bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semi‐interpenetrating polymer network cryogels based on poly(ethylene glycol) diacrylate and collagen as potential off‐the‐shelf platforms for cancer cell research
Authors: Masullo Ugo , Cavallo Anna , Greco Maria Raffaella , Reshkin Stephan J. , Mastrodonato Maria , Gallo Nunzia , Salvatore Luca , Verri Tiziano , Sannino Alessandro , Cardone Rosa Angela , Madaghiele Marta 
Published: January 2021

AbstractIn the present work, we investigated the potential of novel semi‐interpenetrating polymer network (semi‐IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable off‐the‐shelf platforms for 3D cancer cell research. We synthesized semi‐IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long‐term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen‐enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intra‐scaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.
Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth
Authors: Weaver Samantha R , Taylor Earnest L , Zars Elizabeth L , Arnold Katherine M , Bradley Elizabeth W , Westendorf Jennifer J 
Published: January 2021

ABSTRACT
Endochondral ossification is tightly controlled by a coordinated network of signaling cascades including parathyroid hormone (PTH). Pleckstrin homology (PH) domain and leucine rich repeat phosphatase 1 (Phlpp1) affects endochondral ossification by suppressing chondrocyte proliferation in the growth plate, longitudinal bone growth, and bone mineralization. As such, Phlpp1−/− mice have shorter long bones, thicker growth plates, and proportionally larger growth plate proliferative zones. The goal of this study was to determine how Phlpp1 deficiency affects PTH signaling during bone growth. Transcriptomic analysis revealed greater PTH receptor 1 (Pth1r) expression and enrichment of histone 3 lysine 27 acetylation (H3K27ac) at the Pth1r promoter in Phlpp1-deficient chondrocytes. PTH (1-34) enhanced and PTH (7-34) attenuated cell proliferation, cAMP signaling, cAMP response element-binding protein (CREB) phosphorylation, and cell metabolic activity in Phlpp1-inhibited chondrocytes. To understand the role of Pth1r action in the endochondral phenotypes of Phlpp1-deficient mice, Phlpp1−/− mice were injected with Pth1r ligand PTH (7-34) daily for the first 4 weeks of life. PTH (7-34) reversed the abnormal growth plate and long-bone growth phenotypes of Phlpp1−/− mice but did not rescue deficits in bone mineral density or trabecular number. These results show that elevated Pth1r expression and signaling contributes to increased proliferation in Phlpp1−/− chondrocytes and shorter bones in Phlpp1-deficient mice. Our data reveal a novel molecular relationship between Phlpp1 and Pth1r in chondrocytes during growth plate development and longitudinal bone growth. © 2021 American Society for Bone and Mineral Research (ASBMR).
Eugenol–piperine loaded polyhydroxy butyrate/polyethylene glycol nanocomposite‐induced apoptosis and cell death in nasopharyngeal cancer (C666‐1) cells through the inhibition of the PI3K/AKT/mTOR signaling pathway
Authors: Sun Xiaopeng , Veeraraghavan Vishnu Priya , Surapaneni Krishna Mohan , Hussain Sardar , Mathanmohun Maghimaa , Alharbi Sulaiman Ali , Aladresi Aref Ali Mohammed , Chinnathambi Arunachalam 
Published: January 2021

AbstractNasopharyngeal cancer is a malignancy developing from the nasopharynx epithelium due to smoking and nitrosamine‐containing foods. Nasopharyngeal cancer is highly endemic to Southeast Asia. Eugenol and piperine have shown many anticancer activities on numerous cancer types, like colon, lung, liver, and breast cancer. In this study, we amalgamated eugenol and piperine loaded with a polyhydroxy butyrate/polyethylene glycol nanocomposite (Eu‐Pi/PHB‐PEG‐NC) for better anticancer results against nasopharyngeal cancer (C666‐1) cells. In the current study, nasopharyngeal cancer cell lines C666‐1 were utilized to appraise the cytotoxic potential of Eug‐Pip‐PEG‐NC on cell propagation, programmed cell death, and relocation. Eu‐Pi/PHB‐PEG‐NC inhibits cellular proliferation on C666‐1 cells in a dose‐dependent manner, and when compared with 20 µg/ml, 15 µg/ml of loaded mixture evidently restrained the passage aptitude of C666‐1 cells, this was attended with a downregulated expression of mitochondrial membrane potential. Treatment with 15 µg/ml Eu‐Pi/PHB‐PEG‐NC suggestively amplified cell apoptosis in the C666‐1 cells. Furthermore, its cleaved caspase‐3, 8, and 9 and Bax gene expression was augmented and Bcl‐2 gene expression was diminished after Eu‐Pi/PHB‐PEG‐NC treatment. Additionally, our data established that the collective effect of Eu‐Pi/PHB‐PEG‐NC loaded micelles inhibited the expansion of C666‐1 cells augmented apoptosis connected with the intrusion of PI3K/Akt/mTOR signaling pathway.
Effect of fumonisin B1on oxidative stress and gene expression alteration of nutrient transporters in porcine intestinal cells
Authors: Chen Zhigang , Zhou Lihua , Yuan Qiaoling , Chen Huiyu , Lei Hongyu , Su Jianming 
Published: January 2021

AbstractFumonisin B1(FB1) is a common environmental mycotoxin produced by molds such asFusarium verticillioides. The toxin poses health risks to domestic animals, including pigs, through FB1‐contaminanted feed. However, the cytotoxicity of FB1to porcine intestines has not been fully analyzed. In the present study, the effects of FB1on oxidative stress and nutrient transporter‐associated genes of the porcine intestinal IPEC‐J2 cells were explored. FB1decreased IPEC‐J2 proliferation but did not trigger reactive oxygen species (ROS) overproduction. Meanwhile, FB1reduced the expression levels of the transportersl‐type amino acid transporter‐1 (y+LAT1), solute carrier family 7 member 1 (SLC7A1), solute carrier family 1 member 5 (ASCT2), and excitatory amino acid carrier 1 (EAAC1); in addition, FB1reduced the levels of the fatty acid transporters long‐chain fatty acid transport protein 1 (FATP1) and long‐chain fatty acid transport protein 4 (FATP4) as well as glucose transporters Na+/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2). FB1stimulation increased the expression levels of peptide transporter peptide transporter 1 (PepT1) and metal ion transport‐related gene zinc transporter 1 (ZNT1). Moreover, metal ion transporter divalent metal transporter 1 (DMT1) expression was depressed by a higher dosage of FB1. The data indicate that FB1results in aberrant expression of nutrient transporters in IPEC‐J2 cells, thereby exerting its toxicity even though it fails to exert ROS‐dependent oxidative stress.
Iron overload reduces adiponectin receptor expression via a ROS/FOXO1‐dependent mechanism leading to adiponectin resistance in skeletal muscle cells
Authors: Dahyaleh Karam , Sung Hye K. , Prioriello Michelle , Rengasamy Palanivel , Lam Nhat H. , Kim Jae B. , Gross Sean , Sweeney Gary 
Published: January 2021

AbstractIron overload (IO) is a common yet underappreciated finding in metabolic syndrome (MetS) patients. With the prevalence of MetS continuing to rise, it is imperative to further elucidate cellular mechanisms leading to metabolic dysfunction. Adiponectin has many beneficial effects and is a therapeutic target for the treatment of MetS and cardiovascular diseases. IO positively correlates with reduced circulating adiponectin levels yet the impact of IO on adiponectin action is unknown. Here, we established a model of IO in L6 skeletal muscle cells and found that IO‐induced adiponectin resistance. This was shown via reduced p38 mitogen‐activated protein kinase phosphorylation in response to the small molecule adiponectin receptor (AdipoR) agonist, AdipoRon, in presence of IO. This correlated with reduced messenger RNA and protein levels of AdipoR1 and its facilitative signaling binding partner, APPL1. IO caused phosphorylation, nuclear extrusion, and thus inhibition of FOXO1, a known transcription factor regulating AdipoR1 expression. The antioxidant N‐acetyl cystine attenuated the production of reactive oxygen species (ROS) by IO, and blunted its effect on FOXO1 phosphorylation and removal from the nucleus, as well as subsequent adiponectin resistance. In conclusion, our study identifies a ROS/FOXO1/AdipoR1 axis as a cause of skeletal muscle adiponectin resistance in response to IO. This new knowledge provides insight into a cellular mechanism with potential relevance to disease pathophysiology in MetS patients with IO.
Extracellular vesicles mediate cellular interactions in renal diseases—Novel views of intercellular communications in the kidney
Authors: Zhang Ping L. , Liu Ming‐Lin 
Published: January 2021

AbstractThe kidney is a complicated and important internal organ receiving approximately 20% of the cardiac output and mediates numerous pathophysiologic actions. These include selectively filtering macromolecules of the blood, exquisite reclaimation of electrolyctes, urine concentration via an elegant osmotic mechanism, and excretion of an acid load. In addition, the renal tubules carry out secretory functions and produce hormones and cytokines. The kidney receives innervation and hormonal regulation. Therefore, dysfunction of the kidney leads to retention of metabolic waste products, and/or significant proteinuria and hematuria. In the past several decades, the role of extracellular vesicles (EVs) in intercellular communications, and the uptake of EVs by recipient cells through phagocytosis and endocytosis have been elucidated. The new knowledge on EVs expands over the classical mechanisms of cellular interaction, and may change our way of thinking of renal pathophysiology in the subcellular scale. Based on some ultrastructural discoveries in the kidney, this review will focus on the role of EVs in intercellular communications, their internalization by recipient cells, and their relationship to renal pathology.
Improvement of natamycin production by controlling the morphology of Streptomyces gilvosporeus Z8 with microparticle talc in seed preculture
Authors: Yue Chaoping , Xu Haitao , Yu Yingying , Yu Xin , Yu Min , Zhang Chen , You Qian , Xia Shaofan , Ding Zixian , Fu Hao , Zeng Xin , Li Feng 
Published: January 2021

AbstractBACKGROUNDNatamycin, an antifungal agent, has been widely used as a food preservative and medicine for fungal disease therapy. Seed preculture plays a crucial role in natamycin production, while studies on the effects of seed morphology on natamycin biosynthesis and corresponding regulation approaches are still absent.RESULTSCorrelation analyses among spore age, seed morphology and natamycin production showed that old spores tended to form larger mycelial pellets, which gave rise to a significant reduction of natamycin biosynthesis. To solve this problem, microparticle talc was added to regulate the mycelial morphology in seed preculture. Optimal talc addition led to small mycelial pellets with hairy superficial mycelia and loose structure, resulting in higher glucose‐6‐phosphate dehydrogenase activity and energy charge. The seed morphology regulation effectively improved the natamycin titer and decreased the culture time, especially for old spores (age 28 days), with a 1.7‐fold higher natamycin titer and 16.9% culture time reduction. Unfortunately, direct talc addition proved to be infeasible for natamycin fermentation in a 5 L fermentor, which was attributed to physical damage from rapid agitation and excessive talc crashing. Therefore, the morphology engineering strategy was preferred in the seed preculture process rather than formal fermentation for natamycin production.CONCLUSIONThe new strategy proposed in this study could not only improve natamycin production, but also reduced the culture time. Furthermore, this work could provide references for other biochemicals production by filamentous bacteria or fungi, which would be of great significance in industrial antibiotic fermentation. © 2021 Society of Chemical Industry
Animal models of attention‐deficit hyperactivity disorder (ADHD)
Authors: Rahi Vikrant , Kumar Puneet 
Published: January 2021

AbstractAttention‐deficit hyperactivity disorder(ADHD) is a heterogeneous neuropsychiatric disorder characterized by three primary symptoms hyperactivity, attention deficit, and impulsiveness, observed in both children and adults. In childhood, this disorder is more common in boys than in girls, and at least 75% will continue to suffer from the disorder until adulthood. Individuals with ADHD generally have poor academic, occupational, and social functioning resulting from developmentally inappropriate levels of hyperactivity and impulsivity, as well as impaired ability to maintain attention on motivationally relevant tasks. Very few drugs available in clinical practice altogether abolish the symptoms of ADHD, therefore, to find new drugs and target it is essential to understand the neuropathological, neurochemical, and genetic alterations that lead to the progression of ADHD. With this contrast, an animal study is the best approach because animal models provide relatively fast invasive manipulation, rigorous hypothesis testing, as well as it provides a better angle to understand the pathological mechanisms involved in disease progression. Moreover, animal models, especially for ADHD, serve with good predictive validity would allow the assessment and development of new therapeutic interventions, with this aim, the present review collect the various animal models on a single platform so that the research can select an appropriate model to pursue his study.
Scanning electron microscopy analysis of conventional and controlled‐memory nickel titanium files before and after multi‐uses in root canals
Authors: Armagan Safa , Haznedaroglu Faruk 
Published: January 2021

AbstractThe current study aimed to examine changes in the physical properties of conventional and CM nickel–titanium instruments after repeated clinical use, disinfection‐sterilization processes, using scanning electron microscopy (SEM). Sixty extracted mandibular molar mesial roots were used in this ex vivo study. The 60 teeth underwent final apical shaping (#25/.06) by the Revo‐S SU (Revo‐S Group: #25/.06; Micromega; n = 10) and Hyflex CM (Hyflex CM group: #25/.06; Coltene–Whaledent; n = 10) groups. One instrument of each group was used to shape six different teeth (Revo‐S SU in 3 MB and 3 ML canals, and Hyflex CM in 3 MB and 3 ML canals), sequentially. The physical changes evident on the surfaces of the files after sequential use and sterilization processes were analyzed by SEM after the first, third, and sixth use. The first SEM examination was performed immediately after removal from the packages. Following first SEM examination, the files were sterilized before the first use as would be customary in practice. Qualitative evaluations were made by two evaluators, according to the following criteria: tip deformation, cutting edge deformation, debris, and microfracture. Revo‐S showed a significant difference in cutting edge deformation, tip deformation, and microcrack formation, as compared to Hyflex CM. There was no significant difference between the groups in debris with the increasing number of uses. In this study, Hyflex CM (CM nickel–titanium) files showed better performance in terms of deformation and microcrack formation as the number of uses increased than did Revo‐S (conventional nickel–titanium) files.
Self‐assembled Au and Pt nanoparticles in Poly(methyl methacrylate)
Authors: Salvadori Maria Cecília , de Sá Teixeira Fernanda , Cattani Mauro , Brown Ian G. 
Published: January 2021

AbstractNanocomposites formed by metal nanoparticles self‐assembled in an insulator matrix are of great technological importance. Applications include surface enhanced Raman spectroscopy based biosensors, optical devices, photovoltaic cells, and more. Self‐assembling of nanocomposites using low energy ion implantation offers a fast and low cost process. We report here on our work on nanocomposites formed by very low energy ion implantation of gold and platinum nanoparticles into Poly(methyl methacrylate) (PMMA), with description of the nanoparticle evolution as a function of implantation dose. The Au‐PMMA and Pt‐PMMA nanocomposites were characterized by transmission electron microscopy, thus determining the nanoparticle density, their size distribution, and the distance between particles as a function of implantation dose. A comparison between Au‐PMMA and Pt‐PMMA reveals substantial differences in the formation processes of the nanoparticles. The results provide insight into basic nanoparticle formation processes, as well as crucial information important for design applications. In addition, the tunneling decay length ξ and the electron affinity ε of the implantation‐modified PMMA were obtained using a new and simple approach.
Casein‐enhanced uptake and disease‐modifying bioactivity of ingested extracellular vesicles
Authors: Aminzadeh Mark A. , Fournier Mario , Akhmerov Akbarshakh , Jones‐Ungerleider K. Candis , Valle Jackelyn B. , Marbán Eduardo 
Published: January 2021

AbstractExtracellular vesicles (EVs) from cardiac stromal cells, developed as therapeutic candidates, improve dystrophic muscle function when administered parenterally, but oral delivery remains untested. We find that casein, the dominant protein in breast milk, enhances the uptake and bioactivity of ingested heart‐derived EVs, altering gene expression in blood cells and enhancing muscle function in mdx mice with muscular dystrophy. Thus, EVs, administered orally, are absorbed and exert disease‐modifying bioactivity in vivo. Formulating EVs with casein enhances uptake and markedly expands the range of potential therapeutic applications.
Cdc42 functions as a regulatory node for tumour‐derived microvesicle biogenesis
Authors: Wang Jing , Zhuang Xiangjin , Greene Kai Su , Si Ha , Antonyak Marc A. , Druso Joseph E. , Wilson Kristin F. , Cerione Richard A. , Feng Qiyu , Wang Hongyang 
Published: January 2021

AbstractTumour‐derived microvesicles (MVs) serve as critical mediators of cell‐to‐cell communication in the tumour microenvironment. So far, the underlying mechanisms of MV biogenesis, especially how key tumorigenesis signals such as abnormal EGF signalling regulates MV release, remain unclear. Here, we set out to establish reliable readouts for MV biogenesis and then explore the molecular mechanisms that regulate MV generation. We found that Rho family small G protein Cdc42 is a convergent node of multiple regulatory signals that occur in MV biogenesis. The binding of activated GTP‐bound Cdc42 and its downstream effector, Ras GTPase‐activating‐like protein 1 (IQGAP1), is required for MV shedding. Activated Cdc42 maintains sustained EGF signalling by inhibiting the internalization of cell surface receptors, including EGFR and the VEGF oligomer, VEGF90K, and then facilitates MV release. Subsequently, we further demonstrated that blocking these signalling pathways using the corresponding mutants effectively reduced MV shedding and significantly inhibited MV‐promoted in vivo tumour angiogenesis. These findings reveal a complex regulation of MV shedding by tumour cells, shedding light on the regulatory mechanism of MV biogenesis, and potentially contributing to strategies that target MVs in cancer therapy.
Highly efficient magnetic labelling allows MRI tracking of the homing of stem cell‐derived extracellular vesicles following systemic delivery
Authors: Han Zheng , Liu Senquan , Pei Yigang , Ding Zheng , Li Yuguo , Wang Xinge , Zhan Daqian , Xia Shuli , Driedonks Tom , Witwer Kenneth W. , Weiss Robert G. , van Zijl Peter C.M. , Bulte Jeff W.M. , Cheng Linzhao , Liu Guanshu 
Published: January 2021

AbstractHuman stem‐cell‐derived extracellular vesicles (EVs) are currently being investigated for cell‐free therapy in regenerative medicine applications, but the lack of noninvasive imaging methods to track EV homing and uptake in injured tissues has limited the refinement and optimization of the approach. Here, we developed a new labelling strategy to prepare magnetic EVs (magneto‐EVs) allowing sensitive yet specific MRI tracking of systemically injected therapeutic EVs. This new labelling strategy relies on the use of ‘sticky’ magnetic particles, namely superparamagnetic iron oxide (SPIO) nanoparticles coated with polyhistidine tags, to efficiently separate magneto‐EVs from unencapsulated SPIO particles. Using this method, we prepared pluripotent stem cell (iPSC)‐derived magneto‐EVs and subsequently used MRI to track their homing in different animal models of kidney injury and myocardial ischemia. Our results showed that iPSC‐derived EVs preferentially accumulated in the injury sites and conferred substantial protection. Our study paves a new pathway for preparing highly purified magnetic EVs and tracking them using MRI towards optimized, systemically administered EV‐based cell‐free therapies.
A family systems approach to genetic counseling: Development of narrative interventions
Authors: MacLeod Rhona , Metcalfe Alison , Ferrer‐Duch Mariangels 
Published: January 2021

AbstractTo what extent are family systems approaches relevant in the genomics era? What difference does it make to remember the wider social context within which ‘problems’ associated with a genetic diagnosis reside? How does this influence the conversations we have with our patients? These questions will be considered in relation to systemic approaches to genetic counseling practice. Narrative therapy with an emphasis on people's strengths, wishes, and ways of resisting the effects of a problem may be a particularly useful framework for genetic counselors. Narrative practice views people as multi‐storied and is concerned with the question of how we encourage people to tell their stories in ways that make them feel stronger. Increased uptake of genomic testing and the number of people seeking genetic counseling present opportunities to consider new ways of working, particularly around support following a new genetic diagnosis. One option is to realize the potential of group interventions. Family therapy and narrative practices have the potential to encourage communication and for families to learn from each other.
Graphs of bounded depth‐2 rank‐brittleness
Authors: Kwon O‐joung , Oum Sang‐il 
Published: January 2021

AbstractWe characterize classes of graphs closed under taking vertex‐minors and having no and no disjoint union of copies of the 1‐subdivision of for some . Our characterization is described in terms of a tree of radius 2 whose leaves are labeled by the vertices of a graph , and the width is measured by the maximum possible cut‐rank of a partition of induced by splitting an internal node of the tree to make two components. The minimum width possible is called the depth‐2 rank‐brittleness of . We prove that for all , every graph with sufficiently large depth‐2 rank‐brittleness contains or disjoint union of copies of the 1‐subdivision of as a vertex‐minor.