bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I
Authors: Zhang Qi , Cheng Gang , Pan Jing , Zielonka Jacek , Xiong Donghai , Myers Charles R. , Feng Liang , Shin Song Seok , Kim Young Heui , Bui Dinh , Hu Ming , Bennett Brian , Schmainda Kathleen , Wang Yian , Kalyanaraman Balaraman , You Ming 
Published: April 2020

Abstract
Background
Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy.

Methods
The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated.

Results
ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells.

Conclusion
Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis.
Tumor microenvironment complexity and therapeutic implications at a glance
Authors: Baghban Roghayyeh , Roshangar Leila , Jahanban-Esfahlan Rana , Seidi Khaled , Ebrahimi-Kalan Abbas , Jaymand Mehdi , Kolahian Saeed , Javaheri Tahereh , Zare Peyman 
Published: April 2020

AbstractThe dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.
HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines
Authors: Iveland Tobias S. , Hagen Lars , Sharma Animesh , Sousa Mirta M. L. , Sarno Antonio , Wollen Kristian Lied , Liabakk Nina Beate , Slupphaug Geir 
Published: April 2020

AbstractBackgroundHDAC inhibitors (HDACi) belong to a new group of chemotherapeutics that are increasingly used in the treatment of lymphocyte-derived malignancies, but their mechanisms of action remain poorly understood. Here we aimed to identify novel protein targets of HDACi in B- and T-lymphoma cell lines and to verify selected candidates across several mammalian cell lines.MethodsJurkat T- and SUDHL5 B-lymphocytes were treated with the HDACi SAHA (vorinostat) prior to SILAC-based quantitative proteome analysis. Selected differentially expressed proteins were verified by targeted mass spectrometry, RT-PCR and western analysis in multiple mammalian cell lines. Genomic uracil was quantified by LC–MS/MS, cell cycle distribution analyzed by flow cytometry and class switch recombination monitored by FACS in murine CH12F3 cells.ResultsSAHA treatment resulted in differential expression of 125 and 89 proteins in Jurkat and SUDHL5, respectively, of which 19 were commonly affected. Among these were several oncoproteins and tumor suppressors previously not reported to be affected by HDACi. Several key enzymes determining the cellular dUTP/dTTP ratio were downregulated and in both cell lines we found robust depletion of UNG2, the major glycosylase in genomic uracil sanitation. UNG2 depletion was accompanied by hyperacetylation and mediated by increased proteasomal degradation independent of cell cycle stage. UNG2 degradation appeared to be ubiquitous and was observed across several mammalian cell lines of different origin and with several HDACis. Loss of UNG2 was accompanied by 30–40% increase in genomic uracil in freely cycling HEK cells and reduced immunoglobulin class-switch recombination in murine CH12F3 cells.ConclusionWe describe several oncoproteins and tumor suppressors previously not reported to be affected by HDACi in previous transcriptome analyses, underscoring the importance of proteome analysis to identify cellular effectors of HDACi treatment. The apparently ubiquitous depletion of UNG2 and PCLAF establishes DNA base excision repair and translesion synthesis as novel pathways affected by HDACi treatment. Dysregulated genomic uracil homeostasis may aid interpretation of HDACi effects in cancer cells and further advance studies on this class of inhibitors in the treatment of APOBEC-expressing tumors, autoimmune disease and HIV-1.
KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke
Authors: Zhang Xinyu , Wang Lu , Han Zhenxiang , Dong Jing , Pang Defang , Fu Yuan , Li Longxuan 
Published: April 2020

Abstract
Background
Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 have all been reported to be induced after cerebral ischemic stroke (CIS), the close temporal and spatial relationship between expressions of CAMs and KLF4 following CIS and whether and how CAMs and KLF-4 contribute to the development of CIS-induced vascular injury are still unclear.

Methods
Here, we first examined the correlation between serum levels of CAMs/KLF4 and infarct volume in acute CIS patients. Then, we determined the relationship between CAMs and KLF4 in mice after focal cerebral ischemia. Finally, we investigated the mechanism of KLF4 in protecting against oxygen-glucose deprivation-induced brain endothelial cell injury.

Results
Our results demonstrated that patients with moderate to severe CIS had higher serum levels of three CAMs including E-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) but lower levels of KLF4 at 48 h after an acute event as compared to patients with minor CIS. The expression levels of three CAMs as well as KLF4 all correlated well with the infarct volume in all the CIS subjects at that time. Although the expressions of three CAMs and KLF4 were all induced in the ischemic hemisphere following focal cerebral ischemia, the peak timing and distribution patterns of their expression were different: the induction of KLF4 lagged behind that of the CAMs in the ischemic penumbra; furthermore, the dual immunofluorescent studies displayed that high expression of KLF4 was always associated with relatively less cerebral vascular endothelial inflammation response in the ischemic hemisphere and vice versa. Mechanistic analyses revealed that KLF4 alleviated CIS-induced cerebral vascular injury by regulating endothelial expressions of CAMs, nuclear factor-kB, and tight junction proteins.

Conclusions
These data indicate that KLF4 confers vascular protection against cerebral ischemic injury, suggesting that circulating CAMs and KLF4 might be used as potential biomarkers for predicting the prognosis of acute ischemic stroke and also providing a new proof of concept and potential targets for future prevention and treatment of CIS.
Associations of an empirical dietary pattern with cardiometabolic risk factors in Malaysian adolescents
Authors: Emi Nor Aishah , Gan Wan Ying , Mohd Shariff Zalilah , Anuar Zaini Azriyanti , Shamsuddin Nurainul Hana , Appukutty Mahenderan , Appannah Geeta 
Published: April 2020

AbstractsBackgroundThis study aimed to identify a dietary pattern (DP) characterised mainly by high intakes of free sugar and other nutrients hypothesised to be associated with obesity such as dietary energy density (DED), percentage of energy from total fat and fibre density in adolescents from three southern states of Peninsular Malaysia, and its associations with cardiometabolic risk factors.MethodsThis is a cross-sectional study among 335 adolescents who provided both dietary information assessed using a validated food frequency questionnaire (FFQ) and biochemical parameters including lipid profile, blood glucose, serum insulin and homeostatic model assessment-insulin resistance (HOMA-IR). Anthropometric measurements included weight (kg), height (cm) and waist circumference (cm), while body mass index (BMI) in kg/m2was estimated, respectively. Reduced rank regression (RRR) identified a DP with percentage of energy from sugar and total fat, DED and fibre density intake as response variables.ResultsThe identified ‘high sugar, high fibre, high DED and low fat’ DP was characterised by high intakes of sugar-sweetened beverages, fruits, sweets and low intakes of meat and cereal. Adolescents in the highest tertile of the identified DP had about 3.0 (OR = 2.7; 95%CI: 1.3, 5.6) and 2.0 (OR = 1.9; 95%CI: 1.0, 3.5) times higher odds of having dyslipideamia or elevated total cholesterol and LDL-cholesterol level, respectively compared to adolescents in the lowest tertile DP after adjusting for sex, school location, maternal education, physical activity, dietary misreporting and BMI z-score. This DP was not significantly associated with overweight and obesity.ConclusionsHigher adherence to a DP characterised mainly by free sugars and DED was associated with greater odds of having dyslipideamia, elevated total cholesterol and LDL-cholesterol levels in Malaysian adolescents.
A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis
Authors: Suzuki Kazushi , Ohe Rintaro , Kabasawa Takanobu , Aung Naing Ye , Yano Mitsuhiro , Katsumi Shuichiro , Yanagiya Ryo , Yamamoto Masakazu , Toubai Tomomi , Ishizawa Kenichi , Yamakawa Mitsunori 
Published: April 2020

AbstractBackgroundUlcerative colitis (UC) is one of the major types of inflammatory bowel diseases and is associated with a significantly increased risk of not only lymphoproliferative disorders but also lymphomas, of which most cases are related to the long-term usage of immunosuppressants. Here, we demonstrate a very rare case of other iatrogenic immunodeficiency-associated colonic diffuse large B-cell lymphoma (Oii-DLBCL) complicating UC and rectal perforation. In addition, we reviewed the clinicopathological features of previous cases of DLBCL related to UC.Case presentationA 68-year-old man was diagnosed with left-sided UC 26 months prior. Although he was followed by immunosuppressive therapy with azathioprine and infliximab, an emergency total proctocolectomy was performed due to rectal perforation. The resected specimen exhibited irregular wall thickening and elevated multinodular lesions extending from the mid-transverse colon to the rectum, measuring up to 52 cm in length. Histologically, the lesion was diagnosed as Oii-DLBCL and crypt abscess surrounded by mixed inflammatory cell was remained.ConclusionOii-DLBCL complicating UC with rectal perforation is extremely rare. Macro- and microscopic findings are important for early diagnosis of the lesion.
A new technical approach for preparing frozen biological samples for electron microscopy
Authors: Buchner Othmar , Steiner Philip , Andosch Ancuela , Holzinger Andreas , Stegner Matthias , Neuner Gilbert , Lütz-Meindl Ursula 
Published: April 2020

AbstractBackgroundMany methodological approaches have focused so far on physiological and molecular responses of plant tissues to freezing but only little knowledge is available on the consequences of extracellular ice-formation on cellular ultrastructure that underlies physiological reactions. In this context, the preservation of a defined frozen state during the entire fixation procedure is an essential prerequisite. However, current techniques are not able to fix frozen plant tissues for transmission electron microscopy (TEM) without interrupting the cold chain. Chemical fixation by glutaraldehyde and osmium tetroxide is not possible at sub-zero temperatures. Cryo-fixation methods, such as high pressure freeze fixation (HPF) representing the state-of-the-art technique for best structural preservation, are not equipped for freezing frozen samples. In order to overcome this obstacle, a novel technical approach for maintaining the cold chain of already frozen plant samples prior and during HPF is presented.ResultsDifferent algae (Micrasterias denticulata,Klebsormidium crenulatum) and higher plant tissues (Lemnasp.,Ranunculus glacialis,Pinus mugo) were successfully frozen and prepared for HPF at freezing temperatures (− 2 °C, − 5 °C, − 6 °C) within a newly developed automatic freezing unit (AFU), that we manufactured from a standard laboratory freezer. Preceding tests on photosynthetic electron transport and ability to plasmolyse show that the temperatures applied did not impair electron transport in PSII nor cell vitality. The transfer of the frozen specimen from the AFU into the HPF-device and subsequently cryo-fixation were performed without intermediate thawing. After cryo-substitution and further processing, the resulting TEM-micrographs showed excellent ultrastructure preservation of the different organisms when compared to specimens fixed at ambient temperature.ConclusionsThe method presented allows preserving the ultrastructure of plant cells in the frozen state during cryo-fixation. The resulting high quality TEM-images represent an important step towards a better understanding of the consequences of extracellular ice formation on cellular ultrastructure. It has the potential to provide new insights into changes of organelle structure, identification of intracellular injuries during ice formation and may help to understand freezing and thawing processes in plant tissues. It may be combined with analytical TEM such as electron energy loss spectroscopy (EELS), X-ray analyses (EDX) and various other electron microscopic techniques.
Alignment- and reference-free phylogenomics with colored de Bruijn graphs
Authors: Wittler Roland 
Published: April 2020

AbstractBackgroundThe increasing amount of available genome sequence data enables large-scale comparative studies. A common task is the inference of phylogenies—a challenging task if close reference sequences are not available, genome sequences are incompletely assembled, or the high number of genomes precludes multiple sequence alignment in reasonable time.ResultsWe present a new whole-genome based approach to infer phylogenies that is alignment- and reference-free. In contrast to other methods, it does not rely on pairwise comparisons to determine distances to infer edges in a tree. Instead, a colored de Bruijn graph is constructed, and information on common subsequences is extracted to infer phylogenetic splits.ConclusionsThe introduced new methodology for large-scale phylogenomics shows high potential. Application to different datasets confirms robustness of the approach. A comparison to other state-of-the-art whole-genome based methods indicates comparable or higher accuracy and efficiency.
Influence of cement-augmented pedicle screw instrumentation in an osteoporotic lumbosacral spine over the adjacent segments: a 3D finite element study
Authors: Zhou Quan-kun , Zeng Fan-hui , Tu Jian-long , Dong Zhang-qing , Ding Zhi-Hui 
Published: April 2020

AbstractPurposeTo compare the effect of conventional pedicle screw (CPS) and cement-augmented pedicle screw instrumentation (CAPSI) on adjacent segment degeneration (ASD).MethodsA normal male volunteer without a history of spinal disease was selected, lumbar CT data was collected, an intact L3-S1 three-dimensional finite element model was created by software including Mimics, Geomagic, and SolidWorks, and the fixation methods were performed accordingly. A common pedicle screw model and a cement-augmented pedicle screw model of L4–L5 with fusion and internal fixation were constructed. With ANSYS Workbench 17.0, a 500 N load was applied to the upper surface of L3 to simulate the weight of a human body, and a 7.5 N m moment was applied at the neutral point to simulate flexion, extension, left/right bending, left/right rotation of the spine. The peak von Mises stress of intervertebral disc and the range of motion (ROM) on the adjacent segments (L3–4 and L5–S1) were compared.ResultsThe validity of the intact model shows that the ROM of the model is similar to that of a cadaveric study. Compared with the intact model, CPS model and CAPSI model in all motion patterns increased the ROM of adjacent segments. The intervertebral disc stress and the ROM of adjacent segments were found to be higher in the CAPSI model than in the CPS model, especially in L3–4.ConclusionIn general, the biomechanical analysis of an osteoporotic lumbar spine showed that both CPS and CAPSI can increase the ROM and disc stresses of osteoporotic lumbar models, and compared with CPS, CAPSI is more likely to increase the potential risk of adjacent segment degeneration.
Prevalence, indications, and outcomes of caesarean section deliveries in Ethiopia: a systematic review and meta-analysis
Authors: Gedefaw Getnet , Demis Asmamaw , Alemnew Birhan , Wondmieneh Adam , Getie Addisu , Waltengus Fikadu 
Published: April 2020

Abstract
Background
Caesarean section rates have increased worldwide in recent decades. Caesarean section is an essential maternal healthcare service. However, it has both maternal and neonatal adverse outcomes. Therefore this systematic review and meta-analysis aimed to estimate the prevalence, indication, and outcomes of caesarean section in Ethiopia.

Methods
Twenty three cross-sectional studies with a total population of 36,705 were included. Online databases (PubMed/Medline, Hinari, Web of Science, and Google Scholar) and online university repository was used. All the included papers were extracted and appraised using the standard extraction sheet format and Joanna Briggs Institute respectively. The pooled prevalence of the caesarean section, indications, and outcomes was calculated using the random-effect model.

Result
The overall pooled prevalence of Caesarean section was 29.55% (95% CI: 25.46–33.65). Caesarean section is associated with both maternal and neonatal complications. Cephalopelvic disproportion [18.13%(95%CI: 12.72–23.53] was the most common indication of Caesarean section followed by non-reassuring fetal heart rate pattern [19.57% (95%CI: 16.06–23.08]. The common neonatal complications following Caesarean section included low APGAR score, perinatal asphyxia, neonatal sepsis, meconium aspiration syndrome, early neonatal death, stillbirth, and prematurity whereas febrile morbidity, surgical site infection, maternal mortality, severe anemia, and postpartum hemorrhage were the most common maternal complications following Caesarean section.

Conclusion
In this systematic review and meta-analysis, the rate of Cesarean section was high. Cephalopelvic disproportion, low Apgar score, and febrile morbidity were the most common indication of Caesarean section, neonatal outcome and maternal morbidity following Caesarean section respectively. Increasing unjustified Caesarean section deliveries as a way to increase different neonatal and maternal complications, then several interventions needed to target both the education of professionals and the public.
Temporal expression profiling of DAMPs-related genes revealed the biphasic post-ischemic inflammation in the experimental stroke model
Authors: Yamaguchi Atsushi , Jitsuishi Tatsuya , Hozumi Takashi , Iwanami Jun , Kitajo Keiko , Yamaguchi Hiroo , Mori Yasutake , Mogi Masaki , Sawai Setsu 
Published: April 2020

AbstractThe neuroinflammation in the ischemic brain could occur as sterile inflammation in response to damage-associated molecular patterns (DAMPs). However, its long-term dynamic transcriptional changes remain poorly understood. It is also unknown whether this neuroinflammation contributes to the recovery or just deteriorates the outcome. The purpose of this study is to characterize the temporal transcriptional changes in the post-stroke brain focusing on DAMPs-related genes by RNA-sequencing during the period of 28 days. We conducted the RNA-sequencing on day 1, 3, 7, 14, 28 post-stroke in the mouse photothrombosis model. The gross morphological observation showed the ischemic lesion on the ipsilateral cortex turned into a scar with the clearance of cellular debris by day 28. The transcriptome analyses indicated that post-stroke period of 28 days was classified into four categories (I Baseline, II Acute, III Sub-acute-#1, IV Sub-acute-#2 phase). During this period, the well-known genes for DAMPs, receptors, downstream cascades, pro-inflammatory cytokines, and phagocytosis were transcriptionally increased. The gene ontology (GO) analysis of biological process indicated that differentially expressed genes (DEGs) are genetically programmed to achieve immune and inflammatory pathways. Interestingly, we found the biphasic induction of various genes, including DAMPs and pro-inflammatory factors, peaking at acute and sub-acute phases. At the sub-acute phase, we also observed the induction of genes for phagocytosis as well as regulatory and growth factors. Further, we found the activation of CREB (cAMP-response element binding protein), one of the key players for neuronal plasticity, in peri-ischemic neurons by immunohistochemistry at this phase. Taken together, these findings raise the possibility the recurrent inflammation occurs at the sub-acute phase in the post-stroke brain, which could be involved in the debris clearance as well as neural reorganization.