bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of Nutlin‐3 on morphology, cellular proliferation, and apoptosis in rat primary mesenchymal stem cells
Authors: Bajelan Babak , Zaki‐Dizaji Majid , Darabi Shahram , Rajaei Farzad 
Published: November 2018

AbstractIntroductionNutlin‐3 is a powerful antagonist of murine double minute 2/p53 interaction demonstrating promising therapeutic anticancer activity, which has not been clinically approved yet. Mesenchymal stem cells (MSCs) are an important part of the bone marrow niche and support regeneration and proliferation of hematopoietic stem cells after exposure to myelotoxic anticancer agents; however, the effect of Nutlin‐3 compounds on MSCs themselves remains to be elucidated.Materials and MethodsRat‐derived bone marrow‐derived MSCs (BMSCs) were cultured and treated with different concentrations (5, 10, 25, 50, and 100 μM) and times (24, 48, and 72 hr) of Nutlin‐3. The microculture tetrazolium test, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and propidium iodide and annexin‐V assays, and quantitative real‐time reverse‐transcription polymerase chain reaction were performed to assess the effects of Nutlin‐3 on the cell viability, proliferation, and apoptosis in BMSCs.ResultsThe viability of BMSCs in the treated cells with concentrations of 100 μM at 24 hr, 50 and 100 μM at 48 hr, and in all concentrations at 72 hr was significantly (p < 0.05) low. The apoptotic index showed that the TUNEL‐positive BMSCs were significantly higher in concentrations of 25 and 50 μM in comparison to control group (
p < 0.05) and augmented in a dose‐dependent manner. Annexin‐V‐PI staining showed after 72 hr of incubation, there was a slight dose‐dependent increase in total apoptotic cells at 10 and 25 μM of Nutlin‐3, but a massive significant increase at 50 μM.ConclusionHere, we show that rat BMSCs are relatively resistant to Nutlin‐3; however, further in vivo data with long‐term exposure may help to corroborate our findings.
G protein‐coupled receptor 119 is involved in RANKL‐induced osteoclast differentiation and fusion
Authors: Kim Hyun‐Ju , Yoon Hye‐Jin , Park Ji‐Wan , Che Xiangguo , Jin Xian , Choi Je‐Yong 
Published: November 2018

AbstractG protein‐coupled receptor 119 (GPR119) is known to be a promising therapeutic target for type 2 diabetes. Recently, it has been reported that the GPR119 agonist increases bone mineral density in an animal model of diabetes, suggesting that GPR119 may play a key role in bone metabolism. In this study, we investigated the functional role of GPR119 in receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation. We found that the GPR119 expression was markedly increased in preosteoclasts and then downregulated in mature osteoclasts. Activation of GPR119 with AS1269574, a potent selective agonist for GPR119, inhibited the generation of multinuclear osteoclasts from bone marrow‐derived macrophages. Confirming this observation, targeted silencing ofGPR119using short hairpin RNA abrogated the AS1269574‐mediated suppressive effect on osteoclast formation. GPR119 activation attenuated the expression of c‐Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and blocked RANKL‐stimulated phosphorylation of IκBα, c‐Jun N‐terminal protein kinase (JNK), and extracellular signal‐regulated kinase (ERK) but not p38. In addition, GPR119 activation suppressed preosteoclast fusion by downregulating the expression of the dendritic cell‐specific transmembrane (DC‐STAMP), a molecule that is essential for cell–cell fusion in osteoclast formation. Furthermore, ectopic expression of DC‐STAMP restored AS1269574‐mediated inhibition of osteoclast fusion. Taken together, our findings demonstrate that GPR119 plays a negative role in osteoclast differentiation and fusion induced by RANKL, and therefore may represent a potential target for bone resorption‐associated diseases.
MicroRNA: A new player in response to therapy for colorectal cancer
Authors: Sarvizadeh Mostafa , Malekshahi Ziba V. , Razi Ebrahim , Sharifi Hossein , Moussavi Nousin , Taghizadeh Mohsen 
Published: November 2018

AbstractColorectal cancer (CRC) is one of the important malignancies that result in cancer‐related deaths worldwide. Multiple lines of evidence have indicated that different responses to therapy in CRC cells led to the failure of the current therapies. Hence, identification of the underlying cellular and molecular pathways involved in the emergence of different responses from CRC cells could contribute to finding and designing new therapeutic platforms to overcome the present limitations. Among the various targets involved in CRC pathogenesis, microRNAs (miRNAs) have key roles in many signaling pathways that are associated with the initiation and progression of CRC. Increasing evidence has confirmed that miRNAs as epigenetic regulators could play critical roles in the response (resistance or sensitivity) to therapy. Cancer stem cells are well‐known players in resistance to therapy in CRC. They have been shown to play significant roles via inhibition and activation of many miRNA networks. Hence, miRNAs could be involved in the resistance and sensitivity of therapy in CRC cells via affecting different mechanisms, such as activation of cancer stem cells. Here, we summarized the role of various miRNAs in response to therapy of CRC cells. Moreover, we highlighted the roles of these molecules in the function of cancer stem cells, which are known as important players in the resistance to therapy in CRC.
Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA‐mRNA network based on competing endogenous RNAs hypothesis
Authors: Qian Cheng , Li Hang , Chang Danqi , Wei Baozhu , Wang Yanggan 
Published: November 2018

AbstractA mounting body of evidence has suggested that long noncoding RNAs (lncRNAs) play critical roles in human diseases by acting as competing endogenous RNAs (ceRNAs). However, the functions and ceRNA mechanisms of lncRNAs in atrial fibrillation (AF) remain to date unclear. In this study, we constructed an AF‐related lncRNA‐mRNA network (AFLMN) based on ceRNA theory, by integrating probe reannotation pipeline and microRNA (miRNA)‐target regulatory interactions. Two lncRNAs with central topological properties in the AFLMN were first obtained. By using bidirectional hierarchical clustering, we identified two modules containing four lncRNAs, which were significantly enriched in many known pathways of AF. To elucidate the ceRNA interactions in certain disease or normal condition, the dysregulated lncRNA‐mRNA crosstalks in AF were further analyzed, and six hub lncRNAs were obtained from the network. Furthermore, random walk analysis of the AFLMN suggested that lncRNA RP11‐296O14.3 may function importantly in the pathological process of AF. All these eight lncRNAs that were identified from previous steps (RP11‐363E7.4, GAS5, RP11‐410L14.2, HAGLR, RP11‐421L21.3, RP11‐111K18.2, HOTAIRM1, and RP11‐296O14.3) exhibited a strong diagnostic power for AF. The results of our study provide new insights into the functional roles and regulatory mechanisms of lncRNAs in AF, and facilitate the discovery of novel diagnostic biomarkers or therapeutic targets.
CtIP promotes G2/M arrest in etoposide‐treated HCT116 cells in a p53‐independent manner
Authors: Chen Hongyu , Shan Jin , Chen Dandan , Wang Ruoxi , Qi Wenjing , Wang Hailong , Ke Yueshuang , Liu Wenguang , Zeng Xianlu 
Published: November 2018

AbstractAcquired resistance to cytotoxic antineoplastic agents is a major clinical challenge in tumor therapy; however, the mechanisms involved are still poorly understood. In this study, we show that knockdown of CtIP, a corepressor of CtBP, promotes cell proliferation and alleviates G2/M phase arrest in etoposide (Eto)‐treated HCT116 cells. Although the expression of p21 and growth arrest and DNA damage inducible α (GADD45a), which are important targets of p53, was downregulated in CtIP‐deficient HCT116 cells, p53 deletion did not affect G2/M arrest after Eto treatment. In addition, the phosphorylation levels of Ser317 and Ser345 in Chk1 and of Ser216 in CDC25C were lower in CtIP‐deficient HCT116 cells than in control cells after Eto treatment. Our results indicate that CtIP may enhance cell sensitivity to Eto by promoting G2/M phase arrest, mainly through the ATR‐Chk1‐CDC25C pathway rather than the p53‐p21/GADD45a pathway. The expression of CtIP may be a useful biomarker for predicting the drug sensitivity of colorectal cancer cells.
The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study
Authors: Peñaloza Hernán F , Alvarez Diana , Muñoz-Durango Natalia , Schultz Bárbara M , González Pablo A , Kalergis Alexis M , Bueno Susan M 
Published: November 2018

Abstract
An effective pathogen has the ability to evade the immune response. The strategies used to achieve this may be based on the direct action of virulence factors or on the induction of host factors. Myeloid-derived suppressor cells (MDSCs) are immune cells with an incredible ability to suppress the inflammatory response, which makes them excellent targets to be exploited by pathogenic bacteria, viruses, or parasites. In this review, we describe the origin and suppressive mechanisms of MDSCs, as well as their role in chronic bacterial, viral, and parasitic infections, where their expansion seems to be essential in the chronicity of the disease. We also analyze the disadvantages of current MDSC depletion strategies and the different in vitro generation methods, which can be useful tools for the deeper study of these cells in the context of microbial infections.
Novel placental structure in the Mexican gerrhonotine lizard, Mesaspis viridiflava (Lacertilia; Anguidae)
Authors: Stewart James R. , Mendez de la Cruz Fausto R. 
Published: November 2018

AbstractThe evolution of viviparity alters the physical relationship between mothers and offspring and the prevalence of viviparity among squamate reptiles presents an opportunity to uncover patterns in the evolution of placental structure. Understanding the breadth of this diversity is limited because studies of placental structure and function have emphasized a limited number of lineages. We studied placental ontogeny using light microscopy for an embryological series of the Mexican gerrhonotine lizard, Mesaspis viridiflava. This species develops an elaborate yolk sac placenta, an omphaloplacenta, which receives vascular support arising in a structure known only from other gerrhonotine lizards. A prominent feature of the omphaloplacenta is a zone of uterine and embryonic epithelial cell hyperplasia located at the upper shoulder of the yolk mass, often extending above the yolk mass. The omphaloplacenta covers more than one‐half of the surface area of maternal—embryonic contact. The chorioallantoic placenta has a more restricted distribution because the allantois remains in the embryonic hemisphere of the egg throughout development and lies internal to the vascular support for the omphaloplacenta in areas where they overlap. The structural profile of the chorioallantoic placenta indicates a potential for respiratory exchange and/or hemotrophic nutritive transport, while that of the omphaloplacenta suggests that nutritive transfer is primarily via histotrophy. An eggshell is present in the earliest embryonic stages examined but regresses relatively early in development. Placental specializations of this species are consistent with a pattern of matrotrophic embryonic nutrition and have evolved in a unique lineage specific developmental pattern.
Impaired bone healing following treatment of established nonunion correlates with serum cytokine expression
Authors: Cheng Albert , Krishnan Laxminarayanan , Pradhan Pallab , Weinstock Laura D. , Wood Levi B. , Roy Krishnendu , Guldberg Robert E. 
Published: November 2018

ABSTRACTDelayed union and nonunion are a significant concern in long bone fractures and spinal fusions. Treatment of nonunion often entails multiple revision surgeries that further increase the financial, physical, and emotional burden on patients. The optimal treatment strategy for nonunions remains unclear in many cases, and the risk of complications after revision procedures remains high. This is in part due to our limited understanding of the biological mechanisms that inhibit proper bone healing and lead to nonunion. And yet, few preclinical models directly investigate how healing is impacted after establishment of nonunion, with most instead primarily focusing on treatment immediately after a fresh bone injury. Here, we utilized a critical size femoral defect model in rats where treatment was delayed 8 weeks post‐injury, at which time nonunion was established. In this study, acute and delayed treatments with bone morphogenetic protein‐2 (BMP‐2) were assessed. We found that delayed treatment resulted in decreased bone formation and reduced mechanical strength compared to acute treatment, even when BMP‐2 dose was increased by 2.5 times the acute treatment dose. Interestingly, serum cytokine analysis at 12 weeks post‐treatment revealed signs of chronic immune dysregulation after delayed treatment. In particular, non‐responders (rats that did not exhibit defect bridging) demonstrated higher overall expression of inflammatory cytokines, including TNFα and IL‐1β, compared to responders. These findings suggest that re‐establishing long‐term immune homeostasis may be critical for successful bone healing, particularly after nonunion. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:299–307, 2019.
Lateral cartilage defects and medial subchondral surface ratio are associated with knee‐related disability
Authors: Everhart Joshua S. , Abouljoud Moneer M. , Flanigan David C. 
Published: November 2018

ABSTRACTWe sought to determine the relationship between (i) full‐thickness cartilage defects and tibiofemoral subchondral surface ratio (SSR) and (ii) disability and quality of life in patients with mild radiographic osteoarthritis (OA) (Kellgren‐Lawrence grade 2) or without radiographic OA (Kellgren‐Lawrence grades 0 or 1)? A total of 642 participants from the Osteoarthritis Initiative (OAI) with baseline knee MRIs and a Kellgren‐Lawrence grade 2 or less on both bilateral screening radiographs were included. The independent relationship was assessed between (i) full‐thickness cartilage defect presence and tibiofemoral SSR and (ii) Knee Injury and Osteoarthritis Outcome Score (KOOS) quality of life (QOL), KOOS function in sports and recreation (KOOS‐sport/rec), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability score after adjustment for relevant confounders with multivariate regression modeling. The prevalence of medial full‐thickness defects was 10.4% (67/642) and lateral was 18.1% (116/642). Lateral defect presence was associated with worse KOOS‐QOL (beta −3.61 SE 1.04; p = 0.001), KOOS‐sport/rec (beta −4.70 SE 1.38; p = 0.001) and WOMAC‐disability scores (beta 0.02 SE 0.01; p = 0.001); these associations were not influenced by defect size. A larger medial compartment SSR was associated with worse KOOS‐QOL (beta −27.20 SE 6.80; p < 0.001), KOOS‐sports/rec (beta −22.30 SE 9.01; p = 0.01) and WOMAC‐disability scores (beta 0.16 SE 0.04; p < 0.001). In older adults with little to no radiographic osteoarthritis, lateral full‐thickness cartilage defects, irrespective of size, and a larger medial compartment tibiofemoral SSR are potential sources of knee‐related symptoms that are not appreciated on standard radiographs. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:378–385, 2019.
Modified distribution in the polyphenolic profile of rosemary leaves induced by plant inoculation with an arbuscular mycorrhizal fungus
Authors: Seró Raquel , Núñez Nerea , Núñez Oscar , Camprubí Amelia , Grases Josep M , Saurina Javier , Moyano Encarnación , Calvet Cinta 
Published: November 2018

AbstractBACKGROUNDRosemary forms an arbuscular mycorrhizal (AM) symbiosis with a group of soilborne fungi belonging to the phylum Glomeromycota, which can modify the plant metabolome responsible for the antioxidant capacity and other health beneficial properties of rosemary.RESULTSThe effect of inoculating rosemary plants with an AM fungus on their growth via their polyphenolic fingerprinting was evaluated after analyzing leaf extracts from non‐inoculated and inoculated rosemary plants by ultra‐high performance liquid chromatography‐high resolution mass spectrometry (UHPLC‐HRMS). Plant growth parameters indicated that mycorrhizal inoculation significantly increased plant height and biomass. Chemical modifications in the plant polyphenolic profile distribution were found after a principal components analysis (PCA) loading plots study. Four compounds hosting strong antioxidant properties – ferulic acid, asiatic acid, carnosol, and vanillin – were related to mycorrhizal rosemary plants while caffeic and chlorogenic acids had a higher influence on non‐mycorrhizal plants.CONCLUSIONMycorrhization was found to stimulate growth to obtain a higher biomass of plant leaves in a short time, avoiding chemical fertilization, while analytical results demonstrate that there is an alteration in the distribution of polyphenols in plants colonized by the symbiotic fungus, which can be related to an improvement in nutritional properties with future industrial significance. © 2018 Society of Chemical Industry
Identifying the barriers to gastric cancer care at safety‐net hospitals: A novel comparison of a safety‐net hospital to a neighboring quaternary referral academic center in the same healthcare system
Authors: Zaidi Mohammad Y. , Rappaport Jesse M. , Ethun Cecilia G. , Gillespie Theresa , Hawk Natalyn , Chawla Saurabh , Cardona Kenneth , Maithel Shishir K. , Russell Maria C. 
Published: November 2018

BackgroundThe three‐delays model describes delays in seeking, reaching, and receiving care for vulnerable populations needing treatment. The dominant delay for patients with gastric adenocarcinoma (GAC) is unknown. We aimed to define patients with GAC who reached and received care at our regional safety‐net hospital (Grady Memorial Hospital [GMH]) and our neighboring quaternary referral hospital (Emory University Hospital [EUH]).MethodsClinicopathologic data from National Cancer Database (NCDB) participating academic centers were compared with GMH from 2004 to 2014. Outcomes of patients undergoing surgery at GMH were compared to those at EUH.ResultsAt presentation, compared to NCDB centers (n = 69 662), GMH patients (n = 154) were more often black (85.1 vs 17.2%; P < 0.001), uninsured (30.5 vs 4.7%; P < 0.001), have stage IV disease (43.5 vs 30.1%; P = 0.017), and received no treatment (40.3 vs 18.4%; P < 0.001). When only comparing patients who underwent curative‐intent resection at GMH (n = 23) to EUH (n = 137), median overall survival was similar between both groups (GMH: median not reached; EUH: 59.8 mos; P = 0.785).ConclusionAlthough vulnerable patients with GAC within a safety‐net hospital present with later stages of the disease, those who received surgery have acceptable outcomes. Thus, efforts should be made to overcome barriers in seeking care.
National trends in contralateral prophylactic mastectomy in women with locally advanced breast cancer
Authors: Panchal Hinaben , Pilewskie Melissa L. , Sheckter Clifford C. , Albornoz Claudia R. , Razdan Shantanu N. , Disa Joseph J. , Cordeiro Peter G. , Mehrara Babak J. , Matros Evan 
Published: November 2018

AbstractBackground and ObjectivesWomen with unilateral early‐stage breast cancer are increasingly choosing contralateral prophylactic mastectomy (CPM) despite the absence of survival benefits and increased risk of surgical complications. Data are lacking on whether this trend extends to women with clinically locally advanced nonmetastatic (cT4M0) cancer. This study aims to estimate national CPM trends in women with unilateral cT4M0 breast cancer.MethodsWomen aged ≥ 18 years, who underwent mastectomy during 2004 to 2014 for unilateral cT4M0 breast cancer were identified using the National Cancer Database and grouped as all locally advanced (T4), chest wall invasion, skin nodule/ulceration, or both (T4abc), and inflammatory (T4d) cancer. Poisson regression for trends and logistic modeling for predictors of CPM were performed.ResultsOf 23 943 women, 41% had T4abc disease and 35% T4d. Cumulative CPM rates were 15%, 23%, and 18%, for the T4abc, T4d, and all T4 groups, respectively. Trend analysis revealed a significant upsurge in CPM demonstrating 12% annual growth for T4abc tumors, 8% for T4d and 9% for all T4 (all P < 0.001).ConclusionsIncreasing numbers of women with unilateral cT4M0 breast cancer are undergoing CPM. This rising trend warrants further research to understand stakeholders’ preferences in surgical decision‐making for women with locally advanced breast cancer.
Simultaneous detection of multiple hydroxylated polychlorinated biphenyls from biological samples using ultra‐high‐performance liquid chromatography with isotope dilution tandem mass spectrometry
Authors: Zheng Yibin , Cai Delei , Huang Baifen , Han Jianlong , Chen Qing , Zhang Jingshun , Zhang Jie , Wang Xiaofeng , Shen Haitao 
Published: November 2018

AbstractWe established a method for the separation and detection of nine hydroxylated polychlorinated biphenyls in whole blood and urine samples using ultra high performance liquid chromatography coupled with electrospray negative ionization tandem mass spectrometry. Clean‐up procedures involved a filtration step, and optimization involved a pretreatment step consisting of a simple liquid–liquid extraction using hydrated silica‐gel chromatography (5%). Nine hydroxylated polychlorinated biphenyls were separated on an ultra high performance liquid chromatography HSS T3 column using a gradient elution program of 2 mmol ammonium formate aqueous solution (A) and methanol (B). Recovery ranged from 84.0 to 105.4% for the nine different hydroxylated polychlorinated biphenyls in urine with three spiked levels of 0.1, 1, and 2 ng and from 73.5 to 98.6% for the blood with spiked levels of 0.2, 1, and 2 ng. The relative standard deviations were <8.7% (n = 6), and the limits of detection in urine and whole blood for the nine hydroxylated polychlorinated biphenyls were in the range of 1.5–4 and 20–100 pg/g, respectively. This analytical method may enable the simultaneous detection of various hydroxylated polychlorinated biphenyls from complex tissue matrices.