bluuebunny/crossref_metadata_2025 huggingface dataset:
A non‐canonical tumor suppressive role for the long non‐coding RNA MALAT1 in colon and breast cancers
Authors: Kwok Zhi Hao , Roche Veronique , Chew Xiao Hong , Fadieieva Anastasiia , Tay Yvonne
Published: March 2018

Long noncoding RNAs (lncRNAs) constitute one of the largest classes of transcripts and have been widely implicated in various diseases such as cancer. Increasing evidence suggests that several lncRNAs are dysregulated and play critical roles in tumorigenesis. LncRNAs can be regulated by key oncogenes and tumor suppressors, adding complexity to the intricate crosstalk between protein coding genes and the noncoding transcriptome. In our study, we investigated the effect that dysregulation of the key tumor suppressor PTEN has on the noncoding transcriptome. We identified the lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) as a target of PTEN and find that this regulation is conserved in both human and mouse as well as with both chronic and acute PTEN dysregulation. We show that this regulation is at least in part microRNA (miRNA)‐dependent, and characterize the miRNAs that may be mediating this crosstalk. In summary, we establish and characterize a non‐canonical PTEN‐microRNA‐MALAT1 axis that regulates tumorigenesis and describe for the first time that the MALAT1 lncRNA possesses novel tumor suppressive properties in colon and breast cancers.
A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women
Authors: Guinter Mark A. , McLain Alexander C. , Merchant Anwar T. , Sandler Dale P. , Steck Susan E.
Published: March 2018

Increased exposure to estrogen is a risk factor for postmenopausal breast cancer, and dietary factors can influence estrogen metabolism. However, studies of diet and breast cancer have been inconclusive. We developed a dietary pattern associated with levels of unconjugated estradiol and the ratio of 2‐ and 16‐hydroxylated estrogen metabolites in a subsample of Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) participants (n = 653) using reduced rank regression, and examined its association with postmenopausal breast cancer prospectively in the larger PLCO cohort (n = 27,488). The estrogen‐related dietary pattern (ERDP) was comprised of foods with positively‐weighted intakes (non‐whole/refined grains, tomatoes, cruciferous vegetables, cheese, fish/shellfish high in ω‐3 fatty acids, franks/luncheon meats) and negatively‐weighted intakes (nuts/seeds, other vegetables, fish/shellfish low in ω‐3 fatty acids, yogurt, coffee). A 1‐unit increase in the ERDP score was associated with an increase in total (HR: 1.09, 95% CI: 1.01–1.18), invasive (HR: 1.13; 95% CI: 1.04–1.24) and estrogen receptor (ER)‐positive (HR: 1.13, 95% CI: 1.02–1.24) breast cancer risk after adjustment for confounders. Associations were observed for the fourth quartile of ERDP compared with the first quartile for overall breast cancer (HR: 1.14; 95% CI: 0.98–1.32), invasive cases (HR: 1.20, 95% CI: 1.02–1.42) and ER‐positive cases (HR: 1.19; 95% CI: 0.99–1.41). The increased risk associated with increasing ERDP score was more apparent in strata of some effect modifiers (postmenopausal hormone therapy non‐users and non‐obese participants) where the relative estrogen exposure due to that factor was lowest, although the p values for interaction were not statistically significant. Results suggest a dietary pattern based on estrogen metabolism is positively associated with postmenopausal breast cancer risk, possibly through an estrogenic influence.
Is the incidence of advanced‐stage breast cancer affected by whether women attend a steady‐state screening program?
Authors: de Munck Linda , Fracheboud Jacques , de Bock Geertruida H. , den Heeten Gerard J. , Siesling Sabine , Broeders Mireille J.M.
Published: March 2018

In this cross‐sectional population‐based study, we assessed the incidence of advanced breast cancer based on screening attendance. Women from the Netherlands Cancer Registry were included if aged ≥49 years and diagnosed with breast cancer between 2006 and 2011, and data were linked with the screening program. Cancers were defined as screen‐related (diagnosed <24 months after screening) or nonscreened (all other breast cancers). Two cut‐offs were used to define advanced breast cancer: TNM‐stage (III–IV vs 0–I–II) and T‐stage alone (≥15 mm vs <15 mm or DCIS). The incidence rates were adjusted for age and logistic regression was used to compare groups. Of the 72,612 included women diagnosed with breast cancer, 44,246 (61%) had screen‐related breast cancer. By TNM stage, advanced cancer was almost three times as likely to be at an advanced TNM stage in the nonscreened group compared with the screen‐related group (38 and 94 per 100,000, respectively; OR: 2.86, 95%CI: 2.72–3.00). By T‐stage, the incidence of advanced cancer was higher overall, and in nonscreened women was significantly higher than in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78–1.93). Data on actual screening attendance showed that the incidence of advanced breast cancer was significantly higher in nonscreened women than in screened women, supporting the expectation that screening would cause a stage shift to early detection. Despite critical evaluations of breast cancer screening programs, our data show that breast cancer screening is a valuable tool that can reduce the disease burden in women.
Genomic alterations in plasma DNA from patients with metastasized prostate cancer receiving abiraterone or enzalutamide
Authors: Belic Jelena , Graf Ricarda , Bauernhofer Thomas , Cherkas Yauheniya , Ulz Peter , Waldispuehl‐Geigl Julie , Perakis Samantha , Gormley Michael , Patel Jaymala , Li Weimin , Geigl Jochen B. , Smirnov Denis , Heitzer Ellen , Gross Mitchell , Speicher Michael R.
Published: March 2018

In patients with metastatic castrate‐resistant prostate cancer (mCRPC), circulating tumor DNA (ctDNA) analysis offers novel opportunities for the development of non‐invasive biomarkers informative of treatment response with novel agents targeting the androgen‐receptor (AR) pathway, such as abiraterone or enzalutamide. However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients. We analyzed ctDNA in two cohorts including 94 plasma samples from 25 treatment courses (23 patients) and 334 plasma samples from 125 patients, respectively. We conducted whole‐genome sequencing (plasma‐Seq) for genome‐wide profiling of somatic copy number alterations and targeted sequencing of 31 prostate cancer‐associated genes. The combination of plasma‐Seq with targetedARanalyses identified prostate cancer‐related genomic alterations in 16 of 25 (64%) treatment courses in the first cohort, in which we demonstrated thatARamplification does not always correlate with poor abiraterone and enzalutamide therapy outcome. As we observed a wide variability of ctDNA levels, we evaluated ctDNA levels and their association with clinical parameters and included the second, larger cohort for these analyses. Employing altogether 428 longitudinal plasma samples from 148 patients, we identified the presence of bone metastases, increased lactate dehydrogenase and prostate‐specific antigen (PSA) as having the strongest association with high ctDNA levels. In summary, ctDNA alterations are observable in the majority of patients with mCRPC and may eventually be useful to guide clinical decision‐making in this setting.
Targeting EGFR‐mediated autophagy as a potential strategy for cancer therapy
Authors: Sooro Mopa Alina , Zhang Ni , Zhang Pinghu
Published: March 2018

Autophagy is a naturally occurring programed cellular catabolic process stimulated by cellular stress for energy homeostasis maintenance and elimination of harmful substances. It mostly works as pro‐survival mechanism but on the other hand deregulation of autophagy has been linked to non‐apoptotic cell death known as “type II programed cell death.” Emerging evidences indicate that EGFR (epidermal growth factor receptor)‐mediated RAS/RAF/MEK/ERK signaling pathway plays a critical role in the induction of autophagy in various tumors. It has further been established that this signaling pathway is also involved in several other anti‐proliferative events such as apoptosis and senescence. However, the signaling pathway activity and effects are highly dependent on the cell type and the stimulus. It is currently being evident that autophagy induction by RAS/RAF/MEK/ERK pathway through small molecules may be a potential therapeutic strategy for cancer. However, to our best knowledge, the role of EGFR‐mediated RAS/RAF/MEK/ERK signaling pathway in autophagy‐mediated cell death and survival have not previously been reviewed. In this review, we discuss the current state of knowledge on how RAS/RAF/MEK/ERK signaling pathway regulates autophagy and the role of this EGFR‐mediated autophagy in diseases. We further examine the cross‐talk between this EGFR‐mediated autophagy and apoptosis as well as how this process is currently being utilized for cancer treatment and suggest promoting autophagy‐related cell death by small molecules may be exploited to design better therapeutic strategies for early stage and locally advanced tumors.
Treatment and outcome of adult‐onset neuroblastoma
Authors: Suzuki Maya , Kushner Brian H. , Kramer Kim , Basu Ellen M. , Roberts Stephen S. , Hammond William J. , LaQuaglia Michael P. , Wolden Suzanne L. , Cheung Nai‐Kong V. , Modak Shakeel
Published: March 2018

Adult‐onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult‐onset neuroblastoma. Anti‐GD2 immunotherapy is now standard therapy in children with high‐risk neuroblastoma; however, its use has not been reported in adults. Forty‐four adults (18–71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN‐amplification. In the 11 patients with locoregional disease, 10‐year progression‐free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti‐GD2 antibodies, mouse or humanized 3F8. Antibody‐related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5‐year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10‐year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult‐onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long‐term survival. Anti‐GD2 immunotherapy was well tolerated and might be beneficial.
Acceptability of a text message‐based fertility awareness application for family planning in Lucknow, India
Authors: Lerma Klaira , Reyes Griselda , Tiwari Siddharth , Tewari Akhilesh , Hastings Charlotte , Blumenthal Paul D.
Published: March 2018

Objective

To assess user satisfaction and acceptability toward a cell phone‐based short message system (SMS) application for fertility awareness.

Methods

Between July 1 and September 30, 2013, the present observational study recruited women of reproductive age who were presenting for family planning services in Lucknow, India, who were not pregnant, agreed to use the application, and understood basic English. The application collected information on an individual's menstrual cycle and, using the calendar days approach, predicted fertility. Based on an algorithm, the application sent a daily SMS text indicating the participant's fertility status. Participants completed an acceptability survey at the end of the 60‐day pilot period.

Results

There were 21 participants enrolled. All reported that the application was highly acceptable, and found it to be private, secure, and convenient. All participants were interested in receiving future SMS reminders for tracking fertility. Most participants (20 [95%]) reported being likely or very likely to recommend the family planning application to friends.

Conclusion

The application, with the aims of helping participants to identify their most fertile days once a month during ovulation and make informed decisions regarding fertility and contraception, was highly acceptable and might be useful in low‐resource settings worldwide. Larger studies are needed for software optimization and determination of long‐term effectiveness.
Management of unrecognized bladder perforation following suburethral tape procedure
Authors: Milani Rodolfo , Manodoro Stefano , Cola Alice , Palmieri Stefania , Frigerio Matteo
Published: March 2018

Surgical management by retropubic route of an unrecognized bladder perforation after suburethral tape procedure was effective in relieving the symptoms of the patient.
MRI brain image enhancement using brightness preserving adaptive fuzzy histogram equalization
Authors: Subramani Bharath , Veluchamy Magudeeswaran
Published: March 2018

In this article, fuzzy logic based adaptive histogram equalization (AHE) is proposed to enhance the contrast of MRI brain image. Medical image plays an important role in monitoring patient's health condition and giving an effective diagnostic. Mostly, medical images suffer from different problems such as poor contrast and noise. So it is necessary to enhance the contrast and to remove the noise in order to improve the quality of a various medical images such as CT, X‐ray, MRI, and MAMOGRAM images. Fuzzy logic is a useful tool for handling the ambiguity or uncertainty. Brightness Preserving Adaptive Fuzzy Histogram Equalization technique is proposed to improve the contrast of MRI brain images by preserving brightness. Proposed method comprises of two stages. First, fuzzy logic is applied to an input image and then it's output is given to AHE technique. This process not only preserves the mean brightness and but also improves the contrast of an image. A huge number of highly MRI brain images are taken in the proposed method. Performance of the proposed method is compared with existing methods using the parameters namely entropy, feature similarity index, and contrast improvement index and the experimental results show that the proposed method overwhelms the previous existing methods.
State of Knowledge of Irrigation Techniques and Practicalities within Given Socio‐Economic Settings
Authors: Ding Kunlun
Published: March 2018

This paper is based on the General Report of Question 61 of the 23rd Congress of the International Commission on Irrigation and Drainage (ICID). The Question was entitled ‘State of Knowledge of Irrigation Techniques and Practicalities within Given Socio‐Economic Settings’, covering three sub‐questions: adopting precision irrigation and improving surface irrigation to combat water scarcity; using ICT, remote sensing, control systems and modelling for improved performance of irrigation systems; and adaptability and affordability of new technologies under different socio‐economic scenarios. Under the Question, 64 accepted papers covering a wide range of topics of irrigation techniques and practicalities were summarized and reviewed with valuable views and state‐of‐the‐art information/knowledge on the topics concerned. It was concluded that improving surface irrigation and precision irrigation are still the major areas in which to achieve objectives of higher agricultural water use efficiency and productivity; that new technologies and their applications in the irrigation sector can help to achieve the objectives; and that to address ‘adaptability and affordability’ would ensure the real value achieved in practice. Copyright © 2018 John Wiley & Sons, Ltd.
Investigating the deployability of VoIP services over wireless interconnected micro aerial vehicles
Authors: Sanchez‐Aguero Victor , Nogales Borja , Valera Francisco , Vidal Ivan
Published: March 2018

Emerging technological devices, such as Unmanned Aircraft Vehicles (UAV) and Single Board Computers (SBC), are being increasingly employed in recent years, thanks to the advances in electronics and the wide variety of sensors that are endowed. This paper aims at analyzing the viability of deploying multimedia services, focusing on the voice scenario, over wireless interconnected Micro Air Vehicles (MAV), also known as drones. Toward this end, we assessed the performance both of the embedded wireless cards of current drones and also SBCs, which may be carried as payload in existing UAV solutions. Driven by the results obtained in these experiments, we then deployed an operational VoIP service over a network of commercial MAVs, to perform an experimental analysis on the resource capabilities of these devices and demonstrate that this type of service can certainly be used.
An evaluation of the agreement between the conservative dual‐criterion method and expert visual analysis
Authors: Wolfe Katie , Seaman Michael A. , Drasgow Erik , Sherlock Phillip
Published: March 2018

The conservative dual‐criterion (CDC) method was developed to standardize the analysis of single‐subject experimental designs data, but to date its accuracy has been evaluated only by comparing results to the statistical parameters of graphs. Our study investigated agreement between expert visual analysts and the CDC method on 66 AB tiers from published multiple baseline graphs. We found strong agreement between the two methods for certain types of graphs and discuss implications of the findings and areas for future research.
Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing
Authors: Chu Jing , Shi Panpan , Deng Xiaoyuan , Jin Ying , Liu Hao , Chen Maosheng , Han Xue , Liu Hanping
Published: March 2018

Significantly effective therapies need to be developed for chronic nonhealing diabetic wounds. In this work, the topical transplantation of mesenchymal stem cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a novel therapeutic strategy for diabetic cutaneous wound healing. GFP‐labeled MSCs were cocultured with an ADM scaffold that was decellularized from normal mouse skin. These cultures were subsequently transplanted as a whole into the full‐thickness cutaneous wound site in streptozotocin‐induced diabetic mice. Wounds treated with MSC‐ADM demonstrated an increased percentage of wound closure. The treatment of MSC‐ADM also greatly increased angiogenesis and rapidly completed the reepithelialization of newly formed skin on diabetic mice. More importantly, multiphoton microscopy was used for the intravital and dynamic monitoring of collagen type I (Col‐I) fibers synthesis via second harmonic generation imaging. The synthesis of Col‐I fibers during diabetic wound healing is of great significance for revealing wound repair mechanisms. In addition, the activity of GFP‐labeled MSCs during wound healing was simultaneously traced via two‐photon excitation fluorescence imaging. Our research offers a novel advanced nonlinear optical imaging method for monitoring the diabetic wound healing process while the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds seeded with mesenchymal stem cells in diabetic wound healing using multiphoton microscopy. PMT, photo‐multiplier tube.
Combination of blood and biphasic calcium phosphate microparticles for the reconstruction of large bone defects in dog: A pilot study
Authors: Balaguer Thierry , Fellah Borhane H. , Boukhechba Florian , Traverson Marine , Mouska Xavier , Ambrosetti Damien , Dadone Bérengère , Michiels Jean‐François , Amri Ez‐Zoubir , Trojani Christophe , Bouler Jean‐Michel , Gauthier Olivier , Rochet Nathalie
Published: March 2018

We previously reported that biphasic calcium phosphate (BCP) microparticles embedded in a blood clot induces ectopic bone formation in mice and repairs a critical femoral defect in rat. The present pilot study aimed to evaluate in dog and in two models of large defects the efficacy of this composite named “blood for reconstruction of bone” (BRB). We show here that BRB is a cohesive biomaterial easy to prepare from dog autologous blood and to mold to fill large bone defects. First in a model of cylindrical femoral condyle defect, the BRB was compared with BCP particles alone. After 8 weeks, this revealed that the amount of mature bone was slightly and significantly higher with BRB than with BCP particles. Second, in a model consisting in a 2 cm‐long critical interruptive defect of the ulna, the BRB was compared with autologous bone. After 6 months, we observed that implantation of BRB can induce the complete reconstruction of the defect and that newly formed bone exhibits high regenerative potential. Comparison with the results obtained with autologous bone grafting strongly suggests that the BRB might be an efficient biomaterial to repair large bone defects, as an alternative or in addition to autologous bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1842–1850, 2018.
Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits
Authors: Wang Chunyang , Jia Yachao , Yang Weichao , Zhang Cheng , Zhang Kuihua , Chai Yimin
Published: March 2018

Silk fibroin (SF)‐based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF‐blended poly (l‐lactide‐co‐ɛ‐caprolactone) [P(LLA‐CL)] nerve conduit is better than that in a P(LLA‐CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA‐CL) and P(LLA‐CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA‐CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA‐CL) nanofibers was more than seven‐fold higher than that in P(LLA‐CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA‐CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary‐like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10‐mm‐length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA‐CL) group was significantly larger than that in the P(LLA‐CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA‐CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA‐CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070–2077, 2018.
Bioactivity of novel functionally structured titanium‐ceramic composites in contact with human osteoblasts
Authors: Peñarrieta‐Juanito Gabriella M. , Costa Mafalda , Cruz Mariana , Miranda Georgina , Henriques Bruno , Marques Joana , Magini Ricardo , Mata Antonio , Caramês João , Silva Filipe , Souza Júlio C. M.
Published: March 2018

The aim of this study was to analyze the osteogenic cell behavior on the surface of novel functionally graded titanium‐based composites containing bioactive ceramics. Titanium grade V discs (8 × 3 mm) embedding gradual content of hydroxyapatite (TiAlV‐HA) or beta‐tricalcium phosphate (TiAlV‐βTCP) were produced by hot‐pressing technique. Titanium‐ceramic composite discs and Ti grade V (control group) were placed in contact with human osteoblast culture assays. The morphology and adhesion of osteoblasts were inspected by field emission guns scanning electron microscopy (FEGSEM) while cell viability was assessed by fluorometric method. Alkaline phosphatase (ALP) activity and fluorescent microscopic analyses were used to evaluate mineralization on the test and control discs. FEGSEM images showed cells adhered to Ti6Al4V‐ceramic and Ti6Al4V surfaces over a period of 24 h, and therefore, an intense proliferation of osteoblasts and spreading cells was noticed for 7 days. Cell viability increased with time on all the surfaces although TiAlV‐βTCP revealed significant higher percentage of cell viability than that recorded for TiAlV‐HA (p < 0.01). TiAlV‐βTCP also showed the highest hydrophilic character. ALP levels increased on the Ti6Al4V‐ceramic surfaces when compared to the control group. Also, a qualitative analysis of mineralization evidenced an increase in mineral content on TiAlV‐HA or TiAlV‐βTCP groups. Novel functionally graded composites based on Ti grade V and hydroxyapatite or βTCP showed a higher bioactivity in presence of osteoblasts than that recorded on Ti grade V. Also, such functionally graded materials can prevent risks of failures by detachment of bioactive ceramic materials during implant placement. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1923–1931, 2018.
In vitro and in vivo effects of a novel bioactive glass‐based cement used as a direct pulp capping agent
Authors: Hanada Kaori , Morotomi Takahiko , Washio Ayako , Yada Naomi , Matsuo Kou , Teshima Hiroki , Yokota Kazuyoshi , Kitamura Chiaki
Published: March 2018

Direct pulp capping is an important procedure for preserving pulp viability. The pulp capping agent must possess several properties, including usability, biocompatibility, and the ability to induce reparative dentin formation. In this study, a novel bioactive glass‐based cement was examined to determine whether the cement has the necessary properties to act as a direct pulp capping agent. Physicochemical properties of the bioactive glass‐based cement and in vitro effects of the cement on odontoblast‐like cells, as well as in vivo effects on the exposed dental pulp, were analyzed. The cement immersed in water stabilized at pH10, and hydroxyapatite‐like precipitation was induced on the surface of the cement in simulate body fluid. There were no cytotoxic effects on the viability, alkaline phosphatase activity, or calcium deposition ability of odontoblast‐like cells. In the in vivo rat study of an exposed dental pulp model, the cement induced a sufficient level of reparative dentin formation by odontoblast‐like cells expressing odontoblastic markers at the exposed area of the dental pulp. These results suggest that the newly developed bioactive glass‐based cement provides favorable biocompatibility with the dental pulp and may be useful as a direct pulp capping agent. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 161–168, 2019.
Anticoagulation, bleeding, and clotting at donor plasmapheresis
Authors: Evers Josef , Taborski Uwe
Published: March 2018

This article is based on a question of a colleague from North America how coagulation could be triggered between a donor's arm and a fistula needle during plasma donation (synonymous with donor plasmapheresis). The technique of venipuncture and citrate anticoagulation are described. Uncommon and rare problems such as prolonged bleeding, scarring, and thrombosis in plasma donors are discussed. If venous puncture and citrate: blood flow ratio at 1:16 are correctly performed, however, there will be no anticoagulation abnormalities due to plasma donation.
American council on ECP (ACE): Why now?
Authors: Edelson Richard , Wu Yanyun , Schneiderman Jennifer
Published: March 2018

Stimulated by the scientific progress in deciphering the principal elements contributing to the clinical efficacy of extracorporeal photochemotherapy (ECP), the American Council on ECP (ACE) was formed, under the auspices of the American Society for Apheresis (ASFA), to develop a field‐guiding Consensus Report. ACE is composed of thirty nationally recognized ECP experts, clinically spanning cancer, transplantation, and autoimmunity and scientifically bridging immunology, bioengineering, and hematology. The two‐day meeting took place in Manhattan, April 13‐14, 2017, and unanimous consensus on nine pivotal points is herein reported. (1) ECP's clinical evolution must now enter a scientifically driven phase. (2) ECP is currently a bidirectional therapy, both immunizing and tolerizing simultaneously, via a single one‐size‐fits‐all inflexible medical device. (3) To preclude inadvertent tolerization in the cancer setting, or immunization in the transplant rejection setting, polarization of ECP to either immunization or tolerization mode to match the clinical need is now possible and necessary. (4) Cutaneous T cell lymphoma (CTCL) is a genetically driven cancer, whose response to ECP is due to enhanced anti‐cancer immunity. (5) ECP is a dendritic antigen‐presenting cell (DC) based therapy. (6) ECP's efficacy can now be tested in a broad array of cancers. (7) ECP's capacity to tolerize to allotransplants via processing of donor leukocytes merits expedited human investigation. (8) UVA‐8‐MOP‐impacted ECP‐induced DC are potent antigen‐specific tolerizing agents, while UVA‐8‐MOP(8‐Methoxypsoralen)‐spared ECP‐induced DC are potent antigen‐specific immunizing agents. (9) Six pilot clinical trial areas (CTCL, graft‐vs.‐host disease, ovarian carcinoma, anti‐graft cytotoxic antibodies, pemphigus vulgaris, and haplotype mismatched stem cell transplants) are advised. ACE will be an ongoing advisory group for the field, with the goal of overseeing coordinated clinical and fundamental research efforts.
The effect of combined pulsed wave low‐level laser therapy and mesenchymal stem cell‐conditioned medium on the healing of an infected wound with methicillin‐resistant Staphylococcal aureus in diabetic rats
Authors: Kouhkheil Reza , Fridoni Mohammadjavad , Piryaei Abbas , Taheri Soudabeh , Chirani Alireza S. , Anarkooli Iraj J. , Nejatbakhsh Reza , Shafikhani Sasha , Schuger Lucia A. , Reddy Vijaya B. , Ghoreishi Seyed Kamran , Jalalifirouzkouhi Reza , Chien Sufan , Bayat Mohammad
Published: March 2018

This study aims to investigate the combined effects of Pulsed wave low‐level laser therapy (PW LLLT) and human bone marrow mesenchymal stem cell‐conditioned medium (hBM‐MSC‐CM) on the microbial flora and tensiometrical properties of an infected wound model with methicillin‐resistant staphylococcal aureus (MRSA) in an experimental model for Type 1 diabetes mellitus (TIDM). TIDM was induced in rats by streptozotocin (STZ). One full‐thickness excision was made on the backs of the rats. Next, the rats were divided into the following groups: Group 1 was the control (placebo) group; Group 2 received hBM‐MSCs‐CM four times; Group 3 were laser PWLLLT (890 nm, 80 Hz, 0.2 J/cm2); and Group 4 received hBM‐MSCs‐CM +LASER. Wounds were infected with MRSA. Microbiological examinations were performed on days 4, 7, and 15. Tensiometerical examinations were carried out on the 15th day. One‐way analysis of variance showed that laser and CM alone and/or in combination significantly increases the tensiomerical properties of the repaired wounds compared with control wounds. A combination of PW laser and CM was statistically more effective than other treated groups. Two‐way analysis of variance showed that laser and CM alone and/or in combination significantly decreases the colony‐forming units (CFUs) compared with the control group. The application of hBM‐MSC‐CM and PWlaser alone and/or together significantly accelerates the wound‐healing process in MRSA‐infected cutaneous wounds in TI DM in rats. Additionally, a combined application of hBM‐MSC‐CM and PWlaser demonstrates a synergistic effect on the wound‐healing process in MRSA‐infected cutaneous wounds in Type I DM rats.
Cell type‐dependent functions of microRNA‐92a
Authors: Kohram Fatemeh , Fallah Parviz , Shamsara Mehdi , Bolandi Zohreh , Rassoulzadegan Minoo , Soleimani Masoud , Ghanbarian Hossein
Published: March 2018

The role of miR‐17/92 family in development and progression of various cancers has been established. The members of this miRNA family have been shown to be over expressed and target various genes within proliferation, metastasis and angiogenesis pathways. Although all members might be overexpressed in a certain cancer type, only certain members of the family may have roles in progression of that cancer. In this study, we have chosen miR‐92a, a member of the miR‐17/92 family to compare its function in three different cancer cell lines. HL60, MCF7, and Jurkat cell lines were transduced with miR‐92a and proliferation and apoptosis was measured in these cells by cell count, MTT, and caspase assays. Although in comparison to pre‐miR‐17/92, the level of miR‐92a is higher in Jurkat cells compared to MCF7 and HL60 cells, here we have shown that increasing miR‐92a levels results in apoptosis in Jurkat cells and proliferation in MCF7 and HL60 cells. miR‐92a was also microinjected into mice fertilized eggs and after dissection, apoptosis was only observed in white pulp of spleen that is mainly made up of white blood cells. Our results show that miR‐92a possesses a cell‐type dependent function.
MicroRNA‐190b regulates lipid metabolism and insulin sensitivity by targeting IGF‐1 and ADAMTS9 in non‐alcoholic fatty liver disease
Authors: Xu Min , Zheng Xi‐Ming , Jiang Fang , Qiu Wei‐qiang
Published: March 2018

Nonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid accumulation and insulin resistance, yet the underlying molecular mechanisms are poorly understood. MiR‐190b is thought to play a role in hepatocellular carcinoma by modulating insulin resistance; however, its role in NAFLD remains unknown. Here, we found that miR‐190b expression was significantly increased in the liver tissues of patients with NAFLD, compared to normal tissues. Moreover, miR‐190b was upregulated in a high‐fat diet NAFLD mouse model and a free fatty acid‐induced NAFLD cellular model. Knockdown of miR‐190b decreased aspartate transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3‐hydroxy‐3‐methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro. Furthermore, we confirmed that miR‐190b directly targeted IGF‐1 and ADAMTS9. MiR‐190b overexpression suppressed expression of IGF‐1 and ADAMTS9, which were increased by miR‐190b inhibition. Expression of IGF‐1 and ADAMTS9 was inversely correlated with miR‐190b in liver tissues of patients with NAFLD, respectively. We also found that IGF‐1 or ADAMTS9 inhibition partially reversed the effects of miR‐190b on lipid metabolism and insulin signaling in vitro. Taken together, the data reveal that miR‐190b inhibition suppressed lipid accumulation and improved insulin sensitivity by targeting IGF‐1 and ADAMTS9, suggesting that miR‐190b inhibition may be a therapeutic strategy against NAFLD.
Expression profiling of planarians shed light on a dual role of programmed cell death during the regeneration
Authors: Yuan Junsong , Wang Zhihong , Zou Di , Peng Quekun , Peng Rui , Zou Fangdong
Published: March 2018

Most animals hold the ability to regenerate damaged cells, tissues, and even any lost part of their bodies. To date, there is little known about the precise regulatory mechanism of regeneration and many fundamental questions remain unanswered. To further understand the precise regulatory mechanism of regeneration, we used planarian Dugesia japonica as a model and sequenced the transcriptomes of their regenerated tissues at different regeneration stages. Through de novo assembly and expression profiling, we found that Heat shock protein and MAPK pathway were involved into early response of regeneration in D. japonica. In addition, immune response, cell proliferation, and migration were activated during regeneration. Of notes, our results revealed a specific functional role of programmed cell death (PCD) in regeneration of D. japonica. PCD may not only remove the damaged and superfluous tissues for further patterning with regenerated tissues, but also provide signals to trigger neoblasts proliferation and differentiation directly. Together, our results revealed Heat shock protein and MAPK pathway mediated early response of regeneration and found a dual role of PCD in regeneration D. japonica. Meanwhile, we constructed regulatory networks of apoptosis, autophagy, and related signaling pathways and proposed a schematic model, which provided a global landscape of regeneration.
Novel organometallic chloroquine derivative inhibits tumor growth
Authors: Hall Elizabeth A. , Ramsey Jon E. , Peng Zhihua , Hayrapetyan Davit , Shkepu Viacheslav , O'Rourke Bruce , Geiger William , Lam Kevin , Verschraegen Claire F.
Published: March 2018

Autophagy has emerged as a mechanism critical to both tumorigenesis and development of resistance to multiple lines of anti‐cancer therapy. Therefore, targeting autophagy and alternative cell death pathways has arisen as a viable strategy for refractory tumors. The anti‐malarial 4‐aminoquinoline compounds chloroquine and hydroxychloroquine are currently being considered for re‐purposing as anti‐cancer therapies intended to sensitize different tumors by targeting the lysosomal cell death pathway. Here, we describe a novel organometallic chloroquine derivative, cymanquine, that exhibits enhanced bioactivity compared to chloroquine in both normal, and reduced pH tumor microenvironments, thus overcoming a defined limitation of traditional 4‐aminoquinolines. In vitro, cymanquine exhibits greater potency than CQ in a diverse panel of human cancer cell lines, including melanoma, in both normal pH and in reduced pH conditions that mimic the tumor microenvironment. Cymanquine treatment results in greater lysosomal accumulation than chloroquine and induces lysosomal dysfunction leading to autophagy blockade. Using a mouse model of vemurafenib‐resistant melanoma, cymanquine slowed tumor growth greater than hydroxychloroquine, and when used in combination with vemurafenib, cymanquine partially restored sensitivity to vemurafenib. Overall, we show that cymanquine exhibits superior lysosomal accumulation and autophagy blockade than either chloroquine or hydroxychloroquine in vitro; and in addition to its high level of tolerability in mice, exhibits superior in vivo efficacy in a model of human melanoma.
The power of precise bioinformatics prediction of miRNA:mRNA interactions:miR‐4699 as a potential inducer of Wnt signaling pathway
Authors: Hosseini Vahedeh , Mohammadi‐Yeganeh Samira , Ghanbarian Hossein , Hashemi Seyed Mahmoud , Khojasteh Arash
Published: March 2018

microRNAs have attracted interest because of their regulatory effects on gene expression. Experimental detection of potential targets of miRNAs is a laborious task. Considering the expensive techniques of detection, computational approaches for miRNA target prediction can be used as the first step in miRNA research. A large number of tools and algorithms have been developed during the last two decades, led to problems such as confusion in selecting an appropriate tool and false positive or negative results. Therefore, one of the most frequent problems and critical issues of miRNA research is finding a reliable miRNA target prediction tool. In this study, we have proposed a research direction and introduced user‐friendly and current databases and tools with the highest accuracy. To verify whether our proposed research direction is practical, we have provided a case example of predicting a miRNA which can target negative regulators of osteogenesis and experimentally evaluated the accuracy of the prediction results by Real‐Time PCR and Luciferase assay. The results of RT‐qPCR and Luciferase assay indicated a significant decline in expression of Dickkopf‐related protein 1 (DKK1) and tumor necrosis factor ligand superfamily member 11 (TNFSF11) as the key negative regulators of osteogenesis upon overexpression of miR‐4699‐3p. The results emphasize the validity and importance of accurate in silico investigation as the first step in experimental studies. This is the first report detailing the prediction and validation of miR‐4699‐3p target genes. We suggest hsa‐miR‐4699 for further investigation as an osteogenic miRNA for therapeutics purposes.
Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress
Authors: Torre‐Villalvazo Ivan , Bunt Ana E. , Alemán Gabriela , Marquez‐Mota Claudia C. , Diaz‐Villaseñor Andrea , Noriega Lilia G. , Estrada Isabela , Figueroa‐Juárez Elizabeth , Tovar‐Palacio Claudia , Rodriguez‐López Leonardo A. , López‐Romero Patricia , Torres Nimbe , Tovar Armando R.
Published: March 2018

Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may be involved in SAT dysfunction during obesity. The objectives of this study were to assess UPR activation and adiponectin synthesis in: 1) SAT and VAT from mice exposed to acute pharmacologic or chronic obesity‐induced ER stress and in 2) cultured mice primary mature adipocytes or adipocytes differentiated in vitro from SAT and VAT exposed to tunicamycin or thapsigargin. Mice fed a high‐fat diet developed obesity, increased FFA and lower circulating adiponectin in association with lower adiponectin synthesis and increased UPR markers in SAT. Mice subjected to acute ER stress by pioglitazone administration and a low‐dose tunicamycin injection presented a maladaptive UPR activation in SAT along with reduced adiponectin synthesis and secretion and increased lipolysis with respect to VAT, associated with lipid accumulation in skeletal muscle and liver. Primary adipocytes and adipocytes differentiated from SAT exposed to pharmacologic ER stress also developed maladaptive UPR, along with reduced adiponectin synthesis and increased lipolysis with respect to those from VAT. Our results indicate that compared to VAT, SAT is more susceptible to ER stress, leading to increased lipolysis and reduced adiponectin synthesis and secretion.
The overexpression of TcAP1 endonuclease confers resistance to infective Trypanosoma cruzi trypomastigotes against oxidative DNA damage
Authors: Valenzuela Lucía , Sepúlveda Soía , Ponce Iván , Galanti Norbel , Cabrera Gonzalo
Published: March 2018

Trypanosoma cruzi, the causative agent of Chagas’ disease survives to DNA damage generated by ROS/RNS inside to their different hosts. In recent eukaryotes, oxidative DNA damage is repaired mainly by the Base Excision Repair (BER) pathway, being essential the apurinic/apyrimidinic endonuclease activity. Using a pTREX‐gfp vector, the nucleotide sequence that encodes T. cruzi AP endonuclease TcAP1 (orthologue of human APE1) and a putative TcAP1 dominant negative (TcAP1DN), were transfectedand expressed in T. cruzi epimastigotes. TcAP1‐GFP and TcAP1DN‐GFP were expressed in those modified epimastigotes and found in the parasite nucleus. The endonucleases were purified under native conditions and the AP endonuclease activity was evaluated. While TcAP1 presents the expected AP endonuclease activity TcAP1DN does not. Moreover, TcAP1DN partially inhibits in vitro TcAP1 enzymatic activity. Transfected epimastigotes expressing TcAP1‐GFP and TcAP1DN‐GFP were differentiated to infective trypomastigotes. The infective parasites maintained both proteins (TcAP1‐GFP and TcAP1DN‐GFP) in the nucleus. The overexpression of TcAP1‐GFP in epimastigotes and trypomastigotes increases the viability of both parasite forms when exposed to oxidative stress while the expression of TcAP1DN‐GFP did not show any in vivo inhibitory effect, suggesting that endogenous TcAP1 constitutive expression overcomes the TcAP1DN inhibitory activity. Our results show that TcAP1 is important for trypomastigote survival under oxidative conditions similar to those found in infected mammalian cells, then increasing its permanence in the infected cells and the possibility of development of Chagas disease.
High expression of glutamate‐ammonia ligase is associated with unfavorable prognosis in patients with ovarian cancer
Authors: Fan Shaohua , Wang Yanyan , Zhang Zifeng , Lu Jun , Wu Zhiyong , Shan Qun , Sun Chunhui , Wu Dongmei , Li Mengqiu , Sheng Ning , Xie Ying , Zheng Yuanlin
Published: March 2018

Glutamate‐ammonia ligase (GLUL), which is also called GS (glutamine synthetase), is the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP‐dependent reaction. Here, we found higher expression of GLUL in the ovarian cancer patients was associated with worse disease‐free survival (DFS) and overall survival (OS). In addition, GLUL was heterogeneously expressed in various ovarian cancer cells. The mRNA and protein expression levels of GLUL in NIH:OVCAR‐3 and ES‐2 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of GLUL in NIH:OVCAR‐3 or ES‐2 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK signaling pathway in NIH:OVCAR‐3 or ES‐2 cells. Our findings suggest that decreasing expression of GLUL may be a new approach that can be used for ovarian cancer treatment.
Glucocorticoids inhibit notch target gene expression in osteoblasts
Authors: Zanotti Stefano , Yu Jungeun , Adhikari Suyash , Canalis Ernesto
Published: March 2018

Glucocorticoids in excess suppress osteoblast function and cause osteoporosis. We demonstrated that cortisol induces the expression of selected Notch receptors in osteoblasts, revealing a potential mechanism for the skeletal effects of glucocorticoids. However, it remains to be determined whether increased expression of Notch receptors results into enhanced signaling. Following activation of Notch, its intracellular domain (NICD) binds to the DNA‐associated protein recombination signal binding protein for immunoglobulin kappa‐J region (RBPJ) and induces the expression of target genes such as Hey1, Hey2, and HeyL. To determine whether glucocorticoids modulate Notch signaling in the skeleton, 1 month old wild‐type mice were administered prednisolone or placebo and sacrificed after 72 h, and gene expression was analyzed in femoral bone. Prednisolone induced Tsc22d3, a glucocorticoid target gene, and suppressed Hey1 and HeyL expression, which is indicative of inhibited Notch receptor activity or direct Hey downregulation. To determine the mechanisms of Hey suppression, wild‐type osteoblast‐enriched cells were seeded on the Notch cognate ligand Delta‐like (DLL)1 or transfected with constructs expressing the NOTCH1 NICD fragment and exposed to either cortisol or vehicle. Cortisol opposed the induction of mRNA and heterogeneous nuclear RNA for Hey1, Hey2, and HeyL by DLL1, but had no effect on mRNA stability, indicating that glucocorticoids inhibit Hey expression by transcriptional mechanisms. Transactivation studies and electrophoretic mobility shift assays revealed that cortisol did not oppose RBPJ‐mediated transcription or RBPJ/DNA interactions, respectively. In conclusion, glucocorticoids suppress expression of Hey1, Hey2, and HeyL in osteoblasts by RBPJ‐independent transcriptional mechanisms.