bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress pathway
Authors: Li He , Chen Hongying , Li Ruli , Xin Juanjuan , Wu Sisi , Lan Jie , Xue Kunyue , Li Xue , Zuo Caili , Jiang Wei , Zhu Ling 
Published: September 2018

AbstractEndoplasmic reticulum stress (ERS) is usually involved in tumor development and progression, and anticancer agents have recently been recognized to induce ERS. Cucurbitacin‐I showed a potent anticancer action by inducing apoptosis through the inhibition of signal transducer and activator of transcription 3 pathway and triggering autophagic cell death. It is not known whether ERS mediates the cancer cell death induced by cucurbitacin‐I. Here, we investigated the role of ERS in cucurbitacin‐I‐treated SKOV3 ovarian cancer cells and PANC‐1 pancreatic cancer cells. We confirmed that cucurbitacin‐I caused cell death and stirred excessive ERS levels by activating inositol requiring enzyme 1α (IRE1α) and protein kinase R‐like endoplasmic reticulum kinase (PERK), as well as PERK downstream factors, including IRE1α and C/EBP homologous protein, but not activating transcription factor 6 (ATF6α) pathway, which was in parallel with the increased Bax and caspase‐12‐dependent ERS‐associated apoptosis, autophagy and autophagy flux levels and caspase‐independent nonapoptotic cell death. Furthermore, 4‐phenylbutyrate, an ERS inhibitor, suppressed cucurbitacin‐I‐induced apoptosis, autophagy, autophagy flux, and autophagic cell death. Simultaneously, there are positive correlations among ERS and cucurbitacin‐I‐induced reactive oxygen species and Ca
2+. Our results suggested that cucurbitacin‐I‐induced cancer cell death through the excessive ERS and CHOP‐Bax and caspase‐12‐dependent ERS‐associated apoptosis, as well as ERS‐dependent autophagy, autophagy flux, and caspase‐independent nonapoptotic cell death. These novel signaling insights may be useful for developing new, effective anticancer strategies in oncotherapy.
In silico analysis and molecular dynamics simulation of human superoxide dismutase 3 (SOD3) genetic variants
Authors: Pereira G. R. C. , Da Silva A. N. R. , Do Nascimento S. S. , De Mesquita J. F. 
Published: September 2018

AbstractOxidative stress is a major factor in aging processes. Superoxide dismutase 3 (SOD3) plays a key role in the protection of extracellular oxidative stress. Missense mutations in SOD3 have been described to be associated with the occurrence of pulmonary, cardiovascular, and neoplastic diseases. This study aims to analyze the effects of missense mutations on the SOD3 structure and function by modeling a complete SOD3 structure as well as analyzing the differences between the wild‐types and mutants using computational simulations. Here, ten algorithms were used to predict the structural and functional effects of missense mutations. A complete model of SOD3 protein was made by ab initio and comparative modeling using the Rosetta algorithm and validated by PROCHECK, Verify 3D, QMEAN, and ProSa. Molecular dynamics (MD) simulations were performed and analyzed using the GROMACS package. The deleterious potential of the A58T and R231G mutants was not predicted by the majority of the used algorithms. The analyzed mutations were predicted as destabilizing by at least one algorithm. The MD analyses indicated that protein flexibility may be increased by all of the analyzed mutations, while the protein‐ligand stability may be decreased. They also suggested that the variants A91T and R231G increase the overall dimensions of SOD3 and decrease its accessible surface area. Our findings, therefore, indicated that the analyzed mutations could affect the protein structure and its ability to interact with other molecules, which may be related to the functional impairment of SOD3 upon A58T and R231G mutations, as well as their involvement in pathologies.
Cell communication by tunneling nanotubes: Implications in disease and therapeutic applications
Authors: Mittal Rahul , Karhu Elisa , Wang Jay‐Shing , Delgado Stefanie , Zukerman Ryan , Mittal Jeenu , Jhaveri Vasanti M. 
Published: September 2018

AbstractIntercellular communication is essential for the development and maintenance of multicellular organisms. Tunneling nanotubes (TNTs) are a recently recognized means of long and short distance communication between a wide variety of cell types. TNTs are transient filamentous membrane protrusions that connect cytoplasm of neighboring or distant cells. Cytoskeleton fiber‐mediated transport of various cargoes occurs through these tubules. These cargoes range from small ions to whole organelles. TNTs have been shown to contribute not only to embryonic development and maintenance of homeostasis, but also to the spread of infectious particles and resistance to therapies. These functions in the development and progression of cancer and infectious disease have sparked increasing scrutiny of TNTs, as their contribution to disease progression lends them a promising therapeutic target. Herein, we summarize the current knowledge of TNT structure and formation as well as the role of TNTs in pathology, focusing on viral, prion, and malignant disease. We then discuss the therapeutic possibilities of TNTs in light of their varied functions. Despite recent progress in the growing field of TNT research, more studies are needed to precisely understand the role of TNTs in pathological conditions and to develop novel therapeutic strategies.
Cerebroprotective effects of hydrogen sulfide in homocysteine‐induced neurovascular permeability: Involvement of oxidative stress, arginase, and matrix metalloproteinase‐9
Authors: Nath Nibendu , Prasad Himanshu Kishore , Kumar Munish 
Published: September 2018

AbstractAn elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood–brain barrier permeability and leakage. Hydrogen sulfide (H2S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy‐induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H
2S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of
dl‐Hcy/L in drinking for 8–10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H
2S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H
2S. Although H
2S supplementation ameliorated, the effect of HHcy and the levels of H
2S returned to the average level in HHcy animals supplemented with H
2S. Interestingly, H
2S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H
2S could be a beneficial therapeutic candidate for the treatment of Hcy‐associated neurodegeneration, such as stroke and neurovascular disorders.
Cyclic tensile force stimulates BMP9 synthesis and in vitro mineralization by human periodontal ligament cells
Authors: Tantilertanant Yanee , Niyompanich Jitti , Everts Vincent , Supaphol Pitt , Pavasant Prasit , Sanchavanakit Neeracha 
Published: September 2018

AbstractPeriodontal ligament (PDL) cells are mechanosensitive and have the potential to differentiate into osteoblast‐like cells under the influence of cyclic tensile force (CTF). CTF modulates the expression of regulatory proteins including bone morphogenetic proteins (BMPs), which are essential for the homeostasis of the periodontium. Among the BMPs, BMP9 is one of the most potent osteogenic BMPs. It is yet unknown whether CTF affects the expression of BMP9 and mineralization. Here, we demonstrated that continuously applied CTF for only the first 6 hr stimulated the synthesis of BMP9 and induced mineral deposition within 14 days by human PDL cells. Stimulation of
BMP9 expression depended on ATP and P2Y
1 receptors. Apyrase, an ecto‐ATPase, inhibited CTF‐mediated ATP‐induced
BMP9 expression. The addition of ATP increased the expression of
BMP9. Loss of function experiments using suramin (a broad‐spectrum P2Y antagonist), MRS2179 (a specific P2Y
1 receptor antagonist), MRS 2365 (a specific P2Y
1 agonist), U‐73122 (a phospholipase C [PLC] inhibitor), and thapsigargin (enhancer of intracytosolic calcium) revealed the participation of P2Y
1 in regulating the expression of
BMP9. This was mediated by an increased level of intracellular Ca
2+ through the PLC pathway. A neutralizing anti‐BMP9 antibody decreased mineral deposition, which was stimulated by CTF for almost 45% indicating a role of BMP9 in an in vitro mineralization. Collectively, our findings suggest an essential modulatory role of CTF in the homeostasis and regeneration of the periodontium.
Nerve repair and regeneration: Biological tubulization limits and future perspectives
Authors: Riccio Michele , Marchesini Andrea , Pugliese Pierfrancesco , De Francesco Francesco 
Published: September 2018

AbstractPeripheral nerve physiology and regeneration has been observed and investigated in literature but surgical applications to reconstruct and restore motor or sensory functions are still in a developmental phase. The peripheral nerve progresses slowly and incompletely compared with other tissues, it may provoke separations of the nerve stumps and the axonal proliferation of the conduits is restricted to 30 mm. Recent surgical attempts to treat proximal nerve injures include direct nerve restoration, transfer, and autografting measures with favorable results. Moreover, studies are suggesting that engineering tissue tubes maybe as effective as nerve grafting to restore separations of more than 4 cm toward optimal nerve repair.
Microscopic malaria parasitemia diagnosis and grading on benchmark datasets
Authors: Rehman Amjad , Abbas Naveed , Saba Tanzila , Mehmood Zahid , Mahmood Toqeer , Ahmed Khawaja Tehseen 
Published: September 2018

AbstractMalaria parasitemia diagnosis and grading is hard and still far from perfection. Inaccurate diagnosis and grading has caused tremendous deaths rate particularly in young children worldwide. The current research deeply reviews automated malaria parasitemia diagnosis and grading in thin blood smear digital images through image analysis and computer vision based techniques. Actually, state‐of‐the‐art reveals that current proposed practices present partially or morphology dependent solutions to the problem of computer vision based microscopy diagnosis of malaria parasitemia. Accordingly, a deep appraisal of the current practices is investigated, compared and analyzed on benchmark datasets. The open gaps are highlighted and the future directions are laid down for a complete automated microscopy diagnosis for malaria parasitemia based on those factors that have not been affected by other diseases. Moreover, a general computer vision framework to perform malaria parasitemia estimation/grading is constructed in universal directions. Finally, remaining problems are highlighted and possible directions are suggested.Research HighlightsThe current research presents a microscopic malaria parasitemia diagnosis and grading of malaria in thin blood smear digital images through image analysis and computer vision based techniques. The open gaps are highlighted and future directions for a complete automated microscopy diagnosis of malaria parasitemia mentioned.
Effect of natural antioxidants on the physicochemical properties and stability of freeze‐dried microencapsulated chia seed oil
Authors: Rodriguez Erica S , Julio Luciana M , Henning Cynthia , Diehl Bernd WK , Tomás Mabel C , Ixtaina Vanesa Y 
Published: September 2018

AbstractBACKGROUNDChia oil possesses a very high content of polyunsaturated fatty acids, mainly α‐linolenic acid. This characteristic makes this oil possess beneficial properties to health but gives it a high susceptibility to the oxidation process. Microencapsulation and the addition of natural antioxidants are alternatives to protect chia oil against oxidative deterioration. The aim of this study was to investigate the physicochemical characteristics and the oxidative stability of chia seed oil microencapsulated with different natural antioxidants (Guardian Chelox, which is a commercial blend of extracts from chamomile and rosemary, and essential oils from Origanum vulgare, Origanum x majoricum, and Mentha spicata) by freeze‐drying using sodium caseinate and lactose as wall materials.RESULTSThe main physicochemical properties of the microencapsulated chia oil were similar regardless of the presence of antioxidant. The moisture content was 38.1 ± 4.0 g kg−1; the microencapsulation efficiency was higher than 85% in all cases. The freeze‐drying microencapsulation significantly enhanced (P ≤ 0.05) the oxidative stability of the chia oil. The addition of natural antioxidants conferred chia oil additional protection against lipid oxidation, depending on the type and concentration (500 or 1000 mg kg−1 of the emulsion previous to freeze‐drying) of the antioxidant. Among them, Guardian Chelox (1000 mg kg−1), presented the highest induction time obtained by the Rancimat accelerated oxidative stability test and the lowest peroxide values after 90 days of storage (33% relative humidity, 25 ± 2 °C). Overall, the microparticles with antioxidants presented a lower degree of yellowing during storage than the control system.CONCLUSIONThe use of different natural antioxidants confers freeze‐dried microencapsulated chia seed oil additional protection against lipid oxidation. This information is relevant for the application of this oil, which is a rich source of omega‐3 fatty acids, in the food industry. © 2018 Society of Chemical Industry
Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and interval debulking surgery for advanced epithelial ovarian cancer: A feasibility study
Authors: Komiyama Shinichi , Kugimiya Tsuyoki , Kubushiro Kaneyuki 
Published: September 2018

Background and ObjectivesThe optimum treatment strategy for patients with unresectable advanced epithelial ovarian cancer is controversial. This study examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus carboplatin), followed by interval debulking surgery (IDS), for these patients.MethodsIn a prospective nonrandomized study, newly diagnosed patients received four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The primary endpoint was the complete resection rate at IDS. Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications.ResultsTwenty‐three patients were enrolled. The complete resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%). The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events ≥ grade 3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation. Grade 2 complications of IDS included lymphatic complications (13.6%), infections (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic complications, fistula/abscess, or perforation/anastomotic leak, and no complications ≥ grade 3.ConclusionsIn Japanese patients with advanced ovarian cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further investigation of its prognostic effect is warranted.
The role of oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para‐aortic lymphadenectomy
Authors: Zhou Guan‐Nan , Xin Wei‐Juan , Li Xiao‐Qing , Zhang Xu‐Yin , Hua Ke‐Qin , Ding Jing‐Xin 
Published: September 2018

AbstractBackground and ObjectivesThis study is aimed to investigate the possibility of preoperative oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para‐aortic lymphadenectomy.Materials and MethodsIn this retrospective nonrandomized study, of the 30 patients with gynecological malignancies who had indications for laparoscopic para‐aortic lymphadenectomy up to renal vessels, 15 were administered preoperative oral oil (oil a administration) (control group) at our hospital between September 2017 and June 2018. The chylous tube displaying rates, incidences of chylous leakage, and other perioperative data of the two groups were compared.ResultsSuccessful display of chylous tubes was observed in 93.3% (14/15) patients in the oil administration group. The chylous leakage was zero in the oil administration group, and 33.3% (5/15) in the control group. The postoperative drainage duration (4.1 ± 1.0 days vs 7.6 ± 1.4 days,
P = 0.000), somatostatin application time (0 day vs 5.9 ± 0.8 days), and postoperative hospital stay (6.0 ± 2.3 days vs 9.1 ± 2.1 days,
P = 0.001) were significantly shorter in the oil administration group. The total cost is lower in the oil administration group (4972.52 ± 80.54 dollars vs 6260.80 ± 484.47 dollars,
P = 0.000).ConclusionsPreoperative oil administration is a feasible and effective method to display the chylous tubes and to prevent the chylous leakage in para‐aortic lymphadenectomy.
Development, validation and application to real samples of a liquid chromatography with tandem mass spectrometry method for the determination of tetracyclines in beeswax
Authors: Gajda Anna , Antczak Maja , Mitrowska Kamila , Posyniak Andrzej 
Published: September 2018

AbstractBeeswax is a valuable honeybee product, which finds applications in the food and pharmaceutical industries, as well as in cosmetic production. However, some substances used in apiculture, like tetracyclines, can be delivered to hives where they cause contamination of honeybee products such as beeswax. Tetracyclines are commonly used for the treatment of American and European foulbrood diseases, but in the European Union their usage by beekeepers is forbidden. Thus, a sensitive method for the analysis of tetracyclines in beeswax is an important analytical tool. A new liquid chromatography with tandem mass spectrometry method for the analysis of tetracyclines including oxytetracycline, 4‐epioxytetracycline, tetracycline, 4‐epitetracycline, chlorotetracycline, 4‐epichlorotetracycline, and doxycycline in beeswax was developed. The method involved dilution of beeswax in n‐hexane after a melting step, liquid‐liquid extraction with oxalic acid and clean‐up using a weak cation exchange phase. Satisfactory separation was performed on an octadecyl column with 0.1% formic acid and acetonitrile in a total run time of 5 min. The application of this method was evaluated by the analysis of real beeswax samples. The presence of oxytetracycline was confirmed in 5 out of 48 tested beeswax samples, which shows the method can be successfully used to determine the tetracyclines in beeswax.
Application of a micro plasma collection card for the detection of homocysteine by liquid chromatography with tandem mass spectrometry
Authors: Yuan Xiangmei , Lu Youli , Xiao Can , Zhu Jianmin , Zhang Wei , Yu Chen , Li Shuijun 
Published: September 2018

AbstractGenerally, it is recommended that blood samples for homocysteine detection should be centrifuged immediately to separate plasma in order to avoid continuous synthesis by blood cells. The use of a micro plasma collection card may improve sample stability and result accuracy by offering automatic and instant plasma separation. We compare a micro plasma collection method with routine wet plasma to explore applications of the dried plasma spots for homocysteine determination by using liquid chromatography with tandem mass spectrometry. The method was validated for both dried plasma spots and wet plasma. The assay was linear from 0.5–45 μmol/L with good precisions and accuracies. The extraction recovery and matrix effect for dried plasma spots were >97% and 0.98 after internal standard normalization, respectively. It was reproducible for retaining homocysteine in dried plasma spots and kept stable for 30 days. The plasma conversion factor was 7.77 ± 0.7% by calculating the ratio of homocysteine concentration between dried plasma spots and wet plasma (n = 165). Neither hematocrit nor homocysteine concentration affected the plasma conversion factor as long as the hematocrit was within the normal range. The results support the clinical usefulness of the dried plasma spots as a convenient and stable biological matrix for testing homocysteine.
Optimal Timing of Spinal Ultrasound Evaluations for Sacral Dimples in Neonates: Earlier May Not Be Better
Authors: Cho Hyun‐Hae , Lee So Mi , You Sun Kyoung 
Published: September 2018

ObjectivesA spinal ultrasound (US) evaluation during the immediate postnatal period may have limited ability in evaluating filum thickness because of the spinal cord pulsation caused by a crowded subarachnoid space and the cerebrospinal fluid deficiency during this period. This study aimed to determine the optimal timing of spinal US to evaluate sacral dimples in neonates.MethodsThis study included 585 neonates who had a clinically suspicious sacral dimple and underwent spinal US examinations between January 2015 and August 2017. Patients were classified into 1 of 2 groups based on whether measurements of all parameters were possible (group A) or not (group B). Neonatal and maternal clinical factors, including the antenatal history and US parameters, were compared between groups.ResultsGroup A included 443 patients, and group B included 82. Patients in group B were significantly younger (6.2 versus 31.0 days), had a younger corrective age (38.9 versus 42.5 weeks), and had a smaller body weight (3.1 versus 4.6 kg) than those in group A (all P < .005). However, no statistically significant differences were found in other patient or maternal factors (P > .05 for all). The pulsation of the conus medullaris and nerve roots of the cauda equina (14.6% versus 100%), thickening and echogenicity of the filum terminale (2.4% versus 100%), and the presence of a normal subarachnoid space (18.3% versus 100%) were significantly more difficult to detect in group B than in group A (all P < .001).ConclusionsFor an accurate evaluation, which can reduce unnecessary confusion and costs, spinal US can be delayed until neonates grow beyond 31 days, with a corrected age of older than 42.5 weeks and body weight of greater than 4.6 kg.