and mutagenicity (micronucleus test), but they were not cytotoxic, as they did not change the rate of cell proliferation after cytokinesis blockade with cytochalasin B. The ascorbic acid significantly inhibited the genotoxicity induced by
L. muta muta venom in the proportions evaluated (1:0.1 and 1:0.5, venom/ascorbic acid ‐ w/w). Thus, future studies are needed to elucidate the protective mechanisms of ascorbic acid on the genotoxic effects induced by toxins present in snake venoms.
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

Brain 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

Alteration 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

Objectives

Heart 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.

Methods

HF 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.

Results

HF 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.

Conclusions

Rapamycin 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

Oxidative 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

Multiple 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

Traumatic 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

NSD3s, 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

In 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

Aim

A 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.

Methods

Thirty 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.

Results

HFD‐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.

Conclusion

The 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

In 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

Orientia 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

In 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.
Infrared and Raman active vibrational modes in MoS2‐based nanotubes: Symmetry analysis and first‐principles calculations
Authors: Evarestov Robert A. , Bandura Andrei V.
Published: October 2018

The possibility to use the axial point group dynamical representations for the infrared and Raman active modes classification in nanotubes is analyzed. The method proposed allows one to obtain the results of phonon symmetry analysis for nanotubes in Mulliken designations, which are traditional for molecules and crystallographic point groups. The approach suggested is applied to the phonon symmetry analysis in the single‐wall carbon and MoS2‐based nanotubes. First‐principles calculations of phonons in a bulk MoS2 crystal and a monolayer S‐Mo‐S are made. The results obtained are in reasonable agreement with the existing experimental data and other published results. The first‐principles calculations of the phonon frequencies for armchair and zigzag MoS2 nanotubes are performed for the first time. It is shown that the number of infrared and Raman active modes becomes fixed starting from the relatively small nanotube diameters. The correlation of the phonon modes of MoS2 nanotubes with diameters up to 3.64 nm with phonon modes of the S‐Mo‐S monolayer is analyzed. It is demonstrated that the interpretation of the nature of nanotube A‐type modes in the crystallographic factorization of the line group L = TF is the same as for m = 0 modes in the “polymer type” factorization L = ZP where P is the subgroup of the isogonal point group F, T is the translation subgroup of line group and the cyclic group Z includes the one‐dimensional translations and the rotations around the screw axes or the reflections in the glide planes. © 2018 Wiley Periodicals, Inc.
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

Background

CD62P 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).

Methods

The 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.

Results

BUN, 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.

Conclusion

CD62P 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

Linked 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.
Transmission of methicillin‐resistant Staphylococcus aureus in an acute care hospital in Japan
Authors: Matsumoto Kaori , Takeuchi Seisho , Uehara Yoshio , Matsushita Masahide , Arise Kazumi , Morimoto Norihito , Yagi Yusuke , Seo Hiromi
Published: October 2018

Background

Asymptomatic carriers of methicillin‐resistant Staphylococcus aureus (MRSA) are important sources of nosocomial transmission. However, the route of transmission of MRSA is not completely understood. The purpose of this study was to calculate MRSA transmission rates in a hospital with a high MRSA infection/colonization density and inadequate hand hygiene compliance.

Methods

The prevalence of MRSA colonization among 157 patients at the time of admission to and discharge from a medical school hospital in Japan was determined by performing surveillance cultures. All MRSA isolates were evaluated using multilocus sequence typing (MLST) to identify the transmission routes.

Results

Methicillin‐resistant S. aureus was prevalent in 1.9% of our study population. MRSA was acquired during hospitalization at a rate of 4.0/1000 patient‐days. At discharge, 5.1% of the patients exhibited MRSA colonization; this was significantly higher than the prevalence noted upon admission (P < 0.001). MLST documented three possible nosocomial transmission events. MRSA colonization was detected using surveillance cultures prior to being identified by conventional, clinically oriented examinations.

Conclusions

Multilocus sequence typing results suggested that patients who were colonized with MRSA acquired it during hospitalization. These results reinforce the importance of infection control for preventing nosocomial MRSA transmission in hospitalized patients.
Role Tension and Adaptation in a Chinese Agricultural Aid Project in Mozambique
Authors: Zhang Chuanhong , Li Xiaoyun , Connerley Edwin F. , Wu Jin
Published: October 2018

Role theory was applied to analysis of the interaction process of various actors engaged in a Chinese aid project in Africa to explore who drove the implementation process and to reveal the hidden logic of China's foreign aid. The result revealed that the framework imposed by the State created space for actors from China and from Africa to exert agency to achieve common goals. The interaction process was constructed through role consolidation and concessions of different actors, which indicates that the project implementation was not driven by one side but rather by the mutual adaptation of the various actors involved. © 2018 John Wiley & Sons, Ltd.