bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt pathway targeting reduces triple‐negative breast cancer aggressiveness through miRNA regulation in vitro and in vivo
Authors: Mohammadi‐Yeganeh Samira , Hosseini Vahedeh , Paryan Mahdi 
Published: April 2019

AbstractTriple‐negative breast cancer, devoid of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER‐2) expression, is deprived of commonly used targeted therapies. MicroRNAs (miRNAs) are undergoing a revolution in terms of potentially diagnostic or therapeutic elements. Combining computational approaches, we enriched miRNA binding motifs of Wnt pathway‐associated upregulated genes. Our in‐depth bioinformatics, in vitro and in vivo analyses indicated that miR‐381 targets main genes of the Wnt signaling pathway including CTNNB1, RhoA, ROCK1, and c‐MYC genes.The expression level of miR‐381 and target genes was assessed by quantitative real‐time polymerase chain reaction (RT‐qPCR) in MCF‐7, MDA‐MB‐231, and MCF‐10A as well as 20 breast cancer samples and normal tissues. Luciferase reporter assay was performed. Lentiviral particles containing miR‐381 were used to evaluate the effect of miR‐381 restoration on cell proliferation, migration, and invasion of the invasive triple‐negative MDA‐MB‐231 cell line and also in a mouse model of breast cancer.The expression of miR‐381 was lower than that of normal cells, especially in TNBC cell line and breast tissues. Luciferase assay results confirmed that miR‐381 targets all the predicted 3′‐untranslated regions (3′‐UTRs). Upon miR‐381 overexpression, the expression of target genes declined, and the migration and invasion potential of miR‐381‐receiving MDA‐MB‐231 cells decreased. In a mouse model of triple‐negative breast cancer, miR‐381 re‐expression inhibited the invasion of cancer cells to lung and liver and prolonged the survival time of cancer cell‐bearing mice. Therefore, miR‐381 is a regulator of Wnt signaling and its re‐expression provides a potentially effective strategy for inhibition of TNBC.
Inflammation‐dependent downregulation of miR‐194‐5p contributes to human intervertebral disc degeneration by targeting CUL4A and CUL4B
Authors: Chen Zhi , Han Yingchao , Deng Chao , Chen Wei , Jin Linyu , Chen Hao , Wang Kun , Shen Hongxing , Qian Lie 
Published: April 2019

AbstractInflammation is one of the major causes of intervertebral disc degeneration (IDD). Emerging evidence has revealed that increase in the levels of pro‐inflammatory cytokines, such as interleukin 6 (IL‐6) and tumor necrosis factor alpha (TNF‐α), can activate a variety of signaling pathways, eventually resulting in IDD. Here, we show that the two cullin family genes, CUL4A and CUL4B, but not other cullins, are specifically overexpressed in IDD samples compared with healthy controls, and the CUL4A and CUL4B levels are positively correlated with the severity of IDD. In vitro analyses in human osteoblast cells (hFOB1.19), nucleus pulposus cells (hNPCs), and annulus fibrosus cells (hAFCs) indicated that treatment with IL‐6 and TNF‐α can increase CUL4A and CUL4B levels. By performing a microRNA‐based microarray analysis, we found a set of microRNAs (miRNAs) that were differentially expressed in IDD samples compared with samples from healthy controls. Of these miRNAs, miR‐194‐5p, was significantly downregulated in IDD samples and could bind to the three prime untranslated regions (3′‐UTRs) of both CUL4A and CUL4B, thereby downregulating their expression. The in vitro overexpression or downregulation of miR‐194‐5p, with a miR‐194‐5p‐mimic or with anti‐miR‐194‐5p, can cause the repression or induction of both CUL4A and CUL4B, respectively. Interestingly, treatment with IL‐6 and TNF‐α inhibitors in primary hNPCs and hAFCs that were isolated from patients with IDD led to the downregulation of CUL4A and CUL4B. Together, these findings provide insight into how the inflammation‐dependent downregulation of miR‐194‐5p contributes to the pathogenesis of IDD, which may aid in the development of new therapeutic approaches for IDD by directly targeting miR‐194‐5p or CUL4A and CUL4B.
NLRC5 negatively regulates LTA‐induced inflammation via TLR2/NF‐κB and participates in TLR2‐mediated allergic airway inflammation
Authors: Wang Muzi , Wang Lixia , Fang Lei , Li Shuai , Liu Rongyu 
Published: April 2019

AbstractNLRC5, the largest member of the Nod‐like receptor (NLR) family, has been reported to play a pivotal role in regulating inflammatory responses. Recent evidence suggests that NLRC5 participates in Toll‐like receptor (TLR) signaling pathways and negatively modulates nuclear factor‐κB (NF‐κB) activation. In this study, we investigated the interaction between NLRC5 and TLR2 in the NF‐κB inflammatory signaling pathway and the involvement of NLRC5 in TLR2‐mediated allergic airway inflammation. We knocked down TLR2 and NLRC5, respectively in the RAW264.7 macrophage cell line by small interfering RNA (siRNA) and then stimulated the knockdown cells with lipoteichoic acid (LTA). In comparison with the negative siRNA group, the level of NLRC5 expression was lower in the TLR2 siRNA group, with a reduction in the NF‐κB‐related inflammatory response. Conversely, in the NLRC5 knockdown cells, after LTA‐treated the level of TLR2 expression did not change but the expression levels of both NF‐κB pp65 and NLRP3 increased remarkably. Thus, we hypothesize that NLRC5 participates in the LTA‐induced inflammatory signaling pathway and regulates the inflammation via TLR2/NF‐κB. Similarly, in subsequent in vivo experiments, we demonstrated that the expression level of NLRC5 was significantly increased in the ovalbumin‐induced allergic airway inflammation. However, this effect disappeared in TLR2‐deficient (TLR2
−/−) mice and was accompanied by reduced levels of NF‐κB expression and airway inflammation. In conclusion, NLRC5 negatively regulates LTA‐induced inflammatory response via a TLR2/NF‐κB pathway in macrophages and also participates in TLR2‐mediated allergic airway inflammation.
Effect of long‐term exposure of silver nanoparticles on growth indices, hematological and biochemical parameters and gonad histology of male goldfish (Carassius auratus gibelio)
Authors: Forouhar Vajargah Mohammad , Imanpoor Mohammad R. , Shabani Ali , Hedayati Aliakbar , Faggio Caterina 
Published: April 2019

AbstractStudying the impact of emerging pollutants such as nanoparticles is necessary to reveal the adverse effect. In this study, the effects of silver nanoparticles (Ag‐NPs) on hematological, biochemical, and gonad histopathological indices of male goldfish were examined. Sublethal toxicity were calculated based on acute toxicity and three dosages were selected. Live specimen of Carassius auratus gibelio larval were treated in 1, 2, and 3 ppm Ag‐NP with one control group. Blood and tissue samples were extracted after 6 months exposure to sublethal concentrations. Results showed that Ag‐NPs have reduced growth rate and effected on all blood indices significantly. Biochemical analysis revealed that Ag‐NPs significantly reduced blood glucose and total protein than in comparison to the control group and caused significantly differences in the concentrations of serum cholesterol (p < .05). Furthermore, histological observation of intestine after 6 months exposure showed definite alterations in tissue and maximum hypertrophy injuries were found after long‐term exposure to 3 ppm Ag‐NPs concentration. In addition, indicated that long‐term exposure to Ag‐NPs postponed sexual maturity in male gibel carp.
Successful treatment of intractable menstrual migraine with the traditional herbal medicine tokishakuyakusan
Authors: Akaishi Tetsuya , Takayama Shin , Ohsawa Minoru , Kikuchi Akiko , Arita Ryutaro , Nakashima Ichiro , Aoki Masashi , Ishii Tadashi 
Published: April 2019

AbstractIn this report, we present the successful treatment of five consecutive cases of premenopausal women suffering from severe menstrual migraine with tokishakuyakusan (TSS). Two patients were complicated by tension‐type headache (TTH), and another patient was by medication overuse headache (MOH). The effects of triptans were limited in all of them. After starting TSS, they showed dramatic improvement in the severity and frequency of their attacks. The patients with TTH and MOH also showed dramatic improvement in their symptoms. TSS could be a promising alternative choice for patients with intractable menstruation–related headaches that are refractory to conventional treatments, including triptans.
Augmentation with pre‐emptive macrogol‐based osmotic laxative does not significantly improve standard bowel preparation in unselected patients: A randomized trial
Authors: Mangira Dileep , Ket Shara , Dwyer Jeremy , Secomb Robyn , Reynolds John , Brown Gregor 
Published: April 2019

Background and AimThe addition of a laxative prior to a standard bowel preparation (BP) has shown variable results in efficacy, safety, and tolerability of the BP. This study compared the efficacy and tolerability of a macrogol‐augmented BP (M‐BP) with standard BP for routine colonoscopy in unselected patients.MethodsAdults undergoing outpatient colonoscopy were randomized to either M‐BP (one sachet of macrogol‐based osmotic laxative (MBOL) twice daily for eight doses prior to standard preparation) or BP (split‐dose of polyethylene glycol and sodium picosulfate). Bowel cleansing was assessed using the Ottawa BP scale. Risk factors for poor BP, patient satisfaction, and tolerance were recorded.ResultsThis randomized trial was stopped due to futility after 14 months; at that point, 92 subjects were randomized to the study arm and 102 to the control arm. M‐BP had a success rate of 71.7% (95% CI: 58.5–82.7%), while the BP had a success rate of 67.7% (95% CI: 54.9–78.8%), with a Pearson χ2 test P‐value of 0.639, which exceeded the cut‐off for futility (0.313). In subgroup analyses, there were statistically significant decreases in the rates of successful BP in patients taking regular opioids and regular laxatives. Both preparations were well tolerated, with no difference between groups (BP – 5.3% and M‐BP – 6.6% P = 0.66).ConclusionThe addition of MBOL prior to a standard BP in unselected subjects does not significantly improve bowel cleanliness at routine colonoscopy. The role of this laxative in patients at high risk of poor preparation warrants further investigation.
Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8
Authors: Gao Yutong , Yu Xiangdi , Zhang Fangxiang , Dai Jing 
Published: April 2019

AbstractBackgroundTo investigate the potential anti‐tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms.MethodsThe relative expression of ADAM metallopeptidase domain 8 (ADAM8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK‐8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis‐related markers including platelet‐derived growth factor AA, angiogenin, endothelin‐1 and vascular endothelial growth factor were determined by real‐time polymerase chain reaction and western blotting. The anti‐tumoral activity of propofol was investigated with Panc1‐derived xenograft mice model.ResultsADAM8 was significantly induced by hypoxia and efficiently inhibited by co‐treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis‐related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression.ConclusionPropofol specifically inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.
Synthesis of Novel Pterocarpen Analogues via [3 + 2] Coupling‐Elimination Cascade of α,α‐Dicyanoolefins with Quinone Monoimines
Authors: Chen Hui , Zhao Sihan , Cheng Shaobing , Dai Xingjie , Xu Xiaoying , Yuan Weicheng , Zhang Xiaomei 
Published: April 2019

By employing triethylamine as a catalyst, [3 + 2] coupling‐elimination cascade of α,α‐dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
Mutations in the translocon‐associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation
Authors: Ng Bobby G. , Lourenço Charles M. , Losfeld Marie‐Estelle , Buckingham Kati J. , Kircher Martin , Nickerson Deborah A. , Shendure Jay , Bamshad Michael J. ,   University of Washington Center for Mendelian Genomics, Freeze Hudson H. 
Published: April 2019

AbstractThe translocon‐associated protein (TRAP) complex facilitates the translocation of proteins across the endoplasmic reticulum membrane and associates with the oligosaccharyl transferase (OST) complex to maintain proper glycosylation of nascent polypeptides. Pathogenic variants in either complex cause a group of rare genetic disorders termed, congenital disorders of glycosylation (CDG). We report an individual who presented with severe intellectual and developmental disabilities and sensorineural deafness with an unsolved type I CDG, and sought to identify the underlying genetic basis. Exome sequencing identified a novel homozygous variant c.278_281delAGGA [p.Glu93Valfs*7] in the signal sequence receptor 3 (SSR3) subunit of the TRAP complex. Biochemical studies in patient fibroblasts showed the variant destabilized the TRAP complex with a complete loss of SSR3 protein and partial loss of SSR1 and SSR4. Importantly, all subunit levels were corrected by expression of wild‐type SSR3. Abnormal glycosylation status in fibroblasts was confirmed using two markers proteins, GP130 and ICAM1. Our findings confirm mutations in SSR3 cause a novel CDG.A novel frameshift variant in the translocon associated protein, SSR3, disrupts the stability of the TRAP complex and causes a novel Congenital Disorder of Glycosylation.
Advances in understanding of presbycusis
Authors: Tawfik Kareem O. , Klepper Kristin , Saliba Joe , Friedman Rick A. 
Published: April 2019

AbstractThe pathophysiology of age‐related hearing loss (ARHL), or presbycusis, involves a complex interplay between environmental and genetic factors. The fundamental biomolecular mechanisms of ARHL have been well described, including the roles of membrane transport, reactive oxygen species, cochlear synaptopathy, vascular insults, hormones, and microRNA, to name a few. The genetic basis underlying these mechanisms remains under‐investigated and poorly understood. The emergence of genome‐wide association studies has allowed for the identification of specific groups of genes involved in ARHL. This review highlights recent advances in understanding of the pathogenesis of ARHL, the genetic basis underlying these processes and suggests future directions for research and potential therapeutic avenues.
Copolymers of Diallyldimethylammonium Chloride and Vinyl Ether of Monoethanolamine: Synthesis, Flocculating, and Antimicrobial Properties
Authors: Dauletov Yerbol , Nuraje Nurxat , Abdiyev Kaldibek , Toktarbay Zhexenbek , Zhursumbaeva Maryamgul 
Published: April 2019

AbstractN,N‐diallyl‐N,N‐dimethylammonium chloride (DADMAC) and vinyl ether of monoethanolamine (VEMEA) copolymer P(DADMAC‐VEMEA) were synthesized using radical polymerization in water media using ammonium persulfate as an initiator. The synthesis of this copolymer was investigated over a wide composition range at low conversion levels. The viscosity of the copolymers was measured in aqueous 1 M NaCl. Flocculating action and antimicrobial activities of the copolymers P(DADMAC‐VEMEA) against microbacteria and sulfate‐reducing bacteria (SRB) were studied. Synthesized copolymers had flocculating effects and can be used to purify wastewater from particles of bentonite clays. Also, the copolymer with a molar composition [DADMAC]: [VEMEA] = (80÷20):(20÷80) retarded the population of both bacteria, Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) in the diffusion zone. Furthermore, the copolymer with a molar composition [DADMAC]:[VEMEA] = (90÷10):(20÷80) had bactericidal properties against SRB. Minimum inhibitory concentration (MIC) of the copolymer varied from 0.01% to 0.1% depending on the molar composition of the copolymer.
Studies of Superb Microvascular Imaging and Contrast‐Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration
Authors: Jin Lin , Li Ping , Wang Ying‐Chun , Feng Lan , Xu Rong , Yang De‐Bin , Yao Xiao‐Hua 
Published: April 2019

ObjectiveThe aim of this study was to investigate value of superb microvascular imaging (SMI) and contrast‐enhanced ultrasonography (CEUS) in evaluating the neovascularization of early bone regeneration.MethodsTwenty‐five Sprague‐Dawley male rats were implanted with recombinant human bone morphogenetic protein‐2/calcium phosphate cement (rhBMP‐2/) in the muscle space of the left hind limb near the femoral head to establish the rat model of intramuscular ectopic osteogenesis. Ultrasonography and pathologic analysis were performed on the 3rd, 7th, 14th, 21st, and 28th days after modeling. Two‐dimensional ultrasonography, SMI, and CEUS were used to assess neovascularization and bone formation.ResultsPathologic examination showed that different levels of neovascularization were observed in the graft bone over time after modeling, which increased significantly from the 3rd to 14th day, and then gradually decreased. CEUS and SMI showed no obvious microvessels inside the graft bone on the 3rd day. On the 7th day after modeling, a small number of neovascular vessels were observed around the graft bone. On the 14th day, neovascularization was observed in both the peripheral and inner parts of the graft bone. The number of neovascular vessels inside the graft bone had decreased gradually by the 21st and 28th days. The results of SMI and CEUS indexes showed that the vascular index, peak intensity, enhancement intensity, and enhancement rate first increased and then decreased with time. Their peak points were found on the 14th day. Arrival time, time to peak, and enhancement time decreased gradually over time (P < .05).ConclusionThe combined application of SMI and CEUS may be useful in evaluating the neovascularization of early osteoanagenesis.
Visible Light–Induced RAFT Polymerization of Methacrylate with 4‐(N,N‐diphenylamino)benzaldehyde as Organophotoredox Catalyst and the Effect of Temperature on the Polymerization
Authors: Zhang Wenxiu , Zhang Xianhong , Ma Yuhong , Chen Dong , Yang Wantai 
Published: April 2019

AbstractWith UV–vis absorption in the range of 270–435 nm, 4‐(N,N‐diphenylamino)benzaldehyde (DPAB) takes efficient photoreduction quench with 4‐cynao‐4‐(phenylcarbonothioylthio)pentanoic acid (CTP). The polymerization rates of methyl methacrylate (MMA) are 0.019, 0.056, and 0.102 h−1 at 33, 40, and 50 °C, respectively, in the presence of DPAB and CTP under visible‐light irradiation. Dark reaction produces no PMMA at 50 °C for 120 h. The living feature is demonstrated by linearly increasing Mn with the monomer conversions and narrow polydispersity index (PDI), chain extension, and block polymerizations with benzyl methacrylate (BnMA) and poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). With PMMA‐CTP (Mn = 6800, PDI = 1.17), chain extension gives PMMA with Mn = 15 900 and PDI = 1.15. With PMMA‐CTP (Mn = 6000, PDI = 1.21) as macro‐RAFT, PMMA‐b‐PBnMA of Mn = 12 600 (PDI = 1.44) and Mn = 18 500 (PDI = 1.31) are prepared. These results support that there is a positive synergistic effect between polymerization temperature and visible‐light irradiation on the photo‐RAFT without losing the living features.
Impact of advanced age on microvascular reconstruction of the lower facial third: An American College of Surgeons NSQIP study
Authors: Torabi Sina J. , Chouairi Fouad , Dinis Jacob , Alperovich Michael 
Published: April 2019

AbstractBackgroundMicrovascular reconstruction is the standard of care in head and neck reconstruction, though its perioperative safety in an older population has been controversial due to safety concerns, warranting further investigation.Materials and methodsAn “older” (≥71 years) cohort undergoing reconstruction after mandibulectomy/glossectomy was compared to the remaining population in a National Surgical Quality Improvement Program (2008–2016) analysis. Cases required both a mandibulectomy/glossectomy and microvascular or local flap reconstruction (exclusion criteria: missing ages and simultaneous microvascular and local flap reconstruction). Demographics, comorbidities, and procedure types were analyzed on 985 patients (236 [24.4%] were ≥71). Outcomes were compared by reconstruction type. Regressions were performed calculating the impact of age on length of hospital stay (LOHS) and operative time.ResultsAblative procedures were comparable, but older patients received local flaps at higher rates (22.5% vs. 9.6%; p < .001). The older population had more comorbidities (higher ASA class [p < .001], diabetes [p < .001], and hypertension [p < .001]). After Bonferroni correction, univariate subgroup analyses of soft tissue and bone/composite microvascular flaps revealed similar outcomes (except increased medical complications in the older cohort undergoing a bone free flap [p = .002]). Controlling for a variety of factors, older age resulted in longer LOHS (B: 1.4 days; 95% CI: 0.1–2.8 days; p = .035), but not operative time (B: −21.90 min; 95% CI: −52.76 to 8.96 min; p = .164).ConclusionWhile increased age (≥70 years) was associated with a longer LOHS, complication rates were comparable. Although limited by the retrospective nature, evidence supports microvascular reconstruction in the elderly population with comparable outcomes.
Effects of thermosensory aging well demonstrated by cold stimulations with high temporal resolution
Authors: Després Olivier , Lithfous Ségolène , Pebayle Thierry , Casadio Claudia , Dufour André 
Published: April 2019

ABSTRACTIntroduction: The method of limits (MLi) is the most commonly used paradigm to measure the threshold of thermal stimuli. However, the threshold measured by MLi is dependent on reaction time (RT). Because RT in adults increases with age, the inclusion of RT in the MLi paradigm may result in an overestimation of thermal threshold in the older individuals. Methods: A device with a very rapid cooling rate (300°C/s) was employed to measure cool thresholds by using the method of levels (MLe), a method independent of RT, in 11 older patients and 14 younger adults. Results: Compared with the MLi, the MLe resulted in a greater than 2°C gain in threshold measurement accuracy in older patients. Discussion: The MLe confirmed that cool perception threshold is dependent on age. The use of MLe provides new opportunities for the study of mechanisms underlying age‐associated alterations in thermal perception. Muscle Nerve 60: 141–146, 2019