bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of hedgehog ligands in human simple steatosis may protect against nonalcoholic steatohepatitis: Is TAZ a crucial regulator?
Authors: Khajehahmadi Zohreh , Mohagheghi Sina , Nikeghbalian Saman , Geramizadeh Bita , Khodadadi Iraj , Karimi Jamshid , Ghaffari Mohammad Ebrahim , Tavilani Heidar 
Published: May 2019

AbstractThe conversion of simple steatosis into nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD) has attracted many attentions in recent years. The role of the hedgehog (HH) pathway in the regulation of lipogenesis has been addressed in the literature. This study aimed to investigate the levels of the sonic hedgehog (SHH) and Indian hedgehog (IHH) ligands and the correlation of these ligands with levels of proteins involved in the transforming growth factor‐β1 (TGF‐β1) pathway, as well as the evaluation of the transcriptional coactivator with PDZ binding motif (TAZ) expression in human simple steatosis, NASH cirrhosis, and controls. Patients were divided into two groups: the first group consisted of patients diagnosed with simple steatosis (n = 16) and the second group included those diagnosed with NASH cirrhosis (n = 15). As a control group, 18 histologically normal liver tissues were collected in this study. The expression of the TGF‐β1pathway components and SHH and IHH ligands were analyzed by means of the quantitative real‐time polymerase chain reaction and western blot analyses. A significant decrease was found in the hepatic expression of the SHH, IHH, and TGF‐β1 pathways along with the expression of TAZ in tissue specimens with simple steatosis in comparison with patients affected by NASH cirrhosis and controls. Also, the levels of SHH and IHH proteins were significantly correlated with the expression of proteins involved in the TGF‐β1 pathway. Moreover, the expression of the HH pathway ligands was positively associated with the expression of TAZ, supporting the notion that TAZ may play a role in the activation of the HH pathway thereby regulating the expression of its ligands. It seems that in patients with NAFLD, the downregulation of the HH pathway ligands may stem from steatosis; however, at the same time, it may prevent the conversion of simple steatosis into NASH in patients with liver diseases. © 2019 IUBMB Life, 71(9):1382–1390, 2019
Fabrication and properties of an injectable sodium alginate/PRP composite hydrogel as a potential cell carrier for cartilage repair
Authors: Gao Xiang , Gao Liyang , Groth Thomas , Liu Tianfeng , He Dongning , Wang Mingrui , Gong Fan , Chu Jiaqi , Zhao Mingyan 
Published: May 2019

AbstractThree‐dimensional scaffolds like hydrogels can be employed as cell carriers for in vitro or in vivo colonization and have become a major research topic to replace damaged tissue. In the current study, a novel composite hydrogel composed of sodium alginate (SA) and platelet‐rich‐plasma (PRP) varying in blending ratios, cross‐linked with calcium ions, released from calcium carbonate‐D‐Glucono‐d‐lactone (CaCO3‐GDL) was successfully prepared. It was found that addition of PRP changed largely the physical properties and biological performance of the composite hydrogels, which was depending on the blending ratio. The gelation rate and swelling ratio of alginate hydrogels were significantly reduced by the addition of PRP, which produced also a more homogeneous gel structure. Field emission scanning electron microscopy (FE‐SEM) investigation confirmed the incorporation of PRP‐derived proteins in the hydrogel, where a porous structure with a pore size of 200–300 μm was found. On the other hand, an increase in surface roughness was observed after the addition of PRP. The compressive mechanical strength of SA/PRP composite hydrogel was enhanced in comparison to the pure SA gel. The composite hydrogels with the highest PRP content exhibited at a maximum compressive stress of 0.26 MPa a maximum strain of 55%, while the maximum compressive strain of pure SA hydrogels was only 45% at a stress of 0.08 MPa. It was also found that the in vitro degradation of the alginate gel was accelerated by the addition of PRP. In terms of cellular responses, all gels exhibited an excellent cytocompatibility. Indeed, the composite hydrogels supported bone marrow‐derived mesenchymal stem cells proliferation and their chondrogenesis with up‐regulation of chondrogenic marker genes Sox9 and Aggrecan. Overall, the present study suggests a great potential of SA/PRP composite hydrogels as cell carriers for cartilage tissue engineering.
Indocyanine green based fluorescent polymeric nanoprobes for in vitro imaging
Authors: Ege Zeynep R. , Akan Aydin , Oktar Faik N. , Lin Chi C. , Kuruca Durdane S. , Karademir Betul , Sahin Yesim M. , Erdemir Gokce , Gunduz Oguzhan 
Published: May 2019

AbstractIndocyanine green (ICG) provides an advantage in the imaging of deep tumors as it can reach deeper location without being absorbed in the upper layers of biological tissues in the wavelengths, which named “therapeutic window” in the tissue engineering. Unfortunately, rapid elimination and short‐term stability in aqueous media limited its use as a fluorescence probe for the early detection of cancerous tissue. In this study, stabilization of ICG was performed by encapsulating ICG molecules into the biodegradable polymer composited with poly(l‐lactic acid) and poly(ε‐caprolactone) via a simple one‐step multiaxial electrospinning method. Different types of coaxial and triaxial structure groups were performed and compared with single polymer only groups. Confocal microscopy was used to image the encapsulated ICG (1 mg/mL) within electrospun nanofibers and in vitro ICG uptake by MIA PaCa‐2 pancreatic cancer cells. Stability of encapsulated ICG is demonstrated by the in vitro sustainable release profile in PBS (pH = 4 and 7) up to 21 days. These results suggest the potential of the ability of internalization and accommodation of ICG into the pancreatic cell cytoplasm from in vitro implanted ICG‐encapsulated multiaxial nanofiber mats. ICG‐encapsulated multilayer nanofibers may be promising for the local sustained delivery system to eliminate loss of dosage caused by direct injection of ICG‐loaded nanoparticles in systemic administration.
The microRNA‐141‐3p/CDK8 pathway regulates the chemosensitivity of breast cancer cells to trastuzumab
Authors: Song Wenqing , Wu Shiwu , Wu Qiong , Zhou Lei , Yu Lan , Zhu Bo , Gong Xiaomeng 
Published: May 2019

AbstractAimsThis study was conducted to explore the function of microRNA‐141‐3p/cyclin‐dependent kinase 8 (miR‐141‐3p/CDK8) in regulating trastuzumab resistance of breast cancer cells.Materials and MethodsMicroarray analysis was performed to screen microRNAs that are differentially expressed in wild type and trastuzumab‐resistant (TR) breast cancer cell lines. TargetScan helped predict the target gene of miR‐141‐3p. The regulatory relationship was confirmed through a luciferase reporter assay, quantitative reverse transcriptase polymerase chain reaction, and Western blot analysis. The MTT assay, transwell invasion assay, and wound scratch assay were performed to measure the proliferative, invasive, and migratory ability of breast cancer cells, respectively. Tumor cell xenografts in nude mice were conducted to observe the effect of miR‐141‐3p on trastuzumab resistance in breast cancer cells in vivo. The enzyme‐linked immunosorbent assay was used to detect protein secretion.ResultsmiR‐141‐3p was downregulated in the drug‐resistant cell lines. CDK8 was proved to be a target gene of miR‐141‐3p. Transfection of miR‐141‐3p or CDK8 small interfering RNA (siRNA) reversed the resistance to trastuzumab in TR cell lines and suppressed cell invasion and migration. Dysregulation of transforming growth factor beta (TGF‐β) was detected when the expression of CDK8 was silenced by CDK8 siRNA, and downregulation of TGF‐β had a notable effect on reducing the phosphorylation of SMAD2/SMAD3.ConclusionmiR‐141‐3p could restore the sensitivity to trastuzumab in breast cancer cells by repressing CDK8, which might regulate the phosphorylation levels of SMAD2/SMAD3 via TGF‐β.
Overexpression of tensin homolog deleted on chromosome ten (PTEN) by ciglitazone sensitizes doxorubicin‐resistance leukemia cancer cells to treatment
Authors: Mashayekhi Samira , Yousefi Bahman , Tohidi Ehsan , Darband Saber Ghazizadeh , Mirza‐Aghazadeh‐Attari Mohammad , Sadighparvar Shirin , Kaviani Mojtaba , Shafiei‐Irannejad Vahid , Kafil Hossein Samadi , Karimian Ansar , Jadidi‐Niaragh Farhad , Majidinia Maryam 
Published: May 2019

AbstractOvercoming multidrug resistance (MDR) is a final goal of various recent studies, in which combination of different compounds and conventional chemotherapeutics results in circumventing MDR and hence cancer progression. Therefore, we aimed to investigate the effects of peroxisome proliferator‐activated receptors (PPARs)‐γ on MDR in doxorubicin‐resistant human myelogenous leukemia cells. The effect of doxorubicin on cell viability following treatment with ciglitazone was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. The activity of P‐glycoprotein (P‐gp), as one of the membrane transporters, was determined by the rhodamine 123 (Rho 123) assay. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blot were used for the measurement of P‐gp, and tensin homolog deleted on chromosome ten (PTEN) expression at mRNA and protein, respectively. For evaluation of doxorubicin (DOX)‐induced apoptosis by annexin V/PI staining was used. Ciglitazone significantly increases the cytotoxic effects of DOX. In addition, ciglitazone considerably decreased the expression levels and activity of P‐gp in DOX‐resistant K562 cells. Furthermore, upon the ciglitazone treatment, PTEN expression could be increased in K562/DOX cells in a PPARγ–dependent manner. Moreover, ciglitazone significantly enhanced DOX‐induced apoptosis in K562/DOX cells. The combination treatment of K562/DOX leukemia cancer cells with doxorubicin and ciglitazone might be an effective strategy in inducing apoptosis and reversing developed MDR, and more importantly decreasing the adverse side effects of these agents.
Oxymatrine ameliorates insulin resistance in rats with type 2 diabetes by regulating the expression of KSRP, PETN, and AKT in the liver
Authors: Zuo Mei‐Ling , Wang Ai‐Ping , Tian Ying , Mao Li , Song Gui‐Lin , Yang Zhong‐Bao 
Published: May 2019

AbstractInsulin resistance plays a key role in the development and progression of type 2 diabetes mellitus (T2DM). Recent studies found that insulin resistance was associated with the dysfunction of KH‐type splicing regulatory protein (KSRP) expression and AKT pathway, and that oxymatrine possesses an antidiabetic effect. The aim of the present study was to investigate whether the protection of oxymatrine against T2DM was associated with the modulation of the KSRP expression and AKT pathway. Sprague‐Dawley rats were fed a high‐fat diet and injected with streptozotocin intraperitoneally to induce T2DM, which led to an increase in blood glucose levels and insulin resistance, and a decrease in insulin sensitivity and glycogen synthesis concomitant with KSRP downregulation, PTEN upregulation, and AKT phosphorylation deficiency. The administration of oxymatrine decreased blood glucose levels and insulin resistance, increased insulin sensitivity, and improved glycogen synthesis in the liver of T2DM rats, through a reversal in the expression of KSRP, PTEN, and AKT. On the basis of these observations, we concluded that oxymatrine can protect T2DM rats from insulin resistance through the regulation of the KSRP, PETN, and AKT expression in the liver.
circLRP6 regulates high glucose‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells
Authors: Chen Bin , Li Yanhua , Liu Yang , Xu Zhonggao 
Published: May 2019

AbstractAberrant regulation in mesangial cell proliferation, extracellular matrix (ECM) accumulation, oxidative stress, and inflammation under hyperglycemic condition contributes significantly to the occurrence and development of diabetic nephropathy (DN). However, the mechanisms underlying the hyperglycemia‐induced dysregulations have not been clearly elucidated. Here, we reported that high mobility group box 1 (HMGB1) was highly elevated in high glucose (HG)‐treated mesangial cells, and induced the phosphorylation, nuclear translocation, and DNA binding activity of NF‐κB via toll‐like receptor 4 (TLR4). Function assays showed that inhibition of HMGB1 mitigated HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via TLR4/NF‐κB pathway. Increasing evidence has shown that circRNA, a large class of noncoding RNAs, functions by binding with miRNAs and terminating regulation of their target genes. We further investigated whether HMGB1 is involved in circRNA–miRNA–mRNA regulatory network. First, HMGB1 was identified and confirmed to be the target of miR‐205, and miR‐205 played a protective role against HG‐induced cell injure via targeting HMGB1. Then circLRP6 was found to be upregulated in HG‐treated mesangial cells, and regulate HG‐induced mesangial cell injure via sponging miR‐205. Besides, overexpression of miR‐205 or knockdown of circLRP6 inhibited the NF‐κB signaling pathway. Collectively, these data suggest that circLRP6 regulates HG‐induced proliferation, oxidative stress, ECM accumulation, and inflammation in mesangial cells via sponging miR‐205, upregulating HMGB1 and activating TLR4/NF‐κB pathway. These findings provide a better understanding for the pathogenesis of DN.
Convergence of Wnt and Notch signaling controls ovarian cancer cell survival
Authors: Bocchicchio Sebastián , Tesone Marta , Irusta Griselda 
Published: May 2019

AbstractIn the last 40 years ovarian cancer mortality rates have slightly declined and, consequently, it continues to be the fifth cause of cancer death in women. In the present study, we showed that β‐catenin signaling is involved in the functions of ovarian cancer cells and interacts with the Notch system. Wnt and Notch systems showed to be prosurvival for ovarian cancer cells and their inhibition impaired cell proliferation and migration. We also demonstrated that the inhibition of β‐catenin by means of two molecules, XAV939 and ICG‐001, decreased the proliferation of the IGROV1 and SKOV3 ovarian cancer cell lines and that ICG‐001 increased the percentage of IGROV1 cells undergoing apoptosis. The simultaneous inhibition of β‐catenin and Notch signaling, by using the DAPT inhibitor, decreased ovarian cancer cell proliferation to the same extent as targeting only the Wnt/β‐catenin pathway. A similar effect was observed in IGROV1 cell migration with ICG‐001 and DAPT. ICG‐001 increased the Notch target genes Hes‐1 and Hey‐1 and increased Jagged1 expression. However, no changes were observed in Dll4 or Notch 1 and 4 expressions. Our results suggest that Notch and β‐catenin signaling co‐operate in ovarian cancer to ensure the proliferation and migration of cells and that this could be achieved, at least partly, by the upregulation of Notch Jagged1 ligand in the absence of Wnt signaling. We showed that the Wnt pathway crosstalks with Notch in ovarian cancer cell functions, which may have implications in ovarian cancer therapeutics.
Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies
Authors: Afshari Khashayar , Haddadi Nazgol‐Sadat , Haj‐Mirzaian Arvin , Farzaei Mohammad Hosein , Rohani Mohammad Mojtaba , Akramian Freshteh , Naseri Rozita , Sureda Antoni , Ghanaatian Negar , Abdolghaffari Amir Hossein 
Published: May 2019

AbstractFlavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti‐inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.
Mitochondrial proteomics reveals the mechanism of spermatogenic cells apoptosis induced by carbon ion radiation in zebrafish
Authors: Li Hongyan , Zhang Weihong , Zhang Hong , Xie Yi , Sun Chao , Di Cuixia , Si Jing , Gan Lu , Yan Junfang 
Published: May 2019

AbstractThe mitochondrial proteins involved in spermatogenic cells apoptosis in zebrafish after carbon ion radiation (CIR) were screened. The relative biological effectiveness (RBE) of CIR in zebrafish testes was investigated. Apoptosis of testicular cells was measured within 24 hr following 1 and 4 Gy CIR. Immunoblotting was used to assess the levels of mitochondrial apoptotic proteins in testes, and proliferative and apoptotic spermatogenic cells were detected by immunofluorescence after CIR. Label‐free quantitative (LFQ) and parallel reaction monitoring‐based target proteomics (PRM) were combined to screen and validate differential mitochondrial proteins in testes between 4 Gy and control groups at 24 hr after CIR. The RBE of CIR in zebrafish testes was 1.48 ± 0.04, and induction of apoptosis by CIR was higher than that of X‐rays in testicular cells. Mitochondrial apoptotic pathways play a crucial role in spermatogenic cells apoptosis after CIR, with 60 differential mitochondrial proteins identified. Among 20 target proteins, 12 were significantly upregulated, 2 were significantly downregulated in the 4 Gy CIR group. The results of PRM were consistent with label‐free analysis. This is the first study to screen the differential mitochondrial proteins and provide useful information to understand the underlying mechanisms of spermatogenic cell apoptosis in zebrafish following CIR.
The histomorphological structure of the male reproductive system of maize leaf weevil Tanymecus dilaticollis Gyllenhal, 1834 (Coleoptera: Curculionidae)
Authors: Ö. Koçakoğlu Nurcan , Candan Selami , Güllü Mustafa 
Published: May 2019

AbstractThe histomorphology of the reproductive system and the germ cells has been useful to establish phylogenetic relationships in many insects. However, these elements remain little known in the Curculionidae. In this study, histomorphological structure of the male reproductive system of Tanymecus dilaticollis, which is economically important, is described, illustrated using stereomicroscopy, light microscopy, and scanning electron microscopy techniques, and discussed in relation to other Coleoptera species. Results showed that distinctive features of the male reproductive system of T. dilaticollis consist of a pair of yellowish testes, a pair of seminal vesicles, a pair of vasa deferentia, an ejaculatory duct, accessory glands, prostate glands, and aedeagus. Each testis is subdivided into two testicular follicles, enclosed by a peritoneal sheath. Each follicle of the mature testes is full sperm cysts with germ cells at various stages development of spermatogenesis. The testes have four types of germ cells (spermatogonia, spermatocytes, spermatids, and spermatozoa). They are occupied by the growth zone containing spermatogonia and spermatocytes, the maturation zone containing spermatids, while differentiation zone containing spermatozoa. There is a seminal vesicle at the center of each testis. Most mature sperms are stored in the seminal vesicle. Each testis is attached to the vas deferens by a stalk‐like seminal vesicle. In the distal part, vasa deferentia fuse with the ejaculatory duct. It is linked to the aedeagus. The provided results will contribute to the understanding of the reproductive cell biology of Curculionidae.
Gastrointestinal neoplasia in patients with inflammatory bowel disease: Opportunities to enhance preventative strategies
Authors: Young Edward , Lawrence Matthew , Thomas Michelle , Andrews Jane 
Published: May 2019

Background and AimsGastrointestinal (GI) adenocarcinoma, especially colorectal cancer (CRC), is a devastating complication of inflammatory bowel disease (IBD). We sought to examine the role of chronic inflammation and other possible predictors of the development of CRC, as well as assess as yet unexamined factors such as psychological comorbidity and engagement in care.MethodsThis study included all patients involved in a tertiary hospital IBD service diagnosed with CRC between 2007 and 2017. Reports from histological specimens were assessed, and all those with adenocarcinoma, high‐grade dysplasia (HGD), or multifocal low‐grade dysplasia (LGD) originating within IBD‐affected mucosa were included in the study.ResultsA total of 32 patients were included in the study (17 with adenocarcinoma and 15 with HGD/multifocal LGD). The majority had a duration of disease >20 years. Eleven patients (34%, CI 20–52%) had previous disease‐related surgery, and 16 (50%, CI 34–66%) had multiple previous disease‐related admissions. Thirteen patients (62%, CI 41–79%) had >50% of CRP results higher than 8 mg/L. Psychiatric comorbidities were common, with 19 patients (59%, CI 42–74%) having a psychiatric comorbidity or poor engagement in treatment.ConclusionIn this cohort, we have highlighted poor engagement, hesitation to up‐titrate therapy when indicated, and psychological comorbidities as likely contributors to poor disease control and development of GI adenocarcinoma. Based on our data, these easily identifiable clinical care factors should not be overlooked when addressing IBD‐related GI malignancy prevention. Additional research is required to assess a direct causal relationship, but this study would support the incorporation of psychology services into IBD clinics.
Feasibility to Perform T2* Mapping Postcontrast Administration in Reperfused STEMI Patients for the Detection of Intramyocardial Hemorrhage
Authors: Bulluck Heerajnarain , Chowdhury Nazia , Lim Mei Xing , Allen John C. , Bryant Jennifer A. , Chan Mark Y. , Chan Mervyn H.H. , Chin Calvin W.L. , Ho Hee Hwa , Lim Soo T. , Tan Ru‐San , Tan Jack W. , Wong Philip E. , Yeo Khung K. , Cook Stuart A. , Hausenloy Derek J. 
Published: May 2019

Level of Evidence: 1Technical Efficacy: Stage 2
Ethanol production by simultaneous saccharification and cofermentation of pretreated corn stalk
Authors: Zhao Wenxuan , Zhao Fuguang , Zhang Sitong , Gong Qinglong , Chen Guang 
Published: May 2019

AbstractThe recalcitrance of lignocellulosic biomass is a major factor limiting its conversion into biofuels. Therefore, in this study, we pretreated corn stalk with 2% Na2CO3 and 2% H2O2 for time 70 min at 130°C using a corn stalk to liquid ratio of 1:10. The fermentation broth from multicopy Saccharomyces cerevisiae strains engineered for lignocellulase synthesis was used to enzymatically hydrolyze the pretreated corn stalk. The highest monosaccharide yield (102 mmol/L) was obtained using 15 IU endocellulase, 10 IU exocellulase, and 15 IU β‐glucosidase per gram of cellulose and 20 IU xylanase per gram of hemicellulose. Subsequently, the high‐efficiency ethanol‐producing S. cerevisiae strain WXY12, which can produce ethanol from glucose and xylose simultaneously, was added to the fermentation system. The entire process involved ethanol production through simultaneous saccharification and fermentation (SSF). Optimization of the fermentation conditions (yeast powder as a nitrogen source, temperature of 30°C, MgSO4 as a metal ion inducer, rotation speed of 180 rpm, solid–liquid ratio of 1:8, and inoculation amount of 2%) resulted in an ethanol output of 46.87 g/L and a theoretical conversion rate of 27.4%. The results of this study improved corn stalk utilization, reduced hydrolysis costs, and generated high ethanol yields.