bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOTAIR‐induced apoptosis is mediated by sponging miR‐130a‐3p to repress chondrocyte autophagy in knee osteoarthritis
Authors: He Bin , Jiang Dianming 
Published: October 2019

AbstractKnee osteoarthritis (KOA) is a multifactorial disease characterized by the loss of articular cartilage. Hox transcript antisense intergenic RNA (HOTAIR) long non‐coding RNA (lncRNA) is highly expressed in some cases of OA; however, its role in chondrocyte apoptosis in KOA and the mechanism by which HOTAIR mediates apoptosis in chondrocytes are not completely understood. Here, we evaluated the effects of HOTAIR on chondrocyte apoptosis in KOA. Our results showed that HOTAIR expression was significantly upregulated in cartilage tissues located at the femoral condyles or tibial plateaus of OA resection regions when compared with control regions in patients with normal non‐weight‐bearing area femoral condyle articular cartilage. Overexpression of HOTAIR caused a sharp increase in apoptosis rates and a reduction in the viability of chondrocytes. These effects were accompanied by the upregulation of Bax expression and the proteolytic cleavage of caspase 3 expression and downregulation of survivin and Bcl‐2 expression. The silencing of HOTAIR produced the opposite effects. Moreover, the cartilaginous expression of miR‐130a‐3p was notably reduced in the OA resection regions of KOA patients. Luciferase assays showed that HOTAIR‐adsorbed and reduced the levels of miR‐130a‐3p in chondrocytes. Further, inhibition of miR‐130a‐3p remarkably promoted the apoptosis of chondrocytes and repressed cell growth, while the silencing of HOTAIR could rescue the apoptosis mediated by miR‐130a‐3p inhibition. Chondrocyte autophagy was suppressed in a HOTAIR‐dependent, miR‐130a‐3p inhibitor‐mediated manner. Overall, our data revealed that aberrantly high expression of HOTAIR resulted in massive apoptosis events caused by the sponging of miR‐130a‐3p to suppress autophagy in chondrocytes, which, in turn, might trigger KOA. Therefore, inhibition of HOTAIR‐mediated apoptosis might be a potential mechanism that can be targeted by gene therapy of KOA.
Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes
Authors: Zhou Yue , Geng Zhuang , Wang Xiang , Huang Yajing , Shen Liyan , Wang Yangang 
Published: October 2019

SummaryWe aimed to determine whether sodium‐glucose cotransporter type 2 inhibitors (SGLT2is) and incretin‐based agents combination therapy produces more benefits than SGLT2is alone in patients with type 2 diabetes mellitus (T2DM). PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing SGLT2is plus Dipeptidyl‐Peptidase 4 inhibitors (SGLT2is/DPP4is) or glucagon like peptide‐1 receptor agonists (SGLT2is/GLP‐1RAs) against SGLT2is as monotherapy or add‐on to metformin in T2DMs. A total of 13 studies with 7350 participants were included. Combination with GLP‐1RAs exhibited more HbA1c reduction (WMD: −0.8; 95% CI, −1.14 to −0.45%), weight loss (−1.46; 95% CI, −2.38 to −0.54 kg), and systolic blood pressure (SBP) reduction (−2.88; 95% CI, −4.52 to −1.25 mmHg) versus SGLT2is alone but increased the gastrointestinal disorder risk (RR: 1.68; 95% CI, 1.14‐2.47). Combination with DPP4is exhibited an extra effect on HbA1c reduction (−0.47; 95% CI, −0.58 to −0.37%), a neutral effect on weight (0.19; 95% CI, −0.11 to 0.48 kg) and SBP (−0.01; 95% CI, −0.85 to 0.63 mmHg), and ameliorated the genital infections risk (0.73; 95% CI, 0.54‐0.97) versus SGLT2is. Meta‐regression indicated the hypoglycemic efficacy of SGLT2is/DPP4is is higher in Asians than in other ethnics, and the differences in BMI across ethnic groups may mediate this effect. SGLT2is and incretin‐based agents combination therapy is efficacious and safe versus SGLT2is alone in T2DMs. Particularly, combination with GLP‐1RAs shows additional benefits to glycemic, weight, and SBP control to a larger extent than DPP4is, while combination with DPP4is ameliorates the risk for genital infection seen with SGLT2is. We highlight the need for individualized treatment related to the selection of this novel combination therapy.
Genetic diversity and differentiation of Daphnia galeata in the middle and lower reaches of the Yangtze River, China
Authors: Liu Qi , Deng Daogui , Zhang Kun , He Ping , Sun Yuchen , Zhang Tingting , Yang Wei , Liu Wei 
Published: October 2019

AbstractMitochondrial 16S rDNA and CO I gene were used as molecular markers for the analysis of the genetic diversity and differentiation of Daphnia galeata populations in nine water bodies in the middle and lower reaches of the Yangtze River. In the combined 16S rDNA and CO I gene sequences, 54 variable sites and 44 haplotypes were observed among 219 individuals belonging to nine D. galeata populations. Average haplotype diversity and nucleotide diversity were, respectively, 0.72% and 0.56%. The F‐statistics (FST) value of the D. galeata populations was 0.149. According to the results of the neutral test, D. galeata in the middle and lower reaches of the Yangtze River had experienced a bottleneck effect in the history. Molecular variance analysis indicated that the genetic differentiation of the D. galeata populations mainly occurred within populations (85.09%). Greater genetic differentiations of D. galeata among individuals within populations appeared in the populations from the Huaihe River basin, whereas smaller genetic differentiations occurred in the populations from the middle reaches of the Yangtze River. Strong gene flows were all observed between Group I (four populations from the middle reaches of the Yangtze River) and Group ΙΙ (three populations from the middle and lower reaches of the Yangtze River), and Group ΙΙΙ (two populations from the Huaihe River basin). The effective migration rates (M) were 851.49 from Group I to Group ΙΙ and 685.96 from Group I to Group ΙΙΙ, respectively. However, no significant relationship was observed between the genetic differentiation and geographical distance of the nine populations (r = .137, p > .05). Results suggested that the genetic differentiation of D. galeata in the water bodies in the middle and lower reaches of the Yangtze River resulted mainly from geographical isolation.
Functionalization of PEO layer formed on Ti‐15Mo for biomedical application
Authors: Leśniak Katarzyna , Płonka Joanna , Śmiga‐Matuszowicz Monika , Brzychczy‐Włoch Monika , Kazek‐Kęsik Alicja 
Published: October 2019

AbstractIn the present work, deposition of poly(sebacic anhydride) PSBA loaded by amoxicillin, cefazolin, or vancomycin on a previously anodized Ti‐15Mo surface is presented. PSBA loaded by the drug was deposited so as not to lose the functionality of the porous oxide layer microstructure. The morphology was evaluated using scanning electron microscopy, surface roughness, and wettability. The drug concentration was evaluated using high‐performance liquid chromatography. It was determined that the drugs were loaded into coatings in the range of 35.2–122.87 μg/cm2 of Ti sample. The drugs released more than 16% after 0.5 hr of the hybrid coating immersion in artificial saliva. After 3 days, the PSBA coatings were degraded by 51.3 mol %, and after 7 days by 77.8 mol %, which makes it possible to load the material by different, biologically active substances. An antimicrobial investigation of Staphylococcus aureus (DSM 24167) and Staphylococcus epidermidis (ATCC 700296) confirmed the activity of the hybrid layers against the pathogens. Hybrid layer with vancomycin best inhibits the adhesion of the bacteria, whereas coatings with amoxicillin and cefazolin showed a much better bactericidal activity. In this article, the difference in the obtained results is discussed, as well as the possibility of the application of this functional material in biomedicine.
Manganese‐doped green tea‐derived carbon quantum dots as a targeted dual imaging and photodynamic therapy platform
Authors: Irmania Novi , Dehvari Khalilalrahman , Gedda Gangaraju , Tseng Po‐Jen , Chang Jia‐Yaw 
Published: October 2019

AbstractIn this work, manganese‐doped carbon quantum dots (Mn‐CQDs) have been synthesized through a one‐pot hydrothermal method by using waste green tea. The Mn2+ dopants were introduced to impart magnetic resonance capability. Upon optimization of the experimental conditions, magnetofluorescent Mn‐CQDs exhibit an excitation‐dependent blue emission. The abundant functional groups on Mn‐CQDs not only promote water solubility but also allow straightforward functionalization with amine groups. The amine‐terminated Mn‐CQDs were then subsequently conjugated to folic acid (FA) and chlorin e6 (Ce6) to obtain the Mn‐CQDs@FA/Ce6 magnetofluorescent photodynamic therapy (PDT) agent. in vitro studies using three different cells indicated specific targeting of Mn‐CQDs@FA/Ce6 to the overexpressing folate receptor human epithelial carcinoma cell line (HeLa) cancer cells. Furthermore, Mn‐CQDs@FA/Ce6 enhanced magnetic resonance imaging (MRI) signal with an r2/r1 ratio of 5.77. Favorably, by using the Mn‐CQDs@FA delivery system, active Ce6 can reach the cellular interior while its red fluorescence (FL) and reactive oxygen species generation can be retained, as has been verified by confocal microscopy. in vitro cell viability studies verified the biocompatibility of Mn‐CQDs@FA/Ce6 nanohybrid with no significant toxicity up to 500 ppm while PDT treatment with 5 min irradiation (671 nm, 1 W cm−2) was effective in killing >90% of cells. The light‐triggered Mn‐CQDs@FA/Ce6 multifunctional hybrid can serve as a dual‐modal FL/MRI probe and as an efficient PDT agent to detect and eradicate cancer cells remotely.
Analysis of competing endogenous RNA network identifies a poorly differentiated cancer‐specific RNA signature for hepatocellular carcinoma
Authors: Chen Qi‐Feng , Huang Tao , Si‐Tu Qi‐Jiao , Wu Peihong , Shen Lujun , Li Wang , Huang Zilin 
Published: October 2019

AbstractPlenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well‐differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA‐related overall survival (OS) curves were determined using the Kaplan‐Meier method. The lncRNA ARHGEF7‐AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7‐AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1‐, 3‐, and 5‐year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C‐index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7‐AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7‐AS2 may be used as an independent biomarker to predict the prognosis of HCC.
MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2
Authors: Yuan Yuan , Wang Xiaoying , Sun Qiuyu , Dai Xu , Cai Yan 
Published: October 2019

AbstractIn recent years, the role of microRNAs (miRNAs) in pre‐eclampsia (PE) has been demonstrated, while the relevant mechanisms of miR‐16 in PE await to be unearthed. Thus, the aim of this study is to explore whether miR‐16 exerts its function in PE, and we assumed that miR‐16 may be implicated in the occurrence of PE by adjusting the biological functions of trophoblast cells via modulating Notch2. Placental tissues of pregnant women with normal pregnancy and PE were collected to detect the expression of miR‐16, Notch2, and Notch3. The effects of miR‐16 and Notch2 on the biological functions of BeWo and JEG‐3 cells were further determined. Expression of miR‐16 and Notch2 in trophoblast cells was detected by reverse transcription quantitative polymerase chain reaction and western blot assay. Downregulated Notch2 and upregulated miR‐16 and Notch3 were found in placental tissues of PE. There was a negative correlation between Notch2 and miR‐16 expression (r = −0.769), and a positive correlation between Notch3 and miR‐16 expression (r = 0.676; p < .05). Overexpression of miR‐16 inhibited proliferation, migration, and invasion, and facilitated the apoptosis of BeWo and JEG‐3 cells, but overexpression of Notch2 reversed this trend. Overexpression of miR‐16 inhibited Notch2 expression in BeWo and JEG‐3 cells, and Notch2 was the target gene of miR‐16. Our study highlights that overexpression of miR‐16 is involved in PE by regulating the biological functions of trophoblast cells via inhibition of Notch2. This paper provides a new idea for further study of the pathogenesis of PE.
Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR‐1304 to modulate ERBB4 expression
Authors: Chen Minghui , Liu Xiaojuan , Xie Peng , Wang Pengyu , Liu Mingli , Zhan Yongxuan , Wang Hongjun , Feng Yan , Li Yongli 
Published: October 2019

AbstractGlioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real‐time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan–Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit‐8 (CCK‐8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK‐8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR‐1304 and circ_0074026 or ERBB4 3′‐untranslated region (3′‐UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual‐luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients’ tumor size, WHO grade, disease‐free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual‐luciferase reporter assay demonstrated that miR‐1304 interacted with circ_0074026 and ERBB4 3′‐UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR‐1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.
YAP1 inhibits the induction of TNF‐α‐stimulated bone‐resorbing mediators by suppressing the NF‐κB signaling pathway in MC3T3‐E1 cells
Authors: Yang Beining , Sun Hualing , Xu Xiaoxiao , Zhong Heli , Wu Yanru , Wang Jiawei 
Published: October 2019

AbstractYes‐associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone‐remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor‐α (TNF‐α) in MC3T3‐E1 cells. The key osteoclastogenic molecules induced by TNF‐α, namely, interleukin‐6 and receptor activator of nuclear factor‐κB (NF‐κB) ligand, were suppressed after lentivirus‐induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF‐α‐induced activation of the NF‐κB signaling pathway as revealed by the reduced expression of phosphorylated‐p65 and NF‐κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF‐α was reversed by berberine in concentration‐dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption.
BZW2 promotes the malignant progression of colorectal cancer via activating the ERK/MAPK pathway
Authors: Huang Longping , Chen Si , Fan Haijun , Ai Fan , Sheng Weiwei 
Published: October 2019

AbstractColorectal cancer (CRC) is one of the most prevalent malignant solid cancers worldwide involving the dysregulation of multiple signaling molecules. However, the role and corresponding mechanism of basic leucine zipper and W2 domains 2 (BZW2) in CRC development, to our knowledge, has not been reported. We found BZW2 was overexpressed in human CRC tissues compared with that in paired adjacent colorectal samples. BZW2 overexpression was closely associated with tumor T stage (p = .030), metastatic lymph nodes (p = .037), TNM stage (p = .018) and the worse prognosis of CRC patients (p = .009). Moreover, BZW2 was an independent disadvantage prognostic factor (p = .031). BZW2 also showed an increased expression in different invasive CRC cell lines. Its silencing and overexpression diminished and increased cell proliferation, invasion, and migration in Colo205 and HCT116 cells via specifically activating of extracellular‐signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) signaling. Moreover, ERK/MAPK inhibitor PD98059 reverse the enhancement of cell proliferation, invasion, and migration in BZW2 overexpressing HCT116 cells. BZW2 silencing also inhibited subcutaneous tumors growth and p‐ERK expression in vivo. BZW2 promotes the malignant progression of CRC via activating ERK/MAPK signaling, which provided a promising gene target therapy for CRC.
HotBalloon ablation of atrial fibrillation in patients with dextrocardia and situs inversus by “mirror image” approach
Authors: Miyauchi Shunsuke , Nakano Yukiko , Ikeuchi Yoshihiro , Okamura Sho , Okubo Yousaku , Hironobe Naoya , Tokuyama Takehito , Kihara Yasuki 
Published: October 2019

AbstractA 51‐year‐old man with dextrocardia and complete situs inversus who presented with palpitation as a result of drug refractory paroxysmal atrial fibrillation (AF) was referred to our hospital for catheter ablation. Pulmonary vein isolation (PVI) was performed using the HotBalloon technique. We were able to accomplish AF ablation safely and easily using 180 degree‐inversed mirror images of X‐ray fluoroscopy. We have reported successful PVI for AF with dextrocardia using HotBalloon and mirror image of X‐ray fluoroscopy without any complication for the first time.
Starving the Gut: A Deficit of Butyrate in the Intestinal Ecosystem of Children With Intestinal Failure
Authors: Dowhaniuk Jenna K. , Szamosi Jake , Chorlton Sam , Owens Jillian , Mileski Heather , Clause Rose‐Frances , Pernica Jeffrey M. , Bowdish Dawn M. E. , Surette Michael G. , Ratcliffe Elyanne M. 
Published: October 2019

AbstractBackgroundIntestinal epithelial integrity is influenced by short‐chain fatty acids (SCFAs) and is of critical importance for children with intestinal failure (IF) given the known devastating infectious and gastrointestinal complications. The composition of the microbiome in IF represents an important variable in the physiology and prognosis of this disease.AimWe sought to compare the intestinal microbiome and SCFA concentration of children who require parenteral nutrition (PN) with that of children with short‐bowel syndrome (SBS) who have discontinued PN and with age‐matched controls, using high‐throughput sequencing to investigate host‐microbe interactions.MethodsFifty‐three samples were submitted over 6–15 months. Six children with SBS + IF submitted 34 samples, and 6 children with SBS with discontinued PN submitted 15 samples; these were compared with samples from 5 control children. Fecal samples were analyzed by 16S ribosomal RNA partial gene sequencing using the MiSeq Illumina sequencer. SCFAs were measured in stool samples by mass spectrometry.ResultsButyrate quantity was near absent in children with IF compared with that in controls (median 0.37 nmol/mg vs 10.92 nmol/mg; P < .0001). Similarly, commensal anaerobes known to produce SCFA, including Ruminococcaceae and Lachnospiraceae, were reduced in those with SBS. SBS + IF enteric samples demonstrated a 168‐fold increase in the relative abundance of the Escherichia genus seemingly attributable to the species Escherichia coli.ConclusionThe reduced relative abundance of butyrate‐producing Clostridia as well as decreased intestinal butyrate concentration in children with IF support further investigation in therapeutic options that target butyrate‐producing bacterial communities or butyrate supplementation.
Synthesis of metallosupramolecular polymers incorporating cage silsesquioxanes in the main chains
Authors: Hashimoto Mari , Fujii Shunichi , Imoto Hiroaki , Naka Kensuke 
Published: October 2019

ABSTRACTWe first time prepared main‐chain type cage octasilsesquioxane (T8) containing coordination polymers based on transition metal complexes with a bis‐Schiff base T8 ligand (bis‐SA‐T8), which was prepared from para‐bis(3‐aminopropyl)hexaisobutyl‐substituted T8 cage (bis‐T8) with salicylaldehyde. A mono‐Schiff base T8 ligand (SA‐T8) was prepared from 3‐aminopropylheptaisobutyl‐substituted T8 cage (mono‐T8) with salicylaldehyde. Coordination of bis‐SA‐T8 with Cu2+ and Zn2+ in a solution as well as the film state was confirmed by the d–d transition appearing as broad shoulder on the longer wavelength at around 600 nm and the fluorescence at around 440–470 nm, respectively. The resulting metallosupramolecular polymers gave optically transparent films in the visible region by a casting method. However, opaque green and whitish films were obtained in the case of the Cu2+ and Zn2+ complexes with SA‐T8, respectively. The thermal stabilities of the metallosupramolecular polymers were higher than those of the corresponding metal complexes of SA‐T8. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2260–2266